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M Goldman

Publications and source records attributed to M Goldman.

At least 91 records · Page 5Linked to original sources
PubMed2000

IFN-gamma, IL-4, IL-10 and IL-12 gene expression in BCG-Leishmania vaccination of Trypanosoma cruzi-infected mice.

We have previously shown that vaccination of BALB/c mice with a combination of BCG plus killed Leishmania promastigotes, applied by the i.p. route 10 and 3 days before Trypanosoma cruzi inoculation, prolonged their survival and decreased their parasitaemia. In the present study we show that the BCG-Leishmania vaccine induced higher levels of circulating IFN-gamma in acute and chronic infection of mice [on day 25 and 40 post-infection (p.i.) respectively], in comparison to unvaccinated animals (PBS-treated). Though the IFN-gamma mRNA content of spleen cells of vaccinated and infected mice (on day 25 p.i.) was similar to that of unvaccinated animals, the BCG-Leishmania vaccine enhanced significantly the production of IFN-gamma by spleen cells stimulated with T. cruzi antigens. This effect was observed to a lower extent in BCG- and Leishmania-treated mice. The BCG-Leishmania vaccine reduced the expression of the IL-10 mRNA of splenocytes as soon as day 12 p.i., before the peak parasitaemia. Such this effect was not observed in BCG- or Leishmania-treated animals. On day 25 p.i., the BCG plus Leishmania- or BCG-treatment of mice abolished the capacity of spleen cells to produce IL-10 in response to T. cruzi antigens. The levels of mIL-4 RNA and protein production were not modified in any group of mice. T. cruzi infection in BCG-Leishmania-vaccined mice stimulated an early and high production of IL-12 transcripts in spleen cells during the acute phase of the infection, that was prolonged during the chronic phase of infection. This effect was weaker or absent in BCG- and Leishmania-treated animals, respectively. These results indicate that the BCG-Leishmania vaccine stimulates the production of IL-12 and IFN-gamma, but inhibits that of IL-10 and is without effect on IL-4 when mice are infected with T. cruzi. This highlights the key role of endogenously produced IFN-gamma, IL-10 and IL-12 in the control of T. cruzi acute and chronic infection in mice and the favorable modulation of their balance by a vaccination combining BCG and Leishmania.

Animals↗
PubMed2000

Plaque morphology correlates with cerebrovascular symptoms in patients with complex aortic arch plaque.

BACKGROUND: Studies of aortic arch plaques with transesophageal echocardiography have demonstrated that complex aortic arch plaques (CAPs) greater than or equal to 4 mm in thickness are associated with ischemic stroke. Recent studies have demonstrated that the morphological features of plaques may aid in the identification of aortic plaques that are more likely to be associated with embolic stroke. OBJECTIVE: To identify aortic plaques that are more likely to be associated with embolic stroke by means of their morphological features. METHODS: Transcutaneous B-mode ultrasonography was used to image aortic arch plaques in 500 consecutive patients. The criteria used to identify the morphological features of carotid artery plaques that are more likely to be associated with ischemic stroke (heterogeneous rather than homogeneous) were applied to aortic arch plaques. Statistical comparisons were made using the Fisher exact test. RESULTS: Ischemic symptoms (eg, stroke, transient ischemic attack, and amaurosis fugax) were present in 38% of 104 patients with CAP and in 34% of 391 patients without CAP. Nineteen (51%) of 37 patients with heterogeneous CAP were symptomatic. Twenty-one (31%) of 67 patients with homogeneous CAP were symptomatic (P = .04). CONCLUSION: Transcutaneous B-mode ultrasonography of the aortic arch can help to identify heterogeneous plaques that are more likely to be associated with ischemic stroke using morphological criteria derived from studies of carotid artery plaque.

Amaurosis Fugax↗
PubMed2000

IL-5 and eosinophils mediate the rejection of fully histoincompatible vascularized cardiac allografts: regulatory role of alloreactive CD8(+) T lymphocytes and IFN-gamma.

