Palliation of malignant phaeochromocytoma with combination chemotherapy.
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Biomedical subjects
Publications and source records attributed to J Connell.
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In tests on specimens of dried blood, saliva, and urine from 55 human immunodeficiency virus (HIV)-seropositive and 55 HIV-seronegative patients, an immunoglobulin G capture enzyme immunoassay for the detection of antibodies to HIV types 1 and 2, GACELISA, gave 109 of 110, 109 of 109, and 109 of 110 correct results, respectively. This performance, achieved in a laboratory previously unfamiliar with the assay, suggests that GACELISA is a useful new epidemiological tool for the study of HIV infection, equally applicable to all three kinds of specimen.
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We studied patterns of psychophysiological (skin conductance, heart rate) reactivity to sounds and to situations with varying emotional and alerting connotations in child psychiatric outpatients and in healthy controls. Children with emotional disorders were particularly reactive to situations with aversive components, while conduct disorder subjects showed increased reactivity to pleasant situations and decreased responses to neutral but high-intensity stimulation and to withdrawal of stimulation in silence periods. The results indicate patterns of biological reactivity which may underlie different psychiatric disturbances in children.
Click-evoked oto-acoustic emissions and auditory brainstem responses (ABR) have been recorded in 723 babies taken largely from a neonatal intensive care unit to evaluate the use of oto-acoustic emissions as a method of screening for hearing impairment. Twenty-nine infants failed to pass the initial ABR test and repeat ABR tests carried out up to the age of 3 months. The 'sensitivity' and 'specificity' of the oto-acoustic emission test for the ABR test results up to 3 months of age in surviving infants were 93% and 84% respectively. It is proposed that click-evoked oto-acoustic emissions be considered as the initial method to screen for hearing impairment, test failures being followed up by ABR.
Peripheral psychophysiological reactivity (skin conductance and heart rate changes) to mental activity tasks (imagery and listening to music) was examined in child psychiatric day or in-patients with conduct and emotional disorders. Children with predominant antisocial symptomatology showed higher electrodermal than cardiovascular reactivity to the experimental tasks, whilst children with predominant neurotic symptoms showed more marked cardiovascular reactivity. No statistical differences between the groups emerged in response to listening to music, but antisocials were more responsive (with higher skin conductance level increases) to imaging pleasant situations, whereas neurotics were more reactive (increased heart rate levels and decreases in skin conductance) to imaging unpleasant situations. The results are compatible with an enhanced biological responsiveness by antisocials to reward and with neurotics experiencing an unusually marked sense of threat and withdrawal to aversive stimuli.
Seven hundred and twenty-three neonates under intensive care have been tested by evoked otoacoustic emissions (EOAE) and the auditory brain stem response (ABR) to investigate the use of EOAE as a test for hearing impairment. Three hundred and thirty-one have had follow-up tests to the age of at least 2 years. The EOAE test has been found to be practical and quick to perform. The proportion of NICU infants producing a recordable EOAE is 80%, and the sensitivity and selectivity to the ABR result in the period up to 3 months post due date is 93 and 84%, respectively. These figures are high enough and the reduction in time compared to ABR is sufficient for the EOAE to be considered as the primary screen. The follow-up data show mixed results with both false positives and false negatives present. The incidence of severe hearing impairment is close to that expected from retrospective studies at 2 in 331 (1 bilateral, 1 unilateral). Firm conclusions on the sensitivity of EOAE to long-term hearing impairment await the results from larger numbers of infants and further follow up data.
Two novel antiviral pharmacologic strategies were used for therapy of life- and sight-threatening cytomegalovirus (CMV) infection; these were continuous drug infusion by portable pump and individualized patient regimen. 9-(1,3-Dihydroxy-2-propoxymethyl)-guanine (DHPG), an active and recently licensed antiviral drug against cytomegalovirus infection, was administered to five immunocompromised patients with chorioretinitis (all patients), colitis (two), and pneumonitis (three). Through dosage escalation, correlations between plasma levels, toxicity (i.e., myelosuppression), and clinical benefit were ascertained for therapy of acute disease (pneumonitis) as well as long-term therapy (chorioretinitis). Resolution of viremia, pneumonitis, colitis, and chorioretinitis was accomplished with steady-state plasma levels of DHPG approximating the mean ID50 of CMV isolates. The most notable clinical benefit was survival from CMV pneumonia and stabilization of vision. Although no adverse toxicity occurred during the DHPG continuous long-term therapy, survival was limited by the underlying disease.
We recruited 275 full term and preterm infants into a prospective evaluation of continuous four channel electroencephalographic (EEG) monitoring in the diagnosis and prognosis of neonatal seizures. EEG seizure activity was found in 55 infants; clinical signs were completely simultaneous in only 12 of these, they were present but limited in another 20, and were completely absent in the remaining 23. EEG seizure activity, with or without clinical signs, were equally associated with serious cerebral lesions and with adverse clinical outcome. The four channel EEG recording provided sufficient data on abnormality to be prognostically specific in 79% of the 43 infants who either died or had serious neurological impairment.
