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Biomedical subjects

S Martin

Publications and source records attributed to S Martin.

At least 37 records · Page 2Linked to original sources

Liver transplantation for cirrhosis in cystic fibrosis.

BACKGROUND: Liver disease is the third most common cause of death in children with cystic fibrosis (CF). Liver transplantation is an effective treatment in children with hepatic failure. AIMS: The objective of the present study was to review the indications and postoperative course of hepatic transplantation in a cystic fibrosis population. PATIENTS: Five children with CF, at a mean age of 16.5 years, underwent liver transplantation. RESULTS: All patients showed cirrhosis, portal hypertension and hepatic failure. The main postoperative complication was ascites refractory to treatment in two patients. No significant deterioration of the pulmonary function was noted. Two patients died, one of Hodgkin lymphoma and the other of progressive pulmonary failure. CONCLUSION: Liver transplantation was indicated in children with CF when hepatic failure and/or severe portal hypertension was present with well-preserved pulmonary function.

Cystic Fibrosis↗

Self-monitoring of blood glucose in type 2 diabetes and long-term outcome: an epidemiological cohort study.

AIMS/HYPOTHESIS: The aim of this study was to obtain epidemiological data on self-monitoring of blood glucose (SMBG) in type 2 diabetes and to investigate the relationship of SMBG with disease-related morbidity and mortality. METHODS: The German multicentre Retrolective Study 'Self-monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes' (ROSSO) followed 3,268 patients from diagnosis of type 2 diabetes between 1995 and 1999 until the end of 2003. Endpoints were diabetes-related morbidity (non-fatal myocardial infarction, stroke, foot amputation, blindness or haemodialysis) and all-cause mortality. SMBG was defined as self-measurement of blood glucose for at least 1 year. RESULTS: During a mean follow-up period of 6.5 years, 1,479 patients (45.3%) began SMBG prior to an endpoint and an additional 64 patients started SMBG after a non-fatal endpoint. Interestingly, many patients used SMBG while being treated with diet or oral hypoglycaemic drugs (808 of 2,515, 32%). At baseline, the SMBG cohort had higher mean fasting blood glucose levels than the non-SMBG cohort (p<0.001), suggesting that insufficient metabolic control was one reason for initiating SMBG. This was associated with a higher rate of microvascular endpoints. However, the total rate of non-fatal events, micro- and macrovascular, was lower in the SMBG group than in the non-SMBG group (7.2 vs 10.4%, p=0.002). A similar difference was found for the rate of fatal events (2.7 vs 4.6%, p=0.004). Cox regression analysis identified SMBG as an independent predictor of morbidity and mortality, with adjusted hazard ratios of 0.68 (95% CI 0.51-0.91, p=0.009) and 0.49 (95% CI 0.31-0.78, p=0.003), respectively. A better outcome for both endpoints was also observed in the SMBG cohort when only those patients who were not receiving insulin were analysed. CONCLUSIONS/INTERPRETATION: SMBG was associated with decreased diabetes-related morbidity and all-cause mortality in type 2 diabetes, and this association remained in a subgroup of patients who were not receiving insulin therapy. SMBG may be associated with a healthier lifestyle and/or better disease management.

Aged↗

Ovine infection with the agents of scrapie (CH1641 isolate) and bovine spongiform encephalopathy: immunochemical similarities can be resolved by immunohistochemistry.

Immunochemical ("rapid") tests, which recognize a partly protease-resistant conformer of the prion protein (PrP(res)) are now widely used in Europe for the diagnosis of transmissible spongiform encephalopathies (TSEs). Some of these tests can be used to distinguish natural scrapie from experimental bovine spongiform encephalopathy (BSE) in sheep, on the basis of migration pattern differences of PrP(res) in Western immunoblots. However, PrP(res) from sheep inoculated with CH1641 scrapie gives an immunoblot profile similar to that of sheep inoculated with BSE. Therefore, field scrapie strains similar to CH1641 might be misclassified as ovine BSE in the rapid tests currently employed. This study confirmed that the Western blot similarities (size of the unglycosylated band and distinct reactivity with 6H4 and P4 antibodies) between CH1641 and BSE remained consistent regardless of the PrP genotype of the sheep, but the two infections resulted in accumulation of disease-associated PrP (PrP(d)) that could easily be distinguished by the immunohistochemical "peptide mapping" method. This method, which reveals conformational differences of PrP(d) by the use of a panel of antibodies, indicated that PrP(d) from the CH1641 isolate was truncated further upstream in the N terminus than was PrP(d) from other ovine TSEs, including experimental BSE. In addition, the immunohistochemical "PrP(d) profile method", which defines the phenotype of PrP(d) accumulation in the brain of affected sheep, showed that CH1641 infection leads to much more intra-neuronal and considerably less extracellular PrP(d) than does experimental BSE. The overall results demonstrate that a combined Western blotting and immunohistochemical approach is required to discriminate between different TSE strains in sheep.

