ABC of medical computing. Computers in general practice--III.
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Computer Systems↗
Biomedical subjects
R Sharma
Publications and source records attributed to R Sharma.
Neuroprotective use-dependent blockers of Na+ and Ca2+ channels controlling presynaptic release of glutamate.
We have originated a family of N,N'-disubstituted guanidines that block the voltage-activated Ca2+ and Na+ channels governing glutamate release. These compounds, CNS 1237 (N-acenaphthyl-N'-methoxynaphthyl guanidine) and its analogues, are "use dependent" in their ability to attenaute neurotransmitter release: they block glutamate release with greater efficacy under conditions of persistent or repetitive depolarization, as would be encountered under pathophysiological circumstances, relative to their ability to block glutamate release elicited by brief, transient depolarizations more characteristic of normal physiological release events in nonischemic brain. Using electrophysiological and rapid kinetic methods, we have differentiated the use-dependent block of the relevant Na+ and Ca2+ channels governing neurotransmitter release from the mechanism of channel antagonism exhibited by, respectively, the substituted guanidine Na+ channel blocker tetrodotoxin (TTX) and venom peptide Ca2+ antagonists. To characterize use-dependent Na+ channel block by CNS 1237, we have employed whole-cell voltage-clamp recordings from a Chinese hamster ovary (CHO) cell line expressing cloned mammalian type II Na+ channels. These experiments demonstrated that, in contrast to the actions of TTX under the same conditions, the potency of Na+ channel block by CNS 1237 is greatly enhanced by depolarizing stimuli in a frequency-dependent manner. Ca2+ channel-activated glutamate release from brain nerve terminal preparations was measured with approximately 300 msec time resolution over a 5-second period of high K(+)-depolarization, using a rapid superfusion technique. CNS 1237 and analogues, at 1-3 microM, accelerated the decay of glutamate release by 40-70%, reflecting depolarization-induced enhancement of block. In contrast, blockade of glutamate release by the Ca2+ channel antagonist peptide toxins omega-aga IV-A (from spider venom) and omega-conotoxin M-VII-C (from cone snail venom) exhibited "reverse-use-dependence:" at concentrations of 0.3 microM, which blocked the initial amplitude of glutamate release by 40-60%, the decay time constant for glutamate release was significantly increased, indicating depolarization-induced relief of block. These findings establish that CNS 1237 and other members of this compound series are use-dependent blockers of the voltage-activated ion channels governing glutamate release. Studies of CNS 1237 in the rat middle cerebral artery occlusion (MCAO) focal stroke model have indicated infarct size reduction comparable to that observed by the same investigators for the glutamate release blocker (BW 619C89 (Burroughs-Wellcome, now in clinical development). Maximal infarct size reduction is achieved with a 3-mg/kg bolus followed by a 4-hour infusion of 0.75 mg/kg/hr.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Structure-activity studies of RFamide analogues on central neurones of Helix aspersa.
The effects of FMRFamide were compared with those of FMRFamide analogues, FLRFamide, LFRFamide, FFRFamide, LLRFamide, D-FMRFamide, F-D-MRFamide and FM-D-RFamide, and the fragments, MRFamide and LRFamide, on identified central neurones, F1, F2, F5 and E16, of the snail Helix aspersa, using intracellular recording and two electrode voltage clamp techniques. All FMRFamide analogues showed an inhibitory effect on F1 neurones with an order of potency: FLRFamide > FMRFamide > FFRFamide > LFRFamide >> LLRFamide. FMRFamide and FLRFamide exhibited a biphasic response on F2 neurones. At lower concentrations (< 10 microM), both peptides usually only excited while at higher concentrations (> 30 microM), exhibited an excitation followed by an inhibition. FFRFamide only excited F2 while LFRFamide and LLRFamide only inhibited F2. LRFamide and MRFamide (100 microM) were inactive on both F1 and F2. FLRFamide, LFRFamide, LLRFamide, FFRFamide and D-FMRFamide showed cross-interaction on the outward current induced by FMRFamide in F5. All peptides induced an outward current and also reduced the FMRFamide-induced current reversibly. In contrast, MRFamide, LRFamide and F-D-MRFamide failed to have direct effects on these neurones nor interact with the FMRFamide-induced current. We conclude that on F2 neurones Phe is essential for the activation of the RFamide receptor mediating the excitation and Met or Leu are important to activate the RFamide receptors mediating the inhibition. Removal of the N-terminal Phe, to give LRFamide and MRFamide render the peptides inactive. Therefore a tetrapeptide sequence is essential for the biological activity of FMRFamide analogues on these Helix neurones. FLRFamide, LFRFamide, LLRFamide, FFRFamide and D-FMRFamide exhibit a cross-interaction with FMRFamide. It is possible that these peptides also act on the same class of RFamide receptors as agonists to cause cross desensitization.
