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Biomedical subjects

J Doran

Publications and source records attributed to J Doran.

16 recordsLinked to original sources

Disruption of the cystic fibrosis transmembrane conductance regulator gene in embryonic stem cells by gene targeting.

We have successfully disrupted the cftr (cystic fibrosis transmembrane conductance regulator) gene at its endogenous locus in embryonic stem cells by gene targeting. We are using a double replacement strategy to introduce subtle mutations into exon 10. We report here the first step of creating a null mutation by insertion of a functional hprt (hypoxanthine phosphoribosyl transferase) mini-gene into exon 10 of the cftr gene. Targeted embryonic stem cell clones were identified by PCR screening and confirmed by Southern blot analysis. One of the cftr targeted clones has been injected into recipient blastocysts and shown to contribute to chimaeras. The targeted clones will now be used as the starting point for a second gene targeting step to remove the hprt gene in exon 10 with the concomitant introduction of the delta F508 mutation or other mutations.

Animals

Use of the ultrathin choledochoscope in cholecystectomy.

Use of the ultrathin choledochoscope (2mm) was evaluated in 80 patients undergoing routine cholecystectomy. It was used successfully in 67 (84 per cent) patients. There were eight (12 per cent) explorations of the common bile duct and no negative explorations. The instrument was helpful in determining the nature of an equivocal on-table cholangiogram. The ultrathin choledochoscope may be useful in reducing the rate of negative common bile duct exploration.

Adult

First aid and first aiders who work in health food, processing and light engineering in Nottingham.

One hundred and forty nine first aiders working in a health authority, 26 in a light engineering company and 35 in food processing plants completed an anonymous questionnaire about their training and first aid work. Information was also gathered on views about its value, the role of cash bonuses and its promotion amongst other staff. The response rate was 88%. The majority of first aiders were in their 30s and had practised first aid for less than a decade. At least 80% intended to revalidate their certificate and continue to practise. First aid was used most in food processing plants and least in the health authority. Offers of help had seldom been refused. Over 90% of respondents thought first aid was worthwhile.

Data Collection

An objective long-term evaluation of the Angelchik antireflux prosthesis.

This paper reports the long-term results of the Angelchik antireflux prosthesis (ACP) in Nottingham from October 1981 to December 1989 in 42 patients with gastrooesophageal reflux disease (GORD). Pre- and postoperative oesophagoscopy, pH monitoring, acid reflux provocation test (ARPT), manometry and symptom evaluation were documented to assess the benefits of the procedure. There were no operative complications, dysphagia was the commonest postoperative problem and necessitated the removal of four ACPs. In most patients, dysphagia resolved within 1 year of surgery. Recurrence of reflux symptoms resulted in revision surgery in two patients. In general, reflux control was good. We believe that the ACP is a good antireflux operation which gives good long-term reflux and symptom control in the majority of patients. The removal rate of 15% in our series is of some concern but may be due in part to operator skills. The long-term objective follow-up has shown a trend towards a return of GOR and this and the unknown long-term effects of implanted silicone may limit the use of this procedure to the more elderly patient.

Adult

Rowachol--a possible treatment for cholesterol gallstones.

It has been claimed that Rowachol, a proprietary choleretic, is occasionally successful in the treatment of gallstones. In gallstone patients we have examined its effect on the lipid composition of (1) samples of fasting gall bladder bile obtained at the time of cholecystectomy, and (2) T-tube bile on the tenth post-operative day. In a dose of two capsules, three times a day for only 48 hours, Rowachol significantly lowered the cholesterol solubility of both gall bladder (P less than 0.001) and T-tube bile (P less than 0.05). Rowachol in a dose of one capsule three times a day for 48 hours did not alter bile composition, while four capsules four times a day for a similar period caused a significant (P less than 0.05) deterioration in biliary lipid composition. The possible mechanisms of action of Rowachol and their therapeutic implications are discussed.

Adult

Control by stimulus features during fading.

Sixteen children were given four successive circle-size discrimination problems with luminance as the fading stimulus. Children who were first presented with a difficult size discrimination failed to acquire this discrimination. Those who first received an easy discrimination learned the difficult discrimination. At the end of each 10-trial block, two probe stimuli were presented to monitor any shift in control from luminance to size. One probe was the same size as the positive stimulus but of different luminance; the other was the same luminance but of different size. If, in the course of fading, size and luminance both controlled responding, fading was successful. If luminance alone controlled responding until the end of fading, the size discrimination was not established. Dual control, and thus successful fading, resulted when the target stimuli were very discriminable, or when the target stimuli were subtly different provided that previous fading series had first established less subtle discriminations.

