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Biomedical subjects

I Smith

Publications and source records attributed to I Smith.

At least 253 records · Page 14Linked to original sources

The value of computed tomographic (CT) scan surveillance in the detection and management of brain metastases in patients with small cell lung cancer.

One hundred and twenty-seven consecutive patients presenting with small cell lung cancer were entered into a whole-brain CT scan surveillance study, starting at presentation and repeating at 3-monthly intervals for 2 years as an alternative to prophylactic cranial irradiation (PCI). The aim of the study was to detect CNS metastases at an early asymptomatic stage in the hope that prompt CNS radiotherapy could achieve long-term control; at the same time unnecessary PCI with its potential long-term morbidity could be avoided. CNS metastases were found in 56 patients (44%) including 16 (13%) at diagnosis and 40 at a median of 4 months (range 1-27 months) after completing chemotherapy. No patient developed CNS disease while on chemotherapy. Thirty-six patients were asymptomatic at diagnosis (group A) but 20 developed clinical CNS relapse between scans (group B) (interval relapse). Despite prompt radiotherapy 56% of patients in group A and 60% of patients in group B died with active CNS disease. Likewise, there was no survival difference between patients in group A, group B or those who never developed CNS disease. Regular 3-month CT scan surveillance is therefore not an effective substitute for PCI.

Brain Neoplasms↗

Mishaps during transport from the intensive care unit.

We undertook a prospective study of 125 intrahospital patient transports from the ICU in an attempt to identify any factors that could influence the occurrence of mishaps. One third of the transports sustained at least one mishap. Therapeutic intervention scoring system class IV transports had the highest rate of mishaps (35%). We found no relationship of occurrence of mishaps to severity of illness (Acute Physiology and Chronic Health Evaluation, APACHE II), number of lines, monitoring and support modalities, and time out of the ICU. Transports for elective procedures had more mishaps (60%) than occurred for emergencies (40%). Most mishaps occurred either during the procedure, on transports to CT scan, or while waiting at the destination. The numbers and types of escorts as defined by our ICU policy and physician attendance on transport did not clearly reduce mishap risk. Morbidity and mortality were not affected by mishaps. Although certain trends did emerge, no clearly defined predictive factor could be identified. Further study into transport mishaps is warranted.

Accidents↗

A Bacillus subtilis regulatory gene product for genetic competence and sporulation resembles sensor protein members of the bacterial two-component signal-transduction systems.

A Bacillus subtilis gene, required for genetic competence, was identified immediately upstream from the previously characterized gene comA. The comA gene product has been found to exhibit amino acid sequence similarity to the so-called effector class of signal-transduction proteins. DNA sequencing of the new determinant, named comP, revealed that the carboxy-terminal domain of the predicted ComP protein is similar in amino acid sequence to that of several sensor members of the bacterial two-component signal-transduction systems. The predicted amino-terminal domain contains several hydrophobic segments, postulated to be membrane-spanning. In vitro-derived comP disruptions are epistatic on the expression of all late competence genes tested, including comG, comC, comD, and comE, but not on expression of the early gene comB. Although comA has its own promoter, some transcription of comA, especially later in growth, occurs via readthrough from comP sequences. A roughly twofold epistatic effect of a comP disruption was noted on the downstream comA determinant, possibly due to interruption of readthrough transcription from comP to comA. Overexpression of comA fully restored competence to a comP mutant, providing evidence that ComA acts after ComP, and consistent with a role for the latter protein in activation of the former, possibly by phosphorylation. ComP probably is involved in transmitting information concerning the nutritional status of the medium, particularly the presence of nitrogen- and carbon-containing nutrients. ComP was also shown to play a role in sporulation, at least partly interchangeable with that of SpoIIJ, another putative sensor protein.

Amino Acid Sequence↗

Congenital hypothyroidism: physiological and psychological factors in early development.

