Lack of effect of bumetanide on body potassium content in hypertension. 1 Twelve patients with mild hypertension were treated with bumetanide for a six-month period. No evidence was found of hypokalaemia or decreased total exchangeable potassium in subjects with or without additional potassium supplements. 2 Bumetanide was well tolerated by all patients. It caused hyperuricaemia but no episodes of gout occurred. Minor abnormalities of liver function were noted. 3 Bumetanide did not have a sustained antihypertensive action.


Pharmacokinetics of flucloxacillin and cloxacillin in healthy subjects and patients on chronic intermittent haemodialysis. 1 A pharmacokinetic study on flucloxacillin and cloxacillin was performed to investigate the factors contributing to the higher serum concentrations reported for the former after oral administration. 2 The results obtained in a study performed in a group of volunteers with flucloxacillin administered orally and by continuous infusion, were compared with the results of a similar investigation with cloxacillin. Patients on chronic intermittent haemodialysis received flucloxacillin orally and as a single i.v. injection. The results of this part of the study were compared with those of an earlier study on cloxacillin in haemodialysis patients. Serum and urine concentrations of flucloxacillin and cloxacillin were determined by bio-assay, and a one-compartment model was used for the calculations. 3 Higher serum concentrations reached after oral administration of flucloxacillin as compared with cloxacillin were based not only on better oral absorption (53.7% and 32.9%, respectively) but also on slower (renal and extra-renal) elimination (T1/2 : 46 and 32 min, respectively). A significant difference between the apparent volumes of distribution of flucloxacillin and cloxacillin, which could contribute to higher serum concentrations, could not be demonstrated. Considerable individual variation occurs in the rate and amount of oral absorption, especially in patients. The elimination rate of flucloxacillin in haemodialysis patients (T1/2 : 2h 53 min) corresponds with the extra-renal elimination rate in healthy subjects. No influence of haemodialysis on the elimination rate constant of flucloxacillin was found; total plasma clearance was, however, slightly but significantly higher during dialysis.


Studies of the action of some anti-inflammatory drugs on complement mediated immune haemolysis. 1 The effects of various anti-inflammatory and non-anti-inflammatory drugs on complement mediated haemolysis have been studied. Drugs which were significantly protein bound were found to inhibit this form of immune lysis, but only at greater concentrations than achieved therapeutically. 2 Removal of the drugs by prolonged dialysis resulted in restoration of complement activity with the exceptions of phenylbutazone and warfarin sodium. 3 Reconstitution experiments indicated that C2 and some of the later components especially C7 were affected by the drugs. 4 Intra-articular injections of prednisolone (100 mg) in patients with rheumatoid arthritis, failed to produce significant changes in the synovial fluid complement system. 5 None of the drugs affected the binding of antibody to antigen, or the ability of sensitized sheep cells to fix complement.


An investigation into the cardiac and pulmonary beta-adrenoceptor blocking activity of ICI 66,082 in man. 1 Oral ICI 66,082 (200 mg) or water (control treatment) were each administered to six healthy volunteers. 2 The heart rate (HR) and peak flow rate (PFR) were measured at rest and during vigorous exercise before and at intervals up to 24 h after each treatment. 3 ICI 66,082 produced significant reductions in exercise HR at all times compared with the changes after the control treatment (P less than 0.001), whereas with resting HR, corresponding significant reductions only occurred at 2,3 and 4 h (P less than 0.05). 4 Although there was no change in resting PFR, significant reductions in exercise PFR, compared with the changes after the control treatment, occurred at all times excepting at 2 h after ICI 66,082 (P less than 0.025). 5 The findings are consistent with ICI 66,082 possessing partial cardioselectivity. 6 Plasma levels and renal excretion of the drug were determined. Urinary recovery was variable which, together with the plasma concentration/effect relationships obtained, raise the possibility that ICI 66,082 is metabolized in man.


The acute effects of oral (--)-tryptophan in human subjects. 1 The psychotropic effects of a single oral dose of (--)-tryptophan (5 g) in human volunteers were investigated using a series of physiological and psychological tests. 2 Self-ratings of mood showed increase in drowsiness but no euphoria was detected. 3 Severe initial nausea occurred and headache increased; other bodily symptoms were unaffected. 4 Trptophan caused increased activity in the slow wavebands of the EEG but did not alter the other physiological measures. 5 The levels of total and free tryptophan in the plasma increased 8 and 20 fold respectively to peak levels 2 h after ingestion.


Blood level studies with viloxazine hydrochloride in man. 1 The pharmacokinetic characteristics of a new antidepressant, viloxazine hydrochloride, (ICI 58,834, Vivalan), have been investigated in four separate studies. 2 In Study 1, blood levels were measured over a period of 24 h after single doses of viloxazine hydrochloride from 10-100 mg (expressed as base). In Study 2, blood levels were measured over 24 h, during which three single doses of viloxazine hydrochloride (80 mg, expressed as base) were given 4 h apart. In Study 3, blood samples and urine and faeces were collected for 96 h after doses of 40 and 100 mg of [14C] viloxazine hydrochloride (40 muCi). In Study 4, 1 h blood levels were measured at weekly intervals during a comparative clinical trial in which viloxazine was given at a dose of 100 mg four times a day. 3 The half-life of the drug is in the range 2-5 h with maximum blood levels occurring in 1-4 h of the oral dose. Maximum blood levels are proportional to the oral dose given over the range studied (0.76(mug/ml)/(mg/kg)). The drug is very well absorbed orally, only 2% being found in faeces. Repeated dosing at 4 hourly intervals leads to slightly higher blood levels after the second, but not subsequent, doses. No accumulation was seen from week to week in depressed patients. No regular sex difference was seen in the pharmacokinetic characteristics of viloxazine hydrochloride but two females in one study did show a markedly higher maximum blood level and apparently longer half-life than the males. 4 It is concluded that viloxazine is rapidly and almost totally absorbed after an oral dose, and has a shorter half-life than the tricyclic antidepressants; therapy with it should be easily controllable.


Immediate effects on human performance of a 1,5-genzodiazepine (clobazam) compared with the 1,4-benzodiazepines, chlordiazepoxide hydrochloride and diazepam. 1 The immediate effects on human performance of the 1,5-benzodiazepine, clobazam (20 mg), and the 1,4-benzodiazepines, chlordiazepoxide hydrochloride (20 mg) and diazepam (10 mg), were studied by adaptive tracking and measurement of reaction time. Each drug was ingested at 09.00 h and performance was measured at 09 h 30 min (0.5 h), 11 h 30 min (2.5 h), 14 h 30 min (5.5 h) and 18 h 30 min (9.5 h after ingestion). 2 With diazepam decrements in performance on adaptive tracking were observed at 0.5 h and 2.5 h and performance was enhanced at 9.5 h after ingestion. With clobazam performance at individual times did not differ significantly from control, but there was evidence of an improvement in performance during the day. There was no evidence of impaired performance on adaptive tracking after chlordiazepoxide hydrochloride. 3 Reaction time was slowed at 0.5 h and 2.5 h after diazepam and chlordiazepoxide hydrochloride. A decrease in reaction time was observed at 9.5 h after diazepam. No changes in reaction time were observed after clobazam. 4 The subjects as a group differentiated correctly between performance decrements on adaptive tracking after diazepam and the absence of performance decrements after clobazam and chlordiazepoxide hydrochloride. The persistence of the decrement in performance after diazepam was accurately assessed. 5 It is evident that the nature and persistence of impaired performance and the ability to appreciate impaired performance vary considerably between the benzodiazepines, and that the choice of a benzodiazepine should include careful consideration of performance sequelae.


A general equation for the ratio of the areas below the blood or plasma concentration time-curves following intravenous and oral drug administration and its application to inter-subject variations in drug elimination. 1 When a drug is metabolized in the liver the total area under the plasma or blood concentration-time curve following oral drug administration is less than the area obtained after intravenous drug administration. This difference has been termed the 'first-pass effect'. 2 General equations for the areas below the blood or plasma concentration-time curve of a drug following intravenous and oral drug administration are derived. 3 An explicit expression for the ratio of areas below the blood or plasma concentration-time curves following intravenous and oral drug administration is derived. 4 By the application of the derived equations it is shown that the relative contribution of hepatic drug metabolism and urinary excretion to inter-subject variation in drug elimination can be easily ascertained.


Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients. 1 Steady-state serum phenytoin concentrations were measured in adult epileptic patients receiving a maintenance dose of phenytoin (300 mg daily). 2 Serum phenytoin concentration showed a positive correlation with age. 3 Serum phenytoin concentration showed a negative correlation with body weight and with height. Multiple correlation analysis indicated that body weight influenced the concentration to a much greater degree than height. 4 When corrected for body weight and height, the serum phenytoin concentrations in women were lower than those in men, although the difference was not statistically significant. 5 Although each of these factors contributes to the interindividual variation in serum phenytoin concentrations, the contribution of each is small. Other factors, such as genetic differences and the effect of saturation kinetics, are much more important in determining steady-state concentrations. Adjusting the dose according to the age, weight and height of a patient would achieve only a marginal improvement in therapy.


Effect of phenobarbitone on hepatic drug-metabolizing enzymes and urinary D-glucaric acid excretion in man. 1 The activities of some hepatic drug-metabolizing enzymes representative of the four major pathways for the biotransformation of drugs were estimated in diagnostic wedge biopsy specimens obtained from 22 patients with Hodgkin's disease. Twelve patients (nine males and three females) were not on prolonged pre-operative treatment with any known inducing drugs. In this group, hexobarbitone oxidase activity, cytochrome P450 and microsomal protein contents were in the same range as those reported by other workers. 2 Ten patients (five males and five females) were pre-operatively treated with phenobarbitone (90 mg daily) for at least seven days. This resulted in a significant increase of hexobarbitone oxidase activity, cytochrome P450 and microsomal protein contents when the phenobarbitone untreated and treated groups were compared as a whole and provides direct evidence of induction of hepatic mixed function oxidase system. In respect of p-nitroreductase, 1-leucyl-beta-naphthylamide splitting enzyme and UDP glucuronyl transferase, there was no difference between the treated and untreated groups. 3 When untreated and treated patients were compared, the induction of the hepatic mixed function oxidase system, was associated with a significant increase in urinary D-glucaric acid excretion. In treated patients, however, there was no correlation between any of the indices studied and post-phenobarbitone D-glucaric acid content or the rise in D-glucaric acid excretion. However, the correlation between cytochrome P450 content and post-phenobarbitone D-glucaric acid or the rise in D-glucaric acid excretion was only just below statistical significance (r = 0.696 and 0.690 respectively, 0.10 greater than P greater than 0.05) whereas in the untreated group there was no correlation (r = 0.231, P greater than 0.60). 4 In two patients, whose phenobarbitone was discontinued for at least six days prior to surgery, all indices studied had returned to untreated values, except for microsomal protein content which remained significantly elevated.