CD8(+) T lymphocytes are known to inhibit the development of eosinophilia and IL-5 synthesis in models of experimental lung disease. In transplantation, the rejection of fully mismatched cardiac allografts by recipients depleted of CD8(+) T cells is characterized by the recruitment of eosinophils in the rejected organs. We show here that this intragraft eosinophilia is dependent on the production of IL-5 since hearts transplanted into IL-5-deficient recipients depleted of CD8(+) cells did not contain eosinophils. More importantly, allograft survival was significantly extended in these animals. In mixed lymphocyte cultures (MLC), the presence of CD8(+) T cells in the responding cell population inhibited the secretion of IL-5. This inhibition was IFN-gamma dependent since adding neutralizing anti-IFN-gamma antibodies induced the production of IL-5. Furthermore, spleen cells isolated from IFN-gamma receptor (IFN-gammaR)-deficient mice secreted IL-5 upon allogeneic stimulation in primary MLC. In vivo, eosinophilia was observed in allografts rejected by IFN-gammaR-deficient recipients. On the contrary, grafts rejected by IFN-gammaR-deficient mice treated with neutralizing anti-IL-5 antibodies did not exhibit eosinophilic infiltration. Our study reveals the capacity of IL-5-secreting CD4(+) T cells and eosinophils to promote the rejection of heart allograft and demonstrates the importance of CD8(+) T cells and IFN-gamma in regulating this pathway of rejection.

Animals↗
PubMed2000

Repeated concanavalin A challenge in mice induces an interleukin 10-producing phenotype and liver fibrosis.

Weekly injections of Concanavalin A (Con A) were performed in BALB/c mice to evaluate the pattern of cytokine production and liver injury. High serum levels of tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), IL-4, and interferon gamma (IFN-gamma) were found in the serum after the first 2 injections of Con A but rapidly decreased from the third injection. Conversely, IL-10 serum levels after repeated Con A challenge increased by 7 times from week 1 to 20. In vivo depletion studies indicated that CD4(+) T cells are essential in IL-10 production. Hepatocyte necrosis was only observed after the first injections of Con A whereas centrilobular inflammatory infiltrates persisted up to 20 weeks. Perisinusoidal liver fibrosis was also increasingly detected in BALB/c mice, whereas no fibrous change was observed in nude mice after 6 weeks of Con A challenge. The number of stellate cells, detected by immunostaining, increased after 20 weeks of Con A injections. Liver cytokine messenger RNA (mRNA) expression after 20 weeks showed expression of transforming growth factor beta1 (TGF-beta1), IL-10, and IL-4 whereas IL-2 was no more expressed. The present study shows that mice repeatedly injected with Con A develop liver fibrosis. The cytokine-release pattern observed after 1 injection of Con A is rapidly shifted towards an immunomodulatory phenotype characterized by the systemic production of large amounts of IL-10.

Animals↗
PubMed2000

Therapeutic drug monitoring of once daily gentamicin in serum and saliva of children.

UNLABELLED: Gentamicin is widely used in paediatric medicine and therapeutic monitoring is mandatory due to the narrow margin of safety. Saliva sampling may be of potential interest, especially in children in whom blood sampling is often difficult. Experience with once daily intravenous administration of aminoglycosides has grown in recent years. Gentamicin levels were measured in serum and saliva of 55 children treated with the drug (5 mg/kg per day), administered intravenously in three different regimens: thrice (n = 19), twice (n = 18), and once daily (n = 18). No correlation was found between serum gentamicin concentrations and saliva levels when the drug was administered twice or thrice daily, however, there was good correlation when the drug was administered once daily (r2 = 0.96, P < 0.0001). CONCLUSION: In children with uncomplicated infections treated with once daily gentamicin, trough concentrations of the drug can be monitored in saliva.

Child↗
PubMed2000

The etiology of renal scars in infants with pyelonephritis and vesicoureteral reflux.

