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Biomedical subjects

C Roth

Publications and source records attributed to C Roth.

At least 73 records · Page 4Linked to original sources
PubMed1999

Tumor stimulator cell modification by infection with Newcastle Disease Virus: analysis of effects and mechanism in MLTC-CML cultures.

Effects of tumor stimulator cell modification by infection with Newcastle Disease Virus (NDV) are described as analysed in vitro in mixed lymphocyte tumor cell cultures (MLTC). Direct antitumor effects were seen with human melanoma or colon-carcinoma cells in a dose- and time-dependent manner when using live but not UV inactivated virus. When T cell stimulation was measured by [3H]-thymidine uptake, NDV infected tumor stimulator cells did not show an augmentation but rather an inhibitory effect in comparison to non-infected stimulator cells. Virus infected tumor stimulator cells were, however, capable of augmenting the induction of tumor specific cytotoxic T cells in MLTC-CML assays when using murine ESb lymphoma immune cells and syngeneic NDV modified ESb cells as stimulators. A CML stimulatory effect was also shown for NDV modified third party cells and thereof derived conditioned medium. These effects are most likely explained by interferon- which is induced in tumor cells by NDV infection and by interferon-á which is induced in responder cells when stimulated with NDV infected stimulator cells.

Animals↗
PubMed1999

Genetics in the study of mosquito susceptibility to Plasmodium.

Within the past several years, a number of powerful genetic and genomic tools have been developed for use in research on the African malaria vector Anopheles gambiae. While these tools have been developed with a broad range of potential applications in mind, they have been particularly useful in advancing the effort to clone a set of An. gambiae genes that enable a refractory strain of this mosquito to encapsulate and kill a wide variety of different malaria parasites to which this mosquito is normally fully susceptible. This paper describes the latest progress in this map-based cloning research, which involves the collaborative contributions of a number of different laboratories in Europe and the United States.

Animals↗
PubMed1998

Ontogeny of the GNRH-, glutaminase- and glutamate decarboxylase-gene expression in the hypothalamus of female rats.

Amino acid neurotransmitters like gamma-aminobutyric acid (GABA) and glutamate (GLU) are involved in the regulation of hypothalamic gonadotropin releasing hormone (GnRH) release. We investigated, whether there are changes of gene expression in the rat hypothalamus for GnRH, GnRH receptor, as well as glutaminase and glutamate decarboxylase, two enzymes regulating neurotransmitter concentrations of GLU and GABA in the brain during the ontogeny. After reverse transcription-polymerase chain reaction (RT-PCR) we used an ELISA method to quantify PCR products. In 15-day old animals high plasma luteinizing hormone (LH) levels with pronounced variations were found. In 25-day old animals LH values were low, whereas in 35-day old rats LH levels increased significantly indicating the reactivation of the GnRH-pulse generator at the beginning of puberty. In parallel to these changes, the mRNA levels of the GnRH receptor in the mediobasal hypothalamus were high at day 15, significantly lower at day 25 and again high at day 35 after birth (ELISA O.D. GnRH-R day 15: 0.46+/-0.07, day 25: 0.16+/-0.04, day 35: 0.36+/-0.04; p<0.01), but no changes of GnRH receptor gene expression were found in the preoptic area. The mRNA of GnRH in the preoptic area as well as mRNA levels of glutaminase and glutamate decarboxylase in the mediobasal hypothalamus and the preoptic area did not change during ontogeny. We conclude that hypothalamic GnRH receptors are involved in the characteristic changes of LH secretion patterns during sexual maturation. Major changes of GnRH receptor gene expression occurred in the mediobasal hypothalamus and correlated well with plasma LH levels, whereas hypothalamic mRNA levels of GnRH, glutaminase and glutamate decarboxylase did not change within the different age groups. Thus the activity of the GABA- and glutamatergic system during ontogeny may be regulated at the receptor or postreceptor level.

Aging↗
PubMed1998

Human versus porcine insulin in patients with insulin-dependent diabetes mellitus: differences in sleep and the sleep EEG during near-normoglycemia.

To investigate whether porcine insulin (PI) and human insulin (HI) have different effects on brain functions outside of hypoglycemia, sleep and the sleep EEG were recorded in eight insulin-dependent diabetes mellitus (IDDM) patients in three separate sessions of 2 consecutive nights. Near-normoglycemia was confirmed by measurements of capillary blood glucose before and after sleep and at 0145 hours. The treatment effect (PI compared to HI) consisted of a change in the NREM sleep EEG in the spindle frequency range. Spectral power density in the 14-Hz bin was reduced upon transfer from PI (session 1) to HI (session 2) in all subjects, and increased upon reversal to PI (session 3) in all but one subject. There were no significant treatment effects on any other sleep EEG variable or on sleep stages. The subjects rated their sleep as more sound and their state in the morning as more relaxed during PI treatment. They were, however, not blinded to the type of insulin they were using. Porcine insulin and human insulin may exert differential effects on spindle-generating mechanisms in the thalamocortical system. The results indicate that human insulin may affect brain functions differently compared to animal insulin under near-normoglycemic conditions.

