Search PubMed⌕ Search

Biomedical subjects

M Koch

Publications and source records attributed to M Koch.

At least 199 records · Page 11Linked to original sources
PubMed1997

Diet does not ensure normal development in galactosemia.

This review deals with the treatment of inherited classical galactosemia by a lactose-free diet. Although, with dietary treatment, there is a remarkable improvement in the acute phase of the disease, the long-term outcome has been disappointing for most patients, especially regarding the central nervous system and ovarian dysfunction in females. There is a need for new approaches to treatment, in combination with diet therapy, that could improve the outcome of patients with galactosemia.

Galactosemias↗
PubMed1997

Apolipoprotein A, fibrinogen, age, and history of stroke are predictors of death in dialysed diabetic patients: a prospective study in 412 subjects.

BACKGROUND: Diabetic patients with end-stage renal failure (ESRD) have a high cardiovascular morbidity and mortality. The underlying mechanisms are not completely elucidated. The aim of our study was to define predictors of death in diabetic patients with end-stage renal disease. PATIENTS AND METHODS: We performed a prospective study in 35 dialysis centres in Germany between 1985 and 1994. To evaluate predictors and risk factors in this population we examined 412 diabetic patients at the time of admission to dialysis treatment (peritoneal dialysis (PD) or haemodialysis (HD)). Classification of the type of diabetes was done according the criteria of the National Diabetes Data Group [1,2]. Items assessed at the time of admission were coronary artery disease (CAD), peripheral occlusive disease (POD), and stroke. CAD was defined as a history of myocardial infarction with the corresponding changes in the ECG or luminal narrowing by more than 50% in at least one coronary artery upon coronarangiography; POD was defined as claudication and/or brachial-tibial ratio (BTR) less than 0.9 or a history of amputation. Assessment of the nutritional state comprised body mass index, skinfold thickness of the upper arm and lateral thorax area, and urea concentration. Cholesterol, HDL, LDL, apolipoprotein A (ApoA-I) and B (ApoB), triglycerides, lipoprotein(a) (Lp(a)), and fibrinogen were measured. As an index of disturbed cardiac innervation beat-to-beat variation was measured. Outcome measurements were causes of death (i.e. cardiac and non-cardiac) and time of survival. RESULTS: One hundred and eighty of 412 (44%) patients died during the observation period. Patients who died were older (61 +/- 12 versus 53 +/- 15 years P < 0.0001), had lower skin fold thickness (13.1 +/- 6.0 versus 15.1 +/- 7.3 mm P < 0.04), lower ApoA-I (100 +/- 35 versus 111 +/- 32 mg/dl P < 0.005) and higher fibrinogen (515 +/- 146 versus 451 +/- 155 mg/dl P < 0.02). Type II diabetic patients had a lower mean survival time than type I (34 versus 66 months P < 0.0006). The mode of renal replacement therapy (PD or HD) had no adverse effect on survival time. Survivors less frequently had a history of CAD, POD and stroke than non-survivors. In multivariate analysis ApoA-I, fibrinogen, age and stroke were independent predictors of cardiac and non-cardiac death in diabetic patients with end-stage renal failure. Lipid values and nutritional state did not independently predict the overall and cardiovascular mortality. CONCLUSION: This study in dialysed diabetic patients identifies several predictors of death, some of which are susceptible to intervention.

Adult↗
PubMed1997

Relevance of conventional cardiovascular risk factors for the prediction of coronary artery disease in diabetic patients on renal replacement therapy.

