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Biomedical subjects

P Little

Publications and source records attributed to P Little.

At least 91 records · Page 5Linked to original sources
PubMed1991

Primary "brown pigment" bile duct stones.

Bile duct stones from 42 patients were morphologically and chemically analysed. The calculi from 27 patients had important primary bile duct stone (PBDS) features, consisting of a general ovoid shape and fragile structure, with alternating light and dark brown pigmented layers on cross-section. Chemically these stones contained low levels of cholesterol, with high levels of bilirubin and calcium. Subsequent infrared spectroscopy analysis showed that calcium bilirubinate and calcium palmitate were the only calcium salts present. Calcium palmitate was prominent in the light brown layers. A morphological and chemical comparison with gallbladder stones showed that bile duct "stasis stones" were similar in morphological and chemical composition to the brown pigment gallbladder calculi. However, they were distinct from most gallbladder stones, indicating that primary bile duct calculi have an aetiology that is different to 90% of gallbladder calculi. Primary bile duct calculi were observed to occur with or without the presence of a gallbladder, and more interestingly, in the bile duct of two patients with cholesterol gallbladder stones. Bile duct bile of patients with primary choledocholithiasis were always moderately to profusely infected and with abundant calcium bilirubinate precipitation. Moreover, this study has shown that PBDS chemical analyses profiles were consistent and correlated well with their defined morphology. Consequently, PBDS may be accurately identified at the time of operation by morphology. An important aetiological factor would appear to be infection, which would seem to promote bile duct bile stasis and eventual stone growth.

Bile Duct Diseases↗
PubMed1991

A controlled trial of a low sodium, low fat, high fibre diet in treated hypertensive patients: effect on antihypertensive drug requirement in clinical practice.

The effect of a low sodium, low fat, high fibre diet in allowing a reduction of antihypertensive medication was compared with the effect produced by the individual components of this diet in an observer-blind controlled trial using 196 patients with essential hypertension. Patients were followed up 1.5 months after the last change in medication. In the control group a 33% reduction in medication was possible, with 24% of patients off medication altogether. The low fat, high fibre and low sodium groups showed larger reductions in medication (38%, 47% and 45% respectively), but not significant compared with the control group. The combination group had the largest and highly significant medication reduction (64%), and significantly more patients stopped medication (57.5%), compared with the control group. Since compliance assessment closely corresponded to normal clinical practice these results should represent what is possible in routine clinical practice. This is of importance as drug treatment has side effects, and may be associated with increased cardiovascular risk not found with dietary alternatives.

Antihypertensive Agents↗
PubMed1990

Regional localization of polymorphic markers on chromosome 10 by physical and genetic mapping.

The human vimentin gene and a random DNA segment (D10S39) were mapped to the short arm of human chromosome 10 by linkage analysis. A panel of somatic cell hybrids and monosomy cell-lines, which divide chromosome 10 into seven regions, was used to localize 10 polymorphic markers on this chromosome. The physical map locations obtained correlate well with linkage maps of chromosome 10. Two markers which have been shown to be closely linked to the gene for multiple endocrine neoplasia type 2A map distal to a translocation breakpoint in band 10q11.2.

Animals↗
PubMed1990

A controlled trial of a low sodium, low fat, high fibre diet in treated hypertensive patients: the efficacy of multiple dietary intervention.

An 8-week combination low sodium, low fat, high fibre diet was compared to the individual components of this diet in a controlled trial using 193 patients already on treatment for essential hypertension. No significant changes were observed in the high fibre group. The low sodium group showed a decrease in systolic blood pressure which was close to significance. The low fat group showed a small but significant decrease in seated diastolic blood pressure and weight. The combination group showed larger and highly significant decreases in seated and standing systolic blood pressures, seated diastolic blood pressure and weight, as well as a significant reduction in standing diastolic blood pressure. We conclude that multiple dietary intervention in this case in the form of a low sodium, low fat, high fibre diet, is more effective than any single dietary intervention and is useful in patients already on medication.

Adult↗
PubMed1990

The effect of a combination low sodium, low fat, high fibre diet on serum lipids in treated hypertensive patients.

