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Biomedical subjects

D Bach

Publications and source records attributed to D Bach.

At least 73 records · Page 4Linked to original sources

Evaluation of recombinant hirudin (CGP 39,393/TMREVASC) in the prevention of restenosis after percutaneous transluminal coronary angioplasty. Rationale and design of the HELVETICA trial, a multicentre randomized double blind heparin controlled study.

One of the main areas of interest in interventional cardiology is the understanding, and ultimate prevention of restenosis after an initially successful percutaneous transluminal coronary angioplasty. Restenosis is the recurrence of luminal narrowing following angioplasty, and still frustrates the late results in the treatment of angina pectoris. Experimental, pathological and clinical studies suggest that restenosis may occur via activation of the coagulation cascade, platelet activation and thrombus formation. Thrombin itself is identified as the most potent platelet activator, and has a pivotal role in the coagulation system. Furthermore, thrombin directly mediates smooth muscle cell proliferation by stimulating thrombin receptors at the smooth muscle cell surface. Thrombus indirectly induces excessive intimal smooth muscle cell proliferation by means of released mitogens (growth factors), which may contribute to late restenosis. Therefore direct and irreversible thrombin blockade by hirudin is deemed to be effective in the prevention of restenosis following angioplasty. The HELVETICA trial is a multicentre, randomized, double-blind heparin-controlled study, designed to compare the effects of two dose regimens of recombinant-hirudin (CGP 39,393/TMRevasc) with those of heparin on event-free survival, safety, tolerability and luminal renarrowing using quantitative coronary angiography no later than 26 weeks after the coronary angioplasty procedure.

Adult↗

Predictive value of alexithymia: a prospective study in somatizing patients.

In the present study, the potential role of alexithymia in predicting the long-term treatment outcome was investigated prospectively in 30 patients with DSM-III-R somatoform disorders and anxiety disorders. Using SCID interviews, diagnoses were assessed before inpatient treatment and 2 years after discharge. Patients who met criteria for DSM-III-R undifferentiated somatoform disorder at follow-up exhibited higher pretreatment alexithymia scores (as measured by the TAS) as compared with patients who showed remission of their somatoform disorder or patients who never had met criteria for a somatoform disorder. As a result stepwise logistic regression analyses, high alexithymia scores emerged as a significant predictor of persistent somatization, independent of other measures of psychopathology, sociodemographic variables, and measures of illness severity.

Adolescent↗

Rufloxacin once daily versus ciprofloxacin twice daily in the treatment of patients with acute uncomplicated pyelonephritis.

PURPOSE: We compare the bacteriological and clinical efficacy of rufloxacin and ciprofloxacin in patients with acute uncomplicated pyelonephritis. MATERIALS AND METHODS: A total of 110 outpatients was enrolled in a randomized, double-blind multicenter study and treated for 10 days with 200 mg. rufloxacin daily (after a loading dose of 400 mg. on day 1) or 500 mg. ciprofloxacin twice daily. Bacteriological and clinical efficacy was based on the accumulated outcomes assessed at the end of treatment, and at 2 and 4 to 6 weeks. RESULTS: The bacteriological and clinical success rates of rufloxacin and ciprofloxacin were comparable: 55.6% versus 58.8% and 74% versus 71%, respectively (95% confidence interval -28% to +22% and -20% to +25%, respectively). Both study medications were well tolerated. CONCLUSIONS: Rufloxacin once daily is a good alternative in the outpatient treatment of acute uncomplicated pyelonephritis.

Acute Disease↗

The alpha-5 segment of Bacillus thuringiensis delta-endotoxin: in vitro activity, ion channel formation and molecular modelling.