Children diagnosed as congenitally hypothyroid and treated from a very early age were followed up at 1 and 3 years. At 1 year they seemed to be developing normally, unless they were undertreated or had an additional disorder. There were no significant correlations between biochemical or social factors and psychological outcome at 1 year. At 3 years, however, those children whose T4 and/or T3 had been very low initially had significantly lower IQ scores than both other hypothyroid children and matched controls. Children with only moderately low initial T4 and/or T3, however, were doing just as well as their matched controls. Initial levels of TSH, the number of symptoms at first clinical interview and the age at the start of treatment were not good indicators of ability at 3 years. Undertreatment was rare but did appear to affect ability. Psychological outcome at 3 years was also correlated with social class (for both cases and controls). Multiple regression analyses indicated that both low initial T4 (less than 20 nmol/l) and social class contributed significantly to outcome.

Child, Preschool↗

Histopathology of melanocytic lesions in goats and establishment of a melanoma cell line: a potential model for human melanoma.

Melanocytic cells from white Angora goats were studied in vivo and in vitro. The histopathology of pigmented areas of skin from the most common sites of melanoma (solar-exposed areas of the ear, face, and perineum) resembled that of the epidermal melanocytes in Hutchinson's melanotic freckle in humans. Seven melanoma biopsies from 6 Angora goats showed histopathological features in common with human melanoma. A melanoma cell line, GM-1, was established in culture from a lymph node metastasis obtained from an animal that had a primary tumor excised and later developed extensive metastatic disease. GM-1 cells were mainly diploid, amelanotic, proliferated rapidly, spontaneously formed vacuolated cells, and were tumorigenic in nude mice. The species of origin of the GM-1 line was confirmed by isozyme profiles. GM-1 cultured cells and the original biopsy both expressed S-100 protein and tyrosinase antigen. Using GM-1 cells as the immunogen, a monoclonal antibody (MoAb 1F1) was derived that reacted strongly with a 116 kDa antigen in 50% of the GM-1 cells, but had little activity with goat fibroblasts (GM-F) or with human melanoma cells. GM-F, on the other hand, yielded more intense staining than GM-1 with an intermediate filament antibody (IFA), reacting with a 58 kDa antigen in both cell lines. The sensitivity of GM-1 to anticancer agents was similar to that of human melanoma cells. The pathology of caprine melanoma and its association with sun-exposed sites in relatively young animals suggest that it may be a suitable model for studying induction of melanoma by natural sunlight.

Animals↗

Temporal regulation of the Bacillus subtilis early sporulation gene spo0F.

The initiation of sporulation in Bacillus subtilis depends on seven genes of the spo0 class. One of these, spo0F, codes for a protein of 14,000 daltons. We studied the regulation of spo0F by using spo0F-lacZ translational fusions and also measured Spo0F protein levels by immunoassays. spo0F-lacZ and Spo0F levels increased as the cells entered the stationary phase, and this effect was repressed by glucose and glutamine. Decoyinine, which lowers GTP levels and allows sporulation in the presence of normally repressing levels of glucose, induced spo0F-lacZ expression and raised Spo0F levels. The expression of spo0F-lacZ was dependent on spo0A, -0B, -0E, -0F, and -0H genes, a spo0H deletion causing the strongest effect. In most respects, the spo0F gene was regulated in a manner similar to that of spoVG. However, the presence of an abrB mutation did not relieve the dependence of spo0F gene expression on spo0A, as it does with spoVG (P. Zuber and R. Losick, J. Bacteriol. 169:2223-2230, 1987).

Adenosine↗

Intelligence and quality of dietary treatment in phenylketonuria.

The records of the Phenylketonuria Register were examined to determine the factors associated with early intellectual progress in children who had received a diet low in phenylalanine from soon after birth. A total of 1031 children were born between 1964 and 1980 and started treatment before they were 4 months of age, and 808 of them were followed up prospectively. In 263 children born between 1964 and 1971 (cohort 1), the mean intelligence quotient (IQ) at 4 years rose with year of birth from 24 points below revised IQ norms to 10 points below; in 545 born between 1972 and 1980 (cohort 2) there was no further rise in IQ and the mean remained eight points below the norms. IQ fell progressively by roughly four points for each four weeks' delay in starting treatment, for each 300 mumol/l rise in mean phenylalanine concentrations during treatment, and for each five months during the first two years during which phenylalanine concentrations were below 120 mumol/l. Forty six children in cohort 2 had the most favourable treatment characteristics. Their mean IQ, after standardising for social class, was 112.6, and similar to the mean for the same group estimated by multiple regression, and to revised population IQ norms for the period during which the children were tested. The data suggest that many children who are treated early continue to suffer a mild degree of neurological impairment because of the difficulties in fully controlling the metabolic abnormality.

