Biomedical subjects

F Bergmann

Publications and source records attributed to F Bergmann.

At least 55 records · Page 3Linked to original sources

PubMed1996

Blood pressure effects of hydrochlorothiazide, applied to the rat hypothalamus.

In the search for central actions of hydrochlorothiazide (HCTZ), the drug was injected directly into the hypothalamus (HTH) of hypertensive rats. This caused regular fall of blood pressure (BP) and development of a flat dose-response curve-both events resembling corresponding phenomena in systemic injections. In a small number of experiments, the drug caused a rise in BP. This result was enhanced when normotensive rats were injected into the HTH. It is concluded that the rat HTH bears two antagonistic receptors for HCTZ.

Animals↗

PubMed1996

Recent progress in oligonucleotide synthesis.

New blocking group combinations for the machine-aided oligoribonucleotide synthesis on solid phase material have been developed and tested regarding their general application. An acetal function for 2'-OH protection offers a series of advantages in the synthetic approach but special conditions have to be fulfilled in order to guarantee a selective cleavage of the temporary 5'-OH blocking group such as the dansylethoxycarbonyl or even the acid-labile dimethoxytrityl group in the chain elongation process. The final removal of the 2'-O-acetal function in the partially deblocked oligomer proceeds unexpectedly well under weak acidic conditions due to a supposed intramolecular acid catalysis.

Acetals↗

PubMed1996

Results of a screening for von Willebrand disease type 2N in patients with suspected haemophilia A or von Willebrand disease type 1.

A screening program for the detection of patients with von Willebrand disease type 2N (VWD 2N) was carried out in 177 unrelated patients previously diagnosed with haemophilia A and in 199 unrelated patients with VWD type 1 in comparison. By measuring the factor VIII (FVIII) binding capacity of von Willebrand factor (VWF), we detected 13 patients with VWD 2N within 8 unrelated families. The former diagnosis has been haemophilia A in 5 index patients, and VWD in the remaining 3. Included in this study were 14 patients with suspected haemophilia A, whose molecular analysis for mutations in the FVIII gene was unsuccessful. Five of them had VWD 2N. In all patients with the VWD 2N phenotype we were able to identify specific molecular defects in the corresponding DNA sequence of the FVIII binding domain of VWF. The most common defect was R91Q. Four patients from 4 families were homozygous for R91Q, six patients from 3 families were compound heterozygous for R91Q and a silent yet unidentified allele. The VWD 2N phenotype of father, daughter, and son in one family, was based on 2 different genotypes, compound heterozygosity for R91Q and VWD type 1 in the father and the daughter, and homozygosity for R91Q in the son. Two patients from one family were compound heterozygous for T28M and delta C2680-2685 in exon 18, and one patient was compound heterozygous for a novel candidate missense mutation in exon 18(E24K) and delta C2680-2685 in exon 18 which is regarded the most common defect causing severe VWD type 3. FVIII:C values of 0.07 and 0.14 IU/ml were observed in patients with the genotype T28M/delta C2680-2685 whereas in patients being homozygous or compound heterozygous for R91Q, FVIII:C was 0.19 +/- 0.071 IU/ml. In contrast to the other genotypes, E24K/delta C2680-2685 is correlated with a more severe haemophilic phenotype with a FVIII residual activity of only 0.01-0.02 IU/ml. This emphasizes the need for inclusion of the factor VIII binding assay in the diagnostic workup of suspected haemophilia A.

Adult↗

PubMed1995

Severe autoimmune protein S deficiency in a boy with idiopathic purpura fulminans.

Idiopathic purpura fulminans usually occurs in young children and is frequently preceded by a preparatory viral or bacterial infection. Following a severe streptococcal pharyngitis, an 8-year-old boy developed purpura fulminans with disseminated intravascular coagulation and severe protein S deficiency (total antigen < 0.05 u/ml). Despite generous plasma infusions, skin necrosis progressed rapidly into compartment syndrome which required fasciotomy and skin grafting and resulted in the loss of three digits of the right foot. Total protein S remained low for over a month despite plasma supplementation and complete normalization of protein C levels. A polyclonal anti-protein S IgG was demonstrated in the patient's plasma, which decreased to 25% of baseline titre after 1 month and was undetectable 6 months after purpura fulminans, when plasma protein S had returned to normal. Transient, isolated and severe deficiencies of protein S have been reported in patients with idiopathic purpura fulminans and a previous preparatory infection. Autoimmune protein S deficiency may play a key role in the aetiopathogenesis of idiopathic purpura fulminans.

