Pyridostigmine-induced microcephaly.
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Adult↗
Biomedical subjects
N S Shah
Publications and source records attributed to N S Shah.
Primary hypothyroidism presenting as a pituitary gland enlargement with regression following thyroxine therapy.
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Adult↗
Utility of clinical parameters of tissue oxygenation in a quantitative model of irreversible hemorrhagic shock.
The aim of this study was to assess the value of parameters of tissue oxygenation in monitoring the progression to irreversibility in a quantitative model of hemorrhagic shock. Rats were bled to a mean arterial pressure of 40 mmHg and were maintained at this level by further blood withdrawal until the compensation endpoint; this point was defined as the time at which the rat was no longer able to maintain its blood pressure at this level and shed blood was required for transfusion. The shock period was maintained until 0%, 20%, 40%, or 50% of the maximum shed blood volume (MBV) had been returned (n = 10 in each group, total n = 40). The animals were then resuscitated with remaining shed blood plus twice MBV as lactated Ringer's solution to MAP > 80 mmHg. Blood gas and serum lactate samples were measured at baseline, compensation endpoint, and at the time of resuscitation, and 24 h survival was recorded. Increasing the severity of shock progressively worsened the acidosis, with increased base deficit and lacticacidemia, and deterioration in central venous oxygen saturation (CvO2). Tissue oxygenation parameters, particularly CvO2, predicted subsequent mortality. Lactate levels only predicted irreversibility in late, severe shock. This quantitative model of hemorrhagic shock showed that tissue oxygenation parameters can be used to monitor the progression from the decompensated phase of hemorrhagic shock to irreversibility. Furthermore, this experimental study suggests that venous indices may be a valuable tool in reflecting the severity of hemorrhagic insult in a setting when arterial blood samples may not be easily available.
Animals↗
Role of nitric oxide in inflammation and tissue injury during endotoxemia and hemorrhagic shock.
Since the discovery that nitric oxide (.NO) accounts for the biologic activity of endothelial-derived relaxing factor, a torrent of research over the last decade has focused on its role, protective or detrimental, in myriad pathophysiologic conditions. Recently, increasing attention has focused on .NO as a possible mediator of the severe hypotension and impaired vasoreactivity characteristic of circulatory failure. Given the ubiquitous and complex role of .NO in biologic systems, inhibition of .NO synthesis in experimental and clinical studies of shock has yielded mixed, sometimes contradictory, results. Although overproduction of .NO in the vasculature may result in systemic vasodilation, .NO synthesis has also clearly been shown to have a beneficial role in regulating organ perfusion and mediating cytotoxicity. In this review, the pathophysiologic importance of .NO in septic shock and hemorrhagic shock is discussed, and novel therapeutic strategies for manipulation of .NO formation are examined.
Animals↗
Efficacy of inhaled nitric oxide in oleic acid-induced acute lung injury.
OBJECTIVE: To assess the efficacy of inhaled nitric oxide in improving pulmonary hypertension and gas exchange following oleic acid-induced acute lung injury. DESIGN: Prospective, pharmacologic study. SETTING: Surgical research laboratory at the University of Pittsburgh, Pittsburgh, PA. SUBJECTS: Instrumented, intubated pigs weighing 16 to 27 kg. INTERVENTIONS: Intravenous oleic acid and inhaled nitric oxide. MEASUREMENTS AND MAIN RESULTS: All pigs treated with intravenous oleic acid (0.11 mL/kg) developed a severe lung injury with pulmonary hypertension, accompanied by impaired oxygenation, intrapulmonary shunting, and increased extravascular lung water (p < .05 compared with baseline). Following nitric oxide inhalation, although pulmonary hypertension decreased in a dose-dependent fashion, no amelioration in pulmonary gas exchange was observed, as reflected by PaO2 and intrapulmonary shunt. Plasma nitrite and nitrate concentrations, the stable end products of nitric oxide metabolism, did not increase following nitric oxide exposure in this model of severe lung injury. CONCLUSIONS: The effect of inhaled nitric oxide, restricted to relieving pulmonary vasoconstriction in this model of lung injury, may have limited benefit in improving pulmonary gas exchange when diffusion is impaired by severe lung injury and inflammatory thickening of the alveolar-capillary barrier. Nitric oxide inhalation may have better results when used at an earlier, less severe stage of acute lung injury.
