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Biomedical subjects

J A Dodge

Publications and source records attributed to J A Dodge.

At least 55 records · Page 3Linked to original sources
PubMed1996

Surface features of small-intestinal mucosa in childhood diarrheal disorders.

The pathophysiology of diarrhea, especially in the otherwise healthy child, is still poorly understood. The aim of this study was to use the scanning electron microscope (SEM) to examine the surface of the jejunal mucosa of children with chronic nonspecific diarrhea (CNSD) (n = 9) and to compare the findings with specimens obtained from children with (n = 21) and without (n = 11) other gastrointestinal diseases. Light microscopy of the specimens from children with CNSD was normal. However, SEM showed the presence of bacterial colonization with predominantly coccoid organisms in 100% of cases. This colonization was associated with loss of glycocalyx and clumping of the microvilli. The children with celiac disease (n = 9) all showed characteristic appearances with light microscopy, but only one had bacterial colonization on SEM. The surface features of specimens from children with other gastrointestinal disorders (food intolerance, postenteritis syndrome, protracted diarrhea of infancy, and immune deficiency states) were very similar to those from the CNSD group. Bacteria were visible on 89% of specimens, and in half of these cases the organisms were bacilli. SEM of specimens from children with no gastrointestinal disease (ages 11-107 months) suggested an increased density of villi/unit area with advancing age. Bacteria were present in only two cases and did not include bacilli. The findings suggest that bacterial colonization of the surface of the small intestine is common in children with several gastrointestinal diseases and may play a part in their pathogenesis. Routine SEM examination of jejunal biopsies provides information not available from standard light microscopy, which may be relevant to the treatment of children with chronic diarrhea.

Adolescent↗
PubMed1996

Effects of wortmannin analogs on bone in vitro and in vivo.

The possible importance of phosphatidylinositol (PI) 3-kinase activity in bone resorption activity in vitro and in vivo were evaluated with synthetic wortmannin analogs in two in vitro bone resorption assays, two in vitro assays for PI 3-kinase activity and for the first time, in two in vivo rat models. Wortmannin and LY301497 were shown to be potent, dose-dependent inhibitors of the bone resorption activity of differentiating chicken osteoclast-like cells and isolated rat osteoclasts. A similar structure/activity profile and potency relationship was observed for the inhibition of osteoclastic activity and of bovine PI 3-kinase activity with purified enzyme, as well as direct inhibition of the PI 3-kinase activity of chicken osteoclast lysates. These in vitro data identified LY301497 as an inhibitor of bone resorption that is 10-fold more potent than wortmannin itself, and the most potent inhibitor of PI 3-kinase activity identified thus far. Wortmannin and analogs also lowered the osteoclast-dependent serum calcium levels like salmon calcitonin in a rat model of secondary hyperparathyroidism. More directly, oral administration of wortmannin analogs prevented the estrogen deficiency-induced loss of trabecular bone in the metaphysis of proximal tibiae from ovariectomized rats. Wortmannin, and especially LY301497, compared favorably in potency in vivo to orally administered estrogen. Taken together, these data are strong evidence to show that wortmannin analogs directly block osteoclastic activity in vitro and in vivo, and confirm that PI 3-kinase activity is a necessary step in the regulation of bone resorption. PI 3-kinase activity appears to be an important component of ovariectomy-stimulated bone loss in rats. This mechanism is supported by the finding that wortmannin had little effect on the activity of myosin light chain kinase in intact osteoclasts. The use of LY301497 should prove useful in elucidating specific molecular interactions important in bone resorption and other PI 3-kinase-mediated cell processes. These data also suggest the possible therapeutic utility of wortmannin analogs to treat conditions characterized by excessive bone loss, such as hyperparathyroidism or hypercalcemia of malignency.

Androstadienes↗
PubMed1996

Nutritional aspects in cystic fibrosis.

The achievement and maintenance of energy balance in cystic fibrosis (CF) is one of the central aims of management. Growth retardation in affected children and wasting in CF adults remain major clinical problems. We consider the basis for the energy deficit, examine the spectrum of nutrient imbalance and review the current guidelines for dietary management.

