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Biomedical subjects

M Harding

Publications and source records attributed to M Harding.

At least 19 recordsLinked to original sources

Bile salt-stimulated lipase and digestion of non-breast milk fat.

BACKGROUND: 13 Carbon (13C)-lipid breath tests are an effective, noninvasive way of repeatedly measuring fat digestion. The purpose of this study was to assess the contribution of bile salt-stimulated lipase (BSSL) in human milk to the digestion of non-breast-milk fat in Gambian infants. METHODS: Twelve Gambian infants (aged 3-8 months) were studied on 4 days. 13C-Trioctanoin (7.5 mg/kg, digested by BSSL preduodenal and pancreatic lipases) and 13C-cholesteryl octanoate (25 mg/kg, digested by BSSL and pancreatic lipases) were used as substrates. The percentage dose recovery (PDR) of 13C in breath during 5 hours was compared after ingestion of each substrate with fresh, expressed breast milk (FBM) or heated, expressed breast milk (HBM). Gas isotope ratio-mass spectrometry was used to measure 13C enrichment, and breast milk samples were analysed for esterase activity. RESULTS: Heating breast milk significantly decreased esterase activity (mean +/- SD values: FBM = 12.2 +/- 2.9 IU/ml; HBM = 0.5 +/- 0.3 IU/ml), and there was no difference in the volumes of milk ingested on each test day (approximately 50 ml). The PDR of 13C was comparable to that previously described in healthy English infants and was not increased by BSSL. The mean +/- SD PDR of 13C from trioctanoin was 36.3 +/- 8.4% for FBM and 34.6 +/- 6.3% for HBM (NS). From cholesteryl octanoate, the mean +/- SD PDR of 13C was 24.3 +/- 8.7% for FBM and 27.1 +/- 7.5% for HBM (NS). CONCLUSIONS: Bile salt-stimulated lipase may enhance fat digestion in younger or malnourished infants who have a greater degree of pancreatic enzyme deficiency. However, this study suggests that it does not increase the digestion of non-breast-milk fat in healthy, well-nourished infants aged 3 to 8 months from an underprivileged background, who typically ingest frequent small quantities of breast milk.

Caprylates

13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis.

Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The children with cystic fibrosis without pancreatic supplements had a median (range) 13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7), the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7-32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8). There was no significant difference between the median cPDR of normal controls and children with mucosal disease, but there was a highly significant difference between these groups and children with untreated cystic fibrosis. Thirteen children with cystic fibrosis had no 13C recovery in their breath without enzymes and 10 showed marked increases with regular enzymes. In eight children doubling the dose of enzymes caused no or minimal improvement. The mixed triglyceride breath test offers a simple, non-invasive way of assessing the need for pancreatic enzyme supplementation in children with cystic fibrosis and could be used to optimise treatment.

Breath Tests

Payer-hospital collaboration to improve patient satisfaction with hospital discharge.

BACKGROUND: Brigham and Women's Hospital, in Boston, and its major health maintenance organization (HMO), Harvard Community Health Plan, collected data in spring 1994 which revealed that patients were less satisfied with hospital discharge planning than with other elements of care. PROBLEM IDENTIFICATION PROCESS: An interdisciplinary team, formed in November 1994 and composed of eight members from the hospital and HMO, used data from the hospital's Patient Satisfaction Survey, flowcharting, and phone interviews with patients to identify discharge planning-related problems. For example, follow-up contact with patients after discharge was erratic and no clear signal of the successful "hand off" of care from the hospital team to the community team existed. IMPROVEMENT CYCLE 1: Eighty-three percent of the payer's patients that received the improvement strategy developed by the interdisciplinary team-a concierge service-rated discharge planning as excellent or very good, compared to 63% of control patients. IMPROVEMENT CYCLE 2: PLAN SOLUTIONS/STRATEGIES FOR IMPROVING HOSPITAL DISCHARGE PLANNING: The results of the team's Cycle 1 improvement provided information for the team to use in designing a second cycle of incremental improvement activity. For example, to address the lack of clarity about who was responsible for making decisions about discharge and follow-up care, the attending physician was designated the transition-of-care coordinator. Once all the improvements were implemented, Cycle 2 patients who received the intervention rated satisfaction with discharge higher (83% versus 73%) than the control group. CONCLUSIONS: Implications of hospitalwide implementation of discharge planning-related services attempted on one unit are being considered.

Ancillary Services, Hospital

Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle.