Child, Preschool↗

Central nervous system involvement in the erythrophagocytic disorders of infancy: the role of cerebrospinal fluid neopterins in their differential diagnosis and clinical management.

In two children with familial erythrophagocytic lymphohistiocytosis accompanied by neurologic symptoms, total neopterin concentrations in cerebrospinal fluid were 200 times higher than in controls and 10 to 20 times higher than in five children with presumed neurologic disease due to primary viral infections (human immunodeficiency virus, herpes simplex, measles) of the CNS. In one child with familial erythrophagocytic lymphohistiocytosis, clinical remission was accompanied by a fall in neopterin concentrations to normal; in a second child, who died, total neopterin concentrations remained high. In two other children with a diagnosis of infection-associated hemophagocytic syndrome without any neurologic disturbance, neopterin concentrations were also elevated but only to 10 times the concentrations in controls. Total neopterin concentrations in cerebrospinal fluid provide a measure of the severity of macrophage infiltration and activation within the CNS, and are useful in assessing the need for intensive chemotherapy and monitoring the response to treatment.

Biopterins↗

Hazards of sulphur.

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Adenosine Triphosphate↗

Neurodevelopmental delay and focal seizures as presenting symptoms of human immunodeficiency virus I infection.

Three children presenting with neurological symptoms were subsequently diagnosed as being infected with the human immunodeficiency virus I (HIV). All children showed normal development for about 12-18 months of age but later developed psychomotor and developmental regression. One child presented with generalised hypotonia, another with focal seizures, and the third with spastic quadriplegia. Two of the children showed areas of abnormal brain density on computed tomography and in one case there was calcification of the basal ganglia. In two of the children cerebrospinal fluid contained reduced amounts of total folate and elevated concentrations of neopterin. The possibility of a link between the deranged folate metabolism and the neurological symptoms in HIV infection is discussed.

Acquired Immunodeficiency Syndrome↗

A study of inter-reviewer reliability of attacks recorded on ambulatory EEG.

Eleven ambulatory EEG (A/EEG) cassette tapes were sent to 5 reviewers from different EEG laboratories in the U.K. Each tape included one attack recorded from a different patient. Attacks were chosen to include various possible EEG changes that can occur during attacks on A/EEG. Reviewers were asked to give details of EEG changes seen during attacks and to state whether they thought attacks were epileptic. Total agreement about the presence of abnormality was found on 2 tapes. Four out of 5 reviewers agreed on 4 tapes and on the remaining 5 tapes only 2 or 3 reviewers were in agreement. It was concluded that the amount of agreement amongst reviewers was poor but reasonable in view of the degree of difficulty of the tapes which were not a random sample. Compared to the final clinical opinion of referring consultants, these findings would have resulted in 16% false negatives, 7% false positives and 13% of cases in which no decision was made.

Ambulatory Care↗

Blood selenium concentrations and glutathione peroxidase activity.

Selenium concentrations in children and teenagers without a metabolic disorder eating normal diets (group 1), and young patients with classical phenylketonuria and milder forms of hyperphenylalaninaemia being treated with a diet low in natural protein (group 2) were investigated. There was a strong correlation between blood selenium concentration and age in children in group 1 up to 10 years of age. Blood selenium concentrations and glutathione peroxidase activities were significantly lower in the patients who were receiving diets containing reduced amounts of natural protein, and the differences were more than would be expected for age. When the concentrations of selenium in blood from groups 1 and 2 were compared with glutathione peroxidase activity, a strong association was found when blood selenium concentrations were below 1.26 mumol/l. Reduction in glutathione peroxidase activity may be harmful in the long term, and the addition of selenium to therapeutic diets is recommended.

Adolescent↗

Esophageal diverticula.

The clinical and radiological features in four patients with symptomatic mid-esophageal diverticula are reported here. The common clinical symptoms were retrosternal chest pain and dysphagia. Radiologically, three patients had acute obstructions revealed by barium studies and one patient had an esophago-bronchial fistula at the tip of the diverticulum.

Adult↗