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Biomedical subjects

N Mehta

Publications and source records attributed to N Mehta.

At least 55 records · Page 3Linked to original sources

Posttraumatic gustatory neuralgia: a clinical model of trigeminal neuropathic pain.

Six cases are reported in which the primary complaint was episodic, recurrent facial pain that was triggered by a taste stimulus. The pain first occurred days to weeks after head and neck surgery. Patients reported that a food stimulus placed in the mouth evoked episodic, electric shock-like pain in a preauricular location on the surgical side. The smell of food or, less reliably, emotional excitement could also trigger pain. Mandibular movement did not evoke the pain, and between lancinating attacks there was either no pain or only mild discomfort. Following an episode of pain, there was a refractory period during which the pain could not be elicited. Physical examination demonstrated a preauricular sensory loss of variable distribution. No abnormal sweating or vasomotor findings were clinically apparent. No odontogenic, muscular, salivary gland, neurologic, or psychologic pathology was found to explain the clinical symptoms. The pain was not relieved with standard doses of anticonvulsants that are commonly used to treat trigeminal neuralgia. The duration of the recurrent pain symptoms in this group was 8 to 132 months without remission. Gustatory neuralgia may be a discrete syndrome that results from abnormal interactions between salivary efferent fibers and trigeminal sensory afferent fibers in the injured auriculotemporal nerve. The unique features of the disorder make it a potentially useful clinical model for the investigation of autonomic/sensory interactions in neuropathic pain.

Adult↗

Absorption and degradation of metalaxyl in mustard plant (Brassica juncea).

Absorption and degradation of metalaxyl were studied in mustard (Brassica juncea) plants after application as a seed dresser, a foliar spray, and a combination of both under subtropical conditions in India. Results indicated that absorption of metalaxyl increased up to 30 days when it was applied as a seed dresser; thereafter, it started declining and was not detectable after 60 days of sowing. The maximum residues (average, 9.03 ppm) of metalaxyl were found after 1 day of spraying. The dissipation of metalaxyl after initial deposits on mustard plants was almost complete after 15 days of spraying. The safe waiting period of metalaxyl was calculated to be 62 and 8 days for seed dresser and foliar application, respectively. The seeds raised through treatments under study were completely free from any detectable amount of metalaxyl residues.

Absorption↗

Cholecystokinin stimulates heat shock protein 27 phosphorylation in rat pancreas both in vivo and in vitro.

BACKGROUND & AIMS: Mammalian heat shock protein 27 (hsp27) is believed to function under normal physiological conditions and during cellular stress. Recent studies indicate a role for hsp27 in regulating actin-cytoskeletal dynamics. In the present study, secretagogue-regulated phosphorylation of hsp27 in rat exocrine pancreas was investigated both in vivo and in isolated acinar cells. METHODS: Western analysis after two-dimensional electrophoresis was used to measure the phosphorylation of hsp27 after treatment of rats or acinar cells with secretagogues. Cholecystokinin-stimulated mitogen-activated protein kinase-activated protein (MAPKAP) kinase 2 activity was measured after immunoprecipitation of the kinase. RESULTS: hsp27 exists as three isoforms in acini: one nonphosphorylated (pI 6.2) and two phosphorylated (pIs 5.9 and 5.7) forms. Infusion of rats with a secretory or supermaximal dose of cerulein produced an acidic shift in hsp27, indicating an increase in its phosphorylation; the higher dose, known to cause pancreatitis, had a twofold greater effect. In isolated acini, increases in hsp27 phosphorylation were evident at 10 pmol/L and maximal at 1 nmol/L cholecystokinin. The hsp27-specific kinase MAPKAP kinase 2 was activated 2.4-fold with 1 nmol/L cholecystokinin treatment. CONCLUSIONS: hsp27 phosphorylation was stimulated by low and high concentrations of cholecystokinin, both in vivo and in vitro. Phosphorylation was potentially mediated via the MAPKAP kinase 2 intracellular signaling pathway.

Animals↗

Cellular effects of hypercholesterolemia in modulation of cancer growth and metastasis: a review of the evidence.

Hypercholesterolemia and increased cancer risk have been associated, particularly with the high fat diets characteristic of Western societies. We were interested in the possible association between preexisting hypercholesterolemia and the rapidity and extent of tumor metastases in these patients. To date there has been only a few studies that have suggested and explored this determinant of cancer metastases although it may play a role in a subset of patients who develop cancers. This article will review the literature on the effects of LDL-cholesterol on cell proliferation and differentiation and speculate on mechanisms of involvement of a hypercholesterolemic milieu on cancer progression and enhancement of metastatic potential.

