Role of the C-C chemokine receptor-2 in a murine model of injury-induced osteoarthritis.

OBJECTIVE: We previously found in our embryonic studies that proper regulation of the chemokine CCL12 through its sole receptor CCR2, is critical for joint and growth plate development. In the present study, we examined the role of CCR2 in injury-induced-osteoarthritis (OA). METHOD: We used a murine model of injury-induced-OA (destabilization of medial meniscus, DMM), and systemically blocked CCR2 using a specific antagonist (RS504393) at different times during disease progression. We examined joint degeneration by assessing cartilage (cartilage loss, chondrocyte hypertrophy, MMP-13 expression) and bone lesions (bone sclerosis, osteophytes formation) with or without the CCR2 antagonist. We also performed pain behavioral studies by assessing the weight distribution between the normal and arthritic hind paws using the IITS incapacitance meter. RESULTS: Testing early vs delayed administration of the CCR2 antagonist demonstrated differential effects on joint damage. We found that OA changes in articular cartilage and bone were ameliorated by pharmacological CCR2 blockade, if given early in OA development: specifically, pharmacological targeting of CCR2 during the first 4 weeks (wks) following injury, reduced OA cartilage and bone damage, with less effectiveness with later treatments. Importantly, our pain-related behavioral studies showed that blockade of CCR2 signaling during early, 1-4 wks post-surgery or moderate, 4-8 wks post-surgery, OA was sufficient to decrease pain measures, with sustained improvement at later stages, after treatment was stopped. CONCLUSIONS: Our data highlight the potential efficacy of antagonizing CCR2 at early stages to slow the progression of post-injury OA and, in addition, improve pain symptoms.

Pulmonary bone marrow embolism in sickle cell disease.

We report an unusual lethal complication of sickle cell anemia. The patient was admitted with a diagnosis of acute chest syndrome and died shortly after that of respiratory failure. Autopsy revealed numerous deposits of bone marrow hematopoietic tissue occluding the microvascular circulation of the lung. Many causes of acute chest syndrome in sickle cell anemia have been identified, including bone marrow infarction leading to embolism of bone marrow fat. However, the release of bone marrow hematopoietic tissue leading to pulmonary vascular occlusion is not generally recognized premortem by treating physicians.

Etiology, diagnosis, and treatment of tendonitis: an analysis of the literature.

Tendonitis is a common diagnosis in sports medicine. The traditional view of tendonitis is a tendon injury resulting from repetitive mechanical load with a subsequent inflammatory response. The English literature from 1966 to the present on the etiology, diagnosis, and treatment of tendonitis was evaluated. There is some scientific support in the literature for the diagnosis of tenosynovitis and tendinosis as a pathologic entity. Actual inflammation of tendon tissue consistent with tendonitis has not been seen clearly in patho-anatomic studies. Conclusive evidence confirming that repetitive mechanical load is a major etiologic factor could not be found. Similarly, strength deficits, inflexibility, and improper equipment have not been studied in a controlled prospective manner. Other factors such as age and tendon vascularity have been consistently correlated with these injuries although their overall importance remains difficult to assess. There are no controlled studies on treatment through physical therapy aimed at flexibility and/or strengthening. Treatment with anti-inflammatory drugs has been studied extensively. However, only nine of 32 studies are prospective and placebo controlled. Some pain relief was found in five of the nine controlled studies, but healing of the tendon problem was not studied in these short follow-up studies. Twenty-three studies on steroid injections were found. Eight were prospective and placebo controlled studies, with three showing beneficial effects of the injection at follow-up. It was concluded that much of the pathology and etiology of tendonitis remains unclear. The possibility must be considered that current treatment methods may not significantly affect the natural history.

Successful treatment of lymphomatoid granulomatosis using cyclosporin-A after failure of intensive chemotherapy.

We report the successful and maintained response of lymphomatoid granulomatosis using a new approach to therapy, cyclosporin-A, after failure of aggressive multiagent chemotherapy.

Early development of acute myelogenous leukemia following kidney transplantation: possible role of multiple serum cytokines.

We report a patient who at the time of kidney transplantation for polycystic kidney disease was found to have an enlarged inguinal lymph node which later demonstrated evidence of extra medullary granulopoiesis. During the first two weeks following kidney transplantation, a striking leukemoid pattern developed and 2 months after transplant the patient was diagnosed with acute myelogenous leukemia (AML). Retrospective analysis of peripheral blood cytokines over this time revealed elevated levels of GMCSF and gamma IFN at the time of peak peripheral blood WBC with subsequent peaks in IL-4, IL-6 and IL-2 as the peripheral blood WBC fell. A rise in levels of TNF alpha also preceded the peripheral blood WBC rise (although these concentrations were at or below those following uncomplicated kidney transplants). The clinical course of AML in this patient was marked by relentless relapse despite chemotherapy. The possibility of cytokine facilitated tumor growth is discussed.

