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Biomedical subjects

M R Jacyna

Publications and source records attributed to M R Jacyna.

At least 37 records · Page 2Linked to original sources

The diagnosis and management of viral hepatitis.

Recent developments make it possible to identify the causative virus in most cases of acute and chronic viral hepatitis. Improvements in supportive care and the availability of hepatic transplantation have considerably reduced mortality for the fulminant forms of acute viral hepatitis, and advances in antiviral therapy have led to the possibility of cure for some patients with chronic viral hepatitis and improvement for many others. Algorithms are presented as a guide to the diagnosis and management of acute and chronic viral hepatitis.

Acute Disease↗

Massive haemorrhage due to ulcerative colitis presenting as melaena.

We present a patient with known ulcerative colitis who presented with massive lower gastrointestinal bleeding in the form of melaena. Extensive investigations indicated that the source of blood loss was only from the colon, was attributable to the colitis, and settled when the colitis was treated with steroids. Melaena may be due to blood loss from the colon.

Acute Disease↗

Antiviral therapy: hepatitis B.

Antiviral therapy for chronic hepatitis B virus infection can result in clearance of replicating virus from the liver and prevention of progression to cirrhosis in a substantial proportion of patients. Adenosine arabinoside monophosphate, a potent inhibitor of HBV replication, is of limited usefulness because it causes significant neuromuscular toxicity. Acyclovir alone is relatively nontoxic, but is clinically ineffective in eliminating HBV from the liver. Lymphoblastoid or recombinant alpha-interferons are the best option at present and offer up to a 50% chance of long-term inhibition of HBV replication (with only minor side-effects) in patients who acquire the infection in adulthood. However alpha-interferon therapy alone is not effective when infection is acquired from birth. In this latter group of patients, prednisolone pre-treatment followed by alpha-interferon is currently under evaluation.

Antiviral Agents↗

Hepatitis C virus antibodies in subjects with and without liver disease in the United Kingdom.

The prevalence of antibody to hepatitis C virus, evidence of previous or current infection with this agent of parenterally transmitted non-A, non-B hepatitis, was determined in 340 subjects residing in the United Kingdom. The antibody was detected in 3 per cent of unselected blood donors and in 60 per cent of patients with chronic post-transfusion non-A, non-B hepatitis. Evidence for infection was also found in 30 per cent of intravenous drug abusers, and in 75 per cent of haemophiliacs receiving commercial factor VIII concentrate. The infection is uncommon in renal units and amongst sexually promiscuous groups attending sexually-transmitted disease clinics. Although the seropositivity rate in primary biliary cirrhosis and chronic B and delta hepatitis was very low (0-2 per cent), in patients with autoimmune and alcoholic liver disease it was 14-16 per cent which, although lower than that quoted in studies from Spain and Italy, is considerably higher than would be expected by chance. The reason for the high incidence of non-A, non-B hepatitis in this latter group of patients is unclear.

Blood Donors↗

Protracted enteric cryptosporidial infection in selective immunoglobulin A and saccharomyces opsonin deficiencies.

Chronic cryptosporidial infection in man usually occurs in those who are immunocompromised. We report a patient with a one year history of bowel symptoms resulting from persistent cryptosporidial infection of the colon. Investigations showed underlying selective IgA and saccharomyces opsonin deficiencies but no evidence of cell mediated immune dysfunction. Both selective immunoglobulin A and opsonin deficiencies are relatively common in the general population and may be a cause of susceptibility to persistent cryptosporidial infection.

Chronic Disease↗

Mutation preventing formation of hepatitis B e antigen in patients with chronic hepatitis B infection.

Some patients with chronic hepatitis B virus (HBV) infection are HB e antigen (HBeAg) negative, have circulating HBV particles, and often have especially severe chronic hepatitis. To test the hypothesis that the absence of HBeAg production may be due to a change in the nucleotide sequence of the pre-core region of the genome, 18 Greek and 3 non-Greek patients positive for HB surface antigen underwent direct sequencing of HBV-DNA amplified from sera. In 7 out of 8 HBeAg negative patients, two mutations (guanosine to adenosine) were found in the terminal two codons of the pre-core region, giving the sequence TAGGACATG. The remaining patient had the first mutation only. The sequence TGGGGCATG was found in 4 of 5 of the HBeAg positive patients. The first mutation results in a translational stop codon that is predicted to result in failure to produce HBeAg. The rest of the pre-core region in the HBeAg negative patients was otherwise homologous to that of the HBeAg positive patients and to known sequences.

