Effect of prior exercise in Pi/PC ratio and intracellular pH during a standardized exercise. A study on human muscle using [31P]NMR

Seven subjects underwent a standard localized exercise of calf muscles in order to investigate whether the metabolic exercise-induced steady-state, as revealed by the evaluation of inorganic phosphate/phosphocreatine ratio, depends on the conditioning of the muscle just prior to the exercise. The experimental protocols consisted of two separate experiments using first [³¹P]nuclear magnetic resonance spectroscopy and second (on 3 subjects) infrared oxyphotometry to respectively follow variation of energy metabolism and tissular deoxygenation. The exercise consisted of 240 successive plantar flexions (0.5 Hz frequency) against a high load equivalent to SO% of the maximal voluntary contraction. This exercise was accomplished before cold exercise and after warm exercise, a warming-up period bringing to approximately 50% of Vo_2max. The results showed that: (1) steady-state level of phosphate/phosphocreatine and intracellular acidosis was significantly lowered by warming-up; (2) cold and warm exercise steady-state of calculated adenosine diphosphate values were not significantly different; (3) cold exercise rapidly induced a high tissular deoxygenation that is not observed during warm exercise; and (4) time-constant of phosphocreatine resynthesis is lowered after warm exercise but the initial slope of time-evolution is not modified. Parallel experiments also showed that phosphate/phosphocreatine steady-state was not modified in comparison with warm exercise when the same power of exercise was reached by stepwise incrementation of the charge. From these results we postulate that a better tissue oxygenation due to a global or localized warming-up allows to reach the same mechanical performance with a lower decrease of PCr content, owing to a faster adjustment of oxidative metabolism during the transitional period. However the aerobic pathway flux during the steady-state is probably the same before and after the warming-up despite different values of phosphate/phosphocreatine. As a consequence it can be assumed that this ratio is not a good indicator of the rate of muscle oxidative metabolism during the steady-state phase of the exercise.     

Monosodium Glutamate Affects Mealtime Food Selection in Diabetic Patients

Lunch intake was followed in 31 matched pairs of hospitalized diabetic patients over four consecutive days. Pairs of patients were matched for type and duration of diabetes, gender, age and body mass index. Lunches were composed of appetizer, meat, vegetables, starch, cheese, bread and dessert; water, coffee, tea and lemon were available. One patient per pair was randomly ascribed to the experimental group and was served vegetable and starch dishes added with 0·6% monosodium glutamate (MSG). Lunch intake was measured by weighing amounts served and left-overs. Patients in the experimental group ingested more starch food than their matched controls, and less lemon juice and yogurt. However, the total energy load at lunch was not different between groups. This effect on meal time food selection replicates earlier observations made on elderly persons. It is suggested that manipulating palatability of various foods within a meal, and especially by using MSG, is an efficient way to affect food selection in the meal, without inducing hyperphagia.     

The Changes in the Hypothalamo-Pituitary-Gonadal Axis of Streptozotocin-Treated Male Rats Depend from Age at Diabetes Onset

The influence of age at diabetes onset and of capillary microangiopathy on the severity and evolution of hypothalamo-pituitary-gonadal changes was studied morphologically and morphometrically in male rats 4 and 8 months after streptozotocin injection. At each time period we studied 2 groups of rats, one made diabetic before (age 1 month), the other after puberty (age 3 months), and compared them with corresponding controls. The size of hypothalamic axons, numerical density and size of pituitary gonadotrophs, size of testicular tubules, and basement membrane thickness of retinal capillaries were measured. Major differences were found at 8 months. Changes of pituitary glands (i.e. small and numerous gonadotrophs) and testes (i.e. small tubular size) were more important in pre- than in postpubertal diabetic rats. This was a consequence of the aggravating prepubertal diabetes between 4 and 8 months. On the contrary, these changes partially regressed in postpubertal diabetic animals. Pituitary and testicular changes were correlated. Other lesions, such as swollen axonal processes in the hypothalamus, increased thickness of seminiferous epithelium and of capillary basement membranes, though very evident in diabetics, were independent from age at induction. Neither microangiopathy nor glycemia were correlated with any other change which confirmed their secondary role in diabetic neuroendocrine disorders. Thus, two types of diabetic disorders of the hypothalamo-pituitary-gonadal axis could be distinguished: 1) those with irreversible effects on immature yet partially reversible effects on mature structures; and 2) those independent from age at induction.     

