The lateral rectus spine of the superior orbital fissure.
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Biomedical subjects
Publications and source records attributed to N Kumar.
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Percutaneous balloon angioplasty was used to dilate inferior vena cava (IVC) stenosis in 12 patients with Budd Chiari syndrome. There were seven men and five women, aged 32.8 +/- 8.5 years. Angioplasty was performed using balloon 18-20 mm in diameter. In eleven (91.6%) patients, IVC could be successfully dilated. In these eleven patients, the caval diameter at the site of stenosis increased from 2.3 +/- 1.5 to 13.1 +/- 2.8 mm (p < 0.001), the mean IVC pressure decreased from 28.2 +/- 4.1 to 10.5 +/- 3.4 mmHg (p < 0.001) and the gradient across the stenosis decreased from 23.1 +/- 2.2 to 4.2 +/- 1.9 mmHg (p < 0.001). There was appreciable clinical improvement after angioplasty. On a mean followup of 10.8 (3-18) months four (36.4%) patients had restenosis which could be successfully dilated again. These results suggest that balloon dilatation of inferior vena cava stenosis is safe and effective, however, recurrence is common and needs redilatation.
We studied the clinical profile and etiology of 28 cases of ataxic hemiparesis. After a detailed neurological examination, CT scan brain (plain and after IV contrast) was done in all. Age ranged from 18 to 80 years. Acute onset of symptoms was in 22, while 6 had insidious onset. 18 patients had major infarct, while 4 patients had lacunar infarct. 2 patients were found to have haematoma (1 following head injury) and 1 each had tuberculoma, meningioma, glioma and toxoplasma granuloma. The lesions were seen in various parts of brain stem, thalamus, basal ganglion, internal capsule and frontal, parietal and temporal region. Heterogeneity as regards to etiology and localisation is being highlighted.
The study of human malaria has been hampered by the lack of small animal models for the human-infecting malarial parasites. To approach this problem, the erythrocytic stages of the human malarial parasite Plasmodium falciparum were adapted to in vitro growth in the presence of ascites fluid from mice homozygous for the severe-combined immunodeficiency (scid) mutation. Human red blood cells (hRBCs) infected with these adapted parasites were then injected i.p. into nonobese diabetic scid/scid (NOD/LtSz-scid) mice. With daily supplemental intraperitoneal boosts of uninfected hRBCs, parasites were detected in the peripheral circulation of these mice for an average of 7 d after injection. Splenectomy of NOD/LtSz-scid mice increased both the level and duration of parasitemia in the periphery, and it also promoted the circulation of mature sexual stage parasites (gametocytes). When Anopheline mosquitoes were allowed to feed on the splenectomized mice, the gametocytes were ingested by the mosquitoes and developed into oocysts in the mosquito midguts. To our knowledge, these results are the first demonstration of human malarial parasite propagation in mice and transmission of these parasites to the invertebrate vector.
Both CD8+ T cells and IFN-gamma (IFN-gamma) are important components in the regulation of inducible-nitric oxide synthase (iNOS) which contribute to liver stage anti-malarial activity in rodents immunized with irradiated sporozoites. IFN-gamma, provided by malaria-specific CD8+ T cells, stimulates liver cells to produce nitric oxide (NO) for the destruction of infected hepatocytes or the parasite within these cells. To identify the cell source of iNOS in livers from Brown Norway rats challenged with Plasmodium berghei sporozoites, we probed tissue sections with antisera that recognize iNOS and the malarial exoerythrocytic stage parasite. Immunofluorescence analysis of parasitized livers demonstrate that 1) iNOS was found in infected hepatocytes, not Kupffer or endothelial cells; and 2) a higher proportion of infected hepatocytes express iNOS in immunized rats compared with naive animals after challenge. There was no immunoreactivity to the iNOS antisera in liver sections of immunized rats 15 h after sporozoite challenge, however, iNOS activity was present in 18% of the infected hepatocytes by 24 h and reached 81% by 31 h. In contrast, < 10% of the infected hepatocytes displayed iNOS activity in naive or immune animals 48 h after challenge. We also found a significant decrease in the ability of the immunized animals to express iNOS in response to sporozoite challenge by accelerating the removal of pre-existing irradiated-attenuated parasites from hepatocytes with the antimalarial drug, primaquine. Therefore, induction and maintenance of iNOS activity were dependent on intrahepatic persistence of the irradiated-attenuated parasite. These results suggest that liver-iNOS expression following sporozoite challenge is restricted to the infected hepatocyte and dependent on the presence of the irradiated-attenuated parasite in immune animals.
