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Biomedical subjects

M Mackinnon

Publications and source records attributed to M Mackinnon.

At least 37 records · Page 2Linked to original sources
PubMed1993

Family screening for genetic haemochromatosis. What is the most effective method of contact?

OBJECTIVE: To evaluate the effectiveness of various approaches to follow-up screening of family members after genetic haemochromatosis (GH) has been diagnosed in an individual. DESIGN AND SETTING: Thirty-eight patients diagnosed with GH at the Flinders Medical Centre and Repatriation General Hospital in South Australia over a 16-year period were identified by review of case notes. If possible, a questionnaire and a follow-up interview were used to obtain information about the screening that had been done and any obstacles to screening that were encountered. Patients were asked to outline a family tree, and indicate who had and who had not been screened and reasons for not screening. EVALUATION CRITERION: The number of relatives screened or not screened. RESULTS: The families of 71% of patients diagnosed with haemochromatosis were subject to some degree of screening, although complete screening was achieved in only 13%. Approximately a third (30%) of our GH patients were detected by family screening. However, not all relatives who were at risk were screened. Reasons given for not screening were, for example, ignorance about "genetic disease" and fear of treatment. CONCLUSION: Family screening is an important means of detecting new cases of GH. If these findings reflect practice elsewhere, there is a need for education of medical practitioners regarding those who should be screened. More easily accessible information for patients with GH and their relatives would help to overcome some of the problems surrounding identification of the disease.

Attitude↗
PubMed1992

Fine-needle aspiration biopsy for the measurement of hepatic iron concentration.

The potential application of fine-needle aspiration liver biopsy in the documentation of hepatic iron overload has been assessed in iron-loaded rats. Fine-needle aspiration and standard liver biopsy specimens were obtained from three groups of animals supplemented with oral and parenteral iron for 2 to 6 mo. The mean dry weights of standard and fine-needle biopsy specimens were 7.41 +/- 0.77 (+/- S.E.M.) and 0.57 +/- 0.54 mg, respectively. Hepatic iron in fine-needle aspiration biopsy specimens correlated significantly with hepatic iron in standard liver biopsy specimens as measured by biochemical determination, computerized image analysis and histological grading (r greater than 0.9, p less than 0.001). In conclusion, we have shown that fine-needle aspiration biopsy of the liver can obtain sufficient tissue for biochemical measurement of the hepatic iron concentration in an animal model of iron overload. The clinical applications of fine-needle aspiration liver biopsy in human beings with iron overload is currently being investigated.

Analysis of Variance↗
PubMed1990

Uptake and metabolism of high-density lipoproteins by cultured rabbit hepatocytes.

The selective uptake and internalization of core components of high-density lipoproteins (HDL) were examined in primary monolayer cultures of rabbit hepatocytes. Using [14C]sucrose as a surface marker covalently attached to apolipoprotein and [3H]cholesteryl linoleyl ether as a core marker, there was a 5-6-fold greater internalization of cholesteryl ether than sucrose-labeled apolipoprotein during 48 h of culture. The rate of uptake of [3H]cholesteryl linoleyl ether was 263 +/- 29 ng apo HDL/mg cell protein per h during the initial 8 h of culture, but averaged 101 +/- 32 ng apo HDL/mg cell protein per h over the 48 h culture period. Concomitant with this apparent selective uptake of cholesteryl ester core, there was a change in the HDL size distribution, with the appearance of a distinct population of smaller 4.3 nm radius particles in addition to the originally predominant particles of 4.9 nm radius. This was associated with a significant reduction of cholesteryl ester as a percentage of lipoprotein mass from 15.5 +/- 1.2 to 11.0 +/- 1.2 (P less than 0.001) and a reduction in cholesteryl ester:protein mass ratio from 0.30 +/- 0.01 to 0.19 +/- 0.01 (P less than 0.001). There was no change in the mass ratio of HDL triacylglycerol to protein. Thus rabbit hepatocytes in culture exhibit the capacity to selectively extract cholesteryl ester from HDL and produce smaller HDL particles.

Animals↗
PubMed1990

Increase in selective hepatic uptake of high-density lipoprotein cholesteryl esters in the fasted rabbit.

