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Biomedical subjects

C Müller

Publications and source records attributed to C Müller.

At least 289 records · Page 16Linked to original sources

Hypothermic storage alone in lung preservation for transplantation: a metabolic, light microscopic, and functional analysis after 18 hours of preservation.

BACKGROUND: Current lung preservation consists of flushing of the donor organs, with successive hypothermic storage in an inflated state. Recently, hypothermic storage alone was reported to be superior in terms of functional recovery. This study was designed to investigate the metabolic, morphologic, and functional consequences of hypothermic storage alone, in experimental lung preservation. METHODS: Orthotopic left-sided lung transplantation was performed in pigs. Donor lungs were flushed with Euro-Collins solution (n=6) or simply explanted (n=6) and stored for 18 hr at 4 degrees C. After this, left-sided single lung transplantation was performed. Sham-operated animals (n=6) served as control. Morphology and metabolism were analyzed in normal lungs, after ischemia and at the end of reperfusion. Gas exchange and pulmonary hemodynamics of the transplanted organs were measured, after exclusion of the native lung from perfusion and ventilation. RESULTS: Metabolic and morphologic evaluation did not show a significant difference between the groups at the end of ischemia. Lungs preserved by hypothermia alone showed a functional recovery close to sham-operated animals and superior to flushed organs. CONCLUSIONS: Hypothermia alone is a sufficient means of preservation for explanted lungs for at least 18 hr.

Animals↗

sst2 somatostatin receptor expression reverses tumorigenicity of human pancreatic cancer cells.

Among the five cloned somatostatin receptor subtypes (sst1 to sst5), sst2 mediates the antiproliferative effect of somatostatin analogues in vitro. Somatostatin analogues have been shown to inhibit cell growth in vitro and in vivo in pancreatic cancer models that expressed sst2. We recently demonstrated the loss of sst2 gene expression in human pancreatic adenocarcinomas and most of the derived pancreatic cancer cell lines. In the present study, we corrected the sst2 defect in human pancreatic cancer BxPC-3 and Capan-1 cells by stable transfection with human sst2 cDNA. In the absence of exogenous ligand, both BxPC-3 and Capan-1 cells expressing sst2 showed a significant reduction in cell growth. This inhibitory effect was blocked by treatment with antiserum to somatostatin. sst2-expressing cells produced somatostatin-like immunoreactivity that mainly corresponded to somatostatin 14, indicating the induction of a negative autocrine loop. In other respects, sst2 expression in Capan-1 cells induced a significant reduction of clonogenicity in soft agar. Moreover, a significantly reduced (Capan-1 cells) or suppressed (BxPC-3 cells) tumor growth in athymic nude mice was observed. The reversal of tumorigenicity induced by the restoration of sst2 expression suggests that the loss of sst2 contributes to the malignancy of human pancreatic cancers.

Animals↗

[Autoimmunity].

The understanding of the molecular and cellular events leading to autoimmune reactions, and potentially also to autoimmune disorders, is essential for the design of novel, specific approaches in the treatment of patients with autoimmune diseases. A variety of regulatory immune mechanisms are operative in the periphery which control the potentially detrimental action of autoreactive T- and B-cells that have escaped the central selection process in the thymus and the bone marrow respectively. Hence, novel strategies to treat autoimmune disorders exploit and attempt to support these regulatory pathways, which may be deficient in patients with autoimmune diseases. However, despite a large number of studies reporting successful treatment of autoimmune diseases in animal models using these novel strategies, major obstacles have still to be overcome before these novel strategies can be successfully used in the treatment of autoimmune diseases in patients.

Autoantibodies↗

Rational use of polymerase chain reaction--based detection of viral genomes in patients with serologic markers of hepatitis B or C virus infection.

We studied the value of additional diagnostic information obtained by detection of hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA using the qualitative polymerase chain reaction (PCR) in patients with serologic markers of hepatitis B or hepatitis C virus infection. In HBV infection, all HBsAg+HBeAg+ patients and all HBsAg+HBeAg- patients with alanine aminotransferase (ALT) levels > 100 U/L were positive for HBV-DNA by PCR, whereas in HBsAg+HBeAg- patients with ALT < 100 U/L 58% and in HBsAg+HBeAg- patients with normal aminotransferase 45% were found to be positive. In HBsAg+ patients no further clinically useful information can be obtained by PCR as the presence of HBsAg proves infection. However in three of 42 (7%) patients with markers of past HBV infection (antiHBs and/or antiHBc+) HBV-DNA was detected in the serum. Similarly, in some patients with acute hepatitis B HBV-DNA was demonstrable up to four months after the disappearance of HBsAg from serum, pointing to persistence of viremia despite the loss of serological markers of ongoing HBV infection. Demonstrating ongoing HBV infection in patients with serological markers of past infection is valuable additional information in only selected patients. In HCV infection, 10% of anti-HCV+ patients with increased ALT levels had a negative serum HCV-RNA. However, in 20% of those patients HCV-RNA was demonstrated in a serum sample collected later during follow-up, indicating that a single negative HCV-RNA determination cannot be taken as evidence for the resolution of infection.