1,2,4-Trioxane benzylic ethers 8a-e were prepared as simplified, tricyclic versions of the clinically used tetracyclic antimalarial drug artemisinin (1). Five additional artemisinin analogs (9-11) were prepared. Neither water solubility (analogs 8e and 11b) nor chelating ability (analogs 9 and 10), however, produced trioxanes of especially high in vitro antimalarial activity. Trioxane fluorobenzyl ether 8b is the most active in this series (more active than artemisinin) against Plasmodium falciparum parasites in vitro, with substantial activity also in mice infected with Plasmodium berghei parasites and with 10 times higher activity than artemisinin (1) in killing immature P. falciparum gametocytes.
Tricuspid valve pathology in Ebstein's malformation requires replacement when it is not possible to repair or reconstruct this valve. In smaller children, in whom the right-sided atrioventricular valve is severely dysplastic and right ventricular volume is prohibitive, prosthetic replacement is not always possible. We report here on 3 patients who underwent stentless semilunar homograft replacement (top-hat procedure) of tricuspid valve for Ebstein's anomaly with good short-term outcome. This provides an attractive alternative in the management of a certain difficult subset of patients, avoids long term anticoagulation and probably is more durable.
Aortic translocation is a useful surgical option in certain difficult subsets of transposition of great arteries with ventricular septal defect and left ventricular outflow tract obstruction. We report here the use of this technique with pulmonary homograft reconstruction of right ventricular pulmonary artery continuity in a child with transposition of the great arteries, left ventricular outflow tract obstruction, and restrictive ventricular septal defect.
Between 1988 and 1994, 82 consecutive patients (median age 24 years) underwent reconstruction of the aortic valve with glutaraldehyde-treated pericardium. Simultaneously, 29 of 30 mitral valves were repaired. The first 27 patients underwent resection of the free edges and suture of a single strip of bovine pericardium. Transient ischemic changes suggested the need for a change in technique. The subsequent 55 patients underwent total valve reconstruction with an autologous pericardium fixed with glutaraldehyde in the appropriate shape and size according to the patient's aortic annulus. There were one in-hospital and three late deaths. No patient received anticoagulation, and no embolic events were detected. Nine patients required reoperation as a result of failure of mitral valve repair in 4 and severe aortic regurgitation in 5 (endocarditis [n = 2], commissural tear [n = 1], root dilation [n = 1], calcification of one bovine cusp [n = 1] at 58 months). There were no reoperative deaths. Complete linear echocardiographic follow-up of these patients showed low gradients, valve competence, and no progressive deterioration. No difference between techniques was detected.
Extracardiac conduits in the form of allografts and synthetic tubes containing heterograft valves have been used widely in the management of ventricular outflow abnormalities and for establishing ventriculoarterial continuity. These procedures are limited by long-term calcification as well as by formation of neointimal peel, necessitating reoperation. In an effort to continue the search for an alternative conduit, we designed and evaluated a valved sinus-bearing conduit fashioned out of autologous pericardium treated with glutaraldehyde. The construction of the conduit is described. The results of implantation of these conduits in 12 sheep showed no progression of gradients, fresh regurgitation, or evidence of wall or cusp calcification 9 months after implantation.
