[Muscle pain in myositis in a young female patient: what is behind this?] / Muskelschmerzen bei Myositis bei einer jungen Patientin ­ was steckt dahinter?

Myositis is a connective tissue disease which is most frequently diagnosed in women aged 40-60 years. Due to a clear association with underlying malignant diseases, general tumor screening is recommended whenever it is diagnosed. Colorectal carcinoma (CRC) is a common malignant disease, and the typical at-risk group comprised, to date, patients older than 55 years. However, with the rising incidence of so-called early-onset colorectal carcinoma (EO-CRC), an increasingly important patient population is emerging in the 20- to 50-year age range. One reason for the rising incidence is suggested to be an increase in classic risk factors at younger ages. Here, the case of a 34-year-old female patient who presented with the leading paraneoplastic syndrome of myositis and was diagnosed with a sporadic form of CRC is reported. Monitoring of known risk factors as early on as in young adulthood and greater attention in the presence of symptoms such as gastrointestinal hemorrhage or paraneoplastic syndromes seem necessary to compensate for the time delay in diagnosis that currently still exists and the associated worse oncologic outcome.

Kinematic analysis of scapular movements in patients with facioscapulohumeral muscular dystrophy.

The purpose of this study is to evaluate scapular movements by the three-dimensional electromagnetic system during shoulder elevation in FSHMD patients, and to compare the results with healthy individuals. 10 patients with FSHMD and 10 healthy individuals were included in the study. Scapular anterior-posterior tilt, upward-downward rotation and internal-external rotation at 30°, 60° and 90° were evaluated using the three-dimensional electromagnetic system during the elevation of the upper limbs in the scapular plane. Humerothoracic elevation levels on the dominant and non-dominant sides were found to be lower in the patients than healthy individuals (p < .001). Both scapula were rotated downwards at 30° (dominant/non-dominant p < .001) and 60° (dominant p = .009, non-dominant p = .04) of humerothoracic elevation, the scapula was rotated internally at 30° of humerothoracic elevation on the non-dominant side (p = .03), and the scapula was tilted posteriorly at 90° of humerothoracic elevation on the non-dominant side (p = .009) in patients. These existing abnormal patterns of the scapula in the patients increase the risk of impairment, pain, impingement and instability especially in the activities that require arm elevation. It is thought that physiotherapy approaches should first be emphasized to improve scapular stabilization and strengthening exercises should then be performed for the shoulder girdle muscles.

Impedance ratio: a novel marker and a powerful predictor of mortality in hemodialysis patients.

PURPOSE: Impedance ratio (Imp-R) obtained by multifrequency bioimpedance analysis (BIA) has been shown to be associated with volume and nutrition status. In this prospective study, the predictive role of Imp-R for mortality in hemodialysis (HD) patients was investigated. METHODS: Multifrequency (5-50-100-200 kHz) BIA was applied to 493 prevalent HD patients in March-April 2006. Imp-R was defined as the ratio of 200-5 kHz impedance values. Demographical, clinical and laboratory data at the time of the analysis were recorded. All-cause and cardiovascular (CV) mortality were assessed during 3 years of follow-up. RESULTS: Mean age was 57.7 ± 13.9 years, HD duration 52.1 ± 42.6 months and prevalence of diabetes 21.7 %. Imp-R was negatively correlated with nutritional markers including albumin, creatinine and hemoglobin levels. In addition, there was a positive correlation between Imp-R and age, ratio of extracellular water to total body water and high-sensitive C-reactive protein. Over a mean follow-up period of 27.9 ± 11.1 months, 93 deaths (52 from CV reasons) were observed. In the multivariate analysis, Imp-R was significantly associated with all-cause and CV mortality after adjustments [HR 1.13, 95 % CI (1.04-1.23); p = 0.004 and HR 1.15, 95 % CI (1.03-1.27); p = 0.01, respectively]. The risk of all-cause mortality was 3.4 times higher in the fourth quartile of Imp-R (>83.5 %) compared to the first Imp-R quartile (<78.8 %) as reference. Cutoff value of Imp-R for all-cause mortality was 82.0 % with a sensitivity of 65.5 % and specificity of 64 %. CONCLUSION: Impedance ratio measured by multifrequency in standardized conditions BIA is an independent and powerful predictor of both all-cause and CV mortality in hemodialysis patients.

Incidence and importance of c4d deposition in renal allograft dysfunction.