Amino Acid Sequence↗

Randomised controlled trial of interferon alfa (lymphoblastoid interferon) in chronic non-A non-B hepatitis.

OBJECTIVE: To determine the effect of low dose interferon alfa (human lymphoblastoid interferon) on aminotransferase activities in chronic non-A non-B hepatitis. DESIGN: Prospective randomised controlled parallel group study of active treatment versus no treatment carried out over 16 weeks and preceded by baseline measurements at weeks 8 and 4 and time zero. SETTING: HEPATOLOGY outpatient clinics in secondary referral centres. PATIENTS: Fourteen adults with histologically proved chronic hepatitis and persistently raised aminotransferase activities for six months or more. INTERVENTIONS: Seven patients randomised to receive interferon alfa 5 megaunits (MU) daily for one week, reducing to 5 MU thrice weekly for seven weeks, then 3 MU thrice weekly for eight weeks. Controls not treated. END POINT: Control of hepatic enzyme activity in chronic non-A non-B hepatitis. MEASUREMENTS AND MAIN RESULTS: Serum aspartate aminotransferase activity remained raised in controls (mean increase in study period 23.4 U/l) but fell rapidly to normal in the treated group (mean decrease 106.4 U/l). In four cases values were normal by eight weeks and in five cases by 16 weeks. Only minor side effects were recorded (fever, myalgia), which became less common as treatment progressed. CONCLUSIONS: Continuous low dose interferon alfa reduces aspartate aminotransferase activity to normal in most patients with chronic non-A non-B hepatitis and may prevent progression to cirrhosis.

Adult↗

The effect of secretin on sodium ion absorption by the isolated human gallbladder.

Sodium ion (Na+) transport, a principal function of the gallbladder epithelium, was studied by measuring the flux of 22Na across isolated human gallbladder mucosa maintained in a modified 'Ussing' flux chamber. Tissue was obtained from cholecystectomy specimens in symptomatic patients with cholelithiasis. Out of 26 gallbladders studied, 13 had a net Na+ flux from mucosa to serosa which indicated active Na+ absorption. The hormone secretin, when added to the serosal fluid, reversed the direction of net flux in these gallbladders and caused a secretion of Na+ from serosa to mucosa. These results suggest that secretin may be involved in the physiological regulation of fluid transport in the human gallbladder, and also suggest a possible role for this hormone in gallbladder emptying.

Gallbladder↗

Sodium transport in the diseased human gallbladder and the effects of indomethacin.

1. Sodium ion (Na+) transport, a principal function of the gallbladder epithelium, was studied by measuring the flux of 22Na across isolated, inflamed human gallbladder mucosa maintained in a modified 'Ussing' flux chamber. Tissue was obtained from cholecystectomy specimens in symptomatic patients with cholelithiasis. 2. In 30 gallbladders studied, 57% had a net Na+ flux from mucosa to serosa (Na+ absorption), while 23% had a net Na+ flux from serosa to mucosa (Na+ secretion). The remaining 20% showed no overall net Na+ flux. 3. Indomethacin added to the serosal fluid reversed the direction of net Na+ flux in secreting gallbladders and caused an absorption of Na+. In Na+-absorbing gallbladders, indomethacin caused a slight reduction in Na+ absorption. No change in Na+ flux was induced in gallbladders with no initial net Na+ flux. 4. These results demonstrate that instead of absorbing Na+, some inflamed human gallbladders may secrete Na+. As this secretion can be reversed to the more usual absorption by indomethacin, it is likely that this secretion is mediated by prostaglandins.

Biological Transport, Active↗

Studies on the mechanism of non-visualization of diseased human gallbladders during oral cholecystography.

