Self-reported beta-lactam allergy in government and private hospitals in Cape Town, South Africa.

BACKGROUND: Up to a quarter of inpatients in high-income countries (HICs) self-report beta-lactam allergy (BLA), which if incorrect,increases the use of alternative antibiotics, worsening individual health outcomes and driving bacterial resistance. In HICs, up to 95% ofself-reported BLAs are incorrect. The epidemiology of BLA in low- and middle-income African countries is unknown. OBJECTIVES: To describe the epidemiology and de-labelling outcomes of self-reported BLA in hospitalised South African (SA) patients. METHODS: Point-prevalence surveys were conducted at seven hospitals (adult, paediatric, government and privately funded, district andtertiary level) in Cape Town, SA, between April 2019 and June 2021. Ward prescription records and in-person interviews were conductedto identify and risk-stratify BLA patients using the validated PEN-FAST tool. De-labelling was attempted at the tertiary allergy clinic atGroote Schuur Hospital. RESULTS: A total of 1 486 hospital inpatients were surveyed (1 166 adults and 320 children). Only 48 patients (3.2%) self-reported a BLA,with a higher rate in private than in government-funded hospitals (6.3% v. 2.8%; p=0.014). Using the PEN-FAST tool, only 10.4% (n=5/48)of self-reported BLA patients were classified as high risk for true penicillin hypersensitivity. Antibiotics were prescribed to 70.8% (n=34/48)of self-reported BLA patients, with 64.7% (n=22/34) receiving a beta-lactam. Despite three attempts to contact patients for de-labelling atthe allergy clinic, only 3/36 underwent in vivo testing, with no positive results, and 1 patient proceeded to a negative oral challenge. CONCLUSION: Unlike HICs, self-reported BLA is low among inpatients in SA. The majority of those who self-reported BLA were low risk fortype 1 hypersensitivity, but outpatient de-labelling efforts were largely unsuccessful.

Excitotoxic lesions of the mediodorsal thalamic nucleus attenuate intravenous cocaine self-administration.

The present experiments investigated the effects of excitotoxic, axon-sparing lesions of the mediodorsal nucleus of the thalamus (MD) on locomotor activity and i.v. cocaine self-administration. Infusion of quinolinic acid into the MD using a glass micropipette produced well-defined neuronal loss restricted to medial and lateral portions of the MD, sparing adjacent areas such as the lateral habenula and paraventricular thalamic nucleus. MD lesions resulted in delayed habituation to activity cages. In addition, lesioned rats self-administered significantly smaller amounts of cocaine than controls during a 14-day acquisition period, and showed attenuated responding for cocaine doses on the descending limb of the dose-effect function. Since typical titrating patterns of responding were maintained in lesioned rats, and responding on the inactive lever did not differ from sham-operated animals, these present results indicate an enhanced sensitivity to the reinforcing effects of response-contingent cocaine in rats with excitotoxic lesions of the MD.

Excitotoxic lesions of the basolateral amygdala impair the acquisition of cocaine-seeking behaviour under a second-order schedule of reinforcement.

In these experiments we sought to establish the intravenous (i.v.) self-administration of cocaine under a second-order schedule of reinforcement in order: (i) to obtain reliable, drug-free levels of responding with cocaine as a reinforcer, and (ii) to enable investigation of the neural mechanisms by which arbitrary cues gain motivational salience and, as conditioned reinforcers, control over drug-seeking behaviour. Initially, each infusion of cocaine was made contingent upon a response on one of two identical levers and was paired with a 20-s light conditioned stimulus (CS). Responses on the second lever were recorded, but had no programmed consequence. When rats acquired stable rates of self-administration, a second-order schedule of the type FRx(FRy:S) was introduced, with values of "x" being increased progressively to 10 and then "y" from 2 through 8. Priming (i.e. non-contingent) infusions of cocaine were never given. Once the first infusion was obtained under the second-order schedule, further infusions were made contingent on each response (to a maximum of ten infusions/day). Each stage was repeated daily until the first infusion of each session was achieved within a 5-min criterion. Rats with bilateral, excitotoxic lesions of the basolateral amygdala readily acquired the i.v. self-administration of cocaine under a continuous reinforcement schedule, initially administering more infusions and maintaining a slightly elevated level of self-administration than controls. Despite increased numbers of CS/drug pairings, basolateral amygdala-lesioned rats were severely impaired in the acquisition of the second-order schedule of i.v. cocaine reinforcement. Lesioned rats showed a cocaine dose-response function that was shifted upwards relative to control subjects. There was no significant difference between drug-naive amygdala-lesioned and control animals in the locomotor response to intraperitoneal injections of cocaine. These experiments indicate the feasibility and utility of second-order schedules in studying the neurobehavioural basis of cocaine-seeking behaviour. They suggest a dissociation in the neural mechanisms underlying cocaine-taking and cocaine seeking behaviour, and demonstrate the potential importance of the basolateral amygdala in the processes by which previously neutral stimuli gain control over drug-seeking behaviour.

