The biomechanical effects of focused muscle training on medial knee loads in OA of the knee: a pilot, proof of concept study.

BACKGROUND: High dynamic loads of the medial knee are associated with tibiofemoral osteoarthritis (OA) severity and progression. The lower extremity acts as an integrated kinetic unit, thus treatments targeting adjacent segments may promote reductions in the loading of a symptomatic knee. This study examined the biomechanical effects of a lower extremity exercise regimen, emphasizing training of hip abductor musculature, on dynamic knee loads in individuals with knee OA. METHODS: Six subjects with medial compartment knee OA participated in a proof of concept study of a four-week exercise program specifically targeting the hip abductor musculature in combination with traditional quadriceps and hamstring training. Assessments included gait analyses to measure the external knee adduction moment, a surrogate marker of medial knee joint loading as well as WOMAC questionnaires and strength evaluations. RESULTS: All subjects demonstrated a decrease in their external knee adduction moment, with an average decrease of 9% (p<0.05) following the exercise intervention. There was a 78% (p<0.05) decrease in WOMAC knee pain scores. CONCLUSIONS: These results suggest that targeting hip, rather than only knee musculature, may represent an effective biomechanically-based treatment option for medial knee OA.

Pain and its relationship with muscle strength and proprioception in knee OA: results of an 8-week home exercise pilot study.

Muscle strength and proprioception deficits have been recognized in knee OA. Pain is the symptomatic hallmark of knee OA. Indirect evidence suggests that muscle strength and proprioception deficits may be interrelated and that pain may have a confounding influence on the measurement of these factors in knee OA. However, these relationships have never been clearly evaluated. Therefore, the purpose of this investigation was to investigate relationships between pain, muscle strength, and proprioception in subjects with knee OA before and after an 8-week home exercise program. This study evaluated thirty-eight subjects with knee OA. Subjects were taught standard quadriceps strengthening exercises that were to be performed daily at home. Pain, muscle strength, and proprioceptive function were measured at baseline and after 8 weeks of therapy. Significant improvements in pain (42%, p<0.001) and quadriceps muscle strength (30%, p<0.001) were noted. Significant indirect associations were observed between pain and both muscle strength (rho=-0.39, p=0.01) and proprioceptive acuity (rho=-0.35, p=0.03) at baseline. Changes in pain were directly associated with changes in muscle strength (rho=0.45, p=0.005) and proprioceptive acuity (rho=0.41, p=0.01) with exercise. The association of pain with both muscle strength and proprioception should prompt future studies to consider and adjust for the influence of pain on neuromuscular factors in knee OA.

Allogeneic peripheral blood stem cell transplantation in patients with haematological malignancies.

OBJECTIVE: To report the initial data on allogeneic peripheral blood stem cell transplantation for haematological malignancies in Pakistan. DESIGN: A single centre descriptive study. PLACE AND DURATION OF STUDY: Bismillah Taqee Institute of Health Sciences and Blood Diseases Centre from September 1999 to June 2004. PATIENTS AND METHODS: Patients with haematological malignancies were included who had received allogeneic PBSC transplantation of Filgrastim (rhG-CSF) mobilized peripheral blood stem cells from HLA-identical siblings (except one 5/6 antigen sibling) with Busulphan and Cyclophosphamide standard conditioning therapy in all patients. No patient received antibiotics for gut decontamination. Empirical antibiotics included Ceftriaxone and Amikacin for febrile neutropenia, oral Itraconazole for antifungal prophylaxis while oral acyclovir was used for antiviral prophylaxis. All donors and recipients were CMV IgG positive Cyclosporin A / Methotrexate were given for graft versus host disease (GvHD) prophylaxis. Stem cells were harvested using Haemonetics MCS+ cell separator. All patients received G-CSF starting from day +4 until their neutrophil count rose to normal. RESULTS: There were 21 patients with age range of 8-38 years and male to female ratio of 2:1. Engraftment was achieved in all patients; median time to absolute neutrophil count of > 0.5 x 10(9)/l was 10 days (range 8 - 12 days) and platelet count of > 20 x 10(9)/l was 14 days (12-17 days). Acute graft versus host disease ( aGvHD) was seen in 7 patients; one patient had grade IV skin and hepatic GvHD; another patient had grade III gut GvHD, grade II GvHD was seen in 3 patients while grade I skin aGvHD was seen in 2 patients. Median hospital stay was 34 days. Treatment related mortality was seen in 3 patients (18%). Chronic GvHD was seen in 5 patients. Four more patients died during the follow-up period. Malaria was seen in 2 while tuberculosis developed in one case. Relapse was seen in 2 patients. The estimated probability of survival at one hundred day, at one year and five years was 82, 47 and 40 percent respectively. CONCLUSION: Haematopoietic stem cell transplant programme can be developed in a developed country setting. Post transplant complications are similar to what have been reported in the developed countries. In endemic areas malaria could prove to be fatal if not recognised and treated early.

