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Biomedical subjects

J D Sobel

Publications and source records attributed to J D Sobel.

At least 19 recordsLinked to original sources

A case of disseminated Mycobacterium marinum infection in an immunocompetent patient.

An unusual case of Mycobacterium marinum cutaneous infection is described. As a result of marked delay in the diagnosis, extensive local inflammation and destructive osteomyelitis occurred together with cutaneous dissemination in an immunocompetent host. Pathologic fractures in the infected bone necessitated amputation of the involved digit. The most striking feature of this case was the development of multiple widespread cutaneous lesions for several months following amputation of the infected digit and initiation of appropriate antimicrobial therapy. These new cutaneous lesions may reflect local immune and inflammatory reactions to previously disseminated microorganisms.

Amputation, Surgical

Human herpesvirus type 6: review.

Human herpesvirus type 6 (HHV-6), a newly recognized human herpesvirus first described in 1986, is morphologically similar to other herpesviruses but is distinguishable from all of them by some unique in vitro biological effects, specific antigenic analysis, and patterns of endonuclease restriction digests of DNA. In vitro HHV-6 exhibits tropism mainly for T lymphocytes, but it also infects other cells, including B lymphocytes, monocytes-macrophages, glial cells, and fibroblasts. Because HHV-6 causes frequent infection in infants and children, a seroprevalence rate of antibody to this virus of up to 80% has been reported in the United States. Infection in infancy develops as levels of maternal antibody wane, thus resulting in either subclinical infection or an acute febrile illness termed exanthema subitum. Primary infection acquired later in life causes a disease resembling acute infectious mononucleosis. Since HHV-6 shares the capacity to establish latent infection with other herpesviruses, frequent viral reactivation is probably the explanation for the high incidence of serologically proven active HHV-6 infection found simultaneously with active infection due to other herpesviruses as well as in the presence of various immune deficiency conditions.

Herpesviridae Infections

Pathogenesis and treatment of recurrent vulvovaginal candidiasis.

In contrast to women who experience infrequent episodes of candidal vaginitis, patients with chronic and recurrent candidal vaginitis rarely have recognizable precipitating or causal factors. Analysis of vaginal yeast isolated from women with recurrent candidal vaginitis uncommonly reveals a higher percentage of non-albicans Candida species. There is no indication that resistance to azoles is a causal factor, and no other fungal virulence factors have been identified to explain the repeated attacks. Strain typing of sequential clinical isolates by means of molecular techniques indicate a pattern of relapse due to persistent yeast in the vagina rather than frequent vaginal reinfection. Attempts to reduce the number of attacks by treating sexual partners and suppressing a gastrointestinal tract focus have failed. Recent immunological studies suggest the possibility that an acquired Candida antigen-specific immunological deficiency results in uncontrolled vaginal Candida proliferation and hence repeated clinically evident attacks. Although no definitive cure for recurrent candidal vaginitis exists, numerous therapeutic maintenance regimens with azoles are available that effectively control symptomatic infection.

Antifungal Agents

Epidemiology of nosocomial acquisition of Candida lusitaniae.

Candida species are important nosocomial pathogens; however, little is known about the epidemiology of Candida lusitaniae, an organism frequently resistant to amphotericin B. We evaluated 98 patients admitted to the bone marrow transplant and medical intensive care units of a tertiary-care hospital. Each patient with C. lusitaniae was matched with control patients. Restriction fragment analysis of DNA was used to determine strain relatedness. Seven patients (7.1%) with C. lusitaniae were identified; five acquired C. lusitaniae after admission to the study unit. All isolates were susceptible to amphotericin B. There were no differences between patients and controls with regard to duration of stay in the study unit, antibiotic administration, antifungal therapy, immunosuppressive therapy, catheter use, or underlying disease. Temporal and geographic clustering of five patients with identical strains occurred. No common source was identified. Restriction fragment analysis revealed a total of eight strains, and five patients shared one strain type. These results demonstrate exogenous acquisition of C. lusitaniae. The mechanism of acquisition is probably indirect contact transmission between patients.

Adult

Clinical, microbiological, and biochemical factors in recurrent bacterial vaginosis.

