Virus-induced hydrocephalus: development of aqueductal stenosis in hamsters after mumps infection.

Hydrocephalus developed as a sequela of mumps virus infections of suckling hamsters. The initial infection after intracerebral inoculation was limited largely to ependymal cells lining the ventricles. This infection was clinically inapparent but later resulted in a noninflammatory stenosis or occlusion of the aqueduct of Sylvius.

The effect of carbohydrate mouth rinsing on fencing performance and cognitive function following fatigue-inducing fencing.

This study investigated the impact that mouth rinsing carbohydrate solution has on skill-specific performance and reaction time following a fatigue-inducing bout of fencing in epee fencers. Nine healthy, national-level epee fencers visited a laboratory on two occasions, separated by a minimum of five days, to complete a 1-minute lunge test and Stroop test pre- and post-fatigue. Heart rate and ratings of perceived exertion (RPE) were recorded during completion of the fatiguing protocol. Between fights the participant's mouth rinsed for 10 seconds, either 25 ml of 6.7% maltodextrin solution (MALT) or water (PLAC). Blood lactate and glucose were recorded at baseline, pre- and post-testing. Results showed an increase in heart rate and overall RPE over time in both conditions. There were no differences in blood glucose (F(1,8) = .63, P = .4, ηp = .07) or blood lactate levels (F(1,8) = .12, P = .70, ηp = .01) between conditions as a function of time. There was a significant improvement in lunge test accuracy during the MALT trial (F(1,8) = 5.21, P = .05, ηp = .40) with an increase from pre (81.2 ± 8.3%) to post (87.6 ± 9.4%), whereas there was no significant change during the placebo (pre 82.1 ± 8.8%, post 78.8 ± 6.4%). There were no recorded differences between conditions in response time to congruent (F(1,8) = .33, P = .58, ηp = .04) or incongruent stimuli (F(1,8) = .19, P = .68, ηp = .02). The study indicates that when fatigued mouth rinsing MALT significantly improves accuracy of skill-specific fencing performance but no corresponding influence on reaction time was observed.

Brain morphometry and IQ measurements in preterm children.

Although IQ is thought to remain relatively stable in the normal population, a decline in IQ has been noted in children born preterm. It is not clear, however, to what extent the inclusion of children with clear neurological damage has influenced these findings. We examined IQ scores obtained in childhood and then again in adolescence from a group of children born at 30 weeks gestation or less who had been classified as neurologically normal at 7.5-8 years. They showed a significant decline in mean IQ scores over time. MRI scans obtained from a subset of children at adolescence were read as normal in approximately 50% of cases and, in the others, there were no consistent relationships between radiological abnormalities and IQ results. Such children can, however, have relatively subtle brain abnormalities that are not seen on conventional MRI, and we hypothesized that these would be related to declines in IQ. Voxel-based morphometry (VBM) analyses of the MRI scans revealed that absolute IQ scores were related to areas in both the parietal and temporal lobes. The analyses also showed that frontal and temporal lobe regions were associated with the decline in VIQ, while occipital and temporal lobe regions (including the hippocampi) were associated with the decline in PIQ. Hippocampal volume measurements were consistent with the VBM findings. We concluded that preterm children are at risk of declining IQ over time even if they have not suffered obvious neurological damage and that the decline is associated with specific neural regions. Whether this is true of children born at >30 weeks gestation and what other factors predispose to this decline have yet to be determined.

Aldosterone in colonic potassium adaptation in rats.

The influence of adrenalectomy and administration of aldosterone on potassium secretion by colonic epithelium was studied in vivo in rats, particularly in relation to potassium adaptation (induced by feeding a potassium-rich diet) and the response to acute i.v. administration of a potassium load. Adrenalectomy (rats maintained on dexamethasone and saline) impaired the development of potassium adaptation or considerably reduced it if the rats had been previously adapted. The partial adaptation observed in the adrenalectomized rats may be related to the increased plasma potassium concentration developed when these rats received the potassium-rich diet. Within 2 h of acute aldosterone administration, the response of the potassium secretion rate to acute potassium loading in adrenalectomized rats was significantly improved. When aldosterone (2 micrograms/day per 100 g body weight, given by osmotic minipump) was added to the replacement treatment, the plasma concentration of potassium was similar to that of the intact rats, and both potassium adaptation and the response to the acute potassium load were completely restored. Transepithelial potential difference and sodium transport were not stimulated, being similar to the values in intact rats. Considerable changes in potassium secretion induced by acute potassium loading did not significantly affect sodium transport. The findings suggest that the sodium and potassium epithelial pathways are, to a large extent, independently influenced by aldosterone. Aldosterone appears to be essential for complete adaptation and, in a relatively low dose, can completely restore potassium adaptation and the response to acute potassium loads in adrenalectomized rats.