The effect of intramuscular salbutamol in asthmatics. 1 In a double-blind placebo controlled dose-response experiment in six asthmatic patients with reversible airways obstruction the effect of i.m. salbutamol (4 mug/kg, 8 mug/kg or 12 mug/kg) was assessed by improvement in spirometry and change in pulse rate. 2 Salbutamol (8 mug/kg) resulted in a mean increase in FEV1 of 1 litre and a mean increase in pulse rate of 7 beats/minute. 3 It was concluded that salbutamol (8 mug/kg) was the optimal dose.


Bioassay of aldosterone antagonists in normal human subjects: a relationship between the level of plasma uric acid before treatment and apparent drug responses. The activity of single doses of SC-23992, a new aldosterone antagonist, and spironolactone in reversing the effects of fludrocortisone on urinary electrolyte composition in normal subjects was compared with that of placebo in a double-blind crossover study. 2 SC-23992 (50 mg) and spironolactone (125 mg) each significantly increased sodium excretion and the sodium : potassium (Na/K) ratio, and decreased potassium excretion, when compared with placebo. The response to the two active drugs did not differ significantly. 3 The urine Na/K ratio, and log10 Na/K, in response to spironolactone correlated negatively with the level of plasma uric acid measured 12 h before treatment. Similar trends were present after SC-23992 and placebo treatments. 4 It is suggested that the correlations between plasma uric acid and apparent drug response reflect a correlation between plasma uric acid and the aldosterone secretion rate in normal subjects. The sensitivity of this method of bioassay may be improved by suppressing endogenous aldosterone prior to medication.


An implantable transmitter for monitoring heart rate and respiratory frequency in diving ducks. An implantable telemetry transmitter is described for monitoring respiratory frequency and heart rate in animal physiological studies. The ECG is transmitted directly while the respiratory signal, derived from the temperature variation of the air in the respiratory tract, modulates the frequency of a subcarrier oscillator. A magnetic switch allows the implanted device to be switched on and off remotely. Details are given of the high packing density achieved by a modified cordwood method of construction. This system is being used to investigate the changes in heart rate and respiratory frequency associated with spontaneous diving in ducks, and typical results are presented.


Biotelemetric investigation of the regulation of the cardiac frequency in animals with use of telestimulation. Model examinations in the neat. A method for the assessment of behaviour of the cardiac frequency regulation in freely moving animals by means of telestimulation and biotelemetry is described. The results of the examinations allow, in spite of individual variability, a classification of the animals into different types of regulation by consideration of the biorhythm. The assessment of the individual type of regulation in correlation to the biorhythmic structure of the organism is of basic significance for the evaluation of its capacity of performance and adapation.


Calibration and measurement in 3-dimensional monitoring of human motion by optoelectronic means. I. Preliminaries and theoretical aspects. By combinding the obervations from a number of independent direction sensors, the spatial positions of one or more targets may be reconstructed. The theory of calibration and measurement in a computerized, interactive environment is discussed in the terminology of analytical photogrammetry, for applications in the field of biomechanics. The discussion is focussed upon optoelectronic system for movement monitoring in real-time rather than upon photography as is the conventional photogrammetric implementation.


Criteria of quality and methods of measurement in multichannel biotelemetry. In contrast with one-channel biotelemetry, multichannel biotelemetry systems permit the analysis of biological systems by means of cybernetics. Some simple examples are given. The basic concept of a multichannel system is described. The criteria of quality of which the nonevident ones are defined by detailing the test circuits are the following (input criteria): number of channels, bandwidth, voltage range, impedance, maximum voltage outside the signal band, stability of the power supply for transducers, factor of safety against multipath propagation, distance between transmitter and receiver, shock, vibration and temperature range, weight, volume and operating time. Output criteria: signal-to-noise ratio, linearity, crosstalk transfer function, different time lags.


Multichannel biotelemetry.

Multichannel biotelemetry. A summary of considerations for design and application of multichannel biotelemetry systems is given. The advantages but also the problems of wired, wireless, combined and storage telemetry are discussed in connection with its application. Modulation and multiplexing techniques are described extensively; however, this review focuses not only on the transmission of biological data but also on the important aspects of connection of the transmission equipment to the biological subject and display of the biological information. The topic of multichannel biotelemetry is rounded off by a few additional subjects such as telecontrol, information source and classification.


Telemetered epidural pressure.

Telemetered epidural pressure. An implantable transducer capable of telemetering epidural brain pressure during long periods of time is described. The transducer is constructed from conventionally available materials, and routine workshop techniques are used. The coplanarity principle has been applied while the described mounting clamp allows discrete positioning of the transducer relative to the brain. Basically, the transducer consists of a coil-capacitor circuit in which alterations of epidural pressure induce changes in capacity and, thus, the transducer's resonance frequency. An external electromagnetically coupled impedance-measuring device converts the resonance frequency to a pressure analogous voltage. In vitro tests showed that the  transducer had good accuracy and reliability for a period of more than 1 month. An in vivo experiment with a cat showed that the measured epidural pressure was linearly related to ventricular fluid pressure.


Telemetered renal responses in dogs during detection of explosives. The primary objectove of this work was to develop and test a method of measuring and characterizing renal hemodynamic responses in unrestrained dogs. Recordings of left kidney blood flow and abdominal aortic pressure were obtained from unrestrained dogs through the use of a two-channel implanted telemetry system during episodes of search and detection of simulated explosives. In each of a number of sequences, the dog was first given a start signal, and after locating the hidden device, was rewarded with food. Data were assessed at the start, find, and recovery segments. The dynamic flow and pressure, together with a hydraulic renal model, were used to derive the total preglomerular and postglomerular vascular resistances and the mean level of glomerular hydrostatic pressure. Data from three dogs obtained by telemetry and analyzed through the use of the model have shown that compared to the start of the test, the location of hidden explosives results in a decrease in both the level of mean aortic blood pressure and the preglomerular resistance; whereas, the reward results in an elevation of mean blood pressure and preglomerular resistance. The postglomerular resistance varied less than the preglomerular resistance, and mean flow did not vary significantly. This work has shown that the stimulation of a reward and the successful performance of a task lead to significant renal responses in dogs. It has further shown that telemetry, when employed with improved data analysis techniques, permits renal hemodynamics to be assessed in unrestrained animal subjects.


Pulse code modulation telemetry in ski injury research. II. Preliminary results. The excitation between the boot and the ski was measured in maneuvers skied over a variety of snow conditions. A precision pulse-code modulation (PCM) - frequency modulation (FM) telemetry system was custom built to transmit data from strain-gage force transducers mounted inside the test ski to a receiving station about 3 km distant. Field tests gathered cruising data from three basic maneuvers - snowplow, stem christiana, and parallel christiana. Some classic falls resulting from inadvertent release of the ski bindings were also recorded. For comparative purposes, the maneuvers were skied over a standard five-turn slalom course. Examination of the loading histories reveals that: (1) the data are nonstationary random; (2) boot compression for the test binding system exceeds 500 N and is caused by ski flexure; (3) an 80 Hz resonance of the particular toe binding mechanism is excited; (4) combined impulsive loading is significant; (5) the loading is related to the maneuver type; (6) bending components during forward falls exceed the tibia flexural strength even though heel binding release occurs at the laboratory setting, and (7) torsion and bending components exceed tibia fracture levels during elementary ski maneuvers.


Microwave radiometry and its potential applications in biology and medicine: experimental studies. This paper presents experimental data on : (1) the natural emission of microwave radiation by biological systems, and (2) the effect of drugs as well as microwave radiation on specimen microwave emission. Experiments were conducted on guinea pigs, mice, rabbits, and human subjects. The results were obtained with two different radiometers, one of the correlation type and one of the Dicke type, operating in the X-band at about 9 GHz with a sensitivity of approximately 0.1 degrees K. The results demonstrate the feasibility of this technique and suggestions are made for its use in bilogy, medicine, and in the field of biocommunications.


The tort liability of the psychiatrist.

The tort liability of the psychiatrist. It is indisputable that claims against psychiatrists are now reaching a new level of significance. Verdicts are being returned against more defendants, in a widening circle of liability, and for amounts which are ever increasing. The following caveats should be observed by all psychiatrists: 1. Diagnosis The psychiatrist must act with that degree of skill and care common to others in his specialty when diagnosing a patient. The diagnosis should be periodically reviewed. 2. Shock therapies a. The psychiatrist must obtain informed consent before proceeding. If the patient is incapable of consent for any reason, efforts should be made to communicate with a close relative or guardian. b. Proper premedication must be administered. c. Equipment and personnel to handle cardiorespiratory emergencies must be immediately available. d. Diligent care and observation must be supplied for a reasonable period of time after the treatment. 3. Drug therapy a. The psychiatrist must obtain informed consent (see 2-a above). b. Close attention should be paid to the manufacturer's package insert. c. Extreme caution must be observed in prescribing dangerous drugs for a potentially suicidal patient. 4. Suicides Reasonable skill and diligence must be applied a. to determine the likelihood of a patient's committing suicide, and b. to protect the patient once suicidal tendencies have been diagnosed. 5. Injuries to third parties The same considerations apply as were noted in "Suicides." 6. Confidentiality: duty to warn a. Before making any disclosures as to the mental state of his patient, a psychiatrist should be certain that he is protected by privilege (e.g., judicial immunity) or by the prior consent of the patient. b. However, Tarasoff (supra, p. 210 ff.) may impose on the psychiatrist an affirmative duty to warn a party whose life or safety has been threatened in a disclosure to the psychiatrist. Competing interests must be carefully balanced. 7. Commitment The psychiatrist must exercise due care and diligence in examining patients for commitment proceedings, taking care to see that there is probable cause. 8. Psychotherapy a. In addition to ordinary care and skill, the psychiatrist owes his patient the duty of maintaining the trust established in the therapist-patient relationship. b. The psychiatrist bears the burden of establishing the justification of any innovative therapy, particularly should he become sexually or socially involved with the patient. While adherence to the above admonitions will not guarantee verdicts for defendant psychiatrists, it will hopefully reduce the professional, financial, and emotional costs of litigation.


