Alfred Bernhard Nobel (1833-1896)
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Awards and Prizes↗
Biomedical subjects
N Mehta
Publications and source records attributed to N Mehta.
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↗
Changes in high-frequency QRS components during prolonged coronary artery occlusion in humans.
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Adult↗
The failed thoracocentesis.
How often do we consider a differential diagnosis of diaphragmatic hernia in cases of failed thoracocentesis? How many of us remember that omental fat in the chest can behave in a fluid manner, layering along the chest wall, resulting in the misinterpretation of a decubitus view. A case is presented of a diaphragmatic hernia that was missed on conventional chest radiographs resulting in CT having to be performed. A high degree of suspicion is mandatory to reach the final diagnosis. Radiographs could be used more effectively and CT avoided.
Adult↗
Pharmacological properties of 403U76, a new chemical class of 5-hydroxytryptamine- and noradrenaline-reuptake inhibitor.
403U76 (5-chloro-[[2-[(dimethylamino)methyl]phenyl]thio]benzene- methanol hydrochloride) is a potent, competitive, inhibitor of 5-hydroxytryptamine (5-HT) and noradenaline reuptake into rat brain synaptosomes. Inhibition of 5-HT uptake in-vivo by 403U76 was demonstrated by potentiation of the behavioural effects of 5-hydroxytryptophan in rats and mice and blockade of p-induced depletion of 5-HT in rats. The firing of 5-HT-ergic dorsal raphe neurons in rats was decreased after intravenous administration of low doses of 403U76 as would be predicted for a 5-HT uptake inhibitor. 403U76 antagonized tetrabenazine-induced sedation, an effect associated with inhibitors of noradrenaline uptake, but not with inhibitors of 5-HT uptake. Thus 403U76 affects noradrenergic as well as 5-HT-ergic neurotransmission in-vivo. Potential anxiolytic activity was indicated by reductions in isolation-induced vocalizations in neonates after 403U76 treatment. Low intravenous doses of 403U76 were well tolerated and had no sustained cardiovascular effects. There were no deleterious behavioural side-effects at active doses. Effects observed on isolated tissues or transmitter receptors occurred only at very high concentrations and were pharmacologically unimportant. Thus 403U76 can be considered a potential antidepressant/anxiolytic agent that is a potent, selective inhibitor of 5-HT and noradrenaline reuptake.
5-Hydroxytryptophan↗
Multiple dust allergy in a semiurban environs.
Multiple dust allergy in a study of 100 patients of nasobronchial hypersensitivity has been demonstrated by skin testing in Chandigarh and successfully desensitised over a 3-year period. The results are discussed and the multiple factors involved postulated.
Adolescent↗
[Analysis of the junctional rhythm characteristics in patients with nodal reentry tachycardia treated with slow pathway radiofrequency ablation].
PURPOSE: To study the quantitative and qualitative aspects of junctional rhythm (JR) during radiofrequency (RF) catheter ablation of slow pathway in atrioventricular nodal reentrant tachycardia. METHODS: Twenty five patients, 5 males, ages ranging from 15 to 76 years, with recurrent atrioventricular nodal reentrant tachycardia, underwent to RF catheter ablation of slow pathway. During RF applications (40V, duration 60s) electrocardiographic was continuously recorded. The recordings were posteriorly used to study the presence and characteristics of JR (number of episodes, frequency and time of onset) at the effective and ineffective RF sessions. All variables were expressed as median and mean +/- SD. Univariate analysis of the effects of each variable on success or failure of ablation were performed using x2 test. A p value < 0.05 was considered significant. RESULTS: One hundred forty nine RF sessions were performed, 25 effective and 124 ineffective (mean per patient 6, range 1 to 22). JR was present in 18 of 25 effective and 44 of 124 ineffective sessions (p < 0.05). Mean time of appearance was 12s, occurring later this time in 9 of 18 effective and in 10 of 44 ineffective sessions (p < 0.05). Mean number of episodes was 3, occurring higher number in 7 of 18 effective and in 4 of 44 ineffective sessions (p < 0.05). Median of frequency of JR was 100bpm; 11 of 18 effective and 15 of 44 ineffective sessions presented higher frequencies (p < 0.05). CONCLUSION: JR during slow pathway ablation is a sensitive marker of ablation success. JR predictor of success has higher number of episodes, higher frequency and later time of appearance than that one of ineffective sessions.
