A postpartum haemorrhage package with condom uterine balloon tamponade: a prospective multi-centre case series in Kenya, Sierra Leone, Senegal, and Nepal.

OBJECTIVE: To evaluate the effectiveness and safety of an ultra-low-cost uterine balloon tamponade package (ESM-UBT™) for facility-based management of uncontrolled postpartum haemorrhage (PPH) in Kenya, Sierra Leone, Senegal, and Nepal. DESIGN: Prospective multi-centre case series. SETTING: Facilities in resource-scarce areas of Kenya, Sierra Leone, Nepal, and Senegal. POPULATION: Women with uncontrolled postpartum haemorrhage in 307 facilities across the four countries. METHODS: A standardised ESM-UBT package was implemented in 307 facilities over 29 months (1 September 2012 to 1 February 2015). Data were collected via a multi-pronged approach including data card completion, chart reviews, and provider interviews. Beginning in August 2014, women who had previously undergone UBT placement were sought and queried regarding potential complications associated with UBT use. MAIN OUTCOME MEASURES: All-cause survival, survival from PPH, and post-UBT use complications (surgery, hospitalisation, antibiotics for pelvic infection) associated with UBT use. RESULTS: 201 UBTs were placed for uncontrolled vaginal haemorrhage refractory to all other interventions. In all, 38% (71/188) of women were either unconscious or confused at the time of UBT insertion. All-cause survival was 95% (190/201). However, 98% (160/163) of women survived uncontrolled PPH if delivery occurred at an ESM-UBT online facility. One (1/151) potential UBT-associated complication (postpartum endometritis) was identified and two improvised UBTs were placed in women with a ruptured uterus. CONCLUSIONS: These pilot data suggest that the ESM-UBT package is a clinically promising and safe method to arrest uncontrolled postpartum haemorrhage and save women's lives. The UBT was successfully placed by all levels of facility-based providers. Future studies are needed to further evaluate the effectiveness of ESM-UBT in low-resource settings. TWEETABLE ABSTRACT: Evidence for ESM-UBT as a clinically promising and safe method to arrest uncontrolled PPH and save women's lives.

Cost-effectiveness of losartan-based therapy in patients with hypertension and left ventricular hypertrophy: a UK-based economic evaluation of the Losartan Intervention for Endpoint reduction in hypertension (LIFE) study.

The Losartan Intervention for Endpoint reduction in hypertension (LIFE) study demonstrated the clinical benefit of losartan-based therapy in hypertensive patients with left ventricular hypertrophy (LVH), mainly due to a highly significant 25% reduction in the relative risk of stroke compared with an atenolol-based regimen, for a similar reduction in blood pressure. The aim of this economic evaluation was to estimate the cost-effectiveness of losartan compared with atenolol from a UK national health system perspective. Quality-adjusted survival and direct medical costs were modelled beyond the trial using the within-trial incidence of stroke. Survival with stroke, study medication use and quality of life by stroke status were taken directly from the LIFE trial. The LIFE data were supplemented with UK data on lifetime direct medical costs of stroke and life expectancy in individuals without stroke. No additional stroke events or use of study treatment were assumed beyond the trial. Costs and benefits were discounted using current UK Treasury rates. In the base-case analysis, the reduction in stroke-related costs (by 968 sterling pound) offset 86% of the increase in study medication costs (1128 sterling pound) among losartan-treated patients. The incremental cost-effectiveness ratio (ICER) for losartan versus atenolol in hypertensive patients with LVH was 2130 sterling pound per quality-adjusted life year (QALY) gained (3195 Euro/QALY), and this increased to 11,352 sterling pound per QALY gained (16,450 Euro/QALY) when the costs of stroke beyond the first 5 years were excluded. Thus, the clinical benefit of losartan was achieved at a cost well within reported thresholds for cost-effectiveness.

Development and application of fluorescence polarization assays in drug discovery.

Fluorescence polarization technology has been used in basic research and commercial diagnostic assays for many decades, but has begun to be widely used in drug discovery only in the past six years. Originally, FP assays for drug discovery were developed for single-tube analytical instruments, but the technology was rapidly converted to high-throughput screening assays when commercial plate readers with equivalent sensitivity became available. This review will discuss fluorescence polarization assays in current use in drug discovery research as well as those in development that will likely be used in the near future. These assays include targets such as kinases, phosphatases, proteases, G-protein coupled receptors, and nuclear receptors.