Aphasia and the expert medical witness.

Aphasia and the expert medical witness. Psychiatrists have recently been criticized from within and outside the profession for rendering professional opinion in instances where their qualifications are inadequate. In forensic psychiatry, the problem of predicting dangerousness is a notable example. The forensic psychiatrist may also be called to testify as to the present or future competency of the aphasic patient. It therefore behooves the medical expert to be fully aware of the new developments within the field of aphasiology so that in cases involving aphasia the best combined expert testimony can be rendered the court.


The influence on judges' sentencing practices of a mental evaluation. Minimum and Maximum sentences were compared for a sample of 347 prison commitments and for 130 of 347 mental evaluation referrals who finally received prison sentences. It was found that referral for evaluation influenced the probability of remaining in the system until sentencing, but for those sentenced, did not influence the sentence imposed. However, the findings of the evaluation did show a tendency to affect the sentence. Individuals who were found incompetent were less likely to remain in the criminal justice system until sentencing. Those individuals who were initially found incompetent and then became competent and were sentenced, and those individuals who, though found competent, were diagnosed schizophrenic, tended to receive shorter sentences. These findings held even when comparisons were controlled for presence of prior convictions. The implication is that the referral for and findings of the mental evaluation, though not officially a part of trial testimony as to intent or responsibility, do in fact influence the probability of a sentence and, if sentenced, the sentence imposed.


A simple infra-red optometer for accommodation studies. The design of a continuously-recording optometer of minimal mechanical and electronic complexity is described. It operates on the Scheiner principle and has good time response for dynamic measurements. Theoretical and experimental studies show that linearity over an adequate range can be achieved by a suitable choice of system parameters; the response depends partly on Scheiner and partly on defocus effects.


The effect of hypertonic saline on human corneal hydration. Hydrophilic gel contact lenses, presoaked in various strength saline solutions, were held in intimate contact with the in vivo human cornea. A change in corneal water content was observed taking place against the induced osmotic gradient. Direct stimulation of some aspect of the mechanisms controlling corneal hydration is postulated, in a manner which may be similar to that previously reported for the in vitro rabbit cornea.


Physical signs in association with depressive illness in childhood. Although behavioural disturbances associated with depression in childhood are often discussed, descriptions of somatic phenomena are less commonly reported. This paper compares the frequency of neurological signs observed in a group of depressed children with a control group. The possibility that minimal brain dysfunction might play a part in the production of signs is considered. It was found that there was a statistically significant difference between the incidence of physical signs found in the control group and in the depressed children.


White and West Indian infants in London: development from birth to 44 weeks of age. Fifty white and 50 West Indian babies were examined on four occasions between birth and the age of 10 months. The West Indian babies were significantly advanced over the white babies when newborn, but by 6 weeks of age were losing their advantage; there were no significant differences at 6 months and 10 months of age. The ethnic origin, growth pattern, feeding customs and relevant socioeconomic factors were considered and the implications discussed.


The negative inotropic action of propanidid. influence on calcium movements in atrial tissue. Propanidid (Epontol), a general anaesthetic agent with a particularly short action in vivo significantly depressed the contraction amplitude of guinea pig isolated atria. A steep concentration-response curve could be established. Contractile force of electrically driven atria (180/min) was reduced by approximately 50% at a propanidid concentration of 3.5 x 10-4 M in the medium. The negative inotropic effect developed rapidly (less than 10 min). At concentrations of 4.5 x 10-4 M and less propanidid hardly reduced the frequency of spontaneously beating atria. The uptake of extracellular 45 Ca by spontaneously beating atria occurred significantly more slowly in presence of propanidid (4.5 x 10-4 M ), whereas the exchangeable calcium fraction remained unchanged. Accordingly, propanidid reduced the rate of exchange of calcium so that less ionized calcium was available for excitation-contraction coupling. Propanidid (4.5 x 10-4 M) accelerated the uptake of 45Ca by isolated plasma membranes, obtained from guinea pig ventricular muscle. Moreover, the binding capacity for calcium by isolated membranes was increased in presence of propanidid. These observations imply that less ionized calcium is available for activation of the contractile system. It is concluded that the negative inotropic action of propanidid is probably due to the drug's influence on membrane function, thus bringing about an important change in cellular calcium metabolism.


Reserpine-induced catecholamine depletion from small cells in rat sympathetic ganglia. Two reserpine dosage schedules were applied to Wistar rats (a) 5 mg/kg i.p. 6 hr before sacrifice and (b) 5 mg/kg i.p. at 36, 24 and 12 hr prior to sacrifice. Control animals were correspondingly sham-injected. The coeliac-mesenteric ganglion complex was removed and processed either for the Falck-Hillarp fluorescence histochemical technique or fixed in glutaraldehyde followed by 3.5% potassium dichromate for a chromaffin-type reaction. After a single reserpine injection there was a statistically significant (p less than 0.001) reduction in the percentage of 'chromaffin-positive' cells and a statistically significant (p less than 0.001) increase in the percentage of 'chromaffin-negative' cells compared with controls. No obvious reduction in fluorophore emission from small intensely fluorescent (SIF) cells was observed. After prolonged reserpinization (3 x 5 mg/kg) there was a highly significant reduction in the percentage of 'chromaffin-positive' small cells and also a significantly lower (by a factor of 2) level of fluorescent emission from SIF cells. The catecholamine-releasing potential of small cells is demonstrated by these results.


Effect of bombesin on pancreatic secretion and gall bladder motility of the chicken. Bombesin strongly stimulated the chicken pancreatic secretion. When given by i.v. infusion, the threshold dose was of the order of 7.5-45.0 ng/kg/min and maximum enzyme output was obtained at a rate of 60 ng/kg/min. In addition to total enzyme output, enzyme concentration was also increased. Caerulein displayed a more potent stimulant effect, but composition of juice produced by the two polypeptides was similar. Tachyphylaxis occurred only with bombesin. Neither atropine nor gastric acidification affected the response to bombesin. Bombesin was totally ineffective in promoting gall bladder emptying. It is suggested that in the chicken, bombesin acts on the exocrine pancreas indirectly through release of an endogenous pancreozymin possibly devoid of cholecystokinetic activity.


Effect of angiotensin II and its analogs on uptake and release of 14C-5-hydroxytryptamine by rat brain. Uptake of 14C-labelled 5-hydroxytryptamine (14C-5-HT) has been investigated by perfusion of the rat brain ventricular system. When angiotensin II was present during perfusion, a dose-dependent inhibition of 14C-5-HT uptake in rat brain was observed. A similar effect was obtained with angiotensin II analogs (8-alanine angiotensin II or 1-dimethylglycine, 8-isoleucine angiotensin II). The inhibitory effect of angiotensin II can be almost completely blocked with 1-dimethylglycine, 8-isoleucine angiotensin II. In washout experiments, the radioactivity remaining in the brain was greater in the presence of angiotensin II.


Effect of amphetamine and fenfluramine on brain noradrenaline and MOPEG-SO4. I.p. administration of d-amphetamine sulphate and fenfluramine-HCl at various doses induced significant modifications of brain noradrenaline (NA) and MOPEG-SO4 (3-methoxy-4-hydroxyphenylethyleneglycol) in the rat. Both drugs induced a decrease in brain noradrenaline but the two compounes seem to interact with the central noradrenergic system through a different mechanism. The decreased levels of noradrenaline after 1-fenfluramine administration were paralleled by increased MOPEG-SO4 levels. The d-isomer of fenfluramine was less active than the l-isomer. Amphetamine was considerably more effective than l-fenfluramine in reducing NA concentration. However, in spite of the long lasting effect on noradrenaline levels the i.p. administration of amphetamine did not lead to an increased MOPEG-SO4 concentration suggesting a more complex interaction with the noradrenergic system.


Further evidence for nicotinic and muscarinic receptors and their interaction in dog adrenal medulla. Isolated adrenal glands of dogs were perfused through the adrenolumbar vein with Krebs-Ringer phosphate solution. Nicotine or acetylcholine (Ach) significantly increased the proportion of norepinephrine in the effluent whereas muscarine did not alter the relative proportions of epinephrine and norepinephrine. d-Tubocurarine and hexamethonium (C6) inhibited the response to nicotine completely but scarcely affected the response to Ach and significantly potentiated the response to muscarine. Atropine inhibited the response to muscarine completely, that to Ach partially and that to nicotine slightly. Preinfusion of physostigmine potentiated the secretory response to Ach but not that to nicotine and muscarine. When nicotine and muscarine were infused simultaneously, catecholamine (CA) release was greater than the sum of the responses to nicotine and muscarine separately. Continuous infusion of nicotine for 60 min caused block of the adrenal medulla but potentiated CA release in response to Ach and more especially to muscarine. This potentiated release of CA was completely blocked by preinfusion of atropine. Continuous infusion of muscarine for 60 min also blocked CA release and significantly potentiated the response to nicotine, but slightly inhibited the response to Ach. These potentiated and inhibited responses were also completely blocked by preinfusion of d-tubocurarine of C6. On the contrary, during the blockade phase caused by Ach (in combination with physostigmine), nicotine of muscarine did not cause release of CA. In addition, the continuous infusion of nicotine plus muscarinic receptors for acetylcholine in the adrenal medulla and that cholinergic transmission is possible via both mechanisms in isolated adrenal glands. When one type of receptors is blocked by continuous contact with an agonist or by d-tubocurarine or C6, the sensitivity of the other type is increased; inactivation of the one is thus compensated by the increased response due to potentiation of the other.


