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Biomedical subjects

P Kaplan

Publications and source records attributed to P Kaplan.

At least 55 records · Page 3Linked to original sources
PubMed1996

Skeletal and cardiac malformations with thrombocytopenia: a new syndrome?

We describe a female patient with multiple anomalies suggestive of a new syndrome. Manifestations include: VSD and ASD, mild developmental delay, conductive hearing loss, minor facial anomalies, thrombocytopenia, and radiological findings (including carpal fusion). Some of these manifestations may be present in the Keutel syndrome, IVIC syndrome, and the 10qter deletion syndrome. However, none of these syndromes can explain the spectrum of anomalies seen in our patient.

Abnormalities, Multiple↗
PubMed1996

Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome.

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bone marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.

Bone Marrow Transplantation↗
PubMed1996

Expression and regulation of metallothionein mRNA levels in the prostates of noble rats: lack of expression in the ventral prostate and regulation by sex hormones in the dorsolateral prostate.

The rat prostate is composed of two anatomically well-defined regions designated as the ventral prostate (VP) and the dorsolateral prostate (DLP). VP and DLP are known to exhibit marked cytological, biochemical, and functional differences including differential susceptibilities to carcinogens. While the VP is uniquely susceptible to cadmium carcinogenicity [1,2], the DLP is sensitive to sex hormone-induced cancer [3,4]. The role played by the heavy metal binding protein, metallothionein (MT), in the prostate is largely unknown. It is still controversial as to whether MT is expressed in the rat gland. The aim of the present study is to examine the expression pattern of MT mRNA in the rat gland and its probable regulation by heavy metal ions and sex hormones, in order to gain insight into the biological function of MT in the prostate. Northern hybridization and reverse transcriptase-polymerase chain reaction analyses revealed constitutive expression of MT mRNA in the DLP and a lack of expression of the transcript in the VP. In situ hybridization localized the transcript to the epithelium of the DLP, with the lateral prostate epithelium exhibiting the highest level of expression. Administration of cadmium and zinc failed to induce MT transcription in the VP, nor were these treatments effective in elevating levels of MT mRNA in the DLP. A 60% reduction in MT message levels was observed in the DLP following orchiectomy. MT transcript levels in the DLPs of castrates were restored by readministration of androgen to the animals. Long-term treatments (16 weeks) of rats with estradiol-17 beta (E2) or testosterone (T) plus E2 induced a 2.8-fold and a 5-fold increase in MT message content in the DLP, respectively. In sum, MT mRNA was shown to be absent in the VP and was not inducible by heavy metal ions or hormones in this prostatic lobe. These findings substantiate the belief that MT plays a role in heavy metal detoxification and deficiency in its expression may contribute to the unique susceptibility of the VP to cadmium carcinogenicity. By contrast, constitutive expression of MT was demonstrated in the DLP, which was shown to be regulated by androgen and not by exogenously administered heavy metal ions. These results suggest a participatory role of MT in the normal functioning of the DLP. The fact that high levels of MT mRNA were induced in the DLP following long-term estrogenic or conjoint androgenic-estrogenic action alludes to the possibility that MT may serve as an intracellular antioxidant in DLP cells.

Androgens↗
PubMed1996

Increased prevalence of urinary symptoms and voiding dysfunction in Williams syndrome.

Thirteen of 41 patients (32%) with Williams syndrome in a multidisciplinary clinic were noted to have genitourinary symptoms. The predominant features were increased urinary frequency and daytime wetting. Four patients had bladder diverticula and uninhibited detrusor contractions as demonstrated on urodynamic studies. We speculate that there may be an association between increased detrusor pressure, an abnormal bladder matrix, and the presence of diverticula. Early detection of urinary dysfunction through clinical symptoms and appropriate urodynamic studies, with institution of bladder training and anticholinergic medication can improve the patients' voiding patterns, both medically and socially.

Adolescent↗
PubMed1996

Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase.

