A new theory of cochlear function, Part II.

This composite theory is based on the concept of 'Gestalt Function' i.e. the acoustic needs of the 'whole animal' as the vertebrates evolved out of the primordial fish. During the first two hundred million years of terrestrial life, hearing was directed solely to substrate sound. When belatedly the mammals achieved air sensitive hearing they were tiny omnivorous creatures with functional needs comparable with those of the modern rat i.e. (i) A frequency analysing system for communication, and (ii) a low threshold 'startle mechanism' for the detection and localisation of nearby enemy or prey. It is herein suggested that (i) The two functions are subserved respectively, the IHC and OHC, (ii) That the two systems evolved independently, (iii) That they have always acted independently (iv) That they continue to do so. This theory conficts sharply with the widely held 'Siamese twin' theory that the two populations act in tandem to provide for the controversial 'second filter'. It is shown herein that that theory conflicts with basic principles and is devoid of physiological validation.


Critical bandwidth in loudness summation in sensorineural hearing loss.

Critical band estimation was performed in thirty-three patients with sensorineural hearing loss by the method of loudness summation, using noise bands centred around 1 kHZ. In 17 patients the hearing loss was of hereditary origin, in 16 patients of various, mostly unknown, origin. The normal loudness difference between broad band noise and narrow band noise decreased with increasing hearing loss, most pronounced in recruiting ears. Judged individually, 1/3 of the patients appeared to have a widened critical band, but several biases appeared to be responsible for these results. The pooled data indicated a normal critical band, both in patients with hearing losses less than 50 dB HL and in patients with hearing losses greater than or equal to 50 dB HL. Based on this finding, the validity of the critical band as a measure of the frequency selectivity of the ear is discussed and a theory is proposed for the anatomical and functional correlate of the critical band in loudness summation.


Problems with handling the BE10 series hearing aids among elderly people.

Seven items of activity related to patients' ability to handle behind-the-ear hearing aids (BE11/12) were investigated to establish the effects of age, sex and functional disability. One hundred and thirty-six patients were examined; all were first-time users of hearing aids. Over two-fifths of the sample had problems with manipulating the volume control and over a third had difficulty with inserting the earmould and changing the battery. For both men and women, the difficulties with the volume control and earmould were significantly associated with functional disability. Difficulties with these tasks were also significantly related to age and sex. Patients aged 75 years of age or more had greater difficulties than those who were younger and women had more difficulty than men.


Aural rehabilitation of hearing-impaired adults (official policy of the British Society of Audiology).

This report, which outlines the official policy of the British Society of Audiology on the aural rehabilitation of hearing impaired adults, (a) estimates the prevalence of hearing impairment in adults in the United Kingdom; (b) identifies the main problems associated with hearing impairment in adults; (c) outlines the main aural rehabilitative procedures and (d) puts forward recommendations for future developments in this area.


Endocrine emergencies.

Endocrine and metabolic emergencies, although generally uncommon, produce characteristic clinical pictures which should allow rapid diagnosis. The results of confirmatory investigations are often no available in the acute situation, but it is important that the relevant samples should be taken before starting therapy. These are summarized with a synopsis of the recommended treatments for the various conditions in Table 1.


Effects of morphine, physostigmine and raphe nuclei stimulation on 5-hydroxytryptamine release from the cerebral cortex of the cat.

1. The release of 5-hydroxytryptamine (5-HT) from the cerebral cortex and caudate nucleus of brainstem-transected cats and from the cerebral cortex of rats anaesthetized with urethane was determined by radioenzymatic and biological assay. 2. The stimulation of nucleus linearis intermedius of raphe doubles the basal 5-HT release in the caudate nucleus and increases it 3 fold in the cerebral cortex. The effects of the electrical stimulation of the raphe are potentiated by chlorimipramine. 3. Brain 5-HT release is greatly increased by morphine hydrochloride (6 mg/kg i.v.) and by physostigmine (100 microgram/kg i.v.), but not by DL-DOPA (50 mg/kg i.v.). 4. It is suggested that the 5-HT releasing action of physostigmine can contribute to some of its pharmacological effects such as the analgesic effect so far attributed exclusively to its indirect cholinomimetic activity. 5. The 5-HT releasing action of physostigmine seems unrelated to its anticholinesterase activity.


Effects of certain muscarinic antagonists on the actions of anticholinesterases on cat skeletal muscle.

1. The effects of some muscarinic antagonists, namely, N-ethyl-2-pyrrolidylmethyl-cyclopentylphenyl glycollate (PMCG), N-methyl-4-piperidyl-phenylcyclohexyl glycollate (PPCG, racemate and R and S enantiomers) and 4'-N-methyl-piperidyl-1-phenyl-cyclopentane carboxylate (G3063) on organophosphate (sarin, soman)- and carbamate (neostigmine)-induced twitch augmentation have been studied in cat soleus muscle. 2. The results of a preliminary study comparing the potency of sarin and soman in inhibiting the acetylcholinesterase activity of muscle in relation to the effect on the maximal twitch response indicated that there is not a simple relationship between degree of enzyme inhibition by these drugs and alteration of muscle function. 3. The muscarinic antagonists studied were capable of preventing or reversing sarin-, soman- or neostigmine-induced twitch augmentation. Doses sufficient to give complete protection from the effects of the anticholinesterase agents had little or no effect on the twitch response of normal muscle. 4. The protective action of these muscarinic antagonists is dose-dependent but independent of known antagonist actions at muscarinic receptors. 5. The effects of some local anaesthetics (lignocaine, prilocaine, cinchocaine, procaine) and other membrane stabilizers (quinine, ketamine, chlorpromazine, triflupromazine) were compared with those of the muscarinic antagonists in an attempt to elucidate the mode of action of these acetylcholine antagonists. The evidence is insufficient to exclude the involvement of a membrane stabilizing action.


Short and long-term effects of reserpine on the concentration of 1-(4-hydroxy-3-methoxyphenyl)-ethane-1,2-diol (MOPEG-SO4) in the brain of the rat.

1 Reserpine (1.25 mg/kg i.p.) induced an increase (172% of controls) in the concentration of 1-(4-hydroxy-3-methoxyphenyl)-ethane-1,2-diol sulphate (MOPEG-SO(4)) in rat brain and a decrease in the noradrenaline (NA) concentration to 50% of controls 2 h after injection. At this time the MOPEG-SO(4)/NA ratio was 0.28. Thereafter the MOPEG-SO(4) concentration declined and the NA concentration decreased further to 28% of control.2 Higher doses of reserpine (2.5 and 5 mg/kg i.p.) did not induce a larger increase in the concentration of MOPEG-SO(4).3 While a second dose of reserpine (1.25 mg/kg i.p.) given 24 h after the first did not increase the MOPEG-SO(4) concentration, amphetamine (5.0 mg/kg i.p.) administration or electrical stimulation significantly increased the concentration of MOPEG-SO(4).4 NA and MOPEG-SO(4) concentrations were examined during 5 days after a single dose of reserpine (1.25 mg/kg i.p.). While the concentration of NA started to return towards normal after 24 h, that of MOPEG-SO(4) remained at approximately 70% of controls during the entire period.5 The probenecid-induced accumulation rate of MOPEG-SO(4) was significantly lower 3 and 4 days after reserpine and returned to the control value on the fifth day. At this time the concentration of NA had reached 50% of the control value.6 These experiments indicate that MOPEG-SO(4) is not the major metabolite of NA during the initial phase of reserpine-induced NA release. Reserpine acts on the storage pool while amphetamine (like electrical stimulation) acts on the functional pool. During the first phase of post-drug recovery, there is a clear decrease in NA output which appears to be regulated by the concentration of NA in the storage pool.


The protective action of inosine on isolated arteries in hypoxia.

1 The pressor responses to injected noradrenaline (NA) of isolated perfused femoral or renal arteries of the rabbit were studied.2 Vascular smooth muscle is relatively resistant to hypoxia. A combination of hypoxia and dinitrophenol (DNP) respiratory uncoupling was necessary to abolish the pressor response to NA. Loss of the pressor response was assumed to result from decreased capacity of arteries to form adenosine 5'-triphosphate (ATP). Reperfusion of the hypoxic arteries with oxygenated medium resulted in recovery of the pressor response to NA.3 Inclusion of inosine (10 mM) in the hypoxic perfusion medium increased significantly the rate and extent of post-hypoxic recovery of the pressor response to NA.4 Whereas the presence of inosine in the hypoxic perfusion medium aided post-hypoxic recovery, inosine had no direct action on the pressor dose response to NA. Therefore, the action of inosine was protective as opposed to direct.5 The protective action of inosine did not involve potentiation of NA binding to NA-adrenoceptor sites (the equilibrium coefficient, K(eq) for NA-receptor interaction was unaltered by hypoxia and/or inosine).6 The results are discussed in terms of a presumptive mechanism whereby inosine is believed to act by maintaining intracellular adenine nucleotide concentrations in hypoxia.


Effects of procaine and extracellular calcium concentration on response of rat stomach fundus muscle to acetylcholine and 5-hydroxytryptamine.

1. When rat stomach fundus muscle was incubated for 30 min in Tyrode solution from which calcium chloride had been omitted, there was an almost complete abolition of the contractile response to 5-hydroxytryptamine (5-HT) while that to acetylcholine (ACh) was still present. 2. The maximum tension obtainable with ACh remained the same in external calcium concentrations ranging from 0.45 to 3.6 mM, but the pD2 value increased. 3. A concentration of at least 0.9 mM calcium was needed to maintain a maximum contraction with 5-HT, and the pD2 for this agent also increased significantly with increase in calcium content of the medium. 4. The effects of procaine on the responses of the muscle to 5-HT and ACh were similar to the respective changes induced by lowering the calcium concentration, and were reduced by the addition of calcium. 5. Concentrations of 2.2 x 10(-7) to 3.6 x 10(-5) M procaine reduced the effects of both 5-HT and KCl and suppressed the maximum responses. 6. The maximum responses to KCl and 5-HT were restored at higher concentrations of procaine (greater than 3.6 x 10(-4) M), while the effect of ACh was reduced. 7. It is suggested that 5-HT, like KCl, is almost entirely dependent on extracellular calcium for inducing muscle contraction, while ACh may utilize calcium from bound stores.


Shape change of blood platelets--a model for cerebral 5-hydroxytryptamine receptors?

