The c.29T>C polymorphism of the transforming growth factor beta-1 (TGFB1) gene, bone mineral density and the occurrence of low-energy fractures in patients with inflammatory bowel disease.

Gastrointestinal tract conditions are frequently associated with low bone mineral density and increased risk of fractures due to osteoporosis, the latter concerning particularly inflammatory bowel disease (IBD) patients. One of the candidate genes involved in osteoporosis is the transforming growth factor beta-1 (TGFB1) whose polymorphisms may be responsible for the development of this disease. The aim of this study was to analyse the frequency of TGFB1 polymorphic variants and determine the association between the c.29T>C TGFB1 polymorphism, and bone mineral density and fractures in IBD patients. The study subjects included 198 IBD patients [100 suffering from Crohn's disease (CD) and 98 from ulcerative colitis (UC)] and 41 healthy volunteers as a control group. Densitometric bone measurements were obtained using dual energy X-ray absorptiometry. The TGFB1 genotyping was conducted using restriction fragments length polymorphism. We conducted an analysis of genotype distribution's concordance with Hardy-Weinberg equilibrium. We found statistically significant differences in lumbar spine (L2-L4) and femoral neck BMD and T-scores between CD, UC and control subgroups. The distribution of TGFB1 polymorphic variants among CD and UC patients was concordant with Hardy-Weinberg equilibrium. There were no statistically significant differences in densitometric parameters (lumbar spine and femoral neck BMD, T-score, and Z-score) between carriers of different TGFB1 polymorphisms among IBD (CD and UC) patients nor among controls. We have found no statistically significant differences in the prevalence of low-energy fractures between groups of different TGFB1 polymorphic variant carriers. The allele dose effect, recessive effect and dominant effect analysis did not show an association between low-energy fractures and the TGFB1 polymorphisms among CD and UC patients. We have not observed an association between the c.29T>C TGFB1 polymorphic variant and the bone mineral density within the cancellous and cortical bones (L2-L4 and femoral neck, respectively), or the occurrence of fractures among the IBD patients and their family members.

Hind feet position score: A novel trait to genetically reduce lameness incidence.

Lameness is an important health and welfare issue that causes considerable economic losses in dairy herds. The objective of this study was to investigate whether the hind feet position score (HFPS) can be used as an auxiliary trait for genetic evaluation of lameness. The HFPS is evaluated by visual scoring of the position of both the hind-digits to the mid-line of the cow's body. The higher the heel height of the lateral claw, the higher is the HFPS, and the higher is the risk for development of lameness. In total, 3,478 records from 1,064 Fleckvieh cows from 35 farms were obtained between September 1, 2021, and March 5, 2022. Data collection was carried out by the regional milk recording organizations. Hind feet position was scored visually by trained personnel during routine milk performance testing in the milking parlor using a 3-class scoring system: score 1 = 0° to <17° indicating a balanced heel height of both the medial and the lateral claw; score 2 = angle of 17° to 24°; score 3 = angle of >24°. After all cows had been milked, locomotion scoring was performed for each animal using a 5-class scoring system with locomotion scores ranging between 1 (normal) and 5 (severely lame). Using HFPS, sensitivity and specificity were 69.5% and 66.8%, respectively, for detecting lameness defined by locomotion score ≥2. For genetic analyses, a bivariate linear animal model was fitted with fixed effects of herd, parity, lactation stage, and classifier, and random effects of animal and permanent environment. Heritabilities for HFPS and locomotion score were 0.07 and 0.10, respectively, and the genetic correlation between the 2 traits studied was 0.80. These results suggest that the HFPS could be used for genetic evaluations to reduce lameness incidence in dairy cattle.

Spinal surgery for gallstones disease - Case report of a rare differential diagnosis.

INTRODUCTION AND IMPORTANCE: Abdominal pain in the right upper quadrant is very common for patients to present in the emergency department. Finding the correct diagnosis seems straightforward in most cases but can be challenging. CASE PRESENTATION: We present the case of a 75-year-old male with a rare differential diagnosis for right upper quadrant and back pain, initially diagnosed as symptomatic cholelithiasis. After referral to an abdominal surgeon, detailed history taking prior to planned cholecystectomy revealed a record of back pain due to spinal degeneration and fusion surgery, as well as a bulb of the right abdominal wall with hypesthesia in a dermatomal area in the right upper quadrant. Considering these "new" facts, a spinal surgeon was consulted and a foraminal disc hernia of the thoracic vertebrae 11/12 was identified as the cause of symptoms. Instead of the initially planned cholecystectomy, a right-sided facetectomy Th11/12, sequestrectomy and unilateral transpedicular stabilization to decompress the nerve root was successfully performed. CLINICAL DISCUSSION: Although, symptomatic cholelithiasis is one of the most common diagnoses for patients presenting with right upper quadrant pain in the presence of gallstones, other differential diagnoses have to be considered. Thoracic disc herniations can present with atypical symptoms that mimic other non-spinal causes and may pose a diagnostic challenge, sometimes even leading to unnecessary surgery. CONCLUSION: This case highlights a rare differential diagnosis for one of the most common diseases seen by emergency physicians. It emphasizes the risk of working under time pressure, especially in an emergency setting, which may lead to premature diagnostic error and treatment, endangering patient's care and safety.

Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans.

MDM2, a ubiquitin E3-ligase of the RING family, has a key role in regulating p53 abundance. During normal non-stress conditions p53 is targeted for degradation by MDM2. MDM2 can also target itself and MDMX for degradation. MDMX is closely related to MDM2 but the RING domain of MDMX does not possess intrinsic E3-ligase activity. Instead, MDMX regulates p53 abundance by modulating the levels and activity of MDM2. Dimerization, mediated by the conserved C-terminal RING domains of both MDM2 and MDMX, is critical to this activity. Here we report the crystal structure of the MDM2/MDMX RING domain heterodimer and map residues required for functional interaction with the E2 (UbcH5b). In both MDM2 and MDMX residues C-terminal to the RING domain have a key role in dimer formation. In addition we show that these residues are part of an extended surface that is essential for ubiquitylation in trans. This study provides a molecular basis for understanding how heterodimer formation leads to stabilization of MDM2, yet degradation of p53, and suggests novel targets for therapeutic intervention.

Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein, on chemotherapy-induced multilineage myelosuppression in patients with sarcoma.

PURPOSE: To evaluate the clinical safety and ability of PIXY321, a novel fusion protein of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), to ameliorate chemotherapy-induced multilineage myelosuppression. PATIENTS AND METHODS: PIXY321 was administered by subcutaneous injection twice daily (25 to 1,000 micrograms/m2/d) over 14 days to 24 chemotherapy-naive patients with sarcoma in a phase I/II study. Three weeks from the initiation of PIXY321, the first cycle of chemotherapy with cyclophosphamide, doxorubicin, and dacarbazine (DTIC) (CyADIC) was administered over 3 days. Four weeks later, a second cycle of CyADIC was administered, followed by 14 days of PIXY321. RESULTS: Treatment with PIXY321 was well tolerated. Local skin reactions and constitutional symptoms were the main side effects. The dose-limiting toxicity was not encountered; however, headache and fatigue were more frequent at the highest dose (1,000 micrograms/m2). PIXY321 before chemotherapy elicited a modest increase in the WBC count (consisting mainly of mature neutrophils), platelets, and corrected reticulocyte counts (all P < .001). Following chemotherapy, PIXY321 at effective doses (500 to 1,000 micrograms/m2/d), significantly reduced both the degree (mean nadir, 70 v 310/microL; P = .016) and duration (mean days < 500/microL, 6.6 v 3.9 days; P = .002) of neutropenia. Cumulative thrombocytopenia was not observed during the first two cycles of CyADIC (mean nadir platelet count, 103 v 95 x 10(3)/microL, in cycles no. 1 and 2, respectively; P = NS). Compared with our historic control data, the mean nadir platelet count in cycle no. 2 was significantly higher after PIXY321 (1.7-fold, P < .05) than with CyADIC alone or with GM-CSF support. There was a suggestion for a dose response, since the mean percentage change in nadir platelet values from cycle no. 1 to cycle no. 2 increased with the PIXY321 dose (P < .02), with the peak effect observed at 750 micrograms/m2/d. CONCLUSION: These results suggest a potential clinical role for PIXY321 in attenuating the cumulative multilineage hematopoietic toxicity of chemotherapy.

Nutritional status of patients hospitalised in Poland.

