Biomedical subjects
Publications and source records attributed to R Tandon.
Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurologic disease affecting both grey and white matter of the brain in children and young adults. One such case which involved the visual system is described here.
This paper describes the clinical findings in 206 patients with dengue fever (DF) or with dengue hemorrhagic fever (DHF) during the epidemic of 1996 at Lucknow. The age group affected most was 11 to 30 years and 21% of the patients were less than 10 years old. The male:female ratio was 1.9:1. The onset was abrupt in all the patients, severe frontal headache was observed in 97%, myalgia in 90%, skin rash in 40%, vomiting in 29% and arthralgia in knee and hip joints in 9%. Anuria was seen in two patients. Lymphadenopathy was noted in 14%, hepatomegaly in 4%, being associated with mild jaundice in one patient, and splenomegaly in 2% of the patients. Involvement of the heart and lungs was seen in one patient each and no case with encephalitis was recorded. Hemorrhages from various sites were observed in 54% patients and 17 patients had profound shock. The commonest bleeding site was gums. Profound shock was preceded by various warning signs, the commonest being sudden hypotension. Among the patients with profound shock the mortality was 47% while the overall fatality rate was 3.8%. A number of the risk factors existed for a long time in this part of the world, but what precipitated the present epidemic at this time, is not known.
Loss of heterozygosity (LOH) at chromosome band 10q23 occurs frequently in a wide variety of human tumors. A recently identified candidate tumor suppressor gene, PTEN located on 10q23, is mutated in multiple advanced cancers. To explore whether PTEN is associated with human squamous cell carcinoma of the head and neck (SCCHN), DNAs from both normal muscle and tumor tissue in 19 SCCHN were used for detecting LOH at chromosome 10q23 and mutational analysis of PTEN by direct polymerase chain reaction (PCR)-DNA sequencing. LOH at 10q23 was identified in 6/15 SCCHN. Mutation of PTEN was identified in 3/19 SCCHN. Of these 3 patients, 2 had stage IV disease; the third patient, with recurrent, metastatic and stage III disease, showed a 36 bp germline heterozygous deletion within intron 7. Furthermore, a missense mutation at codon 501 (TCT --> TTT: Ser --> Phe) in exon 8 was also found in tumor from the same patient. Our results suggest that PTEN may play a role in the genesis of some SCCHNs.
A unique cytokine, human cytotoxic factor (hCF), has been shown to occur in the sera of patients with dengue fever (DF) and dengue haemorrhagic fever (DHF). The present study was undertaken to investigate the ability of fresh PBMC of such patients to produce hCF. The PBMC were cultured for 24 h and the culture supernatants (CS) were analysed for the presence of hCF by cytotoxicity assay, competitive ELISA and dot blot tests. In 90% of 246 cases CS were positive for hCF by the three tests. CS were positive for hCF in PBMC collected from days 1-20 of illness but not at later periods. Higher cytotoxic activity was observed in CS of days 1-4 of illness and was highest in cases of DHF grade IV and lowest in cases of DF. Dot blot hybridization of RNA extracted from the PBMC of the patients showed the presence of mRNA for hCF in 94% of cases. A similar number of patients showed the presence of hCF in situ in the PBMC smears by fluorescent antibody technique. hCF was found only in CD4+ T cells. The findings thus present direct evidence of the production of hCF by CD4 T cells of cases of DF/DHF.
PURPOSE: To report the occurrence of optic neuritis following oral albendazole therapy for orbital cysticercosis. METHODS: Two patients having definitively diagnosed orbital cysticercosis at the orbital apex developed an acute visual loss 1 week after initiation of oral albendazole. Ultrasonography and magnetic resonance imaging determined that the cause was optic neuritis due to disorganization of the cyst with inflammation of the adjacent optic nerve. RESULTS: Oral corticosteroids (prednisolone 1 mg/kg per day) given for a period of 4 weeks led to resolution of the optic neuritis, with full visual recovery. CONCLUSION: Corticosteroids should be given in addition to albendazole in the treatment of orbital cysticercosis when cysts are in close proximity to the optic nerve.