Adult↗
PubMed1995

Fibrosing colonopathy in cystic fibrosis: results of a case-control study.

Fibrosing colonopathy was first described in cystic fibrosis (CF) children in 1994. We have done a nested case-control study to identify possible associations with this condition. A case ascertainment within the UK CF population to identify any cases that occurred between January, 1984, and April, 1994, found 14 cases, all under 14 years and confirmed by independent histopathological review. All had presented since April, 1993; 12 were boys and six had received some or all of their care in Liverpool. Each case was matched, by date of birth, with four controls from the UK CF Registry. Information was obtained about cases and controls from their case records and by a structured interview with the families. In the 12 months before surgery, there was an association between the occurrence of fibrosing colonopathy and use of high-strength pancreatic enzyme preparations. This association was dose related. Odds ratio per extra 1000 high-strength capsules was 1.45 (95% CI 1.14-1.84). For use of protease, the odds ratio per million extra units per kg was 1.55 (1.19-2.03). For usage of individual high-strength products at any time during the 12 months before surgery some differences were observed; for Creon 25000 the odds ratio was 0.38 (0.10-1.42), for Nutrizym 22 43.4 (2.51-751), and for Pancrease HL 8.4 (1.95-36.1). These last two confidence intervals are extremely wide and compatible with these two products having the same odds ratios. Laxative use was independently predictive (odds ratio 2.42 [1.20-4.94]). We conclude that there is a dose-related association between high-strength pancreatic enzyme preparations and fibrosing colonopathy.

Adolescent↗
PubMed1995

A complex biochemical modulation of intestinal ion transport in rats fed on high-fat diets.

This study investigates the relationship between dietary fat and ion transport in rat intestine. Animals were fed isocaloric diets with high fat content as corn oil, evening primrose oil (Efamol), fish oil, Efamol/fish oil, olive oil, coconut oil, and butter. A low-fat (corn oil) diet was used in a control group. Biopsies of the small intestine from these animals were mounted in an Ussing chamber, and the intestinal mucosal to serosal ion transport was measured as short-circuit current (SCC). The SCC was stimulated in rats fed on diets high in polyunsaturated fatty acids such as corn oil, Efamol, fish oil, and Efamol/fish oil. SCC was also stimulated in rats fed on diets high in monosaturated fatty acids such as olive oil. Animals fed on diets high in saturated fatty acids such as coconut oil and butter, on the other hand, showed an inhibition in the SCC. To determine whether the effect of membrane lipids was mediated by a differential effect on membrane receptor proteins, the response to secretogogue challenge was studied. Biochemical agents and secretogogues including acetylcholine, noradrenaline, dibutyryl-cAMP, calcium ionophore A2318, and prostaglandin E2 were analysed and compared. These agents were able to influence the SCC, showing responses with marked differences between diet groups.

Animals↗
PubMed1995

Stated versus actual lipase activity in pancreatic enzyme supplements: implications for clinical use.

We have carried out an independent investigation of the lipase activity of several pancreatin preparations, including high-lipase preparations of pancreatin that have recently become available. Six preparations from three pharmaceutical companies, Cilag, Duphar, and Merck, were analyzed during the recommended shelf life of the preparation and included a standard and a high-lipase preparation from each manufacturer. All preparations studied showed lipase activity in excess of that which was stated on the packets, and in some cases it was more than twofold. This has important implications for patients and prescribers since changes in apparent enzyme requirements may reflect differences in the potency of batches with time. As it is impossible to evaluate capsule requirements with each new batch prescribed, the presence or relief of symptoms of malabsorption will probably continue to be the way in which most patients monitor their enzyme supplementation on a regular basis. We believe that clinicians need to be aware of the extent of possible intrinsic variation between individual prescriptions before attempting to define possible dose/symptom relationships.

Dose-Response Relationship, Drug↗
PubMed1995

Managing meningitis in children: audit of notifications, rifampicin chemoprophylaxis, and audiological referrals.

