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This study was conducted to investigate whether the testis, aside from its ability to secrete androgen, is able to promote prostatic growth in rats. Increasing quantities of silastic capsules filled with crystalline dihydrotestosterone (DHT) were implanted subcutaneously into adult Sprague-Dawley rats at the time of bilateral epididymo-orchiectomy or sham operation on the testes. Control animals received empty capsules. Twenty-eight days later, the growth of the ventral prostate as measured by wet weight, DNA, and protein content per prostate was significantly greater in rats with intact testes than in orchiectomized rats. An overall increased growth was noted at all doses of exogenous DHT administered. Serum levels of luteinizing hormone in animals treated with DHT were undetectable. Serum levels of testosterone in intact rats treated with DHT were not significantly different from those in castrated rats. These observations suggest a non-androgenic role for the testis and, perhaps, epididymis in promoting prostatic growth in rats, and are consistent with the concept that a non-androgenic substance, produced from the testis and/or epididymis, is able to enhance prostate growth induced by androgen stimulation. The possibility that this phenomenon may play a role in the benign growth of the prostate observed in aging human males with decreased blood levels of androgen warrants consideration.

Two rough methods are given to estimate the combined HIV prevalence in Los Angeles, New York and San Francisco in homosexual men. Both methods are related to the back calculation technique, and use AIDS surveillance data and information obtained from the Multicenter AIDS Cohort Study. Both methods suggest that the combined HIV prevalence is approximately 100,000, with a possible range of 80,000-140,000.

Objective. —To identify clinical and epidemiological factors associated with failure of Pneumocystis carinii pneumonia (PCP) prophylaxis in those receiving primary and secondary prophylaxis. Design. —Longitudinal cohort study of participants infected with human immunodeficiency virus type 1 in the Multicenter AIDS Cohort Study who used PCP prophylaxis regimens after their T-helper lymphocyte counts had decreased to less than 0.200×10 9 /L (200/μL). Main Outcome Measure. —Occurrence or recurrence of PCP. Results. —A total of 476 participants reported taking one or more of the following regimens: trimethoprim-sulfamethoxazole (TMP-SMX), dapsone, and/or aerosolized pentamidine—367 as primary prophylaxis and 109 as secondary prophylaxis after a previous episode of PCP. A total of 92 (20%) developed PCP despite prophylaxis. The mean failure rates per person-year of follow-up were 16.0% for those receiving primary prophylaxis and 12.1% for those receiving secondary prophylaxis ( P =.19). Median times to death after initiation of primary or secondary prophylaxis were 2.0 and 1.2 years, respectively. The main predictor for failure of PCP prophylaxis was profound T-helper lymphocytopenia; 86% of failures occurred after T-helper cell counts decreased to less than 0.075×10 9 /L and 76% occurred after counts decreased to less than 0.050×10 9 /L. In multivariate time-dependent analysis, when compared with counts between 0.100×10 9 /L and 0.200×100 9 /L, the risk ratio for failure with counts less than 0.050×10 9 /L was 2.90 ( P P =.01). Use of TMP-SMX as the prophylaxis regimen was protective but did not eliminate failure (ie, a time-dependent risk ratio of 0.55; P =.03). Conclusions. —These findings strongly support identifying improved methods of PCP prophylaxis once T-helper cell counts decrease to less than 0.075×10 9 /L or 0.100×10 9 /L. Given this severe degree of immunosuppression, an inherently more effective regimen against P carinii is required. ( JAMA . 1995;273:1197-1202)

Objective. —To ascertain whether depressive symptoms as determined by the Center for Epidemiologic Studies—Depression scale (CES-D) predict accelerated mortality and worse medical outcomes in patients infected with human immunodeficiency virus (HIV). Design. —Eight-year cohort study with semiannual follow-up. Setting. —Community volunteers. Participants. —A total of 1809 HIV-seropositive homosexual men without the acquired immunodeficiency syndrome (AIDS) who entered the Multicenter AIDS Cohort Study in 1984 or 1985. Eight-year follow-up data were available on 75% of eligible participants. Outcome Measures. —Times to AIDS, death, and prophylactic treatment, and slopes describing the decline in CD4 count for each individual participant. Results. —Using a conventional definition of depression (CES-D ≥16 at the first study visit), 21.3% of participants were classified as depressed. Depressed participants had lower CD4 counts and reported more AIDS-related symptoms. There were no significant differences between depressed and nondepressed participants on any of the outcome measures ( P >.05 in all cases). In contrast, men reporting AIDS-related symptoms had shorter times to AIDS and to death even after adjusting for CD4 counts ( P Conclusions. —We find no evidence that depressive symptoms independently prognosticate worse outcomes in HIV infection. Because of associations of depression with symptom reports, CD4 counts, and indicators of socioeconomic status, future studies of the relationship between depression and HIV outcome should consider these variables as confounders. ( JAMA . 1993;270:2563-2567)

