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Biomedical subjects

M Caulfield

Publications and source records attributed to M Caulfield.

At least 37 records · Page 2Linked to original sources
PubMed1995

Linkage of the angiotensinogen gene locus to human essential hypertension in African Caribbeans.

The renin-angiotensin system regulates blood pressure and sodium balance. The angiotensinogen gene which encodes the key substrate within this system has been linked to essential hypertension in White Europeans. It has been suggested that people of West African ancestry may have a different genetic basis for hypertension. In this study we have tested whether there is linkage of the angiotensinogen gene to essential hypertension in African Caribbeans from St. Vincent and the Grenadines. DNA from 63 affected sibling pairs with hypertension was tested for linkage by analyzing whether there was excess allele sharing among siblings genotyped using an angiotensinogen dinucleotide repeat sequence. There was significant support for linkage (T = 3.07, P = 0.001) and association of this locus to hypertension (chi 2 = 50.2, 12 degrees of freedom, P << 0.001). A DNA polymorphism which alters methionine to threonine at position 235 (M235T) within the angiotensinogen peptide has been associated previously with hypertension. However, we found no association of this variant with hypertension in this study. These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.

Adult↗
PubMed1994

Linkage of the angiotensinogen gene to essential hypertension.

BACKGROUND: The renin-angiotensin system is a powerful pressor system with a major influence on salt and water homeostasis. Angiotensinogen (also called renin substrate) is a key component of this system; it is cleaved by renin to yield angiotensin I, which is then cleaved by angiotensin-converting enzyme to yield angiotensin II. The observation that plasma angiotensinogen levels correlate with blood pressure and track through families suggests that angiotensinogen may have a role in essential hypertension. We therefore investigated whether there is linkage between the angiotensinogen gene on chromosome 1q42-43 and essential hypertension. METHODS: Samples of DNA from 63 white European families in which two or more members had essential hypertension were tested for linkage of the angiotensinogen gene to this disorder. Affected cousins, nephews, nieces, and half-siblings were included when possible. To test for linkage, we used as a marker a dinucleotide-repeat sequence flanking this gene, and we employed the affected-pedigree-member method of linkage analysis. Two molecular variants of the angiotensinogen gene, one encoding threonine instead of methionine at position 235 (M235T) and the other encoding methionine rather than threonine at position 174 (T174M), were also tested for possible association with essential hypertension. RESULTS: We found significant linkage (t = 5.00, P < 0.001) and association (chi-square = 53.3, P < 0.001) of the angiotensinogen-gene locus to essential hypertension in the 63 multiplex families. This linkage was consistently maintained in the subgroup of subjects with diastolic pressure above 100 mm Hg and in the subgroups classified according to sex. It has been proposed previously that T174M and M235T are associated with essential hypertension. However, we found no association in our population between either polymorphism and this disorder. CONCLUSIONS: This study provides strong and consistent support for the linkage to essential hypertension of regions within or close to the angiotensinogen gene. Precisely how mutations in this region may result in hypertension remains to be determined.

Aged↗
PubMed1994

The results of strictureplasty in pediatric patients with multifocal Crohn's disease.

This study is a retrospective review of eight pediatric patients with multifocal intestinal Crohn's disease who underwent strictureplasty with or without concomitant bowel resection between January 1978 and April 1992. The patients ranged in age from 9.9 years to 18.5 years. Indications for surgery were partial intestinal obstruction (n = 6), failure of medial therapy or steroid dependence (n = 4), growth failure (n = 2), and enterocutaneous fistula (n = 2). Thirty-six strictureplasties were performed in the eight patients (median, 4.5 strictureplasties per patient; range, 1-12). Bowel resection was performed in six of the eight patients in areas where strictureplasty was not feasible. The mean length of resection was 40 cm (range, 15-82 cm). The only complication was intestinal hemorrhage, which was conservatively managed in two patients. The patients were followed for a mean of 19 months (range, 3-55 months). Five patients had a weight below the fifth percentile prior to surgery. Postoperatively, there was a weight gain in seven patients, including all five patients who were originally below the fifth percentile. A statistically significant weight gain was found when a paired t test analysis was applied to the entire group (p = 0.04). Five of six patients who were on steroid medication at the time of surgery were successfully weaned within 1.5-3 months (mean, 2.3 months) from the time of surgery. Seven of eight patients had relief of their intestinal symptoms. Strictureplasty with small-bowel resection, or perhaps strictureplasty alone, in pediatric patients with multifocal intestinal Crohn's disease can improve gastrointestinal symptoms, promote weight gain, and allow discontinuation of steroid medications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Chronic pancreatitis in late childhood and adolescence.

