The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

CA : A Cancer Journal for Clinicians

Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study.

Context.—Interstitial radiation (implant) therapy is used to treat clinically
localized adenocarcinoma of the prostate, but how it compares with other treatments
is not known.Objective.—To estimate control of prostate-specific antigen (PSA) after radical
prostatectomy (RP), external beam radiation (RT), or implant with or without
neoadjuvant androgen deprivation therapy in patients with clinically localized
prostate cancer.Design.—Retrospective cohort study of outcome data compared using Cox regression
multivariable analyses.Setting and Patients.—A total of 1872 men treated between January 1989 and October 1997 with
an RP (n=888) or implant with or without neoadjuvant androgen deprivation
therapy (n=218) at the Hospital of the University of Pennsylvania, Philadelphia,
or RT (n=766) at the Joint Center for Radiation Therapy, Boston, Mass, were
enrolled.Main Outcome Measure.—Actuarial freedom from PSA failure (defined as PSA outcome).Results.—The relative risk (RR) of PSA failure in low-risk patients (stage T1c,
T2a and PSA level ≤10 ng/mL and Gleason score ≤6) treated using RT,
implant plus androgen deprivation therapy, or implant therapy was 1.1 (95%
confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI,
0.3-3.6), respectively, compared with those patients treated with RP. The
RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason
score of 7 or PSA level >10 and ≤20 ng/mL) and high-risk patients (stage
T2c or PSA level >20 ng/mL or Gleason score ≥8) treated with implant compared
with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively.
The addition of androgen deprivation to implant therapy did not improve PSA
outcome in high-risk patients but resulted in a PSA outcome that was not statistically
different compared with the results obtained using RP or RT in intermediate-risk
patients. These results were unchanged when patients were stratified using
the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through
6 vs 7 vs 8 through 10.Conclusions.—Low-risk patients had estimates of 5-year PSA outcome after treatment
with RP, RT, or implant with or without neoadjuvant androgen deprivation that
were not statistically different, whereas intermediate- and high-risk patients
treated with RP or RT did better then those treated by implant. Prospective
randomized trials are needed to verify these findings.

https://jamanetwork.com/journals/jama/articlepdf/187980/JOC80111.pdf

Biochemical Outcome after radical prostatectomy, external beam Radiation Therapy, or interstitial Radiation therapy for clinically localized prostate cancer

Persistent postsurgical pain: risk factors and prevention

Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications.

Aim Compare the circadian trajectory of diuresis between nocturnal polyuria (NP) patients with versus without identifiable contributory comorbidities. Methods Retrospective analysis of frequency-volume charts from male patients with clinically-significant nocturia (>= 2 nocturnal voids) and NP (defined by nocturnal urine production [NUP] >= 90 mL/hour or nocturnal polyuria index [NPi] >= 0.33). Patients with NP and chronic kidney disease, congestive heart failure, and/or undertreated obstructive sleep apnea (OSA) were deemed to have secondary NP. Nocturnal polyuria syndrome (NPS) was defined as NP without edema, loop diuretic use, or the aforementioned conditions. Patients with diabetes insipidus or OSA with appropriate continuous positive airway pressure utilization were excluded. The timing and volumes of nocturnal voids were used to derive "early" and "late" nocturnal diuresis rates (mL/hour of urine produced before and after the first nocturnal awakening, respectively). The likelihood of an early peak nocturnal diuresis rate (ie, early >late nocturnal diuresis rate) was compared between patients with NPS versus secondary NP using both a crude and adjusted odds ratio. Results The likelihood of an early peak nocturnal diuresis rate in patients with NPS compared with secondary NP was 2.58 (1.05-6.31) at NUP >= 90 mL/hour and 1.96 (0.87-4.42) at NPi >= 0.33 on crude analysis, and 2.44 (0.96-6.24) and 1.93 (0.83-4.48) after adjustment, respectively. Conclusions A peak early nocturnal diuresis rate was significantly more likely in patients with NPS at NUP >= 90 mL/hour, with similar odds ratios at NPi >= 0.33 and following adjustment. Delineating nocturic patients by NP subgroup may facilitate more individualized management. Patient Summary Many people have to wake up to urinate because they produce too much urine at night-a condition known as "nocturnal polyuria." Nocturnal polyuria might be caused by drinking too much fluid, other behavioral factors, or conditions that make your body hold on to too much fluid, like heart disease, kidney disease, and sleep apnea. In cases of nocturnal polyuria where no clear cause can be identified, it is thought that patients may suffer from a deficiency in nighttime vasopressin, a hormone that plays a key role in how much urine you produce. In this study, we compared the pattern of nighttime urine production in patients with different causes of nocturnal polyuria, which may lead to more personalized treatment options for patients with this condition.

Time of peak nocturnal diuresis rate between men with secondary nocturnal polyuria versus nocturnal polyuria syndrome

Bladder filling depends upon the coordinated control of a storage chamber, the bladder body, and its outlet, the bladder base and urethra. Bladder emptying results from development of force in the bladder body and relaxation of the outlet. Muscle strips from bladder body reveal phasic characteristics, whereas the strips from urethral wall are tonic. To determine whether the compositions of myosin heavy chain (MHC) isoforms and the level of myosin light chain (MLC) phosphorylation contribute to the regional variation in the contractile states of the bladder smooth muscle, we analyzed the levels of MLC phosphorylation and the expression of myosin isoforms in smooth muscle tissues from different regions of the urinary bladder. Strips of bladder from the dome, mid body, base of the bladder and urethra were removed and analyzed for the levels of MLC phosphorylation at the resting tone. The expression of MHC isoforms that differ in the C-terminus (SM1 and SM2) and in the N-terminal region (SM-A and SM-B), forme...

Myosin light chain phosphorylation at resting level and the composition of myosin isoforms in the bladder body and urethra.

New theories in interstitial cystitis.

The function of the bladder is twofold: 1) to store urine at low pressure, and 2) under control of the nervous system, to generate a contractile force coordinated with a lowered urethral resistance that allows for emptying.20 Clinically, this system is most commonly affected by bladder outlet obstruction, and the response of the detrusor is remarkable in its variability. Experimentally, most investigators agree that after outlet obstruction, there is an increase in bladder mass seen irrespective of the model used. Within most experimental models of partial obstruction (as with humans), there exists a degree of variability in terms of detrusor response. Some bladders enter a state of compensation and are able to sustain elevated voiding pressures and empty satisfactorily. Others enter a state of decompensation and lose their ability to empty effectively.15 The molecular mechanisms for such decompensations are under current investigation, and may involve alterations in cytosolic calcium handling,19,21 disruptions in mitochondrial function,4 and changes in the expression of contractile filaments.1 In the late stages, as the bladder slides into the decompensated state, major depositions of extracellular matrix are seen in a variety of species.3,9,11

Alan J. Wein

Papers

Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications.

Time of peak nocturnal diuresis rate between men with secondary nocturnal polyuria versus nocturnal polyuria syndrome

Myosin light chain phosphorylation at resting level and the composition of myosin isoforms in the bladder body and urethra.

New theories in interstitial cystitis.

Murine in vitro whole bladder physiology.