Objective. —To determine the degree of compliance with clinical standards among hospitals for care of breast cancer patients and account for variations in compliance. Design. —Analysis of cancer registry data submitted to the American Cancer Society, Illinois Division, Chicago, for a concurrent prospective descriptive study of breast cancer, supplemented by other hospital data from public sources. Setting. —Ninety-nine Illinois hospitals evenly distributed among rural counties, counties with small cities outside the Chicago metropolitan area, exurban counties in the Chicago metropolitan area, suburban Cook County, and urban Chicago. Patients. —A total of 5766 newly diagnosed patients with histologically confirmed breast cancer in 1988, representing 84% of the estimated 6900 new cases in the state for that year. Main Outcome Measures. —Descriptive statistics and multiple linear regression analyses of five dependent quality variables from clinical indicators related to early diagnosis, hormone receptor determination, adjuvant therapy, radiation therapy, and axillary lymph node dissection. Results. —At the hospitals studied, (1) late stage (IIb through IV) at diagnosis was associated with urban location, higher proportion of poorly insured patients, fewer breast cancer cases treated, and lower oncology charges (proportion of variance explained, R 2 =.50, P R 2 =.18, P R 2 =.21, P Conclusions. —The findings suggest that there is a group of urban hospitals, generally small and marginally reimbursed, where comprehensive diagnosis and treatment of breast cancer are not obtained. ( JAMA . 1991;266:3429-3432)

2507 homosexual men who were seronegative for human immunodeficiency virus (HIV) at enrollment were followed for six months to elucidate risk factors for seroconversion to HIV. 95 (3.8%) seroconverted. Of men who did not engage in receptive anal intercourse within six months before baseline and in the six-month follow-up period, only 0.5% (3/646) seroconverted to HIV. By contrast, of men who engaged in receptive anal intercourse with two or more partners during each of these successive six-month intervals, 10.6% (58/548) seroconverted. No HIV seroconversions occurred in 220 homosexual men who did not practise receptive or insertive anal intercourse within twelve months before the follow-up visit. On multivariate analysis receptive anal intercourse was the only significant risk factor for seroconversion to HIV, the risk ratio increasing from 3-fold for one partner to 18-fold for five or more partners. Furthermore, data for the two successive six-month periods show that men who reduced or stopped the practice of receptive anal intercourse significantly lowered their risk of seroconversion to 3.2% and 1.8%, respectively. Receptive anal intercourse accounted for nearly all new HIV infections among the homosexual men enrolled in this study, and the hazards of this practice need to be emphasised in community educational projects.

Twenty homosexual men who reported having sexual contact with homosexual men who had the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex were examined to determine their clinical status, immunologic profiles, and the presence of antibody to the human T-cell lymphotropic virus type III (HTLV-III). Of the 20, eight men had one or more signs or symptoms of the AIDS-related complex and 12 were asymptomatic. Antibodies to HTLV-III were present in 14 (70%) of 20 of the sexual contacts as compared with four (10%) of 40 healthy homosexuals without known contact with a patient who had AIDS (P less than .0001). Seropositive contacts had significantly higher mean counts of suppressor lymphocytes and lower helper: suppressor ratios (P less than .05 and .005, respectively) and higher serum levels of IgG than seronegative contacts (P less than .05). It was not possible to determine significant differences in sexual practices, drug use, length of relationship, or numbers of different sexual partners between symptomatic and asymptomatic contacts or between seropositive and seronegative contacts in this study.

To estimate the time interval between human immunodeficiency virus type 1 (HIV-1) seroconversion and acquired immunodeficiency syndrome (AIDS) diagnosis in homosexual men, prospective incident cohorts are difficult to obtain and, if assembled, provide few events owing to the long incubation time. Although seroprevalent cohorts are numerous in size and events, the information is limited due to the unknown times since seroconversion. To combine the information provided by 1,628 seroprevalent men (304 AIDS cases) and 233 seroconverters (12 AIDS cases) being followed in a multicenter study since 1984, the postseroconversion changes in hematologic variables occurring in the incident cohort were used to develop a model that allowed for the imputation of the unknown times since seroconversion for the seroprevalent cohort. Nonparametric life table methods incorporating truncation and censoring were applied for the estimation of the probability distribution of the AIDS-free time after seroconversion. The precision of the estimates was evaluated using bootstrap methods. The analysis suggested that AIDS is unlikely (less than 0.5%) in the first year; 78% of seropositive homosexual men remain AIDS-free 60 months after seroconversion; and the AIDS incidence increases for months 12-36 and levels off at 38 per 1,000 person-semesters for months 42-60. The nonparametric estimate of the incidence rate suggests a median AIDS-free time of 11 years, which is longer than previous estimates based on parametric models.

