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H Berger

Publications and source records attributed to H Berger.

At least 73 records · Page 4Linked to original sources

The 'two-phase closed bottle test'--a suitable method for the determination of 'ready biodegradability' of poorly soluble compounds.

The Two-Phase Closed Bottle test (BODIS test) is a cost-effective supplement of the existing OECD tests for ready biodegradability (OECD 301) due to its entire compatibility with them and its particular suitability for testing poorly soluble compounds. The comparison of a number of test data from this and other ready biodegradability tests showed that the BODIS test has a similar stringency in terms of the attainment of the pass level and the time window criterion as well. A significant influence of the strength of the bacterial inoculum on the test results was not observed.

Bacteria, Aerobic↗

The degradation of corticotropin-releasing factor by enzymes of the rat brain studied by liquid chromatography-mass spectrometry.

The corticotropin-releasing factor (CRF; 41 amino acid residues) is a major regulatory peptide in the response to stress and is distributed over many regions of the brain. We have studied the enzymatic degradation of CRF and related peptides by the CRF-degrading enzyme(s) of the rat brain (CRF-DA) by liquid-chromatographic-mass spectrometric technique and by online tandem mass spectrometric experiments. Peptide fragments of the human/rat CRF (1-41) generated by the CRF-DA of the particulate cell fraction were separated and structurally assigned. Major sites of enzymatic attack were identified at the P1 positions Ser1, Thr11 , His13, Leu15, Arg23, Arg35, and Lys36 with Leu15 as the site of primary cleavage. The CRF-DA was shown to be dominated by a metalloendopeptidase activity inhibited by O-phenanthroline and EDTA. The cytosolic fraction generated a similar degradation pattern with a pronounced cleavage at the Arg35 position.

Animals↗

Corticotropin-releasing factor (CRF) agonists stimulate testosterone production in mouse leydig cells through CRF receptor-1.

The influence of CRF on testosterone production in primary mouse Leydig cell cultures was studied, and the type of CRF receptor (CRF-R) involved in this activity was determined. CRF directly stimulated testosterone production in mouse Leydig cells, but did not influence the maximum human (h)CG-induced testosterone production. The effect was time- and dose-dependent, saturable with an EC50 of 2.84 nM for hCRF, antagonized by the CRF antagonist alpha-helical CRF9-41, and accompanied by intracellular cAMP elevation. The rank order of potency of the natural CRF agonists, hCRF, ovine CRF, sauvagine, and urotensin, corresponded to that of their activities on CRF-R1 in rat pituitary cells and also to that reported for this receptor, but not for CRF-R2, when transfected into various cell lines. Furthermore, the difference in response of mouse Leydig cells to [11-D-Thr,12-D-Phe]- and [13-D-His,14-D-Leu]-ovine CRF corresponded to that measured when COS cells expressing CRF-R1 were activated, but was considerably smaller than that observed for activation of COS cells expressing CRF-R2alpha or -R2beta. The messenger RNA encoding the mouse CRF-R1 was detected by RT-PCR in mouse Leydig cell preparations. In contrast to mouse Leydig cells, CRF agonists had no influence on the basal testosterone and cAMP production by rat Leydig cells, nor did the agonists or antagonist change the hCG-stimulated testosterone and cAMP production by these cells. It is concluded that mouse Leydig cells express CRF-R1, mediating elevation of testosterone production by CRF agonists through cAMP. Because potencies of CRF agonists in activating mouse Leydig cells were more than 10-fold lower compared with their potencies in stimulating rat pituitary cells, it is suggested that the coupling of the CRF-R1 to intracellular signaling in Leydig cells is different from that in corticotropic pituitary cells, at least in quantitative terms.

Adrenocorticotropic Hormone↗

Analysis of the DNA content in Bowen's disease.

The aim of this study was to evaluate the DNA content in Bowen's disease in comparison to healthy epidermis applying image cytophotometry. The material investigated was derived from 50 patients with Bowen's disease and 10 patients with healthy skin. For comparison of both groups the Kruskal-Wallis test was applied. Slides were stained with Feulgen and were evaluated with CAS-200 image analyzer. Only 7/50 morbus Bowen cases represented euploid histogram. The others 43/50 were either conspicious to be aneuploid (29/50) or clearly aneuploid (14/50). In contrast, all normal epidermis (10/10) were clearly euploid. Morbus Bowen cases demonstrated significantly higher 5c exceeding rate (p=0.0012) and significantly more cells in the S-phase (p=0.017). High aneuploidy rate and increased proliferative activity in morbus Bowen cases support the classification of these lesion as carcinoma in situ.

