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Biomedical subjects

F R House

Publications and source records attributed to F R House.

At least 19 recordsLinked to original sources

Legislation restricting paracetamol sales and patterns of self-harm and death from paracetamol-containing preparations in Scotland.

AIMS: To describe how changes in legislation to restrict paracetamol sales have affected overdose discharges and death associated with the drug in Scotland. METHODS: A descriptive analysis of routine death and hospital discharge data for the entire Scottish population between 1995 and 2004. Patients in Scotland participated who were discharged from hospital with a diagnosis of poisoning; deaths in Scotland from diagnosis of poisoning 1995-2003 were also analysed. Outcome measures were changes in mortality and overdose due to poisoning involving paracetamol. A comparison was made of in-hospital and out-of-hospital mortality in fatalities involving paracetamol. RESULTS: The majority of paracetamol-associated deaths were due to co-proxamol. Deaths associated with paracetamol alone or with ethanol occurred principally in hospital and were a minority of deaths overall. The proportion of in-hospital deaths attributed to paracetamol increased (post/pre ratio 1.347; 95% confidence interval 1.076, 1.639; P = 0.013). Overall numbers of cases discharged with poisoning fell. The proportion of these involving paracetamol in any form increased significantly in all groups except young men aged 10 to <20 years. CONCLUSIONS: Legislation has not reduced mortality or proportional use of paracetamol in overdose, both of which appear to have increased in Scotland since pack-size limitations. Other approaches are necessary to reduce the death rate from overdoses involving paracetamol.

Acetaminophen↗

A comparison of mediator and catecholamine release between exercise- and hypertonic saline-induced asthma.

Serum neutrophil chemotactic activity (NCA) and plasma histamine concentrations were measured in 9 asthmatic subjects with exercise-induced asthma after inhalation challenge with ultrasonically nebulized 3.6% hypertonic saline, which was administered either in a dose-dependent manner (HSDR) or as a continuous single dose (HSC), and after cycle ergometer exercise. The mean decreases in FEV1 elicited by HSDR, HSC, and exercise were 26, 27, and 25%, respectively, and were not significantly different. There was an approximate 300% maximal increase in NCA detected after both HSC and exercise challenges. Gel filtration chromatography on columns of Ultragel ACA 34 indicated that the NCA released after HSC provocation and exercise were 600 to 700 kDa. There was an approximate 100% maximal increase in NCA after HSDR challenge, and this was significantly less (p = 0.016) than that after HSC and exercise. Exercise but not hypertonic challenge was associated with a basophilia and a significant increase in plasma histamine. There was a significant increase in plasma norepinephrine concentrations after exercise but not after HSC challenge in 7 asthmatics. Epinephrine concentrations did not change after exercise or HSC inhalation. NCA was measured in 5 subjects subjected to 2 HSC challenges that were separated by 60 min. There was an increase in NCA detected after both provocations. The increase after the second challenge was significantly greater (p = 0.27 x 10(-4)) than that observed after the initial provocation, despite a substantially reduced bronchoconstrictor response after the second challenge.

Adolescent↗

Transcranial measurement of blood velocities in the basal cerebral arteries using pulsed Doppler ultrasound: velocity as an index of flow.

Blood velocities have been measured transcranially, at small Doppler angles, in the middle cerebral artery of normal volunteers. Cerebral blood flow was changed by varying carbon dioxide tension. In four volunteers, the relationships between arterial pCO2 and percentage change in intensity weighted mean, median, and maximum Doppler-shifted frequencies in the internal carotid and middle cerebral arteries were linear with slopes of 2.5 and 2.8% per mm Hg change in pCO2. In 38 volunteers, the relationship between end-expiratory pCO2 and time-averaged maximum Doppler frequency was linear over the range of pCO2 20-60 mm Hg with slopes of 2.5 and 2.9 percentage change per mm Hg, for internal carotid and middle cerebral, respectively. These results are very similar to those reported using direct methods of measuring cerebral blood flow. As the transcranial Doppler method is reproducible, this indicates that changes in middle cerebral blood velocity may be used to monitor changes in flow.

