Ophthalmia neonatorum: a chart review.

Cases of ophthalmia neonatorum diagnosed at Grady Memorial Hospital 1967-1973 were reviewed. Of 302 cases 43 could be diagnosed as gonococcal, 86 chlamydial, 3 gonococcal and chlamydial, 31 staphylococcal, and 5 chemical. Silver nitrate prophylaxis was routinely employed. Gonococcal cases peaked during the third quarter of the year and chlamydial during the fourth quarter. Gonococcal cases were associated with a longer duration of ruptured fetal membranes. Definitive etiologic diagnosis could not be estalished on clinical grounds alone. Chlamydial ophthalmia was more common among black babies but other forms of ophthalmia were equally distributed with respect to race. The risk of gonococcal ophthalmia developing in an infant born to an infected mother was less than 2% if Credé prophylaxis is used. Therapy with topically applied sulfonamides was effective against chlamydial ophthalmia. Therapy with parenterally administered penicillin and topically applied antibiotics was effective against gonococcal ophthalmia.

Clinical approach to urethritis, mucocutaneous lesions, and inguinal lymphadenopathy in homosexual men.

The spectrum of sexually transmitted diseases observed among homosexual men is diverse, but in general includes the same infections observed among heterosexuals. A systematic approach to the diagnosis of these diseases, incorporating sexual history, predominant symptoms, findings from physical examination, and office laboratory evaluation will frequently yield a specific diagnosis. Prompt diagnosis and treatment of patients, and when appropriate, of contacts are of critical importance to the prevention of unnecessary morbidity and further transmission of disease.

Defining the cost of educating undergraduate medical students at the University of Virginia.

PURPOSE: To develop a model for calculating the cost of a four-year undergraduate medical education at the University of Virginia School of Medicine (UVA) in 1994-95. METHOD: All data were based on faculty contact hours (FCHs), the primary driver of cost. (An FCH was an hour during which a faculty member was actively teaching.) First- and second-year data were derived from a published curriculum schedule. Third-year data were derived from hours spent in each clerkship and a series of calculations to assess direct teaching time in each clerkship accurately. Fourth-year data were modeled on an artificial but typical program consisting of the required clerkship in neurology, a two-day course in advanced cardiac life support, and seven elective blocks; electives were chosen based on relative overall popularity. The number of full-time-equivalent (FTE) faculty required was calculated. The salary costs of UVA full-time faculty were calculated. Other total direct costs, including the costs of support and administrative services as well as the costs of the educational contributions of housestaff and contract faculty, were calculated. The overall cost, including direct and indirect costs, was calculated. An average of 139 students per year was assumed. RESULTS: The total number of FCHs was just under 100,000. The number of FTE faculty required was 223. UVA faculty salary and fringe benefits totaled $29,400,000. The costs of support and administrative services totaled $4,100,000; the costs of housestaff and contract faculty totaled $2,300,000. The overall educational costs totaled $49,600,000. CONCLUSION: The overall cost of a four-year medical education at UVA was $357,000 per student. Although the process of calculating this cost was complex and, at times, based on assumptions open to debate, the model developed can be applied to any medical education setting.

Case report: increase in CD4 lymphocyte counts after splenectomy in HIV-infected patients.

The records were reviewed of five human immunodeficiency virus (HIV) type 1-infected patients who underwent splenectomy, four for HIV-associated thrombocytopenia and one for gastric compression secondary to splenomegaly. After splenectomy, the four adult patients all had marked, sustained increases in their absolute CD4 lymphocyte counts; greater increases were observed in CD8 lymphocyte counts, accounting for decreases in the CD4:CD8 ratios. In patients 5 (one of triplets, all of whom were infected with HIV after a blood transfusion), absolute CD4 lymphocyte counts were stabilized after splenectomy; the other siblings manifested a decline in CD4 counts, which was associated with a delay in physical development and recurrent episodes of varicella. Immunohistochemical staining of spleen sections demonstrated significantly higher numbers of CD4 cells in splenic tissue from HIV-infected patients than from patients splenectomized secondary to trauma (2,070 +/- 284 vs. 962 +/- 296; p = 0.025). In addition, the HIV-infected patients had significantly higher percentages of CD4 lymphocytes in splenic tissue than in peripheral blood (49.3 +/- 11.0 vs. 20.3 +/- 7.9; p = 0.005), suggesting that CD4 cells were sequestered in the spleens of these patients. These findings have implications for the management of splenectomized HIV-infected patients with regard to optimal timing of initiation of zidovudine therapy and for prophylaxis of Pneumocystis carinii pneumonia.

