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Biomedical subjects

J Haas

Publications and source records attributed to J Haas.

At least 73 records · Page 4Linked to original sources

Long-term follow-up of infants of mothers with type 1 diabetes: evidence for hereditary and nonhereditary transmission of diabetes and precursors.

OBJECTIVE: To estimate the impact of type 1 diabetes during pregnancy on transgenerational genetically caused and/or fuel-mediated amplification of types 1 and 2 diabetes and to estimate the impact of elevated amniotic fluid insulin levels. RESEARCH DESIGN AND METHODS: A total of 75 white offspring of type 1 diabetic mothers and 49 control subjects of similar age and pubertal stage were examined at 5-15 years of age. All offspring had an oral glucose tolerance test. Glucose, insulin, and C-peptide were measured at 0, 30, 60, and 120 min after loading. Lipids and autoimmune antibodies were measured in fasting plasma. RESULTS: Of the 75 offspring, 4 (5.3%) had overt diabetes, and 16 of 71 (22.5%) had autoimmune antibodies. Offspring of diabetic mothers had significantly higher BMI; symmetry indexes; cholesterol, glucose, insulin, and C-peptide levels; and insulin resistance than control subjects. With the exception of cholesterol, these values were significantly elevated in offspring who had elevated amniotic fluid insulin levels (>8 microU/ml, >48 pmol/l) during pregnancy compared with normoinsulinemic offspring and control subjects. CONCLUSIONS: Offspring of type 1 diabetic mothers have an increased risk for diabetes later in life. The relative risk for type 1 and type 2 diabetes is 71.6 and 3.2, respectively. Type 2 diabetes-associated risk factors, such as high BMI; elevated glucose, insulin, and C-peptide levels; and insulin resistance, are related to the fetal metabolic experience in utero, as reflected by amniotic fluid insulin concentration.

Adolescent↗

Molecular analysis of the CDR3 encoding region of the immunoglobulin heavy chain locus in cerebrospinal fluid cells as a diagnostic tool in lymphomatous meningitis.

The diagnosis of leptomeningeal B-cell lymphoma is based on the identification of malignant B cells in the cerebrospinal fluid (CSF). Frequently, cytology does not allow clear distinction between neoplastic lymphoid cells and reactively transformed mononuclear cells. Individual B-cell clones can be identified on the basis of DNA sequences that encode the highly diverse complementarity-determining region (CDR3) of the immunoglobulin heavy chain locus (IgH). We studied CSF samples from 5 patients with B-cell malignancies and cytological evidence of leptomeningeal involvement, using polymerase chain reaction (PCR)-based high-resolution capillary electrophoresis and automated fluorescence analysis to detect PCR fragments. As controls, we assessed CSF specimens from 7 patients with inflammatory neurological diseases and three samples without pathological findings. In all patients with B-cell malignancies, a single PCR product was generated, indicating that CDR3-specific fragments were derived from monoclonal cell populations. CSF samples from patients with inflammatory diseases yielded multiple CDR3 amplicons, suggesting the presence of a polyclonal B-cell activation. No PCR product could be amplified in normal CSF samples. Automated fluorescence detection of CDR3 fragments is a highly sensitive and rapid method to distinguish neoplastic monoclonal and reactive polyclonal B-cell populations in the CSF.

Base Sequence↗

High dose IVIG in the post partum period for prevention of exacerbations in MS.

The influence of pregnancy on the course of autoimmune diseases is well documented. In multiple sclerosis the European PRIMS study confirmed an ameliorating effect during pregnancy but on increase of exacerbations after delivery. The efficacy of IVIG in autoimmune mediated diseases has been frequently reported. Based on the experiences of Achiron we recommend IVIG to prevent exacerbations after delivery. Since 1995 we recommend 60 g IVIG within 3 days after delivery and 10 g monthly in patients estimated to be on high risk for exacerbation. The data were compared to the PRIMS study. The baseline data were comparable, but the exacerbation rate after delivery in our observation was 33% lower than expected. The lowest risk for an exacerbation within the first 3 months after delivery we observed in women treated with long-term IVIG monthly. Until now the overall tolerance was excellent The results with IVIG after delivery suggest that immunoglobulins may be a promising therapeutical approach not only in MS but also in other autoimmune mediated diseases with a risk of exacerbation after delivery. A European wide study with IVIG after delivery in MS is in preparation to confirm our preliminary data.