Adolescent↗

Single device approach to ultrasound-guided percutaneous transluminal coronary angioplasty and stenting: initial experience with a combined intracoronary ultrasound/variable diameter balloon.

We evaluated the use of both intracoronary ultrasound (ICUS) information and unique balloon characteristics provided by a combined ICUS/variable diameter balloon catheter during coronary interventions to achieve the maximal residual lumen using the least number of devices. In 47 patients, 64 coronary lesions were treated with either sequential percutaneous transluminal coronary angioplasty (PTCA) (n = 40) or stenting (primary [n = 17], secondary [n = 7]). The result after PTCA was judged satisfactory if the lumen cross sectional area (by ICUS) in the lesion exceeded 65% of the mean reference area. Stent implantation was judged according to revised MUSIC trial criteria. PTCA or stenting was successful in all 64 lesions using 47 combination devices and 10 conventional balloons (mean number of balloons per lesion: 0.90). PTCA group: diameter stenosis decreased from 78 +/- 11 to 23 +/- 13% following inflation at 10.3 +/- 3.0 atm. ICUS lumen area was 4.6 +/- 1.9 mm2 (proximal reference: 7.4 +/- 3.3 mm2, distal reference: 5.7 +/- 1.8 mm2) resulting in a residual area stenosis of 28 +/- 15%. Stent group: diameter stenosis was reduced from 77 +/- 14 to 10 +/- 10% after stenting. ICUS defined minimal lumen area in the stent was 8.2 +/- 2.2 mm2 (proximal reference: 8.7 +/- 2.6 mm2, distal reference: 8.0 +/- 2.2 mm2) resulting in a residual area stenosis of 7.2 +/- 14.6%. No patient death, myocardial infarction, or emergency surgery occurred and only one target lesion required re-PTCA during hospitalization. In conclusion, use of a combined ICUS/variable diameter balloon catheter allows a single device strategy for ICUS-guided PTCA and stenting in the majority (84%) of unselected lesions.

Adult↗

Lack of specificity of albumin-mRNA-positive cells as a marker of circulating hepatoma cells.

The aim of the study was to assess the specificity of albumin-messenger RNA (mRNA)-positive cells in peripheral blood as an indicator for circulating malignant hepatocytes. Albumin-mRNA-positive cells in the peripheral blood mononuclear cell (PMNC) fraction were detected by reverse-transcription polymerase chain reaction (RT-PCR). Albumin-mRNA-positive cells in PMNC were found in 12 of 19 (63%) patients with hepatocellular carcinoma, but also in 22 of 25 (88%) patients with chronic hepatitis without evidence for hepatoma, and in 18 of 19 (94%) of patients with acute viral hepatitis. In addition, 8 of 28 (28%) of healthy control individuals had also albumin-mRNA-positive cells in peripheral blood. PMNC known to be spontaneously negative for albumin-mRNA could be induced in vitro to transcribe albumin-mRNA after activation with a variety of substances such as interleukin-1 (IL-1) plus concanavalin A (Con A), IL-2, bacterial lipopolysaccharide, platelet derived growth factor, alpha-fibroblast growth factor, or hepatocyte growth factor. These results show that the majority of patients with acute and chronic liver disease without evidence for hepatocellular carcinoma has albumin-mRNA-positive cells in their PMNC fraction indicating the nonspecificity of that parameter for the presence of circulating malignant hepatocytes. In addition, in vitro experiments suggest that PMNC are capable of transcribing mRNA for albumin at a low level after activation. In vivo-activated PMNC are likely to be the source of positivity in healthy controls, patients with nonmalignant acute and chronic liver disease, and patients with hepatocellular carcinoma.

Adult↗

[Green hair caused by frequent swimming pool use].

Three patients presented with an acquired green discoloration of their scalp hair. History revealed that all of them swam regularly in private swimming pools. Examination of the hair by atomic emission spectroscopy showed that the green discoloration was caused by an excessively high copper content of the hair. This exogeneous discoloration is characteristically related to the uptake of copper from private swimming pools.

Adolescent↗

[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↗

Endogenous glucose production, gluconeogenesis and liver glycogen concentration in obese non-diabetic patients.