Child

The Gritti-Stokes amputation in ischaemia: a review of 134 cases.

The results of 134 Gritti-Stokes amputations for ischaemia are presented. The mortality rate was 11% and healing occurred in 88%, reaffirming the good results already reported for this operation. The long term results are reviewed in an attempt to decide whether the most frequently cited criticisms of this procedure are justified. Stump pain and mobility of the patella were not major problems. The difficulties in fitting a suitable prosthesis are discussed and attention is drawn to the advantages of a new prosthesis that has been developed for this amputation.

Adult

Effect of ioglycamide (Biligram) on bile flow and biliary lipid secretion in man.

Twenty-one anicteric patients with a t-tube in situ were studied between the ninth and 11th postoperative days. Eleven patients were given an intravenous infusion of the biliary contrast agent ioglycamide (Biligram), while the other 10 acted as controls. Bile flow was recorded and the biliary concentrations of ioglycamide, bile salt, phospholipid, and cholesterol estimated in the two groups. The biliary excretion of ioglycamide was associated with a significant choleresis which was probably due to the obligatory coupling of the osmotically active contrast agent molecules with water. Biliary ioglycamide excretion did not significantly alter bile salt secretion rates. In contrast, the biliary secretion of both phospholipid and cholesterol was significantly lowered (P less than 0.001). Unlike chenodeoxycholic acid, ioglycamide significantly reduced bile acid independent cholesterol secretion (P less than 0.01), although secretion rate in terms of mumol of bile acid was essentially unchanged.

Bile

Ioglycamide (Biligram) studies in man--plasma binding, renal and biliary excretion studies in jaundiced and anicteric patients.

When five patients with varying degrees of hepatic impairment and a T-tube in situ were given intravenous ioglycamide at a rate of 2 mg/kg/min for two hours the mean biliary excretion in the first two hours was only 3.2% of the administered dose. In contrast, in five T-tube patients with relatively normal liver function the mean biliary excretion over the same time interval was 20.6%. The mean plasma concentration of ioglycamide achieved at the end of a two-hour intravenous infusion at 2 mg/kg/min was 1427 +/- 187 microgram/ml in six anicteric patients and 1262 +/- 82 in six jaundiced patients. Despite these very similar plasma levels the 24-hour urinary excretion of ioglycamide was 42.3 +/- 3.8% of the administered dose in the patients with jaundice compared with only 18.1 +/- 2.4% in the anicteric group. These differences probably reflect the fact that the percentage of unbound contrast agent in the plasma of the jaundiced group (11.9 +/- 1.9%) was significantly higher than that of the anicteric group (6.4 +/- 0.9%). It is suggested that bilirubin and possibly other substances in the plasma are competing with ioglycamide for binding sites on albumin. These factors need to be borne in mind when performing intravenous cholangiograms on jaundiced patients.

Aged

Routine laboratory assessment of postoperative chest infection: a prospective study.

Postoperative chest infection was studied prospectively in 73 patients in order to evaluate standard laboratory methods of sputum examination and to relate the results to the patients' clinical state and to antibiotic therapy. When a culture medium selective for haemophilus was used in addition to unselective media, homogenisation of the specimen gave no advantage. Laboratory and clinical findings usually corresponded well. Profuse growths of Streptococcus pneumoniae or Haemophilus influenzae were clearly associated with clinical evidence of chest infection but other Gramnegative bacilli and Staphylococcus aureus much less so. Coliforms were more prominent after antibiotic therapy.

Adult

Acute urinary retention in the female.

The causes of acute urinary retention in the female are discussed in relation to 103 cases recorded over a 3-year period. The authors feel that the findings are at variance with traditional teaching on the subject. Rather than being very rare the condition is found, in fact, to be not uncommon. It is found to occur postoperatively and following childbirth. Gynaecological and neurological lesions are reaffirmed as important causes and pathology within the urinary tract is found to be a more frequent component that is usually appreciated. Our findings do not support the view that hysteria is a common cause of acute urinary retention in females.

Acute Disease