Adult↗
PubMed1998

Predictors of treatment efficacy in a clinical trial of three psychosocial treatments for adolescent depression.

OBJECTIVE: To assess the predictors of treatment outcome across treatments, as well as those associated with differential treatment response. METHOD: One hundred seven adolescent outpatients, aged 13 to 18 years, with DSM-III-R major depression were randomly assigned to one of three manual-based, brief (12 to 16 sessions) psychosocial treatments: cognitive-behavioral therapy (CBT), systemic-behavioral family therapy, or nondirective supportive therapy. Those with good and poor outcomes were compared. RESULTS: Continued depression was predicted by clinical referral (versus via advertisement) and was in part mediated by hopelessness. Other predictors of depression were comorbid anxiety disorder and higher levels of cognitive distortion and hopelessness at intake. Achievement of clinical remission was predicted by a higher level of self-reported depression. Poorer functional status was predicted by a higher level of initial interviewer-rated depression. Comorbid anxiety and maternal depressive symptoms predicted differential treatment efficacy. CBT's performance continued to be robust with respect to nondirective supportive therapy, even in the presence of the above-noted adverse predictors. CONCLUSION: Predictors of poor outcome may give clues as to how to boost treatment response. Subjects who come to treatment for clinical trials via advertisement (versus clinical referral) may show more favorable treatment responses. CBT is likely to be a robust intervention even in more complex and difficult-to-treat patients.

Adolescent↗
PubMed1998

Effect of frequent brief awakenings from nonREM sleep on the nonREM-REM sleep cycle.

In the framework of a selective sleep deprivation study, eight young men were repeatedly awakened during 3 nights from nonREM sleep (nonREMS). The mean number of awakenings per night was 27.4, 29.5 and 32.8. In order to avoid excessive suppression of slow wave sleep, no awakening occurred in the first nonREMS episode. Compared to baseline, cycle 2 was significantly prolonged in all 3 nights, and cycle 3 in night 3 only. However, after subtracting the waking intervals, the differences from baseline was eliminated. The results show that the mechanisms underlying sleep cycle control keep track of sleep time and disregard epochs of waking.

Adult↗
PubMed1998

Selective REM sleep deprivation in humans: effects on sleep and sleep EEG.

To investigate rapid eye movement (REM) sleep regulation, eight healthy young men were deprived of REM sleep for three consecutive nights. In a three-night control sleep deprivation (CD) session 2 wk later, the subjects were repeatedly awakened from non-REM sleep in an attempt to match the awakenings during the REM sleep deprivation (RD) nights. During the RD nights the number of sleep interruptions required to prevent REM sleep increased within and across consecutive nights. REM sleep was reduced to 9.2% of baseline (CD nights: 80.7%) and rose to 140.1% in the first recovery night. RD gave rise to changes in the EEG power spectra of REM sleep. Power in the 8.25- to 11-Hz range was reduced in the first recovery night, an effect that gradually subsided but was still present in the third recovery night. The rising REM sleep propensity, as reflected by the increase of interventions within and across RD nights, and the moderate REM sleep rebound during recovery can be accounted for by a compensatory response that serves REM sleep homeostasis. The changes in the electroencephalogram power spectra, which were observed during enhanced REM sleep propensity, may be a sign of an altered quality of REM sleep.

Adult↗
PubMed1998

Hyperphagia in children with craniopharyngioma is associated with hyperleptinaemia and a failure in the downregulation of appetite.

Patients with craniopharyngioma frequently suffer from severe obesity. Leptin induces an inhibition of appetite via hypothalamic receptors. This study was undertaken to investigate whether a relationship exists between serum leptin levels and pituitary/hypothalamic lesions in craniopharyngioma patients. Serum leptin levels were evaluated by RIA in 14 patients (age 7-21 years; 7 females, 7 males) after they had undergone neurosurgical treatment for craniopharyngioma. Normal controls had a positive correlation between leptin levels and body mass index (BMI) with higher levels in the females than in the males. Significantly elevated leptin levels with respect to BMI were found in 11 craniopharyngioma patients who had been affected by a suprasellar tumour, whereas 3 patients with an intrasellar tumour had lower, almost normal serum leptin levels. Our data suggest that craniopharyngioma patients develop hypothalamic obesity because their hypothalamic structures are insensitive to endogenous leptin. The elevated serum leptin concentrations found only in patients with a suprasellar tumour may be explained by a disturbed feedback mechanism from the hypothalamic leptin receptors to the adipose tissue.

