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Biomedical subjects

T G Mant

Publications and source records attributed to T G Mant.

29 records · Page 2Linked to original sources

Comparison of intravenous infusions of iloprost and oral nifedipine in treatment of Raynaud's phenomenon in patients with systemic sclerosis: a double blind randomised study.

OBJECTIVE: To compare the long term effects of short term intravenous infusions of iloprost with those of oral nifedipine in patients with Raynaud's phenomenon associated with systemic sclerosis. DESIGN: Double blind, placebo controlled, randomised group comparison. SETTING: Dermatology outpatient clinic. PATIENTS: Twenty three patients with Raynaud's phenomenon associated with well documented systemic sclerosis (American Rheumatism Association criteria) and with typical abnormalities in fingernail folds on capillaroscopy. INTERVENTIONS: Twelve patients were randomised to receive intravenous infusions of iloprost starting at 0.5 ng/kg/min and increased by 0.5 ng/kg/min every 15 minutes to a maximum of 2.0 ng/kg/min for eight hours on three consecutive days with a further single infusion at week 8. Placebo capsules were given concurrently. Eleven patients were randomised to receive nifedipine, starting at 30 mg daily and increased to 60 mg daily after four weeks for another 12 weeks. Infusions of placebo were given in the same manner as the infusions of iloprost. One patient from each group withdrew because of social reasons and three patients receiving nifedipine withdrew because of side effects. END POINT: Reduction in number, duration, and severity of attacks of Raynaud's phenomenon, reduction in number of digital lesions, increase in digital blood flow. MEASUREMENTS AND MAIN RESULTS: Measurements were taken at 0, 4, 8, 12, and 16 weeks. Both regimens produced a reduction in the number, duration, and severity of attacks of Raynaud's phenomenon. The mean (SE) number of digital lesions was reduced with iloprost (from 3.5 (1.6) to 0.6 (0.3] and with nifedipine (from 4.3 (0.8) to 1.4 (0.5] after 16 weeks. Hand temperature and digital and microcirculatory blood flow were increased with iloprost but not with nifedipine. CONCLUSION: Both iloprost and nifedipine are beneficial in the treatment of Raynaud's phenomenon. With nifedipine, however, side effects are common. Short term infusions of iloprost provide longlasting relief of symptoms, and side effects occur only during the infusions and are dose dependent.

Administration, Oral↗

Pharmacokinetics and tolerance of lomefloxacin after sequentially increasing oral doses.

The pharmacokinetics of five dose levels of lomefloxacin (100, 200, 400, 600, and 800 mg) were examined in a single-dose, double-blind, placebo-controlled study involving 40 subjects. There were eight subjects in each group: five received active drug and three received placebo; each subject was given only one dose. All subjects completed the study, and lomefloxacin was well tolerated at all doses. No drug crystals were noted in the urine at 3 and 6 h after the dose. The mean maximum concentration in serum (Cmax) ranged from 1.11 to 7.46 micrograms/ml for the 100- to 800-mg doses, respectively, and the AUC increased proportionally with the dose. The mean time to Cmax (Tmax) values averaged 64.8 +/- 28.8 min. The elimination half-life and plasma clearance averaged 7.7 +/- 0.52 h and 259 +/- 37 ml/min, respectively. Mean concentrations in urine were highest during the first 4 h after the dose and ranged from 104 to 713 micrograms/ml following the 100- and 800-mg doses, respectively. Concentrations above 20 micrograms/ml in urine were observed in most subjects over 24 h at the three lower doses and averaged over 120 micrograms/ml during the 12- to 24-h interval at the 400-mg dose, thus supporting once-per-day dosing. Excretion rates from urine and the cumulative amount excreted increased in a dose-related fashion. Renal clearance decreased moderately at the higher doses. Thus, lomefloxacin was well tolerated, and dose proportionality was demonstrated by most pharmacokinetic parameters. The 400-mg dose produced concentrations in plasma and urine above the MIC for susceptible pathogens.

4-Quinolones↗

Pharmacokinetics of intravenous and oral sodium 2-mercaptoethane sulphonate (mesna) in normal subjects.

The pharmacokinetics of mesna (sodium 2-mercaptoethane sulphonate) and its inactive disulphide, dimesna, were investigated using high performance liquid chromatography in six normal subjects following intravenous and oral administration of 800 mg mesna. The mean maximum mesna concentration after i.v. administration was 111 (s.d. +/- 28.3) nmol ml-1 and the mean maximum dimesna concentration was 183 (s.d. +/- 41.6) nmol ml-1. Following oral mesna dosing the mean peak mesna concentration was 19.6 (s.d. +/- 10.2) nmol ml-1 but mesna was only found in the plasma of five of the six subjects. The mean peak dimesna concentration was 22.5 (s.d. +/- 12.4) nmol ml-1. Following i.v. mesna administration, the mean half-life of mesna was 21.8 (s.d. +/- 3.1) min and total body clearance 1.23 (s.d. +/- 0.31) l kg-1 h-1. The mean half-life of dimesna was 1.17 (s.d. +/- 0.32) h. It was not possible to determine their half-lives after oral mesna administration. The mean mesna concentration in the 0-4 h urine collection was 9.6 (s.d. +/- 10.7; range 1.4-28.7) nmol ml-1 following i.v. mesna injection. After oral mesna the highest mesna concentration occurred in either the 0-4 or 4-8 h urine collections. The mean peak mesna concentration was 2.5 (s.d. +/- 1.7) mumol ml-1 (c.f. estimated uroprotective concentration of 1.7 mumol ml-1). The mean 4 h urinary clearance of the uroprotective species mesna was 0.413 (s.d. +/- 0.136) l kg-1 h-1. After both i.v. and oral mesna the urinary excretion of mesna is predominantly during the first 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Mercury poisoning after disc-battery ingestion.