Recent studies showed that peritubular capillary deposition of C4d is a marker of humoral immune responses directed against a renal allograft. The aim of this retrospective study was to investigate the incidence, clinical features, and prognostic implications of C4d deposition in renal allograft biopsy specimens. The biopsies had been performed due to acute graft dysfunction. This study of 104 renal allograft biopsies performed in 2004 classified histopathological findings according to Banff criteria. All paraffin-embedded biopsy samples were stained with an immunohistochemical method for C4d deposition. Demographic data, clinical findings, and biochemical findings were obtained from patients' charts. C4d staining was positive in 15/104 (14%) samples. The staining pattern was diffuse in 8 and focal in 7 patients. Nine patients were males. The overall mean age was 33 +/- 6 years. Ten received live-donor grafts. The biopsy occurred at a mean of 1007 +/- 1415 (range, 15-4712) days after the operation with a mean serum creatinine (SCr) level of 2.8 +/- 1.5 (1.25-6.0) mg/dL. Patients were divided into 2 groups according to the occurrence time: early (before 100 days) and late (after 100 days). Among the early group (n = 5), the mean SCr level was 2.8 +/- 1.5 mg/dL; a diffuse staining pattern was seen in 4 (80%) patients. Histological findings were acute rejection in 3, borderline changes in 1, or thrombotic microangiopathy in 1 patient. Two patients were treated with pulse steroids and 3 with ATG, intravenous immunoglobulin, and plasmapheresis. Three patients lost their grafts at the mean of 118 +/- 100 days after the biopsy. In the late group (n = 10), the mean SCr level was 2.8 +/- 1.7 mg/dL with a diffuse staining pattern in 4 (40%) patients. The histological findings included acute rejection in 6, chronic vascular rejection in 2, thrombotic microangiopathy in 1, and chronic allograft nephropathy in 1 patient. Six patients were treated with pulse steroids, and 3 with ATG and intravenous immunoglobulin. Five patients lost their grafts at a mean of 200 +/- 270 days. The overall incidence of C4d deposition was 14%; it was seen both in the early and late posttransplantation period. Although a diffuse staining pattern was more frequently seen in the early period, C4d deposition indicated a poor allograft prognosis in both periods. Introduction of C4d staining into the routine may guide more specific treatments directed toward the humoral alloresponse.

Microcirculatory recruitment maneuvers correct tissue CO2 abnormalities in sepsis.

The rises in tissue partial pressure of carbon dioxide have been observed in critically ill patients with shock and sepsis for a long time and have been proposed to be an earlier and more reliable marker of tissue hypoxia than traditional markers. However, the mechanisms leading to those increases, especially in sepsis and endotoxemia, are not well understood. Recent studies provided further data, supporting the idea that the origin of those increases in partial pressure of CO2 in sepsis as being caused by microcirculatory perfusion deficit resulting in mitochondrial depression by time. Previously, we have termed this condition where despite correction of systemic oxygen delivery variables, regional hypoxia and oxygen extraction deficit persist as microcirculatory and mitochondrial distress syndrome (MMDS). Recent findings support the idea that the progression from early to severe sepsis is accompanied or possibly even caused by microcirculatory dysfunction, which leads to mitochondrial dysfunction by time. Therefore early identification of microcirculatory dysfunction and correction with microcirculatory recruitment maneuvers are needed to ensure adequate microcirculatory perfusion and tissue oxygenation. Microcirculatory imaging, such as SDF imaging technique, appears to be a very useful tool for this task and its combination together with other systemic and regional tissue oxygenation measurements may provide more information regarding the tissue oxygenation and will be a very promising tool for microcirculatory researchers and the management of critically ill patients at the bedside.

The effects of alpha-lipoic acid on nitric oxide synthetase dispersion in penile function in streptozotocin-induced diabetic rats.

Diabetes-induced erectile dysfunction is one of the most prevalent complications of diabetes in males. alpha-Lipoic acid (ALA) and its reduced form, dihydrolipoic acid, are powerful antioxidants. Data strongly suggest that, because of its antioxidant properties, ALA is particularly suited to the prevention and/or treatment of diabetic complications that arise from overproduction of reactive oxygen and nitrogen. The aim of this study was to investigate the localization of nitric oxide synthetase (NOS) in normal and diabetic rat cavernous smooth muscles and to examine the effects of ALA on them. Rats were divided into four groups: control, diabetic, diabetic plus ALA, and ALA only. Penile tissues were taken 15 days after drug application and examined histochemically and immunohistochemically. Comparison of the control and diabetic groups revealed that the axons of nerve cells were not identified with Masson trichrome in the diabetic group, whereas in the control group NOS localization and immunostaining (endothelial NOS [eNOS]) were normal. Diabetic rats administered ALA showed improvement in Masson trichrome, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and eNOS localization compared with untreated diabetic rats. Although there was no difference between the control group and the group administered ALA only, we observed an increase in NADPH-d and eNOS. In erection, eNOS and neuronal NOS (nNOS) may have a significant role. In pathologic conditions, erectile dysfunction may occur as a result of an increase in inducible macrophage-type NOS (iNOS). ALA plays an important role in treatment of erectile dysfunction by decreasing iNOS and increasing other isoforms of NOS.