Breast carcinoma (BCa) cells produce I antigen or I antigen-like substances that may influence serum anti-I. We determined cold hemagglutinins in 170 BCa patients, 97 women with benign breast disease, and 37 female controls of comparable ages to the patients. The results were expressed as an anti-I score. Serum IgM was measured by radial immunodiffusion. The data for the BCa patients were analyzed by pathologic stage (PS) and histologic category. The anti-I score for PS III (28.1 +/- 13.0; mean +/- S.D.) was higher (p less than 0.02), and that for PS IV (11.4 +/- 7.4) lower (p less than 0.02) than the control value (17.7 +/- 10.2). IgM concentrations of the BCa patients as a group or by PS were similar to those of the controls. The mean anti-I scores were higher in mucinous (31.1 +/- 14.9, p less than 0.001) and apocrine BCa (28.6 +/- 16.2, p less than 0.02) compared to the control value. IgM concentrations were elevated in mucinous (218.1 +/- 85.8 mg/dl, p less than 0.01) and apocrine BCa (241.9 +/- 99.0, p less than 0.005) compared to the control value (157.1 +/- 66.9). The results suggest an association of anti-I scores and PS of BCa and suggest an antigenic difference of mucinous and apocrine from infiltrative ductal BCa.

Interviews regarding medical history, life-style, specific drug taking and sexual activities, and physical examinations were administered to 4,955 homosexual men who volunteered for the Multicenter AIDS Cohort Study in Baltimore, Chicago, Los Angeles, and Pittsburgh. Overall, the prevalence of antibodies to human immunodeficiency virus (HIV) in these men was 38.0%. The factor most strongly associated with prevalent HIV infection according to a multiple logistic regression model was rectal trauma, a composite variable which included receptive anal fisting, enemas before sex, reporting of blood around the rectum, and the observation of scarring, fissures or fistulas on rectal examination. Receptive anal intercourse also was strongly associated with HIV infection in the model. The multivariate relative odds for HIV antibody positivity was 7.72 for the highest level of rectal trauma and 3.04 for receptive anal intercourse. Symptoms reported to occur in some persons who subsequently develop acquired immunodeficiency syndrome (AIDS) were frequent among HIV seropositive men (12.9%) but were reported in 8.4% of seronegative men as well. Generalized lymphadenopathy was observed significantly more often in seropositive men (48.8%) compared with seronegative men (11.4%). The prevalence of HIV antibodies was inversely related to the number of T-helper cells and directly related (to a lesser extent) to the number of T-suppressor cells. The results suggest that disruption of the rectal mucosa provides access by HIV to the blood stream and to specific immunologic cells. Since symptoms and generalized lymphadenopathy were often reported among seronegative men, they probably also occur among some seropositive men not currently progressing to AIDS.

The ABO group, Lewis type and secretor status were determined in 546 normal individuals (241 male, 305 female). Their serum was tested at 4 degrees C for agglutination of group O red blood cells; the antibody was presumed to be auto-anti-I; the results were expressed as a score. Among non-A female donors, the score was higher for secretors than nonsecretors (p less than 0.05). Among non-A secretors of both sexes, female donors had a higher score than male donors (p less than 0.05). These results suggest that the level of anti-I in the serum of normal individuals may be affected by the donor's ABO group, secretor status and sex.

A retrospective analysis of survival results for colorectal cancer patients in Illinois was performed by the Cancer Incidence and End Results Committee of the Illinois Division of the American Cancer Society. Cancer registry data on 1,774 patients from 63 hospitals were used to investigate whether the preoperative level of serum carcinoembryonic antigen (CEA) was a prognostic indicator of survival for cancers diagnosed between 1976 and 1978. A direct relationship was found between the preoperative level of serum CEA and both the thickness and stage of the tumor at initial diagnosis. For Stage B2/3 colorectal cancer, the actuarial survival curves corresponding to normal, elevated, and markedly elevated CEA levels were significantly different (p less than 0.0001). The five-year survival rates for these patients were 61, 50, and 32 percent, respectively. Similar trends for patients with Stage C2/3 cancer were observed (p = 0.0058). The corresponding five-year survival rates were 44, 30, and 26 percent, respectively. Using a statewide cancer registry system, the analysis suggested that the preoperative level of serum CEA was an indicator of survival in patients with colorectal cancer, independent of the stage of disease at diagnosis.