Adult↗

[Coronary angiography and change in antioxidative status].

PATIENTS AND METHODS: In a prospective study in 53 patients with stable angina pectoris symptoms the antioxidant status (glutathione peroxidase, glutathione, superoxid dismutase, malondialdehyde and selenium in serum and whole blood) was determined before and 4 to 6 hours after coronary angiography. According to the results of the coronary angiography the patients were classified in a group with "severe" (n = 16) and another with "moderate" coronary alterations. RESULTS: In both groups there was a significant reduction of selenium in serum and whole blood. The enzymes glutathione peroxidase and superoxide dismutase as well as glutathione and malondialdehyde changed only slightly. CONCLUSION: These results can be the cause of an increase of the formation of free radicals during coronary reperfusion (PTCA, implantation of stents in the group with "severe" coronary alterations) but could also be seen as a sign of formation of radicals by the method itself (in patients with "moderate" coronary alterations). Further investigations are indicated. Furthermore the amelioration of the antioxidant status of the organism by scavenger substances (vitamins A, B, C and selenium) should be discussed.

Aged↗

Acyclovir treatment of experimentally induced herpes simplex virus encephalitis: monitoring the changes in immunologic NO synthase expression and viral load within brain tissue of SJL mice.

The effect of acyclovir treatment on viral burden and the expression of immunologic nitric oxide synthase (iNOS) within brains of 42 HSV-1 F infected mice was studied by using a titration PCR assay for HSV-1 DNA and a semiquantitative RT-PCR for iNOS mRNA. iNOS mediated NO-production may possibly be involved in secondary mechanisms of brain injury following virus infection, which may account for treatment failures in human herpes simplex virus encephalitis (HSVE). Following infection, a parallel increase of iNOS mRNA and HSV-1F-DNA occurred with peaks after 7 days that were both significantly lower under acyclovir treatment. Six months post infection viral load had declined, but iNOS mRNA expression in both treated and untreated mice was still enhanced as compared with mock infected controls. This suggests that acyclovir decreases iNOS expression via inhibition of viral replication shortly after infection but fails to influence elevated iNOS within the brain late in the course of experimental HSVE.

Acyclovir↗

Chemotherapy versus radiotherapy versus observation for high-risk cervical carcinoma after radical hysterectomy: A randomized, prospective, multicenter trial.

BACKGROUND: Adjuvant treatment modalities after radical hysterectomy have long been used in an attempt to eradicate microscopic tumor residuals in patients at high risk for recurrence. However, it has not been clearly demonstrated that adjuvant radiation, adjuvant chemotherapy, or both improve the outcome. To evaluate the effect of adjuvant treatment in patients with high-risk cervical cancer after radical hysterectomy, the Austrian Gynecologic Oncology Group conducted a prospective, randomized, multicenter clinical trial between 1989 and 1995. MATERIAL AND METHODS: Seventy-six patients with stage IB-IIB cervical cancer treated with radical hysterectomy with pelvic lymph node metastases and/or vascular invasion randomly received adjuvant chemotherapy (400 mg/m2 carboplatin, and 30 mg bleomycin), standardized external pelvic radiation therapy, or no further treatment. RESULTS: After a median follow-up of 4.1 years (range, 2-7) there were no statistically significant differences (P = 0.9530) in disease-free survival among the three treatment arms. CONCLUSION: The data suggest that adjuvant chemotherapy or radiation do not improve survival or recurrence rates in high-risk cervical cancer patients after radical hysterectomy. The most important treatment for these patients seems to be radical abdominal hysterectomy with systematic pelvic lymphadenectomy.

Carcinoma, Squamous Cell↗

Do primiparas aged 40 years or older carry an increased obstetric risk?

