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Biomedical subjects

J Friedman

Publications and source records attributed to J Friedman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Timing of voiding cystourethrogram in the investigation of urinary tract infections in children.

OBJECTIVE: To determine whether the detection of vesicoureteral reflux (VUR) in children with a urinary tract infection (UTI) is more likely if the voiding cystourethrogram (VCUG) is performed early (within the first 7 days after diagnosis) or late (>7 days after diagnosis). STUDY DESIGN: We conducted a retrospective case review of children <5 years of age admitted with a first episode of UTI to a tertiary care pediatric hospital over a 2-year period. Timing of the VCUG was at the discretion of the attending pediatrician. Differences in age, sex, mean time to performing the VCUG, and incidence of VUR between the 2 groups (VCUG performed early vs late) were compared by using Student t test (for age) and chi(2) test (for sex and incidence of VUR). Potential confounders (age and sex) were included in a multiple logistic regression analysis. RESULTS: A total of 162 patients were eligible for inclusion. Mean age was 181 days, and 43.8% were female. The incidence of VUR was 21.6%. The early group consisted of 82 patients, and the late group consisted of 80. No significant difference was found for age or sex or for the incidence of reflux (17.1% vs 26.3%, P =.219), with a crude odds ratio of.59 (95% CI 0.3-1.2, P >.05). CONCLUSION: The rate of detection of VUR in children with a first episode of UTI does not increase when the VCUG is done early (within the first 7 days of diagnosis) rather than later.

Age Factors↗
PubMed2001

Allelopathic bacteria and their impact on higher plants.

The impact of allelopathic, nonpathogenic bacteria on plant growth in natural and agricultural ecosystems is discussed. In some natural ecosystems, evidence supports the view that in the vicinity of some allelopathically active perennials (e.g., Adenostoma fasciculatum, California), in addition to allelochemicals leached from the shrub's canopy, accumulation of phytotoxic bacteria or other allelopathic microorganisms amplify retardation of annuals. In agricultural ecosystems allelopathic bacteria may evolve in areas where a single crop is grown successively, and the resulting yield decline cannot be restored by application of minerals. Transfer of soils from areas where crop suppression had been recorded into an unaffected area induced crop retardation without readily apparent symptoms of plant disease. Susceptibility of higher plants to deleterious rhizobacteria is often manifested in sandy or so-called skeletal soils. Evaluation of phytotoxic activity under controlled conditions, as well as ways to apply allelopathic bacteria in the field, is approached. The allelopathic effect may occur directly through the release of allelochemicals by a bacterium that affects susceptible plant(s) or indirectly through the suppression of an essential symbiont. The process is affected by nutritional and other environmental conditions, some may control bacterial density and the rate of production of allelochemicals. Allelopathic nonpathogenic bacteria include a wide range of genera and secrete a diverse group of plant growth-mediating allelochemicals. Although a limited number of plant growth-promoting bacterial allelochemicals have been identified, a considerable number of highly diversified growth-inhibiting allelochemicals have been isolated and characterized. Some species may produce more than one allelochemical; for example, three different phyotoxins, geldanamycin, nigericin, and hydanthocidin, were isolated from Streptomyces hygroscopicus. Efforts to introduce naturally produced allelochemicals as plant growth-regulating agents in agriculture have yielded two commercial herbicides, phosphinothricin, a product of Streptomyces viridochromogenes, and bialaphos from S. hygroscopicus. Many species of allelopathic bacteria that affect growth of higher plants are not plant specific, but some do exhibit specificity; for example, dicotyledonous plants were more susceptible to Pseudomonas putida than were monocotyledons. Differential susceptibility of higher plants to allelopathic bacteria was noted also in much lower taxonomical categories, at the subspecies level, in different cultivars of wheat, or of lettuce. Therefore, when test plants are employed to evaluate bacterial allelopathy, final evaluation must include those species that are assumed to be suppressed in nature. The release of allelochemicals from plant residues in plots of 'continuous crop cultivation' or from allelopathic living plants may induce the development of specific allelopathic bacteria. Both the rate by which a bacterium gains from its allelopathic activity through utilizing plant excretions, and the reasons for the developing of allelopathic bacteria in such habitats, are important goals for further research.