Resting, post-absorptive endogenous glucose production (EGP), fractional gluconeogenesis and liver glycogen concentration were assessed in 6 lean and 5 obese non-diabetic subjects undergoing elective abdominal surgery. During the 2 days preceding these measurements, 0.3 g/day U-13C glucose had been added to their usual diet to label their endogenous glycogen stores. On the morning of day 3, EGP was measured with 6,6-2H glucose. Their endogenous 13C glycogen enrichment was calculated from 13CO2 and respiratory gas exchanges. Fractional gluconeogenesis was assessed as 1-(13C glucose/13C glycogen)100. EGP was similar in lean subjects (113 +/- 5 mg/min) and in obese subjects (111 +/- 6). Fractional gluconeogenesis was higher in obese (59 +/- 10%) than in lean subjects (29 +/- 8%). However, overall EGP remained constant due to a decrease in glycogenolysis. Since an increased gluconeogenesis and a decreased glycogenolysis may both contribute to increase liver glycogen concentration in obesity, hepatic glycogen concentrations were assessed in hepatic needle biopsies obtained during surgery. Hepatic glycogen concentrations were increased in obese patients (515 +/- 38 mg/g protein) compared to lean subjects (308 +/- 58, p < 0.05). It is concluded that in obese patients: a) fractional gluconeogenesis is increased; b) overall EGP is unchanged due to a proportional inhibition of glycogenolysis; c) liver glycogen concentration is increased.

Adult↗

Psychotropic drug intake in residents newly admitted to nursing homes.

While several surveys have shown that psychotropic drugs are frequently used by nursing home residents, no studies have been performed to investigate whether the rates of drug use increase during the stay in nursing homes or whether residents have taken these drugs already before admission. Therefore, we investigated 262 residents admitted to rural and urban nursing homes in Austria for prevalence of psychotropic drug intake before admission, shortly after admission, and 6 months later. Two weeks after admission, 72.1% of the residents were being treated with psychotropics, while 6 months later 79.0% were receiving these drugs. The significantly higher rates of psychotropic drug use among the psychiatrically ill and in those suffering from sleeping problems suggest that these drugs were prescribed aptly, but residents without appropriate criteria for drug intake were often also treated with psychotropics. During 3 months before admission to nursing homes, 45.5% of the sample reported having taken psychotropics. In more than half of residents without drug intake before admission, psychotropic treatment was initiated within the first 2 weeks after admission, while during the first 6 months after admission the rate of drug use increased only slightly. This suggests that a large percentage of psychotropic intake is due to nursing home orders.

Age Factors↗

An immunohistochemical analysis of the ontogeny, distribution and coexistence of 12 regulatory peptides and serotonin in endocrine cells and nerve fibers of the digestive tract of the turbot, Scophthalmus maximus (Teleostei).

The ontogeny of endocrine cells and nerve fibers containing immunoreactivities for 12 regulatory peptides and serotonin was studied in the digestive tract of a flatfish, the turbot (Scophthalmus maximus), using antisera specific for mammalian and teleostean hormones. Transient insulin-immunoreactive (-IR) endocrine cells were detected from day 5 to day 10 in stomach and intestine I. Somatostatin (SOM)-IR cells appeared at day 8 in the stomach anlage and intestine I. In contrast to the islet cells, they reacted with antisera against mammalian (m) SOM-14 and salmon (s) SOM-25. Infrequent nerve fibers reacting only with anti-mSOM-14 appeared around day 24. Thus, different forms of SOM seem to be present in the gastro-entero-pancreatic system and the enteric nervous system. Neuropeptide Y (NPY)-, salmon pancreatic polypeptide (sPP)- and mPP-immunoreactivities coexisted throughout development. In entero-endocrine cells, NPY/PP-immunoreactivity was first observed at day 8 and around day 24 in enteric nerve fibers. Glucagon (GLUC)-IR entero-endocrine cells appeared at day 5. No coexistence of NPY/PP- and GLUC-immunoreactivities was observed. The first insulin-like growth factor I (IGF-I)-IR cells were identified around day 8. They seemed to contain none of the other peptides. Their number and distribution exhibited great interindividual differences. Vasoactive intestinal polypeptide (VIP)-IR entero-endocrine cells appeared as late as around day 24. The first VIP-IR nerve fibers, however, were identified at day 5. Infrequent neurotensin (NT)-IR cells appeared along the intestine around day 10 and NT-IR nerve fibers at day 17. The first serotonin (SER)-IR cells were observed in the stomach anlage around day 10 and SER-IR nerve fibers at day 15 throughout the gastro-intestinal tract. Gastrin (GAS)/cholecystokinin (CCK)-IR cells appeared around day 11 in stomach and intestine I. The first substance P (SP)-IR enteric nerve fibers were detected around day 8 and SP-IR endocrine cells at day 11. Pancreastatin (PST)-IR cells were identified in the stomach anlage and intestine I around day 8 and contained NT-, GAS/CCK- and SER-immunoreactivities in coexistence. Thus, several developmental phases can be distinguished: (1) at the onset of exogenous feeding only transient INS-IR cells and VIP-IR nerve fibers are present; (2) a differentiated entero-endocrine system establishes during the early phase of exogenous feeding; (3) before the final differentiation of stomach and gut GAS/CCK-IR cell appear; (4) after metamorphosis most of the different types of regulatory peptide-containing nerve fibers develop, probably setting up the fine regulation of gastro-intestinal blood flow and motility.

