Octreotide for acute variceal bleeding

OBJECTIVE: To review the use o f octreotide for acute variceal bleeding. DATA SOURCES: Articles were obtained through computerized searches involving MEDLINE (from 1997 to October 2000). Additionally, several textbooks containing information on the diagnosis and management of acute variceal bleeding were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: All randomized studies and pharmacoeconomic evaluations that used octreotide therapy for acute variceal bleeding were considered. Randomized controlled trials and meta-analyses involving other therapies for treating variceal bleeding were also reviewed for possible inclusion. DATA EXTRACTION: The primary outcomes extracted from the literature were persistent or recurrent bleeding, need for endoscopic intervention or balloon tamponade, and mortality. DATA SYNTHESIS: Although both endoscopic therapies and medications are used to control bleeding and rebleeding episodes, the endoscopic approach has the additional goal of obliterating the varix. Since rebleeding episodes are common as long as the varix is present, endoscopic and medication therapies cannot be considered interchangeable based on bleeding control alone. However, octreotide by continuous intravenous infusion has demonstrated effectiveness in reducing blood loss and transfusion requirements as both an initial intervention (until definitive sclerotherapy can be performed) or as adjunctive therapy to endoscopic measures. Octreotide can be started quickly, has a relatively rapid onset of action, and does not require someone with endoscopy training to initiate. Additionally, octreotide is relatively free of significant adverse effects. CONCLUSIONS: While additional investigations are needed, particularly in the area of pharmacoeconomics, there is substantial evidence that octreotide is an efficacious therapy with relatively few adverse effects when used in the management of acute variceal bleeding.     

Bacterial joint infections in England and Wales: analysis of bacterial isolates over a four year period

Data from 1158 cases of septic arthritis reported to the Public Health Laboratory Service (PHLS) Communicable Disease Control Centre (CDSC) from England and Wales over a 4 yr period (January 1990 December 1993) are presented. Reports where a bacterial organism was isolated from synovial fluid, or where an organism was isolated from blood cultures where a diagnosis of septic arthritis was reported, were examined. Reports of infection were more common in children (12.7% of infections were in the under 10 age group) and the elderly (54.7% aged 60 or over), and were higher in males in all age groups except in the elderly. The most common causative organisms remain staphylococcal and streptococcal species, comprising 40.6% (470) and 28% (324) of cases, respectively. The most common streptococci seen were Streptococcus pneumoniae and Lancefield group A beta-haemolytic Streptococcus organisms, 60.8% (197/324), although group B, C and G organisms accounted for 33.6% of streptococcal isolates (109/324). Haemophilus influenzae septic arthritis is not exclusive to children as 23.2% (16- 69) of cases occurred over the age of 15. A total of 48% (635) of isolates were identified from both synovial fluid and blood cultures, 32.6% (378) from joint fluid alone and 12.5% (146) from blood cultures. Although this study excludes cases of septic arthritis where no organism was isolated, it presents important bacteriological information from a large number of isolates from England and Wales over a 4 yr period. Risk factors identified include a joint prosthesis, joint disease/connective tissue disorder. immunosuppression and diabetes.      

Absence of human T-cell lymphotropic virus type I coinfection in human immunodeficiency virus-infected hemophilic men

Concern for transmission of human T-cell lymphotropic virus, type 1 (HTLV-1) infection to recipients of infected cellular blood products has prompted development of tests to eliminate blood units with HTLV-I antibodies. Most hemophilic men from the United States became infected with human immunodeficiency virus (HIV) before HIV donor screening and before blood products were processed to inactivate the virus. To assess whether these men might also be infected with HTLV-I, we examined the HTLV-I antibody status of 127 factor VIII (hemophilia A) recipients and 71 factor IX (hemophilia B) recipients. One HIV-seronegative and four HIV-seropositive persons were HTLV-I reactive by enzyme-linked immunosorbent assay (ELISA). Four of five ELISA-reactive serum samples were negative by HTLV-I immunoblot assay (IB); 1 reactive and 1 borderline reactive serum were indeterminate on IB (p19 reactivity), but negative by radioimmunoprecipitation assay (RIPA). Peripheral blood mononuclear cells from one patient with indeterminate HTLV-I IB were negative for HTLV-I genomic sequences by polymerase chain reaction. The other indeterminate patient's serum antibody pattern was stable over a 2-year period, suggesting this was not an instance of early HTLV-I seroconversion. These results reaffirm the safety of factor components in the United States with regard to HTLV-I but emphasize the importance and need for further testing of reactive HTLV-I ELISA results with a second more specific technique.     

Transformed T lymphocytes infected by a novel isolate of human T cell leukemia virus type II

Human T cell leukemia virus type II (HTLV-II) has been isolated from a patient (Mo) with features of leukemic reticuloendotheliosis (LRE) and from a patient with acquired immunodeficiency syndrome (AIDS). We have obtained another isolate of HTLV-II from a patient (CM) with severe hemophilia A, pancytopenia, and a 14-year history of staphylococcal and candidal infections but no evidence of T cell leukemia/lymphoma, AIDS, or LRE. Fresh mononuclear cells and cultured lymphocytes from CM express retroviral antigens indistinguishable by molecular criteria from HTLV-IIMo. Leukocyte cultures from CM yield hyperdiploid (48,XY, +2, +19) continuous lymphoid lines; human fetal cord blood lymphocytes (CBL) are transformed by cocultivation with these CM cell cultures but retain normal cytogenetic constitution. Electron microscopic examination of the CM cultures and transformed CBL reveals budding of extracellular viral particles, intracellular tubuloreticular structures, and viral particles contained within intracellular vesicles. CM cell cultures and the transformed CBL do not require exogenous interleukin 2, have T cell cytochemical features and mature T helper phenotypes, and exhibit minimal T helper and profound T suppressor activity on pokeweed mitogen-stimulated differentiation of normal B cells. These characteristics, which are similar to those observed with the first HTLV-II isolate, may represent properties of all HTLV-II-infected T cells.     

Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG- 2 hepatoma cell line

Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme- linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF- alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.     

Metabolic and energy balance in small- and appropriate-for-gestational-age, very low-birth-weight infants

This study compared nutrient utilization and postnatal weight gain composition in eight appropriate for gestational age (AGA: birth weight 1293 ± 107 g; gestational age 28.8 ± 1.4 weeks) and eight symmetrically growth-retarded (SGA: birth weight 1110 ± 230 g; gestational age 32.7 ± 1.9 weeks), very low-birth-weight (VLBW) infants. There was no significant difference in protein, mineral and energy intake between AGA and SGA infants. Nitrogen absorption (84 ± 3 and 83 ± 4%) and nitrogen retention (356 ± 48 and 352 ± 43 mg/kg/day) were similar in both groups. Fat absorption tended to be lower in AGA (78 ± 15%) than in SGA (87 ± 4%) infants. Calcium, phosphorus and magnesium absorptions were similar in AGA and SGA infants. Metabolizable energy utilization was similar in both groups; about 55% was expended and 45% stored in new tissues. Energy expenditure was 58 ± 4 kcal/kg/day in SGA infants and 61 ± 9 kcal/kg/day in AGA infants. Weight gain and its composition were similar in both groups. We conclude that nutrient and energy utilization are similar in AGA and symmetrically growth-retarded, VLBW infants.