Bacterial Physiological Phenomena↗
PubMed2001

Captopril-induced jaundice: report of 2 cases and a review of 13 additional reports in the literature.

Two elderly patients, treated with captopril for left ventricular dysfunction and diabetes, developed severe cholestatic jaundice for which no alternative explanation could be found. The jaundice resolved completely after discontinuation of the drug. A review of the literature identifies a highly similar and distinctive clinical pattern in another 13 cases reported and suggests that hepatotoxicity is a well-established yet rare adverse effect of captopril. However, the very common use of this drug, together with the severity of the liver injury it may cause, calls for a high index of suspicion and increased awareness of this phenomenon.

Aged↗
PubMed2001

Troglitazone reduces the expression of PPARgamma while stimulating that of PPARalpha in mononuclear cells in obese subjects.

We have recently demonstrated that troglitazone exerts an anti-inflammatory effect in the insulin resistant obese in vivo in parallel with its insulin-sensitizing effect. Because these effects are thought to be mediated through peroxisome proliferator-activated receptors alpha and gamma (PPARalpha and PPARgamma), we have now examined the possibility that troglitazone may modulate the expression of PPARalpha and PPARgamma. Seven obese hyperinsulinemic subjects were administered 400 mg troglitazone daily for 4 weeks. Fasting blood samples were obtained before and during troglitazone therapy at 1, 2, and 4 weeks. Fasting insulin concentrations fell at week 1 and persisted at lower levels till 4 weeks. PPARgamma expression fell significantly at week 1 and fell further at weeks 2 and 4. In contrast, PPARalpha expression increased significantly at week 2 and further at week 4. 9- and 13-hydroxyoctadecanoic acid, products of linoleic acid peroxidation and agonists of PPARgamma, decreased during troglitazone therapy. We conclude that troglitazone, an agonist for both PPARalpha and PPARgamma, has significant but dramatically opposite effects on PPARalpha and PPARgamma. These effects may be relevant to its insulin sensitizing and anti-inflammatory effects.

Adult↗
PubMed2001

The role of soft tissue reconstruction after melanoma resection in the head and neck

INTRODUCTION: Reconstruction after wide local excision of melanomas in the head and neck can be formidable. Many tumors lie close to vital structures, and excision must carefully balance preservation of form and function. For small defects, primary closure or skin grafting is satisfactory. However, it has become increasingly evident that more advanced reconstructive procedures can improve the outcome in terms of both function and aesthetics. This study was undertaken to determine the effectiveness of flap closure after wide local excision of melanomas in the head and neck and to develop a set of surgical recommendations on the basis of our experience. METHOD: We reviewed 35 patients who underwent 39 flap closures at The University of Texas, M. D. Anderson Cancer Center after wide local excision of head and neck melanomas. Local flaps were primarily used to close defects after the resection of superficial or intermediate-thickness melanomas. Pedicle and free flaps were used to cover larger defects resulting from the excision of extensive tumors. The flap closures were compared with an analogous database of 560 melanoma resections that underwent primary closure or skin grafting. RESULTS: The mean age of the patient population was 57 years. The most common location for tumor presentation was the cheek, followed by the ear, forehead, and lip. Pathologic findings most commonly demonstrated superficial spreading melanoma, and the average defect size was 30.7 cm(2). Local flaps were used most often for reconstruction. The only variable that significantly predicted local recurrence was the depth of the tumor. Local, pedicle, or free flaps did not decrease the ability of detecting local recurrence or increase this number compared with primary closure and skin grafting. Major postoperative complications were detected in seven patients. We found flap closure to achieve excellent functional and aesthetic results. CONCLUSION: Although primary closure is the ideal method of reconstruction for small defects, flap closure provides a versatile and safe alternative when simple closure would yield unsatisfactory results. With careful planning, flap closure offers an exceptional functional and aesthetic result and may even enhance contour defects after extensive neck or parotid dissections. Moreover, our experience with flap closure did not appear to delay the detection of local recurrence and may have even served to decrease the incidence of local failure after wide local excision of head and neck melanomas. Copyright 2000 John Wiley & Sons, Inc. Head Neck 23: 8-15, 2001.