Adolescent↗
Intermittent esotropia associated with rippling muscle disease.
PURPOSE: We report a rare myopathy known as rippling muscle disease, with the unique feature of extraocular muscle involvement, presenting as a variable esotropia. METHODS: Chart review with a review of the literature. RESULTS: Neurologic and neuro-ophthalmic examinations as well as electromyography and muscle biopsy confirm that this case closely resembles those described in the literature with the additional feature of a variable esotropia. CONCLUSION: Rippling muscle disease may be associated with intermittent esotropia. The pathophysiology of this disorder is unknown, but the intermittent esotropia is likely related to "rippling" of the medial recti.
Atrophy↗
[Preferential projections for mapping and ablation of tachycardia of the right ventricle outflow. Anatomoradiological study].
PURPOSE: To select ideal radiologic projections for mapping and ablation of tachycardias of right ventricular outflow tract (RVOT). METHODS: Ten hearts from human corpses were studied utilizing radiopaque material to identify the pulmonary valve and three distinct sites on this valve: septal anterior (A), septal posterior (P) and free-wall (L). Next, the hearts were filmed in the frontal plane and in oblique projections with 15 degrees increments to the right and to the left. The projections in which the sites were lateralized on the valve, eased radiologic interpretation and were considered ideal for mapping and ablation. Depending on the proximity of the sites to the lateral extremes of the pulmonary valve, the projections were considered ideal ( ), intermediary (++) and inadequate (+). RESULTS: Projections [table: see text] CONCLUSION: The A site of RVOT was best indicated in the 60 and 45 degrees left anterior oblique projections; the 0 degree postero anterior projection was best for mapping the P site; the L region was best explored in the 60 degrees right anterior oblique projection.
Adult↗
Anatomic basis for disk displacement in temporomandibular joint (TMJ) dysfunction.
This study was designed to investigate the site of lateral pterygoid muscle insertion into the temporomandibular joint (TMJ) disk, and the relationship between that attachment and the disk displacement. One hundred and ten TM joints from 78 cadavers were collected and sectioned in the sagittal plane. Sixty-two unilateral specimens were available and 16 additional specimens were selected randomly from the remaining cadavers in which both condyles were available. Thus statistical comparisons were not confounded by autocorrelation and were based on 78 independent specimens. The sites of muscle attachment in relation to the disk were identified histologically. Of the 78 joints 49 had anterior disk displacement. Of the 42 cases with insertion directly into the disk, 30 had anterior disk displacement. In contrast, only 19 of the 36 disks without direct muscle insertion were displaced. This finding indicated a statistically significant relationship between functional muscle attachment and disk displacement (chi 2 = 9.28, df = 1, p = 0.006). However, the superior head of the lateral pterygoid muscle (SLP) may not be the precipitating factor for anterior disk displacement even though it does coordinate disk movement on closure. Since other factors (e.g., trauma) can result in disk displacement, the SLP can maintain disk displacement only when it inserts directly into the disk. In cases of normal disk arrangement and condylar attachment, the muscle may not play a clinically significant role in disk displacement because disk attachment at the medial and lateral poles of the condyle allows the disk to move freely with the condyle.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Analysis of surfactin synthetase subunits in srfA mutants of Bacillus subtilis OKB105.
The srfA operon of Bacillus subtilis functions in the biosynthesis of the lipopeptide antibiotic surfactin. On the basis of nucleotide sequence and genetic analysis, it is believed to encode three enzymes (E1A, E1B, and E2) that catalyze the incorporation of the surfactin substrate amino acids. Insertion, deletion, and amino acid substitution mutations of srfA were analyzed for subunit composition and activity as determined by assays of both amino acid-dependent ATP-PPi exchange and aminoacyl thioester formation. Insertion mutations in srfAA (encoding E1A, the subunit that incorporates Glu, Leu, and D-Leu) eliminated production and activity of all three enzymes. Deletions within srfAA and extending from srfAA to srfAB (encoding E1B, which incorporates Val, Asp, and D-Leu) abolished the activity and production of all three enzymes. Insertions between srfAA and srfAB and within srfAB eliminate the production and activity of E1B and E2. An insertion mutation in srfAC (encoding E2, which incorporates Leu) abolished the activity of E2 only. Mutations of the active serine in the putative 4'-phosphopantetheine-binding motif of the second and third domains of E1A eliminated thioester formation and severely reduced the ATP-PPi exchange activity of the two domains. However, the same mutation in the first domain of E1B had little effect on Val-dependent ATP-PPi exchange activity but abolished thioester formation. These results indicate that the coding assignments of the srfA genes are srfAA (E1A), srfAB (E1B), and srfAC (E2).
