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Biomedical subjects

T Joseph

Publications and source records attributed to T Joseph.

At least 73 records · Page 4Linked to original sources

[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↗

Giant aneurysm of anterior ethmoidal artery presenting with intracranial hemorrhage. Case report.

This forty-five-year-old woman presented with a history suggestive of an intracranial hemorrhage. Clinical examination indicated mild right pyramidal signs and neck stiffness. Computerized tomography demonstrated contrast enhancement in the region of a left frontal intraparenchymal hematoma with an adjacent subdural hematoma. Angiography revealed the presence of a giant aneurysm on the left anterior ethmoidal artery. Surgical evacuation of the hematoma with excision of the aneurysm and coagulation of the feeding artery was achieved. Postoperative recovery was uneventful. Vascular lesions of the anterior ethmoidal artery and the rarity of a giant aneurysm at this site are discussed.

Aneurysm↗

Correlation of time course of blood cholinesterase activity and toxic manifestations of acute methylparathion in antidote treated rats.

Study was conducted to find out the correlation between red blood cholinesterase (RBC ChE) and plasma butyryl cholinesterase (BuChE) activities and toxic signs of oral methylparathion (MPT) and their recovery pattern with or without atropine treatment in female rats. Enzyme activity was estimated before and after an oral dose of MPT (7.5 mg/kg-1) at various time intervals upto 120 hr. Antidote groups received atropine (10 mg/kg-1, i.p.), either alone or with diazepam (2.5 mg/kg-1, i.p.), at the onset of toxic signs. Inhibition of enzyme activity served as definite index of acute toxicity of MPT. RBC ChE activity correlated with the intensity of toxic signs in no-antidote rats, while in atropine treated groups, there was no correlation. BuChE levels did not correlate with toxic signs in any of the groups except in the fatal group. The resynthesis of both the enzymes was complete in 120 hr study and did not synchronize with the recovery pattern of animals from toxic signs. Compared to BuChE, RBC ChE activity was found to be a more sensitive indicator for the diagnosis of severity of MPT toxicity.

Administration, Oral↗

An inexpensive method for fabrication of intracerebroventricular cannulae for rats.

An inexpensive and simple method to fabricate intracerebroventricular (i.c.v.) cannulae for rats with readily available material is described here. The procedure is cost effective and quick. The cannulae thus designed are suitable for injecting minute quantities (microliters) of drugs/chemicals interacerebroventricularly for acute or chronic experiments in rats.

Animals↗

Involvement of adenosine in postictal events in rats given electroshock.

The effect of a selective adenosine antagonist, 8-cyclopentyl 1,3-dimethylxanthine (8-CPT) was used to examine involvement of adenosine in ictal and postictal events in rats subjected to maximal electroshock (MES). MES induces the ictal event of hindlimb tonic extension (HLTE) followed by postictal depression (PID). 8-CPT 10 mg/kg, ip produced maximal significant reduction of PID without affecting HLTE, further confirming involvement of adenosine in PID. Carbamazepine and sodium valproate were studied independently and were coadministered with 8-CPT to determine if their anticonvulsant activity was modulated by adenosine and if they altered PID. 8-CPT did not antagonize the seizure protection afforded by CBZ or SV. CBZ significantly reduced postictal events whereas SV had no significant effect. These observations further confirm a role for adenosine in postictal phenomena.

Adenosine↗

Studies on the 14 alpha-hydroxylation of progesterone in Mucor piriformis.

Cell-free extracts with high 14 alpha-hydroxylase activity were prepared from induced vegetative cell cultures of Mucor piriformis by grinding in potassium phosphate buffer (0.05 M, pH 8.0) containing glucose (0.25 M), KCl (1 mM), glutathione (1.0 mM) and glycerol (10%). Although the ideal pH for preparing the cell-free extract from vegetative cells was 8.0, the pH optimum of the hydroxylase was found to be 7.6. Microsomes (2.0 mg) prepared from the crude cell-free extract hydroxylated progesterone to 14 alpha-hydroxyprogesterone in approximately 60% yields in 30 min in the presence of NADPH and O2. Microsomes prepared from the uninduced cells did not contain any 14 alpha-hydroxylase activity. The hydroxylase activity was inhibited to a significant extent by CO and p-chloromercuribenzoate whereas moderate inhibition was noticed in the presence of SKF-525A, metyrapone and N-methylmaleimide indicating the possible involvement of the cytochrome P-450 system in the reaction. The membrane bound hydroxylase was solubilized using Triton X-100 and the solubilized fraction contained nearly 35% of the original hydroxylase activity.

Cytochrome P-450 Enzyme Inhibitors↗

Quantum chemical and molecular mechanics studies on the binding of stereoisomers of the oligopeptide antibiotics amidinomycin and noformycin to the minor groove of B-DNA.