Autoantibodies↗

PubMed1994

Genetic heterogeneity of severe von Willebrand disease type III in the German population.

The genetic heterogeneity of severe von Willebrand disease (vWd) type III was estimated by analysing extended haplotypes of eleven intragenic restriction fragment length polymorphisms and one variable number of tandem repeat polymorphism in 32 patients from 28 families from Germany or of German origin. All patients were screened for gross deletions and for mutations at potential "hot spot" regions of the von Willebrand factor (vWf) gene. Disease-associated haplotypes were established in 24 families. Only a few, apparently unrelated families shared common haplotypes suggesting a considerable genetic heterogeneity in the German population of vWd type III patients. Defects causing vWd type III were identified on 14 out of 56 chromosomes (25%). Gross deletions were detected in two families. A complete homozygous deletion of the vWf gene was displayed in one patient. Another patient was compound heterozygous for a large deletion of at least 100 kb of the vWf gene with an additional, as yet unidentified, defect. One homozygous missense mutation was detected in exon 10, and two nonsense mutations were detected in exon 8 and exon 45 of the vWf gene, respectively. A frameshift mutation (delta C) in exon 18 was identified in five families and an additional frameshift mutation (delta G) was found in exon 28 in one family. It appears that delta C is the most common molecular defect in German patients with vWd type III. Its association with a number of different haplotypes suggests repeated de novo mutations at a mutation "hot spot". Evidence is presented that particular molecular defects causing vWd type III are associated with different patterns of inheritance, depending on their location within the vWf gene. Complete deletions of the gene and nonsense mutations in the pro-sequence are correlated with recessive inheritance, whereas frameshift and nonsense mutations in the gene sequence corresponding to the mature vWf subunit tend to be inherited in a dominant fashion.

Adolescent↗

PubMed1994

Safety of alternating ganciclovir and foscarnet maintenance therapy in human immunodeficiency virus (HIV)-related cytomegalovirus infections. An open-labeled pilot study.

In the treatment of cytomegalovirus (CMV) disease in patients with AIDS, a life-long suppression therapy following an induction therapy consisting of ganciclovir or foscarnet is essential. Due to drug-related toxicities, anti-CMV therapy frequently has to be discontinued. To determine whether toxicities and side effects may be reduced with an alternating combination therapy consisting of ganciclovir and foscarnet (ganciclovir: 5 mg/kg every other day; foscarnet: 120 mg/kg every other day), 10 AIDS patients with CMV disease received this maintenance therapy for a median time of 18.5 weeks (5-51 weeks). Side effects were reported from 5 patients (nausea 5, malaise/fatigue 2, penile ulcers 1). Hematological or renal toxicities were mild, 1-week discontinuation of therapy due to neutropenia was necessary in 1 patient. Progression of CMV disease was observed in 3 patients at 2, 6, and 30 weeks of maintenance therapy. Median relapse-free interval for all patients was 105 days. We conclude that combination therapy with ganciclovir and foscarnet can be used safely for induction and maintenance therapy. Therefore, this regimen should be assessed in further trials to evaluate safety, efficacy, and the development of resistance in comparison to ganciclovir or foscarnet monotherapy.

AIDS-Related Opportunistic Infections↗

PubMed1993

Efficacy of pyrimethamine/sulfadoxine in the prevention of toxoplasmic encephalitis relapses and Pneumocystis carinii pneumonia in HIV-infected patients.

The efficacy and safety of 25 mg pyrimethamine plus 500 mg sulfadoxine given twice a week in preventing relapses of AIDS-related toxoplasmic encephalitis was evaluated in an open study. The 56 HIV-infected patients evaluated had responded to intensive treatment with pyrimethamine/clindamycin prior to starting the present prophylactic regimen. Four patients (7 %) experienced relapse while on pyrimethamine/sulfadoxine. The probability of freedom from relapse was > 90% for 12 months and > 80% for 24 months. Side effects comprised mild or moderate allergic reactions which occurred in 23 patients (41 %), leading to discontinuation in four patients (7%). Forty-nine of the 56 patients did not have a history of Pneumocystis carinii pneumonia and did not receive antiparasitic prophylaxis other than pyrimethamine/sulfadoxine; two of them (4 %) developed pneumocystosis. The probability of freedom from pneumocystosis was about 90 % for 24 months. Pyrimethamine/sulfadoxine twice a week appears to be a promising regimen for prevention of toxoplasmic encephalitis, and also appears to provide protection against Pneumocystis carinii pneumonia. Although allergic reactions are usually mild and disappear on continuation, they may limit the value of this regimen.

