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Biomedical subjects

T Joseph

Publications and source records attributed to T Joseph.

At least 19 recordsLinked to original sources

[Cardiomyopathy induced by catecholamines in neuroblastoma].

BACKGROUND: Cardiovascular disorders associated with neural crest tumors are congenital malformations rather than cardiomyopathies. CASE REPORT: A 18 month-old girl developed heart failure one week after discovery of an adrenal neuroblastoma with excessive secretion of catecholamines. Investigation showed dilated cardiomyopathy without myocardial hypertrophy. Besides chemotherapy, the patient was given nitrous derivatives, diuretics and converting enzyme inhibitor. His cardiac condition gradually improved so that partial resection of the tumor was possible 2 years later. CONCLUSIONS: The cardiomyopathy presented by this patient is possibly catecholamine-induced even though catecholamines usually results in myocardial hypertrophy rather than dilated cardiomyopathy. The reason why such a cardiomyopathy has never been reported in patients with neuroblastoma remains unclear.

Adrenal Gland Neoplasms

Developmental changes in crossbridge properties and myosin isoforms in hamster diaphragm.

The aim of this study was to determine the effects of maturation on crossbridge properties and myosin isoform composition in hamster diaphragm muscle. Diaphragm strips were obtained at postnatal Days 1 and 8 and in adults (10 to 12 wk). Peak isometric tension and maximum unloaded shortening velocity (Vmax) increased with age (p < 0.001). The single crossbridge force (pi), the total number of crossbridges normalized per cross-sectional area (m x 10(9)/mm2), the turnover rate of myosin ATPase (kcat), and peak mechanical efficiency (Effmax) were calculated from Huxley's equations. The value of m increased significantly from birth to adulthood (p < 0.001), with no changes in pi or Effmax; kcat increased significantly only after the first week postpartum. There was a strong linear relationship between peak isometric tension and m (p < 0.001). Conversely, changes in Vmax were not related to kcat. Myosin electrophoresis showed that neonatal bands and slow myosin isoforms (S) were present at birth. The number of fast adult myosin isoforms increased progressively from birth to adulthood, whereas S increased during the first week postpartum. In conclusion, development changes in diaphragm muscle force and myosin isoform composition were associated with changes in crossbridge number and kinetics, with no changes in the average force per crossbridge or in mechanical efficiency.

Age Factors

Safety pharmacology of a combination of tinidazole and oxyphenonium bromide.

The effect of a combination of 150 mg tinidazole (CAS 19387-91-8) and 1 mg oxyphenonium bromide (CAS 50-10-2), referred to as the combination, was examined in various animal species to assess its safety. In mice and rats, the combination in the dose range 30-1000 mg/kg p.o. or 250 mg/kg i.p. did not produce behavioural or neurological changes, nor did it influence pentobarbital sleeping time, though, alcohol sleeping time was altered. In anaesthetised dogs, neither blood pressure, ECG, heart rate, respiration or gastrointestinal motility was affected after single intraduodenal administration of the combination 20 and 50 mg/kg or after chronic oral administration of 25 mg/kg daily for 15 days. In isolated organs, viz. perfused rabbit heart, guinea-pig ileum and rat ileum no significant changes were observed following various doses of the combination, compared to tinidazole and oxyphenonium bromide given alone in corresponding concentrations. In conclusion, the pharmacological profile of the aforementioned combination in the dosages employed in mice, rats, guinea-pigs, rabbits and dogs shows that it is safe and well tolerated.

Animals

Influence of adenosine, dipyridamole, adenosine antagonists and antiepileptic drugs on EEG after discharge following cortical stimulation.

The effects of adenosine (100 nM, icv), dipyridamole (DPM, 5 mg/kg, i.p.), adenosine A1 receptor antagonist 8-cyclopentyl-theophylline (8-CPT, 10 mg/kg, i.p.), and aminophylline (AMP) and caffeine (CAF) (at equivalent doses of 35 mg/kg, i.p.), were examined in rats. Anti-epileptic drugs (AEDs) were also administered i.p., viz, carbamazepine (CBZ, 10 mg/kg); phenobarbitone (PB, 10 mg/kg); phenytoin (PHT, 20 mg/kg); valproic acid (VPA, 300 mg/kg); and diazepam (DZP, 10 mg/kg), to study their effects on EEG after discharge (AD) and postictal depression (PID) induced by cortical stimulation. The AD parameters: (1) duration of EEG-AD (sec) and (2) number of spikes was noted both during pre and post drug treatment sessions. Adenosine and DPM had no special effects on AD parameters but showed significant prolongation of PID. All the adenosine antagonists, 8-CPT, AMP and CAF produced significant prolongation of AD duration, increase in number of spikes and reduced the duration of PID to a significant extent. Interestingly, some of the AEDs, viz. CBZ, VPA and DZP showed abolition of all the EEG-AD parameters whereas PB and PHT failed to show any significant effect. The results confirm previous findings on involvement of adenosine in postictal events.