Smokeless tobacco extracts modulate exogenous gene expression in early passage cultured human oral epithelial cells: an in vitro system to study chemical and viral enhancer/promoter interaction.

The increased risk for cancers of the oral cavity from smokeless tobacco use may reflect the interaction of tobacco with genetic factors, such as oncogenes, and other exogenous factors, such as viruses. An in vitro system was developed based on expression of the chloramphenicol acetyltransferase (CAT) reporter gene to study interactions of chemical treatments with viral enhancer/promoters in early passage cell cultures of oral cavity-derived epithelial cells. Expression of CAT in transfected cells was significantly greater with CAT under the control of the cytomegalovirus immediate early enhancer/promoter (pCEP4/CAT) compared to the Rous sarcoma virus long terminal repeat enhancer/promoter (pRSV-cat) and the simian virus 40 (SV40) early promoter (pSV2-cat). No CAT expression was detected using corresponding control plasmids without the CAT reporter gene. Using this system, smokeless tobacco extracts prepared from either dry snuff or moist snuff delayed maximum CAT expression from Day 4 to Day 5, with sustained, significantly increased CAT expression at 12 days compared to the declining CAT expression observed in untreated control cells. Smokeless tobacco extracts can modulate intracellular gene expression. This system provides an in vitro model to test specificity of toxic agents on enhancer/promoter activity and the interaction on exogenous gene expression.

Alterations in nitric oxide activity and sensitivity in early streptozotocin-induced diabetes depend on arteriolar size.

Changes in NO activity may play an important role in the early increase in microvascular flow that has been implicated in the pathogenesis of diabetic microangiopathy. We assessed, in the in situ spinotrapezius muscle preparation of 6 weeks' streptozotocin-diabetic rats (n = 6) and of age-matched controls (n = 8), basal inside diameters of A2-A4 arterioles and the reactivity to topically applied acetylcholine and nitroprusside, before and after N(G)-nitro-L-arginine. In diabetic rats, cholinergic vasodilatation in A2-A4 arterioles was intact. Basal diameter in A3 and A4 arterioles was significantly higher in streptozotocin-diabetic rats. The increased basal diameter in A3 arterioles was partially due to an increased contribution of NO to basal diameter. The response to nitroprusside was impaired in streptozotocin-diabetic rats in A2, but not in A3 and A4 arterioles. Thus, this study shows that NO activity and sensitivity are altered after 6 weeks of streptozotocin-induced diabetes. These streptozotocin-induced changes are anatomically specific and, for arterioles, depend on their position within the vascular tree.

Decreased glutathione levels in acute myocardial infarction.

Although experimental studies have demonstrated that reduced glutathione (GSH) is involved in cellular protection from deleterious effects of oxygen free radicals (OFRs) in ischemia and reperfusion, there are controversial data on the correlation between the levels of erythrocyte GSH and the ischemic process. To clarify, we determined the erythrocyte GSH levels in 21 patients with acute myocardial infarction (AMI), aged 39-70, who were not given thrombolytic therapy and 21 age- and sex- matched healthy controls. Samples of blood were taken on days 1, 3, 5 and 7 from AMI patients and on the same days from the controls. The GSH levels of patients with AMI were significantly depressed by 11.5% as compared to the controls on the second day after infarction (7.44 +/- 1.71 vs 8.41 +/- 1.54 U/gHb p < 0.05). Although the total mean of GSH levels for all days was lower (3.8%) in patients than in the controls, this finding did not reach statistical significance (7.41 +/- 1.71 vs 7.71 +/- 1.27 U/gHb, ns). There was no correlation between the erythrocyte GSH levels and cardiac enzyme concentrations, infarct localization, hemodynamic status according to Killip classification and the frequency of ventricular arrhythmias. This preliminary work suggests that depressed GSH levels may be associated with an enhanced protective mechanism to oxidative stress in AMI. Measurements of erythrocyte GSH can be helpful in the estimation of oxidative stress in the course of AMI. However, further research must be done to determine the primary scavenger in AMI by analyzing all the enzymes and substrates involved in the endogeneous system that controls the effects of OFRs.