The influence of endothelin-1 on human foeto-placental blood vessels: a comparison with 5-hydroxytryptamine. 1. The vasoconstrictor effect of endothelin-1 (3 x 10(-11) M-10(-7) M) was studied in successive generations of blood vessels of the foeto-placental vascular tree. These were the human umbilical arteries and veins, primary surface chorionic plate arteries, secondary chorionic plate arteries, tertiary surface chorionic plate arteries and veins and the secondary stem villus arterioles. The responses to endothelin-1 were compared with those to 5-hydroxytryptamine (10(-9) M-10(-5) M). Arterial preparations were gassed with 2.5% O2, 8% CO2 balance N2 and venous preparations were gassed with 5% O2, 6% CO2 balance N2 to simulate the conditions prevalent in utero. The influence of increasing the oxygen tension to 16% (that prevalent at birth) on the response to endothelin-1 on the umbilical arteries was also investigated. 2. All the arterial vessels tested were some ten times more sensitive to endothelin-1 than to 5-hydroxytryptamine and the venous preparations were ten times more sensitive to endothelin-1 than were their equivalent arteries. Increasing oxygen tension did not affect the responses to endothelin-1 in the umbilical artery. 3. Whilst the amplitude of the endothelin-1-induced response was uniform throughout the foetoplacental vascular tree, including the stem villus arterioles, the maximum response to 5-hydroxytryptamine decrease with successive generations and it had no significant effect on the stem villus arterioles.The ratios of the responses to 10- M endothelin-1: 10-7M 5-hydroxytryptamine in human umbilical arteries, primary surface chorionic plate arteries, secondary chorionic plate arteries,tertiary surface chorionic plate arteries and the secondary stem villus arterioles in the vessels (listed in order of decreasing vessel size) were 1:1.2, 1:0.36, 1:0.33, 1:0.35 and 1:0.04 respectively.4. In conclusion, endothelin-1 is a powerful vasoconstrictor at all levels of the foeto-placental vascular system including the stem villus resistance vessels. It may play an important role in maintaining foeto-plancental vascular resistance at the low oxygen tension which exists in this vascular system in utero.


Regional differences in endothelin converting enzyme activity in rat brain: inhibition by phosphoramidon and EDTA. 1. It has been demonstrated previously that conversion of big endothelin-1 (bET-1) to endothelin-1 (ET-1) is inhibited in vitro and in vivo by phosphoramidon. In addition, ET-1 binding sites and mRNA have been shown within the brain. Here we expand upon our previous observation that rat brain contains phosphoramidon-inhibitable endothelin converting enzyme (ECE) and show that this activity is not uniformly distributed throughout the brain. 2. ECE activity was detected by a bioassay which depended upon the 10,000 fold difference in potency between bET-1 and ET-1 as stimulants of guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in kidney epithelial (PK1) cells of the pig. Data were confirmed by specific enzyme-linked immunosorbent assay (ELISA) employing antibody directed against ET-1/3(17-21). 3. Following homogenization of the whole brain and ultracentrifugation the 100,000 g pellet contained greater than 4 times more ECE activity than the cytosol. Washing of the pellet with KCl (1 M) and extraction with the detergent CHAPS (20 mM) revealed a phosphoramidon-inhibitable ECE within the residual particulate fraction (nominally classified as the cytoskeletal fraction). Phosphoramidon (IC50, approx. 5 microM) or EDTA inhibited the conversion of bET-1 to ET-1 by the cytoskeletal fraction of rat brain by more than 60%.2+ 4. Following dissection of rat brain into olfactory bulb, cerebral cortex, striatum, hippocampus, cerebellum, midbrain (including thalamus), hypothalamus and medulla oblongata (including pons) the greatest ECE was detected in the hypothalamus and medulla oblongata.After fractionation, the ECE-activities in the cytoskeletal fractions prepared from the hypothalamus or medulla oblongata were inhibited concentration-dependently by phosphoramidon or EDTA, with maximum inhibitions of>80% and >70%, respectively.5. These data show that rat brain contains a phosphoramidon- and EDTA-inhibitable ECE which maybe similar to that present in endothelial cells. The localization of this enzyme correlates with published reports of immunoreactive-ET-l, ET-1-binding sites, and messenger RNA for ET-1 in the rat brain, and suggests the presence of the entire synthetic pathway for ET-1.


Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells. 1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the shape or position of the 'notch' in the action potential. 3. Possible mechanisms of action were studied in more detail in the case of compound II (1-(4-methanesulphonamidophenoxy)-3-(N-methyl 3,4 dichlorophenylethylamino)-2-propanol). Prolongation of action potential duration continued to occur in the presence of nisoldipine, and calcium currents recorded under voltage-clamp conditions were not reduced by compound II (1 microM). Action potential prolongation by compound II was also unaffected in the presence of 10 microM tetrodotoxin. 4. Compound II (1 microM) did not influence IK1 assessed from the current during ramp changes in membrane potential (20 mV s-1) over the range -90 to -10 mV. 5. Compound II (1 microM) blocked time-dependent delayed rectifier potassium current (IK) activated by step depolarizations and recorded as an outward tail following repolarization. When a submaximal concentration (50 nM) was applied there was no change in the apparent reversal potential of IK.6. Submaximal concentrations of compound II were without effect on activation of IK with time at a membrane potential of + 40 mV, and no changes were detected in the time constants of the two components of IK decay over the range of potentials - 60 to 0 mV. Compound 11 (50 nM) appeared to cause a small shift in the activation of IK with membrane potential (an apparent shift of approximately 10mV in the depolarizing direction at the mid-point of the curve).7. Log dose-response curves for action potential prolongation and for blockade of IK by compound II were similar. The IC50 for compound II was approximately 30 nM.8. It is concluded that this novel series of compounds prolongs action potential duration, and that in the case of compound II the evidence supports a potent selective effect on the time-dependent potassium current IK, an effect which can account for this prolongation.


