Thiamine triphosphate levels and histopathology. Correlation in Leigh disease

Thiamine and thiamine triphosphate (TTP) values were assayed in various brain regions in 11 controls and 13 patients with subacute necrotizing encephalomyelopathy (SNE, Leigh disease). The TTP values of normal brain were 5% of the total thiamine value. The relative TTP (or % TTP) level was consistently low in the pons, midbrain, and cerebellum of all the SNE brains. Twenty-five percent of the SNE brains had normal TTP levels in the frontal region. The TTP values correlated with the degrees of pathologic involvement in all sampled regions of the brain except the cerebellum. The concentration of thiamine in the mammillary bodies exceeded its concentration elsewhere in both control and SNE brains. The finding of low TTP levels in morphologically abnormal regions supports the hypothesis that TTP deficiency is etiologically related to SNE.     

Systemic methotrexate toxicity. A pharmacological study of its occurrence after intrathecal administration in a patient with renal failure

Methotrexate pharmacokinetic studies, performed on a patient with renal impairment who had toxic effects following 20 mg/sq m of intrathecally administered methotrexate, demonstrated prolonged serum concentrations of the drug, which accounted for the condition. After the return of normal renal function, pharmacokinetic studies were repeated following the same dose and route of administration of methotrexate. On this occasion there was a rapid clearance of serum methotrexate below toxic levels.     

The response of cells in culture to fractionated radiation: a theoretical approach

A mathematical model has been constructed to simulate the response of cells in vitro to fractionated doses of radiation. The model is capable of describing most of the radiobiological functions that are commonly studied. Input data are measurable cell properties. The details of the model and methods of acquiring the input data are outlined and a comparison with experimental observations on two radiobiological functions, survival curves and recovery curves are discussed in some detail.     

Study on the relationship between plasma prolactin levels and androgen metabolism in man

The purpose of the study was to investigate the effect of hyperprolactinemia on the metabolism of androgens in man. A group of 6 normal men was treated for 4 consecutive days, on separate periods, with Sulpiride which is known to raise plasma prolactin (PRL) concentration. The effect of the treatment on plasma steroids was verified in basal conditions and under stimulation by HCG. In the controls, a parallel rise in testosterone (T) and dihydrotestosterone (DHT) was observed in response to HCG stimulation. In experimental hyperprolactinemia, the rise in T in response to HCG, similar to that of the controls, was accompanied by a markedly diminished rise in DHT. Similar results were observed in a patient with hyperprolactinemia following apparent accidental section of the pituitary stalk. These data demonstrate the interference of increased levels of PRL in the metabolism of testosterone into the active DHT form by 5alpha-reductase. They suggest that this mechanism could possibly impair the gonadal function in man.     

Evidence for the presence of components of the alternative (properdin) pathway of complement activation in respiratory secretions

Activation of the alternative complement pathway by respiratory secretory IgA was demonstrated by incubating purified, aggregated preparations of serum and secretory IgA with neat human serum. No depletion of the early components (C1-4) was observed, but 63 and 70% of C3-9, respectively, were consumed. The C3-9-consuming capacity of heat-aggregated nasal secretions from an IgA-deficient volunteer was compared with heat-aggregated nasal secretions from a normal volunteer known to have secretory IgA. The deficient secretions consumed C3-9, whereas the IgA deficient secretions did not. Reconstitution of the nasal secretions from the IgA-deficient volunteer with purified secretory IgA produced alternative pathway activation. Factor B of the alternative complement pathway was found to be present in 16 of 18 bronchoalveolar lavage samples (BALF) from normal volunteers. Simultaneous measurement of lavage and serum albumin and Factor B concentrations rendered it unlikely that Factor B was merely a transudative product from serum in half the samples but rather suggested that it may be a component of lower respiratory tract secretions. The presence of an intact alternative complement pathway in BALF was indicated by showing that cobra venom factor and endotoxin cleaved functionally pure human C3 when mixed with BALF, but had no effect on C3 in the absence of BALF.     

4-aminobiphenyl, 2-naphthylamine, and analogs: analytical properties and trace analysis in five substrates

Methods for monitoring trace levels of 4-aminobiphenyl, 2-naphthylamine, and their hydrochloride salts in waste water, microbiological growth media, potable water, human urine, and mouse blood utilizing spectrophotofluorometry (SPF) are described. The salient elements of the methods are extraction of the residues as the free amine with benzene, rapid cleanup on an alumina column, and quantification of the free amine in methanol via SPF. Potable water solutions of the salts are diluted with 0.01 N aqueous HCL and quantified directly by SPF. Ancillary analytical information concerning gas chromatography of the free amines, partitioning properties of the compounds between solvent pairs, their solubility and stability in water, and thin-layer chromatographic data is presented. The compositions of various admixtures of 1- and 2-naphthylamine or their salts were determined by using SPF with calculations based on simultaneous equations.     

Subjective definitions of tension

To examine the type of proprioceptive information which subjects include in the definition of tension, 52 subjects were asked to indicate the location of where they felt tension while engaging in a simple motor task. Responses indicated that tendon stretch, muscle tension, and other cues are utilized in the subject's definition of tension.     

Attaching community psychiatric nurses to general practice

A scheme for attachment of psychiatric nurses from hospital to group practice in Oxford is described. One community psychiatric nurse can work satisfactorily with eight general practitioners covering a population of about 18,000. From analysis of a working year, it is concluded that this arrangement improves the care of patients in the community by providing psychiatric help at times when it was previously unavailable or unacceptable.The implications of such a scheme for the workings of the primary health care team and the hospital psychiatric service are considered, and a case is made for a further study involving a comparison between practices with and without the attachment of a community psychiatric nurse.     

Aldosterone secretion during high sodium cerebrospinal fluid perfusion of the brain ventricles

Conscious sheep with permanent indwelling cannulae in the lateral ventricles and the cisterna magna were Na depleted and then perfused for 9 h with an artificial CSF solution. There were 3 experimental groups: Group I (n=5) received perfusion with aritifical CSF containing NA 170 MEq./1, Group II (n=7) received perfusion with artificial CSF containing Na 145 mEq./1, Group III (n=7) received no perfusion. In Group I the blood aldosterone level fell from 26.4 +/- 7.4 to 8.6 +/- 2.3 ng/100 ml by 9 h after perfusion. There was no significant change in plasma [Na] or [K], blood angiotensin II or plasma renin concentration. Blood cortisol and corticosterone levels rose. There was also a fall in post-perfusion. Group III showed no significant change in blood aldosterone concentration. Multivariate statistical analysis showed that the fall in aldosterone levels during 170 mEq./l Na perfusion could not be accounted for by changes, either alone or together, of ACTH as evidenced by alteration in blood cortisol or corticosterone, or by change of plasma [Na], [K] or renin concentrations. This data supports the hypothesis of an additional factor which may be of CNS origin being involved in the control of aldosterone secretion.