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 12 TH EDITION

DIPIRO’S
PHARMACOTHERAPY
A PAT H O P H YS I O LO G I C A P P R O AC H

FM.indd 1 13-02-2023 16:51:53

 Assistant Editors
Angela L. Bingham, PharmD, BCPS, Rena A. Gosser, PharmD, BCPS
BCNSP, BCCCP Clinical Ambulatory Pharmacy Manager
Harborview Medical Center
Vice Chair and Clinical Associate Professor
Seattle, Washington
Philadelphia College of Pharmacy
Saint Joseph’s University
Philadelphia, Pennsylvania Lisa M. Holle, PharmD, BCOP
Clinical Professor of Pharmacy Practice
Scott Bolesta, PharmD, BCPS Department of Pharmacy Practice
School of Pharmacy, University of Connecticut
Professor
Storrs, Connecticut
Department of Pharmacy Practice
Nesbitt School of Pharmacy, Wilkes University
Wilkes-Barre, Pennsylvania Amy M. VandenBerg, PharmD, BCPP
Clinical Associate Professor
Robert J. DiDomenico, PharmD, FCCP, College of Pharmacy, University of Michigan
Ann Arbor, Michigan
FHFSA, FACC
Associate Professor and Assistant Head
Department of Pharmacy Practice
College of Pharmacy, University of Illinois Chicago
Chicago, Illinois

FM.indd 2 13-02-2023 16:51:53

 12 TH EDITION

DIPIRO’S
PHARMACOTHERAPY
A PAT H O P H YS I O LO G I C A P P R O AC H

Editors
Joseph T. DiPiro, PharmD Thomas D. Nolin, PharmD, PhD, FCCP,
Professor, School of Pharmacy FCP, FASN
Associate Vice President for Health Sciences
Associate Dean for Research and Sponsored Programs
Virginia Commonwealth University
Associate Professor of Pharmacy and Therapeutics
Richmond, Virginia
School of Pharmacy, University of Pittsburgh
Pittsburgh, Pennsylvania
Gary C. Yee, PharmD
Professor, College of Pharmacy
Vicki L. Ellingrod, PharmD, FCCP
Associate Vice Chancellor for Academic Affairs Dean and John Gideon Searle Professor of Pharmacy
University of Nebraska Medical Center College of Pharmacy
Omaha, Nebraska Professor of Psychiatry, Medical School
University of Michigan
Ann Arbor, Michigan
Stuart T. Haines, PharmD, BCPS, BCACP
Professor, Department of Pharmacy Practice L. Michael Posey, BSPharm, MA
Director, Pharmacy Professional Development President
School of Pharmacy, University of Mississippi PENS Pharmacy Editorial & News Services
Jackson, Mississippi Santa Rosa, California

New York Chicago San Francisco Athens London Madrid Mexico City Milan New Delhi Singapore Sydney Toronto

FM.indd 3 27-02-2023 14:55:24

Copyright © 2023 by McGraw Hill LLC. All rights reserved. Except as permitted under the United States Copyright Act of 1976, no part of this publi-
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 Dedication
To our patients and students, who have challenged and inspired us and given meaning to all our endeavors.
To practitioners who continue to improve patient health outcomes and thereby serve as role models for their colleagues
and students while clinging tenaciously to the highest standards of practice.
To our mentors, whose vision provided educational and training programs that encouraged our professional growth and
challenged us to be innovators in our patient care, research, and education.
To our faculty colleagues for their efforts and support for our mission to provide a comprehensive and challenging educational
foundation for the pharmacists of the future.
And finally to our families for the time that they have sacrificed so that this twelfth edition would become a reality.
—The Editors

FM.indd 5 13-02-2023 16:51:54

 PAST EDITORS OF DIPIRO’S PHARMACOTHERAPY

Peggy E. Hayes, PharmD

Editions 1 and 2

Gary R. Matzke, PharmD, FCP, FCCP, FASN, FNAP

Editions 2–10

Robert L. Talbert, PharmD, FCCP, BCPS, FAHA

Editions 1–10

Barbara G. Wells, PharmD, FCCP, FASHP

Editions 3–10

FM.indd 6 13-02-2023 16:51:54

 Contents
Contributors������������������������������������������������������������������������������������������ xiii
Foreword��������������������������������������������������������������������������������������������xxxiii
e12.  inor Otic Disorders (Cerumen Impaction,
M
Otitis External)�����������������������������������������������������������29
Preface������������������������������������������������������������������������������������������������ xxxv
Lea S. Eiland
e13.  onspecific Respiratory Tract Symptoms
N
SECTION 1 Foundation Issues 1 (with Cough)���������������������������������������������������������������31
Brandon Sucher
Section Editors: Stuart T. Haines, L. Michael Posey, and Thomas D. Nolin e14. Allergic Rhinitis����������������������������������������������������������33
1. Patient Care Process��������������������������������������������������� 1 J. Russell May
Stuart T. Haines, Mary Ann Kliethermes, e15. Oral Health and Systemic Conditions�����������������35
and Todd D. Sorensen Lisa M. Palmisano and Jennifer L. Mazan
e2. Health Literacy and Medication Use��������������������� 9 e16. Oral Hygiene and Minor Oral Disorders�������������37
Oralia V. Bazaldua, Norbert Rosario, and Erica Torres Anna S. Milone, Kristyn M. Williamson, and Maren Hall
e3. E xploring Cultural Diversity and Equity in e17. S kin Care and Minor Dermatologic
Healthcare�������������������������������������������������������������������11 Conditions �������������������������������������������������������������������39
Amanda M. Loya, Jeri J. Sias, Lakesha M. Butler, Rebecca M. Law and Howard I. Maibach
Christopher G. Medlin, and Jessica M. Shenberger-Trujillo
e18. T ravel Health ���������������������������������������������������������������41
e4. Medication Safety�����������������������������������������������������13 Douglas Slain and Scott E. Kincaid
Robert J. Weber
19. Contraception���������������������������������������������������������������������43
e5. Medication Adherence �������������������������������������������15 Shareen Y. El-Ibiary
Fang-Ju Lin, Yen-Ming Huang, and Yunn-Fang Ho
e6.  linical Pharmacokinetics and
C
Pharmacodynamics �������������������������������������������������17
SECTION 3 Special Populations 67
Kristin M. Janzen and Samuel M. Poloyac
Section Editors: L. Michael Posey and Thomas D. Nolin
e7. Clinical Pharmacogenomics ���������������������������������19
Roseann S. Gammal, Larisa H. Cavallari, and e20.  ediatrics: General Topics in Pediatric
P
Y. W. Francis Lam Pharmacotherapy �����������������������������������������������������67
Milap C. Nahata and Carol K. Taketomo
e8. Clinical Toxicology�����������������������������������������������������21
Bryan D. Hayes and Natalija M. Farrell e21.  ediatrics: Oral Nutrition and Rehydration of
P
Infants and Children�������������������������������������������������69
Katherine H. Chessman
e22.
section 2 Common Health Problems 23 Pediatrics: Neonatal Critical Care�������������������������71
Kirsten H. Ohler and Jennifer T. Pham
Section Editors: L. Michael Posey, Joseph T. DiPiro, and Vicki L. Ellingrod e23. Geriatrics: Physiology of Aging�����������������������������73
Krista L. Donohoe, Elvin T. Price, Tracey L. Gendron, and
e9. Fever �����������������������������������������������������������������������������23 Patricia W. Slattum
Jamal Brown and Juan Mosley II
e24. Geriatrics: Medication Use in Older Adults�������75
e10. Pain and Headache���������������������������������������������������25 Emily R. Hajjar, Lauren R. Hersh, and Shelly L. Gray
Ryan C. Costantino, Krista B. Highland, and Laura C. Tilley
e25.  eriatrics: Assessing Health and Delivering
G
e11. Minor Ophthalmic Disorders���������������������������������27 Healthcare to Older Adults�������������������������������������77
Jared Ostroff Leigh Ann Mike, Zachary A. Marcum, and Shelly L. Gray
vii

