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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 325 records · Page 18Linked to original sources
PubMed1997

Distinction between hepatic focal nodular hyperplasia and malignant liver lesions using technetium-99m-galactosyl-neoglycoalbumin.

UNLABELLED: Distinction between hepatic focal nodular hyperplasia (FNH) and malignant liver lesions is essential because of the different therapy strategies, since FNH can be managed conservatively. The aim of this study was to describe the imaging pattern of FNH using the hepatocyte receptor ligand 99mTc-galactosyl-neoglycoalbumin 99mTc-NGA) and to assess the value of this receptor imaging agent in the differentiation of FNH from malignant liver lesions. METHODS: Twelve consecutive patients with histologically confirmed FNH were investigated. The FNH-lesions were asymptomatic and incidentally found by ultrasonography. Nine patients with histologically verified hepatocellular carcinomas and three patients with liver metastases spread from gastrointestinal adenocarcinomas served as controls. RESULTS: All FNH lesions showed normal or even increased uptake of 99mTc-NGA. Whereas malignant liver lesion-to-normal liver ratios amounted to 0.4 +/- 0.2 (mean +/- s.d.), FNH lesion-to-normal liver ratios were 1.7 +/- 0.3 (mean +/- s.d.). CONCLUSION: The receptor imaging agent 99mTc-NGA with concurrent use of SPECT is useful in the differential diagnosis of FNH and malignant hepatic tumors.

Adult↗
PubMed1997

Alcoholism and carcinoma change the intracellular pH and activate platelet Na+/H+-exchange in men.

The occurrence of carcinoma in chronic alcoholics exceeds that of the general population. Cytoplasmic alkalinization, due to the influence of different factors on the transmembrane Na+/H+ exchange (NHE), has been put forward as a triggering event in cell growth and division. In accordance with these findings, the carcinogenic potential of NHE deficient cell types is reported to be diminished. The aim of this study was to investigate whether the intracellular pH and the NHE activity is altered in chronic alcoholics. Seventy-two Caucasian males were assigned to one of four groups: non-alcoholics without carcinoma, chronic alcoholics without carcinoma, non-alcoholics with carcinoma and chronic alcoholics with carcinoma. Alcoholism was diagnosed according to DSM-III-R. The groups did not differ in relation to basic patient characteristics, such as age and blood pressure. Intracellular calcium, pH and NHE in platelets were determined by spectrofluorometry before and after thrombin stimulation. In chronic alcoholics with carcinoma, the intracellular pH was significantly more alkaline and the NHE activity was elevated. In contrast, a decrease in intracellular pH associated with an increased activity of NHE and a more acidic set point was found in chronic alcoholics without carcinoma. Basal and thrombin stimulated intracellular Ca2+ did not differ between groups except in chronic alcoholics with carcinoma in whom a thrombin-induced increase of Ca2+ due to liberation of Ca2+ from intracellular stores was demonstrated. In chronic alcoholics with carcinoma, cytoplasmic alkalinization was observed and this may be an indication of an increase in cell proliferation. The possibility that the increased incidence of carcinomas in chronic alcoholics is related to the increased activity of NHE and whether this may be prevented by NHE inhibitors requires further investigation.

Adult↗
PubMed1996

The release of cytokines, adhesion molecules, and extracellular matrix parameters during and after reperfusion in human liver transplantation.

Poor initial graft function may increase postoperative morbidity including the risk of early allograft rejection. Various mediators, including immunostimulatory cytokines, may be released during reperfusion in relation to the extent of preservation and reperfusion injury. For this purpose, 81 patients with 85 liver transplants were monitored for cytokines, adhesion molecules, extracellular matrix (ECM) parameters, and neopterin at predefined time-points during and after transplantation. To estimate the origin of cytokine release, blood was obtained central and hepatic venously for the first 48 hr after reperfusion and subsequently from a peripheral vein. One-year patient survival was 88.9%; no relation to initial graft function was observed. Poor initial graft function failed to increase the risk for subsequent infectious complications but was associated with an increased risk of early allograft rejection. The incidence of steroid-resistant rejection was significantly increased in patients with poor initial graft function (35.7% versus 12.7% in patients with good and moderate initial graft function; P < or = 0.05). Various cytokines, adhesion molecules, and ECM parameters including sTNF-RII, sIL-2R, IL-8, IL-10, sVCAM-1, E-selectin, hyaluronic acid, sialic acid, and laminin correlated significantly with the extent of preservation and reperfusion injury. Although none of these parameters was more appropriate in determining the extent of preservation and reperfusion injury than currently established parameters (AST, ALT, and color and amount of bile production), the combined increase in these parameters may not only promote tissue repair but may also perpetuate liver allograft injury and thereby cause significant morbidity. Besides cytokines and adhesion molecules, the ECM may play a pivotal role in determining repair or ongoing tissue injury. Ongoing changes at the microvasculature and basement membrane may result in an increase of local and circulating cytokines and adhesion molecules, which increase the risk of subsequent early allograft rejection. Furthermore, the increase in sTNF-RII, E-selectin, and laminin during reperfusion was predictive of subsequent development of acute allograft rejection. These observations may be of value for further strategies to decrease reperfusion injury and prevent early allograft rejection.

