Production of herpes simplex virus type 1 thymidine kinase in the presence of thymidine analogues

Treatment of herpes simplex virus type 1 (HSV-1) infected Vero, BHK, BHKtk- and LMtk- cells with 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd) caused increased synthesis of ICP36 and an increase in HSV-1 thymidine kinase (tk) activity at late times of infection. The overproduced ICP36 was identified as the HSV-1 encoded tk protein by immunoprecipitation. Whereas the thymidine analogue 5'-amino-5'-deoxythymidine (AdThd) caused an increase in HSV-1 tk synthesis and activity in wild type Vero and BHK cells, 5-iodo-2'-deoxyuridine (IdUrd) caused a similar increase only in tk- cells (LMtk-, BHKtk-). In vivo and in vitro stabilization studies using a [35S]methionine pulse-chase experiment or heat inactivation studies with purified HSV-1 tk revealed that stabilization of tk by the analogues could not account for the extent of the observed increase. Since overproduction of tk is observed only at late times of infection, it is suggested that the presence of these thymidine analogues in either the viral DNA or the cellular nucleotide pools is responsible for the observed differential effects.     

B-cell concentration in the apheretic product predicts acute graft-versus-host disease and treatment-related mortality of allogeneic peripheral blood stem cell transplantation

BACKGROUND: The influence of the graft composition on the clinical outcome after allogeneic peripheral blood stem cell (PBSC) transplantation is not well established. METHODS: The cellular composition of the apheretic products obtained from 63 human leukocyte antigen-identical siblings was prospectively correlated with the outcome of patients with hematological malignancies undergoing an allogeneic PBSC transplant after myeloablative conditioning. The concentration of nuclear, mononuclear, CD34+, T-cell subsets, B cells, and natural killer cells in the graft has been analyzed. RESULTS: In univariate analysis, acute graft-versus-host disease (GVHD) correlated with the disease (P=0.002), with the phase of disease at transplant (P=0.01), and with the number of CD20+ cells infused (P=0.05). In multivariate analysis, a dose of CD20+ cells in the graft higher than the median dose remained the only factor negatively affecting the incidence of acute GVHD (P=0.01; 95% confidence interval [CI]: 0.12-0.78). In univariate analysis, treatment-related mortality (TRM) correlated with the disease (P=0.04) and was negatively affected by a dose of infused B cells greater than the median value (28% versus 50%; P=0.02). In multivariate analysis, TRM was close to statistical correlation with the dose of CD20+ cells (P=0.06; 95% CI: 0.02-1.05). No other clinical parameter was influenced by the composition of the graft. CONCLUSIONS: Our results suggest that the concentration of B cells in the apheretic product may predict the incidence of acute GVHD and TRM in patients undergoing an allogeneic PBSC transplantation and open the way to the new preventive and therapeutic strategies for the management of GVHD.     

角质细胞与成纤维细胞混合移植修复裸鼠全层皮肤缺损的初步报告

目的：利用组织工程原理探讨修复全层皮肤缺损的理想方式。方法：以裸鼠为动物模型,在皮肤全层缺损区域分别移植纤维蛋白胶(n=10),纤维蛋白胶角质细胞悬液（n=10）,纤维蛋白胶成纤维细胞悬液（n=10）以及纤维蛋白胶角质细胞成纤维细胞悬液（n=10）,术后每天对伤口进行大体观察,第5,7,10,14,21,35d,分别取材活检行组织学及免疫组织化学检查。结果：移植有角质细胞组（2和4组）的创面愈合快,术后10d组织学提示创面完全上皮化,抗人特异性HLA－1型抗原、抗involucrin染色和抗Ⅶ型胶原染色阳性证明新生上皮由移植的人角质细胞形成,抗involucrin染色阳性又证明角质细胞分化成熟有角质层形成,抗Laminin染色、抗Ⅶ型胶原染色阳性提示早期基底膜形成。组织学检查提示第4组新生上皮有许多类似皮钉样结构。结论：培养的角质细胞,成纤维细胞结合纤维蛋白胶移植到创面上后,可以形成复层分化良好、接近正常结构和功能的新生成肤组织。     

Linking the Disabilities of Arm, Shoulder, and Hand to the International Classification of Functioning, Disability, and Health.

