Israel Medical Association Journal

Background: Idiopathic frozen shoulder is a self-limiting regional skeletal problem of unknown etiology. Clinically, patients first experience a phase of pain, progressing to a freezing stage when glenohumeral motion is lost, followed by a thawing phase when pain gradually subsides and most of the lost motion returns.

Objectives: To identify possible specific and non-specific risk factors for idiopathic frozen shoulder.

Methods: We compared the medical histories, drug treatment, previous hospital as well as health management organization blood tests of 126 new consecutive frozen shoulder patients from a shoulder clinic to those of an age-matched control group of 98 consecutive patients from an orthopedic foot and ankle clinic and to the regional population disease prevalence registry. Frozen shoulder was classified as idiopathic only if there was no history of trauma and no evidence of a rotator cuff tear.

Results: Among the frozen shoulder patients 29.4% had diabetes and 13.5% had thyroid disorders. The risk ratio for diabetes in the frozen shoulder group was 5.9 for males (95% confidence interval 4.1–8.4, P < 0.001) and 5.0 for females (95% CI[1] 3.3–7.5, P < 0.001). The risk ratio for thyroid disorders among females with frozen shoulder was 7.3 (95% CI 4.8–11.1, P = 0.001). No significant difference was found in the prevalence of thyroid disorders between frozen shoulder and the control group, but there was a significantly higher prevalence of diabetes in males and a trend for higher prevalence in females in the frozen shoulder group.

Conclusions: Physicians should be aware that diabetes is a specific risk factor for idiopathic frozen shoulder in both males and females and thyroid disorders are a non-specific risk factor in females only.  

Background: Interleukin-8 is a prototypical inflammatory chemokine that induces leukocyte migration to inflammatory sites. Leukocyte recruitment in response to gradients of this chemokine is attenuated at advanced stages of inflammation to prevent damage to surrounding healthy tissues. Our published studies suggest that over-phosphorylation of focal adhesion kinase in migration-desensitizing conditions is involved in cessation of cell motility. This over-phosphorylation of FAK[1] was induced by IL-8[2] only when the receptor transmitting the chemokine signals was CXCR2, and not CXCR1, indicating that the two IL-8 receptors diverge in their signaling properties.

Objectives: To analyze the regulation of FAK in CXCR2-expressing hematopoietic cells under conditions of migratory desensitization, focusing on the roles played by adhesion-related components in this process.

Methods: Under conditions of migratory desensitization, we determined IL-8-induced cell spreading and FAK localization following disruption of actin filaments, and evaluated the role of integrins in FAK phosphorylation.

Results: The disturbance of intact activity of actin filaments resulted in inhibition of cell spreading and modification of FAK intracellular localization upon IL-8 stimulation. Also, adhesion-dependent pre-stimulation of integrins was required for IL-8-induced FAK phosphorylation.
Conclusions: Intact actin filaments and integrins are required for optimal IL-8-induced FAK phosphorylation in conditions of migratory desensitization. These observations suggest that lack of adequate activity/regulation of adhesion-related components may give rise to FAK activities that are not appropriately controlled, possibly leading to pathological conditions that are associated with perturbed leukocyte migration phenotypes

Background: The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.

Objectives: To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.

Methods: The present study included (part 1): 39 patients with acute TB[1] (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6[2] and IL-10 were measured in serum and in non-stimulated and PPD[3]-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNg[4] and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.

Results: Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNg-SER[5], IFNg-PPD, IL-2R[6]-SER, IL-10-SER, IL-10-NS[7] and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNg were demonstrated in the second part of the study.

Conclusions: Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNg secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis. 

Background: Halofuginone is a novel antifibrotic agent that can reserve the fibrotic process by specific inhibition of collagen type I synthesis.

Objectives: To evaluate the effect of Halo on the development of glomerulosclerosis and interstitial fibrosis in the 5/ 6 nephrectomy rat model.

Methods: Male Wistar rats were assigned to undergo 5/6 NX or sham operation, and then divided into three groups: 5/6 NX rats (NX-Halo and NX-Control) and sham. Systolic blood pressure proteinuria and body weight were determined every 2 weeks. At sacrifice (10 weeks) creatinine clearance was evaluated and remnant kidneys removed for histologic examination, Sirius red staining and in situ hybridization.

Results: Systolic blood pressure increased progressively in both 5/6 NX groups. Halo slowed the increase in proteinuria in 5/6 NX rats. As expected, creatinine clearance was lower in 5/6 NX groups when compared to sham rats. Creatinine clearance was significantly higher in the NX-Halo group at the end of the study period. Histologic examination by light microscopy showed significantly less severe interstitial fibrosis and glomerulosclerosis in Halo-treated rats. The increase in collagen α1 (I) gene expression and collagen staining after nephrectomy was almost completely abolished by Halo.

Conclusions: Halofuginone reduced proteinuria as well as the severity of interstitial fibrosis and glomerulosclerosis in 5/6 NX rats. The renal beneficial effect of Halo was also demonstrated by the blunted decrease in creatinine clearance observed in the treated animals.  
 

Background: Despite significant advances in the therapy of heart failure, many patients still do not receive optimal treatment.

Objectives: To document the standard of care that patients hospitalized with HF[1] in Israel received during a 2 month period.

Methods: The Heart Failure Survey in Israel 2003 was a prospective 2 month survey of patients admitted to all 25 public hospitals in Israel with a diagnosis of HF.

Results: The mean age of the 4102 patients was 73 years and 43% were female. The use of angiotensin-converting enzyme/angiotensin receptor blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6% for ACE[2]-inhibitor/ARB[3] and 64.1% to 52.9% for beta blockers, P < 0.001 for comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or ARB and a beta blocker at hospital discharge also declined from NYHA class I to IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being discharged with an ACE-inhibitor or ARB was the use of these medications at hospital admission. Negative predictors for their usage were age, creatinine, disease severity class, and functional status.

Conclusions: Despite the dissemination of guidelines many patients did not receive optimal care for HF. Reasons for this discrepancy need to be identified and modified.

Objectives: To assess the feasibility and efficacy of high dose preoperative radiotherapy and TATA[1] as a sphincter-preserving method in Jiangsu, an economically well-developed region of China with a population of 70 million people.

Methods: From September 1994 to September 2000, 25 consecutive patients with pathologically confirmed distal rectal adenocarcinoma were treated preoperatively with a total dose of 45–46 Gy at 1.8–2.0 Gy per fraction during 5 weeks. Sphincter-preserving surgery by TATA was performed 4–6 weeks after radiotherapy.　

Results: Acute toxicity of preoperative radiotherapy was tolerable. Eight percent of the patients presented pathologic complete tumor response after preoperative radiotherapy. All patients underwent TATA as scheduled. During a median follow-up of 70 months, the 5 year survival rate was 88%. The 5 year survival rate for those tumors down-staged to pathological T0 or to pT1 was 100%.

Conclusions: High dose preoperative radiotherapy and TATA as a sphincter-preserving method was feasible and efficient in Chinese patients with distal rectal cancer. In this study, the subset of patients with a good response to radiotherapy had a better clinical outcome.