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Biomedical subjects

B Kaplan

Publications and source records attributed to B Kaplan.

At least 181 records · Page 10Linked to original sources
PubMed1998

Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K+ channels.

Drosophila genes reaper, grim, and head-involution-defective (hid) induce apoptosis in several cellular contexts. N-terminal sequences of these proteins are highly conserved and are similar to N-terminal inactivation domains of voltage-gated potassium (K+) channels. Synthetic Reaper and Grim N terminus peptides induced fast inactivation of Shaker-type K+ channels when applied to the cytoplasmic side of the channel that was qualitatively similar to the inactivation produced by other K+ channel inactivation particles. Mutations that reduce the apoptotic activity of Reaper also reduced the synthetic peptide's ability to induce channel inactivation, indicating that K+ channel inactivation correlated with apoptotic activity. Coexpression of Reaper RNA or direct injection of full length Reaper protein caused near irreversible block of the K+ channels. These results suggest that Reaper and Grim may participate in initiating apoptosis by stably blocking K+ channels.

Amino Acid Sequence↗
PubMed1998

Potential interaction of troglitazone and cyclosporine.

BACKGROUND: Troglitazone (Rezulin) is a promising new oral hypoglycemic agent recently approved by the Federal Drug Administration for use in type II diabetes mellitus. Although troglitazone is not metabolized by the cytochrome p450 3A isozyme family, it is a potential inducer of this system. Other medications, e.g., rifampin and phenobarbital, which also induce p450 3A activity, have been reported to significantly decrease cyclosporine (CsA) concentrations. METHODS: We report a case of a stable renal transplant patient who had a decrease in CsA concentration after beginning troglitazone and who subsequently developed an acute rejection episode. We then reviewed all stable renal patients begun on troglitazone over the previous 6 months. RESULTS: The seven transplant patients who had been started on troglitazone therapy experienced a statistically and clinically significant decrease in CsA 12-hr trough levels immediately after the institution of troglitazone therapy. CONCLUSION: A potential interaction exists between troglitazone and CsA. Transplant patients on CsA who receive troglitazone therapy should be monitored closely.

Acute Disease↗
PubMed1998

Decreased protein binding of mycophenolic acid associated with leukopenia in a pancreas transplant recipient with renal failure.

BACKGROUND: Mycophenolate mofetil (MMF) is rapidly hydrolyzed to its active metabolite mycophenolic acid (MPA), which is excreted by the kidney after undergoing glucuronidation to MPAG. MPAG has been shown to accumulate in patients with renal failure. MPA is extensively and avidly bound to human serum albumin. In vitro inhibition of the pharmacologic target, inosine monophosphate dehydrogenase, is dependent on free MPA. It has been demonstrated that high MPAG concentrations decrease MPA protein binding in vitro. In addition, the uremic state is associated with altered protein binding of many drugs. METHODS: We assessed free MPA, total MPA, and MPAG kinetics in a patient with renal failure receiving MMF for a pancreas transplant, who presented with signs of MMF toxicity. MPA, MPAG, and free MPA were measured by high performance liquid chromatography and a validated 14C-MPA ultrafiltration methodology. RESULTS: The MPAG area under the concentration curve (AUC) in this patient was extremely high (5899 microg x hr/ml). The total MPA AUC of 36.8 microg x hr/ml was within the range usually obtained in stable renal patients. The free fraction of MPA and the free MPA AUC were markedly elevated (13.8% and 5.07 microg x hr/ml, respectively). CONCLUSIONS: Patients with severe renal insufficiency may have markedly increased free MPA levels that may not be reflected in total MPA concentrations. These patients may be at increased risk for MMF-related toxicity.

Adult↗
PubMed1998

Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor A1 allele in children at high risk for alcoholism.

BACKGROUND: There is evidence that both reduction in P300 amplitude and the presence of the A1 allele are risk markers for alcoholism. We hypothesized that demonstration of a relationship between the marker and the trait in young children who had not begun to drink regularly would provide evidence for dopaminergic mediation of the reduction in P300 often seen among high-risk children. A previous association between the A1 and the P300 amplitude in screened controls supports the hypothesis that this association occurs in the general population. METHODS: Children were assessed using both visual and auditory paradigms to elicit event-related potentials (ERPs). The P300 component of the ERP was investigated with respect to the genetic variation of the Taq1A D2 receptor in these children. RESULTS: Genetic association between a marker locus (Taq1 A RFLP near the D2 receptor locus) and the amplitude of P300 was found to be present in 58 high-risk children and their relatives (a total of 100 high-risk individuals). CONCLUSIONS: A higher proportion of children from alcoholic families may exhibit lower P300 because more of these children carry the A1 allele than is seen in the normal population.

