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Biomedical subjects

J Krischer

Publications and source records attributed to J Krischer.

At least 19 recordsLinked to original sources
PubMed2004

High frequency of abnormal glucose tolerance in DQA1*0102/DQB1*0602 relatives identified as part of the Diabetes Prevention Trial--Type 1 Diabetes.

AIMS/HYPOTHESIS: Immunological and genetic markers can be used to assess risk of developing type 1 diabetes prior to the onset of clinical symptoms. Autoantibody-positive relatives of patients with type 1 diabetes are at increased risk for disease, while the presence of HLA DQA1*0102/DQB1*0602 is thought to confer protection. Using the unique population identified by the Diabetes Prevention Trial--Type Diabetes (DPT-1), our aim was to determine if these individuals were protected from type 1 diabetes. METHODS: We described metabolic and immunological characteristics of islet cell cytoplasmic autoantibodies-positive relatives with DQB1*0602 identified as part of DPT-1. RESULTS: We found that 32% of DQB1*0602-positive relatives identified through the DPT-1 had abnormalities of glucose tolerance despite the fact that only 19% had multiple type 1 diabetes-associated autoantibodies and only 13% had abnormal insulin secretion, markers typically associated with the disease. In addition, these markers were not associated with abnormal glucose tolerance. In contrast, the DQB1*0602-positive relatives had elevated fasting insulin (117+/-10 pmol/l) and homeostasis model assessment of insulin resistance (HOMA-R) (4.90+/-0.5) values, which are more commonly associated with type 2 diabetes. The later marker of insulin resistance was associated with glucose tolerance status. CONCLUSIONS/INTERPRETATION: Our data indicate that DQA1*0102/DQB1*0602 relatives identified through DPT-1 have a high frequency of abnormal glucose tolerance and a disease phenotype with characteristics of type 1 and type 2 diabetes. Thus, multiple pathways to abnormal glucose tolerance are present within families of these type 1 patients.

Autoantibodies↗
PubMed2000

An annular plaque due to Mycobacterium haemophilum infection in a patient with AIDS.

Infections with mycobacteria are of importance in the differential diagnosis of skin lesions in immunocompromised patients. We report the case of a human immunodeficency virus (HIV)-infected patient who presented with an annular plaque as cutaneous manifestation of Mycobacterium haemophilum. Improvement of the immunologic status is important for successful treatment. Complete resolution was only observed when the antimycobacterial therapy was combined with antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed2000

Teledermatoscopy in Switzerland: a preliminary evaluation.

BACKGROUND: Since devices for digital epiluminescence microscopy and for telemedicine have become affordable, a critical evaluation of this new method has been needed. OBJECTIVE: Our aim was a critical evaluation of teledermatoscopy under routine conditions in private practice. METHODS: Pigmented skin lesions (PSLs) scheduled for excision were documented with a digital epiluminescence microscopy (DELM) system. Images were sent to the PSL consultation at the Department of Dermatology of the University Hospital Geneva, where a diagnosis was established. The histopathologic report including the initial diagnosis was sent afterward. Both approaches were compared concerning diagnostic accuracy. RESULTS: Over a period of 6 months, 55 lesions on 51 patients have been included in this study. Picture quality was good or very good in more than 90%. Diagnostic accuracy of the teledermatoscopy approach was superior to that of the conventional approach for malignant melanocytic lesions. CONCLUSION: We have shown the feasibility of a teledermatoscopic consultation. The gain of diagnostic accuracy in this teledermatoscopic approach, especially for malignant melanocytic lesions, suggests that patients might benefit directly from such a consultation at distance.

Feasibility Studies↗
PubMed2000

Low-stage medulloblastoma: final analysis of trial comparing standard-dose with reduced-dose neuraxis irradiation.

