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Biomedical subjects

J Connelly

Publications and source records attributed to J Connelly.

At least 19 recordsLinked to original sources

Nuclear magnetic resonance spectroscopic and principal components analysis investigations into biochemical effects of three model hepatotoxins.

1H NMR spectroscopy of urine combined with pattern recognition (PR) methods of data analysis has been used to investigate the time-related biochemical changes induced in Sprague-Dawley rats by three model hepatotoxins: alpha-naphthyl isothiocyanate (ANIT), d-(+)-galactosamine (GalN), and butylated hydroxytoluene (BHT). The development of hepatic lesions was monitored by conventional plasma analysis and liver histopathology. Urine was collected continuously postdosing up to 144 h and analyzed by 600-MHz 1H NMR spectroscopy. NMR spectra of the urine samples showed a number of time-dependent perturbations of endogenous metabolite levels that were characteristic for each hepatotoxin. Biochemical changes common to all three hepatotoxins included a reduction in the urinary excretion of citrate and 2-oxoglutarate and an increased excretion of taurine and creatine. Increased urinary excretion of betaine, urocanic acid, tyrosine, threonine, and glutamate was characteristic of GalN toxicity. Both GalN and ANIT caused increased urinary excretion of bile acids, while glycosuria was evident in BHT- and ANIT-treated rats. Data reduction of the NMR spectra into 256 integrated regions was used to further analyze the data. Mean values of each integrated region were analyzed by principal components analysis (PCA). Each toxin gave a unique time-related metabolic trajectory that could be visualized in two-dimensional PCA maps and in which the maximum distance from the control point corresponded to the time of greatest cellular injury (confirmed by conventional toxicological tests). Thereafter, the metabolic trajectories changed direction and moved back toward the control region of the PR map during the postdose recovery phase. The combination of urinary metabolites which were significantly altered at various time points allowed for differentiation between biliary and parenchymal injury. This NMR-PR approach to the noninvasive detection of liver lesions will be of value in furthering the understanding of hepatotoxic mechanisms and assisting in the discovery of novel biomarkers of hepatotoxicity.

1-Naphthylisothiocyanate

The nature of 'transient' and 'partial' psychoses: findings from the Northwick Park 'Functional' Psychosis Study.

Three hundred and twenty-six consecutively admitted patients with definite or possible functional psychotic illnesses to which no diagnostic classification had been applied were followed up after 2.5 years. In 86 cases symptomatology had been inadequate for the patients to enter the functional psychosis study, and in 75 cases this was because the symptoms were partial or transient. These patients were compared at follow-up with those who fulfilled operational criteria for schizophrenic, affective or schizoaffective psychoses. Differences between the 'partial' cases and those fulfilling specific diagnostic criteria were few, but the transient cases fared significantly better. Although the transient illnesses were recurrent, at follow-up at 2.5 years they appeared to have a good outcome in terms of social variables and symptomatology.

Affective Disorders, Psychotic

Measurement of TSH receptor blocking immunoglobulins using 3H-adenine incorporation into FRTL-5 and JPO9 cells: use in a child with neonatal hypothyroidism.

OBJECTIVE: The aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated 3H-cAMP production following incubation of FRTL-5 or JPO9 cells with 3H-adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism. DESIGN: The levels of TBAb, TSAb (thyroid stimulating antibodies), TBII (TSH binding inhibitory antibodies), and the thyroid antibodies anti-thyroid peroxidase and thyroglobulin antibodies were measured in both mother and child over a 6-month post-natal period. PATIENT: The assay for TBAb was used to evaluate a child born with neonatal hypothyroidism whose mother had a history of hypothyroidism due to Hashimoto's thyroiditis. A 99mTc pertechnetate scan showed no evidence of functioning thyroid tissue. At 20 months of age an ultrasound verified a normally positioned thyroid. RESULTS: Initially, high levels of TBII and antithyroid antibodies were present in the serum of both mother and child. In both, the levels of TSAb were undetectable but there were significant levels of TBAb. The levels of TBAb decreased to control levels in the child within 2 months of birth but remained elevated in the mother's serum. CONCLUSIONS: This case of neonatal hypothyroidism associated with the passage of thyroid blocking antibodies demonstrates the utility of this new assay in the differential diagnosis of neonatal hypothyroidism.

Adenine

The effect of stress on hedonic capacity.

Two experiments were conducted to examine the effect of stress on hedonic capacity. In Experiment 1, cadets in the U.S. Army Reserve Officer Training Corps reported experiencing less pleasure while watching amusing film clips after participating in a weekend of field training exercises than they did on a control day. In Experiment 2, college students reported experiencing less pleasure in their daily activities during final exam week than they did at the baseline assessment. Hedonic capacity was associated with positive affect but not with negative affect or reported stress levels. The deleterious effect of stress on hedonic capacity was particularly strong for subjects with family histories of depression.