FM.indd 7 13-02-2023 16:51:54

 viii

e26.  ritical Care: Considerations in Medication

C 45. Chronic Obstructive Pulmonary Disease���������������� 393
Selection, Dosing, Monitoring, and Safety������ 79 Sharya V. Bourdet and Dennis M. Williams
Erin F. Barreto and Amy L. Dzierba 46. Pulmonary Arterial Hypertension������������������������������ 419
e27. Critical Care: Pain, Agitation, and Delirium������ 81 Rebecca L. Attridge Rebecca Moote, and Deborah J. Levine
Caitlin S. Brown and Gilles L. Fraser 47. Cystic Fibrosis�������������������������������������������������������������������� 437
e28. Palliative and End-of-Life Care ���������������������������� 83 Kim G. Adcock, Ha K. Phan, and David Josey Jr.
Mary Lynn McPherson and Jessica E. Geiger e48. Drug-Induced Pulmonary Diseases������������������ 455
CONTENTS

Margaret A. Miklich and Mojdeh S. Heavner

SECTION 4 Cardiovascular Disorders 85

SECTION 6 Gastrointestinal Disorders 457
Section Editor: Stuart T. Haines
Section Editor: Joseph T. DiPiro
e29. Evaluation of Cardiovascular Function������������� 85
Brent N. Reed, Kristin Watson, and Gautam Ramani e49. Evaluation of the Gastrointestinal Tract���������� 457
Keith M. Olsen
30. Hypertension���������������������������������������������������������������������� 87
Eric J. MacLaughlin and Joseph J. Saseen 50. Gastroesophageal Reflux Disease������������������������������ 459
Dianne W. May, Devin L. Lavender, and Satish C. Rao
e31. Acute Hypertensive Crisis �������������������������������������������� 119
Jeffrey J. Mucksavage, Danielle M. Tompkins, and 51. Peptic Ulcer Disease and Related Disorders ���������� 479
Eric J. MacLaughlin Bryan L. Love

32. Dyslipidemia��������������������������������������������������������������������� 121

52. Inflammatory Bowel Disease �������������������������������������� 503
Brian A. Hemstreet
Dave L. Dixon, Daniel M. Riche, and Michael S. Kelly
33. Stable Ischemic Heart Disease������������������������������������ 143
53. Nausea and Vomiting ���������������������������������������������������� 525
Leigh Anne H. Gravatt, Krista L. Donohoe, and
Paul P. Dobesh, Robert J. DiDomenico, and
Mandy L. Gatesman
Kelly C. Rogers
34. Acute Coronary Syndrome ������������������������������������������ 167
54. Diarrhea, Constipation, and Irritable Bowel
Syndrome �������������������������������������������������������������������������� 539
Robert J. DiDomenico, Paul P. Dobesh, and
Patricia H. Fabel and Kayce M. Shealy
Shannon W. Finks
55. Portal Hypertension and Cirrhosis���������������������������� 557
e35. Peripheral Arterial Disease���������������������������������� 197
Julie M. Sease
Kristin Watson and Sarah L. Anderson
e56. Drug-Induced Liver Injury ���������������������������������� 573
36. Chronic Heart Failure������������������������������������������������������ 199 William R. Kirchain and Rondall E. Allen
Robert B. Parker and Jo E. Rodgers
57. Pancreatitis������������������������������������������������������������������������ 575
37. Acute Decompensated Heart Failure������������������������ 231 Scott Bolesta
Brent N. Reed, Stormi E. Gale, and Zachary L. Cox
58. Viral Hepatitis�������������������������������������������������������������������� 591
38. Venous Thromboembolism������������������������������������������ 251 Paulina Deming
Daniel M. Witt, Nathan P. Clark, and Sara R. Vazquez
59. Celiac Disease�������������������������������������������������������������������� 611
39. Stroke���������������������������������������������������������������������������������� 283 Priti N. Patel and Robert A. Mangione
Melody Ryan and Melissa A. Nestor
40. Arrhythmias���������������������������������������������������������������������� 297

41.
Jessica J. Tilton, Stephen T. Phillips, and Jerry L. Bauman
Cardiopulmonary Arrest������������������������������������������������ 335
SECTION 7 Renal Disorders 619
Jeffrey F. Barletta Section Editor: Thomas D. Nolin
e42. Shock Syndromes�������������������������������������������������� 353 e60. Evaluation of Kidney Function�������������������������� 619
Seth R. Bauer, Robert MacLaren, and Brian L. Erstad Linda Awdishu and Thomas C. Dowling
61. Acute Kidney Injury�������������������������������������������������������� 621
SECTION 5 Respiratory Disorders 355 Jenana H. Maker, Lauren K. Roller, and William Dager
62. Chronic Kidney Disease ������������������������������������������������ 641
Section Editor: Stuart T. Haines Lori D. Wazny
e43. Evaluation of Respiratory Function������������������ 355 63. Chronic Kidney Disease: Management of
Megan L. Carreon, Maria I. Velez, Stephanie M. Levine, and Secondary Complications�������������������������������������������� 653
Jay I. Peters Joanna Q. Hudson
44. Asthma�������������������������������������������������������������������������������� 357 64. Hemodialysis and Peritoneal Dialysis ���������������������� 679
Kathryn V. Blake and Jean Y. Moon Kevin M. Sowinski and Mariann D. Churchwell

FM.indd 8 13-02-2023 16:51:55

 ix
65. Drug-Induced Kidney Disease������������������������������������ 699 e83. Eating Disorders����������������������������������������������������1023
Thomas D. Nolin and Mark A. Perazella Steven C. Stoner, Valerie L. Ruehter, and Melissa C. Palmer
e66. Glomerular Diseases���������������������������������������������� 719 e84. Introduction to Substance Use Disorders���� 1025
Duncan B. Johnstone Jessica L. Moreno, Patrick Leffers, and Vicki L. Ellingrod
67. Personalized Pharmacotherapy for Patients with 85. Substance Use Disorders I: Opioids, Cannabis,
Chronic Kidney Disease ������������������������������������������������ 721 and Stimulants����������������������������������������������������������������1027
Morgan A. Butrovich and Thomas D. Nolin Patrick Leffers, Brittany N. Johnson, and Patrick Aaronson

CONTENTS
68. Disorders of Sodium and Water Homeostasis ������ 737 86. Substance Use Disorders II: Alcohol, Nicotine,
Katherine H. Chessman and Jason S. Haney and Caffeine��������������������������������������������������������������������1047
69. Disorders of Calcium and Phosphorus Lori H. Dupree and Robin Moorman Li
Homeostasis���������������������������������������������������������������������� 763 87. Schizophrenia ����������������������������������������������������������������1073
Angela L. Bingham M. Lynn Crismon, Tawny L. Smith, and Peter F. Buckley
70. Disorders of Potassium and Magnesium 88. Depressive Disorders����������������������������������������������������1107
Homeostasis���������������������������������������������������������������������� 783 Amy M. VandenBerg
Rachel W. Flurie
89. Bipolar Disorder ������������������������������������������������������������1133
71. Acid–Base Disorders ������������������������������������������������������ 801 Jordan C. Haygood and Shannon J. Drayton
Anne M. Tucker and Tami N. Johnson
90. Generalized Anxiety Disorder, Panic Disorder,
and Social Anxiety Disorder��������������������������������������1151
SECTION 8 Neurologic Disorders 823 Sarah T. Melton and Cynthia K. Kirkwood

Section Editor: Vicki L. Ellingrod

91. Posttraumatic Stress Disorder and Obsessive-
Compulsive Disorder����������������������������������������������������1173
e72. Evaluation of Neurological Illness������������������������������ 823 Kristen N. Gardner, Jolene R. Bostwick, and
Melody Ryan and Stephen J. Ryan Ericka L. Crouse

73. Alzheimer Disease ���������������������������������������������������������� 825 92. Sleep Disorders��������������������������������������������������������������1187

Ericka L. Crouse, Kristin M. Zimmerman, Emily P. Peron, John M. Dopp and Bradley G. Phillips
Lana J. Sargent, and Sarah E. Hobgood e93. Developmental Disabilities������������������������������1201
Steven R. Erickson
74. Multiple Sclerosis������������������������������������������������������������ 845
Jacquelyn L. Bainbridge, Augusto Miravelle, Pei Shieen