Cancer in the elderly patient. Unique aspects of presentation, management and screening.

The high incidence of cancer in the rapidly expanding geriatric population presents a major challenge to the health care field. Since most cancers present and behave similarly in both older and younger persons, similar approaches to management must be considered in both. The elderly, however, are a heterogeneous group with individuals demonstrating varying degrees of comorbidity and physiologic change. Decisions, therefore, should be based on a sound knowledge of geriatric assessment and the factors important for "successful" aging rather than on chronological age alone.

The relapse of hairy cell leukemia after a 32-year remission.

The optimum therapy for hairy cell leukemia (HCL) is controversial. Dramatic responses to interferon-alpha and 2'-deoxycoformycin overshadow the established role of splenectomy in HCL, and patients currently can avoid surgery altogether. A case is presented of clinical remission lasting 32 years after splenectomy--a prolonged normal life, without medication or medical intervention. When relapse occurred, the patient's response to interferon-alpha was prompt and predictable. Prognostic variables are an important consideration at the time of diagnosis in predicting the response to splenectomy.

Monocyte phagocytic activity in sickle cell disease.

The phagocytic activity of peripheral blood monocytes from sickle cell disease patients and normal controls was studied using a monocyte monolayer assay. Phagocytosis of antibody-coated red cells by monocytes from patients in stable condition and in normal controls did not differ significantly (7.1 +/- 1.5 vs. 5.3 +/- 0.9%). However, monocytes from sickle cell disease patients during vasoocclusive crises demonstrated increased phagocytic activity compared to the normal controls (11.0 +/- 2.7 vs. 5.3 +/- 0.9%, p less than 0.025). Numerous defects in immune response have been described in association with sickle cell disease. However, monocyte phagocytic activity is not deficient and is not a factor in the predisposition to infections.

Pure red cell aplasia due to parvovirus B19 infection in a man with HIV infection.

Infection by parvovirus B19 is common and may become chronic if the patient is immunocompromised, leading to persistent erythroid hypoplasia. Parvovirus should be added to the list of pathogens that can complicate the course of HIV infection and should be considered in the evaluation of severe anemia or red cell aplasia in any immunocompromised patient.

Spontaneous remission of acute leukemia after the termination of pregnancy.

A 28-year-old woman in the third trimester of her pregnancy was found to have acute myelocytic leukemia. The baby was delivered by Cesarean section and her leukemia underwent spontaneous remission. However, 3 months later, she presented with massive painful leukemic infiltration of the breasts as initial manifestation of relapse, followed by systemic symptoms of leukemia. In vitro culture of the leukemic cells demonstrated characteristics of macrophage cell line. This case illustrates a unique sequence of events: spontaneous remission after the termination of pregnancy, which has profound hormonal alterations, and relapse in a very hormone-sensitive organ, the breast, a few months later when the hormonal milieu was resumed. This suggests hormonal dependence of her leukemic cells and potential for hormonal manipulation in a certain subset of human leukemia.

Danazol therapy renders red cells resistant to osmotic lysis.

Danazol, an attenuated androgen, is useful in endometriosis, idiopathic thrombocytopenic purpura (ITP), and autoimmune hemolytic anemia (AIHA). However, its mechanism of action is unknown. We investigated the possibility that danazol affects cell membranes directly. Red cell osmotic fragility was studied in patients receiving danazol. A significant decrease in osmotic fragility was observed. Accompanying the change, peripheral blood smears showed many target cells and electron microscopy revealed extra folds in erythrocyte membranes. Twenty-two patients were studied prospectively before and after danazol. Osmotic fragility decreased significantly (P less than 0.001) in 1 month of therapy and progressed with further treatment. A rebound increase (P less than 0.01) was observed in 1 month after discontinuation of danazol among 16 patients. Incubation experiments showed that danazol-induced changes are not reversed with normal sera. Patient sera did not induce the changes in normal red cells. Danazol in vitro protected red cells from osmotic lysis at low concentrations but enhanced lysis at high concentrations. We suggest that danazol alters red cell membranes directly to increase their surface area, inducing target cell formation and increasing their resistance to osmotic lysis.

SCUBA tank corrosion as a cause of death.

Corrosion of compressed air breathing tanks may result in dangerous oxygen depletion. In every SCUBA mishap the residual air should have, as one of the tests, a measurement of oxygen content. The tank should also have a visual inspection. All compressed air breathing tanks should have a routine visual inspection on a regular basis, even if the tank is made or lined with corrosion resistant material.