Once-weekly treatment with oral ketoconazole for superficial fungal infections.
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Adult↗
Biomedical subjects
R Segal
Publications and source records attributed to R Segal.
Segmental neurofibromatosis of the sciatic nerve: case report.
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Adult↗
HLA-DR1 and rheumatoid arthritis in Israeli Jews: sequencing reveals that DRB1*0102 is the predominant HLA-DR1 subtype.
Rheumatoid arthritis (RA) is associated with the HLA-DR4 cellular subtypes Dw4 and Dw14 in Caucasians, with Dw15 in Japanese, and possibly with HLA-DR1 in Israeli Jews. Sequencing studies in Caucasians have shown that these molecules share a common amino acid sequence in the third hypervariable region of the DR molecule (AA 67-74: LLEQRRAA or LLEQKRAA), suggesting that this sequence is primarily associated with RA. An important argument in favor of this shared-epitope hypothesis has been the reported association between DR1 and RA in Israeli Jews. However, a later report did not confirm this association, and cellular typing showed that Israeli DR1 consists of three or more subtypes, suggesting that new subtypes might be present. Since no sequencing data on Israeli HLA-DR1 genes have been reported, we sequenced the first domain (AA 10-91) of the DRB1 gene in 12 DR1-positive Israeli RA patients, 5 healthy controls and a homozygous typing cell (HTC), defining the major Jewish cellular HLA-DR1 subtype. DRB1*0102 (DR1 Dw20) was found in 8 RA patients, 3 controls and the HTC "LVA". DRB1*0101 (DR1 Dw1) was found in 4 RA patients and 2 controls. No other DR1 subtypes were encountered. In all 20 DR1 haplotypes, the DRB1*0101 or 0102 allele was associated with DQA1*0101 and DQB1*0501, being identical to the Caucasian DR1 haplotypes. Thus, at the sequence level, we found no basis for the reported extensive cellular heterogeneity of DR1 in the Israeli population.(ABSTRACT TRUNCATED AT 250 WORDS)
Alleles↗
Risk for adverse events among patients receiving intravenous histamine2-receptor antagonists.
OBJECTIVE: To identify risk factors for adverse drug reactions (ADRs) in patients receiving intravenous histamine2-receptor antagonists (H2-RAs). DESIGN: The study hypothesis was evaluated by performing a logistic regression procedure with a backward elimination of the explanatory variables associated with ADRs. MAIN OUTCOME MEASURES: ADRs temporally associated with the use of intravenous H2-RAs served as the dependent variable. Background information about the patients and drug use evaluation criteria in three general areas were entered into the regression analysis. SETTING: Hospitals were selected from the southeastern US, based on their willingness to participate and their characteristics. Participating hospitals exhibited a variety of sizes and ownership arrangements. PATIENTS: 1200 adult patients who were receiving intravenous H2-RAs. RESULTS: Seven percent of patients experienced a presumed ADR (PADR) to intravenous H2-RAs. The only risk factor for ranitidine was for patients who did not have their dosage corrected for renal function ("overdose"); these patients were twice as likely to experience a PADR compared with patients who received the correct dosage as determined by their renal function. Two risk factors for cimetidine were identified: (1) patients taking cimetidine with another medication known to cause a drug interaction; and (2) patient age. No risk factors were identified for famotidine. CONCLUSIONS: The two risk factors for ADRs identified in this study are preventable. Healthcare providers should strive to prevent ADRs by adjusting patients' dosages based on their renal function and by monitoring patients receiving cimetidine with another medication known to interact with cimetidine.
Age Factors↗
Use of i.v. cimetidine, ranitidine, and famotidine in 40 hospitals.
The drug experiences of 1200 patients receiving i.v. histamine H2-receptor antagonists were studied. Forty hospitals in five southeastern states participated in a drug-use evaluation (DUE). In addition to supplying background information, a pharmacist at each hospital used a standardized form to perform a concurrent review of 30 consecutive adult patients who had been started on i.v. cimetidine, ranitidine, or famotidine. In addition to the patient's age and the prescriber's medical specialty, specific DUE criteria included the reason given in the medical record for use; dosage regimen and adjustments made on the basis of the patient's renal function; other GI drugs taken concurrently; pharmacist intervention; simultaneous use of oral medications; occurrence of adverse events; H2-antagonist use with specified drug products known to affect serum drug concentrations of one or both medications; and use of gastric pH monitoring. Therapy with i.v. H2 antagonists was usually started by internal medicine specialists or surgeons, and most of the evaluated patients received such therapy for prevention of stress-related mucosal damage. According to estimated creatinine clearance, 34% of patients were in need of dosage adjustments, but such adjustments were made in only 49% of these. Forty percent of patients began therapy while taking at least one medication orally, and almost one fourth of patients were receiving an additional drug for the treatment of an acid-peptic or related indication. The occurrence of adverse events was similar for the three H2 antagonists studied. The findings identify several problematic areas in the way H2 antagonists are used in clinical practice.