Animals↗

Functional magnesium deficiency in critically ill patients identified using a magnesium-loading test.

OBJECTIVE: To determine the feasibility of the magnesium-loading test in the critically ill and to validate serum ionized magnesium assay using the magnesium-loading test as a reference in this same patient population. DESIGN: Double-blind, randomized, controlled clinical investigation. SETTING: Tertiary level intensive care unit. PATIENTS: Forty-four consecutive critically ill patients without evidence of renal insufficiency. INTERVENTION: Patients were randomly allocated to receive 30 mmol (7.5 g) of magnesium sulfate daily for 3 days, or an equivalent amount of normal saline. MEASUREMENTS AND MAIN RESULTS: We recorded baseline characteristics, and serial serum biochemical measurements included creatinine, glucose, sodium, potassium, phosphate, total calcium, ionized calcium, total magnesium, and ionized magnesium. Serum assays were accompanied by 24-hr urine collections of creatinine and magnesium over the 3-day period. Baseline characteristics were comparable in both groups. In patients receiving magnesium, serum ionized magnesium and total magnesium concentrations were increased by 43% (p = .0001) and 59% (p = .0002), respectively, on day 1 as compared with the control group. Magnesium excretion in the control group averaged 4.8 +/- 2.3 mmol/day during the 3-day study period, while the magnesium excretion in the magnesium-loaded group was significantly increased to 22.7 +/- 10.9 mmol/day (p < .0001). Following day 1 magnesium loading, patients who excreted < 70% of the total magnesium (30 mmol infused magnesium plus 4.8 mmol basal excretion) were termed as functionally magnesium-deficient retainers (n = 12), and patients who excreted > 70% of the total magnesium were termed as nonretainers (n = 7). In addition, magnesium retainers on day 2 (nine of ten patients) and day 3 (five of six patients) excreted > 70% of the total magnesium, indicating a replenishment of body magnesium stores. In contrast, nonretainers on day 2 (four of five patients), and day 3 (four of four patients) continued to excrete excess amounts of magnesium. In the retainer group, only two patients had a low serum ionized magnesium concentration, while two other patients had low total serum magnesium values. In addition, magnesium retention was associated with low ionized calcium and high phosphate values. CONCLUSIONS: The magnesium-loading test is feasible and appears to be valid based on its performance during the 3-day evaluation. Using the magnesium-loading test as a reference, serum ionized magnesium appears to be an insensitive biochemical marker of functional hypomagnesemia. Larger cohort studies using the magnesium-loading test will help establish the true prevalence of magnesium deficiency and its associated risk factors in critically ill patients.

APACHE↗

Nutrient accretion in preterm infants fed formula with different protein:energy ratios.

BACKGROUND: Although standard formulas for preterm infants promote intrauterine rates of weight gain, fat deposition in preterm infants fed these formulas has been reported to be considerably higher than that in the fetus. We hypothesized that a preterm infant formula with a higher protein:energy (P:E) ratio would promote accretion rates of fat, fat-free mass, and minerals closer to those of the fetus. METHODS: As part of a larger study to determine whether accretion rates of fat and fat-free mass closer to those of the fetus can be achieved with a higher P:E ratio, we present a descriptive analysis of 72-h nutrient balance studies performed on a subset (n = 15/30) of the infants randomly assigned to be fed formula with a P:E ratio of either 3.2 g/100 kcal or 2.6 g/100 kcal. RESULTS: Despite the higher intake and net absorption of nitrogen by infants fed the higher P:E formula, there was no statistically significant difference in net nitrogen retention between groups. There also were no statistically significant differences between groups in digestible energy, metabolizable energy, energy expenditure, or energy storage. Thus, partitioning of stored energy as protein and fat did not differ between groups. The retention of calcium, phosphorus, sodium, potassium, copper, and zinc also did not differ between groups, and nitrogen intake did not affect mineral retention. CONCLUSIONS: In this study, formula for preterm infants with a P:E ratio of 3.2 g/100 kcal vs. 2.6 g/100 kcal provided no apparent benefit in terms of the proportion of fat to lean tissue accretion as determined from nutrient balance data.

Calcium↗

Bilateral intraabdominal ganglioneuroblastoma in an adult.

Ganglioneuroblastoma is an unusual tumour in an adult. We present a case of bilateral intraabdominal ganglioneuroblastoma in an adult patient. The two tumours had different morphological features and origins. The appearances on ultrasound, CT and MRI are discussed. To the best of our knowledge, this is the first case of bilateral ganglioneuroblastoma reported in an adult patient with ultrasound, CT and MRI findings.