Pulmonary autograft replacement of the aortic valve offers an attractive option in the younger patient with growth potential and long-term survival. In our institution between January 1990 and August 1994, 78 patients have undergone this procedure. The mean age was 18.6 +/- 7.36 years (range, 1 to 41 years). The etiology was rheumatic in 63 patients (80.7%). Aortic regurgitation was the predominant lesion in 60 patients (76.9%). Significant mitral regurgitation requiring operation was present in 22 patients (28.2%). All patients underwent pulmonary autograft replacement of the diseased aortic valve and the mitral valve was repaired in 22 patients. There were no hospital mortality, endocarditis, or thromboembolism in the series up to date. There have been two late non-cardiac deaths. Five patients (6.4%) required reoperation, one for mitral repair failure and four for autograft failure. Acute rheumatic valvulitis was demonstrated in one of the reoperated patients. Echocardiography of 68 patients followed up more than 2 months show progression of aortic regurgitation more than 2/4+ in 12 patients (15.4%). Four of these patients have been reoperated without mortality. In conclusion, although the Ross procedure remains a safe and attractive alternative in aortic valve operation, the progression of aortic regurgitation, especially in the younger patient with rheumatic etiology, remains a concern.
BACKGROUND: Mitral valve operations require excellent exposure. The description of an extended vertical transseptal atriotomy by Guiraudon and associates promises to provide optimal exposure of the mitral valve. A prospective study was carried out to evaluate the merits of the extended vertical transseptal atriotomy in comparison with the conventional left atriotomy for mitral valve operations. METHODS: Conventional atriotomy was performed in 24 patients (group I) whereas 65 patients underwent the extended vertical transseptal offroach (group II). They were similar in age, sex, cause of disease, New York Heart Association functional class, left atrial size, and left ventricular function. The early postoperative rhythm changes in these two groups were compared. Statistical studies to analyze the significance of incidence of junctional arrhythmia in these two groups were carried out. RESULTS: Of the 24 patients in group I, 3 had development of transient junctional rhythm after operation, lasting less than 24 hours. None had this arrhythmia at the time of discharge. Of the 65 patients in group II, junctional rhythm was documented in 25, with a rate of occurrence of 38% (95% confidence interval, 27.6% to 52.2%). At the 6-week follow-up, 3 patients still had this junctional rhythm, with a failure to recover rate of 12% (3 of 25). CONCLUSIONS: The surgical exposure was considered excellent and closure of the atriotomy was thought to be easy in group II. However, this should be balanced against a significant (38%) incidence of transient junctional rhythm in the early postoperative period in group II, probably from injury to sinus node artery or atrial conduction pathways.
We have reported previously the production of Plasmodium falciparum transmission-blocking monoclonal antibodies (mAb) recognizing a reduction-insensitive cross-reacting epitope in the gametocyte antigen Pfg27 and the gamete surface antigens Pfs230 and Pfs48/45. In this study, the amino acid sequence of this epitope in Pfg27 was determined. First, the epitope was localized near the N terminus of the protein by probing recombinant overlapping fragments spanning Pfg27 with transmission-blocking mAb in immunoblot experiments. The amino acid sequence of the epitope was then determined by using overlapping synthetic peptides spanning the smallest immunoreactive recombinant fragment in an ELISA. The sequence KPLDKFGNIYDYHYEH (amino acids 10-25 in the Pfg27 sequence) was shown to contain two overlapping epitopes recognized by transmission-blocking mAb. Comparison of the sequence of the gene encoding Pfg27 in seven different P. falciparum strains demonstrated that these sequential epitopes are totally conserved. Immunization of mice with synthetic peptides derived from Pfg27, conjugated with keyhole limpet hemocyanin (KLH) and formulated in Freund's adjuvant or alum, resulted in the production of antibodies capable of recognizing the peptides as well as the native Pfg27.