Mouse brain catecholamines, 5-hydroxytryptamine and the antinociceptive activity of pethidine. The involvement of brain 5-hydroxytryptamine (5-HT), noradrenaline and dopamine in the antinociceptive activities of pethidine and morphine has been compared in the mouse. Differences have been shown in the activities of pethidine and morphine in mice treated with either 5-hydroxytryptophan or reserpine. No differences between the activities of pethidine and morphine were demonstrated in mice treated with either alpha-methyl-p-tyrosine, L-dopa or p-chlorophenylalanine. In reserpinised mice, pethidine's antinociceptive activity was either potentiated, unaffected or antagonised, dependent upon the reserpine dose schedule. Pethidine was shown to be able to raise brain 5-HT concentrations in reserpinised mice. This effect was also dependent upon the reserpine dose schedule used. Morphine, which was antagonised by all reserpine dose schedules, did not raise noradrenaline or dopamine in control or reserpinised mice. Although the reserpine schedule, which potentiated pethidine's antinociceptive activity, was the same as that in which pethidine had the most marked effects upon 5-HT, no definite connections between the two observations could be made. Naloxone abolished the antinociceptive activity of pethidine in reserpinised mice, but not the rise in 5-HT.


In vivo effects of angiotensin antagonists on plasma aldosterone in the dog. The effects of infusions of equimolar doses of Sar1-Ile8-angiotensin II and of Sar1-Ala8-angiotensin II on plasma aldosterone, plasma renin activity and arterial blood pressure were compared in normal dogs. Plasma aldosterone increased significantly after Sar1-Ile8-angiotensin II whereas it was unaffected by Sar1-Ala8-angiotensin II. Changes in blood pressure and renin activity were small without marked differences between both groups of animals. The experiments demonstrate a clear steroidogenic potency of Sar1-Ile8-angiotensin II. Therefore, Sar1-Ala8-angiotensin II should be preferred as antagonist of the action of angiotensin II in the adrenal gland.


The effect of verapamil on potassium fluxes in canine cardiac Purkinje fibres. Electrophysiological studies of verapamil on isolated cardiac tissue show its effects to occur during Phase 2 and Phase 4 of the cardiac action potential and to be a result of blocking the slow inward Ca2+ current. It is important to know if verapamil effects the transmembrane movement of ions other than Ca2+. By studying uptake and efflux of 42K by canine cardiac Purkinje fibres in the presence and absence of verapamil (1.1 x 10-6 M-4.4 X 10-6 M), it was found that the drug inhibits both 42K uptake (15%) and efflux (30%).


The effect of selective lesioning of brain catecholamine-containing neurons on the activity of various anorectics in thr rat. An intraventricular injection of 6-hydroxydopamine to rats pretreated with pargyline, a procedure which produces a marked decrease of brain catecholamines without significant changes in the serotonin levels, significantly antagonizes the anorectic effect of amphetamine, phentermine, mazindol and diethylpropion, while the reduction of food intake induced by other drugs such as fenfluramine, p-chloroamphetamine, SE 780 and SKF 1-39728 is not significantly affected. The data suggest an involvement of brain catecholamines in the anorectic effect of amphetamine, phentermine, mazindol and diethylpropion whereas other mechanisms appear to be involved in the activity of the other anorectics studied.


The effect of nomifensine on the depletion of brain serotonin and catecholamines induced respectively by fenfluramine and 6-hydroxydopamine in rats. Nomifensine, at a dose of 10 mg/kg i.p., completely antagonized the decrease of brain dopamine induced by an intraventricular injection of 6-hydroxydopamine. The decrease of brain noradrenaline was also significantly antagonized by nomifensine. Desipramine antagonized the effect of 6-hydroxydopamine on noradrenaline but not on dopamine. The decrease of brain serotonin induced by fenfluramine was antagonized by chlorimipramine but not by nomifensine. The findings indicate that nomifensine specifically blocks the uptake mechanism for catecholamines in the brain without significant effects on serotonin.


Vaginal cytology after the menopause.

Vaginal cytology after the menopause. The methods by which oestrogen activity can be assessed cytologically are described. Hormone production does not cease with the onset of the menopause. In about 10% of post-menopausal women there is evidence of high oestrogenic activity until far into old age and in a further 40-45% moderate levels of oestrogens are maintained. Oestrogen administration should, therefore, not carried out routinely under the illusion that it constitutes preservation of youth, but should be reserved for such women in whom serious hormone deficiency can be demonstrated.


[Specific radioimmunoassay of pancreatic glucagon. Results in new-born and in child (author's transl)]. Rabbits were immunized with polymerized glucagon and specific antisera obtained. Antiserum used at a dilution of 1/24 000 (final concentration) exhibited a cross reaction of 1,6% with enteroglucagon. Radioimmunoassay of serum glucagon employed dextran coated charcoal and 125 I glucagon. Mean concentration in normal fasting children was 153 pg/ml +/- 27 (S.E.M.) and the molar ratio of insulin/glucagon was between 1,9 and 3,9. In the case of premature, dysmature and diabetic children or children from diabetic mothers, the levels did not differ significantly from normal. Results of glucagon secretion stimulation tests using arginine insulin combinations are also reported.


Interactions of insulin and epinephrine in human metabolism: their influence on carbohydrate and lipid oxidation rate. Two groups of normal male subjects were given an infusion of insulin and an infusion of epinephrine + insulin respectively. Blood glucose, plasma free fatty acids (FFA), insulin, growth hormone, cortisol, and urinary catecholamines were determined. Continuous indirect calorimetry was used to measure metabolic rate and oxidation rates of carbohydrate and lipids. The first group (n equals 7) received a 30-minute insulin infusion (0.1 IU/kg). While blood glucose and plasma FFA decreased, carbohydrate oxidation and metabolic rate significantly increased after some delay, whereas lipid oxidation decreased. The increase in carbohydrate oxidation amounted to 5 g/120 min. The decrease in blood glucose during insulin administration did not correlate with the increase in carbohydrate oxidation. In the second group (n equals 7), a 150-minute epinephrine infusion (900 mug in 500 ml saline) was administered, and superimposed upon it, a similar insulin infusion initiated after 60 min. Epinephrine alone increased blood glucose and plasma FFA levels, and decreased insulinemia. The rise in the metabolic rate was sharp and significant. After a short but significant increase the oxidation rate of carbohydrate decreased, whereas that of lipids markedly rose. This increase significantly correlated with that in FFA. Addition of insulin markedly decreased the elevated FFA levels and lowered blood glucose. After some delay this was followed by a marked increase in carbohydrate oxidation and a decrease in lipid oxidation. In this test the total increase in carbohydrate oxidation was 11 g/120 min. In comparison with the insulin test, this double amount seems to correlate well with the higher blood glucose levels measured before insulin administration. The results suggest that insulin indirectly stimulates carbohydrate oxidation by facilitating glucose transport into the cells and lowering FFA levels, and that epinephrine favours lipid oxidation through its lipolytic effects and its suppression of insulin release.


Arterial pressure in clinically apparent diabetics. The relationship between arterial blood pressure and clinically apparent diabetes mellitus was examined by measuring blood pressure, under standardised conditions, in 735 ambulant diabetic patients attending St. Mary's and King's College Hospital, London. Other biometric, clinical and family data were also systematically collected. A large proportion of first degree relatives of the diabetics and a control group of first degree relatives of non-diabetics were also seen and examined; they were also tested for the presence of unsuspected diabetes. Blood pressure in diabetics was evaluated in two ways. Mean pressures (systolic and diastolic) were calculated by age and sex and compared with similar data from two British non-diabetic populations. In addition, age and sex adjusted blood pressure "scores" were derived for each of the diabetic propositi and for the relatives by calculating the degree to which their pressures deviated from the mean of a corresponding age/sex group of non-diabetics. These deviations were then made comparable by standardising them for the systematic change in variance with age and sex. Using both "raw pressures" and "adjusted scores" the influence of age, sex, obesity, arm girth, response to diagnosis and ethnic, obstetric and anamnestic features were examined. Analysis of the influence of various characteristics of the diabetic state on blood pressure was made; this included mode of presentation, known duration; insulin dose and degree of metabolic control. Finally the relationship of blood pressure levels to the long-term sequels of diabetes was analysed with special reference to renal disease, eye changes, neuropathy and arterial disease. No systematic difference between arterial blood pressure in diabetics and a suitable control population was detected. Younger patients, females more than males, tended to have somewhat higher mean diastolic pressures but these were balanced by rather lower mean pressures in older diabetics. There was evidence of raised pressure levels at the time of diagnosis of diabetes, particularly in older patients, which "settled" with time for reasons which were not clear. The relationship of arterial pressure with adiposity was comparable to that in non-diabetics. After allowance for age and sex, blood pressures and scores were not related to the mode of onset of the diabetes. In the youngest onset group, however, known duration of diabetes appeared to correlate positively with arterial pressure in excess of the effect of age. Insulin dose and metabolic characteristics of the diabetes showed little clear association with arterial pressure but, as expected, patients with evidence of renal disease had higher mean pressures. However, cause-effect relationship between raised pressure and renal disease in diabetics may operate in both directions. Some elements of retinopathy were positively correlated with blood pressure; others were not. The role of co-existing renal disease in determining this association was examined...


