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Biomedical subjects

J Sobel

Publications and source records attributed to J Sobel.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stability of cutaneous anergy in women with or at risk for HIV infection. HIV Epidemiology Research Study Group.

OBJECTIVE: To study the stability of cutaneous anergy in women with or at risk for HIV infection. DESIGN: Prospective multicenter cohort study METHODS: Interviews, CD4+ lymphocyte counts, and intradermal skin testing with mumps, Candida, and tetanus toxoid antigens were performed on two occasions at a median interval of 74 weeks in 436 HIV-seropositive and 252 seronegative at-risk women; only 10 (2%) HIV-seropositive women were taking highly active antiretroviral therapy at the time of delayed-type hypersensitivity (DTH) testing. Anergy was defined as induration <2 mm to all three antigens. RESULTS: Skin test reactivity at repeat testing was seen in 202 of 233 (87%) HIV-seronegative women who were not anergic at baseline, compared with 10 (53%) of 19 seronegative women who were anergic at baseline (relative risk [RR], 1.7; 95% confidence interval [CI], 1.07-2.5). Anergy at retesting was seen in 108 of 169 (64%) HIV-seropositive women who were previously anergic, compared with 77 of 267 (29%) who were not previously anergic (RR, 2.2; 95% CI, 1.8-2.8). Among initially anergic seropositive women, CD4+ lymphocyte counts were lower at both initial and follow-up testing in those who remained anergic than in those who reacted at follow-up (p < .001). The relative risks for anergy at retesting of initially anergic seropositive women, compared with initially reactive seropositive women, were related to CD4+ level; 2.5 (95% CI, 1.4-4.3) for CD4+ counts < 200 cells/mm3, 2.0 (95% CI, 1.5-1.7) for CD4+ counts 200-500 cells/mm3, and 1.6 (95% CI, 0.9-2.8) for CD4+ counts >500 cells/mm3. CONCLUSIONS: Although anergic HIV-seropositive women may become reactive, cutaneous anergy predicts a higher likelihood of anergy at retesting as well as lower CD4+ counts. Stability of anergy is greatest in HIV-seropositive women with low CD4+ counts.

CD4 Lymphocyte Count↗
PubMed1999

Surveying vendors of street-vended food: a new methodology applied in two Guatemalan cities.

Lack of reliable data about street vendors, who are difficult to survey, has hampered efforts to improve the safety of street-vended food. A two-phase method for sampling vendors, surveying first in areas of concentrated vending activity identified by local authorities and second in randomly selected areas, was developed and implemented in two Guatemalan cities where street-vended food had been implicated in cholera transmission. In a 4-day survey in Escuintla, 59 vendors (42 from phase 1, 17 from phase 2) were interviewed. They demonstrated good knowledge of food safety and cholera but unsafe practices, implying that more effective, practical training was needed. In a 6-day survey in Guatemala City, 78 vendors (77 from phase 1, 1 from phase 2) were interviewed. Sixty-eight (87 %) vendors stored water, usually in wide-mouthed vessels prone to contamination; this led to a field test of a new system for safe water storage. Useful information for public health planning and intervention can be gathered rapidly with this new method for surveying street vendors.

Adolescent↗
PubMed1998

Management of elevated intracranial pressure in patients with Cryptococcal meningitis.