Oral cholecystography is a well established method for studying the human gallbladder and radiological non-visualization of the gallbladder has been shown to correlate highly with the presence of disease. The exact mechanism by which diseased gallbladders fail to visualize is unclear, but may be due to a failure of the gallbladder to concentrate the luminal contents. Concentration of gallbladder contents is achieved by the reabsorption of water, the driving force for which is active sodium (Na+) absorption. Therefore Na+ transport was studied by measuring the flux of Na22 across isolated human gallbladder mucosa (obtained at cholecystectomy) and compared with the results of oral cholecystography and histological grading. In 27 gallbladders studied, 59% absorbed Na+, whilst the remainder secreted Na+. Comparison with histological grading showed that as gallbladders became more diseased they absorbed less Na+ and were more likely to secrete Na+. In addition, gallbladders that absorbed Na+ were significantly more likely to visualize on cholecystography than those that secreted Na+. These results indicate that some diseased human gallbladders secrete, rather than absorb, Na+ and suggest that the mechanism for radiological non-visualization is failure of fluid absorption and the development of active fluid secretion.

Cholecystography↗

The influence of cardiac staffing resources on permanent cardiac pacemaker implantation rates.

In Tayside region, from 1976 to 1986, the number of permanent pacemakers implanted per year more than doubled, with the increase particularly marked over the latter five years. In order to determine the factor(s) which had caused this increase in implantation rates, a retrospective analysis of patients undergoing pacemaker implantation during the period 1981-1986 was undertaken. No change in the number of elderly in the population, age of patients, mode of referral, waiting time before insertion or clinical indications for pacing was observed to account for this change. The advent of ambulatory ECG monitoring may have contributed to this increase, but the appointment of an extra cardiologist in Tayside in 1982 was believed to have been more important. These results suggest that the number of pacemakers implanted in a region is highly dependent on the number of cardiological staff in that region available for their insertion.

Aged↗

Absorption of 'non-absorbable' markers and an improved method for determining cholesterol absorption rates.

The determination of uptake rates for lipids across absorptive epithelia, using radiolabelled compounds has normally used non-absorbable volume markers to correct gross tissue counts for contamination by adherent mucosal fluid. There is evidence however to indicate that the macromolecules traditionally used as non-absorbable markers are in fact absorbed. This may result in an overestimate of the apparent adherent mucosal fluid with consequent errors in the calculation of lipid uptake. An in-vitro method was used to assess cholesterol absorption by human gallbladder from artificial bile, containing 3H-dextran 70,000 as a 'non-absorbable' volume marker. Both cholesterol and dextran were transported through the mucosa and appeared on the serosal side of the gallbladder. Confirmation of dextran absorption was obtained by electron microscopic examination of the gallbladder epithelium. By using the serosal appearance of dextran as a guide to the amount of absorbed (intracellular) dextran in the tissue samples, we have derived a formula to calculate tissue dextran absorption and, from the revised adherent mucosal volume, have consequently obtained more realistic estimates of tissue lipid uptake. In this study, comparison made between the previous estimate of lipid uptake compared to this new calculation, showed that the previous technique significantly underestimated true lipid uptake.

Absorption↗

Management of non A, non B hepatitis: the problem and its treatment.

Non A, non B (NANB) hepatitis is caused by at least three, as yet unidentified, viruses and can occur as a result of blood transfusions, the use of blood products, covert or overt percutaneous exposure and epidemic waterborne outbreaks of infection. The three types of viruses are characterised by their incubation times; a short time of 2-4 weeks, a longer time of 6-12 weeks and a intermediate period for the waterborne NANB hepatitis virus. Acute NANB hepatitis is milder than HBV hepatitis with lower peak transaminase levels. However, some develop into fulminant hepatitis with a lower survival rate of 0.13%. Ten to 100% of acute patients progress to chronic NANB hepatitis. It was found that alpha-lymphoblastoid interferon at levels of 3-5 megaunits (MU) thrice weekly returned transaminase levels to normal within 6-8 weeks. Approximately 80% had normal levels by the eighth week of treatment and this was maintained on 2.5-3 MU thrice weekly; a well tolerated dose. Long term, low-dose therapy is needed to maintain remission.

Acute Disease↗