1. In blood platelets of rabbits isolated by a stractan gradient and incubated in a protein-poor medium, tryptamine, 5-hydroxytryptamine (5-HT) and derivatives, quipazine and mescaline caused a shape change. This shape change was inhibited by low concentrations of methysergide. 2. The most potent antagonists of the 5-HT-induced shape change included ergoline derivatives and neuroleptic drugs, which showed high stereoselectivity. 3. (+)-Lysergic acid diethylamide ((+)-LSD), psilocine and some N',N'-dimethylated tryptamines acted as mixed agonist-antagonists. 4. The compounds found to be agonists or mixed agonist-antagonists on platelets have previously been shown to act also as 5-HT agonists in the central nervous system (CNS). 5. With regard to 5-HT antagonists, the 5-HT receptors of platelets reacted differently from those described earlier in brain areas with dense 5-hydroxytryptaminergic innervation, but showed similarities to 5-HT receptors investigated previously in spinal cord, cerebral cortex and possibly reticular formation. 6. It is concluded that platelets may be considered with caution as models for some, but not for all, 5-HT receptors in the CNS.


Stimulation of specific [3H]-ouabain binding to microsomal preparations from rat heart and skeletal muscle by thyroid hormones: effects of 6-hydroxydopamine.

1. Surgical thyroidectomy decreased specific [3H]-ouabain binding to heart ventricular microsomes by 43% and gastrocnemius muscle microsomes by 34%. Administration of triiodothyronine to euthyroid rats enhanced specific [3H]-ouabain binding to heart and skeletal muscle membrane by 60% and 33% respectively. 2. Treatment of thyroidectomized rats with triiodothyronine increased specific [3H]-ouabain binding by 44% in skeletal muscle membrane preparation and 428% in cardiac microsomes. 3. Specific [3H]-ouabain binding decreased by 55% in heart and 53% in gastrocnemius muscle preparations following chemical sympathectomy with 6-hydroxydopamine. 4. Treatment with triiodothyronine of euthyroid rats which had been sympathectomized did not significantly alter specific [3H]-ouabain binding to heart or skeletal muscle membrane preparations. 5. Administration of triiodothyronine to thyroidectomized and sympathectomized rats increased specific [3H]-ouabain binding by 80% in heart and 83% in skeletal muscle membrane preparations. 6. These results suggest that triiodothyronine may influence specific [3H]-ouabain binding to thyroid hormone nonresponsive tissue such as sympathetic nerve endings. Therefore, the present observations are incompatible with the hypothesis that induction of (Na+ +K+)-adenosine triphosphatase of skeletal muscle membrane is the molecular mechanism for the calorigenic actions of thyroid hormones.


The role of histamine H1- and H2-receptors in the generation of thromboxane A2 in perfused guinea-pig lungs.

1. When isolated perfused lungs from normal and ovalbumin sensitized guinea-pigs were challenged with histamine and 2-methylhistamine (agonists for H1-receptor), a release of thromboxane A2-like substance was observed. The effect of histamine on production of thromboxane A2 (TXA2) in sensitized lungs, was more pronounced than in normal lungs (P less than 0.01). 2. Specific activation of histamine H2-receptors in normal lungs with large doses (100 micrograms) of dimaprit and 4-methylhistamine, does not produce thromboxane-like or prostaglandin-like substances. 3. Perfusion of the lungs with pyrilamine (10 micrograms/ml) inhibited the release of arachidonate metabolites induced by histamine H1-receptor stimulation, whereas cimetidine (5 micrograms/ml) was ineffective. 4. It is concluded that only the stimulation of histamine H1-receptors appears to be responsible for generation of thromboxane A2 and other prostaglandin-like substances in normal guinea-pig lungs. In sensitized lungs, an increased ability of histamine to release TXA2 could be due to a possible interconversion of H2 into H1-receptors.


Action of prostaglandin dehydrogenase inhibitors on prostaglandin uptake in rat isolated lung.

1. The effects of some inhibitors of 15-hydroxy-prostaglandin dehydrogenase (PGDH) have been studied on the inactivation of prostaglandin E2 (PGE2) and 16, 16-dimethyl PGE2 in rat isolated lung. 2. Bioassay was used to show that the inactivation of PGE2 and its methyl analogue, was inhibited by frusemide (10(-3) M), N-ethyl maleimide (10(-5) M) and 5,5'-dithio-bis-2-nitro-benzoic acid (10(-2) M), but not by caffeine (2.5 x 10(-3) M). 3. The efflux of radioactivity from lung following injection of [14C]-PGE2 was faster in lungs treated with frusemide, N-ethyl maleimide or bromcresol green, than in untreated lungs. 4. Caffeine (10(-3), 10(-2) M) did not change the rate of 14C-efflux from lungs following injection of [14C]-PGE2. 5. From these results it is concluded that those PGDH inhibitors that prevented prostaglandin inactivation in isolated lungs did so by inhibiting uptake of prostaglandin rather than by inhibiting PGDH.


Effects of verapamil, dantrolene and lanthanum on catecholamine release from rat adrenal medulla.

1. The release of catecholamines (CA) from rat adrenal incubated in vivo in Locke solution was studied. 2. Acetylcholine-induced release of CA and CA release by 56 mM KCl were inhibited by verapamil and lanthanum chloride which block calcium permeability. 3. CA secretion induced by salbutamol or by theophylline was unaffected by either verapamil or lanthanum chloride. 4. Dantrolene-sodium inhibited the CA secretion induced by theophylline but only partially reduced potassium-induced release of CA. 5. Verapamil enhanced the secretion of CA induced by salbutamol (in a calcium-free medium). 6. Tyramine-induced secretion of CA was unaffected by lanthanum chloride, verapamil or dantrolene-sodium. 7. It is suggested that cyclic adenosine 3',5'-monophosphate-mediated CA secretion (induced by theophylline or salbutamol) depends on release of calcium from intracellular stores, and that CA secretion induced by tyramine is independent of intra- or extracellular calcium.


On the role of 5-hydroxytryptamine in drug-induced antinociception.

1. The effects of four specific inhibitors of 5-hydroxytryptamine (K-HT) uptake on morphine-, methadone- or pethidine-induced antinociception was studied in rats. Antinociception was assessed by means of hot plate (55 degrees C) reaction times. The effect of the compounds on the uptake of [3H]-5-HT into rat whole brain synaptosomes was also investigated. 2. Pretreatment with Org 6582, citalopram, zimelidine or femoxetine at doses devoid of antinociceptive activity potentiated morphine- but not methadone- or pethidine-induced antinociception. 3. A temporal correlation existed between the ability of Org 6582 to potentiate morphine-induced antinociception and to block synaptosomal [3H]-5-HT uptake. 4. 5-HT plays a critical role in the antinociceptive effect of morphine but not of methadone or pethidine.


Assessment of the effects of vasoactive intestinal peptide (VIP) on blood flow through and salivation of the dog salivary gland in comparison with those of secretin, glucagon and acetylcholine.

1. The vascular bed of the submandibular gland in situ was perfused with blood through the glandular artery at a constant pressure in anesthetized dogs. All drugs were administered intra-arterially. 2. Vasoactive intestinal peptide (VIP), secretin and acetylcholine produced a dose-dependent increase in blood flow through the artery (vasodilatation) but glucagon was almost ineffective. 3. Dose-blood flow response curves for VIP and secretin were parallel, and VIP was about 100 times as potent as secretin on a molar basis. Dose-blood flow response curves for acetylcholine were flatter than those for VIP and secretin. Acetylcholine was approximately as potent as secretin on a molar basis. 4. No tachyphylaxis developed to the vasodilator action of VIP. 5. The vasodilator responses to VIP and to electrical stimulation of the chordolingual nerve were scarcely modified by (-)-hyoscyamine in doses that fully antagonized the vasodilator response to acetylcholine. 6. VIP, secretin and glucagon were ineffective in eliciting salivary secretion. 7. The possibility that VIP is released from parasympathetic vasodilator nerves and mediates the atropine-resistant vasodilatation in the dog submandibular gland is discussed.


Investigation of the role of calcium in the supersensitivity produced by cocaine in cat spleen strips.

1. Cocaine (2 x 10(-6) M and 10(-5) M) produced 2 and 7 fold shifts to the left of the dose-response curve to (-)-noradrenaline recorded isotonically in isolated splenic capsular strips of the cat. 2. The same concentrations of cocaine also produced increases in the maximum response of the tissue to 117% and 126.7% of control. 3. Desmethylimipramine (DMI, 10(-7) to 10(-6) M) produced no significant potentiation of the response of cat spleen strips to (-)-noradrenaline. At 10(-5) M DMI decreased the maximum response. 4. Cocaine (10(-5) M) produced a 3.3 fold shift to the left of the dose-response curve whereas DMI (10(-6) M) had no effect on the dose-response curve to oxymetazoline in cat splenic capsular strips. 5. Cocaine (10(-5) M) in the presence of phentolamine (10(-6) M) produced a shift to the left and an increase in the maximum response to K+, an agonist which is believed to produce muscle contraction by increasing the membrane calcium flux. 6. Cocaine (10(-5 M) had no effect on the dose-response curve to angiotensin which is believed to contract vascular muscle by releasing calcium from intracellular storage sites. 7. The potentiating effect of cocaine (10(-5) M) on responses of spleen strips to (-)-noradrenaline was blocked by the calcium flux inhibitor SKF 525A (2.65 x 10(-5) M). 8. It is concluded that the results are compatible with the view that cocaine enhances the influx of calcium across the cell membrane during responses to agonists that utilize the extracellular pool of calcium and that this effect is responsible for a large part of the potentiation of the response.


The action of microelectrophoretically applied (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI) on single cortical neurones.

1. The technique of microelectrophoresis was used in order to compare the actions of the imidazoline derivative, (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI), with those of dopamine and phenylephrine on single neurones in the cerebral cortex of the rat anaesthetized with halothane. 2. DPI and phenylephrine were almost exclusively excitatory, whereas dopamine could evoke both excitatory and depressant responses. 3. In the case of excitatory responses, DPI appeared to be more potent than dopamine, and was approximately equipotent with phenylephrine. 4. The dopamine antagonist, haloperidol, could discriminate between excitatory responses to DPI and dopamine: responses to dopamine were abolished, whereas responses to DPI, and to a control agonist, acetylcholine, were unaffected. 5. The alpha-adrenoceptor antagonist, phenoxybenzamine, antagonized equally excitatory responses to DPI and phenylephrine. Responses to acetylcholine were not affected. 6. It is concluded that DPI does not stimulate dopamine receptors on cortical neurones; the excitatory responses of these cells to DPI may be mediated by alpha-adrenoceptors.