Adenosine

Sequence heterogeneity of Nef transcripts in HIV-1-infected subjects at different stages of disease.

Nef transcripts were analyzed from peripheral blood mononuclear cells of 10 HIV-1-infected subjects with 9-822 CD4+ lymphocytes/cu mm, including 4 individuals with a probable common source infection. There was no relationship between the phylogenetic position of the various nef sequences and the disease state of the person from whom they were derived. The nef open reading frame was disrupted in all three clones from only 1 subject. Functional analyses of a representative clone from each of the remaining 9 subjects showed that all nef alleles were capable of CD4 cell surface down-regulation, but only three nef alleles suppressed the induction of IL-2 transcription.

Amino Acid Sequence

Pyridoxine 4'-alpha- and 5'-alpha-D-glucosides are taken up and metabolized by isolated rat liver cells.

Uptake and metabolism of pyridoxine-4'-alpha-D-glucoside and pyridoxine-5'-alpha-D-glucoside by freshly isolated rat liver cells were studied using the membrane filtration method. The presence of the pyridoxine-alpha-glucosides at either 0.5 or 5.0 micromol/L had no inhibitory effect on the uptake of pyridoxine (0.5 micromol/L) by hepatocytes. The amount of pyridoxine-alpha-glucoside transported into the cells was only 10-12% of that of pyridoxine. The initial rates of uptake of the pyridoxine-alpha-glucosides were linear with concentrations up to 50 micromol/L. On entry into the cells, 78% of pyridoxine-5'-alpha-glucoside and 15% of the pyridoxine-4'-alpha-glucoside were hydrolyzed at the end of 60 min. Because pyridoxine-5'-alpha-glucoside is hydrolyzed readily and does not interfere with the transport of pyridoxine, the glucoside, if present in animal- or plant-derived foods, may be available as a source of vitamin B-6.

Animals

Mechanical and energetic effects of cromakalim on guinea pig left ventricular papillary muscle.

The mechanical and energetic effects of the adenosine triphosphate-sensitive potassium channel opener cromakalim at 50 microM and 100 microM were determined on guinea pig left ventricular papillary muscles and compared with those of low calcium concentration (n = 9 in each group). Both concentrations of cromakalim induced a negative inotropic effect (decrease in maximum shortening velocity at preload only and maximum extent of muscle shortening at preload only, P < .01 and P < .001 at 50 and 100 microM, respectively; maximum isometric active force normalized per cross-sectional area during the isometric twitch, P < .001; positive peak of the isometric force derivative normalized per cross-sectional area, P < .001) and a negative lusitropic effect (decrease in maximum lengthening velocity at preload only and negative peak of the isometric force derivative normalized per cross-sectional area, P < .01 and P < .001 at 50 and 100 microM, respectively). At 100 microM, the decrease in relaxation parameters was more marked than that in contraction parameters under isotonic conditions, as shown by the decrease in the slope of the relationship between peak lengthening velocity and maximum extent of muscle shortening (P < .01); this result reflects an intrinsic negative relaxant effect. No relaxant effect was found under isometric conditions at either concentration. The mechanical effects of low calcium were similar to those of cromakalim 100 microM, which suggests that the drug acted mainly by reducing the cellular calcium entry. Despite the negative mechanical effect of cromakalim, mechanical efficiency was preserved. This could partly explain the cardioprotective effect of cromakalim during ischemia.

Action Potentials

Correlation between the severity of symptoms in organophosphorus poisoning and cholinesterase activity (RBC and plasma) in humans.

This study was undertaken to examine the correlation, if any, between the inhibition of red blood cell cholinesterase (RBC ChE), plasma cholinesterase (PChE) and cerebrospinal fluid acetyl cholinesterase (CSF AChe) and the severity of symptoms in patients poisoned with organophosphorus (OP) compounds. Baseline values of the cholinesterases (RBC, Plasma & CSF) were established in our laboratory using a modified colorimetric method. OP poisoned patients were divided into 3 groups - mild, moderate and severe based on clinical symptoms. We observed a severity dependent inhibition of both RBC ChE and PChE, in acute poisoning. Sequential post exposure estimations of the ChEs upto 5 days not reveal any rise in the values though there was substantial clinical improvement. Our findings therefore indicate that the correlation of ChE values with severity of symptoms are applicable only in the initial stages of acute poisoning. AChE could not be detected in CSF in two severely neurotoxic patients who subsequently expired. The clinical significance of this observation needs to be examined further.