OBJECTIVES: The incidence and severity of growth retardation in children with type 1 Gaucher disease and the response to enzyme replacement therapy with alglucerase were studied. STUDY DESIGN: A retrospective analysis of growth in 99 children and adolescents with type 1 Gaucher disease before treatment, and in 54 of those subjects during treatment, was done. Growth was compared with gender, age, and dosage of replacement enzyme. RESULTS: Linear growth was normal in the first 1 to 2 years of life and then decelerated. Height was at or below the 5th percentile in 50% of all subjects immediately before treatment. The mean z score was -1.49 (95% confidence interval, -1.83 to -1.16), corresponding to the 6.8th percentile for height. Seventy-two percent were below the 50th percentile and 50% were at or below the 5th percentile for mid-parental height (p <0.001). One and one-half years after treatment was started, the estimated mean z score for all subjects was -1.01, which corresponds to the 16th percentile for height. Normal growth was achieved within 4 to 30 months in eight of nine subjects who were at or below the 5th percentile. It occurred only in those receiving higher doses (60 to 120 U/kg per 4-week period) of alglucerase. There was a significant association between z scores for height before treatment and liver enlargement (r= 0.57; p < 0.01). CONCLUSIONS: Half of the subjects who manifest type 1 Gaucher disease in childhood have growth retardation. Treatment with adequate amounts of modified enzyme replacement was effective in normalizing linear growth.

Adolescent↗
PubMed1996

Lessons from the late diagnosis of isovaleric acidemia in a five-year-old boy.

Chronic, intermittent isovaleric acidemia was undiagnosed in a boy with an increased anion gap metabolic acidosis until the boy was 5 years of age. This case emphasizes the importance of maintaining a high index of suspicion for inborn errors of metabolism in patients with metabolic acidosis, even in late childhood.

Acid-Base Equilibrium↗
PubMed1996

Immunocytochemical localization of growth factors and their receptors in human pre-embryos and Fallopian tubes.

We utilized indirect immunocytochemistry to demonstrate the presence of growth factors and their receptors in human pre-embryos and Fallopian tubes. In pre-embryos, only transforming growth factor-alpha (TGF-alpha) and the intracellular domain of epidermal growth factor receptor (EGFR) were found at the 4-cell stage. In 8- to 14-cell pre-embryos, TGF-alpha, the intracellular and extracellular domains of EGFR, and insulin-like growth factor-I and its receptor were found. Antibodies against TGF-alpha stained all Fallopian tube specimens, while the extracellular domains of EGFR was only found in specimens from patients with either blood type A or AB. These results suggest a cross-reactivity between the extracellular domain of the EGFR and blood group antigens. Our novel demonstration of growth factor receptor staining in human pre-embryos shows that growth factor receptor localization is dependent on the developmental stage of human pre-embryos. We have also established a potentially important link between the Fallopian tube which secretes growth factors and the localization of growth factor receptors in pre-embryos. These findings are compatible with the hypothesis that tubal secretions are embryotrophic for the early development of the pre-embryo.

Adult↗
PubMed1996

Molecular definition of the chromosome 7 deletion in Williams syndrome and parent-of-origin effects on growth.

Williams syndrome (WS) is a developmental disorder with variable phenotypic expression associated, in most cases, with a hemizygous deletion of part of chromosomal band 7q11.23 that includes the elastin gene (ELN). We have investigated the frequency and size of the deletions, determined the parental origin, and correlated the molecular results with the clinical findings in 65 WS patients. Hemizygosity at the ELN locus was established by typing of two intragenic polymorphisms, quantitative Southern analysis, and/or FISH. Polymorphic markers covering the deletion and flanking regions were ordered by a combination of genetic and physical mapping. Genotyping of WS patients and available parents for 13 polymorphisms revealed that of 65 clinically defined WS patients, 61 (94%) had a deletion of the ELN locus and were also hemizygous (or noninformative) at loci D7S489B, D7S2476, D7S613, D7S2472, and D7S1870. None of the four patients without ELN deletion was hemizygous at any of the polymorphic loci studied. All patients were heterozygous (or noninformative) for centromeric (D7S1816, D7S1483, and D7S653) and telomeric (D7S489A, D7S675, and D7S669) flanking loci. The genetic distance between the most-centromeric deleted locus, D7S489B, and the most-telomeric one, D7S1870, is 2 cM. The breakpoints cluster at approximately 1 cM to either side of ELN. In 39 families informative for parental origin, all deletions were de novo, and 18 were paternally and 21 maternally derived. Comparison of clinical data, collected in a standardized quantifiable format, revealed significantly more severe growth retardation and microcephaly in the maternal deletion group. An imprinted locus, silent on the paternal chromosome and contributing to statural growth, may be affected by the deletion.