75.
Wong, Matthew J. Makelky Sr., and Sarah Rajkovic

Epilepsy������������������������������������������������������������������������������ 869
SECTION 10 Endocrinologic Disorders 1203
Viet-Huong V. Nguyen, Sunita Dergalust, and Section Editor: Stuart T. Haines
Edward Chang
94. Diabetes Mellitus ����������������������������������������������������������1203
76. Status Epilepticus������������������������������������������������������������ 905 Jennifer M. Trujillo and Stuart T. Haines
Elizabeth A. Hall, Stephanie J. Phelps, and
James W. Wheless e95. Acute Hyperglycemia������������������������������������������1239
Paul M. Szumita, James F. Gilmore, and Jennifer M. Trujillo
77. Acute Management of the Brain Injury Patient���� 921
Bradley A. Boucher and G. Christopher Wood 96. Thyroid Disorders����������������������������������������������������������1241
Michael P. Kane and Gary Bakst
78. Parkinson Disease������������������������������������������������������������ 935
Jessa M. Koch, Khashayar Dashtipour, and Jack J. Chen 97. Adrenal Gland Disorders ��������������������������������������������1267
Steven M. Smith, Christopher R. Piszczatoski, and
79. Pain Management ���������������������������������������������������������� 953 John G. Gums
Christopher M. Herndon, Courtney M. Kominek, and
Amanda M. Mullins e98. Pituitary Gland Disorders����������������������������������1289
Joseph K. Jordan, Amy Heck Sheehan, and Kashif M. Munir
80. Headache Disorders�������������������������������������������������������� 981
Kimberly B. Tallian and Natalie T. Heinrich
SECTION 11 Gynecologic and Obstetric
SECTION 9 Psychiatric Disorders 1001 Disorders 1291
Section Editor: Vicki L. Ellingrod Section Editor: Vicki L. Ellingrod

e81. Evaluation of Psychiatric Illness����������������������1001 99. Pregnancy and Lactation��������������������������������������������1291

Mark E. Schneiderhan, Leigh Anne Nelson, Alicia B. Forinash and Kylie N. Barnes
Jeffrey R. Bishop, and Steven J. Bauer
100. Menstrual-Related Disorders ������������������������������������1313
82. Attention Deficit Hyperactivity Disorder��������������1003 Kathleen M. Vest and Danielle C. Mayer
Danielle L. Stutzman, Julie A. Dopheide, and Steven
Pliszka

FM.indd 9 13-02-2023 16:51:55

 x
101. Endometriosis����������������������������������������������������������������1333 e116. Drug-Induced Ophthalmic Disorders������������1609
Kathleen M. Vest and Sarah E. Lynch Rena A. Gosser
102. Menopausal Hormone Therapy��������������������������������1343
Devra K. Dang and Judy T. Chen
SECTION 16 Dermatologic Disorders 1611
Section Editor: L. Michael Posey
SECTION 12 Urologic Disorders 1365
CONTENTS

117. Acne Vulgaris������������������������������������������������������������������1611

Section Editor: L. Michael Posey Debra Sibbald and Cathryn Sibbald
103. Erectile Dysfunction������������������������������������������������������1365 118. Psoriasis����������������������������������������������������������������������������1639
Mary Lee and Roohollah Sharifi Rebecca M. Law and Wayne P. Gulliver
104. Benign Prostatic Hyperplasia������������������������������������1393 119. Atopic Dermatitis����������������������������������������������������������1661
Mary Lee and Roohollah Sharifi Rebecca M. Law and Wayne P. Gulliver
105. Urinary Incontinence����������������������������������������������������1413 120. Alopecia����������������������������������������������������������������������������1677
Eric S. Rovner, Kristine M. C. Talley, and Sum Lam Rebecca M. Law, Le Hanh Dung Do, and
Howard I. Maibach
e121.  ermatologic Drug Reactions,
D
SECTION 13 Immunologic Disorders 1431 Contact Dermatitis, and Common
Skin Conditions ����������������������������������������������������1693
Section Editors: Gary C. Yee and Thomas D. Nolin Rebecca M. Law, David T. S. Law, and Howard I. Maibach

e106. Function and Evaluation of the

Immune System ������������������������������������������������������������1431
Daniel A. Zlott and Geoffrey M. Thiele
SECTION 17 Hematologic Disorders 1695
107. Systemic Lupus Erythematosus��������������������������������1433 Section Editor: Gary C. Yee
Beth H. Resman-Targoff
122. Anemias����������������������������������������������������������������������������1695
e108. Drug Allergy ����������������������������������������������������������1455 Kristen M. Cook and Devon M. Greer
Mary L. Staicu, Christopher M. Bland, and Bruce M. Jones
123. Coagulation Disorders ������������������������������������������������1715
109. Solid-Organ Transplantation��������������������������������������1457 Heidi Trinkman, Timothy L. McCavit, and Lauren Duran
Nicholas W. Lange, David M. Salerno, and
Douglas L. Jennings
124. Sickle Cell Disease ��������������������������������������������������������1733
Jin Han, Santosh L. Saraf, and Victor R. Gordeuk
e125. Drug-Induced Hematologic Disorders����������1753
SECTION 14 Rheumatologic Disorders 1481 Elisa M. Greene and Tracy M. Hagemann

Section Editors: L. Michael Posey and Thomas D. Nolin

110. Osteoarthritis������������������������������������������������������������������1481
SECTION 18 Infectious Diseases 1755
Lucinda M. Buys and Sara A. Wiedenfeld Section Editor: Joseph T. DiPiro
111. Rheumatoid Arthritis����������������������������������������������������1501 e126. L aboratory Tests to Direct Antimicrobial
Stephanie Gruber, Bianca Harris, and Susan Hylland
Pharmacotherapy������������������������������������������������1755
112. Osteoporosis ������������������������������������������������������������������1523 Jordan R. Smith, Brian J. Werth, and Katie E. Barber
Mary Beth O’Connell, Jill S. Borchert, Erin M. Slazak, and 127. Antimicrobial Regimen Selection����������������������������1757
Joseph P. Fava Katie B. Olney and David S. Burgess
113. Gout and Hyperuricemia��������������������������������������������1555 128. Central Nervous System Infections��������������������������1771
Michelle A. Fravel and Michael E. Ernst Delaney E. Hart, Christina Koutsari, Michael A. Wankum,
and Ramy H. Elshaboury
129.
SECTION 15 Ophthalmic Disorders 1577 Lower Respiratory Tract Infections��������������������������1791
Evan J. Zasowski and Martha G. Blackford
Section Editor: L. Michael Posey 130. Upper Respiratory Tract Infections��������������������������1813
Grace C. Lee, Bradi L. Frei, and Christopher R. Frei
114. Glaucoma ������������������������������������������������������������������������1577
Richard Fiscella, Ohoud Owaidhah, and 131. Influenza ��������������������������������������������������������������������������1825
Deepak P. Edward Jessica C. Njoku

115. Age-Related Macular Degeneration ����������������������1595 e132. Coronavirus Disease (COVID-19) ��������������������1839
Alisa K. Escano and Casey S. Washington Jason M. Pogue, Erin K. McCreary, and Julie Ann Justo

FM.indd 10 13-02-2023 16:51:55

 xi
133. Skin and Soft Tissue Infections����������������������������������1841 152. Lung Cancer��������������������������������������������������������������������2255
Douglas N. Fish Keith A. Hecht and Eve M. Segal
134. Bacteremia and Infective Endocarditis������������������1869 153. Colorectal Cancer����������������������������������������������������������2277
Daniel B. Chastain Lisa M. Holle, Jessica M. Clement, and Lisa E. Davis
135. Tuberculosis��������������������������������������������������������������������1893 154. Prostate Cancer��������������������������������������������������������������2303
Rocsanna Namdar and Charles A. Peloquin Daniel J. Crona and Amber B. Cipriani
136. Gastrointestinal Infections and Enterotoxigenic 155. Lymphomas��������������������������������������������������������������������2323