Animals↗
Redox mechanism for the generation of holes in TlBa1-xSrxLaCuO5+ delta : A neutron-diffraction study.
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Journal Article↗
Developmental expression and corticosterone inhibition of adenosine deaminase activity in different tissues of mice.
The activity expression and corticosterone inhibition of adenosine deaminase (ADA) were studied in the spleen, stomach, and liver of mice at various postnatal ages. The specific activity of ADA is very low in the spleen and stomach of 5- and 10-day-old mice, and increases significantly (2.5- to 3.0-fold) in 20- and 30-day-old animals. Its level shows a further increase in the spleen of 60-day-old mice while stomach increase of ADA is not significant. In contrast, the activity of ADA is significantly higher in the liver of 5- and 10-day-old mice, decreases markedly (2.5-fold) in 20- and 30-day-old animals and shows a sharp increase in the liver of 60-day-old mice. Corticosterone administration brings a marked inhibition in the activity of ADA at all ages studied in the spleen and stomach whereas it inhibits the liver ADA only at 30 and 60 days postnatal age. These findings suggest an age- and tissue-specific expression of ADA activity and also indicate corticosterone as an inhibitory regulator of this enzyme.
Adenosine Deaminase↗
Angiodysplasia and lower gastrointestinal tract bleeding in elderly patients.
Angiodysplasia of the colon is one of the most common causes of major lower intestinal tract bleeding in the elderly; it occurs predominantly in the cecum and on the right side of the colon and is thought to result from degenerative changes associated with aging. The clinical presentation is varied, ranging from hematochezia or melena to iron-deficiency anemia resulting from long-term blood loss. Accurate diagnosis may require a combination of diagnostic techniques, such as angiography, nuclear scanning, and colonoscopy. The management plan should be individualized for each patient depending on severity, rate of rebleeding, and issues of comorbidity. Although conservative medical management is a reasonable option for many patients, endoscopic treatment has generally replaced surgery as the first line of definitive treatment for angiodysplasias in most of these patients. The risk of rebleeding is a considerable problem, and surgical therapy yields better results in this aspect. The role of hormonal therapy is not clearly established.
Angiodysplasia↗
Angiosarcoma of the breast. Initial misdiagnosis is still common.
Primary angiosarcoma of the breast is a rare and often misdiagnosed disease. The most common clinical presentation is a painless mass in the affected breast, but the often varied presentation and the high incidence of histologic misdiagnosis make early detection rare. The tumor size and the histologic type correlate with the prognosis. The treatment for angiosarcoma of the breast is early and complete surgical excision of the mass with adequate margins. Axillary dissection is not indicated because the predilection for nodal metastasis is rare. The definitive role of adjuvant therapy remains undetermined. Chemotherapy and radiotherapy may play an important role in survival; however, the data are inconclusive. A high index of suspicion for angiosarcoma is a crucial tool in its proper diagnosis and treatment. It should always be noted that a vascular lesion that is associated with any breast mass is an angiosarcoma until proven otherwise.