Haemophilic arthropathy in the joints of the hands and feet.

Radiographs of the hands and feet of 72 haemophilic patients were reviewed for peripheral joint involvement. Fifty patients or 69% had changes in the small joints of their hands and/or feet with a total of 160 abnormal joints. In the hands the metacarpo-phalangeal joints were predominantly involved (42 of 50 joints), and in the feet, the metatarso-phalangeal joints (68 of 110 abnormal joints), as well as the posterior subtalar joint (36 of 110 joints). Röntgen abnormalities were characterized by irregularity and/or flattening of the articular cortices. The involvement of the small peripheral joint in haemophilic patients has not been a primary consideration in previous clinical and radiographic studies because of the more common and more debilitating changes in the large joints. The recognition of involvement of the small joints is described to avoid misinterpretation of the röntgen findings and to appreciate the incidence of involvement, especially with the increased availability of replacement therapy.


Intrathoracic rib: radiographic features of two cases.

Two cases of intrathoracic rib are presented. In one of these the anomalous rib was not supernumerary, and the investing layers of pleura caused the rib to appear abnormally dense. The relevant literature is briefly reviewed.


Ultrasound in the detection of chronic liver disease (the "bright liver").

The association of high amplitude echoes returned from the liver and advanced cirrhosis is well recognized. We have become increasingly aware of a bright liver echo pattern in relatively mild cases of cirrhosis and in other chronic liver diseases. The pattern is very characteristic but non-specific in pathological terms. We have undertaken a small pilot study based on the observation of this characteristic ultrasound appearance to assess its clinical significance. Recognition of this pattern has always corresponded with liver disease of one of five types: cirrhosis, fatty infiltration, portal tract fibrosis, severe hepatitis or longstanding congestive cardiac failure. Although the use of ultrasound appears to be sensitive in the detection of generalized liver disease, it is relatively non-specific.


The radiation dose to patients from EMI brain and body scanners.

Absorbed doses throughout the head of a Rando standard man phantom have been measured during simulated neurological examination with the EMI Mk I brain scanner and the second generation CT 1010 brain scanner. Similar measurements have been made with the CT 5005 whole-body scanner which have also included scans through thoracic and abdominal sections of the phantom. Lithium borate thermoluminescent dosimeters placed at regular intervals throughout, and on either side of the scanned volume, have enabled estimates to be made of the total energy imparted to the phantom by each scanner as well as the absorbed dose at various locations including organs of interest in health physics such as the lens of the eye, thyroid and gonads. Isodose curves have been plotted for the central transverse section of each simulated examination. Results are reported for both the standard and high accuracy scan speed options on the two scanners where this choice is available. It would appear that all three machines when operated at their standard scan speeds impart no more energy to the phantom than that associated with a few conventional radiographs of the same part of the body. Maximum skin doses vary from 30 to 56 mGy (3.0 to 5.6 rad) being highest for the CT 1010 scanner. Use of the high accuracy scan option increases the energy imparted and the maximum skin doses by a factor of about five, while providing much enhanced tissue density discrimination. In the case of the body scanner this higher value of energy imparted becomes comparable to that associated with lengthy fluoroscopic examinations like barium enemas. Recent work by EMI involving further refinements to the collimation system has reduced the dose levels by typically 50%. Some preliminary results with this new system are included to indicate the likely degree of improvement, but a detailed account will be the subject of a separate paper.


The response of six mouse tumours to combined heat and X rays: implications for therapy.

The response of six types of mouse tumour to single doses of X rays alone or to X rays in combination with moderate hyperthermia (42.5 degrees C/60 min) has been assessed using delay in tumour regrowth. Thermal sensitization was observed in five of the six tumours. The degree of sensitization varied with the size of the X-ray dose, being larger at higher doses. The degree of sensitization also depended on the sequence and separation of the heat and irradiation. The thermal sensitization has been measured in terms of the X-ray doses to produce the same level of tumour damage with or without heat, i.e. thermal enhancement ratios. These TER values, measured for X-ray doses in excess of 20 Gy, are not greater in any of the tumours than in a range of normal tissues, if the X rays and heat are given in close succession. Separation of the heat and X rays reduces the TER values slightly, but some effect is still apparent at 3--24 hours. In normal tissues the effect of heat is totally lost within four hours. Comparison of these tumour data with published normal tissue data indicates a therapeutic advantage if the heat and X rays are separated by more than one hour. This therapeutic gain is most reliably achieved and heat given after irradiation.


The influence of blood flow on temperature distribution in the exteriorized mouse intestine during treatment by hyperthermia.

The non-uniform effects of hyperthermia observed in mouse intestine when heating is achieved by immersion of an exteriorized loop of jejunum in a hot bath were quantified. Intestinal damage was assayed by crypt destruction and correlated with local temperature and distance from major mesenteric blood vessels. The rate of rise of temperature during heating was much greater in regions far from blood vessels than in those close to vessels. Equilibrium temperatures in regions close to vessels were as much as 2 degrees C below liquid bath temperature. Such temperature differentials agreed well with those predicted from the heterogeneity observed in crypt destruction. Both histological and thermometric data suggest that major blood vessels may influence tissue temperature over a distance of approximately 2 mm and, within this region, temperature gradients of 1 degree C per mm may exist. These findings raise questions concerning the interpretation of previously reported data from water-bath heating of both tumours and normal tissues. They also emphasize the need for consideration of the influence of blood flow on heating patterns during hyperthermal treatment of patients.


Disease cost in a surgical ward.

Data relating to the cost of caring for individual patients were collected for all patients in a general surgical ward over a six-month period. From this the cost per patient was calculated for various diseases and was found to be related to duration of stay. Postoperative morbidity was important in determining cost. A system that calculates cost by means of units based on the use of resources rather than by cash cost accounting is probably the most suitable for a clinician who has to monitor resources.


Therapeutic effect of cimetidine in patients undergoing haemodialysis.

Blood concentrations of cimetidine were measured and the therapeutic effect of the drug assessed patients undergoing maintenance haemodialysis. Thirteen patients were given a single oral 200-mg dose of cimetidine a mean of 2.7 hours before the start of dialysis. Dialysing for 6--12-6 m2 hours led to a mean fall of 71% in blood cimetidine concentration during haemodialysis. Nine patients with various upper gastrointestinal lesions diagnosed endoscopically were treated for up to six weeks with a reduced cimetidine dose of 200 mg 12-hourly; two patients received two courses of treatment. Repeat endoscopy after treatment disclosed satisfactory healing, and the drug did not accumulate. This lower dose regimen is recommended for patients receiving dialysis who develop upper gastrointestinal lesions for which a histamine H2-receptor antagonist is indicated.


Hyperuricaemia in hypertension: role of alcohol.

Hyperuricaemia was present in 18 out of 73 men with untreated mild hypertension and was related significantly to alcohol intake, serum aspartate transaminase activity, and obesity. In the whole group the mean serum urate concentration correlated highly significantly with alcohol intake and activities of serum aspartate and alanine transferases but not with ponderal index, serum creatinine concentration, age, or blood pressure. Hypertension and hyperuricaemia are related at least in part through their common association with frequent alcohol use. A serum urate concentration exceeding 0.5 mmol/l (8--4 mg/100 ml) in a man with untreated hypertension is highly suggestive of heavy alcohol consumption. There was no evidence that hyperuricaemia had a deleterious effect on renal function.


Nutrient intake, adiposity, and diabetes.

To study the role of nutritional factors in the genesis of diabetes, estimations of blood sugar concentration, food intake, and adiposity (as body mass index; BMI) were carried out on three normal population samples--namely, 961 employees of Beecham Ltd, 1005 employees of the Greater London Council, and 1488 middle-aged male civil servants (Whitehall study). Blood sugar concentrations and indices of glucose tolerance correlated positively with the degree of adiposity but tended to be negatively correlated with total food energy intake and its component nutrients (total carbohydrate, sucrose, and fat). This inverse trend was largely accounted for by highly significant inverse correlations between food energy intake and adiposity, a relation found in both sexes and in all three population samples and which extended across the whole range of nutrient intake and BMI. These findings suggest that greater degrees of adiposity are associated with lower than average food energy intakes and hence lower total energy expenditures. The association of increased adiposity with low food energy consumption may indicate an underlying "low energy throughput" state, and it may be the mechanisms of this, as well as the obesity, that are responsible for disease.


Divergent views of hospital staff on detecting and managing hypertension.

A questionnaire about detecting and managing hypertension was answered by 76 out of 110 (69%) doctors and 116 out of 195 (63%) qualified nurses in a large hospital. There was no general agreement on the method of taking diastolic blood pressures or on the level of hypertension requiring treatment. Most of the clinicians treated mild hypertension, although no proof exists that such treatment is beneficial. Almost everyone questioned agreed that measuring blood pressure in all patients attending hospital is important. Agreement should be reached, however, on which phase of diastolic blood pressure should be used.


Childhood cancer and drugs in pregnancy.

A study was carried out on 11 169 matched case-control pairs of children aged up to 15 years included in the Oxford Survey of Childhood Cancers to see whether an association exists between cancer in children and drugs given to their mothers during pregnancy. The mothers of children who developed cancer reported about 25% more illnesses during pregnancy than mothers of healthy control children. Two specific illnesses, pulmonary tuberculosis and epilepsy, were investigated. For these there was a higher than average case-control excess of reports and there had been a suggestion that the drugs used in treatment, isoniazid and phenytoin, might be carcinogenic. The results of this investigation provide no real evidence for any association between the drugs taken by the mothers during pregnancy and subsequent cancer in the child.


Fats and atheroma: a retrial.