CONTENTS
Poisonings������������������������������������������������������������������������1913 Alexandre Chan, Chia J. Tan, and Shawn P. Griffin
Andrew M. Roecker and Brittany N. Bates
156. Ovarian Cancer ��������������������������������������������������������������2351
137. Intra-Abdominal Infections����������������������������������������1929 Grace A. Martin and Judith A. Smith
Alan E. Gross, Jamie L. Wagner, and Keith M. Olsen
157. Acute Leukemias������������������������������������������������������������2369
e138. Parasitic Diseases��������������������������������������������������1947 David DeRemer and Tara A. Higgins
Alireza Fakhriravari, Ana Elizabeth Markez, and
Jason M. Cota
158. Chronic Leukemias��������������������������������������������������������2391
Karen M. Fancher and Jill M. Comeau
139. Urinary Tract Infections������������������������������������������������1949
Julianna M. Fernandez and Elizabeth A. Coyle
159. Multiple Myeloma ��������������������������������������������������������2411
Amy M. Pick and Jared E. Matya
140. Sexually Transmitted Infections��������������������������������1967
Yvonne J. Burnett and Humberto R. Jimenez
e160. Myelodysplastic Syndromes ����������������������������2429
Jill S. Bates and Jolynn Knoche Sessions
141. Bone and Joint Infections ������������������������������������������1989
Bryan T. Alexander and Scott J. Bergman
e161. Renal Cell Carcinoma������������������������������������������2431
Erin B. Bailey and David D. Stenehjem
142. Sepsis and Septic Shock����������������������������������������������2003
S. Lena Kang-Birken and Sul R. Jung
162. Melanoma������������������������������������������������������������������������2433
Cindy L. O’Bryant and Christina M. Davis
143. Superficial Fungal Infections ������������������������������������2021
Thomas E. R. Brown and Linda D. Dresser
e163. Hematopoietic Cell Transplantation��������������2453
Elizabeth Dimaggio and Janelle Perkins
144. Invasive Fungal Infections������������������������������������������2039
Peggy L. Carver and Gregory A. Eschenauer
145. Infections in Immunocompromised Patients������2067
Scott W. Mueller and Douglas N. Fish
SECTION 20 Nutritional Disorders 2455
146. Antimicrobial Prophylaxis in Surgery ��������������������2099 Section Editor: Thomas D. Nolin
Salmaan Kanji
164. Assessment of Nutrition Status
147. Vaccines and Immunoglobulins ������������������������������2115 and Nutrition Requirements��������������������������������������2455
Mary S. Hayney Katherine H. Chessman and Angela L. Bingham
148. Human Immunodeficiency Virus Infection����������2129 165. Parenteral Nutrition������������������������������������������������������2481
Peter L. Anderson, Kristina M. Brooks, and Todd W. Mattox and Catherine M. Crill
Courtney V. Fletcher
166. Enteral Nutrition������������������������������������������������������������2501
Diana W. Mulherin
167. Obesity������������������������������������������������������������������������������2519
SECTION 19 Oncologic Disorders 2155 Amy Heck Sheehan, Judy T. Chen, and Jack A. Yanovski
Section Editor: Gary C. Yee
Index 2545
149. Cancer: The Disease and Treatment������������������������2155
Lisa M. Cordes and Sandra Cuellar
150. Supportive Care in Cancer������������������������������������������2209
Amber B. Clemmons and Ashley E. Glode
151. Breast Cancer������������������������������������������������������������������2229
Bonnie Lin Boster, Neelam K. Patel, and Jaime Kaushik

SI unit conversions were produced by Ed Randell, PhD, DCC, FCACB, Division Chief and Professor of Laboratory Medicine,
Department of Laboratory Medicine, Eastern Health Authority and Faculty of Medicine, Memorial University of Newfoundland,
St. John’s, Newfoundland, Canada

FM.indd 11 13-02-2023 16:51:55

 Conflict of Interest Disclosure and Mitigation
Contributors to Pharmacotherapy: A Pathophysiologic Approach must disclose relevant financial and other interests with entities that
produce, market, sell, or distribute medications, health products, or services related to the medication use process. All contributors com-
pleted, signed, and submitted a conflict of interest (COI) disclosure statement to the Editors. Starting with the 11th edition, the COI
disclosure was submitted after an invitation has been extended and before a contributor agreement was signed.
After reviewing the COI disclosure statement submitted by a contributor, the Editors developed and approved a plan to mitigate any
and all potential COIs that might be reasonably perceived by the readers of Pharmacotherapy: A Pathophysiologic Approach to unduly
influence the contributor’s favorable or unfavorable portrayal of any product or service. The mitigation plan included, but was not
limited to, assigning a coauthor with no COIs to work with the contributor, subjecting the contribution to external peer review, or asking
the contributor to divest the interest(s).
No contributor may receive a payment or services from a third party (commercial entity, government agency, professional o­ rganization,
private foundation, etc.) for any work product submitted to Pharmacotherapy: A Pathophysiologic Approach.
Starting with the 11th edition, potential contributors who are employees of a commercial entity that produces, markets, sells, or
distributes medications or healthcare products are not invited or re-invited to contribute.
COI disclosures for all contributors to Pharmacotherapy: A Pathophysiologic Approach will be made available to readers online. The
internet address for the COI disclosure page will be published in the Contributors section of the text.

FM.indd 12 13-02-2023 16:51:56

 Contributors
Patrick Aaronson, PharmD, DABAT Linda Awdishu, PharmD, MAS
Clinical Associate Professor and Emergency Medicine Practitioner Professor of Clinical Pharmacy, Division Head of Clinical
University of Florida Health Pharmacy, Director of Simulation and Interprofessional
Jacksonville, Florida Education
Chapter 85 Skaggs School of Pharmacy and Pharmaceutical Sciences,
University of California, San Diego
Kim G. Adcock, PharmD, CCRC La Jolla, California
Professor of Pharmacy Practice and Director of Faculty and Chapter e60
Academic Affairs
School of Pharmacy, University of Mississippi Erin B. Bailey, PharmD, BCOP
Professor of Pediatrics and Director of the Office of Clinical Pharmacist
Interprofessional Education University of Utah Health, Huntsman Cancer Institute
University of Mississippi Medical Center Salt Lake City, Utah
Jackson, Mississippi Chapter e161
Chapter 47
Jacquelyn L. Bainbridge, PharmD, MSCS
Bryan T. Alexander, PharmD, BCIDP, AAHIVP Professor, Departments of Clinical Pharmacy and Neurology
Pharmacy Coordinator, Outpatient Antimicrobial Therapy Skaggs School of Pharmacy and Pharmaceutical Sciences,
Program University of Colorado, Anschutz Medical Campus
Nebraska Medicine Aurora, Colorado
Omaha, Nebraska Chapter 74
Chapter 141
Gary Bakst, MD
Rondall E. Allen, BS, PharmD Head, Division of Community Endocrinology
Provost and Vice President for Academic Affairs Albany Medical Center
University of Maryland Eastern Shore Albany, New York
Professor, Pharmacy Practice and Administration Chapter 96
Salisbury, Maryland
Chapter e56 Katie E. Barber, PharmD
Associate Professor
Peter L. Anderson, PharmD School of Pharmacy, University of Mississippi
Professor Jackson, Mississippi
University of Colorado Anschutz Medical Campus Chapter e126
Aurora, Colorado
Chapter 148 Jeffrey F. Barletta, BS, PharmD
Professor and Vice Chair of Pharmacy Practice
Sarah L. Anderson, PharmD, BCACP, BCPS College of Pharmacy, Midwestern University
Scientific Director Glendale, Arizona
Clinical Care Options Chapter 41
Denver, Colorado
Chapter e35 Kylie N. Barnes, PharmD, BCPS
Clinical Associate Professor
Rebecca L. Attridge, PharmD, MSc, BCPS, BCCCP University of Missouri–Kansas City School of Pharmacy
Principal, Pharmacotherapy Kansas City, Missouri
The Craneware Group Chapter 99
Colorado Springs, Colorado
Chapter 46

xiii

FM.indd 13 13-02-2023 16:51:56

 xiv
Erin F. Barreto, PharmD, MSc Jeffrey R. Bishop, PharmD, MS, BCPP
Associate Professor of Medicine and Pharmacy Associate Professor
Mayo Clinic College of Pharmacy
Rochester, Minnesota University of Minnesota
Chapter e26 Minneapolis, Minnesota
Chapter e81
Brittany N. Bates, PharmD, BCPS
CONTRIBUTORS