Analysis of the effects of intra-accumbens SKF-38393 and LY-171555 upon the behavioural satiety sequence.

The outcome of intra-accumbens infusions of the dopamine D1 receptor family agonist SKF-38393 and the D2 receptor family agonist LY-171555 upon measures taken during the behavioural satiety sequence was assessed (0.01 micrograms, 0.1 micrograms, 1.0 micrograms in each case). Each drug was infused either separately, or together as a co-infusion in order to examine the functional relationship between these dopamine receptor subtypes within the nucleus accumbens. Measures of feeding did not change following infusions of SKF-38393 or LY-171555, whether infused separately or together. However, following separate infusion of the lowest dose tested of each drug (0.01 micrograms), the onset of resting was advanced. Moderate to high doses of SKF-38393 and LY-171555 (0.1 micrograms, 1.0 micrograms) infused separately resulted in a marked increase in activity at the expense of resting. Co-infusion of 0.01 micrograms of each drug also resulted in a dramatic increase in activity. Thus, measures of feeding behaviour were unchanged following excitation of D1 and D2 dopamine receptor families within the nucleus accumbens. In marked contrast, locomotor behaviour appeared to be under the potent synergistic control of these receptor families.

Isolation rearing enhances the locomotor response to cocaine and a novel environment, but impairs the intravenous self-administration of cocaine.

Male Lister hooded rats were raised from weaning either alone (isolation reared) or in groups of five (socially reared controls). At 5 months of age, experiments began. Experiment 1 examined the effect of isolation rearing upon the locomotor response to a novel environment, and the locomotor stimulant effect of an injection of cocaine (10 mg/kg). Isolation reared animals were more active in a novel environment, and were more responsive to the locomotor stimulant action of cocaine. In succeeding experiments, the effects of isolation rearing on the reinforcing efficacy of intravenous cocaine were assessed. Animals were never "primed" with noncontingent infusions of cocaine at any time during these experiments. In experiment 2, the effect of isolation rearing upon the acquisition of the intravenous self-administration of cocaine was examined. Two levers were present in the operant chambers. Depression of one lever resulted in the intravenous delivery of a 1.5 mg/kg infusion of cocaine, responses on the second, control lever were recorded but had no programmed consequences. Isolation reared animals acquired a selective response on the drug lever at a slower rate than socially reared controls. In experiment 3, a full cocaine dose-response function was examined. Isolation rearing shifted the cocaine dose-response function to the right. In addition, isolation rearing impaired the selectivity of the response on the drug lever at lower doses of cocaine. In experiment 4, the effect of isolation rearing upon the response to a conditioned reinforcer associated previously with cocaine delivery was observed. In the absence of cocaine, the contingent presentation of the conditioned reinforcer enhanced selectively the rate of response by socially reared controls. However, isolation reared animals were unresponsive to this manipulation. These data are discussed with reference to dysfunctional cortico-limbic-striatal systems, and their interactions with the mesoaccumbens dopamine projection.

Isolation rearing impairs the reinforcing efficacy of intravenous cocaine or intra-accumbens d-amphetamine: impaired response to intra-accumbens D1 and D2/D3 dopamine receptor antagonists.

Male Lister hooded rats were raised from weaning either alone (isolation reared) or in groups of five (socially reared controls). At 5 months of age, bilateral guide cannulae were implanted within the nucleus accumbens, and experiments began. The effect of isolation rearing upon the reinforcing efficacy of the intravenous self-administration of cocaine (experiment 1), or the bilateral intra-accumbens self-administration of d-amphetamine (experiment 2) was assessed. Self-administration was made contingent upon the acquisition of a novel lever-pressing response. Two identical levers were available within each operant chamber. Responding on one lever resulted in the delivery of drug (experiment 1: cocaine, 1.5 mg/kg per infusion; experiment 2: d-amphetamine, 0.25 micrograms/side), responding on the second, control lever was recorded but had no programmed consequences. Animals were not "primed" with noncontingent infusions at any time. For experiment 1, animals received intra-accumbens infusions of the D1 dopamine receptor antagonist SCH-23390, or the D2 dopamine receptor antagonist sulpiride over two test sessions. Within each session, animals received a cumulative series of doses of each dopamine receptor antagonist. A validation group received doses of each antagonist according to more conventional methods (one dose per session). In either case, intra-accumbens infusions of SCH-23390 or sulpiride enhanced the rate of the self-administration of cocaine in socially reared controls. However, isolation rearing impaired this response to intra-accumbens infusions of the dopamine receptor antagonists. Experiment 2a examined the acquisition of the intra-accumbens self-administration of d-amphetamine. Socially reared controls acquired readily a selective response upon the drug lever. However, isolation reared animals acquired a selective response at a greatly retarded rate. In experiment 2b, a full d-amphetamine dose-response function was examined. Isolation rearing impaired the response to a range of doses of d-amphetamine. In experiment 2c, the infusate (1 microgram d-amphetamine per infusion) was adulterated with either SCH-23390 or sulpiride. Adulteration with either dopamine receptor antagonist enhanced the rate of response by socially reared controls. Isolation rearing impaired this response to SCH-23390, and blocked the response to sulpiride. These data are discussed in relation to the functioning of cortico-limbic-striatal systems, with particular reference to the mesoaccumbens dopamine projection.