Administration, Inhalation↗
Physiologic and molecular characterization of the role of nitric oxide in hemorrhagic shock: evidence that type II nitric oxide synthase does not regulate vascular decompensation.
To determine the role of nitric oxide (NO) in decompensated and irreversible hemorrhagic shock, rats were subjected to hemorrhagic shock (HS) for 3 or 5 h. Lung, liver, and plasma samples were studied for evidence of NO formation using Northern analysis and immunohistochemistry for Type II NOS, as well as measurement of plasma nitrite/nitrate, cyclic GMP, and nitrosylated hemoglobin levels. Comparisons were made with similarly instrumented time-matched sham rats. Type II NOS mRNA and protein were detectable in lung and liver only in the irreversible phase of HS (5 h). A large accumulation of nitrosylated hemoglobin and nitrite/nitrate appeared in the irreversible phase. Significant accumulation of cyclic GMP or nitrite/nitrate was not detectable in the decompensation phase. Despite the hemodynamic decompensation at 3 h of HS, Type II NOS mRNA and protein expression, as well as NO metabolites were not elevated. To assess whether NO plays a physiologically significant role in decompensation, rats in the decompensation phase and sham animals were subjected to nonspecific NOS inhibition. Both groups displayed a similar magnitude and duration of blood pressure elevation. Hemodynamic decompensation in HS is not mediated by Type II NOS induction. NO production increases only after prolonged HS; significant NO production is observed only in severe, irreversible HS.
Animals↗
A long-term review of the Shah Permavent tube.
A retrospective study of 74 Shah Permavent tube insertions is presented. These were inserted into 74 ears of 55 patients during the period between 1985 and 1988. At the time of review, 35 tubes had extruded spontaneously, 11 tubes had been removed for recurrent infections, 10 tubes had been removed electively and 10 tubes were still in situ. On examination of the ears approximately 12 months after the tubes had extruded, the overall rate of tympanic membrane perforation was 18.2 per cent. In ears in which the Permavent tube extruded spontaneously the perforation rate was 22.2 per cent. In ears which the tube was removed because of infection the perforation rate was 20.0 per cent. However in ears in which the tube was removed electively the perforation rate was zero. This finding has implications in the use and management of long-term ventilation tubes.
Adolescent↗
Diaphragm levels as determinants of P axis in restrictive vs obstructive pulmonary disease.
BACKGROUND AND OBJECTIVE: Verticalized P axes in adults with obstructive lung disease have long been appreciated as characteristic of emphysema. After demonstrating P axes in restrictive lung disease to have a significantly different orientation (intermediate to horizontal), it was hypothesized that opposite effects on diaphragm level by obstructive disease (low diaphragm) and by restrictive disease (high diaphragm) could explain the axis differences, because the right atrium is attached via the inferior vena cava and adjacent pericardium to the right leaf of the diaphragm. METHODS: Electrocardiograms and chest radiographs were analyzed independently in a new series of 20 consecutive patients with purely obstructive and 19 consecutive patients with purely restrictive pulmonary disease. P axes were calculated to the nearest 5 degrees and grouped as vertical (+65 degrees to +90 degrees), intermediate (+40 degrees to +60 degrees), and horizontal (< +50 degrees). Chest radiographs established the right diaphragmatic level by posterior rib number or interspace with interspaces designated as "0.5" plus the number of the rib above. RESULTS: P axes for obstructive vs restrictive disease were different (p < 0.001) as in our previous investigation. In the present series, 19 of 20 electrocardiograms in patients with obstructive disease had vertical P axes between +70 degrees and +90 degrees; in 11 of 19 patients with restrictive disease, P axes were less than +40 degrees (horizontal); 6 were between +40 degrees and +60 degrees (intermediate); and only 2 were vertical. Diaphragm levels were between rib/interspace numbers 10.5 and 12.5 in all patients with obstructive disease. Diaphragm levels among patients with restrictive disease were higher and, like their P axes, more widely distributed: 10 of 19 between rib levels 8.0 and 9.5; only 4 at 10.5 or lower. Thus, vertical P axes corresponded to low (rib/interspace 10.5 to 12.5) and intermediate to horizontal P axes with higher (8.0 to 11.0 rib) diaphragm levels (p < 0.001). CONCLUSION: Because the separate P-axis distributions in restrictive and obstructive lung disease parallel the separate diaphragm levels and because the right atrium is necessarily carried by attachments to the right diaphragmatic leaf, it is likely that the consequent positional effects on the right atrium contribute to or cause the significantly different P-axis orientations in restrictive and obstructive pulmonary disease.
