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Biomedical subjects

J Samuel

Publications and source records attributed to J Samuel.

At least 73 records · Page 4Linked to original sources

The in vitro evaluation of nucleoside analogues as probes for use in the noninvasive diagnosis of herpes simplex encephalitis.

1-(2-Deoxy-2-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) and the 5-iodo (FIRU), 5-bromo (FBrRU), 5-chloro (FClRU) and 5-fluoro (FFRU) analogues of 1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)uracil were examined in four in vitro tests designed to evaluate their potential as radiopharmaceuticals in a non-invasive diagnostic test for herpes simplex encephalitis (HSE). The tests involved, (a) cellular uptake studies--which showed that all five nucleosides are selectively trapped in rabbit kidney cells infected with herpes simplex virus, type I, which codes for its own thymidine kinase; (b) incubation studies--which showed that, in human platelets, FIAU, FIRU and FFRU are not degraded by thymidine phosphorylase (an enzyme which catalyzes the glycosidic bond cleavage of physiological nucleosides); (c) a transport study, using mouse erythrocytes--which indicated that all five nucleosides have good affinity for a NBMPR-sensitive nucleoside transporter, with inhibition constants (Ki values in the range of 0.177-0.41; and (d) determination of octanol/water partition coefficients--which (log P = -0.14 to -1.67) indicated that FIAU is the most lipophilic of the five compounds studied, and may therefore cross the blood-brain barrier most readily. We conclude from the results that FIAU is the most promising compound for further evaluation in HSE animal models. The combination of tests described in this study provide a useful screening protocol for evaluation of other nucleoside analogues of potential use in a diagnostic test for HSE.

Animals↗

Effect of acyclovir on the uptake of 131I-labelled 1-(2'fluoro-2'-deoxy-beta-D-arabinofuranosyl)-5-iodouracil in herpes infected cells.

Selective uptake of nucleoside analogues by herpes simplex virus infected cells may serve as the basis for a specific non-invasive diagnostic test for herpes simplex encephalitis. We have examined the effect of acyclovir on the selective uptake of [131I] 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)-5-iodouracil in herpes simplex virus infected primary rabbit kidney cells. Infected cells treated with acyclovir continued to concentrate [131I] 1-(2'-fluoro-2'-deoxy-beta-D-arabinofuranosyl)-5-iodouracil for up to 24 h after the addition of the antiviral agent. These results indicated that therapy with acyclovir for as long as 24 h would not prevent the selective trapping of nucleoside analogues. This has important implications for the use of nucleoside analogues in diagnostic brain scans to detect herpes simplex encephalitis.

Acyclovir↗

Nerve/muscle pedicle graft for bilateral vocal cord palsy.

The nerve-muscle pedicle graft was successfully used in six of the seven patients admitted with bilateral vocal cord palsy. The diagnostic evaluation included bilateral vocal cord palsy for more than six months; passive mobility test of the arytenoids under general anaesthesia; and exclusion of an organic lesion as a cause of the vocal cord paralysis. The post-operative assessment was done by indirect or direct laryngoscopy. An improvement in phonation and respiration was noted 4 to 10 weeks after the operation. An exertional test was performed. Identification of the origin of ansa cervicalis from the hypoglossal nerve facilitated the operation.

Adult↗

Lateral sinus thrombosis (a review of 45 cases).

Forty-five cases of lateral sinus thrombosis were recorded in King Edward VIII Hospital from 1978 to 1984. Eighty-two per cent of the patients were under the age of 15 years. Associated complications recorded were: 9 patients with meningitis, 4 with posterior-fossa abscess, 1 patient suffering from posterior fossa empyema; 4 presented with facial palsy and 1 with tuberculous mastoiditis. Four deaths were recorded. Findings at mastoidectomy showed a prevalence of infective granulations (60 per cent) over cholesteatoma (40 per cent) as a cause of the extension of infection. The surgical protocol for the management of lateral sinus thrombosis was mastoidectomy, needling the sinus and removal of the thrombus, if necessary. Medical treatment consisted of Ampicillin and Metronidozol.

