Search PubMed⌕ Search

Biomedical subjects

H Sauer

Publications and source records attributed to H Sauer.

At least 181 records · Page 10Linked to original sources

Intracellular Ca2+ release and Ca2+ influx during regulatory volume decrease in IMCD cells.

Volume changes and cytosolic Ca2+ concentration ([Ca2+]i) of inner medullary collecting duct (IMCD) cells under hypotonic stress were monitored by means of confocal laser scanning microscopy and fura 2 fluorescence, respectively. Reduction of extracellular osmolality from 600 to 300 mosmol/kgH2O by omission of sucrose led to an increase in cell volume within 1 min to 135 +/- 3% (n = 9), followed by a partial regulatory volume decrease (RVD) to 109 +/- 2% (n = 9) within the ensuring 5 min. In parallel, [Ca2+]i rose from 145 +/- 9 to 433 +/- 16 nmol/l (n = 9) and thereafter reached a lower steady state of 259 +/- 9 nmol/l. Under low-Ca2+ conditions (10 nmol/l) RVD was not impeded and reduction of osmolality evoked only a transient increase of [Ca2+]i by 182 +/- 22 nmol/l (n = 6). Preincubation with 100 mumol/l 8-(N,N-diethylamino)octyl-3,4,5-trimethoxy-benzoate hydrochloride (TMB-8) or 20 mmol/l caffeine, both effective inhibitors of Ca2+ release from intracellular stores, in low Ca2+ as well as in high Ca2+, inhibited the Ca2+ response and abolished RVD. The temporal relationship between Ca2+ release from intracellular stores and Ca2+ entry was analyzed by determining fura 2 quenching, using Mn2+ as a substitute for external Ca2+. Intracellular Ca2+ release preceded Mn2+ influx by 17 +/- 3 s (n = 10). Mn2+ influx persisted during the whole period of exposure to hypotonicity, indicating that there is no time-dependent Ca2+ channel inactivation. Preincubation with TMB-8 or caffeine reduced Mn2+ influx to the control level, indicating that activation of Ca2+ channels in the plasma membrane occurs via intracellular Ca2+ release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Brain-derived neurotrophic factor enhances function rather than survival of intrastriatal dopamine cell-rich grafts.

Brain-derived neurotrophic factor (BDNF) has been shown to promote the survival of dopaminergic neurons from the substantia nigra in cell culture. In order to assess whether a similar survival-promoting effect is present also in vivo, we grafted fetal nigral tissue to the dopamine-depleted striatum of 6-hydroxydopamine-lesioned rats receiving two-week intraventricular infusions or daily intrastriatal injections of BDNF, NGF, or vehicle. When infused chronically at a high dose (12 micrograms/day) into the lateral ventricle, BDNF caused a behavioral syndrome of reduced food and water intake, body weight loss, and locomotor hyperactivity in comparison to NGF- and vehicle-infused graft recipients. NGF-infused graft recipients displayed a transient weight loss during the first week of infusion. At 15 days, amphetamine-induced turning was significantly attenuated to 3% of pregraft values in BDNF-infused recipients, whereas functional graft effects were not present in NGF- or vehicle-infused animals. Survival of tyrosine hydroxylase-immunoreactive graft cells, however, was similar in all treatment groups. Notably, NGF- and BDNF-infusions led to a significant size increase of cholinergic host neurons in the medial septal nucleus and the vertical limb of the diagonal band ipsilateral to the infusion, whereas there was no cholinergic neuron hypertrophy in vehicle-infused animals. Daily intrastriatal injections of BDNF (2 micrograms) produced no weight loss or locomotor hyperactivity, but also enhanced functional graft effects in BDNF-injected, as compared to vehicle-injected animals. Survival rates of grafted tyrosine hydroxylase-immunoreactive cells were, however, similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

Congenital diaphragmatic hernia presenting after the newborn period.