The controversy over medical endorsement of dietary measures to reduce cholesterol intake has been reconsidered. The results of several published reports that apparently do not confirm the association between diet, cholesterol concentrations, and ischaemic heart disease (IHD) were found to be largely inapplicable to the argument. Results of primary prevention trials, however, suggested that lowering the cholesterol concentration had a beneficial effect in reducing morbidity from IHD. The "average Western diet" is particularly associated with accelerated or premature atherosclerotic disease, yet the saturated fatty acid component of the diet may be only one of several factors relevant to IHD. Such diets are usually high in refined carbohydrate and total energy intake. Disordered nutrition generally, and other environmental and constitutional factors seem to be important in the aetiology of IHD. A prudent diet, incorporating decreased intake of fats, simple sugars, and refined carbohydrate, with polyunsaturated fats comprising less than 25% of total energy intake, may be the best method of reducing the incidence of IHD and other diseases of overnutrition.


Upper gastrointestinal endoscopy: its effects on patient management.

Out of 95 patients referred for upper gastrointestinal endoscopy after a barium-meal examination, 44 underwent a change in management. Some changes were minor but in 12 patients a decision on surgery was required. Seven of these patients were among a group of 13 for whom the referring consultant would have recommended laparotomy had endoscopy not been available, while the other five were subjected to an unplanned laparotomy. These findings support the practice of performing endoscopy on patients whose symptoms are not fully explained by barium-meal examination, especially patients aged over 45. In such cases the procedure also seems to be cost-effective.


Carcinoembryonic antigen in breast-cancer tissue: a useful prognostic indicator.

Sections of breast carcinomas removed from 69 patients six to 13 years previously were examined using an immunoperoxidase technique to determine whether carcinoembryonic antigen (CEA) was present. Patients who had CEA-negative tumours had significantly higher five- and 10-year survival rates. The difference was not related to the stage of the disease, postoperative treatment, or histological type of tumour. These results suggest that immunohistological assessment of CEA in breast-cancer tissue may provide more precise prognostic information.


Occult aortic stenosis as cause of intractable heart failure.

During a three-year period 10 patients with critical aortic stenosis were referred to a cardiac referral centre with symptoms and signs of intractable cardiac failure and low cardiac output. In nine patients the correct diagnosis was not suspected at the referring hospital, and in the remaining patient the true severity of the aortic stenosis was not appreciated and cardiomyopathy was suggested as an additional diagnosis. The most common referral diagnoses were severe mitral regurgitation (four patients), congestive cardiomyopathy (two patients), or both (three patients). Only two patients had soft ejection systolic murmurs at the base of the heart radiating into the neck, and such a murmur appeared in a third patient during medical treatment. The carotid pulses were of small volume but the characteristic slow-rising, anacrotic nature of the pulse could not be appreciated clinically. The diagnosis was suspected in nine patients because of aortic valve calcification detected by lateral chest x-ray examination in seven patients and by x-ray screening of the heart in two, and because of abnormal aortic valve echoes in the echocardiogram of all five patients in whom the aortic valve could be seen. Eight patients underwent aortic valve replacement despite seemingly poor preoperative left ventricular function. Three patients died, of whom two had severe coexistent coronary artery disease. The five survivors all returned to normal lives and needed little or no medication.Critical aortic stenosis should be actively sought in patients with severe heart failure of unknown cause since surgery may enable them to resume their normal lives.


Variation in hospital stay after inguinal herniorrhaphy.

A study was carried out of 1086 men aged 16-65 inclusive who were admitted under nine consultants to eight hospitals in Wessex for elective repair of an inguinal hernia. The mean postoperative stay was 5.7 +/- SD 2.7 days. For different consultants operating at any one hospital the mean postoperative stays were similar, whereas for consultants who operated at more than one hospital they were significantly different. The postoperative stay was also significantly related to the size of the hospital, development of postoperative complications, time spent on the waiting list, type of repair used, bilateral herniorrhapy, and the use of convalescent facilities. The hospital therefore appears to exercise a greater influence in determining the mean postoperative stay than does the individual consultant.


What shall we teach undergraduates?

The opinions of 600 randomly selected doctors on what should be taught to undergraduates in clinical years were analysed. The respondents gave a high priority to general medicine, paediatrics, general surgery, casualty, and gynaecology, but a low priority to forensic medicine, plastic surgery, radiotherapy, anaesthetics, radiology, and rehabilitation medicine. Doctors thought that these should be taught to postgraduates. The two major groupings of doctors--general practitioners and consultants--gave essentially the same priorities. Undergraduate curricula cannot include all major specialities, so the results of this analysis may provide a useful basis for selecting the most suitable subjects. Criteria for including other specialties might be the ability and enthusiasm of the teachers and well-thought-out and academically sound teaching programmes.


Blood-pressure screening and supervision in general practice.

Since April 1975 all men aged 35-69 years registered with four general practices in west central Scotland have had their blood pressure checked whenever they visit the surgery. Although the practice locations range from rural to city centre and observers comprise receptionists, nurses, and doctors, a standard procedure has been adopted for the examination, recording, follow-up, and management of high blood pressure. The results confirm that raised blood pressure is common and often goes undetected. Even when hypertension is known, casual blood pressure readings often exceed accepted normal levels. The findings also show that a population may be routinely examined through normal contact with the family doctor, and that this can provide a convenient, acceptable, and effective means of detecting and reducing raised blood pressure.


Value of cytology for detecting endometrial abnormalities in climacteric women receiving hormone replacement therapy.

Over six months 113 endometrial specimens from 110 menopausal women receiving hormone replacement therapy were examined by two cytologists and two histopathologists. Specimens were obtained by aspiration with the Isaacs cell sampler immediately before Vabra suction curettage, both procedures being performed in the outpatient department without anaesthetic. The histologists agreed with each other on the classification of 85 specimens (75.2%) and the cytologists agreed on the classification of 44 (38.9%). In only 15 cases (13.3%) did all four observers agree. Of the three cases of cystic or adenomatous hyperplasia detected histologically, only one was diagnosed by cytology. Furthermore, both cases of adenocarcinoma escaped detection by cytology, though a third case--later confirmed-"was suspected by one cytologist alone. Use of the Isaacs endometrial cell sampler cannot be advocated for routine screening of women with climacteric symptoms receiving hormone replacement therapy. Efforts should be made to establish the correct dose and duration of treatment with an oestrogen-progestogen preparation in order to avoid over-stimulating the endometrium and the need for regular screening for endometrial abnormalities.


Changes in fatty-acid composition of body fat before and after birth in Tanzania: an international comparative study.

Changes in the fatty-acid composition of human adipose tissue before birth and during infancy and childhood were studied in Tanzania and compared with data for British and Dutch infants in relation to their diet. From the 32nd to the 37th week of gestation in Tanzania the proportion in the body fat of the unsaturated fatty acid linoleic acid tended to rise, suggesting an adequate supply of this essential fatty acid from the mother to the fetus. At term 2.5% of the total fatty acids of the body fat was linoleic acid, which corresponded with values in Dutch newborn infants but was significantly higher than those in British infants. During infancy in Tanzania the composition of the fat showed a dramatic increase in the proportions of the saturated fatty acids lauric acid and myristic acid, which did not occur in Dutch and British infants. The proportion of linoleic acid increased to 8%. These changes were a reflection of the fatty-acid composition of the fat in the human milk that the infants received. During weaning (1-2 years of age) the fatty-acid composition changed only slightly. The specific fatty-acid composition of the fat in Tanzanian breast milk may have a beneficial influence on the extent of intestinal absorption in the newborn child.


Campylobacter colitis.

Eleven consecutive patients with diarrhoea from whose stools campylobacter were isolated were investigated by sigmoidoscopy and rectal biopsy. Eight had definite proctitis, and in seven biopsy specimens were abnormal with histological changes ranging from non-specific colitis to gross colitis with goblet-cell depletion and crypt-abscess formation. Nine of the patients passed blood in their stools, and in all but one abdominal pain was a feature of the illness. Severe campylobacter colitis may be clinically, sigmoidoscopically, and histologically difficult to differentiate from ulcerative colitis and is a differential diagnosis in acute colitis.


Optimal timing of doses of chenic acid in patients with gall stones.

Sixteen patients with gall stones were treated with chenic acid (14-16 mg/kg/day) given at three different times in random order for one month each. Before treatment the mean (+/- SE of mean) cholesterol saturation index (SI) of fasting gall-bladder bile was 1.28 +/- 0.06. During bedtime administration of chenic acid the mean SI fell to 0.78 +/- 0.04, which was significantly lower than that obtained with administration in the morning (0.92 +/- 0.05) or with three divided doses at mealtimes (0.92 +/- 0.04). The bile remained supersaturated in seven patients when they received a single morning dose, in five patients when they received mealtime doses, but in only one patient when a single bedtime dose was given. There was no significant difference in side effects between the three different dose timings, or in the proportion of bile acids present in the bile as chenic acid. This enhanced effect obtained with bedtime administration may be due to the enterohepatic circulation of bile acids being maintained during overnight fasting.


Respiratory influence on heart rate in diabetes mellitus.

To find a simple and accurate test of autonomic nervous dysfunction in diabetes mellitus, 41 insulin-dependent diabetics and 25 controls were investigated. The diabetics, none of whom had symptoms of autonomic dysfunction, were tested for retinopathy and sensory neuropathy. Each subject also performed maximal deep-breathing procedures while undergoing electrocardiographic recording: in normal subjects the intervals are shortened during inspiration and prolonged during expiration, and a difference in the heart rate between inspiration and expiration of 10% or less seems to indicate autonomic dysfunction. This difference was calculated as an E:I ratio of the mean of the longest R-R interval during maximal expiration to the mean of the shortest during maximal inspiration. Ten of the 18 patients found to have sensory neuropathy had abnormal E:I ratios, and among those with absent ankle reflexes the proportion was even higher (9 out of 11). The E:I ratio also seemed to be as accurate as traditional tests for autonomic dysfunction and easier to perform. Diabetics with autonomic dysfunction have an increased risk of acute cardiorespiratory death during and after surgery, and maximal deep breathing and calculation of the E:I ratio may be a useful test to perform on diabetics at risk.


Diabetes after infectious hepatitis: a follow-up study.

Eleven patients (nine men, one woman, and one girl) aged 11-62 years who developed diabetes mellitus after an attack of infectious hepatitis during the Eastern Nigerian epidemic of 1970-2 were followed up for two to nine years. One patient aged 60 years remained diabetic after the original illness. In the remaining 10 patients the diabetes remitted after three to nine months (mean 6.7 months) but in four it recurred after a remission lasting one and a half to four years (mean 2.6 years). Results of this follow-up study seem to confirm that the pancreas is sometimes permanently damaged during infectious hepatitis.