We aimed to investigate, by means of dimercaptosuccinic acid (DMSA) scan, the relations between vesicoureteral reflux (VUR) and its degree, pyelonephritis during infancy, and renal parenchymal findings. Seventy-four infants with pyelonephritis, 44 girls and 30 boys (mean age at their first pyelonephritic episode 4.12 months, median 3 months), were enrolled in the study. Voiding cystourethrography (VCU) and ultrasonography (US) were performed within 6 weeks following the infection. DMSA was performed at least 4 months after the urinary tract infection (UTI). The renal parenchymal pathology was defined as focal or multifocal defects or as a split renal uptake of less than 45%. DMSA scintigraphy revealed that 19% (14/74) of the children had renal damage. Renal parenchymal findings were observed only when VUR was present, and its grade was above 3/5. No abnormality was found in 51 renal units without reflux, 9 with VUR grade 1/5, and 54 with grade 2/5. Renal pathology was observed in 9/24 renal units with VUR grade 3, 3/8 with grade 4, and 2/2 with grade 5. No correlation was found between renal parenchymal defects and clinical presentation of the pyelonephritis, type of the microorganism, presence of bacteremia, or the number of recurrent infections. In adequately treated infants, renal damage is probably due to a reflux-associated, preexisting, congenital renal parenchymal pathology and not to the inflammatory process. We suggest that DMSA scintigraphy should not be performed routinely in every infant with UTI and should be reserved primarily for children with VUR grade 3 and above.

Cicatrix↗
PubMed2000

Helper T-cell responses elicited by Der p 1-pulsed dendritic cells and recombinant IL-12 in atopic and healthy subjects.

BACKGROUND: Environmental allergens, such as Dermatophagoides pteronyssinus group 1 antigen (Der p 1), induce T(H2)-type responses in atopic patients, whereas healthy individuals have T(H1)-type responses to the same antigens. Because of their efficient synthesis of IL-12, dendritic cells (DCs) are potent inducers of T(H1)-type immune responses. OBJECTIVE: We sought to determine whether DCs would skew allergen-specific T(H2)-type responses from atopic individuals. METHODS: Purified CD4(+) T cells from healthy donors or atopic individuals were cultured in the absence or presence of recombinant (r)IL-12 with DCs derived from PBMCs and pulsed with Der p 1. Supernatants of DC-T cell cocultures were assayed by ELISA for IL-5 and IFN-gamma. RESULTS: A T(H1)-type response developed in purified CD4(+) T cells from healthy donors in response to Der p 1-pulsed DCs, as indicated by high levels of IFN-gamma in culture supernatants. In contrast, CD4(+) T cells from atopic donors displayed a T(H2)-type profile characterized by high levels of IL-5 and low levels of IFN-gamma. The addition of rIL-12 (10 ng/mL) to DC-T cell cocultures resulted in the induction of IFN-gamma secretion by Der p 1-specific CD4(+) T cells from atopic patients, whereas their production of IL-5 was not inhibited. Using flow cytometry after intracytoplasmic staining, we found that IFN-gamma and IL-5 were secreted by distinct CD4(+) T-cell subpopulations. CONCLUSION: The cytokine profile of Der p 1-specific T(H2)-like cells from atopic individuals is maintained when the allergen is presented by DCs, even in the presence of exogenous rIL-12.

Allergens↗
PubMed2000

Decrease in asthma mortality rate in Israel from 1991-1995: is it related to increased use of inhaled corticosteroids?

BACKGROUND: Asthma mortality rates (AMRs) during the last several decades increased in many countries with developed medical services, including Israel. The reasons for this trend were never established. Recent data suggested that this trend is changing. OBJECTIVES: We sought to compare the AMR in Israel during 1991-1995 with that of the previous decade and to investigate a possible correlation between mortality rates and use of inhaled corticosteroids (ICSs) and beta(2)-agonists. METHODS: Statistical data on the AMR in Israel during 1981-1995 were extracted. Data were analyzed for 5- and 10-year periods (1981-1990) and compared with a 5-year period (1991-1995). Data on ICS and beta(2)-agonist sales were extracted from the marketing companies' official reports. RESULTS: The mean AMR per 100,000 population per year during 1981-1990 in the 5- to 34-year-old group was 0.393 +/- 0.055 and decreased to 0.202 +/- 0. 046 during the 1991-1995 period (P =.03). There was no significant difference between changes in mean AMR in the 35- to 64-year-old or in the 5- to 64-year-old group during the same periods (4.568 vs 4. 063 and 2.480 vs 2.133). The mean ICS unit sales rates (per 100,000 population per year) between 1982-1990 and 1991-1995 were 21.70 and 190.45, respectively (P <.05). The correlation between ICS sales and AMR was -0.631 (P =.016). Sales of beta(2)-agonists did not change significantly during the study period. CONCLUSIONS: We identified a trend of decreased AMRs in Israel during 1991-1995. The decline in AMRs paralleled the increase in ICS sales, whereas the sales of inhaled beta(2)-agonists did not change significantly. One may speculate that the decrease in AMR may be the result of better anti-inflammatory treatment, as reflected by the increased use of ICSs. The feasibility of reducing AMRs in a country such as Israel, with low AMRs to start with, by improving medical treatment is encouraging.