BACKGROUND: The most important predictor of early mortality in patients with HIV-associated cryptococcal meningitis is mental status at presentation; patients who present with altered mental status have up to 25% mortality. Historically, cerebrospinal fluid (CSF) diversion in HIV-negative patients with cryptococcal meningitis and signs of elevated intracranial pressure (ICP) has improved survival. In an effort to affect survival and morbidity rates in patients with HIV-associated cryptococcal meningitis, we have initiated aggressive management of elevated ICP in patients with focal neurologic deficits, mental obtundation, or both. METHODS: We identified 10 patients with HIV-associated cryptococcal meningitis who presented with symptoms consistent with elevated ICP, including headache, mental obtundation, papilledema, and cranial nerve palsies. Elevated opening pressure was defined as > 20 cm CSF during lumbar puncture. In patients with elevated opening pressures who had focal neurologic deficits or mental status changes refractory to serial lumbar puncture, management consisted of immediate placement of lumbar drains for continuous drainage of CSF to maintain normal ICP (10 cm CSF). Patients with persistent elevations of spinal neuraxis pressure following lumbar drainage underwent placement of lumbar peritoneal shunts. RESULTS: All patients returned to their baseline level of consciousness following normalization of ICP. Two patients were weaned from lumbar drainage. Eight patients eventually required placement of lumbar peritoneal shunts for persistently elevated ICP despite successful antifungal therapy. Follow-up ranged from 1 to 15 months. One shunt infection occurred, one lumbar peritoneal shunt was converted to a ventriculoperitoneal shunt, and one shunt was removed. CONCLUSIONS: Elevated ICP in patients with HIV-associated cryptococcal meningitis is a significant source of morbidity and mortality. The use of lumbar drainage and selective placement of lumbar peritoneal shunts in the management of elevated ICP in patients with HIV-associated cryptococcal meningitis can ameliorate the sequelae of elevated ICP.

Adult↗
PubMed1998

A prolonged outbreak of Shigella sonnei infections in traditionally observant Jewish communities in North America caused by a molecularly distinct bacterial subtype.

During 1994-1996, Shigella sonnei outbreaks occurred in 8 North American traditionally observant Jewish communities. These communities remain relatively separate from neighboring populations while maintaining close contact by travel with coreligionists in other cities. Epidemiologic investigations suggested community-to-community transmission via travel. Outbreak-related and control isolates of S. sonnei from each city were subtyped by pulsed-field gel electrophoresis (PFGE) to confirm an epidemiologic linkage between outbreaks. Forty-three (94%) of 46 outbreak-related isolates had closely related PFGE patterns, constituting a single subtype; 33 (94%) of 35 control isolates demonstrated unrelated PFGE patterns. Several patterns differing by < or = 3 bands were identified within the outbreak subtype; one of these accounted for 65% of outbreak isolates. Hence, a single subtype of S. sonnei caused an international outbreak involving 8 traditionally observant Jewish communities, but not neighboring populations, over a 2-year period, suggesting sustained propagation of the epidemic strain between communities.

DNA, Bacterial↗
PubMed1998

Reduction of fecal contamination of street-vended beverages in Guatemala by a simple system for water purification and storage, handwashing, and beverage storage.

Street-vended foods and beverages, an integral part of urban economies in the developing world, have been implicated in cholera transmission in Latin America. To improve the microbiologic quality of market-vended beverages in Guatemala, we tested a simple system consisting of dilute bleach (4.95% free available chlorine) for water purification, narrow-mouth plastic vessels with spigots for disinfecting and storing water and for preparing and storing beverages, handwashing soap, and education in using the system. We conducted a randomized controlled intervention trial among 41 vendors who received the intervention and 42 control vendors, comparing total and fecal coliform bacteria and Escherichia coli contamination of market-vended beverages, stored water, and vendors' hands. Samples were obtained at baseline and at each of six weekly follow-up visits. At baseline, fecal coliform bacteria were found in 40 (48%) market-vended beverages and E. coli in 14 (17%). When compared with samples from control vendors, a significant decrease in total coliform (P < 0.001) and fecal coliform (P < 0.001) bacteria in samples of stored water and beverages sold by intervention vendors was observed over the course of the study. The vessel system was well accepted by vendors. This simple inexpensive system consisting of hypochlorite disinfectant, plastic vessels, soap, and education can significantly reduce fecal contamination of market-vended beverages.

Adolescent↗
PubMed1997

Monocytes and tissue factor promote thrombosis in a murine model of oxygen deprivation.