Adolescent↗
The influence of aging on the induction and manifestations of experimental systemic lupus erythematosus.
The influence of age on autoimmunity was studied in a model in which experimental systemic lupus erythematosus (SLE) is induced in normal mice by the injection of a human monoclonal anti-DNA antibody expressing a common idiotype designated 16/6 Id. The resulting disease is expressed by the production of a variety of autoantibodies and clinical manifestations characteristic to human SLE. Female BALB/c mice, at ages of 2 and 12 months, were immunized with the 16/6 Id. Mice were tested periodically for the presence of autoantibodies. The production of all autoantibodies tested was significantly lower in the older mice as compared to the group of young mice. Clinical manifestations which included leukopenia, increased erythrocyte sedimentation rate and proteinuria were similar in both age groups. Kidney evaluations revealed differences among the two groups of mice. While in all kidney sections of young mice multiple immune complex deposits were detected, in the group of older mice half had similar pathology while the rest either were negative or had only segmental and partial glomerular immune complex depositions. Thus, aging is associated with a decrease in the capacity to respond to the pathogenic anti-DNA, 16/6 Id, by the production of antibodies and autoantibodies and in the expression of a milder disease.
Aging↗
Induction of experimental systemic lupus erythematosus (SLE) in mice with severe combined immunodeficiency (SCID).
A model in which experimental SLE is induced in normal mice by the injection of a human anti-DNA MoAb expressing a common idiotype 16/6 Id has been established in our laboratory. In the present study we have attempted the induction of experimental SLE in mice with SCID by the transfer of lymphocytes obtained from mice with experimental SLE. Disease could not be induced by direct immunization of SCID mice with the 16/6 Id nor by transfusion of normal splenocytes and immunization with the 16/6 Id thereafter. In contrast, disease was induced in SCID mice which were transplanted with splenic lymphocytes obtained from SLE afflicted BALB/c mice. The disease was expressed by the presence of high titres of antibodies and glomerular immune complex deposits were present in the kidney sections of these mice. Mice that received spleen cells from donors with experimental SLE together with the 16/6 Id developed higher titres of autoantibodies and had, in addition to the immune complex deposits, glomerular histological pathology. The model of experimental SLE induction in SCID mice should help in the elucidation of the role of different cell types in the pathogenesis of SLE.
Animals↗
Increased incidence of urinary tract infection in patients with rheumatoid arthritis and secondary Sjögren's syndrome.
The incidence of lower urinary tract infection in 120 women with rheumatoid arthritis and secondary Sjögren's syndrome was evaluated retrospectively. Thirty one patients (26%) had secondary Sjögren's syndrome. Recurrent urinary tract infection was significantly more common in these patients (11/31) than in patients without Sjögren's syndrome (4/89). Habitual leucocyturia was also more common in patients with secondary Sjögren's syndrome (18/31) than in patients with rheumatoid arthritis without Sjögren's syndrome (8/89). Of seven patients with vaginal sicca symptoms, six had recurrent urinary tract infection. Urinary 24 hour mucopolysaccharide excretion in 20 patients with Sjögren's syndrome was similar to the excretion in 10 patients without Sjögren's syndrome. These results show that recurrent urinary tract infection is significantly more common in women with rheumatoid arthritis and secondary Sjögren's syndrome. A local deficit in protective urinary mucosal secretion or other immune mechanisms may be responsible for this susceptibility.
Adult↗
Tortuous peripheral arteries: a cause of focal neuropathy. Case report.
Segmental ulnar neuropathy has been reported as a result of ulnar nerve compression due to posttraumatic false aneurysms of the ulnar artery and, more infrequently, due to thrombosis or true aneurysms of the same vessel. The authors present a case of segmental sensory ulnar neuropathy in the wrist which intraoperatively demonstrated impingement on the ulnar nerve by a tortuous ulnar artery. The symptomatic relief and electrophysiological improvement that occurred immediately following neurovascular decompression confirm that the vascular anomaly was the cause of neuropathy. Pulsatile pressure applied to the nerve trunk may have triggered ectopic stimulation of sensory fibers manifested by a tingling and burning sensation. There was immediate resolution of paresthesia following mobilization of the impinging vessel from the nerve. Subsequent rapid electrophysiological recovery may be explained by improvement in focal nerve microcirculation following vascular decompression. Tortuosity (megadolichoectatic anomaly) of intracranial arteries has been related to cranial nerve or brain-stem dysfunction; however, this appears to be the first report in the literature of a case in which such association has been found to occur extracranially, involving a peripheral nerve.