Adult↗
Comparative evaluation of classical intrafascial-supracervical hysterectomy (CISH) with transuterine mucosal resection as performed by pelviscopy and laparotomy--our first 200 cases.
A novel way of performing endoscopic intrafascial supracervical hysterectomy is presented. By using the endoscopic approach for dissection as well as uterine extraction using the serrated-edged macro-morcellator, we avoid giving the patient a colpotomy incision and its inherent post-operative discomfort. A further modification involves nearly complete excision (95%) of uterocervical mucosa using a calibrated resection tool, thus eliminating the possible subsequent development of cervical stump neoplasia. Sparing of the cardinal ligament insertion provides support to the cervical stump. Hemorrhage and genitourinary complications are prevented by avoiding dissection of the parametrium at the level of endocervix. Comparison of data of the pelviscopic CISH procedure with the laparotomy approach in our preliminary series (n = 190) confirms our claims as to its safety. Data on long-term postoperative evaluation are ongoing, but the initial reports deny any postoperative discomfort. Larger randomized studies are required to prove its value compared with the existing techniques. We believe that with its multitude of benefits, the classic intrafascial serrated-edged macro-morcellated (SEMM) hysterectomy (= CISH) may emerge as an attractive alternative to conventional hysterectomy.
Adult↗
First-pass metabolism of alcohol. Absence of diurnal variation and its inhibition by cimetidine after evening meal.
To determine whether the first-pass metabolism (FPM) of orally consumed alcohol varies with the time of day, 12 healthy male subjects were tested with both oral and intravenous alcohol (0.3 g/kg), in the morning and evening, always 1 hr after the same standard meal. The results revealed no significant differences in FPM (81.6 +/- 11.6 vs 92.8 +/- 10.6 mg/kg) or in any other index of alcohol absorption and metabolism. Eleven subjects were also tested in the evening after treatment with cimetidine, an H2-antagonist that inhibits gastric alcohol dehydrogenase activity in vitro. Compared to baseline, cimetidine (1 g/day for eight days) significantly decreased FPM (from 100.1 +/- 8.0 to 52.6 +/- 11.4 mg/kg, P < 0.01) and increased the systemic bioavailability of alcohol (from 66 +/- 3 to 82 +/- 4%, P < 0.01), as well as peak blood alcohol concentrations (from 4.3 +/- 0.4 to 5.9 +/- 0.5 mM, P < 0.05) and areas under the curve (from 5.1 +/- 0.5 to 7.0 +/- 0.5 mM/hr, P < 0.01). The results indicate the absence of diurnal variation in FPM and suggest that patients given cimetidine should be warned of its possible interaction with alcohol regardless of the time of day.
Administration, Oral↗
Morphometric analysis of intestinal mucins under different dietary conditions and gut flora in rats.
Elucidation of the mechanisms that alter the biosynthesis, turnover, and degradation of intestinal mucins is relevant to the understanding of both the normal gut ecosystem and various intestinal diseases. In this study image analysis was used to quantify the effects of diet and microbial flora on the mucin composition of goblet and deep crypt cells, the number and volume density of mucin-containing cells, and the staining density of their stored mucins in the small and large intestine of germ-free and conventionally maintained rats fed two different diets. One was a coarsely ground commercial rodent diet containing crude fiber of cereal origin and the other a purified diet composed of finely powdered ingredients, including cellulose as a source of fiber. The changes in mucin production were also analyzed in germ-free rats colonized with a human flora. Feeding a commercial diet reduced the volume density of cells containing neutral and sulfomucins in the jejunum of conventional rats and the staining density of neutral and acidic mucins in the germ-free rats. Both rat and human floras reduced the number of cells containing acidic and sulfomucins and the staining density of neutral mucins in the small intestine of animals fed on a purified diet. However, inoculation of human flora increased the staining density of stored neutral and sulfated mucins in the cells of the large intestine. The results demonstrate that the dietary changes are influential in modifying the amount and proportion of mucins in the small intestine and the microbial flora in the large intestine.