Of 479 homosexual men immunized with three 20-microgram doses of the hepatitis B vaccine, approximately 15% failed to develop protective titers of antibody to the surface antigen of hepatitis B virus (greater than 10 sample ratio units [SRU]). We revaccinated 34 nonresponders with an additional three doses of vaccine and compared their immunologic status with that of 14 control men who had responded to initial vaccination. Most men (15 of 19) who had measurable antibody to hepatitis B surface antigen (SRU, 2.1-9.9) after initial vaccination responded to revaccination, whereas ten of the remaining 15 nonresponders (SRU, less than 2.1) did not. No single immunologic measure distinguished ultimate responders from nonresponders; however, the initial responders differed from delayed responders and nonresponders by having higher numbers of total lymphocytes, B, T, and T helper and suppressor cells.

A dosimetry study of factors affecting the extent of tissue damage inflicted upon the canine renal cortex by the Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser was undertaken. Laser parameters and renal tissue conditions were varied independently in duplicate in the following manner: (1) power - 5, 10, 20, 50, 75, 100 watts with a spot size of 1.2 mm; (2) exposure duration - 1, 2, and 4 seconds; (3) kidney perfusion and temperature--renal artery unclamped (perfused) without cooling; renal artery clamped (non-perfused) without cooling; and renal artery clamped with cooling. Five days following application of the laser, the animals were sacrificed and serial sections of the renal cortex were examined for maximum depth and width of tissue damage and ablation. Multiple linear regression analysis of the data indicated a direct linear relationship between the joules (watts X seconds) of energy delivered to the renal cortex and the depth and width of tissue damage and ablation (p less than 0.001 for joule regression coefficient for each variable). Seconds and/or watts alone were not major predictors of the outcome after accounting for joules. Clamping the main renal artery significantly reduced the depth and width of laser damage when compared to the perfused kidney (p less than 0.001 for each variable). The depth of damage was similar in the cooled and the non-cooled non-perfused kidney. These data suggest that increased laser energy and kidney perfusion significantly increase renal cortical laser induced damage. Adjustment of these parameters may permit controlled tumor ablation or tissue incision with minimal damage to adjacent normal tissue.

Tumor cells elaborate and release into the circulation a variety of glycoproteins. An enzyme-linked immunosorbent assay (ELISA) was developed to monitor carbohydrate structures secreted into the circulation. Among these antigens are the structures specific for the blood group I antigens, which are incompletely converted to ABH antigens on the membranes of tumor cells. The I antigens in the sera of 67 women with breast carcinoma (BCa), 58 with benign breast disease (BBD), and 47 controls were measured by the ELISA. In this assay, I antigen from ovarian cyst mucin was bound to the wells of polystyrene microtiter plates. The monoclonal human anti-I antibody (Hy) was added to the wells along with perchloric acid extracts of patient and control sera at five different dilutions. The anti-I binding to the solid-phase I antigen was determined after incubation steps with peroxidase-labeled anti-human IgM and substrate. The amount of sera extracts giving 50% inhibition of anti-I (Hy) binding was determined from the inhibition curves which were corrected by integrating the slope values into that of the standard curve obtained with extracts of normal sera. The I antigens were significantly higher in pathologic stage (PS) IV sera (P less than 0.001), and comparable in PS I, PS II, and PS III and BBD sera to those in control sera. The anti-I (Hy) binds strongly Gal 1,4 GlcNAc 1,6 Gal (alpha GalNAc); Gal 1,4 GlcNAc 1,6 (Gal 1,4 GlcNAc 1,3) Gal; and to a lesser extent Gal 1,4 GlcNAc 1,3 Gal 1,4 GlcNAc (0.06, 0.09, and 0.35 mM, giving 50% inhibition, respectively). It was concluded that similar or related structures may be expressed on the membrane of metastatic BCa cells.

Hepatitis B surface and core antibodies were measured in 512 community hospital employees at increased risk for developing infection with hepatitis B virus. Antibody was detected in 140 (27 percent) participants. Multivariate logistic regression analysis indicated that seropositivity was strongly associated with the prevalence of hepatitis B in an employee's country of birth and with age. These results suggest that reported differences among hospitals in hepatitis B seropositivity may in part be a reflection of the national origin of its employees. These data also indicate that each hospital should assess its own risk for hepatitis B infection and that prevaccination serologic testing is particularly worthwhile in hospitals having large numbers of foreign-born employees.