Assistant Professor of Pharmacy Practice Martha G. Blackford, PharmD, BCPS

Ohio Northern University Clinical Pharmacologist and Toxicologist
Ada, Ohio Akron Children’s Hospital
Chapter 136 North Canton, Ohio
Chapter 129
Jill S. Bates, PharmD, BCOP
National PHASER Pharmacy Program Manager Kathryn V. Blake, PharmD, BCPS
Durham VA Health Care System Director, Center for Pharmacogenomics and Translational Research
Associate Professor of Clinical Education Nemours Children’s Health
Eshelman School of Pharmacy Jacksonville, Florida
Durham VA Health Care System Chapter 44
University of North Carolina
Chapter e160 Christopher M. Bland, PharmD, BCPS
Clinical Professor
Seth R. Bauer, PharmD, BCCCP College of Pharmacy, University of Georgia
Critical Care Clinical Specialist Antimicrobial Stewardship Pharmacist
Cleveland Clinic St. Joseph’s/Candler Health System
Clinical Assistant Professor Athens, Georgia
Cleveland Clinic Lerner College of Medicine Chapter e108
Cleveland, Ohio
Chapter e42 Scott Bolesta, PharmD, BCPS
Professor
Steven J. Bauer, MD Nesbitt College of Pharmacy, Wilkes University
Medical Director of Certified Community Mental Health Clinic Wilkes-Barre, Pennsylvania
Human Development Center Chapter 57
Duluth, Minnesota
Chapter e81 Jill S. Borchert, PharmD, BCPS, BCACP
Professor and Vice Chair
Jerry L. Bauman, PharmD College of Pharmacy
Dean Emeritus and Distinguished Professor Emeritus Midwestern University
College of Pharmacy, University of Illinois at Chicago Downers Grove, Illinois
Chicago, Illinois Chapter 112
Editor-in-Chief
Journal of the American College of Clinical Pharmacy Bonnie Lin Boster, PharmD, BCOP
Lenexa, Kansas Clinical Pharmacy Specialist
Chapter 40 University of Texas MD Anderson Cancer Center
Houston, Texas
Oralia V. Bazaldua, PharmD, BCACP Chapter 151
Professor/Clinical
The University of Texas Health Science Center Jolene R. Bostwick, PharmD
Ambulatory Care Clinical Pharmacy Specialist Assistant Dean for Co-curriculum and Professional Development
University Health System San Antonio and Clinical Professor of Pharmacy, Department of Clinical
San Antonio, Texas Pharmacy, and Clinical Pharmacist, Michigan Medicine
Chapter e2 University of Michigan College of Pharmacy
Ann Arbor, Michigan
Scott J. Bergman, PharmD, BCIDP Chapter 91
Nebraska Coordinator Antimicrobial Stewardship, Clinical
Professor Bradley A. Boucher, PharmD, MCCM
College of Pharmacy Interim Dean and Professor
University of Nebraska Medical Center Department of Clinical Pharmacy and Translational Science
Omaha, Nebraska College of Pharmacy
Chapter 141 University of Tennessee Health Science Center
Memphis, Tennessee
Angela L. Bingham, PharmD, BCPS, BCNSP, BCCCP Chapter 77
Vice Chair and Clinical Associate Professor
Philadelphia College of Pharmacy Sharya V. Bourdet, PharmD, BCPS
Saint Joseph’s University Associate Chief of Pharmacy for Acute Care and Education
Philadelphia, Pennsylvania San Francisco VA Medical Center
Chapters 69, 164 Associate Professor of Clinical Pharmacy
University of California San Francisco School of Pharmacy
San Francisco, California
Chapter 45

FM.indd 14 13-02-2023 16:51:56

 xv
Kristina M. Brooks, PharmD Megan L. Carreon, MHA, RRT, RRT
Assistant Professor-Research Assistant Professor, Division of Respiratory Care
University of Colorado Anschutz Medical Campus UT Health San Antonio
Aurora, Colorado University of Texas Health Science Center
Chapter 148 San Antonio, Texas
Chapter e43
Caitlin S. Brown, PharmD, BCCCP

CONTRIBUTORS
Neurocritical and Emergency Medicine Pharmacist Peggy L. Carver, PharmD
Mayo Clinic Associate Professor
Assistant Professor of Pharmacy & Emergency Medicine College of Pharmacy
Mayo School of Medicine University of Michigan
Minneapolis, Minnesota Clinical pharmacist, Infectious diseases
Chapter e27 Ann Arbor, Michigan
Chapter 144
Jamal Brown, PharmD, BCGP
Associate Professor of Pharmacy Practice Larisa H. Cavallari, PharmD
College of Pharmacy, Florida A&M University Professor of Pharmacotherapy and Translational Research
Tampa, Florida College of Pharmacy
Chapter e9 University of Florida
Gainesville, Florida
Thomas E. R. Brown, PharmD Chapter e7
Associate Professor
Leslie Dan Faculty of Pharmacy Alexandre Chan, PharmD, MPH, BCPS, BCOP
University of Toronto Founding Chair and Professor of Clinical Pharmacy
Toronto, Ontario University of California, Irvine
Chapter 143 Clinical Pharmacist
Chao Family Comprehensive Cancer Center
Peter F. Buckley, MD Irvine, California
Chancellor Chapter 155
University of Tennessee Health Science Center
Memphis, Tennessee Edward Chang, MD, PhD
Chapter 87 Clinical Neurophysiology Fellowship Program Director
Harbor UCLA Medical Center
Yvonne J. Burnett, PharmD, BCIDP West Carson, California
Associate Professor of Pharmacy Practice Chapter 75
University of Health Sciences and Pharmacy in Saint Louis
Clinical Pharmacy Specialist, Infectious Diseases Daniel B. Chastain, PharmD, BCIDP, AAHIVP
Missouri Baptist Medical Center Clinical Associate Professor
St. Louis, Missouri College of Pharmacy
Chapter 140 University of Georgia
David S. Burgess, PharmD Athens, Georgia
Professor and Chair, Department of Pharmacy Practice & Science Chapter 134
College of Pharmacy
University of Kentucky
Jack J. Chen, PharmD, BCPS, BCGP
Consultant
Lexington, Kentucky
Clinical Movement Disorders
Chapter 127
Chino Hills, California
Lakesha M. Butler, PharmD, BCACP, CDFT Chapter 78
Associate Vice President, Inclusion, Diversity and Health Equity
and Clinical Professor Judy T. Chen, PharmD, BCPS, BCACP, CDCES
College of Pharmacy Clinical Associate Professor
University of Florida College of Pharmacy
Gainesville, Florida Purdue University
Chapter e3 Clinical Pharmacy Specialist, Women’s Health
Indianapolis, Indiana
Morgan A. Butrovich, PharmD Chapters 102, 167
PhD Candidate
University of Pittsburgh School of Pharmacy Katherine H. Chessman, BS-Pharm, PharmD, BCPS,
Pittsburgh, Pennsylvania BCNSP
Chapter 67 Professor and Chair, Clinical Pharmacy and Outcome Sciences
College of Pharmacy
Lucinda M. Buys, PharmD, BCACP
Medical University of South Carolina
Clinical Pharmacist and Clinical Services Director
Clinical Pharmacy Specialist, Pediatrics/Pediatric Surgery/
Siouxland Medical Education Foundation
Intestinal Rehabilitation
Sioux City, Iowa
MUSC Shawn Jenkins Children’s Hospital
Chapter 110
Charleston, South Carolina
Chapters e21, 68, 164

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 xvi
Mariann D. Churchwell, PharmD, BCPS Ryan C. Costantino, PharmD, MS, BCPS, BCGP, CPHIMS
Professor Chief, Data Science Branch
University of Toledo College of Pharmacy and Pharmaceutical Enterprise Intelligence & Data Solutions Program Management
Sciences Office
Clinical Pharmacy Specialist Program Executive Office, Defense Healthcare Management Systems
Toledo, Ohio San Antonio, Texas
Chapter 64 Chapter e10
CONTRIBUTORS

Amber B. Cipriani, PharmD, BCOP Jason M. Cota, PharmD, MS, BCIDP

Precision Medicine Pharmacy Coordinator Vice Chair and Professor of Pharmacy Practice
UNC Health Medical Center Feik School of Pharmacy. University of the Incarnate Word
University of North Carolina San Antonio, Texas
Clinical Assistant Professor Chapter e138
UNC Eshelman School of Pharmacy
Chapel Hill, North Carolina Zachary L. Cox, PharmD
Chapter 154 Professor
Lipscomb University College of Pharmacy
Nathan P. Clark, PharmD, BCPS Heart Failure Clinical Pharmacy Specialist
Clinical Pharmacy Cardiovascular Services Manager Vanderbilt University Medical Center
Kaiser Permanente Colorado Nashville, Tennessee
Denver, Colorado Chapter 37
Chapter 38
Elizabeth A. Coyle, PharmD, BCPS
Jessica M. Clement, MD Associate Dean for Academic Affairs, Clinical Professor
Medical Director of Oncology Research College of Pharmacy, University of Houston
Hartford HealthCare Cancer Institute Houston, Texas
Hartford, Connecticut Chapter 139
Chapter 153 Catherine M. Crill, PharmD, FCCP, BCNSP
Amber B. Clemmons, PharmD, BCOP Associate Professor
Clinical Professor Departments of Clinical Pharmacy & Translational Science and
College of Pharmacy Pediatrics
University of Georgia Director of Experiential Learning and International Programs
Clinical Pharmacy Specialist - Hematology/Bone Marrow College of Pharmacy, University of Tennessee Health Science Center
Transplantation Memphis, Tennessee
Augusta University (AU) Medical Center Chapter 165
Augusta, Georgia M. Lynn Crismon, PharmD, DABCP, BCPP
Chapter 150 Behrens Centennial Professor of Pharmacy
Jill M. Comeau, PharmD, BCOP College of Pharmacy
Associate Professor of Clinical Sciences University of Texas at Austin
College of Pharmacy Professor of Psychiatry
University of Louisiana Monroe Dell Medical School
Gratis Assistant Professor of Internal Medicine University of Texas at Austin
Feist-Weiller Cancer Center Austin, Texas
LSU-Health Shreveport Chapter 87
Monroe, Louisiana Daniel J. Crona, PharmD, PhD, CPP
Chapter 158 Associate Professor
Kristen M. Cook, PharmD, BCACP Division of Pharmacotherapy and Experimental Therapeutics
Clinical Associate Professor, College of Pharmacy Eshelman School of Pharmacy
University of Nebraska Medical Center Clinical Pharmacist Practitioner
Ambulatory Care Pharmacist Genitourinary Malignancies, Department of Pharmacy
Nebraska Medicine University of North Carolina Medical Center
Omaha, Nebraska Chapel Hill, North Carolina
Chapter 122 Chapter 154