Relatives and friends group in a psychiatric ward.

To enable relatives and friends of psychiatric patients in a 30-bed acute admission ward to meet the staff team together a relatives and friends group was initiated. The group was intended to provide a forum for questions about the patients' illness and treatment; allow feelings, such as anger and anxiety, about the patient's illness to be expressed; and enable relatives and friends to share their experiences and offer advice and support to each other. A study was designed to assess the feasibility of the group scheme. Relatives and friends were invited to the day room of the admission ward each Wednesday evening for one hour. The visitors chose their own topics for discussion and the staff team tried to answer questions and to facilitate a free exchange of views. An account of each meeting was documented, including details of attenders, the nature of the topics raised, and a simple measurement of some of the emotions expressed by the visitors. Overall, the effect of the meetings seemed positive and productive, for they allowed relatives and friends to ask questions about many topics, to express pent-up emotions, and to gain a better understanding and tolerance of the patient's illness. The relatives and friends group has become an integral part of treatment on the wards. Now that the feasibility of such a group is established, further studies are required to evaluate its efficacy.


Psoriasis and cancer.

The incidence of skin cancer in patients with psoriasis seems to be low, despite repeated use of known carcinogens in treating the disorder. This may be due to a reduced capacity of psoriatic skin to metabolise precarcinogens because of impaired arylhydrocarbon hydroxylase (AHH) activity. If this hypothesis is correct, and impaired AHH activity in psoriatic skin is shared by other tissues, the incidence of cancers associated with environmental carcinogens may also be reduced in patients with psoriasis. Since the disease is probably genetically transmitted as a dominant trait, it may have persisted because it confers genetic advantage. This hypothesis, though speculative, provides a basis for further study.


Continuous narcotic infusions for relief of postoperative pain.

Relief of acute pain after surgery or trauma is still inadequate in many centres, most patients being treated with intermittent intramuscular injections of narcotic analgesics. Over the past three years continuous intravenous narcotic infusions have been used at this hospital to treat postoperative pain; recently a system has been devised whereby an hourly dose is given and the dispenser recharged every hour. The method used is cheap and reliable, and signs of overdosage may be easily checked by nursing staff. Side effects rarely occur. Fifty patients who had received intravenous infusions after undergoing major abdominal surgery were sent a questionnaire to assess postoperative pain, and the results were compared with those from 50 matched controls who had received intramuscular injections. Of those who replied, only four patients who had received the infusion had found the pain distressing compared with 13 controls. Continuous narcotic infusions are most effective in relieving postoperative pain and may be given cheaply and reliably.


Glycosylated haemoglobin concentrations in newly diagnosed diabetics before and during treatment.

Concentrations of total glycosylated haemoglobins (Hb A1) were measured in 40 diabetics at diagnosis and at monthly intervals after treatment with chlorpropamide, insulin, or diet alone was begun. The mean Hb A1 concentration at presentation in 16 patients treated with chlorpropamide was significantly higher than that in 12 patients treated with insulin, and the duration of glycaemic symptoms was much longer in the chlorpropamide-treated group. In contrast, the mean plasma glucose concentration was similar in both groups. The mean concentrations of Hb A1 and plasma glucose at diagnosis in the 12 patients treated by diet alone were lower than those in the other two groups, and most of these patients were free of symptoms. Treatment quickly relieved symptoms and lowered plasma glucose in all patients. The Hb A1 concentration fell significantly with treatment such that after two months there was no significant difference between the three groups, although results remained above the normal range. These findings support the theory that the Hb A1 concentration reflects the blood glucose control over the previous one to two months and suggest that the duration of hyperglycaemia may be important in determining the Hb A1 concentration as well as the absolute blood glucose concentration.


Evaluation of two regimens to immobilise the knee after injections of yttrium-90.

Two regimens to immobilise the knee after injection were compared in patients receiving intra-articular yttrium-90 for persistent synovitis of the knee, the patients being randomly allocated to receive either complete bed rest or full mobilisation with the affected knee in a firm splint. There was no difference in the percentage of the radioisotope retained in the knee or in that taken up by other tissues between the two regimens. It is concluded that after intra-articular injections of yttrium-90 strict bed rest in hospital is unnecessary.


Mobile orthoptic service for primary screening of visual disorder in young children.

A mobile orthoptic service was begun in 1976. General practitioners, clinic doctors, and health visitors referred 4544 preschool children to the service in 18 months. Of the children referred, no defect was detected in 3138 (69%), 927 (20%) were recalled for a second assessment within 12 months, and 479 (11%) were referred for treatment. Out of 261 who received treatment in Oxford, 24 (9%) received aftercare. Benefits of the service included a 25% decrease during 1976-7 in inappropriate referrals of preschool children to the specialist hospital. The chance of inappropriate referral was reduced by a factor of 30 if a child was referred to the mobile service instead of to the eye hospital. A prevention programme such as the mobile orthoptic service can improve the rate of detection of visual disorder in young children, while providing the support needed by primary-care doctors and nurses for visual screening of preschool children easily and cheaply.


The object of the sensory cortex.

The phenomenon of "transfer" is used to draw attention to the point that whereas the brain stem animal can solve a variety of individual problem ad hoc, only the intact animal appears to be able to use the result of one problem to solve a closely related problem. It is suggested that this is because information is organized in the cortex as objects and concepts, rather than as a set of more or less elaborate features. The shortcomings of a hierarchical system of feature detectors as a model of cortical organization are examined, and compared with a distributive model. It is pointed out that our ways of thinking about complex tones--e.g. their pitch and harmonic structure--is related to the fact that sound suffers a Fourier transform at the cochlea, and it is this transform which is represented in the brain stem. It is suggested that an analogous integral transform may equally naturally represent the data as "objects" in the cortex. The resistance of such transforms to degradation by ablation, and the implication for single neurone behaviour are discussed.


Ontogenetic aspects on visual "size-constancy" phenomena in the midwife toad Alytes obstetricans (Laur.).

About 2 weeks after metamorphosis, midwife toads Alytes obstetricans judge the size of a prey object mainly in scales of visual angle. For distant objects they show a tendency to respond to absolute object size. About 6 months later the juvenile animals are able to judge absolute prey size in relation to the stimulus distance ("size constancy" phenomenon). This ability is not necessarily based on learning or previous experience.


Ultrastructural study of degeneration and regeneration in the amphibian tectum.

The processes of degeneration and reinnervation in the optic tectum of Xenopus laevis have been detailed by quantitative ultrastructural analysis. The tecta were denervated either permanently, by removing the contralateral eye, or temporarily, by cutting the optic tract. After denervation the total number of synapses decreases rapidly within 4 days of a stable level of about 40% of the original number. Vacated postsynaptic sites are subsequently removed by phagocytosis. When regenerating axons arrive in the tectum they make synaptic contact by inducing new postsynaptic membrane specializations. The ultrastructural sequence of reinnervation by optic axons resembles initial synaptogenesis.


Loss of axosomatic synapses in the dentate gyrus of aged rats.

Axosomatic synapses involving granule cells of the dentate gyrus were studied by means of quantitative electron microscopic analysis in young adult (3-month-old) and aged (25-month-old) rats. The number of axosomatic synapses per unit length of neuronal soma membrane was found to be significantly lower (by 15%) in aged animals than in young adults. This decrease in synaptic numbers is not associated with age-related changes in the size of neuronal soma profiles or in the length of their plasma membranes. The ratio between the total length of synaptic appositions and the membrane length of a neuronal soma profile was diminished by 22% in aged rats, whereas the mean length of synaptic apposition was 10% less in these animals than in young adults. These data, taken together, suggest that an absolute loss of axosomatic synapses occurs with advanced age. It appears, therefore, than not only the loss of axodendritic synapses, described previously, but also the loss of axosomatic synapses, found here, contributes to the process of age-related partial deafferentation of neurons in the rat dentate gyrus.


Glutamate as a CNS transmitter. I. Evaluation of glucose and glutamine as precursors for the synthesis of preferentially released glutamate.

Slices of the molecular layer of the dentate gyrus of the hippocampal formation were incubated with either [14C]glucose, [14C]pyruvate or 14C glutamine and the efflux of endogenous and radioactive glutamate was monitored under various conditions. After prelabeling with either [14C]glutamine or [14C]glucose elevation of K+ concentration to 56 mM (Ca2+ free) increased efflux of endogenous and [14C]glutamate. Introduction of Ca2+ into the elevated K+ medium further increased the efflux of endogenous glutamate and radioactive glutamate derived from any of the precursors tested. In glutamine containing media, the increase in glutamate efflux as well as basal efflux was considerably higher than in the absence of glutamine and the specific activity of glutamate release was higher than that in tissue. Thus glutamine was superior to glucose or pyruvate as precursor and most specifically labeled the putative transmitter pool of glutamate. Similar experiments were carried out 4 and 14 days after a unilateral lesion in the entorhinal cortex which provides about 60% of the total synaptic input to the dentate granule cells. The Ca2+ dependent release of glutamate derived from either glucose or glutamine was markedly reduced on the operated side. This result suggests that the transmitter pool of glutamate is in perforant path terminals and can be synthesized from glucose or glutamine.


Glutamate as a CNS transmitter. II. Regulation of synthesis in the releasable pool.

Slices of the molecular layer of the dentate gyrus of rat hippocampus were used to study the regulation of glutamate synthesis and release. Net glutamate synthesis increased dramatically during conditions which stimulated the release of glutamate. The rate of glutamine incorporation into glutamate released into the medium was increased almost immediately upon stimulation with a 56 mM KCl, 3 mM CaCl2 medium. Synthesis appeared to be regulated both by glutamine uptake and the activity og glutaminase. Glutamine uptake was stimulated in the presence of 56 mM KCl and 3 mM CaCl2. The increased glutamine uptake was not due to a decrease in efflux, was unrelated to tissue glutamate levels, and could be dissociated from the rate of glutamate biosynthesis. The presence of Ca2+ ions and depolarization seemed necessary. Glutaminase activity was regulated by end product inhibition: increased levels of tissue glutamate resulted in a decrease in glutamate synthesis. Glutamine in the presence of 56 mM KCl increased the rate of glucose incorporation into glutamate over that seen without glutamine.


Blockade by benzodiazepines of the selective high increase in dopamine turnover induced by stress in mesocortical dopaminergic neurons of the rat.

