Correlation between fall in blood pressure and in vivo amine release after alpha-methylDOPA

Blood pressure (BP), hypothalamic tissue concentrations and the in vivo overflow of endogenous and alpha-methylated catecholamines were measured in urethane anaesthetised rats after alpha-methylDOPA (mDOPA) administration (200 mg/kg i.p.). Four hours after mDOPA, BP fell to its lowest value, 60% of control, and slowly returned towards control levels by 24 h. This was closely correlated with the evoked overflow of alpha-methylnoradrenaline (mNA, r = 0.9) and noradrenaline (NA, r = 0.7) but not dopamine (DA) or alpha-methyldopamine (mDA). However, the tissue content of mNA rose much more gradually and was not maximal until after 12 h while mDA content followed the development of the hypotension. The results provide direct evidence for a false transmitter role for mNA in the brain, and suggest that the release of newly synthesised mNA is responsible for the hypotensive effect of mDOPA. Differences in the time course of overflow and storage of NA and mNA suggest the presence of separate transmitter storage and releasable pools.     

A simple, sensitive method for the determination of extracellular catecholamines in the rat hypothalamus using in vivo dialysis

The design, construction and characterisation of a dialysis probe suitable for perfusing any deep brain structures is described. Using high-performance liquid chromatography with electrochemical detection (HPLC-ECD) the effects of flow rate, concentration, dialysate composition and temperature on the recovery within the dialysate of authentic catecholamines are detailed. The dialysis probe was used to collect endogenous catecholamines from the anterior hypothalamus of urethane-anaesthetised rats. Following organic phase extraction of the in vivo samples, a small basal release of noradrenaline (NA) of 37 +/- 4 pg/30 min sample was found. Potassium stimulation markedly elevated the release of NA and dopamine from the anterior hypothalamus in a calcium ion and dose dependent manner. It appears therefore that the dialysis probe described here, in conjunction with HPLC-ECD, can be used to follow changes in neuronally released catecholamines within the anterior hypothalamus, providing a valuable tool to study the role of these neurotransmitters in physiological and pharmacological function.     

The value of remanipulating Colles' fractures

The value of remanipulating a Colles' fracture which has redisplaced after primary reduction was assessed in 50 patients. In those over 60 years old, remanipulation failed to achieve a lasting improvement in position, while the majority of those under 60 years maintained a significant improvement in dorsal angulation. It is concluded that the elderly patient does not benefit from this procedure.     

The poor quality of early evaluations of magnetic resonance imaging

To study the quality of early research on the clinical efficacy of diagnostic imaging with magnetic resonance, we assessed 54 evaluations published in the first four years after introduction of this modality using ten commonly accepted criteria of research methodology. The terms sensitivity, specificity, false-positive or false-negative, accuracy, and predictive values were used infrequently. Nineteen percent of the evaluations used three terms appropriately, 48% used one or two terms, and 33% used none. Data were presented appropriately for one or more of the five terms in 59% of evaluations. A "gold standard" comparison with the results of an independent procedure, such as surgical or autopsy findings, was presented in 22% of evaluations. Results of another imaging procedure were described in 63% of evaluations. Only one evaluation clearly described a prospective study design, although 11 evaluations apparently were planned in advance. Not one evaluation contained an appropriate statistical analysis of the distributions of quantitative readings, "blinded" image readers to diagnosis or other test results, measured observer error, or randomized the order of magnetic resonance imaging and other imaging procedures. We conclude that health care professionals paying for expensive innovative diagnostic technology should demand better research on diagnostic efficacy.     

Help-seeking among illicit drug users: some differences between a treatment and nontreatment sample.

A number of both medical and nonmedical disciplines have expressed concern regarding the large numbers of individuals that fail to present to services, despite experiencing problems similar to those of active help-seekers. Such a concern is most pertinent in the field of substance misuse, particularly in terms of the role of injecting drug users in the spread of HIV and AIDS. This study looked at two samples of problem drug takers in London: 120 seeking help (the "agency group") and 120 not seeking help (the "non-agency group"). A number of factors were examined to distinguish the two groups, including sociodemographic profiles, drug histories, and self-reported "concern" and "need for help" in a wide variety of life areas. Data analysis highlighted the significance of "concern" and "need for help" in specified life areas.     

Comparison of a modified microagglutination technique for HBsAg with the standard technique and a new RIA system.