Journal Article↗
PubMed2001

The role of soft tissue reconstruction after melanoma resection in the head and neck.

INTRODUCTION: Reconstruction after wide local excision of melanomas in the head and neck can be formidable. Many tumors lie close to vital structures, and excision must carefully balance preservation of form and function. For small defects, primary closure or skin grafting is satisfactory. However, it has become increasingly evident that more advanced reconstructive procedures can improve the outcome in terms of both function and aesthetics. This study was undertaken to determine the effectiveness of flap closure after wide local excision of melanomas in the head and neck and to develop a set of surgical recommendations on the basis of our experience. METHOD: We reviewed 35 patients who underwent 39 flap closures at The University of Texas, M. D. Anderson Cancer Center after wide local excision of head and neck melanomas. Local flaps were primarily used to close defects after the resection of superficial or intermediate-thickness melanomas. Pedicle and free flaps were used to cover larger defects resulting from the excision of extensive tumors. The flap closures were compared with an analogous database of 560 melanoma resections that underwent primary closure or skin grafting. RESULTS: The mean age of the patient population was 57 years. The most common location for tumor presentation was the cheek, followed by the ear, forehead, and lip. Pathologic findings most commonly demonstrated superficial spreading melanoma, and the average defect size was 30.7 cm2. Local flaps were used most often for reconstruction. The only variable that significantly predicted local recurrence was the depth of the tumor. Local, pedicle, or free flaps did not decrease the ability of detecting local recurrence or increase this number compared with primary closure and skin grafting. Major postoperative complications were detected in seven patients. We found flap closure to achieve excellent functional and aesthetic results. CONCLUSION: Although primary closure is the ideal method of reconstruction for small defects, flap closure provides a versatile and safe alternative when simple closure would yield unsatisfactory results. With careful planning, flap closure offers an exceptional functional and aesthetic result and may even enhance contour defects after extensive neck or parotid dissections. Moreover, our experience with flap closure did not appear to delay the detection of local recurrence and may have even served to decrease the incidence of local failure after wide local excision of head and neck melanomas.

Adolescent↗
PubMed2000

A major locus for myoclonus-dystonia maps to chromosome 7q in eight families.

Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21.

Chromosome Mapping↗
PubMed2000

Providing after-hours on-call clinical coverage in academic health sciences centres: the Hospital for Sick Children experience.

An increasing number of admissions of patients requiring complex and acute care coupled with a decreasing number of pediatric postgraduate trainees has caused a shortage of house staff available to provide after-hours on-call coverage in the Department of Pediatrics at Toronto's Hospital for Sick Children. The Clinical Assistant program created to deal with this problem was short on staff, did not provide adequate continuity of care and was becoming increasingly unaffordable. The Clinical Departmental Fellowship program was created to address the problem of after-hours clinical coverage. The program is aimed at qualified pediatricians seeking additional clinical or research training in one of the subspecialty divisions in the Department of Pediatrics. We describe the hiring process, job description and evolution of the program since its inception in 1996. This program has been mutually advantageous for the individual fellows and their sponsoring divisions as well as the Department of Pediatrics and the Hospital for Sick Children. We recommend the introduction of similar programs to other academic medical departments facing staff shortages.

Academic Medical Centers↗
PubMed2000

BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer.