Acoustic Stimulation↗
PubMed1998

Three births after preimplantation genetic diagnosis for cystic fibrosis with sequential first and second polar body analysis.

OBJECTIVE: The purpose of this study was to determine the accuracy and feasibility of sequential polar body removal and analysis for preimplantation genetic diagnosis of mendelian disorders. STUDY DESIGN: Three couples with risk factors for cystic fibrosis had preimplantation genetic diagnosis with the use of sequential polar body analysis. After stimulation, oocytes were harvested and the first polar bodies were removed and analyzed on the day of aspiration. The following day, after fertilization, the second polar bodies were aspirated. Only embryos known to have inherited the normal maternal allele were transferred. RESULTS: All three couples had successful pregnancies resulting in the births of unaffected infants. CONCLUSIONS: Preimplantation diagnosis with the use of sequential polar body removal is feasible and can prevent the establishment of genetically abnormal pregnancies for couples at risk.

Alleles↗
PubMed1998

The effects of relative timing of sirolimus and cyclosporine microemulsion formulation coadministration on the pharmacokinetics of each agent.

INTRODUCTION: Sirolimus and cyclosporine (INN, ciclosporin) share the same cytochrome P4503A metabolic pathways, and both drugs are substrates for p-glycoprotein countertransport. These factors most likely affect the bioavailability of both drugs. This study served to examine whether the timing of the administration of cyclosporine and sirolimus might significantly affect the relative bioavailability of one or both of these drugs. METHODS: In this randomized crossover trial, 24 stable kidney transplant recipients who were treated after transplant with a combination of sirolimus, cyclosporine, and prednisone for at least 3 months before study initiation, received individualized doses of sirolimus once daily and cyclosporine in the microemulsion formulation twice a day. A total of 20 patients completed the full crossover design. Patients were randomized to one of two dosing schedules: 10 of the patients who completed the study received the morning doses of sirolimus and cyclosporine concomitantly for the first 7 days (schedule I), and from days 8 to 14 the sirolimus dose was administered 4 hours after the morning cyclosporine dose. Ten of the patients received the sirolimus dose 4 hours after the morning cyclosporine dose for the first 7 days (schedule II), and from days 8 to 14 they received concomitant morning doses of cyclosporine and sirolimus. Pharmacokinetic profiles of sirolimus and cyclosporine performed on all patients on days 7, 14, and 15 yielded the area under the concentration-time curve (AUC), peak concentration (Cmax), time to Cmax (tmax), trough cyclosporine concentration (Co), and trough sirolimus concentration (Co) values. RESULTS: Sirolimus AUC and sirolimus trough levels were consistently and significantly higher when both cyclosporine and sirolimus were administered concomitantly than when they were administered 4 hours apart. No effect attributable to timing of drug administration could be found on cyclosporine pharmacokinetic parameters. CONCLUSION: This study shows that the relative timing of administration of cyclosporine and sirolimus significantly affects the blood concentrations of sirolimus.

Adult↗
PubMed1998

Transcutaneous electrical nerve stimulation (TENS) for adjuvant pain-relief during labor and delivery.

OBJECTIVE: We examined the efficacy of transcutaneous electrical nerve stimulation (TENS) in general and the new Freemom TENS device (LifeCare, Israel) in particular, for pain relief during labor and delivery. METHODS: The study group consisted of 104 women. Forty-six nulliparas (44.2%) and 58 multiparas (55.8%), all of whom used the TENS device for pain relief during labor. All participants completed a questionnaire on the degree of pain relief afforded them by TENS during the delivery and related questions. The objective evaluation was based on the documented labor and delivery parameters including medical interventions during delivery. RESULTS: The majority of subjects (72% of the nulliparas and 69% of the multiparas) considered TENS effective for the relief of pain during labor. Most of them (67% of the nulliparas and 60% of the multiparas) responded positively to the use of TENS in future deliveries. Sixty-five percent of the multiparas considered TENS at least as effective as the other pain relief methods they had used before. TENS significantly reduced the duration of the first stage of labor P < 0.001 for nulliparas, P < 0.005 for multiparas and it significantly decreased the amount of analgesics administered to individual patients. No significant difference was found in fetal heart rate tracings, Apgar scores and cord blood pH between the study group and an equal number of matched controls who used other forms of pain management. CONCLUSIONS: TENS is an effective non-pharmacological, non-invasive adjuvant pain relief modality for use in labor and delivery. TENS application reduced the duration of the first stage of labor and the amount of analgesic drug administered. There were no adverse effects on mothers or newborns.

