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Biomedical subjects

P Kramer

Publications and source records attributed to P Kramer.

At least 19 recordsLinked to original sources

Effects of cyclosporin A on glomerular barrier function in the nephrotic syndrome.

1. To elucidate the mechanisms by which cyclosporin A diminishes proteinuria, we studied 20 patients with severe nephrotic syndrome. Biopsy-established pathologies included minimal change disease (n = 5), membranous glomerulopathy (n = 6), membranoproliferative glomerulonephritis (n = 5) and focal segmental glomerulosclerosis (n = 4). Before, at the end of a 90 day course of cyclosporin A, and finally 1 month after stopping cyclosporin A we determined 24 h protein excretion. Measurements of glomerular filtration rate, effective renal plasma flow, fractional clearance rates of albumin and immunoglobulins with different charges and the transglomerular sieving of uncharged dextrans of broad size distribution were used to study the effects of cyclosporin A on renal perfusion and the glomerular filtration barrier. The findings were analysed with a theoretical model of solute transport. 2. Among the different forms of glomerulopathy the response to low-dose cyclosporin A (trough levels 32.0-36.9 ng/ml) varied markedly. In minimal change disease, proteinuria decreased from 9.5 +/- 3.1 to 1.3 +/- 0.2 g/24 h (mean +/- SEM, P less than 0.01). This response was due to restoration of the charge selectivity of the glomerular barrier. The depressed value of the glomerular permeability coefficient also returned to normal. Glomerular filtration rate, effective renal plasma flow and renal vascular resistance did not change. Proteinuria returned after stopping cyclosporin A, although it did not reach pretreatment levels. In membranous glomerulopathy, proteinuria fell from 9.9 +/- 1.5 to 1.8 +/- 0.3 g/24 h (P less than 0.01). Changes in protein excretion and dextran sieving were compatible with an increase in glomerular permselectivity and a decrease in filtrate flow through the 'shunt' pathway. Glomerular filtration rate was maintained, although effective renal plasma flow fell significantly. Proteinuria relapsed after stopping cyclosporin A. In membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis proteinuria did not respond to cyclosporin A, although cyclosporin A exerted important haemodynamic effects. 3. In minimal change disease and membranous glomerulopathy cyclosporin A exerts its beneficial effects on proteinuria through changes in the properties of the glomerular barrier, resulting in increased charge and size selectivity, respectively.

Adult

Prepubertal reduction of the ovarian follicle population by combined LH-releasing hormone antagonist treatment and unilateral ovariectomy influences follicle characteristics but not the ovulation rate at first oestrus.

The effect on first ovulation of the massive reduction of the total pool of ovarian follicles during the infantile and late juvenile period was studied in rats. Treatment with an LH-releasing hormone antagonist (LHRH-A) during infancy (5 mg/kg body weight on days 6, 9, 12 and 15 of life) was combined with unilateral ovariectomy performed on either day 15 (early ULO) or 2-5 days before the expected day of first ovulation (late ULO). Rats were killed on the day of first or second oestrus, when blood was collected and the (remaining) ovaries were prepared for differential counting of follicles and corpora lutea. In addition, blood was sampled 8 h after ULO and the ovaries studied histologically in the group of rats which were unilaterally ovariectomized 2-5 days before first ovulation. The time of first ovulation was not influenced by treatment with LHRH-A, early or late ULO, or a combination of LHRH-A treatment and ULO. Ovulation rate after LHRH-A treatment was decreased, but was still within the normal range in intact rats and in early ULO rats compared with saline-treated controls. Serum FSH concentrations 8 h after ULO performed 2-5 days before first ovulation were similar in saline- and LHRH-A-treated rats (845 +/- 59 and 801 +/- 99 (S.E.M.) micrograms/l respectively) and had increased compared with intact controls (216 +/- 15 micrograms/l). Treatment with LHRH-A resulted in a reduction of more than 50% in healthy and atretic follicles, and late ULO reduced the number of healthy follicles even further.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Outcomes assessment and program evaluation: partners in intervention planning for the educational environment.