In vitro inhibition by endothelins of thrombin-induced aggregation and Ca2+ mobilization in human platelets. 1. The in vitro effects of endothelins (ET-1 and ET-3) on human platelets were investigated by measurement of the aggregatory responses of washed platelets to thrombin and by the determination of cytosolic pH (pHi) and free Ca2+ concentration ([Ca2+]i) determined with the fluorescent indicators, BCECF and Fura-2. 2. ET-1 and ET-3 at concentrations ranging from 10(-10) to 5 x 10(-7) M, did not promote platelet aggregation but inhibited in a dose-dependent manner the aggregation induced by 0.05 u ml-1 thrombin (P less than 0.002 and less than 0.001, respectively) with maximal effects reached at 10(-8) M (17 +/- 3 and 15 +/- 2%, n = 11, P = 0.002 for each). 3. Even at 5 x 10(-7) M, ET-1 and ET-3 did not cause a measurable change in basal [Ca2+]i and pHi. When tested in combination with thrombin, 5 x 10(-7) M ET-1 and ET-3 decreased the transient peak of [Ca2+]i by 17 +/- 7 and 28 +/- 7% (n = 7 and 11, P = 0.03 and P = 0.002). No effect on pHi variations was detected. In the virtual absence of external Ca2+, 5 x 10(-7) M ET-3 inhibited the peak of [Ca2+]i by 18 +/- 6% (n = 6, P = 0.02). 4. The anti-aggregating agents, prostacyclin (PGI2, 10(-8)-10(-7) M) and nitroprusside (NP, 10 ng-50 micrograms l-1) also induced a dose-dependent inhibition of the thrombin-induced [Ca2+]i peak (P = 0.001 for each).A combination of 10-9M PGI2 and 1O ng P' NP augmented the inhibitory effect of each drug(PGI2 alone 52 +/-11, plus NP 90 +/- 2; NP alone 26 +/- 4, plus PGI2 69 +/- 5% inhibition of [Ca2 ], peak, n = 6 for each, P <0.01 and P <0.001, respectively). Platelet preincubation with 5 x 10-7M ET-3 increased by 34+/-11% (n = 6, P = 0.0 14) the inhibitory effect of NP 1O ng without a significant influence on the PGI2 effect.5. In conclusion, endothelins ET-1 and ET-3 can reduce in vitro the aggregating response of human platelets to thrombin by a mechanism that is probably due to decrease Ca2+ mobilization.


Mode of action and comparative efficacy of pharmacological agents that inhibit calcium-dependent dehydration of sickle cells. 1. Selected Ca-channel antagonists were tested at 20 microM as inhibitors of Ca(2+)-uptake in human sickle red cells. Nitrendipine, fendiline, and bepridil (and its stereoisomers), were found to be as effective as methoxyverapamil (D-600) in inhibiting a fraction (25%) of Ca(2+)-uptake. In contrast cetiedil and Org 30701 were ineffective. 2. The drugs were subsequently tested as inhibitors of Ca(2+)-induced K+ efflux (Gardos) from sickle cells. They all showed inhibitory activity, with the order of efficacy nitrendipine greater than fendiline greater than bepridil greater than cetiedil greater than Org 30701. 3. With a 15 h programme of deoxygenation/reoxygenation cycles in a gas exchanger, it was shown that the inhibitors protected against cellular dehydration and loss of filterability in the order nitrendipine greater than fendiline greater than bepridil greater than cetiedil greater than Org 30701. However, significant stomatocytosis occurred at high concentrations of cetiedil, and bepridil (including its stereoisomers and analogues) impairing cell deformability. 4. It is concluded that Ca-antagonists may partially block both Ca(2+)-uptake and Ca(2+)-induced K+ efflux. The latter pathway is significant in contributing to sickle cell dehydration and nitrendipine is the most effective inhibitor of this route.


Classification of platelet and vascular prostaglandin D2 (DP) receptors: estimation of affinities and relative efficacies for a series of novel bicyclic ligands. With an appendix on goodness-of-fit analyses. 1. The DP receptors located on platelets and vasculature were examined in a human washed platelet preparation and in isolated rings of rabbit external jugular vein. 2. A series of eight novel bicyclic compounds were studied for their effects in the two assays. Seven produced agonism, inhibition of aggregation or vascular relaxation, and one compound was 'silent' in both assays. 3. The operational model of agonism (Black & Leff, 1983) was fitted simultaneously to concentration-effect curve data for the seven agonist compounds. The affinity and efficacy estimates so obtained were tested for similarity between the two tissues by analysis of variance, showing that the model could be fitted to both sets of data by assuming the same relative affinity and efficacy values. However, absolute affinity estimates were consistently lower in the vascular preparation. 4. Analysis of two of the seven agonists as antagonists was also possible. This provided pKB estimates which supported the agonist affinity estimates. The eighth compound was also analysed as an antagonist. It, like the other seven, demonstrated a difference in affinity between the two tissues. 5. The results of this study support the view that platelet and vascular DP receptors are similar, assuming that the systematic difference in affinity estimates for the series of compounds between the two tissues is the consequence of receptor micro-environment and/or accessory binding site differences.


Adenosine-induced bronchoconstriction of isolated lung and trachea from sensitized guinea-pigs. 1. The bronchoconstriction of airway-perfused lungs and contraction of superfused tracheal spirals from guinea-pigs in response to adenosine were examined. 2. In lungs from untreated animals, adenosine had little effect unless the perfusion pressure was raised with carbachol (1.1 microM), when it caused a fall in perfusion pressure. However, if removed from guinea-pigs sensitized with ovalbumin (5 mg and 10 mg i.p. 14 and 12 days before use), adenosine was bronchoconstrictor, exerting bronchodilator effects only at high (1 mg) doses. The constrictor response to adenosine (300 micrograms) was significantly greater than that in lungs from untreated or sham-injected animals. 3. In superfused trachea from untreated animals, adenosine exerted only relaxant responses. In tissues from ovalbumin-sensitized guinea-pigs adenosine produced contractile responses, with relaxation appearing only at high (1 mg) doses. 4. Thus sensitization by antigen challenge revealed a bronchoconstrictor response of isolated airway preparations to adenosine. This is related to the clinical situation where only asthmatic subjects respond to adenosine by bronchoconstriction and suggests that the sensitization may destabilize inflammatory cells for mediator release by adenosine. 5. The response to a second exposure to adenosine was consistently reduced (lungs) or converted to a relaxation (trachea) indicating tachyphylaxis and consistent with a mediator release mechanism. 6. The P1-purinoceptor antagonist, 8-phenyltheophylline (3.9 microM), antagonized the relaxant responses to higher doses of adenosine. However, it did not affect the contractile responses to lower doses of adenosine. Whether this is due to P,-purinoceptors not being involved in the contractile response, or whether preferential blockade of the relaxant response leaves the contraction unopposed and apparently unblocked, remains to be established.


The origins of delusion.

The origins of delusion. Although delusion remains one of the basic problems in psychopathology, attempts to understand its pathogenesis have been dominated by unsubstantiated speculation. Previous psychodynamic formulations have recently given way to increasing interest in measurement, and testing of models derived from cognitive psychology. However, the formation, elaboration, and persistence of delusional beliefs may be an expression of the convergence of numerous causal influences, each exerting an effect at a different stage in the evolution of the belief. This review takes a structured overview of the literature, placing the numerous part theories and scant experimental findings within a general model of delusional development. It argues for a return to systematic research on symptoms rather than complex diagnostic formulations to facilitate better understanding of the development of delusional disorders and stimulate further interest in therapeutic intervention.