Aged↗

Comparison of ploidy status of melanoma metastases in different locations.

The main aim of this study was to evaluate the DNA content and ploidy status of 29 melanoma metastases in lymph nodes, as well as 10 liver, 12 brain, 13 lung and 2 gastrointestinal metastases. All cases investigated were either suspicious to be aneuploid or clearly aneuploid. This study demonstrates differences of ploidy related parameters between melanoma metastases of different locations. The 5c exceeding rate values were the lowest in lymph node metastases and the highest in melanoma cells in the brain (p<0.05). The rate of cells in S-phase ranged between 12% in gastrointestinal metastases and 23% in liver metastases. The melanoma cells, which formed liver metastases had smaller area, lower mass and bigger shape factors in comparison with melanoma cells in lymph nodes.

Adult↗

Nociceptin (orphanin FQ): high-affinity and high-capacity binding site coupled to low-potency stimulation of guanylyl-5'-O-(gamma-thio)-triphosphate binding in rat brain membranes.

G protein activation by the agonist-occupied nociceptin- (orphanin FQ-) receptor in rat cerebral cortex was studied by characterizing the nociceptin-stimulated binding of the radiolabeled guanylyl triphosphate (GTP) analog 35S-guanylyl-5'-O-(gamma-thio)-triphosphate (GTPgammaS). Using 3H-Tyr14- and 125I-Tyr14-nociceptin in saturation and displacement receptor binding studies, a single high-affinity (Kd 21.6-116.7 pM) and high-capacity binding site for nociceptin (orphanin FQ) in membranes and sections of rat cerebral cortex was identified. Stable GTP analogs and NaCl lowered the affinity only moderately by 2- to 3-fold, but under these conditions nociceptin stimulated the binding of 35S-GTPgammaS to G proteins in the membranes with a potency about 100-fold lower (EC50 9.11 nM). It was estimated that this stimulation was due to a 29-fold increase in the affinity from Kd 45. 8 to 1.57 nM of only about 6.5% of the basal binding sites for GTPgammaS, and that at least 10 G protein binding sites could be stimulated by one receptor site. The link of this nociceptin-stimulated binding of GTP to the nociceptin receptor was further evidenced by the specificity of stimulation, as seen with nociceptin, nociceptin(1-13), D-Ala7-nociceptin and nociceptin(1-9), which paralleled that of their receptor affinities. Furthermore, the distribution in rat brain regions of the binding of 35S-GTPgammaS stimulated by nociceptin differed from that stimulated by the mu opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol)]-enkephalin. Especially, no stimulation by nociceptin was observed in caudate putamen, where also the absence of ORL1 receptors had been reported. The putative coupling of the high-affinity nociceptin receptor to the low-potency stimulation of GTPgammaS binding in rat cerebral cortex might be explained by the switch of a low part of occupied nociceptin binding sites to a very low-affinity state being stabilized at high peptide concentrations and catalytically stimulating the GTP binding.

Analgesics, Opioid↗

[Medical management of homeless persons].

Germany's health care system is based on statutory health insurance funds and the legal obligation of those physicians who work on a contractual basis with the health insurance companies to guarantee the outpatient medical care of the insured. Despite the widely acknowledged efficiency of this system it fails to have the desired effect on those sections of the population who cannot enforce their claims for help or who do not meet the requirements of institutional working conditions. Mostly concerned are homeless people with an additional drug problem or mental disease, immigrants as well as children from socially disadvantaged families. Their number increases especially in the big cities, but legal and organisational limitations render the necessary and time-consuming support impossible, which requires to call on and follow up on patients. The city of Cologne has temporarily established a mobile medical service at the public health department for the subsidiary care of the people concerned. The medical team treats its patients--unbureaucratically and without prerequisites on the part of the patients--in a mobile ambulance or in facilities of social institutions, which take care of drug addicts and homeless people. The physicians who work on a contractual basis with the health insurance companies cooperate with this service to take on this social-compensatory common task. The health insurance companies do not feel obliged to cooperate, although a great number of the patients are insured. Let us hope that the latest and current legislation will provide improvements for the patients concerned. Its aim is to provide an opportunity of medical treatment by the public health department and the opportunity to afterwards charge the costs of the treatment to the insurance branches of the social security system.

Ambulatory Care↗

Evidence for extensive and non-specific translocation of oligopeptides across plasma membranes of mammalian cells.