The selective hepatic uptake of high-density lipoprotein cholesteryl esters was determined in primary hepatocyte cultures of cells from normal, cholestyramine-fed and 48-h-fasted rabbits. The HDL was labeled in the apoprotein moiety with [14C]sucrose and in the core component with [3H]cholesteryl linoleyl ether. The uptake of the apoprotein label did not differ between groups (indicating no change in holoparticle HDL uptake), but in contrast, the uptake of the cholesteryl ether label was significantly increased in hepatocytes from cholestyramine-fed and fasted animals. After 40 h of culture, the ratio of 3H to 14C uptake was 4.96 in controls cells, 7.15 in cholestyramine-treated cells and 10.24 in fasted hepatocytes from short-term fasted animals. Thus short-term fasting was associated with a 2-fold increase in the selective hepatic uptake of HDL core components, indicating that selective hepatic uptake of HDL cholesteryl esters is a physiologically responsive process.

Animals↗
PubMed1990

Renal disease in chronic arthritis of childhood. A study of urinary N-acetyl-beta-glucosaminidase and beta 2-microglobulin excretion.

Urinalyses of randomly obtained samples from children with various types of chronic arthritis revealed proteinuria in 2.3% of patients, hemoglobinuria in 3.5%, erythrocyturia in 4.1%, and leukocyturia in 5.3%; these frequencies are within the range found by screening school children. However, raised urinary levels of N-acetyl-beta-glucosaminidase and/or beta 2-microglobulin (both sensitive measures of renal tubular damage) were found more frequently in children with chronic arthritis than in controls (P less than 0.0001). Abnormalities of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin excretion were associated with active arthritis as measured by physician global estimate of disease activity, with a polyarticular onset of juvenile rheumatoid arthritis, and with the use of slow-acting antirheumatic drugs or the concurrent use of more than 1 nonsteroidal antiinflamtory drug. Abnormal renal tubular function appears to be common in chronic arthritis of childhood. The long-term consequences of this abnormality remain to be elucidated.

Acetylglucosaminidase↗
PubMed1990

Computerized measurement of iron in liver biopsies: a comparison with biochemical iron measurement.

The measurement of stainable hepatic iron using a microcomputer image analysis system was compared with standard biochemical measurements of liver iron content in 103 liver biopsy specimens--29 of idiopathic hemochromatosis, 51 of alcoholic liver disease and 23 of various nonalcoholic liver diseases. Sections were stained using Perls' method for iron; the mean area staining positively for iron was measured and expressed as a percentage of the area of biopsy measured. Biochemical (biochemical hepatic iron [mumol/gm dry wt]/age) and morphometrical (morphometrical hepatic iron [%]/age x 100) hepatic iron indices were calculated. Patients in the idiopathic hemochromatosis group had significantly higher biochemical hepatic iron concentrations (p less than 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 284 (range = 119 to 631), 21 (range = 2 to 65) and 15 (range = 3 to 31) mumol/gm dry wt, respectively. The biochemical hepatic iron index was also significantly higher (p less than 0.001) in the hemochromatosis group compared with the alcoholic liver disease and nonalcoholic liver disease groups: 5.8 (range = 2.1 to 13.7), 0.4 (range = 0 to 1.6) and 0.4 (range = 0 to 1.1), respectively. Computerized measurements were significantly higher in the hemochromatosis group (p less than 0.001) compared with the alcoholic liver disease and nonalcoholic liver disease groups: 9.72% (range = 1.50% to 29.26%), 0.13% (range = 0% to 1.20%) and 0.03% (range = 0% to 0.40%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1989

Prevalence of genetic haemochromatosis among diabetic patients.

Since diabetes mellitus is a frequent manifestation of haemochromatosis the prevalence of the disease was investigated in 418 patients attending a diabetic clinic. 21 (5%) patients had a persistently high serum ferritin (men, over 400 micrograms/l; women, over 300 micrograms/l) and 5 of these had transferrin saturations consistently over 55%. Idiopathic haemochromatosis was confirmed by liver biopsy in 4 patients, all of whom had a hepatic iron index greater than 2.0. The prevalence rate of previously unrecognised idiopathic haemochromatosis was thus 9.6 per 1000 (general population prevalence 1 in 250), suggesting that screening of diabetic patients for this genetic disease may be more cost-effective than screening in the general population.