Irish orthopaedic patients' attitudes to blood transfusion.

This study was designed in response to perceived increased public anxiety about the risks of allogenic blood transfusion. A questionnaire was completed by 203 patients attending an elective orthopaedic hospital. The questionnaire examined patients' factual knowledge about various aspects of transfusion, their attitudes to blood transfusion and confidence in the safety of blood products. Despite recent publicity, only 124 patients (61%) regarded blood transfusion as a risk for hepatitis transmission while 172 patients (85%) knew of the risk of blood transmission of HIV. 22 patients (11%) reported that they would have no concerns about receiving a blood transfusion, while at the other extreme, 9 (5%) would not be willing to receive blood under any circumstances. 162 patients (80%) felt that allogenic blood transfusion was either entirely safe or that there was an acceptable small risk associated with it. A majority of responders (109 patients, 54%) reported they would favour autologous transfusion if available. Current practices and alternatives to traditional allogenic blood transfusion are discussed in the context of elective orthopaedic surgery.

Sigmoid perforation following radiation therapy in patients with cervical cancer.

OBJECTIVE: We describe the clinical presentation, evaluation, management, and outcome of patients experiencing sigmoid perforation following radiation therapy for cervical cancer. METHODS: A database consisting of over 5000 patients with stage IB-IIIB cervix cancer treated between 1963 and 1992 revealed 35 patients with sigmoid perforation. Twenty-seven were diagnosed and managed at one institution, and they form the study group. RESULTS: The median age at the time of perforation was 50 years, and the median follow-up care was 78 months (range 6-396). The median time from completion of radiotherapy to perforation was 13 months (range 3-98). The mean interval from the first documented complaint to the index admission was 90 days. Nine (33%) of 27 patients were treated with high-dose radiation therapy. The most common complaint was abdominal pain in 25 (93%) patients, nausea occurred in 12 (44%) patients, weight loss in 12 (44%) patients, and vomiting in 10 (37%) patients. The pain was described as mild in 16 (73%) of 22 patients. Only 5 (18.5%) of 27 patients had physical signs of acute peritonitis, 8 (30%) of 27 patients had some form of tenderness, and 11 (41%) of 27 had a benign exam. A total of 20 (74%) patients had an abdominal radiograph, and 12 (44%) patients had a contrast enema for evaluation. Evidence of perforation was present in 5 (25%) of 20 plain abdominal radiographs and 1 (8%) of 12 contrast enemas. Following admission, 17 (63%) patients were observed initially with subsequent surgery after symptoms either failed to resolve or worsened. The median duration under observation was 4 days (range 1-23). Surgery was performed immediately in 8 patients (30%), and 2 (7%) were observed without operation. In these 2 patients, perforation was diagnosed postmortem. Seventeen (68%) of 25 patients had a localized abscess. Three of the patients who underwent immediate exploration and 7 who had surgery after a period of observation died postoperatively (10/25, 40%). Five (55%) of 9 patients in the group who received high-dose radiation therapy died because of sigmoid perforation. When the time frame of presentation was evaluated, we noted that 10 (50%) of 20 patients died between 1960 and 1979 and 1 (14%) of 7 died between 1980 and 1992. CONCLUSIONS: Sigmoid perforation following pelvic radiation for cervical cancer does not usually present with the typical signs of a ruptured viscus. A high degree of suspicion remains a priority in the care of radiated patients who present with abdominal pain given the atypical presentation of perforation in this group.

Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1.

The minichromosome maintenance (MCM) proteins, together with the origin recognition complex (ORC) proteins and Cdc6, play an essential role in eukaryotic DNA replication through the formation of a pre-replication complex at origins of replication. We used a yeast two-hybrid screen to identify MCM2-interacting proteins. One of the proteins we identified is identical to the ORC1-interacting protein termed HBO1. HBO1 belongs to the MYST family, characterized by a highly conserved C2HC zinc finger and a putative histone acetyltransferase domain. Biochemical studies confirmed the interaction between MCM2 and HBO1 in vitro and in vivo. An N-terminal domain of MCM2 is necessary for binding to HBO1, and a C2HC zinc finger of HBO1 is essential for binding to MCM2. A reverse yeast two-hybrid selection was performed to isolate an allele of MCM2 that is defective for interaction with HBO1; this allele was then used to isolate a suppressor mutant of HBO1 that restores the interaction with the mutant MCM2. This suppressor mutation was located in the HBO1 zinc finger. Taken together, these findings strongly suggest that the interaction between MCM2 and HBO1 is direct and mediated by the C2HC zinc finger of HBO1. The biochemical and genetic interactions of MYST family protein HBO1 with two components of the replication apparatus, MCM2 and ORC1, suggest that HBO1-associated HAT activity may play a direct role in the process of DNA replication.

Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial.

CONTEXT: The optimal antimicrobial regimen and treatment duration for acute uncomplicated pyelonephritis are unknown. OBJECTIVE: To compare the efficacy and safety of a 7-day ciprofloxacin regimen and a 14-day trimethoprim-sulfamethoxazole regimen for the treatment of acute pyelonephritis in women. DESIGN: Randomized, double-blind comparative trial conducted from October 1994 through January 1997. SETTING: Twenty-five outpatient centers in the United States. PATIENTS: Of 378 enrolled premenopausal women aged at least 18 years with clinical diagnosis of acute uncomplicated pyelonephritis, 255 were included in the analysis. Other individuals were excluded for no baseline causative organism, inadequate receipt of study drug, loss to follow-up, no appropriate cultures, and other reasons. INTERVENTIONS: Patients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days (with or without an initial 400-mg intravenous dose) followed by placebo for 7 days (n = 128 included in analysis) vs trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days (with or without intravenous ceftriaxone, 1 g) (n = 127 included in the analysis). MAIN OUTCOME MEASURE: Continued bacteriologic and clinical cure, such that alternative antimicrobial drugs were not required, among evaluable patients through the 4- to 11-day posttherapy visit, compared by treatment group. RESULTS: At 4 to 11 days posttherapy, bacteriologic cure rates were 99% (112 of 113) for the ciprofloxacin regimen and 89% (90 of 101) for the trimethoprim-sulfamethoxazole regimen (95% confidence interval [CI] for difference, 0.04-0.16; P = .004). Clinical cure rates were 96% (109 of 113) for the ciprofloxacin regimen and 83% (92 of 111) for the trimethoprim-sulfamethoxazole regimen (95% CI, 0.06-0.22; P = .002). Escherichia coli, which caused more than 90% of infections, was more frequently resistant to trimethoprim-sulfamethoxazole (18%) than to ciprofloxacin (0%; P<.001). Among trimethoprim-sulfamethoxazole-treated patients, drug resistance was associated with greater bacteriologic and clinical failure rates (P<.001 for both). Drug-related adverse events occurred in 24% of 191 ciprofloxacin-treated patients and in 33% of 187 trimethoprim-sulfamethoxazole-treated patients, respectively (95% CI, -0.001 to 0.2). CONCLUSIONS: In our study of outpatient treatment of acute uncomplicated pyelonephritis in women, a 7-day ciprofloxacin regimen was associated with greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen, especially in patients infected with trimethoprim-sulfamethoxazole-resistant strains.

Comparison of moxifloxacin and cefuroxime axetil in the treatment of acute maxillary sinusitis. Sinusitis Infection Study Group.

The aim of this prospective, multicenter, randomized, double-masked clinical trial was to compare the efficacy and safety of moxifloxacin with those of cefuroxime axetil for the treatment of community-acquired acute sinusitis. Five hundred forty-two adult patients with symptoms and radiographic evidence of acute maxillary sinusitis received a 10-day oral regimen of either moxifloxacin (400 mg once daily) or cefuroxime axetil (250 mg twice daily). Acute signs and symptoms at presentation had lasted >7 days but <4 weeks. Clinical response at the end of therapy (7 to 14 days after treatment) was the primary efficacy variable. Four hundred fifty-seven of the patients (223 moxifloxacin, 234 cefuroxime axetil) were included in the clinical efficacy analysis. Moxifloxacin was found to be similar in effectiveness to cefuroxime axetil at the end-of-therapy visit (90% vs. 89%, respectively; 95% confidence interval, -5.1% to 6.2%). Clinical relapse at the follow-up visit was reported for only 8 patients (3 moxifloxacin, 5 cefuroxime axetil). No clinically significant differences were observed with respect to the number of patients experiencing a successful clinical response based on demographic or infection characteristics. Five of the 542 enrolled patients were lost to follow-up. Of the 537 patients in the intent-to-treat population, drug-related adverse events were reported in 37% of moxifloxacin-treated patients and in 26% of cefuroxime axetil-treated patients (P = 0.006). Adverse-event profiles were comparable in the 2 treatment groups, with the exception of nausea, which was reported by 11% of moxifloxacin-treated patients compared with 4% of cef uroxime axetil-treated patients (P = 0.003). In this study, moxifloxacin was as effective as cefuroxime axetil in the treatment of community-acquired acute sinusitis.