After exposure of bovine aortic endothelial cells to various small peptides (tetra- to undeca-mer), extensive transport of the peptides across the plasma membrane was observed in the concentration range 10(-7) to 10(-2) M. The observed transport events, which contradict the generally anticipated poor permeability of peptides across plasma membranes, exhibited high complexity and showed no saturability up to a concentration of 10(-2) M. Evidence was found for the involvement of mdrp-like transporters as well as of energy-independent facilitated diffusion events. The peptide levels within the cells approximated those of the incubation solution within 30 min, indicating high capacity and velocity for the involved transport processes. Correspondingly, preloaded cells exported about 80% of the internalized peptide within 5 min at 37 degrees C. Analogous results were found after peptide exposure to several other mammalian cell types, indicating a more general importance of the transport phenomena described here. Our findings contradict the prevailing opinion that the often observed lack of activity of externally administered peptides against their targets within intact cells is accounted for primarily by poor cellular uptake and point to export processes counteracting the uptake to be more important in this context.

Animals↗

[ARDS and Wegener granulomatosis].

UNLABELLED: Wegener's granulomatosis is a distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tract and glomerulonephritis. This disease can present as a clinical picture which resembles sepsis and adult respiratory distress syndrome (ARDS). Wegener's disease requires immunosuppression which can have detrimental consequences when used in sepsis. The following case report illustrates the diagnostic difficulties encountered by intensive care physicians treating severe pulmonary failure and multiple organ dysfunction in Wegener's granulomatosis appearing as ARDS with sepsis. CASE REPORT: A 19-year-old female patient had developed acute respiratory and renal failure after a prolonged period (many months) of antibiotic resistant otitis, sinusitis and mastoiditis. The patient had required intubation at another hospital and there was a history of tension pneumothorax and cardiopulmonary resuscitation during mechanical ventilation. Emergency extracorporeal membrane oxygenation (ECMO) for acute hypercapnic and hypoxic respiratory failure was instituted and the patient was transported to our institution while on ECMO. The patient was treated empirically for suspected pulmonary and systemic infection and received hydrocortisone (0.18 mg/kg/h) as part of a protocol-driven treatment of septic shock in addition to antibiotic and antimycotic regime. The use of ECMO was required for 10 and mechanical ventilation for another 50 days after admission. After successful extubation, central nervous system dysfunction became evident with a somnolent and generally unresponsive patient. When the hydrocortisone dose was gradually tapered, the clinical status of the patient further deteriorated, pulmonary gas exchange worsened and she developed renal failure with proteinura and hematuria. A renal biopsy was performed demonstrating vasculitis and focal segmental glomerulonephritis, a systemic granulomatous vasculitis was suspected; the serum was tested for anti-proteinase 3 antibodies (PR3-ANCA) and turned out to be positive (17.5 U/ml; normal range < 7 U/ml). The morphologic findings from renal biopsy, the positive test for antiproteinase 3 antibodies and the pulmonary-renal involvement with evidence of multisystem disease established the diagnosis of Wegener's granulomatosis. Immunosuppressive therapy with cyclophosphamide and prednisolone was instituted resulting in rapid improvement with recovery of pulmonary, renal and central nervous system function within two weeks. The use of ECMO in this patient served as a life-saving immediate measure usefull to "buy time" until a definite diagnosis could be established. ARDS represents an uniform pulmonary reaction to a large number of different noxious stimuli and disease entities. This case demonstrates that intensive care physicians caring for critically ill patients with ARDS should include even rare causes of pulmonary injury into their differential diagnosis.

Acute Kidney Injury↗

[surgical relevance of diagnostic imaging in abdominal tumors--decision making in retroperitoneal tumors].

The indication for surgical treatment of tumors of the retroperitoneum should not depend on findings of radiological examinations, because all radiographic procedures lack tissue specificity. Instead, it can only be determined histologically after an open biopsy or resection of the tumor, which should always be attempted. With the help of appropriate radiological examinations, a retroperitoneal mass will not only be detected, but the relationship to the adjacent anatomical structures will also be delineated. Therefore, valid information for planning the operation and estimating the morbidity and mortality can be provided for the surgeon.

Diagnostic Imaging↗

[Interventional radiologic procedures in postoperative complications after liver transplantation].