Acylation↗
Risk factors for systemic hypersensitivity reactions after booster vaccinations with human diploid cell rabies vaccine: a nationwide prospective study.
To determine the incidence of and risk factors for adverse reactions following the boosters, we conducted a nationwide prospective study of persons receiving pre-exposure booster vaccination with human diploid cell rabies vaccine (HDCV). Persons who had previously received three pre-exposure doses of HDCV and whose rabies neutralizing antibody titres were < or = 1:5 were enrolled in the study if they stated that they intended to receive a booster. Of the 98 persons enrolled in the study, 40 (41%) were in risk groups for whom boosters are not recommended. Three (3%) of 98 developed generalized urticaria or wheezing within 1 day of receiving boosters and three others (3%) developed urticaria 6 to 14 days after the booster. No differences were found between individuals with reactions (either type) and those with no adverse reaction according to age, gender, occupation, history of previous allergies, or time since or route of primary vaccination. Reactions were somewhat more common among persons who received primary vaccinations by the intramuscular route (i.m.) and booster vaccinations by the intradermal route (i.d.) (3/15, 20%) or primary vaccinations i.d. and booster vaccinations i.m. (2/10, 20%), and somewhat less common among persons who received both these vaccinations i.d. (1/52, 2%) or i.m. (0/7). The number of persons who develop allergic reactions may be minimized by administering vaccinations only when vaccination is strictly indicated. The influence of the route of primary and booster vaccinations on the development of reactions deserves further study.
Adult↗
The effect of bilateral gastric vagotomy and histamine stimulation on parietal cell activity in streptozotocin induced diabetic rat model.
Disturbances in gastric secretions are commonly associated with diabetes mellitus and are usually attributed to autonomic neuropathy. Systematic documentation of the effects of experimental diabetes on parietal cell functions are not available. This study has been designed to evaluate the acid secretory status of the parietal cells in streptozotocin (STZ) induced rat model of diabetes mellitus by assessing the effect of bilateral gastric vagotomy and histamine administration on them. Results show that bilateral gastric vagotomy in the control rats as well as in experimental diabetes lowers the acid secreting capacity of the parietal cells. In the diabetic rats, however, vagotomy does not further decrease the gastric acid secretion. Histamine stimulation augments the acid secretory response in the controls but this rise is substantially prevented in the diabetic state. Histamine challenge following vagotomy in normal controls elicits a sharp rise in gastric acid secretion though not to the same extent as seen in rats with intact vagi. In the diabetic rats however, histamine fails to augment acid secretion after vagotomy. Diabetes is thus seen to severely impair the acid secretory response of the parietal cells and their responsiveness to histamine.
Animals↗
Sequential chemoimmunotherapy in the treatment of metastatic melanoma.
PURPOSE: A phase II study that alternates the sequence of chemotherapy (carmustine [BCNU], cisplatin [CDDP], and dacarbazine [DTIC]) and biologic therapy (interleukin-2 [IL-2] and interferon alfa-2 alpha [alpha IFN]) was performed to establish a safe and efficacious way to sequence these forms of treatment for metastatic melanoma. PATIENTS AND METHODS: Patients who had measurable metastatic melanoma, a Karnofsky performance status of greater than or equal to 70, and no clinically significant cardiac or pulmonary dysfunction were eligible for entry onto this trial. Responses to treatment were assessed after a treatment cycle by two tumor evaluations at least 4 weeks apart. RESULTS: Forty-two consecutive patients with metastatic melanoma were treated with this sequential chemoimmunotherapy. Transient thrombocytopenia and neutropenia were observed frequently, but neither hemorrhage nor infection occurred in any of the patients. Of the 42 patients, 10 achieved a complete response (24%), 14 achieved a partial response (33%), two achieved a minor response (5%), eight had stable disease (19%), and eight (19%) had progressive disease. The median time to disease progression for all patients was 7 months. The median survival for all patients entered onto the trial was 11.5 months. A vitiligo-like depigmentation was induced in many patients by this treatment. CONCLUSIONS: Cytotoxic chemotherapy can be administered safely immediately before or immediately after IL-2 and alpha IFN. Sequential chemoimmunotherapy administered as previously described yields a response rate of more than 55%. The overall survival curve suggests that a proportion of patients may achieve a long-term benefit from this treatment. Also, cutaneous depigmentation induced by this treatment suggests that immune modulation may contribute to the antimelanoma effect of this treatment.
