Binding of [3H]-5-hydroxytryptamine to human coronary artery and bypass graft vessels.

OBJECTIVES: 5-Hydroxytryptamine (5-HT) has a wide range of vascular effects mediated via specific receptors and it has been suggested to be a mediator in ischemic heart disease. The aim of the present study was to localise the 5-HT receptors within the vessel wall. METHODS: Epicardial coronary arteries obtained from patients undergoing cardiac transplantation, internal mammary arteries from heart donors and saphenous veins from patients undergoing coronary bypass surgery, were sectioned and incubated with [3H]-5-HT for in vitro receptor autoradiography. RESULTS: Microscopic analysis of high resolution autoradiographic images revealed a similar pattern of [3H]-5-HT binding in epicardial coronary and internal mammary artery, where it predominated in the lamina muscularis. In the saphenous vein, binding increased towards the adventitia which showed dense, displaceable binding to the vasa vasorum as well as to nerve-like structures, from which binding was only partially displaced. Computer-assisted densitometric analysis of low resolution autoradiographs revealed a high degree of specific binding to all vessels examined. CONCLUSIONS: The distribution of the [3H]-5-HT binding is different in the saphenous vein compared to epicardial coronary and internal mammary artery. The dense binding to vasa vasorum in the saphenous vein suggests a role for 5-HT in closure of these nutrient vessels, which could contribute to the formation of atherosclerotic changes in saphenous vein grafts.

Central distribution of substance P, calcitonin gene-related peptide and 5-hydroxytryptamine in vagal sensory afferents in the rat dorsal medulla.

The central distribution of vagal afferents in the medulla containing either substance P, calcitonin gene-related peptide or 5-hydroxytryptamine was examined using a double-labelling technique and laser scanning confocal microscopy. Areas of the nucleus tractus solitarii, dorsal motonucleus of the vagus nerve and area postrema were scanned for double-labelled axon profiles. Analysis of this material revealed that all three neurochemicals were contained within the central terminals of vagal nerve sensory neurons. However, the distribution of vagal nerve afferents containing each of these putative transmitters differed. Afferents containing 5-hydroxytryptamine were detected mainly in the areas postrema and the adjacent nucleus tractus solitarii, with a smaller number in the ventral subnuclei of the solitary tract. In contrast afferents containing calcitonin gene-related peptide were found primarily in the medial and commissural regions of the nucleus tractus solitarii. Afferents containing substance P-immunoreactivity were surprisingly few in number and did not appear to be associated with any particular region. These results establish the presence of 5-hydroxytryptamine, substance P and calcitonin gene-related peptide in the central axons of vagal sensory afferents. Furthermore, the differential distribution of afferents immunoreactive for these neurochemicals seen in this study, together with previous demonstrations of the viscerotopic organization of vagal sensory afferents suggests a possible "chemical coding" for individual end organs.

Distribution of 125I-labelled insulin-binding sites in peripheral tissues of the normal and diabetic rat: an autoradiographic study.

In-vitro autoradiography was used to demonstrate the regional distribution of 12I-labelled insulin-binding sites in the liver, kidney and heart of normal rats and rats made diabetic with streptozotocin. The distribution of insulin-binding sites in the liver of control rats was uniformly high, while in the kidney of control rats there was weak 125I-labelled insulin binding in the medulla and dense binding in the cortex. In the hearts of control rats a high density of 125I-labelled insulin-binding sites was evident both in the atrial and ventricular muscle. Non-ketotic diabetes mellitus caused a marked increase in 125I-labelled insulin-binding sites in both the liver and kidney with the former tissue exhibiting a time-dependent (7 to 62 days) increase. There was no apparent effect of diabetes on insulin-binding sites in the heart. Since experimental diabetes causes (1) a decrease in circulating insulin concentration and (2) impaired insulin action at many target tissues, the increase in 125I-labelled insulin-binding sites observed in the present study may represent a compensatory 'up regulation' of insulin receptors.

Identification of [(125)I]endothelin binding sites in human coronary tissue.

