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Biomedical subjects

R D Helme

Publications and source records attributed to R D Helme.

89 records · Page 5Linked to original sources

The prognostic significance of intraventricular haemorrhage.

It is a generally held view that intraventricular haemorrhage carries a poor prognosis in cases of intracranial haemorrhage. We tested this view by retrospective analysis of the records of 258 patients who had intracranial blood on CT scans seen over a seven-year period. The mortality and morbidity for intraventricular and non-intraventricular haemorrhage were compared for the three major causes of intracranial bleeding, viz. aneurysm, trauma, and spontaneous intracerebral haemorrhage. No significant difference was found between the two groups for each aetiological category. It was concluded that the CT scan finding of intraventricular blood has no prognostic significance.

Brain Injuries↗

Immunohistochemical localization of substance P in postmortem rat and human spinal cord.

The stability of substance P-like immunoreactivity was examined in postmortem rat and human spinal cord using radioimmunoassay and indirect fluorescence immunohistochemistry. The distribution of fluorescence in rat and human spinal cord was unchanged at intervals up to 48 hours (h) and 87 h, respectively. Fine linear fluorescent fibers were seen only in rat spinal cord processed at time intervals up to two h postmortem; they were never observed in human spinal cord, which was routinely obtained more than 6 h postmortem. The content of substance P-like material in human spinal cord nd its immunohistochemical appearance was not affected by age, the nature of the terminal illness, or autopsy delay. However, no correlation was found between intensity of fluorescent staining and content as measured by radioimmunoassay. It may be possible to use postmortem analysis of substance P in diseases of the central nervous system, but radioimmunoassay and immunohistochemistry should be used concurrently.

Animals↗

Enkephalins and Endorphins. Clinical, pharmacological and therapeutic implications.

During the past 8 years there has been substantial progress in our understanding of the structure, distribution and action of endogenous opioid peptides. Currently, there appear to be 2 groups of peptides; those derived from beta-lipotropin and an enkephalin-related group. Some of these peptides have been shown to be distributed widely in the central nervous system and in endocrine tissues. The activity of the peptides probably occurs at several receptors but only 1 relatively specific (mu-receptor) antagonist, naloxone, is well studies. Although there have been many clinical studies of the action of opioids in man, no novel therapeutic applications have yet been established in clinical practice. Of the many areas of involvement attributed to opioids, those of analgesia, reproductive endocrinology, opiate dependence, and certain as yet undefined subtypes of major psychoses seem reasonably promising. Speculation surround opioid involvement in other disorders such as spinal trauma, septic shock, alcohol dependence, "functional' gastrointestinal disease, diabetes and asthma is of considerable interest but is supported by less clinical evidence. It seems that as research in opioids advances, the putative physiological opioid "spheres of influence' widen. At the same time, opioid mechanisms of action are being revealed to be more subtle and complex than previously thought. As a consequence, the expectations of rapid therapeutic application of opioid peptides and their antagonists are being modified and refined and realistic research strategies applied. In view of the work reviewed in this paper it seems reasonable to expect that such work will pay dividends in the not too distant future.

Acupuncture Therapy↗

Substance P in the trigeminal system at postmortem: evidence for a role in pain pathways in man.

It is suspected that substance P has a role in primary afferent neurotransmission specifically concerned with nociception. This hypothesis has been developed from studies using experimental animals. In the present study indirect immunofluorescence has been used to examine the distribution of substance P-containing neurones in the human trigeminal system. The 5 specimens examined were obtained at autopsy. The antibody has been characterised by radio-immunoassay. In addition, neutralisation tests were performed. Approximately 15% of the neuronal perikarya observed in the trigeminal ganglia contained substance P-like material. The central nerve terminal distribution of these neurones was observed in the peripheral layers of nucleus caudalis and the caudal regions of the nucleus interpolaris. Peripheral distribution of fibres, presumably axon terminals, was observed in the dermis of the scalp subjacent to the epidermis. Rarely, fibres penetrated the lower layers of the epidermis. Nerve fibres were seen in the media and adventitia at the origin of the major cerebral vessels, the middle meningeal, muscular and scalp arteries. Nerve fibres were not observed elsewhere in muscle, in the leptomeninges or dura mater, except in and immediately adjacent to the venous sinuses. The distribution of substance P-containing neurones correlates closely with clinical studies which document the blood vessels and skin as the major pain sensitive structures of the scalp and cranium. This is evidence in man that substance P is involved in nociceptive pathways.