Clinical conditions associated with local or systemic hypoxemia can lead to prothrombotic diatheses. This study was undertaken to establish a model of whole-animal hypoxia wherein oxygen deprivation by itself would be sufficient to trigger tissue thrombosis. Furthermore, this model was used to test the hypothesis that hypoxia-induced mononuclear phagocyte (MP) recruitment and tissue factor (TF) expression may trigger the local deposition of fibrin which occurs in response to oxygen deprivation. Using an environmental chamber in which inhaled oxygen tension was lowered to 6%, hypoxic induction of thrombosis was demonstrated in murine pulmonary vasculature by 8 h based upon: (a) immunohistologic evidence of fibrin formation in hypoxic lung tissue using an antifibrin antibody, confirmed by 22.5-nm strand periodicity by electron microscopy; (b) immunoblots revealing fibrin gamma-gamma chain dimers in lungs from hypoxic but not normoxic mice or hypoxic mice treated with hirudin; (c) accelerated deposition of 125I-fibrin/fibrinogen and 111In-labeled platelets in the lung tissue of hypoxic compared with normoxic animals; (d) reduction of tissue 125I-fibrin/fibrinogen accumulation in animals which had either been treated with hirudin or depleted of platelets before hypoxic exposure. Because immunohistochemical analysis of hypoxic pulmonary tissue revealed strong MP staining for TF, confirmed by increased TF RNA in hypoxic lungs, and because 111In-labeled murine MPs accumulated in hypoxic pulmonary tissue, we evaluated whether recruited MPs might be responsible for initiation of hypoxia-induced thrombosis. This hypothesis was supported by several lines of evidence: (a) MP depletion before hypoxia reduced thrombosis, as measured by reduced 125I-fibrin/fibrinogen deposition and reduced accumulation of cross-linked fibrin by immunoblot; (b) isolated murine MPs demonstrated increased TF immunostaining when exposed to hypoxia; and (c) administration of an anti-rabbit TF antibody that cross-reacts with murine TF decreased 125I-fibrin/fibrinogen accumulation and cross-linked fibrin accumulation in response to hypoxia in vivo. In summary, these studies using a novel in vivo model suggest that MP accumulation and TF expression may promote hypoxia-induced thrombosis.

Animals↗
PubMed1997

An outbreak of gastroenteritis and fever due to Listeria monocytogenes in milk.

BACKGROUND: After an outbreak of gastroenteritis and fever among persons who attended a picnic in Illinois, chocolate milk served at the picnic was found to be contaminated with Listeria monocytogenes. METHODS: In investigating this outbreak, we interviewed the people who attended the picnic about what they ate and their symptoms. Surveillance for invasive listeriosis was initiated in the states that receive milk from the implicated dairy. Stool and milk samples were cultured for L. monocytogenes. Serum samples were tested for IgG antibody to listeriolysin O. RESULTS: Forty-five persons had symptoms that met the case definition for illness due to L. monocytogenes, and cultures of stool from 11 persons yielded the organism. Illness in the week after the picnic was associated with the consumption of chocolate milk. The most common symptoms were diarrhea (present in 79 percent of the cases) and fever (72 percent). Four persons were hospitalized. The median incubation period for infection was 20 hours (range, 9 to 32), and persons who became ill had elevated levels of antibody to listeriolysin O. Isolates from stool specimens from patients who became ill after the picnic, from sterile sites in three additional patients identified by surveillance, from the implicated chocolate milk, and from a tank drain at the dairy were all serotype 1/2b and were indistinguishable on multilocus enzyme electrophoresis, ribotyping, and DNA macrorestriction analysis. CONCLUSIONS: L. monocytogenes is a cause of gastroenteritis with fever, and sporadic cases of invasive listeriosis may be due to unrecognized outbreaks caused by contaminated food.

Animals↗
PubMed1997

Decreasing disability in chronic back pain through aggressive spine rehabilitation.