Because so little is known about the pathogenesis of recurrent bacterial vaginosis (BV), a longitudinal microbiological study was conducted on 13 women with recurrent BV treated sequentially with conventional metronidazole therapy. A rapid clinical response characterized by disappearance of mal odor and an improvement in vaginal discharge occurred in 92% of 31 clinical episodes of BV, with patients no longer satisfying the composite clinical criteria for the diagnosis of BV. However, prospective evaluation of these asymptomatic women revealed profound residual biochemical and microbial abnormalities which were best evident on Gram stain and wet mount examination of vaginal secretions. Other common residual abnormalities included mild persistent elevation of vaginal pH and polyamine and fatty acid levels and the presence of clue cells in small numbers. Residual abnormalities could be quantified to create an overall symptom code which predicted recurrence, and it was found that the severity of residual abnormalities was inversely related to the time required until the next recurrence occurred. The severity and prevalence of residual abnormalities following clinically successful therapy support the concept that BV recurrence, especially when it is early, represents a relapse rather than a reinfection. This concept may have important therapeutic implications.

Adult

Quantitation of urinary Tamm-Horsfall protein in children with urinary tract infection.

It has been suggested that urinary Tamm-Horsfall protein (THP) prevents colonization of the urinary tract by binding uropathogens. We tested the hypothesis that low urinary THP levels may predispose to urinary tract infection (UTI) by measuring THP levels in children. We studied a cohort of 35 girls with uncomplicated recurrent UTI (group 1) that was compared with 27 patients with myelomeningoceles undergoing clean intermittent catheterization (group 2) and 16 female controls (group 3). We measured urinary THP in both aggregated (aTHP) and disaggregated form (dTHP), leukocyte esterase activity, urine chemistries and culture. No significant differences in dTHP or aTHP levels were seen between groups 1 and 3, but group-1 patients had higher dTHP levels than group-2 patients (p < 0.008). History of reflux or the presence of bacteriuria or pyuria at the time of urine collection did not affect dTHP levels; in contrast, pyuria or bacteriuria at the time of sampling was associated with markedly lower aTHP levels when compared with sterile samples (p < 0.0001). For all groups, measured quantities of dTHP did not correlate with aTHP levels. We conclude that excretion of dTHP in children with history of recurrent UTI is not reduced. In contrast, concentrations of aTHP are profoundly depressed in children during times of UTI, suggesting a role for THP in the pathogenesis of UTI. Assaying THP in its aggregated form may prove valuable when studying its physiologic function and merits further investigation.

Bacteriuria

Bacterial vaginosis: treatment with clindamycin cream versus oral metronidazole.

In a randomized, double-blind study, 48 women with symptomatic bacterial vaginosis were assigned to receive either 5 g of 2% clindamycin vaginal cream daily or 500 mg metronidazole oral tablets twice a day for 7 days. After completion of therapy, there was no significant difference in cure rates (clindamycin 72% versus metronidazole 87%). One month later, 61% of the patients in each group were still cured. Adverse reactions were mild in both groups. We conclude that clindamycin cream is a safe, well tolerated, and effective alternative to oral metronidazole for treatment of bacterial vaginosis.

Administration, Oral

Vulvovaginitis.

Often trivialized by the medical profession, vaginitis in adult women is not only extremely common but the source of considerable stress, and it often results in marked suffering. Epidemiologic studies described in this article indicate the high prevalence of vaginitis and the large number of causes. Although the majority of infections in women are due to BV, VVC, and trichomoniasis, it is clear that many other causes exist, and we have yet to discover the cause of many clinical syndromes. Considerable progress in understanding the pathogenesis of the three common vaginitides has been made. Although excellent progress has been made by the pharmaceutical industry in providing new drugs for vaginitis, any further progress will require a better understanding of cause and pathogenesis. Vaginitis causes major symptoms and is more than a nuisance problem. Clinicians owe it to their patients to make efforts to make an accurate diagnosis and not to rely on empiric therapy.

Adult

Detection of circulating candida enolase by immunoassay in patients with cancer and invasive candidiasis.

BACKGROUND: Invasive candidiasis is a major nosocomial infection that is difficult to diagnose. Few biochemically defined markers of invasive candidiasis are known. Initial findings suggested that the presence of candida enolase in the blood may be a novel marker for invasive candidiasis. METHODS: We tested 170 patients at high risk for invasive candidiasis for candida enolase antigenemia. All the patients had cancer and neutropenia. We detected antigen using a double-sandwich liposomal immunoassay for candida enolase in serially collected serum samples. Invasive candidiasis was proved by finding candida species in deep nonmucosal tissue, blood cultures, or both. Antigen testing was performed with the investigator blinded to tissue or culture diagnosis. RESULTS: Among 24 patients with proved invasive candidiasis, 149 serum samples were tested for enolase antigenemia; 80 were positive and 69 negative (sensitivity per sample, 54 percent). Multiple sampling improved the detection of antigenemia, which was found in 11 of 13 proved cases of deep tissue infection (85 percent) and in 7 of 11 proved cases of fungemia (64 percent). Specificity was 96 percent as measured against control groups including patients with mucosal colonization, bacteremia, and other deep mycoses. Antigenemia was detected in the absence of fungemia in 5 cases of deep tissue candidiasis, but was not detected in 6 cases of fungemia alone. CONCLUSIONS: Candida enolase antigenemia is a novel marker for invasive candidiasis. It may be a useful indicator of deep infection in patients with cancer and neutropenia and may complement the diagnostic usefulness of blood cultures.