BACKGROUND: It is unclear whether older primiparas are at increased risk for complications of pregnancy other than an increased cesarean section rate. The aim of this study was to compare the rate of complications of pregnancy and delivery of primiparas aged 40 years or older with those of primiparas aged 20 to 30 years. METHODS: We reviewed the maternal and neonatal hospital records of 59 consecutive primiparas aged 40 years or older who delivered at our institution between 1986 and 1995. A total of 118 primiparas aged 20 to 30 years who preceded and followed the cases served as controls. RESULTS: The mean duration of gestation was significantly shorter in primiparas > or = 40 years of age. Induction of labor was more common and the cesarean delivery rate was higher (47 vs 12%) in older primiparas. The mean birth weight was significantly lower in the offspring of the cases. The perinatal mortality rate was 5% in the primiparas over 40 years and 0% in the control group; fetal malformations were found in 5% (vs 1%) of the children of older primiparas. CONCLUSIONS: In our series, older primiparas were at increased risk for prematurity, preeclampsia, and perinatal mortality. The high rate of cesarean section in older primiparas is due mainly to a higher incidence of obstetric complications. These data suggest that the prenatal care of older primiparas in the third trimester should concentrate on the early detection of premature contractions and signs of preeclampsia.

Adult↗

[Leptomeningeal dissemination of chronic lymphatic leukemia. Molecular genetic detection in cerebrospinal fluid].

The diagnosis of leptomeningeal dissemination of chronic lymphatic leukemia (CLL) by conventional cytology is unreliable because cytomorphologic criteria of malignancy are often lacking. Immunophenotyping of leukocyte differentiation antigens may also be of limited diagnostic value due to the small number of cells in cerebrospinal fluid (CSF) samples. Molecular methods may support the specific diagnosis of leptomeningeal infiltration of CLL. We present an 54 old patient who was diagnosed with CLL five years ago. Despite clinical signs of leptomeningeal involvement neither magnetic resonance imaging (MRI) nor conventional CSF analysis were suggestive of lymphomatous meningitis. Using PCR we selectively amplified the highly variable and clone-specific CDR3 region of the locus encoding the immunoglobulin heavy chain (IgH) in DNA obtained from both CSF and peripheral blood cells. Analysis of PCR products by high resolution gel electrophoresis revealed a single DNA fragment respectively indicating the presence of a monoclonal cell population in both compartments. DNA sequence analysis of the amplified CDR3 segments confirmed the clonal identity of cells and the leptomeningeal dissemination of CLL.

B-Lymphocytes↗

[Late fields in magnetcardiography and late potentials in electrocardiography after acute myocardial infarction].

UNLABELLED: A high specificity and a high positive prediction has been reached in risk stratification for a sudden cardiac death after acute myocardial infarction (AMI) by combining multiple methods. But sensitivity and negative prediction are still not satisfying. There are the same physiological processes underlying magnetocardiography (MCG) and electrocardiography (ECG). Nevertheless, the signals in each method contain different information. METHODS: We studied the cardiac magnetic fields in 50 patients after AMI and in 32 probands and calculated the magnetic late field (LF), according to Simsons late potential (LP) analysis. We defined normal values, according to the 95% confidence interval of the probands (QRS < =97 ms, RMS > = 0. 6, LAS < 25 ms). RESULTS: We compared the results of LF and LP analysis regarding pathologic-nonpathologic and found 76% of the patients with the same results in both methods. Four patients had magnetic signals with low amplitude in the ST segment in contrast to the ECG result, while 6 patients with a "LP positive" diagnosis based on RMS and LAS only, did not show LF. In addition, we have found the magnetic QRS complex to be shorter than the electrical one. DISCUSSION: In general, the results of LF measurement are similar to the ones of LP measurement. Presumably, there are intracardial currents, which are not detectable by ECG. Further studies are needed to evaluate the prognostic value in patients at high risk for cardiac arrhythmias.

Adult↗

Five-year results after anti-incontinence operations.

OBJECTIVE: This study was undertaken to evaluate continence rates 5 years after anterior colporrhaphy, anterior colporrhaphy with needle suspension of the bladder neck, and Burch colposuspension. STUDY DESIGN: Among 544 women with stress incontinence who were operated on between 1989 and 1993, 327 women (60%) underwent clinical and urodynamic reevaluation 5 years after the operation. Choice of surgical procedure was made on the basis of clinical and urodynamic findings and of physician preference. Continence was defined as no loss of urine during cystometry or during coughing with the bladder filled to 300 mL. RESULTS: The 327 patients underwent a total of 334 operations. The objective overall continence rates at 5 years were 61% (65/107) after anterior repair, 49% (59/121) after anterior repair with needle suspension, and 79% (84/106) after Burch colposuspension. Continence rates after anterior colporrhaphy were 82% (32/39) among patients with mild stress incontinence but 49% (33/68) among those with moderate or severe incontinence (P <.02). Continence rates among patients with moderate or severe incontinence were 49% (59/121) after anterior repair with needle suspension and 79% (84/106) after the Burch operation (P <.02). CONCLUSION: Anterior colporrhaphy can cure mild stress incontinence but is inadequate to correct severe incontinence. Additional needle suspension may be of benefit for patients with moderate to severe incontinence. Abdominal colposuspension is superior to the vaginal operations for long-term cure of stress incontinence.