Atrial Function↗
Efficacy of inhaled nitric oxide in a porcine model of adult respiratory distress syndrome.
OBJECTIVE: To assess the efficacy of inhaled nitric oxide (NO) in reducing pulmonary hypertension in a porcine model of adult respiratory distress syndrome. DESIGN: Nonrandomized, controlled experiment without blinding. SETTING: Surgical research laboratory. PARTICIPANTS: Twelve pigs, matched equally for body weight. INTERVENTION: Acute lung injury was induced by intravenous injection of oleic acid. Animals were then divided into either a control group, for monitoring without any further intervention, or a NO-treatment group, in which NO was administered at concentrations of 10 to 80 ppm, with each step separated by a NO-free interval to assess duration of effect. MAIN OUTCOME MEASURES: Pulmonary artery pressure, systemic blood pressure, PaO2, intrapulmonary shunt fraction, and extravascular lung water. Nitrosylated hemoglobin, arterial methemoglobin, and plasma nitrite and nitrate concentrations. RESULTS: All animals responded to oleic acid injection with rapid development of pulmonary hypertension and deterioration of PaO2 and intrapulmonary shunt fraction. Inhaled NO reversed these changes in a concentration-dependent manner. Cessation of NO administration led to a prompt return of pulmonary hypertension. A small but significant drop in systemic blood pressure was observed only at the highest concentration of NO administered (80 ppm). Extravascular lung water almost doubled following oleic acid injury. This increase was sustained in all animals for the remainder of the experiment. Significant increases in circulating methemoglobin and plasma nitrite and nitrate concentrations were measured during NO inhalation. CONCLUSION: Inhaled NO appears to be a selective pulmonary vasodilator and may prove to be useful in improving gas exchange in adult respiratory distress syndrome.
Administration, Inhalation↗
Use of the trimmed Shah permavent tube in the management of glue ear.
Twenty-five children (mean age six years) with de novo bilateral ear effusions received a 'trimmed' high grade silicone (HGS) Shah permavent ventilation tube in one ear and a conventional polyethylene Shah grommet in the other. The extrusion rate and the degree of tympanosclerosis formation was examined. At 29 months the conventional grommet had extruded in 90 per cent of children and a recurrent middle ear effusion was found in over 50 per cent of these ears. The average length of stay for the conventional grommet was 12.5 months. Five permavent tubes had extruded, one was extruding but the remainder were all in place and patent. Comparing ears on each side the amount of tympanosclerosis was worse in the ear with the conventional grommet in 47 per cent of children and worse on the permanent side in 11 per cent of the children. The 'trimmed permavent' appears to act as a medium to long-term grommet which self extrudes without serious complications. Its use at the primary operation in young children may save repeated insertions of conventional grommets.
Child↗
Middle ear lipoma.
We report a case of primary middle ear lipoma diagnosed in the right ear of a five-year-old child with concurrent bilateral middle ear effusions. The lipoma occupied a site favoured by congenital cholesteatoma and was occlusive to the eustachian tube contributing to its dysfunction. This is the first case of de novo middle ear lipoma diagnosed in the UK, and the third in world literature. Our CT scans are suggestive of a similar but smaller lesion in the left ear of the same child.
Child, Preschool↗
Electrocardiographic features of restrictive pulmonary disease, and comparison with those of obstructive pulmonary disease.
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Adult↗
Parvovirus B19 infection associated with reticulocytopenia and chronic autoimmune hemolytic anemia.
A previously healthy 11-year-old white female presented with a Coomb's positive hemolytic anemia and reticulocytopenia. The patient was treated with prednisone (6.4 mg/kg/day) and had a stable hemoglobin with subsequent recovery of reticulocytes by 7 days. Bone marrow aspiration showed hypercellularity with arrest of red cell maturation. The patient's serum contained specific IgM and IgG antibodies to parvovirus B19. Our report confirms parvovirus B19 as a cause of reticulocytopenia at presentation in autoimmune hemolytic anemia. Immunosuppressive therapy with prednisone did not appear to significantly prolong the course of the B19 infection.
Anemia, Hemolytic, Autoimmune↗
Age-dependent alterations in the accumulation of l-methadone in the brain synaptosomes and other subcellular fractions.