Adult↗
Glaucoma after pediatric lensectomy/vitrectomy.
Glaucoma after pediatric cataract surgery, once well recognized, now occurs only rarely after modern lensectomy/vitrectomy. The authors performed directed glaucoma evaluations of 34 eyes of 26 children. Based on intraocular pressures of 26 mmHg or greater, glaucoma was diagnosed in 8 (24%) eyes of 7 (27%) children. Glaucoma was found more commonly among children followed more than 60 months and was diagnosed up to 105 months after surgery. Typically, the glaucoma was open angle and asymptomatic. Four children had had previously normal pressures recorded. With longer follow-up, it is likely that more children will be diagnosed with glaucoma after lensectomy/vitrectomy procedures. The authors believe such patients should be followed as glaucoma suspects for the rest of their lives.
Cataract Extraction↗
Pulmonary management during extracorporeal membrane oxygenation.
Traditional lung management during extracorporeal membrane oxygenation (ECMO) calls for low inspiratory and expiratory pressures with low ventilator rate to achieve lung rest. However, rapid weaning of pressures to severely injured lungs commonly leads to marked increase in pulmonary opacification as seen on chest x-ray and loss of volume. We postulated that a sufficiently high level of PEEP could prevent this deterioration. Forty-six newborns, who required ECMO therapy for refractory respiratory failure, were maintained on 8 to 14 cm H2O PEEP. The peak pressure was 20 to 24 cm H2O, rate 10 to 15 breath/min, and FIO2 0.21. Forty-one (89%) of 46 patients survived to discharge. The duration of ECMO was significantly decreased compared to the national average (82.4 +/- 43 vs. 117.5 +/- 59 h). The lungs of most patients remained adequately expanded and free of severe pulmonary opacification. Eleven of 40 patients did show significant worsening of chest x-ray compared to baseline, but only one of 18 who were on PEEP of greater than or equal to 12 cm H2O showed such deterioration. No unexpected complications were encountered. These data suggest that the use of high PEEP during ECMO safely prevents deterioration of lung function and promotes more rapid lung recovery. PEEP levels of 12 to 14 cm H2O appear to be most effective.
Extracorporeal Membrane Oxygenation↗
Polyunsaturated fatty acids stimulate superoxide formation in tumor cells: a mechanism for specific cytotoxicity and a model for tumor necrosis factor?
Some neoplastic cell lines are readily killed when incubated in the presence of polyunsaturated fatty acids (PUFA). In an attempt to elucidate this phenomenon, we studied PUFA-driven superoxide (O2-) production by cultured NS-1 cells (murine lymphoid tumor cells). We find: (1) Even in the absence of added PUFA, NS-1 cells generate O2- (i.e., reduce nitroblue tetrazolium). (2) addition of PUFA increases O2- by greater than 50%. (3) Artificial loading of NS-1 cells with liposome encapsulated superoxide dismutase prevents the majority of spontaneous and PUFA-driven NBT reduction. We conclude that PUFA drives O2- generation by tumor cells, that this generation is largely intracellular, and that this phenomenon may help explain toxicity of PUFA for tumor cells.
Animals↗
Hemodynamic response to treadmill exercise in normal volunteers: an assessment by Doppler ultrasonic measurement of ascending aortic blood velocity and acceleration.
Accurate assessment of ascending aortic blood velocity indices and reproducibility of a Doppler ultrasonic system during exercise were determined; the Doppler technique was then used to assess the effects of age, sex, and beta blockade on exercise hemodynamics. Doppler-determined velocity correlated well with an invasive electromagnetic system. Reproducibility of Doppler variables during three exercise tests was high (coefficient of variation less than 10%) and did not deteriorate appreciably with exercise. Peak velocity (PV) and maximum acceleration (MA) were inversely related to age, the relationship being more significant during exercise, whereas the systolic velocity integral showed no such relationship either at rest or during exercise. Doppler variables showed no difference between sexes, except at high levels of exercise. Beta blockade markedly attenuated the exercise response as shown by significant decreases in both MA and PV during exercise. The Doppler velocity data presented in this study provide a reference against which previously documented changes in exercising ischemic patients can be better related.
Adult↗