Amino Acid Sequence↗

Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of G(z).

RATIONALE: G(z) is a member of the G(i) G protein family associated with dopamine D2-like receptors; however, its functions remain relatively unknown. The aim of the present study was to investigate prepulse inhibition (PPI) of acoustic startle, locomotor hyperactivity and dopamine D2 receptor binding in mice deficient in the alpha subunit of G(z). METHODS: We used automated startle boxes to assess startle and PPI after treatment with saline, amphetamine, apomorphine or MK-801. We used photocell cages to quantitate locomotor activity after amphetamine treatment. Dopamine D2 receptor density was determined by autoradiography. RESULTS: Startle responses and baseline PPI were not different between the Galpha(z) knockout mice and wild-type controls (average PPI 46+/-4 vs 49+/-3%, respectively). Amphetamine treatment caused a marked disruption of PPI in Galpha(z) knockouts (average PPI 22+/-2%), but less so in controls (average PPI 42+/-3%). Similar genotype-dependent responses were seen after apomorphine treatment (average PPI 23+/-3% vs 40+/-3%), but not after MK-801 treatment (average PPI 29+/-5 vs 33+/-2%). Amphetamine-induced locomotor hyperactivity was greater in Galpha(z) knockouts than in controls. There was no difference in the density of dopamine D2 receptors in nucleus accumbens. CONCLUSIONS: Mice deficient in the alpha subunit of G(z) show enhanced sensitivity to the disruption of PPI and locomotor hyperactivity caused by dopaminergic stimulation. These results suggest a possible role for G(z) in neuropsychiatric illnesses with presumed dopaminergic hyperactivity, such as schizophrenia.

Amphetamine↗

Innervation zone shift with changes in joint angle in the brachial biceps.

Empirical evidence is presented suggesting that the innervation zone of the brachial biceps shifts relative to recording electrodes with changes in joint angle. Myoelectric signal data were acquired from five subjects using a 16-channel linear electrode array, and analyzed to determine a reversal in signal propagation direction indicating innervation zone location. An analysis of the effect of joint angle changes on innervation zone location yielded statistically significant results (ANOVA, alpha = 0.05, p < 0.001) suggesting that the innervation zone moves between 5 and 30 mm in a direction distal to the shoulder as the arm is extended, statistically independent of force level (ANOVA, alpha = 0.05, p > 0.2).

Adult↗

[Assessment of the tetanus immune status in plasma donors of the Blood Donor Service of the Bavarian Red Cross].

BACKGROUND AND OBJECTIVE: Tetanus is nowadays largely under control, as a result of the preventive immunization programme. This prophylactic measure is important also because there is no specific treatment. In Germany tetanus occurs almost exclusively in elderly, not adequately immunized persons. This study determined the existing immune status of plasma donors in the region of Ingolstadt, Bavaria. SUBJECTS AND METHODS: Tetanus IgG antibody concentrations were measured with the ELISA test in serum of 1742 plasma donors (891 women, 851 men, age range 18-64 years). RESULTS: An adequately protective immunity against tetanus was found in 98.7% of men and 94.1% of women, while 5 women and 3 men had no protection. Demographic data indicated that the immunization protected males longer than females, regardless of age, especially in those over 50 years of age (85% of females, 99% of males). CONCLUSION: Adequate tetanus protection was achieved in the overwhelming majority of test subjects. This demonstrates that the prevalence of protection is lower in females than in males, a difference most marked in those over 50 years of age. It is important that this age group in particular should, as part of health care, be informed by their medical practitioner of the dangers of tetanus and the advantages of immunization.