OBJECTIVE: To evaluate the scope of the available therapeutic armamentarium in attention-deficit hyperactivity disorder (ADHD). METHOD: The literature of medication trials in ADHD was systematically reviewed, with attention to issues of psychiatric comorbidity, age, gender, and ethnic background. RESULTS: One hundred fifty-five controlled studies of 5,768 children, adolescents, and adults have documented the efficacy of stimulants in an estimated 70% of subjects. The literature clearly documents that stimulants not only improve abnormal behaviors of ADHD, but also self-esteem, cognition, and social and family function. However, response varied in different age groups and with certain comorbid conditions. In addition, there is an impressive body of literature documenting the efficacy of tricyclic antidepressants on ADHD in more than 1,000 subjects. Studies of alternative antidepressants, antipsychotics, antihypertensives, and other compounds were also reviewed. CONCLUSIONS: The available literature indicates the important role of psychopharmacological agents in the reduction of the core symptoms of ADHD and associated impairments. More research is needed on alternative pharmacological treatments and to further evaluate established therapeutics beyond school-age Caucasian boys. In addition, more research is needed on the efficacy of treatment for comorbid ADHD, use of combined medications, and the combination of medication and psychosocial treatment.

Adolescent

Growth deficits in ADHD children revisited: evidence for disorder-associated growth delays?

OBJECTIVE: To reevaluate the hypothesis that stimulants cause growth deficits in children with attention-deficit hyperactivity disorder (ADHD). METHOD: Growth deficits in height and weight were examined in 124 children and adolescents with ADHD and 109 controls, using appropriate correction by age and parental height measures and attending to issues of pubertal stage, treatment, and psychiatric comorbidity. RESULTS: Small but significant differences in height were identified between ADHD children and controls. However, height deficits were evident in early but not late adolescent ADHD children and were unrelated to use of psychotropic medications. There was no evidence of weight deficits in ADHD children relative to controls, and no relationship between measures of malnutrition and short stature was identified. CONCLUSIONS: ADHD may be associated with temporary deficits in growth in height through mid-adolescence that may normalize by late adolescence. This effect appears to be mediated by ADHD and not its treatment.

Adolescent

Six-week, double-blind, placebo-controlled study of desipramine for adult attention deficit hyperactivity disorder.

OBJECTIVE: Despite the increasing awareness of attention deficit hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder; most of the trials have focused on the psychostimulants. Because the tricyclic anti-depressant desipramine has been found to be effective in treating ADHD in pediatric groups, the authors tested its efficacy in adults with ADHD. METHOD: The authors conducted a randomized, 6-week, placebo-controlled, parallel-design study of desipramine at a target daily dose of 200 mg in 41 adult patients with DSM-III-R ADHD. They used standardized structured psychiatric instruments for diagnosis and, as the dependent variables (outcome), used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. RESULTS: There were highly significant differences in the reduction of ADHD symptoms between adults receiving desipramine and placebo. Within the desipramine-treated group, there were clinically and statistically significant differences between baseline and the week 6 end point for 1) reduction of 12 of 14 symptoms of ADHD and 2) decreases in the broad categories of hyperactivity, impulsivity, and inattentiveness. In contrast, placebo-treated patients showed no differences between baseline and end point for any of the ADHD symptoms assessed. According to strict, predefined criteria for response, 68% of desipramine-treated subjects and no subjects in the placebo group were considered positive responders. Response to desipramine was independent of dose, level of impairment, gender, or lifetime psychiatric comorbidity with anxiety or depressive disorders. CONCLUSIONS: These results, similar to findings in children and adolescents with ADHD, indicate that desipramine is effective in the treatment of ADHD in adults.

Adolescent

Metabolic fuel utilisation in obese women before and after weight loss.

OBJECTIVE: To test the hypothesis that weight rebound following slimming diets may be caused by an adaptive alteration in fuel utilisation involving a suppression of fat oxidation thus favouring fat storage in adipose tissue. DESIGN: Repeat measurements before and after two 14 d cycles of controlled weight loss using a very low energy diet (1.9MJ/d). SUBJECTS: Eight moderately obese women (body weight: 85.6 +/- 10.1 kg, BMI: 31 +/- 2 kg/m2, age: 42.6 +/- 10.1 years). MEASUREMENTS: Energy expenditure and substrate balances using 24-h whole-body indirect calorimetry and naturally labelled 13C-glucose. RESULTS: Aggregate weight loss was 5.1 +/- 0.8 kg. Twenty-four hour energy expenditure declined by 12% (8359 +/- 282 to 7366 +/- 191 kJ/d, p < 0.001). Net fat utilisation was not significantly depressed (4009 +/- 366) to 3613 +/- 191 kJ/d, NS), and the proportion of energy derived from fat was unchanged at 48.0% before weight loss and 49.0% after weight loss. CONCLUSION: The well-recognised phenomenon of reduced energy expenditure is unlikely to be a major cause of weight regain. The results do not support the theory that altered fuel selection in post-obese subjects may be the cause of difficulty in maintaining weight loss.

Adaptation, Physiological

Changes in the incidence and mortality of testicular cancer in Scotland with particular reference to the outcome of older patients treated for non-seminomatous germ cell tumours.