Adult↗
PubMed1996

[Reversible bilateral changes in cerebral proton-spin tomography in eclampsia].

HISTORY AND CLINICAL FINDINGS: Case 1: A 19-year-old primigravida was hospitalised in the 24th week of pregnancy after a series of grand-mal seizures. Investigation showed the classical eclamptic triad of oedema, hypertension and proteinuria. Case 2: 6 days post-partum a 24-year-old primipara developed hypertension and typical clinical prodromata. Subsequently she had a series of sometimes initially focal grand-mal seizures. TREATMENT AND COURSE: In both cases seizures ceased following pharmacological treatment. The pregnancy in the first case remained intact. Cerebral magnetic resonance imaging (MRI) demonstrated characteristic findings in both cases, in case 1 bilateral disseminated supratentorial foci of oedema without space-occupying features, in case 2 occipital white matter oedema and several supratentorial foci. All changes were completely reversible, in case 1 after 10 days, in case 2 after 16 days. CONCLUSIONS: Together with the clinical findings the focal changes on MRI provide a characteristic picture. MRI can thus be an important aid to the diagnosis of eclampsia and will prevent a misinterpretation as focal encephalitis or venous sinus thrombosis.

Adult↗
PubMed1996

Sarcoidosis recurrence following lung transplantation.

Sarcoidosis is a rare indication for lung transplantation. In this article, our experiences with recurring sarcoidosis following lung transplantation are described. Literature concerning recurrence of the disease in kidney, liver, heart and lung transmission of sarcoidosis via transplanted organs are discussed.

Humans↗
PubMed1996

Apoptosis and immunohistochemical bcl-2 expression in colorectal adenomas and carcinomas. Aspects of carcinogenesis and prognostic significance.

BACKGROUND: The bcl-2 oncoprotein confers a survival advantage to cells by inhibiting programmed cell death (PCD) or apoptosis. Overexpression of bcl-2 probably plays a role in colorectal carcinogenesis. The aims of our study were to determine bcl-2 expression and PCD index in colorectal adenomas and carcinomas in correlation with p53 expression, Ki-67 index, and histopathology, and to test their prognostic significance in patients with colorectal carcinomas. METHODS: Immunohistologic staining for bcl-2 (MoAb clone 124), the proliferation-associated Ki-67 antigen (MoAb MIB1), and p53 (MoAb DO1) was performed on archival material from 44 colorectal adenomas and 95 adenocarcinomas (TNM classifications pT2 and -3, pN0, and M0). The PCD was visualized by enzymatic detection of DNA fragmentation. RESULTS: bcl-2 was expressed in 86% of the adenomas and 67% of the carcinomas. Mean PCD and Ki-67 rates were 1.7 +/- 0.14% and 35 +/- 13% in adenomas and 1.9 +/- 0.15% and 28 +/- 14% in carcinomas, respectively. In carcinomas, bcl-2 expression was correlated with a low PCD index (< 1.5%; P = 0.005). Furthermore, a high Ki-67 index (> or = 25%) was associated with a high PCD index (> or = 1.5%; P < 0.0001). p53 accumulation was seen in 16% of adenomas and in 42% of carcinomas, and did not correlate with bcl-2 expression or PCD index. In the univariate analyses, significantly longer disease free survival intervals were observed in three groups: all patients with bcl-2-positive carcinomas (P < 0.05); the subgroup of carcinomas with bcl-2 expression and low PCD index (P = 0.037); and the subgroup of bcl-2-positive and p53-negative carcinomas (P = 0.021). In the multivariate analysis, however, only tumor stage and p53 expression were independent risk factors for prognosis. CONCLUSIONS: Our data indicate that bcl-2 expression is characteristic of the early phase of colorectal carcinogenesis. Its physiologic function as an inhibitor of PCD is preserved in most colorectal carcinomas, whereas p53 is apparently not involved in the regulation of PCD in colorectal neoplasias. bcl-2 expression in colorectal carcinomas is associated with a better clinical course. This correlation became even more evident in the subgroups of patients with carcinomas that also had low PCD index or lacked p53 immunoreactivity.