Antigens, Fungal

Urinary excretion of Tamm-Horsfall protein in elderly women.

The incidence of urinary tract infection is higher in the geriatric population than in younger adults despite the exclusion of patients with known risk factors. Tamm-Horsfall protein, a renal glycoprotein excreted in urine, may constitute a natural defense mechanism against ascending urinary tract infection by binding mannose-sensitive fimbriated microorganisms. We hypothesized that the quantity of Tamm-Horsfall protein excreted is decreased in the elderly. Native aggregated Tamm-Horsfall protein was measured in urine samples from 24 young women (group 1, mean age 33 years) and 47 female nursing home patients (group 2, mean age 84 years) using enzyme-linked immunosorbent assay techniques. Another 16 elderly women (group 3, mean age 85 years) had active urinary tract infection. The aggregated Tamm-Horsfall protein was then disaggregated by dilution and quantified. Significant differences in mean urinary disaggregated Tamm-Horsfall protein concentrations were found between groups 1 (64.22 mg./l.) and 2 (35.07 mg./l.), and between groups 1 and 3 (34.71 mg./l.), respectively. In contrast, mean aggregated Tamm-Horsfall protein levels were significantly higher in group 2 (1.56 mg./l.) than in group 1 (0.92 mg./l.) or group 3 (0.97 mg./l.). Our studies show that urinary disaggregated Tamm-Horsfall protein concentration is decreased in the elderly, and that aggregated Tamm-Horsfall protein is increased compared to younger adults. The aggregated Tamm-Horsfall protein concentration is decreased in the elderly during episodes of urinary tract infection.

Adolescent

Bacterial etiologic agents in the pathogenesis of urinary tract infection.

Most of the information available concerning virulence factors of uropathogens is based on studies of Escherichia coli, the commonest cause of urinary tract infections. Earlier studies revealed several phenotypic Escherichia coli virulence factors that influenced both the anatomic level and severity of urinary tract infection. Virulence factors included O antigen serotype, presence and quantity of K capsular polysaccharide, adherence to uroepithelial cells, resistance to serum bactericidal activity, hemolysin, and aerobactin production. The introduction of DNA hybridization methodology has provided a valuable tool for reevaluation of the epidemiology of Escherichia coli infection as well as an alternative to the conventional phenotypic approach for studying the genotypic basis for virulence.

Animals

Effect of Tamm-Horsfall protein on chemoluminescence response of polymorphonuclear leukocytes to uropathogenic Escherichia coli.

Mannose residues on the outer membranes of polymorphonuclear leukocytes (PMNL) are capable of binding mannose-sensitive Escherichia coli. Tamm-Horsfall protein, a major urinary glycoprotein, has also been shown to bind mannose-sensitive E. coli via mannose-containing side chains. The effect of Tamm-Horsfall protein on the interaction between PMNL and mannose-sensitive E. coli was studied by measuring luminol-dependent chemoluminescence after bacterial stimulation. In the presence of 0.475, 4.75, 47.5, and 475 mg/l Tamm-Horsfall protein, chemoluminescence responses were reduced in a dose-dependent fashion by 8.7%, 38.1%, 60.3%, and 96.1%, respectively. Addition of 0.003 units/ml alpha-mannosidase reversed the effect of increasing concentrations significantly. Thus, urinary Tamm-Horsfall protein seems to compete with PMNL for mannose-sensitive E. coli in a mannose-sensitive fashion, thereby significantly reducing the role of PMNL as a defense mechanism in the urine of patients with urinary tract infection.

Escherichia coli

Comparison of restriction enzyme analysis and pulsed-field gradient gel electrophoresis as typing systems for Candida albicans.