The effect of a combination low sodium, low fat, high fibre diet on serum lipids in 184 treated hypertensive patients was analysed in a controlled trial. The combination diet caused a small but significant reduction in serum triglyceride and total cholesterol. This was apparently due to the low fat component of the diet, since a low fat diet alone also caused a similar reduction in total cholesterol, whereas a high fibre diet or a low sodium diet alone caused no significant changes in serum lipids. Analysis of the medication subgroups suggests that diuretics may allow more favourable changes in lipid profile than betablockers. The combination diet and the low fat diet both caused a significant reduction in HDL cholesterol. Thus there was no significant change in the HDL ratio for the combination group and a significant decrease in this ratio for the low fat group. Furthermore the magnitude of changes in total and LDL cholesterol in the low fat and combination groups was much smaller compared to previously observed changes in untreated patients. The overall limited benefit of the combination diet, and possibly adverse effect of the low fat diet, may contribute to the limited effect of therapeutic intervention on mortality from ischaemic heart disease seen in previous studies.

Adrenergic beta-Antagonists↗
PubMed1989

Antidepressants in 'depressed' schizophrenic inpatients. A controlled trial.

Fifty-eight actively psychotic inpatients who initially met criteria for long-standing schizophrenia and subsequently met Research Diagnostic Criteria for a current episode of schizoaffective disorder (mainly schizophrenic) with a depressive syndrome, and who scored at least 30 (mean = 55, SEM = 1.6) on the Brief Psychiatric Rating Scale and 17 (mean = 23, SEM = 0.7) on the Hamilton Rating Scale for Depression, were treated for 5 weeks with haloperidol hydrochloride and benztropine. Haloperidol and benztropine treatment was continued, while those patients who consistently scored greater than 17 on the Hamilton Rating Scale for Depression were randomly assigned to the following double-blind treatment groups for 4 weeks: adjunctive amitriptyline hydrochloride, desipramine hydrochloride, or placebo. Adjunctive desipramine or amitriptyline showed no significant therapeutic advantage, when compared with haloperidol and placebo, on the Brief Psychiatric Rating Scale or the Hamilton Rating Scale for Depression. After 4 weeks of combine therapy, patients receiving adjunctive amitriptyline or desipramine, as compared with those receiving adjunctive placebo, tended to score higher on the Brief Psychiatric Rating Scale hallucinatory behavior item and on the thinking disturbance factor than patients receiving placebo. These results suggest that adjunctive antidepressants are not indicated for the treatment of depressive symptoms in actively psychotic schizophrenic inpatients. Adjunctive antidepressants may retard the rate of resolution of psychosis in this population.

Adolescent↗
PubMed1989

Bacteria and gallstone nucleation.

This preliminary study reports for the first time that there might be a possible association between bacteria and the aetiology of some cholesterol calculi. The gall-bladder biles from 225 cholecystectomy patients underwent bacteriological and microscopic study. Cholesterol calculi from 13 patients (10.2%) were observed to be associated with gall-bladder bile profusely infected with at least one bacterial species that was shown to possess beta-glucuronidase activity, an enzyme that is thought to promote calcium bilirubinate precipitation in bile. Concomitantly, the associated gall-bladder bile was 'high' in calcium bilirubinate precipitation and the precipitate was also detected in the centre of the gallstones. Moreover, in approximately half of these patients (six of 13), the cholesterol gallstones' nuclear areas also contained calcium palmitate, which is also thought to be due to bacterial activity. The results also support the hypothesis that bacteria with active beta-glucuronidase (for example, Escherichia coli) can significantly influence the aetiology of brown pigment gallstones. In contrast, bacteria were observed to have no role in black pigment gallstone formation, as their associated gall-bladder biles were always observed to be sterile.

Adult↗
PubMed1988

Comparative tumorigenicity of 1-nitropyrene, 1-nitrosopyrene, and 1-aminopyrene administered by gavage to Sprague-Dawley rats.

The carcinogenic activities of 1-nitropyrene, a mutagenic component of diesel exhaust, and its reduced derivatives 1-nitrosopyrene and 1-aminopyrene were evaluated in male and female Sprague-Dawley rats. Within 24 h of birth, groups of 22-36 rats were treated by gavage with trioctanoin or the appropriate compound in trioctanoin once weekly for 16 weeks. The approximate total doses per rat were as follows: 1-nitropyrene, high dose (800 mumol); 1-nitropyrene, low dose (320 mumol); 1-nitrosopyrene (320 mumol); 1-aminopyrene (320 mumol). The experiment was terminated after 94 weeks. The main site of tumor induction was the mammary glands of female rats. Percentages of incidences of mammary adenocarcinomas in female rats were as follows: 1-nitropyrene, high dose (63%); 1-nitropyrene, low dose (42%); 1-nitrosopyrene (19%); 1-aminopyrene (4%) trioctanoin (3%). These incidences were significantly greater than those of controls for the female rats treated with either 1-nitropyrene or 1-nitrosopyrene. Low and generally insignificant incidences of tumors of a variety of other sites were also observed in rats treated with 1-nitropyrene. The induction of mammary tumors by 1-nitropyrene confirms the results of a previous study (Hirose et al., Cancer Res., 44: 1158-1162, 1984). The present results also demonstrate that, under the conditions of this bioassay, 1-nitropyrene was significantly more carcinogenic than either 1-nitrosopyrene or 1-aminopyrene.

