Acute effects of acetazolamide on cerbral blood flow in man

We have followed the time course of the effect of the carbonic anhydrase inhibitor acetazolamide injected i. v. in unanesthetized healthy human beings. The dose administered was 500 mg as a bolus. Cerebral blood flow (CBF) was measured continuously before, during and after the injection, using a pulsed ultrasound doppler system, which measured the instantaneous mean velocity across the lumen of the internal carotid artery, just below its entrance into the skull. Ventilation, heart-rate, end-expiratory PCO₂- arterial PCO₂, pH and systemic blood pressure was also measured. We found that acetazolamide caused a rise in CBF which could be detected as early as 2 min after the injection. A maximal average response of 75% increase in CBF was seen after 25 min. The half-time of the declining phase of the response was 95 min. There were no systematic differences in the CO₂ reactivities, given as ACBF/ΔPACO₂ in % of CBF at normocapnia, before and after acetazolamide injection, regardless of the absolute PACO₂ level. The present dose of the drug caused no change in ventilation, alveolar and arterial PCO₂ or in arterial blood pH indicating that the carbonic anhydrase was not fully inhibited. Our observations show that acetazolamide nevertheless caused a rapid vasodilation in the brain and over a wide range of PCO₂′s. We suggest that this agent has a local vasodilator effect on the cerebral arterioles, unrelated to its specific effects as a carbonic anhydrase inhibitor.     

Ultrasound study of the cranial venous system in the human new-born infant and the adult

A pulsed doppler ultrasound technique has been used to measure changes in blood velocities in the superior sagittal sinus, the jugular veins and intracranial and extracranial arteries in 13 neonates, and in the jugular veins and an extracranial artery in 13 adults, during unilateral and bilateral jugular venous compressions. The results have enabled us to determine how the subject under examination functionally uses his cranial venous drainage system in the resting state, and whether or not he can shunt obstructed venous flow through other cranial venous channels. We have found great variability between the subjects. In the resting situation the range of possibilities from total dependence on one jugular vein alone to usage of both jugular veins and the vertebral veins exists. Shunting of blood on jugular compression from either or both jugular veins to the vertebral veins may occur, and contralateral shunting between the jugular veins may be possible in both directions, in one direction or not at all.     

Effects of sympathetic stimulation on cerebral and ocular blood flow Modification by hypertension,hypercapnia, acetazolamide,PGI2 and papaverine

The effect of unilateral, electrical stimulatio of the cervical sympathetic chain in rabbits anesthetized with pentobarbital sodium and vasodilated by hypercapnia, acetazolamide, papaverine or PGI₂ was investigated to determine to what extent the sympathetic nerves to the brain and the eye cause vasoconstriction and prevent overperfusion in previously vasodilated animals. Evans blue was given as a tracer for protein leakage. Blood flow determinations were made with the labelled microsphere method during normotension and acute arterial hypertension. Hypertension was induced by ligation of the thoracic aorta and in some animals metaraminol or angiotensin was also used. Acetazolamide caused a two to threefold increase in cerebral blood flow (CBF) and hypercapnia resulted in a fivefold increase. CBF was not markedly affected by papaverine or PGI₂. In the choroid plexus, the ciliary body and choroid, papaverine and hypercapnia caused significant blood flow increases on the control side. Sympathetic stimulation induced a 12 % blood flow reduction in the brain in normotensive, hypercapnic animals. Marked effects of sympathetic stimulation at normotension were obtained under all conditions in the eye. In the hypertensive state the CBF reduction during sympathetic stimulation was moderate, but highly significant in hypercapnic or papaverine-treated animals as well as in controls. Leakage of Evans blue was more frequently seen on the nonstimulated side of the brain. In the eye there was leakage only on the control side except in PGI₂-treated animals where 2 rabbits had bilateral leakage. The effect of sympathetic stimulation on the blood flow in the cerebrum and cerebellum in vasodilated animals seems to be small or absent if the blood pressure is normal. In the eye pronounced vasoconstriction occurs under these conditions. In acute arterial hypertension sympathetic stimulation protects both the cerebral and ocular barriers even under conditions of marked vasodilation.     