The objective of this study was to explore whether the items from a specific outcome measure, that is, Disabilities of the Arm, Shoulder, and Hand (DASH), for quantifying limb symptoms and functions in musculoskeletal disorders fit into the framework of the International Classification of Functioning, Disability and Health (ICF). All DASH items were compared to the ICF according to eight linking rules. Two groups of researchers performed the linking independently, and the results were compared by correlation. The 30 DASH items and four items from the optional modules were linked to 63 ICF categories and 11 chapters: 15 categories belong to the ICF body functions component and 48 to the activities and participation component. There were no items coded under the components body structure or environmental factors. Kappa index showed an agreement of 0.73 (p<0.001). The results showed that the content of the DASH does link well with the ICF framework. Clinicians and researchers must attend to the fact that certain domains and categories from the ICF are not covered by the DASH. Limitations of the instrument may be overcome by simultaneously using other instruments that address the intended content.     

Evaluation of dopaminergic tone in hyperprolactinemia. III. Thyroid-stimulating hormone response to metoclopramide in differential diagnosis and postoperative follow-up of prolactinoma patients

Recently, it has been shown that patients with a PRL-secreting pituitary adenoma have a greater thyroid stimulating hormone (TSH) release after dopamine (DA)-receptor blockade than normal subjects. We have compared the TSH and PRL responses to metoclopramide (MCP) in normal and postpartum lactating women with those in 28 patients with hyperprolactinemia of different origin. Patients with a PRL-secreting pituitary adenoma were also tested after transsphenoidal removal of the tumor in order to establish the prognostic value of this test in such patients. Following MCP administration, percent increases in plasma PRL levels were greater in normal female subjects than postpartum lactating women. Plasma TSH levels did not increase in postpartum women and had a modest increment in normal subjects. In patients with hypothalamic tumors and empty sella syndrome plasma PRL and TSH levels showed modest or no increases after MCP administration. In ten patients harboring a microprolactinoma, plasma TSH levels showed an exaggerated increment after DA-receptor blockade. Postoperatively, despite normal or borderline PRL levels in the immediate postoperative period, a TSH response to MCP was present (in five patients one to two weeks after the operation, and in five patients one to three years after the operation), suggesting an increased DA activity even in the absence of hyperprolactinemia. In conclusion, the TSH test can easily detect increased DA-activity in patients with a microprolactinoma both preoperatively and postoperatively. It is possible that some patients with increased DA-activity in presence of normal PRL levels and normal PRL responsiveness to stimulation will experience a recurrence of hyperprolactinemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drain after elective laparoscopic cholecystectomy. A randomized multicentre controlled trial

Background

Routine drainage after laparoscopic cholecystectomy is still debatable. The present study was designed to assess the role of drains in laparoscopic cholecystectomy performed for nonacutely inflamed gallbladder.

Methods

After laparoscopic gallbladder removal, 53 patients were randomized to have a suction drain positioned in the subhepatic space and 53 patients to have a sham drain. The primary outcome measure was the presence of subhepatic fluid collection at abdominal ultrasonography, performed 24?h after surgery. Secondary outcome measures were postoperative abdominal and shoulder tip pain, use of analgesics, nausea, vomiting, and morbidity.

Results

Subhepatic fluid collection was not found in 45 patients (84.9?%) in group A and in 46 patients (86.8?%) in group B (difference 1.9 (95?% confidence interval ?11.37 to 15.17; P?=?0.998). No significant difference in visual analogue scale scores with respect to abdominal and shoulder pain, use of parenteral ketorolac, nausea, and vomiting were found in either group. Two (1.9?%) significant hemorrhagic events occurred postoperatively. Wound infection was observed in three patients (5.7?%) in group A and two patients (3.8?%) in group B (difference 1.9 (95?% CI ?6.19 to 9.99; P?=?0.997).

Conclusions

The present study was unable to prove that the drain was useful in elective, uncomplicated LC.     