Chicoric acid analogues as HIV-1 integrase inhibitors.

The present study was undertaken to examine structural features of L-chicoric acid (3) which are important for potency against purified HIV-1 integrase and for reported cytoprotective effects in cell-based systems. Through a progressive series of analogues, it was shown that enantiomeric D-chicoric acid (4) retains inhibitory potency against purified integrase equal to its L-counterpart and further that removal of either one or both carboxylic functionalities results in essentially no loss of inhibitory potency. Additionally, while two caffeoyl moieties are required, attachment of caffeoyl groups to the central linking structure can be achieved via amide or mixed amide/ester linkages. More remarkable is the finding that blockage of the catechol functionality through conversion to tetraacetate esters results in almost no loss of potency, contingent on the presence of at least one carboxyl group on the central linker. Taken as a whole, the work has resulted in the identification of new integrase inhibitors which may be regarded as bis-caffeoyl derivatives of glycidic acid and amino acids such as serine and beta-aminoalanine. The present study also examined the reported ability of chicoric acid to exert cytoprotective effects in HIV-infected cells. It was demonstrated in target and cell-based assays that the chicoric acids do not significantly inhibit other targets associated with HIV-1 replication, including reverse transcription, protease function, NCp7 zinc finger function, or replication of virus from latently infected cells. In CEM cells, for both the parent chicoric acid and selected analogues, antiviral activity was observable under specific assay conditions and with high dependence on the multiplicity of viral infection. However, against HIV-1- and HIV-2-infected MT-4 cells, the chicoric acids and their tetraacetylated esters exhibited antiviral activity (50% effective concentration (EC50) ranging from 1.7 to 20 microM and 50% inhibitory concentration (IC50) ranging from 40 to 60 microM).

Phosphonate inhibitors of protein-tyrosine and serine/threonine phosphatases.

In all, 15 aryl-containing phosphonates have been synthesized and tested for their effect on protein-tyrosine phosphatase (PTPase) activity. Two compounds, (naphth-2-yl) difluoromethylphosphonic acid (12) and (napthy-1-yl) difluoromethylphosphonic acid (13) have been found to inhibit dephosphorylation of [32P]insulin receptors by PTP-1B, a protein tyrosine phosphatase (PTPase), with IC50 values of 40-50 microM. Compound 12 competitively inhibited insulin-receptor dephosphorylation by PTP-1B. Compound 12 also inhibited PTP-1B-catalysed dephosphorylation of a synthetic tyrosine phosphorylated substrate poly(Glu80-Tyr20) at the same potency, indicating that 12 acted via interaction with the PTPase. Additionally, 12 inhibited insulin-receptor PTPase(s) and epridermal-growth-factor-receptor PTPase(s) present in solubilized membranes from CHO (Chinese-hamster ovary)/HIRc and A431 cells respectively. IC50 values of 40-50 microM were obtained in all cases with compound 12. Of note is the fact that these compounds did not have any effect on insulin-receptor autophosphorylation. Nine out of the 15 compounds potently inhibited serine/threonine phosphatase PP-2A activity without any effect on serine/threonine phosphatase PP-1 when tested at a concentration as high as 675 microM. The most potent compounds acting toward PP-2A had IC50 values of 45-50 microM. These PP-2A inhibitors could be useful tools for studying serine/threonine-phosphatase-mediated signal transduction. Two compounds, 12 and 13, inhibited both tyrosine phosphatase PTP-1B and serine/threonine phosphatase PP-2A with similar potency; IC50 values being 40-50 microM in both cases. Details of the synthesis of compounds 10, 11 and 13 are given in Supplementary Publication SUP 50177 (6 pages), which has been deposited at the British Library Document Supply Centre, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1995) 305, 9.

Extracorporeal circulation as a blood conservation technique for extensive pelvic operations.

