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Biomedical subjects

M Ziegler

Publications and source records attributed to M Ziegler.

At least 109 records · Page 6Linked to original sources

[The significance of hypothermia in polytrauma patients].

Hypothermia is a frequent event in trauma patients and appears to be related to posttraumatic organ dysfunction, although in elective surgery hypothermia is known to prevent ischemia reperfusion injury. Retrospectively, we analyzed data of 641 trauma patients treated in our institution between 1988 and 1993. At hospital admission the core temperature (cT) was > 34 degrees C in the majority (64%) of all patients, < 34 degrees C in 23.6% and < 32 degrees C in 12.4%. At 24 99% had cT of > 34 degrees C. Lethality was twice as high (53%) in patients with cT < 32 degrees C as in patients with cT > 34 degrees C (28%). Analysis of correlation revealed that hypothermia was paralleled by a longer rescue time, greater severity of limb injury, and hypoxia. It also appeared that hypothermia is not an independent prognostic factor for posttraumatic lethality. The different effects of hypothermia in trauma and elective surgery may be due to a lack of energy-storing phosphates such as adenosine triphosphate (ATP). Ongoing investigations will identify the role of ATP in trauma-related hypothermia.

Acid-Base Equilibrium↗

Identification and purification of a bovine liver mitochondrial NAD(+)-glycohydrolase.

Nonenzymatic ADP-ribosylation of mitochondrial proteins is thought to play a role in the regulation of Ca2+ efflux from mitochondria. It has been shown that intramitochondrial ADP-ribose is generated by a specific NAD(+)glycohydrolase, which catalizes hydrolysis of NAD+ to ADP-ribose and nicotinamide. We purified this enzyme from bovine liver mitochondrial membranes. The final preparation had a 1660-fold purified enzyme activity and contained a main protein band with an apparent molar mass of 32,000 in a SDS-polyacrylamide gel. The identity of this protein band with NAD(+)-glycohydrolase was verified by renaturation of its enzymatic activity. Partial amino acid sequence information was obtained from two enzyme fragments after proteolytic cleavage of the protein band in the SDS-polyacrylamide gel. Searches in protein databases revealed that an arginine ADP-ribosyl hydrolase harbours two stretches of amino acids that are highly similar to the partial NAD(+)-glycohydrolase sequences.

Amino Acid Sequence↗

Ulcerative type of colitis associated with the use of high strength pancreatic enzyme supplements in cystic fibrosis.

A 2 1/2-year-old girl with cystic fibrosis, who presented with hematochezia, developed an inflammatory ulcerative type of colitis with mild interstitial fibrosis and colonic narrowing while being treated with high strength pancreatic enzyme supplements. Findings of contrast enema, endoscopy, and colonic biopsy are described. The spectrum of colonic disease associated with the use of high strength pancreatic enzyme supplements in cystic fibrosis patients is discussed.

Child, Preschool↗

Effects of enalapril on T and B cell function in rats after myocardial infarction.

The cellular mechanisms following myocardial infarction remain poorly characterized. It is believed that an inflammatory and immunologic process may be involved and that the beneficial effects of enalapril on remodeling may, in part, work through an immune mechanism. To characterize the effect of enalapril on immune alterations in the late phase of ventricular remodeling after myocardial infarction, rats underwent left coronary artery ligation followed by 6 weeks of either enalapril or placebo treatment. Infarct sizes, heart weights, and volumes were compared. Peripheral and splenic leukocyte and lymphocyte subsets, along with T cell blastogenesis, were quantified in enalapril treated rats 6 weeks after coronary ligation and compared to untreated control rats. Additionally, antibody production to a de novo antigen, keyhole limpet hemocyanin, was assessed with and without treatment. Average infarct size was equivalent among enalapril-treated myocardial infarction rats and untreated infarct rats. There was, however, less left and right ventricular hypertrophy in the enalapril treated group. Enalapril completely prevented the 42% increase in white blood count, the 88% increase in neutrophils, and the 28% increase in lymphocyte count seen in untreated infarct rats. Both untreated and enalapril treated rats tended toward a decrease in T helper:suppressor ratio. All rats treated with enalapril, however, had a significant increase in the T helper:suppressor ratio versus untreated control rats (F = 3.6, P = .018). Blastogenesis was markedly increased in T cells from infarcted animals. This was mitigated by treatment with enalapril. Additionally, immunoglobulin G antibody production was significantly lessened in rats treated with enalapril. The results of this study suggest that alterations in immunoregulatory cell type and function occurs following myocardial infarction. The beneficial effects of the angiotensin-converting enzyme inhibitor enalapril may be, in part, due to its mitigating effects on immune cell release and activation following myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