Arm↗
Treatment with bifonazole shampoo for seborrhea and seborrheic dermatitis: a randomized, double-blind study.
Forty-four patients with seborrhea and seborrheic dermatitis of the scalp were treated with either bifonazole shampoo (22 patients) or the vehicle shampoo (22 patients) in a randomized, double-blind vehicle-controlled study. The patients were instructed to wash their scalps 3 times weekly for 6 weeks and were examined every 3 weeks. Responses were evaluated by clinicians using a clinical grading of scaling, erythema and overall improvement, and also by the patients, who assessed pruritus and overall improvement, using a scale of 0 to 3. The improvement following the bifonazole shampoo was found to be significantly greater than that achieved with the vehicle shampoo in regard to the clinical evaluation of scaling (p = 0.01) as well as patient evaluation of pruritus (p = 0.008) and overall improvement (p = 0.03). No major adverse side effects were recorded.
Adolescent↗
A framework for evaluating the work of pharmacists.
This article reviews the major appraisal methods used in health care organizations and offers a competing "systems model" for conducting performance appraisals in pharmacy departments. The value of the proposed appraisal system is that it reminds management not to view the area of performance appraisal as "keep it simple." Rather, management should recognize that performance appraisal should be viewed as a system (more correctly, a subsystem) that interacts with and affects all parts of a pharmacy department's drug use system. The performance appraisal system is complex and dynamic, requiring a significant resource commitment from management and all workers within the department.
Employee Performance Appraisal↗
[Mycetoma with black granules: first case in a native of Israel].
We present a case of black grain mycetoma caused by Madurella mycetomatis. The diagnosis was made on the basis of conventional light microscopy and mycological studies. After 12 months of oral therapy with ketoconazole, the patient showed partial response. This is the first native Israeli case of black grain mycetoma.
Adult↗
A novel 21-kDa protein as a serum marker for benign and malignant urogenital tumors: preliminary communication.
A novel 21-kDa protein (p21) was isolated from auto-immune complexes, found in sera of 14 patients with malignant urogenital tumors and isolated on Protein A-Sepharose. Isolated complexes were analyzed in 15% polyacrylamide-SDS minigels. After staining with Coomassie blue R, the bands were scanned with a clinical densitometer. The level of p21 in sera of cancer patients was 3 times higher than that found in normal individuals. An attempt was made to correlate consecutive levels of p21 in the sera of these cancer patients with the clinical course. In 4 cases a significant decrease (57-75%) in the level of p21 was observed in parallel with response to treatment. In 9 of 10 cases where no response or tumor progression was observed, the relative abundance of p21 increased or remained unchanged. Thus, the level of p21 was indicative of progression or regression of the disease in 13 out of 14 patients. Similar high levels of p21 in sera were also found in 22 patients with benign hyperplasia of prostate. The p21 protein was not immunoreactive with known anti-ras antibodies such as Y13-259, 142-24E05 and anti-rap1. Partial amino acid analysis of this protein showed no complete homology to any known protein, but a partial homology to known bacterial proteins involved in DNA replication or transcription was observed. Monitoring of the novel p21 levels before and after treatment may be useful in follow-up of cancer patients, providing evidence of response to treatment.
Adult↗
Promoter activity and distance constraints of one versus two Sp1 binding sites.
In the simple adenovirus 2 early 1B (E1B) promoter, moving the single Sp1 transcription factor binding site (GC box) from its wild-type position eight base pairs (bp) from the TATA box to 30 bp upstream is equivalent to its deletion (Wu, L., and Berk, A. (1988) Genes & Dev. 2, 403-411). In more complex promoters, multiple upstream elements regulate transcription over greater distances. To understand these spacing constraints, we placed two GC boxes in phase at various distances from the E1B TATA box. Whereas one GC box at eight bp from TATA increases transcription in vivo 5-fold compared with TATA alone (Wu, L., Rosser, D. S. E., Schmidt, M. C., and Berk, A. (1987) Nature 326, 512-515), two GC boxes increased in vivo transcription 25-30-fold. Transcriptional stimulation by two GC boxes fell off rapidly in vivo at 30 bp from TATA, remained approximately constant through 50 bp, then decreased again at 70 bp. Consequently, two GC boxes have a multiplicative effect at eight bp from TATA and continue to stimulate transcription at a greater distance from TATA than a single Sp1 site. Quantitatively different results were observed for in vitro transcription using a nuclear extract; a more linear fall off with increasing distance from TATA was observed. Separating the two GC boxes progressively decreased transcription. E1A stimulation of these promoters in vivo indicates that Sp1 transcription control is independent of E1A transactivation.