Animal Feed↗
Simplified cryopreservation of mammalian cell lines.
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Adenocarcinoma↗
Serial echocardiography for decision making in rapid two-stage arterial switch operation.
BACKGROUND: Rapid two-stage arterial switch operation is advocated in infants with simple transposition presenting late. Accurate assessment of left ventricular preparation is crucial to successful outcome. The role of echocardiography alone in surgical decision making remains unclear. METHODS: Seventeen patients with simple transposition (mean age, 4 months) underwent pulmonary artery banding and modified Blalock-Taussig shunt (first stage) to prepare the left ventricle for the arterial switch operation (second stage). Serial echocardiography was performed in the interval phase to assess left ventricular growth. Sixteen patients underwent arterial switch operation after a mean interval of 10.4 +/- 4 days, with 14 successful conversions. There was one mortality (5.9%) and two conversions to a Senning repair. RESULTS: In all patients a mean increase in left ventricular mass (40.8 +/- 17.8 g/m2 to 81.4 +/- 25.4 g/m2) and posterior wall thickness (3.37 +/- 0.47 mm to 4.63 +/- 0.58 mm) was recorded. Left ventricular end-diastolic internal diameter increased in all except the two switch failures. In all the successful cases the left ventricle had assumed a circular shape on cross-section with the interventricular septum contracting in synergy with the left ventricular mass. In the two failures, however, the interventricular septum had remained flat. CONCLUSIONS: Echocardiography can be used reliably in surgical decision making in rapid two-stage arterial switch operation. Increase in left ventricular mass, left ventricular posterior wall thickness, and left ventricular end-diastolic internal diameter toward normal combined with an acquisition of circular left ventricular configuration with the interventricular septum contracting in synergy with the left ventricular mass appear to best predict successful outcome.
Anastomosis, Surgical↗
Inhibitory action of SKPYMRFamide on acetylcholine receptors of Helix aspersa neurons: role of second messengers.
1. SKPYMRFamide, a novel FMRFamide-like endogenous peptide reversibly decreases excitatory responses (depolarization and inward current) evoked by local ionophoretic application of acetylcholine (ACh) onto the soma of identified neurons F1, F2, F4 and F5/6 of the land snail, Helix aspersa. 2. Threshold concentrations of SKPYMRFamide for an inhibitory action on ACh-induced responses are 0.5-1 mumoll-1. This modulatory action of peptide is dose- and time-dependent. 3. It is concluded that SKPYMRFamide inhibits ACh receptors through activation of specific binding sites on the plasma membrane. 4. The possible role of different second messengers in the modulatory influence of SKPYMRFamide on ACh receptors was tested using 13 modulators of different second messenger systems. 5. The results indicate that SKPYMRFamide may inhibit ACh receptors through activation of one or more of the following systems: phospholipases C, A2, NO-synthase, soluble guanylate cyclase and lipoxygenases which elevate basal intracellulal levels of NO, cGMP, arachidonic acid, acyclic eicosanoids, inositol-1,4,5-trisphosphate (I(1,4,5)P3), I(1,4,5)P3-dependent Ca(2+)-mobilization followed by activation of calmodulin and Ca2+/calmodulin-dependent protein kinase II. Protein kinases A, C and cyclic eicosanoids do not appear to participate in modulatory action of SKPYMRFamide.
Acetylcholine↗
Description of a 3D conformal neutron and photon radiotherapy technique for prostate cancer.