The role of hypothermia in trauma patients.

Hypothermia is a frequent event in trauma patients and appears to be related to post-traumatic organ dysfunction, although in elective surgery hypothermia is known to prevent ischaemia reperfusion injury. Retrospectively we have analysed data from 641 trauma patients treated in our institution between 1988 and 1993. On admission to hospital the core temperature (cT) was > 34 degrees] C in the majority (64%) of patients, followed by 23.6% with a cT < 34 degrees C and 12.4% with a cT < 32 degrees C. After 24 h 99% were warmed up to < 34 degrees C. Mortality was twice as high (53%) in patients with a cT < 32 degrees C compared with patients with a cT < 34 degrees C (28%). Analysis of correlations revealed that hypothermia was associated with a longer rescue time, more severe injuries of the limbs and central hypoxia. It also showed that hypothermia is not an independent prognostic factor for post-traumatic mortality. The different effect of hypothermia in trauma compared with elective surgery may be due to a lack of energy-storing phosphates like adenosine triphosphate (ATP). Further current investigations will identify the role of ATP in trauma-related hypothermia.

Body Temperature↗

Transcutaneous PO2 measurement in compound fractures.

The transcutaneous assessment of tissue oxygenation has become a useful method for evaluating microcirculatory disorders in different diseases. In this clinical experimental pilot study, the impact of compound fractures on tissue oxygenation was examined. Using a special probe placed directly into the muscle, tissue oxygenation was measured at the site of tissue injury as well as at one non-injured site within the same fractured extremity. A non-injured extremity was also measured as a control. At the injured site tissue oxygenation was significantly increased during the first 4 days after trauma compared with the non-injured extremity (40.7 +/- 1.8 mmHg versus 23.5 +/- 4.1 mmHg). At the same time the non-injured site of the fractured extremity appeared to be significantly less oxygenated compared with the non-injured extremity (13.2 +/- 2.3 mmHg versus 23.5 +/- 4.1 mmHg). After day 4 until the end of the study (day 10) a complete return to normal values was noted at both sites. In conclusion, it is most likely that, due to a change of microcirculation within the fractured extremity, the injured site is temporarily oversaturated by oxygen and this is associated with low oxygenation at the non-injured site on the same extremity. As the microcirculatory status may be important in making decisions about trauma surgery (e.g. whether or not to amputate), transcutaneous oxygen measurement is a practical and useful method in trauma care.

Adolescent↗

Regulation of prostatic smooth muscle contractility by intracellular second messengers: implications for the conservative treatment of benign prostatic hyperplasia.

