Occupational relevance of subclavian vein thrombosis in association with thoracic outlet syndrome

OBJECTIVES: Primary subclavian vein thrombosis ("effort thrombosis") is not generally recognized as a work-related disorder, and more knowledge is required on the particular biomechanical risks. An extensive biomechanical risk analysis was performed for a possible work-related case. CASE REPORT: A hard-working 43-year-old race-course farrier received successful surgical treatment for subclavian vein thrombosis. No congenital abnormalities were apparent. At work, the farrier spent 75% of his time with his back bent (generally at > 70 degrees) with his right shoulder flexed and abducted, a position that thereby increased the pressure on the subclavian vein. High average (and peak) stress ratings for the neck and shoulder postures are accompanied by high levels of force and considerable repetitiveness. CONCLUSIONS: Taken together, these forms of biomechanical overload suggest that the leading cause of the subclavian thrombosis suffered by this farrier could have been occupational. Case-control studies on this neglected topic are needed to investigate possible associations between subclavian vein thrombosis and specific occupational activities.     

Dispersal of Staphylococcus aureus into the air associated with a rhinovirus infection.

OBJECTIVE: To determine whether healthy adult nasal carriers of Staphylococcus aureus can disperse S. aureus into the air after rhinovirus infection. DESIGN: We investigated the "cloud" phenomenon among adult nasal carriers of S. aureus experimentally infected with a rhinovirus. Eleven volunteers were studied for 16 days in an airtight chamber wearing street clothes, sterile garb, or sterile garb plus surgical mask; rhinovirus inoculation occurred on day 2. Daily quantitative air, nasal, and skin cultures for S. aureus; cold symptom assessment; and nasal rhinovirus cultures were performed. SETTING: Wake Forest University School of Medicine, Winston-Salem, North Carolina. PARTICIPANTS: Wake Forest University undergraduate or graduate students who had persistent nasal carriage of S. aureus for 4 or 8 weeks. RESULTS: After rhinovirus inoculation, dispersal of S. aureus into the air increased 2-fold with peak increases up to 34-fold. Independent predictors of S. aureus dispersal included the time period after rhinovirus infection and wearing street clothes (P < .05). Wearing barrier garb but not a mask decreased dispersal of S. aureus into the air (P < .05). CONCLUSION: Virus-induced dispersal of S. aureus into the air may have an important role in the transmission of S. aureus and other bacteria.     

Laparoscopic feeding jejunostomy technique as part of staging laparoscopy

Placement of a feeding jejunostomy tube is indicated for patients who need enteral access but where a gastrostomy is not feasible. This paper presents the technique and results of laparoscopic placement of feeding jejunostomy tubes in patients presenting with esophagogastric cancer. From December 2002 to February 2004, patients diagnosed with esophagogastric cancer with a potentially resectable lesion underwent staging laparoscopy. Laparoscopic feeding jejunostomy was performed on patients who were potential candidates for chemotherapy with palliative intent or neoadjuvant treatment prior to resection surgery. Surgical technique, recovery of bowel function, commencement of feeding jejunostomy, total time tube was in situ, and perioperative complications were analyzed. Of the 22 patients who underwent staging laparoscopy, a feeding jejunostomy tube was placed in 18. The remaining 4 patients were deemed to have advanced disease precluding any therapeutic options and underwent placement of esophageal stents. Feeding tubes remained in situ for a median time period of 76 days. Fourteen patients required enteral support and tubes were used for a median of 30 days. Complications from tube placement included 2 cases of wound infections, 1 of minor leak and 1 tube dislodgment. Patients were followed up for a median time of 112 days. Findings from current series suggest that placement of a feeding jejunostomy tube at the time of staging laparoscopy is a safe and reliable means of providing and maintaining nutrition for patients presenting with esophagogastric cancers.     

