Bactericidal action of ampicillin/sulbactam against Mycobacterium leprae.
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Biomedical subjects
Publications and source records attributed to K Prabhakaran.
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Rats subjected to electrical stimulation of hippocampus (30 min/day for 4 days) showed an increase in the neutrophils in the peripheral blood when compared to sham (P < 0.01) and controls (P < 0.001). They also showed a significant decrease in lymphocytes, when compared to control rats (P < 0.001). Both sham and stimulated animals showed a significant decrease in total white blood cell count when compared to controls (P < 0.001). The phagocytic index of stimulated animals showed a significant increase from control (P < 0.001) and sham (P < 0.001). In addition, the stimulated animals showed a significant (P < 0.001) decrease in plasma corticosterone level when compared to sham and controls.
Mycobacterium tuberculosis and Mycobacterium leprae develop resistance against the drugs used to treat tuberculosis and leprosy, respectively. Now multidrug-resistant tuberculosis is spreading in many countries, especially with the emergence of AIDS. Multidrug treatment is being promoted at present to eradicate leprosy. Since M. leprae may also become multidrug-resistant, new approaches have to be adopted for controlling mycobacterial diseases. Mycobacteria usually synthesize beta-lactamase and are insensitive to beta-lactam antibiotics. M. tuberculosis contains a constitutive beta-lactamase; de-repression of beta-lactamase has been reported in M. leprae. Three different beta-lactam/beta-lactamase-inhibitor combinations (ampicillin/sulbactam, amoxicillin/clavulanate and piperacillin/tazobactam) were used to suppress the growth of several strains of mycobacteria (including M. tuberculosis H37Rv) in vitro. Ampicillin/sulbactam is a potent bactericidal agent against M. leprae multiplying in mouse foot pads. In the present work, ampicillin/sulbactam showed higher activity than the other drug combinations. The beta-lactam/beta-lactamase inhibitors are likely to be effective as rational therapeutic agents against mycobacterial infections.
With the advent of antenatal ultrasound, the focus on sacroccocygeal teratoma has shifted from management at birth to management in the antenatal period. Multidisciplinary approach involving the obstetrician, neonatologist and paediatric surgeon is necessary to achieve good results. Two cases of antenatally detected sacrococcygeal teratomas are reported, one at 24 weeks and the other at 26 weeks of gestation. The tumour was benign in both cases and in both cases, delivery was done at full term. In one case, it was a normal vaginal delivery and in the other, an elective lower segment caesarean section was performed. Close ultrasound follow-up during pregnancy had excluded cardiac failure, hydropic changes and other congenital anomalies which could have altered the management of the pregnancy. Accurate diagnosis of such tumours during antenatal periods may in future allow intrauterine fetal interventional surgery for a premature fetus. The tumour was surgically dealt with successfully in each case on the third day after birth with good clinical results at the end of one year and eight months respectively.
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The multiplication of Mycobacterium leprae in foot pads of experimentally-infected mice was suppressed by intramuscular administration of ampicillin combined with sulbactam or YTR-830H, two potent inhibitors of beta-lactamase in the bacteria. The antibiotic or the inhibitors by themselves were inactive. Ampicillin/sulbactam also inhibited the growth of drug-resistant M. leprae which grew in the presence of rifampin or dapsone. The finding provides a new approach to treat leprosy and to overcome drug resistance of the mycobacteria.
Neurotropism is one of the unusual properties of Mycobacterium leprae. The organism contains glutamic acid decarboxylase that generates gamma-amino-butyric acid (GABA) which is an inhibitory neurotransmitter. The binding of GABA by M. leprae in vitro was studied by using 3H-GABA as substrate. The bacteria had high-affinity binding sites for the amino acid. The uptake was a specific saturable process with a Km of 66.7 pM, pH optimum of 7.3 and a temperature optimum of 37 degrees C. The binding did not seem to be time-dependent, being complete in about 5 min. None of the known antagonists and agonists of GABA uptake by neurons, showed any significant effect on M. leprae; the receptors in the bacteria are apparently of a non-neuronal type, and different from those reported in spermatozoa and Pseudomonas.
Hepatoblastoma is an uncommon liver neoplasm in children but its intraatrial extension through the inferior vena cava is extremely rare. The case described is a 3-year-old boy in whom profound hypothermia and circulatory arrest were used to resect a hepatoblastoma and its extension to the right atrium. This technique allows maximal resection and relief of venous obstruction from atrial extension of hepatoblastoma.
Diagnosis of gut duplications are often only made intraoperatively as they are uncommon and do not feature strongly in the differential diagnoses. A case of caecal cystic duplication mimicking intussusception is discussed with the aim of improving diagnostic accuracy in future cases. A 7 month old boy presented with the classical triad of abdominal pain, bleeding per rectum and a palpable mass. Barium enema revealed a mass in the caecum suggestive of an intussusceptum. Repeated attempts at hydrostatic reduction were unsuccessful as the mass was immobile. Laparotomy revealed cystic duplication of the caecum without intussusception. The bleeding per rectum was due to an ulcer in the colonic epithelium overlying the cyst.
