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Biomedical subjects

M J Burt

Publications and source records attributed to M J Burt.

At least 19 recordsLinked to original sources

Gallstone prevalence in Christchurch: risk factors and clinical significance.

AIMS: To determine the frequency, risk factors and clinical significance of gallstones in a New Zealand population. METHODS: One thousand names were randomly selected from the Christchurch electoral rolls to recruit controls for a study on the prevalence of gallstones in diabetics. Three hundred and eighteen subjects (169 females, 149 males) were recruited and in this study we analyse this control group for gallstone disease. All subjects completed a questionnaire, provided a fasting blood sample and underwent an ultrasound examination of their gallbladder unless they had previously undergone a cholecystectomy. RESULTS: Overall gallstone disease, defined as previous cholecystectomy or a positive scan for gallstones was seen in 20.75% of the 318 subjects recruited. Gallstone disease was more frequent in females (23.1%) compared to males (18.1%) but this difference was not statistically significant. For both genders there was a significant increase in gallstones with age. On univariate analysis, risk factors for gallstone disease included age, increased body mass index, family history of gallstones and decreased alcohol intake in females. However, only age and family history were significant on multiple logistic regression. There was no difference in the frequency of dyspeptic symptoms or abdominal pain between those with or without gallstones confirmed on scanning. The ratio of cholecystectomy to silent gallstones was higher in females (46.2%) than in males (22.2%). CONCLUSION: Gallstones are prevalent in the New Zealand Community (20.8% overall). Risk factors are increasing age and family history. Gallstones detected on scanning were not associated with an increased incidence of dyspeptic symptoms or abdominal pain.

Age Distribution↗

Use of (99m)Tc-DISIDA biliary scanning with morphine provocation for the detection of elevated sphincter of Oddi basal pressure.

BACKGROUND: Endoscopic biliary manometry is useful in the assessment of patients with types II and III sphincter of Oddi dysfunction, but it is time consuming and invasive. AIM: To investigate the role of (99m)Tc-DISIDA scanning, with and without morphine provocation, as a non-invasive investigation in these patients compared with endoscopic biliary manometry. SUBJECTS AND METHODS: A total of 34 patients with a clinical diagnosis of type II (n = 21) or III (n = 13) sphincter of Oddi dysfunction were studied. Biliary scintigraphy with 100 MBq of (99m)Tc-DISIDA was carried out with and without morphine provocation (0.04 mg/kg intravenously) and time/activity curves were compared with the results of subsequent endoscopic biliary manometry. RESULTS: Eighteen (nine type II, nine type III) of the 34 (53%) patients had sphincter of Oddi basal pressures above the upper limit of normal (40 mm Hg). In the standard DISIDA scan without morphine, no significant differences were observed in time to maximal activity (Tmax) or percentage excretion at 45 or 60 minutes between those with normal and those with abnormal biliary manometry. However, following morphine provocation, median percentage excretion at 60 minutes was 4.9% in those with abnormal manometry and 28.2% in the normal manometry group (p = 0.002). Using a cut off value of 15% excretion at 60 minutes, the sensitivity for detecting elevated sphincter of Oddi basal pressure by the morphine augmented DISIDA scan was 83% and specificity was 81%. Also, 14 of the 18 patients with abnormal manometry complained of biliary-type pain after morphine infusion compared with only two of 16 patients in the normal manometry group (p = 0.001). CONCLUSIONS: (99m)Tc-DISIDA with morphine provocation is a useful non-invasive investigation for types II and III sphincter of Oddi dysfunction to detect those with elevated sphincter basal pressures who may respond to endoscopic sphincterotomy.

Adult↗

Seroprevalence of Helicobacter pylori in the adult population of Christchurch: risk factors and relationship to dyspeptic symptoms and iron studies.

AIM: To determine the prevalence of Helicobacter pylori infection in subjects randomly selected from the Christchurch population and to determine the risk factors and symptoms related to the infection. METHODS: A list of names was randomly generated from the 1996 electoral roll and subjects were sequentially contacted and invited to participate. A questionnaire on dyspeptic symptoms was completed and the subject's serum was analysed for H. pylori antibodies using the Roche method. Equivocal samples were retested by the Meridian method. RESULTS: One thousand and sixty-four subjects participated in the study. In four subjects results for H. pylori were indeterminate and these subjects were excluded from analysis. Of the remaining 1060 subjects, 254 (24.0%) were seropositive for H. pylori. The seropositivity in males (n=444) was 25.9% and in females (n=616) 22.6%. On multivariate analysis age, ethnicity, low income and smoking > 20 cigarettes per day were all independent predictors of H. pylori seropositivity. H. pylori positive subjects had shorter stature compared to those who were seronegative. The symptom scores for dyspepsia were similar in both the seropositive and seronegative subjects. In males the serum iron levels were lower in seropositive subjects but there were no significant differences in serum ferritin in either males or females between seropositive and seronegative subjects. CONCLUSION: H. pylori is a common infection in the Christchurch community with the prevalence increasing significantly with age. H. pylori positive subjects had shorter stature and in males lower serum iron levels were observed. Infection was not associated with an increased risk of dyspeptic symptoms.

