The role of coagulation disorders in patients with retinal vein occlusion.

BACKGROUND: The role of a hypercoagulable state in the pathogenesis of retinal vein occlusion (RVO) has not been conclusively established. AIM: To analyse the prevalence of thrombophilia in RVO. DESIGN: Prospective case-control study. METHODS: All the patients diagnosed with RVO were referred to an Internal Medicine clinic and compared with sex- and age-matched individuals from a population-based cohort. Demographic, clinical and laboratory variables (including a thrombophilia panel) were analysed. RESULTS: One hundred and seventy patients (93 men and 77 women; 68 ± 11 years) and 170 controls (80 men and 90 women; 67 ± 10 years) were included. RVO was peripheral in 113 cases. Genetic thrombophilia was detected in 13% of patients. Acquired thrombophilia was observed in 10% of cases and 4.7 % of controls (P < 0.01). Sixty-three percent of cases and 24.6% of controls had serum hyperhomocysteinemia (odds ratio [OR] 5.2, IC 95% 2.7-10.1; P < 0.0001) : In RVO patients aged <50 years (n = 11), 36.4% had genetic thrombophilia (P = 0.04), as well as 50% of those without vascular risk factors (n = 18; P = 0.01). Forty-one (24%) patients with RVO received antiplatelet agents and 13 (7.6%) were on anticoagulants due to preexistent atrial fibrillation. CONCLUSIONS: We suggest that, in patients with RVO, hyperhomocysteinemia and antiphospholipid syndrome should be ruled out. Moreover, a study of genetic thrombophilia should only be considered in those aged <50 years or without cardiovascular risk factors. Antiplatelet therapy with aspirin is probably the treatment of choice of RVO, to reduce the overall vascular risk. Anticoagulation should only be considered in patients with high-risk thrombophilia.

Complete response in severe thrombotic microangiopathy post bone marrow transplantation (BMT-TM) after multiple plasmaphereses.

A 44-year-old male with Ph+ chronic myeloid leukaemia (CML) underwent histoidentical allogeneic bone marrow transplantation 18 months after initial diagnosis. He received pretransplant conditioning with busulphan and cyclophosphamide (Bucy). GVHD prophylaxis consisted of methotrexate, cyclosporine (CsA) and methylprednisolone. On day +50, he developed a microangiopathic haemolytic anaemia with indirect bilirubinaemia, 10% fragmented red cells (FC) and an elevated LDH (1213 U/l: normal range 100-185 U/l). Clinical symptoms consisted of edema and hypertension. The patient was not febrile and had no neurological changes. A clinical diagnosis of severe (grade 4) multifactorial (acute GVHD, CMV infection and cyclosporine) BMT-TM was made. He responded following 19 plasma exchanges with replacement with fresh frozen plasma.

The first report of familial adult T-cell leukemia/lymphoma in Argentina.

Here we describe two Caucasian brothers who developed adult T-cell leukemia/lymphoma (ATLL), within a short period of time. These two patients have never left Argentina. Their parents are dead and according to the family history it is possible that the mother may have been affected by spastic paraparesis. The daughters reported that their mother had suffered from increasing difficulty in walking for many years which finally made it impossible for to her walk. There are no other data to support the presumptive diagnosis. One of the patients presented with acute disease while the other had a lymphoma type disorder. Both were positive for HTLV 1. The first patient died with disease progression ten months after diagnosis and the second is in partial remission 13 months after diagnosis. Immunophenotyping showed CD4+, CD5+, CD3+, CD2+, CD8 (-). Two asymptomatic brothers with positive HTLV 1 serology were detected. This is the first family case that has been reported in Argentina.

Graft versus host disease in autologous stem cell transplantation.

Relapse remains the major cause of mortality in haematological malignancies treated with autologous stem cell transplantation (ASCT). Graft versus tumour reaction (GVT) associated to autologous graft versus host disease (GVDH) may contribute to eliminate minimal residual disease (MRD) after ASCT. Eighty patients with several diagnostics were submitted to ASCT. After stem cell infusion, patients randomised in 4 groups. Groups were treated as follows: Group A received either a IFN (alpha Interferon--1,000,000 U/d), Cyclosporine A (CSA--1 mg/-kg/d intravencus) for 28 days, and granulocyte-macrophage colony stimulating factor (GM-CSF-250/m2/d) until engraftment; B: CSA (same dose and way) and GM-CSF; C: CSA (1 mg/kg/d orally) and GM-CSF and D: only GM-CSF. Patients were inspected daily and if skin rash was detected, a skin biopsy was obtained at that moment, otherwise biopsies were obtained at day 21 after ASCT. GVHD was positive in 23 patients (13 from group A and 10 from group B). All cases were grades I and II. A majority of CD4+ T lymphocytes was seen in skin infiltrates. No significant differences were seen in WBC and platelets engraftment times, antibiotic administration or hospitalisation days required among the four groups. With a median follow up of 18 months, there were no differences in disease free survival (DFS) or overall survival (OS) between the patients who developed GVHD and the others. However, considering that myeloma cells do not express antigen MCH II, which is necessary for GVT effect, we excluded patients with multiple myeloma (MM) from survival analysis, thus obtaining a significant difference in OS results between patients who developed GVHD and those in whom this reaction was not observed (81% vs 58% p:0.05). We conclude that pharmacological induction of GVHD in ASCT is possible with CSA administration (1 mg/kg/d i.v.). Development of GVHD showed a better outcome for patients in our study except for those patients with MM. This results must be confirmed by a longer follow up of our patients and further studies.