Adolescent↗

Use of Xe-133 gas in the detection of foreign bodies in the lower respiratory tract.

Six patients with a clinical picture of inhaled foreign body and normal chest radiograph were selected for a study with Xenon 133 screening of the lung. The scan was positive in 3 cases from whom a foreign body was removed. The remaining 3 cases in whom the scan was negative were discharged and an uneventful follow-up was recorded. Xenon 133 scanning was found to be useful in the selection of patients for bronchoscopy.

Child, Preschool↗

Oncocytic cyst of the larynx. A case report.

Cystic oncocytoma of the larynx is rare, and found mainly in older patients; there is a female preponderance. It arises mainly from the ventricle. These lesions are considered to be metaplastic or hyperplastic rather than neoplastic. Regardless of the pathogenesis, complete excision is associated with a good prognosis. A case is reported.

Adenoma↗

Pharmacokinetics and metabolism of E-5-(2-[131I]iodovinyl)-2'-deoxyuridine in dogs.

E-5-(2-Iodovinyl)-2'-deoxyuridine (IVdU) is a potent inhibitor of herpes simplex virus type 1 replication in vitro. The selective antiviral activity of IVdU is due to preferential phosphorylation by the herpes simplex virus type 1-encoded thymidine kinase. This selective sequesteration provided the rationale for the development of radioiodinated IVdU as a potential radiopharmaceutical compound for use in noninvasive diagnosis of herpes simplex virus encephalitis. We studied the pharmacokinetics and the in vivo metabolism of [131I]IVdU in dogs. The radioactive components in plasma were characterized and quantitated by radio high-pressure liquid chromatography. During incubation with dog blood, [131I]IVdU was metabolized to the corresponding base (E)-5-(2-iodovinyl)uracil. 131I-labeled (E)-5-(2-iodovinyl)uracil accounted for 73% of the total radioactivity present in plasma after 2 h of incubation, suggesting that phosphorolysis of the nucleoside is the major degradation pathway of IVdU in blood. The in vivo studies showed that there was an initial rapid clearance of the tracer from blood, followed by a second very slow clearance phase. Evaluation of the renal excretion of the radiotracer showed that only 8% of the injected dose was excreted by kidneys over an 8-h period. IVdU was rapidly metabolized to three radioactive compounds. Two of these metabolites, the base (E)-5-(2-iodovinyl)uracil and iodide, were characterized. The radioactivity associated with these metabolites was responsible for the slow clearance phase. Our results suggest that the development of [131I]IVdU as a radiopharmaceutical compound will require measures to prevent its rapid degradation in vivo.

Animals↗

Intracranial otogenic complications: a persisting problem.

Three hundred thirty-five cases of acute mastoiditis with complications due to extension of infection beyond the mastoid are reported. Two hundred twenty-four of those presented with intracranial sepsis. Meningitis occurred in 83 cases, brain abscess in 53, extradural abscess in 49 cases, and lateral sinus thrombosis in 39 cases. Intracranial complications are frequently seen in this group of patients with neglected otitis media. The complications occurred frequently in children and young adults (74%) with an overall mortality rate of 14%. Meningitis was the most common complication (37%); brain abscess had the highest mortality rate (36%). The overall mortality rate from intracranial complications was reduced in comparison with previous reported series. This is attributed to antibiotic treatment, the use of CT scan in excluding other intracranial complications, and close cooperation between the otologist and neurosurgeon.

Adolescent↗

The use of piracetam in vertigo.

A pilot study with piracetam (Nootropil; UCB) was performed in 5 selected dizzy patients who had a diagnosis of presbyvertigo or vertebrobasilar insufficiency. The study was monitored by assessing the effect of piracetam on the pursuit-tracking system. All patients showed a remarkable improvement in their pursuit tracking, in addition to marked subjective improvement in their vertigo.