The effects of electrical foot shock on the activity of the ascending dopaminergic neurons were estimated in the rat by measuring the changes in DOPAC and DA levels in discrete brain areas. DOPAC and DA levels were estimated with a radioenzymatic method in microdiscs of tissues punched out from serial frontal sections of the brain. A marked rise in the ratio of DOPAC/DA levels resulting from an increase of DOPAC and a decrease of DA levels was found in the cerebral frontal cortex at the end of a 20 min stress. The effect was less pronounced in stress of shorter duration from 3 to 10 min and was only related to a reduction of DA levels. Using the DOPAC/DA ratio as an index of the activity of the neurons, the mesocortical dopaminergic neurons were found to be selectively activated under stress since this ratio was increased in the frontal and cingular cortices but not in limbic structures such as the septum, the amygdala and the nucleus accumbens or in the striatum. Finally, pretreatment of the rats with diazepam (5 mg/kg i.p.) or chlordiazepoxide (10 mg/kg i.p.) prevented the increase in the DOPAC/DA ratio in the frontal cerebral cortex of rats submitted to the 20 min stress.


On the characteristics of mitochondrial monoamine oxidase in pancreas and adipose tissues from genetically obese mice.

The substrate specificity of mitochondrial monoamine oxidase (MAO) in pancreatic and adipose tissues of obese mice and their lean counterparts was determined. The pancreatic MAO of obese mice had a greater specific activity than that of the lean mice. The white adipose tissue MAO was found to be more active than the brown adipose MAO in both groups of mice. While there was no appreciable difference in the MAO activities of brown adipose tissues between obese and lean mice, the enzyme from the white adipose tissue of obese mice had a higher specific activity than that of the lean mice. The higher MAO activity in white adipose tissue was observed when tyramine or serotonin was employed as substrate but not with benzylamine. Examination of mitochondrial MAO from epididymal adipocytes revealed marked differences in the properties of the enzyme between whole adipose tissue and isolated adipocytes. The inhibition characteristics of MAO from these tissues were studied with the specific inhibitors clorgyline and deprenyl.


Preparation and mass spectral behaviour of some 5 beta-cholenoic acids.

Monounsaturated 5 beta-cholanoic acids with double bonds in rings A, B, and C were prepared by POCl3 and ZnCl2 dehydration from natural bile acids with selectively blocked hydroxyl functions. The yields ranged from 15 to 100%. The products were purified by thin-layer and AgNO3 thin-layer chromatography and the structures were confirmed by nuclear magnetic resonance spectroscopy and mass spectrometry. The methyl ester acetates of the unsaturated 5 beta-cholanoic acids possessed chromatographic properties closely similar to those of the corresponding saturated bile acids. Several characteristic fragments were seen in the mass spectra which, in conjunction with the chromatographic properties, permitted an unambiguous distinction between different monounsaturated acids, and between saturated and unsaturated bile acids of the same number and configuration of functional groups. The 20 5 beta-cholenoic acids examined represent all of the simple chemical and enzymatic dehydration products of natural bile acids and can be completely identified by their combined chromatographic and mass spectral properties.


Influence of magnesium and polyamines on the reactivity of individual ribosomal subunit proteins to lactoperoxidase-catalyzed iodination.

30S and 50S subunits, in the presence of either 20 mM Mg2+ or 6 mM Mg2+ and 5mM spermidine plus 25 mM putrescine, were observed to completely associate to form 70S monosomes as monitored by sucrose gradient sedimentation. Subunits maintained under the above ionic conditions were compared with 30S and 50S particles at low (6 mM) magnesium concentration with respect to the reactivity of individual ribosomal proteins to lactoperoxidase-catalyzed iodination. Altered reactivity to enzymatic iodination of ribosomal proteins S4, S9, S10, S14, S17, S19, and S20 in the small subunit of ribosomal proteins, L2, L9, L11, L27, and L30 in the large subunit following incubation with high magnesium or magnesium and polyamines suggests that a conformation change in both subunits accompanies the formation of 70S monosomes. The results further demonstrate that the effect of Mg2+ on subunit conformation is mimicked when polyamines are substituted for magnesium necessary for subunit association.


Synthesis and turnover of sulfogalactoglycerolipid, a membrane lipid, during spermatogenesis.

The synthesis and turnover of sulfogalactoglycerolipid (SGG) were studied by in vivo labelling of SGG with 35S. The loss of [35S]SGG from the testes and its appearance in the vas deferens plus epididymis were followed with time. DNA was labelled by administration of [3H]thymidine and the behavior of the two isotopes was compared. The results demonstrate that SGG snythesis occurs only in very early spermatocytes and that, once made, the compound does not turn over. The SGG is lost from the testes when germinal cells die or mature into spermatozoa.


Circular dichroism studies of native and chemically modified Ca2+-dependent protein modulator.

The structural features of the native Ca2+-dependent protein modulator and two chemically modified derivatives, namely, nitrotyrosyl modulator and alkylated modulator, were examined by circular dichroism. The binding of Ca2+ to the native molecule was accompanied by an increase in helical content from 40 to 49%, with little effect on the local environments of aromatic residues in the modulator. The Mg2+ and Mn2+ do not elicit the conformational change induced by the binding of Ca2+, which also stabilizes the modulator against urea denaturation. The overall secondary structure of nitrotyrosyl modulator is indistinguishable from that of the native protein and undergoes a similar conformational change upon binding Ca2+. These observations are in agreement with the fact that nitration has no effect on modulator functions. Furthermore, nitrotyrosyl modulator interacts with troponin I only in the presence of Ca2+, as detected by circular dichroism (cd). On the other hand, alkylation of five methionine residues on the modulator with benzyl bromide affects protein conformation, as evidenced by a reduced helical content of only 35%. Alkylated modulator retains the ability of the native protein to bind Ca2+ although the affinity of this derivative for Ca2+ is reduced some three orders of magnitude relative to the native protein, with Kd = 3.2 X 10(-4) M. The results with the alkylated modulator, in conjunction with previous cd studies on N-chlorosuccinimide oxidized modulator are utilized to advance a model for the Ca2+ activation of modulator protein, based on three conformational states of the molecule.


Naphthalenone production in Aspergillus parvulus.

The naphthalenones asparvenone and its 6-O-methyl ether are produced by Aspergillus parvulus during vegetative growth in batch-mode, shaken cultures in a glucose-glycine-salts medium. The secondary metabolites first appear around the time when hyphae of developing spores begin to make contact with each other, i.e. at a very early stage of culture development. Resuspension in new medium of mycelium that is producing the naphthalenones fails to inhibit production. When A. parvulus is grown in parallel on a glucose-glycine-salts medium and on a glucose-malt-peptone medium, the naphthalenones appear first in the richer medium despite the fact that biomass proliferation is relatively unrestricted in that medium. Radiolabelled [1-14C]-acetate is taken up quickly by the fungus (k = 0.09 min-1) and is incorporated effectively into the naphthalenones.


Crude oil utilization by fungi.

Sixty fungal isolates, 34 obtained by a static enrichment technique from soils of northern Canadian oil-producing areas and 26 from culture collections, were screened for their ability to grow on n-tetradecane, toluene, naphthalene, and seven crude oils of varying composition. Forty cultures, including 28 soil isolates, were capable of growth on one or more crude oils. The genera most frequently isolated from soils were those producing abundant small condida, e.g. Penicillium and Verticillium spp. Oil-degrading strains of Beauveria bassiana, Mortieriella sp., Phoma sp., Scolecobasidium obovatum, and Tolypocladium inflatum were also isolated. Qualitative and quantitative differences were noted among the capacities of different crude oils to sustain the growth of individual fungal isolates. Data are presented which show that ability to grow on a pure n-alkane is not a good indicator of ability to grow on crude oil. Degradation of Rainbow Lake crude oil by individual isolates was demonstrated by gravimetric and gas-chromatographic techniques. The problems involved in determining the response and the potential of fungi to degrade oil spilled in the environment are discussed.


Effect of irradiance upon the population of Pseudomonas coronafaciens in leaves and symptom expression of halo blight of rye.

The toxin-induced chlorosis caused by Pseudomonas coronafaciens is influenced by irradiance. Three levels of irradiance caused differences in symptom expression but did not affect the rate of increase or final population of viable cells of P. coronafaciens in rye leaves. Distinct and faint halo blight symptoms appeared in 3--4 days in full light (1425 microW cm-2), and 58% shade (598 microW cm-2) respectively. No symptoms or only faint symptoms appeared after 7 days at 86% shade (202 microW cm-2). When plants kept in 58 and 86% shade were moved to full light 5 days after inoculation, lesion size and chlorosis increased rapidly during the next 2 days. On the 7th day after inoculation, the size of lesions from the 58 and 86% shade treatments exceeded those in full light by 2.5 and 5 times, respectively. A chlorosis index based on lesion size and chlorophyll loss within lesions also reflected this trend although chlorophyll loss was greater in lesions in full light for 7 days. Conditions of low irradiance such as that caused by overcast weather and (or) a dense leaf canopy followed by bright sunshine can cause greater losses from halo blight than a continuous period of high irradiance. Sympton expression may be masked by low irradiance but increase of inoculum is not impaired. Although increased light enhances chlorosis, toxin diffusion or production may be reduced.


The production of chaetoglobosins, sterigmatocystin, O-methylsterigmatocystin, and chaetocin by Chaetomium spp. and related fungi.

Production of mycotoxins by Chaetomium spp. and related fungi on rice culture was examined by a combination of cytotoxicity tests using HeLa cells and thin-layer chromatography. Three species, C. mollipilium, C. rectum, and C. subaffine, as well as C. cochliodes and C. globosum, were proved to produce chaetoglobosins. From cultures of four strains of Chaetomium sp., assigned to C. thielavioideum, and one strain of Farrowia sp., chaetocin, sterigmatocystin, and O-methylsterigmatocystin were isolated. Morphological characteristics of the producers of sterigmatocystins are described.


Ultrastructure of midgut events in the pathogenesis of Bacillus sphaericus strain SSII-1 infections of Culex pipiens quinquefasciatus larvae.