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome

Cyclosporin A (CsA) is an effective therapy for children with long-lasting nephrotic syndrome (NS). Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity. Trough levels are commonly used to monitor the drug concentration. We report a retrospective clinical and histological analysis of 18 children (12 males, 6 females) with steroid-dependent nephrotic syndrome (15 patients) and partially steroid-sensitive nephrotic syndrome (3 patients) treated with CsA for a long-term period (mean 4.9 years, range 2.2–6.9). Before CsA treatment all patients had normal creatinine clearance. CsA was started at a dose of 5 mg/kg per day administered orally in two divided doses and adjusted to maintain the mean CsA blood concentration between 250 and 350 ng/ml obtained from abbreviated area under the curve (AUC). A renal biopsy was performed after a mean period of 3.9 years (range 2.2–6.2) from the start of CsA treatment. Tubular, interstitial, and arteriolar lesions were evaluated in order to assess CsAN. The mean CsA dose and the mean CsA blood concentration were 4.4 mg/kg per day (range 3.6–5.8) and 276.6 ng/ml (range 162–346), respectively. No child had a worsening creatinine clearance during CsA treatment and follow-up after CsA discontinuation. If compared with the year before the start of CsA treatment, NS relapses and prednisone (PDN) dose significantly decreased during CsA treatment, 4/year versus 0.8/year (P <0.0001) and 0.9 mg/kg per day versus 0.2 mg/kg per day (P <0.0001), respectively. Histological analysis showed 15 patients with minimal change disease and 3 with focal segmental glomerulosclerosis. Clear-cut lesions diagnostic of CsAN were never found and only mild lesions were observed in 5 children (suggestive of CsAN in 2 patients and consistent with CsAN in 3 patients). Long-term CsA treatment is confirmed to be effective in preventing NS relapses and reducing PDN dose. Renal function is not a reliable indicator of CsAN. With the mean CsA blood concentrations used in our patients CsAN presented a low incidence (28%) and was generally mild. Renal biopsy should be performed 2–3 years from the start of long-term CsA treatment, especially if the mean CsA blood concentrations are not regularly monitored.     

P-QOL: a validated questionnaire to assess the symptoms and quality of life of women with urogenital prolapse

To develop a simple, valid, reliable questionnaire to assess the severity of symptoms and their impact on the quality of life in women with urogenital prolapse. Women recruited from gynaecology outpatient clinics were asked to complete a prolapse quality of life questionnaire (P-QOL) before their hospital visit. At the time of the visit, they were examined supine using the International Continence Society (ICS) prolapse score (POP-Q). A second P-QOL was posted and completed by patients 2 weeks later. The validity was assessed by measuring levels of missing data, comparing symptom scores between affected and asymptomatic women and comparing symptom scores with objective prolapse stages. The internal reliability was assessed by measuring the Cronbach alpha coefficient; 155 symptomatic and 80 asymptomatic women were studied. Severity according to P-QOL strongly correlated with the vaginal examination findings (p<0.01, rho>0.5). The total scores for each P-QOL domain were significantly different between symptomatic and asymptomatic women (p<0.001). All items achieved a Cronbach alpha greater than 0.80 showing good inter-rater reliability. The test-retest reliability confirmed a highly significant correlation between the total scores for each domain. A P-QOL questionnaire for English-speaking patients has been developed which is reliable and valid.Editorial Comment: This paper introduces a new questionnaire to assess the symptoms and quality of life of women with urogenital prolapse. The authors have compared symptomatic woman with asymptomatic women in the evaluation of this new tool. Using well-controlled statistical analysis, a patient-directed diagnostic tool has been formulated. The role of this questionnaire and its applicability to clinical practice is widespread. This gives the clinician the ability to correlate symptom bother with actual physical findings. Additionally, quality of life parameters can be used in the postoperative period to gain insight into patients subjective assessment of their surgical outcomes     

Isolated hepatocytes versus hepatocyte spheroids: in vitro culture of rat hepatocytes

The use of hepatocytes that express liver-specific functions to develop an artificial liver is promising. Unfortunately, the loss of specialized liver functions (dedifferentiation) is still a major problem. Different techniques, such as collagen entrapment, spherical multicellular aggregates (spheroids), and coculture of hepatocytes with extracellular matrix, have been used to improve the performance of hepatocytes in culture. The aim of this study was to compare two different models of hepatocyte isolation in culture: isolated hepatocytes (G1) and hepatocyte spheroids (60% hepatocytes, 40% nonparenchymal cells, and extracellular matrix) (G2). To test functional activity of hepatocytes, both synthetic and metabolic, production of albumin and benzodiazepine transformation into metabolites was tested. G2 showed a high albumin secretion, while a decrease after 15 days of culture in G1 was noted. Diazepam metabolites were higher in G2 than in G1 in all samples, but had statistical significance at days 14 and 21 (p < 0.01). The glycogen content, after 30 days of culture, was very low in G1 (14.2 +/- 4.4%), while in G2 it was 72.1 +/- 2.6% (p < 0.01). Our study confirms the effectiveness of a culture technique with extracellular matrix and nonparenchymal cells. Maintenance of a prolonged functional activity has been related to restoration of cell polarity and close cell-to-cell contact. We showed that isolated hepatocytes maintain their functional activity for a period significantly reduced, when compared to the hepatocyte spheroids. We confirmed the role of extracellular matrix as a crucial component to promote hepatocyte homeostasis, and the close link between cellular architecture and tissue-specific functions.     

