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Biomedical subjects

D Hirsch

Publications and source records attributed to D Hirsch.

At least 19 recordsLinked to original sources
PubMed2005

Pituitary and bilateral adrenal enlargement: an unusual presentation of hepatocellular carcinoma.

Pituitary metastases account for about 1% of operated pituitary lesions. Most derive from primaries in the breast or lung. Pituitary metastases from hepatocellular carcinoma (HCC) have rarely been reported. We describe a patient in whom headache and left external ophthalmoplegia were the only presenting signs of a clinically silent and radiographically undetectable HCC, that had metastasized to the pituitary and both adrenal glands. Pituitary histology and adrenal needle biopsy failed to establish the final diagnosis, which was reached only after surgical exploration of the abdomen. This case illustrates the difficulties encountered in the histopathological diagnosis of pituitary metastasis and the need for good clinical judgment when confronting pituitary tumors with atypical features.

Adrenal Gland Neoplasms↗
PubMed2005

Three novel mutations in POU1F1 in Israeli patients with combined pituitary hormone deficiency.

BACKGROUND: POU1F1, a pituitary-specific transcription factor of the class 1 POU family, is crucial for the development and differentiation of the anterior pituitary gland. Mutations in the POU1F1 gene have been shown to be responsible for a syndrome of combined pituitary hormone deficiency (CPHD), including prolactin, growth hormone and thyroid-stimulating hormone deficiencies. METHODS: Five patients with CPHD from three families were evaluated. The clinical and biochemical data were taken from the medical records. DNA was analyzed by polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), and sequencing. RESULTS: Molecular analysis yielded three novel mutations in POU1F1: W193X, Q242R (-2 bp), and F262L. CONCLUSIONS: Three novel POU1F1 mutations were detected in Israeli patients with CPHD. Two of them, a W193X missense mutation and a deletion of two adenine bases at position 242Q, may lead to the production of a truncated protein that lacks the entire POU homeodomain or part of it, respectively. The third mutation, F262L, resides in the POU homeodomain and hence might change the activity of the protein.

Arginine↗
PubMed2003

Oxidative stress in cardio renal anemia syndrome: correlations and therapeutic possibilities.

Cardiovascular injury has been shown to be the most critical factor affecting quality of life and mortality in patients suffering from chronic renal failure. Oxidative stress has been thought to be an important risk factor for cardiovascular disorders. As oxidative stress parameters with high cardiovascular risk factor 4-hydroxynonenal and other aldehydic lipid peroxidation products, F2-isoprostanes, homocysteine, and cholesterol oxidation products were measured in chronic renal failure patients. 4-Hydroxynonenal and some cholesterol oxidation products correlated well with the degree of renal anemia. F2-isoprostane levels were related to inflammation, whereas homocysteine was increased due to malnutrition. Further, cholesterol oxidation products correlated well with the consumption of lipophilic antioxidants such as alpha-tocopherol. There was an almost linear correlation between the left ventricular mass index and 4-hydroxynonenal. Both parameters furthermore showed an inverse relationship to hemoglobin concentration. The correction of renal anemia by means of erythropoietin therapy led to an efficient strengthening of the antioxidative defence system. The improvement of the antioxidative capacity is of complex nature comprising both enzymatic pathways and low molecular antioxidants. The correction of renal anemia with its well documented reduction of the cardiovascular risk can be regarded as an antioxidative therapy, demonstrating the clinical efficiency of antioxidative protection in patients with chronic renal failure.

Anemia↗
PubMed2002

Delay in the clinical diagnosis of breast cancer: estimating its effect on prognosis, with particular reference to medical litigation.

Medical malpractice litigation is increasing. Delay in diagnosis is the commonest basis for litigation involving the treatment of breast cancer. When delay in diagnosis has occurred, any losses for which a plaintiff seeks compensation require estimates to be made of any change in prognosis over the period of the delay relative to the extent of disease found when treatment is finally undertaken. We have examined the natural history of breast cancer and have attempted to provide evidence-based quantitative guidelines for the evaluation of the losses which may be claimed in malpractice cases.

Journal Article↗
PubMed2002

Oxidative stress in chronic renal failure as a cardiovascular risk factor.

