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Biomedical subjects

J Krischer

Publications and source records attributed to J Krischer.

At least 37 records · Page 2Linked to original sources
PubMed1998

Treatment of acyclovir-resistant herpetic ulceration with topical foscarnet and antiviral sensitivity analysis.

BACKGROUND: Herpes simplex virus (HSV) can produce persistent mucocutaneous disease in patients with the acquired immunodeficiency syndrome (AIDS). In this case report, we evaluate the efficacy, safety and viral resistance after topical foscarnet in severe genital ulceration due to acyclovir-resistant HSV-2. CASE REPORT: A 45-year-old African woman was known for an HIV infection with severe immunosuppression (CD4 <100/mm3). She had received a long-term prophylaxis with acyclovir (400 mg b.i.d.) for a recurrent genital herpes. Few weeks after stopping this prophylaxis, she developed large genital ulcerations progressing despite valacyclovir treatment (1,000 mg t.i.d.). Cultures were positive for HSV-2, resistance to acyclovir was shown by the plaque reduction assay and topical foscarnet was tried. Treatment consisted of a 20-min application of topical foscarnet 2.4% twice a day. Dramatic improvement was observed with rapid antalgia, and cicatrization of the genital ulcerations was observed after 50 days. HSV could not be detected on the mucosal surface. Initially, HSV-2 was resistant to acyclovir but sensitive to foscarnet. After 1 month of topical treatment, HSV-2 became sensitive to acyclovir and was still sensitive to foscarnet. Finally, after 6 weeks of treatment, no virus could be detected by culture. CONCLUSION: Topical foscarnet (2.4%) is a convenient treatment for chronic genital herpes. Resistance to acyclovir disappears few weeks after stopping this drug and sensitivity to foscarnet persists during the 50 days of treatment.

Acyclovir↗
PubMed1998

DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma.

PURPOSE: We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA alkyltransferase (AGT). PATIENTS AND METHODS: Thirty-three patients with newly diagnosed glioblastoma multiforme (GBM) and five patients with newly diagnosed anaplastic astrocytoma (AA) were treated with Temodal at a starting dose of 200 mg/m2 daily for 5 consecutive days with repeat dosing every 28 days after the first daily dose. Immunochemistry for the detection of the human DNA mismatch repair proteins MSH2 and MLH1 and the DNA repair protein AGT was performed with monoclonal antibodies and characterized with respect to percent positive staining. RESULTS: Of the 33 patients with GBM, complete responses (CRs) occurred in three patients, partial responses (PRs) occurred in 14 patients, stable disease (SD) was seen in four patients, and 12 patients developed progressive disease (PD). Toxicity included infrequent grades 3 and 4 myelosuppression, constipation, nausea, and headache. Thirty tumors showed greater than 60% cells that stained for MSH2 and MLH1, with three CRs, 12 PRs, three SDs, and 12 PDs. Eight tumors showed 60% or less cells that stained with antibodies to MSH2 and/or MLH1, with 3 PRs, 3 SDs, and 2 PDs. Eleven tumors showed 20% or greater cells that stained with an antibody to AGT, with 1 PR, 2 SDs, and 8 PDs. Twenty-five tumors showed less than 20% cells that stained for AGT, with 3 CRs, 12 PRs, 4 SDs, and 6 PDs. CONCLUSION: These results suggest that Temodal has activity against newly diagnosed GBM and AA and warrants continued evaluation of this agent. Furthermore, pretherapy analysis of tumor DNA mismatch repair and, particularly, AGT protein expression may identify patients in whom tumors are resistant to Temodal.

Adult↗
PubMed1997

Impact of PUVA therapy on HIV viremia: a pilot study.