Accountability of educational institutions is a current trend in academia. Outcomes assessment provides a method of evaluating educational programs to ensure they are meeting their objectives. This paper presents an overview of outcomes assessment and describes its relationship to and integration with program evaluation. It also describes the implementation of an outcomes assessment program at Kean College of New Jersey, Union, New Jersey. A model for assessment within occupational therapy programs, which parallels a model for intervention planning, is introduced and discussed.

Curriculum

High-resolution mapping of the X-linked hypohidrotic ectodermal dysplasia (EDA) locus.

The X-linked hypohidrotic ectodermal dysplasia (EDA) locus has been previously localized to the subchromosomal region Xq11-q21.1. We have extended our previous linkage studies and analyzed linkage between the EDA locus and 10 marker loci, including five new loci, in 41 families. Four of the marker loci showed no recombination with the EDA locus, and six other loci were also linked to the EDA locus with recombination fractions of .009-.075. Multipoint analyses gave support to the placement of the PGK1P1 locus proximal to the EDA locus and the DXS453 and PGK1 loci distal to EDA. Further ordering of the loci could be inferred from a human/rodent somatic cell hybrid derived from an affected female with EDA and an X;9 translocation and from studies of an affected male with EDA and a submicroscopic deletion. Three of the proximal marker loci, which showed no recombination with the EDA locus, when used in combination, were informative in 92% of females. The closely linked flanking polymorphic loci DXS339 and DXS453 had heterozygosities of 72% and 76%, respectively, and when used jointly, they were doubly informative in 52% of females. The human DXS732 locus was defined by a conserved mouse probe pcos169E/4 (DXCrc169 locus) that cosegregates with the mouse tabby (Ta) locus, a potential homologue to the EDA locus. The absence of recombination between EDA and the DXS732 locus lends support to the hypothesis that the DXCrc169 locus in the mouse and the DXS732 locus in humans may contain candidate sequences for the Ta and EDA genes, respectively.

Base Sequence

Dopamine beta-hydroxylase gene excluded in four subtypes of hereditary dystonia.

The hereditary dystonias include a clinically heterogeneous group of movement disorders varying in symptoms, age of onset, and drug responsiveness. Dopamine beta-hydroxylase (DBH), the enzyme that converts dopamine to norepinephrine, has been implicated in dystonia because of increased serum levels of DBH in some patients, the influence of catecholaminergic drugs on the human phenotypes, and altered norepinephrine levels in several brain regions in dystonia patients and in genetically dystonic rodents. In addition, markers linked to the dystonia gene in two ethnic groups map close to the DBH locus on human chromosome 9q34. Here we evaluate the inheritance of restriction fragment length polymorphisms near the DBH gene in families with four subtypes of hereditary dystonia: Jewish and non-Jewish, early onset, generalized idiopathic torsion dystonia (ITD); dopa-responsive dystonia; and myoclonic dystonia. In all families, obligate recombination events were observed between the DBH and dystonia genes, thus excluding the DBH gene as the primary defect.

Adolescent

A model for perceived spatial frequency and spatial frequency discrimination.

The responses of labelled spatial frequency channels are combined to generate an index of perceived spatial frequency. Spatial frequency discrimination thresholds are shown to be inversely related to the slope of the function of the index vs spatial frequency, when it is plotted on log-log co-ordinates.

Discrimination, Psychological

Tumor localization in nude mice bearing human breast carcinoma xenografts using 111In-DTPA conjugates of monoclonal antibodies.

Biodistribution of monoclonal antibody T43 and its F(ab')2 111In-DTPA conjugates were determined in nu/nu mice bearing human breast tumor and rat pituitary tumor xenografts. T43 localized in the target tumor with tumor/blood ratios of 3.9 (P less than 0.01) and 4.5 (P less than 0.05) at 48 and 72 h, respectively. T43 F(ab')2 fragments localized with tumor/blood ratio of 14.2 (P less than 0.1) at 72 h. Tumors as small as 4 mm were detected without computer subtraction technique. These studies suggest that T43 and T43 F(ab')2 might be useful reagents in radioimaging.