[Changes in bone mass in hepatic cirrhosis, chronic obstructive pulmonary disease, insulin-dependent diabetes, and primary hyperparathyroidism]. / Modificaciones de la masa ósea en la cirrosis hepática, la enfermedad pulmonar obstructiva crónica, la diabetes dependiente de la insulina y el hiperparatiroidismo primario.

BACKGROUND: Liver cirrhosis, chronic obstructive pulmonary disease (COPD), insulin-dependent diabetes mellitus and primary hyperparathyroidism are frequent diseases which are considered as risk factors for the development of osteoporosis. However, review of the literature has shown that the studies published on the aforementioned are far from conclusive. METHODS: By double energy X-ray absorptiometry the bone mineral density (BMD) of the lumbar spine and neck of the femur were determined in 29 patients with liver cirrhosis, 92 with chronic obstructive pulmonary disease (59 treated with corticoids), 81 with insulin-dependent diabetes mellitus and 30 primary hyperparathyroidism (7 operated). RESULTS: Cirrhotic patients had a normal BMD in both localizations. In patients with COPD, without corticoids, a decrease of 6% was found in the spine and or 13.5% in the neck of the femur while in patients with COPD with corticoids the decrease was of 12% and 7% respectively. Diabetic patients had normal BMD in the spine and a decrease of 6% in the neck of the femur and in patients with hyperparathyroidism a decrease of 6% and normality were found, respectively. CONCLUSIONS: The repercussion of cirrhosis, insulin-dependent diabetes, and primary hyperparathyroidism on bone mineral density is nul or slight. In patients with chronic obstructive pulmonary disease treated with corticoids decrease in density of the spine is approximately that of a standard deviation. In patients with the latter not treated with corticoids a similar decrease is found in the neck of the femur.

[Treatment of gram negative bacilli bacteremia with intramuscular ceftriaxone in home care]. / Tratamiento de bacteriemias por bacilos gramnegativos con ceftriaxona intramuscular en hospitalización domiciliaria.

BACKGROUND: Bacteremias by gram negative bacilli (BGNB) are serious diseases which normally require hospital admission. In accordance with the pharmacokinetic characteristics of ceftriaxone, the possibility of treating such processes with home care (HC) and the existence of advantages for both the patient and the hospital were evaluated. METHODS: Twenty patients were prospectively studied. Upon obtaining clinical stability in the hospital the possibility of following home care (HC) treatment was evaluated. Ceftriaxone was administrated at intramuscular doses of 1g/24 h. The clinical and bacteriologic response, patient satisfaction and treatment time were estimated. RESULTS: The origin of the bacteremia was varied as was the type of gram negative bacilli responsible. All the patients evolved favorably with no relevant secondary effects. The mean length of treatment was 12.75 days per patient. The antibiotic was mainly administered at home (83%), permitting a mean reduction of 10.5 hospital stays per patient. The social and psychologic advantages for the patients were evident. CONCLUSIONS: This study confirms the possibility of treating stable phase gram negative bacilli bacteremias at home efficiently with the supervision of home care teams leading to a substantial reduction in hospital expenses and patient satisfaction.

[Different behavior of bone turnover markers in endocrine (extrinsic) and structural (intrinsic) osteopathies]. / Diferente comportamiento de los marcadores del recambio óseo en las osteopatías endocrinológicas (extrínsecas) y en las estructurales (intrínsecas).

Alkaline phosphatase, osteocalcin and hydroxyproline levels were evaluated in patients with the following conditions: primary hyperparathyroidism, renal dialysis, hyperthyroidism, Cushing's syndrome, long term corticosteroid therapy, Paget's disease, osteoblastic metastases, osteolytic or mixed metastases, and nutritional osteomalacia. In all cases the levels of the three substances were increased, with the following exceptions: a) in endogenous or exogenous hypercortisolism states osteocalcin level was reduced and those of alkaline phosphatase and hydroxyproline were unchanged; and b) in blastic or lytic metastases osteocalcin level was unchanged. In general, alkaline phosphatase and hydroxyproline levels had a higher sensitivity than those of osteocalcin in structural bone disease (Paget's disease, blastic or lytic metastases), whereas the converse was true for endocrine bone disease (the remaining conditions except osteomalacia, which is mixed, both structural and endocrine; in this syndrome, the three substances showed the same sensitivity.

