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Biomedical subjects

N Kennedy

Publications and source records attributed to N Kennedy.

At least 73 records · Page 4Linked to original sources
PubMed1991

Abnormal esophageal transit in patients with typical reflux symptoms but normal endoscopic and pH profiles.

There is a small, well-known cohort of patients who, despite classic reflux symptoms, have a normal esophageal pH profile and endoscopic picture. The treatment of these patients has proved problematic. In an attempt at determining the pathophysiology of this subgroup, we investigated the esophageal transit, using the radiolabeled solid bolus esophageal egg transit technique, in 58 such patients: 25 males, 33 females, mean age 39.5 years (range: 13 to 65 years). The egg transit was normal in 31 (53.4%) patients. In the remaining 27 (46.6%) patients, the condensed image analysis showed the following specific abnormal transit patterns: "step" delay pattern, demonstrating segmental hold-up in mid- or distal esophagus in 16 (59.3%); nonspecific delay in 6 (22.2%); oscillatory pattern in 3 (11.1%); and total nonclearance during the study period (4 minutes) in 2 (7.4%) patients. The patients with abnormal transit patterns had demographic parameters and symptom scores similar to those found in patients with normal transit. This study shows that almost 50% of patients with reflux symptoms and negative pH and endoscopy have abnormal esophageal transit, and almost two thirds of these patients display segmental transit delay in the lower half of the esophagus. The effect on symptomatology by prokinetic agents in the patient subgroup needs evaluation.

Adolescent↗
PubMed1991

Cost efficiency of bone scans in breast cancer.

A total of 110 consecutive females who presented in 1987 with primary carcinoma of the breast were staged according to the UICC TNM staging system. Of these, 90 patients had bone scans at presentation, of which seven were positive. The rate of positive initial scans for Stages I-II was 3.5%. Of these only one patient subsequently had bone metastases confirmed, to diagnose which by bone scan, the estimated cost was pounds 1300. Follow-up information was obtained for 95 patients, repeat scans being performed in 22 who had symptoms suggestive of bone metastases. Ten patients with negative initial scans converted to scan-positive within a mean time of 15 months. Only four of these had radiological confirmation of bone metastases. The cost of detecting bone metastases by follow-up scan was approximately pounds 80 per patient. The false-positive rate and the false-negative rate were both calculated as 10%. The specificity of the test was calculated as 90%. It is recommended that bone scanning should be reserved for patients with Stages III and IV disease and to evaluate symptoms suggesting bone metastases.

Adult↗
PubMed1991

Evidence for hypomotility in non-ulcer dyspepsia: a prospective multifactorial study.

A prospective multifactorial study of symptoms and disturbance of gastrointestinal function has been undertaken in 50 patients with non-ulcer dyspepsia. Objective tests including solid meal gastric emptying studies, gastric acid secretion, E-HIDA scintiscan for enterogastric bile reflux, and hydrogen breath studies were carried out in all patients and validated against control data. Gastroscopy and biopsy were carried out in non-ulcer dyspepsia patients only. Non-ulcer dyspepsia patients were categorised on the basis of predominant symptoms as: dysmotility-like dyspepsia (n = 22); essential dyspepsia (n = 14), gastro-oesophageal reflux-like dyspepsia (n = 11); and ulcer-like dyspepsia (n = 3). In the total non-ulcer dyspepsia population, solid meal gastric emptying was delayed (T50 mean (SEM) = 102 (6) minutes (patients) v 64 (6) minutes (controls), (p less than 0.01) and high incidences of gastritis (n = 26) and Helicobacter pyloridis infection (n = 18) were found. An inverse correlation was observed between solid meal gastric emptying and fasting peak acid output (r = -0.4; p less than 0.01). Indeed gastric emptying was particularly prolonged in eight patients (T50 mean (SEM) = 139 (15) minutes) with hypochlorhydria. In the non-ulcer dyspepsia population oral to caecal transit time of a solid meal was delayed (mean SEM = 302 (14) minutes (patients) v 244 (12) minutes (controls) (p less than 0.01]. Seven patients had a dual peak of breath hydrogen suggestive of small bowel bacterial overgrowth. No association was observed between symptoms and any of the objective abnormalities. This multifactorial study has shown that hypomotility, including gastroparesis and delayed small bowel transit, is common in non-ulcer dyspepsia and may be related to other disorders of gastrointestinal function. No relation between symptoms and disorders of function, however, has been shown.

Adult↗
PubMed1990

Adaptation to a marginal intake of energy in young children.

