Calcium Concentration-dependent Mechanisms through which Ketamine Relaxes Canine Airway Smooth Muscle

Background: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation.

Methods: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectrophotometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay.

Results: In smooth muscle strips stimulated with submaximal (0.1 micro Meter) and maximal (10 micro Meter) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 micro Meter and 850 micro Meter for tissue contracted by 0.1 micro Meter or 10 micro Meter acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+] sub i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations.     

Use of latex agglutination testing in diagnosing pediatric meningitis.

BACKGROUND. Latex agglutination (LA) tests are ordered frequently on cerebral spinal fluid (CSF) specimens obtained from pediatric patients to identify pathogenic bacteria as early as possible in an acute infection. METHODS. Six hundred ten LA tests were performed on 176 patients suspected of having meningitis. RESULTS. Five patients with meningitis had positive LA tests. We found that the CSF white blood cell (WBC) count, and differential were the best predictors of meningitis. CONCLUSIONS. By limiting the use of LA tests to those patients having CSF with abnormal WBC counts or with positive Gram stains, the number of tests ordered would have been reduced. This practice would greatly reduce laboratory expense.     

Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry.

This series of experiments compared isolation-reared and socially reared rats for their locomotor activity, behavioural stereotypy, and monoamine function both postmortem and in vivo using intracerebral dialysis. In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC). Isolation-reared rats also showed increased sensitivity to the sedative effects of a low dose of apomorphine hydrochloride (0.1 mg/kg) but did not differ from social controls following higher doses of the drug (0.5, 1.5, or 3.0 mg/kg, SC). Isolates showed a decrease in the intensity of apomorphine-induced stereotyped behaviours but no change in stereotypy induced by AMPH. In Experiment 2, isolates had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens (NAC) or caudate putamen (CPu). Isolated rats also had a lower 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC (but not in the PFC or CPu) compared to controls. Experiment 3 used intracerebral dialysis to examine monoamine function in vivo following isolation rearing. Isolates showed greater increases in extracellular DA and greater decreases in DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu. There were no apparent differences in the perfusate concentrations of either dopamine (DA), dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug administration. However, consistent with the results of Experiment 2, isolates had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from the CPu. Experiment 4 measured postsynaptic DA function in CPu tissue slices following isolation. Isolation rearing did not affect cAMP accumulation in response to stimulation of D1 DA receptors by DA (0, 2.7, 9, or 30 microM). In addition, isolation rearing did not affect the coupling between D1 and D2 receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction by 10 microM quinperole hydrochloride (LY 171555). These results are discussed in terms of the possible relationship between these neurochemical findings and the behavioural disturbances following isolation rearing of rats.     

Principles of screening and congenital dislocation of the hip.

The call for screening for an increasing number of surgical diseases is becoming louder and more frequent. There is a general perception that screening is ''good'' but it is important to consider the evidence carefully. There is one surgical disease that provides considerable experience of the process of screening over a period of 30 years and this is congenital dislocation of the hip (CDH). In retrospect, it is clear that screening for this disease has not been a total success. Although some specialised centres have achieved excellent results, in the country as a whole screening has been a failure. The reasons for this are analysed and emphasis is placed on the principles of screening which are briefly summarised. The results of various studies on screening and experiments on the basic functional anatomy of the neonatal hip are described. The initial results of our method of selective ultrasound screening appear to be encouraging and some evidence of a possible collagen abnormality in CDH is presented. As a general principle, however, it is suggested that strict randomised controlled trials should take place before national screening programmes are started.     

Megavoltage pituitary irradiation in the management of prolactinomas: long-term follow-up

OBJECTIVE To determine the long-term effects of external beam megavoltage radiotherapy (RT: 4500 cGy via three portals at 180 cGy or less total daily dose) on endocrine function in prolactinomas. DESIGN Longitudinal study following radiotherapy with periodic re-assessment at regular intervals, at least 2 months off dopamine agonist therapy. PATIENTS Thirty-six female patients, age range 19-50 years, with either macroprolactinomas (12 patients) or microprolactinomas (24 patients), but without significant suprasellar extensions. MEASUREMENTS Clinical appraisal, and anterior and posterior pituitary assessment: basal levels at yearly intervals or less, with dynamic screening with TRH, LHRH and hypoglycaemic stimulation every 2-3 years. RESULTS Before RT, serum prolactin (PRL) levels ranged from 1150 to 34,000 mU/l; after RT (mean 8.5 years, range 3-14), serum PRL fell to normal (i.e. less than 360 mU/l) in 18 of the 36 patients (50%), and to just above the normal range (378-780 mU/l) in a further 10 (28%). Two patients had PRL levels at their last follow-up higher than those at presentation, with one patient showing evidence of tumour recurrence on CT scan. A total of eight of the 36 patients (23%) developed post-RT gonadal deficiency by the end of follow-up at 8 +/- 3.1 years (+/- SD, range 3-11), but six were aged over 40 years at that time. GH deficiency was frequent, occurring in 94% of patients, usually from 2 to 3 years post-RT, while TSH deficiency and reduced ACTH reserve was uncommon (each 14%), and occurred later. In the subgroup of 12 patients with macroprolactinomas, results were broadly comparable. CONCLUSIONS Megavoltage RT produces a progressive fall in serum prolactin in the great majority of patients with prolactinomas, with a relatively low incidence of TSH or ACTH deficiency. As it is now clear that dopamine agonist therapy alone provides sufficient management for microprolactinomas, RT may be used for the long-term control of macroprolactinomas, together with interim dopamine agonist therapy. It allows pregnancy to be safely undertaken but, in view of the delayed onset of gonadal deficiency, its administration should be timed with respect to the desired onset of conception in women.     

Low oxygen extraction fraction in tumours measured with the oxygen-15 steady state technique: effect of tissue heterogeneity.

Several reports have described decreased oxygen extraction fractions in tumours relative to those in normal tissues as measured with the oxygen-15 steady state technique and positron emission tomography. The present simulation study was carried out to assess the influence of tissue heterogeneity on these measured values. It was found that, within the range analyzed, tissue heterogeneity always resulted in underestimations of mean values of oxygen extraction fraction. It must, therefore, be concluded that the oxygen-15 steady state technique is not an accurate method for the assessment of the oxygen status of tumours. This finding should also apply to other pathological conditions, where a significant degree of tissue heterogeneity can not be excluded. More generally, this study demonstrates the need for detailed analyses of sensitivities of tracer kinetic procedures to tissue heterogeneity.