[Effect of active metabolites of vitamin D on manifestations of primary hyperparathyroidism]. / Influencia de los metabolitos activos de la vitamina D en las manifestaciones del hiperparatiroidismo primario.

We have evaluated the serum levels of 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1.25-OHD) in 33 patients with primary hyperparathyroidism and normal renal function, relating them with the clinical expression of the disease and other biochemical parameters. The level of 1.25-OHD of the patients was significantly higher than in healthy controls [51 +/- 18 vs 36 +/- 10 pg/ml (122 +/- 43 vs 86 +/- 24 pmol/l), p less than 0.001], although it was higher than the upper limit of the normal range in only 36% of patients. By contrast, the level of 25-OHD was diminished [11.0 +/- 6.3 ng/ml (27.5 +/- 15.7 nmol/l) in the patients and 19.9 +/- 10.5 ng/ml (49.7 +/- 26.2 nmol/l) in the controls, p less than 0.01]. A positive correlation was found between PTH and 1.25-OHD (r = 0.40, p less than 0.05) and a negative one between PTH and 25-OHD (r = -0.40, p less than 0.05). Calcemia was correlated with PTH (r = 0.77, less than p 0.001) but not with 1.25-OHD (partial r = 0.22). There was no correlation between vitamin D metabolites and calciuria, nor between the former and the biochemical indexes of bone remodelling. There were no significant biochemical differences between patients with renal calculi and those without them. It was concluded that PTH level appears as the major determinant factor of 1.25-OHD serum level. The serum level of vitamin D metabolites does not seem to clearly influence calcemia, calciuria, bone remodelling or the development of calculi.

[Bone marrow transplantation in chronic myeloid leukemia]. / Transplante de médula ósea en leucemia mieloide crónica.

Chronic Myelogenous Leukemia (CML) is an oncohematological disease characterized by a clonal proliferation concerning the primitive hematopoietic cell. A typical cytogenetic alteration known as Philadelphia Chromosome (Ph1), a 9:22 chromosomic translocation which produces a hybrid gene BCR/ABL, is present in 95% of the patients. Nineteen CML patients (9 female and 10 male) underwent Bone Marrow Transplantation (BMT). Median age was 32 years (range 9 to 47); 15 of them were in chronic phase (CP), and 4 in accelerated phase (AP). At diagnosis, all patients were Ph1+, BCR/ABL+. The conditioning regimen consisted of busulphan and cyclophosphamide while patients in AP received etoposide as well. Seventeen patients received cyclosporine A, methotrexate and methylprednisone as prophylaxis for Graft Versus Host Disease (GVHD) while 2 patients received only the first two drugs. The 9.22 translocation was determined by means of RT-PCT technique using the primers NB1+, Abl3, B2A, CA3 and A2. The sensitivity of the method was 1 x 10(-6). Among the 19 patients who entered the protocol, 14 are alive and in clinical, hematological and cytogenetic remission (Ph1-) and 3 patients died due to acute GVHD, 1 due to graft failure and 1 due to Hemolytic Uremic Syndrome. Of the 4 transplanted patients in AP, 3 are alive and in complete remission. The patients had a 74% survival, with a median follow-up of 655 days. Complete hematopoietic chimerism was demonstrated in 16 patients, with the study of 3 loci, D1S80, APO B and D17S30. No relationship was found between post BMT hybrid BCR/ABL (RT.PCR) persistence and disease relapse; the presence of acute and/or chronic GVHD did not influence the BCR/ABL positivity. In our experience, BMT has proved to be the only therapeutic alternative for CML with complete clinical, hematological and cytogenetic remission and a mean survival of 74%, comparable to the international experience.

[Differential factors of tumor etiology for iron deficiency anemia of probable gastrointestinal origin]. / Factores diferenciales de etiología tumoral de la anemia ferropénica de probable origen digestivo.