Important aspects of the management of meningitis in children include notification to local officers for control of communicable diseases; chemoprophylaxis for index cases and close contacts in cases of meningococcal or Haemophilus influenzae meningitis; and a formal hearing assessment for all survivors. A retrospective audit of these aspects of management was carried out for children admitted with meningitis in 12 months from 1 September 1990 to 31 August 1991 at the Royal Belfast Hospital for Sick Children. Only 20 of 36(56%) cases were notified by medical staff. Chemoprophylaxis was arranged for all close family contacts but to only five of the 23(22%) index cases for whom it was indicated. Appointments for audiological testing were arranged for only 19 of the 32(59%) survivors. Subsequently all doctors, including each intake of junior doctors, were given written information on the importance of notification and locally agreed guidelines for chemoprophylaxis and hearing assessments for survivors before discharge. Guidelines were also displayed prominently in each ward. A repeat audit from January 1992 to December 1992 showed significant improvement in these aspects of care. Twenty eight of 32 cases (88%) were notified, chemoprophylaxis was given to 20 of 22(91%) index cases for whom it was indicated, and 25 of 29(86%) survivors had hearing assessments arranged before discharge. Correct management of some aspects of care cannot be assumed, even if statutory (notification), nationally agreed (chemoprophylaxis), or generally agreed good practice (hearing assessments). These aspects of care improved after the first audit but the authors conclude that the notification rate remains below 100% and a repeat audit is necessary.

Adolescent↗
PubMed1994

Neonatal infection does not affect the immunoreactive trypsinogen screening test for cystic fibrosis.

We aimed to discover whether neonatal infection affected levels of the immunoreactive trypsin (IRT) assay, which is used as a screening test for cystic fibrosis. Forty babies who had clinical features suggesting infection had blood spot specimens for IRT taken at the same time as blood for culture. Of 27 babies believed clinically to have infection, 19 had positive blood cultures and eight had negative culture. In retrospect, 13 were not thought to have infection. The mean (SD) IRT results in these three groups were 15 (8), 11 (4), and 16 (6) micrograms/L, respectively. The mean (SD; range) IRT result for all 40 babies was 14 (7; 10-39). Not only did no babies have elevated IRT results at routine neonatal screening, but none have presented with clinical features suggestive of cystic fibrosis since hospital discharge. Neonatal infection does not appear to cause elevated IRT levels and should therefore not cause false-positive results in mass neonatal screening.

C-Reactive Protein↗
PubMed1994

Effect of exercise on the nasal transmucosal potential difference in patients with cystic fibrosis and normal subjects.

BACKGROUND: Normal subjects have a negative nasal transmucosal potential difference (TPD) at rest which becomes more negative with exercise. Patients with cystic fibrosis have a more negative resting nasal TPD than controls. The present study was designed to determine the effects of exercise on the TPD of patients with cystic fibrosis. METHODS: Seven subjects with cystic fibrosis and seven control subjects had their usual TPD measured at rest, and during and after a 12 minute period on an exercise bicycle designed to produce a pulse rate of 80% of their maximum predicted value. RESULTS: The normal subjects developed a more negative nasal TPD during exercise which returned towards normal at the completion of the rest period. The patients with cystic fibrosis had higher resting values which became less negative during exercise. At the end of the exercise period there was no difference between the two groups. At the end of the recovery period the results for the patients with cystic fibrosis had returned to their resting values. CONCLUSIONS: Exercise reduces the abnormally high resting values for nasal TPD in patients with cystic fibrosis. Elucidation of the mechanism for this change may help to produce functional improvement for patients with this disease.

Adolescent↗
PubMed1993

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency--diagnosis, plasma carnitine fractions and management in a further patient.

Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD), the third enzyme of the mitochondrial beta-oxidation pathway, carries out the dehydrogenation of 3-hydroxyacyl-CoA compounds of 12-18 carbon length. To date only nine cases of LCHAD deficiency have been documented. We report a further patient who as a neonate developed non-specific gastrointestinal symptoms and at 5 months of age cardiomyopathy, recurrent hypoketotic hypoglycaemia and gross alterations of plasma carnitine fractions. Dietary management with medium chain triglycerides led rapidly to clinical improvement. There was a close correlation between the clinical condition, plasma carnitine fractions and cardiac function. At 2 years of age she is developing normally.

3-Hydroxyacyl CoA Dehydrogenases↗