Do chemical modifications dissociate between the enzymatic and pharmacological activities of beta bungarotoxin and notexin?

We have measured enzymatic, hemolytic and anticoagulant activities, lethal potencies and effects on contractions of the phrenic nerve-diaphragm preparation, by chemically modified derivatives of beta bungarotoxin (beta BuTX) and notexin, two presynaptically acting toxins which have PLA2 activity. The following chemical modifications of beta BuTX were tested: alkylation and methylation of histidine 48, alkylation of tryptophan 19, sulfonylation of tyrosine 68, oxidation of methionines 6 and 8, semicarbazide addition under varied conditions to carboxyl groups, varied extents of carbamylation or trinitrophenylation of lysines and guanidination of all lysines with or without trinitrophenylation of the N-terminal asparagine. Only the histidine, tryptophan and tyrosine residues were modified in notexin. The results obtained were compared with those previously obtained using chemically modified derivatives of Naja nigricollis and Naja naja atra PLA2 enzymes which do not have a specific presynaptic site of action. The results with oxidized methionine and lysine-modified derivatives of beta BuTX are supportive of the suggestions of others that the N-terminal region and basic residues away from the enzymatic active region contribute towards the beta type presynaptic neurotoxicity of the PLA2 toxins. Using modified derivatives of beta BuTX and notexin, the dissociations between enzymatic activities and pharmacological properties were not as marked as previously observed with N. nigricollis and N. n. atra PLA2; nevertheless, several dissociations were noted. We conclude that, just as with non-presynaptically acting PLA2 enzymes, some pharmacological actions of presynaptically acting PLA2 toxins may occur independently of phospholipid hydrolysis.     

Acute posterior multifocal placoid pigment epitheliopathy complicated by central retinal vein occlusion.

A case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) complicated by a central retinal vein occlusion five weeks after presentation is described. After eight months' follow-up there was mild residual visual impairment, macular scarring, and angiographic changes. The association of these two conditions is discussed.     

The versatility of the contoured AO plate as a mode of fixation for proximal femoral fractures

Proximal femoral fractures, especially in young adults, usually are high-energy injuries associated with severe comminution. Presently available fixation devices such as the blade plate and DHS are difficult to apply in comminuted cases, their application requires the use of an image intensifier, and their versatility is limited. This report describes the use of the AO plate molded according to the proximal femoral anatomy in 21 cases (seven subtrochanteric and 14 trochanteric fractures) in which high-energy injuries were sustained. Eleven cases were primarily bone grafted. Postoperative mobilization was started by an average of 5.4 weeks. All cases united by an average of 3.2 months. There were six excellent, ten good, three fair, and one poor result (one patient died). This method was found to be superior to conventional devices as it offers more versatility in placement of screws and plate contouring. The inventory of implants is also reduced, and there is no need for specialized instruments, a significant factor in Third World countries.     

Ewing's sarcoma of the foot bones: an analysis of seven cases

Seven cases of Ewing's sarcoma presenting with primary lesions of the foot bones are described. Difficulty and delay in making the initial diagnosis are the hallmarks of the problems encountered at this site. Although radiation therapy plays an important role for control of disease in Ewing's sarcoma, surgery along with chemotherapy appears to give better results. Lesions of the forefoot are amenable to surgery; however, no guidelines are available in the literature for hindfoot lesions. Chemotherapy has revolutionized the outcome, and its use along with surgical intervention is recommended in all cases of Ewing's sarcoma of foot bones.     

A new approach to hysteroscopic cannulation of the fallopian tube

Hysteroscopic cannulation of the fallopian tube has become an essential part of the treatment of interstitial fallopian tube obstruction. This report describes the use of a flexible instrument that can be introduced through a rigid hysteroscope for the purpose of hysteroscopic tubal cannulation.     

The colonic mesenteric margin is most susceptible to injury in an experimental model of colonic ulceration

BACKGROUND: Crohn's disease ileal ulcers and indomethacin-induced jejunal ulceration in the rat tend to occur in the mucosa nearest to the mesentery (mesenteric margin), an area of the bowel wall that has a critical blood supply. Mercuric chloride induces caecal and colonic ulceration in the Brown Norway rat. AIM: To examine whether the mesenteric margin is more sensitive to injury by a substance known to be vasculotoxic in the caecum and colon. METHODS: Brown Norway rats received a single subcutaneous dose of either mercuric chloride 1 mg/kg or saline. The gastrointestinal tract was examined macro- and microscopically for lesions 48 h later. The vascular anatomy of the normal rat colon and caecum was also examined using the carbon ink perfusion technique. RESULTS: Mercuric chloride induced caecal and colonic ulceration preferentially along the mesenteric margin of the bowel wall. Histologically, the lesions showed mucosal necrosis and neutrophil infiltration. There was also extensive vascular degeneration/necrosis with microaneurysm formation and extensive submucosal haemorrhage. Cellular infiltration of the vasculature was not a feature. The caecal and colonic mesenteric margins in control rats were supplied by small end arteries. CONCLUSIONS: The colonic and caecal mesenteric margins are susceptible to injury by mercuric chloride, a chemical known to induce haemorrhagic vasculopathy in the rat gastrointestinal tract. The large bowel mesenteric margin may be susceptible to injury by mercuric chloride because of the critical blood supply to that side of the bowel wall.     