This paper describes the temporal pattern of germ cell testicular cancer in Scotland between 1960 and 1990. The effect of age on the prognosis of patients with non-seminomatous germ cell tumours (NSGCT) has been assessed by studying all patients presenting in the West of Scotland between 1975 and 1989. Between 1960 and 1990, the number of testicular germ cell tumours registered has increased more than 2-fold; mortality rates have declined equally dramatically. Univariate and multivariate analysis of the data obtained on 440 patients with NSGCT showed age was not a prognostic factor influencing survival. 52 were patients over 40 years at presentation; their 5 years survival was 71% compared with 79% in the younger patients (n = 388). This small survival difference is probably explained by the higher proportion of older patients treated before 1980. Treatment for this older group should be approached with the same curative intent as for younger patients and the same expectation of success.

Adolescent

The epidemiology of non-seminomatous germ cell tumours in the west of Scotland 1975-89.

A total of 438 males resident in the six West of Scotland Health Board areas were notified to the cancer registry with a diagnosis of teratoma between 1 January 1975 and 31 December 1989. Non-registration was between 2% and 3.4%; a further 44 cases were ascertained through independent listings in the major tertiary referral centres. There were four (1%) duplicate registrations and 16 (4%) were incorrect on the basis of pathology (three) or residence (13). Of these, most (26) were registered with alternative diagnoses and eight were registered on the pre-1985 manual system. The positive correlation between socioeconomic status and incidence was confirmed by linking residential postcode at diagnosis to the Carstairs and Morris Deprivation Index. There was an increasing incidence, both overall and for men aged 15-44 years, with doubling times of 20 and 25 years respectively. The increase was confined to men resident in the more deprived postcode sectors; the incidence rate among men from the most affluent areas remained unchanged throughout the period of study.

Adolescent

The relationship between tic disorders and Tourette's syndrome revisited.

OBJECTIVE: The relationship between Tourette's syndrome (TS) and chronic tic disorder is of great clinical and scientific importance because of uncertainties in both prognosis and pharmacotherapeutic strategies. One approach to evaluating the relationship between TS and chronic tics is to examine whether they share similar neuropsychological and psychiatric correlates. METHOD: Children with TS (n = 32) and children with chronic tics (n = 39) were ascertained from an unselected sample of the children referred for psychopharmacological treatment and examined using standardized diagnostic assessments and testing procedures. RESULTS: Children with TS and those with chronic tics were similar to each other and different from controls in clinical correlates that included psychiatric comorbidity, as well as school, neuropsychological, and psychosocial impairments. Patients with TS also had higher rates of obsessive-compulsive disorder, oppositional defiant disorder, and simple phobia than did patients with chronic tic disorder. CONCLUSIONS: These findings indicate that TS and chronic tic disorder are part of the same disease entity, with TS being a more severe form of tic disorder.

Achievement

Does delayed diagnosis or scrotal incision affect outcome for men with non-seminomatous germ cell tumours?

OBJECTIVE: To ascertain whether delayed diagnosis or type of orchidectomy affected outcome for men with non-seminomatous germ cell tumours (NSGCT). PATIENTS AND METHODS: The case notes of 454 men resident in the west of Scotland with a diagnosis of NSGCT between 1975 and 1989 were retrospectively reviewed. The clinical record was available for 442 (97%) and included information on time to diagnosis in 92% and diagnostic surgery in 97%. The study end-point for orchidectomy was loco-regional recurrence and for diagnostic delay was survival. RESULTS: A significant minority of men (10.4%) underwent a scrotal orchidectomy or had a scrotal incision before an inguinal orchidectomy (9.4%). More scrotal incisions were performed on patients under the care of general surgeons (28%) than of urologists (12.1%). Of the men who had scrotal surgery, one of 78 (1.3%; 95% CI, 0-4%) developed loco-regional disease as the initial site of recurrence, compared with none of 318 men undergoing inguinal orchidectomy. The median time to diagnosis was 3 months. There was no relationship between time to diagnosis and tumour extent at presentation. A diagnostic delay of > 3 months was associated with inferior survival in univariate analysis, but delayed diagnosis was not an independent influence on survival after adjustment for the major prognostic factors--tumour extent, year of diagnosis and treatment unit. CONCLUSIONS: These results suggest that scrotal incision is unlikely to affect the risk of loco-regional recurrence and that effective cytotoxic therapy has probably reduced the prognostic importance of delayed diagnosis on survival of men with NSGCT.

Adolescent

ADHD and thyroid abnormalities: a research note.

Contradictory findings have been reported on associations between ADHD and thyroid abnormalities including the syndrome of generalized resistance to thyroid hormone. We systematically reviewed thyroid function in a large group of children and adolescents with ADHD (N = 132). We failed to find evidence of generalized resistance to thyroid hormone. Although mild laboratory abnormalities in thyroid function were observed in a minority of ADHD subjects, they were not different than rates reported in the literature for normal children.

Adolescent

Reverse transcriptase-PCR assay for detection of hog cholera virus.

A reverse transcriptase-PCR strategy was developed for the detection of hog cholera virus. Hog cholera virus template was amplified from tissue culture fluids and from tissues and blood of infected pigs, but not from samples containing other pestiviruses. Restriction endonuclease analysis identified samples as historic or recent isolates.

Animals