An investigation into the role of the pedunculopontine tegmental nucleus in the mediation of locomotion and orofacial stereotypy induced by d-amphetamine and apomorphine in the rat.

As the pedunculopontine tegmental nucleus has an important anatomical position as an output station for the striatum, its role in the mediation of behaviour stimulated by d-amphetamine and apomorphine was investigated. Bilateral ibotenate lesions were made in either the pedunculopontine tegmental nucleus or, as a control, in the adjacent deep mesencephalic nucleus; sham lesions were made using phosphate buffer. Over the 14 days after surgery there were no significant differences in the rats' body weight or food intake. Deep mesencephalic lesioned rats spilled more food and drank more water (never more than 5 ml more) than controls or pedunculopontine tegmental lesioned rats. Spontaneous locomotion and that elicited by d-amphetamine or apomorphine were not affected by ibotenate lesions of either the pedunculopontine tegmental nucleus or deep mesencephalic nucleus. At higher doses of d-amphetamine and apomorphine, however, excessive biting and licking were observed in the pedunculopontine tegmental nucleus, but not deep mesencephalic nucleus, lesioned rats. Such orofacial stereotypies are never observed in normal rats after systemic injection of d-amphetamine. Post mortem analysis showed that ibotenate lesions of the pedunculopontine tegmental nucleus had destroyed cholinergic and non-cholinergic neurons there but had left the deep mesencephalic nucleus intact; ibotenate lesions of the deep mesencephalic nucleus destroyed neurons in that structure but not the pedunculopontine tegmental nucleus. These data demonstrate that lesions in the pedunculopontine tegmental nucleus and deep mesencephalic nucleus have different effects, measured histologically and behaviourally; that neither spontaneous locomotion nor that stimulated by d-amphetamine or apomorphine is dependent on the integrity of the pedunculopontine tegmental nucleus; and that the pedunculopontine tegmental nucleus plays an important role in mediating orofacial activity stimulated by these drugs. The data are discussed in terms of their implications for understanding outflow from the caudate-putamen and nucleus accumbens.

Does frontal-plane asymmetry in compensatory postural responses represent preparation for stepping?

The bilateral symmetry of feet-in-place responses to postural perturbations in the anterior-posterior direction has not been well studied. This paper presents evidence that right- and left-leg responses that appear to be approximately symmetrical in the sagittal plane may actually involve an asymmetry in the frontal plane, namely, a lateral weight shift. Comparison with trials where subjects stepped suggests that these lateral weight shifts represent early preparations for stepping responses that are aborted before the foot is actually lifted. Thus, it would seem that compensatory stepping involves a sequence of discrete modifiable stages, rather than a single immutable motor program. Moreover, postural responses that appear to be similar in the sagittal plane may actually be seen to involve quite different postural strategies, i.e. in terms of preparation for stepping, when viewed in the frontal plane.

Influence of expectation and arousal on center-of-pressure responses to transient postural perturbations.

Central modulation of postural responses to external perturbations appears to be a function of subject expectation, which in turn depends on: 1) prior experience within the testing paradigm, and 2) available information specific to the impending perturbation. Conceivably, the effects of expectation could be mediated, in part, through arousal-related mechanisms. This study investigated the influence of expectation of "postural threat" on center-of-pressure responses to transient translational platform perturbations in 23 healthy young males. The influence of prior experience was assessed first by performing a series of repeated trials using moderately large perturbations. The effect of providing specific prior information was then evaluated by administering small "low-threat" and large "high-threat" perturbations, with and without prior precued information about the perturbation magnitude. Also assessed were the associations between the postural responses and changes in arousal, the latter indicated by heart rate and skin conductance measures. The results showed that prior testing experience had a profound influence on postural strategy selection and execution, whereas the influence of precued prior information was rather more subtle. A tendency to lean forward prior to perturbation was influenced both by experience and prior information. Marked decreases in arousal occurred over the course of the earliest trials, and there was also some evidence that prior information affected arousal. Although causal relationships cannot be established, the results did show evidence of association between arousal and postural responses, suggesting that arousal could have affected postural strategy selection and execution.