This paper discusses specific techniques for rehabilitation of chronic low back pain through aggressive physical therapy with behavioral support. The rationale for approaching the outcome dimensions of impairments in back function and pain-related disability as opposed to chronic pain symptoms is explained. This approach requires that impairments in back function are systematically identified through the quantification of trunk flexibility, straight leg raising, back extensor strength, lifting ability, and endurance. The described treatment approach focuses on eliminating those impairments through aggressive, quota-based exercise and is usually completed within 8 weeks. It requires only a modest amount of space and equipment. Useful behavioral techniques for extinguishing pain behaviors, lessening pain beliefs, and for promoting wellness are described. Results from a treatment program using these techniques demonstrate normal back function and reduced disability for a majority of treated persons. Applying such a program to the VA population is an important challenge.

Back Pain↗
PubMed1993

IL-6 down-modulates the cytokine-enhanced antileishmanial activity in human macrophages.

IL-6 is a cytokine synthesized by T cells and macrophages (M phi). It has pleiotropic effects on diverse cell types and is recognized for its "pro-inflammatory" properties. In mice, IL-4, IL-5, IL-6, and IL-10 are produced by Th-2 cells. Because IL-10 suppresses Th-1 clones, and IL-4 broadly deactivates M phi, experiments were carried out to investigate the in vitro effects of recombinant human IL-6 on cytokine activation of human M phi. Pretreatment with IL-6 induced a dose- and time-dependent suppression of IFN-gamma (1000 U/mL) and TNF-alpha (25 ng/mL) activation of M phi for the killing of L. amazonensis. At doses greater than 0.1 to 100 ng/mL, IL-6 inhibited IFN-gamma and TNF-alpha activation by 21 to 93% and 36 to 82%, respectively. IL-6 alone had no effect on M phi viability and intracellular L. amazonensis growth. Blockade of M phi activation was greatest when IL-6 was added 24 or 48 h before infection and treatment with IFN-gamma or TNF-alpha. Furthermore, mAb against IL-6 abrogated the inhibitory activity of IL-6. Similarly IL-6 pretreatment suppressed M phi activation for antileishmanial capacity by IL-3, granulocyte-monocyte-CSF (GM-CSF) and IL-1 beta. Because cytokine induction of antileishmanial activity is associated with enhancement of oxidative capacity, the effect of IL-6 on this mechanism was evaluated. Pretreatment with IL-6 down-modulated TNF-alpha (25 ng/mL) enhancement of M phi oxidative capacity in a dose- and time-dependent manner. A similar depression of oxidative capacity was observed for GM-CSF and IL-3 but not for IFN-gamma. Furthermore, NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor) had no effect on IFN-gamma and TNF-alpha activation of antileishmanial activity and nitrites/nitrates were not reliably assayed from M phi culture supernatants. These findings suggest that IL-6 down-modulates cytokine activation of M phi antileishmanial capacity by inhibiting oxygen-dependent and undefined oxygen-independent mechanisms.

Animals↗
PubMed1992

Azole therapy for trichosporonosis: clinical evaluation of eight patients, experimental therapy for murine infection, and review.

We studied the in vivo antifungal activity of azoles in humans and in a murine model of disseminated trichosporonosis. Eight patients infected with Trichosporon species were treated with fluconazole, SCH 39304, or miconazole for 2-26 weeks. Four patients had fungemia, two patients had disseminated trichosporonosis, and one patient each had soft-tissue infection and cystitis. Response of trichosporonosis to azoles was seen in all eight patients, although one patient died with disseminated aspergillosis while still receiving SCH 39304. A literature review indicated that responses to ketoconazole or miconazole were noted in four patients with trichosporonosis. In the experimental infection, amphotericin B, SCH 39304, and fluconazole were effective in prolonging survival and reducing fungal counts in the kidneys of mice infected with a clinical strain of Trichosporon beigelii. Fluconazole but not amphotericin B prolonged survival of mice infected with a clinical strain of Trichosporon capitatum. We conclude that azoles represent effective therapy for infection with Trichosporon species.

Adult↗
PubMed1992

Diminished in vitro production of interleukin-1 and tumor necrosis factor-alpha during acute visceral leishmaniasis and recovery after therapy.