Adolescent↗

Effective treatment of symptomatic diabetic polyneuropathy by high-frequency external muscle stimulation.

AIMS/HYPOTHESIS: Diabetic distal symmetrical sensory polyneuropathy (DSP) affects 20-30% of diabetic patients. Transcutaneous electrical nerve stimulation (TENS) and electrical spinal cord stimulation have been proposed as physical therapies. We performed a controlled, randomised pilot trial to compare the effects of high-frequency external muscle stimulation (HF) with those of TENS in patients with symptomatic DSP. METHODS: Patients with type 2 diabetes and DSP (n=41) were randomised to receive treatment with TENS or HF using strata for non-painful (n=20) and painful sensory symptoms (n=21). Both lower extremities were treated for 30 min daily for three consecutive days. The patients' degree of symptoms and pain were graded daily on a scale of one to ten, before, during and 2 days after treatment termination. Responders were defined by the alleviation of one or more symptoms by at least three points. RESULTS: The two treatment groups were similar in terms of baseline characteristics, such as age, duration of diabetes, neurological symptoms scores and neurological disability scores. The responder rate was significantly higher (p<0.05) in the HF group (80%, 16 out of 20) than in the TENS group (33%, seven out of 21). Subgroup analysis revealed that HF was more effective than TENS in relieving the symptoms of non-painful neuropathy (HF: 100%, seven out of seven; TENS: 44%, four out of nine; p<0.05) and painful neuropathy (HF: 69%, nine out of 13; TENS: 25%, three out of 12; p<0.05). The responders did not differ in terms of the reduction in mean symptom intensity during the trial. CONCLUSIONS/INTERPRETATION: This pilot study shows, for the first time, that HF can ameliorate the discomfort and pain associated with DSP, and suggests that HF is more effective than TENS. External muscle stimulation offers a new therapeutic option for DSP.

Adult↗

Crystallization kinetics of polydisperse colloidal hard spheres. II. Binary mixtures.

In this paper we present measurements of the crystallization kinetics of binary mixtures of two different sized hard sphere particles. The growth of the Bragg reflections over time were analyzed to yield the crystallite scattering vector, the total amount of crystal, and the average linear crystal size. It was observed that a particle size distribution skewed to higher sized particles has a less detrimental effect on the crystal structure than a skew to smaller sized particles. In the latter case we observe that initial crystallite growth occurs at only a small number of sites, with further crystallization sites developing at later times. Based on these measurements we elaborate further on the previously proposed growth mechanism whereby crystallization occurs in conjunction with a local fractionation process in the fluid, which significantly affects the kinetic growth of crystallites in polydisperse systems.

Journal Article↗

[Malaria in the emergency room. Results of the emergency treatment of 137 patients with symptomatic malaria].

OBJECTIVE: To assess characteristics and outcome of emergency patients with acute malaria. PATIENTS AND METHODS: We retrospectively assessed the clinical and laboratory parameters of 137 consecutive patients (87 males, 50 females; median age 37 years, range 17 - 67 years) presenting with acute malaria to our tertiary care center between 1992 and 2002. RESULTS: Falciparum malaria was diagnosed in 116/137 and tertian malaria in 19/137 patients; a single patient was infected with both parasites while in another case the type of parasite remained unclear. Infections were acquired in Africa (121), Asia , and in the Americas . One traveler visited multiple continents. Only 36 % (50/137) of patients had used malaria chemoprophylaxis. 128/137 patients were treated as in-patients; 22 of these had to be treated on an intensive care unit. According to the criteria of the German Society of Tropical Medicine, 44/137 (32 %; 95 % confidence interval (CI): 25 - 40 %) patients suffered from complicated malaria. The overall mortality rate was 2/137 (1.5 %; 95 % CI: 0,4 - 5.2 %); the mortality rate of complicated malaria tropica was 2/44 (4,5 %; 95 % CI 1,3 - 15 %). Patients with complicated malaria were significantly older than those with uncomplicated malaria. Median length of hospital stay was 4 days in uncomplicated and 9 days in complicated cases. Based on costs of EUR 2500 per case, an attack rate of > 3 % in East African travelers and a cost of EUR 55 for a chemoprophylaxis with mefloquine, chemoprophylaxis is cost-effective. CONCLUSION: In our retrospective analysis, complicated malaria tropica was associated with older age. Although malaria causes considerable morbidity, the overall mortality from severe malaria is low. Reinforcement of chemoprophylaxis especially in travelers to Africa could reduce malaria cases and is cost-effective.