BACKGROUND: Diabetic patients undergoing renal replacement therapy have a high cardiovascular mortality. As the rate of patients with diabetic nephropathy rises, adequate risk stratification subsequent to renal transplantation is warranted. It was the aim of our study to elucidate whether conventional risk factors are valid predictors of coronary artery disease in this group of patients with chronic renal failure subsequent to transplantation. METHODS AND RESULTS: Between 1989 and 1993, 105 consecutive diabetic patients (70 men, 35 women, 77 type I and 28 type II diabetics, mean age 43 +/- 12 years) were examined during the first six months of dialysis treatment. Coronary angiography was performed in all patients regardless of clinical symptoms of coronary artery disease (CAD). In 38 patients (36%) CAD was documented (single-vessel disease: 17 patients, double-vessel disease: 6 patients, triple-vessel disease: 15 patients). Manifestations of coronary atherosclerosis were seen in 49 patients (47%). Angina pectoris was present in 9 out of 38 patients (24%), the sensitivity to detect CAD was 43% and 52% for ST-segment depression assessed at rest. Risk factors for atherosclerosis like hypertension, smoking, cholesterol (total cholesterol, HDL-,LDL-cholesterol), triglycerides as well as concentrations of lipoprotein (a) and fibrinogen were not significantly different in patients with or without coronary artery disease. Atherosclerotic manifestations of cerebral and peripheral arteries as well as manifestations of diabetic microangiopathy like retinopathy did not correlate with the prevalence of CAD. In 11 out of 38 patients (29%) cardiac interventions (3 x CA BG, 8 x PTCA) were performed. All of them were defined as transplantable after myocardial revascularisation. CONCLUSIONS: Clinical symptoms as well as the cardiovascular risk profile are not valid predictors of CAD in diabetic patients with chronic renal failure. Therefore coronary angiography should be performed in all diabetic patients prior to renal transplantation.

Adult↗
PubMed1997

Corticotropin-releasing factor in the caudal pontine reticular nucleus mediates the expression of fear-potentiated startle in the rat.

The fear-potentiated startle paradigm is a valuable model for the investigation of the neuronal basis of fear. Previous studies have demonstrated that the neuropeptide corticotropin-releasing factor (CRF) plays an important role in fear-related processes, notably in the potentiation of the acoustic startle response. The present study investigated the role in fear-potentiated startle of CRF in the caudal pontine reticular nucleus, a brain nucleus that mediates the acoustic startle response. First, we showed that the central nucleus of the amygdala gives rise to a CRFergic projection to the caudal pontine reticular nucleus. In the second experiment, we iontophoretically applied CRF to caudal pontine reticular nucleus neurons and extracellularly recorded the activity of these neurons. CRF had a mainly excitatory effect on the tone-evoked activity of the neurons. In our third experiment, we injected the CRF antagonist alpha-helical CRF into the caudal pontine reticular nucleus of awake rats. Here, alpha-helical CRF dose-dependently blocked fear-potentiated startle, but had no effect on the baseline startle amplitude. The present results show that CRF-containing neurons which project from the central nucleus to the caudal pontine reticular nucleus are important for the enhancement of startle by fear, and further characterize the hypothetical neuronal circuitry underlying the expression of fear-potentiated startle.

Analysis of Variance↗
PubMed1997

Identification of an essential Caulobacter crescentus gene encoding a member of the Obg family of GTP-binding proteins.

We have identified an essential Caulobacter crescentus gene (cgtA) that encodes a member of a recently identified subfamily of GTPases (the Obg family) conserved from Bacteria to Archaea to humans. This evolutionary conservation between distantly related species suggests that this family of GTP-binding proteins possesses a fundamental, yet unknown, cellular role. In this report, we describe the isolation and sequence of the cgtA gene. The predicted CgtA protein displays striking similarity to the Obg family of small, monomeric GTP-binding proteins, both in the conserved guanine nucleotide-binding domains and throughout the N-terminal glycine-rich domain that is found in many members of the Obg family. Disruption of the cgtA gene was lethal, demonstrating that this gene is essential for cell growth. Immunoblot analysis revealed that CgtA protein levels remained constant throughout the C. crescentus cell cycle.

Alleles↗
PubMed1997

Pyogenic infectious spondylitis: clinical, laboratory and MRI features.

Pyogenic infectious spondylitis (PIS) is an uncommon but serious inflammatory disorder of the discovertebral junction with frequent involvement of neural structures including the spinal cord. We report a series of 41 patients (age range 21-75 years, mean age 59 years) with primary PIS confirmed by signal abnormality of the intervertebral disk and adjacent vertebral bodies on magnetic resonance imaging. The prevailing clinical symptom was focal back pain aggravated by percussion in 90% of patients. Radicular signs or symptoms were present in 59% and spinal cord symptoms in 29% of patients, respectively. Evidence of inflammation consisted of an elevated sedimentation rate in 76%, leukocytosis in 61% and fever in 61% of individuals. Predisposing factors such as diabetes mellitus, previous nonspinal surgery and other sites of infection or inflammation were identified in 17 (41%) patients and 30 (73%) were older than 50 years. The lumbar spine was most often affected and PIS was associated with an epidural abscess in 15 (37%) patients. Increased alertness for PIS in the context of focal back pain with clinical or laboratory signs of inflammation is needed to speed up its detection.