Animals

Initial ovulation rate and follicle population after injection of inhibin-neutralizing antiserum in the late-prepubertal rat.

In late-prepubertal female rats passive immunoneutralization of endogenous inhibin was achieved by injection of inhibin antiserum. Effects on follicle population, timing of sexual maturation, ovulation rate at first and second oestrus and serum FSH levels were studied. Rats were injected with antiserum, (non-immune) control serum from castrated sheep (castrated serum) or their IgG fractions, or with saline on day 33 or 3 or 2 days (days -3/-2) before the expected day of first ovulation, day 38.5 +/- 0.2 (n = 70). Blood was collected from different subgroups at 8, 24 and 48 h, and at first and second oestrus after injection. At necropsy, ovaries were histologically prepared for differential counting of follicles (48 h and first oestrus) and counting of corpora lutea (CL; first and second oestrus) as an index of ovulation rate. Results from rats injected with either serum or its IgG fraction were not different, as was the case when rats were injected with either castrated serum or saline. Thus, results from groups treated with antiserum and antiserum IgG were combined and labelled 'antiserum', and the castrated serum, castrated serum IgG and saline-treated groups were combined and labelled 'control'. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by 43% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Ovulation rate, follicle population and FSH levels in cyclic rats after administration of an inhibin-neutralizing antiserum.

Ovulation rate, follicle growth, serum FSH and oestradiol concentrations were studied after a single intraperitoneal injection of inhibin antiserum in 5-day-cyclic rats. Control rats received (non-immune) serum from castrated sheep or saline. Rats were injected at 10.00 h on dioestrus-1 (D1), i.e. the day following the day of oestrus, or at 17.00 h on dioestrus-2 (D2). The ovaries were excised at necropsy 48 h after injection, or at first or second oestrus after injection. After routine histology fresh corpora lutea were counted and/or differential follicle counts were made. Results from rats injected with either (non-immune) serum from castrated sheep or with saline were not different and were therefore combined to form the control group. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by approximately 39% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin. Rats were injected on D1 and killed at first oestrus. The number of fresh corpora lutea was significantly higher in antiserum-treated rats than in controls (13.9 +/- 0.4 vs 11.8 +/- 0.4; P less than 0.05). Other rats injected on D1 were killed either 48 h or at the second oestrus after injection. Blood was collected 8, 16, 24 and 48 h and at first and second oestrus after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The N-methyl-D-aspartate receptor antagonist MK-801 delays the onset of puberty and may acutely block the first spontaneous LH surge and ovulation in the rat.

The physiological role of activated hypothalamic N-methyl-D-aspartate (NMDA) receptors during the final phase of female sexual maturation was explored in the rat. The effects of administration of the specific non-competitive receptor antagonist MK-801 on the occurrence of first ovulation and on LH secretion were studied. Injections of MK-801 (0.1-0.2 mg/kg body wt, s.c.) were given once or twice daily, starting at 28 or 35 days of age and continuing up to the day of first ovulation, resulted in a significant delay of this ovulation. Rats that were treated daily with 0.2 mg MK-801/kg, starting on days 30 or 34 and continuing up to day 38, but not including the day of first pro-oestrus, also showed retarded first ovulation. No decrease in serum LH concentration, compared with control rats, could be detected in these rats. Acute treatment with MK-801 (one or two injections of 0.2, or one injection of 0.5 mg/kg) given at 11.30 h (and 16.00 h) on the day of first pro-oestrus produced partial (1 x 0.2 mg/kg) or complete (2 x 0.2 and 1 x 0.5 mg/kg) blockade of first ovulation; blocked rats ovulated 1 day later. Serum LH concentrations at 16.00 h on the day of pro-oestrus were significantly decreased in all MK-801-treated groups compared with saline-injected control rats. At 19.00 and 22.00 h LH concentrations remained low in all non-ovulating MK-801-treated rats, but increased in the MK-801-treated rats and ovulated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Retroperitoneal fibrosis: report of 12 cases and a review of the literature.