Adult↗

Body mass index and outcome of incontinence surgery.

OBJECTIVE: To analyze the influence of body mass on the outcome of surgery for urinary incontinence. METHODS: Among 291 women operated on for stress incontinence, 187 (64%) were available for follow-up at 5 years. Eighty women had anterior colporrhaphy, 49 anterior colporrhaphy with needle suspension of the bladder neck, and 58 Burch colposuspension. Body mass index was calculated preoperatively and at follow-up. Women were classified as being of normal weight (body mass index [BMI] 20-25), overweight (BMI 26-30), or obese (BMI greater than 30). Reported continence rates were analyzed according to BMI for each operation and the BMIs of continent patients were compared with those of incontinent patients. RESULTS: The continence rates at 5-year follow-up for anterior colporrhaphy, anterior colporrhaphy with needle suspension of bladder neck, and Burch colposuspension were 58, 51, and 86%, respectively (P < .001). The continence rates did not differ significantly among the three BMI groups for each procedure. A statistical power of 26% was found for the hypothesis that the outcome of the procedures does not depend on BMI. The preoperative and postoperative BMIs of continent and incontinent women for each procedure did not differ significantly. CONCLUSION: We did not find preoperative obesity to be a risk factor for failure of incontinence surgery, but the power of our study was limited.

Adult↗

Herpes simplex virus encephalitis: chronic progressive cerebral MRI changes despite good clinical recovery and low viral load - an experimental mouse study.

Cranial magnetic resonance imaging (MRI) is a sensitive diagnostic tool for the in vivo detection of morphological abnormalities in herpes simplex virus encephalitis (HSVE). We performed a long-term MRI study in a mouse model of HSVE. Cranial MRI findings were compared with the viral load within brain tissue, the presence of HSV DNA in the cerebrospinal fluid (CSF), a daily clinical assessment and post-mortem neurohistopathological studies. A 1.5 T cranial MRI scanner with standard spin-echo sequences was used. Viral load within the brain and the presence of HSV DNA in cerebrospinal fluid were determined by a polymerase chain reaction assay. Clinically, animals were severely affected within the first 2 weeks and recovered thereafter. Focal histopathological and MRI abnormalities involved predominantly limbic structures, a pattern that mimics human disease. Severity and extent of abnormalities had increased at 6 months despite clinical improvement. HSV DNA was present in CSF during the acute disease only. Brain viral load peaked at day 10 and declined thereafter. MRI as an in vivo monitoring approach may reveal chronic progressive changes in HSVE, despite clinical recovery and low viral load in the brain. Secondary, not directly virus-mediated, mechanisms of tissue damage may contribute to tissue damage of HSVE.

Animals↗

Mutations in the COL5A1 coding sequence are not common in patients with spontaneous cervical artery dissections.

BACKGROUND AND PURPOSE: The dermal connective tissue of most patients with spontaneous cervical artery dissections (sCAD) contains abnormal collagen fibers. This suggests a predisposing connective tissue defect. The ultrastructural abnormalities in the skin of patients with sCAD have similarity with the morphological alterations in patients with Ehlers-Danlos syndrome type II, a dominant hereditary disorder that has been correlated in some patients to mutations within the genes encoding type V collagen. The aim of this study was to assess the alpha 1 chain of type V collagen (COL5A1) as a candidate gene for sCAD. METHODS: We searched for mutations in the COL5A1 gene in cDNA from cultured fibroblasts of 19 patients with sCAD using single-strand conformational polymorphism analysis and nucleotide sequence analysis of polymerase chain reaction-amplified fragments of the whole COL5A1 coding sequence. RESULTS: We detected 1 missense mutation leading to a predicted amino acid (192D/N) substitution within the N-terminal propeptide in 2 siblings. All other patients showed regular COL5A1 sequences with some silent polymorphisms. CONCLUSIONS: Mutations in the COL5A1 gene do not appear to be a major factor in the etiology of sCAD.

Adult↗

Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.

