Lack of optimal T-cell reactivity against the hepatitis C virus is associated with the development of fibrosis/cirrhosis during chronic hepatitis

Chronic hepatitis C virus (HCV) infection develops in 85% of exposed individuals and 20% develop cirrhosis. However, the pathogenesis of this process is not well-understood. The objective of this study was to determine whether HCV-reactive T cells play a role in the process of development of cirrhosis during chronic HCV infection. We analyzed 21 human leukocyte antigen (HLA)-A2 patients with chronic HCV infection (9 with histology of inflammation and 12 with histology of fibrosis/cirrhosis). The frequency of CD8(+) T cells reactive to 12 HCV-derived epitopes was determined by an interferon-gamma enzyme-linked immunospot (ELISPOT) assay. The frequency of CD4(+) Th1 and Th2 cells reactive to the HCV core antigen was determined by interferon-gamma and interleukin-5 ELISPOT assays, respectively. Patients with histology of inflammation showed a significantly higher CD8(+) T-cell response to five HCV-derived epitopes (YLLPRRGPRL [core], CINGVCWTV [NS3], LLCPAGHAV [NS3], ILAGYGAGV [NS4B], and GLQDCTMLV [NS5B]) as compared with patients with histology of fibrosis/cirrhosis. Also, patients with histology of inflammation showed a significantly higher CD4(+) Th1 response to the HCV core antigen as compared to patients with histology of fibrosis/cirrhosis. These results indicate that a lack of an optimal T-cell response to HCV is associated with the development of cirrhosis during chronic HCV infection.     

In vivo release and turnover of secreted platelet antiheparin proteins in rhesus monkey (Macaca mulatta)

Human and rhesus monkey platelets secrete at least two antiheparin proteins: platelet factor 4 (PF4) and low affinity platelet factor 4 (LA-PF4). Neither of these proteins showed species-related antigenic differences. As determined by radioimmunoassay, the levels of PF4 and LA-PF4 antigen per 10(9) monkey platelets amounted to 10.7 and 20.3 microgram, respectively. One milliliter of monkey plasma prepared from blood collected into an anticoagulant composed of EDTA, prostaglandin E1, and theophylline solution contained 22.4 ng LA-PF4 and 8.0 ng PF4. Concentrations of these two platelet-specific proteins in monkeys closely resembled levels found in human platelets and plasma. Infusion of prostacyclin (PGI2) (100 or 300 ng/kg/min) into monkeys for 15 min resulted in a significant decrease of plasma levels of LA-PF4 antigen and of PF4 by 40%--60% (p < 0.0001). This decrease was related to the inhibitory effect of PGI2 on the secretion of platelets stimulated by a catheter or by venipuncture. Longer infusion of PGI2 did not produce further significant change. The supernate obtained after aggregation of human platelets stimulated by thrombin was injected into monkeys receiving PGI2 infusion. The disappearance of LA-PF4 antigen in monkey plasma followed a biphasic exponential curve with half-lives for the fast and slow components of 8.4 and 63 min. PF4 disappeared faster but followed the same pattern (half-lives for the fast and slow component of 2.1 and 70 min). Analysis of the experimental data suggests that the low levels of secreted platelet proteins in monkey plasma are related to their minimal in vivo release and to their rapid clearance.     

Correction of Lower Limb Deformities Using Ilizarov's Technique

Background

India accounts for approximately 10 million orthopaedically handicapped children and adults with limb deformity. Ilizarov ring fixator could treat most of these deformities.

Methods

Twenty cases of deformities of lower limb managed with Ilizarov technique during period between March 2001 and February 2003 were studied.

Results

55% were in the age group of 11-30 years. Out of the 20 cases studied, 6 were congenital talipes equino varus, 8 were fixed flexion deformity of knee, 4 were equines deformity of the ankle and 2 were malunited fracture shaft of tibia.4 patients who had recurrence were operated for fixed flexion deformity of the knee. The main complication encountered was pin tract infection, which was seen in 15(75%) cases. In 16(80%) cases, the results were excellent with no recurrence of deformity and patients were able to walk independently. In 4 (20%) cases, recurrence was mild to moderate (10 to 20) but all of them were able to ambulate idependently and carry out their routine activities.

Conclusion

Ilizarov ring fixator is a superior compared to conventional methods for correction of deformities of lower limb.Key Words: Ilizarov method, Ligamentotaxis, Distraction     

Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity     

Cutting balloon angioplasty for resistant venous anastomotic stenoses

Conventional angioplasty of stenoses at the venous anastomosis has been demonstrated to be an important endovascular adjunct to mechanical thrombectomy of clotted arteriovenous dialysis grafts. In some cases, however, severe venous anastomosis stenosis is resistant to angioplasty. Cutting balloon angioplasty may have an advantageous role in these difficult situations in order to avoid surgical revision. In this series of 350 patients receiving percutaneous, endovascular declotting procedures, 9 patients had high-grade venous anastomotic stenoses (opening less than 2 mm) that could not be remedied with either conventional or high-pressure noncompliant peripheral angioplasty balloons. These nine patients had the lesions opened with the use of 4 mm x 10 mm cutting balloons and placement of self-expanding nitinol stents at the venous anastomosis during the same angiography procedure. Patients were followed for patency and functionality of the graft. In all cases, immediate technical success occurred. Among these patients, the vessels have remained patent for as long as 20 months of follow-up and grafts have remained functional. Cutting balloon angioplasty may have a potential therapeutic role in resistant venous anastomotic stenoses.     

Pneumothorax preceding pulmonary blastoma in a child

Serial plain radiographic, ultrasound and CT findings of an unusual case of pulmonary blastoma are described with a review of the literature.