PURPOSE: To evaluate prospectively the effects on survival, relapse-free survival, and patterns of relapse of reduced-dose (23.4 Gy in 13 fractions) compared with standard-dose (36 Gy in 20 fractions) neuraxis irradiation in patients 3 to 21 years of age with low-stage medulloblastoma, minimal postoperative residual disease, and no evidence of neuraxis disease. PATIENTS AND METHODS: The Pediatric Oncology Group and Children's Cancer Group randomized 126 patients to the study. All patients received posterior fossa irradiation to a total dose of 54 Gy in addition to the neuraxis treatment. Patients were staged postoperatively with contrast-enhanced cranial computed tomography, myelography, and CSF cytology. Of the registered patients, 38 were ineligible. RESULTS: The planned interim analysis that resulted in closure of the protocol showed that patients randomized to the reduced neuraxis treatment had increased frequency of relapse. In the final analysis, eligible patients receiving standard-dose neuraxis irradiation had 67% event-free survival (EFS) at 5 years (SE = 7.4%), whereas eligible patients receiving reduced-dose neuraxis irradiation had 52% event-free survival at 5 years (SE = 7.7%) (P =.080). At 8 years, the respective EFS proportions were also 67% (SE = 8.8%) and 52% (SE = 11%) (P =.141). These data confirm the original one-sided conclusions but suggest that differences are less marked with time. CONCLUSION: Reduced-dose neuraxis irradiation (23.4 Gy) is associated with increased risk of early relapse, early isolated neuraxis relapse, and lower 5-year EFS and overall survival than standard irradiation (36 Gy). The 5-year EFS for patients receiving standard-dose irradiation is suboptimal, and improved techniques and/or therapies are needed to improve ultimate outcome. Chemotherapy may contribute to this improvement.

Adolescent↗
PubMed2000

Hypoluminescence microscopy of pigmented skin lesions.

Since the 'renaissance' of epiluminescence microscopy (ELM), histological correlation of ELM structures has been the subject of many investigations. Direct correlation is difficult because of the methodological differences between ELM and histopathology. In order to further understand the features of pigmented skin lesions (PSLs), we studied whether hypoluminescence microscopy (HLM) had any advantages over ELM. Twenty pigmented skin lesions scheduled for surgical excision were chosen randomly for this study. After excision, the lesions were studied using standard ELM and an HLM technique. For the latter, illumination was performed from the dermal side. The HLM pattern was clearly different from that of ELM. In all lesions the 'deeper' (dermal) structures became more visible. Some structures already visible in ELM appeared more visible, particularly structures apparently localized in deeper layers of the PSL. For highly pigmented lesions the difference in the two approaches was striking. With the HLM technique details became visible, and structures which were hardly or not visible with the classic ELM approach could be easily distinguished and evaluated. In conclusion, HLM is a simple, easy to use, reproducible ex vivo technique that is able to provide additional information to the conventional ELM technique.

Diagnosis, Differential↗
PubMed1999

Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives.

We report here our prospective study of 15,224 non-diabetic, first-degree relatives of probands with immune-mediated (type 1) diabetes (IMD), of which 135 were found to eventually develop diabetes. We determined islet cell, insulin, GAD65, insulinoma-associated antigen-2 and 2beta autoantibodies (ICA, IAA, GAD65A, IA-2A and IA-2betaA), on the first available serum samples. The latter three autoantibodies were however assayed on subsets of the relatives with and without ICA, IAA and/or GAD65A, plus most of the relatives who developed diabetes. Of the relatives who progressed to diabetes, 94% had at least one of these autoantibodies on the first screening, while ICA proved to be the most sensitive single marker (sensitivity 74%). Risk of diabetes was however negligible when ICA was found in the absence of the others (5-year risk=5.3%), but increased dramatically whenever two or more autoantibodies were present (5-year risk=28.2% and 66.2%, respectively). The most predictive combination of markers was ICA plus IA-2A and/or IA-2beta A. Loss of first phase insulin release to IVGTT also occurred only in those ICA-positive relatives who had one or more of the other autoantibodies. The data suggests that significant beta-cell damage is seen only when the underlying autoimmunity has spread to multiple antigenic islet cell determinants. Combinations of the autoantibodies occurred most often in relatives with the highest risk HLA-DR/DQ phenotypes. These data document that only relatives positive for at least two or more of these five autoantibodies are at significant risk of diabetes themselves. Intervention trials for the prevention of type 1 diabetes could be designed based on testing for these autoantibodies alone, without the need for HLA typing and IVGTT testing.

