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Biomedical subjects

S Kaye

Publications and source records attributed to S Kaye.

At least 19 recordsLinked to original sources
PubMed1992

A microtitre format point mutation assay: application to the detection of drug resistance in human immunodeficiency virus type-1 infected patients treated with zidovudine.

An assay for the analysis of point mutations in DNA fragments amplified by the polymerase chain reaction is described. The method was applied to the analysis of mutations leading to single amino acid changes in the reverse transcriptase gene of human immunodeficiency virus type-1 that are associated with decreased sensitivity of the virus to the effects of the nucleoside analogue zidovudine. The assay uses a microtitre format allowing large numbers of clinical samples to be analysed, and is a quantitative assay giving information on the relative proportions of wild-type and mutant sequence at the point being analysed. The analysis of mutations in codons 67, 70, 215, and 219 of the RT gene in samples taken at various time points after the commencement of zidovudine therapy shows a high variability in the rate at which these mutations arise and in the proportions of wild-type and mutant sequences observed. The method we describe has wide application to the analysis of other point mutations in clinical or research studies.

Base Sequence↗
PubMed1992

The rebirth and blooming of forensic medicine, Milton Helpern Lecture.

This features a presentation by Dr. Sidney Kaye on the occasion of the Milton Helpern Lecture at the annual meeting of the National Association of Medical Examiners near Fort Myers in Florida in 1989. The author experienced the "golden age" of forensic medicine as a student and associate of Dr. Alexander Gettler in the New York Medical Examiner's Office. He also worked with Dr. Rutherford Gradwohl in the St. Louis Police Department and was one of the founders of the American Academy of Forensic Sciences. He was the toxicologist in the Virginia medical examiners' system before moving to Puerto Rico. His discussion is a historical review of his experiences in developing forensic sciences.

Awards and Prizes↗
PubMed1992

A new motion responsive pacemaker: first clinical experience with an acceleration sensor pacemaker.

A new accelerometer-based adaptive rate pacemaker (EXCEL VR) was evaluated to investigate its behavior at nominal settings during treadmill exercise testing and postural changes. Eight patients with sinus rhythm were selected to compare intrinsic heart rate to sensor mediated rate. Throughout exercise treadmill testing, changes in the sensor mediated rate closely paralleled actual physiological changes. The Pearson product moment correlation of pacing rate with sinus frequency, calculated for all patients, was r = 0.82 (P = 0.001). Change in the patient's physical position resulted in immediate change in sensor rate, which corresponded appropriately to the type of position change and activity level. Average (+/- SD) pacing rate was 62.4 +/- 2.7 beats/min supine; 67 +/- 3.8 beats/min sitting; 69.8 +/- 6.4 beats/min standing; 81.6 +/- 8.7 beats/min slow walking; and 96.8 +/- 1.3 beats/min fast walking. After 4 minutes of recovery, the average pacing rate dropped to 65 +/- 3 beats/min. The interaction between the accelerometer and the pulse generator at nominal settings was accurate and infrequently required the use of its many programming options. The accelerometer sensor and pulse generator algorithm in this device during postural change and exercise resulted in physiological-like changes in sensor mediated heart rate.

Acceleration↗
PubMed1992

Ondansetron compared with metoclopramide in the control of emesis and quality of life during repeated chemotherapy for breast cancer.