Adult↗

Haemochromatosis gene mutations Cys282Tyr and His63Asp are not increased in Type 2 diabetic patients compared with the Canterbury (New Zealand) general population.

Genetic predisposition to haemochromatosis may be an important aetiological factor in some cases of Type 2 diabetes. Our aim was therefore to test the hypothesis that the haemochromatosis gene mutations Cys282Tyr and His63Asp are more prevalent in Type 2 diabetic patients compared with the Canterbury, New Zealand general population. We studied 230 consecutive patients referred to the Diabetes Services with age > or = 30 years and considered to have Type 2 diabetes. DNA was extracted from whole blood and amplified by polymerase chain reaction prior to restriction fragment length polymorphism analysis. The frequency of the mutations was compared with that observed previously in 1064 subjects from the Canterbury general population by chi2 testing. Iron was measured by a colorimetric method, transferrin by rate nephelometry and ferritin by immunoassay. There were 2/230 (0.8%) Cys282Tyr homozygous subjects in the diabetic group compared with 5/1064 (0.5%) NS in the general population. Although there was a trend to lower incidence of Cys282Tyr heterozygosity in the diabetic group, there was no significant difference for any of the six genotype frequencies between the two groups. Haemochromatosis gene mutations Cys282Tyr and His63Asp are therefore not increased in Type 2 diabetics compared with the general population. Transferrin saturation was a sensitive marker (100%) of genetic haemochromatosis, although ferritin had low specificity (77.8%). Genetic susceptibility to haemochromatosis is not an important aetiological factor for diabetes, and targeted screening of diabetic patients for haemochromatosis is not indicated.

Adult↗

Gallbladder volume: comparison of diabetics and controls.

Diabetics are known to have an increased prevalence of gallstones. The aim of this study was to investigate whether diabetics have increased gallbladder volumes that would predispose to stasis, nucleation of cholesterol crystals, and gallstone formation. The gallbladder volume of 271 diabetic subjects and 277 controls was determined by ultrasound using the ellipse formula. Gallbladder volume was also determined by the sum of the cylinders method in 143 cases with a strong correlation (r = 0.89) between the two methods. Using analysis of variance, gallbladder volume was influenced by both diabetic type (NIDDM = 33.68 cm3, IDDM = 26.84 cm3, controls = 29.05 cm3; P = 0.018) and the presence of gallstones (gallstones = 32.04 cm3, no gallstones = 27.58 cm3; P = 0.018). The variation in gallbladder volume between NIDDM, IDDM, and control subjects was influenced by the presence of gallstones (P = 0.024, interaction term from ANOVA). Significant differences (P < 0.001) were only found between NIDDM vs IDDM and NIDDM vs control in the nongallstone group (NIDDM = 34.33 cm3, IDDM = 25.08 cm3, control = 25.17 cm3). Males had significantly larger gallbladder volumes than females: 31.98 cm3 vs 27.74 cm3 (P = 0.023). After the inclusion of BMI, HDL cholesterol, triglyceride, and age in a statistical model with gender and diabetic type in those without gallstones, significant differences were still found between NIDDM and IDDM (P = 0.013) and NIDDM and controls (P = 0.005), demonstrating that NIDDM is an independent predictor for increased gallbladder volume.

Adult↗

Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor.

The aim of this study was to determine whether 12 months of therapy with Simvastatin, an HMG CoA reductase inhibitor, would dissolve gallstones. Twenty-seven subjects entered the study, all had a fasting oral cholecystogram, ultrasound examination, and fasting serum lipids prior to therapy. In addition, 22 subjects had their gallbladder ejection fraction, after CCK, determined by radionucleotide scanning. Eleven subjects had the cholesterol saturation index (CSI) of bile calculated before and at the end of 12 months of therapy. Of the 27 subjects, 26 completed 12 months of treatment with Simvastatin 20 mg daily. There was a significant fall in the total serum cholesterol (27%, P < 0.0001), LDL cholesterol (31%, P < 0.0001), triglyceride (34%, P < 0.0001) but no change in HDL after 12 months of therapy. Simvastatin treatment resulted in a 28% fall in the CSI of bile at the end of therapy (P < 0.01). The concentrations of individual bile acids did not change with therapy, and apart from a slight but significant increase in arachidonate, there were no other significant changes in the fatty acid composition of the biliary phospholipids. After 12 months of Simvastatin therapy there was a small decrease in the gallstone diameter but complete dissolution of gallstones was not achieved in any subjects. In conclusion 12 months of therapy with Simvastatin was effective in lowering the serum lipids and the CSI of bile but was not effective in dissolving gallstones.

