PCR-mediated search for herpes simplex virus DNA in sections of brain from patients with multiple sclerosis and other neurological disorders.

Herpes simplex virus (HSV) has been shown to cause central nervous system demyelination in experimental animals and several studies have implicated HSV in the aetiology of multiple sclerosis (MS). We have used the polymerase chain reaction to look for DNA of both type 1 HSV (HSV-1) and type 2 HSV (HSV-2) in formalin-fixed paraffin-embedded brain tissues from patients with MS and other neurological diseases. Primers which amplify a fragment of the normal cellular gene c-myc were included in the reactions to assess the preservation of DNA in the tissue samples. 77 plaques of demyelination from 23 patients with MS were examined. HSV-1 DNA was amplified from only one plaque. This plaque involved the trigeminal root entry zone in the pons and it is suggested that the presence of viral DNA was related to the site examined rather than to the demyelination per se. HSV-2 DNA was amplified from none of the plaques. As expected, HSV-1 DNA was detected in the brains of 6 patients who died of HSV-1 encephalitis and HSV-2 DNA was amplified from the brain of a neonate with congenital HSV-2 infection. In sections of brain from 39 patients with a wide range of other neurological diseases HSV-1 DNA was detected in the pons of only 1 patient, who had AIDS associated with cytomegalovirus ventriculitis; subsequent investigation confirmed the presence of concomitant HSV-1 brain stem infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional vascular resistance and heart rate responses mediated through H1- and H2-histamine receptors in the unanaesthetised rabbit

The effects of histamine infusions (10—100 μg/kg/min) on heart rate and hindlimb, carotid, mesenteric and renal vascular resistance were investigated in unanaesthetised rabbits after “total” autonomic effector block to abolish reflex effects. Histamine caused a rise in heart rate that was predominately due to stimulation of H₂-receptors (blocked by metiamide). Hindlimb and carotid vascular resistance did not change significantly during histamine infusion. However, after blocking H₂-receptors with metiamide histamine infusions produced dose-related vasoconstriction in these beds while after H₁-receptor block with mepyramine histamine caused dose-related vasodilatation indicating that H₁- and H₂-receptors mediated opposite vascular effects which were of similar magnitude. By contrast, histamine infusion caused vasodilatation in both the mesenteric and renal vasculature before giving antagonists. This dilatation was mediated by both H₁- and H₂-receptors as either receptor antagonist attenuated the response. These studies suggest that H₁-receptors in the same species mediate vasoconstriction in some beds and vasodilatation in others while H₂-receptors mediate vasodilatation in all the beds studied and also account for most of the increase in heart rate.     

Reversible inhibition of neuronal uptake by benextramine, an irreversible presynaptic alpha-adrenoceptor antagonist

Benextramine, a covalently binding alpha-adrenoceptor blocking agent, potentiated the action of noradrenaline but not isoprenaline in guinea pig isolated right atria. This potentiation was probably caused by inhibition of neuronal uptake. When the benextramine was washed from the tissues for 60 min, no potentiation of the action of noradrenaline was observed. This easily reversed inhibition of neuronal uptake by benextramine contrasts with the effects of desipramine and phenoxybenzamine because the potentiating effect of these drugs was unaffected by 60 min of washing. The presence of benextramine also caused a small tachycardia in both rabbit and guinea pig right atria which was probably due to the release of endogenous noradrenaline. Clonidine a presynaptic alpha 2-adrenoceptor agonist, inhibited the responses to electrical field stimulation. Pretreatment with benextramine greatly diminished the effect of clonidine. This alpha 2-adrenoceptor antagonism was not reversed by washing the benextramine from the tissue for 240 min. We conclude that benextramine is a readily reversible inhibitor of neuronal uptake and an irreversible antagonist of presynaptic alpha 2-adrenoceptors.     

Airway auscultationA new method of confirming tracheal intubation

Unrecognised accidental oesophageal intubation remains an important cause of morbidity and mortality in anaesthetic practice. We have evaluated a new method of distinguishing tracheal from oesophageal intubation using a simple adaptation of an ordinary stethoscope which is inserted into the patient end of the breathing system. We call this technique 'airway auscultation'. Characteristic sounds are heard with the stethoscope during inflation and deflation which allow the observer to diagnose the position of the tube. When the tube is in the trachea loud breath sounds are heard. In contrast, when the tube is in the oesophagus either squeaks or a flatus-like noise is heard or else there is no sound. In 100 healthy adults two observers rapidly identified 99 intubations correctly in a randomised single-blind trial. We recommend further widespread evaluation of this device as it appears to be an effective, simple and rapid method of detecting oesophageal intubation and confirming tracheal intubation which may be of particular use in situations where capnography is not available.     

