Availability of essential medicines: A primary health care perspective

The present study was undertaken to assess the availability of the essential medicines to the people of Kunijarla, Khammam district, AP. This was done in two steps: 1) Comparison of PHC-EML (primary health care essential medicines list) with AP-EML (Andhra Pradesh essential medicines list) and NEML (National essential medicines list); and 2) Assessment of availability of the listed medicines in adequate quantity to meet the needs of people of kunijarla. Results showed that the PHC-EML is on par with AP-EML and NEML. The hospital has 100% availability of the listed medicines; however, there was a need for certain add-on drugs like phenytoin tablets, valproic acid, and activated charcoal since they were prescribed frequently and were not included in PHC-EML. All the drugs which were listed in PHC-EML were being used and none were considered as non-utility supply. Suggestions were given for the revision of PHC-EML according to the criteria for identifying medicines for inclusion in the revised list which was mentioned in NEML.     

Atrial fibrillation ablation in patients with gastroesophageal reflux disease or irritable bowel syndrome—the heart to gut connection!

Purpose

An association between atrial fibrillation (AF) and gastroesophageal reflux disease (GERD) and/or irritable bowel syndrome (IBS) is increasingly being identified; yet the role of radiofrequency catheter ablation (RFA) of AF has not been systematically evaluated in these patient populations.

Methods

We performed a prospective matched case–control study of AF patients with GERD and/or IBS who underwent RFA for AF in two centers in North America. AF patients with GERD and/or IBS (gastrointestinal [GI] group) were matched by age, gender, and type of AF at each of the centers with an equal number of AF patients without GERD or IBS (non-GI group).

Results

Sixty patients were included in the study with 30 in each group. Mean age of the population was 45 years with 14 (47 %) males and 21 (87 %) patients with paroxysmal AF in each group. More patients in the GI group had identifiable GI triggers for AF episodes. During RFA, more patients in the GI group had a “vagal response” compared to non-GI group (60 vs 13 %; p?<?0.001). Left atrial scar as identified by electroanatomical mapping was more common in patients in the non-GI group compared to the GI group (57 vs 27 %; p?=?0.018). At 1-year follow-up, 56 (93 %) of the patients were free from AF with no difference between both groups.

Conclusions

Majority of AF patients with GERD and/or IBS have triggered AF and a positive vagal response during RFA. RFA is equally effective in this patient population when compared to those without GERD or IBS.     

Globin-coupled heme containing oxygen sensor soluble adenylate cyclase in Leishmania prevents cell death during hypoxia