Lisa M. Cordes, PharmD, BCACP, BCOP Ericka L. Crouse, PharmD, BCPP, BCGP
Oncology Clinical Pharmacy Specialist Associate Professor
Office of Clinical Research and National Cancer Institute, National Virginia Commonwealth University School of Pharmacy
Institutes of Health Clinical Pharmacy Specialist – Psychiatry
Washington, D.C. VCU Health
Chapter 149 Richmond, Virginia
Chapters 73, 91

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 xvii
Sandra Cuellar, PharmD, BCOP Robert J. DiDomenico, PharmD
Clinical Associate Professor Associate Professor and Assistant Head of Pharmacy Practice
College of Pharmacy University of Illinois Chicago
University of Illinois Chicago, Illinois
Clinical Oncology Pharmacist Chapters 33, 34
UI Health
Chicago, Illinois Elizabeth Dimaggio, PharmD, BCOP

CONTRIBUTORS
Chapter 149 Clinical Pharmacy Specialist
Blood and Marrow Transplantation and Cellular Immunotherapy
William Dager, PharmD, BCPS, MCCM H. Lee Moffitt Cancer Center
Cardiovascular Pharmacist Specialist Tampa, Florida
University of California, Davis Medical Center Chapter e163
Clinical Professor of Pharmacy
University of California San Francisco School of Pharmacy Dave L. Dixon, PharmD, BCACP, CLS
Clinical Professor of Medicine Nancy L. and Ronald H. McFarlane Professor of Pharmacy
University of California Davis School of Medicine Virginia Commonwealth University School of Pharmacy
Sacramento, California Chair
Chapter 61 Department of Pharmacotherapy & Outcomes Science
Richmond, Virginia
Devra K. Dang, CDCES, FNAP Chapter 32
Associate Clinical Professor of Pharmacy Practice
Department of Pharmacy Practice Le Hanh Dung Do, MD
University of Connecticut College of Pharmacy Attending Physician
Storrs, Connecticut Hiep Loi Cosmetic Surgery Hospital
Chapter 102 Ho Chi Minh City, Vietnam
Chapter 120
Khashayar Dashtipour, MD, PhD
Associate Professor of Neurology and Basic Sciences Paul P. Dobesh, PharmD, BCCP
Loma Linda University Professor of Pharmacy Practice and Science
Loma Linda, California College of Pharmacy
Chapter 78 University of Nebraska Medical Center
Cardiology Clinical Pharmacy Specialist
Christina M. Davis, PharmD, BCOP Nebraska Medicine
Clinical Oncology Pharmacy Specialist Omaha, Nebraska
University of Colorado Hospital Chapters 33, 34
Denver, Colorado
Chapter 162 Krista L. Donohoe, PharmD, BCPS, BCGP
Associate Professor
Lisa E. Davis, PharmD, FCCP, BCPS, BCOP Virginia Commonwealth University School of Pharmacy
Clinical Professor Richmond, Virginia
R. Ken Coit College of Pharmacy Chapters e23, 53
University of Arizona
Clinical Pharmacist Julie A. Dopheide, PharmD, BCPP
University of Arizona Cancer Center Professor of Clinical Pharmacy, Psychiatry and the Behavioral
Tucson, Arizona Sciences
Chapter 153 University of Southern California School of Pharmacy
Keck School of Medicine
Paulina Deming, PharmD Los Angeles, California
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 xviii
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Charleston, South Carolina Ann Arbor, Michigan
Chapter 89 Chapter e93
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CONTRIBUTORS
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The Project Gutenberg eBook of The man who won
This ebook is for the use of anyone anywhere in the United States
and most other parts of the world at no cost and with almost no
restrictions whatsoever. You may copy it, give it away or re-use it
under the terms of the Project Gutenberg License included with this
ebook or online at www.gutenberg.org. If you are not located in the
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you are located before using this eBook.

Title: The man who won

Author: Mrs. Baillie Reynolds

Release date: February 11, 2024 [eBook #72820]

Language: English

Original publication: London: Hutchinson & Co, 1905

Credits: Al Haines

*** START OF THE PROJECT GUTENBERG EBOOK THE MAN

WHO WON ***
 The Man Who Won

BY

MRS. BAILLIE REYNOLDS

(G. M. ROBINS)

AUTHOR OF
"PHOEBE IN FETTERS," "THE DREAM AND THE MAN," ETC.

"Let a man contend to the uttermost

For his life's set prize, be it what it may."
—ROBERT BROWNING,

LONDON
HUTCHINSON & CO.
PATERNOSTER ROW
1905
 Printed by Cowan & Co., Limited, Perth.

To
M. ADELINE HUGHES
UNTIRING SYMPATHISER
TENDER CRITIC
DEAR FRIEND

CONTENTS

CHAP.

I LUTWYCHE'S
II MILLIE
III THE RIVALS
IV THE GUARDIANSHIP OF CAROL MAYNE
V A BOER BURYING
VI THE FLINGING OF THE GAGE
VII IN THE GARRET
VIII THE RESCUE
IX THE SCANDALISING OF SLABBERT'S POORT
X FRANSDALE
XI MELICENT'S COUSINS
XII THE JARRING ELEMENT
XIII LANCE BURMESTER IS CONSCIOUS OF A PERSONALITY
XIV THE BREAKING-IN OF MELICENT
XV A CLEVESHIRE TEA-PARTY
XVI BREAKING BOUNDS
XVII A CRISIS AT THE VICARAGE
XVIII A NEW HOME
XIX AN UNMARKED FESTIVAL
XX CAPTAIN BROOKE
XXI MIRAGE
XXII RECOGNITION
XXIII REBELLION
XXIV UNREST
XXV THE WAY OUT
XXVI THE END OF THE FIRST ROUND
XXVII THREE MONTHS' TRUCE
XXVIII THE GATES OF SPRING ARE OPENED
XXIX THE FRIENDSHIP GROWS
XXX TREACHERY
XXXI REPUDIATION
XXXII THE FRANSDALE SPORTS
XXXIII CALUMNY
XXXIV THE DISCOMFITURE OF OTIS
XXXV CONFESSION
XXXVI WHAT CHANCED UPON THE MOORS
XXXVII THE HOUSE IS BUILT

THE MAN WHO WON

 CHAPTER I

LUTWYCHE'S
"Handsome, were you? 'Tis more than they held,
More than they said. I was ware, and watched.
I was the scapegrace, this rat belled
The cat, this fool got his whiskers scratched."
—ROBERT BROWNING.

The talk had waxed political, and the audience was frankly bored. The
man who had been haranguing his mates was hurt at the somewhat too
obvious lack of appreciation which his truly democratic sentiments
received.

"Ef yer could quit twinin' yerself araound that thar' post a spell, an'
listen to a bit o' horse-sense"—he broke off angrily.

"It's usually hoarse when you take the floor, Amurrica," was the surly
reply; "but it's blasted little sense I've ever heard come outer your head."

"Ef you was to listen, it 'ud make a powerful deal o' difference to what
you heard," snapped Amurrica, whose eloquence was his chief vanity.

"I ain't good at listening," indifferently replied the blond and bearded
giant, who was "twinin' hisself araound the post," "onless a man's talkin';
an' that's a fact."