Ovarian cancer is a component of the autosomal-dominant hereditary breast-ovarian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in approximately 2% of the Jewish population. Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ovarian cancers attributable to founding mutations in BRCA1 and BRCA2 in the Jewish population and the familial cancer risks associated with each, we interviewed 213 Jewish women with ovarian cancer at 11 medical centers in North America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in this population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2. We obtained a detailed family history on all women we studied who had cancer and on a control population of 386 Ashkenazi Jewish women without ovarian or breast cancer. A founder mutation was present in 41.3% of the women we studied. The cumulative incidence of ovarian cancer to age 75 years was found to be 6.3% for female first-degree relatives of the patients with ovarian cancer, compared with 2.0% for the female relatives of healthy controls (relative risk 3.2; 95% CI 1.5-6.8; P=.002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4-3.0; P=.0001). Only one nonfounder mutation was identified (in this instance, in a woman of mixed ancestry), and the three founding mutations accounted for most of the observed excess risk of ovarian and breast cancer in relatives.

Adult↗
PubMed2000

Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients.

BACKGROUND: HHV-6 is a ubiquitous virus and its infection usually occurs in childhood and then becomes a latent infection. HHV-6 reactivation has been shown to play a role in the pathogenesis of AIDS and several other diseases. OBJECTIVES: To determine what role HHV-6 infection or reactivation plays in the pathogenesis of multiple sclerosis (MS) and chronic fatigue syndrome (CFS). RESULTS: Twenty-one MS and 35 CFS patients were studied and followed clinically. In these patients, we measured HHV-6 IgG and IgM antibody levels and also analyzed their peripheral blood mononuclear cells (PBMCs) for the presence of HHV-6, using a short term culture assay. In both MS and CFS patients, we found higher levels of HHV-6 IgM antibody and elevated levels of IgG antibody when compared to healthy controls. Seventy percent of the MS patients studied contained IgM antibodies for HHV-6 late antigens (capsid), while only 15% of the healthy donors (HD) and 20% of the patients with other neurological disorders (OND) had HHV-6 IgM antibodies. Higher frequency of IgM antibody was also detected in CFS patients (57.1%) compared to HD (16%). Moreover, 54% of CFS patients exhibited antibody to HHV-6 early protein (p41/38) compared to only 8.0% of the HD. Elevated IgG antibody titers were detected in both the MS and the CFS patients. PBMCs from MS, CFS and HD were analyzed in a short term culture assay in order to detect HHV-6 antigen expressing cells and to characterize the viral isolates obtained as either Variant A or B. Fifty-four percent of MS patients contained HHV-6 early and late antigen producing cells and 87% of HHV-6 isolates were Variant B. Isolates from CFS, patients were predominately Variant A (70%) and isolates from HD were predominately Variant B (67%). Moreover, one isolate from OND was also Variant B. Persistent HHV-6 infection was found in two CFS patients over a period of 2.5 years and HHV-6 specific cellular immune responses were detected in PBMCs from ten CFS patients. CONCLUSION: In both MS and CFS patients, we found increased levels of HHV-6 antibody and HHV-6 DNA. A decrease in cellular immune responses was also detected in CFS patients. These data suggest that HHV-6 reactivation plays a role in the pathogenesis of these disorders.

Antibodies, Viral↗
PubMed2000

Autologous CD34+ enriched peripheral blood progenitor cell (PBPC) transplantation is associated with higher morbidity in patients with lymphoma when compared to unmanipulated PBPC transplantation.

High-dose chemotherapy followed by CD34+ enriched peripheral blood progenitor cell (PBPC) transplantation is used for the treatment of primary refractory or relapsed Hodgkin's and non-Hodgkin's lymphomas. The CD34+ enrichment procedure, while reducing tumor burden, may compromise immunological reconstitution in the transplanted patient and result in increased rates of post-transplant infection. We compared infectious complications in patients with lymphoma who were treated with high-dose chemotherapy and supported either with CD34+ enriched PBPC (n = 19) or unmanipulated PBPCs (n = 24). Analysis was limited to patients discharged from initial hospitalization for transplantation with a minimum of 1 year followup and free of lymphoma recurrence. We found a statistically significant increase in the number of patients with one or more infectious events in the CD34+ transplant group (14/19) compared with the unmanipulated PBPC group (9/24, P < 0.01). Greater numbers of patients with two or more infectious events were observed in the CD34+ group (7/19 vs 2/24, P < 0.03) and an increased incidence of bacterial infections was observed in the CD34+ group (10/19 vs 5/24, P < 0.05). Two deaths due to infectious complications were observed in the CD34+ group. There was no significant difference in blood lymphocyte or monocyte recovery between the groups. These data demonstrate a significant increase in the long-term incidence of infectious events in lymphoma patients transplanted with autologous CD34+ enriched PBPCs compared to unmanipulated PBPCs. Thus, patients who undergo CD34+ enriched PBPC transplantation should be followed closely for infectious complications and prolonged infectious prophylaxis should be considered.