Abscess↗
PubMed1997

Apolipoprotein B, fibrinogen, HDL cholesterol, and apolipoprotein(a) phenotypes predict coronary artery disease in hemodialysis patients.

Patients with end-stage renal disease have a markedly elevated risk for coronary artery disease (CAD). Lipids and most lipoproteins, however, seem to be not predictive for CAD in these patients. Although there is clear evidence that lipoprotein(a) [Lp(a)] is significantly elevated in these patients, no study with a sufficiently large group of hemodialysis patients has investigated the relationship between CAD and Lp(a), as well as the genetically determined apolipoprotein(a) [apo(a)] phenotype. This cross-sectional study determines the prevalence of CAD in relation to the cardiovascular risk profile in an unselected population of 607 hemodialysis patients, of which 33% were diabetic patients. Twenty-six percent (n = 158) of all patients suffered from CAD as diagnosed by a definitive myocardial infarction (n = 102) and/or at least one stenosis >50% of a coronary artery (n = 143). In univariate analysis, several classic risk factors, including the concentration of lipids, lipoproteins, apolipoproteins, and fibrinogen, correlated with CAD. Lp(a) in patients with CAD showed only a tendency to higher levels, without reaching significance, compared with patients without CAD (26.6 +/- 30.8 mg/dl versus 22.1 +/- 30.4 mg/dl, P = 0.10). The frequency of low molecular weight apo(a) isoforms, however, was significantly greater in the group with CAD (34.8% versus 23.6%, P < 0.01). Stepwise logistic regression analysis found seven variables associated with CAD: apolipoprotein B, the low molecular weight apo(a) phenotype, male sex, age, fibrinogen, diabetes mellitus, and HDL cholesterol. The association of these variables with CAD differed depending on age. These results indicate that, besides classic risk factors such as age, sex, and diabetes mellitus, additional factors of the lipoprotein and fibrinolytic system contribute to the high prevalence of CAD in hemodialysis patients.

Adult↗
PubMed1997

Development of insulin resistance and elevated blood pressure during therapy with cyclosporine A.

OBJECTIVES: Essential hypertension and insulin resistance frequently coexist; cyclosporine A (CsA) is known to induce hypertension which has been used as a model for essential hypertension. The present study aimed to evaluate whether elevated blood pressure and insulin resistance coexist during CsA therapy to prove the similarity between essential hypertension and CsA induced hypertension. DESIGN: Normotensive patients who underwent keratoplasty were investigated before and during single therapy with CsA (2-4 mg/kg body weight) in an open A-B Trial. PATIENTS: Eighteen lean, normotensive patients without metabolic disorders with normal renal function and without family history of hypertension or metabolic abnormalities. MAIN METHODS: Insulin sensitivity index was determined by the modified frequent sampling intravenous glucose tolerance test (FSIGT) and blood pressure was determined by indirect ambulatory blood pressure monitoring. RESULTS: Mean insulin sensitivity index (S1) was significantly reduced (p < 0.03) during treatment with CsA (4.4 +/- 2.6 x 10(-4) vs 2.8 +/- 2.0 x 10(-4)/min per microU/ml), whereas mean systolic daytime blood pressure increased from 126.4 +/- 10.8 mmHg to 135.7 +/- 11.8 mmHg (p < 0.02), as well as the corresponding diastolic blood pressure from 76.8 +/- 8.7 mmHg to 82.8 +/- 9.3 mmHg (p < 0.05). CONCLUSIONS: CsA therapy induces elevated blood pressure and insulin resistance as seen in patients with essential hypertension, thus CsA induced hypertension is considered to have pathophysiological similarities to essential hypertension.

Adult↗
PubMed1996

NMDA receptors in the pontine brainstem are necessary for fear potentiation of the startle response.