Adult↗
PubMed1996

Determination of coenzyme Q in human plasma.

Coenzyme Q10 (CoQ10) levels in human plasma were determined by high-performance liquid chromatography (HPLC) with UV detection. CoQ10 was dissociated from lipoproteins by methanol and subsequently cleaned-up on silica gel and octadecyl silica solid-phase extraction cartridges. HPLC separation was performed on a C18 reversed-phase column. The methanol-hexane mobile phase provided a greater possibility of separation procedure adjustment allowing the shortest possible elution time without loss of resolution than a two-alcohol mobile phase. Quantitation was based on the peak heights using a standard addition method. The lower limit of detection was 8 ng on-column, corresponding to 90 micrograms ubiquinone per litre of plasma in an actual sample. Thirty-one randomly selected plasma samples from apparently healthy, 18 to 56-year-old individuals (males and females) were analyzed for total CoQ10. The average level in these subjects was 0.47 +/- 0.18 mg/l with the range of 0.26-1.03 mg/l. The method was also applied to the determination of ubiquinone plasma level changes in one healthy volunteer over a period of one month and after oral intake of CoQ10.

Adolescent↗
PubMed1995

Cystic kidney disease in Hajdu-Cheney syndrome.

We report on 2 unrelated patients with Hajdu-Cheney acroosteolysis syndrome, who had cystic kidneys with ultrasonographic changes similar to those of autosomal dominant polycystic kidney disease. Neither had a family history of Hajdu-Cheney syndrome or polycystic kidneys, nor manifestations of any other syndrome. On the basis of the findings in these 2 patients and a review of published cases, we suggest that cystic kidneys are an important component of Hajdu-Cheney syndrome.

Fatal Outcome↗
PubMed1995

Reversible metabolic myopathy in biotinidase deficiency: its possible role in causing hypotonia.

A 5-year-old girl diagnosed with biotinidase deficiency at 9 months of age demonstrated limb and axial hypotonia which improved on biotin therapy. In this patient, electromyographic (EMG) studies prior to treatment were compatible with a mild myopathic process. Serial EMGs performed on biotin therapy demonstrated a gradual resolution of the myopathy. This is the first documented case of a reversible myopathy in a patient with biotinidase deficiency, which may contribute to the clinical findings of hypotonia.

Amidohydrolases↗
PubMed1995

Relationship between circulating human chorionic gonadotropin levels and premature luteinization in cycles of controlled ovarian hyperstimulation.

OBJECTIVE: To determine if premature luteinization (serum P levels > 1.1 ng/mL on or before the day of hCG administration) during controlled ovarian hyperstimulation (COH) is associated with elevated levels of serum hCG. SETTING: Tertiary fertility center. DESIGN: Retrospective evaluation of ovum donors undergoing COH. PATIENTS: Forty-four women underwent COH. Comparisons of serum hCG levels and hormonal and cycle characteristics were made between cycles with premature luteinization (group I) and without premature luteinization (group II). RESULTS: Group I (16 women) were similar to women in group II in age, amount of hMG, and the ratio of FSH:hMG received. Both groups received hCG on similar days, but women in group I had higher peak E2 levels. Serum hCG levels increased and correlated with serum P levels in group I only and were higher on the day of hCG administration (group I 1.8 +/- 0.9 mIU/mL versus group II 1.2 +/- 0.45 mIU/mL; conversion factor to SI unit, 1.00). Peak E2 and LH levels, ampules of hMG and the FSH:LH ratio, and day of hCG administration did not correlate with hCG levels. Human chorionic gonadotropin exposure, as measured by area under the curve, was significantly higher in group I compared with group II. CONCLUSION: Higher serum levels of hCG and integrated hCG exposure are found in COH cycles with premature luteinization compared with cycles without premature luteinization. Higher hCG levels may be due to decreased clearance of hCG from the circulation and/or the hCG content of hMG.