Adolescent↗
PubMed1998

[123I-scintigraphy and perchlorate depletion test in the diagnosis of congenital hypothyroidism].

AIM: Thirty eight children suffering from congenital primary permanent hypothyroidism were studied to determine the diagnostic impact of 123I scintigraphy in comparison to laboratory findings and ultrasonography. METHODS: In all patients 123I scintigraphy was performed after intravenous administration of 3.7 MBq 123I. If accumulation of the radiotracer in thyroid tissue occurred a perchlorate discharge test was performed subsequently. RESULTS: Scintigraphy revealed athyrosis in 7 children. In 9 children a lingual thyroid was observed. Deficiency in iodine organification was diagnosed by a significant discharge of 123I in 15 patients. In four of these children the diagnosis of Pendred's syndrome could be established. Ectopic thyroid tissue could be demonstrated only by scintigraphy where clinical examination and sonography failed in the diagnosis in all cases. Hypoplasia of the thyroid gland as it was diagnosed in 2 cases by ultrasonography appeared to be unlikely because a normal 123I uptake was seen in these patients. In 2 patients with scintigraphic proven athyrosis an orthotopic gland had been falsely considered by ultrasound. In 44% of our patients the final diagnosis could only be established if 123I scintigraphy and perchlorate discharge test were performed. CONCLUSION: This findings suggest that scintigraphy is indispensible in the correct diagnostic work up of congenital hypothyroidism.

Child↗
PubMed1997

The influence of the spatial structure of focal hepatic lesions on volume measurements performed with two and three-dimensional sonography using the ellipsoid formula.

A total of 63 patients with localized hepatic lesions were examined using two and three-dimensional sonography. The tumor volumes were calculated by means of the ellipsoid formula, compared with an experimentally determined reference volume and subsequently differentiated into correct and erroneous measurements according to the WHO criteria for tumor volumes. In a second test series, an analysis of the tumor shapes was carried out using parallel projections. It could be seen that 65% of the erroneous measurements resulted from the use of the ellipsoid formula, a procedure which is used to determine the volume of hepatic lesions. In the third part of this study, it was found that findings which are difficult to measure are frequently not recognized as such by the investigator making use of two-dimensional sonography. As a consequence, the volume measurements of focal hepatic lesions in oncology patients being considered for particular therapies should preferably be carried out with the aid of planimetric measurements rather than with the use of the ellipsoid formula.

Biometry↗
PubMed1997

Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

Expression of AP-2 transcription factors has been detected previously in embryonic renal tissues. We show here that AP-2beta -/- mice complete embryonic development and die at postnatal days 1 and 2 because of polycystic kidney disease. Analyses of kidney development revealed that induction of epithelial conversion, mesenchyme condensation, and further glomerular and tubular differentiation occur normally in AP-2beta-deficient mice. At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. Addressing the molecular mechanism we show that transfection of AP-2 into cell lines in vitro strongly suppresses c-myc-induced apoptosis pointing to a function of AP-2 in programming cell survival during embryogenesis. The position of the human AP-2beta gene was identified at chromosome 6p12-p21.1, within a region that has been mapped for autosomal recessive polycystic kidney disease (ARPKD). Sequence analyses of ARPKD patients and linkage analyses using intragenic polymorphic markers indicate that the AP-2beta gene is located in close proximity to but distinct from the ARPKD gene.

Animals↗
PubMed1997

[Neonatal Basedow's disease in twins from a mother with severe T3 hyperthyroidism].