PURPOSE: Postoperative complications contribute significantly to the morbidity and mortality of liver transplant patients. The management of these complications requires a multidisciplinary approach in which interventional radiology plays an integral role. Indications, techniques, and results of radiological interventions in the management of the liver transplant patient are presented. MATERIAL AND METHODS: During a 10-year period, 52 out of 420 liver transplant recipients underwent radiological interventions, including angioplasty (n = 20), embolization (n = 2), percutaneous drainage (n = 11), and biliary interventions (n = 19). RESULTS: Nine out of ten arterial stenoses located at the anastomoses (n = 8), within the liver (n = 1) and in the coeliac trunk (n = 1) were successfully treated by balloon dilatation. Angioplasty of supra- or infrahepatic anastomotic stenoses of the i.c.v. (n = 5) provided long-term success only in combination with stent implantation. Portal vein stenoses and chronic thrombosis were treated by balloon dilatation and stent insertion via transhepatic catheterization of the portal vein. Late strictures of bile-duct anastomoses can be managed by ante- or retrograde interventions. If biliary complications are related to inflammatory or septic problems, the prognosis of graft survival is poor. CONCLUSION: Interventional radiological procedures are very useful in the management of vascular and biliary complications after liver transplantation. These techniques provide a cure in many situations, and thus, surgical interventions may be avoided in selected cases.

Anastomosis, Surgical↗

[Radiologic interventions in anastomosis complications after lung transplantation].

PURPOSE: Bronchial and arterial anastomotic stenoses are major complications after lung transplantation. Interventional techniques provide a definitive cure in certain cases. MATERIAL AND METHODS: Three out of four patients had ischemia-related stenoses of the bronchial anastomoses postoperatively; one patient developed malacia of the bronchus main stem 1 year after transplantation. Four patients has stenoses of the arterial anastomoses, which resulted in hemodynamic instability and reduced perfusion of the graft. RESULTS: Stent implantation in the bronchial anastomoses (n = 3) and in the main stem (n = 1) improved ventilation and oxygen saturation in all patients. The stents were incorporated by mucosal overgrowth, as demonstrated by endoscopy, as early as 6 weeks after implantation. Balloon dilatation (n = 3) and stent implantation (n = 1) were successfully performed in 4 patients with stenoses of the arterial anastomoses. The mean transstenotic pressure gradient of 9.5 mm Hg was reduced to 2.2 mm Hg after angioplasty. Lung perfusion shifted towards the grafts, as shown by 99mTc perfusion scans. CONCLUSION: The minimally invasive techniques of interventional radiology are very effective in the treatment of anastomotic complications after lung transplantation and may avoid surgery in certain cases.

Adult↗

Influence of continuous levels of fentanyl in rats on the mu-opioid receptor in the central nervous system.

The highly potent and efficacious mu-opioid agonist fentanyl was SC infused into rats with submaximal analgesic doses (0-1.14 mumol/kg/day) continuously for 8 days, checked by the constant daily urinary recovery of intact drug (0.43 +/- 0.031% of the daily dose). Tail-flick latencies measured at 24 (day 1) and 48 h (day 2) after starting the infusion were increased in a dose-dependent fashion compared with those before the infusion (day 0). However, at day 8, the latencies were increased only weakly, not significantly, revealing tolerance to the antinociceptive activity of fentanyl. Fentanyl at all doses showed no significant effect on the capacity (Bmax) and affinity (Kd) of the mu-opioid receptor binding of DAMGO to whole brain (Bmax 126.2 +/- 3.00 fmol/mg protein, Kd 1.00 +/- 0.04 nM) and spinal cord (Bmax 48.24 +/- 2.71 fmol/mg protein, Kd 1.93 +/- 0.13 nM) membranes gained from the rats after killing them at day 8. Gpp(NH)p increased the Kd for brain and spinal cord sites by 3.09 and 2.65, respectively, independent of the fentanyl dose. The infusion with fentanyl did not after the basal and forskolin-stimulated adenylate cyclase activity in the whole brain membranes, nor did it change the inhibition of the forskolin-stimulated activity by DAMGO. It is concluded that, in rats, constant long-term body levels of highly potent mu-agonists result in a tolerant state that, however, does not produce overall changes in the parameters of their specific receptor sites in the CNS, i.e., receptor capacity and affinity, and in the events closely related to them, i.e., their regulation by GTP and of adenylate cyclase. This does not exclude such possible changes to be restricted to specific regions in the CNS.

Adenylyl Cyclases↗

Primary shunt perfusion detected by colour flow Doppler imaging and its impact on liver allograft survival.