Adult↗
PubMed2000

Immune cytopenias as the presenting finding in primary Sjögren's syndrome.

A diagnostic delay of several years in primary Sjögren's syndrome is common, even in patients who present with sicca symptoms. It is much more likely in cases with prominent symptomatic extraglandular involvement. We report on three such patients who presented as Coomb's positive haemolytic anaemia, systemic symptoms with agranulocytosis and gingival bleeding due to immune thrombocytopenia, to alert clinicians to the fact that primary Sjögren's syndrome may present as clinically significant immune-mediated cytopenia in the absence of sicca symptoms. Sjögren's syndrome, a common autoimmune disorder, should be considered in the differential diagnosis of apparently 'idiopathic' cytopenias and actively sought by directed history, Schirmer test and autoantibody screening.

Adult↗
PubMed2000

Qualitative study of pregnancy and childbirth experiences in Somalian women resident in Sweden.

OBJECTIVE: To explore the attitudes, strategies and habits of Somalian immigrant women related to pregnancy and childbirth, in order to gain an understanding as to how cultural factors might affect perinatal outcome. METHODS: Interpreter assisted qualitative in depth interviews around topics such as attitudes and strategies regarding childbirth. PARTICIPANTS: Fifteen women from the Somalian community in a city in Sweden, between the ages of 20 and 55 years with delivery experience in Somalia and Sweden. RESULTS: The interviews describe how the women themselves perceived their experiences of childbirth in the migrant situation. Many voluntarily decreased food intake in order to have a smaller fetus, an easier delivery and to avoid caesarean section. The participants considered a safe delivery to be the same as a normal vaginal delivery They reduced food intake in order to diminish the growth of the fetus, thereby avoiding caesarean section and mortality. The practice of food intake reduction, while rational for the participants when in Somalia, was found less rational in Sweden and may lead to suboptimal obstetric surveillance. CONCLUSIONS: Somalian women have childbirth strategies that differ from those of Swedish women. These strategies should be seen as 'survival behaviours' related to their background in an environment with high maternal mortality. The hypothesis generated is that there is a relationship between the strategies during pregnancy and adverse perinatal outcome among Somalian immigrants. Considering the strong association of the habits to safe birth, it seems doubtful whether the women will change their habits as long as health care providers are unaware of their motives. We suggest a more culturally sensitive perinatal surveillance.

Adult↗
PubMed2000

Localization of the sites mediating desensitization of the beta(2)-adrenergic receptor by the GRK pathway.

