Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement.

Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.

Efficacy and tolerability of fixed-dose combination of dexketoprofen and dicyclomine injection in acute renal colic.

Objective. To evaluate the efficacy and tolerability of a fixed-dose combination of dexketoprofen and dicyclomine (DXD) injection in patients with acute renal colic. Patients and Methods. Two hundred and seventeen patients were randomized to receive either DXD (n = 109) or fixed-dose combination of diclofenac and dicyclomine injection (DLD; n = 108), intramuscularly. Pain intensity (PI) was self-evaluated by patients on visual analogue scale (VAS) at baseline and at 1, 2, 4, 6, and 8 hours. Efficacy parameters were proportion of responders, difference in PI (PID) at 8 hours, and sum of analogue of pain intensity differences (SAPID). Tolerability was assessed by patients and physicians. Results. DXD showed superior efficacy in terms of proportion of responders (98.17% versus 81.48; P < 0.0001), PID at 8 hours (P = 0.002), and SAPID(0-8 hours) (P = 0.004). The clinical global impression for change in pain was significantly better for DXD than DLD. The incidence of adverse events was comparable in both groups. However, global assessment of tolerability was rated significantly better for DXD. Conclusion. DXD showed superior efficacy and tolerability than DLD in patients clinically diagnosed to be suffering from acute renal colic.

Efficacy and Tolerability of Intramuscular Dexketoprofen in Postoperative Pain Management following Hernia Repair Surgery.

Objective. To evaluate the safety and efficacy of intramuscular dexketoprofen for postoperative pain in patients undergoing hernia surgery. Methodology. Total 202 patients received single intramuscular injection of dexketoprofen 50 mg or diclofenac 50 mg postoperatively. The pain intensity (PI) was self-evaluated by patients on VAS at baseline 1, 2, 4, 6, and 8 hours. The efficacy parameters were number of responders, difference in PI (PID) at 8 hours, sum of analogue of pain intensity differences (SAPID), and onset and duration of analgesia. Tolerability assessment was done by global evaluation and adverse events in each group. Results. Dexketoprofen showed superior efficacy in terms of number of responders (P = .007), PID at 8 hours (P = .02), and SAPID( 0-8 hours ) (P < .0001). It also showed faster onset of action (42 minutes) and longer duration of action (6.5 hours). The adverse events were comparable in both groups. Conclusion. Single dose of dexketoprofen trometamol 50 mg given intramuscularly provided faster, better, and longer duration of analgesia in postoperative patients of hernia repair surgery than diclofenac 50 mg, with comparable safety.

Functional MR imaging of hand motor cortex in a case of persistent mirror movement.

Persistent mirror movements are unwanted movements restricted to muscles homologous to those moved intentionally on the opposite body half. It is rarely observed and the functional MRI findings in a case of persistent mirror movement are described.

Synthesis and anthelmintic activity of 3,6-disubstituted-7H-s-triazolo(3,4-b)(1,3,4)thiadiazines.

A series of 3,6-disubstituted-7H-s-triazolo(3,4-b)(1,3,4)thiadiazines was synthesized by the condensation of the appropriate 3-substituted-4-amino-5-mercapto (1,2,4) triazoles with substituted phenacyl bromides in alcoholic medium. These compounds have been studied for their in vivo anthelmintic activity in albino mice. A number of compounds showed promising activity when given by the oral route.

Private practitioners and their role in the resurgence of malaria in Mumbai (Bombay) and Navi Mumbai (New Bombay), India: serving the affected or aiding an epidemic?

The increased emphasis on privatization of the health care sector in many developing countries by international financial institutions and national governments expects an expanding role for private health care practitioners in the management of major communicable diseases such as tuberculosis, malaria, acute respiratory infections (ARIs) and sexually transmitted diseases (STDs). Largely unexamined in the Indian context, however, is the socio-cultural context, the micro-level political environment in which private practitioners carry out their activities, and the quality of care they provide to their patients. Examining these aspects is significant given the impressive growth of the country's private health sector during the past decade. This paper reports the results of an ethnographic study carried out in Mumbai (Bombay) and Nav Mumbai (New Bombay), India on private general practitioners (GPs) and their role in the management of malaria at a time when these two neighboring cities were in the midst of the worst malaria epidemic in over 60 years. Described are the characteristics of a sample of 48 private practitioners from the two cities, and their clinics. This is followed by a discussion of the data gathered through untructured interviews with practitioners and patients, and complemented by observational data on doctor-patient encounters gathered at 16 clinics over a 9-month period. The findings of the study suggest that many practitioners in Mumbai and Navi Mumbai were poorly qualified and did not play a supportive role in the two cities' public health departments to bring the epidemic under control. The majority of the practitioners adopted diagnostic and treatment practices that were not consistent with the guidelines laid down by WHO and India's National Malaria Eradication Programme. Very few practitioners, especially those practicing in low-income areas, relied on a peripheral blood-smear test to make a diagnosis. Practitioners whose clientele was mostly the poor commonly resorted to giving one-day treatment to febrile patients that included injectable antimalarials and broad spectrum antibiotics. Such practitioners justified their mode of diagnosis and treatment by asserting that they were only responding to the demands placed on them by their patients who could not afford a blood-smear test or a full prescription. The paper argues that practitioners who acquiesced to patient demands were at once exacerbating the health problems of their patients and jeopardizing the prospects for the epidemic to be brought under control. Driven primarily by the need to retain the patronage of patients and maintain one's popularity in a highly competitive health arena, many providers practiced medicine that was unethical and dangerous. The paper concludes by discussing the ramifications of this study for malaria control in Mumbai and Navi Mumbai, and highlights a few salient health policy issues concerning the growth of the private health sector in India and its regulation.