Adult↗
PubMed1988

Healing and relapse of severe peptic esophagitis after treatment with omeprazole.

We have studied the response of erosive or ulcerative esophagitis to treatment with omeprazole and its subsequent relapse on cessation of therapy in 196 patients. In the first phase of the study omeprazole (20 or 40 mg daily) was compared with placebo in 64 patients. After 4 wk there was endoscopic healing in 81% (25 of 31) of omeprazole-treated patients and in only 6% (2 of 32) of placebo-treated patients. Endoscopic healing of esophagitis was accompanied by symptom relief and histologic healing of ulceration. In the second (dose finding) phase a further 132 patients were randomized to omeprazole (20 or 40 mg daily) and endoscopic healing was assessed. In patients with the mildest grade of ulcerative esophagitis (grade 2), healing occurred at 4 wk in 87% receiving 20 mg and in 97% receiving 40 mg. In patients with grade 3 esophagitis, 67% (20 mg) and 88% (40 mg) were healed. Less than half the patients with grade 4 esophagitis (Barrett's ulcers or confluent ulceration) healed with either 20 mg (48%) or 40 mg (44%). Regression analysis in the 164 omeprazole-treated patients showed no evidence that healing was influenced by factors other than severity of esophagitis at entry and omeprazole dose. In phase 3 of the study the rate of endoscopic relapse was determined in 107 endoscopically healed patients after stopping omeprazole. Erosive or ulcerative esophagitis recurred in 88 of 107 (82%) by 6 mo. Neither initial dose, grade of esophagitis, nor smoking was shown to influence relapse rate. Omeprazole is a highly effective treatment for peptic esophagitis. The 40-mg/day dosage produces endoscopic healing slightly more quickly than the 20-mg/day dosage, and the initial endoscopic gradings are of prognostic value. Relapse occurs rapidly when treatment is stopped.

Adult↗
PubMed1987

Enprostil and ranitidine: comparative efficacy and safety in patients with duodenal ulcer.

This randomised, double-blind, double-dummy, multiclinic study of duodenal ulcer healing compared the efficacy and safety of enprostil with ranitidine. The six week trial admitted 164 patients with endoscopically demonstrated duodenal ulcer. Ratings of symptoms and adverse events were collated from patients' daily diaries, and endoscopy was repeated to verify healing after four weeks and, if appropriate, after six weeks. Medication used was enprostil (35 micrograms capsule) or ranitidine hydrochloride (150 mg tablet) with matching placebos twice daily. After six weeks, 81% of patients treated with enprostil and 95% of those treated with ranitidine had healed ulcers, a statistically significant difference (p = 0.007). There were no differences between treatment groups for the number of days until the daytime ulcer pain completely ceased. Night-time ulcer pain ceased significantly earlier in the group receiving ranitidine (p = 0.019) and was less severe during the week before the last visit (p = 0.001); daytime pain for ranitidine users was also less severe (p = 0.020) during this week. Mild to moderate adverse experiences were reported by 44% of enprostil and 35% of ranitidine patients. There were no severe adverse events. In conclusion, both enprostil and ranitidine were found to be safe and effective in the treatment of duodenal ulcer. However, the ranitidine regimen used in this trial produced better results than the enprostil regimen.

Clinical Trials as Topic↗
PubMed1987

Detection of alpha-1-antitrypsin in hepatocytes in acute and chronic hepatitis.

Twelve of sixteen consecutive needle biopsies of liver with either acute or chronic hepatitis showed positive immunohistochemical staining for alpha-1-antitrypsin (AAT). Only two of the positive biopsies contained numerous, large periodic acid-Schiff positive, diastase resistant (PAS-D) globules in periportal hepatocytes; both patients were Pi MZ but only one had a low serum AAT concentration. The other 15 patients had normal or elevated serum AAT. The accumulation of AAT in hepatocytes, demonstrated by sensitive immunohistochemical staining, may indicate increased synthesis and/or impaired secretion of AAT occurring in association with various types of hepatitis.