Data from a general population sample of 621 healthy homosexual men are used to evaluate the social and emotional effects of HIV antibody status, clinical signs detected by medical examination, and subjectively perceived symptoms. Participants are unaware of their serologic status at the time of data collection, thus allowing the effects of the virus to be separated from reactions to the knowledge of serologic status. The data show that seropositivity for HIV is not associated with elevated levels of social or emotional impairment. Clinical signs lead to impairment in baseline data, but these effects do not persist at a second wave. This weakening suggests that the effects are mediated by psychological pathways rather than biologic ones. This suspicion is confirmed in further analyses, which show that the effects of clinical signs are mediated by subjectively perceived symptoms. These results show that neither social nor emotional impairment is likely to be a prodromal sign of HIV infection in otherwise healthy homosexual men. The substantial levels of distress found among these men is more directly influenced by psychological determinants than biologic ones. This suggests that physicians should be aware of the psychological toll imposed on gay men who develop health problems in the current atmosphere of uncertainty regarding risk of AIDS.

STUDY OBJECTIVE To study the natural history of human immunodeficiency virus type 1 (HIV-1) infection, we used an in-vitro amplification technique to detect HIV-1 nucleic acid sequences in sequential aliquots of peripheral blood mononuclear cells from homosexual men enrolled in the Multicenter AIDS Cohort Study. DESIGN AND PATIENTS Blinded, longitudinal study of 24 homosexual men who were positive for HIV-1 antibodies at a recent follow-up visit. MEASUREMENTS AND MAIN RESULTS Coded clinical samples were evaluated using two enzyme-linked immunosorbent assays (whole virus and gp120-gp41 fragment), Western blot, a p24 antigen capture assay, virus cocultivation, and in-vitro amplification of conserved regions from the HIV-1 gag and env open-reading frames. In 20 of the 24 men an HIV-1 enzymatically amplified product was detected before HIV-1 antibody seroconversion: at 42 months before seroconversion in two cases; at 36 months in one case; at 30 months in one case; at 24 months in four cases; at 18 months in eight cases; at 12 months in one case; and at 6 months in three cases (median, 18 months). In the four other men, detection of an HIV-1 enzymatically amplified product was concurrent with confirmation of antibody seroconversion by Western blot. CONCLUSIONS There is a long and variable interval between virus acquisition and a diagnostic serum antibody response, perhaps due to the prolonged, persistent infection characteristic of the lentiviruses (family Retroviridae).

The adherence of 74 Escherichia coli strains to vaginal and buccal epithelial cells from women with recurrent urinary tract infections was studied. The strains were isolated from the urine, vaginal introitus or anal mucosa of women with recurrent bacteriuria. Vaginal and anal isolates were judged to be associated with urinary tract infection if they had the same biotype and serotype as the strain isolated subsequently from the urine. Adherence levels of urinary and anal isolates, and vaginal isolates associated with urinary tract infection were similar for vaginal and buccal cells. Adherence of vaginal isolates not associated with urinary tract infection was significantly lower than adherence of urinary isolates for vaginal (p less than 0.001) and buccal (p less than 0.005) epithelial cells. A positive nonlinear correlation between vaginal and buccal adherence was observed for urinary (r equals 0.87, p less than 0.0001), vaginal (r equals 0.70, p less than 0.0005) and anal (r equals 0.32, p equals 0.047) isolates. Strains of O-serogroups commonly and less commonly associated with bacteriuria had similar adherence. The results suggest that adherence of vaginal isolates is associated with the ability to cause urinary tract infections. The strong correlation between vaginal and buccal cell receptivity suggests that susceptibility to such infections may be controlled by genotypic traits.

Accurate description of the prevalence of neurological impairment in healthy individuals who are infected with human immunodeficiency virus type 1 (HIV-1) has relevance for public health policy, for employment issues, and for planning future health needs. Within the Multicenter AIDS Cohort Study, we determined the cross-sectional prevalence of neurological abnormalities in 270 HIV-1 seropositive homosexual and bisexual men in Centers for Disease Control Groups II and III, using a control group of 193 HIV-1 seronegative homosexual men. Utilizing a neurological and neuropsychological screening battery, we found no differences in the prevalence of neuropsychiatric symptoms or in neuropsychological performance. One hundred nineteen subjects with abnormalities on screening tests completed additional neuropsychological testing and had neurological examinations. The majority had normal results and the frequency of neurological abnormalities and impaired neuropsychological performance was not significantly increased among HIV-1 seropositive subjects. Most of the abnormalities could be attributed to causes other than HIV-1. One subject had mild HIV-1-related dementia, yielding a prevalence of 3.7:1,000 (95% confidence interval: 0.19-23.7:1,000). Magnetic resonance imaging demonstrated sulcal prominence and focal areas of high signal intensity in white matter in 63% of HIV-1 seropositive subjects and 48% of uninfected control subjects. Abnormalities in cerebrospinal fluid were noted in 23 (85%) of 27 HIV-1-infected individuals. Our studies indicate that the prevalence of dementia and other HIV-1-related neurological disorders is very low among healthy HIV-1 seropositive homosexual men. The confounding effects of factors such as substance abuse or preexisting medical conditions must be considered in the neurological evaluation of such patients.