AIM: Screening and extended assessment of the nutritional status of patients on admission and on discharge from hospital were carried out. DESCRIPTION: The studies were carried out in four teaching hospitals, four provincial hospitals and four county hospitals in Poland. SUBJECTS: Screening examinations were carried out for 3310 randomly selected patients (every 10th patient admitted to hospital, including 1916 female cases aged from 16 to 92 y and 1394 male patients aged from 16 to 100 y). Extended examinations were carried out on 210 patients aged from 16 to 87 y (including 122 female and 88 male). MAIN ASSESSMENT PARAMETERS: Anthropometric (height, weight, body mass index (BMI), waist-to-hip ratio (WHR), arm circumference) and biochemical indices (erythrocyte count, haemoglobin concentration, white blood cell count, blood lymphocyte count and serum albumin serum concentration). The extended examinations included determination of antioxidant vitamins (A, C, E), vitamin B(12) and folic acid. RESULTS: On admission to hospital, 10.43% of the patients surveyed had a BMI below 20 kg/m(2), in 20.74% of patients serum albumin concentration was below 3.5 g/dl, indicating possible protein energy malnutrition. In addition, 21.02% had lymphocyte count below 1.5 x 10(3)/mm(3). During hospitalisation, deterioration in the nutritional status of the patient population occurred. On discharge from hospital, the percentage of patients with BMI < 20 kg/m(2) increased to 11.21% and the percentage with low blood albumin (<3.5 g/dl) increased to 28.57%. On admission, vitamin C deficiency was present in 51.8% of patients, folic acid deficiency in 32%, vitamin E deficiency in 10%, vitamin B(12) deficiency in 6.8% and vitamin A deficiency in 1.4%. Vitamin deficiencies were present equally in malnourished, overweight and obese patients. CONCLUSIONS: In patients admitted to hospitals in Poland, malnutrition risk demonstrated by BMI was observed in 10.43% of patients. On the basis of biochemical indices, increased nutritional risk was demonstrated in 21% of patients. Vitamin malnutrition was seen in the majority of patients. A significant correlation between weight, BMI, arm circumference, blood lymphocyte count and the number of days spent in hospital was observed. SPONSORSHIP: The Committee of Scientific Research and the Ministry of Health-PBZ 012-14.

Extraskeletal myxoid chondrosarcoma. Long-term experience with chemotherapy.

Extraskeletal myxoid chondrosarcoma (EMC) is a rare low-grade soft tissue sarcoma that has been reported to have an indolent nature history, and relatively good prognosis. The majority of primary tumors are located in the extremities and they tend to be bulky at presentation. Studies with long-term follow-up have revealed the development of distant metastases in virtually all patients, eventually resulting in death. We reviewed our experience with EMC over the last three decades. The patient population was identified through a search of the database maintained by the Departments of Patient Studies, Pathology, and Melanoma-Sarcoma Medical Oncology. Eleven patients with histologically confirmed diagnosis of EMC were identified. The median age was 59 (37-81 years), and there were nine males and two females. Nine patients had an extremity location and the remaining two had a chest wall and abdominal wall primary, respectively. The median size of the primary tumor was 10 cm (range: 4-17 cm) in maximum dimension. Ten of the eleven patients received chemotherapy, mainly with doxorubicin- and dacarbazine-based regimens. One patient is currently on beta-interferon. No objective responses were noted, to a median of 4 (2-6) cycles of chemotherapy. Three patients were treated with ifosfamide as a second-line chemotherapy without any benefit. Three patients have expired, two patients are alive with no evidence of disease, and six patients are alive with disease. The median follow-up is 5 years (range: 1.33-17 years) from diagnosis. Although small numbers preclude adequate assessment, there is no evidence of efficacy of standard soft-tissue sarcoma chemotherapy in patients with EMC.

Alterations of growth hormone, cortisol, luteinizing hormone, and insulin concentrations in early-postnatal calves affected with diarrhea.

The aim of the study was to investigate the influence of diarrheic infections during the early postnatal phase of calves on the concentrations of hormones controlling reproduction and metabolism. Blood samples were collected from 20 male and female calves via jugular vein catheters every 15 min for 6 hr at Days 3, 9, and 21 of life. The animals were classified into three groups. Group 1 (controls): healthy calves (n = 9). Group 2: calves affected with diarrhea at Day 9 (n = 7). Group 3: calves with diarrhea at Days 3 and 9 (n = 4). Infections occurred spontaneously and were mainly due to E. coli infections. All affected calves had recovered at Day 21. Mean GH concentrations in the calves in Groups 2 and 3 compared to control calves had increased by Day 3 (P<0.01; P<0.001). Cortisol levels of calves in all groups were highest at Day 3 and decreased thereafter (P<0.001). Cortisol concentrations were lower at Day 3 in animals in Groups 2 (P<0.001) and 3 (P<0.05) than in controls. Pulsatile LH release was detectable at Days 9 and 21 only in healthy calves. Insulin increased at Day 9 during diarrhea. The results indicate that cortisol concentrations decreased whereas GH concentrations were increased before diarrhea was observed. The onset of pulsatile LH release was delayed in diarrheic calves. It is concluded that diarrhea exerts effects upon the release of reproductive and metabolic hormones in early postnatal calves.