Disturbance of T cell-mediated immunity has been reported in acute visceral leishmaniasis (AVL). In a study of 16 patients with AVL, defective production of interleukin-1 (IL-1) by peripheral blood mononuclear cells was demonstrated in response to leishmania antigens, heat-killed Listeria organisms, and lipopolysaccharide when compared to posttherapy values or controls. This global defect in IL-1 production was corrected after successful therapy. Twelve of 16 patients responded with a greater than or equal to 2.5-fold increase in IL-1 production that correlated with clinical cure, P less than .01. Depressed production of tumor necrosis factor (TNF) was leishmania antigen-specific and similarly recovered after therapy. In vitro TNF production during the follow-up period did not correlate with clinical status but high serum levels were associated with AVL. Since T cells are activated by processed antigens presented on class II major histocompatibility molecules and by newly synthesized IL-1, defective IL-1 production may contribute to the immunosuppression observed in AVL.

Acute Disease↗
PubMed1992

Interleukin-3 induces antimicrobial activity against Leishmania amazonensis and Trypanosoma cruzi and tumoricidal activity in human peripheral blood-derived macrophages.

The ability of interleukin-3 (IL-3) to induce antimicrobial and tumoricidal activity was evaluated. Macrophages infected with two intracellular protozoa, Leishmania amazonensis or Trypanosoma cruzi, were treated with cytokines. IL-3 induced a dose-dependent enhancement of microbistasis against leishmanias, and the activity of IL-3 (100 ng/ml) was comparable to that of gamma interferon (IFN-gamma) (1,000 U/ml). In addition, IL-3 in combination with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage CSF (M-CSF) or with IFN-gamma reduced infection and lowered the required dose. IL-3 similarly activated macrophages to inhibit intracellular replication of T. cruzi. Furthermore, IL-3 induced antibody-independent tumoricidal activity against melanoma cells that was dose dependent and comparable to that of lipopolysaccharide and GM-CSF. The mechanisms by which IL-3 induced antimicrobial activity may involve at least the augmentation of oxidative capacity. IL-3, at concentrations of 0.5 ng/ml or greater, led to a significantly increased oxidative burst which paralleled the inhibition of protozoan replication. The enhancement of oxidative capacity by IL-3 (5 ng/ml or higher) was comparable to that of IFN-gamma. The induction of tumoricidal activity was associated with the production of tumor necrosis factor alpha (TNF-alpha), which in this system may feed back to enhance the macrophage inhibition of leishmanias, as demonstrated by neutralization of IL-3 activation by anti-TNF-alpha antibody. Thus, peripheral blood macrophages remain responsive to IL-3, as demonstrated by enhanced antimicrobial and tumoricidal activity. IL-3 may have potential clinical applications because of these properties and its effect on myelopoiesis.

Animals↗
PubMed1990

Urinary excretion of Tamm-Horsfall protein in women with recurrent urinary tract infections.

Since MS-fimbriated bacteria adhere to Tamm-Horsfall protein, it has been suggested that Tamm-Horsfall protein may trap urinary pathogens and prevent them from colonizing the mucosal surfaces of the urinary tract. To test the hypothesis that low urinary Tamm-Horsfall protein excretion rates predispose to urinary tract infection we obtained serial urine samples from 17 women with and 18 without a history of recurrent urinary tract infection. None of the women had known structural abnormalities of the urinary tract. Concentrations of Tamm-Horsfall protein in urine were measured with a sensitive enzyme-linked immunosorbent assay method. On the average, 3 urine samples per person collected within 3 to 6 months were analyzed. The mean Tamm-Horsfall protein excretion of women with recurrent urinary tract infection was 57.0 mg./l. and that of controls was 66.3 mg./l.; this difference was not statistically significant. The mean coefficient of variation was 44.2 and 62.1%, respectively. We conclude that urinary Tamm-Horsfall protein concentration is not significantly decreased in women with recurrent urinary tract infection compared with controls, and that excretion varies widely in repeat samples obtained from the same individual.

Adult↗