Late-presenting congenital diaphragmatic hernia (CDH) is often difficult to diagnose and delay in treatment is common. Seven patients were operated beyond the newborn period for left-sided Bochdaleck hernia. Their age ranged from 1 month to 9 years. Six of them became symptomatic within the 1st year of life (1 week to 9 months of age). Either feeding difficulties or recurrent respiratory infections were initially present. In all of them chest X-rays were performed but delay in diagnosis ranged from 1 week to 5 years. All diaphragmatic defects could be closed by an abdominal approach without postoperative complications. Clinical symptoms disappeared postoperatively. In children with respiratory complaints or feeding difficulties one should be aware of late presenting CDH. A careful analysis of chest films and searching for "connecting" bowel segments passing through the diaphragmatic defect may help to avoid incorrect diagnosis and undesirable delay in treatment. Confusion with pneumonia or pneumothorax can be diminished by placing a feeding tube and instillation of contrast material. Ultrasound should be used supportively in all suspected diseases of the diaphragm.

Child↗

Choledochocele: importance of histological evaluation.

Choledochocele is a rare abnormality of unknown etiology that consists of cystic or diverticular dilatations of the intramural part of the common bile duct. The authors present a case of choledochocele with a common channel in a 15-year-old boy who had a 5-year history of intermittent right upper abdominal pain. In a review of the literature, macroscopic variations were noted as well as different types of epithelial lining inside the choledochocele. Whereas in young children mostly duodenal mucosa is described, biliary tract epithelium and undifferentiated epithelium are predominant later on. Etiologically, congenital intraluminal duodenal diverticulum should be suggested in relation to the pathogenesis of choledochocele. Treatment is total excision and reinsertion of both ducts in cases of biliary or undifferentiated epithelium; endoscopic sphincterotomy or marsupialization is indicated only when duodenal mucosa covers both sides of the choledochocele.

Adolescent↗

Preservation of the ileocecal valve and right colon in total colonic aganglionosis.

A new surgical technique for the treatment of total colonic aganglionosis is described. Preservation of the right colon and the ileocecal valve is possible by performing an end-to-back anastomosis between a prececal short ileum segment and the uneffected ileum, and by creating a side-to-side anastomosis between an isolated ileal loop and the right colon. The ileorectal anastomosis is performed with a curved EEA 21 circular stapler (USSC, Norwalk, CT). After a neonatal ileostomy, the operation is performed as a one-stage procedure. The advantage of preserving the right colon and the ileocecal valve is discussed.

Anastomosis, Surgical↗

The recruitment process for a multicenter study on the long-term prophylactic treatment of affective disorders.

The paper reports on the process of patient recruitment for a controlled clinical multicenter study on the treatment of affective disorders. Two thirds of the patients screened did not participate because prophylactic treatment was either unnecessary or not justified for medical reasons. Further, a number of patients equal to that eventually allocated to the trial refused to participate for personal, idiosyncratic reasons. In spite of this, the patients in the trial were very similar to those not participating with respect to relevant variables such as age, sex, number of and intervals between previous episodes or severity of the present episode.

Adult↗

3H-spiperone binding capacity in mononuclear cells: a family study.

1. A family study was carried out using a putative biological vulnerability trait in families of schizophrenics and schizoaffective indexprobands to investigate, if the clinical phenotype and a biological marker for schizophrenia are cosegregating within families. 2. The binding capacity of the dopamine antagonist spiperone to mononuclear cells was investigated in 21 indexprobands and a total of 147 first and second degree relatives. 3. Increased binding capacity could be found in 17 indexprobands and in their affected relatives, independently from clinical diagnosis and in 22% of their normal relatives. 4. No increased binding capacity was found in 4 indexprobands and in their affected relatives and not n any of the unaffected relatives. These results indicate, that increased spiperone binding may cosegregate with the risk for functional psychoses and that families, loaded with psychiatric disturbances may be distinguished on a biological basis.

Adult↗

[Adjuvant chemo- and hormone therapy of breast cancer].

During the past few years "consensus statements" on the adjuvant treatment of patients with breast cancer have been issued periodically (the last one in the spring of 1992). Many physicians have interpreted such a tabellary synopsis as a "push-button" treatment, which is, of course, beside the point, since the text of the original publications for several subgroups of patients defines this treatment as "optional". In fact, physicians cannot decide by themselves, which treatment a patient should have. All patients must be shown both sides of the medal, i.e. a small chance to live longer and the risk of side effects, and finally each individual patient has to decide for herself on the basis of "informed consent". In case of widespread acceptance, as mentioned by some authors, that nearly all patients should be treated in some adjuvant manner, a large group which does not need any adjuvant treatment at all, will remain undefined. This group comprises at least 50% of all women ever treated for primary breast cancer. All physicians should consider it to be an urgent responsibility to define this group. This can be achieved only by means of studies, which include untreated or placebo-treated controls.