This was a multicentre, randomised, double-blind, parallel-group study which included female breast cancer patients, receiving their first of 6 scheduled courses of chemotherapy (cyclophosphamide greater than or equal to 500 mg/m2). Patients received an intravenous dose of 16 mg dexamethasone with either 8 mg ondansetron or 60 mg metoclopramide before chemotherapy, followed by oral dosing with 8 mg ondansetron or 20 mg metoclopramide 3 times daily for 5 days. A total of 93 patients were treated with ondansetron and 94 patients with metoclopramide. On day 1 of their first course of treatment 91 and 60% of patients in the ondansetron and metoclopramide groups respectively were free of emesis (p less than 0.001). Over the 5-day treatment period, the corresponding figures were 81 and 48% (p less than 0.001). The results for nausea also revealed highly statistically significant treatment differences (p less than 0.001) in favour of ondansetron for both day 1 and day 1-5 analyses of the first treatment course. Over the series of courses, 67% of patients receiving ondansetron completed all 6 courses with a maximum of 2 emetic episodes on their worst day, compared with 28% of patients receiving metoclopramide (p less than 0.001). A similar analysis for nausea revealed that 49% of patients receiving ondansetron completed all 6 courses with 'none' or 'mild' nausea compared with 27% of patients receiving metoclopramide (p less than 0.001). These differences were reflected in quality of life data (Rotterdam Symptom Checklist). After the first course of treatment, a statistically significant improvement (p = 0.002) in the psychological subscale scores was observed after ondansetron compared with metoclopramide. No differences were observed in the physical or functional activity subscales after the first course. However, the quality of life results over the series of courses revealed a more pronounced difference in favour of ondansetron in the psychological subscale scores (p less than 0.001) as well as trends in favour of ondansetron in the physical (p = 0.096) and functional activity (p = 0.056) subscales. Extrapyramidal symptoms were reported in 19% of patients in the metoclopramide group and resulted in 15% of patients withdrawing from their randomised anti-emetic schedule, either during or between treatment courses. Other adverse events were generally minor in nature and did not necessitate withdrawal from treatment. In conclusion, this study shows that ondansetron is significantly superior to metoclopramide (each with a single pre-treatment dose of dexamethasone) in the control of emesis over 6 courses of chemotherapy for breast cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Intrathecal IgG synthesis and specificity of oligoclonal IgG in patients infected with HIV-1 do not correlate with CNS disease.

The CSF/serum immune response to HIV 1 was studied in 24 patients admitted for investigation. The level of antibody to HIV-1 and specificity of oligoclonal IgG were determined in blood and cerebrospinal fluid (CSF). The majority of patients demonstrated elevated levels of intrathecal IgG synthesis, with levels of HIV-1-specific antibody frequently being significantly higher in CSF than in serum. In 16 of 21 patients the CSF/serum antibody ratio indicated active intrathecal synthesis. Oligoclonal banding was present in CSF from all 24 patients. Immunoprinting of serum and CSF demonstrated antigenic specificity (p24, gp 160, RT) of the clonal antibodies in all of 12 patients though the patterns of reactivity in CSF did not necessarily correspond with that of serum. Although a specific association of particular patterns with HIV CNS disease was not found we feel that these markers should be included in longitudinal studies of HIV-related diseases of the CNS. The specificity of oligoclonal antibodies, both in CSF and in serum was demonstrated, and this specificity may be a useful marker for longitudinal studies in HIV-1 antibody-positive asymptomatic patients.

AIDS Dementia Complex↗
PubMed1991

Carboplatin-based combination chemotherapy for advanced carcinoma of the cervix.

A combination of carboplatin, vincristine, methotrexate and bleomycin (COMB) was given to 29 patients with locally advanced, metastatic or recurrent cervical carcinoma. A total of 85 cycles of chemotherapy were given, with half of the patients receiving greater than 3 cycles. Both the response rate (32.1%) and the median duration of response (30 weeks) were relatively disappointing. Renal toxicity was minimal, but one-third of our patients experienced severe (WHO grades 3 and 4) nausea and vomiting. This combination showed little advantage over carboplatin used as a single agent.

Adult↗
PubMed1991

Long term results of cyclophosphamide, adriamycin and platinum chemotherapy in advanced epithelial ovarian cancer.