OBJECTIVE: The authors sought to replicate and extend previous observations of improvement in some EEG sleep measures during the course of antipsychotic treatment in schizophrenia patients. METHOD: Fourteen medication-free patients with schizophrenia underwent 2 nights of sleep EEG monitoring before and after 3-4 weeks of treatment with clinically determined doses of haloperidol or thiothixene. RESULTS: Measures of sleep continuity improved consistently. REM latency increased, although five of 14 patients continued to exhibit short REM latencies (less than 60 minutes). Stage 3 sleep increased during neuroleptic treatment, while stage 4 sleep did not change. CONCLUSIONS: These data demonstrate partial improvement of some but not all EEG sleep measures in schizophrenic patients through the course of neuroleptic treatment. They suggest that shortened REM latency and disturbed sleep continuity might represent reversible state abnormalities, while reduced slow-wave sleep may represent a more persistent trait abnormality in schizophrenia.
The response to electroconvulsive therapy (ECT) was monitored with sleep polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with major depressive disorder (MDD). Patients included in this study met research diagnostic criteria for MDD and had been free of psychotropic medication for at least 10 days before SPS were performed. We compared ECT responders and nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters, regardless of the clinical response, changed significantly with ECT. The presence of delusions was significantly associated with SOREM post-ECT. The presence of sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS performed during a course of ECT may help identify patients at risk of responding less well to this modality of treatment.
1. Structural neuropathologic abnormalities have been associated with severe psychiatric illnesses, including bipolar disorder, major depressive disorder, and schizophrenia. In the latter, ventricular enlargement has been variably associated with symptom severity and poor treatment response. In patients with severe depressive disorders, the relationship between cortical and subcortical pathology and ventricle enlargement, symptom severity, and response to treatment is far from clear. 2. The present study investigated the relationship between structural CNS pathology, symptom severity and treatment response in patients undergoing ECT. It was hypothesized that patients with greater neuroanatomic abnormalities would demonstrate greater initial symptom severity and poorer response to ECT. 3. The subjects were 57 patients with unipolar or bipolar depression admitted for ECT treatment. Symptom severity was quantified using the Hamilton Depression Rating Scale (HRSD) at baseline and post-ECT. 4. Lateral and third ventricle-brain ratio (LVBR, 3VBR) were determined from CT scans and cortical atrophy was rated by a faculty neuroradiologist. 5. Contrary to our first hypothesis, structural pathology was not associated with baseline symptom severity. In terms of treatment response, the number of treatments required to achieve benefit was correlated with larger 3VBR; CT variables were not related to total post-treatment or change in HRSD score. Third ventricle enlargement may be an index of generalized pathology or regional brainstem abnormalities that influence ECT response rate by limiting individual seizure efficacy or neurochemical responsiveness, thereby necessitating a greater number of ECT treatments, without significant impact on overall response.
BACKGROUND: A relationship between the anticonvulsant and antidepressant properties of electroconvulsive therapy (ECT) has been hypothesized. The goal of this study was to see whether the anticonvulsant effects of ECT could be measured in a clinical setting and whether there was any relationship between the anticonvulsant effects of ECT and the antidepressant response to it. METHODS: We examined the temporal relationship between change in seizure duration (as an index of anticonvulsant activity) and improvement in Hamilton Rating Scale for Depression scores in a retrospective sample of 114 depressed patients who received 145 courses of ECT. A linear mixed effects model was utilized for analysis so that the repeated measures nature of the data could be taken into account. RESULTS: Both seizure duration and depression scores decreased significantly through the course of ECT. However, no evidence was found for a relationship between decrease in seizure duration and clinical improvement as measured by Hamilton ratings. CONCLUSIONS: The process underlying the reduction in seizure duration through a course of ECT may not be related to antidepressant efficacy.
OBJECTIVE: In this study healthy volunteers received thiothixene with and without a 3-day pretreatment with paroxetine to determine if paroxetine decreased the clearance of thiothixene. METHOD: Ten healthy medication-free volunteers (4 women and 6 men, mean age 38 +/- 12 years) were randomized to receive a single 20 mg oral dose of thiothixene on two separate occasions. On one occasion thiothixene was given concurrently, and following 3 days of pre-treatment with oral paroxetine (20 mg/day). On the other occasion thiothixene was given without paroxetine pre-treatment. The two study days were separated by a minimum period of 2 weeks. On both study days, after the administration of thiothixene, 10 ml blood samples were collected over the next 72 h. RESULTS: None of the pharmacokinetic parameters of thiothixene were significantly altered by a 3-day treatment with paroxetine. DISCUSSION: It is likely that the CYP2D6 isoenzyme is not responsible for a high proportion of thiothixene clearance, but one cannot exclude the possibility that a longer paroxetine pretreatment might have caused some inhibition of thiothixene clearance.