Chromosomal aberrations and schizophrenia. Autosomes. Chromosomal aberrations associated with schizophrenic disorders may suggest regions in which to focus a search for genes predisposing to schizophrenia by a linkage strategy. As for other genetic illnesses, chromosomal abnormalities may also provide useful tools for subsequent physical mapping, fine localisation, and isolation of important susceptibility genes. Identification of several chromosomal aberrations may be especially important, given the unknown pathophysiology, the paucity of known brain genes, and the probable genetic heterogeneity of schizophrenia and manic-depression. However, because psychiatric disorders are common and inherited in a complex manner, researchers must use caution when drawing inferences about associations with chromosomal aberrations. Reported abnormalities involving autosomes (chromosomes 1-22) associated with psychotic disorders are reviewed. Their relevance to linkage studies localising genes for schizophrenia was estimated by standardised criteria for specificity, diagnosis, family history, and overall weight of evidence. Four 'possibly relevant' chromosomal regions were identified: 5q, 11q, 18q, and 19p. This paper outlines strategies for future studies to detect new chromosomal aberrations associated with major psychotic disorders that may be relevant to isolating the genes for schizophrenia.


Assessment of DSM-III-R personality disorders by self-report questionnaire: the role of informants and a screening test for co-morbid personality disorders (STCPD). A modified version of the revised Personality Diagnostic Questionnaire (PDQ-R), based on DSM-III-R personality disorders (PDs), was completed by 60 psychiatric patients. An informant's version was also completed by 60 relatives or friends nominated by each subject. Discrete DSM-III-R PDs were rare; the mean number of PDs per subject was 4.5. Cluster analysis showed that only antisocial PD was a basis for classification of patients, while most patients formed two groups which were mainly distinguished by quantitative differences related to the total scores of positive PD criteria. A shorter version of the questionnaire can be used as a screening test for co-morbid PDs (STCPD) which can predict the number of co-morbid DSM-III-R PDs. The total scores of positive PD criteria from the STCPD were usually (and significantly) higher than the corresponding scores from informants' questionnaires, but when an informant's total score exceeded that of the patient, this indicated a subject's under-reporting.


Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine. In a double-blind, parallel group trial, 78 subjects with social phobia received moclobemide (a new reversible inhibitor of monoamine oxidase A) phenelzine, or placebo. After eight weeks, both active drugs-phenelzine somewhat more than moclobemide--were clinically and statistically significantly more effective than placebo, as assessed by rating scales. There was some further improvement between weeks 8 and 16, particularly in the moclobemide group; at week 16, 82% of the moclobemide and 91% of the phenelzine-treated patients were almost asymptomatic. Moclobemide was, however, much better tolerated than phenelzine. Patients withdrawn from active drugs had relapsed by week 24, providing additional support for the efficacy of the active drugs.


Plasma melatonin levels in anorexia nervosa. Plasma melatonin levels were measured at three-hourly intervals over 24 hours in 11 women with untreated anorexia nervosa, and in nine healthy women of normal weight. The circadian rhythm was unaltered but the nocturnal secretion of melatonin was significantly greater in anorectics. It is possible that this was related to nocturnal hypoglycaemia.


Suicide and self-burning among Indians and West Indians in England and Wales. Suicide levels in England and Wales during 1979-83 were low among males from the Indian subcontinent (SMR 73) and significantly high in young Indian women (age-specific ratios 273 and 160 at ages 15-24 and 25-34 respectively). Suicide levels were low in Caribbeans (SMRs 81 and 62 in men and women respectively) and high in East Africans (SMRs 128 and 148 in men and women respectively). The excess in East Africans (most of whom are of Indian origin) was largely confined to younger ages. Immigrant groups had significantly higher rates of suicide by burning, with a ninefold excess among women of Indian origin. The pressures leading to higher suicide levels among young women of Indian origin highlight the need for making appropriate forms of support and counselling available to this community.


Hysterical conversion. I: A history.

Hysterical conversion. I: A history. 'Hysterical conversion' dates from a century before Freud, from an important attempt to rationalise the nosological status of hysteria. Freud's own concept of 'conversion' followed as a quite independent synthesis of 19th-century medical thinking on the subject. Subsequent analytical usage of 'conversion' which has influenced the description of hysterical syndromes within mainstream psychiatry, has not been consistent with Freud's own.


Hysterical conversion. II: A critique.

Hysterical conversion. II: A critique. The career of the diagnosis of conversion hysteria is reviewed at a time when it is threatened with expulsion from classifications of psychiatric disorder. Criticism of its face validity has not led to adequate diagnostic alternatives, and has been insensitive to its unusual form as a category as well as the contribution it has made to the stability of the classificatory system around it.


Prenatal exposure to influenza does not cause schizophrenia. Claims have been made that maternal infection with influenza during pregnancy is a cause of schizophrenia in the child. These assertions are based upon some apparently significant associations between the timing of influenza epidemics in the general population and birth rates of people who later suffered from schizophrenia. Such associations have not been present in studies of the 1919 and 1957 epidemics, with sample sizes larger than those on which the claims were made. More decisively, in an investigation of the subsequent psychiatric admissions of people born a few months after the 1957 epidemic, it was found that the children of 945 mothers who actually suffered from influenza during the second trimester of pregnancy were at no greater risk of developing schizophrenia than children of mothers who were not infected. In contrast to the predictions of the influenza hypothesis of 26.5 extra cases by broad diagnostic criteria and 15.8 cases by narrow criteria, the numbers observed in children of mothers exposed to influenza in the second trimester were 3 and 1 cases respectively, close to the expected rate. It is concluded that prenatal influenza and schizophrenia are unrelated.


Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic. "The birth dates of schizophrenic inpatients in eight health regions in England and Wales were reviewed for any effect of the 1957 A2 influenza epidemic. 5 months after the peak infection prevalence, the number of births of individuals who later developed schizophrenia was 88% higher than the average number of such births in the corresponding periods of the 2 previous and the next 2 years. This finding is in accordance with a study from Helsinki and with clinical and neuropathological evidence of aberrant fetal brain development in the pathogenesis of schizophrenia."


Failure of a binaural comprehension deficit to select responders to earplug use in schizophrenia. Previous studies have suggested that on the Auditory Comprehension Test, a significant proportion of schizophrenics demonstrate a binaural comprehension deficit. To test whether wearing an earplug in their more poorly performing ear would be beneficial, we studied 34 in-patient schizophrenics and noted a binaural deficit in 12 (35%). Of these, eight patients subsequently wore an earplug in each ear for at least one week. We found no effect of the earplug on psychopathology.


REM latency in endogenously depressed adolescents. Twenty-three adolescents with DSM-III major depressive disorder (endogenous subtype) and 23 normal controls were studied polysomnographically (PSG). The depressed group showed significantly shortened REM latencies (P = 0.005) and longer sleep latencies (P = 0.04). No other PSG measures differentiated the two groups. The implications of these findings for adolescent depression are discussed.