Cholinesterases

Higher AUCs on oral administration of omeprazole and felodipine in Indian volunteers--are they clinically important?

Bioavailability studies with single oral doses of omeprazole 20 mg (enteric coated formulation) and felodipine 10 mg (extended release formulation) were performed in Indian volunteers to confirm that adequate plasma concentrations are obtained in Indian subjects. Plasma samples were analysed by chromatographic methods. The AUCs of omeprazole were about 3 fold higher and those of felodipine 2 fold higher than AUCs reported in Western subjects. This has no toxicological implications with respect to omeprazole, but whether lower dose of omeprazole may be sufficient in Indian patients with acid related diseases would require acid inhibition studies. In the case of felodipine the higher AUCs in Indian subjects suggest a need for a lower strength formulation (2.5 mg) to fine-titrate the dosage to obtain optimal antihypertensive effects with minimal adverse effects.

Administration, Oral

[Myocardial infarction caused by thrombosis of the left coronary artery in a patient with thrombocythemia].

Myocardial infarction is not exceptional in patients with essential thrombocythaemia. This infarction is often related to the formation of in situ coronary thrombosis with no associated atheromatous lesions. The authors report the case of a thrombocythaemic patient with anterior infarction due to thrombosis of the left coronary artery. The clinical course is often more severe than in nonthrombocythaemic patients. The pathophysiological mechanisms remain unclear, but appear to be related to qualitative rather than quantitative platelet abnormalities.

Adult

A prospective randomized study to assess the efficacy of post-operative nasal medication after endonasal surgery.

Post-operative nasal medications are commonly used following routine septal or turbinate surgery but their efficacy in removing blood clots, improving the sensation of a patent airway and promoting healing are unknown. This prospective randomized trial of patients undergoing septal and/or turbinate surgery assessed the efficacy of three commonly used nasal medicines, 0.5 per cent ephedrine hydrochloride nasal drops, betamethasone sodium phosphate (Betnosol) nose drops and alkaline nasal douches, in producing the sensation of a patent airway in the 14 days following surgery. Ninety-seven patients were randomized into the three treatment groups and a control group who received no nasal medication. Patients assessed their nasal patency by means of a visual analogue scale (VAS) and any complications of treatment were recorded. Statistical analysis of the 76 complete sets of results using the Mann-Whitney U-test showed that there was a significant difference in the distribution of all of the treatments for each of the time intervals (p < 0.05). Glass rank biserial correlation coefficients were all small (rg < 0.085) but the most significant differences were between ephedrine and the control group at two hours, two, seven and 10 days (0.02, 0.054, 0.057, 0.085 respectively), alkaline nasal douches being most significant at four and 14 days (0.06 and 0.0722 respectively).

Adolescent

Uptake and metabolism of riboflavin-5'-alpha-D-glucoside by rat and isolated liver cells.

The effect of riboflavin alpha-D-glucoside, isolated from rat liver, on the uptake of riboflavin was studied using freshly isolated rat liver cells. The transport characteristics and metabolic fate of the glucoside were also determined using the radioactive compound. The initial (1-min) uptake of 1 mumol/L [3H]riboflavin glucoside (2.90 +/- 0.29 pmol/10(6) cells) was higher than that of 1 mumol/L [3H]riboflavin (1.35 +/- 0.30 pmol/10(6) cells). However, the accumulation of glucoside after 60 min was significantly lower than that of riboflavin. The presence of up to 30 mumol/L glucoside had no significant effect on the initial uptake of [3H]riboflavin (3 mumol/L, 10(9) cells/L). Measurement of the kinetic parameters for glucoside gave an apparent Kt value of 83.4 +/- 12.4 mumol/L and a Vmax of 208.6 +/- 17.9 pmol/(10(6) cells.min). Decreases in the temperature of incubation decreased uptake rate. Replacement of Na+ with other monovalent cations did not affect uptake. The presence of D-glucose (1 mumol/L to 5.5 mmol/L) had no inhibitory effect on uptake of 1 mumol/L [3H]riboflavin glucoside. The results indicate that the transport of riboflavin glucoside may not involve the transport mechanisms for riboflavin or D-glucose. Metabolic studies with isolated hepatocytes showed that the glucoside was hydrolyzed to yield riboflavin upon entry into the cell. The vitaminic efficiency of this compound was tested by feeding it to growing male rats. These experiments indicate that the glucoside and free riboflavin are comparable sources of the vitamin.