In vitro receptor autoradiography has been used to study the distribution of [(125)I]endothelin binding sites in human coronary tissue from patients undergoing cardiac transplantation. Dense binding of [(125)I]endothelin was associated with the smooth muscle of epicardial coronary arteries as well as to perivascular regions of these vessels. Binding was also associated with the ventricular myocardium. There was an increased binding of [(125)I]endothelin to atheromatous tissue, both coronary arteries and vein graft. The [(125)I]endothelin binding sites identified using in vitro autoradiography are likely to be functionally relevant since endothelin causes a concentration-dependent contraction of segments of human epicardial coronary arteries in vitro and also has positive inotropic activity on isolated human cardiomyocytes. The presence of specific binding sites for [(125)I]endothelin on coronary tissue and the increased binding in atheromatous tissue suggest that endothelin is a peptide which may play a role in the maintenance of vascular tone and/or the pathogenesis of ischaemic heart disease.

Demonstration of glutamate immunoreactivity in vagal sensory afferents in the nucleus tractus solitarius of the rat.

To investigate whether glutamate is a neurotransmitter in vagus nerve sensory afferents terminating in the nucleus tractus solitarius, these terminals were identified by the anterograde transport and their glutamate content examined using the post-embedding immunogold technique. After injection of horseradish peroxidase into the nodose ganglion anterogradely labelled axonal boutons were visualized throughout the nucleus of the solitary tract (nTS), the dorsal motonucleus of the vagus nerve (DVN), predominantly ipsilateral to the injection, and to a lesser extent in the area postrema. Electron microscopic analysis of 47 anterogradely labelled boutons in the nTS following post-embedding immunocytochemistry for glutamate revealed that 43 of these boutons (> 91%) contained a level of glutamate immunoreactivity significantly greater (P < 0.001%) than that observed in the surrounding tissue. The observed enrichment of glutamate immunoreactivity in boutons identified as vagus nerve sensory afferents indicate that glutamate may be a transmitter in these neurones.

gamma-Aminobutyric acid immunoreactive structures in the nucleus tractus solitarius: a light and electron microscopic study.

gamma-Aminobutyric acid immunoreactive perikarya and boutons in the nucleus tractus solitarius of the cat were examined at both the light and electron microscopic level. Immunoreactive neurones were found predominantly in the parvocellular subdivision of the nucleus tractus solitarius and to a lesser degree in all the other subdivisions of the nucleus tractus solitarius and the dorsal vagal motonucleus. All the immunoreactive perikarya observed were similar in size and morphology. gamma-Aminobutyric acid immunoreactive boutons were observed throughout the nucleus tractus solitarius. However, in contrast to its high content of immunoreactive perikarya the parvocellular subdivision contained the lowest density of immunoreactive boutons. Ultrastructural examination of immunoreactive boutons in the different regions of the nucleus tractus solitarius revealed that they formed synaptic specializations, predominantly with dendritic shafts, all of which were of the symmetric type. This pattern of innervation was observed throughout the medial, commissural, ventrolateral and parvocellular subdivisions of the nucleus tractus solitarius.

A functional study of uncrossed and crossed pulmonary afferent fibres in the cervical vagus nerves of the cat.

The functional distribution of uncrossed and crossed pulmonary afferent fibres in the cervical vagus nerves has been studied in the anaesthetized cat using acute and chronic unilateral pneumonectomized preparations. The heart and lungs were sympathectomized routinely. The vagal afferent pathways of three pulmonary reflexes were investigated: the Hering-Breuer respiratory reflex, the lung inflation cardio-accelerator reflex, and the pulmonary chemoreflex. Inflation of the remaining lung caused temporary inhibition of inspiration. It also resulted in acceleration of the heart, but only when the background cardiac vagal tone was augmented. These respiratory and cardiac responses were abolished in most animals by ipsilateral cervical vagotomy; however, in some, a small response persisted and this was abolished by contralateral vagotomy. Stimulation of pulmonary C-fibre endings with right atrial injections of phenylbiguanide caused a reduction in respiration, bradycardia and systemic hypotension, responses which occurred with a latency of 2.9 +/- 0.15 s. They were mostly abolished by ipsilateral cervical vagotomy, but reduced responses persisted in a few animals. The residual responses were abolished by contralateral cervical vagotomy and by selective denervation of the lung. These results indicate that most afferent fibres subserving the three pulmonary reflexes studied run in the ipsilateral cervical vagus, representing the uncrossed pathway. Some afferent fibres, however, cross to the contralateral cervical vagus. Degenerative changes in cells of the contralateral nodose ganglion in chronic unilateral pneumonectomized animals support these findings.