During a two year period prospective continuous electroencephalographic (EEG) monitoring of 275 infants identified seizure activity in 55 cases, 31 of whom were treated with anticonvulsant drugs on clinical grounds. EEG and clinical response was complete in only two and equivocal in another six. Clinical response with persistent EEG seizures occurred in 13 and neither clinical nor EEG response in 10. There was no significant improvement in the generally poor neurological outcome compared with that in 24 infants whose seizures were not treated because of limited or absent clinical manifestations. Background EEG abnormality (as an index of associated cerebral dysfunction) was a guide to potential lack of response to anticonvulsant drugs; it was also predictive of subsequent clinical outcome irrespective of treatment. This study shows that commonly used anticonvulsant drugs (phenobarbitone, paraldehyde, phenytoin, and diazepam) have little effect on seizure control or neurological outcome in neonatal seizures associated with haemorrhagic, hypoxic, or ischaemic cerebral lesions. In view of the variable clinical appearance of EEG seizure activity, continuous EEG monitoring should be an essential feature of further study of neonatal anticonvulsant treatment.
The hearing of 346 babies taken largely from a neonatal intensive care unit has been tested by otoacoustic emissions and brain stem electric response audiometry. A total of 336 (97%) of the babies have been followed up by hearing tests from the age of 8 months. The otoacoustic emission test has been found to be practical with a mean test time of 12.1 minutes compared with 21.0 minutes for brain stem electric response. An otoacoustic emission was recorded bilaterally in 274 (79%) babies. Twenty of the 21 surviving infants who failed brain stem electric response in the neonatal period did not produce an emission. It is concluded that the otoacoustic emission test would make a good first screen to be followed by the brain stem electric response if no otoacoustic emission was present. There is poor agreement between the test results in the neonatal period and those of the follow up period, however, indicating the need for continuous monitoring of those babies failed by brain stem electric response.
Northern blotting and hybridization histochemistry were used to evaluate the ontogeny and cellular distribution of the mRNAs of the cytochrome P-450 enzymes: cholesterol side-chain cleavage (P-450scc), 17 alpha-hydroxylase (P-450(17 alpha] and 21-hydroxylase (P-450c21) in 40 ovine fetal adrenals from 42 days of gestation until term (151 days). The genes for P-450(17 alpha) and P-450scc were expressed strongly in tissue from young (40-60 days) and old fetuses (120 days to term), but to a very minor degree in 90-120 day fetuses. P-450c21 showed a steady increase throughout gestation. In the morphologically immature an unzoned adrenal of the 40-50 day fetus there was some differentiation in gene expression, all cells containing P-450scc and P-450c21 but a few lacking P-450(17 alpha). Once morphological zonation had occurred (80 days), P-450(17 alpha) was confined to the fasciculata. After 120 days there was a radial maturation pattern of the fasciculata cells morphologically, adult-type cells first appearing at the medullary border. However, P-450(17 alpha) and P-450scc mRNAs were equally well expressed in all sections of the fasciculata. The conclusions were: 1) the previously demonstrated triphasic cortisol biosynthetic capacity of ovine fetal adrenals was correlated with the presence, absence, and reappearance of mRNAs P-450(17 alpha) and P-450scc; 2) morphological appearance of fetal adrenocortical cells and expression of three major steroidogenic enzyme genes were not correlated.
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The contribution of early continuous four-channel EEG monitoring to the evaluation of intraventricular hemorrhage in acutely ill preterm infants mechanically ventilated for acute respiratory distress was assessed in a prospective study of 54 infants of less than 34 weeks' gestation. Early abnormal EEG results correlated significantly with later outcome. They often preceded ultrasound evidence of hemorrhage and provided prognostically significant functional correlation with the grade of hemorrhage. Continuous EEG monitoring allows collection of significant data with minimal interference and could contribute to clinical management of high-risk preterm infants.
This report is an analysis of mortality in the population of Niue Island over the years 1978-82. The overall level of mortality in Niue is low. Life expectancy at birth is correspondingly high (66.5 years). Because of the extensive migration of Niueans during the period of study the death rate may be underestimated and the life expectancy correspondingly overestimated. Infant mortality has dropped from over 200 deaths per 1000 live births during the 1940s to around 10 per 1000 during the period under study. The major causes of premature mortality in Niuean males were injury/poisoning followed by cardiovascular disease. In females infection, injury/poisoning and neoplasia were the major causes of mortality. The 1980 epidemic of dengue fever had an appreciable effect on mortality in this small population. Except for dengue fever, the pattern of mortality in Niue is similar to that in many developed countries. Preventive efforts against metabolic and cardiovascular disease (including hypertension and diabetes) should continue in order to control mortality from these causes, Mosquito programmes, and emergency measures if epidemics threaten, are required so that deaths from haemorrhagic dengue are prevented.
Continuous monitoring by electroencephalography (EEG) was performed in 31 preterm infants with echodense ultrasound lesions using the Oxford Medilog four channel recorder. In 12 infants these densities preceded cyst formation, eight in the periventricular and four in the subcortical region. In the 19 other infants the densities resolved. The most severe EEG depression occurred in the four infants with subcortical cysts, who also had the poorest outcome. Six of eight infants with periventricular lesions had lesser degrees of abnormality though all infants had moderate to severe handicap at follow up. Similar abnormalities were seen on EEG recording in three infants in whom the densities resolved without cyst formation and these infants also had an abnormal outcome. An abnormal EEG recording provides a sensitive early guide to the severity and prognosis of these lesions, even before they can be seen on ultrasonography.
A case is presented of a 56 year old man with a history of idiopathic pancreatitis and multiple admissions for Klebsiella sepsis from an intra-abdominal focus, who in February 1980, developed spontaneous jejunal perforations on two occasions due to multiple ulcers in the small intestine associated with multiple hepatic metastases from a gastrin-secreting islet-cell tumor (gastrinoma) of the pancreas. On searching the literature, no other record could be found of an association between pancreatitis and a gastrinoma, although in this patient the two disease processes appear to be inextricably related.
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