Twelve patients with retroperitoneal fibrosis (RPF) over a 10-yr period (1980-1990) are reviewed. The clinical manifestations, radiographic findings as well as treatment and follow-up are discussed and a review of the literature is presented. Nowadays the diagnosis can be established with near-certainty by means of computed tomographic scan (CT). In case of diagnostic problems, CT- or ultrasound guided percutaneous needle biopsy can aid the diagnosis. There is now considerable evidence that RPF can be treated effectively with corticosteroids and should be considered the treatment of choice, surgery being confined to medical failures or those who do not tolerate steroids. Early and frequent CT follow-up may demonstrate the beneficial response to steroids, thereby obviating the need for exploratory or therapeutic surgery. In steroid-resistant cases, when there is no doubt about the initial diagnosis, azathioprine or cyclophosphamide may be used. Long-term follow-up is recommended in all patients.

Adrenal Cortex Hormones

Percutaneous balloon mitral valvuloplasty in a pregnant woman with mitral stenosis, sickle cell crisis and acute pulmonary edema. A case report.

A woman with acute congestive heart failure secondary to mitral stenosis and sickle cell crisis was treated successfully with a combination of an exchange transfusion and percutaneous balloon valvuloplasty. That combination provided an alternative to surgical mitral commissurotomy, with its significant risks for both the mother and fetus. The patient was able to undergo an uncomplicated pregnancy course despite the increased risk of cardiac decompensation in the intrapartum and postpartum period.

Adult

Cyclic changes in conjunctival smears from menstruating females.

Cytohormonal evaluation has become an accurate procedure for the assessment of estrogenic effect on the vaginal and buccal mucosa. Both show a cyclical variation in the maturation index (an "estrogenic value" based on epithelial maturation). Conjunctival smears were taken from the temporal conjunctiva of 11 premenopausal and 7 postmenopausal females on a near-daily basis. No females had evidence of ocular surface disease, including keratoconjunctivitis sicca. After fixation and Papanicolaou staining, maturation indices for each specimen based on the differential morphology were red in a single blind fashion by a Papanicolaou cytologist. Cyclical variations paralleling the menstrual cycle in eight of nine premenopausal women were noted with maturation index values ranging from 30 (low estrogen effect) to 82 (high estrogen effect), peaking on day 11 or 21 of the menstrual cycle. No cyclical change was found in postmenopausal smears and smears of subjects with endocrine abnormalities. Maturation index values ranged from 30 to 38. Conjunctiva appears to be an estrogen-sensitive epithelium.

Cell Division

Effects of a luteinizing hormone-releasing hormone antagonist in late-juvenile female rats: blockade of follicle growth and delay of first ovulation following suppression of gonadotropin concentrations.

Subcutaneous injections of an antagonist against luteinizing hormone-releasing hormone (LHRH-A, Org, 30276) were administered to late-juvenile female rats. The effects on timing of vaginal opening and first ovulation on serum gonadotropin concentrations and on follicle growth were studied. The dose of 100 micrograms LHRH-A/100 g body wt, given on Days 28, 31, and 34, did not influence timing of first ovulation. After administration of 500 micrograms LHRH-A/100 g body wt, ovulation was retarded by 4.7 days if injections were given on Days 28 and 31; by 6.7 days if given on Days 28, 31, and 34; and by 11.5 days if given on Days 28, 31, 34, and 37. Serum LH and FSH concentrations 3 days after the first, second, and third injections of 500 micrograms LHRH-A were significantly (p less than 0.01) lower than in saline-treated controls. Ovarian follicle counts showed decreased numbers of (antral) Class 2, 3, and 4 follicles 3 days after injection of 500 micrograms LHRH-A/100 g body wt on Day 28; a significantly higher number of Class 1 follicles and a further decrease in Class 2, 3, and 4 follicles 3 days after the second LHRH-A injection; and total absence of Class 3, 4, and 5 follicles 3 days after the third LHRH-A injection. Six days after the third LHRH-A injection, Class 3 and 4 follicles reappeared in the ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hepatitis B vaccination of haemodialysis patients: randomized controlled trial comparing plasma-derived vaccine with and without pre-S2 antigen.