Acute pancreatitis is unusual in pediatric patients, and chronic pancreatitis is even less common. Between 1983 and 1988, we diagnosed 24 patients in late childhood and adolescence with chronic pancreatitis. Our review revealed that chronic pancreatitis presents as recurrent abdominal pain in late childhood and adolescence. Individual laboratory and radiological investigations may be normal during acute exacerbations of pain, but the determination of serum amylase and lipase concentrations--combined with ultrasonography--will accurately identify most patients. We found that endoscopic retrograde cholangiopancreatography is a valuable tool in the diagnosis of structural abnormalities. Surgical intervention may reduce symptoms in patients with structural abnormalities. There is a tendency toward decreased frequency and severity of pain as the patients increase in age.

Adolescent↗
PubMed1994

Percutaneous endoscopic gastrostomy placement in children.

Percutaneous endoscopic placement of gastrostomy tubes in children has become common since its introduction in 1980. Indications and technique for placement, as well as complications in children are discussed. A summary of the recent experience with percutaneous endoscopic jejunostomy is also provided.

Child↗
PubMed1992

Indomethacin and protein binding of methotrexate.

Indomethacin, a non-steroidal anti-inflammatory drug is known to increase the efficacy and toxicity of methotrexate, the widely used anti-cancer drug in man. The mechanism for this interaction has not been clearly established. However, since these drugs bind with albumin, a possible displacement of methotrexate by indomethacin from albumin might explain this interaction. To investigate the possible interaction an in-vitro protein-binding displacement study was carried out in 17 normal volunteers and in two groups of eight cancer patients. One group of patients had active disease and the other was in complete clinical remission. Serum samples were obtained and protein levels estimated. The protein binding of methotrexate was measured alone and with indomethacin using equilibrium dialysis. Statistical analysis of results suggested that the binding of methotrexate is not influenced by indomethacin, confirming that methotrexate is not displaced by indomethacin.

Adult↗
PubMed1992

Protein binding of indomethacin, methotrexate and morphine in patients with cancer.

The in vitro protein binding of indomethacin, morphine and methotrexate has been studied in two groups of ten patients each suffering from different types of cancers and compared with twenty normal adult subjects. One group of patients had active disease and the other group was in complete clinical remission. Serum samples were obtained from each subject and the concentrations of albumin and alpha-1 acid glycoprotein (AGP) were measured. Protein binding of drugs was determined using equilibrium dialysis. Alpha-1 acid glycoprotein levels were increased in patients and this effect was more pronounced in active disease (1802 +/- 1025 mg/l) than in remission (931 +/- 273 mg/l). Albumin levels were reduced in active disease (47.67 +/- 15.91 milligrams), but not in remission (61.86 +/- 6.62 milligrams), as compared to control values (58.98 +/- 9.9 milligrams). The protein binding of methotrexate and indomethacin were both reduced in active disease (34.17 +/- 7.12% and 96.26 +/- 0.93% respectively) in comparison with normal subjects (39.33 +/- 4.68% and 96.89 +/- 0.47% respectively), but that of morphine was not changed. In patients there was a strong negative correlation between albumin and alpha-1 acid glycoprotein levels (r = -0.75, p < 0.01) but the correlation in controls was not significant. This study found only weak association between the binding of the drugs studied and the protein levels. It is concluded that reduction in methotrexate dose levels may reduce toxicity in patients with active cancer.

Adult↗