Between January 1980 and December 1983, 57 consecutive patients with advanced epithelial ovarian cancer (FIGO Stage IIc n = 5; III n = 45; IV n = 7) were treated with 6 cycles of cyclophosphamide 600 mg/m2, adriamycin 30-45 mg/m2 and platinum 50 mg/m2 (CAP) at 3 weekly intervals. Pathological complete remission (CR) was documented in 10 (18%) and 4 with no residual disease after primary cytoreductive surgery were free from progression (FFP). There were 19 partial remissions (PR) giving a 51% overall response rate. The median duration of CR was 33 months from second look surgery. Median survival (MS) for all patients was 22 months. Multivariate analysis indicated that response to chemotherapy was the most important prognostic factor, with MS for CR of 53 months, PR 23 months and stable or progressive disease 11 months (p = 0.001). Most CR (8 of 10) occurred in patients with minimal residual disease (no single lesion greater than 2.0 cm), but extent of disease, though significant in univariate analysis of prognostic factors was not an independent predictor of survival. Six patients (11%) are alive and tumour free with a minimum follow-up of 7 years. All had FIGO Stage III disease at presentation and four had no residual tumour after primary surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Effect of regB on expression from the P1 and P2 promoters of the Pseudomonas aeruginosa regAB operon.

Exotoxin A production in Pseudomonas aeruginosa is dependent on two regulatory genes, regA and regB, which are located in tandem on the chromosome. Expression of regA and regB is controlled by two promoters (P1 and P2) situated upstream of the regAB locus. We have studied the effect of the regA and regB gene products on transcription from the regAB promoters. Transcriptional and translational fusions, under the control of the P. aeruginosa regA promoters, were used to analyze the regulation of these promoters in a variety of genetic backgrounds. When the regA P1 promoter was supplied in trans to strains lacking expression of regB (PAO1) or lacking transcription of the regAB operon (PA103-29), little activity from the P1 promoter was detected. In contrast, activity from the P2 promoter was not affected in either PAO1 or PA103-29. Sequence analysis of the regAB operon of PA103-29 detected two mutations. One of the mutations is predicted to result in a premature stop codon in the regA open reading frame. We complemented PA103-29 with a construction containing regA and an inactive regB or a construction containing both regA and regB to directly analyze the effect of regB on transcription of the regAB operon. When PA103-29 was complemented with regA but not regB, we could not detect any transcription from the P1 promoter. Complementation of PA103-29 with both regA and regB resulted in a high level of transcription from the P1 promoter and a corresponding early transcriptional activation of toxA. Our results indicated that induction of transcription from the P1 promoter requires the regB open reading frame and thus the regAB operon is autogenously regulated in P. aeruginosa.

ADP Ribose Transferases↗
PubMed1991

Treatment of flexor tenosynovitis of the hand ('trigger finger') with corticosteroids. A prospective study of the response to local injection.

We developed a protocol to maximize medical therapy for "trigger finger." Fifty-eight patients with 77 episodes of flexor tenosynovitis of the hand that was resistant to rest, therapy with nonsteroidal anti-inflammatory drugs, and/or splinting were treated with single or multiple injections of depo-methylprednisolone acetate or triamcinolone acetonide. Patients were prospectively followed up for an average of 4.6 years. Results showed that symptoms and signs resolved in 61% after a single injection. Recurrent episodes, after prolonged pain-free intervals, occurred in 27% and were effectively re-treated with injection. In 12% of cases, either injection failed or early recurrence required surgical release. Local adverse reactions to injection, including pain at the injection site, stiffness, ecchymosis, or atrophy of subcutaneous fat, were self-limited. No episodes of postinjection infection or tendon rupture occurred. The medical management of flexor tenosynovitis with local corticosteroid injection(s) is effective in nearly 90% of cases and is free from serious adverse reactions.

Anti-Inflammatory Agents↗
PubMed1990

Analysis of carboxyhemoglobin and cyanide in blood from victims of the Dupont Plaza Hotel fire in Puerto Rico.

Ninety-seven people died from a fire that occurred in the Dupont Plaza Hotel in Puerto Rico on 31 Dec. 1986. All, except four who died later in the hospital, were found dead at the scene. All of the fatalities at the hotel (except for eight) were burned beyond recognition. Blood from seventy-eight of the victims was screened for carboxyhemoglobin at the Institute for Forensic Sciences in Puerto Rico and was then sent to the National Institute of Standards and Technology, Gaithersburg, Maryland, for analysis of carboxyhemoglobin and cyanide concentrations. The blood data indicated that carbon monoxide and hydrogen cyanide, singly or combined, were probably not responsible for the majority of the deaths that occurred in the badly burned victims. On the other hand, the significantly higher carboxyhemoglobin in the nonburned victims indicated that carbon monoxide alone or combined with hydrogen cyanide probably played a major role in the cause of their deaths.