HISTORY AND CLINICAL FINDINGS: Dizygotic twin sisters were born to a woman who, shortly before becoming pregnant, had developed Graves' disease with markedly elevated triiodothyronine (T3) levels and highly positive TSH receptor antibody titres (TRAb: 169 mU/ml). From the second week of life onwards they had a goitre and hyperexcitability, tachycardia and failure to thrive were noted. In addition, twin I had mild exophthalmos. As thyrostatic treatment of the mother was very difficult, intrauterine hypothyroidism or transitory hyperthyroidism had presumably occurred in the twins. INVESTIGATIONS: Twin I had maximal thyroxine (T4) concentration of 26.2 micrograms/dl, while it was 24.7 micrograms/dl in twin II with suppressed TSH. Both twins had high concentrations of TRAb and antibodies against thyroid peroxidase. DIAGNOSIS, TREATMENT AND COURSE: With the diagnosis of neonatal Graves' disease established, both twins were treated with propranolol (2 mg/kg.d) and phenobarbitone (2-4 mg/kg.d). Twin I, whose symptoms were more severe, also received propylthiouracil (5 mg/kg.d) until euthyroidism had been achieved. Although twin II became euthyroid spontaneously, she gained weight only slowly and microcephaly developed together with definite motor and mental retardation. It remains unclear whether these were consequences of intrauterine hypothyroidism or post-partum hyperthyroidism. CONCLUSION: Graves' disease during pregnancy demands interdisciplinary collaboration between gynaecologist, physician and paediatrician to prevent severe sequelae in the children. Early risk assessment is possible by measuring the TSH receptor antibody titre in umbilical blood.

Adrenergic beta-Antagonists↗
PubMed1997

[How risky is lung resection today?--perioperative morbidity and mortality in open thorax surgery].

We retrospectively analyzed hospital morbidity and mortality following primary open lung surgery from August 1990 to December 1994 in 187 consecutive patients. 180 pulmonary resections and 7 exploratory thoracotomies were performed in 141 men and 46 women, with mean age 60.4 +/- 11.9 years. 142 patients were aged < 70 years (median 58.5), and 45 (25%) > 70 years (median 73). Tumor stage as well as preoperative ASA classification and FEV1 were similar in these age groups. No difference could be found in hospital morbidity of elderly compared to younger patients (> or = 70 years: 40%; < 70 years: 40.8%), but 30-day mortality was higher in elderly (8.9% versus 2.8% in younger subjects). Elderly patients who died postoperatively presented a higher preoperative risk (ASA 2.75) compared to nonfatal cases in the same age group (ASA 2.18). Morbidity and mortality increased with the extent of surgery; the 30-day mortality was nil in the group of wedge and segmental resections (0/23), 1.9% in lobectomies (2/106) and 7.8% in pneumonectomies (4/51). Our results in general match those of comparable centers in Switzerland and the international literature. Since the overall complication rate was not increased compared to younger patients, we assume that polymorbidity of single cases was the cause of higher mortality after extended open lung surgery in septuagenarians and octogenarians. In consequence, the scope of surgery should be reduced as far as possible. In addition, the perioperative risk for the senescent patient can be improved by identification of high risk cases. With this attitude we take the view that lung resection can honestly be recommended to the elderly also.

Adolescent↗
PubMed1997

A clinical psychotherapy trial for adolescent depression comparing cognitive, family, and supportive therapy.

BACKGROUND: Previous studies in nonclinical samples have shown psychosocial treatments to be efficacious in the treatment of adolescent depression, but few psychotherapy treatment studies have been conducted in clinically referred, depressed adolescents. METHODS: One hundred seven adolescent patients with DSM-III-R major depressive disorder (MDD) were randomly assigned to 1 of 3 treatments: individual cognitive behavior therapy, systemic behavior family therapy (SBFT), or individual nondirective supportive therapy (NST). Treatments were 12 to 16 sessions provided in as many weeks. Intent-to-treat analyses were conducted using all follow-up data. RESULTS: Of the 107 patients enrolled in the study, 78 (72.9%) completed the study, 4 (3.7%) never initiated treatment, 10 (9.3%) had exclusionary criteria that were undetected at entry, 8 (7.5%) dropped out, and 7 (6.5%) were removed for clinical reasons. Cognitive behavior therapy showed a lower rate of MDD at the end of treatment compared with NST (17.1% vs 42.4%; P = .02), and resulted in a higher rate of remission (64.7%, defined as absence of MDD and at least 3 consecutive Beck Depression Inventory scores < 9) than SBFT (37.9%; P = .03) or NST (39.4%; p = .04). Cognitive behavior therapy resulted in more rapid relief in interviewer-rated (vs both treatments, P = .03) and self-reported depression (vs SBFT, P = .02). All 3 treatments showed significant and similar reductions in suicidality and functional impairment. Parents' views of the credibility of cognitive behavior therapy improved compared with parents' views of both SBFT (P = .01) and NST (P = .05). CONCLUSIONS: Cognitive behavior therapy is more efficacious than SBFT or NST for adolescent MDD in clinical settings, resulting in more rapid and complete treatment response.

Adolescent↗
PubMed1997

Short stature and failure of pubertal development in thalassaemia major: evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin secretion.