There was a giggle of appreciation among the half-dozen men and

youths collected at the gate of the farm enclosure.
 "No good, Amurrica; chuck it! Bert'll git there every time," said
someone cheerfully.

Amurrica snorted.

"Talkin', indeed! Why, you low-downers in this all-fired continent of

Africa, you don' know what talkin' means!"

"Usually means lyin' over in America, don't it?" said Bert casually.

His eyes were fixed on vacancy as he spoke; the chatter of the group
around him was nothing but a weariness, like the buzzing of flies. His mind
was fixed upon what was going on in the low frame house, with the
corrugated iron roof, that stood within the enclosure. He was experiencing
something more like anxiety than he had ever felt before in all his four-and-
twenty years.

It was oppressively hot. For miles and miles, the pitiless sun lit up the
endless veldt, which undulated all around the little township: wild, yet with
a dreadful sameness in it.

"As it was in the beginning, is now and ever shall be," seemed written
upon the face of the desert; yet here and there its dignity was scarred, its
monotony interfered with, by the ugliness and meanness of human
habitation. The beginnings of civilisation, without simplicity as they were
without harmony, jarred every sense. The places seemed to be devoid of
self-respect or privacy; to consist, in fact, entirely of back premises. Rows
of dingy linen flapped upon lines, on ground where the grass was
irregularly worn away here and there by the treading of feet. Collections of
old meat tins, old kettles, old shoes, heaped upon kitchen refuse, burdened
the stale air with miasma. A wretched-looking, lean-to building bore a huge
board with the flaunting inscription:

MOUNT PLEASANT BOARDING-HOUSE FOR

GENTLEMEN
 The gentlemen who boarded there were mostly assembled to-night at
the gate of "Lutwyche's."

A little farther away the Vierkleur Hotel fluttered its flag in the heavy
air, and rang at night to the coarse laughter and oaths of a set of idlers,
attracted to what had been a purely agricultural district by the finding of
diamonds.

Lutwyche's lay silent, sweltering in the heat. Round the stoep of the
farm-house hungry poultry were congregated; to-day they were being
neglected, and they were wisely determined not to suffer in silence.

It was a critical moment in history. All Europe was waiting to know

what President Kruger was going to do. It was the period which preceded
the sending of his historical ultimatum. The town for days had been buzzing
with rumours of war, and Amurrica had spoken great things in the saloon of
the Vierkleur. But local interests are strong, and it was not of British
supremacy that the men were thinking now.

The sun was going down. They had all, as Amurrica said, quit work,
and they were assembled by the barbed wire fence to gather news of the
Englishman who lay dying under the corrugated iron roof of Lutwyche's.

Even the quarrelling was listless. It could be seen that Bert's heart was
not in it. Where the heart of the huge young Boer was was matter of pretty
common knowledge, though there was not a man in the settlement who
would have dared to tell him so, except Amurrica, who had his own reasons
for not indulging in the perilous amusement.

Presently the door of the silent house opened, and a Kaffir girl came
out, with a dirty rug in her hand, from which she proceeded to shake clouds
of stifling acrid dust.

"Here, Minnie, Topsy, Hattie, whoever you are, how's the boss—eh?"
called one of the loungers.

The girl showed all her teeth in an apparently endless grin.

 "You young gentlemen carled to inquire?" she cried, in high
appreciation of the family importance. "You brought yo' visitin'-cards—
eh?"

"Shut it," said Bert savagely. "How is Mr. Lutwyche?"

"He don' seem not just the right thing to-day, sir, with missus's
compulments," grinned the girl, wildly elated by her momentary distinction.

To her intense delight, this last sally caused a giggle among the loafers.
She edged nearer to the barbed wire fencing, to prolong this truly delightful
conversation; and for a minute or two, idiotic questions and answers
pattered across the farm boundary, while Bert's brow grew blacker and
blacker.

Suddenly a silence, instant and deep, fell on the gathering. The Kaffir
girl scuttled behind a shed with noiseless celerity. From the door of the farm
issued two people—Tante Wilma, the Englishman's Boer wife, and striding
beside her corpulent bulk, the slim, energetic figure of Carol Mayne, the
English mission priest in charge of the station. Tante Wilma wore her most
repulsive expression, her sandy eyebrows lowering over her cunning little
eyes. Ten years ago she had been a handsome woman, in a redundant style;
but six children and an invalid husband had reduced her form to
shapelessness and her temper to rags and tatters.

She hated the English cleric, and could not bear that he should come
and see her husband. The Boer Predikant would have sat and sympathised
with her over his coffee for a couple of hours after his professional visit to
the sick man. Carol Mayne never seemed to have an adequate idea of the
importance of this woman, who owned half Slabbert's Poort, and had
married her English overseer, a widower with a little girl of his own.

She was evidently accompanying the young man from the house much
against her will. About half way across the yard, becoming perhaps aware
of the audience at the gate, the clergyman halted, just out of earshot. He
seemed earnestly recommending some particular course of conduct to Mrs.
Lutwyche, who stood sullenly before him, hostility in every line of her
coarse face.
 The group of men at the gate dropped away silently, singly or in pairs,
avoiding the parson; and Bert was left alone, his sullen scowl fixed upon
the house, as though willing it to render up the face he had stood there for
hours longing to see.

After a while, Mr. Mayne, having finished his colloquy with Tante
Wilma, lifted his hat with that unconscious English University manner
which had piqued her in her husband, but which now she hated as only the
ignorant can hate the thing that they can never understand. The young
Englishman's parting salutation, delivered so entirely as a matter of course,
belonged to an order of things which, had she been able, Tante Wilma
would have destroyed, ravaged, trampled under her gross feet.

She stood glowering upon him as he made straight for the gate by which
Bert still lounged. And she was pleased to note that the young man made no
effort to open it for his passage.

"Good evening, Mestaer!" said Mr. Mayne, as he reached the gate.

"How's the world treating you?"

"I'm —— if I care how it treats me," was the engaging response.

The smile that passed over Mayne's face was particularly humorous and
winning.

"Don't care came to a bad end," he said, "and that's what I particularly
hope won't happen to you. Are you going my way?"

"No; I'm staying here, if you're so mighty curious to know my plans,"

was the answer, given with a discourtesy so studied that to notice it would
be to allow the speaker to fancy that he had "scored."

The rudeness must, of course, have been obvious to the priest, but he
disregarded it entirely. A smile again flickered over his face, as of one who
holds a trump card. "Well, then, good-night!" he said briskly, opening the
gate at once, and passing through it with an air of having no time to waste.
 Bert cast another look at the silent house. Nobody was in sight but the
big Boer woman slouching back to the doorway. He lowered the point of
his rapier, so to speak.

"Say—how's he goin' on?" he asked.

Mr. Mayne at once dropped his appearance of hurry, and closed the gate
slowly.

"Well," he said, "he's just lingering. It may last two or three weeks yet.
God help him!"

Bert beat his clenched fist softly on the top bar of the gate.

"Look here!" he burst out, as if the words were torn from him, "they let
you go in and out—you can tell—you oughter know. Is she givin' that girl
hell?"

"I think things are going on much as they have done this last six
months," said Mayne, speaking reluctantly.

"But what'll it be when he's gone? I ask you that? What kind of a life's
she goin' to lead then?"

Mayne hesitated. "I don't know," he said at length, with a touch of

reserve.

"You know how the she-devil hates her," hissed Bert. "She won't keep
her, never fear. She'll chuck her out to any of these blanked scum around the
town, and then say the girl's disgraced her, and she'll have no more to do
with her! I know Tante Wilma!"

Mayne looked keenly and kindly at the excited speaker. He was sorry
for him, from the bottom of his heart; but what to say he did not know,
without betraying confidence.

"I think you see things in too black a light," he said at last. "Mrs.
Lutwyche is not without a sense of duty, though we know she is not good-
tempered. And Millie is not friendless, nor incapable of taking her own
part."

Bert lifted his leonine head, and pointed with a gesture of his hand
towards the house.

"He told me, with his blanky British pride, that he'd sooner see her in
her coffin than married to a man with an ounce of Boer blood in him—him
that let a Boer woman marry him," he growled. "He knows my mother was
English; I told him. I'd take care of her."

Mr. Mayne was able to follow the trend of the jerky, disconnected
sentences.

"Millie's young yet to think of marriage," he said.

"She'll have to think about something worse, before he's cold in his
grave, or I'm much mistaken," said Bert, scowling.

The clergyman pondered.