The increased sympathetic neurotransmission in benign prostatic hyperplasia (BPH) results in a alpha 1C-adrenoceptor-mediated increase in prostatic smooth muscle tone which seems to be responsible for the dynamic infravesical obstruction occurring in BPH. The prostatic smooth muscle contractions evoked by norepinephrine can be efficiently blocked by alpha 1-adrenoceptor blockers. Moreover, an impressive number of clinical trials illustrated the beneficial results of alpha 1-adrenoceptor blockers in the treatment of BPH. However, despite knowledge of alpha 1-adrenergic neurotransmission and the clinical application of its blockade by selective alpha 1-adrenoceptor antagonists, very little is known about the intracellular pathways involved in the regulation of prostatic smooth muscle contractility. To study the intracellular mechanism of the alpha 1C-adrenoceptor-induced prostatic smooth muscle contraction, the patch-clamp technique in the whole-cell configuration mode combined with the Fura-II fluorescence technique was used in human, enzymatically isolated smooth muscle cells obtained from patients undergoing transurethral resection of the prostate because of symptomatic BPH. Furthermore changes in prostatic smooth muscle contractility were registered in organ bath experiments. Application of the selective alpha 1-adrenoceptor agonist phenylephrine (PE) increased the L-type Ca(2+)-channel current (ICa) dose dependently from 8 up to 18.5 microA/cm2, simultaneously elevating the free cytoplasmic Ca2+ concentration ([Ca2+]i) up to 1.9 microM. Pretreating the myocytes with pertussis toxin, an exotoxin of Bordetella pertussis which inactivates GTP-binding proteins (G proteins) of the Gi and G(o) family by ADP ribosylation, reduced the PE-induced ICa stimulation by 71.5 +/- 5.6% (n = 21). Dialysis of the cytosol with the second messenger inositol-1,4,5-trisphosphate (IP3), which releases Ca2+ from intracellular non-mitochondrial, IP3-sensitive Ca2+ pools, imitated the PE-evoked responses. Pretreating the myocytes with the Ca(2+)-release blockers ryanodine (10-100 microM, n = 8), thapsigargin (0.1 microM, n = 11) or low-molecular weight heparin (n = 14) largely attenuated the PE-evoked responses. The experimental results suggest a coupling of alpha 1-adrenoceptors to phospholipase C-converting phosphoinositol-4,5-bisphosphate into diacylglycerol, an endogenous activator of the protein kinase C and IP3 which releases Ca2+ from intracellular stores stimulating ICa via Ca(2+)-calmodulin-dependent protein kinase induced phosphorylation of voltage-dependent Ca2+ channels. This knowledge could be of interest for conservative treatment in symptomatic BPH.

Calcium Channel Blockers↗

Penile sympathic skin response in erectile dysfunction.

Penile sympathic skin response (PSSR) was measured in 20 normal patients and in 46 patients with erectile dysfunction (ED). PSSR could be registered in 80% of normal patients. The latencies were 1,100-1,600 ms. In patients with ED, latencies were 1,240-3,640 ms. A reproducible normal latency of PSSR (< 1,600 ms) indicates a normal sympathic innervation of the penis. Long latencies (> 1,800 ms) indicate neuropathy of unmyelinated nerval fibers. The loss of a reproducible answer however allows no exact diagnostic information. PSSR is a useful diagnostic test for detecting neuropathy of unmyelinated nerval fibers as a possible cause of ED.

Adult↗

[Orthotopic urinary bladder replacement in the woman. Initial clinical experiences].

Ileum neobladder after cystectomy is mainly reserved for male patients. Female patients are normally excluded from this kind of urinary diversion for fear of incontinence following orthotopic bladder substitution. In addition as in the male, the question of urethral recurrence of urothelial carcinoma is still not settled. We report on seven cases of successful orthotopic bladder reconstruction in females by means of an ileum neobladder according to Hautmann with follow up of up to 4.5 years. One of these patients had a complicated bladder-vaginal fistula and almost complete loss of bladder function because of a shrunken bladder after radiation therapy for a cervical carcinoma and the other six had undergone radical cystectomy because of bladder carcinoma. The ileum neobladder is anastomosed with the preserved urethral stump. The original method of ileum neobladder is extended by a colposuspension plasty according to Marshall-Marchetti, which is the means of achieving continence. The first results are encouraging and open further possibilities for bladder reconstruction in the female.

Adenocarcinoma↗

[Transcutaneous po2 measurement in follow-up of severe soft tissue injuries of open fractures].