Psychotic illness following 'mabi bark tea' consumption. A first episode of psychosis occurred in a young woman of West Indian parentage and one of identical twins following a brief period of high consumption of a drink made from Colubrina plant extract (mabi bark). The course of the psychosis is described and possible underlying mechanisms and the relationship to amphetamine psychosis are discussed.


Delusional infestation associated with post-herpetic neuralgia and EEG abnormalities. An 80-year-old widow with delusional infestation in association with post-herpetic neuralgia and EEG abnormalities in the left anterior parietal lobe responded to combined pimozide and carbamazepine. Aetiological factors are reviewed in relation to the literature.


Severe deprivation in childhood: a case report from Thailand. A 3 1/2-year-old girl was incarcerated in a bamboo cage after it was feared she had contracted rabies. Six years later, when she was released, she had lost almost all motor control, displayed a number of stereotypies, was incontinent of both faeces and urine, and was diagnosed as having grand mal epilepsy. After four years of treatment (aged 13) she had shown considerable improvement and her mental age was seven years.


Personality disorder and self-wounding.

Personality disorder and self-wounding. At least 1 in 600 adults wound themselves sufficiently to need hospital treatment. More men than women do it, although more women receive psychological treatment. Many have a history of sexual or physical abuse. Self-wounding differs from other self-harm in being aimed neither at mutilation nor at death. Self-wounding coerces others and relieves personal distress. Repeated self-wounding is one criterion of borderline personality disorder but we prefer to consider it an 'addictive' behaviour rather than an expression of a wider disorder. Psychological management may need to be augmented by drug or social treatment. Carers, including professional carers, usually need help to contain the turbulence that self-wounding produces.


Child psychiatric disorders: are they classifiable? Classification of child (including adolescent) disorders is reviewed within six areas: requirements for a good taxonomy, current systems of classification for children, data-capture methods, reliability and validity, the link between child and adult disorders, and directions for future developments. While substantial progress has been made, there is a continuing need for comparisons of different systems, more systematic yet practicable data capture, proper psychometric analyses of criteria and categories, intensive studies of clinical validity, closer attention to the similarity of, and links between, child and adult categories, and better definition and targeting of those disorders with a serious outcome.


Presymptomatic testing for Huntington's disease in Wales 1987-90. Between 1987 and 1990 a large series of at-risk individuals has been referred to our Huntington's disease (HD) presymptomatic testing programme. A detailed protocol for assessment and counselling has been followed. Out of 238 serious inquiries, 36% were potentially suitable for the testing programme, but 19% chose not to continue. Reasons for exclusion included the presence of clinical features of HD and being under the age of 18 years. Out of 40 final results given to 38 individuals, 23 indicated a lowered risk, 11 an increased risk, while five results were uninformative, two of these becoming informative on repeat testing. This series contained more women than men, and was disproportionately from the higher socio-economic groups. Motives for requesting a test principally related to child-bearing, informing existing children, and planning for the future. No significant psychiatric symptoms have been reported in the short term, but difficult counselling problems were presented by the high proportion of applicants who already showed clinical signs of HD. It is concluded that a detailed counselling protocol is essential in testing for HD, as many applicants are ill-prepared; this will assume even greater importance when the HD gene is identified and a test for specific mutations is available. The experience of presymptomatic testing for HD provides important general lessons which are likely to be applicable to other inherited neurological and psychiatric disorders.


The Scottish first episode schizophrenia study. VIII. Five-year follow-up: clinical and psychosocial findings. The Scottish Schizophrenia Research Group. Forty-four schizophrenic patients were followed up for five years after their first admission to hospital for a first episode of illness. Thirteen (30%) of 43 patients had not relapsed; 28 of the 30 patients who did relapse did so within the first 42 months. The relapses occurred despite antipsychotic drug therapy. Also, 24% of patients had at least one course of ECT. Only 19% of the patients at five years were in open employment; unemployment was strongly associated with relapse. Eighteen per cent had neither relapses nor schizophrenic symptoms at follow-up. Poor outcome at five years was associated with greater psychological distress among relatives at first admission. At five years 43% of relatives continued to show case level psychological stress.


Dangerous behaviour preceding first admissions for schizophrenia. Of 253 patients in their first schizophrenic episode, 52 behaved in a way threatening to the lives of others before their admission to hospital. These 52 patients were studied from data collected at the time of their initial presentation. Despite a history of illness in excess of 1 year in 24 cases, and evidence that violence was motivated by psychotic symptoms in 23 cases, fewer than half of the patients were admitted to hospital as a direct result of their dangerous behaviour. Life-threatening behaviour was more common where the patient had been ill for longer, and where there were delusions of being poisoned.


Seasonality of admissions in the psychoses: effect of diagnosis, sex, and age at onset. A summer peak was found in first admissions to hospitals in England and Wales between 1976 and 1986 for both affective psychoses and schizophrenia, but not for neurotic conditions or personality disorders. There was no significant relationship between age at first admission and season of admission. The summer peak was most prominent for mania, where it was present in both sexes; for schizophrenia, it was present only in females. These findings suggest that schizophrenia in females, and mania in both sexes, have some aetiological or precipitating factor in common.


Diurnal rhythms and symptom severity in panic disorder. A preliminary study of 24-hour changes in panic attacks, generalised anxiety, and avoidance behaviour. Diurnal changes in the frequency of panic attacks and symptoms of generalised anxiety, phobic anxiety and phobic avoidance in 34 panic-disorder patients and 40 normal controls were evaluated. The panic-disorder patients had significant diurnal changes in generalised and phobic anxiety, but not phobic avoidance. Increased severity of symptoms and prominent diurnal changes were most evident in the panic-disorder patients with a history of depression. Although panic attacks were distributed throughout the 24-hour period, patients with a current episode or history of depression tended to have more frequent panic attacks in the morning or early afternoon. These observations challenge the traditional belief that 'anxious neurotic' patients are relatively asymptomatic upon awakening in the morning and then develop more severe symptoms of anxiety later in the day.


Cortisol and prolactin responses to d-fenfluramine in non-depressed patients with obsessive-compulsive disorder: a comparison with depressed and healthy controls. Cortisol and prolactin responses to d-fenfluramine were measured in 10 drug-free normothymic patients with obsessive-compulsive disorder (OCD). The results were compared with these responses in 10 healthy controls and in 10 major depressives. The endocrine responses in OCD were significantly attenuated when compared to the healthy controls; however, the results were not specific to OCD as the depressives' responses were similarly blunted.