BACKGROUND: Treatment by ultraviolet radiation (UV) during human immunodeficiency virus (HIV) infection is controversial, since exposure of HIV-infected cells in vitro to UV enhances HIV replication in vitro. METHODS: Four consecutive AIDS patients with psoriasis and CD4 count lower than 20/mm3 were treated with 8-methoxypsoralen and UVA (PUVA). HIV viremia expressed as long of HIV-1 RNA copies/ml of plasma was quantified 10 min before and 1 h following UVA exposure, every week during PUVA therapy and at the end of treatment. The Psoriasis Area Surface Index (PASI) score was used to quantify the severity of psoriasis. RESULTS: No significant change in HIV-1 RNA level was observed in the 18 paired samples analyzed before and 1 h after PUVA (median: -0.05 log HIV-1 RNA, range: -0.50-0.21, p = 0.10). After 12-31 UVA exposure for a total dose of 15.5-196 J/cm2 over a period of 6-15 weeks, viremia changes from baseline in the 4 patients were -0.61, -0.07, 0.36 and 0.39 log HIV RNA. In 1 patient without antiviral treatment, a persistent decrease in viremia and transient increase in CD4 cell count were observed. PUVA was well tolerated and associated with significant improvement of the PASI score in 3 patients. CONCLUSION: HIV viremia is not significantly modified by PUVA therapy in AIDS patients with psoriasis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Epiluminescent light microscopy of melanocytic lesions after dermoepidermal split.

BACKGROUND: In vivo epiluminescent light microscopy (ELM) of pigmented skin lesions reveals numerous elementary structures. Among them, the pigment network (PN), black dots (BD) and brown globules (BG) constitute important semiologic features. Based on histological extrapolations, it has been postulated that PN should reflect the presence of melanin in the epidermis and its honeycomb aspect should result from the dermoepidermal architecture. OBJECTIVE: To demonstrate this directly by analyzing separately by ELM the epidermal and dermal sides of melanocytic lesions. METHODS: We split the epidermis from the dermis of 10 pigmented lesions (6 lentigos, 4 nevocytic nevi) by incubation with dispase. ELM images were done in vivo before excision, then ex vivo on the whole specimen and separately on the split epidermis and dermis. Epidermal and dermal specimens were finally controlled by histology. RESULTS: PN was observed only on the epidermal side of the split. Its organization was remarkably conserved after the procedure as compared with prior in vivo images. In contrast, pigmentation observed on dermal sides of the splits showed no organized pattern and corresponded to melanophages. BG were found on the dermal side and BD on the epidermal side of the split lesions, which confirms previous hypotheses. CONCLUSION: By subtracting the dermal pigmentation and vessels from the image, the split technique has thus established the epidermal origin of the PN and given a more detailed ELM analysis of network components.

Culture Techniques↗
PubMed1996

Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group.

BACKGROUND: The value of autologous bone marrow transplantation in the treatment of children with acute myeloid leukemia (AML) is unknown. We compared autologous bone marrow transplantation with intensive consolidation chemotherapy as treatments for children with AML in first remission. METHODS: We induced remission with one course of daunorubicin, cytarabine, and thioguanine, followed by one course of high-dose cytarabine (3 g per square meter of body-surface area for six doses). Patients in remission after the second course of induction therapy were eligible for randomization. Between June 1988 and March 1993, 552 of 649 enrolled patients who could be evaluated (85 percent) entered remission. A total of 209 patients were not eligible for randomization; of the remaining 343 patients, 232 were randomly assigned to receive six courses of intensive chemotherapy (117 patients) or autologous transplantation (115 patients). Of the original 649 patients, 189, including 21 with Down's syndrome, were nonrandomly assigned to receive intensive chemotherapy. RESULTS: The rates of event-free survival and overall survival for the entire group at three years were 34 +/- 2.5 percent and 42 +/- 2.6 percent, respectively. For patients who were randomly assigned to one of the two treatment groups, the mean (+/- SE) rates of event-free survival three years after randomization were not significantly different in the two groups when examined by intention-to-treat analysis: 36 +/- 5.8 percent for the intensive-chemotherapy group as compared with 38 +/- 6.4 percent for the autologous-transplantation group; and the relative risk of treatment failure for the chemotherapy group as compared with the autologous-transplantation group was 0.81 (P = 0.20 by the log rank test; 95 percent confidence interval, 0.58 to 1.12). Overall survival at three years followed a similar pattern. There was a lower relapse rate (31 percent vs. 58 percent, P < 0.001) but a higher rate of treatment-related mortality (15 percent vs. 2.7 percent, P = 0.005) in the group treated with autologous transplantation than in the intensive-chemotherapy group. The event-free survival at three years for the nonrandomized intensive-chemotherapy group was 39 +/- 5.1 percent, and for a contemporaneous group of patients each of whom received a histocompatible bone marrow transplant from a sibling, it was 52 +/- 8.0 percent. CONCLUSIONS: Treatment of children with AML in first remission with either autologous bone marrow transplantation or intensive chemotherapy prolongs event-free survival equally.