Administration, Inhalation↗
PubMed2000

Intranasal midazolam as a treatment of autonomic crisis in patients with familial dysautonomia.

To evaluate the efficacy and safety of intranasal midazolam in the treatment of autonomic crises in children with familial dysautonomia, intranasal midazolam was administered at the hospital to six patients during nine episodes of autonomic crisis. Treatment was successful in seven of nine episodes of autonomic crisis in five of six patients, with a mean interval to response of 9.25 +/- 1.25 minutes. The parents of five patients in whom the treatment was successful were instructed to use midazolam at home. At home, 16 additional episodes were treated by the parents, with successful control achieved in 14 (87%). The mean interval to response was 12.8 +/- 2 minutes. No significant side effects were observed at the hospital or at home after intranasal administration of midazolam. Midazolam, given intranasally, is effective and safe in the management of autonomic crises in patients with familial dysautonomia, either in the hospital or at home by the parents after appropriate instruction.

Acute Disease↗
PubMed2000

High prevalence of diarrhea but infrequency of documented Clostridium difficile in autologous peripheral blood progenitor cell transplant recipients.

Autologous peripheral blood progenitor cell (PBPC) transplant recipients frequently receive multiple antibiotics for neutropenic fever in addition to high-dose chemotherapy. Although there are many possible causes for diarrhea in this population, empiric therapy for possible C. difficile colitis is common in some centers. This study sought to define the frequency of diarrhea and of a positive C. difficile toxin assay in PBPC transplant recipients. Data were collected on 80 patients enrolled in a randomized trial of two different antibiotic regimens during PBPC transplant. Data included the presence or absence of diarrhea, all microbiologic studies performed during the transplant admission, and all antimicrobials administered during the transplant admission. Of 80 patients enrolled, 61 (76.3%) developed diarrhea. Only 3/61 (4.9%) had a positive C. difficile toxin assay. A total of 122 C. difficile toxin assays were performed; for each positive C. difficile assay, 41 stool samples were analyzed. Twenty courses of oral metronidazole (18/20 empiric) and 10 courses of oral vancomycin (8/10 empiric) were given. A total of 25 of 61 patients with diarrhea (41%) received therapy for possible C. difficile. Diarrhea is common during autologous PBPC transplant but a positive C. difficile assay is uncommon. The practice of empiric therapy for C. difficile in this population in a non-outbreak setting should be re-evaluated. Bone Marrow Transplantation (2000) 25, 67-69.

Administration, Oral↗
PubMed2000

Clonal Th2 lymphocytes in patients with the idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (HES) and Gleich's syndrome are related disorders characterized by persistent or recurrent hypereosinophilia of unknown origin. Elevated IgE levels and polyclonal hypergammaglobulinaemia are considered as markers of benign outcome in this setting as they are generally associated with predominant cutaneous manifestations and favourable response to glucocorticoid therapy. In a previous study, we identified a clonal population of CD3-CD4+ Th2-like lymphocytes secreting interleukin (IL)-5 and IL-4 in peripheral blood of a patient fulfilling the diagnostic criteria of HES with associated serum hyper-IgE. We now extend this observation by describing identical findings in three additional patients, and we compare their clinical and biological parameters with five other patients with HES. Chromosomal abnormalities were detected in purified CD3-CD4+ Th2 cells from three patients, among whom one developed anaplastic null cell lymphoma. We therefore suggest that a careful search for T-lymphocyte clonality and cytogenetic changes should be included in the work-up of HES for adequate management.

