Intramuscular haloperidol or lorazepam and QT intervals in schizophrenia

The objective of this study was to estimate the effects of intramuscular haloperidol and lorazepam on the QT interval in volunteers with schizophrenia. Intramuscular haloperidol and intramuscular lorazepam are standard treatments in the acute management of agitation and aggression. Although prolongation of the QT interval and sequelae, including torsade de pointes and death, have been reported for haloperidol (but not lorazepam), formal studies have been lacking. Volunteers with schizophrenia (n = 12) were administered a single intramuscular injection of 7.5 mg haloperidol or 4 mg lorazepam in a blinded, randomized, placebo-controlled crossover design. Serial EKGs and concurrent blood samples were obtained over 6 hours following each injection. Changes in the QT interval were evaluated, as were plasma drug and prolactin concentrations. Haloperidol injection increased the heart rate-corrected QT interval an average of 5.1 msec using Bazett's correction (QTb 90% confidence interval [CI]: 0.3, 9.8), 3.6 msec using Fridericia's correction (QTf 90% CI: 0.02, 7.2), and 4.2 msec using an empirically derived "baseline correction" (QT(ii) 90% CI: 0.3, 8.0). Effects of lorazepam on QT were nullified by correction for the heart rate elevation (QTb 3.8 msec, 90% CI: 0.6, 7.1; QTf 0.0 msec, 90% CI: -3.2, 3.4; QTii -2.3 msec, 90% CI: -6.6, 2.0). An association between QT prolongation and occurrence of extrapyramidal symptoms was observed. On average, intramuscular haloperidol led to minimal prolongation of the QT interval. This propensity is of theoretical concern in individuals with risk factors for torsade de pointes but seems unlikely to be a problem in the vast majority of patients.     

Anticancer activity of bacteriophage T4 and its mutant HAP1 in mouse experimental tumour models

BACKGROUND: Previously, we have shown the ability of the bacteriophage T4 and its substrain HAP1 (selected for a higher affinity to melanoma cells) to reveal antimetastatic activity in a mouse melanoma model. Here, we investigated the potential phage anticancer activity in primary tumour models. MATERIALS AND METHODS: Mice were inoculated subcutaneously with B16 or LLC cells (collected from in vitro culture). Bacteriophages T4 and HAP1 were injected intraperitoneally daily (8 x 10(8)pfu/mouse, except the experiment concerning the dose-dependence). RESULTS: Treatment with purified preparations of bacteriophage T4 resulted in significant reduction of tumour size, the effect being dose-dependent. HAP1 was more effective than T4 and its activity was also dose-dependent. Parallel experiments with non-purified bacteriophage lysates resulted in significant stimulation of tumour growth. CONCLUSION: These data suggest that purified bacteriophages may inhibit tumour growth, a phenomenon with potentially important clinical implications in oncology.     

Furosemide responsiveness, non-adherence and resistance during the chronic treatment of heart failure: a longitudinal study

BACKGROUND AND METHODS: Loop diuretic therapy is an essential part of chronic systolic heart failure (CH)F management, yet response to treatment can be variable. We analysed diuretic responsiveness in 39 stable patients with CHF in the community over 2 years. We measured serum ACE as a marker of adherence to ACE inhibitor therapy and urinary furosemide as a marker of diuretic adherence and action. Patients' clinical outcome was stable and not hospitalized (Group 0); alive but hospitalized (Group 1); or dead during follow up (Group 2). RESULTS: Prescribed furosemide dose was variable (range 20-370 mg generally once daily) and progressive dose increments were common. Failed furosemide adherence (defined as < 10% of a dose excreted in 24 h urine where normal average excretion = 50% of an oral dose) during static prescribed dosing was infrequent relative to all days of therapy; yet was equally common across all outcome groups. Furosemide non-adherence appeared to be independent of non-adherence with ACE inhibitor (as marked by serum ACE activity > 20 U l(-1)) treatment. Furosemide responsiveness (mm of sodium excreted per mg furosemide in urine) showed no relationship to prescribed dose and paradoxically tended to rise in patients with higher basal aldosterone concentrations. Furosemide responsiveness fell by outcome class despite increased dose. Within-patient responsiveness remained relatively constant although highly variable between individuals. CONCLUSIONS: Furosemide responsiveness varied greatly between individuals but was constant within an individual. Non-adherence with furosemide was less common among those who died and appeared to occur at different time points from non-adherence with ACE inhibitor treatment, which was slightly more common in all outcome groups. Patients who died were prescribed higher furosemide doses and had greater furosemide excretion yet had similar sodium excretion. The main factor in response to chronic furosemide therapy was intrarenal diuretic resistance. Gross non-adherence was less important.     

Enhanced T cells interactions with extracellular matrix proteins in infertile women with endometriosis

Essential features of endometriosis involve interactions with extracellular matrix (ECM). Recent data emphasize the important role of ECM proteins in the regulation of T cell function. The aim of this study was to determine activated T cell adhesion to ECM proteins in infertile women with endometriosis. Nine women with endometriosis diagnosed by laparoscopy according to the Revised American Fertility Society classification and ten normal healthy women with a previous successful pregnancy outcome were studied. We investigated phorbol acetate myristate (PMA) or phytohemaglutinin (PHA) activated peripheral blood T cell adhesion to the following proteins of ECM: collagen IV (C-IV), elastin (E) and fibronectin (Fn). In addition, CD4, CD8, CD29, CD45RO expression on peripheral CD3(+) T cells were studied using flow cytometry. We determine that PHA-activated T cell adhesion to C-IV and Fn are significantly higher in infertile women with endometriosis when compared to normal healthy women (P<0.05). No significant differences were noted in T cell's surface antigens expression between study groups. Our data suggest the existence of disturbed T cell-ECM interactions in infertile women with endometriosis. Further studies are needed to determine the role of these abnormalities in the pathogenesis of endometriosis.     

Mutations in bacteriophage T4 genome

Bacteriophage (phage) T4 belonging to T-even phages is one of the best known phages with a completely deciphered genome sequence. As a model of living systems, T4 phage has many technical advantages. It can be very easily grown in large quantities, manipulated by classical genetics, and engineered by site-directed mutagenesis. Many substances have been first tested for mutagenicity in T-even phages. The results of these tests were very often applicable to higher organisms due to similar mechanisms of mutagenesis. T4 phage is also important in phage therapy, which represents an alternative treatment of bacterial infections since the bacterial resistance to antibiotics has become a serious medical problem. The site-directed mutagenesis is a method that enables to introduce mutations which can influence phage affinity to bacteria and can be a practical technique for enriching phage collections and for widening specificity of phages for new bacterial strains now insensitive to phage therapy.     

Postoperative complications in patients with peritonitis

One thousand three hundred and ten patients with peritonitis have undergone surgery: local limited peritonitis was in 230 patients, local unlimited--in 342, general--in 738 patients. After surgery suppuration of the wound was seen in 92 (7.1%) patients, phlegmons of the abdominal wall--in 16 (1.3%), progressive peritonitis--in 40 (3.1%), abscesses of abdominal cavity--in 13 (1.0%), eventration--in 19 (1.5%), adhesive intestinal obstruction--in 17 (1.3%). Laparoscopy was used for diagnosis of intraabdominal complications in 47 patients. This allowed to avoid unjustified laparotomies in 20 patients. Application of laparoscopy is limited by degree of bacterial contamination of peritoneal exudates. Early adhesive intestinal obstruction in 7 patients was treated with endoscopic procedure. Sonography is effective in diagnosis of intraabdominal complications, detection of site of safe puncture before postoperative laparoscopy and drainage of abscesses.