The Edinburgh cohort of HIV-positive drug users: pattern of cognitive impairment in relation to progression of disease. To examine the neuropsychiatric effects of infection with HIV, 220 drug users (27 HIV negative, 193 HIV positive) completed tests evaluating premorbid intelligence, memory, non-verbal performance, information processing speed, and mood. When these measures were compared cross-sectionally by the severity of HIV illness, symptomatic patients (in CDC stage IV) were impaired on Trails B, two-choice decision time, delayed recall of the Wechsler Logical Memory Test and most components of the Auditory Verbal Learning Test. These findings imply reduced capacity for concentration, speed of thought and memory. When 101 patients were retested a mean of 16 months after their initial assessment, performance on Trails A and B, Block Design and delayed recall of the Wechsler Logical Memory Test deteriorated more for patients at, or progressing within, CDC stage IV, than performance of patients at stage III. The results broadly correspond to the cross-sectional findings. However, there was a decline in all tests of memory function for the sample independent of clinical staging. This may be evidence of brain involvement before the appearance of other symptoms. Self-rated measures of mood did not change cross-sectionally, progressively, or interactively with time and stage of HIV illness, and cannot account for the changes in cognitive function observed. Change in drug use, similarly, does not account for the cognitive findings. Four (5%) of the retested subjects developed AIDS dementia complex, but most of the performance and memory impairments seen were subclinical despite the destructive neuropathology presumed to underlie intellectual decline in patients with HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)


Stressful life events and Graves' disease. "The role of stressful life events in the onset of Graves' disease (toxic diffuse goitre) is controversial. However, the numerous early clinical reports that supported such an association were not adequately controlled and specificity of the diagnosis could be questioned. Later studies have not shown a causal relation, but these studies were small, did not have proper controls, or epidemiological methods were inappropriate. To assess possible associations between life events, heredity, social support, and Graves' disease, we have done a population-based case-control study in a defined area with about 1 million inhabitants. Over 2 years, 208 (95%) of 219 eligible patients with newly-diagnosed Graves' disease and 372 (80%) of all selected matched controls answered an identical mailed questionnaire about marital status, occupation, drinking and smoking habits, physical activity, familial occurrence of thyroid disease, life events, social support, and personality. Compared with controls, patients claimed to have had more negative life events in the 12 months preceding the diagnosis, and negative life-event scores were also significantly higher (odds ratio 6.3, 95% confidence interval 2.7-14.7, for the category with the highest negative score). Individuals who had relatives with thyroid disease (especially first-degree and second-degree relatives) were more likely to have Graves' disease (3.6, 2.2-5.9). Slightly more patients than controls were divorced (1.8, 1.0-3.3) and reported a less frequent intake of alcohol (0.4, 0.2-0.8). When results were adjusted for possible confounding factors in multivariate analyses, risk estimates were almost unchanged. These findings indicate that negative life events and hereditary factors may be risk factors for Graves' disease."


Mental play in Gilles de la Tourette's syndrome and obsessive-compulsive disorder. A new phenomenon, found only in Gilles de la Tourette (GTS) patients, and which we have called 'mental play', is described. It was compared with the phenomenon of counting, which occurred in both GTS and obsessive-compulsive patients. In the GTS patients both mental play and counting were best characterised as playful impulsions. In contrast to the GTS patients, the counting of the obsessive-compulsive patients was in line with their obsessive-compulsive behaviour. These findings suggest that repetitive symptoms in GTS patients, even when they share superficial similarities with obsessive-compulsive symptoms, should not be diagnosed automatically as obsessive-compulsive.


Bulimia nervosa in Hong Kong Chinese patients. In contrast to the West, bulimic disorders are rarer than anorexia nervosa in Hong Kong. Four female normal-weight bulimic patients with mostly typical clinical features and conspicuous morbidity are reported. The case histories support the hypothesis that binge-eating is used to regulate unpleasant effect.


Chromosomal aberrations in a patient with severe psychopathology. The case of a female patient showing aggressive, compulsive, destructive behaviour, ritualistic faecal smearing, and hyperactivity is presented. The behaviour is long standing, therapy-resistant, and its aetiology is unknown, although it is seemingly associated with chromosomal abnormalities secondary to abnormal plasma factors.


Lower incidence and increased male:female ratio in schizophrenia. Patients with an ICD-9 diagnosis of psychotic disorder were assessed for DSM-III-R schizophrenia. Rates of schizophrenia were found to be higher in males (39.8 per 100,000) than females (22.4 per 100,000). The DSM-III-R incidence supports recent studies which suggest a decrease in rates of schizophrenia across time, and also suggests that men suffer from both more schizophrenia and a more severe form of the disease.


Catatonia and the neuroleptic malignant syndrome--a single entity? Separate episodes of both catatonia and the so-called 'neuroleptic malignant syndrome' (NMS) occurred within the same patient. The only evidence for NMS in this case was prior administration of a neuroleptic and the presence of generalised muscular rigidity. It is suggested that it is misleading to view these conditions as separate diagnostic entities and that NMS is probably more correctly incorporated into the catatonic disorders.


Carbamazepine-induced systemic lupus erythematosus. A 21-year-old woman suffering from bipolar affective disorder developed systemic lupus erythematosus (SLE) with characteristic laboratory findings, 18 months after starting carbamazepine maintenance treatment. SLE receded after withdrawal of carbamazepine and treatment with anti-inflammatory drugs. Although both the spontaneous occurrence of SLE and the psychosis as a sign of CNS involvement of SLE cannot be excluded, SLE could be considered as an adverse effect of carbamazepine.


Déjà vu experiences and reduplicative paramnesia. A schizophrenic patient with different forms of experiences of inappropriate familiarity is described. The authors discuss traumatic experiences as aetiological factors in déjà vu experiences and reduplicative paramnesia. Finally, the differential diagnostic problem in psychotic and dissociative phenomena is stressed.


Dimensions of everyday memory in young adulthood. This paper reports the findings of two studies on everyday memory in young adulthood. In Study 1, 387 male and female college students (18-22 years old) completed the 25-item Cognitive Failures Questionnaire (CFQ; Broadbent, Cooper, Fitzgerald & Parkes, 1982). Principal components analysis yielded five internally consistent factors: distractibility; misdirected actions; spatial/kinaesthetic memory; interpersonal intelligence; and memory for names. Further, each of these dimensions was interpretable within an information-processing framework. Study 2 examined the relation of the five everyday memory dimensions obtained in Study 1 to measures of working memory and traditional intelligence in a separate sample of 32 college students. Findings obtained in Study 2 suggest that attentional processes may be important components of the everyday memory construct.


The effect of a five-month delay on children's and adults' eyewitness memory. Child witnesses must endure a delay of around six months between observing or being the victim of an alleged offence and being required to give evidence in a criminal court. While the legal profession seem to believe that young children's memories are particularly sensitive to the passage of time, developmental psychology can offer little relevant data to support or refute this presumption. In the present study, children aged six and nine years and adults witnessed a staged event and were subsequently interviewed in the days following the event and/or five months later. Results indicate that while all witnesses forgot information over this period, the younger children (six years) recalled slightly less information than the older children and the adults. The total amount of incorrect information recalled did not increase over the same period. Two different interviewing techniques were used--cued recall vs. 'enhanced' recall--the latter incorporating some aspects of the cognitive interview procedure. No differences were found relating to the interview techniques employed. The results underline the importance of recording initial interviews with child witnesses wherever possible.