Adult↗
PubMed2000

Cold liver ischemia-reperfusion injury critically depends on liver T cells and is improved by donor pretreatment with interleukin 10 in mice.

Kupffer cells are thought to mediate most of the deleterious effects of liver ischemia-reperfusion injury. The role of liver T cells and the impact of resident cell deactivation by interleukin 10 (IL-10) have never been addressed. Using a model of ex vivo liver cold ischemia and reperfusion, we assessed liver injury, tumor necrosis factor (TNF) and interferon gamma (IFN-gamma) release from livers of balb/c mice, nude mice, nude mice reconstituted with T cells, and gadolinium balb/c pretreated mice. The anti-inflammatory cytokine IL-10 was then used to define the best strategy of administration potentially able to modulate ischemia-reperfusion injury. For this purpose IL-10 was administered to the donor before liver harvesting, in the preservation medium during cold ischemia or during reperfusion. TNF and IFN-gamma were released time dependently and paralleled liver injury after reperfusion of cold preserved livers. Reperfused livers from nude or gadolinium pretreated mice disclosed a dramatic decrease in TNF and IFN-gamma release. Tissue injury was reduced by 51% in the absence of T cells and by 88% when Kupffer cells were deactivated. This effect was reverted by T-cell transfer to nude mice. Only donor pretreatment with IL-10 or IL-10 infusion during reperfusion led to a significant decrease in liver injury, TNF, and IFN-gamma release (-66% or -41%, -95% or -94%, and -70% or -70%, respectively). In conclusion, liver resident T cells are critically involved in cold ischemia-reperfusion injury and pretreatment of the donor with IL-10 decreases liver injury and the release of T-cell- and macrophage-dependent cytokines.

Animals↗
PubMed2000

Early inflammatory response after elective abdominal aortic aneurysm repair: a comparison between endovascular procedure and conventional surgery.

OBJECTIVE: To determine the nature of and to compare the inflammatory responses induced by (1) endovascular and (2) conventional abdominal aortic aneurysm (AAA) repair. MATERIAL AND METHODS: Twelve consecutive patients undergoing elective infrarenal AAA repair were prospectively studied. Seven patients were selected for endovascular procedures (the EAAA group); five patients underwent open surgery (the OAAA group). Three control patients undergoing carotid thromboendarterectomy were also included. Serial peripheral venous blood samples were collected preoperatively, immediately after declamping or placement of the endograft, and at hours 1, 3, 6, 12, 24, 48, and 72. Acute phase response expression of peripheral T lymphocyte and monocyte activation markers and adhesion molecules (flow cytometry), soluble levels of cell adhesion molecules (enzyme-linked immunosorbent assay), cytokine (tumor necrosis factor alpha, interleukin-6, and interleukin-8) release (enzyme-linked immunosorbent assay), and liberation of complement products (nephelometry) were measured. RESULTS: Regarding acute phase response, the EAAA and OAAA groups showed significant increases in C-reactive protein (P <.001 and P =.001), body temperature (P =.035 and P =.048), and leukocyte count (P <.001 and P <.001). Similar time course patterns were observed with respect to body temperature (P =.372). Statistically significant different patterns were demonstrated for C-reactive protein (P =.032) and leukocyte count (P =.002). Regarding leukocyte activation, a significant upregulation of peripheral T lymphocyte CD38 expression was observed in the OAAA group only (P =.001). Analysis of markers such as CD69, CD40L, CD25, and CD54 revealed no perioperative fluctuations in any group. Regarding circulating cell adhesion molecules, the EAAA and OAAA groups displayed significant increases in soluble intercellular adhesion molecule-1 (P =.003 and P =.001); there was no intergroup difference (P =.193). All groups demonstrated high soluble von Willebrand factor levels (P =.018, P =. 007, and P =.027), there being no differences in the patterns (P =. 772). Otherwise, soluble vascular cell adhesion molecule-1, soluble E-selectin, and soluble P-selectin did not appear to vary in any group. Regarding cytokine release, although a tendency toward high tumor necrosis factor alpha and interleukin-8 levels was noticed in the EAAA group, global time course effects failed to reach statistical significance (P =.543 and P =.080). In contrast, interleukin-6 showed elevations in all groups (P =.058, P <.001, and P =.004). Time course patterns did not differ between the EAAA and OAAA groups (P =.840). Regarding complement activation, the C3d/C3 ratio disclosed significant postoperative elevations in the EAAA and OAAA groups (P =.013 and P =.009). This complement product release was reduced in the EAAA group (P <.001). CONCLUSIONS: The current study indicated that both endovascular and coventional AAA repair induced significant inflammatory responses. Our findings showed that there were no large differences between the procedures with respect to circulating cell adhesion molecule and cytokine release. Moreover, the endoluminal approach produced a limited response in terms of acute phase reaction, T lymphocyte activation, and complement product liberation. This might support the concept that endovascular AAA repair represents an attractive alternative to open surgery. Given the relatively small sample size, further larger studies are required for confirmation of our observations.