Adolescent↗

Inflammation and type 2 diabetes: results from KORA Augsburg.

Type 2 diabetes is associated with a systemic low-grade inflammation. First data provided by cross-sectional studies from as early as the 1960s demonstrated elevated systemic levels of glycoproteins and acute-phase reactants and increased leukocyte counts in type 2 diabetes patients. Subsequently, prospective studies showed that elevated concentrations of several acute-phase proteins and cytokines are predictive of later type 2 diabetes. Immune gene variants in man and in animal models were found to affect insulin resistance and diabetes incidence. Antidiabetic treatment by medication, diet or physical activity results in a significant decrease of systemic immune mediator concentrations. Immunological analyses of the KORA Survey S4 (1999/2001) allowed us to show that levels of circulating acute-phase proteins like CRP and of IL-6 are highly correlated and associated not only with overt type 2 diabetes, but already with impaired glucose tolerance (IGT) pointing out a role of these mediators in the pathogenesis of type 2 diabetes. On the contrary, TNFalpha was neither coregulated with CRP nor associated with diabetes status. Our study therefore shows that type 2 diabetes is accompanied by a non-random and differential upregulation of components of the innate immunity and suggests that this inflammatory condition is involved in the aetiology of the disease. Future work will extend the range of analysed immune mediators to chemokines and will also investigate the association of immune markers with indices of obesity to elucidate the relevance of this traditional risk factor for low-grade inflammation.

Acute-Phase Proteins↗

Genetics of type 2 diabetes: impact of interleukin-6 gene variants.

The KORA studies serve as a powerful tool for the genetic analysis of complex diseases like type 2 diabetes or the metabolic syndrome. These studies include more than 2,000 prevalent and incident type 2 diabetes cases. DNA of these patients is available to be used in genetic studies. Up to now the analyses have focussed on genes coding for proteins being involved in the inflammatory response. Interleukin-6 (IL-6) as the key mediator of the acute phase reaction is of interest. Elevated protein concentrations of IL-6 in the blood have been shown to predict type 2 diabetes. We investigated the association of the IL-6 single nucleotide polymorphism (SNP) C-174G with type 2 diabetes in a case-control study of 704 elderly participants of the KORA Survey S4 (1999/2001). When BMI, HDL cholesterol, physical activity, hypertension, hormone replacement therapy and smoking were considered as covariables the SNP C-174G showed a trend for association with type 2 diabetes (- 174G: OR 1.20, 95 % CI 0.90 - 1.59, p = 0.21).

Adult↗

Procalcitonin and C-reactive protein levels in HIV-positive subjects with tuberculosis and pneumonia.

Pulmonary tuberculosis (PTB) and pneumococcal community-acquired pneumonia (PCAP) are common causes of lower respiratory tract infections in HIV-seropositive patients and may have similar clinical and radiological features. This study aimed to assess the value of serum procalcitonin (PCT) and C-reactive protein (CRP) levels in HIV-seropositive patients with pneumonia, and to investigate their potential role in differentiating pneumococcal from mycobacterial infections. HIV-seropositive patients admitted with pneumonia were evaluated prospectively, 34 with PTB and 33 with PCAP. All 33 patients in the PCAP group and 20 of 34 patients in the PTB group had elevated PCT levels (>0.1 ng x mL(-1)). All patients in both groups had elevated CRP levels (>10 mg x L(-1)). The PTB group had significantly lower CD4 T-lymphocyte counts, lower CRP levels, lower white cell counts, and lower PCT levels than the PCAP group. Receiver operating characteristic analysis showed that optimal discrimination between PTB and PCAP could be performed at a cut-off point of 3 ng x mL(-1) for PCT (sensitivity 81.8%; specificity 82.35%) and 246 mg x L(-1) for CRP (sensitivity 78.8%; specificity 82.3%). In conclusion, HIV-seropositive patients with pneumococcal community-acquired pneumonia had significantly higher procalcitonin and C-reactive protein levels than those with pulmonary tuberculosis. A procalcitonin level >3 ng x mL(-1) and a C-reactive protein level >246 mg x L(-1) were both highly predictive of pneumococcal infection.