[Report about two cases of gastroenteritis caused by Plesiomonas shigelloides (author's transl)]. / Bericht über zwei Fälle von akuter Gastroenteritis durch Plesiomonas shigelloides

Plesiomonas shigelloides was isolated out of the feces from two patients. In one case the patient (she just arrived back from Kenia) had cholera-like symptoms. In the other case the nonspecific symptoms led to an appendectomy. In this case the association of the clinical symptoms with the bacteriological results is doubtful. Plesiomonas shigelloides belongs to the genus III. (Plesiomonas) of the family II. (Vibrionaceae) Part 8. (gram-negative facultatively anaerobic rods). Some of Plesiomonas shigelloides strains share a common O antigen with Sh. sonnei. Literature about infectious gastroenteritis in humans due to Plesiomonas shigelloides is very spare. This is the reason why the pathogenicity of this bacterium on humans is not comonly known. After on year of stool-research, with a relative small number of specimens, we found Plesiomonas shigelloides twice. This is the reason why we could assume that this bacterium is more often in feces than we thought till now.

Histochemical studies of the rat epididymis after treatment with alpha-chlorohydrin (U-5897).

PIP: Histochemical studies of the rat epididymis after treatment with alp ha-chlorohydrin (U-5897) are presented. 14 sexually mature male rats received either daily subcutaneous injections of 50 mg U-5907/kg body weight or distilled water for 20 days. The animals were sacrificed the day following the last injection. U-5897 induced temporary sterility as demonstrated by blocked transport of spermatozoa, and spermatogenic cells eliminated from the spermatogenic epithelium which became blocked in the caudal part of the epididymis. This resulted in the distension of the segment of the distal part of the epididymal duct and to the thinning of the epithelium which lined the altered segment. Alkaline and acid phosphatases, nonspecific esterases, succinate and glucose-6-phosphate dehydrogenases and reduced nicotinamide-adenine dinucleotide tetrazolium reductase in the unchanged part of the epididymal duct were comparable to control rats whereas the altered part of the epididymis showed these activities to much weaker degrees or to be absent altogether.^ieng

[Electron microscopic studies in ulcerative colitis]. / Elektronenmikroskopische Untersuchungen bei Colitis ulcerosa.

In 26 patients with the classical clinical picture of an ulcerous colitis and in 8 healthy control persons in the course of a rectoscopy in about 15 cm depth tissue was taken bioptically and underwent an electron-microscopic investigation. Moreover, enzyme-histological examinations were performed. Summarizingly, clear references to immune-pathological processes for development and course of ulcerous colitis are the result.

Nutrition and development of gastric cancer.

Gastric cancerogenesis is a multistage process. Dietary studies may contribute to elucidation of that complex problem.

Adenosine influences the high-affinity uptake of transmitter glutamate and aspartate under conditions of hepatic encephalopathy.

The high-affinity uptake of transmitter glutamate and aspartate in hippocampal slices incubated in sera from patients with hepatic encephalopathy was dramatically reduced in neuropil areas by more than 50% compared with the control level. Adenosine compensates for these reduction in reuptake capacity in a concentration-dependent fashion reaching normal values at 500 microM adenosine. The renormalization of glutamate and aspartate uptake caused by adenosine might reasonably be expected to have potential therapeutic implications for the treatment of hepatic encephalopathy.

Remarkable, overlooked and new microfungi in North Rhine-Westphalia, Germany.

During our investigations of the micro flora in NRW in the years of 1999 and 2000 we were able to collect and identify some new and rare species of micro fungi as parasites and saprophytes on wild and ornamental plants. Some of them are new for Germany: Podosphaera xanthii on Coreopsis verticillata; Cercospora traversiana on Trigonella foenum-graecum; Passalora dubia on Atriplex hortensis; Ophiobolus cirsii on Carduus spec.; Periconia britannica on Polemonium coeruleum; Ascochyta leptospora on Agropyron repens; Apomelasmia urticae on Urtica dioica; Cryptodiaporthe salicina on Salix caprea; Dasyscyphus nidulus on Anemone hupehensis; Rhopographus filicinus on Pteridium aquilinum; Sillia ferruginea on Corylus avellana; Sirococcus spiraeae on Spiraea spec. and Forsythia x intermedia. Examples of these findings are in the Herbarium ESS (Mycotheca Parva, Slg. Feige/Ale-Agha).

[Diagnostic value of fine needle aspiration biopsy in liver and pancreas diagnosis with computer tomography control]. / Diagnostischer Wert der Feinnadelaspirationsbiopsie in der Leber- und Pankreasdiagnostik unter Computertomographiekontrolle.

The aspiration biopsy with thin-needles controlled by computer tomography permits an aimed, safety and nearly not dangerous investigation of patients with liver and pancreas diseases. The cytologic examination allows the differentiation of neoplastic tumors from other processes.