Adolescent↗
PubMed1998

Fracture of the clavicle in the newborn following normal labor and delivery.

OBJECTIVE: Earlier works have associated neonatal clavicular fracture (0.2-3.5% of all deliveries) with a range of procedural, fetal and maternal risk factors; more recent studies, however, have failed to firmly identify any one or a combination of them. In the present work we sought to determine possible ante/intra-partum risk factors for this condition. STUDY DESIGN: Using a retrospective case-controlled approach, we examined a series of maternal, fetal and pregnancy or delivery-related variables in 87 cases (out of 403) of fractured clavicle of the newborn diagnosed in our department from 1986 to 1994. All infants were delivered vaginally (in the occipito-anterior position) at term by a specialist obstetrician and underwent peripartum sonographic fetal weight estimation. All variables were compared with those of an equal number of infants born immediately before or after each affected infant and delivered by the same obstetrical team. RESULTS: Fractured clavicles were found in 1.65% of the total number of deliveries during the study period. Neonatal clavicular fracture was significantly and directly related to the duration of the second stage of labor, peripartum sonographic fetal weight estimation, and neonatal length, and inversely related to maternal height; nevertheless, all values in both the study and control groups were within normal range. Logistic regression analysis showed that these antenatal variables significantly affect the chances of clavicular fracture, but due to the high false-positive rate they cannot serve clinically as a comprehensive antenatal prediction index. CONCLUSIONS: The majority of clavicular fractures occur in normal newborns following normal labor and delivery. The risk factors we identified statistically do not offer a method for clinical prenatal prediction. This work provides statistical evidence of the nature of this complication of early newborn life.

Adult↗
PubMed1998

Preimplantation diagnosis of common aneuploidies by the first- and second-polar body FISH analysis.

PURPOSE: A low pregnancy rate in in vitro fertilization (IVF) patients of advanced maternal age may be caused by aneuploidies originating from non disjunction in the first or second meiotic divisions. We introduced genetic testing of oocytes by sampling and fluorescent in situ hybridization (FISH) analysis of the first and second polar bodies, to avoid fertilization and transfer of aneuploid oocytes in IVF patients of advanced maternal age. METHODS: Three hundred and sixty-three IVF patients 34 years and older participated in the study. Using micromanipulation procedures, the first and second polar bodies were removed following their extrusion from the oocytes and studied by FISH, using probes specific for chromosomes 13, 18, and 21 to detect oocytes with common aneuploidies. RESULTS: Of a total of 538 IVF cycles, 3250 oocytes were available for FISH analysis, with conclusive FISH results in 2742 oocytes (84.3%). As many as 1102 (40%) of oocytes were predicted to be aneuploid and not transferred. Of 1640 embryos predicted to be normal, 1145 were transferred in 467 treatment cycles, resulting in 107 pregnancies (23%), from which 67 healthy children have been born, 32 pregnancies spontaneously aborted, and 15 pregnancies are ongoing after being confirmed normal by prenatal diagnosis. CONCLUSIONS: Preimplantation diagnosis by first- and second-polar body FISH analysis allows us to avoid the age-related risk of common aneuploidies in IVF patients of advanced maternal age.

Aneuploidy↗
PubMed1998

Vaginal delivery following caesarean section-the use of oxytocin and prostaglandins.

Five hundred and twenty women with one previous caesarean section underwent a trial of labour in our department during the past five years. They were divided into three groups-those receiving oxytocin, those receiving prostaglandins, and those unstimulated who had spontaneous labour. The obstetric outcomes were compared. Rates of vaginal delivery in the three groups were 65%, 67% and 72%, respectively. No mother died and there were no cases of complete uterine rupture. Our results confirm similar reports that vaginal delivery after a previous caesarean section can be safely achieved in about two-thirds of patients. Serious complications are minimal when the use of oxytocin and prostaglandins is carefully monitored.

Journal Article↗
PubMed1998

Management of meconium-stained neonates.