Myocardial injury has been shown to be the most critical factor influencing quality of life and mortality in patients with chronic renal failure. Oxidative stress has been postulated to be an important risk factor for cardiovascular disorders. One reason for oxidative stress in patients with renal failure is the underlying disease itself. Renal toxicity, ischemia/reperfusion and immunological disorders of the kidney result in an elevated formation of reactive oxygen species active in the pathogenesis of kidney disease. However, treatment procedures were also shown to induce oxidative stress. Increased formation of free radicals leads to an accelerated lipid peroxidation (LPO). Furthermore, secondary aldehydic LPO products, e.g. malondialdehyde (MDA) and 4-hydroxynonenal (HNE), are formed which were shown to deplete antioxidants, inhibit protein syntheses, mitochondrial respiration, and enzyme functions. F2-isoprostanes, also metabolites of polyunsaturated fatty acids, represent an additional in vivo marker of oxidative stress. Both isoprostanes and aldehydic LPO products can be removed by hemodialysis, however, this suggests only in part their binding to other molecules which cause tissue damage. Protein carbonyls are end-products of such interventions. Oxysterols, another form of free-radical initiated oxidation products, were shown to initiate atherosclerosis and plaque formation increasing dramatically the risk of coronary heart disease. Today there is no doubt that the correction of the oxidant/antioxidant imbalance in patients with chronic renal failure is an important approach for the reduction of the risk of those patients to develop cardiovascular disorders. The complete correction of renal anemia represents an effective means of strengthening antioxidant capacity and, therefore, of reducting cardiovascular risk potential.

Cardiovascular Diseases↗
PubMed2000

Generation of mammalian cells stably expressing multiple genes at predetermined levels.

Expression of cloned genes at desired levels in cultured mammalian cells is essential for studying protein function. Controlled levels of expression have been difficult to achieve, especially for cell lines with low transfection efficiency or when expression of multiple genes is required. An internal ribosomal entry site (IRES) has been incorporated into many types of expression vectors to allow simultaneous expression of two genes. However, there has been no systematic quantitative analysis of expression levels in individual cells of genes linked by an IRES, and thus the broad use of these vectors in functional analysis has been limited. We constructed a set of retroviral expression vectors containing an IRES followed by a quantitative selectable marker such as green fluorescent protein (GFP) or truncated cell surface proteins CD2 or CD4. The gene of interest is placed in a multiple cloning site 5' of the IRES sequence under the control of the retroviral long terminal repeat (LTR) promoter. These vectors exploit the approximately 100-fold differences in levels of expression of a retrovirus vector depending on its site of insertion in the host chromosome. We show that the level of expression of the gene downstream of the IRES and the expression level and functional activity of the gene cloned upstream of the IRES are highly correlated in stably infected target cells. This feature makes our vectors extremely useful for the rapid generation of stably transfected cell populations or clonal cell lines expressing specific amounts of a desired protein simply by fluorescent activated cell sorting (FACS) based on the level of expression of the gene downstream of the IRES. We show how these vectors can be used to generate cells expressing high levels of the erythropoietin receptor (EpoR) or a dominant negative Smad3 protein and to generate cells expressing two different cloned proteins, Ski and Smad4. Correlation of a biologic effect with the level of expression of the protein downstream of the IRES provides strong evidence for the function of the protein placed upstream of the IRES.

Animals↗
PubMed2000

Nano-electrospray mass spectrometry with a modified commercial IonSpray source

Electrospray mass spectrometry is a standard tool for the investigation of biological samples. Due to the high flowrates of the standard sources, large sample amounts are required and it is almost impossible to spray physiological solutions due to their aqueous medium. The introduction of microelectrospray sources has made it possible to decrease the sample amounts needed and enabled the use of buffered solutions. In this work, a nanoES-like source based on a modification of an existing IonSpray source is introduced. In contrast to other nanoES sources available, the modification presented allows a fast change between the nanoES and the normal IonSpray modes. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

The treatment and outcome of cancer patients with thromboses on central venous catheters.

Thromboses are a common complication of central venous catheters in cancer patients. This study was performed to analyze retrospectively the treatment and outcome of all patients with venous thromboses related to central venous catheters at a major cancer center. From 1992 through 1995, 319 oncology patients with central venous catheters underwent radionuclide venography (RNV) at the Dana-Farber Cancer Institute for suspected catheter or venous thrombosis. The treatment and outcome of patients found to have venous thromboses were evaluated. Of the 319 patients, 112 were found to have evidence of venous thrombosis. The median age and platelet counts were not significantly different between the patients with and without thromboses. The most common indication for obtaining RNV was difficulty in aspirating or infusing material through the catheter. Patients who had pain or edema, or both, of the neck or upper extremity were more likely to have a venous thrombosis. Regardless of therapeutic intervention, including anticoagulation with heparin or coumadin, or both; line removal or replacement; or a combination thereof, no patients had a major adverse outcome such as pulmonary embolism, compromise of limb, or death. Only 4 patients did not have resolution of their presenting symptoms, all of whom were treated with line replacement. The overall survival of patients with and without thromboses was not significantly different. Either anticoagulation or removal of the central venous catheter (or both) appears to be adequate treatment for catheter-related thrombosis. A prospective trial to evaluate these approaches may be worthwhile so that the use of unnecessary procedures may be avoided in this patient population.