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OBJECTIVE: The authors tested the hypothesis that photic visual stimuli cause a greater blood flow activation response in subjects with schizophrenia than in normal subjects. METHOD: Eleven medicated patients with schizophrenia and 10 normal subjects were studied with [15O]H2O positron emission tomography to measure perfusion during photic stimulation at four different rates. RESULTS: The activation at three out of four rates of visual stimulation was greater for the patients with schizophrenia than it was for the normal subjects. CONCLUSIONS: Further investigation into the mechanisms of activation during sensory stimulation in schizophrenia is warranted.
Dysphagia and aspiration are two devastating sequelae of stroke. Recent work has shown that laryngopharyngeal (LP) sensory deficits are associated with aspiration in stroke patients with dysphagia. The phenomenon of silent LP sensory deficits, where the patient exhibits no subjective or objective evidence of dysphagia, yet has an LP sensory deficit, has not been previously described. The aim of this study was to evaluate the sensory capacity of the laryngopharynx in stroke patients who had no subjective or objective complaints of dysphagia. We determined the sensory threshold in the laryngopharynx using air pulse stimulation of the mucosa of the pyriform sinus and aryepiglottic fold. Eighteen stroke patients (mean age 65.6 +/- 11.5 years) and 18 age-matched controls were prospectively evaluated. Normal thresholds were defined as < 4.0 mm Hg air pulse pressure (APP). Deficits were defined as either a moderate impairment in sensory discrimination thresholds (4.0 to 6.0 mm Hg APP) or a severe sensory impairment (> 6.0 mm Hg APP). Stroke patients were followed up for 1 year to determine the incidence of aspiration pneumonia (AP) as verified by chest radiography. In 11 of the stroke patients studied, either unilateral (n = 6) or bilateral (n = 5) severe sensory deficits were identified. The elevations in sensory discrimination thresholds were significantly greater than those in age-matched controls (7.1 +/- 0.6 mm Hg APP versus 2.5 mm Hg APP; p < .01, Wilcoxon score). Among patients with unilateral deficits, sensory thresholds were severely elevated in all cases on the affected side compared with the unaffected side (p < .01, Wilcoxon score). Moreover, the sensory thresholds of the unaffected side were not significantly different from those of age-matched controls. Aspiration pneumonia did not occur in the patients with normal LP sensation or in the patients with unilateral severe LP sensory deficits. However, in the 5 patients with bilateral, severe LP sensory deficits, 2 developed AP, both within 3 months of their LP sensory test. The results of this study showed, for the first time, that stroke patients without subjective or objective clinical evidence of dysphagia could have silent LP sensory deficits. These impairments could contribute to the development of AP following stroke. The findings in this study suggest that LP sensory discrimination threshold testing should not be restricted only to patients with clinical dysphagia.
BACKGROUND AND OBJECTIVES: Continuous administration of aerosolized beta 2-agonists has been suggested as an effective treatment for severe reversible airways disease. To facilitate continuous therapy and avoid a feed system for small-volume nebulizers (SVNs), a large-volume medication nebulizer (Vortran HEART) was developed. The goal of this study was to determine actual drug delivery of the HEART and conventional SVNs for both adult and pediatric breathing patterns. DESIGN: Output studies were conducted on comparable samples of CIS-US AeroTech II and Hospitak PowerMist SVNs and Vortran HEART large-volume continuous nebulizers. To duplicate clinical aerosol delivery via an aerosol mask, drug particles were inhaled through the mouth of a model of a human face for two test breathing patterns (adult = tidal volume (Vt) of 500 mL, 20 breaths/min, duty cycle of 40%; pediatric = VT of 100 mL, 35 breaths/min, duty cycle of 40%), generated by a ventilator. Radiolabeled particles of saline solution, confirmed to behave identically to albuterol, were collected on absolute filters at the mouth of the face to measure the actual mass of albuterol particles delivered to the airway opening. RESULTS: The AeroTech II and PowerMist SVNs delivered 5.14 and 3.74 mg/h, respectively, for the adult breathing pattern and 2.97 and 2.48 mg/h, respectively, for the pediatric breathing pattern. Drug delivery rates of the HEART were a function of drug concentration and ranged from 0.87 to 3.48 mg/h for the adult breathing pattern. For the pediatric breathing pattern, drug delivery rate was a function of drug concentration and inspired minute ventilation and ranged from 0.41 to 1.83 mg/h. CONCLUSION: Our data demonstrate that drug delivery to the patient, expressed as inhaled mass over time, is similar for continuous nebulization (HEART system) and intermittently filled SVNs. In addition, for all nebulizers, the influence of the pediatric breathing pattern needs to be considered. Continuous nebulization permits the redistribution of health-care personnel and may reduce the costs of therapy.