Acute Disease↗
PubMed1996

The use of omeprazole for resistant oesophagitis in children.

Following failure of conventional therapy for reflux oesophagitis, 15 children were treated with omeprazole 20 mg daily for a period of up to three months initially. Treatment resulted in a marked symptomatic improvement as measured by incidence of pain, vomiting, dysphagia and haematemesis. Four children failed treatment and required fundoplication. No complications from the use of omeprazole were recorded and some children have continued long-term treatment.

Adolescent↗
PubMed1996

Results of a prospective randomized trial comparing standard dose neuraxis irradiation (3,600 cGy/20) with reduced neuraxis irradiation (2,340 cGy/13) in patients with low-stage medulloblastoma. A Combined Children's Cancer Group-Pediatric Oncology Group Study.

PURPOSE: To determine in a prospective randomized trial the effect on survival, progression-free survival, and patterns of relapse of a decrease in the neuraxis radiation dose from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions in patients with newly diagnosed medulloblastoma between 3 and 21 years of age with low T stage (T1, T2 and T3A), minimal postoperative residual tumor, and no evidence of dissemination (M0). METHODS AND MATERIALS: Between June 1986 and November 1990, the Children's Cancer Group and the Pediatric Oncology Group randomized 126 patients in a two-arm study comparing the two different doses of neuraxis irradiation. In both arms, the posterior fossa received 5,400 cGy in 30 fractions. All patients were staged with myelography, postoperative lumbar cerebrospinal fluid cytology, and postoperative contrast-enhanced cranial computerized tomography to ensure no evidence of dissemination and no more than 1.5 cm3 residual tumor volume. Overall survival, progression-free survival, and patterns of recurrence were carefully monitored. Prospective endocrine and psychometric studies were performed to determine the benefit of decreasing the neuraxis radiation dose. RESULTS: Following an interim analysis at a median time on study of 16 months, the study was closed, since a statistically significant increase was observed in the number of all relapses as well as isolated neuraxis relapses in patients randomized to the lower dose of neuraxis radiation. CONCLUSIONS: In patients with newly diagnosed medulloblastoma considered to have a good prognosis on the basis of low T stage, minimal residual tumor after at least subtotal resection, and no evidence of dissemination after thorough evaluation, there is an increased risk of early relapse associated with lowering the dose of neuraxis radiation from 3,600 cGy in 20 fractions to 2,340 cGy in 13 fractions.

Adolescent↗
PubMed1996

Therapy of refractory or recurrent childhood acute myeloid leukemia using amsacrine and etoposide with or without azacitidine: a Pediatric Oncology Group randomized phase II study.

PURPOSE: A randomized study compared the combination of amsacrine (100 mg/m2/d on days 1 to 5) and etoposide (200 mg/m2/d on days 1 to 3) with the same two agents plus azacitidine (250 mg/m2/d on days 4 to 50) for the therapy of induction-resistant or relapse childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: One hundred sixty-seven assessable children with AML who either had failed to respond to primary induction therapy (group 1, n = 41) or had relapsed (group 2, n = 126) were randomized. RESULTS: Overall, there were 56 complete responses (34%; SE 4%). Among primary refractory patients (group 1), the complete response rate was higher with the three-drug regimen (18% vs 53%, P = .03). In the relapsed patients (group 2), there was no difference in complete response rates related to treatment (31% vs 35%, P = .3). There were 17 early deaths. The major toxicities for both regimens were myelosuppression and infection. CONCLUSION: The overall complete response rate of 34% in this patient population is indicative of effective antileukemic activity. For patients with relapsed leukemia, the addition of azacitidine to etoposide and amsacrine did not improve response. The suggested advantage of the three-drug regimen for induction failures warrants further investigation.

Adolescent↗
PubMed1995

Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription.