The pre-S2 protein of the hepatitis B virus envelope evokes anti-pre-S2 antibodies and enhances the anti-HBs response after vaccination in mice. In order to evaluate the immunogenicity of the pre-S2 Ag in man, 102 HBsAg, anti-HBs, anti-HBc-negative haemodialysis patients were vaccinated at random according to one of four vaccination schedules: 5 micrograms plasma vaccine Pasteur (containing 1% pre-S2) or 20 micrograms plasma vaccine MSD (no pre-S2) at 0, 1, 2, 4, 6 and 12 months; or 10 micrograms Pasteur or 40 micrograms MSD at 0, 1, 2 and 6 months. Anti-HBs levels were measured by RIA and expressed in IU l-1; anti-pre-S2 response was evaluated by both EIA and Western blot analysis. Eighty-four per cent (95% confidence interval: 75-93) of the patients exhibited an anti-HBs response of 2 IU l-1 or more and 71% (95% confidence interval: 61-81) reached an anti-HBs level of at least 10 IU l-1 within 13 months of the start of vaccination. Anti-HBs response correlated with age (the response rate decreased with increasing age) but not with either the type of vaccine or dosage. An anti-pre-S2 response was observed in 16% (EIA) and 46% (Western blot) of the patients immunized with the Pasteur vaccine and none (EIA, Western blot) of the MSD group. The level of anti-pre-S2 antibodies correlated with high anti-HBs titres; an anti-pre-S2 response occurred in only one anti-HBs-negative patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of immunomodulator thymopentin on impaired seroresponse to influenza vaccine in patients on haemodialysis.

In a double-blind placebo-controlled multicentre study, the effect of the immunomodulator thymopentin (TP5) on the antibody production to trivalent influenza vaccine was tested in 108 patients on chronic intermittent haemodialysis (HD). Antibody production was determined in pre- and postvaccination sera. Compared to a group of 35 young healthy adult control subjects, HD patients showed a clearly impaired seroresponsiveness to all three vaccine components, regardless of treatment with TP5 or placebo. We conclude that TP5 administration is not able to enhance humoral immunity in patients on chronic intermittent HD.

Adolescent

Short- and long-term effects of an LHRH antagonist given during the prepubertal period on follicle dynamics in the rat.

The effects of the suppression of the high gonadotrophin concentrations normally present by the end of the second week of life on ovarian follicle dynamics were studied in immature rats. Gonadotrophins were suppressed by treatment with an LHRH antagonist (LHRH-A; Org. 30276) on days 6, 9, 12 and 15, and the total population of ovarian follicles was studied at 15 and 28 days, on the day of first oestrus and on the day of oestrus at or following 90 and 300 days of age. Primordial follicles were counted and growing follicles were counted and measured. In rats treated with LHRH-A, follicle recruitment into the growing pool was clearly diminished; the number of growing follicles was significantly (P less than 0.01) lower up to the day of first oestrus and the pool of primordial follicles was significantly (P less than 0.05) larger at 15 and 28 days. Ovarian weights were significantly lower in rats treated with LHRH-A until at least 90 days of age. However, on the day of oestrus at or after 90 and 300 days of age, there were no differences in either the pool of primordial follicles or the pool of growing follicles between rats treated with LHRH-A and control rats. There was also no difference between groups in the number of fresh corpora lutea at these ages. It was concluded that the early peak in gonadotrophin concentrations in immature rats causes substantial recruitment of follicles into the growing pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals