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Biomedical subjects

R Mathur

Publications and source records attributed to R Mathur.

At least 37 records · Page 2Linked to original sources

Family studies in patients with the sleep apnea-hypopnea syndrome.

OBJECTIVE: To determine whether familial factors affect development of the sleep apnea-hypopnea syndrome and upper airway caliber. DESIGN: A case-control study. SETTING: Tertiary, referral clinical sleep laboratory. PARTICIPANTS: 51 first-degree relatives of patients with the sleep apnea-hypopnea syndrome and 51 controls matched for age, sex, height, and weight who were drawn at random from a family practice register. To avoid studying the familial nature of obesity, only relatives of index patients with body mass indices less than 30.0 kg/m2 were recruited. MEASUREMENTS: Assessment of sleep-related symptoms; breathing, sleep, and oxygenation patterns on overnight polysomnograms; upper airway dimensions by acoustic reflection; and facial structure by lateral cephalometry. RESULTS: More relatives of patients with the sleep apnea-hypopnea syndrome reported snoring (24 relatives compared with 7 controls; P < 0.001) and daytime sleepiness (28 relatives compared with 16 controls; P = 0.01). Relatives had more apneas and hypopneas per hour (median of 13/h [95% CI, 3 to 82/h] for relatives compared with median of 4/h [CI, 0 to 53/h] for controls; P < 0.001), more arousals from sleep (30/h [CI, 11 to 87/h] for relatives compared with 17/h [CI, 4 to 59/h] for controls; P < 0.001), poorer sleep quality, and more oxygen desaturations. Relatives also had narrower upper airways with retroposed maxillae and mandibles and longer soft palates with wider uvulae. CONCLUSION: The sleep apnea-hypopnea syndrome has a strong familial component. The familial tendency may be caused by differences in facial structure.

Adult

Effects of meso-2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate on beryllium-induced biochemical alterations and metal concentration in male rats.

The effects of two chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane 1-sulfonate (DMPS) on the mobilization, distribution, hepatic and hematopoietic toxicity of beryllium were compared in male rats exposed to beryllium. Animals were exposed to beryllium nitrate (0.5 mg/kg, orally, daily 5 days/week) for 21 days. Twenty-four hours after the last dose they were injected with a chelating agent (DMSA or DMPS) (25 or 50 mg/kg, twice daily for 5 days). The administration of DMSA and DMPS at a dose of 50 mg/kg marginally elevated the fecal excretion of beryllium. DMPS was effective in depleting beryllium from the liver, spleen and kidneys. However, DMPS (50 mg/kg) results in the redistribution of beryllium to blood. Beryllium-induced inhibition of hepatic alkaline phosphatase and hepatic adenosine triphosphatase (ATPase) were restored considerably with the chelating agents. Also, hepatic and renal histopathological lesions were less marked in rats treated with DMPS (50 mg/kg) compared with those treated with beryllium per se and DMSA. These effects were more prominent at the 50-mg/kg dose of chelating agents than at 25 mg/kg. These results suggest that treatment with DMPS has some beneficial effects in experimental beryllium intoxication.

Animals

Time course of resolution of persistent air leak in spontaneous pneumothorax.

Persistent air leak (PAL) following tube drainage for spontaneous pneumothorax (SP) is a potentially troublesome complication. The optimum time to intervene surgically is not known. We therefore investigated the rate of resolution of PAL (defined as continued air leak at 2 days after tube insertion) in patients treated medically. We retrospectively reviewed the records of 214 patients presenting with SP over 5 yr. One hundred and forty-two (67%) had tube drainage and in 73 (51%) of these a PAL developed. Overall median time to resolution in the 43 patients with PAL treated medically was 8 days from tube insertion, but PAL resolution was longer in those with underlying lung disease (n = 19) than those without such disease (11 days vs. 7 days, P = 0.05). In patients with normal lungs 20/24 had resolved by 9 days but subsequently the rate of resolution was much slower. In those with abnormal lungs only 8/19 had resolved by 9 days (P < 0.05 compared with those with normal lungs) but the rate of resolution in such patients appeared to change little subsequently. The size of the initial SP did not influence the rate of resolution of PAL. For patients with PAL and normal lungs, surgery at 7-9 days from tube insertion would provide a reasonable opportunity for the PAL to resolve with medical treatment. For those with underlying lung disease there is no clear optimal time and decisions need to be taken on an individual basis.

Adolescent

Effect of breathing, pressure and posture on palatoglossal and genioglossal tone.

1. Patency of the upper airway is critical to respiration. Although about half of patients with the sleep apnoea/hypopnoea syndrome obstruct their upper airway at the retropalatal level, the respiratory actions of the palatal muscles have been little studied. We have therefore tested the hypothesis that the nasopharyngeal dilator muscle palatoglossus is activated during inspiration and by negative pressure. 2. Using intramuscular wire electrodes inserted perorally, we have compared the response of palatoglossus and genioglossus to breathing, posture change and airway negative pressure in 10 normal awake subjects before and after topical anaesthesia. The results are expressed as a percentage of maximal electromyogram. Data were analysed by repeated-measures analysis of variance. 3. Inspiratory activity was exhibited by both genioglossus [inspiratory, 10% +/- 2% (SEM); expiratory, 6% +/- 1%, P = 0.001] and palatoglossus (inspiratory, 16% +/- 5%, expiratory, 10% +/- 3%, P = 0.016), but only genioglossus exhibited increased activity on lying (supine 10% +/- 2%, erect 6% +/- 1% maximum, P = 0.01). 4. One hundred milliseconds after negative pressure application, activity increased in both genioglossus (7% +/- 2% and 13% +/- 3% respectively, P = 0.02) and palatoglossus (8% +/- 2% and 23% +/- 6% respectively, P < 0.001). After lignocaine surface anaesthesia to the nose and pharynx both genioglossus and palatoglossus still increased their activity in response to negative upper airway pressure, the extent of the increase being decreased for palatoglossus (P = 0.02) but not for genioglossus. 5. Thus, palatoglossus has respiratory activity and is activated by negative upper airway pressure.

Adult

Frequency of EEG arousals from nocturnal sleep in normal subjects.

Brief arousals are clinically important and increasingly scored during polysomnography. However, the frequency of arousals during routine polysomnography in the normal population is unknown. We performed overnight polysomnography in the 55 of 59 control subjects from a family practice list who were approached and agreed to undergo polysomnography. Awakenings were scored according to the criteria of Rechtschaffen and Kales and briefer arousals according to three different criteria, including the American Sleep Disorders Association (ASDA) definition. There was a mean of 4 [95% confidence interval (CI), 1-15) Rechtschaffen and Kales awakenings per hour, whereas the ASDA definition gave 21 (95% CI, 7-56) per hour slept. Arousal frequencies increased significantly (p < 0.001) with age in our subjects, who ranged from the late teens to early 70s. The high upper limit of the frequency of brief arousals was not altered by exclusion of patients who snored or had witnessed apneas or daytime sleepiness. It is important that those scoring arousals on routine polysomnography recognize that high arousal frequencies occur in the normal population on 1-night polysomnography.

Adult

Lateral condylar fractures of the humerus in children: fixation with partially threaded 4.0-mm AO cancellous screws.

Thirty-seven children with fresh, displaced (more than 2 mm in any direction) fractures of the lateral condyle of the humerus were treated by open reduction and internal fixation with a partially threaded 4.0-mm diameter AO lag screw. They were reviewed at a mean follow-up of 4.8 years. Painless, full-elbow movements were obtained in 36 cases. Delayed union, with loss of 10 degrees of elbow motion, was observed in one case (2.72%). Radiologically, less than 4 degrees of varus deviation, compared with the contralateral side, was found in four cases (10.8%). Mild fishtailing was observed in three cases (8.18%). Nonunion, avascular necrosis or clinically significant premature epiphysial fusion was not observed. Elbow function was excellent, irrespective of minor radiologic abnormalities.

Bone Screws

Effect of posture, route of respiration, and negative pressure on palatal muscle activity in humans.

Sleep apnea is worse in the supine posture and is associated with retropalatal airway narrowing or occlusion. We have, therefore, examined the effects of posture, negative pressure, and route of respiration on palatal muscle activity in 13 nonsnoring awake male subjects by using electromyography. Electromyographic activity of the levator palatini and palatoglossus was expressed as a percentage of maximum activity. Both the levator palatini (P = 0.002) and palatoglossus (P = 0.002) exhibited phasic inspiratory activity. Overall, posture did not affect the levator palatini (F = 1.58; P = 0.23) or palatoglossus (F = 0.98; P = 0.34) activity, but analysis by route of respiration showed the palatoglossus to be more active when the subjects were nose breathing supine (F = 6.64; P = 0.02). Levator palatini activity was lower when nose breathing was compared with mouth breathing in both the erect and supine postures (F = 6.67; P < 0.02). Nose breathing with the mouth held open caused an increase in palatoglossal activity (P = 0.04). Negative-pressure application (0 to -12.5 cmH2O) caused significant increases in levator palatini (P < 0.001) and palatoglossus (P < 0.001) activity, 100 ms after pressure stimulus, irrespective of route. However, the palatoglossus required significantly greater negative pressures to cause activation when applied via the nose compared with the mouth (P < 0.05). These observations indicate that the levator palatini and palatglossus have respiratory activity and are reflexly activated by negative pressure.

Adult

Therapeutic efficacy of combined meso 2,3-dimercaptosuccinic acid and calcium disodium edetate treatment during acute lead intoxication in rats.

1. The therapeutic ability of Ca disodium EDTA and meso 2,3-dimercaptosuccinic acid (DMSA) was studied, both individually and when given in combination, in reducing lead concentration in blood and other soft tissues, and in restoring lead induced altered biochemical variables in acute lead intoxicated rats. 2. Combined treatment with the above two chelating agents was more beneficial in reducing blood and hepatic lead compared to treatment with these drugs alone. Kidney lead concentration however, remained high following combined treatment, indicating the possibility of extra renal burden following treatment. 3. Lead sensitive biochemical variables also responded more favourably to combined treatment than treatment with these drugs alone. However, clinical biochemical indices indicate caution regarding the use of this new treatment regimen, and further investigation is required.

Alanine Transaminase

Hypocholesterolemic activity of nut shell extract of Semecarpus anacardium (Bhilawa) in cholesterol fed rabbits.

Administration of S. anacardium nut shell extract to cholesterol fed rabbits resulted in a significant reduction in serum cholesterol (-73.3%) and serum LDL-Chol. (-80%). The extract feeding also prevented the accumulation of cholesterol/triglycerides in liver, heart muscle and aorta and caused a regression of plaques (75.3-83.5%). These results indicate that S. anacardium is hypocholesterolemic in action and prevents cholesterol induced atheroma. Possible mechanism of action is discussed.

Animals

Ki-67 reactivity in breast carcinoma analyzed by a computer-assisted image system: preliminary results.

The proliferative index of 63 breast carcinomas was measured on Ki-67 immunostained frozen tissue sections with a computer-assisted image analysis system. The mean proliferative index in estrogen-positive breast carcinomas was lower than in estrogen-negative carcinomas. An inverse relationship between proliferative index and short-term disease-free survival was noted.

Breast Neoplasms

Amygdalar involvement in pain.

The limbic system has been implicated in the modulation of pain. The aim of this study was to determine the role of amygdala in different types of pain, viz., phasic and tonic. Unilateral stimulation of central nucleus of amygdala (CeA), basolateral nucleus (BL) and medial amygdaloid (MeA) in conscious rats resulted in the reduction of the tonic formalin-induced pain. The thresholds for simple vocalization (SV) and vocalization after-discharge (VA) were elevated during amygdalar stimulation in the tail-flick (phasic pain) test. However, the threshold for tail-flick (TF) evoked by electric shock was not affected. Tail-flick latency (TFL) to noxious heat was accentuated during amygdalar stimulation. These results suggest that amygdala had a modulatory role in the descending endogenous pain control mechanisms.

Amygdala

Correction of anemia and iron deficiency in vegetarians by administration of ascorbic acid.

Twenty-eight strict vegetarians were given 500 mg ascorbic acid twice daily after lunch and dinner for two months. Hemoglobin and certain iron status parameters were measured before and after the treatment. Ascorbate treatment increased mean hemoglobin by 8%, serum iron by 17% and transferrin saturation by 23% and decreased total iron binding capacity by 7%. All these changes were statistically significant. The rise in serum ferritin was 12%. The serum protein or copper level did not indicate their dietary deficiency, while initial serum ascorbate level were low which rose by 60% on therapy. It is concluded that ascorbate supplementation is a better method of improving hematologic and iron status than iron salt administration.

Adolescent

Prevention of hypercholesterolemia and atherosclerosis in rabbits after supplementation of Myristica fragrans seed extract.

Myristica seed extr. administration to hypercholesterolemic rabbits reduced serum cholesterol and LDL Cholesterol by 69.1% and 76.3% respectively and also lowered cholesterol/phospholipid ratio by 31.2% and elevated the decreased HDL-ratio significantly. Myristica seed extr. feeding also prevented the accumulation of cholesterol, phospholipids and triglycerides in liver, heart and aorta and dissolved atheromatous plaques of aorta by 70.9-76.5%. Fecal excretion of cholesterol and phospholipid were significantly increased in seed extract fed rabbits.

Animals

Poly ADP ribosylation as a possible mechanism of microwave--biointeraction.

Electromagnetic fields (EMFs) affect the metabolism of the body including the nervous, endocrine, cardiovascular, hematological as well as the reproductive system. EMFs are environmental pollutants, thus posing a health hazard which can cause steric changes in the molecule located at the cell surface. Microwaves are known to cause chromosomal abberations and act as tumor promoters. The process involves a stream of signals from cell membrane to nucleus and other organelles. The present investigations aim to understand the mechanism of biological effects of microwaves (2.45 GHz). The effect was studied on poly ADP-ribosylation, which is a post translational modification of chromatin protein catalysed by the enzyme poly ADPR polymerase using NAD+ as the substrate. Poly ADP-ribosylation has been shown to be involved in several aspects of chromatin structure and function. Twenty-three days old rats weighing 42-48 gms were exposed at a microwave dose level of 1.0 mW/cm2. After exposure for sixty days the animals were sacrificed and an estimation of poly ADPR polymerase activity was undertaken in different organs of these animals. There was an increase of 20% in its activity in liver, 35% in testis, whereas brain showed a 53% decrease in diencephalon and 20% decrease in the cortex in the exposed animals as compared to their respective controls. There was no change in enzyme activity in spleen and kidney. This was accompanied by concomitant changes in NAD+ levels. The above results may be cited as important events in carcinogenesis and tumor promotion related to microwave exposure and the signal transduction mechanism involved. The goal is to shed light on complex ecogenetic interactions leading to cancer modulation of gene expression by epigenetic mechanism.

Animals

Protective action of a herbal preparation Liv-52 against beryllium toxicity in rats.

An Ayurvedic medicine, Liv-52 has been studied as a prophylactic against beryllium induced toxicity in rats. Administration of beryllium per se caused severe degenerative and necrotic changes in liver, kidney, lungs and spleen. Its administration reduced glycogen content, activity of alkaline phosphatase and adenosine triphosphatase in these organs. On the contrary, activities of acid phosphatase and glucose-6-phosphatase were increased significantly. In Liv-52 primed rats significant recoupment was observed in all the parameters.

Alkaline Phosphatase

Modulation of the cytotoxic activity of tumor necrosis factor by protein tyrosine kinase and protein tyrosine phosphatase inhibitors.

The mechanism by which tumor necrosis factor (TNF) inhibits cell growth is not known. The importance of tyrosine phosphorylation in mediating the cytotoxicity of TNF has been suggested from previous studies. In this report, we investigated the effects of both tyrosine kinase (TK) and protein tyrosine phosphatase (PTP) inhibitors on the cytotoxic effects of TNF. TNF-induced changes in cellular PTPase activity were also examined. Incubation of tumor cells with genistein or tyrphostin, known TK inhibitors, protected against TNF cytotoxicity in a dose-dependent manner. Protection by TK inhibitors was observed at early time points after the start of TNF incubation. Preincubation of tumor cells with sodium orthovanadate, a known PTPase inhibitor, also protected against TNF cytotoxicity only at early time points after addition of TNF. Activation of total cellular PTPase activity by TNF was observed at early times of TNF incubation only in TNF-sensitive cell lines. Immunoblot analysis revealed that TNF enhanced tyrosyl phosphorylation of the epidermal growth factor receptor (EGFR) only in TNF-sensitive cell lines. No other substrates were tyr-phosphorylated after addition of TNF. The results suggest that both cellular PTKs and PTPases play a significant role in orchestrating the early events in the cytotoxic response of TNF. The nature and types of PTKs and PTPases involved in this process need further investigation.

Catechols