Several methods have been described to improve the therapeutic ratio of radiotherapy in patients with locally advanced carcinoma of the prostate (LACaP). Studies have shown improved survival and local control in patients treated with neutron irradiation as opposed to photons alone. However, an increased complication rate was observed when conformal field design was not utilized. A 3D conformal mixed neutron/photon technique for LACaP has been developed at this institution. Field shaping for the neutron component is achieved with a multirod collimator. Prior to treatment, all patients undergo a conventional simulation followed by a treatment planning computed tomography (CT) scan. Contours of target and normal structures are entered into the 3D treatment planning system. Beam apertures are designed utilizing beam's eye view display. The photon dose is given in 10 fractions at 1.8 Gy each to the prostate and seminal vesicles (PSVs) and pelvic lymph node (PLN) volumes. The neutron dose is given in 15 fractions at 1.0 Gy per fraction to the PSV volume and 0.6 Gy to the PLN volume. The neutron portion includes a partial transmission block to achieve this dose differential. The treatment planning process, including beam weighting and custom block design, is described. Using these techniques, the neutron dose distributions to the target volumes, bladder, and rectum were comparable to those seen with four-field conformal photon irradiation.
Humans↗
The uptake and metabolism of cystamine and taurine by isolated perfused rat and rabbit lungs.
Cystamine has been reported to be taken up and metabolized to taurine by the rat lung slices. The objectives of the present study were to compare the uptake and metabolism of cystamine and taurine in isolated perfused lungs of rats and rabbits and examine the action of glutathione (GSH) on these processes. The uptake and metabolism of [14C]cystamine and [14C]taurine were studied at 20 microM concentrations each in isolated, ventilated, perfused rat and rabbit lungs. In some experiments, 1 microM GSH was included in the perfusate prior to the addition of cystamine. The perfusate and lung homogenate samples were analyzed for cystamine and its metabolites. [14C]cystamine uptake with and without GSH was 13 and 14% in rat lungs and 37 and 32% in rabbit lungs. [14C]taurine uptake was 10% in rat and 37% in rabbit lungs. The levels of radiolabeled cystamine and its metabolites were (nmol/g lung): 20.0 +/- 10.0 and 11.5 +/- 7.0 cystamine, 4.7 +/- 0.5 and 3.2 +/- 0.5 hypotaurine and 56.0 +/- 16.0 and 49.4 +/- 6.0 taurine, for rat and rabbit lungs, respectively, when perfused without GSH; and 18.0 +/- 1.0 and 2.5 +/- 0.5 cystamine, 6.6 +/- 0.5 and 18 +/- 10 hypotaurine and 60.0 +/- 12.0 and 33.6 +/- 9.0 taurine, when perfused with GSH, for rats and rabbit lungs, respectively. Taurine did not undergo any further metabolism in either of the lungs. These studies show that cystamine is taken up and metabolized to taurine via hypotaurine by both rat and rabbit lungs in a manner similar to that seen in rat lung slices. However, rat lungs have much greater capacity to metabolize cystamine to taurine than rabbit. Inclusion of GSH did not significantly alter the ability of lungs to sequester cystamine from the perfusate but the metabolism of hypotaurine to taurine was markedly decreased in rabbit lungs. Taurine was not metabolized any further. It is concluded that rat and rabbit lungs take up cystamine from the systemic circulation, metabolize it via hypotaurine to taurine, and effuse most of the latter in to the circulation.
Animals↗
Corrosive esophageal strictures: predictors of response to endoscopic dilation.
Twenty-one patients with corrosive esophageal strictures underwent contrast-enhanced CT of the chest to determine (1) the esophageal wall thickness at the stricture site and (2) its correlation with number of sessions required for adequate dilation. Average esophageal wall thickness was defined as the mean thickness of all four walls at the site of the stricture, whereas the size of the thickest wall was taken as maximal esophageal wall thickness. Average esophageal wall thickness (8.52 +/- 0.61 mm; range, 5.4 to 13.5 mm) and maximal esophageal wall thickness (11.63 +/- 0.83 mm; range, 5.4 to 20 mm) were significantly higher in patients with corrosive esophageal strictures than normal esophageal wall thickness (2.70 +/- 0.04 mm, p < .01). These patients required a mean of 5.70 +/- 1.42 sessions for achieving adequate dilation. Age, sex, grade of dysphagia, and cause and site of the stricture did not influence the number of sessions required for adequate dilation. On multivariate analysis, maximal esophageal wall thickness (p < .01) but not average esophageal wall thickness or stricture length was independently associated with the number of sessions required for adequate dilation. Patients with maximal esophageal wall thickness of 9 mm or more required a significantly higher number of sessions for adequate dilation than did those with wall thickness of less than 9 mm (7.57 +/- 1.80 versus 1.42 +/- 0.27, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Acids↗
Univentricular repair. Early and midterm results.