Albino Sprague-Dawley rats (1, 8, 12 and 20 days old) were injected intraperitoneally with l-[3H-1]-methadone (5 mg/kg containing 50 muCi/kg), and sacrificed at 15 min, 1 h and 3 h. Whole brain was homogenized in 0.32 M sucrose-Tris buffer and the homogenates were subjected to differential centrifugation to separate nuclei, mitochondria, microsomes, soluble cytosol, myelin, membrane and synaptosomes. Methadone levels in each fraction were examined. The methadone contents in the whole brain (sum of all fractions) of 1- and 8-day-old rats were significantly higher relative to those of 12- and 20-day-old rats at all time intervals. The most striking finding in this study was that during development, the percentage of methadone content in the synaptosomal fraction progressively increased relative to other subcellular fractions; interestingly, there was an associated decrease in the percent levels in the soluble cytosol suggesting a shift of methadone from cytosol to synaptosomes. These alterations in brain synaptosomal accumulation of methadone could result from the progressive increase in the affinity of methadone for synaptosomes as these particles become enriched in the protein and lipid contents and possibly increase in opiate receptor density during the neuronal maturation and the synaptogenesis of the developing brain.
Aging↗
Regional localization of [14C] methylphenidate in rabbit brain.
1. Neuroanatomical distribution of [14C] methylphenidate has been examined in rabbit brain following intracerebroventricular administration. 2. After about a week of implantation of cannula, in lateral ventricle, in albino rabbits, [14C] methylphenidate was injected through the cannula. The distribution of [14C] methylphenidate was examined at 15, 60 and 180 min after the injection in twelve brain regions. 3. The highest levels were observed at the first sampling time (15 min), in medulla and cervical spinal cord. Pons, caudate, tegmentum and hypothalamus also showed significant uptake of [14C] methylphenidate. Cerebral cortex and thalamus showed very low uptake. 4. The uneven distribution suggests a special affinity of methylphenidate for certain brain regions. The implications of this finding for the central actions of methylphenidate are discussed.
Animals↗
The influence of nisoldipine--a "calcium entry blocker" on drug induced stereotyped behavior in rats.
In view of potential ability of calcium entry blockers to affect Ca2+ fluxes in neurons, the effects of nisoldipine on phencyclidine (PCP) and apomorphine (APO) induced stereotyped behavior have been examined in 3 and 4 week old rats. The rats (3 and 4 weeks old) were pretreated with either 0.2 ml of saline + ethanol mixture (10:1 v/v) or nisoldipine (25 mg/kg) i.p., 5 min before the i.p. administration of PCP (5 mg/kg) or APO (10 mg/kg). While nisoldipine pretreatment significantly blocked the PCP induced stereotypy in 3 and 4 week old rats, the APO induced stereotypy was not altered. These preliminary data suggest that nisoldipine specifically blocks PCP induced stereotypy probably by antagonizing it effects at the presynaptic level. The significance of this finding in relation to mechanism of action of PCP and calcium entry blockers is discussed.
Age Factors↗
Platelet serotonin uptake in depressed patients: circadian effect.
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Adult↗
Age-dependent variations in the distribution of methaqualone in rat.
Rats at 1, 4, 8, 12, 20 and 60 postnatal days received orally 5 mg/kg 14C-methaqualone (MTQ) and were sacrificed at 0.5, 1.5 and 6 h. Several tissues were analyzed for unchanged MTQ. In most cases, concentrations reached peak levels at 1.5 h. Highest concentrations were found in the liver followed by the lung, spleen, heart, kidney, eye, and brain. Levels of MTQ were higher in all organs of 1- to 12-day-old rats at all time intervals than the corresponding organs of 20- and 60-day-old rats, apparently resulting from initial higher accumulation and slower rate of disappearance. The 1.5-hour brain:plasma concentration ratio in 8-day-old rats was 0.82 and progressively declined to 0.27 in 60-day-old rats; a similar trend with respect to changes in concentration ratio also occurred for the eye, spleen, kidney, and heart. The fact that the age-related reduction in tissue:plasma concentration ratios occurred in several tissues including brain suggests generalized decreases in tissue accumulation of MTQ. The reduction in brain:plasma concentration ratios, therefore, cannot be ascribed to the blood-brain barrier which develops progressively with the advancing age.
Aging↗