Squamous cell carcinoma of the renal pelvis with stones and inferior vena cava infiltration. Case report

We report a rare case of a 50 year old man with renal squamous cell carcinoma (SCC) who first came to our attention with renal colic and fever not responding to antibiotic or analgesic treatment. He had a long history of kidney stones, but had not undergone any imaging in the last 5 years. Physical examination revealed tenderness and a palpable mass in the right flank and lumbar region. A whole body CT scan was performed, revealing an 11 cm mass in the right kidney infiltrating the inferior vena cava. There were areas of calcification within the mass and multiple stones within the renal pelvis. The tumor was considered unsuitable for resection according to radiological and clinical criteria. The mass was biopsied percutaneously under CT guidance and histological examination revealed squamous cell carcinoma of the renal pelvis. The patient was treated with neoadjuvant chemotherapy and embolization of the renal artery. He died one month after diagnosis. To our knowledge this is the second reported case in the world of renal SCC infiltrating the inferior vena cava and with kidney stones.     

Efficacy of laparoscopic appendectomy in appendicitis with peritonitis

Laparoscopic appendectomy (LA) is safe and effective in cases of peritonitis, perforation, and abscess. We investigated our conversion rate and clinical outcomes in this patient population, as well as preoperative factors that predict operative conversion. A retrospective nonrandomized cohort of 92 patients underwent LA for acute appendicitis with peritonitis, perforation, or abscess at our institution between 1997 and 2002. Thirty-six of the 92 were converted to open appendectomy (OA), yielding a conversion rate of 39 per cent. The presence of phlegmon (42%), nonvisualized appendix (44%), technical failures (8%), and bleeding (6%) were reasons for conversion. Preoperative data had no predictive value for conversion. CT scan findings of free fluid, phlegmon, and abscess did not correlate with findings at the time of surgery. Total complication rates were 8.9 per cent in the LA group as compared to 50 per cent in the converted cohort. Postoperative data showed LA patients stayed 3.2 days versus 6.9 days for converted patients (P = 0.01). LA patients had less pneumonia (P = 0.02), intra-abdominal abscess (P = 0.01), ileus (P = 0.01), and readmissions (P = 0.01). LA is safe and effective in patients with appendicitis with peritonitis, perforation, and abscess, resulting in shorter hospital stays and less complication.     

Relationship between plasma insulin and left ventricular mass in normotensive participants of the Gubbio Study

BACKGROUND: There is substantial but not conclusive evidence that insulin resistance is related to left ventricular mass (LVM) in hypertensive individuals. To what extent this association is mediated by the relationship between plasma insulin and body size and build is still debated, and is poorly explored in nonhypertensive people. OBJECTIVE: To explore the relationship between insulin or insulin resistance and LVM in a population-based sample of nonhypertensive participants of the Gubbio Study. METHOD: Echocardiographic LVM was determined in 91 nondiabetic, nonhypertensive individuals aged 45-54 years, participating in a population-based screening. LVM normalized for height2.7 was used in the analyses; LV hypertrophy was defined as a value of > or = 50 g/m2.7 in men or > or = 47 g/m2.7 in women. Fasting plasma insulin and glucose were measured and the Homeostasis Model Assessment (HOMA) index was used as a measure of insulin resistance. RESULTS: LVM was positively and significantly correlated with body mass index (BMI) (P < 0.01), waist circumference (P < 0.01) and HOMA index (P < 0.05), whereas correlations with plasma glucose and triglycerides did not reach statistical significance (P = 0.07 for both); all correlations were offset after adjusting for BMI. Fasting plasma insulin and HOMA index were not significantly different in subjects with or without LV hypertrophy (70.8 +/- 27.8 vs. 77.7 +/- 29.6 pmol/l and 2.2 +/- 1.0 vs. 2.6 +/- 1.4, respectively). Bivariate analysis performed stratifying participants above or below the 75th percentile of the sex-specific distribution for BMI (29.1 and 29.4 kg/m2 for males and females, respectively) and plasma insulin (84 pmol/l for either gender), did not result in appreciable differences in LVM due to insulin levels. Similar results were obtained replacing the HOMA index for insulin in the analysis. CONCLUSION: In nonhypertensive individuals left ventricular mass is not associated with plasma insulin independently of body mass index.