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Biomedical subjects

K Prabhakaran

Publications and source records attributed to K Prabhakaran.

At least 19 recordsLinked to original sources

Management of a floating sternum after repair of pectus excavatum.

PURPOSE: The aim of this study was to examine the authors' experience with patients who have floating sternum after correction of pectus excavatum via the classical Ravitch procedure. A floating sternum is defined as a sternum in which the only attachment to the chest wall is its superior (cranial) border, and in which the body is secured only by the manubrium and whatever lateral and inferior fibrous bands are present. Typically, a floating sternum is caused by either extensive resection of the costal cartilages and perichondrium during correction of pectus excavatum or failure of proper regrowth of these cartilages. METHODS: The authors retrospectively assessed the charts of all patients diagnosed with a floating sternum noting age at original correction of pectus excavatum, time from original correction of pectus excavatum to diagnosis of floating sternum, age at correction of floating sternum, complaints before stabilization of the sternum, methods of repair, and postoperative complications. RESULTS: Between July 1993 and June 1999, floating sternum was diagnosed in 7 patients. The mean age of patients who underwent operative correction of a floating sternum was 28.9 years (range, 16 to 42 years). The mean time interval between original correction of pectus excavatum, or "redo," and diagnosis of a floating sternum was 9.9 years (range, 2 to 20 years). Complaints before correction of the floating sternum included sternal pain and instability, exercise intolerance, and difficulty breathing. Operative repair consisted of mobilizing the lateral and inferior edges of the sternum, detaching the fibrous perichondrium, performing anterior sternal osteotomies, and finally supporting the sternum with substernal Adkins struts. All 7 patients had successful stabilization of the sternum. Two of 7 patients underwent 2 procedures to successfully stabilize the sternum. One patient has Adkins struts still in place because of hematopoetic malignancy. Six of 7 patients are now without symptoms. CONCLUSIONS: A floating sternum is a morbid phenomenon that may manifest many years after the original procedure. It can cause significant sternal pain, chest wall instability, and respiratory dysfunction, which are the hallmark indications for correction. Repair of a floating sternum can be accomplished successfully.

Adolescent↗

Cumulative experience with pediatric living related liver transplantation.

PURPOSE: This study reports the authors' cumulative experience with pediatric living related orthotopic liver transplantation. METHODS: The charts of all patients who received living-related liver transplantation to study complications of transplant surgery, immunosuppression, rejection, and overall survival rate were reviewed retrospectively. RESULTS: Between November 1992 and October 1998, 30 children underwent living-related liver transplantation. Patients were between the ages of 3 months and 7 years of age (mean, 28 months). All received left lateral segmental living-related transplants. At the time of transplant, 14 of 30 patients were listed as United Network of Organ Sharing (UNOS) status 3, 11 were listed as UNOS status 2B, and 5 were listed as UNOS status 1. Indications for transplant included biliary atresia (n = 21), alpha-1-antitrypsin deficiency (n = 2), hepatitis C (n = 2), giant cell hepatitis (n = 2), hepatoblastoma (n = 1), valproic acid toxicity (n = 1), and hemangioendothelioma (n = 1). All donors were parents except for one uncle. There were no major donor complications. Minor complications included wound infection (n = 4), ventral hernia (n = 2), postoperative gastric dysmotility (n = 2), and 1 case of central line-related pneumothorax (n = 1). All but 4 recipients received primary tacrolimus immunosuppressive regimens, and the other 4 underwent conversion from cyclosporine. Initial tacrolimus therapy was begun at 0.15 mg/kg/dose PO/NG every 12 hours. Concomitant immunosuppression included methylprednisolone and mycophenolate mofetil. Fifty-three percent of patients experienced at least 1 episode of rejection, and 27% experienced multiple episodes. Immediate postoperative complications included primary nonfunction (n = 2), vascular thrombosis (n = 3), biliary leaks (n = 3), and infections (n = 17). Two patients (n = 2) required retransplantation. Complications of immunosuppressive therapy included persistent systemic hypertension (n = 6), renal tubular acidosis (n = 3), short-term hyperglycemia (n = 2), neurotoxicity (n = 2), nephrotoxicity (n = 2), food allergies (n = 8), and posttransplant lymphoproliferative disease (n = 4). All patients with PTLD were treated with immunosuppression reduction or withdrawal. Two of 4 had disease progression requiring chemotherapy. The majority of complications were treated with dose adjustments. There were 4 early deaths (13%): 1 of primary nonfunction, 2 of sepsis, and 1 of arrhythmia and renal failure. There was 1 late death of recurrent disease. Twenty-five patients (83%) are alive at 3 months to 6 years post-transplant. CONCLUSION: Living-related orthotopic liver transplantation is an effective intervention for pediatric patients with end-stage disease.