The action of testosterone (T) on the sex accessory organs, such as ventral prostate (VP) and seminal vesicles (SV) is amplified by its 5 alpha-reduction to dihydrotestosterone (DHT). This does not happen in the case of muscle (levator ani, LA) which contains little or no 5 alpha-reductase activity. It has been suggested that the regulation of gonadotropins by T may also be mediated by its 5 alpha-reduced metabolites. We investigated this question by utilizing two types of androgens: (1) T and 17 alpha-methyl-testosterone (17MT), whose potency increases following 5 alpha-reduction; and (2) 19-nortestosterone (NT) and 17 alpha-methyl-19-nortestosterone (17MNT) whose potency decreases following 5 alpha-reduction. Castrated rats were used to investigate the ability of these androgens to stimulate VP, and SV (androgenic action) and LA growth (anabolic action) and to suppress the post-castration rise in LH levels. In addition, modification of these actions by a 5 alpha-reductase inhibitor (5 alpha-RI) was studied. Compared to T, NT was approximately 5 times less potent in stimulating VP and SV. By contrast, it was twice as potent as T in stimulating LA growth. Similarly, 17MNT was 5 times less androgenic but twice as anabolic as 17MT. The antigonadotropic potency of both the 19-nor compounds was 2-3 times greater than that of their respective 19-methylated parent compounds. The similarity in their anabolic and antigonadotropic potency suggested that 5 alpha-reduction is not a factor in their antigonadotropic action. This was confirmed by the use of the 5 alpha-RI. Treatment of rats receiving the androgens with 5 alpha-RI showed that it decreases the androgenic activity of T and 17MT while it increases the androgenic activity of NT and 17 MNT. In all cases the anabolic activity and the antigonadotropic potency remained unchanged. It is concluded that the regulation of pituitary gonadotropin secretion by T does not depend upon its 5 alpha-reduction to DHT.
Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As androgenic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this report suggest that these differences result, in part, from the differential metabolism of the steroids in individual tissues and the varied activities of the individual metabolites. In the accessory sex organs (e.g. the prostate) testosterone is 5 alpha-reduced to dihydrotestosterone (DHT) which, due to its higher affinity for androgen receptors (AR), amplifies the action of testosterone. In contrast, when 19-nortestosterone (NT) is 5 alpha-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic potency remains unchanged since significant 5 alpha-reduction of the steroids does not occur in the muscle. 7 alpha-methyl-19-nortestosterone (MENT) does not get 5 alpha-reduced due to steric hindrance from the 7 alpha-methyl group. Therefore, the androgenic potency of MENT is not amplified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compared to testosterone. Part of the biological effects of testosterone are mediated by its aromatization to estrogens. The fact that MENT is also aromatized to 7 alpha-methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.
Fifty-one patients with a mean age of 31.2 years underwent aortic valve replacement with glutaraldehyde-treated autologous pericardium. Pure aortic regurgitation was present in 28 (54.9%), stenosis in 9, and mixed disease in 14. Simultaneous mitral valve repair was done in 17 patients and replacement in 1. There were no hospital and two late deaths. Three patients required reoperation because of failure of the pericardial valve as a result of infective endocarditis in two (5 and 31 months after operation) and commissural tear at 8 months in another. One patient underwent reoperation at 24 months because of failure of the mitral valve repair. The pericardial aortic valve, which had 2+ regurgitation since the first operation, was also replaced. Macroscopic and microscopic examination findings in the excised pericardium were excellent. No thromboembolic events have been detected and no patient received anticoagulation therapy except one after mitral valve reoperation and replacement with a mechanical valve. The actuarial survival was 84.53% +/- 12.29% at 60 months, freedom from failure of the aortic reconstruction 83.83% +/- 8.59%, and freedom from any event 72.59% +/- 12.79%. Doppler echocardiographic study at most recent follow-up showed a mean gradient of 12.56 +/- 8.10 mm Hg and mean regurgitation on a scale from 0 to 4+ of 0.80 +/- 0.66. Although the maximum follow-up is only 5 years, the results obtained so far encourage us to continue replacing the aortic valve with stentless autologous pericardium.