[Myocardial infarction in diabetics (author's transl)]. In 160 patients admitted during the first 8 days following myocardial infarction during the period November 1st 1974 - March 15th 1975, the prevalence of diabetes was 17%. Among 655 patients treated for a month in a convalescence centre following the acute phase of myocardial infarction during the period January 1st 1974 - March 15th 1975, the prevalence of diabetes was 17.5%. Mortality rate during the first 8 post infarction days was 28% in diabetics and 13% in non-diabetic patients in the coronary care Unit; over the subsequent month, the mortality rate was 7.7% in diabetics and 3.7% in non-diabetics while at the convalescence Centre. The higher mortality rate from myocardial infarction in diabetics could not be contributed to a greater severity or more wide spread nature of the coronary artery disease as evidenced by the results of coronary cineangiography performed in diabetic and non-diabetic patients with severe ischaemic heart disease. In the cases in which an aorto-coronary by-pass was performed, there was no apparent difference in the response of diabetics compared to non-diabetic subjects. Despite progress in intensive treatment of myocardial infarction, mortality rate of this disease in diabetics remain very high. Reduction of the incidence of ischaemic heart disease in diabetics requires early identification and reversal of all of the many risk factors for arterial disease.


Studies on juvenile--type diabetes in children. Assessment of control under treatment with constant and variable doses of insulin with or without addition of biguanides. Studies were carried out in juvenile-type diabetics in a home for diabetic children which offered the advantages of both "normal" living conditions and strict medical and dietetic control. In 43 insulin-dependent, juvenile diabetics, blood glucose was determined at least 3 times, and some times on 6 occasions, per 24 hours on 3 days a week over 3 months. Blood glucose was estimated in every case of suspected insulin reaction. Determination of cholesterol, triglyceride, growth hormone and antibodies against bovine and porcine insulin were also carried out. Randomized groups of patients were treated alternately with 1) constant, 2) variable insulin doses, 3) addition of biguanides (metformin). Calculated parameters included mean daily blood glucose, mean of absolute differences between daily blood glucose values, daily insulin requirements, frequency of verified insulin reactions and mean blood glucose profiles pre- and postprandially. Addition of biguanides did not decrease blood glucose differences nor the frequency of hypoglycemic episodes. Daily insulin doses were lowered by the drug. Variable insulin doses appeared to be superior to constant ones. Daily insulin requirements were positively correlated with age and weight of patients. Elevated levels of cholesterol were lowered by biguanides. In suspected cases of insulin reaction, blood glucose levels above 100 mg/100 ml were found in more than 40%. No differences existed in insulin requirements, age and duration of diabetes between childhood diabetics with or without significant titers of insulin antibodies. Three postprandial blood glucose determinations gave no essential information over and above the 3 preprandial estimations as far as blood glucose fluctuations were concerned. No smoothing effect of biguanides was apparent from the study whereas an insulin-sparing effect is exerted by these drugs as well as a lowering of elevated levels of cholesterol.


Biosynthesis of basement membrane collagen in cultures of renal glomerular and tubular epithelial cells. Confluent cultures of renal glomerular or tubular epithelial cells were incubated with [14C] proline and [3H] lysine. The incorporation rate of both radioactive precursors was found to be linear for up to 12 h. The synthesis and secretion of basement membrane collagenous polypeptides was demonstrated by the presence in the culture media of non-dialyzable 4-hydroxy [14C] proline and hydroxy [3H] lysine. After gel filtration of the culture media on Sephadex G-100 columns, glomerular and tubular basement membrane polypeptides were identified in the chromatographic fractions by radioimmunoassay. They were further purified by affinity chromatography, using Sepharose cyanogen-bromide coupled with specific rabbit anti-human glomerular or tubular basement membrane antibodies. Absorbed labelled membrane polypeptides were eluted from the Sepharose by acidic medium at 4 degrees C. This membrane material represented 3-4% of the total proteins synthesized by glomerular and tubular cells. The glomerular and tubular basement membrane polypeptides purified by affinity chromatography exhibited a molecular weight of approximately 140,000; 80% of the total hydroxy [3H] lysine was recovered as glucosyl-galactosyl-hydroxy [3H] lysine. Analysis of the carbohydrate content of labelled basement membrane polypeptide chains originating from glomerular or tubular cells incubated with [14C] glucose of [14C glucosamine indicated the presence of glucose, galactose, mannose, glucosamine, and galactosamine. No fucose, mannosamine or sialic acid were detectable. The data demonstrate that glomerular and tubular epithelial cells are able to synthesize basement membrane collagenous polypeptides in culture. This property might provide a useful tool for the study of the biosynthesis of similar material by diseased kidneys.


Characterization of phenformin and metabolites in plasma. A colorimetric assay of biguanides was adapted for small volumes of plasma and its specificity was improved. This method is based on the reaction of guanidine groups with alpha-naphtol-diacetyl. Interference of endogenous guanidine derivatives and of the water-soluble metabolites of phenformin can be excluded by the extraction procedure. Counting of plasma fractions from 14C-phenformin-injected rats and thin-layer chromatography, before and after treatment with beta-glucuronidase, were also performed: the results suggest that after adequate extraction of plasma, the colorimetric assay measures specifically the biologically active phenformin. Results of this assay in plasma from biguanide-induced lactic acidotic patients and rats are given and compared with controls : results are consistent with the hypothesis of an accumulation of biologically active biguanide in such cases.


[Inhibition of rubella virus hemagglutination by dextran sulfates of high molecular weight]. High molecular weight Destran-sulphates greatly affect rubella virus hemoagglutinin. The inhibition is to be related to the molecular weight. D.S. with p.m. 1,2 X 10(4) show no inhibitory activity, while D.S. 5 X 10(5), and furthermore D.S. p.m. 2 X 10(6) inhibit hemoagglutination. The inhibition appears to be related not to the effect of D.S. on red cells but to the interaction of D.S. with rubella hemoagglutinin. The entity of inhibition is a function of the concentration of D.S. in the test specimen: as much more intense is the former, as much higher is the latter. It is to be noticed however that also relatively little concentrations show to possess a clear inhibitory activity. Concentrations of 0,006 mg/ml and 0 ,05 mg/ml of D.S. (p.m. 2 X 10(6)) cause a lost of hemoagglutinin titre, showing respectively two and four twofold diluition lower titres than controls.


Cytological effects of amoxycillin treatment on psychrophilic Staphylococcus aureus Pi 116. Inpsychrophilic S. aureus Pi 116, treatment with Amoxycillin at 37 degrees C produced giant cells, thick cross walls and thin cell walls, cell walls were unaffected at 2 degrees C, however.


[A new technic for determination of antibiotics in the renal parenchyma]. The determination of antibiotics in the renal tissue is of real value only if the blood and the residue urine are removed from the kidney. The Authors report a new technique dealing with the washing of the organ "in situ" by means of an artery-vein perfusion succeeded by the sucking of the residue urine from the ureter. The experiments were carried on male albino rats with the following antibiotics: indanylcarbenicillin, tobramycin, fosfomycin and cefazolin.


[Epidemiology of toxoplasmosis. Results of 5 years of serodiagnostic surveys]. The results obtained by antibodies titration in 1500 subjects, in connection with Toxoplasma infection, are discussed. The determinant influence of some factors is statistically evaluated and recent Italian and foreign results are considered, according to the epidemiology of Toxoplasmosis.


[Selection in Polyporus versicolor of mutants producing laccase]. Following preceeding research on the production of laccase in Polyporus versicolor the A. has studied the various cultural conditions which are favourable to a good production of the enzyme. By selecting U.V. induced mutants it has been possible to isolate strains with a high production of the enzyme, in which the enzyme is either constitutive or inducible.


[Effects of a synthetic peptide on the cytotoxic activity of the lymphocytes of animals with tumors]. The influence of Peptichemio on cell immunity was studied by examining the in vitro response of lymphocytes from animals bearing a tumour treated with the drug. Two experimental tumours with different features, i.e. an adenocarcinoma (ADK-1t) and a plasmacytoma (MOPC-460) were used. The former was more sensitive to Peptichemio. The colony inhibition test was used for the ADK-1t and 51Cr release for the MOPC-460 owing to the fact that two different methods of culture in vitro were employed. In the case of ADK-1t 4mg/Kg Peptichemio given on alternate days, five times beginning from the 3rd day after challenge, was followed by 40% reduction in lymphocyte toxicity by comparison with the controls. In the case of MOPC-460, on the other hand, no significant lymphocyte toxicity was observed, even in the controls. It was concluded that, in both cases, Peptichemio at this dose does not interfere with the immunity response of the host to any great extent, and is selectively active against neoplastic cells.


[Synergism of dicloxacillin and broad-spectrum penicillins]. On the basis of the proved protective activity showed by isoxazolyl penicillins on other antibiotics, a comparative study about the action of dicloxacillin over four penicillins with a broad spectrum was carried on. Either the experiments "in vitro" (antibacterial activity, growth dynamics, determination of beta-lactamase inactivation) then those "in vivo" have proved a real protection. A comparative study on different associations was also performed.


[Flucloxacillin].

[Flucloxacillin]. The pharmacological and clinical properties of flucloxacillin, a new isoxazolilpenicillin, are reported. This drug shows a low acute and chronic toxicity, and enteric absorption clearly higher than cloxacillin and oxacillin. Its binding capability with serum proteins, though rather high, is nevertheless lower than dicloxacillin. The antibacteric activity of flucloxacillin is particularly evident in Gram-positive bacteria and above all on penicillinases producing staphylococci. Flucloxacillin has proved to have successfull effect in the clinical therapy of several infections, particularly of respiratory apparatus and soft tissues.


[Action of a synthetic peptide on some syngeneic tumors]. The protective effect of intraperitoneal Peptichemio at different doses in a population of syngeneic mice with four experimental tumours is described. The drug is much used in oncology en account of its low toxicity and is both alkylating and antimetabolic. It was found more effective against plasmacytomas and less so against a spontaneous adenocarcinoma (ADK lt) Activity was noted at the lowest dose employed (4 mg/Kg five times on alternate days), which had no more than a slight immunodepressor effect and was unattended by sideeffects, as well as at the highest dose (10 mg/Kg). Evaluation of mean diameters and survival in the experimental animals and in the controls made it clear that the drug possessed almost general effectiveness, in addition to being most active against plasmacytomas.


[The antibacterial action of the amoxicillin-flucloxacillin combination]. A mixture of amoxycillin, semisynthetic penicillin beta-lactamase susceptible, and flucloxacillin, an isoxazolylpenicillin, in combination 1:1 was tested. This mixture shows real synergic effect "in vitro" on beta-lactamase producing Gram-positive and Gramnegative bacteria and an additive effect on the other microrganisms. Good results have been obtained "in vivo" and a protective effect of flucloxacillin on enzymatic degradation of amoxycillin by beta-lactamase was found.


Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma. The effect of tumor bulk resection on survival was studied in 102 patients with stages II and III ovarian cancer. A multiple linear regression equation provuded both simultenaous control of multiple confounding variables and an assessment of these variables as independent predictors of survival. The most important factors were the histologic grade of the tumor and the size of the largest residual tumor mass after operation. Survival time was uniformly poor if the diameter of the largest residual tumor mass exceeded 1.5 cm irrespective of total tumor volume (mean=12.7 months, SE=1.6 mo). Survival time was inversely proportional to residual mass size under 1.6 cm, and surgery improved survival relative to reduction in mass size below this limit. Extensive resections of tumor bulk with failure to remove all masses greater than 1.5 cm in diameter did not influence survival. Surgery provides optimum benefit when all gross tumor can be excised safely.


Current status of the second-look operation in ovarian carcinoma. A second-look operation was performed ten times in 240 patients with advanced carcinoma of the ovary treated initially by surgery and postoperative chemotherapy with triethylenethiophosphoramide. Patients undergoing the second-look operation for carcinoma of the ovary were grouped according to removal or retention of ovaries at initial operation and presence of residual tumor before the second surgery. Those whose retained ovaries were removed after complete tumor disappearance have done well. The second-look operation was of limited use where there was palpable residual tumor. Second-look surgery should be performed for patients with retained ovaries and complete clinical regression of tumor after administration of chemotherapy and in selected patients in whom interval treatment permits surgical clearance of tumor. Reduction of tumor target may warrant a second-look operation before the use of newer antitumor drugs.


Importance of maximum procedure in ovarian cancer. The maximum surgical procedure for the treatment of ovarian cancer is based on a number of sound theoretical concepts. These concepts are based on current knowledge of the biologic behavior of tumors as well as principles of chemotherapy and radiotherapy. These concepts have not been tested in a prospective randomized study. Discussed are the need for such a study and the great difficulties to be faced in achieving such a study.


Radiation therapy in the management of carcinoma of the ovary. The results in 212 patients treated with radiation therapy for various stages of carcinoma of the ovary are reported. The role of radiation therapy in the management of these patients is analyzed in the light of available data. Radiation therapy may improve the survival of patients with stage I ovarian cancer (with poorly differentiated lesions or extension through the capsule) and the survival of patients with stage II ovarian tumors. The patients with stage III ovarian lesions may benefit by a combination of irradiation and chemotherapy. A multidisciplinary approach to ovarian carcinoma must be promptly established, with participation of gynecologic surgeons, radiation therapists, pathologists, and chemotherapists. More thorough staging procedures and well-defined pathologic classifications are necessary. The biologic and pathologic behavior of these tumors must be further elucidated. The limitations of each treatment method must be exactly defined. Based on this information, rational treatment schemes may be formulated. Controlled clinical trials are necessary to evaluate the effectiveness of optimal surgery, irradiation, and chemotherapy, or their combinations.


Radioisotopes in treatment of stage Ia ovarian cancer. The role of radioisotopes in the treatment of ovarian carcinoma is discussed. The University of Iowa experience with prophylactic treatment of stage Ia ovarian cancer with radiogold is presented. Cumulative survival in 56 patients with epithelial cancers was 94.3%. In a prospective study, we compare the use of radiogold and total abdominal irradiation in the treatment of stage Ia ovarian carcinoma.


Ovarian cancer, with special regard to types of radiotherapy. Different techniques for whole abdominal irradiation after tumor removal from patients with ovarian cancer are discussed. The concept of subclinical disease is stressed.


Prognostic importance of histologic type in ovarian carcinoma. It is widely accepted that there exists a simple relationship between histologic type and prognosis in ovarian cancer. There are, however, multiple reasons to believe that if there is such a relationship, it is complex and involves many interacting factors. The factors concerned relate both to the biologic natures of the several neoplasms in this group and to the practical limitations to adequate evaluation imposed by clinical circumstances. Many questions remain to be answered before a prospective comparison of various treatment modalities can be expected to produce truly conclusive results.


Postoperative treatment of early cancer of the ovary: a random trial between postoperative irradiation and chemotherapy. One hundred and forty-nine patients with early cancer of the ovary who were suitable for postoperative radiotherapy were treated in a random study in which the efficacy of whole abdominal irradiation with additional irradiation to the pelvis was compared to that of chemotherapy with melphalan. The number of patients without evidence of disease at 2 years indicates that both treatments give similar results. However, the survivals among patients with stage I ovarian cancer showed an improvement for women treated with irradiation, survivals among patients with stage II ovarian cancer showed only a minor difference between women treated with irradiation and those treated with chemotherapy, and survivals among patients with stage III ovarian cancer improved for women treated with chemotherapy. The complications resulting from both treatments differed greatly. Melphalan was well tolerated; it caused serious bone marrow depression in only one patient. The blood counts of all patients after completing their prescribed chemotherapy promptly returned to normal levels. Seven patients treated with irradiation developed small bowel injury requiring surgery. Six of these patients, however, were treated with irradiation to the pelvis followed by strip irradiation to the entire abdomen. Since this treatment plan probably gives excessive doses of irradiation to the pelvis, it has been discontinued.


Epithelial carcinoma of the ovary:prognostic importance of histologic grade. Although this report contains only a few cases of epithelial carcinoma of the ovary and is not complete, it does suggest several new points and confirms other points reported in the literature: 1) increasing stage of cancer correlates well with decreased survival; 2) higher histologic grade of cancer correlates with decreases survival; 3) patients with a given stage of ovarian cancer having higher grades of malignancy have poorer survival; and 4) lower grade tumors are most frequently associated with lower stages of cancer, and higher grade tumors are most frequently associated with advanced stages.


Results of the Gynecologic Oncology Group trials on ovarian cancer: preliminary report. Preliminary results of three prospective controlled ongoing Gynecologic Oncology Group studies in ovarian carcinoma are discussed. The first study involves "Postoperative Treatment of Women With Resectable Ovarian Cancer With Radiotherapy, Melphalan, or No Further Treatment" (77 evaluable patients). Although there is a trend favoring chemotherapy, the differences as yet are not statistically significant. The second protocol evaluates "Postoperative Treatment of Women With Stage III Ovarian Cancer by Radiotherapy or Melphalan, Either Alone or in Both Sequences" (141 evaluable patients). The progression-free interval is shorter with either therapeutic modality alone and longer with the two combinations of radiation and chemotherapy. The third protocol deals with "Treatment of Women With Disseminated or Recurrent Advanced Ovarian Cancer With Melphalan Alone, in Combination With 5-FU, in Combination with 5-FU and Dactinomycin, or in Combination with Cytoxan, 5-FU, and Dactinomycin" (200 evaluable patients). In terms of progression-free interval, the study favors combination chemotherapy.


Ovarian tumor antigens: a new potential for therapy. A murine tumor-associated alpha-globulin was identified by immunofluorescence, cytotoxicity, and immunoelectrophoresis. The antiserum resulting from heterologous immunization with the segregated antigen was tolerated in multiple injections and was therapeutic; host cell participation by macrophages and lymphocytes led to the therapeutic result. Investigation of human ovarian carcinoma demonstrated an alpha-globulin which shares antigenic specificity with other tumor-associated antigens. The successful scanning of a tumor mass with a heterologous antibody directed against a tumor-associated antigen demonstrated the feasibility of applying these techniques to clinical cancer.


Electron microscopy, tissue culture,and immunology of ovarian carcinoma. The ultrastructure of the major histologic types of ovarian carcinoma was investigated as part of a multilateral study of this tumor. The nuclear and nucleolar changes in size, shape, and structure correlated well with the degree of malignancy and tumor grading. Cytoplasmic organelles and intercellular junctions were abundant and fairly well differentiated even in ovarian carcinomas of higher grade and stage. Active processes of synthesis and secretion taking place in most of these tumors were suggested by the presence of a richly granulated endoplasmic reticulum, dilated cisternae, and numerous secretory granules. Seventy-eight different ovarian carcinomas of all histologic types were cultured in vitro for periods of up to 300 days, and their morphology in light and electron microscopy was compared to that of the original tumors. The cultures displayed a consistent pattern of growth which led to the conclusion that ovarian cancer cells in vitro preserve their salient features and are representative of the tumors of origin. Heterologous antisera raised with pooled extracts of various types of ovarian carcinomas reacted specifically in immunodiffusion and immunofluorescence tests only with ovarian carcinomas and not with normal ovaries, benigh ovarian tumors, and nonovarian malignant neoplasms, indicating the presence of a cross-reacting specific antigen for ovarian carcinomas. In other studies, autologous antibodies were isolated from antigen-antibody complexes recovered from peritoneal effusions of patients with ovarian carcinomas. These antibodies displayed a high degree of specificity against ovarian carcinoma cells when tested in immunofluorescence assays.


World Health Organization classification and nomenclature of ovarian cancer. A World Health Organization (WHO) committee of representatives from seven nations published a histologic typing of ovarian tumors in 1973. Their typing of common epithelial tumor was based largely on the classification by the International Federation of Gynaecology and Obstetrics (FIGO), and the single most important concept to emerge from the FIGO and WHO classifications was the distinction among common epithelial tumors between tumors of borderline malignancy and carcinomas. A second general category of ovarian tumors, some of which are clinically malignant, was designated by the WHO committee as sex cord-stromal tumors (neoplasms containing granulosa, theca, collagen-producing stromal, Sertoli, and/or Leydig cells). The WHO classification of germ cell tumors emphasized the necessity of careful examination of the gross specimen with jucicious sampling for microscopic evaluation. The classification and nomenclature used within an institution should be the one most conductive to mutual understanding and optimal patient care; however, when that nomenclature has to be translated into one with more widespread acceptance, the WHO classification, based on the earlier and widely adopted classification of FIGO, is presently the most deserving of universal usage.