Adenocarcinoma↗
PubMed1988

Carcinogenicity of quinoline, 4- and 8-methylquinoline and benzoquinolines in newborn mice and rats.

The relative tumorigenic activity of quinoline, 4-methylquinoline, 8-methylquinoline, and all three isomeric benzoquinolines was evaluated in newborn CD-1 mice and Sprague-Dawley rats. In the newborn-mouse bioassay, 0.25, 0.5 and 1.0 mumol of each compound in dimethylsulphoxide was administered by ip injection on days 1, 8 and 15 of life, respectively. The bioassay was terminated when the mice were 1 yr old. The incidence of liver tumours observed for those male mice treated with either quinoline or 4-methylquinoline was greater than 78%. 8-Methylquinoline, naphthalene, benzo[f]quinoline, benzo[h]quinoline and phenanthridine did not exhibit significant tumorigenic activity in this bioassay. In contrast to these results, none of these compounds induced a significant incidence of liver tumours in female mice. Each of these aza-arenes was administered to newborn Sprague-Dawley rats by supra-scapular injections of 200 mumol/kg body weight in dimethylsulphoxide on the first day of life, 100 mumol weekly at wk 2-7, and 20 mumol at wk 8. This bioassay was terminated when the rats were 78 wk old. No significant difference in tumour incidence was observed between the pups that had been treated with these aza-arenes and the controls. These data indicate that quinoline and 4-methylquinoline are more potent tumorigens than any of the three isomers of benzoquinoline evaluated in this study. In contrast to the potent hepatocarcinogenic activity observed for both quinoline and 4-methylquinoline in newborn mice, no significant tumorigenic activity was observed with these aza-arenes in newborn rats.

Animals↗
PubMed1988

Absence of methylation of a CpG-rich region at the 5' end of the MIC2 gene on the active X, the inactive X, and the Y chromosome.

We have identified and characterized a Hpa II tiny fragment (HTF) island associated with the promoter region of the pseudoautosomal gene MIC2. The MIC2 HTF island is unmethylated on both the active and inactive X chromosome and is similarly unmethylated on the Y chromosome. Unlike the majority of genes borne on the X chromosome, MIC2 fails to undergo X chromosome inactivation. HTF islands associated with X chromosome-linked genes that are inactivated are highly methylated on the inactive or transcriptionally silent homologue. The failure of MIC2 to undergo X chromosome inactivation correlates with the lack of methylation of the HTF island at the 5' end of the gene. These results provide further evidence that DNA methylation plays an important role in the phenomenon of X chromosome inactivation.

Antigens, Surface↗
PubMed1988

Comparative tumor-initiating activity of methylene-bridged and bay-region methylated derivatives of benz[a]anthracene and chrysene.

Polycyclic aromatic hydrocarbons (PAHs) with a methylene-bridge spanning the bay region are often detected in higher concentrations in the environment than PAHs which have a bay-region methyl substituent. The tumor-initiating activity of methylene-bridged bay-region derivatives of chrysene and benz[a]anthracene was evaluated on the skin of female CD-1 mice. 4,5-Methylenechrysene elicited twice as many tumors as chrysene at each of the doses tested. At total initiation doses of 1.5, 0.5 and 0.15 mumol/mouse 4,5-methylenechrysene gave rise to 8.5, 6.8 and 1.1 tumors/animal respectively. There was a 100% incidence of tumor-bearing mice at the two higher doses and a 65% incidence at the lowest dose. This methylene-bridged hydrocarbon was less tumorigenic than 5-methylchrysene at each dose tested. Animals treated with 1,12-methylenebenz[a]anthracene developed 7.6, 4.9 and 1.6 tumors/animal at total initiating doses of 4.0, 2.0 and 0.5 mumol/mouse. The incidence of tumor-bearing mice was 90% at the higher doses and 75% at the lowest dose tested. 12-Methylbenz[a]anthracene was more tumorigenic than the methylene-bridged derivative at each dose. The keto-derivative of 1,12-methylenebenz[a]anthracene did not display significant (P greater than 0.05) tumor-initiating activity at these dose levels. Results from these bioassays indicate that methylene-bridged bay-region derivatives of chrysene and benz[a]anthracene contribute to the overall genotoxicity of environmentally occurring PAHs.

Animals↗