Adenoma↗
PubMed1996

Psychiatric disorders in gynaecological, surgical and medical departments of general hospitals in an urban and a rural area of Austria.

A total of 728 patients admitted to the medical, gynaecological and surgical departments of one urban and one rural general hospital in Austria were investigated for psychiatric morbidity. Using the Clinical Interview Schedule and its case criteria, the prevalence of psychiatric morbidity was found to be highest in medical departments (38.2%), followed by surgical departments (32.5%), and lowest in gynaecological departments (20.7%). Among medical and surgical patients, dementia and substance abuse disorders were the most frequent psychiatric categories, while in gynaecological departments neurotic disorders showed the highest frequency. For the sample as a whole, single status (i.e. unmarried, widowed or divorced), lower social class and rural catchment area of the general hospital predicted a high prevalence of psychiatric morbidity in a logistic regression analysis, while complications of childbirth, pregnancy or the puerperium, and diseases of the skin or the musculoskeletal system showed a negative association with psychiatric illness.

Adolescent↗
PubMed1996

Intercurrent complications in chronic alcoholic men admitted to the intensive care unit following trauma.

OBJECTIVE: A chronic alcoholic group following trauma was investigated to determine whether their ICU stay was longer than that of a non-alcoholic group and whether their intercurrent complication rate was increased. DESIGN: Prospective study. SETTING: An intensive care unit. PATIENTS: A total of 102 polytraumatized patients were transferred to the ICU after admission to the emergency room and after surgical treatment. Of these patients 69 were chronic alcoholics and 33 were allocated to the non-alcoholic group. The chronic-alcoholic group. met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in these patients was > or = 60 g. Diagnostic indicators included an alcoholism-related questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin. MEASUREMENT AND RESULTS: Major intercurrent complications such as alcohol withdrawal syndrome (AWS), pneumonia, cardiac complications and bleeding disorders were documented and defined according to internationally accepted criteria. Patients did not differ significantly between groups regarding age, TRISS and APACHE score on admission. The rate of major intercurrent complications was 196% in the chronic alcoholic vs 70% in the non-alcoholic group (p = 0.0001). Because of the increased intercurrent complication rate, the ICU stay was significantly prolonged in the chronic-alcoholic group by a median period of 9 days. CONCLUSIONS: Chronic alcoholics are reported to have an increased risk of morbidity and mortality. However, to our knowledge, nothing is known about the morbidity and mortality of chronic alcoholics in intensive care units following trauma. Since chronic alcoholics in the ICU develop more major complications with a significantly prolonged ICU stay following trauma than non-alcoholics, it seems reasonable to intensify research to identify chronic alcoholics and to prevent alcohol-related complications.

Adolescent↗
PubMed1996

Dose increase augments response rate to interferon-alpha in chronic hepatitis C.

Approximately 50% of patients with chronic hepatitis C respond to treatment with interferon-alpha. The aim of this randomized controlled trial was to evaluate whether an increase in dose of interferon-alpha augments response rate. One hundred thirty-eight patients with newly diagnosed chronic hepatitis C received a three-month course of 3 MU IFN-alpha2b administered every two days. All patients were anti-HCV and HCV-RNA (PCR) positive. Prior to treatment, a liver biopsy was performed. Complete response was defined by normal serum ALT concentrations and disappearance of HCV-RNA. After three months, 60 nonresponders were randomized (stratified according to histology) either to continue 3 MU interferon-alpha2b every two days for another six months (group A, total dose: 410 MU) or to receive increasing doses of interferon-alpha2b (6 MU every two days for three months, followed by 10 MU every two days for three months) (group B, total dose: 870 MU). Serum ALT concentrations were measured monthly and HCV-RNA at three-month intervals. Liver biopsy was repeated six months after end of treatment. Pretreatment characteristics of the randomized patients were: group A: N = 30; male/female: 20/10; age: 54 +/- 10 years; CPH 9, CAH 8, cirrhosis 13; mean ALT 108 +/- 98 units/liter; group B: N = 30; male/female: 21/9; age: 57 +/- 15 years; CPH 10, CAH 9, cirrhosis 11; mean ALT 90 +/- 40 units/liter. At the end of treatment six patients in group B but none in group A became responders [P = 0.011 (Fisher's exact test), intent-to-treat analysis]. All six responders were noncirrhotics. High-dose interferon was not tolerated by six patients in group B. Noncompliance resulted in five dropouts in group A and one in group B. During the six-month follow-up, four of the six responders relapsed. A patient in group A with increased serum ALT concentration but negative HCV-RNA at the end of treatment became a full responder after six months. Of nonresponders to 3 MU interferon alpha2b every two days for three months, 20% responded to higher interferon doses, but none to continued standard dose. Prolonged treatment with interferon may be necessary to obtain a sustained response. However, treatment with higher-dose interferon was not tolerated in 20% of the patients.