To determine the optimal length of the flexible fiberoptic sigmoidoscope we performed a randomized, blinded comparison study of the standard 60-cm instrument with a prototype 30-cm instrument with identical design features. Ninety-six male patients referred for symptom evaluation underwent examination with both instruments in random order by different examiners; positive examinations were followed by colonoscopy or surgery. Performance of the 30-cm sigmoidoscope compared with the 60-cm instrument revealed that the former was significantly more likely to yield a complete examination (74 vs. 32 examinations, p less than 0.002), took less time to perform (6.4 vs. 9.8 min, p less than 0.0001), and was more acceptable to patients and physicians. The 30-cm instrument was not significantly less effective than the 60-cm instrument in detecting polyps (21 vs. 25), adenocarcinoma (six for each), and inflammatory lesions. For these reasons, we conclude that the 30-cm flexible sigmoidoscope has a role in the evaluation of colorectal complaints.

The prognosis of patients with stage D bladder cancer is dismal. This report expands the results of our efforts to modify the clinical course of such patients by administration of doxorubicin hydrochloride sandwiched around pelvic radiation. Pathologic stage D bladder cancer was recognized in 19 patients by evaluation of tissue obtained by radical cystectomy and pelvic lymphadenectomy (8), pelvic lymph node dissection (5) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with doxorubicin hydrochloride before and after radiation was initiated 3 to 4 weeks postoperatively. The treatment regimen consisted of 1) 60 mg. per M.2 doxorubicin intravenously every 3 weeks for 3 cycles, 2) 5,000 rad external radiation to the entire pelvis in 5 to 6 weeks and 3) doxorubicin for 5 cycles. The observed survival rates were 37 per cent at 3 years and 28 per cent at 5 years. The median survival time was 16 months. Five patients had no evidence of disease 13 to 63 months postoperatively. One patient underwent salvage cystectomy for recurrent bladder carcinoma at 33 months and had no evidence of disease at 74 months. One patient was alive with recurrent disease at 13 months. Three patients who died did not complete the protocol owing to metastatic disease, 8 lived 6 to 52 months without recognized disease and died of metastases, and 1 died of a second primary. The extent of surgical excision was not associated significantly with survival. Of 8 patients treated with radical cystectomy 7 suffered a significant obstruction of the small bowel that required decompression or bypass surgery and all 7 recovered completely. These preliminary observations indicate encouraging results with a high but manageable morbidity for this regimen.

Summary Cortical thickness of the second metacarpal bone and lumbar spine fractures were determined radiographically in twenty-one Caucasian corticosteroid-dependent asthmatics (mean age, 61-2 years; range 47-73 years). The mean number of prednisone years per patient of continuous corticosteroid treatment averages 9.7 (range 5.0-21.5 years), and the mean accumulated dose of prednisone was 46.7 g (range 10.7-160 g). Thirteen of twenty-one (61.9%) patients had cortical thickness between 1 and 2 standard deviations (s.d.) below the age- and sex-specific mean for normals, but only four (19%) patients fell below 2 s.d. Although the study indicated decreased cortical thickness in the prednisone-treated group, in only one (4.8%) patient were vertebral fractures present, an incidence not unexpected in this age group. In serious chronic asthma, concern for bone structure should not prohibit the cautious use of appropriate corticosteroid regimens at the lowest possible maintenance dose.