The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5 kg/m2) with serum DHEAS concentrations below 4.1 micromol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD) for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h; AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36 micromol/L x h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17beta-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156 vs. 700 +/- 209 pmol/L x h (P < 0.0001); AUC 0-12 h for estrone, 1443 +/- 269 vs. 2537 +/- 434 vs. 3254 +/- 671 pmol/L x h (P < 0.0001)]. In conclusion, 50 mg DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.

Aged↗

Effect of intrathecal fentanyl dose on the duration of labor analgesia.

The short duration of effective analgesia produced by intrathecal fentanyl (ITF) at doses ranging from 5 to 25 micrograms limits the drug's use for the management of labor pain. The understanding of the potential of ITF related to duration of analgesia in the labor patient is derived from studies of and clinical experience with ITF at doses not exceeding 25 micrograms and less. We hypothesized that by increasing the dose beyond 25 micrograms, a prolonged duration of analgesia could be achieved. The purpose of the present study was to compare the difference in duration of effective analgesia and adverse effects produced by 25, 37.5, and 50 micrograms of ITF. A sample population of 60 term parturient women with uncomplicated singleton pregnancies who were in active labor and requesting pain control were randomly assigned to 1 of 3 groups: group 1, 25 micrograms (n = 20); group 2, 37.5 micrograms (n = 20); and group 3, 50 micrograms (n = 20). The ITF was then administered by an anesthesia provider blinded to the dose via a combined spinal epidural technique. The time from injection to the time of request for subsequent pain control (considered the duration of effective analgesia), maternal and fetal vital signs, and adverse effects were recorded at specific intervals until the patient requested activation of the epidural catheter or delivery occurred, ending participation in the study. Statistical analysis using a 1-way analysis of variance and considering a P value of < .05 to be significant revealed no difference in duration of effective analgesia between the groups. Statistical differences in the incidence of adverse effects, particularly uterine hyperstimulation, hypotension, pruritus, nausea, and fetal heart rate decelerations were not evident using the Fisher Irwin test and a significance of P < .05. The findings of the present study demonstrate that there is no real advantage of using doses of ITF greater than 25 micrograms in quality and duration of effective labor analgesia.

Analgesia, Obstetrical↗

9-Hydroxy-9-(3-methylbut-3-en-1-ynyl)-9H-fluorene-1-carbonitrile.

The N atom in the title compound, C19H13NO, lies -0.0365 (14) A from the plane formed by the fluorene system, and the C [symbol: see text] N distance is 1.143 (2) A. The C [symbol: see text] C distance is 1.191 (2) A, and the ethynyl group deviates slightly from linearity, with C-C [symbol: see text] C-C bond angles of 172.0 (1) and 176.1 (2) degrees. Terminal CH2 and CH3 groups are 50:50 disordered, with equal C-C distances of 1.408 (3) and 1.406 (3) A.

Crystallography, X-Ray↗

Cord blood insulin to assess the quality of treatment in diabetic pregnancies.

According to the Pedersen hypothesis, fetal hyperinsulinism is the major cause for adverse neonatal outcome. We investigated associations between insulin levels in cord blood and fetal complications. Three groups of 21 insulin-dependent diabetic patients with different insulin levels in cord blood were matched according to White Classes. Insulin levels in cord blood of < 20 microU/ml were considered normal (controls), 20-50 microU/ml intermediate group, and > 50 microU/ml high (cases). The mean (+/-S.D.) insulin level in cord blood in the three groups was 10.7+/-5.6, 28.6+/-8.1, and 104.0+/-61.0 microU/ml, respectively. Controls and cases showed significant differences in birth weight > 90th percentile (9.5% vs. 76.2%), premature birth < 37 weeks (4.8% vs. 71.4%), caesarean delivery (28.6% vs. 66.4%), hypoglycaemia of the neonate (14.3% vs. 61.9%), cushingoid appearance (4.8% vs. 42.9%) and respiratory distress syndrome (0% vs. 33.3%). The results of the intermediate group were between the controls and the cases. Insulin levels in cord blood > 20 microU/ml represent a continuum of increasing diabetogenic fetopathy. We consider neonates with insulin levels in cord blood < 20 microU/ml as metabolically healthy, those with 20-50 microU/ml as having mild fetopathy, and those with > 50 microU/ml as having marked fetopathy, respectively.

Adult↗