Sodium transport and the cellular sodium transport pool of colonic epithelium: effects of sodium loading, aldosterone and lithium.

The cellular sodium transport pool and sodium transepithelial fluxes were investigated in vivo in rat distal colon in relation to sodium loading by intravenous infusion (3.5 h), and to short (4 h) and prolonged (72 h) i.v. administration of aldosterone. Considerable natriuresis and increase in body sodium content were produced by the sodium load but there was no significant effect on the transcellular sodium flux (active absorption from lumen to plasma) or on the sodium transport pool. Both short and prolonged aldosteronism produced similar increases in the transport pool and in the transcellular sodium flux, but the transepithelial electrical potential difference (p.d.) was significantly greater in rats given the prolonged infusion. Addition of amiloride to the solution in the lumen of the colon almost completely abolished the p.d., the transport pool and the transcellular sodium flux of the rats receiving prolonged infusion, but had much less effect in those given the short infusion. The time-course of recovery of p.d. following prolonged aldosteronism was similar to that described for the turnover rate of rat colonic epithelial cells. Lithium within the lumen had no significant effect in untreated rats but after prolonged aldosterone infusion lithium reduced the p.d. and the transcellular sodium flux although the transport pool was not reduced. These findings are consistent with the hypothesis that aldosteronism renders the apical membranes of the epithelial cells permeable to lithium and that intracellular accumulation of lithium depresses active sodium transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone and thyroid hormone interaction on the sodium and potassium transport pathways of rat colonic epithelium.

The effect of hypothyroidism on potassium adaptation (shown by increased potassium secretion in response to potassium loading) and on the action of aldosterone on potassium secretion and sodium fluxes was examined in the rat distal colon. Potassium adaptation, particularly the response to an acute potassium load, was impaired by hypothyroidism which also considerably reduced the rise of transepithelial electrical potential difference (p.d.) of total and transcellular (active) lumen-to-plasma sodium fluxes and of potassium secretion normally produced by aldosterone. These changes were, in part, corrected by a short period (3 days) of tri-iodothyronine replacement. Moreover in aldosterone-treated hypothyroid rats, amiloride in the lumen was considerably less effective in reducing the p.d. and sodium fluxes than in aldosterone-treated normal rats. The intracellular sodium transport pool was greater in the hypothyroid than in the normal rats (5.0 +/- 1.1 (S.E.M.) nmol/mg dry weight compared with 2.9 +/- 0.2 nmol/mg dry weight; P less than 0.02). Aldosterone increased the pool in the normal but not in the hypothyroid rats while amiloride had little effect on the pool in the aldosterone-treated hypothyroid rats but almost abolished it in aldosterone-treated normal rats. Aldosterone plays a major part in the adaptation of colonic sodium and potassium transport to sodium depletion or potassium excess; these adaptations were much impaired in hypothyroid animals. The present results are consistent with a deficiency in aldosterone induction of potassium- and amiloride-sensitive sodium pathways in the apical membrane of colonic epithelial cells in hypothyroid rats, a deficiency which limits the stimulant effect of aldosterone on sodium and potassium transport.

Effect of aldosterone on lithium permeability of rat colon mucosa.

The effect of aldosterone on the ionic composition of colonic epithelial cells and on lithium absorption rate was studied by experiments on rats in vivo. Aldosterone considerably increased the rate of sodium absorption without measurably altering the sodium and potassium content of the epithelium. Aldosterone did not alter the electrical resistance of the tissue. With lithium in the lumen, the net sodium fluxes in the colon were similar in normal and aldosterone-stimulated rats but the rate of diffusion of lithium across the epithelium was greater in the aldosterone-stimulated group. The amount of lithium accumulating in the epithelial layer was also considerably increased by aldosterone stimulation. Aldosterone appears to increase the permeability of the mucosal (luminal) barrier allowing increased entry of lithium into the colonic epithelial cells.

In-vivo studies of a human-thyrotrophin preparation.

The effects on thyroid function of a new preparation of human thyrotrophin (hTSH) were studied in four subjects whose endogenous production of TSH had been suppressed by administration of thyroxine (T4). The hTSH, prepared from human cadaveric pituitary glands and highly purified using a monoclonal antibody technique, was given as an intravenous bolus of 2 i.u. hTSH. Serum TSH levels rose rapidly to a maximum of about 150 mu./l and then declined exponentially with a half-life of 100 min. After injection, the hTSH distributed rapidly in a volume averaging about 13 litres which corresponded approximately to the expected extracellular fluid volume of the subjects. Serum free tri-iodothyronine and free T4 rose significantly, reaching a maximum between 4 and 8 h after injection of hTSH; serum thyroglobulin was not altered significantly. The rise of thyroid pertechnetate uptake, a measure of the thyroid iodide uptake, occurred later, being only slightly increased at 8 h after administration of hTSH and reaching a maximum at 24 h.