Atlantoaxial instability and abnormalities of the odontoid in Down's syndrome.

Radiography of the lateral neck was performed on all children with Down's syndrome aged 4-15 in the Southern Derbyshire health district (n = 67) and a random selection of adults (n = 94). Atlantoaxial instability, defined as a gap of over 4 mm, was present in seven (10%) children and two (2%) adults. Odontoid hypoplasia, defined as an odontoid peg two standard deviations below the mean in an age matched population, was present in 15 (22%) children and 14 (15%) adults, with accessory odontoid ossicles present in two (2%) and two (3%) respectively. No one was found to have symptoms or clinical signs of spinal cord compression. Atlantoaxial instability was therefore found to be commoner in children than adults. Different programmes of management are suggested, in terms of regular clinical examination for signs and symptoms and by radiographic screening. Particular care should be taken with those who have both atlantoaxial instability and odontoid hypoplasia or accessory ossicles as they are at particular risk of spinal cord damage.

10-year survey of 485 sterilisations. Part I--Sterilisation or hysterectomy?

A survey was made of all sterilisations performed in an obstetric and gynaecological unit in Dunfermline in 1965-74 to determine the outcome and complications. Altogether 547 women were sterilised by the modified Pomeroy method, and 485 (88.7%) were interviewed and examined. No sterilisation was followed by serious complications, and the incidence of even minor complications was low (4.12%). There were no subsequent pregnancies. Altogether 57 women had to be referred for gynaecological operations in the years after sterilisation but only 18 of these had to have hysterectomies. At interview 59 women were found to have gynaecological symptoms (menstrual disorders in 46), and examination showed that 83 women had a gynaecological condition, which was in most cases unsuspected by the patient. Most of these conditions were minor but three women had carcinoma-in-situ of the cervix. Although 46 women suffered menstrual disorders after sterilisation 104 had done so at some time before the operation. These results therefore offer little support for the wider use of hysterectomy as a form of sterilisation.

PIP: A survey was made of all steriilzations performed in an obstetric and gynecological unit in Dunfermline, Scotland, in 1965-1974 to determine the outcome and complications. Altogether 547 women were sterilized by the modified Pomeroy method, and 485 (88.7%) were interviewed and examined. No sterilization was followed by serious complications, and the incidence of even minor complications was low (4.12%). There were no subsequent pregnancies. Altogether 57 women had to be referred for gynecological operations in the years after sterilization but only 18 of these had to have hysterectomies. At interview 59 women were found to have gynecological symptoms (menstrual disorders in 46), and examination showed that 83 women had a gynecological condition, which was in most cases unsuspected by the patient. Most of these conditions were minor but 3 women had carcinoma in situ of the cervix. Although 46 women suffered menstrual disorders after sterilization 104 had done so at some time before the operation. These results therefore offer little support for the wider use of hysterectomy as a form of sterilization.

10-year survey of 485 sterilizations. Part II: patients' views on their sterilization.

As part of a study of the complications after sterilisation 485 of the 547 women who had been sterilised by a modified Pomeroy procedure in one unit over 10 years were interviewed. They were asked whether they regretted being sterilised and about the quality of their sex lives, mental health, social relationships, and marriages. Most women were pleased to have been sterilised, only 24 regretting it. Regret was more pronounced among women who had been sterilised in association with a third caesarean section, those sterilised for medical reasons, and those whose marriages had ended in divorce. In each case where a woman regretted a sterilisation that had been performed on the recommendation of a psychiatrist, the psychiatrists were still prepared to defent their opinions. On their sex lives, mental health, social relationships, and marriages, more women reported improvement than deterioration, and in most cases the deterioration could not be attributed to the sterilisation. The overall benefits from sterilisation to the women in this series therefore seemed to outweigh substantially the adverse consequences experienced by a few.

Value of cystography in urinary tract infections.

Fifty-one children with a bacteriologically proven urinary tract infection had both an intravenous urogram (IVU) and a micturating cystogram. The IVU was normal in 35. Only 6 of these children showed reflux in the cystogram, affecting 7 of the 70 ureters at risk. Since reflux on its own does not cause renal damage, which occurs only with super-added infection, detection of reflux is not important providing the urine is kept sterile. We suggest that cystography be deferred providing the IVU is normal until recurrent infections occur while under hospital care, and, with this policy this unpleasant and sometimes hazardous investigation could be avoided in many children with a single urinary tract infection.

Lipogranuloma of bone.

Five cases of lipogranuloma of bone are described. The possible aetiology and nomenclature of the condition are discussed.