Adult↗

A technique of doubling the cremasteric muscle in large inguinal hernia repair in infants and children--a late follow-up.

Between 1969 and 1988, 259 large inguinal hernias in 241 male infants and children were repaired, using a technique of doubling the cremasteric muscle, representing 1.12% of all inguinal hernia repairs in this time period. In a late follow-up, 4 to 20 years postoperatively, 195 patients (81%) with 204 hernia repairs by doubling of the cremasteric muscle were re-evaluated. Postoperative complications occurred in 3 patients, one recurrence of the hernia, one testicular atrophy after an incarcerated hernia and one trapped testicle. The technique of doubling the cremasteric muscle in large inguinal hernia repair in male infants and children represents an alternative and safe operative procedure without further complications.

Abdominal Muscles↗

The anion transport inhibitor DIDS increases rat hepatocyte K+ conductance via uptake through the bilirubin pathway.

1. In confluent primary cultures of rat hepatocytes, membrane effects of the anion transport inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) were recorded with conventional microelectrodes. In addition, cell pH and cell Ca2+ were monitored by use of the fluorescent dyes BCECF and fluo-3, respectively. Uptake of DIDS was determined by measuring intracellular DIDS fluorescence between 470 and 520 nm (excitation wavelength 390 nm). 2. In the presence of 0.2 mM DIDS, membrane voltages hyperpolarized from -44.0 +/- 1.8 to -73.1 +/- 1.9 mV (n = 16). This change was monophasic and occurred with a time constant of 170 +/- 25 s. The effect was only partly reversible. 3. Cable analysis revealed a concomitant decrease in the specific cell membrane resistance from 3.2 to 1.5 k omega cm2. 4. In ion substitution experiments, a 10-fold elevation of external K+ (from 2.5 to 25 mM) depolarized cell membranes by 6.2 +/- 1.5 mV (n = 5). In the presence of 0.2 mM DIDS, this membrane response was increased 5-fold to 32.2 +/- 4.1 mV. 5. Replacement of Cl- by 99% with gluconate depolarized the cells by 9.3 +/- 1.9 mV. In contrast, with 0.2 mM DIDS present, Cl- removal led to a membrane hyperpolarization of 5.9 +/- 0.9 mV (n = 4). 6. DIDS had no effect on cytosolic pH or Ca2+. 7. To determine the sidedness of the DIDS effect, i.e. to analyse if the increase in K+ conductance is mediated by uptake of the compound, DIDS was added in the presence of different substrates of hepatocellular anion transport. Taurocholate (50 microM) and frusemide (0.5 mM), which are both taken up via the sinusoidal multi-specific bile acid transporter, did not change DIDS-induced membrane hyperpolarization. 8. In contrast, 0.5 mM bromosulphthalein (BSP), a substrate of the bilirubin transporter, competitively inhibited the membrane hyperpolarization elicited by various concentrations of DIDS (0.1-1.0 mM). 9. Hepatocellular uptake of BSP is known to be, in part, Cl- dependent and to be competitively inhibited by Indocyanine Green. When 0.2 mM DIDS was added to a superfusate, in which 99% of Cl- had been exchanged by gluconate, the velocity of membrane hyperpolarization was decreased by 45%. In the presence of Indocyanine Green (0.1 mM) DIDS-induced membrane hyperpolarization was reduced to approximately 20%. 10. Addition of 0.2 mM DIDS to hepatocyte monolayers led to a time-dependent increase in cell fluorescence which was absent at 4 degrees C and which was completely blocked by 0.5 mM BSP.(ABSTRACT TRUNCATED AT 400 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Can computerised tomography be used to predict early treatment response in schizophrenia?