Acute intermittent porphyria, seizures, and antiepileptic drugs: a report on a 3-year-old Nigerian boy.

A 3-year-old Nigerian boy was treated with phenobarbitone after having a nonfebrile seizure. Two weeks later his urine was found to contain porphobilinogen, indicating that latent acute intermittent porphyria had been unmasked by phenobarbitone. The drug was discontinued and carbamazepine was substituted. The urine became free of porphobilinogen and the patient remained well. In developing countries phenobarbitone is the most widely used anticonvulsant; it must be avoided in acute intermittent porphyria, and carbamazepine may be tolerated.

Cerebrospinal fluid/serum lactic acid in febrile convulsions.

Cerebrospinal fluid/serum lactic acid was prospectively assayed in 42 patients with febrile convulsions. Patients were divided into two groups for analytical purposes. Those with brief febrile seizures (30 patients) and the remaining 12 patients had prolonged febrile seizures. CSF and serum lactic acid values were within normal range in patients with brief seizures while elevated values were obtained in patients with prolonged seizures. The mean CSF lactic acid on admission was significantly higher (P less than 0.001) in patients with prolonged seizures than corresponding values in those with brief seizures. Mean serum lactic acid on admission was also significantly higher in patients with prolonged febrile seizures compared to the corresponding mean value in patients with brief seizures (P greater than 0.001). Patients who recovered with neurological deficits had significantly higher CSF lactic acid on admission (P greater than 0.001). Similarly 8 patients who had recurrent febrile convulsions had significantly higher CSF lactate on admission. It is suggested that measurement of CSF lactate can be used as a biochemical marker to identify children with prolonged seizures and those who are likely to have recurrent febrile seizures.

Epilepsy in children in Benin City, Nigeria.

The pattern of epilepsy in children in Nigeria showed little difference from that seen in children in western countries, except that birth asphyxia was relatively common as a cause and there was a longer time between onset of seizures and parents seeking medical care. It was estimated that good control of seizures was achieved in 52.9% of children, but more than a quarter attended the clinic only once or twice and the reasons for this are not known. The response to medication was less satisfactory for children under 1 year, a result consistent with most other studies. Some uncommon forms and associations of epilepsy were recognised. An EEG was not essential for management but was useful for the diagnosis of syndromes. Treatment was equally effective when commenced 5 years or more after the onset of seizures. The anti-convulsant used for most children was phenobarbitone which had to be discontinued in only two cases because of side-effects. Phenobarbitone has been successfully used to treat epilepsy by primary health workers in rural Africa and this is expected to continue in the future.

Sickle cell disease, pneumococcal meningitis and paraplegia with recovery.

A 10-year-old boy without previous illness was found to have sickle cell disease and pneumococcal meningitis. On completion of 10 days of treatment with penicillin, the only abnormality still present was paraplegia. Movements of the legs recovered gradually, and after 3 months he was walking normally. Paraplegia is rare in sickle cell disease and the prognosis is not always poor.

Malaria with bacteraemia in acutely febrile preschool children without localizing signs: coincidence or association/complication?

Data were collected on 642 preschool children who presented consecutively to casualty with fever and no localizing signs. Four hundred and forty-six (69%) had malaria parasitaemia. The proportion of children with bacteraemia was similar in those children with malaria (43/446, 9.6%) and those without malaria (24/196, 12.2%, P < 0.5). The pathogens in both groups of children were mainly Staphylococcus aureus and coliform bacteria. Although children with malaria/bacteraemia had a significantly higher prevalence of anaemia (P = 0.001), hepatosplenomegaly (P < 0.01) and combination of hepatosplenomegaly and severe anaemia (P = 0.02), compared with children with malaria alone, there was no correlation between the severity of parasitaemia and prevalence of malaria with bacteraemia. The association of malaria with bacteraemia appears to be coincidental.