AIDS-Related Opportunistic Infections↗

PubMed1993

Acute and long-term efficacy of antituberculous treatment in HIV-seropositive patients with tuberculosis: a study of 36 cases.

Thirty-six consecutively observed HIV-seropositive patients with tuberculosis, including 31 patients with AIDS, who received antituberculous treatment, were followed up to evaluate its efficacy. Treatment with standard antituberculous regimens was intended except when an individual's condition required a modified therapeutic approach. Therapeutic failure occurred in five patients (14%) while on treatment, one also had a post-treatment relapse. Treatment failure was associated with drug resistance and non-compliance in three patients and in another two, both of whom died early in the course of their disease, with HIV-related conditions other than tuberculosis. The median relapse-free post-treatment follow-up time in 24 patients in whom treatment did not fail was 13 months (range 4-67). Standard antituberculous treatment is highly effective in the immediate and long-term treatment of HIV-related tuberculosis provided that drug susceptibility and treatment compliance are confirmed.

Acquired Immunodeficiency Syndrome↗

PubMed1992

The toxicity of macrocyclic trichothecenes administered directly into the rat brain.

The tested macrocyclic trichothecenes are produced by Myrothecium fungi and by the plant Baccharis megapotamica. The toxicity of five macrocyclic trichothecenes has been measured by intracerebral and subcutaneous injection into rats. It is assumed that the toxic effects are based on inhibition of protein synthesis. Intoxication of rats by these compounds finds expression in slowly progressing respiratory depression and paralysis of skeletal muscles. The macrocyclics are derived from verrucarol, which lacks ring D and exhibits only low toxicity. The high toxicity of the macrocyclics, established by intracerebral and subcutaneous applications, may thus be attributed to the presence of the large ring D.

Animals↗

PubMed1992

Diffuse alveolar hemorrhage secondary to superwarfarin ingestion.

A 27-year-old woman with severe vitamin K deficiency presented with hemoptysis and diffuse pulmonary infiltrates. She rapidly developed respiratory failure requiring ventilatory support. Surreptitious ingestion of brodifacoum, a long-acting warfarin derivative, was ultimately found to be the cause of her coagulopathy and DAH.

4-Hydroxycoumarins↗

PubMed1991

The role of von Willebrand factor in pre-eclampsia.

The von Willebrand factor (vWF) has gained considerable interest in recent years as a marker of endothelial cell activation or insult and by virtue of its interactions with platelets and vessel walls. Altered patterns of vWF multimers were found to occur frequently in patients with thrombotic thrombocytopenic purpura in the acute and chronic stages. This disorder shares some clinical and laboratory findings with pre-eclampsia, including thrombocytopenia. Recent studies have also suggested that abnormalities of endothelial cell metabolism play a central role in the pathophysiology of pre-eclampsia. In order to determine if vWF could be instrumental in the disease process and the thrombocytopenia of pre-eclampsia we analyzed the ante- and postpartum structural and functional distribution of vWF. This data was correlated with hematological parameters such as platelet counts and the clinical severity of the disease. We found no consistent changes of vWF in association with thrombocytopenia or clinical severity. However, functional vWF was lower in postpartum samples of severely affected pre-eclamptics as compared to normal controls. This finding may reflect endothelial cell exhaustion after stimulation or cellular injury. Elevated titers of fibrin split products and thrombocytopenia were evident in severe pre-eclampsia, as seen in DIC, despite factor VIII coagulant levels within the normal range. Our data is consistent with the hypothesis of endothelial cell dysfunction in pre-eclampsia. However, the mechanism of thrombocytopenia in this disorder does not appear to be related to alterations in the structure or biological function of vWF.

Adult↗

PubMed1991

Metabolism of T-2 toxin by rat brain homogenate.

HT-2 toxin was the sole metabolite formed when T-2 toxin was treated with homogenate from brain without its blood content. Homogenate from brain with its full blood content produced--besides HT-2 toxin--T-2 triol, neosolaniol, 4-deacetylneosolaniol and T-2 tetraol, i.e. the same metabolites formed by incubation of T-2 toxin with whole rat blood.

Animals↗

PubMed1991

Quantitative and qualitative platelet abnormalities during pregnancy.