Isolated hepatocyte transplantation for Crigler-Najjar syndrome type 1

Crigler-Najjar syndrome type 1 (CN1) is an inherited disorder characterized by the absence of hepatic uridine diphosphoglucuronate glucuronosyltransferase (UDPGT), the enzyme responsible for the conjugation and excretion of bilirubin. We performed allogenic hepatocyte transplantation (AHT) in a child with CN1, aiming to improve bilirubin glucuronidation in this condition. A 9-year-old boy with CN1 was prepared with plasmapheresis and immunosuppression with prednisolone and tacrolimus. When a graft was made available, 7.5 x 10(9) hepatocytes were isolated and infused into the portal vein percutaneously. After 2 weeks phenobarbitone was added to promote the enzymatic activity of UDPGT of the transplanted hepatocytes. Nocturnal phototherapy was continued throughout the studied period. Total bilirubin was considered a reliable marker of allogenic cell function. There was no significant variation of vital signs nor complications during the infusion. Mean +/- SD bilirubin level was 530 +/- 38 micromol/L before and 359 +/- 46 micromol/L after AHT (t-test, p < 0.001). However, the introduction of phenobarbitone was followed by a drop of tacrolimus level with increase of alanine aminotransferase (ALT) and increase of bilirubin. After standard treatment of cellular rejection bilirubin fell again but from then on it was maintained at a greater level. After discharge the patient experienced a further increase of bilirubin that returned to predischarge levels after readmission to the hospital. This was interpreted as poor compliance with phototherapy. Only partial correction of clinical jaundice and the poor tolerability to nocturnal phototherapy led the parents to refuse further hepatocyte infusions and request an orthotopic liver transplant. After 24 months the child is well, with good liver function on tacrolimus and prednisolone-based immunosuppression. Isolated AHT, though effective and safe, is not sufficient to correct CN1. Maintenance of adequate immunosuppression and family compliance are the main factors hampering the success of this procedure.     

C-erb-B2 (HER2/neu) expression in synovial sarcoma of the head and neck

BACKGROUND: Synovial sarcoma is a malignant mesenchymal tumor composed of varying proportions of spindle and epithelial cell components. Because of the histologic and immunohistochemical similarity of synovial sarcoma to epithelial carcinomas, we hypothesized that the human epithelial growth factor receptor 2 (C-erb-B2, also termed HER2/neu) may contribute to the tumor phenotype and provide a new therapeutic target for this soft tissue tumor. METHODS: Three head and neck, one chest wall, and seven extremity synovial sarcomas were evaluated for C-erb-B2 (HER2/neu) expression by immunohistochemistry, Western immunoblotting, and fluorescence in situ hybridization (FISH). RESULTS: The head and neck cases demonstrated immunohistochemically strong positive staining, whereas tumors from other anatomic locations showed neither positive nor cytoplasmic restricted staining. Antigen-targeted antibody therapy (trastuzumab) was initiated in two patients. CONCLUSIONS: These results demonstrate that C-erb-B2 (HER2/neu) may play a role in the tumorigenesis of synovial sarcoma; and, therefore, antigrowth factor therapies may provide a previously unrecognized pharmaceutical approach to soft tissue tumors. The data also suggest that although synovial sarcoma of the head and neck and synovial sarcoma of the extremities have similar morphologic features, they may be clinically and mechanistically distinct entities.     

A new European perspective of influenza pandemic planning with a particular focus on the role of mammalian cell culture vaccines

Sixteen EU scientists and doctors were interviewed about pandemic planning using psychometric methods applied to a scientific problem for the first time. Criticism was aimed at countries which have no plan whatsoever, the majority of nations. Many such countries have not invested in scientific infrastructure and public health. Amongst the 15 or so published pandemic plans a lack of detail was identified. Of particular need was investment into avian virus vaccine stocks (H1-15), prepared licenses of vaccine and pre purchase and agreed distribution, investment into stocks of antivirals, antibiotics and masks. Most but not all members of the group predicted a global outbreak within 5 years, most probably starting in SE Asia. However it was recognised that a pandemic could start anywhere in the world which had juxtaposition of young people, chickens, ducks and pigs. Mammalian cell culture production using wild type virus with the production factory at category III levels of security was exemplified. Antivirals would be essential to ameliorate the first wave of infection although significant quantities of cell grown vaccine could be produced if, as in 1918, 1957 and 1968 there is a long period between the first virus isolation and person to person spread. The wider scientific community is more energised than previously for very serious preparations to be in place way before the outbreak begins as this is a major public health problem, completely dwarfing concerns about bioterrorism.