Adult↗

The degree of serological sensitization to cat allergen in patients with or without cat at home.

BACKGROUND: The relationship between exposure to cat/dog in domestic environments and development of allergic sensitization to pet allergens is still controversial. OBJECTIVE: To test the role of indirect exposure to cat, we aimed to evaluate the amounts of cat specific IgE in sensitized subjects with or without cat at home. METHODS: Three hundred six adult patients with a previous diagnosis of allergic sensitization to cat allergens (by skin prick test) were enrolled for this study. Among 306 men and women sensitized to cat (and other allergens), 150 owned a cat for at least 10 years ( direct exposure) and 156 had never owned this animal (indirect exposure). An internal questionnaire specifically designed for the study was completed by the same allergists during the screening consultation: the results of skin prick tests, personal and clinical data, periods of symptoms and characteristics of cat ownership were carefully recorded. Specific IgE to cat extract was determined by the Pharmacia CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) and Immulite 2000 (Diagnostic Products Corporation, Los Angeles, USA) RESULTS: Although specific IgE to cat allergen were significantly higher in patients with cat at home (F = 42.77; p < 0.001), high amounts of these antibodies were found also in sera of subjects indirectly exposed to cats. DISCUSSION: The results of our study demonstrate that the degree of serological sensitization to cat allergens may be relevant also in subjects without any direct contact with cats (indirect exposure).

Air Pollution, Indoor↗

Detection of differentially expressed genes in synovial fibroblasts by restriction fragment differential display.

OBJECTIVE: To identify differentially expressed genes in synovial fibroblasts and examine the effect on gene expression of exposure to TNF-alpha and IL-1beta. METHODS: Restriction fragment differential display was used to isolate genes using degenerate primers complementary to the lysophosphatidic acid acyl transferase gene family. Differential gene expression was confirmed by reverse transcription-polymerase chain reaction and immunohistochemistry using a variety of synovial fibroblasts, including cells from patients with osteoarthritis and self-limiting parvovirus arthritis. RESULTS: Irrespective of disease process, synovial fibroblasts constitutively produced higher levels of IL-6 and monocyte chemoattractant protein 1 (MCP-1) (CCL2) than skin fibroblasts. Seven genes were differentially expressed in synovial fibroblasts compared with skin fibroblasts. Of these genes, four [tissue factor pathway inhibitor 2 (TFPI2), growth regulatory oncogene beta (GRObeta), manganese superoxide dismutase (MnSOD) and granulocyte chemotactic protein 2 (GCP-2)] were all found to be constitutively overexpressed in synoviocytes derived from patients with osteoarthritis. These four genes were only weakly expressed in other synovial fibroblasts (rheumatoid and self-limiting parvovirus infection). However, expression in all types of fibroblasts was increased after stimulation with TNF-alpha and IL-1beta. Three other genes (aggrecan, biglycan and caldesmon) were expressed at higher levels in all types of synovial fibroblasts compared with skin fibroblasts even after stimulation with TNF-alpha and IL-1. CONCLUSIONS: Seven genes have been identified with differential expression patterns in terms of disease process (osteoarthritis vs rheumatoid arthritis), state of activation (resting vs cytokine activation) and anatomical location (synovium vs skin). Four of these genes, TFPI2, GRObeta (CXCL2), MnSOD and GCP-2 (CXCL6), were selectively overexpressed in osteoarthritis fibroblasts rather than rheumatoid fibroblasts. While these differences may represent differential behaviour of synovial fibroblasts in in vitro culture, these observations suggest that TFPI2, GRObeta (CXCL2), MnSOD and GCP-2 (CXCL6) may represent new targets for treatments specifically tailored to osteoarthritis.

Adult↗