NIH consensus development statement on management of hepatitis B.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on the management of hepatitis B. PARTICIPANTS: A non-DHHS, nonadvocate 12-member panel representing the fields of hepatology and liver transplantation, gastroenterology, public health and epidemiology, infectious diseases, pathology, oncology, family practice, internal medicine, and a public representative. In addition, 22 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the Minnesota Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: The most important predictors of cirrhosis or hepatocellular carcinoma in persons who have chronic HBV are persistently elevated HBV DNA and ALT levels in blood. Other risk factors include HBV genotype C infection, male sex, older age, family history of hepatocellular carcinoma, and co-infection with HCV or HIV. The major goals of anti-HBV therapy are to prevent the development of progressive disease, specifically cirrhosis and liver failure, as well as hepatocellular carcinoma development and subsequent death. To date, no RCTs of anti-HBV therapies have demonstrated a beneficial impact on overall mortality, liver-specific mortality, or development of hepatocellular carcinoma. Most published reports of hepatitis therapy use changes in short-term virologic, biochemical, and histologic parameters to infer likelihood of long-term benefit. Approved therapies are associated with improvements in intermediate biomarkers, including HBV DNA, HBeAg loss or seroconversion, decreases in ALT levels, and improvement in liver histology (Table). Although various monitoring practices have been recommended, no clear evidence exists for an optimal approach. The most important research needs include representative prospective cohort studies to define the natural history of the disease and large RCTs of monotherapy and combined therapies, including placebo-controlled trials, that measure the effects on clinical health outcomes. Table. Criteria Useful in Determining for Whom Therapy is Indicated: Patients for whom therapy is indicated: Patients who have acute liver failure, cirrhosis and clinical complications, cirrhosis or advanced fibrosis and HBV DNA in serum, or reactivation of chronic HBV after chemotherapy or immunosuppression; Infants born to women who are HBsAg-positive (immunoglobulin and vaccination). Patients for whom therapy may be indicated: Patients in the immune-active phase who do not have advanced fibrosis or cirrhosis. Patients for whom immediate therapy is not routinely indicated: Patients with chronic hepatitis B in the immune-tolerant phase (with high levels of serum HBV DNA but normal serum ALT levels or little activity on liver biopsy); Patients in the inactive carrier or low replicative phase (with low levels of or no detectable HBV DNA in serum and normal serum ALT levels); Patients who have latent HBV infection (HBV DNA without HBsAg). We recommend routine screening for hepatitis B of newly arrived immigrants to the United States from countries where the HBV prevalence rate is greater than 2%. Screening will facilitate the provision of medical and public health services for infected patients and their families and provide public health data on the burden of disease in immigrant populations. The screening test should not be used to prohibit immigration.

Biopharmacology of syphilotherapy.

Data collected from experimental rabbit syphilis and from in vitro studies with nonpathogenic treponemes can be extended only with great caution to human syphilis. The following tentative conclusions may be drawn: penicillin acts on Treponema pallidum by interfering with cell wall synthesis. Concentrations of penicillin greater than 0.1 mug/ml do not have increased treponemicidal effect. Regimens producing penicillinemia for at least 8 days are considerably more efficient than treatment yielding high peak serum levels of brief duration. Treponemal residence in antibiotic-protected sites increases the need for long duration therapy. Other antibiotics are less effective than penicillin, and patterns of antibiotic interaction against treponemes do not match those seen with other bacteria.

Current therapy of vulvovaginitis.

Trichomoniasis is reliably treated with a single 2-g dose of metronidazole; however, with this regimen simultaneous treatment of sexual partners is particularly important. Trichomoniasis in pregnant women, who should not receive metronidazole, might be treated initially with clotrimazole vaginal suppositories, which appear to cure about 50% of cases. Topical antifungal agents of the imidazole class are superior to polyenes in treating vulvovaginal candidiasis. Boric acid powder applied intravaginally in gelatin capsules for 14 days appears as effective as imidazoles. Nonspecific vaginitis is now recognized as involving infection with anaerobic bacteria of the vaginal flora as well as Gardnerella vaginalis. The condition is most successfully treated with a seven-day course of metronidazole, which probably acts by eradicating the anaerobes. In addition, metabolites of metronidazole may act directly on G. vaginalis. Sulfanilamide-aminacrine-allantoin preparations are much less effective than specific therapies and have no role in the treatment of vulvovaginitis.

Canine prostatic secretions kill Trichomonas vaginalis.