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation

Summary. There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high‐sensitivity interleukin‐6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. Methods: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0–3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed‐up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. Results: At follow‐up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS₂ score: HR 2.21 (1.46–3.35, P < 0.001) for high hsTnT and 1.97 (1.29–3.02, P = 0.002) for high hsIL6, for adverse cardiovascular events. For all‐cause mortality, the HRs were 1.79 (1.13–2.83, P = 0.013) and 2.48 (1.60–3.85, P < 0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS₂ and CHA₂DS₂‐VASc) were improved by the addition of hsTnT and/or hsIL6 (all P < 0.05). Conclusion: In a large ‘real world’ cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long‐term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.     

Identification and characterization of human B-cell epitopes in recombinant antigens of Leishmania aethiopica

Recombinant DNA fragments from Leishmania aethiopica that code for epitopes which react with human antibodies have been characterized by cross-hybridization studies and DNA sequence analysis. Twenty clones could be grouped into seven different groups (I–VII), probably representing seven different L. aethiopica antigens. The DNA sequences of representative clones from the seven groups have been obtained and the amino acid sequence of the respective recombinant antigens established. The recombinant antigens have been analysed by epitope scanning with patient sera, and octapeptides that contain potential B-cell epitopes have been identified in all seven recombinant antigens. These octapeptides have further been tested with additional patient sera and control sera, and three octapeptides (HAFCHEEG, YHSSVVHD and SYAPCSLK) were found to contain major epitopes recognizing specific antibodies in nine, seven and four, respectively, of the twenty sera tested. Fifteen of the twenty sera reacted with one or more of these three octapeptides.     

A Follow-up Study of Children with Neonatal Herpes Simplex Virus Infections with Particular Regard to Late Nervous Disturbances

Forty-five children with neonatal herpes simplex virus (HSV) infection, representing all known cases in the diagnostic records of four virological laboratories within a 15-year period, were followed up. Twelve children had died. Sixteen of the 33 survivors were healthy. Thirteen children had severe disabilities: all of them showed severe mental retardation; moreover, 11 were tetraplegic, one was hemiplegic with hydrocephalus and one had a pronounced behavioural abnormality. Four children had slight to moderate disabilities: one child was mildly mentally retarded and three, although mentally normal, had hemiplegia and delayed speech development, one of them having a learning disorder as well. Of these 17 neurologically impaired children 16 had ophthalmological abnormalities. EEG recordings were made in 29 patients in the neonatal period. They were markedly abnormal in 24 patients, 14 of whom had localized periodic complexes. An abnormal EEG was a bad prognostic sign. The neurological outcome was better in the HSV-l-infected children (10 cases) than in the HSV-2-infected ones (35 cases). Progressive or recurrent encephalitis was strongly suspected in two preterm children.     

Self-Reported Health Status and Use of Medical Care by 3500 Adolescents in Western Sweden. I

ABSTRACT. Some 3500 adolescents answered a questionnaire anonymously. The sample represented 85 % of the students between the ages 13 to 16 and 65 % of the students between 17 to 18 in the three communities studied. The students all had middle class backgrounds. Self-reported illness differed considerably from data found in epidemiological surveys. The self-reported medical panorama was dominated by concerns about acne, tiredness, headaches, stomach pains, sports injuries and allergic disorders. One quarter to one third of the students reported such problems. Overall, 85% of the students reported that they were "completely healthy", at the same time as they also reported an average of 3.1 medical complaints. Self-initiated appointments with physicians were reported with an average of 5.5 during the last year, which is high. About 40% of the students had one complaint for which they wanted to see a physician. About 15% reported that they had had suicidal thoughts.