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

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Early viral replication in lymph nodes provides HIV with a means by which to escape NK-cell-mediated control

Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR(+) NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR(+) NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK-cell-mediated innate pressure.     

Autoimmune responses against renal tissue proteins in long-term surviving allograft recipients

Major histocompatibility complex antigens (MHC) are classical targets of recipient responses to allotransplants. However, the role of an immune response directed against autologous graft tissue determinants is poorly defined. In this study, we investigated (i) whether autologous kidney tissue extract can induce an immune response to autologous kidney proteins in normal rats, and (ii) if a similar autologous response develops in the long-term surviving LEW.1A recipients of an MHC-mismatched LEW.1W kidney (RT1^u to RT1^a). LEW.1A rats immunized with allo- or syngeneic soluble kidney extracts developed a T-cell response to self antigens as shown by the frequency of specific IFN-γ-producing T cells from LEW.1A rats in the presence of extracts (ELISPOT). In contrast, they responded only marginally to dominant RT1^u determinants. The ELISPOT against fractions of soluble autologous kidney extracts separated by an FPLC gel-filtration system indicated a preferential response to megalin, a high molecular weight protein that has been shown to be involved in experimental Heymann nephritis. In a model of long-term kidney allograft survival by anti-CD28 administration, recipients also developed humoral but not cellular responses to megalin. Our data suggest that autoimmune processes develop in long-term surviving kidney allograft recipients.     

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