BACKGROUND: Diagnosis of iron deficiency anemia (IDA) of probably gastrointestinal (GI) tract origin is a difficult task for the clinician. OBJECTIVE: To know the incidence of GI lesions in our setting; the possibility to predict cancer with clinical and laboratory parameters; the diagnostic utility of capsule endoscopy, and the follow-up in those patients. PATIENTS AND METHOD: We performed a prospective study in our Internal Medicine Department, from April 2005 to December 2007, of patients with IDA. RESULTS: A total of 129 patients (42 men, 87 women) were studied. There was 27 (20.9%) malignancies (21 colon, 5 stomach, 1 esophagus ); 39 (30.2%) benign upper GI lesions; 12 (9.3%) benign lower GI disorders; 16(12.4%) synchronous GI lesions; 2 (1.6%) celiac sprue, and 33 (25.6%) without identifiable lesions. We found significant differences between patients with and without malignancy in NSAID use, weight loss, leukocyte and platelet count, and alkaline phosphatase levels. Diagnosis sensitivity of capsule endoscopy in obscure GI bleeding was 27%. We did not found any malignancy during the follow-up of patients without an initial diagnosis. CONCLUSIONS: In IDA, colonoscopy (or contrast barium enema in certain circumstances) is the most important exploration to rule out malignancy. Only NSAID use is useful to exclude cancer. Patients without identifiable lesions have a favorable prognosis. A moderate frequency of synchronous lesions was found. We recommend a complete conventional GI endoscopic study if no evident bleeding lesion is found during the initial endoscopic procedure. Capsule endoscopy and celiac disease serology are useful in obscure gastrointestinal bleeding.

Cytokine production by peripheral blood cells in postmenopausal osteoporosis.

It has been suggested that the release of cytokines with bone-resorbing activity from cells of the immune system might have a role in the pathogenesis of osteoporosis. We measured the secretion of the bone-resorbing products tumor necrosis factor, interleukin 1 beta and PGE2 by peripheral blood mononuclear cells from seven healthy postmenopausal women and 12 patients with postmenopausal osteoporosis. No differences were observed between both groups either in unstimulated cultures or in cultures activated with calcitriol, endotoxin or phorbol esters. These results give no support for a role of peripheral blood immune cells in postmenopausal bone loss.

Stress decreases the serum level of osteocalcin.

During a study undertaken to characterize the time course of the osteocalcin response to bone fractures, lower than normal values of serum osteocalcin (1.7 +/- 0.9 vs. 3.3 +/- 1.3 ng/ml, P < 0.001) were found in the basal samples (blood obtained 48-72 h after fracturing). Suspecting that such a decrease could be due to the stress response induced by the fracture, for corticosteroids are known to diminish serum osteocalcin, we extended our study to another two stressful situations of high stress: acute myocardial infarction and elective abdominal surgery. Indeed, the concentration of osteocalcin was also significantly diminished in both of these (2.0 +/- 0.9 ng/ml, P < 0.0005; 1.5 +/- 1.0 ng/ml, P < 0.0001). To further characterize this phenomenon, the time course of osteocalcin changes during the 24 h following abdominal surgery was studied in a second group of patients. The decrease was found to begin soon after surgery. In order to exclude the immobilization present in those three situations as the cause of the decrease in serum osteocalcin, a group of patients with retinal detachment was studied. Their serum osteocalcin levels were normal. It is concluded that serum osteocalcin levels decrease in stressful situations. Therefore, they should be interpreted cautiously when used as a marker of osteoblastic activity in this setting.

Vitamin D therapy modulates cytokine secretion in patients with renal failure.

In studies in vitro calcitriol (1,25-dihydroxyvitamin D3) inhibits lymphocyte proliferation and modulates several monocyte functions, including the secretion of prostaglandins and monokines. However its effects on monokine production in vivo are not known. Therefore we studied the secretion of interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF) by peripheral blood mononuclear cells (PBMC) from 7 patients on periodic hemodialysis, before and after oral treatment with calcitriol (0.5 microgram daily) for 1 month. Calcitriol therapy resulted in significant increases in the phorbol myristate acetate (PMA)-induced secretion of IL-1 and IL-6 (p = 0.04 and 0.03, respectively). This was a transient effect, observable by day 7 of therapy, but no longer evident by day 30. However, calcitriol induced a progressive reduction of TNF secretion (down to 53% of control values by day 30, p = 0.02). There were no correlations between the individual changes in calcium/PTH and cytokine release. These results show that doses of calcitriol within the therapeutic range induce marked changes in cytokine secretion by PBMC from uremic patients.

Hyperparathyroidism is responsible for the increased levels of osteocalcin in patients with normally functioning kidney grafts.

Osteocalcin or bone Gla protein (BGP) is the most abundant noncollagenous protein of the skeleton. Serum BGP levels are thought to provide a valuable index of bone formation. We measured serum BGP and other parameters of mineral metabolism in 68 patients with functioning kidney grafts. The duration of the graft ranged from 1 to 131 months (mean 23). Serum BGP was positively correlated with parathyroid hormone (r = 0.56, p less than 0.001). BGP was inversely correlated with glomerular filtration rate (r = -0.44, p less than 0.001) and with the total cumulative dose of corticosteroids received after transplantation (r = -0.26, p less than 0.05). No correlation was observed between BGP and 1,25(OH)2D, nor between BGP and serum aluminum. All patients with increased BGP in the presence of normal renal function had persistent hyperparathyroidism. The activity of the parathyroid glands and corticosteroid treatment seem to be the main pathophysiological factors influencing BGP levels after successful kidney grafting.