Administration, Oral

Aminophylline alters pharmacokinetics of carbamazepine but not that of sodium valproate--a single dose pharmacokinetic study in human volunteers.

Pharmacokinetic interaction of aminophylline with single dose sodium valproate (400 mg) and carbamazepine (200 mg) was evaluated in normal healthy volunteers using a cross over design. Neither the serum concentrations nor the pharmacokinetic parameters of sodium valproate (SV) were altered by the coadministration of aminophylline (AMP). In contrast AMP significantly decreased the plasma concentrations of carbamazepine (CBZ). The Cmax of CBZ was significantly lowered from 1.73 +/- 0.18 to 0.94 +/- 0.08 microgram/ml and the AUC o-t was significantly decreased from 76.19 +/- 6.20 to 52.66 +/- 1.84 micrograms/h/ml (P < 0.05). The pharmacokinetic parameters of CBZ that were altered in the presence of AMP were: the Tmax and t1/2 which was prolonged about threefold from 5.60 +/- 1.60 to 16.80 +/- 7.94 h and 44.88 +/- 4.50 to 125.07 +/- 29.09 h, respectively. The Vd was marginally increased from 2.19 +/- 0.13 to 3.85 +/- 0.57 L/kg and the Cl was decreased from 34.07 +/- 3.78 to 25.26 +/- 5.15 mL/min. None of these alterations are statistically significant. Bioavailability of CBZ was reduced by 29% in the presence of AMP, while that of SV was increased by about 8%. Results are of clinical significance because simultaneous administration of CBZ and AMP may reduce the efficacy of CBZ in epileptic patients.

Administration, Oral

Tracheoplasty without stent, using preshaped cryopreserved cartilage allografts in neonatal pigs.

The management of congenital and acquired laryngotracheal stenosis in children often includes tracheoplasty with different materials. Autologous cartilage is the most commonly described graft for tracheal reconstruction. In 12 1-week old piglets a tracheal defect was created and repaired using cryopreserved allografts sculpted before preservation into a newly designed shape. In half the animals (group 1), a free pericardial autograft was interposed on the luminal surface of the cartilage graft. A stent was not used in any animal. The animals grew normally and were killed after 2 months. The grafted tracheas showed maintenance of their structural support, and no evidence of narrowing of the grafted area in comparison to the trachea above the graft. The lumen was lined by ciliated respiratory epithelium. There was no identifiable pericardium at the time of sacrifice and no differences between the two groups. This study shows that in neonatal pigs, cartilage allografts, sculpted before cryopreservation, are a suitable alternative to autografts to cover tracheal defects and can be used without stenting. No advantages were identified when interposing a free pericardial graft.

Animals

The assessment of the risk of cross-infection with a multi-use nasal atomizer.

Atomizers working on the Venturi principle are used by otolaryngology departments in the UK to spray cocaine and other local anaesthetic and vasoconstricting solutions into the nasal cavities. These devices are rarely cleaned, nor is the cocaine in the reservoir changed between patients. This study aimed to assess the risk of cross-infection with such an atomizer of the Down's design. Nutrient broth from a sterile atomizer was sprayed into the nasal cavities of 12 healthy volunteers on three occasions, the tip of the nozzle was withdrawn between sprays into the right nostril, but not between sprays into the left. On each occasion the tip of the nozzle, a nutrient broth rinse of the inner tube of the nozzle and the residue of broth in the reservoir of the atomizer were cultured and the colonies compared with those from a nasal swab collected previously. The results show transmisson of bacteria from the nasal vestibule on to the tip, into the nozzle and into the reservoir of the atomizer. Examination of the minimum inhibitory concentration values of 10% cocaine with and without Nipasept preservative indicated poor antibacterial properties. We conclude that the use of an atomizer on more than one patient poses a risk of cross-infection, and recommend their replacement with a single-use disposable nasal atomizer.

Administration, Intranasal

Intraspinal mesenchymal chondrosarcoma. Case report.

A 52-year-old man presented with symptoms of progressive cervical radiculomyelopathy. A myelogram showed an intradural block at the C-6 level. Magnetic resonance T1-weighted imaging revealed a hypointense, sausage-shaped mass extending from C-3 to C-6, located posterolaterally on the right side and pushing the spinal cord to the left and anteriorly. At surgery, a mass was found attached solely to the pia mater, with a normal arachnoid and dura mater overlying it. The mass was excised completely and microscopic examination identified a mesenchymal chondrosarcoma. The patient was symptom-free 6 months after surgery.

Chondrosarcoma, Mesenchymal