Difficult pelvic operations for malignancy or complex benign conditions can be associated with extensive blood loss. Religious beliefs that preclude transfusion and the known risks of homologous blood have prompted investigators to seek alternatives to transfusion. We used the Haemonetics-V50 Cell Separator (Haemonetics Corporation) to provide for extracorporeal circulation of the patient's own blood with associated normovolemic hemodilution as a means of conserving blood during operations. This technique was used in eight patients undergoing extensive pelvic operations. The procedure was accepted by Jehovah's Witnesses and was well tolerated by all patients. Estimated blood loss ranged from 75 to 2,000 milliliters. One instance of mild intraoperative disseminated intravascular coagulation was encountered. Two patients were given homologous transfusions. While clinical judgment is necessary to determine the safety of complicated operations, this technique is useful in expanding surgical options for some patients who object to blood transfusion.

Enterovesical fistula following radiotherapy for gynecologic cancer.

Enterovesical fistula is a rare complication of pelvic radiotherapy. Recurrent disease is the cause of fistulization in most patients. We identified 14 patients who developed enterovesical fistula in the absence of tumor recurrence. These women were at high risk for radiation morbidity due to prior surgery, pelvic inflammatory disease, adjuvant hyperbaric oxygen, or locally high doses of radiotherapy caused by suboptimal geometry and technique. All patients underwent radiographic imaging including barium enema, intravenous pyelogram, and upper gastrointestinal study with small bowel follow-through. The range of radiation morbidity was great: some patients had small fistulae, others had extensive fistulization and radionecrosis. Six patients had colovesical fistulae, five had enterovesical fistulae, and three had fistulae involving both the small and large bowel. Twelve patients underwent 13 surgical procedures. Healing or successful repair of the fistula was achieved in 1 of 3 patients treated with diversion (loop colostomy), 2 of 4 patients treated with isolation of the fistulized bowel loop and urinary conduit, and 5 or 6 treated with bowel resection with or without urinary conduit. Two of three perioperative deaths occurred in the isolation group managed without urinary conduit and were related to ongoing sepsis. Surgical procedures which resect necrotic fistulized bowel and result in complete separation of the gastrointestinal and genitourinary tracts provided the best results in patients with radiation-induced enterovesical fistulae. CT scan of the abdomen and pelvis is recommended in the evaluation of the majority of patients with suspected enterovesical fistula.

Phosphate depletion arrests progression of chronic renal failure independent of protein intake.

Following 5/6 nephrectomy, 18 rats were fed a normal diet. After 30 days, serum creatinine (SCr), urine protein excretion and urine volume were increased compared to pre-nephrectomy (0.27 +/- 0.1 vs. 1.62 +/- 0.6 mg/deciliter, 17.0 +/- 10.3 vs. 257.6 +/- 13.4 mg/24 hr, and 16.6 +/- 4.4 vs. 39.2 +/- 11.7 ml/24 hr, respectively, all P less than 0.001). At this time, when serum phosphorus (SPi) and serum calcium (SCa2+) were normal, the rats were separated into two groups, matched and paired by body weight and SCr, and housed separately in metabolic cages. Animals of one group ingested a normal diet supplemented with dihydroxyaluminum aminoacetate (DHAAA), 15 g%, to induce phosphate depletion (PD). The second group ingested the same diet supplemented with 7.5% glycine and was the phosphate replete (PR) group. All rats were pair fed throughout the study to maintain similar caloric, protein, carbohydrate, vitamin, and mineral intakes. At six weeks after separation, SPi was decreased in PD vs. PR group (2.85 +/- 0.8 vs. 6.71 +/- 1.2 mg/deciliter, P less than 0.001) and SCa2+ was increased in the PD group (11.98 +/- 0.7 vs. 10.03 +/- 0.7 mg/deciliter, P less than 0.001). Urine urea nitrogen, body weight, and sodium, potassium and solute excretion were similar between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Probes for narcotic receptor mediated phenomena. 7. Synthesis and pharmacological properties of irreversible ligands specific for mu or delta opiate receptors.

Syntheses of affinity reagents for opiate receptors based on the fentanyl, endo-ethenotetrahydrooripavine, and etonitazene carbon-nitrogen skeletons are described. The isothiocyanate, bromoacetamido, and methylfumaramido alkylating functions were employed in these compounds, some of which had previously been shown to be mu specific (12, BIT) and delta specific (8, FIT and 19, FAO) in vitro. Antinociceptive activity of the title compounds was determined in the mouse hot-plate test, which revealed that certain compounds in each class showed morphine-like activity. The binding EC50 values against [3H]Dalamid for opiate receptors in NG108-15 (delta receptors) and rat brain membranes (mu + delta receptors) are also reported. With this type of experiment, it was possible to independently measure the apparent affinity of the etonitazene congeners 12-14 for the mu and delta receptors.