Regan isoenzyme and human chorionic gonadotropin in ovarian cancer. Among 833 cancer patients whose sera were investigated for Regan isoenzyme and among 1,319 cancer patients from a different population whose sera were assayed for human chorionic gonadotropin (HCG), those patients with neoplasms of the testis or ovary showed the highest frequency of both placental proteins. Among another 22 patients with ovarian cancer, for whom both placental proteins were measured, 59% showed Regan isoenzyme and 68% showed HCG in ascitic fluids, whereas the figures were 65% and 30%, respectively, for sera. In 55% of both fluids and sera, there was a positive correlation of Regan isoenzyme with HCG (positive or negative). Almost invariably, the ascitic fluid was richer in Regan isoenzyme and HCG than the serum when both were collected on the same day. Progressively increasing levels of each placental protein generally correlated with the spread of the disease, though there were instances when only one was expressed. Evidence indicated the existence of two forms of alkaline phosphatase in ovarian cancer, Regan and non-Regan; the latter was assumed to be of fetal origin. Ultrastructural studies of one ovarian cancer revealed a morphologic entity, i.e., mitochondria enveloped by inverted tubules of endoplasmic reticulum.


Peritoneal fluid profiles.

Peritoneal fluid profiles. Peritoneal fluid in women is very sensitive to many physiologic and pathologic gynecologic and obstetric conditions. Peritoneal fluid specimens can be obtained from women easily by culdocentesis. Routine assay for the presence or absence of malignant cells in peritoneal fluid from women with early ovarian cancer is indicated to determine the prognosis for the patient and the necessity for further therapy. The serial cytologic and biochemical evaluation of peritoneal fluid seems to be the best currently available means to determine persistent or recurrent ovarian cancer as well as to monitor therapy in a woman with normal clinical and roentgenographic examinations.


Ultrasound as an aid in the diagnosis and management of ovarian carcinoma: preliminary report. Ultrasonic scanning was used to assist in the diagnosis and management of ovarian tumors. Tumor response to therapy was evaluated with sequential ultrasound examinations in conjunction with clinical observations. Contact B-mode scanning and physical examination were complementary in demonstrating a change in tumor size, delineating small amounts of ascites, and identifying early omental implants. The information was used to guide the patient's management by chemotherapy.


Prognostic importance of histologic grading in ovarian carcinoma. Our data on ovarian epithelial carcinoma show that within a given stage, regardless of the histologic cell type, the increasingly higher grades have an increasingly poorer prognosis. This suggests that more intensive therapy be considered for all patients with ovarian epithelial carcinomas than is currently undertaken. Specifically, this means that, in addition to the standard modalities, chemotherapy should be considered for all tumors beyond grade 1, stage 1a.


Chemical comparison of intimal elastin in the human cerebral and coronary arteries and aorta. A preliminary note. The purpose of our experiments was to clarify the relationship between the susceptibility to atherosclerosis and chemical composition in the human cerebral, coronary arteries and aorta, and the concentration and composition of human arterial intimal elastic tissues were measured. In the cerebral arteries, the concentration of hot alkali-insoluble elastin was higher than that of the coronary arteries and aortas, and gradually decreased with age. Age-related changes of the elastin in the coronary arteries were quite small. The total polar amino acids and crude ash contents of arterial elastins were affected by age and treatment of elastic tissue wheteher or not EDTA-decalcification was applied prior to alkali-extraction. No significant differences in the amino acid composition of elastin was founded between the cerebral, coronary and aortic intimas and no significant changes to elastin, and or collagen, which can explain the slow development of atherosclerosis in the cerebral artery, were founded. Therefore, from these results, the slower development rate of cerebral atherosclerosis, as compared with other arteries, can not be sufficiently concluded.


Comparison of morphology of isolated cells obtained from aortas of normal and cholesterol fed rabbits. Cells from aortas of healthy newborn and adult rabbits were liberated by digestion with trypsin and collagenase. In the same way were obtained free cells from the aortas of rabbits with far advanced experimental atherosclerosis. More than 90 p. 100 of the cells from all groups were viable. Isolated cells were used for electron microscopic examination. In material obtained from aortas of newborn rabbits, endothelial cells, fibroblasts and smooths muscle cells were present. In adult rabbits two kinds of endothelial cells, fibroblasts, several varieties of myocytes and foam cells were found. The bulk of aortic cells isolated from rabbits with experimental atherosclerosis consisted of endothelial cells and smooth myocytes. The cytoplasm of all myocytes contained lipid vacuoles. The lipid-loaded myocytes corresponded to the typical foam cells. Lipid content was relatively scanty in the endothelial cells. The presence of myocytes foam cells like in the aortas of healthy adult rabbits, identical as in material from experimental atherosclerosis, may support the view that these cellular changes so far considered as typical for atherosclerosis are common, and may be treated as an exponent of the natural process of aging of the vascular wall.


Composition and macromolecular structure of intima in normal and arteriosclerotic human aorta. Proteoglycanes, glycoprotein, fibrous collagen and elastin proteins were isolated from normal human aortic intima and from sclerotic lipid and calcium plaques and examined by electron microscope and thermal analysis. Differences between the structure and compositon of normal human aortic wall and aortic lipid plaques are chiefly found in the proteoglycan containing fraction. The calcium plaque shows structural changes in the fibrillar protein components.


In vitro cultivation and identification of aortic endothelium from miniature pig. Pieces of miniature pig aorta were explanted endothelial face down directly on the bottom of Petri dishes. On removal of the aorta fragments after 2-4 days of incubation single cells or small groups of viable endothelium were found attached. The cells developed into a permanent line (at present over 18 passages) and were identified as pure endothelial cells both by light- and electron microscopic examination.


Trauma as an essential factor in atherogenesis-ultimate proof. Intimal foam-cell plaques developed within three weeks on the shoulders of cuts through aortic rings within diffusion chambers implanted subcutaneously into rabbits fed cholesterol. Since hemodynamic and thrombogenic factors were excluded the development of cholesterol-atherosclerosis and the localization of the plaques were the result of an interplay of three factors: trauma, a cholesterol-rich plasma insudate, and a susceptible aortic intima.


Atherosclerotic occlusions in anomalous left circumflex coronary arteries. A report of two unusual cases & a review of pertinent literature. Two cases of atherosclerotic occlusion of anomalous left circumflex coronary arteries having origin from a common ostium with the left coronary artery are documented. The atheromatous lesion was found at the same site in each case, i.e. the junction of the segment bound to the posterior wall of the aorta and its freer course in the atrioventricular sulcus. It appears that these junctions have an increased susceptibility to atherosclerotic changes, to local hemodynamic factors and local trauma related to the sudden change from a fixed artery to one lying relatively unfixed in the fibro-fatty tissue of the atrioventricular sulcus.


[Development of elastin of human aortas during ontogenesis]. The formation of the elastic fiber was followed up in nine human aortas from foetus or newborn. During this period of ontogenesis an evolution of the elastic residue with increasing age was observed. There was a decrease in the association of structural glycoproteins or microfibrils with elastin. The insolubility of elastin increased with age, together with the increasing crosslinkage of the fiber, characterized by the ratio (sum of desmosines/lysine).


Immunological studies with aortic and venous tissue antigens. I. The antigen structure of vascular tissues. Fractionation of intact and arteriosclerotic aortic and venous intimas was performed. The distribution of the obtained fractions (CTC, CSC, collagen, SGP and elastin), their disc-electrophoretic and immunological behaviour was studied. With the process of arteriosclerosis a decrease of the structural proteins (collagen, SGP, elastin) and an increase in the amount of some proteins of plasmatic origin could be demonstrated. By the use of absorbed immune sera in the immunoelectrophoretic patterns of aortic and venous CTC-extracts two vessel wall specific arcs were found.


Immunological studies with aortic and venous tissue antigens. II. Antibodies to vascular antigens. In the sera of patients with different clinical manifestations of arteriosclerosis antibodies were demonstrated against the CTC-extract in about 50 p. 100 of the cases. Using venous CTC-extracts positive results were obtained in patients with phlebothrombosis in 70 p. 100 of the cases. Cross reactions between the aortic and venous tissues were not detected.


Results of psychosocial adjustment to long-term colostomy. 114 patients with permanent colostomy for carcinoma of the rectum were compared by questionnaire and interview with 110 cancer patients, having undergone colonic resection but not bearing a colostomy. The patients' own assessment of their health was for the colostomy group even better than for the controls. The emotional state before and after surgery showed significant degrees of hopelessness, depressions and fear especially for young women awaiting colostomy. Social contacts were considered as far as visits of friends or cinema, theatre are concerned. Sexual activity decreased significantly for 75% of colostomized men. In 40% organic lesions led to impotence. The Giessen test revealed significant rates of social impotence, negative social resonance and depression for men with colostoma.


Three cases of cardiospasm treated successfully with psychotherapy. Catamnestic remarks. 3 cases of cardiospasm successfully treated by psychotherapy are reported and some catamnestic conclusions and remarks are given after a follow-up of the patients for 10, 9 and 8 years, respectively. Unlike the clinical symptomatology, which was almost identical in all 3 cases, the precipitating factors, the deeper meaning and the unconscious symbolism of the symptoms were quite different but specific for each one of the patients. Some more thoughts are also given in the paper with reference to the clinical criteria to be considered when evaluating the final therapeutic results of the technique of the therapy applied.


How are 'psychosomatic' patients different from 'psychoneurotic' patients? Two groups of white male patients of the same racial stock were selected on the basis of their acceptance or rejection by psychiatric residents for extended treatment. The group of patients eagerly accepted were mostly college students with anxiety, several of a phobic type, while the completely rejected group was composed of rheumatoid arthritic patients. Examination of samples of verbal transcript material showed that previously determined criteria, established on the basis of content analysis of interview transcripts, place the arthritic patients very much in the 'unsuitable for psychoteraphy' category, whereas the selected patients were highly 'suitable'. Verbal patterns in several different contexts are compared to show the differences 'concretely'; in addition, another such comparison shows the abundance of psychosomatic diseases in the families of the arthritic patients. Comparison of verbal material shows that patients with anxiety tend to be acutely sensitive to the future and to human relations, especially those with physicians in a personal sense. Arthritic patients, on the other hand, 'worry' much less, attend little to the future, incongruguously report that they are 'in command of' feelings. In a hospital psychiatric ward, anxious patients soon adapt with relief; the arthritic in such a ward insists that he follows his own idea of the behaviour of the hospitalized patient, complete with night clothes and bed rest. The conclusion suggested is that the two types of patients live in quite separate 'universes of discourse'.