Adult↗

The influence of iron on chronic hepatitis C.

It has recently been suggested that the hepatic iron concentration can be used to predict the response to interferon in patients with chronic hepatitis C. An hepatic iron concentration greater than 1100 microg/g appears to identify a group of patients that are unlikely to respond to alpha-interferon. It is not known whether this relationship can be explained by associated variables such as age, gender or disease severity or whether the hepatic iron concentration itself influences the response to interferon. Furthermore, the hepatic iron concentration is of no value in discriminating responders from non-responders in patients with hepatic iron concentrations less than 1100 microg/g. The possibility of improving response rates to interferon by pretreatment venesection needs to be explored but currently only limited data are available. Venesection results in a significant fall in the serum transaminases but the preliminary results regarding the efficacy of subsequent interferon therapy are unclear. Until the results of prospective controlled trials are available it is concluded that the available evidence does not support venesection before interferon therapy for chronic hepatitis C.

Confounding Factors, Epidemiologic↗

The significance of haemochromatosis gene mutations in the general population: implications for screening.

BACKGROUND: Haemochromatosis is associated with mutations in the HFE gene but the significance of these mutations in the general population is unknown. AIMS: To determine the frequency of HFE gene mutations in the general population, their effect on serum iron indexes, and their role in screening for haemochromatosis. METHODS: Deoxyribonucleic acid (DNA) from 1064 randomly selected subjects was analysed for the C282Y and H63D mutations in the HFE gene. Serum iron, transferrin saturation, and ferritin were measured and individuals with increased iron indexes were investigated to confirm or exclude a clinical diagnosis of haemochromatosis. RESULTS: Mutations were identified in 409 individuals (38.4%) with heterozygote (carrier) frequencies of 13.2% and 24.3% for the C282Y and H63D mutations respectively. Heterozygosity for either mutation significantly increased serum iron and transferrin saturation but despite a similar trend for ferritin, this was only significant for C282Y homozygotes. Five individuals (0.47%) were homozygous for the C282Y mutation, three of whom had haemochromatosis confirmed by liver biopsy (0.28%). The other two C282Y homozygotes would not have been detected by phenotypic screening alone. CONCLUSIONS: HFE mutations are present in 38.4% of the population, affect serum iron indexes, and are important determinants of iron status. The population frequency of genetically defined haemochromatosis (C282Y homozygosity) is approximately one in 200 and is higher than the prevalence of clinically apparent haemochromatosis.

Female↗

Gallbladder polyps: prospective study.

The aim of this study was to describe the natural history of gallbladder polyps. Thirty-eight subjects who had been previously identified as having gallbladder polyps in an epidemiologic study of gallstone prevalence in 627 diabetic subjects and matched controls were followed longitudinally. Follow-up sonograms were obtained on 33 and 22 of the 38 subjects at 2 and 5 years, respectively. Prevalence for gallbladder polyps in this population was 6.7%, with a marked male predominance (odds ratio 2.3). No statistical difference in prevalence was found between diabetic subjects and nondiabetic controls. Ninety percent of the polyps were less than 10 mm in diameter, with no polyp being larger than 12 mm. During the follow-up period no changes suggestive of malignant transformation were observed. In conclusion, we found that gallbladder polyps were relatively common and that few significant changes occurred over a 5 year period. In asymptomatic subjects in whom gallbladder polyps less than 10 mm in diameter are found incidentally, the likelihood of malignant transformation is low.

Adult↗

Molecular analysis of HLA-H gene mutations in New Zealand patients with haemochromatosis.

AIM: To determine the frequency of HLA-H gene mutations in New Zealand patients with haemochromatosis. METHODS: The Cys282Tyr and His63Asp mutations in the HLA-H gene were analyzed by polymerase chain reaction, restriction enzyme digestion and electrophoresis in two separate patient groups. The first was a group of 20 Christchurch patients with a definite clinical diagnosis of haemochromatosis. The second group consisted of 33 patients, with a provisional diagnosis of haemochromatosis, attending Dunedin Hospital for therapeutic venesection. RESULTS: All 20 Christchurch patients and 25 of the 33 (76%) Dunedin patients were homozygous for the Cys282Tyr mutation. After review of the clinical data, histology and response to venesection a diagnosis of haemochromatosis could be confidently excluded in six of the remaining eight patients. Despite atypical features, a diagnosis of haemochromatosis could not be excluded in the final two patients, one of whom was a compound heterozygote for the two mutations. CONCLUSIONS: Homozygosity for the Cys282Tyr mutation is closely associated with haemochromatosis in New Zealand patients. Molecular analysis of the HLA-H gene is indicated in the assessment of patients with iron overload including those currently being treated by venesection.