The fate of Bacillus sphaericus strain SSII-1 cells ingested by Culex pipiens quinquefasciatus (= C. pipiens fatigans, C. fatigans, C. quinquefasciatus of authors; Diptera: Culicidae) larvae and the cytological events preceding death of the host were observed using electron microscopy. Bacillus sphaericus cells were digested rapidly in the anterior and central midgut. The outer cell wall layer and cytoplasmic ground substance disappeared soon after ingestion. Cytolysosomes became prominent in midgut cells as these cells gradually separated from one another. All bacteria, including B. sphaericus, were confined within the peritrophic membrane until after death of the host. Digestion by the larval host is confirmed as a possible mechanism for release of B. sphaericus toxin from the bacterial cells.


Penetration into caterpillar cells of virus-like particles injected during oviposition by parasitoid ichneumonid wasps.

Particles originating from the ovarial calyx epithelium of two different species of ichneumonid wasp are injected into host caterpillars during oviposition. At 1 3/4 h post oviposition, many calyx fluid particles are either associated with or have oenetrated through the basement membranes surrounding various tissues. Shortly thereafter, apparently intact particle nucleocapsids are observed in both the cytoplasm and nucleus of host cells. An unusual tubular protrusion of the viral envelope appears to be involved in either or both of penetration of basement membranes and entry of nucleocapsids into host cells.


Further studies of a new pathogenic mycobacterium (M. haemophilum sp. nov.).

Mycobacterium haemophilum is an acid-fast rod-shaped organism, originally isolated from deep subcutaneous granulomata of a patient with Hodgkin's disease. Like the other two mycobacterial skin-pathogens, M. ulcerans and M. marinum, M. haemophilum has a maximum temperature for growth below 37 degrees C. Mycobacterium haemophilum is distinguished from all other species examined by its requirement of haemin for growth and its complete lack of catalase activity. Extraneous catalase cannot replace haemin as a growth factor for this organism. Mycobacterium haemophilum can also be differentiated from other species by the patterns of electrophoresis of protein extracts and by gas-liquid chromatography of saponificated and methylated lipid extracts. A monospecific-agglutinating antiserum against M. haemophilum was obtained by adsorption of an immunoserum with M. intracellulare. A number of slow-growing mycobacterial species develop on monolayers of McCoy fibroblasts, and growth on these tissue cultures can be observed much earlier than on artificial media. Mycobacterium haemophilum is characterized by exclusively intracellular development.


Populations of the spinach wilt pathogen, Fusarium oxysporum f. sp. spinaciae, in the root tissues, rhizosphere, and soil in the field.

Populations of Fusarium oxysporum f. sp. spinaciae in root tissues and rhizosphere soil of diseased spinach plants were higher than in the root tissues and rhizosphere soil of healthy plants. Populations in soil rhizosphere were higher than in nonrhizosphere soil. The fungus populations were very low in the root tissues of the nonsusceptible strawberry, broccoli, chinese cabbage, and mustard grown in the infested field. The populations were low at the beginning of the season, increased, and remained high during the summer, then dropped in the fall. The fungus populations ranged from 1600 to 2600 propagules/g in the top 10 cm of soil, declined sharply between 11 and 20 cm, and were nondetectable between 41 and 60 cm.


Inhibitory effect of cocoa powder on the growth of a variety of bacteria in different media.

The inhibitory effect of cocoa powder on 102 organisms belonging to 13 genera was determined. All organisms tested were inhibited by 5% cocoa. Shigella, Staphylococcus, Micrococcus, and Bacillus were the most sensitive. The degree of inhibition depended on the organism, temperature of incubation, and the medium in which the cocoa powder was suspended. Of six media tested, lactose broth and nutrient broth were the most inhibitory, while non-fat dry milk was the least inhibitory. Supplementing NB with tryptone or casein reduced the toxicity of cocoa.


Formation of abdominal cyst secondary to ventriculoperitoneal shunting.

The formation of an abdominal cyst is an uncommon complication of ventriculoperitoneal shunts. Three cases are presented in this paper and 21 previously reported cases and reviewed. The authors believe that decreased absorptive power of the peritoneum as a result of adhesions from previous multiple abdominal procedures or infection (particularly by Staphylococcus epidermidis), or both, is of etiologic significance. The patients presented with abdominal swelling and tenderness due to a malfunctioning shunt. Early diagnosis is possible by roentgenography of the abdomen and radioisotope scanning of the shunt. Paracentesis with conversion of the shunt to a ventriculoatrial or ventriculocisternal type is the treatment of choice.


Adenocarcinoma of the trachea: palliative response to cobalt-60 irradiation.

The prognosis of mucus-secreting adenocarcinoma of the trachea is grim. Its large size and infiltrative nature prohibit surgical resection and the response to radiation therapy has been poor. The authors report a case in which notable initial palliation was achieved through cobalt-60 therapy resulting in regression of the patient's tumour and a longer survival than that previously reported in patients with this disease.


Squamous cell carcinoma arising in chronic osteomyelitis.

Analysis of three cases and a review of the recent literature on squamous cell carcinoma arising in osteomyelitis confirm that this is an uncommon condition which may run a less benign course than was earlier believed. The disease affects chiefly middle-aged and older men, usually involves the lower extremity and most often occurs in the tibia. Development of a malignant tumour is heralded by increased pain and foul-smelling drainage in the presence of a fungating ulcer. Increased bone destruction is seen on the roentgenograms. A consistent finding is the long duration of infection but the authors stress that sinus drainage of long duration is not essential: the carcinoma can arise in scar overlying quiescent osteomyelitis as is occasionally seen in burn scars. Amputation is the treatment of choice.


Nephrotoxicity and ototoxicity following irrigation of wounds with neomycin.

Renal failure and ototoxicity developed in two patients following wound irrigation with neomycin. In both patients the renal failure was reversible, but the deafness was progressive despite withdrawal of the neomycin. In one patient the serum neomycin concentration was still markedly elevated (42 microgram/ml) 2 days after use of the drug was discontinued. The authors suggest that irrigation of large open wounds with neomycin is dangerous since toxic blood concentrations may ensue. The benefits conferred by neomycin irrigation should be weighed against the possible danger of permanently impaired hearing.


Localization of pheochromocytoma by selective venous catheterization and assay of plasma catecholamines.

The diagnosis of pheochromocytoma rests primarily on determination of the 24-hour urinary excretion of catecholamines and their metabolites. In most cases nephrotomography and selective arteriography or venography, or both, are sufficient to localize the tumour. Selective venous catheterization and the assay of plasma catecholamines should be considered for pheochromocytoma localization in: (a) patients in whom standard techniques fail to localize the tumour; (b) patients who exhibit idiosyncratic reactions to the angiographic contrast materials; (c) young patients or patients with familial pheochromocytoma, including those with multiple neurofibromatosis or multiple endocrine adenomatosis, type 2; (d) patients with recurrent, malignant, or suspected multicentric or extra-adrenal tumours; and (e) patients excreting only norepinephrine in the urine. The validity of the results is particularly dependent on the skill with which venous catheterization is carried out.


[Shunt glomerulonephritis: clinical and histopathological manifestations].

In patients with cerebrospinal fluid internal shunts, immune complex glomerulonephritis sometimes develops. Of two new cases the first was classic, while the second was in an adult who had had a ventriculoatril shunt for 8 years; furthermore, the patient had acute renal failure and is the first to have been reported to have Peptococcus septicemia. Shunt glomerulonephritis is characterized by the following: (a) its occurrence following, most often, Staphylococcus albus infection in a patient who usually has a ventriculoatrial shunt; (b) transitory improvement of the symptoms by antibiotherapy only; and (c) full recovery if the prosthesis is removed. Laboratory studies show a low serum concentration of the C3 component of complement, the presence of cryoglobulins and a positive rheumatoid factor test. These abnormalities are reversible with removal of the prosthesis. Optical microscopy of a renal biopsy specimen in the two cases showed cellular proliferation of the glomerular tuft, electron microscopy demonstrated subepithelial deposits and immunofluorescent studies revealed intramembranous and intramesangial immune complexes. These features are similar to those observed in experimental nephritis induced in animals by foreign protein.


Human somatotropin and lipotropin: relation between structure and activity.

Hormones of the anterior pituitary gland have been divided into three groups according to their chemical and biologic properties. Recent advances in knowledge of the relation between structure and activity of human somatotropin and beta-lipotropin are discussed.


Idiopathic calcium nephrolithiasis. 1. Differences in urine crystalloids, urine saturation with brushite and urine inhibitors of calcification between persons with and persons without recurrent kidney stone formation.

The propensity of urine to promote calcium stone formation was compared in 64 patients with recurrent idiopathic calcium nephrolithiasis and 30 healthy individuals without such a history. The rates of excretion of urine crystalloids, the urine saturation with brushite (CaHPO4-2H2O), the ability of the urine to calcify collagen in vitro, and the concentration of urine inhibitors of collagen calcification were measured. The patients had a reduced urine citrate excretion rate in addition to an increased urine calcium excretion rate, while the rates for urine magnesium, phosphate, uric acid and oxalate were not significantly different in the two groups of subjects. The urine concentration of magnesium, phosphate and uric acid was decreased in the patients because of the higher urine volume. The urine creatinine excretion rate correlated with the rates of excretion of urine calcium, magnesium, phosphate, uric acid and oxalate in both groups, which suggested that increased lean body mass, possibly associated with greater food intake, may be an important determinant of crystalloid excretion. The urine of the patients was significantly more saturated with brushite than the urine of the control subjects and resulted in greater collagen calcification when incubated in vitro. The urine concentration of inhibitors of collagen calcification, however, was not significantly different in the two groups. Thus, the urine of patients with recurrent idiopathic calcium nephrolithiasis is more highly saturated with brushite, largely as a result of an increased urine calcium excretion rate, and contains a lower concentration of magnesium and citrate, substances that tend to prevent the precipitation and growth of crystals in urine.


Idiopathic calcium nephrolithiasis. 2. Differences between hypercalciuric and normocalciuric persons with recurrent kidney stone formation and persons without such a history.

