Extracranial-intracranial bypass surgery for the management of vasospasm after subarachnoid hemorrhage

A case is presented which demonstrates the potential utility of the extracranial-intracranial bypass procedure for the treatment of vasospasm after subarachnoid hemorrhage. Extracranial-intracranial bypass surgery offers another alternative to the treatment of patients with vasospasm who have failed aggressive medical management.     

Both alpha- and beta-adrenoreceptors contribute to the central depressor effect of catecholamines

We compared the effects of alpha 2- and beta-adrenoreceptor blockade on the central actions of catecholamines and metabolites of alpha-methyldihydroxyphenylalanine, epinephrine, alpha-methylnorepinephrine, and alpha-methylepinephrine were studied. I.c.v. and nucleus tractus solitarii (NTS) injections were carried out under anesthesia. Following i.c.v. injection, both epinephrine and methylepinephrine rapidly reduced blood pressure and heart rate, but the effects of methylnorepinephrine occurred somewhat later. Following microinjection into the nucleus of the solitary tract, epinephrine, methylepinephrine, and methylnorepinephrine all caused hypotension and bradycardia. The hypotensive effects of all 3 amines in the NTS were attenuated in additive fashion by yohimbine, an alpha 2 adrenoreceptor antagonist, and timolol, a beta-adrenoreceptor antagonist, whereas only yohimbine attenuated the bradycardia. The combination of yohimbine and timolol abolished the effects of the amines. These data suggest that in the NTS both alpha 2 and beta adrenoreceptor stimulation contribute to the hypotensive effects of these amines, but that only alpha 2 adrenoreceptors are principally involved in the heart rate response.     

Pressure suppresses serotonin release by guinea pig striatal synaptosomes

Exposure to high pressure produces neurologic changes in humans which manifest as tremor, EEG changes, and convulsions. Since previous studies have implicated the involvement of the serotoninergic system in these symptoms, it was of interest to study serotonin release at high pressure. Synaptosomes isolated from guinea pig striatum were used to follow serotonin efflux at 68 ATA. The major observation was a decrease in [3H]serotonin release from depolarized striatal synaptosomes at 68 ATA. In view of the role of serotonin as an inhibitory neurotransmitter in this area, the observed decrease in synaptic release leads us to conclude that decreased serotoninergic activity in striatal neurons probably is contributing to the hyperexcitability associated with HPNS.     

Assessment of sodium and potassium intakes

The sodium, potassium and creatinine contents of three non-consecutive 24-h urine samples collected by 34 selected adult individuals (10 m; 24 f) living in Cork City were determined. The pooled mean 24-h excretion of sodium and potassium in collections adjudged to be complete were 152 mmol and 78 mmol, respectively. There was no significant difference between group average weekday and weekend-day excretion of Na or K, for either males or females. This suggests that weekend 24-h urinary collections, which most subjects find more convenient, are suitable for studies of sodium and potassium intakes of groups. The ratios of intra- to inter-individual variation for 24-h urinary sodium were 1.4 and 2.1 for males and females, respectively. The corresponding ratios for 24-h urinary potassium were 6.6 for males and 4.9 for females. These ratios indicated that there were large individual day-to-day variations in urinary sodium and potassium excretion in this group. It was estimated that a sample size of 35-60 individuals would be required to estimate group mean sodium and potassium intakes by means of single 24-h urine collections.     

Disc haemorrhages and glaucoma in a general ophthalmic practice

The composition of the clientele from an ophthalmological practitioner's office is described with special reference to the occurrence of glaucoma and disc haemorrhages (h in singular; hh in plural). This study could not be planned as an epidemiological survey and gives no clue to sensitivity or specificity of hh in glaucoma. During a period of about 10 years ending with 1986 there were 731 patients with h and/or glaucoma. When detected, 185 patients had h but no glaucoma, 33 had both h and glaucoma and 513 had glaucoma but no h. During the follow-up period hh were detected in 83 cases of glaucoma, and glaucoma developed in 27 cases with hh. The detection rate of hh among glaucoma was low but steady, indicating that hh may occur at any stage of the glaucoma process. This study shows no predilection for hh in cases with general hypertension or diabetes, nor is the frequency of hh among pseudoexfoliation cases significantly lower than among cases without this stigma.     