Allogeneic peripheral blood stem cell transplantation for aplastic anaemia: a single centre experience.

OBJECTIVE: To assess the feasibility of stem cell transplantation in local setting. SETTING: A tertiary care haematology centre. STUDY DESIGN: This is a single centre retrospective analysis of the outcome of allogeneic peripheral blood stem cell transplantation for severe aplastic anaemia. OBJECTIVES: Preliminary data on stem cell transplantation in Pakistan. PATIENTS AND METHODS: Aplastic anaemia is an uncommon disorder with a high mortality without treatment. Immunosuppression and bone marrow transplantation remains the mainstay of treatment. Stem cell transplantation facility became available in Pakistan in 1999, since then both allogeneic and autologous procedures are carried out for severe aplastic anaemia, b-thalassaemia major and haematological malignancies. Between April 2000 and July 2002, 20 allogeneic peripheral blood stem cell transplants were carried out for aplastic anaemia from HLA identical siblings. Donors were primed with G-CSF 10 mcg/kg/day subcutaneously for 4 days; stem cells were harvested on 5th day using Haemonetics MCS+ cell separator. Cyclophosphamide was used for conditioning; cyclosporin A and methotrexate were given for graft versus host disease prophylaxis. RESULTS: Eighteen out of 22 patients survived transplant in a follow up period of 788 days. The causes of death were intra-cranial haemorrhage on day +7, herpes encephalitis on day +180, graft failure and mucour mycosis on day +353 and TB meningitis on day +544. Allogeneic peripheral blood stem cell transplantation resulted in 81% event free survival in our hands. CONCLUSION: Allogeneic peripheral blood stem cell transplantation is feasible and life saving in an otherwise fatal disorder. This could be carried out effectively in Pakistan.

Peripheral blood stem cell transplantation in children with beta-thalassemia major.

OBJECTIVE: To share the preliminary data on stem cell transplantation in Pakistan. DESIGN: This is a single center retrospective analysis of the outcome of allogeneic peripheral blood stem cell (PBSC) transplantation in b-thalassemia major patients. PLACE AND DURATION OF STUDY: Bismillah Taqee Blood Diseases Centre, Karachi; a tertiary care hematology center from September 1999 to September 2002. PATIENTS AND METHODS: Twelve patients with b-thalassemia major received allogeneic PBSC transplantation from HLA identical sibling donors except in one case where mother was the donor. All patients received busulphan and cyclophosphamide conditioning therapy and cyclosporin A/methotrexate for graft versus host disease (GVHD) prophylaxis. Donors were primed with G-CSF for 4 days and stem cells were harvested using Haemonetics MCS + cell separator on 5th day. All patients received G-CSF starting from day + 4 until their neutrophil count rose to normal. RESULTS: Engraftment was achieved in all patients except one who required a second dose of bone marrow graft on day +21. Median time to achieve absolute neutrophil count of > 0.5 x 10(9)/l was 9.0 days (range 8-31 days) and platelet count of > 20 x 10(9)/l was 14 days (12-35 days). Acute GVHD was seen in 3 patients, one patient had grade IV gut GVHD; another patient had grade III gut GVHD while third patient had grade II skin GVHD. Median hospital stay was 29 days. Six patients were well and transfusion independent 3 to 36 months posttransplant. One episode of primary graft failure required a second dose of bone marrow harvest. Another episode of graft rejection received two doses of donor lymphocytes infusion. There were 4 deaths due to grade IV gut GVHD because of uncontrolled systemic Candida infection and one due to hepatic veno-occlusive (VOD) disease. CONCLUSION: Allogeneic peripheral blood stem cell transplantation can be safely and economically carried out in Pakistan. Although there had been 4 deaths during 36 months follow-up, with increasing understanding and experience the outcome is expected to improve.