Ab initio calculations (Hartree-Fock) using the 6-31G basis set have been performed on two chiral oligopeptide antitumor antibiotics amidinomycin 5 and noformycin 6. The latter are DNA minor groove binding agents related to the A.T recognizing netropsin 4 and distamycin 3 but, unlike the latter, bear stereocenters (two for 5 and one for 6) that may be expected to affect binding to the B-DNA receptor. Geometry optimized conformations, energies and distribution of electrostatic charges within the molecules were derived. The rotational barrier for bond C3-C6 in 6 was calculated to be ca. 6 kcal.mole-1 and the dipole moment for 6 was 7.69D and for 5 was 5.58D. The ab initio derived parameters of the geometry optimized conformations of the different possible stereoisomeric forms of 5 and 6 were used to interpret their different interactions with the minor groove of DNA at both A.T and G.C sequences and the results were compared with molecular mechanics calculations. The order of binding of the four stereoisomers of 5 at the preferred (A.T)n sequences by both ab initio and molecular mechanics calculations is 1S,3R > RR > RS > SS. The predicted energy differences for complexation with DNA of the other stereoisomers from that of 1S,3R are: RR (4.2%); RS (6.7%) and SS (21.5%). In the case of noformycin the 4R structure binds more effectively than the enantiomer. Considerations of phasing in the computed distances between hydrogen bond donating sites in the DNA-bound antibiotics provide further insight into the binding processes. In the complexes of noformycin 6 the N-N1-N4 and N1-N5 distances (9.05 and 9.15 A respectively for 4R-6 and 9.23 and 9.26 A respectively for 4S-6) are close to the optimum value of 9.1 A for effective binding. In the case of amidinomycin 5 the best agreement with the optimum value occurs with the strongest binding diastereomer 1S,3R (N1-N3 = 8.91, N1-N4 = 9.41 A). The unexpected result, consistent in both ab initio and molecular mechanics treatments, is that, in contrast to the cases of kikumycin 1 and anthelvencin 2, the natural 3S configuration of 5 and 4S of 6 do not confer maximal binding efficiency. This suggests that biogenetic factors in the generation of the oligopeptide antibiotics lead to maximum DNA binding in the cases of kikumycin and anthelvencin but not in the cases of amidinomycin and noformycin.

Anti-Bacterial Agents↗

Alterations in spliced and unspliced HIV-1-specific RNA detection in peripheral blood mononuclear cells of individuals with varying CD4-positive lymphocyte counts.

Reverse transcriptase-polymerase chain amplification reactions (RT-PCR) were used to identify transcripts for HIV-1 structural and regulatory proteins in peripheral blood mononuclear cells of a cohort of 48 patients. At least one set of PCR primers was capable of detecting HIV-1 transcripts in 94% of patients. Unspliced gag-pol transcripts were detected with gag or pol primer sets in 60 and 63% of samples, respectively. A significant inverse correlation was noted between transcript identification with the gag primer set and the number of CD4-positive lymphocytes in the blood sample and the clinical stage of infection. Single-spliced env transcripts were identified in 44% of individuals. Multiple-spliced tat or nef transcripts were detected in 6.2 and 53% of individuals, respectively. These findings indicate that viral transcripts are expressed throughout the course of HIV-1 infection.

Base Sequence↗

Iatrogenic complications in adult intensive care units: a prospective two-center study.

OBJECTIVES: a) To evaluate the frequency, types, severity, and morbidity of iatrogenic complications; b) determine associated factors that favor iatrogenic complications; and c) suggest new or more efficient protective measures that may be taken to improve patient safety. DESIGN: Prospective, observational study. SETTING: Two ICUs in France. PATIENTS AND METHODS: The study included 382 patients (age > or = 15 yrs; 400 consecutive admissions). Patients were monitored by two physicians in each ICU to assess all iatrogenic complications occurring during their ICU stay, with the exception of adverse effects of drugs. An iatrogenic complication was defined as an adverse event that was independent of the patient's underlying disease. RESULTS: We observed 316 iatrogenic complications in 124 (31%) of the 400 admissions. Of these iatrogenic complications, 107 (in 53 [13%] of the 400 admissions) complications were major, three leading to death. Severe hypotension, respiratory distress, pneumothorax, and cardiac arrest represented 78% of the major iatrogenic complications. Fifty-nine percent of the major iatrogenic complications had clearly identified associated factors. Human errors accounted for 67% of these factors. Patients > 65 yrs (adjusted odds ratio = 2.6, 95% confidence interval: 1.4 to 4.9) and those patients admitted with two or more organ failures (adjusted odds ratio = 4.8, 95% confidence interval: 2.5 to 9.2) were more likely to develop major iatrogenic complications. High or excessive nursing workload also led to an increased risk of major iatrogenic complications. Persistent morbidity, secondary to iatrogenic complications at the time of discharge, was present in five survivors. The risk of ICU death was about two-fold higher for the patients with major iatrogenic complications than in the remaining patients after adjusting for the Organ System Failure Score and the prognosis of the disease (relative risk = 1.92, 95% confidence interval: 1.28 to 2.56). CONCLUSIONS: Major iatrogenic complications were frequent, associated with increased morbidity and mortality rates, related to high or excessive nursing workload, and were often secondary to human errors. To improve patient safety in our ICUs, preventive measures should be targeted primarily on the elderly and the most severely ill patients. Special attention should be given to improving the organization of workload and training, and promoting wider use of noninvasive monitoring.

Adult↗