Estimating Potency for the E max-Model Without Attaining Maximal Effects

The most widely applied model relating drug concentrations to effects is the E_max model. In practice, concentration–effect relationships often deviate from a simple linear relationship but without reaching a clear maximum because a further increase in concentration might be associated with unacceptable or distorting side effects. The parameters for the E_max model can only be estimated with reasonable precision if the curve shows sign of reaching a maximum, otherwise both EC₅₀ and E_max estimates may be extremely imprecise. This paper provides a solution by introducing a new parameter (S₀ ) equal to E_max/EC₅₀ that can be used to characterize potency adequately even if there are no signs of a clear maximum. Simulations are presented to investigate the nature of the new parameter and published examples are used as illustration.     

“Vinylogs” and “Acetylenylogs” of β-Adrenergic Agents

Vinylogous (Groups III and V ) and acetylenologous (Group IV ) analogs of the classical β-adrenergic agents — stimulants and blockers — were prepared in order to evaluate the effect of degree of saturation, position of unsaturation and rigidity of the chain linking the aromatic ring and the amino containing functional group on biological activity. Derivatives from Group III , which represent 4-aryl-3-butenyl-2-ol-amine analogs of Group II , retained β₁-adrenoceptor antagonist activity albeit substantially less potent (50–200-fold) than that possessed by their aryloxy counterparts. Consistent with the SAR for Group II compounds, substitution at position 2 of the aromatic ring yielded the most potent antagonists ( 5a, 5d, 5g ), with K_B's ranging from 73–93 nM while 3,4-dichloro substitution ( 5e ) markedly reduced antagonist potency (K_B = 2,400 nM). Agonist activity was also noted for 5b and 5d , suggesting that these compounds may be best classified as partial agonists. Representatives from Groups IV and V were inactive as antagonists at the β₁-adrenoceptor confirming the importance of the spatial relationship between the hydroxyl and the amino nitrogen.     

Measurements of Blood Pressure, Oedema and Proteinuria in a Pregnant Population of New Zealand

Summary: This is the first report of the largest study of blood pressure measurement in pregnancy in a New Zealand population using standardized definitions and methodology. Over 3,800 women who delivered in an 8-month period in the Wellington region were included in the study. Blood pressure measurement and the presence of oedema and proteinuria were recorded from booking until delivery and in the puerperium. Only 2.7% of women were unable to be contacted after delivery for details on outcomes. The results established normal ranges for blood pressure throughout pregnancy. The data show that Mood pressure greater than 140/90 until 35 weeks' gestation is outside 2 standard deviations at all gestations and justifies using these measurements as the definition of hypertension in pregnancy. The fall in blood pressure in the 2nd trimester was less than 1 mm Ffg per week in both the systolic and diastolic pressures. This fall was smaller than previously recorded in other studies. Gestational hypertension was the commonest blood pressure abnormality occurring in 15.2% of the population. This represented 69% of the pregnant women with a hypertensive disorder. The overall incidence of both gestational hypertension and preeclampsia was 18.5% which is higher than reported in other parts of the world. In this study obesity was significantly associated with hypertensive disorders in pregnancy. An arm circumference of >33 cm, one of the measurements of obesity, was found in 6.8% of the study population. Even after the effect of arm circumference was taken into account, hypertensive disorders were also more common in Pacific Island women. Ankle oedema was significantly associated with the development of both gestational hypertension and preeclampsia but the incidence of oedema was noted in only 11.9% of the subjects.     

An analysis of astrocytic cell lines with different abilities to promote axon growth

The adult mammalian central nervous system (CNS) lacks the capacity to support axonal regeneration. There is increasing evidence to suggest that astrocytes, the major glial population in the CNS, may possess both axon-growth promoting and axon-growth inhibitory properties and the latter may contribute to the poor regenerative capacity of the CNS. In order to examine the molecular differences between axon-growth permissive and axon-growth inhibitory astrocytes, a panel of astrocyte cell lines exhibiting a range of axon-growth promoting properties was generated and analysed. No clear correlation was found between the axon-growth promoting properties of these astrocyte cell lines with: (i) the expression of known neurite-outgrowth promoting molecules such as laminin, fibronectin andN-cadherin; (ii) the expression of known inhibitory molecules such tenascin and chondroitin sulphate proteoglycan; (iii) plasminogen activator and plasminogen activator inhibitor activity; and (iv) growth cone collapsing activity. EM studies on aggregates formed from astrocyte cell lines, however, revealed the presence of an abundance of extracellular matrix material associated with the more inhibitory astrocyte cell lines. When matrix deposited by astrocyte cell lines was assessed for axon-growth promoting activity, matrix from permissive lines was found to be a good substrate, whereas matrix from the inhibitory astrocyte lines was a poor substrate for neuritic growth. Our findings, taken together, suggest that the functional differences between the permissive and the inhibitory astrocyte cell lines reside largely with the ECM.