A case is described of a 2-year-old girl who swallowed an alkaline disc battery containing mercuric oxide. Two days after ingestion it disintegrated in the stomach necessitating laparotomy to remove the battery casing and most of its contents. Postoperatively her blood mercury concentration rose to 340 micrograms/l and subsequently she developed small bowel obstruction due to adhesions. She was treated with dimercaprol but blood mercury concentrations did not fall until after a second laparotomy to relieve the obstruction and to remove residual mercury salts from the colon. The corrosive effects of swallowed disc batteries are well documented. The maximum blood concentration of mercury reported in this case is 17 times the 'acceptable level of mercury in the blood' and nearly double the highest level recorded previously after disc-battery ingestion. A policy for management of swallowed batteries is suggested.

Child, Preschool↗

Coma and metabolic acidosis early in severe acute paracetamol poisoning.

Coma and profound metabolic acidosis early in acute paracetamol poisoning have been described in three patients. Of five further patients (four female, one male, aged 17-80 years) with severe poisoning (plasma paracetamol concentration greater than 800 mg/l, 4-12 h postingestion), four were deeply unconscious on admission and two had a severe metabolic acidosis. Signs of hepatorenal damage were minimal and no additional poisons were detected except salicylates (plasma concentration 290 mg/l) in one instance. Plasma paracetamol half-lives were prolonged (median 9.4 h, range 4.8-39 h) and one patient sustained massive hepatic damage and a further patient died despite treatment with intravenous acetylcysteine. Paracetamol poisoning, when associated with exceptionally high plasma concentrations, can give rise to coma and metabolic acidosis in the absence of hepatic failure or other drugs. Although unusual, other such presentations may not have been recognized because a toxicology screen was not performed.

Acetaminophen↗

Acute carbon tetrachloride poisoning in 19 patients: implications for diagnosis and treatment.

Acute carbon tetrachloride poisoning in 19 patients was confirmed by means of laboratory analysis of blood specimens. The whole-blood carbon tetrachloride concentrations ranged from 0.1-31.5 mg/l. Vomiting (11 patients), abdominal pain (5), diarrhoea (4), and coma/drowsiness (6) were the commonest symptoms and signs. Out of 13 patients treated with intravenous acetylcysteine 7 showed mild hepatic damage, 1 had moderate hepatic damage, and 1 with a history of alcoholism sustained massive hepatorenal damage and needed haemodialysis. Of the 6 patients (1 lost to follow-up) who were not given acetylcysteine 3 had hepatorenal failure and needed dialysis, and 1 died. The possibility of carbon tetrachloride poisoning after ingestion of, or exposure to, chlorinated hydrocarbons and in patients presenting with hepatic or renal impairment without obvious cause should not be ignored. Prompt treatment with acetylcysteine may minimise subsequent hepatorenal damage.

Acetaminophen↗

Ethanol poisoning.

A 3-year-old boy with severe ethanol poisoning metabolised ethanol more rapidly than expected (0.33 g/l/hour or 7.16 mmol/l/hour) and recovered fully with conservative management. It is concluded that active elimination techniques are unnecessary for most children with acute ethanol poisoning.

Alcoholic Intoxication↗

Adverse reactions to acetylcysteine and effects of overdose.

Since the introduction in 1979 of intravenous acetylcysteine (Parvolex) as an antidote for overdosage of paracetamol the National Poisons Information Service and the manufacturer have been notified of 38 adverse reactions that were anaphylactoid in nature and 19 accidental overdoses. The most common feature of the anaphylactoid reaction to normal dosage was rash; other features reported included angioedema, hypotension, and bronchospasm; all the patients recovered. The features associated with an overdose of acetylcysteine were similar but more severe; two patients died, but the extent to which the overdose of acetylcysteine may have been implicated was not clear in either case.

Acetylcysteine↗

Investigation of a case of prednisolone malabsorption.

Malabsorption of prednisolone administered as enteric coated tablets was suspected following therapeutic failure in an asthmatic. This was investigated by cortisol estimation and a Synacthen test and substantiated by the demonstration of abnormally low absorption of prednisolone from these tablets which nevertheless were normally absorbed by a volunteer. The absorption of prednisolone from conventional tablets in this patient was normal.

Asthma↗