Abdominal Neoplasms↗

The incidence and nature of fibrous continuity between the sphenomandibular ligament and the anterior malleolar ligament of the middle ear.

The purpose of this study was to determine the structural interrelationship between the temporomandibular joint (TMJ) and the middle ear, in terms of fibrous continuity between the sphenomandibular ligament (SML) of the mandible and the anterior malleolar ligament (AML) of the middle ear. Thirty-seven specimens of the TMJ and middle ear were obtained from adult human cadavers. The temporal bone, petrotympanic fissure, mandibular fossa, and middle ear were dissected en bloc, fixed, sectioned, stained, and observed microscopically. Of the 37 specimens, 67.6% had a continuity of the SML through the fissure passing near the malleus of the middle ear. The AML was present at the fissure in 64.9% of the specimens, with 58.3% passing through and not stopping at the fissure. Results indicated a fibrous continuity between the SML and the AML. Structural differences between the two ligaments were also noted. The SML contained randomly arranged fibrous connective tissue with numerous interposed blood vessels. The AML had a smooth arrangement of fibers within the connective tissue, and few blood vessels were apparent. The clear anatomic relationship observed strongly supports the contention of a functional interrelationship between the TMJ and the middle ear.

Aged↗

Alterations in macrophage G proteins are associated with endotoxin tolerance.

Previous studies have suggested that endotoxin tolerance induces macrophage desensitization to endotoxin through altered guanine nucleotide regulatory (G) protein function. In the present study the binding characteristics of the nonhydrolyzable GTP analogue GTP gamma [35S] to macrophage membranes from endotoxin tolerant and control rats were determined. Membranes were prepared from peritoneal macrophages harvested from rats 72 h after two sequential daily doses of vehicle or Salmonella enteritidis endotoxin (100 micrograms/kg on day 1 and 500 micrograms/kg on day 2). GTP gamma [35S] bound to a single class of sites that were saturable and displaceable in control and endotoxin tolerant macrophage membranes. The maximum specific binding of GTP gamma [35S] was significantly (P < 0.01) decreased in membranes from tolerant rats compared to control (Bmax = 39 +/- 7 pmol/mg protein in control vs. 11 +/- 2 pmol/mg protein in endotoxin tolerant; n = 5). There were no significant differences in the Kd values. To determine whether the reduced GTP gamma S binding was due to decreases in G proteins, macrophage membrane G protein content was determined by western blotting with specific antisera to Gi1,2 alpha, Gi3 alpha, Gs alpha, and the beta subunit of G. Scanning densitometric analysis demonstrated differential decreases in tolerant macrophage membrane G proteins. Gi3 alpha was reduced the most to 48 +/- 8% of controls (n = 3), and this reduction was significant compared to those of other G proteins. Gi1,2 alpha and G beta were reduced to 73 +/- 5% (n = 3) and 65 +/- 4% (n = 3) of control values, respectively. Gs alpha(L) and Gs alpha(H) were reduced to 61 +/- 5% (n = 3) and 68 +/- 3% (n = 3) of control, respectively. These results demonstrate that endotoxin tolerant macrophages exhibit decreased membrane GTP binding capacity and differential reductions in the content of specific G proteins. The cellular mechanisms leading to such alterations in G proteins and their functional significance in the acquisition of endotoxin tolerance merit further investigation.

Animals↗

Tissue-arterial PCO2 difference is a better marker of ischemia than intramural pH (pHi) or arterial pH-pHi difference.

Gastric intramucosal pH (pHi) is often calculated by the Henderson-Hasselbalch equation, using arterial plasma [HCO3-]ap and PCO2 measured in saline obtained from a silastic balloon tonometer after equilibration in the lumen of the stomach. A pHi value less than approximately 7.3 pH units is often taken as evidence of intestinal ischemia. An alternative measure is tissue PCO2 (PtCO2)-PaCO2 difference [P(t-a)CO2]. The idea is that PtCO2 will increase slightly relative to PaCO2 as O2 supply decreases, and then increase strikingly when flow decreases to a critical value, because of liberation of CO2 from tissue Hco3- by anaerobically generated strong acid. A third method is arterial plasma pH (pHap)-pHi difference [pH(ap-i)]. We used mathematical simulations to test the hypotheses that calculated pHi is independent of arterial acid-base status; and pH(ap-i) provides the same information as does P(t-a) CO2. Using the Van Slyke version of the arterial whole blood [standard base excess] ([SBE]aWB) equation, it was found that a change in [SBE]aWB at constant PaCO2 and constant PtCO2 produces a change in calculated pHi (P = 0), such that the relation between changing [SBE]aWB and changing pHi is predictable by a single polyomial equation (R2 = .999). pH(ap-i) avoids this confounding influence of [SBE]aWB. However, it was further shown that pH(ap-i) can be associated with a wide range of P(t-a)CO2, depending on the magnitude of pH(ap-i), and on the PaCO2 at which P(t-a)CO2 is measured. We conclude that P(t-a)CO2 is a more reliable index of gastric oxygenation than is pHi alone or pH(ap-i).