The relationship between early treatment response and CT variables was investigated in 50 consecutively admitted patients with DSM-III schizophrenia. Treatment response was defined as the absolute BPRS improvement during patients' hospital stay and was found to be significantly correlated (P < 0.05) with the frontal horn ratio (r = -0.36), ventricular ratio (r = -0.32), width of the third ventricle (r = -0.37), width of the frontal interhemispheric fissure (r = -0.33), and average width of the three largest cortical sulci (r = -0.46). According to the results of multiple regression analysis, 35% of the variance in the treatment response was accounted for by the average width of the three largest cortical sulci, the ventricular ratio and the frontal horn ratio. Thus, cerebral abnormalities associated with poor treatment response do not seem to be limited to one particular morphological site, but involve different brain regions.

Adult↗

[Congenital post-traumatic aggravated choledochal cyst].

We present a case of congenital choledochal cyst with late aggravation after an abdominal trauma, which needed surgical resection of the cyst and cholecystectomy followed by hepato-digestive porto-jejunal anastomosis. This case shows, that inspite of minimal changes in the beginning later aggravation-for example after trauma-can be observed. Sonography is a noninvasive, non-ironising method and appears to be adequate for diagnosis and pre- and postoperative monitoring, but can not replace endoscopic, retrograde-choledochopancreaticography.

Abdominal Injuries↗

Preoperative systemic etoposide/ifosfamide/doxorubicin chemotherapy combined with regional hyperthermia in high-risk sarcoma: a pilot study.

From November 1990 to September 1991, 23 adults with high-risk, nonmetastatic sarcomas (20 soft-tissue sarcomas and 3 chondrosarcomas) were entered in a pilot protocol (RHT-91) involving regional hyperthermia combined with systemic chemotherapy followed by surgery. Of these patients, 12 had undergone previous surgery and/or radiation, 5 had received previous multidrug chemotherapy, and 6 were previously untreated. A tumor size of > 8 cm and/or an extracompartmental tumor location (11 patients) or local recurrence (12 patients) were defined as high-risk factors in addition to tumor grading (21 patients had grade 2 or 3 sarcomas). Regional hyperthermia was produced by an electromagnetic deep-regional-heating device. For systemic chemotherapy, all patients received etoposide/ifosfamide/doxorubicin (EIA) and mesna, with regional hyperthermia being given only on days 1 and 4 in repeated EIA/regional hyperthermia cycles every 3 weeks. Tumor temperatures (range, 40 degrees-44 degrees C) were measured by invasive thermometry in all patients during each regional hyperthermia treatment. A total of 181 regional hyperthermia treatments were applied within the pelvic region (11 patients) or extremities (12 patients) bearing relatively large tumors (mean volume, 848 cm3). By the cutoff date for this analysis (October 15, 1991), 13 patients had undergone surgery after receiving 2-6 (mean, 3.8) cycles of EIA chemotherapy combined with regional hyperthermia; all tumors except one were resected without disfiguration. In 22 evaluable patients (minimum, 2 EIA plus regional hyperthermia cycles), the clinical response rate was 27%, with 6 patients showing partial responses (PRs). In addition, a pathologic response to preoperative thermochemotherapy was evaluable in 13 patients, with 4 responders (31%) having > 50% histologic necrosis. In all, 3 of the responders (1 PR and 2 patients with > 50% histologic necrosis) relapsed within 3 months of surgical resection. The other 7 responding patients (5 PRs and 2 patients with > 50% histologic necrosis) showed stable disease with local tumor control. The study (RHT-91) is continuing as a multicenter phase II trial (opened on November 19, 1991) in patients with high-risk soft-tissue sarcomas to test the potential of preoperative thermochemotherapy in regard to local control and survival.

Adolescent↗

[Discrete motor and sensory disorders (neurologic soft signs) in the acute course of endogenous psychoses].

Neurological soft signs (NSS) were investigated in 67 patients with DSM-III schizophrenia (remitting course, n = 23, chronic course, n = 27) and affective psychosis (n = 17). Patients were examined on admission, 7 days later and before discharge when being in a stable condition. In all diagnostic groups the NSS scores varied in the clinical course with a significant decline towards discharge. The variation of the NSS in the clinical course was further investigated with respect to psychopathological and clinical variables. Significant correlations between NSS, thought disorders, negative symptoms and a worse premorbid adaptation were found. To characterize NSS more precisely, all subjects executed a battery of standard neuropsychological tests on discharge. This step revealed significant correlations between NSS, graphomotoric and mnestic performance, the subscale "thought processes" of the Tübinger Luria Christiansen Scale and--to a lower extent--attentional performance. Our study provides two major findings: first, NSS vary in the clinical course and second, NSS are associated with other neuropsychological, such as mnestic and attentional, disorders. Thus, one may hypothesize, that NSS do not only reflect a primary motoric and sensoric deficiency but may be characterized as heterogeneous phenomena which occur frequently in the clinical course of endogenous psychosis.