UNLABELLED: In patients with beta-thalassaemia major, frequent blood transfusions combined with desferrioxamine chelation therapy lead to an improved rate of survival. Endocrine disorders related to secondary haemosiderosis such as short stature, delayed puberty and hypogonadism are major problems in both adolescent and adult patients. A total of 32 patients with beta-thalassaemia major undergoing treatment at the Children's Hospital, University of Göttingen were examined. Fourteen of these were short in stature. Growth hormone (GH) secretion was investigated in 13 patients exhibiting either a short stature or reduced growth rate. The stimulated GH secretion of 10 patients in this subgroup lay within the normal range. Studies of their spontaneous GH secretion during the night revealed that these patients had a markedly reduced mean GH and reduced amplitudes in their GH peaks. Low insulin-like growth factor (IGF)-I levels were seen in the growth-retarded thalassaemic patients. Eight were subjected to an IGF generation test and showed a strong increase in both IGF-I and insulin-like growth factor binding protein (IGFBP)-3 levels indicating intact IGF-I generation by the liver. Hypogonadotropic hypogonadism was found to be present in both the male and female patients with impaired sexual development. After priming with LH-releasing hormone (GnRH) per pump in 2 female and 5 male patients, no change in either their serum oestradiol or testosterone levels or in LH/FSH response to GnRH was observed suggesting that they were suffering from a severe pituitary gonadotropin insufficiency. Three male patients at the age of puberty but exhibiting short stature. low GH, low IGF-I and hypogonadism received low dose long-acting testosterone. After 3 12 months of therapy there was a marked growth spurt, higher nocturnal GH levels and an increase in both IGF-I and IGFBP-3. CONCLUSION: Reduced GH secretion and low IGF-I in thalassaemic patients are related to a neurosecretory dysfunction due to iron overload rather than to liver damage. Hypogonadotropic hypogonadism is caused by the selective loss of pituitary gonadotropin function. In patients with both GH deficiency and hypogonadism, low dose sexual steroid treatment should be considered either as an alternative or an additional treatment before starting GH therapy.

Adolescent↗
PubMed1997

Involvement of gamma amino butyric acid (GABA) in the postnatal function of the GnRH pulse generator as determined on the basis of GnRH and GnRH-receptor gene expression in the hypothalamus and the pituitary.

In many species the GnRH pulse generator functions early postnatally to become arrested during infancy. In rats highly variable LH levels in 15-day-old animals are suggestive that LH is being released by the pituitary in pulses whereas between day 20 after birth and puberty LH levels are low indicating that the GnRH pulse generator is arrested. In the present study we show on the basis of consecutively withdrawn blood samples in 15-day-old animals that LH pulses are indeed present at that age. The proper function of GnRH receptors in the pituitary is crucially dependent on pulsatile GnRH release from the hypothalamus. In addition, GnRH receptors have been demonstrated in the medial preoptic area and in the mediobasal hypothalamus of adult rats. In 15-day-old animals the functional GnRH pulse generator results in upregulated GnRH receptor gene expression as demonstrated by quantitative RT-PCR. It is not known what neural mechanisms are involved in turning the GnRH pulse generator off during infancy and a GABAergic brake has been discussed. Indeed, when 30-day-old animals were injected with the GABA-A receptor blocking drug bicuculline, this resulted in increased serum LH levels indicating that a tonic GABAergic inhibition is indeed operative at this age.

Aging↗
PubMed1997

Diagnostic value of 123iodine scintigraphy and perchlorate discharge test in the diagnosis of congenital hypothyroidism.

AIM: Forty children suffering from congenital primary permanent hypothyroidism were studied to determine the diagnostic impact of 123I scintigraphy in comparison to laboratory findings and ultrasonography. METHODS: In all patients 123I scintigraphy was performed after intravenous administration of 3.7 MBq 123I. If accumulation of the radiotracer in thyroid tissue occurred a perchlorate discharge test was performed subsequently. RESULTS: Scintigraphy revealed athyrosis in 7 children. In 11 children a lingual thyroid was observed. Deficiency in iodine organification was diagnosed by a significant discharge of 123I in 15 patients. In four of these children the diagnosis of Pendred's syndrome could be established. Ectopic thyroid tissue could be demonstrated only by scintigraphy where clinical examination and sonography failed in the diagnosis in all cases. Hypoplasia of the thyroid gland as it was diagnosed in 2 cases by ultrasonography appeared to be unlikely because a normal 123I uptake was seen in these patients. In 2 patients with scintigraphic proven athyrosis an orthotopic gland had been considered by ultrasound. In 50% of our patients the final diagnosis could only be established if 123I scintigraphy and perchlorate discharge test were performed. CONCLUSION: This findings suggest that scintigraphy is indispensible in the correct diagnostic work up of congenital hypothyroidism.

Child↗