A total of 202 patients (62 with tricuspid atresia and 140 without tricuspid atresia) underwent univentricular repair at our unit from January 1990 to September 1994. Of these patients, 182 had nonfenestrated and 20 had fenestrated interatrial baffles. Early mortality was 15.9% (29/182) in the group with nonfenestrated baffles and 5% (1/20) in the group with fenestrated baffles. The follow-up period ranged from 2 to 58 months. Seven late deaths occurred, and five patients were lost to follow-up. Of 160 patients who have been evaluated in the outpatient department in the past 3 months, 142 (88.75%) required no cardiac medicines and were in functional class I. Risk factors analyzed for early mortality and significant effusion were age, preoperative diagnosis, type of Fontan modification, cardiopulmonary bypass time, aortic crossclamp time, pulmonary artery size, associated pulmonary arterioplasty, takedown of systemic-pulmonary artery shunt, and pulmonary artery debanding, along with the Fontan operation. Bypass time exceeding 120 minutes was associated with a higher early mortality (12/47 vs 18/155; p = 0.0187). Bypass time exceeding 120 minutes (p = 0.0456) and aortic crossclamp time exceeding 60 minutes (p = 0.0278) were associated with significant postoperative effusion. Other factors were not associated with any significantly increased risk for early mortality or postoperative effusions. Fenestration of the interatrial baffle appeared to decrease early mortality, although the numbers are too small to be statistically significant. The prevalence of effusions did not differ significantly between the group with fenestrated baffles and the group without fenestrated baffles.
Cardiopulmonary Bypass↗
Alternating conformal neutron and photon irradiation for locally advanced adenocarcinoma of the prostate.
The substantial local failure rate for patients with locally advanced carcinoma of the prostate (LACaP) following photon irradiation, the association of local failure with a poor prognosis, and the promising results of mixed neutron/photon (40%/60%) radiotherapy supplied the rationale for this study. The purpose of this study was to evaluate the combined advantages of mixed neutron/photon (75%/25%) irradiation, 3D treatment planning, as well as fully conformal beam shaping capabilities in reducing the morbidity associated with neutron irradiation. The first 35 patients treated with this technique are the basis for this analysis. After CT stimulation and treatment planning, the normal tissue and target structures were entered into the 3D planning system. The neutron dose was delivered in 15 fractions at 1.0 Gy/fraction (NGy) to the prostate and seminal vesicles (PSV) and 0.6 NGy/fraction to the pelvic lymph nodes (LN). The photon dose was given in 10 fractions of 1.8 Gy each to both the PSV and LN volumes. Neutron and photon dose-volume histograms (DVHs) were generated in each patient for the prostate, seminal vesicles, lymph nodes, bladder, and rectum. The adequacy of the neutron and photon components of the treatment were compared with respect to target volume and normal tissue irradiation. Based on the DVH analysis, the prostate and seminal vesicles received the prescribed dose with both neutrons (99% +/- 2%) and photons (99% +/- 2%). There was no significant difference in the dose to the bladder and rectum for both the neutrons and photons. The acute treatment related reactions have been mild, with only one grade III bladder reaction. The 3D conformal technology utilized in this study has been shown to allow for the delivery of neutron irradiation with no increase in dose to the adjacent normal tissues compared with that achieved with conformal photon treatment. Further follow-up will reveal whether the dosimetric advantage demonstrated by this technique translates into an improved therapeutic ratio.
Adenocarcinoma↗