The effect of D-mannose and D-glucose on bacteriuria due to Escherichia coli with mannose-sensitive adhesins was investigated in adult male Sprague-Dawley rats undergoing diuresis. Inocula of 10(5), 10(7), or 10(8) bacteria in 0.1 ml of normal saline or 2.5% or 10% D-mannose or D-glucose were injected intravesically and urine was cultured 1, 3, 5, 7 and 9 days later. The levels of bacteriuria on days 1 and 5 were significantly lower in rats inoculated with 10(5) E coli and 10% D-mannose than in controls (p less than 0.05 and 0.01 respectively) and the percentages of rats with less than 100 bacteria/ml were higher on days 1 and 3 (p = 0.05 and 0.02 respectively). Bacteriuria was significantly lower in rats inoculated with 10(7) bacteria and 10% D-mannose than in controls on days 5 and 7 (p less than 0.01 for each day) and the percentage of rats with less than 100 bacteria/ml was higher on day 7 (p = 0.01). D-glucose reduced bacteriuria significantly only with a concentration of 10% after instillation of 10(5) E. coli (p less than 0.05, day 1). The results indicate that D-mannose and D-glucose can significantly reduce bacteriuria within 1 day and that their efficacy is dependent upon the concentration of both saccharide and bacteria.

Adherence of Escherichia coli to human uroepithelial cells obtained from the midstream urine of healthy women, nd to vaginal and buccal cells obtained from 11 healthy women and 24 patients who had had at least three urinary tract infections in the preceding year was studied. Bacteria labeled with [3H] uridine were used, and unattached organisms were separated from the epithelial cells by vacuum filtration through a polycarbonate membrane filter (5-micrometers-pore-size). A day-to-day variation in the receptivity of uroepithelial cells was noted. The range and rapidity of change in adherence to both vaginal and buccal cells were greater in patients than in controls. Adherence to vaginal cells was greater in patients than in controls (10.1 +/- 0.92 vs. 3.8 +/- 0.47 bacteria per cell [mean +/- S. E.], P less than 0.001), as was adherence to buccal cells (1.7 +/- 1.29 vs. 7.1 +/- 0.49, P = 0.002). There was a very strong, positive non-linear correlation between vaginal and buccal cell receptivity (R = 0.87, P less than 0.0001). The data suggest that susceptibility in women to urinary-tract infections is associated with widespread, fluctuating changes in the adhesive characteristics of epithelial cells.

Urethral meatal colonization with potential urinary tract pathogens was studied before bacteriuria in 31 consecutive acute spinal cord injury patients on an open ward (137 cultures) and 18 renal homotransplant patients in reverse isolation (80 cultures). All patients required indwelling urethral catheterization and no antimicrobials were given. Daily quantitative cultures of the urethral meatus, and bladder and drainage bag urine were obtained. The urethra was the source for 11 of 31 episodes of bacteriuria (35 per cent). Urethral meatal colonization with the organism responsible for bacteriuria, that is Escherichia coli (5 episodes), Staphylococcus aureus (2), Streptococcus faecalis (2) and Staphylococcus epidermidis (2), was persistent and present from 2 to 5 days before bacteriuria. In each ward 81 per cent or more of the cultures obtained on day 1 of catheterization showed no gram-negative colonization. Subsequently, the gram-negative colonization density increased in both groups but the increase was significant (p less than 0.001) only for patients on the open ward. Similar trends were observed for gram-positive colonization. The prevalence of potential pathogens was similar for patients whether or not they suffered bacteriuria. An increased density of bacterial colonization was associated with increased susceptibility to bacteriuria but the specific urethral meatal flora was not always predictive of the species responsible for bacteriuria.

The effect of D-mannose on adherence of 73 Escherichia coli strains to vaginal and buccal epithelial cells from women with recurrent urinary tract infections, and on agglutination of human and guinea pig erythrocytes was tested. Urinary, vaginal or anal isolates from women with such infections were used. Of the strains 66 (90 per cent) demonstrated adherence to epithelial cells. D-mannose inhibited completely the adherence of 25 strains (42 per cent) that adhered to vaginal cells and inhibited an additional 11 strains (18 per cent) by at least 50 per cent. Similar results were obtained with buccal cells. The inhibitory effect of D-mannose was similar regardless of the origin of the strains. Hemagglutination frequently was inhibited by D-mannose but no consistent association between hemagglutination, and epithelial cell adherence and the effect of D-mannose was observed. The results suggest that mannose-sensitive as well as mannose-resistant adhesins frequently mediate Escherichia coli adherence to vaginal epithelial cells, and may contribute to vaginal colonization and cystitis.

Clinical and laboratory evaluations of 181 men were performed; the population studied included 131 homosexual or bisexual men (who were stratified into one of three groups on the basis of symptomatology and abnormal findings on physical examination), 39 heterosexual men (who served as controls), and 11 men with acquired immunodeficiency syndrome (AIDS). The presence of specific symptoms and/or lymphadenopathy in homosexual men was associated with perturbation of immunoregulation. A large percentage of asymptomatic, homosexually active men had abnormalities in lymphocyte numbers, subpopulations, and subclasses. Symptomatic individuals had clinical findings, immunologic alterations, and abnormalities of hematopoiesis similar to those found in patients with AIDS. These data suggest that clinical evaluation in conjunction with laboratory studies may serve to identify individuals at increased risk of developing AIDS.