Receptors for thyroid-stimulating hormone in normal and pathological human thyroid tissues.

The receptors for TSH have been studied in human thyroid tissue to assess their density and binding characteristics in various disease states. A single set of similar independent receptors appeared to be present in both healthy and pathological thyroid tissue. Their binding affinity for bovine TSH averaged 1.1 X 10(10) l/mol in healthy tissue and, with the exception of papillary carcinoma which showed some reduction, was not significantly altered in the various disease states studied. No receptors with low binding affinity were found. The number of receptors was significantly greater in toxic diffuse goitre and in hyperfunctioning follicular adenoma (but these tissues came from patients given antithyroid drugs and often iodine preoperatively), and was reduced in Hashimoto's thyroiditis. In well-differentiated thyroid carcinoma, the number of receptors was similar to or greater than in normal tissue, but in undifferentiated and medullary carcinoma, and in lymphoma of the thyroid, receptors were completely absent. Tracer-binding data obtained with human TSH were uniformly lower than the corresponding data obtained with bovine TSH, but showed an analogous pattern of differences amongst the various normal and pathological tissues.

Comparison of binding of bovine and human thyroid-stimulating hormone to receptor sites on human thyroid membranes.

The binding of 125I-labelled bovine TSH (bTSH) to a wide range of human thyroid membrane preparations was compared with that of 125I-labelled human TSH (hTSH). Much higher binding percentages were obtained with the 125I-labelled bTSH. This was because the receptors had a higher binding affinity for bTSH than for hTSH. No differences in tracer purity, nor differences in optimal conditions for the binding of bTSH or hTSH, nor tracer degradation contributed significantly to the better binding of 125I-labelled bTSH. Good correlation was found between binding percentages for 125I-labelled bTSH and 125I-labelled hTSH over the range of thyroid specimens. Useful information on human TSH receptors is, therefore, obtainable from binding studies with 125I-labelled bTSH. The TSH displacement curves yielded linear Scatchard plots whenever the tracer and displacing hormones were of the same species. The data were, therefore, consistent with a simple binding reaction between TSH and a single set of independent receptor sites.

Treatment of Graves' disease by carbimazole: high dose with thyroxine compared to titration dose.

A comparative study of high-dose (HD, carbimazole 60 mg plus thyroxine 100-150 micrograms daily) and titration-dose (TD) regimens of carbimazole was carried out in 70 patients with Graves' disease, the patients being assigned randomly to one or other regimen. The treatment was given for 1 year and follow-up was for 2 years after stopping treatment. In both groups, recurrence of hyperthyroidism occurred, most commonly during the first 6 months (35% of HD and 44% of TD). By 2 years after stopping treatment, recurrence had occurred in 50% of the HD and 66% of the TD group. The differences were not significant. Thyroid antibodies, serum thyroglobulin and pertechnetate uptake fell similarly in both groups during treatment. Cigarette smoking was similar in both the groups and did not influence the frequency of relapse. In both HD and TD groups, when relapsing patients were examined according to whether they relapsed early (within 6 months or less) or late it was found that those who relapsed late were, in respect of goitre size, pertechnetate uptake and presence of detectable plasma TSH, similar to the patients who did not relapse at all. In conclusion, the changes in the measured variables and the progress of the patients was similar whether treated by the HD or TD regimen.

The long-term hazards of the treatment of thyroid cancer with radioiodine.

Two-hundred and fifty-eight patients treated with high-activity 131I for thyroid cancer and on prolonged follow-up have been reviewed to determine long-term hazards and their relation to the radiation dose received. The expectation of life of those dying from causes other than cancer was slightly reduced in the female patients. A small, significant excess of deaths from cancer of the bladder and from leukaemia was found which, assuming that these were due to radiation, gave inferred risk-rates respectively of 0.4 and 4.9 deaths per 10(4) PYG (patient-year-grays) to the bladder wall and red marrow. Of 31 younger patients (eight male, 23 female), four of the marriages have been infertile. The fertile marriages produced a total of 44 live births. Considerable gonad irradiation (estimated 0.8-2.7 Gy) was compatible with apparently normal fertility. Despite the high level of irradiation of the salivary glands, no malignancies and only one adenoma was found. Impaired pulmonary function occurred in only one of the patients who had diffuse bilateral metastases. In this patient, tumour in the lung was persistent throughout, so that radiation was probably not alone responsible.

Serum thyroglobulin in the investigation of patients presenting with metastases.

Serum thyroglobulin (Tg) is often very elevated in patients with metastatic thyroid carcinoma and, in 18 out of 40 patients examined, serum Tg was found to exceed 400 micrograms/l. In only two of 55 patients with benign nodular thyroid disease did serum Tg exceed 400 micrograms/l. In patients presenting with metastases of unknown origin, the finding of a very elevated serum Tg concentration may therefore be of value as an indicator that the metastases are due to thyroid carcinoma. During a period in which 128 new patients with differentiated thyroid carcinoma were seen, in five who presented with metastatic disease the initial estimation of serum Tg had proved useful in suggesting the thyroid origin of the metastases.

