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Biomedical subjects

R M Craven

Publications and source records attributed to R M Craven.

7 recordsLinked to original sources

The locus coeruleus in schizophrenia: a postmortem study of noradrenergic neurones.

Despite evidence for an abnormality of noradrenergic function in schizophrenia, it remains unclear whether the number of noradrenergic neurones is normal in patients with the disorder. In postmortem, formalin-fixed tissue from 15 schizophrenic patients and 18 controls matched for age and gender, we made estimates of the number and size of tyrosine-hydroxylase-immunoreactive cells in the locus coeruleus (LC). No significant difference was detected between these groups in the cross-sectional area or diameter of immunoreactive cell profiles. Profile number was not significantly affected by gender, side of the brainstem (left or right), postmortem interval or time in formalin; however, the levels of immunoreaction product (optical density) correlated significantly with our profile counts, which were lower on average in the schizophrenic group. When optical density was included as a covariate in our comparison (a repeated-measures analysis of variance) of schizophrenic and control cases, we found no difference between these groups in the number of neurones counted. An age-related decrease in profile number was detected, but no effect of age on our estimates of cell size was apparent. Our results highlight the importance of accounting for potential confounding variables, including variations in the quality of immunostaining, in investigations of this type. The findings presented here concur with previous studies suggesting that noradrenergic dysfunction in schizophrenia is not associated with an anatomical abnormality at the level of the LC.

Aged↗

The dorsal raphe nucleus in schizophrenia: a post mortem study of 5-hydroxytryptamine neurones.

The 5-hydroxytryptamine (5-HT, serotonin) system has been implicated in the pathophysiology and treatment of schizophrenia. In this study, we addressed the hypothesis that a deficit of 5-HT neurones, either inherited or acquired, is central to the developmental pathology of the disorder. We examined putative 5-HT neurones of the dorsal raphe nucleus (DRN) in post mortem, formalin-fixed tissue from 15 schizophrenic patients and 20 control subjects matched for age and gender. No significant difference was detected between these groups in the number or size (cross-sectional area or diameter) of tryptophan-hydroxylase-immunoreactive cell profiles viewed in transverse sections collected from the level of the trochlear decussation to the emergence of the trigeminal nerve. Profile number was not affected by age, gender, side of the brainstem (left or right) or post mortem interval; however, time in formalin correlated negatively with the number of neurones counted. Moreover, a significant negative correlation was detected between time in formalin and the levels of immunoreaction product (optical density), which in turn correlated positively with our profile counts. A positive correlation was found between the age of subjects and our estimates of cell size. Our results do not support the proposal that an abnormality in the number and/or size of DRN 5-HT neurones is central to the aetiopathology of schizophrenia.

Adult↗

Ventilation of a model lung using various cricothyrotomy devices.

In this study we developed a model lung to compare the effectiveness of ventilation using four different cricothyrotomy devices. The Ravussin 13G cannula (VBM Medical), the Quicktrach cannula 4 mm ID (VBM Medical), the Melker cannula 6 mm ID (Cook) and a cuffed tracheal tube 6 mm ID were used in turn to ventilate the model lung through a cricothyrotomy over a range of upper airway resistances. The 6 mm cuffed tracheal tube provided consistently good ventilation independent of upper airway resistance. The 6 mm ID Melker device provided at least reasonable and at best very good ventilation, whatever the patency of the upper airway. The Ravussin cannula could ventilate well with the jet ventilator with low upper airway resistance but could not ventilate at all with complete upper airway obstruction. The Quicktrach performed poorly with low upper airway resistance but well with increased upper airway resistance. With its easier insertion, fewer complications compared to a surgical cricothyrotomy, and the ability to use it with a standard anaesthetic circuit, the authors feel that the 6 mm Melker canula is the technique of choice for emergency trans-tracheal ventilation.

Airway Obstruction↗

5-HT1A and 5-HT2 receptors differentially regulate the excitability of 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro.

We have used intracellular recording techniques to examine the effects of 5-hydroxytryptamine (5-HT, serotonin) on 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro. Bath-applied 5-HT (30-300 microM) had two opposing effects on the membrane excitability of these cells, reflecting the activation of distinct 5-HT receptor subtypes. As demonstrated previously in the rat, 5-HT evoked a hyperpolarization and inhibition of 5-HT neurones, which appeared to involve the activation of an inwardly rectifying K(+) conductance. This hyperpolarizing response was blocked by the 5-HT(1A) receptor-selective antagonist WAY-100635 (30-100 nM). In the presence of WAY-100635, 5-HT induced a previously unreported depolarizing, excitatory response of these cells, which was often associated with an increase in the apparent input resistance of the neurone, likely due to the suppression of a K(+) conductance. Like the hyperpolarizing response to 5-HT, this depolarization could be recorded in the presence of the Na(+) channel blocker tetrodotoxin. In addition, the response was not significantly attenuated by the alpha(1)-adrenoceptor antagonist prazosin (500 nM), indicating that it is not due to the release of noradrenaline, or to the direct activation of alpha(1)-adrenoceptors by 5-HT. The 5-HT(3) receptor antagonist granisetron (1 microM) and the 5-HT(4) receptor antagonist SB 204070 (100 nM) failed to reduce the depolarizing response to 5-HT; however, ketanserin (100 nM), mesulergine (100 nM) and lysergic acid diethylamide (1 microM) significantly reduced or abolished the depolarization, indicating that this effect of 5-HT is mediated by 5-HT(2) receptors.

Animals↗

Continuous auditory monitoring--how much information do we register?

We have studied response times of 30 anaesthetists to a standardized episode of arterial oxygen desaturation in a simulated patient, randomized to the use of either a fixed or variable pitch pulse oximeter. We wished to determine if a variable auditory signal was important in detecting adverse events. A variable pitch pulse signal had a shorter time to recognition of desaturation (P < 0.0001), with a mean response time of 32 s, compared with 129 s for the fixed pitch signal.

Acoustic Stimulation↗

Polyuric megalocystis.

We diagnosed and treated 5 children with huge bladders and hydroureteronephrosis secondary to polyuria, resulting from either familial nephrogenic diabetes insipidus, medullary cystic disease, central diabetes insipidus secondary to panhypopituitarism or psychogenic polydipsia. Polyuria was documented by the measurement of 24-hour urine volumes. The possibility of anatomic and physiologic outlet obstruction was eliminated by flowmetry, voiding cystourethrography and endoscopy.

Adolescent↗

Intraureteral tumor demonstrated by computed tomography.

Two cases of papillary carcinoma of the bladder are presented in which the ureter could not be demonstrated by standard radiographic techniques. Computed tomography (CT) allowed identification of the tumor filled ureter. Intraureteral papillary tumor has a radiographic density (CT number) above that of water but less than that of the enveloping ureter.

Carcinoma, Transitional Cell↗