Globin and adenylate cyclase play individually numerous crucial roles in eukaryotic organisms. Comparison of the amino acid sequences of globins and adenylate cyclase from prokaryotic to eukaryotic organisms suggests that they share an early common ancestor, even though these proteins execute different functions in these two kingdoms. The latest studies of biological signaling molecules in both prokaryotic and eukaryotic organisms have discovered a new class of heme-containing proteins that act as sensors. The protein of the globin family is still unknown in the trypanosomatid parasites, Trypanosome and Leishmania. In addition, globin-coupled heme containing adenylate cyclase is undescribed in the literature. Here we report a globin-coupled heme containing adenylate cyclase (HemAC-Lm) in the unicellular eukaryotic organism Leishmania. The protein exhibits spectral properties similar to neuroglobin and cytoglobin. Localization studies and activity measurements demonstrate that the protein is present in cytosol and oxygen directly stimulates adenylate cyclase activity in vivo and in vitro. Gene knockdown and overexpression studies suggest that O₂-dependent cAMP signaling via protein kinase A plays a fundamental role in cell survival through suppression of oxidative stress under hypoxia. In addition, the enzyme-dependent cAMP generation shows a stimulatory as well as inhibitory role in cell proliferation of Leishmania promastigotes during normoxia. Our work begins to clarify how O₂-dependent cAMP generation by adenylate cyclase is likely to function in cellular adaptability under various O₂ tensions.Human pathogen Leishmania promastigotes inhabit the midgut of a sandfly, where they are densely packed together and the environment of these promastigotes is then likely to become hypoxic or even anoxic (1). Although biologists have long known that Leishmania species can survive under limited oxygen (2), the underlying mechanism remains unclear.O₂, CO, and NO are physiologically indispensable but sometimes toxic to living organisms (3). Hence, the machinery for sensing these molecules and responding to them is vital for survival. Recently, a new class of the heme-containing sensor proteins has been discovered (4). These are different from well-known heme proteins, such as O₂ carriers (hemoglobin/myoglobin), oxygen activators (cytochrome P450/peroxidases), and mediators of electron transfer (cytochrome c/cytochrome b₅) (5, 6). Heme-based sensor proteins usually consist of an N-terminal heme-containing sensor domain and a C-terminal effector domain (7). The structures of heme-based sensor proteins are changed upon binding of O₂, CO, or NO gases with the heme domain. This structural change influences the effector domain for proper functioning.Cyclic AMP (cAMP) is a vital signaling molecule that controls diverse biological functions in many organisms, including virulence factors from a range of pathogens (8, 9). The second messenger cAMP is universally generated by adenylate cyclase (AC), which catalyzes the cyclization of ATP to cAMP. AC is regulated by various molecules including bicarbonate (10), calcium (11), and hormones (12). Although cAMP is found in the trypanosomatid parasite Leishmania, little is known about its function (13, 14).In this paper we report the heme containing AC from Leishmania major (HemAC-Lm). To understand the biochemical functions of this protein, we cloned, expressed, and characterized the HemAC-Lm protein. Evidence has been presented to show that a globin domain present at the N terminus of HemAC-Lm plays an important role in O₂ binding and controls the catalytic activity of the C-terminal AC domain. Our results provide evidence for the existence of an O₂-dependent cAMP regulation that is a prerequisite for decreasing oxidative stress under hypoxia.     

Evaluation of vitamin E against deltamethrin toxicity in broiler chicks

Deltamethrin toxicity was studied in broilers and vitamin E was evaluated for therapeutic management. Day old male broiler chicks were randomly divided into 3 groups consisting of 6 chicks in each. Group 1 was maintained as control for 6 wks, group 2 was fed on deltamethrin (100 mg/kg feed) for 6 wks and group 3 was fed on deltamethrin for the first 4 wks and during the subsequent 2 wks with vitamin E (300 mg/kg feed) with out deltamethrin. Weekly body weights, feed conversion ratio, glutathione (GSH) concentration and high density lipoproteins (HDL) were significantly (P < 0.05) reduced, while the activities of glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R), catalase, aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), and the lipid profile and renal biomarkers were increased significantly (P < 0.05) in group 2 and 3 at the end of 4th wk as compared to group 1. Following treatment with vitamin E during the last 2 wks in group 3, all the parameters in study revealed improvement. From this study, it is concluded that deltamethrin induces toxicity by oxidative damage in biological system and supplementing vitamin E in feed is useful in treating accidental toxicity.     

Monoclonal anti-leukemia inhibitory factor antibody inhibits blastocyst implantation in the rhesus monkey