Adenoviridae↗
[Sulfasalazine in rheumatoid arthritis].
Sulfasalazine (SLZ) is now a second-line treatment in rheumatoid arthritis (RA), as well as in psoriatic arthritis and ankylosing spondylitis. 54 patients with active RA were treated with enteric coated SLZ (2 g daily) in a 24-week open study. Clinical and laboratory parameters of disease activity were monitored initially and thereafter at 2-week intervals for the first 2 months, and then at 4-week intervals until the end of the 24-week study. There was significant clinical improvement at the end, as shown by scores for joint pain (Ritchie), grip strength and morning stiffness (p less than 0.0001, less than 0.0001 and less than 0.01, respectively, by paired t test). Clinical improvement was accompanied by significant decrease in erythrocyte sedimentation rate and increase in hemoglobin (p less than 0.002 and less than 0.016, respectively). There was improvement in some cases as early as 3 weeks after starting therapy. The drop-out rate was significant: 19/54 (35%), most (13) due to side-effects, mainly gastrointestinal; none of the side-effects were serious. Our results, similar to those of other studies, indicate that despite the high rate of side effects, SLZ is an effective, second-line drug for RA.
Arthritis, Rheumatoid↗
A variant of HLA-DR4 determines susceptibility to rheumatoid arthritis in a subset of Israeli Jews.
HLA-DR4 is associated with risk for developing rheumatoid arthritis (RA) in most populations. In Israeli Jews, in whom the Dw10 subtype of DR4 predominates, no association of RA with DR4 has been found. The inability to detect an association could be due to the high frequency of DR4-Dw10. We used DNA typing with amplification by the polymerase chain reaction and dot-blotting with allele-specific oligonucleotides to determine DR4 variants in 131 Jewish RA patients living in Israel and 134 controls. In both Ashkenazi Jews and non-Ashkenazi Jews, the rare variant Dw15 (previously identified in Japanese populations and in Japanese patients with RA) was found to be the main allele associated with the risk of developing RA (relative risk = 9.2, corrected P less than 0.001). However, this low-frequency allele could be responsible for susceptibility in only 11.5% of the patients. Susceptibility for rheumatoid factor-positive RA was associated with Dw4 and Dw15; the risk for rheumatoid factor-negative RA was associated only with Dw14. The distribution of the HLA-DQ alleles associated with DR4 showed that more than half of the RA patients with Dw15 also had HLA-DQw2. The frequencies of DQw7 and DQw8 were not different in RA patients compared with controls. The results suggest that, as in other populations, susceptibility for the development of RA in Israeli Jews is associated with DRB1 locus alleles of the DR4 group.
Alleles↗
Familial erythema nodosum.
Erythema nodosum (EN) is a hypersensitivity reaction associated with many diseases. We describe a family in which 4 sisters had acute or recurrent EN. HLA typing showed a common haplotype in the affected members of the family. A review of familial EN and HLA distribution in EN is presented.
Acute Disease↗
The use of visible light-cured resin system in maxillofacial prosthetics and neuro-orthopedic surgery.
The use of visible light-cured (VLC) resin was evaluated in contrast to more traditional chemical-cured resins for reconstruction of the spine in experimental rats. Such procedures are used to reconstruct vertebra in humans following corpectomy for neoplastic destruction of the spine. Numerous disadvantages exist in the use of chemical-cured resins, including excessive heat generated during the polymerization, cytotoxic effects of the nonpolymerized monomers on adjacent tissues, increased risk of infection due to impaired immunity, and distortion problems with the polymers. A new visible light-cured resin, Triad, was tested for use in maxillofacial prosthetics and for vertebral body replacement in neuro-orthopedic surgery. This study evaluated the biocompatibility of the VLC resin system as a bone implant material. The results of this study have shown the VLC resins underwent polymerization without substantial exothermic reaction and the biologic testing indicated that they are nontoxic and biocompatible. Some of the advantages noticed by using VLC resin are accuracy of fit and ease of fabrication and manipulation.
Acrylic Resins↗