Burns↗
PubMed1990

Epidural analgesia. Effect on the likelihood of a successful trial of labor after cesarean section.

From October 1984 to April 1986, 237 women who had had an earlier cesarean section underwent a trial of labor (TOL). The delivery outcomes for 87 who received epidural analgesia were compared retrospectively with those for the 150 who did not. There were no overt uterine ruptures. The rates were similar for successful TOL, uterine scar dehiscence, blood transfusions, endometritis and one- and five-minute Apgar scores. The rate of operative vaginal delivery was higher in the epidural group. When epidural subjects were divided into vaginal and cesarean delivery groups, the failed-TOL group differed from the successful-TOL group in greater maternal weight gain, heavier and longer infants, higher rate of oxytocin administration, less cervical dilation and higher station at epidural activation. When the oxytocin-treated subjects were excluded, however, the epidural and no-epidural patients had the same successful TOL rates (94% and 92%, respectively) and spontaneous vaginal delivery rates (70% and 76%, respectively). Epidural analgesia, when controlled for oxytocin use, appears to have no effect on the failed-TOL or operative vaginal delivery rate.

Adult↗
PubMed1990

Oxytocin use after previous cesarean: why a higher rate of failed labor trial?

When used for patients undergoing trial of labor after previous cesarean, oxytocin is associated with an increased failure rate. Previous reports have not studied why this occurs. From October 1984 to April 1986, 237 patients with previous cesareans underwent a trial of labor. The delivery outcomes of 73 women who received oxytocin were compared with those of the 164 who did not. Rates were similar for uterine scar dehiscence, uterine rupture, operative vaginal delivery, blood transfusions, endometritis, and low Apgar scores. Successful trial of labor occurred in 68% in the oxytocin group, compared with 89% in the no-oxytocin group. Failed trial of labor was significantly more frequent in patients who received oxytocin for induction of labor than in those who did not. When subjects who received oxytocin were divided into induction (N = 47) and augmentation (N = 26) groups, successful trial of labor occurred in 58% of the former group versus 88% of the latter group. Other characteristics of the augmentation group were spontaneous labor, greater cervical dilation and effacement at initiation of oxytocin, shorter duration of infusion, and lower oxytocin infusion rates. For patients who have had previous cesareans and who desire trial of labor, oxytocin by controlled infusion is safe. Successful trial of labor may be enhanced by awaiting spontaneous labor or inducing with a favorable cervix.

Adult↗
PubMed1989

Phase II studies of mitozolomide in melanoma, lung and ovarian cancer.

Seventy-seven patients were treated with oral mitozolomide to assess the activity of this drug in melanoma, lung and ovarian cancer. Partial responses were seen in five of 18 evaluable patients with small cell lung cancer (SCLC) and three of 20 with melanoma. No activity was apparent in non small cell lung or epithelial ovarian cancer. The major toxicity was myelosuppression which necessitated reduction in the initial dosage from 115 to 90 mg/m2. However, even at this dose level, unpredictable WHO grade 4 toxicity occurred in non-pretreated patients. Thrombocytopenia was more common than leucopenia and eight patients required platelet transfusion for spontaneous or tumour-related haemorrhage. Myelotoxicity was considered responsible for two deaths and was a significant contributory factor in a further three. Non-haematological toxicity was minor. Thus, despite demonstrable activity in SCLC and melanoma, unpredictable myelosuppression is likely to preclude further assessment in combination chemotherapy regimes in these tumours.

Adult↗
PubMed1988

Quantification of brainstem auditory evoked responses for patient monitoring.

A method of quantifying the integrity of the brain stem auditory evoked responses (BAERs) is applied to specific cases in both the ICU and OR to demonstrate its usefulness as an adjunct to peak latency evaluation. This measure is particularly valuable when peak identification is difficult as a result of poor waveform coherence. Examples are included to demonstrate that this method can also give independent information from peak latency.

Brain Stem↗