Protective effect of intrarenal calcium membrane blockers before or after renal ischemia. Functional, morphological, and mitochondrial studies.

The present study examined whether a pre- or postischemic infusion of verapamil (V) or a postischemic infusion of nifedipine (N), drugs which block calcium (Ca++) influx across plasma membranes, provides protection against ischemic acute renal failure (ARF) in dogs. Renal hemodynamics and excretory function were examined 1 h (initiation phase) and 24 h (maintenance phase) after a 40-min intrarenal infusion of norepinephrine (NE). In each case, the uninfused contralateral kidney served as control. Four groups were studied: (a) dogs receiving NE alone; (b) dogs receiving an intrarenal infusion of V for 30 min before NE (V + NE); (c) dogs in which intrarenal V was infused for 2 h, beginning immediately after completion of NE infusion (NE + V); and (d) dogs in which intrarenal N was infused for 2 h, beginning immediately after completion of NE infusion (NE + N). Glomerular filtration rate (GFR) in the NE kidneys, as assessed by inulin clearance, at 1 and 24 h averaged 2.4 +/- 1.1 and 5.0 +/- 2.0 ml/min, respectively, as compared with control kidney GFRs of 28.0 +/- 3.5 and 43.8 +/- 5.0 ml/min, respectively (both at least P less than 0.01). In the V + NE group, GFR at 1 and 24 h averaged 15.0 +/- 5.5 and 31.0 +/- 4.5 ml/min, respectively, both at least P less than 0.05 as compared with values from NE kidneys. GFRs in the NE + V group averaged 15.0 +/- 2.4 and 16.3 +/- 3.6 ml/min at 1 and 24 h, both at least P less than 0.02 as compared with values from NE kidneys. GFR in the NE + N group averaged 18.6 +/- 6.0 ml/min at 24 h (P less than 0.05 as compared with GFRs in the NE kidneys). In addition, function of cortical mitochondria (Mito) was examined at the end of the 40-min NE infusion and after 1 and 24 h of reperfusion in the NE alone and NE + V groups. Mito respiration, assessed by acceptor control ratios, was reduced at each period in the NE alone kidneys. After 24 h, these Mito had accumulated Ca++ and exhibited reduced Ca++ uptake and increased Ca++ release rates. Mito from NE + V kidneys respired normally, did not accumulate Ca++, and exhibited no alterations in Ca++ uptake or release. Light and electron microscopy also demonstrated morphological protection of V against tubular necrosis and cell injury. Mito from the NE + N kidneys also respired normally and did not accumulate significant amounts of Ca++. The results of the present studies therefore demonstrated that chemically dissimilar calcium entry blockers exert substantial functional, cellular, and morphological protection against experimental ischemic ARF. These findings are compatible with the hypothesis that increased cytosolic Ca++ is critically important in the maintenance of renal vasoconstriction and the development of cellular necrosis with subsequent tubular obstruction in NE-induced ischemic ARF. V or N may provide protection against renal injury by retarding any increase in cytosolic Ca++ in renal vasculature and epithelium.

A 280-day tolerance-efficacy study with mibolerone for suppression of estrus in the cat.

Mibolerone, a synthetic anabolic steroid, prevented estrus in domesticated cats when orally given a daily dose of 50 microng over a 180-day period. Doses of 20 microng daily and 50 microng given once a week failed to prevent estrus. Treatment with the 50-microng dose each day for 6 months had no apparent effects on subsequent estrus, mating, queening, or litter size. Kittens born to queens which had been treated did not have obvious developmental defects. Systemic metabolic changes produced by treatment were detected only in thyroid function, as revealed in dose- and time-related changes in serum cholesterol concentrations, thyroid gland weights, and thyroid histology. Clinical evidence of thyroid dysfunction was not apparent during the 6 months of treatment. Clinical and microscopic evidence of slight masculinization was apparent in cats after 3 months of treatment with 20 or 50 microng per day. Masculinizing changes consisted of thickening of the cervical dermis and clitoral hypertrophy. Behavioral changes were not observed. The apparent mechanism of action of mibolerone in the cat is the suppression of the release of pituitary luteinizing hormone.