Adolescent

Intracranial ependymoma in children: analysis of prognostic factors.

Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25-36 Gy to the neuro-axis, 45-55 Gy to tumor bed), 12 received local field irradiation (29-60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had post-radiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear.

Adolescent

Malignant blue nevus.

To elucidate the histologic features and biologic behavior of malignant blue nevus (MBN), 12 cases were analyzed in which the tumor showed no junctional activity and arose in a blue nevus background. Seven patients were men and five were women; their mean age was 48.8 years. Eight lesions were on the scalp, and no patient had a family history of melanoma. The histologic appearance of most lesions was a nodule or nodules of malignant cells in a blue nevus. Mitoses were present in all lesions with atypical forms in eight; however the mitotic rate exceeded two per ten high-power fields in only one lesion. Four lesions had necrosis, and four had a heavily pigmented malignant component. Four patients had recurrences; ten patients had metastases, and eight died of their disease. Therefore MBN is an aggressive neoplasm.

Adult

Is housing a public health issue? A survey of directors of public health.

OBJECTIVE: To determine the views of directors of public health on the importance of housing for public health and their departments' and health authorities' participation in housing issues. DESIGN: Postal self administered questionnaire survey. SETTING: All district health authorities in England and health boards in Wales, Scotland, and Northern Ireland. SUBJECTS: All 221 district directors of public health in England and chief administrative medical officers in Wales, Scotland, and Northern Ireland. MAIN OUTCOME MEASURE: Response to questionnaire consisting of fixed and open ended questions on housing issues. RESULTS: The response rate was 89% (196/221). Housing was perceived as a major health problem by 33% (65/196) of directors. Positive responses were most likely from inner city districts. In 47% (93/196) of departments there was a formal time commitment to housing issues with a median time of one session/week (range one per month to 10 per week). The main function was allocation of medical priority for public sector rehousing. Overall, 73% (144/196) reported some participation in this process. Reported participation in joint care planning and links with non-statutory housing organisations were uncommon. 53% (104/196) of directors had included housing issues in their annual health report. In 16% (32/196) of districts specific services for the homeless had been set up. CONCLUSIONS: Although concern about the impact of current housing policy on public health was shown by a substantial number of directors, the main activity was still allocation of medical priority despite a background of increasing housing need and homelessness. The underlying need is for greater advocacy to produce a healthy housing policy for all, and the annual public health report could be used to promote this objective.

Attitude to Health

Pseudofungi in a lymph node. A case report with energy dispersive X-ray elemental analysis.

A case of pseudofungi in axillary lymph nodes is presented. They resembled septate hyphae and were stained with a periodic acid-Schiff stain. Gomori methenamine silver stain failed to stain them. Because of morphologic similarity to true septate fungi and positive staining with periodic acid-Schiff stain, these structures can be misinterpreted as septate hyphae forming true fungal organisms. Further studies, some of which included energy-dispersive x-ray elemental analysis and special stains, revealed that they were composed of iron, phosphorus, and calcium. The relationship of these pseudofungi to previously published cases and clues that enable one to make a correct diagnosis are described.

Aged

An unusual case of variegate porphyria with possible homozygous inheritance.

We report an unusual case of variegate porphyria in a young girl with epilepsy, mental retardation and premature adrenarche. Symptoms of porphyria commenced about the age of 12 years and death occurred about 18 months later. The patient had very low protoporphyrinogen oxidase activity in her cultured fibroblasts. Both parents had half the normal activity of this enzyme in lymphocytes and are heterozygous for the abnormal gene for variegate porphyria. Therefore, it is possible that the patient was a homozygous variant. Anticonvulsant therapy and low hepatic 5 alpha reductase activity were probably other contributing factors to the severity of the condition in this patient.

Animals

Use of hospital services by homeless families in an inner London health district.

Over the past decade the number of families in London who were considered officially to be homeless appreciably increased. In response to this many families have been given temporary accommodation, usually in bed and breakfast hotels, while awaiting permanent rehousing. About 200 of the roughly 600 hotels in London that provide such accommodation are located in the area of the former Paddington and North Kensington Health Authority, now part of Parkside Health Authority. The use made by the homeless population of hospital services was studied by finding out the numbers of inpatients admitted to hospital and the numbers presenting to the walk in paediatric clinic and the casualty department at one hospital. These figures were compared with those for local residents and the overall workload. The bed and breakfast population were high users of inpatient beds, the casualty department, and the paediatric clinic. Overall, about one tenth of the beds were used by these people. The health authority receives no additional funding for this group of patients. Further research is needed to find out if the high use of hospital services made by these patients reflects their increased morbidity or their inability to obtain primary care services.

Catchment Area, Health