Aged↗
PubMed2000

Diagnosis of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected patients with polymerase chain reaction: a blinded comparison to standard methods.

Pneumocystis carinii pneumonia (PCP) is an important cause of morbidity and death among persons with human immunodeficiency virus (HIV) infection. Polymerase chain reaction (PCR) analysis of respiratory specimens has been investigated as a rapid diagnostic method. We have previously reported on the utility of this technique for diagnosing PCP in HIV-infected patients. In this report we evaluate PCR used in a blinded study design to avoid biases inherent to retrospective and nonblinded studies. The diagnosis of PCP was established on the basis of clinical findings and morphological studies of bronchoalveolar lavage (BAL) and/or lung biopsy specimens before PCR testing. PCR was performed without knowledge of the diagnosis. PCR results were graded from "negative" to 3+ on the basis of intensity of the banding pattern. Forty-seven patients were enrolled in the study, including 18 with proven PCP and 29 with other conditions. PCR was positive at grade 1 or higher for all 18 patients with PCP (100% sensitivity), at grade 2 or higher for 13 patients (72.2% sensitivity), and at grade 1 or higher for 4 of the 29 control patients (specificity of 86.2%). If a grade 2 or higher was required for diagnosis, the specificity improved to 100%. Results were reproducible with testing of a second aliquot for 46 of 47 patients (97.8%). Our findings confirm that PCR is a sensitive and reproducible test for detection of P. carinii in BAL specimens. Problems with false-positive results for control patients, however, limit the applicability of this method.

AIDS-Related Opportunistic Infections↗
PubMed2000

Hepatitis C lookback.

Hepatitis C was responsible for the majority of cases of posttransfusion hepatitis before the introduction of a specific screening test for blood donors. Infected recipients may remain asymptomatic for many years, but cirrhosis and hepatocellular carcinoma may develop decades after infection. Lookback, or the identification of recipients of potentially contaminated blood, is now being conducted in many countries, including Holland, Denmark, the United Kingdom, Canada, New Zealand, and the United States. In targeted lookback, recipients of blood from donors subsequently found to be positive for hepatitis C are notified and advised to undergo testing. In general lookback, all patients who received blood before being tested for hepatitis C are advised to undergo testing. Difficulties with both forms of lookback illustrate the importance of vein-to-vein tracking of blood products, including the potential utility of a centralized registry of blood product recipients.

Blood Donors↗
PubMed2000

Does long-term itraconazole prophylaxis result in in vitro azole resistance in mucosal Candida albicans isolates from persons with advanced human immunodeficiency virus infection? The National Institute of Allergy and Infectious Diseases Mycoses study group.