Expedition stress and personality change. There have been few attempts to investigate the widespread assumption that short-term challenges can have beneficial effects on personality. An expedition to India organized by the British Schools Exploring Society provided such an opportunity. The Gordon Personal Profile Inventory showed that the expedition was associated with increased ascendancy, emotional stability, sociability and responsibility, and decreased cautiousness. Women tended to benefit more than men. The results suggest that the expedition was associated with positive personality changes, though other explanations of the findings cannot be ruled out.


Short-term retention of spatial information. Four experiments investigated the recall of a subspan set of spatial locations over short intervals of 5 and 15 s. The intervals were filled by one of three activities: simple tapping, repeated tapping at spatial targets and backwards counting. Spatial tapping, which decreases spatial memory span, led to further small but significant errors in recall, as did backward counting. These errors were larger than those found with simple tapping over the same intervals. Backwards counting led to further decreases in recall performance if it was also present during encoding, but this was not the case for spatial tapping. Spatial tapping had little effect on recall of three digits, whereas backwards counting had a large effect, which was much larger than that found with spatial memory items in any condition. The results are interpreted in terms of the use of place-keeping functions in spatial memory sequences, which may not be specific to spatial material.


Phonological priming of lexical retrieval in speech production. We report a series of three experiments exploring phonological priming effects in speech production. In all cases, subjects repeated aloud auditorily presented primes and then named picture targets. Experiment 1 showed that targets were named faster when prime and target shared phonemes but only when these occupied the same word or syllabic positions. Experiment 2 showed that the degree of facilitation was unaffected by the lexicality of the prime or whether shared phonemes occurred early or late in the syllable. Experiment 3 examined the effect of the lexicality of the prime at different intervals between response and prime in an attempt to tease apart contributions to the effect from automatic and strategic processes. The results are considered in relation to current accounts of lexical retrieval.


Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. Cytokine release at the cartilage/pannus junction (CPJ) may be involved in cartilage destruction and tissue repair in rheumatoid arthritis (RA). Tissue samples of CPJ from 12 RA patients were examined for the presence of cytokines using immunohistochemical techniques with immunoaffinity purified F(ab')2 antibodies raised against recombinant human cytokines. Twenty-four areas of distinct CPJ at which a discrete junction between cartilage and overlying pannus exists were observed. In all specimens, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha. IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta 1 were detected in cells in pannus particularly along the surface of cartilage and at the site of cartilage erosion. Double immunofluorescence staining showed that most cytokine containing cells also labelled with a macrophage marker (CD68). About 50% of blood vessel endothelial cells stained for GM-CSF. Twelve areas of diffuse fibroblastic CPJ, at which an indistinct margin is seen between cartilage and pannus were examined. At this site, TGF-beta 1 was the only cytokine detected in fibroblast-like cells. None of these cytokines were detected in synovial tissue at the normal synovium/cartilage junction. Chondrocytes from all 11 normal specimens as well as those from RA patients stained for IL-1 alpha, TNF-alpha, IL-6, GM-CSF and TGF-beta 1, especially those close to subchondral bone. However, IL-1 beta, interferon-gamma and lymphotoxin were not detected in either the normal synovium/cartilage junction or rheumatoid CPJ.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of steroid hormones on proliferation of peripheral blood mononuclear cells in patients with rheumatoid arthritis. Sex steroids are believed to modulate the immune system in rheumatoid arthritis (RA). Since receptors for sex steroids are present on T-lymphocytes, which are thought to play a major role in the pathogenesis of RA, it is suggested that gonadal steroids can mediate their immunomodulating effect directly on T-lymphocytes. Recently a specific method for activating T-lymphocytes with immobilized anti-CD3 monoclonal antibodies was described. We investigated the influence of oestradiol, progesterone, testosterone and cortisol on lymphocytes stimulated by anti-CD3 mAb and PHA of postmenopausal women, comparing female patients with rheumatoid arthritis and age-matched control patients. The results show that oestradiol, progesterone and testosterone do not influence lymphocyte proliferation when stimulated with anti-CD3 mAb or phytohaemagglutinin (PHA). Cortisol, however, can suppress lymphocyte proliferation even at physiological concentrations in both patients with RA and controls. Inhibition of proliferation by cortisol is dose-related and has no significant correlation with RA disease activity. This inhibition differs individually and might explain the often variable response to corticosteroids in vivo.


Antilactoferrin antibody in systemic lupus erythematosus. Lactoferrin is a secondary granule protein of neutrophils. Seventy-nine systemic lupus erythematosus patients who fulfilled the ARA criteria for classification were tested for antibody against human lactoferrin (LF-ab) by ELISA. Thirty-one of these (39.2%) demonstrated elevated levels. There was significant correlation between LF-ab positivity and disease duration. Clinical flare was common with positive LF-ab (P less than 0.05). Disease manifestations were independent of antibody status except for an increased incidence of lymphadenopathy and crescentic gomerulonephritis among those who had LF-ab. No consistent immunofluorescence pattern could be demonstrated on alcohol-fixed neutrophils for the LF-ab positive sera. It is suggested that LF-ab is related to lupus activity, and can be useful as a marker for disease monitoring.


Increased spontaneous release of cytidine deaminase by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus. Cytidine deaminase activity (CD) in the neutrophil culture supernatants (PMN SUP) of 27 patients with systemic lupus erythematosus (SLE) was measured using a spectrophotometric method. Compared with the controls (5.449 +/- 1.358 U/5 x 10(6) PMN), the CD activity in the spontaneous culture supernatants of PMN was significantly increased in active (10.003 +/- 2.637 U/5 x 10(6) PMN) but not in inactive (5.358 +/- 1.624 U/5 x 10(6) PMN) SLE. However, after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 x 10(-7) M), the ratio of enzyme activity between stimulated and spontaneous PMN supernatants was decreased in active SLE (0.794 +/- 0.178) compared with normal controls (1.300 +/- 0.225). In contrast, the enzyme activity in the cytoplasm of either stimulated or non-stimulated PMN was not different among these three groups. These results suggest that CD of PMN is releasable and can be enhanced by chemotactic factor stimulation in normal PMN. The increased spontaneous release of CD by active SLE PMN is one of the indicators for the disease activity in these patients.


The prevalence of diagnosed systemic lupus erythematosus in whites and Indian Asian immigrants in Leicester city, UK. The prevalence of diagnosed systemic lupus erythematosus (SLE) during 1989 in the adult Indian Asian and White populations of the city of Leicester has been determined. Fifty cases (19 Asian, 31 White) fulfilling the 1982 revised ARA criteria for SLE were identified from a population of 191,469 (37,684 Asian, 153,785 White). Five different sources were used to ascertain cases. The overall prevalence of SLE in Whites was 20.2 per 100,000. Asians of both sexes had a significantly higher prevalence than Whites. Prevalence in males was 31.5 and 7.0 per 100,000 in Asians and Whites respectively; in females the figures were 69.7 and 31.7 per 100,000. Overall, lupus was 3.0 times more common in Asians than Whites. This is the first prevalence study of SLE in Indian Asians and suggests that, like the Black races and the Chinese, they have a greater frequency of SLE than Whites.


