High-dose atorvastatin therapy in severe heterozygous familial hypercholesterolaemia

Lipid targets can be difficult to attain in familial hypercholesterolaemia. To compare atorvastatin with simvastatin- fenofibrate and simvastatin-cholestyramine therapy, we studied 54 patients with familial hypercholesterolaemia over periods of 2-6 months on each therapeutic regimen. The atorvastatin regimen reduced total cholesterol by 41.2 +/- 11.2%, LDL by 45.6 +/- 15.5%, triglycerides by 33.8 +/- 24.8%, and increased HDL by 2.3 +/- 37.0%. Simvastatin- fenofibrate therapy achieved reductions of 33.9 +/- 8.5% in cholesterol, 42.0 +/- 12.2% in LDL, 34.7 +/- 38.3% for triglycerides, and a 25.4 +/- 55.1% increase in HDL. Simvastatin-cholestyramine gave a reduction of 31.3 +/- 11.8% in cholesterol, 36.0 +/- 14.4% in LDL, 13.7 +/- 36.3% in triglycerides, and a 1.1 +/- 30.3% rise in HDL. The atorvastatin regimen was marginally but not significantly better than simvastatin-fenofibrate in improving the LDL:HDL ratio, LDL:apoB and and apolipoprotein B:A1 ratios. Eleven patients (20.4%) had side- effects: two discontinued atorvastatin due to side-effects; two patients had rashes; six had myalgia and two had diarrhoea. Gastrointestinal side-effects were described in 16 (30.1%) patients on simvastatin-cholestyramine therapy and four cases of myalgia (11.2%) were seen with simvastatin-fenofibrate. In nine patients on atorvastatin (20.4%) a 30% or greater fall in HDL was observed, compared to five patients with resin therapy (9.2%) and two with fibrate therapy (5.5%). There were no significant differences in liver or muscle biochemistry between the regimens, but atorvastatin did raise transaminase and creatine kinase concentrations significantly compared to pre-treatment values (p = 0.001). Atorvastatin significantly improves the lipid profile in most patients compared with other regimens. It has a comparable incidence of side-effects to combination therapy regimens.      

Characterization of the epitope recognized by a monoclonal antibody highly specific for blood group M antigen

The mouse monoclonal antibody M2A1 of IgG1 class, which is highly specific for blood group M antigen, was obtained and characterized by means of hemagglutination, enzyme-linked immunosorbent assay, immunoblotting, and inhibition assays. The use of modified M glycoprotein preparations for inhibition tests and of variant McN and Henshaw red cell membranes for immunoblotting showed that M2A1 recognized an epitope including the NH2-terminal serine and sialic acid residues of glycophorin A, whereas the fifth glycine residue was not involved. The reactivity of the antibody with M antigen was distinctly dependent on ionic strength and pH; the optimum was at pH 8 to 9. The alpha-amino group of terminal serine residue was not necessary for the reaction with M2A1 antibody, and the results obtained suggested that the positive charge of this group contributed to decreasing antigen-antibody reactions at pH below 8. The reaction of the antibody with blood group N antigen was not detectable in any of the assays used.     

Head-Up Tilt Test in Patients with High Pretest Likelihood of Neurally Mediated Syncope: An Approximation to the "Real Sensitivity" of this Testing

This study was designed to examine the "true sensitivity" of a specific head-up tilt (HUT) testing protocol using clinical findings. The HUT protocol used 45 minutes at 60 degrees for the baseline portion and intermittent boluses of 2, 4, and 6 micrograms of isoproterenol in the second phase. Eighty-eight patients (40 men and 48 women; mean age of 33.8 +/- 16 years) with recurrent syncope and high pretest likelihood of neurally mediated syncope were included. The following were considerated as high pretest likelihood criteria: (1) at least two syncopal episodes; (2) no structural heart disease and normal baseline ECG; (3) age < 65 years; (4) a typical history of neurally mediated syncope, triggering factors plus premonitory signs; and (5) short duration of symptoms and fast recovery without neurological sequelae. Fifty-four patients (61%) had a positive tilt test (34/88 baseline [39%] and 20/50 with isoproterenol [40%]). The shorter time interval between the last syncopal episode and baseline HUT test was the only predictor for a positive response (P < 0.003). Conversely, this time interval was not predictor of positive responses during isoproterenol-tilt testing. In conclusion: (1) we claim a "sensitivity" for this combined protocol of 61%; and (2) our results indicate that patients with syncope of unknown origin must be tilted nearest as possible to the last syncope to increase the positive responses of HUT test.     