STUDY OBJECTIVES: The function of jet nebulizers has been measured traditionally by gravimetric methods, i.e., by weighing nebulizers before and after nebulization. Newer techniques measure aerosol output directly by analyzing aerosolized drug or tracer, i.e., radioactive 99mTc. Because of evaporation, the equivalence of these methods is uncertain. The aim of this study was to determine if the gravimetric method is an accurate measure of aerosol production under different conditions of aerosol generation (i.e., nebulizer type, flow rate, pressure, volume fill, and concentration of solution used to nebulize a drug). METHODS: In the first phase of the study, we measured the aerosol output of nine commercially available jet nebulizers (AvaNeb; Up-Draft-Hudson RCI; Cirrus-Intersurgical Inc; DeVilbiss 646-DeVilbiss; Powermist-Hospitak, Inc; Respirgard II-Marquest Medical Products; Seamless-Seamless/Dart Respiratory; Salter; Salter Labs; Airlife-Baxter Health Care) run under commonly used conditions (2.5 mL volume fill, 2.0 mL normal saline solvent, 0.5 mL albuterol, flow of 6 L/min, and pressures averaging 15.0 +/- 2.3 [mean +/- SD] pounds per square inch [on the] gauge [psig] provided by a DeVilbiss PulmoAide compressor) with simultaneously measured gravimetrics and filtered radioactivity. Each nebulizer was run to dryness with data acquired every 2 min. The change in the weight of the nebulizer and radioactivity captured on the filter were expressed as percentages of the total in the nebulizer solution. In the second phase of the study, the experiments were repeated using the same nebulizers with a volume fill of 5 mL (diluted to half normal saline solution plus albuterol), flow of 10 L/min, and pressures of 35.6 +/- 8.8 psig. RESULTS: The cumulative (sum of all 2-min runs) weight loss for each individual nebulizer ranged from 25.00 to 64.55% and cumulative aerosol captured varied from 12.63 to 38.76%. While different, the weight loss and aerosol captured were closely correlated (y = -0.62 + 0.62x; r = 0.961, p < 0.0001). Changing volume fill and concentration of solvent did not affect this correlation (p = 0.921 and 0.373, respectively). However, changing flow from 6 L/min to 10 L/min significantly (p = 0.02) affected the relationship (y = -3.80 + 0.83x; r = 0.969, p < 0.001). CONCLUSIONS: When compared with direct methods such as filtering generated particles, the gravimetric method of assessing nebulizer function overestimates aerosol output by 1.8 +/- 0.18 times, presumably because of the loss of solvent during nebulization. However, the relationship between methods is predictable and appears unaffected by changing the type of nebulizer, volume fill, and concentration of solvent. Changes in nebulizer flow and pressure significantly affected the correlation. Gravimetric methods can be used as simple and convenient screening techniques for comparing jet nebulizers under a wide range of experimental conditions.
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Effect of twice daily administration of aspirin eyedrops on the onset and progression of cataract induced by 30% galactose diet was studied. On the 30th day of galactose feeding while all control group rats showed complete stage IV opacity, those receiving aspirin eyedrops showed only mild cataractous changes of stage I. In vitro studies showed that addition of aspirin to the medium significantly decreased dulcitol formation (p < 0.01) and maintained glutathione levels (p < 0.02). Intraocular penetration studies using isolated goat cornea showed excellent penetration by salicylate indicating feasibility of topical administration. The results of the present study demonstrate that topical aspirin possesses significant anticataract activity in galactosemic cataract.
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