Child↗

Regulation by protein kinase of phagocytosis of Mycobacterium leprae by macrophages.

Mycobacterium leprae multiplies within host macrophages. The mechanism of internalisation of the bacteria by the phagocytic cells is unknown. In this study, M. leprae was purified from the foot pads of experimentally infected nu/nu mice. Peritoneal macrophages were harvested from BALB/c mice or C57 beige (bg/bg) mice. The effect of protein kinase inhibitors (erbstatin, genistein or staurosporine for BALB/c and bg/bg mice, plus herbimycin for bg/bg mice) on phagocytosis of the mycobacteria by the macrophage monolayers was tested. The untreated (control) macrophages phagocytosed M. leprae. Phagocytosis by BALB/c macrophages was inhibited by erbstatin and staurosporine but not by genistein; all the protein kinase inhibitors prevented uptake of M. leprae by bg/bg cells. The results demonstrate that protein kinase regulates phagocytosis of M. leprae by macrophages. The mechanism might prove to be a rational drug target for mycobacteria that multiply intracellularly.

Animals↗

Laparoscopic nephroureterectomy in children.

BACKGROUND/PURPOSE: Laparoscopic surgery is playing an increasingly important role in pediatric urology. It has emerged as an alternative means of performing nephroureterectomy. The authors report their experience with laparoscopic nephroureterectomy in children. METHODS: Between July 1996 and August 1997, six patients aged between 3 months and 5 years, 9 months (average, 35 months) underwent laparoscopic nephroureterectomy. The transperitoneal approach was used in all cases. RESULTS: Operating times ranged from 110 to 265 minutes, averaging 176 minutes. No early or late postoperative complications were noted. Five of six patients resumed oral feeding on the first postoperative day. Four of six patients were discharged on the second postoperative day. CONCLUSIONS: Laparoscopic nephroureterectomy is a safe and feasible alternative to the open method in children. It is associated with good surgical results and favorable postoperative patient recovery.

Child, Preschool↗

Esophageal intramural pseudodiverticulosis associated with a web in a 12-year-old boy.

Esophageal intramural pseudodiverticulosis (EIPD) is a rare benign disorder characterized by dilation of the submucosal glands. Its etiology and pathogenesis are largely unknown. So far, less than 10 pediatric cases of EIPD have been reported. The authors present the case of a 12-year-old boy with EIPD that was associated with a cervical esophageal web. He was treated successfully with dilation therapy.

Child↗

Bactericidal action of ampicillin/sulbactam against intracellular mycobacteria.