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability in the Rat

Bioavailability of Soil-Bound TCDD: Dermal Bioavailability inthe Rat. SHU, H., TEITELBAUM, T., WEBB, A. S., MARPLE, L., BRUNCK,B. DEI ROSSI, D., MURRAY, J., AND PAUSTENBACH, D. (1988). Fundam.Appl. Toxicol. 10, 335-343. 2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD), an unwanted by-product formed during the manufactureof hexachlorophene and phenoxyherbicides, has been found asan environmental contaminant in many U.S. and Western Europeansites. This study examines in the rat the degree of dermal absorptionof TCDD bound to soil. Such information would assist regulatoryagencies in evaluating the degree of exposure of humans whocome in contact with TCDD-contaminated soil. Several parameterswhich may influence dermal absorption were studied, includingTCDD dose, duration of contact, presence of crankcase oil asa co-contaminant, and environmentally contaminated vs laboratory-preparedsoil. The dermal penetration of TCDD following 4 hr of contactwith skin was approximately 60% of that following 24 hr of contact(P 0.05). Following 24 hr of contact with the skin, the degreeof dermal uptake of TCDD contaminated soil was approximately1% of the administered dose. Under the conditions of the presentstudy, the degree of uptake does not appear to be influencedto any significant extent by the concentration of TCDD on soil,the presence of crankcase oil as co-contaminants, or by environmentallyvs laboratory-contaminated soil. Although a number of parametersexamined in this study did not significantly influence the degreeof dermal absorption of TCDD in the rat following 24 hr of contactwith the contaminated soil, the unqualified use of the 1% valueto estimate human exposure would overestimate human exposure,since there is general agreement among researchers that ratskin tends to be more permeable than human skin to highly lipid-solublecompounds such as TCDD.     

Electrophysiologic and histopathologic correlations in a case of permanent form of reciprocating tachycardia

A case of permanent junctional reciprocating tachycardia withpost-mortem documentation of an accessory atrioventricutar pathwayas the substrate of the arrhythmia is reported. Tachycardiahad lasted for 15 years and showed a retrograde P wave (P')and R–P' longer than P'–R interval. The tachycardiacircuit utilized a concealed posterior septal accessory pathwayas the retrograde limb. Because the arrhythmia was disablingand unresponsive to pharmacological treatment, the patient underwentclosed chest ablation of the His bundle. After the procedure,no anterograde or retrograde conduction over the normal conductionsystem was observed; anterograde conduction over the anomalouspathway showed decremental properties. Because of previous myocardialinfarction, the patient developed a ventricular aneurysm anddied suddenly 5 months after His bundle ablation. Histologicalexamination of the heart revealed a group of tiny fibromuscularbundles joining the lower rim of the coronary sinus outlet tothe summit of the interventricular septums; the anomalous atrioventricularconnection pursued a sinuous, tortuous path. The geometricaldisposition of the accessory pathway may have been responsiblefor the decremental properties of conduction observed duringlife.     

Lack of Influence of Atrioventricular Delay on Stroke Volume at Rest in Patients with Complete Atrioventricular Block and Dual Chamber Pacing

Dual chamber pacing (DDD) maintains atrioventricular (AV) sequence; AV delay programmability modifies the relationship between atrial and ventricular contraction. To evaluate the hemodynamic effects of such a modification, ten patients with a DDD unit for complete AV block were studied by time-motion (M-mode) and Doppler echocardiography during inhibited ventricular pacing (VVI), atrial-triggered ventricular pacing (VDD) and atrioventricular sequential pacing (DVI) at different AV delay (90, 140, 190, 240 msec). A significant improvement in stroke volume (SV) (15%-20%, P less than 0.05) was seen during DDD versus VVI pacing; no changes, however, were observed in the same patient with different AV delay or during DVI versus VDD pacing. These data suggest that programming of AV delay does not affect systolic performance at rest; longer diastolic filling times recorded during DDD pacing with "short" AV delay (90-140 msec) do not seem to be a hemodynamically relevant epi-phenomenon of PM programming.     

Thyroid function in a population of children with attention deficit hyperactivity disorder

To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated.

Method:

Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed.

Results:

The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%.

Conclusion:

Routine thyroid hormone screening is not indicated in children with non-familial ADHD.     

The influence of HLA-matched sibling donor availability on treatment outcome for patients with AML: an analysis of the AML 8A study of the EORTC Leukaemia Cooperative Group and GIMEMA

To determine whether patients with a HLA-identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention-to-treat principles was performed within the framework of the EORTC-GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease-free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P = 0.01, RR 0.78, 95% confidence interval 0.63–0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P = 0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.