Primary dysfunction (PDF) and eventual primary nonfunction (PNF) of liver allografts have been characterized by various clinical and laboratory parameters reflecting graft function, cellular integrity and extrahepatic influence following orthotopic liver transplantation (OLT). During the past 6 yr we have been able to demonstrate that this potentially devastating condition is routinely accompanied by a pathological initial perfusion pattern detected by colour flow doppler imaging (CFDI) within hours following OLT. In the majority of PDF cases (n = 30) CFDI revealed increased vascular resistance in regard to arterial blood flow to the malfunctioning graft, with a resulting 1-yr graft survival rate of 80% following the institution of early prostaglandin therapy in this group of patients. A completely different perfusion pattern was noticed by CFDI in a total of 13 cases with grossly decreased arterial resistance, resulting in an apparently supranormal arterial blood supply together with a reduced portal inflow in comparison to primarily functioning grafts. The presence of this pathologic graft perfusion was explained by the formation of arterio-portal shunts within the graft during conservation and reperfusion, leading to a 1-yr graft survival of merely 46.1%.

Arterial Occlusive Diseases↗

[Geriatric rehabilitation needs in Cologne: the concept of "integrated geriatric rehabilitation"].

Given a growing number of elderly people and the related consequences for the health care system, such as increasing numbers of persons with chronic diseases or in need of long-term nursing care, the present rehabilitation system must be extended and new services be introduced. Hospitals in Cologne report that an average 48% of their geriatric patients are in need of rehabilitation measures. Taking into account the patients' willingness and capacity to undergo rehabilitation treatment, the figure reduces to 30%. Based on the number of geriatric patients treated in hospital each year, rehabilitation facilities for 15416 geriatric patients a year have to be provided. About two thirds of the patients require continued hospital treatment after the acute phase. Obviously, these treatments are not only performed in the geriatric departments of the hospitals, as only 161 geriatric beds are available in Cologne. One third of the patients could be taken care of on a partial hospitalization or outpatient basis after the acute phase. Thus, limiting a patient's length of stay in hospital could have a cost-containment effect. As partial hospitalization and outpatient rehabilitation facilities are lacking, the Cologne "Geriatrics" study group has developed a concept of "integrated geriatric rehabilitation", suggesting the establishment of mobile rehabilitation teams. The concept aims at developing a cooperative network linking outpatient with partial hospitalization and inpatient services, and including the physicians at community level.

Aged↗

Cell renewal, cell differentiation and programmed cell death (apoptosis) in pilomatrixoma.

Pilomatrixoma is a benign tumour of the cutaneous adnexa. Histologically, pilomatrixoma comprises masses of immature basophilic cells, small numbers of polygonal squamoid cells, few transitional cells, and clusters of 'shadow cells'. The mechanism leading to the formation of shadow cells is still unknown. Skin biopsy specimens of pilomatrixoma (n = 15) were studied histologically, immunohistologically, and by applying the in situ end-labelling technique. The basal layer of the basophilic cells induced most of the proliferating cells with high expression of bcl-2 and cytokeratin 19. The overlying basophilic cells showed a negligible mitotic activity, a high significant accumulation of p53 protein, and a heterogeneous, but progressive loss of bcl-2 and cytokeratin 19. They developed either into squamoid cells or into transitional cells. The squamoid cells were characterized as differentiated cells resembling mature keratinocytes of stratified mucosa. The transitional cells could be shown to represent apoptotic cells proceeding to shadow cells. The data suggest that apoptosis is the main mechanism leading to the development of the dead shadow cells and is most probably responsible for the banal biological behaviour of pilomatrixoma. Apart from that, pilomatrixoma represents a suitable biological model to study apoptosis in humans.

Apoptosis↗

[Interventional therapy of intra-abdominal abscess: outcome and limits].

The postoperative course following digestive surgical procedures was prospectively analysed in 2985 patients between 6/92 and 12/96. A CT-guided percutaneous drainage of intraabdominal abscesses was performed in 144 patients (4.8%). In 123 patients (85.4%) percutaneous abscess drainage (PAD) was successful, additional surgery was not required. Twenty-one patients (14.6%) underwent additional surgery. Reasons for drainage failure were abscesses caused by internal fistulas (8 patients), pancreas involvement of the abscesses (5 patients), infected clots impossible to drain (3 patients), multiple abscesses (3 patients) and persistent abscess formation despite drainage (2 patients). Puncture-related complications were seen in 8 patients (5.5%). Puncture-related mortality was 0.7%.

Abdominal Abscess↗