Candida species are an important cause of infection in immunocompromised hosts and the leading cause of nosocomial fungal infections. Study of the epidemiology of Candida infection has been difficult because of lack of a reliable typing system. We describe a typing system utilizing contour-clamped homogeneous electric fields (CHEF), which is a modified version of pulsed-field gradient gel electrophoresis, and compared it with restriction enzyme analysis (REA) of genomic DNA. The study was done with 35 Candida albicans clinical isolates from separate patients. CHEF and REA were performed on each isolate, and the patterns were compared. The REA procedure revealed 17 strain types while the CHEF procedure was able to distinguish 23 strain types of C. albicans. The CHEF technique yields unique patterns of chromosomal bands that can be used to distinguish clinical isolates and demonstrates greater sensitivity than REA.

Candida albicans

Individualizing treatment of vaginal candidiasis.

Clinicians have a vast array of effective antimycotics for the treatment of vaginal candidiasis. Multiple topical formulations are available, yet there is little evidence to suggest that formulation per se influences outcome. A growing number of highly effective oral systemic antimycotic agents provide the practitioner with additional options. Treatment regimens have also changed with the introduction of shorter, often single-day/single-dose courses of therapy. Not all therapeutic agents have the same activity against vaginal fungal pathogens in that topical azoles tend to be more active than nystatin. Differences in patient characteristics, however, are more important than the differences between antimycotic agents and therapeutic regimens in determining selection of the appropriate antimycotic. Patients with vaginal candidiasis vary with regard to duration and severity of symptoms and past frequency of attacks, distribution of inflammation, and pregnancy status. The clinician should consider all these variables both in selecting the appropriate antimycotic agent and the route of administration and in planning the duration of therapy. Individualized therapy offers additional benefits to patients, who may then enjoy the maximum advantages of antimycotics now available.

Administration, Intravaginal

Vaginal infections in adult women.

Often trivialized by the medical profession, vaginitis in adult women is not only extremely common but is the source of considerable distress and often results in marked suffering. Epidemiologic studies described in this article indicate the high prevalence of vaginitis and the large number of causes. Although the majority of infections in women are due to bacterial vaginosis, VVC, and trichomoniasis, it is clear that many other causes exist, and we have yet to discover the etiology of many clinical syndromes. Considerable progress has been made in understanding the pathogenesis of the three common vaginitides. Although excellent progress has been made by the pharmaceutical industry in providing new drugs for vaginitis, any further progress will require a better understanding of etiology and pathogenesis. Vaginitis causes major symptoms and is more than a nuisance problem. Clinicians owe it to their patients to attempt to make an accurate diagnosis and not to rely on empiric therapy.

Atrophy

A new slide latex agglutination test for the diagnosis of acute Candida vaginitis.

Two hundred two slide latex agglutination (SLA) tests were performed on 137 women attending a vaginitis clinic to evaluate the efficacy of this new test in diagnosing acute symptomatic Candida vaginitis. In 77 patients with acute Candida vaginitis, the SLA test revealed a positive reaction in 56 patients, reflecting a sensitivity of 72.7%, lower than that observed with the 10% potassium hydroxide microscopic examination (sensitivity 90%). False negative SLA reactions could not be accounted for by lower numbers of yeast cultured from the vagina or by the presence of nonalbicans strains of Candida. Following successful antimycotic therapy, the SLA test promptly became negative in all mycologically negative patients. Application of the SLA test in asymptomatic healthy control women revealed extremely few false positive reactions for Candida (5.6%). This easily performed and rapid slide latex agglutination test should provide a useful adjunct to the diagnosis of Candida vaginitis, but only for physicians who do not routinely perform microscopy on vaginal secretions.

Antigens, Fungal

Quantitation of Tamm-Horsfall protein binding to uropathogenic Escherichia coli and lectins.

In quantitative experiments using ELISA, binding of Tamm-Horsfall protein (THP) to uropathogenic Escherichia coli was studied with monoclonal antibody to THP. Adherence to E. coli bearing type 1 fimbriae was proportional to THP concentration and size of the bacterial inoculum. Type 1 fimbriae-bearing E. coli bound 50 times more THP than did non-type 1-fimbriated or P-fimbriated strains. Concanavalin A and wheat germ agglutinin bound THP in a dose-dependent fashion, whereas pokeweed mitogen and Vicia villosa B4 isolectin did not. Addition of mannose and N-acetylglucosamine reduced adherence of THP to concanavalin A and wheat germ agglutinin by 50%-80%. Sugar inhibition studies suggested that the fimbrial receptor site for THP has lectin-like properties and that THP binds to fimbriae via its mannose side chains. This quantitative assay is useful for studying the interaction between THP, uroepithelial cells, and bacteria in vitro.

Agglutination Tests