The fear-potentiated startle model in rats is a valuable animal test for the investigation of the neural and neurochemical basis of fear. In this model, rats are trained to associate a neutral stimulus with an aversive stimulus, so that after conditioning the conditioned stimulus alone elicits a state of fear leading to an exaggerated acoustic startle response. The fear-potentiated startle model does not require instrumental responding for the indication of states of fear. The acoustic startle response is mediated by a simple brainstem circuit, with the caudal pontine reticular nucleus as an interface that receives input from startle-enhancing circuits. In the present study, we tested the hypothesis that N-methyl-D-aspartate (NMDA) receptors on neurones of the caudal pontine reticular nucleus are involved in the mediation of fear-potentiated startle. After fear-conditioning, we injected the NMDA receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP-5), into the caudal pontine reticular nucleus of awake rats and tested the effect on the expression of fear-potentiated startle. Injections of AP-5 (0.125-0.5 nmol) into the caudal pontine reticular nucleus dose dependently attenuated fear-potentiated startle without affecting the baseline amplitude of the acoustic startle response. The results suggests that, in the caudal pontine reticular nucleus, glutamate may mediate fear-potentiated startle via NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1996

Synthesis and cytotoxic and antitumor activity of esters in the 1,2-dihydroxy-1,2-dihydroacronycine series.

Seven 1,2-dihydroxy-1,2-dihydroacronycine and 1,2-dihydroxy-1,2-dihydro-6-demethoxyacronycine esters and diesters were synthesized via osmic oxidation of acronycine or 6-demethoxyacronycine followed by acylation. The 6-demethoxyacronycine derivatives were found to be inactive, whereas in contrast, all of the acronycine derivatives were more potent than acronycine itself when tested against L1210 cells in vitro. Four selected acronycine derivatives (17,19, 21, and 22) were evaluated in vivo against murine P388 leukemia and colon 38 adenocarcinoma implanted in mice. All compounds were markedly active against P388 at doses 4-16-fold lower than acronycine itself. Against the colon 38 adenocarcinoma, the three compounds 17, 21, and 22 were highly efficient. 1,2-Diacetoxy-1,2-dihydroacronycine (17) was the most active, all the treated mice being tumor-free on day 23.

Acridines↗
PubMed1996

Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials.

BACKGROUND: The policy of prevention of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal mucosal injury is still a matter of discussion. Indeed, no consensus exists as to whether cotherapy with histamine type 2 (H2) blockers or misoprostol is cost-effective. METHODS: Placebo-controlled randomized clinical trials on the use of H2 blockers or misoprostol, as preventive agents (published between) January 1970 and December 1994), were identified through MEDLINE and reference lists from literature reviews. Crude rates of endoscopic lesions with short-term (< 2 weeks) and long-term (> 4 weeks) NSAID treatment were systematically assessed by 3 independent observers based on the intention-to-treat principle. The method of DerSimonian and Laird was used for pooling data. Heterogeneity was evaluated by using the Q statistic and the plots described by L'Abbe and colleagues. RESULTS: Twenty-four trials met the criteria for entry into the study. Gastric ulcer was found to be significantly reduced by misoprostol-both in short-term (pooled rate difference [RD], -13%, 95% confidence interval [CI], -26% to -1%) and long-term (RD, -8%; 95% CI, -18% to -1%) NSAID treatment-but not by H2 blockers. The risk for duodenal ulcer was significantly reduced by H2 blockers (RD, -2%; 95% CI, -5% to -0.2%) and by misoprostol (RD, -3%; 95% CI, -6% to -0.1%) in long-term but not in short-term administration. CONCLUSIONS: The use of misoprostol, but no that of H2 blockers, was beneficial in the prevention of NSAID-induced gastric ulcers. The number of patients to be treated to prevent 1 gastric ulcer with short- and long-term NSAID treatment is 11 and 15, respectively, for an intermediate baseline risk of 10%. Misoprostol and H2 blockers were beneficial in the long-term prevention of duodenal ulcers; misoprostol or H2 blockers in the short-term prevention of duodenal ulcers remains to be confirmed.

Adolescent↗
PubMed1996

Amygdala kindling does not change emotional responding as measured by the acoustic startle response in the rat.

Human patients with limbic epilepsy are often prone to anxiety and depression. The present study investigated the effect of seizures on emotional responding in the kindling model of complex-partial seizures. Male Wistar rats received electrodes into the right basolateral amygdala and were subsequently kindled until fully generalized seizures could be elicited. These rats did not show a change in the magnitude of the acoustic startle response (ASR) compared to the response amplitude before kindling, or compared to unimplanted controls and to only partially kindled rats. Since the ASR amplitude is a sensitive measure for anxiety or fear, these findings suggest that amygdala kindling does not induce a state of anxiety or fear. However, when analyzing the time course of the ASR within a session, the normally occurring habituation of the ASR was absent in electrode-implanted rats suggesting that the physiological changes induced by electrode implantation interfere with response habituation. Kindling even tended to sensitize the ASR in electrode-implanted rats. Finally, the effect of carbamazepine which is both anticonvulsant and antipsychotic was tested. Carbamazepine significantly reduced the ASR in control and partially kindled rats while this effect was less pronounced in fully kindled rats. It is concluded that amygdala kindling does not change emotional responding as measured by the ASR in rats.