Alpha interferon-2a (Roferon-A) in the treatment of diffuse cutaneous systemic sclerosis: a pilot study. UK Systemic Sclerosis Study Group. Intramuscular alpha-interferon improved or stabilized skin score in 10/14 (71%) patients with diffuse cutaneous systemic sclerosis. In 64% of patients, their treating physicians rated it as having stabilized or improved the disease. However, it had no significant effect on grip strength, digital contractures, respiratory function or visceral involvement. Type I collagen synthesis was significantly reduced in fibroblasts cultured from clinically 'uninvolved' skin but not in those from lesional skin. Amino-terminal procollagen III peptides in the interferon treated group were not significantly reduced after 6 months of therapy but showed a trend towards stabilization and reduction compared to disease matched controls on no therapy.


Bronchiectasis and rheumatoid disease: is there an association? Rheumatoid arthritis is associated with a number of pleuropulmonary disorders. A retrospective study of the frequency of rheumatoid disease in patients with bronchiectasis and pulmonary fibrosis was performed. The results suggest that the frequency of bronchiectasis and rheumatoid disease is similar to that of the well established, but rare, association between pulmonary fibrosis and rheumatoid arthritis. We therefore suggest that bronchiectasis should be remembered as a pulmonary association of rheumatoid disease which occurs as commonly as pulmonary fibrosis.


Mixed connective tissue disease--goodbye to all that. Since it was first described mixed connective tissue disease (MCTD) has been the subject of much debate. In particular the question of whether it is a truly distinctive disease entity has been challenged. It seems clear that the original description of MCTD as a mild disorder, rarely affecting the lungs or kidneys and requiring small doses of corticosteroids only, is no longer tenable. In this review a historical analysis of the clinical and serological features is presented. It is suggested that the concept of MCTD as a distinct disease entity is better replaced by the term 'undifferentiated autoimmune rheumatic/connective tissue disorder'. Many of these patients will later 'convert' into scleroderma or lupus; some will remain undifferentiated.


Clinically normal skin becomes sclerodermatous when transplanted into a sclerodermatous area. A 56-year-old female with systemic sclerosis developed sclerodermatous change in clinically normal forearm skin 10 months after this was transplanted to the tip of her right index finger. This observation implicates local factors in the pathogenesis of the disease.


Sensorineural hearing loss in juvenile chronic arthritis. An 18-year-old female with pauciarticular juvenile chronic arthritis is described who has developed a profound bilateral sensorineural hearing loss. The association of sensorineural hearing loss with juvenile chronic arthritis has not been reported before.


Distraction, choice and self-esteem effects on cognitive response facilitation. From an integration of distraction-conflict theory and cognitive dissonance theory, it was hypothesized that distraction would increase, rather than disrupt, the proarguing of persons who had been given high choice to engage in discrepant behaviour, and would increase, rather than disrupt, the counterarguing of persons who had been given low choice to engage in such behaviour. Furthermore, it was expected that this cognitive response facilitation effect would more likely occur for persons high in self-esteem. The results supported the hypotheses and were interpreted as also confirming the notion that dissonance-related processes occur at the cognitive response level.


Use of ultrasound in osteomyelitis.

Use of ultrasound in osteomyelitis. The use of ultrasound in osteomyelitis has been studied in 25 patients clinically suspected of osteomyelitis. A sonographic diagnosis of osteomyelitis was made if fluid was present in direct contact with the bone, without intervening soft tissues. This was thought to represent an inflammatory exudate dissecting in a subperiosteal and/or extraperiosteal location. Ultrasonographically 15 patients were found to have osteomyelitis, proved either by surgical drainage or needle aspiration. Seven patients had soft-tissue abscesses, one had cellulitis and two patients had no abnormality.


Direct and CT measurements of canals and foramina of the skull base. This investigation is based on measurements of 60 macerated adult European skulls from the Alexander-Ecker Collection at the Anatomy Department of the University of Freiburg. Computer tomographical (CT) and anatomical measurements were compared to assess the accuracy of the CT representation of osseous structures. Nine structures were examined: the optic canal; the superior orbital fissure; the foramen rotundum; the foramen ovale; the foramen spinosum; the foramen Vesalii (venosum); the carotid canal; the internal auditory canal, and the hypoglossal canal. The results show a good and even excellent correlation if the cranial opening is approximately at a right angle to the scanline. For this reason, the results of the coronal examination of the internal auditory canal are less satisfactory, and the coronal and axial measurements of the hypoglossal canal show only a moderately good correlation.


Subluxation of the patella: evaluation of patellar articular cartilage with MR imaging. In patients with subluxation of the patella, injury of the patellar articular cartilage is frequently observed, and correct evaluation of this cartilage injury is extremely important for the management of these patients. Magnetic Resonance (MR) studies were performed on 102 patellofemoral (PF) joints of 51 patients with subluxation of the patella and 20 PF joints of 10 healthy volunteers. In 77 of the 102 PF joints with subluxation, arthroscopy and/or operation were performed. MR images were obtained with spin-echo and FLASH sequences, and para-axial images were obtained. We retrospectively analysed the MR findings of the 77 joints with special attention to the surface and thickness of the cartilage, and classified them into four grades. These MR grades were compared with the grades on arthroscopy, and the following results were obtained: MR grade 0, normal cartilage (n = 27, sensitivity 90.9%, specificity 74.2%); MR grade 1, thickening of the cartilage (n = 24, sensitivity 50%, specificity 89.1%); MR grade 2, surface irregularity of the cartilage (n = 20, sensitivity 85%, specificity 94.7%); MR grade 3, loss of the cartilage (n = 6, sensitivity 100%, specificity 100%). Although the early changes observed by arthroscopy were underestimated from the MR images, MR imaging proved to be extremely useful for evaluating moderately or advanced patellar cartilage injury.


What is the clinical disadvantage of discarding old radiographs? Survey of patients not re-examined for a long time. The clinical disadvantage of discarding old radiographs was evaluated in patients who had not been re-examined for more than 8 years after their last radiological examination, 38,772 in total. During the 1 year survey, 158 (0.41%) of them underwent re-examination after a long interval. Retrospective evaluation revealed that in only 12 patients (0.032%) were the old films useful. This survey suggested that the clinical risk of not referring to films more than 8 years old would be less than 0.049%. We consider this acceptable, and have formulated new guidelines of storage of films.


Intracardiac metastases from germ cell tumours--an unusual but important site of metastasis. Two cases of intracardiac deposits from testicular teratomas diagnosed by echocardiography and angiocardiography, respectively, are described. The importance of recognizing this as an uncommon site of metastasis from germ cell tumours is discussed.