A peptide with a sequence corresponding to the highly conserved alpha-5 segment of the Cry delta-endotoxin family (amino acids 193-215 of Bacillus thuringiensis CryIIIA [Gazit and Shai (1993) Biochemistry 32, 3429-3436]), was investigated with respect to its interaction with insect membranes, cytotoxicity in vitro towards Spodoptera frugiperda (Sf-9) cells, and its propensity to form ion channels in planar lipid membranes (PLMs). Selectively labelled analogues of alpha-5 at either the N-terminal amino acid or the epsilon-amine of its lysine, were used to monitor the interaction of the peptides with insect membranes. The fluorescent emission spectra of the 7-nitrobenz-2-oxa-1,3-diazole-4-yl (NBD)-labelled alpha-5 peptides displayed a blue shift upon binding to insect (Spodoptera littoralis) mid-gut membranes, reflecting the relocation of the fluorescent probes to an environment of increased apolarity, i.e. within the lipidic constituent of the membrane. Moreover, midgut membrane-bound NBD-labelled alpha-5 peptides were protected from enzymic proteolysis. Functional characterization of alpha-5 has revealed that it is cytotoxic to Sf-9 insect cells, and that it forms ion channels in PLMs with conductances ranging from 30 to 1000 pS. A proline-substituted analogue of alpha-5 is less cytolytic and slightly more exposed to enzymic digestion. Molecular modelling utilizing simulated annealing via molecular dynamics suggests that a transbilayer pore may be formed by alpha-5 monomers that assemble to form a left-handed coiled coil of approximately parallel helices. These findings further support a role for alpha-5 in the toxic mechanism of delta-endotoxins, and assign alpha-5 as one of the transmembrane helices which form the toxic pore. The suggested role is consistent with the recent finding that cleavage of CryIVB delta-endotoxin in a loop between alpha-5 and alpha-6 is highly important for its larvicidal activity [Angsuthanasombat, Crickmore and Ellar (1993) FEMS Microbiol. Lett. 111, 255-262].

4-Chloro-7-nitrobenzofurazan↗

Secondary structure and membrane localization of synthetic segments and a truncated form of the IsK (minK) protein.

IsK, also referred to as minK, is a membrane protein consisting of 130 amino acids and localized mainly in epithelial cells but also in human T lymphocytes. Depending on the cRNA concentration that was injected into Xenopus oocytes, IsK and its truncated forms can induce either a K+ current alone or both K+ and Cl- currents [Attali et al. (1993) Nature 365, 850-852]. To obtain information on the secondary structure and the topology of IsK in a membrane-bound state, the synthesis, fluorescent-labeling, and structural and functional characterization of five polypeptides of 20-63 amino acids within the rat IsK protein were examined. The alpha-helical content of the segments, assessed in methanol using circular dichroism, suggests that both the N-terminal and transmembrane segments of IsK adopt alpha-helical structures. Binding experiments and the blue shift of 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled peptides suggest that while both the alpha-helical transmembrane segment and the N-terminal of IsK are located within the lipid bilayer, the linking segment between the two segments lies on the surface of the membrane. The fluorescence energy transfer, between donor and acceptor-labeled truncated IsK, suggests that it aggregates within phospholipid membranes. Although a protein whose sequence is similar to that of truncated IsK can induce K+ channel activity when expressed in Xenopus oocytes, the inability of a truncated IsK to form functional K+ channels in planar lipid membranes supports increasing evidence that the protein alone cannot form a K+ channel.

4-Chloro-7-nitrobenzofurazan↗

[Significance of various examination methods in the management of prostatic cancer].

The authors investigated the sensitivity and specificity of four methods: rectal digital examination, prostate specific antigen (PSA), prostatic acid phosphatase (PAP) and transrectal ultrasound in the diagnosis of 100 prostate cancer and 50 suffering in benign prostatic hypertrophy patients. In 21 patients the prostate cancer was proved by perineal punch biopsy and in 79 cases by biopsy and by TUR as well. Because of its simplicity the rectal investigation has to be first one, after that the PSA has to be determined. The specificity of transrectal ultrasound is low. The determination of PAP in addition of PSA is not necessary.

Acid Phosphatase↗

Prevalence and recovery of aspiration poststroke: a retrospective analysis.