The zinc content of prostatic secretions is thought to be an important nonspecific defense against urinary tract infection in men. This investigation measured killing by prostatic fluid of Trichomonas vaginalis, a common sexually transmitted pathogen, and related this activity to zinc concentration. We used a canine model which closely resembles the human male genital tract. Prostatic secretions from all dogs killed all T. vaginalis isolates. There appear to be several mechanisms for killing of trichomonads by prostatic fluid. At prostatic fluid zinc concentrations comparable to those in normal men (greater than or equal to 3.2 mM), the rate of killing of trichomonads was proportional to the zinc concentration. At intermediate zinc levels, killing occurred by both zinc-dependent and zinc-independent mechanisms. A zinc-independent mechanism was responsible for antitrichomonal activity at relatively low zinc levels (less than 1.6 mM), comparable to those in the prostatic fluid of men with chronic prostatitis. This study suggests that the variable clinical spectrum of trichomoniasis in men may result from a balance between the zinc sensitivity of the T. vaginalis strains on one side and the content of both zinc and zinc-independent factors in prostatic fluid on the other.

Zinc sensitivity of Trichomonas vaginalis: in vitro studies and clinical implications.

The high zinc concentration (2.3-15.3 mM) in human prostatic secretions may be an important defense of the male lower urinary tract against infection by Trichomonas vaginalis. Trichomonads were rapidly killed by zinc salts at concentrations similar to those in prostatic fluid of normal men. There was some variation in the zinc sensitivity of 15 clinical isolates of T. vaginalis (minimal inhibitory concentration, 0.8-6.4 mM). A time-kill technique showed subtle differences in the kinetics of zinc killing of trichomonad strains. It was possible to select relatively zinc-resistant substrains of T. vaginalis from a zinc-sensitive population. Zinc resistance was a stable characteristic after multiple passages of substrains in growth medium without supplemental zinc. Variations in the zinc sensitivity of infecting T. vaginalis strains or in the zinc content of host prostatic secretions may be significant determinants of the natural history of T. vaginalis infection in men.

Use of a time-kill technique for susceptibility testing of Trichomonas vaginalis.

The emergence of metronidazole-resistant Trichomonas vaginalis and questions about the safety of metronidazole are significant concerns in treatment of trichomoniasis. At 24 h, a microtiter assay was used to test antimicrobial susceptibility of 16 recent isolates; the MICs of metronidazole ranged from less than 0.06 to 25 micrograms/ml. Observable motility as an endpoint correlated imperfectly with survival as measured in pour plates. Quantitative pour plate cultures of six T. vaginalis isolates after timed exposures to antimicrobial drugs demonstrated exquisite sensitivity to metronidazole with minimal trichomonacidal concentrations of 0.025 to 0.100 micrograms/ml. Killing of some T. vaginalis isolates by clotrimazole and rosoxacin occurred only at concentrations of 100 micrograms/ml. Resistance to both rosoxacin and clotrimazole correlated with increasing resistance to metronidazole (P less than 0.01).

Contact-dependent cytopathogenic mechanisms of Trichomonas vaginalis.

The cytopathogenic mechanisms of Trichomonas vaginalis have been debated since the 1940s. We examined the following three proposed pathogenic mechanisms: contact-dependent extracellular killing, cytophagocytosis, and extracellular cytotoxins. Serial observations of Chinese hamster ovary (CHO) cell monolayers exposed to trichomonads revealed that (i) trichomonads form clumps, (ii) the clumps adhere to cells in culture, and (iii) monolayer destruction occurs only in areas of contact with T. vaginalis. Kinetic analysis of target cell killing by trichomonads revealed that the probability of CHO cell death was related to the probability of contact with T. vaginalis, supporting the observation by microscopy that trichomonads kill cells only by direct contact. Simultaneous studies of 111indium oxine label release from CHO cells and trypan blue dye exclusion demonstrated that T. vaginalis kills target cells without phagocytosis. Filtrates of trichomonad cultures or from media in which trichomonads were killing CHO cells had no effect on CHO cell monolayers, indicating that trichomonads do not kill cells by a cell-free or secreted cytotoxin. The microfilament inhibitor cytochalasin D (10 micrograms/ml) inhibited trichomonad killing of CHO cell monolayers by 80% (P less than 0.0001). In contrast, the microtubule inhibitor vinblastine (10(-6) M) caused only 17% inhibition of trichomonad destruction of CHO cell monolayers (P less than 0.020), whereas colchicine (10(-6) M) had no effect. T. vaginalis kills target cells by direct contact without phagocytosis. This event requires intact trichomonad microfilament function; microtubule function appears not to be essential.