IS/IT market support systems: augmenting UK primary health care groups

The election of the Labour government in May 1997 has seen the continuation of advanced market reforms intended to modernize the UK National Health Service (NHS). The planning and implementation of information systems and technology (IS/IT) following these structural changes is both widespread and significant. An information strategy for the NHS, published recently, is intended to provide an initial seven-year program of life-long electronic health records for everyone in the United Kingdom. This article explores the potential role of these systems in the specific provision of the new primary health care groups. It argues that, if primary care physicians adopt appropriate delivery channels and service packages and are proactive in the use of IS/IT, then the outcome will produce more patient choice, less nonattendance, and consequently improved primary health care provision.     

Analysis of changes in sexual function in women undergoing pelvic organ prolapse repair with abdominal or vaginal approaches

Introduction and hypothesis

To examine changes in sexual function after abdominal and transvaginal pelvic organ prolapse repair.

Methods

Women enrolled in our prospective, longitudinal prolapse database with abdominal sacrocolpopexy (ASC) or transvaginal (TVR) pelvic organ prolapse (POP) repair with or without mesh, between 19 December 2008 through 4 June 2014. The Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and the Pelvic Floor Distress Inventory (PFDI?-20) were mailed preoperatively, and at 6 and 12 months postoperatively. Patients completed Global Response Assessments to rate their overall satisfaction.

Results

Two hundred and four of the 300 women met the inclusion criteria: 74 out of 204 (36 %) had ASC and 130 out of 204 (64 %) had TVR. Seventy-two out of seventy-four ASCs were performed robotically and 2 were open. Baseline demographics were similar except that the ASC patients were significantly younger (60 vs 63, P?=?0.019) and had a higher rate of apical repair (77 % vs 55 %). Thirty-six out of seventy-four ASC (48.7 %) and 63 out of 128 TVR patients (49.2 %) were sexually active at baseline (P?=?0.94). Sixteen out of thirty-eight ASC (42.1 %) and 18 out 63 TVR patients (28.6 %; P?=?0.16) reported dyspareunia at baseline. Seventy-two out of seventy-four ASC (97 %) and 86 out of 130 TVR patients (66 %) had mesh-augmented repairs. There was no difference in sexual activity or dyspareunia between the groups at the 6- or 12-month follow-up. PISQ and PFDI scores improved significantly in both the ASC and TVR groups over time compared with the baseline (p?<?0.0001). Most women in the ASC (77.5 %) and TVR (64.8 %) groups were satisfied with the results of prolapse surgery at 12 months.

Conclusions

Sexual function and pelvic floor symptoms improved in a similar manner in patients after abdominal and transvaginal POP surgery.

     

Epidemiological investigation of a jaundice outbreak in Kishangarh,Rajasthan, India, 2014

Aim

To study the distribution of jaundice cases among university students and clinical profile of positive cases to initiate the control measure inside university premises.

Subject and methods

An epidemiological survey was conducted to collect the information regarding a jaundice outbreak among the students residing in hostels at the Central University of Rajasthan, Kishangarh, and Ajmer, India in October and November 2014. Fifteen hundred twenty-six students were screened for this epidemiological investigation by door-to-door survey throughout all of the student hostels and their physical and clinical data were collected from hospital records.

Results

The distribution of this outbreak of jaundice disease was 71.5 % male and 28.6 % female among the detected cases, whereas only 4.5 and 2.5 % of the total male and female students respectively, were affected by jaundice while living in the university premises. This indicates that male students had a higher risk of infection than female students. Students from the age group 20 to <24 years were more susceptible for jaundice infection as compared to other, confirmed by elevated levels of serum bilirubin, aspartate transaminase and alanine aminotransferase reported at the time of diagnosis. Moreover, out of total 56 jaundice cases, 30 were from Rajasthan state, and remainders were from other states.

Conclusions

Elevation in serum bilirubin, aspartate transaminase and alanine aminotransferase and physical symptoms indicates jaundice outbreak at the university. This study warrants the time needed to check water sources and water sanitation to avoid drinking-water contamination.

     

Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist

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