Alanine Transaminase↗
PubMed1996

Glutamate immunoreactivity of insular cortex afferents to the nucleus tractus solitarius in the rat: a quantitative electron microscopic study.

Corticosolitary axons and their terminals were labeled by the anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, after injections into the rat insular cortex. The ultrastructure of these cortical afferents was analysed in the medial and commissural subnuclei of the nucleus tractus solitarius. Cortical terminals had a mean area of 0.36 microns 2, and were among the smallest terminals in the nucleus. They made single, asymmetric synaptic contacts with thin dendritic stems or with spines. The average diameter of the dendrites postsynaptic to cortical axons was 0.59 microns, and significantly smaller (P < 0.01, Kolmogorov-Smirnov test) than the mean (0.87 microns) of the population of dendrites in the same region of the nucleus tractus solitarius. Cortical boutons contained closely packed round and clear synaptic vesicles of diameter ca. 28 nm, a few mitochondria, and no dense core vesicles. Postembedding immunogold analysis showed that the anterogradely labeled cortical axon terminals were immunoreactive to glutamate, but not to GABA. Cortical afferents had on average four times the glutamate immunoreactivity (assessed by gold particle density) than local dendrites or terminals making symmetric synaptic contacts. Similarly, most of the unlabeled axon terminals participating in asymmetric synaptic contacts were highly enriched in glutamate immunoreactivity, suggesting that glutamate may be a most prevalent transmitter in the nucleus tractus solitarius. Terminals immunoreactive to GABA always made symmetric synapses, mostly with dendritic shafts and perikarya. We concluded that insular cortex axons made single, asymmetric synaptic contacts with thin, probably distal dendrites in the nucleus tractus solitarius. Cortical terminals are immunoreactive to glutamate, and morphologically different from primary afferents and from terminals immunoreactive to GABA.

Afferent Pathways↗
PubMed1996

Bone mass and soft tissue composition in adolescents with anorexia nervosa.

The relationship between bone mass and compartments of soft tissue was studied in 22 adolescent women with anorexia nervosa (mean, 17 years). Results were compared to data on age- and gender-matched controls. Bone mass of the lumbar vertebrae and femoral neck, fat and lean tissue was measured by dual energy X-ray absorptiometry (DXA). Bone mass in the central third of the skeleton, by neutron activation analysis (NAA), and body protein, by prompt gamma ray analysis (PGA), was measured on patients, but not controls. The patients had significantly lower values than controls in total weight (26%), lean tissue (16%), fat (60%), bone mass of lumbar spine (14%), and femoral neck (15%). The mean calcium bone index (CaBI), the central skeletal calcium normalized for body size based on height, was significantly lower than the value for external controls, (0.86 +/- 0.10 vs. 0.97 +/- 0.10). The nitrogen index (NI), body protein normalized for height, showed a similar reduction from external controls (0.84 +/- 0.10 vs. 1.0 +/- 0.10). Bone mass (both DXA and NAA data) was strongly correlated to lean tissue and to protein; the correlations to fat were weaker. Follow-up studies after 7-26 months in 12 patients showed a modest increase in weight (mean, 4.9 kg) which was due, primarily, to an increase in fat with only insignificant increase in lean tissue and in protein. In bone mass, there was either no change or further loss. Only four restored body weight to normal (BMI > 20) and they achieved normal menstruation, but even these four responders showed no increase in bone mass. Our studies confirm that adolescent females with anorexia nervosa suffer losses not only in all compartments of body composition, but also demonstrate that the restoration of bone mass lags behind improvement in soft tissue compartments. These results were independent of methods used for the measurements.

Absorptiometry, Photon↗
PubMed1996

Rapid quantitative analysis of protein tyrosine residue phosphorylation in defined cell populations in whole blood and bone marrow aspirates.

We developed a rapid method for quantification of tyrosine phosphorylation in immunophenotypically defined cell populations in specimens of whole blood and unprocessed bone marrow. Samples were formaldehyde-fixed and cells were permeabilized. Phosphotyrosine residues and surface antigens were simultaneously stained by monoclonal antibodies and visualized by flow cytometry. The accuracy of the method was confirmed by demonstration of an increase of phosphotyrosine levels in pp60v-src transformed fibroblasts. In blood of healthy donors, monocytes and granulocytes showed higher levels of phosphotyrosine than lymphocytes. CD34+ peripheral blood stem cells showed slightly increased tyrosine phosphorylation compared to autologous lymphocytes. Significantly elevated levels of phosphotyrosine were demonstrated in leukaemic blasts compared to lymphocytes (P = 0.01).