Summary: A homozygous 32-bp deletion in the gene encoding CCR5, a major coreceptor for HIV-1, leads to resistance to infection with HIV-1, and heterozygosity for the deletion is associated with delayed disease progression in persons infected with HIV-1. We investigated the effect of CCR5 heterozygosity on disease progression as measured by both CD4+ T-cell count decline and the occurrence of clinical AIDS symptoms. Using a unified statistical model for CD4 count progression and AIDS development, we examined whether the effect of CCR5 heterozygosity on clinical AIDS is direct or indirect through its effect on CD4 counts. Based on data from the Multicenter AIDS Cohort Study, we noted a protective effect of CCR5 heterozygosity on both CD4 cell count progression and on AIDS occurrence. Furthermore, we found that this protective effect on the occurrence of AIDS was completely mediated through an effect on the CD4 marker. Additional adjustment for the effect of an initial viral load measurement indicate that CCR5 heterozygosity did not have predictive value for either CD4 progression or the development of AIDS beyond its association with early viral load.

The association of tumor size and lymph node metastasis in endometrial cancer clinically confined to the uterus was evaluated in 91 patients. Other factors possibly associated with lymph node metastasis were also analyzed. Tumor size was independently associated with lymph node metastasis when analyzed by multivariate analysis (P = .022). Patients with tumors less than or equal to 2 cm in diameter had only a 5.7% incidence of lymphatic metastases. When tumors exceeded 2 cm in diameter or involved the entire endometrial surface, metastases occurred in 21.7 and 40.0% of patients, respectively. Measuring tumor size at surgery, or possibly preoperatively by hysteroscopy, will help predict which patients are at increased risk for lymph node metastasis. There were no lymph node metastases in patients with tumors less than or equal to 2 cm in diameter and invasion of less than half of the myometrium. For these patients, extended surgical staging with pelvic and aortic lymph node biopsies may not be indicated.

Little is known about early knee osteoarthritis (OA). The significance of lesions on magnetic resonance imaging (MRI) in older persons without radiographic OA is unclear. Our objectives were to determine the extent of tissue pathology by MRI and evaluate its significance by testing the following hypotheses: cartilage damage, bone marrow lesions, and meniscal damage are associated with prevalent frequent knee symptoms and incident persistent symptoms; bone marrow lesions and meniscal damage are associated with incident tibiofemoral (TF) cartilage damage; and bone marrow lesions are associated with incident patellofemoral (PF) cartilage damage.In a cohort study of 849 Osteoarthritis Initiative (OAI) participants who had a bilateral Kellgren/Lawrence (K/L) score of 0, we assessed cartilage damage, bone marrow lesions, and meniscal damage using the MRI OA Knee Score, as well as prevalent frequent knee symptoms, incident persistent symptoms, and incident cartilage damage. Multiple logistic regression (one knee per person) was used to evaluate associations between MRI lesions and each of these outcomes.Of the participants evaluated, 76% had cartilage damage, 61% had bone marrow lesions, 21% had meniscal tears, and 14% had meniscal extrusion. Cartilage damage (any; TF and PF), bone marrow lesions (any; TF and PF), meniscal extrusion, and body mass index (BMI) were associated with prevalent frequent symptoms. Cartilage damage (isolated PF; TF and PF), bone marrow lesions (any; isolated PF; TF and PF), meniscal tears, and BMI were associated with incident persistent symptoms. Hand OA, but no individual lesion type, was associated with incident TF cartilage damage, and bone marrow lesions (any; any PF) with incident PF damage. Having more lesion types was associated with a greater risk of outcomes.MRI-detected lesions are not incidental and may represent early disease in persons at increased risk of knee OA.

The HLAs of the major histocompatibility complex in humans have been associated statistically with many diseases [1]. The possibility that recurrent UTIs in women are controlled in part by genotypic traits was suggested by the observation that adherence of Escherichia coli in vitro to both vaginal and buccal cells was greater for patients with such infections than for healthy control subjects and that there was a strong correlation between vaginal cell and buccal cell receptivity [2]. A3 antigen was identified in 12 (34%) of the patients. This frequency was significantly higher in patients than in healthy control subjects, but it was not significantly different from the frequency observed in the reference population. After correction for the number of comparisons made, there was no statistically significant difference between patients and control subjects with any other antigen. These data suggest that HLA A3 may be associated with increased risk of recurrent UTIs.