Adult↗
PubMed1995

Cerebral artery stenoses in Williams syndrome cause strokes in childhood.

Extensive narrowing of lumens of many cerebral arteries caused strokes with brain damage and chronic hemipareses in two children with Williams syndrome. Increased irritability, loss of consciousness, and seizures were initial signs. Arterial stenoses are not limited to the supravalvular aorta and pulmonary arteries in patients with Williams syndrome.

Adult↗
PubMed1995

Painful keratoderma and photophobia: hallmarks of tyrosinemia type II.

Tyrosinemia type II (Richner-Hanhart syndrome), which is caused by a deficiency of hepatic tyrosine aminotransferase, results in elevated plasma and urinary tyrosine concentrations. We describe a young boy who was seen at 6 months of age with red eyes, photophobia, and eye pain that were not suspected to be caused by tyrosinemia II until painful plantar keratoderma developed at 2 1/2 years of age. Treatment with a diet low in tyrosine and phenylalanine reversed the manifestations of the disease.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

Psychostimulants apparently reverse sexual dysfunction secondary to selective serotonin re-uptake inhibitors.

Sexual dysfunction secondary to selective serotonin re-uptake inhibitors (SSRIs) is an almost universal, yet pooly understood phenomenon. Not uncommonly, this unpleasant side effect leads to noncompliance. Since SSRIs have been so successful clinically, it is time to find a safe and effective treatment for this side effect. This paper reports on five cases in which low dosages of the psychostimulants, dextroamphetamine and methylphenidate, administered on a p.r.n. basis, reversed the sexually inhibiting side effects of the SSRIs fluxetine, setraline, and paroxetine in patients with and without attention deficit hyperactivity disorder. In addition, the women experienced enhanced levels of arousal, orgasmic sensation and excitement during the resolution phase (afterglow) of the sexual response cycle on psychostimulants, and the men noted firmer erections.

Adult↗
PubMed1995

Abnormal morphology of fibrillin microfibrils in fibroblast cultures from patients with neonatal Marfan syndrome.

The Marfan syndrome (MFS) is a connective tissue disorder manifested by variable and pleiotropic features in the skeletal, ocular, and cardiovascular systems. The average life span in MFS is about 35 years. A group with much more severe cardiovascular disease and a mean life span of approximately 1 year also exists. We refer to this latter group as "neonatal Marfan syndrome" (nMFS). Fibrillin defects are now known to be the cause of MFS and nMFS. Immunofluorescence studies were the first to demonstrate this association. Here we describe immunofluorescence studies in a series of 10 neonates and summarize their salient clinical features. In vitro accumulation of fibrillin reactive fibers was assayed using monoclonal antibodies to fibrillin in hyperconfluent fibroblast cultures. As was previously observed in MFS, fibroblast cultures from nMFS patients showed an apparent decrease in accumulation of immunostainable fibrillin. Significantly, however, the morphology of the immunostained fibrils in the nMFS cultures were abnormal and differed not only from control cultures, but also from those seen in cultures of MFS fibroblasts. The nMFS fibrils appeared short, fragmented, and frayed, characteristics that are not seen in MFS. Both the clinical and fibrillin morphology data provide evidence to suggest a useful subclassification of nMFS in the spectrum of MFS.

Cells, Cultured↗