Actuarial Analysis↗
PubMed2000

House-dust-mite allergen concentrations (Der f 1) and mold spores in apartment bedrooms before and after installation of insulated windows and central heating systems.

BACKGROUND: It has been hypothesized that changes in heating systems and insulation of homes in developed countries have generated an indoor climate favorable to organisms that excrete allergens inducing sensitization and allergic disease. The purpose of this study was to determine the influence of the installation of highly insulated windows and central heating systems on indoor climate, and mite-allergen (Der f 1) and mold spore concentrations. METHODS: The bedrooms of 98 apartments were examined before and 7 months (mean) after installation of insulated windows and central heating systems. The air-exchange rate, temperature, and humidity were measured. In settled dust on carpets and mattresses, the number of colony-forming mold spores and the Der f 1 concentration were determined. The inhabitants completed a questionnaire about their lifestyles and housing conditions. RESULTS: The air-exchange rate decreased from geometric mean 0.73 to 0.52 per hour (P=0.029). Temperature (mean 13.4 vs 17.5 degrees C, P<0.001), and absolute humidity (mean 4.6 g vs 6.2 g H2O/kg air, P<0.001) increased. Relative humidity remained nearly unchanged (mean 47.6 vs 49.1%). Der f 1 concentrations on carpets (geometric mean 0.65 vs 1.28 microg/g dust, P < 0.001) and mattresses (geometric mean 1.56 vs 2.40 microg/g, P=0.002) increased. Among the fungi that were analyzed, only the thermotolerant species Aspergillus fumigatus increased (geometric mean 20 vs. 60 colony-forming units/g carpet dust, P = 0.02). CONCLUSIONS: The findings of this study suggest that the installation of insulated windows and central heating systems is associated with an increase of Der f 1 concentrations in carpet and mattress dust and of A. fumigatus in carpet dust in apartment bedrooms.

Air Pollution, Indoor↗
PubMed2000

A sensitive gas chromatography-mass spectrometry assay reveals increased levels of monohydroxyeicosatetraenoic acid isomers in human plasma after extracorporeal photoimmunotherapy and under in vitro ultraviolet A exposure.

Extracorporeal photoimmunotherapy (photopheresis) is a highly effective therapy in the treatment of various disorders. Although extracorporeal photoimmunotherapy has been successfully used for more than 10 y, its mechanism of action is still unclear. The formation of reactive oxygen species have been implicated in extracorporeal photoimmunotherapy, but malonyl dialdehyde as a marker of systemic lipid peroxidation did not increase significantly during treatment. To investigate further the involvement of reactive oxygen species in extracorporeal photoimmunotherapy, we have introduced a highly sensitive negative ion gas chromatography-mass spectrometry based method for quantitating oxygenated arachidonic acid isomers (hydroxyeicosatetraenoic acids) in plasma samples of patients treated with extracorporeal photoimmunotherapy. In the plasma of healthy volunteers pmole amounts of 2-, 3-, 5-, 8-12-, and 15-hydroxyeicosatetraenoic acid were detected and we observed a dose-dependent augmentation in these metabolites when the blood was irradiated with increasing doses of ultraviolet A in the presence of the photosensitizer 8-methoxypsoralen. Analysis of plasma samples obtained from patients before and after extracorporeal photoimmunotherapy revealed a characteristic increase in total hydroxyeicosatetraenoic acid levels, particularly of 5-hydroxyeicosatetraenoic acid which contributed 80% to the sum of all hydroxyeicosatetraenoic acid isomers. Chiral phase high-performance liquid chromatography indicated almost equal amounts of 5S- and 5R-hydroxyeicosatetraenoic acid suggesting that the majority of lipid peroxidation products are formed via nonenzymatic oxidation reactions.

Gas Chromatography-Mass Spectrometry↗
PubMed2000

Traffic exposure and allergic sensitization against latex in children.