Adult↗

Axillary 5 alpha-androst-16-en-3-one in men and women: relationships with olfactory acuity to odorous 16-androstenes.

Axillary 5 alpha-androst-16-en-3-one (5 alpha-androstenone) levels were found to be significantly higher in men than in women but do not vary between left and right axillae, are not related to age, handedness or degree of hirsutism (in women) nor to anosmia to this steroid. In men (but not in women), levels are related linearly to axillary cholesterol concentrations but not to squalene. Olfactory thresholds for 5 alpha-androstenone varied widely, the lowest recorded being 0.2 ppb, but there was no difference in thresholds between men and women. Women (70%) found the smell 'repellant' but anosmia did not differ greatly between men and women (9-20%). Anosmia to the smell of 5 alpha-androst-16-en-3 alpha-ol was most marked in women (90%) rather than in men (45%). Axillary 5 alpha-androstenone values were generally consistent with the 'musky' or 'strong' smells of male axillary extracts, compared with the 'sweet' smell of those from female subjects.

Adolescent↗

The influence of enterogastric reflux on gastric juice bacterial growth, nitrite, and N-nitroso compound concentrations following gastric surgery.

Detailed analyses were carried out in 207 fasting gastric juice samples obtained at endoscopy or with a nasogastric tube from 50 patients with partial gastrectomy, 43 with vagotomy, 20 with gastric carcinoma and 50 controls. Significantly higher mean pH, nitrite and N-nitroso compound (N-NO) concentrations and nitrate-reducing bacterial cultures were noted following partial gastrectomy compared with normal controls and comparable to findings in gastric cancer. A highly significant relationship (p less than 10(-6)) was also demonstrated between pH and N-NO concentrations, highest levels of which were seen following Billroth II gastrectomy, significantly higher (p = 0.02) than Billroth I, whereas the only change observed following proximal gastric vagotomy was a nearly threefold rise in N-NO compared with normal controls. However, vagotomy and pyloroplasty produced gastric juice changes comparable to those seen with gastrectomy and gastric carcinoma. Thus, the most marked changes were observed following surgical procedures involving increased enterogastric reflux and these findings lend further support to the possible involvement of N-nitroso compounds in the development of gastric cancer following both Billroth I and II gastrectomy and vagotomy with pyloroplasty.

Carcinoma↗

Effect of cimetidine on the absorption and efficacy of orally administered furosemide.

In six normal subjects who received single oral doses of 400 mg cimetidine and 40 mg furosemide, the area under the furosemide plasma concentration-time curve was increased in two subjects by less than 50%, in two by 59% and 75%, and remained unchanged in two: overall the mean increase of approximately one-third achieved statistical significance. This increase was not accompanied by any significant effects on other pharmacokinetic parameters or urine volume, sodium or potassium excretion during the 8 h subsequent to drug administration. Furosemide produced no effects on cimetidine pharmacokinetics. In another group of subjects, administration of 1.0 g cimetidine/day in divided doses before dosing with 40 mg furosemide produced no significant effects on furosemide plasma levels or in its effects on urinary water and electrolyte excretion.

Absorption↗

N-nitroso compounds in gastric juice and their relationship to gastroduodenal disease.