The resistance of mycobacteria to beta-lactam antibiotics is attributed to their ability to synthesize beta-lactamase. In our previous studies, beta-lactam/beta-lactamase-inhibitor combinations suppressed the growth of several mycobacteria in axenic cultures and ampicillin/sulbactam was bactericidal to Mycobacterium tuberculosis H37Rv in vitro, and to Mycobacterium leprae multiplying in mouse foot-pads. Since both these organisms multiply in phagocytic cells in the host, it is important to know whether the drug combination is active against mycobacteria multiplying in macrophages. We tested the action of ampicillin/sulbactam against four potentially pathogenic (to humans or to animals) mycobacteria, M. simiae, M. haemophilum, M. avium, M. microti, when phagocytosed by mouse macrophages. Bacteria were exposed to monolayers of peritoneal macrophages harvested from BALB/c mice. Unphagocytosed bacilli were removed and three concentrations of ampicillin/sulbactam were tested. Optimum activity was observed at 100 mg/l which killed 58-97% of the mycobacteria within macrophages, as determined by the CFU. beta-Lactam/beta-lactamase-inhibitors, especially ampicillin/sulbactam, might provide an effective alternative therapy against infections caused by mycobacteria resistant to other drugs.

Ampicillin↗

Bactericidal action of oral ampicillin/sulbactam against Mycobacterium leprae.

We reported previously that an injectable form of ampicillin/sulbactam, Unasyn, was bactericidal to Mycobacterium leprae multiplying in mouse foot pads. In this study, we examined the effect of an orally active form of ampicillin/sulbactam, Sultamicillin, on the growth of M. leprae in mice. Three concentrations of the drug, mixed with the feed, were administered from the start until the mice were killed at 6 months; 0.01% of the drug inhibited bacterial growth by 54%, 0.10% by 74% and 0.20% by 93%. To test whether oral ampicillin/sulbactam was bactericidal, 0.50% of the drug, mixed with the feed, was administered to experimentally infected mice for 3 months during the logarithmic phase of bacterial growth, and then discontinued; multiplication of the bacilli was monitored monthly for the next 8 months. The results showed that orally active ampicillin/sulbactam is bactericidal to M. leprae.

Administration, Oral↗

Postantibiotic effect of ampicillin/sulbactam against mycobacteria.

The postantibiotic effect (PAE) is an important pharmacodynamic property of antibiotics. Most drugs continue to exert a suppressive effect on the growth of bacteria, both in vitro and in vivo, even after the drug concentrations have fallen below detectable levels. Only limited information is available on the PAE of slow-growing organisms like mycobacteria. The PAE of ampicillin/sulbactam (Unasyn) was investigated against six species of mycobacteria, viz Mycobacterium avium, M. africanum, M. bovis BCG, M. simiae, M. scrofulaceum and M. tuberculosis H37Ra, by spectrophotometry. The cell counter method was also used in one set of experiments. The bacteria were exposed to ampicillin/sulbactam for 2 h, 24 h, 72 h or 7-10 days. Five concentrations, 5, 10, 50 or 100 micrograms/ml, of the drug were tested. Afterwards, the bacteria were washed free of Unasyn and allowed to multiply. Treatment of the mycobacteria for 2 h did not produce any PAE, although 100 micrograms/ml of the drug caused slower growth. Exposure to 50, 60, or 100 micrograms/ml, resulted in a prolonged PAE of approximately 3 days. The data on the PAE of Unasyn may be of clinical relevance in determining dosage regimens of the drug.

Ampicillin↗

Infections in paediatric renal transplant recipients.

A retrospective study of all children who had undergone renal transplantation at the National University Hospital was undertaken in order to investigate the types and frequency of infections in paediatric renal transplant recipients. A total of 13 children ranging in age from 3 to 17 years were transplanted over a 7-year period from 1989 to 1996. The mean follow-up period was 40.5 months. Ten patients (77%) had at least one episode of infection post-transplant, 70% of which occurred within the first 6 months post-transplant. These infections included urinary infections (8), disseminated cytomegalovirus (CMV) disease (4), Pneumocystis carinii pneumonia (1) and mycoplasma pneumonia (1). Urinary tract infections were significantly associated with the presence of ureteral stents. CMV disease was significantly associated with the use of mycophenolic acid in the early post-transplant period. Infection therefore continues to be a major cause of morbidity in paediatric renal transplant recipients.