Acid-Base Equilibrium↗

Single lead DDD system: a comparative evaluation of unipolar, bipolar, and overlapping biphasic stimulation and the effects of right atrial floating electrode location on atrial pacing and sensing thresholds.

Single lead DDD pacing using unipolar or bipolar stimulation is limited by high atrial threshold. Overlapping biphasic (OLBI) waveform stimulation via atrial floating ring electrodes may preferentially enhance atrial pacing and avoid diaphragmatic pacing. Single lead DDD pacing with OLBI atrial pacing was studied in 12 patients (6 men and 6 women; mean age 74 +/- 7 years) with complete heart block. At implantation, atrial bipolar rings (area 27 mm2, separation 10 mm) were positioned at radiological defined high, mid, and low right atrial (RA) levels, and P wave amplitude and atrial and diaphragmatic pacing thresholds were determined in each position using unipolar, bipolar, and OLBI stimulation in random order. Although statistically insignificant, both the maximum and minimum sensed P wave amplitudes tended to be lower in the low RA position. Independent of the stimulation modes, minimum atrial pacing threshold occurred in the mid-RA. At mid-RA, the atrial pacing threshold was significantly lower with OLBI pacing compared with either unipolar or bipolar mode (3.9 +/- 2.2 V vs 6.7 +/- 3.5 V and 6.9 +/- 3.5 V, P < 0.05). Although the diaphragmatic thresholds were similar, OLBI pacing modes in the mid-RA and final location significantly improved the safety margin for avoidance of diaphragmatic pacing compared with unipolar mode. There was no correlation between atrial pacing and sensing threshold. At predischarge testing, all but one patient who developed atrial fibrillation had satisfactory atrial capture and a stable atrial pacing threshold (day 0: 2.6 +/- 1.1V vs day 2:3.2 +/- 1.3V, P = NS). However, diaphragmatic pacing occurred in four of 11 (36%) patients, especially in the upright position (sitting and standing). Our preliminary clinical results suggest that OLBI pacing via atrial floating ring electrodes can reduce the atrial pacing threshold. To optimize atrial pacing and sensing, the bipolar electrodes should be located at the mid-RA level first, although the high RA is an alternative. Despite significant improvements in the safety margin for diaphragmatic pacing with OLBI pacing, diaphragmatic stimulation remains a clinical problem.

Aged↗

Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down's syndrome. Quantitative regional analysis and comparison with Alzheimer's disease.

OBJECTIVE: To investigate whether changes in the cerebral cortex exhibit similar distribution patterns in both disorders of Down's syndrome and Alzheimer's disease, we performed a comparative neuropathologic study of patients with these disorders to further clarify the possible relationships between these dementing conditions. DESIGN: The regional and laminar distribution and density of neurofibrillary tangles and senile plaques were analyzed in the cerebral cortex of a series of 16 patients (aged 6 to 74 years) with Down's syndrome and in 10 elderly individuals with Alzheimer's disease. RESULTS: Quantitative analyses revealed that the time course of neurofibrillary tangle formation in Down's syndrome displays regional patterns comparable with those observed in aging and Alzheimer's disease with layer II of the entorhinal cortex being affected first in Down's syndrome, followed by the hippocampus proper and neocortex. The oldest patients with Down's syndrome had neurofibrillary tangle densities sometimes higher than in patients with Alzheimer's disease. At variance with Alzheimer's disease, amyloid deposition was widespread in all of the cortical areas investigated and was observed much earlier than neurofibrillary tangle formation. Patients with Down's syndrome also frequently had higher senile plaque densities than patients with Alzheimer's disease. CONCLUSIONS: These results indicate that the development of pathologic changes in patients with Down's syndrome does not parallel that observed in elderly individuals and patients with Alzheimer's disease in all respects. However, the comparable development patterns of neurofibrillary tangle formation suggest that detailed analysis of patients with Down's syndrome may be useful to further our knowledge of the mechanisms underlying the installation of the neuropathologic alterations leading to the demonstrated loss of select neuronal populations in Alzheimer's disease.

Adolescent↗