Six male children, aged 8-28 months, were studied for three consecutive periods of 1 week each. They were given diets that provided 1.7 g protein/kg per d and supplements of minerals and vitamins, with a metabolizable energy intake during the 1st, 2nd and 3rd week of 419, 293 and 335 kJ (100, 70 and 80 kcal)/kg per d, diets 1, 2 and 3 respectively. All the food offered was consumed. Each child was weighed at the same time each day on an electronic balance. On the 6th and 7th day of each study period urine and stool were collected for 24 h to assess nitrogen balance. Using linear regression analysis it was shown that all children gained weight on diet 1, 2.3 (SD 1.3) g/kg per d, and five of six children gained weight on diet 3, the mean for the whole group being 2.7 (SD 2.3) g/kg per d, not significantly different. On diet 2 all children lost weight, -5.4 (SD 1.3) g/kg per d, highly significantly different from each of the other dietary periods. Using asymptotic regression analysis it could be shown that the rate of weight loss during the first part of the week on diet 2, -11 g/kg per d, was greater than at the end of the week, -2 g/kg per d, with a tendency towards a steady weight by day 7. Apparent N retention (mg/kg per d) was positive at the end of each of the three dietary periods: diet 1, 112 (SD 25); diet 2, 54 (SD 34); diet 3, 82 (SD 20). In five of the six children there was a marked reduction in stool frequency on diet 2 compared with diet 1, that was maintained to the period on diet 3. The findings suggest that during the period on diet 2 there was a saving of energy of the order of 105 kJ (25 kcal)/kg per d, which lasted through into the period on diet 3.

Adaptation, Physiological↗
PubMed1988

Reflux oesophagitis and oesophageal transit: evidence for a primary oesophageal motor disorder.

Patients with reflux oesophagitis have a diminished capacity for distal oesophageal clearance. This is considered to be secondary to acid reflux damage to the oesophageal wall. We have postulated that the observed oesophageal dysmotility is a primary phenomenon. Using 24 hour oesophageal pH monitoring and the solid bolus oesophageal egg transit test, we evaluated the oesophageal transit of 55 patients, with symptomatic reflux oesophagitis, and 16 healthy volunteers. The transit for the entire oesophagus was significantly prolonged in the patient group. This delay was evident in all three segments of the oesophagus. Amongst the patients, there was significant correlation between the oesophageal transit time and the number of prolonged reflux events. No correlation was found, however, between symptom score or severity of endoscopic oesophagitis and transit time. These results would indicate that the oesophageal dysmotility is an integral part of gastrooesophageal reflux disease, and is more of a cause than an effect.

Adolescent↗
PubMed1987

New physiological method of evaluating oesophageal transit.

A method of measurement of oesophageal transit time in the upright posture of a chewed solid bolus has been developed and assessed in normal volunteers (n = 16) and in 32 patients with oesophageal disease: organic stricture (n = 5), oesophageal motility disorders (n = 19) and reflux oesophagitis without stricture formation (n = 8). The test involves swallowing a 10 ml poached egg white bolus labelled with 99mTc sodium pertechnetate and external scanning by a gamma camera. An on-line computer program allows detailed analysis by the condensed image technique (which demonstrates the pattern of oesophageal transit) and activity-time curves for the whole, the upper, middle and lower thirds of the oesophagus. The reproducibility of the test is good (coefficient of variation of the total transit of 14 per cent). The results on the normal volunteers have shown that oesophageal transit slows in an aboral direction with transit being faster in the upper, when compared with the middle and lower thirds. The test clearly differentiates patients with oesophageal disease from the normal. The condensed image analysis appears to be useful in outlining the pattern of transit in patients with motility disorders. Patients with reflux oesophagitis have delayed oesophageal transit.

Adult↗
PubMed1987

The solid bolus oesophageal egg transit test: its manometric interpretation and usefulness as a screening test.

The standardized 99mTc-labelled solid bolus oesophageal egg transit test (OET) was developed for assessing oesophageal motility. Its value in detecting oesophageal motility disorders was compared with oesophageal manometry in 102 symptomatic patients. Of 32 patients with normal OET, 22 (68.8 per cent) had normal manometry, whereas of 61 patients with abnormal manometry, 51 (84 per cent) had abnormal OET (chi 2 = 15.82, P less than 0.001). The computer-generated condensed image of the OET clearly defined five transit patterns: normal (n = 32); oscillatory (n = 21); non-clearance (n = 16); 'step' delay (n = 16) and non-specific delay (n = 17). The oscillatory pattern occurred in only one patient with normal manometry, but in all six with manometrically defined achalasia and two with diffuse oesophageal spasm. The predictive value of a positive (abnormal) OET test in detecting abnormal motility (both specific and non-specific disorders) was 73 per cent, and for specific motility disorders was 100 per cent. The predictive value of a negative (normal) test in excluding specific motor disorders was 94 per cent. Manometric tertiary contractions and low amplitude waves occurred in 6/32 and 1/32 patients with normal OET but in 31/70 and 21/70 with abnormal OET (chi 2 = 5.14, P less than 0.02; chi 2 = 7.85, P less than 0.001 respectively). Patients showing oscillation demonstrated significantly more tertiary contractions (17/21) and low amplitude waves (12/21) compared with 20/81 and 10/81 patients without oscillation (chi 2 = 20.47, P less than 0.001; chi 2 = 17.22, P less than 0.001 respectively). The solid bolus oesophageal transit test provides an objective screening test of specific oesophageal motility disorders and should be performed before oesophageal manometry.

Adult↗
PubMed1986

The endogenous mouse mammary tumour virus locus Mtv-8 contains a defective envelope gene.