BACKGROUND: Latex antigens have been found in urban air samples and in debris deposited near freeways. OBJECTIVE: We investigated whether exposure to road traffic in a large city is associated with allergic sensitization against latex in children. METHODS: A population-based sample of 2505 children aged 5 to 11 years was examined in a cross-sectional study in the city of Dresden, Germany. Specific IgE levels against latex and a panel of common aeroallergens (timothy grass, rye, birch, mugwort, Cladosporium herbarum, Dermatophagoides pteronyssinus, cat dander, and dog dander) was determined by using a fluorescence immunoassay (CAP Pharmacia). Traffic exposure was assessed by (1) parental self-report on traffic frequency and truck traffic in the street of residence, (2) traffic counts, and (3) measurements of benzene at 182 points on a 1-km(2) grid for 1 year, which were used to estimate the children's individual exposure at the home address. RESULTS: Eight hundred fifty-four (34.1%) of the children were sensitized against any of the allergens, and 150 (6.0%) had specific IgE (>0.35 kU/L) against latex. The prevalence of latex sensitization was not positively associated with self-reported traffic exposure, traffic counts in the street of residence (adjusted prevalence odds ratio for >5000 vs < or =5000 cars/d, 0.7; 95% confidence interval, 0.4-1.3), or benzene exposure (adjusted prevalence odds ratio for an increase of 1 microg/m(3) air, 0.8; 95% confidence interval, 0.7-1.05). CONCLUSION: The data suggest that exposure to road traffic is not associated with allergic sensitization to latex in children.

Automobiles↗
PubMed2000

Effect of single versus multiple courses of antenatal corticosteroids on maternal and neonatal outcome.

OBJECTIVE: Treatment of pregnant mothers with a single course of antenatal corticosteroids significantly reduces neonatal mortality and morbidity. Multiple weekly courses are often given. However, the safety and efficacy of repeated courses of antenatal corticosteroids have not been adequately studied. STUDY DESIGN: A retrospective study was performed for 609 mothers and their 713 infants who were treated with 1 to 12 courses of antenatal corticosteroids. Data for 369 singleton preterm infants born at < or =34 weeks' gestation, 210 multiple gestations, and 134 infants delivered at > or =35 weeks' gestation were analyzed separately. RESULTS: The incidence of respiratory distress syndrome was 45% for single-course and 35% for multiple-course groups (P =.005; odds ratio, 0.44; 95% confidence interval, 0.25-0.79). The multiple-course group also had significantly less patent ductus arteriosus (20% vs 13%; P =.016). Incidence of death before discharge and other neonatal morbidities were similar. The multiple-course group had a reduction of 0.46 +/- 0.19 cm in head circumference at birth (P =.013) when adjusted for gestational age and preeclampsia. The 2 groups had similar birth weights. Infants born at > or =35 weeks' gestation, multiple-gestation infants, and infants who were born >7 days after the last corticosteroid dose had similar outcomes, regardless of the number of courses they received. Mothers treated with multiple courses compared with a single course had a significantly higher incidence of postpartum endometritis (P =.013), even though they had a lower incidence of prolonged rupture of membranes (24% vs 33%, P =.06) and similar cesarean delivery rates. CONCLUSION: Exposure to multiple courses of antenatal corticosteroids compared with a single course resulted in a significant reduction in the incidence of respiratory distress syndrome in singleton preterm infants delivered within a week of the last corticosteroid dose. This was associated with a reduction in birth head circumference and an increased incidence of maternal endometritis. Whether the potential benefits of repeated therapy clearly outweigh the risks will ultimately be determined in randomized prospective controlled trials.

Adrenal Cortex Hormones↗
PubMed2000

Cushing's syndrome presenting as a schizophrenia-like psychotic state.

Neuropsychiatric abnormalities, of which depression is the most common, are frequently associated with Cushing's syndrome. The following paper describes a 58-year-old woman in whom a prolonged psychotic state--schizophrenia-like--was the presenting sign of Cushing's syndrome. The psychiatric symptoms disappeared shortly after the cortisol level has been normalized. Due to the variety of symptoms, both organic and psychiatric, which may occur with Cushing's syndrome, a high suspicion index is advisable. Suspect clinical findings should always prompt the appropriate endocrine work-up.

Cushing Syndrome↗
PubMed2000

Prevention of glutaraldehyde-fixed bioprosthetic heart valve calcification by alcohol pretreatment: further mechanistic studies.