"Do you want me to speak to her father for you?" he presently asked,
point-blank.

Bert hesitated; he grew red, then pale.

"Don't like to be beholden to me, do you?" said Mayne cheerfully.

"Well, I sympathise with you. But you and I are just walking round the
question, you know, Mestaer. The whole point is, what does Millie say?
Will she have you?"

The colour again rushed over the crestfallen face of Bert. "Gals like that
don' know what they want," he grunted.

"Then it would be very wrong to push her into a life-long contract."

"She don' know what's good for her," repeated Bert. "She'd oughter be
arranged for; that's the way to do it. She'd not repent it if she married me."
 "Well, look here; I'll make a bargain. If Millie comes to me and says
she's willing to marry you, I'll speak to Mr. Lutwyche; but you know quite
as well as I do, he would never hear of it against her will."

Hereupon Bert damned first British pride, then his own Boer ancestry,
then Tante Wilma, who had caused her husband to contemn all Boers for
her sake.

"Swear-words won't help your cause, be sure of that," observed Mayne

drily. "English girls aren't going to be won that way."

"Think I'd say words like that to her?"

"More than probably. Well, good-night! I'm due at the Mission; not
coming, are you?"

"No," breathed Bert, and said no more; for his eyes were fixed upon a
little shadowy figure, moving under the shadow of the stoep.

Mayne saw it too, and walked quietly away.

CHAPTER II

MILLIE
"The world was right when it called you thin."
—ROBERT BROWNING.

The sun had dropped, as the red billiard ball slips into the pocket,
suddenly behind the heaving mass of veldt. Darkness was advancing with
tropical, seven-leagued stride, and all things were grey.
 The pale figure detached itself from the shadows, and resolved itself
into the advancing form of a frail, undeveloped girl of fifteen or sixteen. A
strange eye would have been lost in wonder, at the first glance, as to what
Bert Mestaer could see here, on which to fix his turbulent affections.

His lady-love was skinny, hollow-chested, stooping and round-backed;

her arms were almost like sticks.

She wore a soiled calico gown, too long behind for its length in front.
Her pale-coloured hair was drawn off her white face, and plaited into an
untidy pig tail which hung down her back. Certain small wisps of it escaped
in front, and made what looked in the dim light like the rudiments of a
nimbus about her head. She was drawn down on one side by the weight of
the heavy, clanking, copper bucket which she carried.

The well was right across the yard, quite near the gate where Bert stood,
and his large person was very visible; but the girl came on with no sign that
she saw him; and, reaching the well, hooked her bucket on the chain, and let
it down, with a stony, expressionless countenance.

Bert leaned over the gate; the expression of his face had altered
completely.

"Millie," he said, below his breath, "Millie!"

She gave him a listless glance, from weary, heavy-lidded, dark-blue

eyes.

"Oh, good evening!" she said curtly.

He unlatched the gate, came through, and took the windlass out of her
hand.

"Thought you promised not to come inside," she remarked.

"Only jest ter wind up this"—perhaps the thought of Mayne and the
swear-words flitted across his mind, for he pulled up short, and merely
finished lamely with—"this 'ere bucket."
 "What's an ear-bucket?" asked Miss Lutwyche, with cold contempt.

He winced like a child from a cane, but made no retort, merely setting
all his finely developed muscles a-play, as he raised the gleaming bucket
from the depths. When it was at the top, he paused.

"How's he to-night, Millie?"

"Mean my father?"

"Yes, Mr. Lutwyche."

"Oh, same's usual."

Bert's chest heaved with the burden of all he wished to say, and dare
not. Some instinct, deep down in him, warned him not to speak to the girl of
her father's fast-approaching end. And yet—he thought of all that Mayne
had said! Now was his chance, if ever, to declare his passion. He wondered
whether Mayne, or anybody else, knew how distant were the terms between
him and Millie, what an impregnable barrier she stood behind, how far he
was from being on such a footing as might be supposed to immediately
precede a proposal of marriage. His tongue clave to the roof of his mouth,
and he felt the sweat break out upon him.

The girl moved, leaned over to detach the bucket from the hook. He
started, and reaching quickly forward, brought it down upon the side of the
well where he stood.

"I'm goin' to carry it indoors for you," he said sheepishly.

She turned, without a word of thanks, and began to walk back to the
house.

He strode beside her, in the gathering gloom, his whole being aching
with the desire to comfort her.

"Millie," he said at last, "if—if she does anythin' to yer—if she gets too
bad, or lays hands upon yer, you jest come to me, or send for me, won't
yer?"
 The girl let fall a laugh of such quiet scorn that he felt openly sneered
at.

"D'you think I'm afraid of her, then?" she asked.

"No," he said warmly; "you've got the pluck of the—" he checked and
almost choked—"the pluck of a dozen. But she's stronger than you."

"Is she?" said Millie drily.

He pondered on that answer.

There spoke the careless insolence of the Briton. He admired it, while
he writhed under it; but he understood why it made Tante Wilma want to
scratch her eyes out.

They had reached the stoep. Nobody was about. He set down the bucket
and faced her squarely.

"Millie," he almost gasped, "look here! Give me a word! You know I'd
——"

She broke in. "I got no time to talk. I must take this water inside. Good-
night!"

His choler rose. "A chap may do what he will for you, and you can't
even throw him a word!"

Her languid expression changed; the dark blue eyes flashed wide awake
in the twilight.

"I didn't understand you wanted to be paid for carrying the pail!"

"Oh, damn you!" cried Bert, hurt beyond endurance; and he flung away
in rage that was not far from tears.

It seemed that the moment he was gone, the girl forgot him utterly. She
turned away and went inside the sitkamer without a backward glance.
 The sitkamer was full of her father's half-Boer children: two great boys
of eight and nine years old, and three or four younger fry. They were rolling
about on the floor, playing, fighting and cuffing. Millie took no more notice
of them than if they had been mice or black-beetles. She filled the kettle
from her pail, and set it to boil, and then, going to a cupboard, got a fresh
egg, which she proceeded to whisk up in a tumbler, with delicate care.

Tante Wilma rolled into the room, sat down by the stove, took the
coffee-pot off the rack, and poured herself out a cupful, which she
proceeded liberally to "lace" with something stronger. She sat sipping it,
looking furtively at her step-daughter as she moved, her small face grimly
set, noiselessly to and fro. It is very rarely indeed that a Boer woman takes
to drink. When she does, she becomes a creature to be avoided.

When her arrangements were complete, Millie took the tray and went
out of the room, followed by malevolent glances.

"White rat!" growled Xante Wilma, in the Taal.

The children started a kind of chorus:

"White rat! White rat!

Ours is the corn that makes you fat!"

"Not much longer then," muttered the half-tipsy Vrouw. "Another week
or two will see the end of it now; and then—out she goes! Aha! She'll wish
before long that she had kept a civil tongue in her head. As sure as I'm a
living woman, one thrashing I'll give her before she goes! Oh, there's a long
account I've got against her—it wants paying, that it does! Much we've had
to bear from him, but most from her that encouraged him from a baby to
defy me. But I'll take it out on her, once he's gone, the little insolent,
English devil!"
 CHAPTER III

THE RIVALS
"But as if he loved you! No, not he.
Nor anyone else in the world, 'tis plain;
Who ever heard that another, free
As I, young, prosperous, sound and sane,
Poured life out, proffered it—'Half a glance
Of those eyes of yours, and I drop the glass!'"
—ROBERT BROWNING.

Bert Mestaer flung open the door of his farm kitchen, and strode in.

All was clean and quiet. His supper, covered up in a saucepan, had been
left on the stove. Anna, his Boer housekeeper, had long since retired to her
heavy slumbers.

The eye of the master roved round the kitchen that night, like one who
saw it for the first time. He gazed upon the ceiling, and noted that it needed
fresh lime-wash. He contemplated the shining rows of plates on the dresser,
as though taking a new pride in his possessions; and then, moving forward,
he pushed open a door at the opposite side of the room, and found himself
in darkness and coolness. He struck a light, held it to a candle on the table,
and his critical glance travelled round the parlour which had been his
mother's pride.

There was a piano; he had a dim memory of her sitting there, playing to
him, the hymns that had charmed her own English childhood—

"Once in Royal David's city—"

the sound of the tune floated across the brain which for so long had heard
no such strains. He saw himself, a boy with yellow curls, in which she had
delighted, lifting his piercing childish treble at her bidding. What would she
not have given for the English Mission which had come to Slabbert's Poort