Acute Disease↗

Do NMDA receptor antagonists protect against MPTP-toxicity? Biochemical and immunocytochemical analyses in black mice.

We investigated whether excitatory amino acids acting at the N-methyl-D-aspartate (NMDA) subtype of the L-glutamate receptor contribute to the dopaminergic neurotoxicity induced by systemic administration of the Parkinson's syndrome-inducing toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57Bl/6 mice. The MPTP-regimen chosen (30-40 mg/kg body weight subcutaneously) resulted a 60-70% depletion of striatal dopamine (DA) content and a 20% reduction of tyrosine hydroxylase immunoreactive (TH-IR) cells in the substantia nigra pars compacta 20 days after administration. Repeated systemic coadministration of the non-competitive NMDA receptor antagonist MK-801 or of the novel competitive NMDA receptor antagonist CGP 40116 did not protect against MPTP-induced striatal DA depletion 20 days after toxin administration. Additionally, no short-term protective effects of MK-801 on striatal DA content were observed 24, 48, and 96 h, respectively, after exposure to MPTP. A slight and non-significant attenuation (approximately 10%) of the MPTP-induced decrease in the number of nigral TH-IR cells was observed after MK-801- and CGP 40116-treatment. We conclude that neurotoxicity of systemically administered MPTP is not substantially antagonized by NMDA receptor antagonists in mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Long distance directed axonal growth from human dopaminergic mesencephalic neuroblasts implanted along the nigrostriatal pathway in 6-hydroxydopamine lesioned adult rats.

Dissociated ventral mesencephalon of 6 to 8-week-old human embryos were implanted by stereotaxic injection at different sites along the nigrostriatal pathway in adult rats, previously subjected to a 6-hydroxydopamine lesion of the intrinsic mesotelencephalic dopamine pathways. The recipients were immunosuppressed by daily injections of cyclosporin A to prevent rejection. At 13-20 weeks after transplantation, the implanted human neurons and their associated fiber outgrowths were visualized with a species-specific antibody recognizing human, but not rat, intermediary neurofilaments (HNF). From implants placed in the host rostral mesencephalic region, HNF-positive axonal projections were seen to extend in large numbers rostrally along the medial forebrain bundle and the internal capsule, and ramify within the caudate putamen, the ventral striatum and the amygdaloid nuclei (a distance of about 5-6 mm), and more sparsely in the frontal cortex and the olfactory bulb (a distance of about 10 mm). From implants placed in the internal capsule, abundant HNF-positive axons extended in the rostral, but not caudal, direction along the myelinated fiber bundles into the caudate putamen and the ventral striatum. Tyrosine hydroxylase (TH) immunohistochemistry revealed that the vast majority of the rostrally projecting HNF-positive axons were also TH-positive, and that the graft-derived axons gave rise to dense TH-positive terminal networks, above all in large areas of the previously denervated caudate putamen. From control implants of cortical neuroblasts, axonal projections were seen along the medial forebrain bundle and the internal capsule, but the axons were TH-negative and showed only sparse projections to the striatal areas. Instead, dense projections were seen, e.g., in the frontal cortex. The results demonstrate a remarkable ability of human mesencephalic neuroblasts to extend axons along the trajectories of the nigrostriatal and mesolimbocortical pathways to reach and innervate the principal striatal and limbic target areas in the forebrain. This shows that the basic requirements for the formation of long axonal pathways may be present in the adult mammalian central nervous system (CNS) at least for certain types of projection neurons. Furthermore, it implies that the developing human neuroblasts can escape the inhibitory features known to be present along myelinated growth trajectories in the adult mammalian brain. In addition, the present approach may offer new possibilities for functional neural grafting in the rat Parkinson model, since transplanted nigral neurons placed in their natural position within the rostral mesencephalon could provide an anatomically and functionally more integrated system than the standard model with ectopically placed intrastriatal nigral grafts.

Animals↗