Normocalciuric and hypercalciuric patients with idiopathic recurrent calcium nephrolithiasis were compared with healthy individuals without such a history to examine the factors that predispose normocalciuric patients to stone formation. The urine calcium excretion rate was higher in the normocalciuric patients than in the control subjects (227 v. 183 mg/24 h; P less than 0.01), but the urine calcium concentration was not significantly different. The urine magnesium and citrate excretion rates and concentrations were lower in the normocalciuric patients than in the control subjects (P less than 0.001), while the urine uric acid and oxalate excretion rates and concentrations and the urine saturation with brushite (CaHPO4-2H2O) were not significantly different. These results suggest the importance of slight increases in the urine calcium excretion rate together with decreased urine magnesium and citrate excretion rates in normocalciuric persons with recurrent calcium stone formation. The urine of the hypercalciuric patients was more highly saturated with brushite than the urine of the normocalciuric patients and the control subjects, and the excretion rates of uric acid and oxalate were increased in the hypercalciuric patients. The hypercalciuric patients had a higher urine creatinine excretion rate than the normocalciuric patients and a higher daily urine volume than the control subjects, which suggests that differences in lean body mass or fluid and food intake, or both, may be important determinants of these differences in crystalloid excretion. As in the normocalciuric patients, the urine citrate excretion rate and concentration were decreased in the hypercalciuric patients compared with the control subjects.


Videotape educational program for people with asthma.

A videotape educational program was produced for use in adults with asthma. The program provided an overview of lung function, the physiologic abnormalities and treatment of asthma, and the approach to common problems encountered by the patients. Its benefits were examined in a randomized controlled study. The efficacy of the program in 62 patients whose mean duration of illness was 17 years was assessed by comparing the level of knowledge of the experimental group immediately after viewing the tape with that of the controls, who had not seen it; the experimental group scored significantly higher than the control group. Retention of knowledge attributed to the program was assessed after a mean interval of 16 months. The knowledge test score of the experimental group was found to have decreased to the level of the control group. The main areas in which the experimental group lost knowledge were self-care and drug therapy for asthma. The medical status of the two groups did not change appreciably over the period of the study.


Analysis of sudden unexpected death in southern Ontario, with emphasis on myocarditis.

The records of all 2427 autopsies performed at the Brantford (Ont.) General and Paris (Ont.) Willett hospitals from Jan. 1, 1969 to Aug. 15, 1978 were reviewed. Of the 1299 cases of sudden unexpected death investigated by a coroner almost 28% were due to unnatural causes--violence or poisoning. The main cause of natural sudden death was coronary artery disease, which accounted for 43.3% of all the sudden unexpected deaths. In 20 cases the cause of death was thought to be viral myocarditis, and in 9 of the 20 there was serologic evidence of at least previous coxsackievirus disease. Two of the nine cases were of special interest because of the finding of giant-cell myocarditis in one and aortic valve disease in the other. Eleven of the 20 persons were aged 13 to 46 years. These findings support the view that the most serious manifestation of enterovirus infection today is cardiac damage by coxsackieviruses.


Role of medical teams in a community disaster plan.

In London, Ont. two mock disaster exercises have indicated the need for re-evaluating the role of medical disaster teams. To coordinate and direct these teams a medical on-site coordinating team, composed of three emergency physicians with an expanded and more clearly defined role, was formed. The role of the triage teams deployed from the hospital to assess and resuscitate casualties is reviewed in detail. In addition, the communication systems, availability and deployment of medical supplies, identification of medical personnel and tagging of casualties are discussed. Because a mass casualty episode is possible in any community, disaster planning and clear outlining of the role of medical disaster teams are needed.


Anesthesia equipment malfunction: origins and clinical recognition.

Equipment malfunction is a problem of particular importance during anesthesia and resuscitation. A review of published reports shows that the most common clinical events involve endotracheal tubes, the inspired oxygen concentration, the volume of inspired anesthetic vapours and gases, and pressures in the breathing or ventilation system. It is concluded that protection of a patient from equipment malfunction depends on: (a) appropriate application of standards set by a national standards association; (b) careful evaluation of equipment prior to purchase; (c) comprehension of equipment function by the user; (d) conscientious routine servicing of all systems concerned with anesthesia and resuscitation, and checking after service and before clinical use; (e) preanesthesia testing of equipment, including the use of an oxygen analyser in the breathing circuit; (f) early inclusion of equipment malfunction in the differential diagnosis of events during anesthesia; and (g) rapid action that cannot present a new hazard to the patient to correct the results of apparatus malfunction.


Metatarsophalangeal fusion for hallux valgus: indications and effect on the first metatarsal ray.

Arthrodesis of metatarsophalangeal joint was performed in 31 cases of severe hallux valgus. With the surgical technique used, which is described in detail, internal fixation and plaster cast immobilization were not necessary. Analysis of the results suggested that the operation is indicated for severe deformities in elderly patients, preferably women. The basic metatarsal deformity was corrected by the procedure.


Sex differences in the utilization of health services for psychiatric problems in Saskatchewan.

Comprehensive data on all pscyhiatric patients in Saskatchewan show that women are substantially higher users of health services for psychiatric problems than are men. Women: 1) use up to twice as many services as men in the private sector, but use almost the same number of public sector services; 2) tend to be treated for psychosomatic and neurotic disorders on an outpatient basis; 3) have only a slightly greater chance than men of being hospitalized; and 4) are less likely than men to have organic or addictive diagnoses. These differentials in utilization cannot be explained by age, diagnoses and/or marital status. Sex is the best predictor of utilization. These results are largely consistent with utilization and epidemiological literature. It seems more likely that these sex differences in utilization result from the interaction of biology, sex roles, and the functioning and labelling processes of the health system rather than from any single factor. Combining Andersen's components of health behaviour with Freidson's lay-professional construction of illness continuum yields a possible framework for understanding sex differences in the utilization of psychiatric health services.


A review of women's psychotropic drug use.

This paper reviews current knowledge regarding the use of psychotropic drugs by women, who are more likely than males to be frequent and, particularly, steady users. Age and work status are also correlated with use in both sexes. Differences between the sexes in help-seeking behaviour, paths to the health care system and physician prescribing practices are also examined.


Middle income, divorced female heads of families: their lifestyles, health and stress levels.

Forty-five, French-Canadian female heads of families with adequate incomes and high educational levels were identified through newspaper ads. At time of interview, the subjects had been separated or divorced for from one to three years. Interviews showed that, unlike previous reports of divorced women and female heads of families, this group enjoyed relatively good health and normal stress levels, and were generally positive about being head of the family. Among the positive changes, the majority emphasized their greater autonomy, freedom, and sense of selfhood. Some mentioned improved relations with their children. On the negative side, loneliness, absence of the father (particularly for their sons), and limited social lives were most often mentioned. It was concluded that the role of head of family is perfectly acceptable for many economically viable women, though not necessarily ideal.


Successful coping styles in professional women.

This paper describes the experiences of seven women mental health professionals who met in a leaderless group over a period of a year and a half. There is a discussion of the conflicts for women in four major areas--competition, dependency needs, economic success and the search for role models, and the suggestion of possible successful resolutions in these conflict areas. The resolutions are a result of individual experiences and discussions in the group.


The directive sex therapies in psychiatric outpatient settings.

The treatment techniques and associated outcome studies of the directive sex therapies (DST) are briefly reviewed and data on the treatment of 12 couples are presented. The directive sex therapies have achieved rather impressive results but only with highly selected populations. Studies, such as the present, with a range of patients more typical of psychiatric outpatient settings have consistently achieved lower success rates. The important effect of patient selection on outcome with DST has, to date, received little attention. The present authors discuss selection criteria for DST in the light of the literature and the outcome in their own cases.


The psychiatrist-woman patient relationship.

This paper contends that the psychiatrist-woman patient relationship is affected by a number of powerful, yet often subtle, pressures. There are three major interacting sets of factors: the medical and mental health systems and the process of medicalization of life that has taken place over the last century; the psychiatrist, his or her training, attitude and theoretical background; and the woman patient, her socialization and view of the world which is based on perspectives formulated from a male viewpoint. As a result of these factors, any woman referred to a psychiatrist is likely to be given a psychiatric diagnosis, her problems viewed as individual and intrapsychic, the societal obstacles she faces ignored or minimized, and treatment probably geared to helping her adapt to traditional expectations. The implications for therapy are discussed, with emphasis on the need to appreciate how women have been forced into a second-hand understanding of the world. Alternatives to traditional psychotherapy are discussed briefly, stressing the need for recognition and use of these resources.


Early symptoms of bioplar affective psychosis: research and clinical implications.

Review of the available literature shows that BP psychosis rarely reveals itself earlier in life, either by alternate psychiatric illness or by impairment in educational or occupational achievement. There is some evidence from early onset cases that the illness can evolve slowly but systematic studies are lacking. The possibility is raised that what was previously regarded as a premorbid "affective" (cyclothymic or hypomanic) personality may represent the early stages of the illness itself. This view requires prospective validation. Some research implications are discussed.


Two shootings.

These two cases illustrate varying ways in which paranoid states can result in violence. The first case is a non-schizophrenic, non-alcoholic lifestyle, and the second shows the more classical paranoia associated with immigration, symptomatic use of alcohol, homosexual fears, and schizophrenic thought disorder.


Clinical aspects of the countertransference.

Some of the ways in which countertransference reactions may manifest themselves are outlined in a series of case examples, which also illustrate how the therapist's recognition of the countertransference brought to light hitherto unrecognized transference resistances, thereby permitting their interpretation and progress in therapy. A number of technical steps for dealing with the countertransference are outlined, along with the reminder that while attention to the countertransference is important the therapist's principal focus must remain with the patient.


Evaluating the competence of psychotherapists.

Pressure is increasing to develop methods for evaluating the competence of psychotherapists, not only in the field of education but also in clinical practice. The skills required of a psychotherapist have not yet been defined clearly, and are probably specific to kinds of patient and types of problem. However, there is a concensus that the capacity to establish a trusting relationship and to demonstrate concern, are essential. This relationship provides a "power-base" from which to influence the patient through a variety of elements which include "interpretation", modeling, and identification. Psychoanalysts assert that the "working through" of the transference is essential, but this is disputed by others. The evidence regarding the value of experience as a psychotherapist is unclear. Again there are conflicting reports. It appears that reasonable competence in technique can be acquired (through modeling) within the first year of training. It may be that the reason why experience does not emerge more strikingly as a positive factor, is that in the published material the more experienced psychotherapists treated the more difficult patients, and therefore the outcome of their treatment suffered. This paper touches on recent approaches at McMaster University to evaluate the competence of trainees; one by setting instructional objectives in family therapy, the other by means of a process analysis of videotaped interviews, in which residents and their supervisors participated. A single simulated patient was interviewed at two points in time, to indicate change and development in the psychotherapeutic techniques of the trainees.