Acute Disease↗
PubMed1996

Characterization of autoantibodies to natural killer cells in HIV-infected patients.

Natural killer (NK) cells in HIV-infected patients have a reduced ability to generate non-MHC restricted cytotoxicity to a variety of target cells. The authors investigated antibodies to NK cells in HIV-infected patients and evaluated effects of these antibodies to NK cell numbers and function. Antibodies to NK cells were determined in 160 HIV-infected patients and 35 healthy controls. Flow cytometric whole blood methods were developed to detect antibodies to NK cells. Antibodies to asialo-GM1 were detected by TLC immunostaining. The presence of antibodies to NK cells was demonstrated in plasma of about one-third (54/160) of HIV-infected patients but rarely in controls (2/35). Auto-antibodies bound to NK cells in vivo and were detected by a strong increase of surface immunoglobulin (Ig) on NK cells of HIV-infected patients. Anti-NK cell antibodies were warmreactive antibodies rather of IgG than of IgM phenotype. The prevalence of specific antibodies to asialo-GM1 was low (12.5%). Numbers of circulating NK cells did not differ significantly between antibody positive (99.5/microliters) and antibody negative (141/microliters) patients (P = 0.3). However, pre-incubation of healthy donors' NK cells with autoantibody positive plasma significantly inhibited cytotoxicity to K562 leukaemic cells (P = 0.002). Autoantibodies to NK cells in HIV-infected patients are present in the plasma of one-third of HIV-infected patients and are bound to NK cells in vivo. There is evidence that these autoantibodies can induce NK cell defects similar to those seen in vivo.

Antibodies, Anti-Idiotypic↗
PubMed1996

Bronchoplastic resection for non-small-cell lung cancer.

During the past 12 years, among 1478 operations for non-small-cell lung cancer (NSCLC), 102 (6.9%) bronchosplastic resections were performed. There were 74 lobectomies, 19 bilobectomies, and 9 pneumonectomies done by means of 72 sleeve-, 28 wedge resections, and 2 resections of the tracheal bifurcation. Atelectasis was observed in 6%, whereas anastomotic dehiscence occurred in 4%. Local complete resection was achieved in 81%. The 30-day mortality amounted to 4%. Our results demonstrate that bronchoplastic procedures represent a safe therapeutic option in the operative treatment of central NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Beta-carbolines in chronic alcoholics following trauma.

In our society every second polytraumatized patient is a chronic alcoholic. A patient's alcohol-related history is often unavailable and laboratory markers are not sensitive or specific enough to detect alcohol-dependent patients who are at risk of developing alcohol withdrawal syndrome (AWS) during their post-traumatic intensive care unit (ICU) stay. Previously, it has been found that plasma levels of norharman are elevated in chronic alcoholics. We investigated whether beta-carbolines, i.e. harman and norharman levels, could identify chronic alcoholics following trauma and whether possible changes during ICU stay could serve as a predictor of deterioration of clinical status. Sixty polytraumatized patients were transferred to the ICU following admission to the emergency room and subsequent surgery. Chronic alcoholics were included only if they met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use and their daily ethanol intake was > or =60 g. Harman and norharman levels were assayed on admission and on days 2, 4, 7 and 14 in the ICU. Harman and norharman levels were determined by high pressure liquid chromatography. Elevated norharman levels were found in chronic alcoholics (n = 35) on admission to the hospital and remained significantly elevated during their ICU stay. The area under the curves (AUC) showed that norharman was comparable to carbohydrate-deficient transferrin (CDT) and superior to conventional laboratory markers in detecting chronic alcoholics. Seventeen chronic alcoholics developed AWS; 16 of these patients experienced hallucinations or delirium. Norharman levels were significantly increased on days 2 and 4 in the ICU in patients who developed AWS compared with those who did not. An increase in norharman levels preceded hallucinations or delirium with a median period of approximately 3 days. The findings that elevated norharman levels are found in chronic alcoholics, that the AUC was in the range of CDT on admission and that norharman levels remained elevated during the ICU stay, support the view that norharman is a specific marker for alcoholism in traumatized patients. Since norharman levels increased prior to the onset of hallucinations and delirium it seems reasonable to investigate further the potential role of norharman as a possible substance which triggers AWS.

Journal Article↗