Aged↗

Hamartomas of the head and neck. A report of 4 cases.

Hamartomas in the head and neck region are unusual, and few reports of such lesions are found in the literature. Four cases of hamartoma are described. Two were lymphoid hamartomas (1 occurred in the neck and 1 in the parotid gland), the third was a vascular hamartoma of the ethmoid, and the fourth was found in the neck and was composed of cartilage and fibrofatty tissue.

Adolescent↗

Effects of desipramine on stimulation-induced contractions of the vas deferens of rats pretreated either chronically with desipramine or acutely with idazoxan.

In the present studies the effects of desipramine on the functional sensitivity of the prejunctional alpha 2-adrenoceptors of the vas deferens were studied in pithed rats; contractions of the tissue were evoked by electrical stimulation (6 Hz) of the spinal sympathetic outflow. Twenty-four hours after a single dose of desipramine (10 mg/kg, intraperitoneally) the inhibitory dose-response curves to either UK 14 304 or desipramine itself did not differ significantly from those seen in control animals, whereas both were displaced significantly to the right after 15 days pretreatment with desipramine. Thus the functional responsiveness of the prejunctional alpha 2-adrenoceptors of the vas deferens was reduced by chronic but not acute pretreatment with desipramine. In acute studies desipramine (0.3-4.3 mg/kg, intravenously) inhibited electrically induced contractions of the vas deferens of pithed rats. In the presence of the selective alpha 2-adrenoceptor antagonist idazoxan (1 mg/kg, intravenously) desipramine potentiated nerve stimulation. Although idazoxan (10-1440 micrograms/kg, intravenously) itself potentiated electrically induced contractions of the vas deferens the potentiation observed was markedly less than that obtained in rats pretreated acutely with desipramine (0.3 mg/kg, intravenously). Acute simultaneous blockade of both prejunctional alpha 2-adrenoceptors and uptake into nerve terminals can produce maximal potentiation of the contraction of the vas deferens to sympathetic nerve stimulation. Results are discussed in relation to the hypothesis that the combination of an uptake inhibitor and a prejunctional alpha 2-adrenoceptor antagonist, by enhancing noradrenergic transmission, may provide an antidepressant therapy with rapid onset of action.

Adrenergic alpha-Antagonists↗

Surgery for correction of bilateral choanal atresia.

A transnasal approach was employed in 28 neonates (26 blacks and 2 whites) with bilateral choanal atresia. In each patient the atresia was perforated microsurgically with the drill, followed by insertion of a Portex endotracheal tube for a period of three months. By this method a satisfactory nasal respiration was established immediately. Removal of the posterior part of the vomer is crucial to the successful result. During the follow-up, one death was recorded in a microcephalic neonate, unrelated to the operation and another four patients required repositioning of the tube under general anesthesia. We feel that the above technique is simple and definitive with negligible complications.

Female↗

Otogenic complications with an intact tympanic membrane.

A review of 21 cases of complications of acute otitis media with a hyperemic, dull, bulging but intact tympanic membrane is presented. All cases had a retroauricular swelling. In 10 cases, a subperiosteal abscess was found, 1 of them complicated with a posterior fossa abscess, 2 had meningitis, 3 had Bezhold's abscess, 2 had thrombosis of the lateral sinus, 1 had a cerebellar abscess, 1 had cerebellitis, and 2 presented with facial nerve palsy. Ninety percent of the patients were below the age of 13. An incomplete course of antibiotic treatment was found to have been given in seven cases (30%) prior to admission. Surgical therapy consisted of a cortical mastoidectomy and a wide myringotomy. Ventilating tubes were inserted in three patients. The mastoid radiography demonstrated cloudiness, and CT scan was performed in six patients with suspected intracranial complications. The present study stresses that an intact tympanic membrane with minimal changes may be regarded by the medical profession with a low index of suspicion and can lead to severe otogenic complications. The disease can be masked by an improper antibiotic therapy.

Abscess↗