This retrospective study was undertaken to review aspiration documented by videofluoroscopic modified barium swallow (VMBS) examination in a group of patients admitted to a stroke rehabilitation unit. Forty-two of 54 patients tested demonstrated evidence of aspiration of thin liquids on VMBS performed an average of over 5 weeks following the onset of stroke. However, only patients in whom there was clinical concern of aspiration (54 of 255 stroke patients admitted to the rehab unit) were tested with VMBS evaluation. With this limitation in mind, aspiration was demonstrated in at least 9.9% of all unilateral right hemispheric patients, 12.1% of unilateral left hemispheric, 24% of bilateral hemispheric, and 39.5% of brainstem stroke patients. Of the 42 patients in whom aspiration of thin liquids was demonstrated, 31 underwent repeat VMBS studies an average of 6 weeks after the initial VMBS. 7 of these 31 (22.6%) no longer showed aspiration on VMBS. Eighteen of the 42 patients (43%) clinically stopped aspirating over this 6-week period.

Aged↗

Preoperative staging and early postoperative complications in radical prostatectomy. Experiences in 35 cases.

It is already a textbook item that in patients with prostatic cancer stage T1-T2 N0M0 radical prostatectomy is the only curative treatment. Radical prostatectomy is indicated also for patients in stage T3 N0M0 who underwent antiandrogenic (Fugerel) treatment for 3 months with the aim of reducing tumour volume. In the following 35 cases will be scrutinized, with special regard to preoperative staging and early postoperative complications.

Humans↗

Alexithymia and somatization: relationship to DSM-III-R diagnoses.

In previous studies, results from psychometric measures suggested an association between alexithymia and somatization. However, alexithymia has not been examined in relation to somatoform disorders and other standard psychiatric diagnoses. In the present study, the prevalence of DSM-III-R diagnoses was determined by SCID interviews among 45 psychiatric inpatients with functional somatic syndromes. In addition, the Toronto Alexithymia Scale (TAS) and the SCL-90-R were administered. Of the sample, 42.2% scored in the alexithymic range of the TAS. The alexithymic patients presented significantly more psychological turmoil and overall psychopathology on the SCL-90-R, as well as a significantly higher number of current DSM-III-R diagnoses. However, alexithymia was unrelated to DSM-III-R somatoform disorders and other DSM-III-R diagnoses, as well as the course of illness. These results suggest that assessing clinical features in addition to psychometric measures seems to be necessary for further validating the potential role of the alexithymia construct in somatic symptom formation.

Adolescent↗

Complications following caval interruption.

Caval interruption is widely regarded as the treatment of choice for the prevention of recurrent pulmonary embolism (PE). The safety, ease of insertion and "convenience" of the devices are the main arguments for filter placement. Today many filters are placed for prophylactic reasons, sometimes without an established diagnosis of pulmonary embolism or underlying deep venous thrombosis. Early and late complications have been published but the rate is reported to be low, although only limited numbers of patients have been followed. In an 18-year period 11 patients with problems following caval interruption were treated, 10 with acute complications, one with chronic caval occlusion. Six were treated conservatively, five underwent venous thrombectomy and a.v.-fistula. The device was removed in four. During the same period only three permanent filters were placed in our hospital (two with complications). Caval interruption is useful in selected high-risk patients and is the least invasive but not necessarily the best treatment. Provided stringent criteria are applied, the early and late complications can be accepted in order to prevent sudden death in patients with threatening massive PE. Extended or more liberal indications for caval interruption are neither necessary nor justified.

Adult↗

[The spectrum of the findings of arterial digital subtraction angiography in patients following kidney transplantation].

Digital subtraction angiography (DSA) was performed in 53 of 417 patients with renal transplants. The incidence of clinical apparent vascular complications was 9.1% of all patients with renal transplants (38/417). The most frequent vascular disorders were formed by arterial stenoses at 5.0% of the cases followed by arterial obstructions in 1.7% of the patients. Rare vascular complications were arteriovenous fistulas (0.7%), aneurysms (0.5%) and venous thromboses (0.2%). Because of the high diagnostic value of intraarterial DSA, all patients with renal transplants with a complicated postoperative course should be eligible for angiographic control. In case of a suspected vascular disorder intraarterial DSA should be performed at an early stage.