Of the N-nitroso compounds derived from precursors in gastric juice, only a very small proportion are in the form of volatile N-nitrosamines. However, about 40% of the remainder can be converted by methylation into a form(s) suitable for gas chromatography. In this way, at least 20 individual peaks were detected with the Thermal Energy Analyzer as detector. N-Nitroso compounds have been determined as a group in the fasting gastric juice of normal individuals and patients with conditions including duodenal ulcer, gastric ulcer, atrophic gastritis, pernicious anaemia, gastric carcinoma, dyspepsia with normal endoscopy or subjected to operative procedures, such as vagotomy or partial gastrectomy. Both the levels of N-nitroso compounds and pH values increased significantly with age in normal subjects and in those with pathological conditions. Sex and cigarette smoking had no significant influence. In particular, a positive correlation was found between pH and the level of N-nitroso compounds, with a p value of less than or equal to 10(-6). Their concentration rose from a geometric mean of 0.11 mumol.1(-1) at pH 1.0-1.5, to a value of 1.3 mumol.1(-1) within the pH range 6.5-9.0. Whilst quantitative bacteriology was not carried out, a highly significant relationship was also observed between the concentration of N-nitroso compounds and the availability of nitrate-reducing bacteria. Thus, conditions conducive to gastric cancer are associated with higher levels of compounds responding to group analysis as N-nitrosamines and/or N-nitrosamides.

Adolescent↗

Gastric juice N-nitrosamines in health and gastroduodenal disease.

The concentrations of total extractable N-nitroso compounds, pH, and nitrite levels were measured in fasting gastric juice, which was also cultured for bacteria, from 50 healthy volunteers and 217 patients with common upper gastrointestinal complaints. The concentrations of N-nitroso compounds and pH levels rose significantly with age. Sex and cigarette smoking had no significant effect. There was a positive correlation between pH and N-nitroso concentration, and between pH and an increase in the concentration of nitrites. A significant relation was demonstrated between raised N-nitroso and nitrite levels and growth of nitrate reductase-positive microorganisms. These results demonstrate for the first time in man the interrelations of N-nitrosamine concentration, pH, gastric juice nitrite, and nitrate-reducing bacteria. The findings are considered in relation to the risks of development of gastric cancer in man.

Adolescent↗

Effect of cimetidine on gastric juice N-nitrosamine concentration.

Total extractable N-nitroso compounds, pH, and nitrite levels were measured in, and microorganisms were cultured from, the fasting gastric juice of 140 patients taking the H2-receptor antagonist cimetidine and from 267 subjects, including 50 healthy volunteers, not taking cimetidine. Significantly higher mean N-nitrosamine concentrations and pH levels were demonstrated in the cimetidine-treated patients; N-nitrosamine concentration increased with pH. In 30 patients studied, cimetidine treatment significantly increased gastric pH and N-nitrosamine concentrations, while in 23 patients withdrawal of cimetidine treatment resulted in a significant reduction of pH but not of N-nitrosamine concentrations. The gastric juice nitrite level was often raised and nitrate-reducing bacteria cultured were similar to those associated with other causes of hypochlorhydria. These results demonstrate for the first time a relation between gastric juice N-nitrosamine concentration, pH, and cimetidine treatment, and the findings are discussed in relation to gastric cancer induction.

Achlorhydria↗

Serum carbenoxolone: ulcer-healing and metabolic effects.

The relationship of serum carbenoxolone to dosage, age, sex, efficacy and side-effects were studied in 92 patients. Log serum carbenoxolone was correlated with dose and with age, and was higher in women. Serum levels were not significantly different in those patients with duodenal (or gastric) ulcer whose ulcers had or had not healed after allowance was made by analysis of variance for the effects of age and sex. However, oedema and hypokalaemia were associated with higher serum levels. These results support the concept that the ulcer-healing effect of carbenoxolone is topical rather than systemic.

Adult↗

Comparison of the effect of drugs upon some commonly used measures of bowel transit time.

1 To study the effect of drugs on methods of assessment of gut transit time a double-blind study of the effect of single doses of placebo, oxyphenisatin, anthracene purgatives, (+)-norpseudoephedrine and a combined preparation of (+)-norpseudophedrine and senna was carried out in ten normal volunteers. Gut transit time was assessed by dye and radio-opaque marker methods. 2 It was possible to demonstrate the effect of the anthracenes but not oxyphenisatin on gut transit time. 3 More sophisticated statistical techniques were required to demonstrate the retarding effect of the sympathomimetic amine and its reversal by senna. 4 Statistical analysis shows that assessment of intestinal transit time by dye or pellet methods gives identical information.

Adult↗