Adolescent↗
PubMed1999

Pseudoporphyria induced by nabumetone.

Nabumetone is a nonsteroidal anti-inflammatory drug, which has only rarely been associated with photosensitivity. We report a case of bullous lesions arising over photoexposed areas in a patient treated with nabumetone.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Malassezia spp carriage in patients with seborrheic dermatitis.

The role of Malassezia spp in seborrheic dermatitis (SD) is controversial. To compare the cutaneous density and the cultural characteristics of Malassezia in persons with or without SD, quantitative cultures were obtained by stripping the forehead with a tape placed on Leeming and Notman medium. Plates were incubated at 37 degrees C in a plastic bag, and colonies were counted after 14 days. High yeast density was defined as > 100 colony forming units (CFU)/tape. Volunteers were divided into four groups depending on their HIV serology [HIV (+) versus HIV (-) or unknown] and their clinical status (with or without SD). 126/129 cultures were positive (97.7%). Malassezia spp density was low on clinically normal skin in all HIV (-) persons (40/40) but was high in 8/34 (24%) HIV (+) persons without SD (p < 0.001). In SD patients, high densities were found in 10/22 (45%) HIV (+) and in 17/33 (52%) HIV (-) persons. The strains could be divided into three basic groups on the basis of their cultural characteristics. Colony morphology type A predominated on normal skin (72%), and morphology type C predominated on persons with SD (78%). High yeast density can be present without skin symptoms. The pathogenicity of Malassezia seems more likely to be determined by the subtype present on the skin rather than by its density.

Adult↗
PubMed1998

Regression of Kaposi's sarcoma during therapy with HIV-1 protease inhibitors: a prospective pilot study.

BACKGROUND: Early studies using HIV protease inhibitors (PI) showed regression of Kaposi's sarcoma (KS) lesions in some patients. OBJECTIVE: Our purpose was to determine prospectively the influence of PI on HIV-related KS. METHODS: KS lesions of nine patients with progressive cutaneous disease were prospectively evaluated clinically and by means of epiluminescence microscopy before and during PI therapy. HIV viremia and CD4 cell count were measured in parallel. RESULTS: All patients experienced reduction or initial stabilization of KS lesions during the first 4 to 8 weeks of HIV-1 PI therapy. After a median follow-up of 7 months and according to AIDS Clinical Trials Groups criteria, six patients had a partial response, two showed stable disease, and in one noncompliant patient KS progressed, requiring chemotherapy. With epiluminescence microscopy, a reduction in skin surface alterations, lesional size, and color intensity was demonstrated in six of nine patients. PI induced a median decrease in viremia of 1.66 log and a median increase in the CD4 count of 49 cells/mm3. CONCLUSION: In this series, HIV PI therapy reduced or stabilized KS. The efficacy of HIV-1 PI in KS may result from the improvement in cellular immunity. These results suggest the use of PI in AIDS-related KS regardless of the level of CD4 lymphocyte count and HIV viremia.

CD4 Lymphocyte Count↗
PubMed1998

Neutrophil eccrine hidradenitis in a patient with AIDS.

Neutrophilic eccrine hidradenitis (NEH), first described as a rare, transient, and benign complication of various chemotherapy regimens for acute leukemia, has also been observed in other conditions, including three HIV-positive patients and even in otherwise healthy individuals (1-3). A similar histological pattern was described after intradermal bleomycin injections into normal human skin (4). We report the first case of NEH in a hemophilic HIV infected patient treated with stavudine, a new reverse transcriptase inhibitor.

Acquired Immunodeficiency Syndrome↗