Acute Disease↗
PubMed1986

Metabolism of high density lipoproteins by the perfused rabbit liver.

The role of the liver in the catabolism of high density lipoproteins (HDL) was examined in isolated perfused rabbit livers. Using 125I-labeled rabbit HDL the disappearance of labeled apolipoproteins from the perfusate was biphasic with 7% of the label removed after 20 min and a further 6% between 20 and 90 min. In contrast, with HDL labeled with [3H]cholesteryl esters 35% of label had been removed after 90 min. The effect of liver perfusion on HDL size and composition was further studied by recirculating rabbit HDL for 120 min. In control experiments HDL was incubated at 37 degrees C for 120 min with nonperfused media and with media that had been liver perfused. The added HDL was predominantly particles of 4.8-4.9-mm radius, and incubation with nonperfused and preperfused media produced no significant change in size. However, liver perfusion resulted in particles predominantly 4.2-4.3-mm radius. Hepatic perfusion also significantly reduced HDL cholesteryl ester composition as a percentage of lipoproteins mass from 13.3 +/- 2.2% in control incubations to 10.7 +/- 3.1% (p less than 0.001), and cholesteryl ester:protein mass ratio was reduced from 0.31 +/- 0.06 in control to 0.24 +/- 0.10 (p less than 0.001) after 120 min of liver perfusion. Thus interaction of rabbit HDL with rabbit liver results in smaller HDL particles significantly depleted of core cholesteryl esters.

Animals↗
PubMed1984

Peripheral nerve morphometry in stroke patients.

Sural nerve biopsy specimens from affected and non-affected limbs of stroke patients were examined morphometrically. Two principle abnormalities of peripheral nerve were found in hemiparetic and hemiplegic limbs. First, the frequency of abnormal teased nerve fibers was significantly increased with abnormal internodes frequently "clustered" and showing a 50% or more reduction in myelin thickness. Second, the mean diameter of myelinated nerve fibers was reduced. These results suggest a primary atrophy of peripheral nerve fibers in the affected limbs of stroke patients with secondary demyelination. Possible aetiological factors include disuse, transynaptic degeneration, ischemia, pressure effect, and decreased axoplasmic flow. It would seem that the structural integrity of peripheral nerve is frequently compromised following a cerebral lesion.

Adult↗
PubMed1982

Cimetidine in the management of symptomatic patients with duodenitis: a double-blind controlled trial.

Twenty-one adult outpatients with dyspepsia and endoscopically proven duodenitis without chronic ulceration completed a double-blind trial of either cimetidine (1 g/day) or placebo. Treatment with cimetidine for 6 weeks resulted in a significant improvement in symptoms and in the endoscopic appearance of the duodenitis when compared to treatment with placebo. The symptomatic and endoscopic improvement, however, was not associated with any significant change in the histological grading of the duodenitis.

Cimetidine↗
PubMed1980

The effect of overnight biliary drainage on the hepatic excretion of bromosulphophthalein.

The excretion of bromosulphophthalein (BSP) was studied in rats after depletion of their bile salt pool by overnight biliary drainage. Peak biliary BSP excretion was significantly lower (80% of control value) in animals with a depleted bile salt pool; however, treatment with phenobarbital for 5 days before bile salt depletion prevented a reduction in BSP excretion. These studies support the observation that the hepatic excretion of bile salt is an important factor influencing the biliary excretion of BSP.

Animals↗
PubMed1980

Transhepatic embolisation of gastro-oesophageal varices in the management of variceal haemorrhage.

The difficulty of controlling variceal haemorrhage has led to the recent development of methods designed to sclerose the bleeding vessels. This study describes the application of percutaneous transhepatic portal catheterization with embolisation and sclerosis of varices in eight consecutive patients admitted with bleeding oesophago-gastric varices. Portal hypertension was documented and varices demonstrated in each case. Bleeding ceased rapidly in seven patients, two patients rebled 1-3 weeks after the procedure, and five patients were subsequently discharged from hospital. In no instance was death related to continued gastrointestinal haemorrhage. Initial experience with transheptic embolisation of bleeding oesophago-gastric varices indicates that this technique is effective in controlling variceal haemorrhage.

Adult↗