Adult↗

Renal functional reserve in patients with IgA glomerulopathy.

UNLABELLED: Seven patients with histologically proven IgA nephropathy and modest impairment of renal function, and 2 patients with IgA nephropathy and nephrotic syndrome were investigated, compared to a control group of 9 healthy individuals, to study the effects of amino acids on glomerular and tubular function, and to evaluate renal functional reserve in IgA nephropathy with different clinical course. Inulin and PAH clearances were used to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF); proximal and distal tubular fluid delivery and reabsorption were measured by lithium clearance, before and after submission of a standardized amino acid solution. GFR and ERPF increased significantly during amino acid load in healthy individuals and patients without nephrotic syndrome, while filtration fraction (GFR/ERPF) remained constant. Lithium clearance (CLi) and fractional lithium excretion (CLi/GFR) rose significantly in both groups, whereas the reabsorbed volume of fluid in the proximal tubule did not change. In the distal tubule, fractional volume excretion decreased significantly during amino acid load whereas the reabsorbed volume significantly increased. Baseline values of the two groups did not differ significantly. Two patients with nephrotic course of IgA nephropathy showed a distinct decrease in glomerular and tubular function, and a loss of renal functional reserve after amino acid load. CONCLUSIONS: Despite distinct alterations in renal biopsy, IgA nephropathy without nephrotic course presents with a still adequately preserved kidney function and renal functional reserve. A single determination of renal function with noninvasive functional tests does not give valid prognostic information concerning glomerular and tubular function. Therefore, a repeated measurement of renal function at defined intervals might reveal clinical progression of renal disease. The results of the lithium clearance might indicate an increase in tubular function after amino acid load, indicating a tubular adaptation in state of hyperfiltration.

Adult↗

[Results of selective kidney DSA in suspicious computerized tomography findings--retrospective evaluation of 122 cases].

The superiority of computer tomography in the detection and staging of renal malignomas has been proven in numerous studies. In this retrospective analysis, the significance of the pre-surgically still widely and routinely performed, selective kidney angiography was investigated. The written computer tomographical and angiographic findings of 122 patients were classified according to malignancy stage urgency. They were then compared to progression, and surgical finding respectively. Angiography had the greatest influence on the therapeutic procedure in those patients having only a slight computer-tomographical suspicion of tumor. An operation was waived by 12 patients. A small hypernephroma (pT 2 showing typical tumor vessels was found in two patients. Inoperability excepted, a surgical denudation was performed in all patients with computer tomographical tumor typical, or suspicious finding, irrespective of the angiographic result. The diagnosis was surgically confirmed in all patients having a tumor-specific angiogram. Yet besides benign tumors, 4 hypernephromas and 5 other malignomas were found in those patients showing an angiographically classified, vessel-free formation.

Adult↗

Spectroscopic and functional characterization of the putative transmembrane segment of the minK potassium channel.

MinK (Isk) is a voltage-dependent K+ channel whose gene has been recently cloned and which consists of 130 amino acids [Takumi, T., Ohkubo, H., & Nakanishi, S. (1988) Science 242, 1042-1045]. The protein contains one putative transmembrane segment by hydropathy analysis. Whether this putative transmembrane segment is involved in the function of the protein was studied. A 32 amino acid peptide (residues 41-72) with the sequence SKLEALYILMVLGFFGFFTLGIMLSYIRSKKL, containing the hypothesized transmembrane domain, designed TM-minK, was synthesized and fluorescently labeled. The alpha-helical content of TM-minK, assessed in methanol using circular dichroism (CD), was 57%. The fluorescent emission spectrum of 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-labeled TM-minK displayed a blue shift upon binding to small unilamellar vesicles (SUV), reflecting a relocation of the fluorescent probe to an environment of increased apolarity, i.e., within the lipid bilayer. The increase in NBD's fluorescence upon mixing NBD-labeled TM-minK with small unilamellar vesicles (SUV) was used to generate a binding isotherm, from which was derived a surface partition coefficient of 5.5 x 10(4) M-1. Fluorescence energy transfer measurements between carboxyfluoresceine-labeled and rhodamine-labeled analogues suggest that TM-minK aggregates within membranes. In addition, single-channel experiments revealed that TM-minK can form single channels in planar lipid membranes only when a trans negative potential is applied. The findings herein experimentally support a role of the transmembrane segment of minK both in the assembly and as a constituent of the pore formed by the protein.