We reported previously that daily injections of isophane insulin prevented both hyperglycemia and insulitis in nonobese diabetic (NOD) mice (Atkinson, M., N. Maclaren; and R. Luchetta. 1990. Diabetes. 39:933-937). The possible mechanisms responsible include reduced immunogenicity of pancreatic beta-cells from "beta-cell rest" and induced active immunoregulation to insulin (Aaen, IK., J. Rygaard, K. Josefsen, H. Petersen, C. H. Brogren, T. Horn, and K. Buschard. 1990. Diabetes. 39:697-701). We report here that intermittent immunizations with insulin or its metabolically inactive B-chain in incomplete Freund's adjuvant also prevent diabetes in NOD mice, whereas immunizations with A-chain insulin or with BSA do not. Adoptive transfer of splenocytes from B-chain insulin-immunized mice prevented diabetes in recipients co-infused with diabetogenic spleen cells, an effect that was abolished by prior in vivo elimination of either CD4+ or CD8+ cells. Insulin immunization did not reduce the extent of intraislet inflammation (insulitis); however, it did abolish expression of IFN-gamma mRNA within the insulitis lesions. Immunizations with insulin thus induce an active suppressive response to determinants on the B-chain that converts the insulitis lesion from one that is destructive to one that is protective.

Animals↗
PubMed1994

Redistribution of intracellular Ca2+ stores during phagocytosis in human neutrophils.

Subcellular gradients of cytosolic free Ca2+ concentration, [Ca2+]i, are thought to be critical for the localization of functional responses within a cell. A potential but previously unexplored mechanism for the generation of gradients of [Ca2+]i is the accumulation of Ca2+ stores at the site of Ca2+ action. The distribution of the Ca2+ store markers Ca(2+)-dependent adenosine triphosphatase and calreticulin was investigated in resting and phagocytosing human neutrophils. Both proteins showed an evenly distributed fine granular pattern in nonphagocytosing cells, but became markedly concentrated in the filamentous actin-rich cytoplasmic area around the ingested particle during phagocytosis. This redistribution began at early stages of phagocytosis and did not depend on an increase in [Ca2+]i. Thus, accumulation of Ca2+ stores in a restricted area of the cell may contribute to the generation of localized increases in [Ca2+]i.

Actins↗
PubMed1994

GAD65 autoantibodies increase the predictability but not the sensitivity of islet cell and insulin autoantibodies for developing insulin dependent diabetes mellitus.

The clinical onset of insulin-dependent diabetes (IDD) can be predicted by determination of autoantibodies to several pancreatic-islet cell antigens. Islet-cell autoantibodies (ICA) and insulin autoantibodies (AA) are most commonly used. We have developed a recombinant human glutamic acid decarboxylase (GAD65) radioimmunoassay and measured autoantibodies to GAD65 (GAD65A) in the sera of 73 documented prediabetic individuals, 76 newly-diagnosed patients, 103 relatives of IDD probands at increased risk for the development of IDD because they were positive for ICA and/or IAA, 72 ICA and IAA negative relatives, and 207 healthy controls. Our data demonstrate that GAD65A are strongly associated with the currently established autoantibody markers of IDD. Their presence in prediabetic subjects with only ICA or IAA enhances their risk for progression to IDD, yet does not much enhance the screening sensitivity already available through conventional ICA and IAA for IDD prediction.

Adolescent↗
PubMed1994

Hyperfractionated irradiation and concurrent cisplatin in brain stem tumors: a Pediatric Oncology Group pilot study (9139).

A phase I Pediatric Oncology Group Study was performed combining 7,020 cGy hyperfractionated irradiation (117 cGy twice daily separated by 6 h) with increasing concurrent doses of cisplatin given with the intent of radiosensitization as treatment for children with newly diagnosed brain stem tumors. Cisplatin was infused over 120 h on weeks 1, 3, and 5 during a 6-week radiotherapy course. The following cisplatin dose levels were studied: (1) 50 mg/m2/120 h, (2) 75 mg/m2/120 h and (3) 100 mg/m2/120 h. Sixteen of 17 children completed therapy. One child expired after 2 days of treatment secondary to massive intratumoral hemorrhage. At cisplatin dose level 3 (100 mg/m2/120 h), grade 2-4 myelosuppression was encountered in 3 of 5 evaluable patients. Otherwise, no other excessive toxicities, including renal and ototoxicity, were noted.

Adolescent↗