Haemodynamic response to ketanserin in rabbits with Page hypertension: comparison with prazosin

The role of alpha 1-adrenoceptors in the hypotensive response to ketanserin was studied in conscious normotensive (sham-operated) and Page hypertensive (two-kidney, two wrapped) rabbits. Ketanserin (0.01, 0.1 and 1 mg/kg i.v.) was administered at 30 min intervals on four experimental days: no pretreatment; after prazosin 1 mg/kg and infusion; after pharmacological 'total' autonomic effector block (TAB) and with repeated three point methoxamine dose-response lines. Only the highest dose (1 mg/kg) of ketanserin lowered blood pressure and dilated the iliac vascular bed (Doppler flowmeter) in both wrap and sham-operated rabbits. Prazosin pretreatment and TAB prevented these effects. Ketanserin (1 mg/kg) also caused significant alpha 1-adrenoceptor antagonism as measured by a 2.5-fold shift in the methoxamine dose-response lines. In separate experiments prazosin (0.01-0.1 mg/kg i.v. bolus) caused similar falls in blood pressure and alpha 1-adrenoceptor block as ketanserin 0.3 and 1 mg/kg. The only difference observed between prazosin and ketanserin was the substantial reflex tachycardia to prazosin that was absent after ketanserin. These results suggest that in normotensive rabbits and in rabbits with Page hypertension the hypotensive response to ketanserin can be explained by alpha 1-adrenoceptor antagonism.     

Role of insulin in the growth of fetal rat tissues

The effect of insulin on the growth of fetal rat tissues was investigated using a transplant system. Paws from 15-day-old fetal rats were transplanted under the kidney capsule of 1-month-old syngeneic hosts, where they grew and differentiated normally. After 11 days of incubation, growth of transplants in hosts made diabetic by streptozotocin injection was reduced by 37% compared to growth in nondiabetic controls, but tissue differentiation and bone formation were normal in the absence of insulin. Injections of insulin (2 U, twice daily) into diabetic hosts restored paw growth to normal. Growth of transplants in hypophysectomized (HX) and in HX-diabetic hosts was reduced to the same degree (i.e. by 65%). Thus, the growth decrements produced by host hypophysectomy and diabetes are not additive. In contrast to the results with insulin-deficient hosts, the transplants failed to differentiate normally in the HX hosts. Injections of exogenous insulin (3 U, twice daily) to produce transient hyperinsulinemia failed to increase transplant growth in intact hosts over 11 days of incubation. The transplants were exposed to frequent periods of hyperglycemia and hyperinsulinemia by injecting 0.66 g glucose/100 g BW four times per day into intact hosts during 6 days of incubation. This treatment also failed to stimulate transplant growth. These results indicate that normal growth of transplanted fetal paw tissue is partially dependent on insulin, but whether the insulin acts directly or indirectly to support growth is not known. Supranormal insulin levels or frequent periods of hyperglycemia with hyperinsulinemia are not capable of producing overgrowth of the fetal paws. The HX, diabetic, and HX-diabetic host rats did not grow, as judged by tail length increase, and they lost weight. Accordingly, the juvenile host tissues have an obligatory dependence on insulin and GH for normal growth, but the fetal tissue is only partially dependent, because the paw transplants continued to grow in an internal milieu that was severely deficient in insulin and/or pituitary hormones. Overall, the results indicate that insulin is necessary for normal growth of the skeletal and connective tissues of the transplanted paw, but its effects are more growth supporting than growth promoting in these tissues.     

Clinical and electron microscopic studies of a case of glycolipid lipoidosis (Fabry''s disease)

A case of glycolipid lipoidosis (Fabry's disease) in a 27-year-old man is recorded. The case is unusual in that despite extensive disease evidenced by widespread skin lesions, ocular abnormalities, and proteinuria, renal function was only minimally impaired. Electron microscope studies of kidney and skin showed that most cells contained the characteristic lipid described in this condition.