The effects of prolonged itraconazole exposure on the susceptibility of Candida albicans isolates to itraconazole and fluconazole have not been well characterized. A recent placebo-controlled study of long-term itraconazole antifungal prophylaxis in persons with advanced human immunodeficiency virus infection afforded the opportunity to address this question. Mucosal Candida sp. isolates were obtained from subjects who developed oropharyngeal or esophageal candidiasis, and in vitro susceptibilities of the last isolate obtained at removal from the study as a prophylaxis failure were compared in itraconazole and placebo recipients. More subjects in the placebo group (74 of 146 [51%]) than in the itraconazole group (51 of 149 [34%]) developed mucosal candidiasis (P = 0.004). A total of 112 isolates were recovered from 56 of the 74 (76%) subjects with mucosal candidiasis assigned to the placebo group, compared to 97 isolates from 45 of the 51 (88%) subjects in the itraconazole group. C. albicans accounted for 98% of isolates in the placebo group and 89% of isolates in the itraconazole group. The itraconazole MIC at which 50% of the isolates tested were inhibited (MIC(50)) for last-episode isolates from the itraconazole group was 0.125 microg/ml compared to 0.015 microg/ml for the placebo group subjects, P = 0.0001. The MIC(50) of fluconazole for the last isolates from the itraconazole group was 1.5 microg/ml compared to 0.5 microg/ml for the placebo subjects (P = 0.005). A lower proportion of isolates recovered from subjects on itraconazole therapy were classified as susceptible to itraconazole (63%) compared to isolates from the placebo group (96%) (P = 0.001). Similarly, a lower proportion of C. albicans isolates from subjects on itraconazole therapy were susceptible to fluconazole (78%) compared to isolates from the placebo group (96%) (P = 0.01). Also, the proportion of isolates that were not fully susceptible to itraconazole or fluconazole was greater in patients assigned to the itraconazole group than the placebo group (itraconazole susceptibility, 37 and 4%, respectively (P = 0.001); fluconazole susceptibility, 23 and 4%, respectively (P = 0.01). In conclusion, long-term itraconazole prophylaxis in patients with AIDS is associated with reduction in susceptibility to itraconazole and cross-resistance to fluconazole.

AIDS-Related Opportunistic Infections↗
PubMed2000

Investigation of the increased incidence of gonorrhoea diagnosed in genitourinary medicine clinics in England, 1994-6.

OBJECTIVES: To determine important risk factors associated with cases of gonorrhoea in England, and whether any particular risk groups were associated with the substantial rise in numbers of cases seen between 1994 and 1996. DESIGN: Two retrospective cross sectional surveys. SETTING: 70 randomly selected genitourinary medicine (GUM) clinics in England. SUBJECTS: 10% of all gonorrhoea patients attending GUM clinics in England in 1994 (847 patients) and 1996 (1146 patients). MAIN OUTCOME MEASURES: For risk factors in 1996 (study 1), unadjusted rates per 100,000 population aged 14-70 and relative rates (RR) with 95% confidence intervals (CIs). For the change in risk factors between 1994 and 1996 (study 2), adjusted odds ratios (ORs) with 95% CIs, derived from logistic regression analyses of data on patients in 1996, with patients in 1994 as the comparison group. RESULTS: The incidence of gonorrhoea in 1996 was higher in homosexual males (812 per 100,000; RR = 30.2, CI = 25.2 to 36.0) compared with heterosexual males (27 per 100,000); in black Caribbeans (467 per 100,000; 21.4, 17.9 to 25.5) and black Africans (235 per 100,000; 10.8, 7.5 to 15.5) compared with white people (22 per 100,000); and in previous GUM clinic attenders (433 per 100,000; 37.93, 35.46 to 40.56) compared with those who had not attended previously (11 per 100,000). However, most patients were either white or heterosexual. Heterosexual patients in 1996 were significantly more likely to have reduced sensitivity to penicillin (2.55, 1.20 to 5.41) than those in 1994. Male homo/bisexual patients in 1996 were significantly more likely to be from the north west (3.77, 1.45 to 9.80) and to have either reduced sensitivity (2.63, 1.03 to 6.73) or complete resistance (1.98, 1.03 to 3.78) to penicillin, compared with those in 1994. CONCLUSIONS: Homo/bisexual men and the black Caribbean population in England experience a disproportionate burden of gonococcal infections, however, the bulk of diagnoses are in white heterosexuals. No single risk group was associated with the rise in numbers of cases between 1994 and 1996. Resistance to penicillin is widespread and has increased in homo/bisexual men, and it is possible that a rise in treatment failures has, to some extent, enhanced transmission of gonorrhoea and contributed to the rise in numbers of diagnoses in this group.

Adolescent↗