Resurgence of malaria in Bombay (Mumbai) in the 1990s: a historical perspective.

Bombay has achieved extraordinary success in controlling its malaria problem for nearly six decades by relying primarily on legislative measures and non-insecticidal methods of mosquito abatement. In 1992, however, malaria reemerged in Bombay with a vengeance. During 1992-1997, the city witnessed a manifold increase in the number of malaria cases diagnosed and treated by the public health system. The large number of malaria patients treated by private practitioners was not recorded by the municipal malaria surveillance system during this period. In 1995, at the peak of the resurgence, public health officials of the Municipal Corporation of Greater Bombay (MCGB) confirmed that 170 persons in the city had died due to malaria. The crisis was unprecedented in Bombay's modern public health history. In response to intense criticism from the media, the city's public health officials attributed the resurgence to the global phenomenon of mosquito-vector resistance to insecticides, and Plasmodium resistance to antimalarial chemoprophylaxis and treatment. Local scientists who investigated the problem offered no support to this explanation. So what might explain the resurgence? What factors led the problem to reach an epidemic level in a matter of two or three years? In addressing the above principal questions, this paper adopts a historical perspective and argues that in the resurgence of malaria in Bombay in the 1990s, there is an element of the 'presence of the past'. In many ways the present public health crisis in Bombay resembles the health scenario that characterized the city at the turn of the 19th century. It is possible to draw parallels between the early public health history of malaria control in Bombay, which was punctuated by events that followed the bubonic plague epidemic of 1896, and the present-day malaria epidemic punctuated by the threat of a plague epidemic in 1994. As such, the paper covers a long period, of almost 100 years. This time-depth is used to illustrate how malaria control programs in Bombay and in other parts of India have evolved through a combination of local historical forces and political expediencies in the context of technological developments. The boom in construction activities in Bombay following the liberalization of the Indian economy in 1991, and the local politics affecting administrative practices of the MCGB, are discussed as crucial factors in the crystallization of the present-day malaria resurgence in Bombay. The paper concludes by arguing that malaria in urban India is a serious problem that cannot be neglected. In the case of Bombay, the solution to the crisis can be found, in part, by reexamining the historical and political issues that have determined the nature and magnitude of the problem over the last century.

Pharmacies, self-medication and pharmaceutical marketing in Bombay, India.

Studies of pharmaceutical practice have called attention to the role played by pharmacists and pharmacy attendants in fostering self-medication and medicine experimentation among the public. Left undocumented is the extent to which clients passively follow the advice of pharmacy personnel or question their motive or expertise. While research has focused on pharmacists and pharmacy attendants as agents encouraging self-medication and medicine experimentation, adequate attention has not been paid to pharmacist-client interactions that are sensitive to the social, cultural, and economic context in which medicine sales and advice occur. This paper highlights the context in which pharmacy attendants engage in "prescribing medicines" to the public in Bombay, India. An ethnographic description of pharmacies and pharmaceutical-related behavior in Bombay is provided to demonstrate how reciprocal relationships between pharmacy owners, medicine wholesalers and pharmaceutical sales representatives (medreps) influence the actions of pharmacy staff. Attention is focused on the role of the medicine marketing and distribution system in fostering prescription practice, pharmacy "counter-pushing" and self-medication. In documenting the profit motives of different players located on the drug sales continuum, it is argued that the economic rationale and the symbiotic relations that exist between doctors, medreps, medicine wholesalers and retailers, need to be more closely scrutinized by those advocating "rational drug use".

Atrial entrapment of flow directed pulmonary artery catheter-a technique for non-surgical removal.

A 43 year old patient who underwent mitral valve replacement had pulmonary artery catheter inserted before induction of anaesthesia. The catheter could no be removed postoperatively by routine manoeuvres in the intensive care unit. Fluoroscopy in the cardiac catheterization revealed a straight course of the catheter indicating the probability of its inclusion in the left atrial suture line. The pulmonary artery catheter was successfully removed percutaneously in the cardiac catheterization laborartory. The procedure is described.

Reconsidering the popularity of primary health centers in India: a case study from rural Maharashtra.