It is not known how Mycobacterium leprae obtains energy for survival and growth in the host tissues; the organism does not grow in vitro. In the studies reported here, M. leprae incorporated labelled ATP, which was blocked by cyanide, unlabelled ATP or ADP, but not by adenosine or Pi. It seems that the organism takes up unhydrolysed ATP by an active transport process. The bacterium contained a membrane-bound, vanadate-sensitive E1 E2-ATPase (which creates a transmembrane potential driving transport of solutes into cells). The enzyme was not inhibited by N-ethylmaleimide, suggesting that it is not an F0F1-ATPase which catalyses ATP synthesis. Apparently, M. leprae derives energy-rich compounds from the host cell.
Water and soil samples were collected from natural habitats of the nine-banded armadillo and tested for the presence of acid-fast organisms by injection into the foot pads of experimental mice. Sixteen months post inoculation an acid-fast organism was isolated from the foot pad and spleen of one of the mice. The isolate exhibited diphenoloxidase activity as determined by its ability to convert D-3,4-dihydroxyphenylalanine to the corresponding quinone. The same organisms grown in vitro lacked detectable diphenoloxidase activity. However, diphenoloxidase activity was observed in acid-fast organisms harvested from spleen tissue of mice experimentally inoculated with a pure culture of the isolate. The environmental isolate was tentatively classed with the Mycobacterium avium-intracellulare complex.
There are few reports of colonoscopy in children. Twenty-six children with bleeding per rectum were examined colonoscopically to determine the aetiology of the bleeding. A total of 32 colonoscopies were performed. Except for 5 children who needed general anaesthesia, all the rest were performed with pethidine and diazepam sedation. The mean age of these 26 children was 63.5 months (SD 57.5 months, range 2 weeks to 180 months). Ten children had histologically confirmed colitis. Five had bleeding juvenile polyps and these were removed endoscopically. One had lymphoid hyperplasia and one had chronic solitary sigmoid ulcer. The rest were normal. It is concluded that colonoscopy can be performed safely in children and it is a good diagnostic and therapeutic procedure.
This communication reports the association of changes in ultrastructure of Mycobacterium leprae with alterations in its permeability. To study morphologic changes of the organisms under different conditions (of temperature and exposure to NaOH and trypsin), ultrathin sections of the bacteria were cut and examined in an electron microscope. In the untreated bacilli and those washed with trypsin, the cytoplasmic membrane and the cell wall (peptidoglycan layer) remained intact; dapsone showed little effect on diphenoloxidase of the bacteria. M. leprae is unique among mycobacteria in possessing an unusual form of the enzyme diphenoloxidase. The antileprosy drug dapsone is a potent inhibitor of the enzyme, but it does not readily penetrate the bacteria where the cell envelope remains intact. The cell wall of M. leprae exposed to -80 degrees C or washed with NaOH was partially detached from the cell membrane; dapsone readily penetrated these organisms and inhibited the bacterial enzyme. In the above preparations, the cytoplasmic membrane appeared undamaged and the bacteria remained viable, as evidenced by multiplication in mouse foot pads. At 50 degrees C, the peptidoglycan layer became completely separated from the membrane and the cytoplasm was partially denatured. These organisms were permeable to dapsone, but were no longer viable. At 100 degrees C, the structural organization of the bacilli was completely destroyed, and of course, they lost their enzyme activity as well as viability. Evidently, the intact cell wall layer mediates the exclusion of dapsone from M. leprae, and there is no correlation between its viability and permeability. The ultrathin sections also reveal the internal organization and cytoplasmic inclusions of M. leprae, as never before seen.
The value of anorectal manometry as a diagnostic tool for Hirschsprung's disease (HD) was assessed in 50 children presenting with chronic constipation. Anorectal manometric studies and rectal biopsy were performed on all children. Biopsy specimens were stained with hematoxylin and eosin and serial sections were examined for ganglion cells. Forty-five children had concordant manometric and histologic results, 15 of whom were positive for HD and 30 negative. In five children, the results were discordant. Using histologic aganglionosis as the reference point for the final diagnosis of HD, the overall accuracy of anorectal manometry as a discriminative test was 90.0%. The sensitivity, specificity, and positive and negative predictive values of manometric studies for the diagnosis of HD were 0.79, 0.97, 0.94, and 0.88, respectively. Factors responsible for the inaccuracies of manometric studies are discussed.
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Sonography has become an important diagnostic adjunct in the evaluation of vomiting infants who are suspected to have infantile hypertrophic pyloric stenosis (IHPS). Two commonly used sonographic criteria, viz. pyloric diameter (D) and pyloric muscle wall thickness (T) were evaluated in 14 consecutive vomiting infants. The D and T were significantly larger in the IHPS group compared to the non IHPS group (1.40 +/- 0.34 cm vs 0.95 +/- 0.19 cm, p = 0.04; 4.4 +/- 1.1 mm vs 2.5 +/- 0.6 mm, p less than 0.01). By a combination of sonographic criteria (D greater than or equal to 1.2 cm & T greater than or equal to 3 mm), all the 4 non IHPS patients and 9 out of 10 IHPS patients were correctly diagnosed. The positive and negative predictive values were 1.00 and 0.80, respectively. However, using reported diagnostic criteria of D greater than or equal to 1.5 cm or T greater than or equal to 4 mm would have missed 60% and 20% of the IHPS cases, respectively. With proper choice of diagnostic criteria, sonography is a useful diagnostic tool in the evaluation of vomiting infants for IHPS patients.