Diagnostic methods for chlamydial infections in a high-risk population.

An enzymeimmunoassay test performed well in comparison with cell culture in detecting chlamydial infections among 209 women at a public health clinic, detecting 73% of the infected patients. Clinical and epidemiological criteria alone identified only 52%. The authors consider the test an essential supplement to other criteria when looking for chlamydial infection in a high risk population.

Pharmacodynamics of cefazolin in the presence of normal and impaired renal function.

The excretion of cefazolin, a new cephalosporin antibiotic, was studied in subjects with normal and impaired renal function. Twelve subjects with creatinine clearances ranging from 0 to 144 ml per min per 1.73 m(2) were given a single 500-mg intramuscular dose of cefazolin. Serum and urine levels were determined at intervals by agar diffusion. Peak serum levels in normals ranged from 44 to 70 mug/ml and occurred 30 to 60 min after injection. The mean serum half-life in normals was 1.6 h, and this was prolonged from 20 to 40% by simultaneous administration of probenecid. The total elimination constant varied linearly with the creatinine clearance in patients with renal impairment. The serum half-life in anephric patients was about 42 h. The fractional clearance of the drug varied directly with the serum level. Peak urine levels ranged from 60 to over 2,000 mug/ml, and more than 90% of the dose was recovered in the urine of normals during the first 24 h. The data suggest that cefazolin is cleared primarily by the glomerulus, with tubular and biliary secretion playing a secondary role.

A comparison of rosoxacin with ampicillin and probenecid in the treatment of uncomplicated gonorrhea.

Rosoxacin, a beta-lactamase-resistant, pyridyl quinolone derivative with in vitro activity against Neisseria gonorrhoeae, was compared to an oral regimen of ampicillin plus probenecid for the treatment of uncomplicated gonococcal infection. Fifty-seven patients were evaluated for the effectiveness of the two antibiotics. Thirty (97%) of 31 patients receiving rosoxacin were cured of their infection as were 25 (96%) of 26 patients who received the oral regimen of ampicillin plus probenecid. Both drug regimens were associated with a significant number of side effects. Of the ampicillin-treated group, 29% had diarrhea and/or abdominal cramping. Of the rosoxacin-treated patients, 52% had reactions classified as central nervous system effects; these included headaches, dizziness, euphoria, and drowsiness.

Beta-hemolytic activity of Trichomonas vaginalis correlates with virulence.

The reasons that some women develop symptomatic trichomonal vaginitis, whereas many other infected women remain asymptomatic, are unclear, but it has been suggested that Trichomonas vaginalis strains vary in their intrinsic virulence. We describe beta-hemolytic activity in T. vaginalis which correlates with virulence in patients as well as in an animal model and in tissue culture. Fresh T. vaginalis isolates from four women with severe, symptomatic trichomoniasis had high-level (86.3 +/- 6.6%) hemolytic activity, whereas isolates from three completely asymptomatic women had low-level (45.3 +/- 8.4%) hemolytic activity (P less than 0.001). Hemolytic activity also correlated with the production of subcutaneous abscesses in mice (r = 0.74) and with destruction of CHO cell monolayers (r = 0.94). All of the 20 clinical isolates of T. vaginalis tested possessed hemolytic activity. The beta-hemolysin may be a virulence factor for T. vaginalis.

Trichomonacidal activity of human polymorphonuclear neutrophils: killing by disruption and fragmentation.

Polymorphonuclear neutrophils (PMNs) were shown to kill Trichomonas vaginalis in vitro; 10(2)-10(3) trichomonads were incubated with 3 x 10(6) PMNs on tissue culture plates, and surviving organisms were enumerated in pour plates. After 60 min of aerobic incubation at 37 C, 100% (+/- 0) of the trichomonads had been killed, and nitroblue tetrazolium was reduced at the interface between the PMNs and trichomonads. The importance of oxidative microbicidal systems was confirmed by the observations that only 12% +/- 12% of trichomonads were killed under anaerobic conditions and that aerobic killing was eliminated by the addition of catalase or superoxide dismutase. PMNs killed trichomonads in fresh or absorbed serum but not in bovine serum albumin, in heat-inactivated serum, or in the presence of 1 mM trypan blue; this finding suggested a role for alternative pathway activation of complement. Phase-contrast cinemicrography and electron microscopy revealed the pursuit and surrounding of individual trichomonads by groups of PMNs that were able to fragment the large protozoa and to phagocytize the pieces.