We examined the use of a new scoring system for the meconium-stained infant, which was designed to help the neonatologist decide on the appropriate therapeutic approach in the delivery room. Eighty meconium-stained infants were scored for: presence of fetal distress; meconium quality; performance of nasopharyngeal suctioning before the first breath and clinical condition in the first minute of life. Management consisted of gentle oropharyngeal suctioning or intubation and tracheal suctioning. Clinical outcome was compared with that of 100 meconium-stained infants born a year earlier. All babies in the control group underwent laryngoscopy and 30% were subsequently intubated. Universal laryngoscopy was not performed in the study group, and only 22.5% of these infants were intubated. The clinical outcome of the studied babies was identical to that of the newborns treated by the standard procedure. The use of the meconium intubation score eliminated the need for universal delivery room laryngoscopy for meconium-stained infants and significantly reduced the number of intubations performed.

Journal Article↗
PubMed1998

A limited sampling strategy for the estimation of eight-hour neoral areas under the curve in renal transplantation.

Neoral, the microemulsion formulation of cyclosporine (CsA), demonstrates more consistent bioavailability than the corn oil formulation Sandimmune. Because of Neoral's rapid peak and metabolism, 8-hour dosing has to be used in many pediatric and some adult patients to maintain adequate CsA peak-to-trough ratios. Although the area under the curve (AUC) is considered the best estimate of total drug exposure, it requires repeated blood sampling. Abbreviated AUC profiles yielding excellent estimates of Neoral AUC with twice daily dosing have been described, but no such abbreviated strategy exists for 8-hour dosing. One hundred fifty-two pharmacokinetic profiles in 23 patients were used to derive and prospectively test a limited two-sample strategy to predict Neoral AUCs in pediatric and adult patients on 8-hour dosing regimens of Neoral. The formula was derived from 69 full 8-hour CsA pharmacokinetic profiles in nine children who underwent renal transplantation. Stepwise forward linear and multiple-curve regression techniques assessed the relative importance of single and combination concentration time points to predict AUC. The abbreviated profiles were validated by comparing the mean prediction error for each regression equation. The abbreviated profile calculated by second (C2)- and fourth (C4)-hour levels (AUC = 129 + 1.84 x C2 + 4.39 x C4) correlated well with the full AUC (r2 = 0.96; p < 0001). Mean prediction error was -0.4% +/- 5.48%, and no values fell outside the clinically acceptable 15% prediction error limit. Prospectively applying the formula to 83 AUCs of 14 adults who underwent renal transplantation and were taking Neoral three times a day demonstrated an excellent fit (r2 = 0.93; p < 0.001), with 94% of predicted values falling inside the +/-15% limit. The authors describe the development of a clinically acceptable, limited sampling strategy to predict 8-hour Neoral AUCs in children and adults who underwent renal transplantation.

Adolescent↗
PubMed1998

Modified topical photodynamic therapy of superficial skin tumors, utilizing aminolevulinic acid, penetration enhancers, red light, and hyperthermia.

BACKGROUND: Photodynamic therapy (PDT) is a noninvasive selective therapy for a specific group of skin tumors. OBJECTIVE: In this study we used a modified topical medication in which ethyleneamine tetra acetic acid (EDTA) and dimethylsulphoxid (DMSO) were added to 5-aminolevulinic acid 20% (ALA) followed by exposure to a novel high output light source emitting red and infrared irradiation. METHODS: ALA 20%-EDTA 2%-DMSO 2% in a water in oil cream base was applied to the tumors. After 12 hours the tumor was exposed to red (585-720 nm; 150 mW/cm2) and near infrared irradiation (1.25-1.6 mm; 50 mW/cm2) for 10-15 minutes by the VersaLight incoherent filtered light source. RESULTS: Complete responses were achieved after one to three ALA-PDT treatments in 26/31 lesions of superficial or small nodular basal cell carcinoma (BCC) (84%), and in four of five in superficial squamous cell carcinoma (SCC) (80%). Complete clearance was achieved in one patient with Bowen's disease of the penis. CONCLUSIONS: Topical PDT utilizing ALA 20%-EDTA 2%-DMSO 2% as the photosensitizer and VersaLight as the light source is a noninvasive, nearly painless treatment with excellent therapeutic and cosmetic results. Our data show the efficiency of this therapy for patients with certain subtypes of BCC, SCC, and Bowen's disease.

Administration, Cutaneous↗