Animals↗

Perinatal ultrasonography and magnetic resonance imaging findings in congenital hydrocephalus associated with fetal intraventricular hemorrhage.

OBJECTIVE: We present the case histories of three premature infants with congenital posthemorrhagic hydrocephalus. STUDY DESIGN: The timing of the lesion was monitored in utero in two of the three cases. Magnetic resonance imaging studies (prenatal in one case, within 24 hours of birth in all three cases) established the duration of the lesions and thereby added to the ultrasonographic findings. RESULTS: All three patients demonstrated a similar pattern of lesions, consisting of (1) unilateral germinal matrix hemorrhage with cystic resorption, (2) residual blood in the cerebrospinal fluid with a "granular" ependymal reaction, (3) asymmetric ventriculomegaly predominating on the side of the hemorrhage with mild atrophy and periventricular cysts, and (4) partial hypoplasia of the ipsilateral thalamus. On the basis of two cases in which information about the pregnancy was available and in which fetal oligohydramnios without ruptured membranes was detected, we assume that this pattern of lesions may have resulted from a hypoxic-ischemic episode followed by intraventricular hemorrhage. CONCLUSIONS: Because these three infants with congenital hydrocephalus were born during a period of only 18 months in a perinatal center serving a region with 16,000 live births per year, we speculate that a posthemorrhagic cause for congenital hydrocephalus underestimated.

Adult↗

Lymphangioleiomyomatosis: recurrence after single lung transplantation.

Lymphangioleiomyomatosis (LAM) is a rare disease which afflicts young women of childbearing age. Recently, it has been listed as an indication for lung transplantation. We describe a case of recurrent LAM in a 31-year-old woman occurring in the allograft of a male donor after single lung transplantation. Nonisotopic in situ hybridization shows that the smooth muscle cell proliferation is of donor origin.

Adult↗

Differences in angiogenic potential of classically vs alternatively activated macrophages.

Macrophages (M phi) are important for angiogenesis during inflammation, wound repair, and tumor growth. However, well-characterized M phi subsets such as IFN-gamma-induced, classically activated (ca) M phi or IL-4/glucocorticoid-induced, alternatively activated (aa) M phi have not been thoroughly examined for a positive or negative association with angiogenesis. While caM phi populate early inflammatory reactions and high-turnover granulomas, aaM phi occur in healing wounds and chronic inflammation. In contrast to caM phi-dominated lesions, aaM phi-rich lesions are highly vascularized. In order to determine their angiogenic potential in vitro, these M phi subsets as well as unstimulated control macrophages (coM phi) were analyzed by RT-PCR for mRNA expression of 10 angiogenic factors after 3 and 6 days of culture. Early during activation, caM phi and coM phi expressed equal levels of 8 of 10 angiogenic factors (PDGF-A, MK, TNF-alpha, TGF-beta 1, PDGF-B, HGF, TGF-alpha, IGF-1), while aaM phi showed expression of only 4 of these factors (TGF-beta 1, PDGF-B, HGF, GF-1). After maturation, TGF-alpha and IGF-1 showed a shift in mRNA expression from caM phi to aaM phi resulting in a considerably enhanced expression of these factors in day-6 aaM phi as compared to day-6 caM phi and coM phi while PDGF-A, MK, and TNF-alpha remained suppressed in day 6 aaM phi. In all M phi subsets including controls, mRNA expression of aFGF and bFGF was minimal or absent while TGFG-beta 1, HGF, and ODGF-B were constitutively expressed. In order to functionally integrate angiogenic factor mRNA expression profiles, mitogenic activity of M phi subsets towards microvascular endothelium was assessed by cocultivation. Coculture experiments revealed that endothelial proliferation induced by aaM phi was 3.0-3.5x higher than induced by caM phi. In conclusion, mature aaM phi are well equipped to play an important role in protracted M phi-associated angiogenic processes. Presumably due to expression of predominantly angio-inhibitory cytokines such as TNF-alpha by caM phi but much less by aaM phi, caM phi exhibit only a low angiogenic potential in vitro and in vivo despite considerable expression of angiogenic factor mRNA.