Blood Vessels↗

Immunological studies of brain-specific antigens.

Central nervous system antigens have been investigated, using immunofluorescence, to demonstrate the presence of antisera raised against regional homogenates of neonatal and adult rat brain. Heterologous antisera raised in rabbits against regions of rat brain contained several antibodies demonstrated by immunofluorescence. Brain-specific activity directed against neuronal and glial elements was difficult to characterise. Regional and age-dependent specificity of the antisera was not demonstrated. Homologous antisera could not be raised against neonatal rat brain regions, but low titre antibodies to neurones were detected in rats over 21 days old. These animals did not develop experimental allergic encephalomyelitis (EAE). In other rats which developed EAE following a different immunisation schedule similar antibodies were seen. It is concluded that heterologous antisera raised against unpurified antigens have too wide a spectrum of antibody specificities for use as anatomic markers. Homologous antisera are difficult to obtain in sufficiently high titre. There is production of antibodies towards neurones in one form of EAE.

Animals↗

Substance P in the central nervous system.

A radioimmunoassay has been developed for measuring substance P-like immunoreactivity. Assay sensitivity was 0.7fmoles of substance P. Using the radioimmunoassay substance P-like immunoreactivity was detected in postmortem tissue samples from the central nervous system of rats and humans. Immunofluorescence studies confirmed the localisation of substance P in the dorsal horn of the spinal cord.

Animals↗

Tachykinin-induced vasodilatation in rat skin measured with a laser-Doppler flowmeter: evidence for receptor-mediated effects.

Vasodilatation was induced by perfusion of the tachykinins substance P (SP), neurokinin A and neurokinin B and the analogues [Glp6, D-Pro9]SP-(6-11) and [Glp6, L-Pro9]SP-(6-11) over the base of vacuum-induced blisters on the rat footpad. Vasodilatation was measured as change in blood flow using a laser-Doppler flowmeter. The tachykinins induced vasodilatation in a dose-response manner with a threshold of approximately 3 pmol and pD2's of 6.48, 6.13 and 6.21 for SP, neurokinin A and neurokinin B respectively. The D- and L-Pro analogues of [Glp6, Pro9]SP-(6-11) also induced vasodilatation in a dose-dependent manner. The L-Pro analogue was more potent than the D-Pro analogue (D/L ratio of the EC50's = 21) which suggests the involvement of an NK-1 type receptor in the mediation of small vessel vasodilatation. The vasodilatation to SP was reduced by 64% and 59% in capsaicin- and antihistamine-pretreated animals respectively, demonstrating the involvement of capsaicin-sensitive primary afferent nerves and mast cells in the vasodilatation component of the neurogenic inflammatory response.

Animals↗

Pain in older persons.

Chronic pain is more prevalent in older persons than in young adults. In this review the physiological, pathological, and psychological reasons for altered pain sensibility in older persons are explored and strategies for the management of pain in older persons described. The evidence suggests that altered physiology of peripheral and central pain mechanisms combine with psychological attitudes, such as stoicism and reluctance to confirm the presence of pain, to raise pain threshold. However, once pain is experienced, older persons describe the same severity, quality, and psychological disturbance as younger persons. There is some evidence to suggest that the complaint of pain in the presence of pathology is reported less often in older persons. On the other hand, the presence of persistent or recurrent clinical pain may have a greater impact on the psychological, social, and physical function of older adults. It is also clear, however, that further empirical studies are required in order to delineate the age-related differences and similarities in the chronic pain experience. Management of chronic pain in the elderly requires meticulous diagnosis of the causal pain mechanisms as well as a holistic approach which gives due regard to psychological and social consequences of pain.

Affect↗