Selenium 75 contamination in iodine 131 solutions.

During investigations on athyreotic patients given large test doses of 131I, whole-body counting has shown the presence of 75Se contamination in some patients. The investigations were carried out to measure the small long-term component of 131I retention in such patients. In an earlier paper (Smith and Edmonds, 1977), we concluded that the effects of 75Se contamination were negligible in the patients described. Subsequent studies on a further small group of similar patients, however, have indicated that the levels of contamination are variable, and this report is intended as a warning of the possibility of measurement error due to this contamination in metabolic studies similar to those to be described. The effects of 75Se contamination observed in two out of five patients studied have been assessed.

Measurement of serum TSH and thyroid hormones in the management of treatment of thyroid carcinoma with radioiodine.

1. Serum levels of TSH, thyroxine (T4) and triiodothyronine (T3) have been measured during treatment and follow-up of patients with thyroid carcinoma. 2. Serum TSH and thyroid hormone levels were initially normal. Three weeks after total thyroidectomy, TSH was elevated in about 50% of patients and after a subsequent therapy dose of 131I it exceeded 30 mU/l in 90% of patients. Occasionally, TSH did not rise until after the second dose of 131I. Low serum T4 and T3 concentrations were associated with the increase of TSH. 3. Withdrawal of l-thyroxine replacement treatment in athyreotic patients for four weeks before test doses of 131I, led to falls of serum T4 and T3 concentration and a progressive rise of serum TSH after the first weeks but there was considerable variation in the final level reached. In the majority, values greater than 30 mU/l were attained despite some patients having received l-thyroxine for many years. A few patients on prolonged thyroxine maintenance had little or no increase in TSH despite considerable reduction in serum T4 and T3 concentrations. 4. The 131I concentration (muCi/g) developed in tumour tissue was also examined in relation to the serum TSH level. In general a tumour should not be considered as incapable of concentrating 131I adequately until serum TSH levels have exceeded 30 mU/l.

Measurement of exchangeable sodium: 22Na or 24Na?

A case is made for the use of 22Na in low activities in preference to 24Na for routine diagnostic estimation of exchangeable sodium, and is based chiefly on considerations of availability, cost and radiation dosimetry. A method in which only 37 kBq (1 microCi) 22Na is administered orally is shown to be sufficiently accurate and to possess distinct advantages in terms of cost and convenience with a committed radiation dose no greater than that for a measurement using 24Na.

US-Canada Great Lakes Regional Specimen Bank Feasibility Study.

A study to examine the feasibility of establishing a Regional Specimen Bank in the Great Lakes area of the United States and Canada has recently been initiated by the Michigan Audubon Society. There are several existing formal and informal specimen banking facilities active in the region but their combined adequacy has not been evaluated. This feasibility study will establish the need and use of a regional bank and the institution(s) necessary to satisfy this need will be recommended. The study will address the scope required to meet present and future needs including the types of specimens to be represented in the bank, geographic coverage and protocols for collection, shipping, processing, analysis and storage. A management policy of the bank will be developed encompassing business operation, costs, governing structure and personnel requirements. The legal requirements of the bank will be determined with regards to the acquisition of samples, transport across national boundaries, access to specimens and information, and liability during operation. An effective information dissemination network will be recommended that is compatible with national and international partners, will facilitate technology and information transfer and support the quality and status of the bank. Determination of secure, long-term funding sources will be one of the key elements to ensuring a safe repository. This feasibility study is funded by the Great Lakes Protection Fund.

Absorption and secretion of fluid and electrolytes by the rectum.

Although the amounts of ions and water absorbed and secreted by the rectum are small compared to those of other parts of the colon, rectal epithelium is capable of generating and maintaining considerable ionic gradients. Absorption of Na+ and Cl- and secretion of K+ and HCO-3 leads to relatively low concentrations of the former and high concentrations of the latter within the lumen. Detailed examination of the transport processes indicates that the epithelial mechanisms can be interpreted in terms of ionic movements through transcellular and paracellular pathways. These results show that the epithelium is relatively tight and largely amiloride-sensitive. Active Na+ absorption and apparent active K+ and HCO-3 secretion occur. The secretion of HCO-3 is related to Cl- and organic anion absorption. Mineralocorticoids increase the transepithelial potential difference (p.d.) as well as stimulating Na+ absorption and K+ secretion. Rectal epithelium may, with various physiological or pathological stimuli, become overtly secretory of a predominantly NaCl containing fluid but it remains uncertain whether some secretion is normally present although masked by absorption.