In a 1-year period, 15 of 4048 pregnant women were found to have thrombocytopenia during their first prenatal visit. Their qualitative and quantitative platelet abnormalities were followed up prospectively for 1 to 6 months post partum. Platelet counts returned to normal in 14 of 15 patients 4 to 6 weeks post partum. von Willebrand factor antigen and ristocetin cofactor activity were low in three of 15 patients 4 to 6 weeks post partum, but had been normal during the antepartum period. Two of these three patients had prolonged bleeding times ante partum and post partum. All three patients subsequently were found to have mild type I von Willebrand disease. Six patients had detectable platelet antibodies. Neonatal thrombocytopenia was found in one term infant of a patient with mild thrombocytopenia and negative platelet antibodies. This study suggests that mild, transient, isolated thrombocytopenia can occur in an otherwise normal pregnancy and its incidence may be lower than previously reported. Extensive testing is not indicated unless there is an associated prolonged bleeding time. The possibility of von Willebrand disease or a qualitative platelet disorder should be considered.

Adolescent↗

PubMed1991

Central effects of cycloheximide alone and of its combination with T-2 toxin.

The antibiotic cycloheximide inhibits protein synthesis in eukaryotic cells. This overall effect is similar to that of T-2 toxin, but the mechanism of intoxication by these two inhibitors are different. This is shown here by intracerebral injections of mixtures of T-2 toxin and cycloheximide, leading to potentiation of their toxic effects. The histopathology of cerebral intoxication by the two compounds is similar, but after cycloheximide the lesions appear earlier, and repair is faster.

Animals↗

PubMed1991

New approaches towards automated oligoribonucleotide synthesis.

Several protecting group combinations have been investigated to achieve an automated oligoribonucleotide synthesis on a solid support. The use of 2'-O-tert-butyldimethylsilyl-5'-O-monomethoxytrityl-ribonucleoside -3'-(p-nitrophenylethyl, N,N-diethyl)-phosphoramidites in conjunction with beta-eliminating blocking groups at the aglycone gave satisfactory results. An inverse protecting group strategy based upon analogously substituted 5'-O-2-dansylethoxycarbonyl-2'-O-4- methoxytetrahydropyran-4-yl-phosphoramidites can be regarded as another promising approach.

Base Sequence↗

PubMed1991

Hypertension induced by hypothalamic transplantation from genetically hypertensive to normotensive rats.

The role of the hypothalamus (HTH) in the pathogenesis of genetic hypertension was studied in spontaneously hypertensive rats (SHR). It is currently believed that, in this strain, the genetic defect manifests itself mainly in the HTH. We examined this hypothesis by grafting HTH neurons from embryos of SHR or control Wistar Kyoto (WKY) rats into the HTH of adult normotensive WKY rats. Changes in host systolic blood pressure (SBP) were monitored, and alterations in vasoactive intestinal polypeptide (VIP) gene expression of the host brain were studied. In rats grafted with HTH tissue from SHR embryos (G-SHR), the blood pressure rose by 31% as compared with that in the grafted control group. The blood pressure climbed gradually over a period of 6 weeks to its highest level, which was maintained for at least 3 months following grafting. Along with the elevated blood pressure, the heart weight increased by 80% compared to controls. Behavioral changes were also evident in the G-SHR rats, and these were similar to those of the native SHR strain. In situ hybridization histochemistry showed a 40% elevation in VIP transcripts in the suprachiasmatic nucleus of the host G-SHR brain compared to controls. These studies demonstrate that transplantation of embryonic SHR HTH tissue into brains of adult normotensive rats results in the development of hypertensive characteristics in the host. It thus appears that the HTH is a prime candidate for the source of changes leading to spontaneous hypertension in mammals.

Animals↗

PubMed1989

Structure-activity relationships for the direct toxic action of trichothecenes on rat brain.

Three classes of 12,13-epoxytrichothecenes, differing in the number of hydroxy or acetoxy substituents, were implanted or injected into rat brain to establish structure-toxicity relationships. A free 3 alpha-hydroxy group increases toxicity more than 10-fold, when compared to trichothecenes lacking this substituent. The 8 alpha-hydroxy group enhances toxicity about 4-fold.

Administration, Topical↗

PubMed1989

Comparison of the toxicity of two trichothecenes applied topically to brain and liver of rats.

T-2 toxin has been found previously to be markedly more toxic upon intracerebral than upon systemic administration. In order to study the generality of this difference, we have applied to brain and liver of albino rats two different types of trichothecenes: T-2 toxin as a representative of 'simple' and myrotoxin B as a representative of 'macrocyclic' members of this series. Myrotoxin B, when applied intracerebrally, was about 100 times more poisonous than T-2 toxin. In contrast, upon intrahepatic injection both compounds exhibited similar degrees of toxicity. The different behavior of the two trichothecenes in the organs tested may be due to local metabolic factors.

Animals↗