The transcutaneous assessment of tissue oxygenation has become an useful method in evaluating microcirculatory disorders in different diseases. In this clinical experimental pilot study the impact of compound fractures on tissue oxygenation was examined. Using a special probe placed directly into the muscle, tissue oxygenation was measured at the site of tissue injury as well as at one non-injured site within the same fractured extremity. Furthermore, also one non-injured extremity was measured as a control. At the injured site tissue oxygenation was significantly increased during the first 4 days after trauma as compared to the non-injured extremity (40.7 +/- 1.8 mmHg vs. 23.5 +/- 4.1 mmHg). At the same time the non-injured site of the fractured extremity appeared to be significantly less oxygenated as compared to the noninjured extremity (13.2 +/- 2.3 mmHg vs. 23.5 +/- 4.1 mmHg). After day 4 until the end of the study (day 10) a complete return to normal values was noted at both sites. In conclusion it is most likely that due to a change of microcirculation within the fractured extremity the injured site is temporarily oversaturated by oxygen combined with lacking oxygenation at the non-injured site. As the microcirculatory status may be important in making decision in trauma surgery (e.g. whether or not to amputate) the method of transcutaneous oxygen measurement is a practical and useful method in trauma care.

Adolescent↗

[Gnathostomiasis after a stay in Thailand].

During a 4-week holiday in Thailand a 13-year-old boy from Germany briefly fell ill with diarrhoea without blood-tinged stools and fever. 5 months later oedematous, reddish swellings occurred, at first on the right upper arm, later over the right side of the chest. Especially at night these swellings were associated with severe local and generalized itching. Bilaterally the axillary lymph-nodes were hard and slightly enlarged. There was a marked eosinophilia of 56%, the white count was 22,700/microliters and the serum level of IgE was raised to 1777 IU/ml. No worm eggs or larvae were found in the stool. Enzyme-linked immunosorbent assay, using larvae of Gnathostoma spinigerum as antigen, demonstrated antibodies against this nematode. Gnathostomiasis having been diagnosed treatment was started with albendazole (200 mg twice daily for 21 days), after which the boy was symptom free. After 2 months the eosinophilia had regressed to 10%, the white cell count was normal and the antibody titre had fallen.

Adolescent↗

Asymmetric expression of protein kinase CK2 subunits in human kidney tumors.

Renal clear cell carcinomas and the corresponding ipsilateral control tissues were investigated for protein kinase CK2 activity and subunit ratio. The average protein kinase CK2 activity from 21 different kidney samples was 318 U/mg and that from the corresponding tumors 610 U/mg. The subunit ratio of protein kinase CK2 alpha in tumors/normal tissue (T/N) was 1.58 and that of the protein kinase CK2 beta (T/N) was 2.65. The data suggest that the generally described increase in protein kinase CK2 activity in tumor cells may to some extent result from a deregulation in subunit biosynthesis or degradation. This at least partly owing to the presence of excess enzymatically active protein kinase alpha-subunit but also to a significantly higher presence of the non-catalytic beta-subunit.

Adenocarcinoma, Clear Cell↗

Close proximity of Cys64 and Cys140 in the delta subunit of Escherichia coli F1-ATPase.

The delta subunit of the F1-ATPase from Escherichia coli contains 2 cysteine residues, one at position 64 and the second at position 140 of the amino acid sequence. These residues were specifically labeled with sulfhydryl reagents in this study without labeling other -SH groups in the enzyme. Modification of Cys140 by maleimides such as N-ethylmaleimide or fluorescein maleimide resulted in a reconstitutively active enzyme that was indistinguishable from the native protein. Labeling of Cys64 with or without concomitant labeling of Cys140 resulted in a reconstitutively inactive enzyme. The ATPase activity of either form of the labeled enzyme was unaffected. However, labeling of Cys64 was accompanied by dissociation of the delta subunit from the enzyme. These observations suggest a role for the microenvironment of Cys64 in interactions of the delta subunit with other subunits in the enzyme. Two types of evidence support the conclusion that the 2 cysteine residues of the delta subunit are in close proximity. First, incorporation of pyrene maleimide into both delta cysteines led to excimer formation. Second, incubation of F1 with 5,5'-dithiobis(2-nitrobenzoic acid) resulted in quantitative formation of a disulfide bond between Cys64 and Cys140, presumably via disulfide interchange. The enzyme containing the internally cross-linked delta subunit exhibited an undiminished ability to support proton pumping when reconstituted into F1-depleted membrane vesicles. The presence of 2 closely apposed cysteinyl residues in the delta subunit of the native enzyme places constraints on the type of structure that may be proposed for the subunit.