4-Chloro-7-nitrobenzofurazan↗

Nephrotoxicity of cyclosporine in humans: effect of cyclosporine on glomerular filtration and proximal tubular reabsorption.

The chronic nephrotoxic effects of cyclosporine (CsA) include proximal tubular atrophy and vacuolization. This study investigated the effect of CsA on renal hemodynamics and segmental electrolyte transport in CsA-treated patients. The clearance of inulin (CIn) and PAH para-amino-hippuric acid (CPAH) was determined; proximal tubular function was studied using a lithium clearance method and calculating tubular phosphate reabsorption per milliliter of glomerular filtrate (TP/CIn). Twenty patients without renal disease were investigated: ten treated with CsA because of nonrenal grafting (group 1) and ten healthy volunteers (group 2). The results obtained were compared with those from 20 renal allograft recipients, of whom ten were treated with CsA and methylprednisolone (group 3) and ten with azathioprine and methylprednisolone (group 4). CIn and CPAH were significantly impaired in patients treated with CsA. No significant impairment of lithium clearance as induced by CsA was observed. The fractional excretion of lithium was slightly increased in patients treated with CsA compared to their respective controls. TP/CIn was lower in graft recipients compared to controls; no impairment of phosphate reabsorption as induced by CsA was found. The fractional tubular excretion of lithium was slightly increased compared to controls, rising evidence that proximal tubular reabsorption of lithium was decreased. Tubular reabsorption of phosphate was not impaired. The decrease in glomerular filtration and renal perfusion during chronic treatment with CsA was accompanied by a reduced proximal reabsorptive capacity, as was shown by lithium clearance. Our data do not support the hypothesis that functional parameters of the proximal tubular system can be used as indicators of CsA-induced nephrotoxicity.

Absorption↗

Improved visualization of carcinoid liver metastases by indium-111 pentetreotide scintigraphy following treatment with cold somatostatin analogue.

Five patients with hepatic metastases of midgut carcinoid underwent somatostatin receptor scintigraphy with indium-111 pentetreotide before and during treatment with octreotide. Octreotide treatment changed the biodistribution of 111In-pentetreotide significantly. Whereas the radioactivity in liver, spleen and kidney decreased, hepatic metastases showed increased contrast. In one patient, liver metastases could only be detected during octreotide treatment. These data suggest that the diagnostic reliability of somatostatin receptor scintigraphy in carcinoid liver metastases is not necessarily compromised by octreotide therapy. Because of different biodistributions, the detection of liver metastases may even be improved during octreotide therapy.

Carcinoid Tumor↗

Thermotropic behavior of phosphatidylcholine-glucosyl ceramide mixtures: effects of phospholipid acyl chain composition and interaction with water.

The thermotropic behavior of multilamellar vesicles composed of mixtures of dimyristoyl phosphatidylcholine-glucosyl ceramide and of egg phosphatidylcholine-glucosyl ceramide was investigated using differential scanning calorimetry. Macroscopic demixing of the lipid components occurred when multilamellar vesicles were prepared from mixtures of glucosyl ceramide and egg phosphatidylcholine by conventional methods. This problem was overcome by a technique based on spray drying of the lipid mixture. The results obtained for the two systems are compared with data available for dipalmitoyl phosphatidylcholine-glucosyl ceramide mixtures (Biochemistry 22 (1983) 3497-3501). All three phosphatidylcholines perturb the complex thermotropic behavior of glucosyl ceramide. The data suggest that the interference with intermolecular interactions among glycosyl ceramide molecules by phospholipid molecules is related to the molecular miscibility of the two components. This is strongly dependent on the acyl chain composition of the phosphatidylcholine and the water activity of the ambient aqueous phase.

Calorimetry, Differential Scanning↗