Angiogenesis Inducing Agents↗

Two Encephalitozoon cuniculi strains of human origin are infectious to rabbits.

The microsporidian Encephalitozoon cuniculi can infect a wide variety of mammals including man. In this study, E. cuniculi isolates of animal origin were compared with 6 isolates obtained from HIV-infected patients. Based on results of Western blot analysis, random amplified polymorphic DNA (RAPD) and the sequence of the rDNA internal transcribed spacer (ITS) the isolates were classified into 3 groups with the repeated element 5'GTTT-3' in the ITS being a reliable genetic marker. Five isolates from Swiss patients were found to be homologous to isolates from Swiss rabbits (strain I). The sixth isolate from a patient from Mexico differed by all methods and could be attributed to E. cuniculi strain III that has been described from 2 dogs from the USA. All of these isolates were distinguished from isolates from blue foxes from Norway (strain II). Intraspecific nucleotide divergence of the SSU rRNA gene of E. cuniculi belonging to the 3 strains was in the same low range (0.00-0.15%) as was found for the corresponding sequence of 2 E. hellem isolates. Groups of 2 rabbits were infected by oral inoculation of 10(7) E. cuniculi spores (2 isolates from strain I of human and rabbit origin, 1 from strain III) as shown by antibody responses and the re-isolation of the parasites from brain material. The results provide further evidence that per oral transmission of the parasite between various hosts is feasible.

Animals↗

Effect of chronic intracerebroventricular infusion of insulin on brown adipose tissue activity in fed and fasted rats.

OBJECTIVES: Carbohydrate feeding stimulates, and fasting decreases the sympathetic nervous system activity and brown adipose tissue (BAT) thermogenesis. This study was performed to assess the hypothesis that these effects were secondary to changes in insulin concentrations in the central nervous system. METHODS: BAT sympathetic activity was assessed by comparing 3H-GDP binding to isolated mitochondria of innervated and denervated interscapular BAT of three groups of 10 week old male Wistar rats: food-restricted, 48 h fasted or ad libitum fed. During the three days preceding this measurement, animals received a continuous intracerebroventricular (ivc) infusion of insulin (0.48 U/d) or vehicle. RESULTS: In food-restricted rats, 3H-GDP binding to mitochondria of innervated BAT was 41% higher than that to denervated BAT. Icv insulin did not stimulate 3H-GDP binding in innervated BAT. In 48 h fasted rats, 3H-GDP binding to mitochondria of innervated BAT was reduced by 30-50%, while the activity of denervated BAT was minimally affected. Icv insulin did not prevent this fasting-induced drop in BAT. In rats fed ad libitum, icv insulin decreased food intake by 17% (P < 0.05) and increased 3H-GDP binding to innervated BAT by 27% (P < 0.05). CONCLUSION: Intracerebroventricular insulin stimulates BAT activity in rats fed ad libitum but not in food-restricted or fasted rats. This demonstrates that the decrease in BAT activity observed during fasting is unlikely to be due to a decrease in insulin concentration in the nervous system.

Adipose Tissue, Brown↗

Distribution of pulmonary ventilation and perfusion measured simultaneously in awake goats.

Gravity has been regarded as the major determinant for local pulmonary perfusion and ventilation. Recent reports, describing major gravity independent heterogeneity in both variables, have questioned the importance of gravity. We asked to what extent ventilation and perfusion were related, and if they showed similar distributions along the vertical axis in the lung. We gave 99mTc-aerosols as tracers for ventilation and radioactive microspheres as blood flow tracers in five awake goats over 4 min. Ventilation and perfusion were determined in approximately 1.5 cm3 pieces of the lung. For both variables the vertical distribution could vary considerably from lung to lung, but within each lung the two distributions were similar. Both ventilation and perfusion were heterogeneously distributed (CV approximately 40% for both), they were highly correlated (r = 0.81) and the average 25-75-interpercentile interval for ventilation to perfusion ratio (0.84-1.13) was significantly less wide than for both ventilation (0.76-1.38) and perfusion (0.76-1.40). Some pieces were considerably overventilated while a few were correspondingly underventilated. This could indicate that perfusion is adjusted to ventilation in normoxic lungs with a low sensitivity to overventilation.

Animals↗