Cysteine↗

DNA aneuploidy in prostatic adenocarcinoma: a frequent event as shown by fluorescence in situ DNA hybridization.

Fluorescence in situ hybridization (FISH) using specific DNA probes for chromosomes 1, 7, 10, and Y was performed on 53 prostatic tissue samples obtained from 33 radical prostatectomy specimens and two benign control specimens. The 53 samples from carcinomatous prostates included 33 cancerous and 20 noncancerous samples. Additionally, four metastatic lymph node specimens were examined. Clonal chromosome abnormalities were observed in 78% of the tumors studied. They were detected in a higher proportion in stage pT2 and pT3 tumors (86% and 88%, respectively) compared with stage pT1 tumors (25%). No stage pT4 tumor was analyzed. There was evidence of remarkable focal intratumoral heterogeneity documented by the study of two samples from the same tumor in three of six cases. Comparing FISH determined ploidy patterns with DNA flow cytometry (FCM) in 22 samples, FISH showed aneuploidy whereas FCM showed none.

Adenocarcinoma↗

Antibody response in rats against non-toxic glucose sensor membranes tested in cell culture.

Several glucose sensors have been developed, but none are commercially available. The most urgent in vivo problem is the drift of glucose sensor output with time, which may be caused by leakage or denaturation of glucose oxidase, and events at the body-sensor interface such as protein coating, encapsulation with cells, toxicity of the device and inflammation. In the present study, a specific immune response against the outer cellulose acetate membrane of a glucose sensor implanted into rats has also been proved. The immune response against polymeric membranes can be confirmed by detection of specific immunoglobulin G antibodies to cellulose acetate, polyurethane and regenerated cellulose after implantation of the respective membrane. The individually different antibody formation against polymers in rats was amplified by one application of complete Freund's adjuvant in combination with the first implantation. The cell culture results using the fibroblast cell line L-929 showed only a minor toxicity of regenerated cellulose, whereas the other polymers had no effect on cell growth and viability. From the results of this study, it is proposed to integrate immunogenicity as a further parameter for evaluation of the biocompatibility and biosafety of materials or medical devices which are provided for implantation.

Animals↗

No association between anti-bovine serum albumin antibodies and islet cell reactive antibodies in newly diagnosed type 1 diabetic patients.

Serological findings have suggested that antibodies (Ab) to bovine serum albumin (BSA-Ab) are associated with type 1 diabetes mellitus. The aim of our study was to evaluate a competitive fluid-phase radioimmunoassay for detecting BSA-Ab using different incubation times and to study a possible association of these BSA-antibodies with autoantibodies (AAb) frequently detected in type 1 diabetic patients. For the overnight incubation time, there was an enormous overlap in the [125I]BSA binding by serum samples between 52 newly diagnosed type 1 diabetic patients (mean [125I]BSA binding 23.6 +/- 17.4%) and 54 healthy blood donors (mean [125I]BSA binding 10.2 +/- 15.7%). By an incubation time of only 3 min the BSA-antibody prevalence was found to be 15.4% (8/52) for type 1 diabetic patients and 3.7% (2/54) for control subjects. However, there was no association between BSA-Ab and type 1 diabetes-associated antibodies as cytoplasmic islet cell antibodies (ICA), or glutamate decarboxylase autoantibodies. Our results confirm that (i) BSA-Ab occur more frequently in newly diagnosed type 1 diabetic patients compared with a healthy control group and (ii) that the BSA-Ab detected by the fluid-phase radioimmunoassay with an incubation time of 3 min are more disease-associated than the [125I]BSA binding after an overnight incubation. The competitive BSA-Ab fluid-phase radioimmunoassay described is a simple and rapid method to detect antibodies specifically reactive with BSA. It is suggested that the humoral immune reactivity to BSA in type 1 diabetic patients probably reflects an unspecific defect of the immune system and gives no additionally diagnostic value about the type 1 diabetes.

Adolescent↗