Adult↗

Review: the surgical management of ulcerative colitis.

The treatment of ulcerative colitis requires careful review of the medical and surgical options. The surgical procedure of choice is proctocolectomy with ileal pouch-anal anastomosis. This procedure removes the diseased mucosa, effectively curing the disease whilst maintaining the normal route of defecation and continence. Other surgical options that may be considered in selected patients include proctocolectomy with either a Brooke ileostomy or a Kock pouch, and abdominal colectomy with ileorectal anastomosis. The choice of operation requires consideration of the advantages and disadvantages of a particular procedure and must be tailored to an individual patient's needs and circumstances.

Colectomy↗

37 kBq 14C-urea breath test and gastric biopsy analyses of H. pylori infection.

BACKGROUND: The treatment of H. pylori-associated gastroduodenal disease is increasingly aimed at bacterial eradication which requires follow-up assessment of therapeutic effectiveness and re-infection. A simplified 37 kBq 14C-urea breath test for H. pylori infection has been developed. METHODS: The 37 kBq 14C-urea breath test was compared with biopsy urease (CLO) and histological analyses of gastric-biopsies obtained from 63 patients undergoing endoscopy. RESULTS: The 30-min breath test correlated closely with biopsy findings, had a sensitivity of 100%, a specificity of 95% and a positive predictive value of 92%. CONCLUSIONS: The simplified, low-dose, 14C-urea breath test is a convenient, low-cost, transportable means of facilitating the management of H. pylori-associated diseases.

Biopsy↗

Isolation and characterisation of cosmids to intervals within a 4.5Mb region at 6p21.3.

The gene responsible for hereditary haemochromatosis (HH) has recently been identified. One mutation in this gene, termed HFE, has been found in all Australian HH patients. We previously identified a predominant HH ancestral haplotype covering 4.5Mb at 6p21.3, and showed that patients with two copies of this haplotype express a more severe form of the disorder. One key question to now be resolved is why haplotype related variation in phenotypic expression of HH is present if all patients tested have the same HFE mutation. A cosmid resource covering the 4.5Mb HH ancestral haplo type region was obtained. These cosmids provide the material for the completion of a transcript map of this region, and will assist the identification of candidate modifiers of HFE expression.

Chromosomes, Artificial, Yeast↗

Evaluation of alpha interferon for the treatment of chronic hepatitis B infection in Christchurch.

AIM: To evaluate alpha interferon for the treatment of chronic replicative hepatitis B infection in Christchurch patients. METHODS: Ten patients were divided into two groups depending upon whether their average pretreatment ALT levels were greater than twice the upper limit of normal (group 1, 6 subjects) or less than twice the upper limit of normal (group 2, 4 subjects). Interferon alpha-2a (4.5 mega units) was administered three times a week for 24 weeks with the addition of a preceding priming course of prednisone in group 2. RESULTS: At 6 months post treatment only one patient in group 1 had seroconverted (HBeAg to anti-HBe), however, the remaining five patients seroconverted from 18-32 months after therapy. This response was associated with normalisation of the transaminases and in 5/6 subjects a fall in the HBV DNA levels. In group 2 one subject seroconverted by 6 months despite a shortened course of Interferon. A delayed seroconversion (18 months) was observed in one patient and another had a partial response with the development of anti-HBe but associated with persistence of HBeAg. The remaining patient has not responded. CONCLUSIONS: Interferon alpha-2a was effective in promoting a seroconversion HBeAg to anti-HBe in patients with chronic hepatitis B and transaminases elevated to twice the upper limit of normal, although in most cases this response was delayed. Larger studies will be required to determine the role of steroid priming in those with less active disease.

Adult↗

A 4.5-megabase YAC contig and physical map over the hemochromatosis gene region.

We have constructed a yeast artificial chromosome (YAC) contig over the candidate hemochromatosis gene region. This contig comprises 16 YACs from the CEPH, Washington University, and ICI YAC libraries and covers 4.5 Mb at 6p21.3-6p22. The complete contig has been restriction mapped, enabling the precise relationship between the YACs to be determined and the mapping of a total of 12 STSs. Nine of these are highly polymorphic STSs that are closely linked to hemochromatosis; this series includes D6S265 and D6S1260, which comprise the most proximal and distal markers linked to HC. This is the first YAC contig that spans the hemochromatosis candidate region, and it provides valuable resource material for the cloning of this and other genes in the region distal to the MHC class I complex.

Base Sequence↗

Haemochromatosis--a clinical update.

Haemochromatosis is now known to be a common genetic disorder, with a carrier rate of about 1 in 10 in populations of Northern European origin. With early diagnosis and treatment, life expectancy is normal, yet it remains underdiagnosed.

Biopsy↗