BACKGROUND AND AIM OF THE STUDY: Calcification is a major cause of failure of bioprosthetic heart valves derived from glutaraldehyde-crosslinked bovine pericardium or porcine aortic valve (PAV) cusps. Recently, we have shown that ethanol pretreatment of PAV cusps prevents calcification in animal models. METHODS AND RESULTS: In this study we showed that ethanol pretreatment was equally effective in preventing calcification of glutaraldehyde-crosslinked bovine pericardium (control Ca2+ = 121.16+/-7.49 microg/mg tissue; ethanol-pretreated Ca2+ = 2.95+/-0.78 microg/mg). Furthermore, other low-molecular weight alcohols such as methanol and isopropanol were also effective in mitigating calcification of PAV cusps. Storage of ethanol-pretreated cusps in glutaraldehyde before implantation allowed partial return of calcification, suggesting a role for ethanol-glutaraldehyde interactions in preventing calcification. However, when ethanol-pretreated cusps were stored in ethanolic glutaraldehyde up to one month, the anti-calcification effect of ethanol persisted. The conditions whereby PAV cusps were crosslinked in pure, non-aqueous, alcoholic glutaraldehyde solutions were also examined. The crosslinking was equivalent to the standard aqueous glutaraldehyde crosslinking as indicated by thermal denaturation temperatures (Td) obtained by differential scanning calorimetry (DSC) and resistance to collagenase digestion. However, these cusps had lower water content and showed a marked decrease in spin-lattice relaxation times (T1) obtained by solid-state proton nuclear magnetic resonance (NMR). Moreover, these cusps calcified heavily in the 21-day rat subdermal implants. Thus, alcohol treatment during glutaraldehyde crosslinking was not useful. CONCLUSION: Glutaraldehyde storage after ethanol pretreatment aggravates calcification; moreover, alcoholic-glutaraldehyde crosslinking solutions are not beneficial for anti-calcification. Ethanol pretreatment of glutaraldehyde-pretreated bovine pericardium prevents its calcification.

2-Propanol↗
PubMed1999

Expression cloning of LDLB, a gene essential for normal Golgi function and assembly of the ldlCp complex.

The Chinese hamster ovary (CHO) cell mutants ldlC and ldlB, which exhibit almost identical phenotypes, define two genes required for multiple steps in the normal medial and trans Golgi-associated processing of glycoconjugates. The LDLC gene encodes ldlCp, an approximately 80-kDa protein, which in wild-type, but not ldlB, cells associates reversibly with the cytoplasmic surface of the Golgi apparatus. Here, we have used a retrovirus-based expression cloning system to clone a murine cDNA, LDLB, that corrects the pleiotropic mutant phenotypes of ldlB cells. The corresponding mRNA was not detected in ldlB mutants. LDLB encodes an approximately 110-kDa protein, ldlBp, which lacks homology to known proteins and contains no common structural motifs. Database searches identified short segments of homology to sequences from Drosophila melanogaster, Arabidopsis thaliana, and Caenorhabditis elegans, and the essentially full-length homologous human sequence (82% identity); however, as was the case for ldlCp, no homologue was identified in Saccharomyces cerevisiae. We have found that in wild-type cell cytosols, ldlCp is a component of an approximately 950-kDa "ldlCp complex," which is smaller, approximately 700 kDa, in ldlB cytosols. Normal assembly of this complex is ldlBp-dependent and may be required for Golgi association of ldlCp and for the normal activities of multiple luminal Golgi processes.

3T3 Cells↗
PubMed1999

Glomerulonephritis in a neonate with atypical congenital lupus and toxoplasmosis.

The development of glomerulonephritis as a complication of neonatal lupus or congenital toxoplasmosis is extremely rare. We report a case of membranous glomerulonephritis occurring in a neonate with toxoplasmosis and atypical congenital lupus, including high-titer antinuclear antibodies and hypocomplementemia. This case illustrates that glomerulonephritis in the neonate may be induced by passively transferred maternal antibodies.

Basement Membrane↗
PubMed1999

Treatment of antithyroid drug-induced agranulocytosis by granulocyte colony-stimulating factor: a case of primum non nocere.

A 48-year-old woman who was treated for thyrotoxicosis with methimazole developed agranulocytosis. The methimazole was stopped and treatment with subcutaneous granulocyte colony-stimulating factor (G-CSF) was initiated. Administration of the drug for 8 days did not effectively shorten the recovery period compared with the average reported in the literature without the drug, and may have triggered additional iatrogenic complications. A search of the literature yielded 15 instances of severe antithyroid-drug-induced granulocytopenia (ATDIA) (granulocyte count of less than 0.1 x 10(9)/L) treated with G-CSF. Of the 16 patients, including the 1 reported here, only 3 displayed significant shortening of the agranulocytic period after treatment. We conclude that routine therapeutic application of G-CSF in afebrile severe ATDIG is not justified, and in some cases may generate a cascade of iatrogenic adverse events.

Aged↗