INTRODUCTION: Leukemia inhibitory factor (LIF) appears important in the process of blastocyst implantation in primates. In the present study, we investigated the effect on pregnancy outcome of the administration of a monoclonal antibody (mAb) to recombinant human (rh) LIF (anti-LIF mAb) into the uterine cavity of mated female rhesus monkeys during the peri-implantation period. METHODS: Two milligrams of either mouse mAb to rhLIF or isotype-matched immunoglobulin (Ig) was administered into the uterine cavity on estimated Day 5 or Day 8 after ovulation either through the vagina (n=33) or through the oviduct (n=29) of successfully mated females. RESULTS: There was a significant (p<.04) decline in pregnancy outcome in groups treated with anti-LIF mAb (8 pregnancies from 32 animals) compared with control animals (24 pregnancies from 30 animals). There was, however, no significant difference in pregnancy inhibition between a group of animals subjected to vaginal route treatment and a group of animals subjected to oviductal route treatment, as well as between a group subjected to anti-LIF mAb on Day 5 after ovulation and a group subjected to anti-LIF mAb on Day 8 after ovulation. No significant change was seen in the number of viable pregnancy in animals treated with 6 mg of anti-LIF mAb (5 pregnancies from 16 animals) compared with animals treated with 2 mg of anti-LIF mAb (8 pregnancies from 32 animals). Serum profiles of estradiol, progesterone, monkey chorionic gonadotropin and mouse IgG did not show any difference among different treatment subgroups during the luteal phase. However, among animals treated with anti-LIF mAb, the mean area under the curve for serum mouse IgG in pregnant animals (234+/-55 microg/mL day) was significantly (p<.01) less than that of nonpregnant animals (1325+/-97 microg/mL day). CONCLUSION: The results of the present study put forward the proof of concept that LIF plays a critical role in the process of blastocyst implantation in the rhesus monkey.     

Multiple cardiac metastases from Ewing's sarcoma

Ewing's sarcoma commonly arises from bone and sometimes from extraskeletal soft tissues. It commonly metastasizes to the lungs, bone, bone marrow and brain. Cardiac metastasis is extremely uncommon. The present report discusses a case of Ewing's sarcoma metastasizing to the heart at the time of initial presentation.     

Primary care,HMO enrollment,and hospitalization for ambulatory care sensitive conditions: a new approach

OBJECTIVE: To examine the association of primary care availability, HMO enrollment, and other person and location variables with potentially preventable hospitalization for adults in New York State, compared with other types of hospitalization. DATA SOURCES/STUDY SETTING: Hospital discharges of New York residents in the age group 20-64 hospitalized either in New York or in three contiguous states: New Jersey, Pennsylvania, or Connecticut using 1995 statewide discharge files from the Health care Cost and Utilization Project (HCUP) maintained by the Agency for Health care Research and Quality. STUDY DESIGN: A multinomial logit model uses the individual discharge as the unit of analysis. ACS admissions are compared with marker admissions (urgent but non-ACS) and referral sensitive surgeries (more discretionary), controlling for severity of illness. PRINCIPAL FINDINGS: Higher primary care density was associated with a lower likelihood of ACS admission, compared with marker admissions, without increasing referral-sensitive admissions. The study also supports the hypothesis of ACS admissions being less likely for private HMO enrollees than for other insured adults. This result was not found for Medicaid HMO enrollees, even by comparison to other Medicaid enrollees. CONCLUSIONS: A key policy-relevant result is the negative association of primary care physicians per capita with the likelihood of ACS admissions, without an offsetting association with resource costs via referral-sensitive admissions. The method allowed for examining the possible effects of personal and area variables on one type of hospital admission (ACS) by contrast with other specific types of admissions. This type of analysis could be strengthened in several ways for a defined population when better data on individual patients and several time periods are used.     

Study of Thrombophilia in Recurrent Pregnancy Loss

Objectives

Recently, it has been found that women who have thrombophilia have increased risk of fetal loss. This study was designed to corroborate the association of elevated factor VIII level, protein C and protein S deficiencies, and the presence of LAC in women with recurrent pregnancy loss.

Materials and Methods

53 patients with history of two or more pregnancy losses and 47 healthy age-matched subjects with no history of pregnancy loss and who have delivered at least one term infant without any complication were enrolled into the study.

Results

Thrombophilic defect was present in 64.15 % of patients of study group. Protein S deficiency (50.94 %) was the most common thrombophilic defect observed. Spontaneous abortion (SA), preterm birth (PTB), and intrauterine growth retardation (IUGR) were the most important pregnancy complications observed. The strongest associations of pregnancy complications were observed with protein S deficiency (87.5 %) and with elevated factor VIII (66.66 %) level.

Conclusion

This study observed strong association of thrombophilia with unexplained recurrent pregnancy loss.