Play therapy in the treatment of hebephrenia. This paper has attempted to outline a multiple technique therapy designed for the treatment of hebephrenia. The first phase of the technique utilizes play therapy, followed by an interchange of therapist and patient's drawings, and finally, analytic psychotherapy. These three phases may be characterized, respectively, as expressive, expressive-communicative, and communicative.


[New findings concerning cardiac proteins binding the coronary dilating substances of the hypothalamus]. We had previously shown that the protein component obtained from heart muscle by 0.1--0.2 saturation with ammonium sulfate exhibits a coronarodilatatory effect. Later on we succeeded in isolating from this protein complex, through dialysis, two coronaoractive low molecular compounds, one of which is apparently a neurohormone. In the present study we isolated, purified and studied the features of this protein complex. The results of gel filtration on Sephadex G-100 confirmed the presence of two different coronaroactive neurohormone binding proteins in heart muscle. The active fractions have been also purified through ion exchange chromatography on diethylaminoethyl cellulose. The purity of these fractions was tested through electrophoresis on 7.5% polyacrylamide gel. In the last stage of purification the active proteins moved towards the anode by one zone.


[Metabolic activity of the N-acetylneuraminic acid of the principle gangliosides of the brain]. The turnover rate of N-acetylneuraminic acid of brain gangliosides (GT1, GD1b, GD1a, GM1) was studied following the injection of 2-14C-acetate. The specific activity of N-acetylneuraminic acid in GD1a and GM1 was found to be higher than in GD1b. The administration of aminasine reduced the specific activity of N-acetylneuraminic acid whereas chlorhydrate increased that of major brain ganglosides.


[Character of loosely and tightly bound human cerebral gangliosides and methods of preparatory extraction]. The quantitative isolation of loosely and tightly bound gangliosides of human brain has been studied following various ways of extraction. Hot methanol extraction (Bogoch's method) gave a higher level of tightly bound gangliosides than by extraction with the Folch method. Both kinds of gangliosides were found to have the same fractional composition on thin layer chromatography on silicagel. A single extraction method of gangliosides giving high yields is proposed.


[Phospholipid composition of the cerebral proteolipids of rats of different ages]. Some properties and phospholipid composition of proteolipids (PL) of brain of 10, 20, 30 and 120--180 days old rats were studied following their isolation by the emulsion centrifugation method of Folch. The content of crude and purified PL and the phospholipids bound to them gradually increased with age. The PL isolated from brains of 10-day old rats are different in their properties and composition from that of PL of adult brain. Their optical density is 2-2,5 times smaller (E1% 1cm lambda 278 mmk). This may be due to their lower content of cyclic amino acids. The content of lecithin and monophosphoinositides in PL decreases with age while that of serienphosphatides and especially polyglycerophosphatides increases. The content of acidic phosphatides tightly bound to PL protein also increases. All of these changes occur mainly between the 10th and 20th days after birth. It would seem that this period is important for the formation of PL and their involvement in the composition of membranes.


[AMP-aminohydrolase activity of the nuclear fraction of rat brain]. AMP-aminohydrolase activity has been found not only in mitochondrial and soluble fractions but also in nuclear fraction of rat brain. The regulation of nuclear AMP-aminohydrolase activity differs from that of mitochondrial and soluble fractions. 1. Hexokinase does not enhance deamination of AMP in intact nuclei while it activates the enzyme in extracts of acetone powder of nuclear fractions. 2. The AMP-aminohydrolase activity of rat brain nuclear fraction is considerably inhibited by GTP and phosphate but in contrast to other fractions the stimulatory effect of ATP on enzyme activity is preserved.


[Forms of deposition of phosphoorganic cholinesterase inhibitors in the brain]. The content and hydrophobic properties (distribution coefficient in hexan : water) of organophosphorus inhibitors OPT of the following structure--R-O (CH3)/P/O/S C2H4SC2H5 have been studied in rat brain. On enlargement of the O-alkyl radical from ethyl to isopropyl and pinacolin hydrophobecity increases from 1 to 12 and 39, while the relative content of the chloroform extractable free OPT in brain, under conditions of uniform distribution, decreases from 11--18% to 3.2%. On incubation of the homogenate at 37 degrees C the further inhibition of the specific cholinesterase of the brain indicates the presence of an absolutely free form of OPT, the amount of which is not dependent on the degree of its hydrophobicity.


[Inductive synthesis of acetylcholinesterase in the brain during learning and training of rats]. In rats learning to use nonpreferred paw is accompanied by an increase of acetylcholinesterase (AChE) of specific areas of rat cerebral cortex and pyramidal neurones of CA3 and CA4 of the hippocampus. Following achievement of new behavioural reactions high AChE activity is preserved longer in the neacortex, the enzyme activity in the pyramidal neurones of the hippocampal cortex coming to normal. Following preliminary intracranial administration of puromycin the increase of AChE activity during learning is no more observed. This indicates the activation of the genetic apparatus during learning and training as a result of which synthesis of membrane proteins including AChE is enhanced. A close correlation between learning and the inductive synthesis of AChE is observed. Lateralization of the chemical traces of learning in specific areas of rat cerebral cortex are observed as increased activity of AChE. Changes in AChE activity in various hemispheres of rat brain during learning are thought to be due to assymetric changes in the excitatory level of cortical sites during the formation of new behavioural reactions. The specific localization of biochemical changes in the brain is certainly more favorable from an energetic aspect and may by regarded as an evolutionary compensatory process. The interrelationship of the activation of the synthetic apparatus of the cell with the reception of external informations is one of the expressions of adaptation during codations of functions of the organism more advantageous from an evolutionary point of view.


Acute renal failure and typhoid fever.

Acute renal failure and typhoid fever. Over a two-year period, out of 40 adult Ghanaians admitted to the renal unit of Korle Bu Hospital with acute renal failure, 6 (15%) had typhoid fever. During this period approximately 500 cases of typhoid were admitted to this Hospital. Prominent features in these cases were a blackwater fever syndrome and leucocytosis. These features in a patient with typhoid should suggest the possibility of complicating acute renal failure. Three patients showed a deficiency of glucose-6-phosphate dehydrogenase (G-6-P.D.) in their red blood cells. It is suggested that typhoid is likely to be an important cause of acute renal failure in areas where it is endemic and G-6-P.D. deficiency common.


Biliary tract disease and sickle cell anaemia in Korle Bu Teaching Hospital, Accra. This study has examined the incidence of biliary tract disease in the general medical and surgical wards of the Korle Bu Teaching Hospital as well as the prevalence of the disease in patients attending the Sickle-cell Clinic. There were 72 confirmed cases of biliary tract disease (0.5 percent hospital admissions) of which 17 or 23.9 percent had a positive sickling (AS, SS, SC). When SS and SC patients only were considered the incidence of biliary tract disease was significantly higher than the rest of the population. The incidence in biliary tract disease among patients attending the Sickle-cell Clinic was in this semiprospective study found to be 14.6 per cent; analysis of several clinical variables indicated that haemolysis was an important causative factor. There were however several other unexplained factors which emphasize the need for a more detailed prospective study in this area.


Systemic copper and sex steroids uptake by rat tissues. Subcutaneous injection of copper sulphate into the rat produced a significant depression in the relative and absolute uptake of oestradiol by the uterus. With progesterone, an enhancement in the absolute count uptake in the uterus, muscle, liver and kidney occurred. The absolute uptake of oestradiol in muscle, liver and kidney were also enhanced.


Clinical measurement of trend in fertility of women attending family planning clinics in Ghana. 1. The need for a simple method of measuring trend in fertility in family planning programme has been stated. 2. The theory of the numerator analysis of age and parity or age and number of living children and its variants the "three area" and the "four quadrant methods" have also been stated. 3. The data from the Korle Bu Teaching Hospital have been analysed. 4. The finding was that the proportion of women of the high fertility group is reducing while that of women in lower fertility is increasing with time. 5. The relevance of this type of analysis to national family planning programme has been emphasised.


Experience with Morgan perfusion contact lens in treating eye infections and burns. The effects of a new therapeutic perfusion contact lens upon heavy infections and severe burns had been observed in 30 cases. We conclude that this method is advantageous, where there is a shortage of nursing personnel. We also consider the advisability of instructing sick bay attendants in large factories and military personnel in the use of the contact lens in order to bridge the critical phase between injury and hospital treatment.


The interface between statistics and health planning. This essay is a brief review of some of the major limitations, and the nature of the underlying assumptions, in the use of Statistics in Health Planning: it poses pertinent questions which the Health Planner must face when using Statistics; and draws attention to System Dynamics, a relatively new Research technique which may be applied to studies in human ecology and other complex systems.


Cost of selected health institutions in the Central Region 1972-1973. An account is given in the paper of a costing exercise conducted at four institutions in the Central Region, using 1972/1973 data. Attention is initially drawn to the conceptual and practical difficulties involved in the collection and interpretation of data. Detailed estimates for each institution-Cape Coast hospital, Saltpond hospital, Swedru health centre and Kissi health post are then presented. Finally a tentative suggestion for a supplementary statistical system covering institutional cost is broached.


Reflections on the health budget. A preliminary analysis of the 1974/75 Ministry of Health budget. This paper describes the 1974/75 Budget, and analysis it in terms of allocations to Medical Care, Public Health and Training functions as well as by allocations to Regions. 80% of the Health Vote goes into Curative or Medical Care, 12% into the Preventive Services, 6% into Trining and the rest to Headquarters. It brings out the great disparities among the Health Care System of the various Regions, and suggests also that the method of the presentation of the Health Budget makes it difficult to understand resource allocations within the Health Sector.