Angiotensin‐converting enzyme inhibition increases glucose‐induced insulin secretion in response to acute restraint

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Diabetes mellitus in India: The modern scourge

India has a high prevalence of diabetes mellitus and the numbers are increasing at an alarming rate. In India alone, diabetes is expected to increase from 40.6 million in 2006 to 79.4 million by 2030. Studies have shown that the prevalence of diabetes in urban Indian adults is about 12.1%, the onset of which is about a decade earlier than their western counterparts and the prevalence of Type 2 diabetes is 4–6 times higher in urban than in rural areas. The risk factors peculiar for developing diabetes among Indians include high familial aggregation, central obesity, insulin resistance and life style changes due to urbanization. Screening for gestational diabetes and impaired glucose tolerance among pregnant women provides a scope for primary prevention of the disease in mothers as well as in their children. The problems of obesity and impaired glucose tolerance (IGT) (important predisposing factors) are not confined to adults alone but children are also increasingly getting affected. Most long standing macro and micro vascular complications are also more common among Indian diabetics as compared to other races and ethnic groups. A strong familial clustering of diabetic nephropathy among Indian Type 2 diabetics has also been noted. Clustering of cardiovascular risk factor like Syndrome X is common among urban Indians. The rising incidence of diabetes and its complications are going to pose a grave health care burden on our country. Timely effective interventions/measures and screening tests for complications at the time of diagnosis becomes imperative not only for early detection, but also to prevent progression to end stage disease. Screening for gestational diabetes among pregnant women would also go a long way in primary prevention of the disease. Life style changes/interventions and drugs like rosiglitazone are the current strategies that can prevent and/or delay the onset of diabetes. Simple interventional strategies like “Eat less, Eat on time and Walk more” can go a long way in preventing these chronic disorders among present as well as in the future generations.     

Urodynamic Management of Neurogenic Bladder in Spinal Cord Injury

Background

A spinal cord injury is devastating and produces profound changes in the life style of the individual and his family. It is difficult to predict bladder and sphincter behaviour on the basis of clinical somatic neurological deficits.

Methods

A prospective study of 100 spinal cord injury patients was conducted to establish a bladder management protocol. The urodynamic variables were assessed frequently. Clean Intermittent Catheterization (CIC) along with antimuscarinic drugs was instituted and response monitored. Nonresponders were offered Intradetrusor Botulinum toxin.

Result

Spinal shock lasted for upto six months and only 8% could be converted to CIC during the acute phase. A total of 82% patients underwent three to four urodynamic studies which revealed an increase in cystometric capacity and a decrease in the maximum detrusor pressures. This lowered the incidence of incontinence episodes and prevented upper urinary tract damage. Botulinum toxin provided only temporary relief.

Conclusion

Aggressive management of neurogenic bladder (NB) dysfunction is a crucial component of the rehabilitation programme for spinal cord injury patients. Repeated urodynamic studies are an essential aid in managing the evolving nature of the bladder dysfunction. Meticulous bladder management protocol can prevent upper urinary tract complications.Key Words: Spinal cord injury, Neurogenic bladder, Urodynamics     

A Medical Curriculum for all seasons - a dialogue

Ten years have now passed since the College of Medicine of the University of Malawi was opened. The College''s Curriculum is firmly based on community needs. We describe the genesis and implementation of the curriculum of the College of Medicine and how it has persisted over the past ten years. The challenges that have so far been met are outlined.     

Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital

A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics.     

Reconstruction of Complex Abdominal Wall Defects

Introduction

Reconstruction of large abdominal wall defects not amenable to primary closure remains a challenging problem. These defects result from trauma, previous surgery, infection and tumour resection. The primary objectives of abdominal wall reconstructions are to protect abdominal contents and provide functional support. The abdominal wall reconstruction aims at providing basic component parts, i.e. skin, soft tissue and fascia. For large soft tissue defects, pedicled or free flap closure can be used. In clean wounds, fascial replacement is accomplished with synthetic mesh provided there is adequate soft tissue coverage.

Methods

We treated a total of 20 consecutive patients with complex abdominal wall defects utilizing various reconstructive procedures. There were 15 males (75%) and 5 females (25%). The aetiology included dehiscence of laparotomy wounds in eight (40%), following ablative surgery for malignant tumours in seven (35%), trauma in three (15%) and congenital defects in two (10%) cases. The reconstructive procedures consisted of onlay prolene mesh in seven (35%), Gore-Tex (PTFE) dual mesh both as inlay and onlay in five (25%), facial partition release technique in three (15%), inlay prolene mesh covered with omentum and split skin graft in two (10%), inlay prolene mesh covered with expanded skin in two (10%), and Gore-Tex dual mesh covered with latissimus dorsi myocutaneous flap in one (5%) case. Postoperatively none developed mesh infection or extrusion. Three patients with malignant aetiology received postoperative radiotherapy. During follow up, one patient developed ventral hernia cephalad to the repair and one died due to recurrence of abdominal wall malignancy.

Conclusion

The reconstruction of an abdominal wall defect requires a comprehensive plan of preoperative and post operative care of the patient and aims toward restoration of abdominal structural integrity by a variety of procedures. The use of new biomaterials and tissue expanders provides reliable and durable abdominal wall closure along with good aesthetic results.Key Words: Abdominal wall defect, Mesh repair, Abdominal wall reconstruction