A further modification of the standard RPHA technique (Hepatest, Wellcome Reagents) for the detection of HBsAg is described. This modification does not require a centrifugation step which is required by the other modifications that have been described previously and consequently takes a little longer to perform. It does, however, retain the advantages of increased sensitivity and decreased costs which are also features of the other modifications. A series of 939 routine clinical specimens were used to evaluate the method described and to evaluate a new RIA kit for the detection of HBsAg (Hepatube, Wellcome Reagents). Of 53 specimens found to be positive for HBsAg by RIA, 50 (94% were detected by the modified Hepatest RPHA as opposed to 47 (89%) by the standard technique.     

A quantitative method for measuring in vitro synthesis of IgA and IgG by human rectal mucosa: studies on normal controls and patients with hypogammaglobulinaemia.

A quantitative technique has been developed for measurement of immunoglobulin production by human rectal mucosa in vitro. The technique overcomes the problem of serum proteins trapped in the tissue by parallel measurements of Ig and human serum albumin (HSA) over a 6 day period. IgG, IgA, IgM and HSA were measured in supernatant fluids using sensitive radioimmunoassays. The technique has demonstrated IgG and IgA synthesis by rectal mucosa in vitro. The conclusion that the observed IgA and IgG was synthesized in vitro was supported by the demonstration that the production could be increased by pokeweed mitogen and blocked by emetine. This culture system has been applied to measure Ig synthesis by the rectal mucosa of immunodeficient patients.     

The effects of haemorrhage in the unanaesthetized rabbit

1. The circulatory response following acute loss of 26% of the blood volume was examined in unanaesthetized rabbits. The groups of animals studied were normal rabbits; adrenalectomized rabbits; animals subjected to prolonged treatment with guanethidine in which peripheral adrenergic nerve transmission is blocked, but which can reflexly liberate adrenal medullary hormones; animals subjected to combined adrenalectomy and guanethidine treatment with no functional adrenergic effectors; in each case with or without administration of atropine. The responses of animals with section of the carotid sinus and aortic nerves were also examined.

2. The spontaneous rate of replacement of the blood volume after haemorrhage by reabsorption of extravascular fluid was the same in all the above preparations, the blood volume returning to normal 3-4 hr after bleeding.

3. The `passive' effects of haemorrhage were examined in animals without functioning autonomic effectors and include a large fall in right atrial pressure and cardiac output, arterial hypotension, no significant change in total peripheral resistance, and a bradycardia of gradual onset. Reflex autonomic effector activity in normal animals minimizes the fall in atrial pressure, cardiac output and arterial blood pressure, and produces a significant increase in total peripheral resistance and tachycardia. Increased sympathetic nerve activity and secretion of adrenal medullary hormones each play an important and complementary part in the normal circulatory response to haemorrhage of the rabbit. There is also reflex reduction in vagal efferent activity.

4. Reflexes from the carotid sinus and aortic arch limit the fall in arterial pressure for the first 4 hr after haemorrhage. These reflexes also account for the tachycardia normally observed after haemorrhage. The baroreceptor reflexes rather than the chemoreceptors appear to be dominant in these responses.

5. Twenty-four hours after haemorrhage the haemodynamic pattern is similar in all preparations irrespective of their autonomic effector status: blood volume, right atrial pressures and cardiac outputs are all elevated, and the arterial pressure has virtually recovered, consistent with the development of hypervolaemic anaemia at this time.

     

Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

AIM--To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules. METHODS--Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin. Biopsy specimens taken from skin before, during, and after cyclosporin treatment were stained immunohistochemically for CD 54 (ICAM-1), CD 29 (beta-1 integrins), and CD18 (beta-2 integrins). RESULTS--There was a highly significant (p < 0.01) clinical response after 12 weeks of cyclosporin as assessed by the Psoriasis Area and Severity Index (PASI) score. The staining of CD 29 on keratinocytes of affected and unaffected psoriatic skin was not affected by cyclosporin. Epidermal CD54 was variably expressed in active psoriatic plaques and changed unpredictably after cyclosporin (p = NS). Staining for CD18 on large epidermal dendritic cells was reduced after cyclosporin (p < 0.02). The expression of CD18 by large epidermal dendritic cells during treatment correlated strongly with the PASI score at that time and one month after stopping cyclosporin (p < 0.02). CONCLUSIONS--Persistence of epidermal staining for CD 54 in psoriasis is compatible with a good clinical response to cyclosporin. Residual staining for CD 18 on large epidermal dendritic cells may be a useful marker for early clinical relapse.