Rectal diazepam solution in the treatment of convulsions in the children's emergency room.

Rectal diazepam solution was administered to 55 convulsing children in the Children's Emergency Room. In 71%, the convulsion ceased within 5 min, and in 7%, between 5 and 10 min. In 16%, rectal diazepam was ineffective but there was a rapid response to intravenous diazepam. Convulsions that had lasted less than 15 min before treatment responded more often (81%) than those that had lasted more than 15 min (46%). Four children had transient respiratory depression. Though intravenous diazepam is superior, rectal diazepam solution is adequate for controlling most acute convulsions in children, and has the advantage that it can be administered by paramedical workers.

Convulsions with fever as a presenting feature of bacterial meningitis among preschool children in developing countries.

The authors report 522 infants and young children aged between one month and six years who presented with convulsions and fever as emergencies in Nigeria. 22 had bacterial meningitis, six of whom lacked the usual signs of meningitis. Although features of complex febrile convulsions were significantly associated with bacterial meningitis, it is concluded that, as an aid to the early diagnosis of bacterial meningitis, all preschool children convulsing with fever in developing countries should have a lumbar puncture. This may reduce the contribution of meningitis to chronic neurological disabilities. The necessity for such a policy is illustrated by a case report of a young infant with convulsions and fever caused by meningitis, seen at a general hospital.

Convulsions with fever of acute onset in school-age children in Benin City, Nigeria.

Of 92 school-age children who had convulsions with fever (CWF) of acute onset, seen in a 1-year period in an emergency room in Benin City, Nigeria, 49 per cent had malaria parasitaemia, 15 per cent bacterial meningitis, 8 per cent focal extracranial infections, and 1 per cent bacteraemia while 27 per cent had acute fever of undetermined origin. The prevalence of meningitis increased with presence of temperature > or = 40 degrees C (P < 0.01), focal seizures (P < 0.05), and rousable coma (P < 0.05). Bacterial meningitis is an important illness in school-age children with CWF, although malaria parasitaemia is the commonest infection.

Neurological diseases as seen at the outpatient Paediatric Neurology Clinic in Benin City.

There is a paucity of literature about the pattern of neurological diseases in children attending out-patient departments in Africa. In this study more boys than girls presented at our clinic. Almost all the principal diseases seen are eminently preventable. There appears to be no effective immunization programme. There is need for epidemiological studies to ascertain the true incidence of subacute sclerosing panencephalitis in view of the high incidence of measles in the community.

Convulsions with malaria: febrile or indicative of cerebral involvement?

Evaluation of 446 infants and young children (6 months to 5 years olds) with malaria parasitaemia showed a significant relationship (P < 0.05- < 0.001) (a) between coma and age, pattern of convulsions, haematocrit, and blood glucose, and (b) between the severity of parasitaemia and risk of convulsions, prevalence of hepatosplenomegaly, and severe anaemia. No significant relationship was observed between convulsions and temperature or haematocrit. Comatose children were older and had a higher prevalence of repeated convulsions, severe anaemia, and hypoglycaemia than non-comatose children. Convulsions, hepatosplenomegaly, and severe anaemia were more prevalent in children with moderate-severe parasitaemia. It is concluded that convulsions with malaria are more often a manifestation of cerebral dysfunction rather than being simply febrile in nature. All forms of cerebral dysfunction in malaria, including repeated convulsions, should be managed as being clinical manifestations of cerebral malaria.

Acute fevers of unknown origin in young children in the tropics.

Bacteremia was documented in 14 of 156 previously healthy children with temperatures of at least 40.0 degrees C but without focal signs, seen in an emergency department; 116 children had malaria, and no infections were identified in 26. Concurrent malaria infection was frequent in children with bacteremia. The highly febrile child without focal signs in the tropics requires evaluation for bacteremia even when a diagnosis of malaria has been confirmed.