Most evaluations of India's primary health care (PHC) program have been critical of the ways government primary health centers have been functioning. It has been commonly noted that utilization of health services is poor and community participation in the PHC outreach program low. Additionally, medical officers and health center staff are often accused of being negligent in their duties. In this paper I argue that it is worthwhile examining how a popular primary health center functions in a context marked by a growing demand for Western medicines. Attention is drawn to the ingenious ways in which health personnel respond to client demands and government medicine shortages. The case of a popular primary health center in rural Maharashtra is presented. This health center is both the site of public and private health care. Discussed is the manner in which rural populations in India maximize available health care options given time, cash and transportation constraints. Current thinking about community health financing is considered in light of existing health care utilization patterns, community evaluation of free services, perceptions of entitlement and the likely response of practitioners to such schemes.

Influence of meal composition on the postprandial response of the pituitary-thyroid axis.

Ingestion of food can result in an acute decline of serum thyrotropin (TSH) concentrations, but it is not known whether meal composition and/or stomach distension are influential. Normal men and women were given a normocaloric or hypocaloric, isobulk meal at lunch and at dinner in a randomized design. The normocaloric, but not the isobulk, meal resulted in a significant decline in serum TSH at both lunch and dinner; thyroid hormones and cortisol were not affected significantly. These findings suggest that meal composition is influential in the acute postprandial decline of serum TSH in man. A possible mechanism is food-induced elevation of somatostatin and consequent suppression of TSH secretion.

Percutaneous absorption of Octopirox.

[14C]Octopirox administered to rats by intubation or injection was excreted mostly in the faeces (65-85% of the dose) with smaller amounts (6-19%) in the urine. Blood levels after intubation of Octopirox (4.8 mg/kg body weight) reached a maximum equivalent to 0.137 micrograms/ml at 2 hr and declined to 0.007 micrograms/ml at 48 hr after administration. Tissue levels were low, the greatest was the liver with the equivalent of 3 micrograms Octopirox at 6 hr after intubation. With female rats skin penetration of Octopirox at 1% (v/v) in shampoo without rinsing was 65.1 micrograms/cm2 under non-occlusive conditions for 48 hr. When the skin was rinsed after a 10-min contact, penetration was reduced to 3.4 micrograms/cm2 under occlusive, and 2.0 micrograms/cm2 under non-occlusive conditions. Skin penetration of Octopirox was dependent on duration of contact up to 10 min before rinsing. Penetration at 1% Octopirox increased significantly from 2.4 micrograms/cm2 after 2.5 min exposure to 4.5 micrograms/cm2 after 10 min contact, but there was no further increase in penetration with a 20-min application. Skin penetration and deposition of Octopirox were both proportional to Octopirox concentration between 0.1 and 1% (w/v); skin penetration increased from 0.31 to 3.6 micrograms/cm2 while deposition increased from 0.8 to 7.6 micrograms/cm2. There was no significant difference between the penetration through clipped skin and hairy skin from an application of 1% Octopirox for 5 min followed by rinsing. Under non-occlusive conditions, penetration was 1.5 micrograms/cm2 for both types of skin. Blood levels after topical application (15.4 mg/kg body weight) without rinsing and with occlusion reached the equivalent of 0.32 micrograms/ml at 6 hr. However, when the skin was rinsed and protected with a non-occlusive patch blood levels were reduced to a maximum equivalent to 0.02 micrograms/ml at 1 hr after application. The safety factor estimated for the consumer using a shampoo containing 1% Octopirox is 29,400, so that the possibility of systemic effects due to absorption through the skin is remote.

Photochemical reaction of 7,8-dihydrorhodopsin at low temperatures.

The photoreaction of 9-cis-7,8-dihydrorhodopsin was examined at liquid nitrogen temperatures (-180 degrees C) in order to elucidate the photochemical events in visual pigments. This rhodopsin analog was prepared by incubating 9-cis-7,8-dihydroretinal with bovine opsin in the dark. 9-cis-7,8-Dihydrorhodopsin (lambda max = 427 nm) was cooled to -180 degrees C, and then irradiated at -180 degrees C with a 390 nm light, resulting in formation of its bathochromic product (lambda max = 465 nm). This result indicates that the presence of four double-bonds adjacent to the Schiff base nitrogen is sufficient to allow formation of a bathochromic product. Thus, the mechanism of formation of bathorhodopsin (in bovine rhodopsin system) may be considered as some change of the interaction between the conjugated double-bond system from C-9 to the Schiff base nitrogen and its surrounding charges in opsin, caused by rotation of 11-12 double-bond.

An evaluation of electroencephalographic monitoring for carotid study.

Continuous electroencephalogram (EEG) monitoring was used during 213 carotid endarterectomies in 157 patients to identify cerebral ischemia. General anesthesia was used for all patients. An intraluminal shunt was not used routinely, but was inserted in 23 operations when EEG abnormalities associated with ischemia appeared. EEG changes occurred in 31 operations (14.5 percent). Four patterns of abnormal recordings were identified and are discussed. Six patients developed ischemic EEG changes in association with hypotension during endarterectomy. In two of these patients changes appeared with a blood pressure drop of only 20 mm. Hg below preoperative levels. Four patients with internal carotid artery back pressures of 75 to 100 mm. Hg developed EEG abnormalities which disappeared after shunt insertion. Our experience emphasizes the value of continuous EEG monitoring in detecting inadequate cerebral perfusion.