The human beta(2)-adrenergic receptor (betaAR) is rapidly desensitized in response to saturating concentrations of agonist by G protein-coupled receptor kinases (GRKs) and cAMP-dependent protein kinase A (PKA) phosphorylation of the betaAR, followed by beta-arrestin binding and receptor internalization. betaAR sites phosphorylated by GRK in vivo have not yet been identified. In this study, we examined the role of the carboxyl terminal serines, 355, 356, and 364, in the GRK-mediated desensitization of the betaAR. Substitution mutants of these serine residues were constructed in which either all three (S355,356,364A), two (S355,356A and S356, 364A), or one of the serines (S356A and S364A) were modified. These mutants were constructed in a betaAR in which the serines of the PKA consensus site were substituted with alanines (designated PKA(-)) to eliminate any PKA contribution to desensitization, and they were stably transfected into human embryonic kidney 293 cells. Treatment of the PKA(-) mutant with 10 microM epinephrine for 5 min caused a 3. 5-fold increase in the EC(50) value and a 42% decrease in the V(max) value for epinephrine stimulation of adenylyl cyclase. Substitution of all three serines completely inhibited the epinephrine-induced shift in the EC(50). Both double mutants, S355,356A and S356,364A, showed a nearly complete loss of the EC(50) shift, whereas the single substitutions, S356A and S364A, caused only a slight decrease in desensitization. None of the mutations altered the epinephrine-induced decrease in V(max,) which seems to be downstream of the receptor. The triple mutation caused a 45% decrease in epinephrine-induced internalization and a 90 to 95% reduction in phosphorylation of the betaAR relative to the PKA(-) (1.9+/- 0.2- and 16.6+/-3.8-fold phosphorylation over basal, respectively). The double mutants caused an intermediate reduction in internalization (20-21%) and phosphorylation (43-52%). None of the serine mutations altered the rate of betaAR recycling. Our data demonstrate that the cluster of serines within the 355 to 364 betaAR domain confer the rapid, GRK-mediated, receptor-level desensitization of the betaAR.

Adenylyl Cyclases↗
PubMed2000

Relationship of cognitive functioning, adaptive life skills, and negative symptom severity in poor-outcome geriatric schizophrenia patients.

The authors assessed whether cognitive functioning and negative symptoms are related to functional outcome across severity of negative symptoms and examined relationships between symptom domains in patients with high versus low negative symptom severity. The interrelationships between cognitive functioning and functional skills in poor-outcome geriatric schizophrenic patients were compared between those who were in the first (n = 81) and the fourth quartiles (n = 127) of negative symptom severity based on the normative data in the Positive and Negative Syndrome Scale. It was found that negative symptoms and cognitive functioning were the strongest correlates of functional status in geriatric poor-outcome schizophrenic patients--regardless of negative symptom severity. Interestingly, the greater the severity of negative symptoms, the less strongly negative symptoms were related to functional outcome. The present findings demonstrate that the relationship of cognitive functioning to social and adaptive functioning remains significant despite differing levels of negative symptom severity.

Activities of Daily Living↗
PubMed2000

Effects of insulin on prenylation as a mechanism of potentially detrimental influence of hyperinsulinemia.

To investigate the cause and effect relationship between hyperinsulinemia and the increased amounts of farnesylated p21Ras, we performed hyperinsulinemic euglycemic clamps in normal weight volunteers as well as in normal mice and dogs. Insulin infusions significantly raised the amounts of farnesylated p21Ras in the white blood cells of humans, in liver samples of mice and dogs, and in aorta samples of mice. Obese hyperinsulinemic individuals and dogs (made hyperinsulinemic by surgical diversion of the pancreatic outflow from the portal vein into the vena cava) displayed increased amounts of farnesylated p21Ras before the hyperinsulinemic clamps. Infusions of insulin did not alter the already increased levels of farnesylated p21Ras in these experimental models. To further investigate the role of acquired insulin resistance in modulating insulin's effect on p21Ras prenylation, we induced insulin resistance in rats by glucosamine infusion. Insulin-resistant glucosamine-treated animals displayed significantly increased farnesylated p21Ras in response to insulin infusion compared to that in control saline-treated animals. Transgenic models of insulin resistance (heterozygous insulin receptor substrate-1 knockout mice, A-ZIP/F-1 fatless mice, and animals overexpressing glutamine:fructose-6-phosphate amidotransferase) contained increased amounts of farnesylated p21Ras. We conclude that hyperinsulinemia, either endogenous (a prominent feature of insulin resistance) or produced by infusions of insulin, increases the amounts of farnesylated p21Ras in humans, mice, and dogs. This aspect of insulin action may represent one facet of the molecular mechanism of the potentially detrimental influence of hyperinsulinemia.

Adult↗