Acoustic Stimulation↗
PubMed1996

Screening and identification of familial defective apolipoprotein B-100 in clinical samples by capillary gel electrophoresis.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder. It is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor, as a consequence of a substitution of adenine by guanine in exon 26 of the apolipoprotein B-100 gene, coding for the putative LDL receptor-binding domain of the mature protein. This disorder is associated with a strikingly high incidence of arteriosclerosis and tends to cause disease and premature death. In this communication we describe a rapid capillary gel electrophoretic method in combination with molecular biology techniques to facilitate the diagnosis of FDB. Mutation screening for FDB is performed by an allele-specific amplification followed by capillary gel electrophoresis (CGE). For the combined polymerase chain reaction (PCR)-CGE method, a total analysis time of only 3 h is needed, a period that is normally necessary for the run and for staining of the gel only, not including the time for PCR, gel casting, etc. In our pilot study 4 of 43 hypercholesterolemic patients were found to have the predominant apoB 3500 codon mutation. The verification is demonstrated by DNA-sequencing. This pilot study will be followed by a large cohort analysis of the south-west German population to determine the frequency of FDB in this area. The PCR-CGE method on the Dionex capillary electrophoresis system (CES I) allows rapid, fully automated detection of the mutation resulting in the unequivocal diagnosis of FDB.

Adult↗
PubMed1996

Pleasure-attenuation of startle is disrupted by lesions of the nucleus accumbens.

The nucleus accumbens (NAC) and the amygdala have been implicated in processes by which reinforcers control instrumental behaviour. Reinforcement has both motivational and motor components, and it is necessary to differentiate between these two aspects. The acoustic startle response (ASR) is attenuated in the presence of a secondary reinforcer. In contrast to other paradigms used for investigating mechanisms of reward, the "pleasure-attenuated startle" (PAS) paradigm indicates the rewarding properties of a treatment by an attenuation rather than by reinforcement of a response, thus allowing determination of the motivational impact of a treatment independent from its motor stimulating effects. Here, we report that the ASR was attenuated in the presence of a positive conditioned stimulus in shamoperated animals and in rats with lesions of the amygdala, but not in animals bearing 6-hydroxydopamine lesions of the NAC. These findings suggest that the catecholaminergic innervation of the NAC is important for behavioural control by conditioned reward.

Acoustic Stimulation↗
PubMed1996

Somatostatin in the pontine reticular formation modulates fear potentiation of the acoustic startle response: an anatomical, electrophysiological, and behavioral study.

The amplitude of the acoustic startle response (ASP) in rats is increased in the presence of a cue that has previously been paired with an aversive stimulus such as a footshock. This phenomenon is called fear-potentiated startle and is a model to study the neuronal and neurochemical mechanisms of the acquisition and expression of fear. The present study investigated the role in fear-potentiated startle of somatostatin in the caudal pontine reticular nucleus (PnC) by a combination of anatomical, electrophysical, and behavioral methods. The PnC is an essential part of the primary startle circuit and is also the recipient of modulatory influences. First, we showed that the central gray (CG), which is involved in fear conditioning, is the main source of somatostatinergic input to the PnC. In the second experiment, we iontophoretically applied the somatostatin receptor agonist sandostatin on PnC neurons and extracellularly recorded the activity of PnC neurons. Sandostatin had no effect on tone-evoked or spontaneous activity, but markedly attenuated the increase of neuronal activity seen after the administration of glutamate. In our third experiment, we injected different doses of sandostatin into the PnC of awake rats. Sandostatin blocked fear potentiation of the ASR but had no effect on the baseline ASR amplitude. The present study indicates that the somatostatinergic projection from the CG to the PnC is important for the modulation of fear-potentiated startle. We present a possible neural circuitry for the expression of fear-potentiated startle based on these data and previous findings.

Acoustic Stimulation↗