Adolescent↗

Suppression of the growth of six potentially-pathogenic mycobacteria by beta-lactam/beta-lactamase-inhibitors.

Drug-resistant tuberculosis and opportunistic infections by mycobacteria in immunocompromised subjects are not readily controlled with the antimycobacterial drugs now available. beta-Lactam antibiotics, the most widely used antibacterial agents, are ineffective against mycobacteria since they synthesize beta-lactamases. The beta-lactam/beta-lactamase-inhibitor combinations are used at present to treat infections caused by other beta-lactamase-positive organisms. Six potentially-pathogenic mycobacteria: Mycobacterium avium, M. chelonei, M. haemophilum, M. microti, M. scrofulaceum and M. simiae, were cultured in 7H9 medium (containing Tween 80 and albumin, dextrose, catalase) at 37 degrees C for 10-14 days, with or without various concentrations (2-100 micrograms/ml) of ampicillin/sulbactam, amoxicillin/clavulanate and piperacillin/tazobactam. More than 50-80% inhibition of the mycobacterial growth was observed at drug levels of 40-100 micrograms/ml in the medium; the drugs were active even when the detergent (Tween 80) was omitted. Against four of the mycobacteria, ampicillin/sulbactam proved to be the most active. The beta-lactam/beta-lactamase-inhibitor combinations may be of use as rational therapeutic agents against mycobacterial infections.

Anti-Bacterial Agents↗

Age- and sex-related changes in lymphocyte subpopulations of healthy Asian subjects: from birth to adulthood.

Flow cytometric analysis of lymphocyte subsets were evaluated in 391 healthy Asian subjects ranging in age from birth to 40 years. Lymphocyte subsets were analysed using specific monoclonal antibodies: CD20 (B cells), CD3 and CD2 (T cells), CD16 and CD56+ (NK cells), CD4/CD3+ (helper-inducer T cells), CD8/ CD3+ (suppressor/cytotoxic T cells), HLA-DR expression on CD3 and CD25 (Tac) on CD3. The total white cell count, absolute lymphocyte counts, and B cell percentages peaked in infancy and declined steadily with age. Absolute counts of each subset, which were derived from absolute lymphocyte counts, also followed this trend. Increases with age were seen in the NK, T cell (CD2, CD3), and CD8 percentages. Males tended to have higher NK and CD8 percentages than females, and, conversely, females had higher CD3 and CD4 percentages than males. Comparison of our results with studies involving Caucasian subjects indicated higher NK percentages in our Asian population and lower CD4 absolute counts in the males of our population. These results indicate the presence of age, sex, and probable racial differences in lymphocyte subset expression. Our results may serve as reference standards for the Asian population.

Adolescent↗

Properties of lysophospholipase in Mycobacterium leprae.

Lysophospholipids are key intermediates in the metabolism of phospholipids. Cytoplasmic membranes of both eukaryotes and prokaryotes are made of phospholipid bilayers. Phospholipases are activated during phagocytosis. Lysophospholipids generated by phospholipase A2 or A1 degrade cell membranes and can cause cell lysis. An active lysophospholipase, that hydrolyzes lysophospholipids, was detected by the radioisotope technique in Mycobacterium leprae. About two-thirds of the enzyme was particulate and one-third cytoplasmic. Optimum activity was at 37 degrees C, and at pH 6.0. Temperatures above 70 degrees C completely inactivated the enzyme. The compound AACOCF3, a trifluromethylketone analog of arachiodonic acid, inhibited the activity; the inhibition appeared to be of the uncompetetive type. The K(m) of the enzyme was 2.5 x 10(-4)M, suggesting a fairly strong affinity for the substrate. Lysophospholipids have been shown to be microbicidal to invading organisms. Possession of lysophospholipase by M. leprae is apparently one of the methods by which the bacilli overcome the defense mechanisms of the host.

Arachidonic Acids↗