The Mtv-8 associated provirus, GR40, is not expressed in vivo. However, upon transfection into rat XC cells, the two MMTV specific mRNAs of 35S and 24S are transcribed. Further, the level of these transcripts is augmented when the transfected cells are grown in the presence of dexamethasone (Ponta et al., 1983). No virus can be detected in the medium of the transfected cells. Intracellular protein analysis of these transfected cells shows that although apparently authentic gag proteins are synthesized, a novel protein of 68 kDa is the only env related protein detectable. The sequence of the env gene of GR40 was determined and the predicted amino acid sequence of the env protein obtained. A premature termination codon is present 68 amino acids before the COOH-terminus of the known MMTV env precursor Pr73env. This would result in an env protein of about 68 kDa, in agreement with the size of the env protein found in GR40 transfected cells. The lack of the carboxy terminus may be responsible for the non-processing of the aberrant env precursor protein, p68.

Amino Acid Sequence↗
PubMed1985

Hormonal response region in the mouse mammary tumor virus long terminal repeat can be dissociated from the proviral promoter and has enhancer properties.

The proviral DNA of mouse mammary tumor virus (MMTV) contains a regulatory region closely associated with its promoter, which subjects transcription to the control of glucocorticoid hormones. Delimitation analysis of a chimeric MMTV long terminal repeat-thymidine kinase gene (LTR-tk) has shown that the hormonal regulation sequence is confined to 202 nucleotides preceding the LTR-specific RNA initiation site. A second RNA initiation site (tk-specific mRNA) placed close to the regulatory MMTV sequence by in vitro recombination is also subjected to hormonal stimulation in transfected cells. A series of plasmids with deletions around the LTR cap site progressing from 3' to 5' was made and functionally tested. In vitro deletion of MMTV LTR sequences comprising the RNA initiation sequence and the "TATA" box do not effect hormonal regulation at the tk-specific mRNA start site. Nucleotides up to position -59 from the LTR initiation site could be deleted without influence on the glucocorticoid regulation, whereas deletions to position -65 abolished the hormonal effect on the tk gene transcription. A short MMTV LTR segment containing nucleotides -236 to -52 from the LTR initiation site was recombined with the tk gene or the alpha-globin gene. This fragment confers hormonal inducibility onto the heterologous genes over distances of 0.4 or 1.1 kilobases. The hormonal response region functions when it is placed either 5' or 3' of the regulated gene in both of the possible orientations and is reminiscent of an enhancer sequence.

Animals↗
PubMed1984

Inquiries into perinatal and early childhood deaths in a health care district.

A controlled study was made of stillbirths and deaths of children under 2 years of age born to families residing within the boundaries of the Exeter District Health Authority between 1 October 1980 and 30 September 1981. The study was concerned primarily with methodology and feasibility; the numbers involved were, with few exceptions, too small to permit significant conclusions to be drawn. In practice, the design and implementation of the project proved to be effective. It is suggested that if adopted as a routine service procedure in each health district, information not currently available may be retrieved. This information has epidemiological importance and will also help to identify local problems.

Confidentiality↗
PubMed1983

Subfragments of the large terminal repeat cause glucocorticoid-responsive expression of mouse mammary tumor virus and of an adjacent gene.

After transfection of mouse mammary tumor virus (MMTV) proviral DNA into cultured cells, the DNA is transcribed in a glucocorticoid-sensitive fashion. The large terminal repeat (LTR) region of MMTV is 1,328 nucleotides long and contains the regulatory information necessary for the hormonal response. We have constructed a MMTV LTR-thymidine kinase (tk) chimeric gene and have tested the biological activity of molecules containing various deletions in the LTR after transformation of LTK- APRT- mouse cells. In the TK+ transformants, both a LTR- tk chimeric RNA and an authentic tk RNA are correctly initiated and transcribed. The synthesis of the chimeric RNA as well as that of the tk RNA is hormonally regulated. A plasmid containing 202 nucleotides of LTR DNA 5' to the RNA initiation site is fully sensitive to glucocorticoids; 50 nucleotides still cause a residual inducibility.

Cell Transformation, Neoplastic↗
PubMed1983

A deletion mutant of mouse mammary tumour virus, lacking 516 nucleotides of the 5' long terminal repeat sequence, can be expressed in a hormone-responsive fashion.

In vitro manipulation of proviral DNA of mouse mammary tumour virus (MMTV) was used to construct mutants with defined deletions at the 5' end of the proviral gene. In the mutants 516, 1400 and 2000 nucleotides were removed from the 5' end. The deleted proviral DNA was tested for transcription and glucorticoid hormone regulation of viral RNA expression upon cotransfection into rat XC tk- cells with a thymidine kinase gene. Intact proviral DNA contained in the plasmid vector pBR322 and the deletion mutant pGR16 delta 516, missing 516 nucleotides of the 5' long terminal repeat (LTR) sequence, were transcribed in a hormone responsive fashion and produced RNA species of 35S and 24S. Deletion of the entire LTR sequence abolished MMTV transcription and the hormonal effect.

DNA, Viral↗