The radiology and terminology of cryptogenic organizing pneumonia. The clinical features, radiographic and computed tomographic findings of nine patients with histological proof of cryptogenic organizing pneumonia were analysed. Patients present with cough, dyspnoea and malaise and commonly have bilateral multifocal consolidation on chest radiography, which may show resolution or relapse with or without steroid treatment. A good response to steroids is the rule, usually with complete radiological resolution or minimal residual scarring. The relative merits of the terms cryptogenic organizing pneumonia and bronchiolitis obliterans organizing pneumonia, both currently used to describe this entity, are discussed.


The radiological imaging of bronchial atresia. The clinical and radiological findings in three cases of bronchial atresia are presented. Bronchial atresia has a characteristic plain radiographic appearance in the majority of cases. Computed tomography may be required to confirm the diagnosis. The condition often presents to the radiologist as an incidental finding on the chest radiograph in a patient undergoing investigation for an unrelated problem.


An alternative approach to contrast-detail testing of X-ray image intensifier systems. The difficulties of making the results of threshold contrast-detail diameter tests on X-ray image intensifier systems consistent with published performance standards are discussed. The current approach to contrast-detail testing is described and an alternative method intended to give greater consistency for all image intensifier input field diameters proposed. The current and alternative test conditions are compared on two image intensifier systems. The results obtained show that the contrast-detail curves for image intensifier systems with a wide range of input field diameters can be effectively normalized to be directly comparable to a common reference standard by applying the proposed alternative test conditions. The implications of this result on the interpretation of the contrast-detail test are discussed.


Accelerated fast neutron therapy: a pilot study. The clinical role of fast neutron therapy has been limited by excessive late normal tissue damage. A pilot study of accelerated fractionation of fast neutron therapy was performed, based on the rationale that this should result in an increase in the response in acute reacting tissues (normal and malignant), with no change in late damage and a consequent increase in the therapeutic ratio. Further accelerated fractionation should improve the local control of rapidly proliferating tumour, without the potential problem of inadequate reoxygenation inherent in accelerated photon schedules. 6 or 12 fractions of 62 MeV (p-Be) neutrons were given over 12 days to 27 sites in 23 patients with locally advanced tumours. With a dose reduction of 12% (18 Gy), acceptable skin and oral mucosa early reactions were obtained. A larger dose reduction (15%) was required at pelvic sites. The incidence of late EORTC/RTOG grade 4 toxicity was 46%. The overall response rate was 76% with a complete response rate of 16%. For locally advanced breast cancer, the complete response rate was 9%, which compares unfavourably with previous results with conventional neutron fractionation schedules. The combination of a low overall complete response rate and excessive late normal tissue toxicity suggests that accelerated fractionation of fast neutrons does not lead to an improvement in the therapeutic ratio, and that late normal tissue damage will continue to be dose limiting.


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


Image comparison techniques for use with megavoltage imaging systems. In this paper we describe software facilities for enabling patient positioning studies using the megavoltage imaging system developed at the Royal Marsden Hospital and Institute of Cancer Research. The study focuses on the use of the system for three purposes: patient position verification (by comparing images taken at treatment simulation with megavoltage images taken at treatment time); reproducibility studies (by analysing a set of megavoltage images); and set-up correction (by adjusting the set-up until the megavoltage image obtained at treatment registers with the simulation image). The need is discussed for suitably presented simulator images, a method of determining field boundaries and the possibility of delineating soft-tissue interfaces. Several algorithms of different types, developed specifically for the purpose of intercomparison of planar projection images, are presented. The techniques employed and their usefulness, in both the qualitative and the quantitative sense, are discussed. The results are presented of a phantom and clinical study, to evaluate the rigour and reproducibility of the algorithms. These results indicate that measurements can be made to an accuracy of about 1-2 mm, with a similar value for interobserver reproducibility for the best image comparison techniques available.


Asymptomatic temporal lobe injury after radiotherapy for nasopharyngeal carcinoma: incidence and determinants. Computed tomography (CT) scans were performed on a cohort of 60 patients for detection of temporal lobe injury (TLI) at 1-3.5 years after radiation therapy for nasopharyngeal carcinoma. Nine cases of TLI were identified, five of which were asymptomatic. The earliest case of asymptomatic TLI was found at 2.2 years after radiation therapy and the earliest symptomatic case at 2.3 years. A significantly higher incidence of TLI was found in patients with decreased temporal lobe shielding consequent to omitted eyeshield to the anterior photon beam and in patients treated with a hyperfractionation schedule giving 67.2 Gy in 42 fractions in 6 weeks. The incidence in these subgroups at 2-3.5 years after radiation therapy was 56% (5/9 patients) and 35% (8/23 patients), respectively. No patient in this study had TLI in the absence of these two factors. The implications of the results are discussed.


Primary choroid plexus papilloma of the cerebellopontine angle: magnetic resonance imaging, computed tomographic and angiographic appearances. The computed tomographic, angiographic and magnetic resonance imaging (MRI) appearances of a benign primary choroid plexus papilloma of the cerebellopontine angle are reported. Although benign, this tumour showed local invasion of the petrous temporal bone and mastoid air cells. The differential diagnosis of cerebellopontine angle lesions is discussed. Papilloma is suggested by the presence of a vascular, calcified, enhancing extra-axial mass in or around the cerebellopontine angle. MRI may show evidence of high vascularity and internal haemorrhage. Differentiation from other cerebellopontine tumours, most particularly meningioma, may not be possible on radiological features.


How frequent is chronic lumbar arachnoiditis following intrathecal Myodil? Chronic lumbar arachnoiditis has numerous causes, including the introduction of contrast media into the lumbar subarachnoid space. The oily contrast medium Myodil (iophendylate) is often cited but the true incidence of symptomatic lumbar arachnoiditis due solely to the presence of Myodil is unknown. A retrospective review of 98 patients in whom Myodil was introduced by ventriculography or cisternography, i.e. remote from the lumbar spine, revealed no cases of chronic lumbar arachnoiditis. All patients were monitored closely for periods ranging from 1 to 28 years. We conclude that, in these circumstances, it is rare for Myodil to produce symptomatic arachnoiditis.


The prognostic importance of CT features in primary intracranial lymphoma. The correlation of computerized tomography (CT) features with survival of 28 patients with primary intracranial lymphoma was analysed retrospectively. Severe perifocal oedema, periventricular tumours and lesions which were non-homogenously enhancing or non-enhancing were found to be associated with a poor prognosis. The prognosis when multiple lesions were present was almost the same as that of a solitary lesion (p = 0.95). Ring enhancing lesions had considerably longer survival. Lesions in the frontal region and those close to the meninges, enhancing homogeneously, had a better prognosis.


Transverse geniculate ligament of the knee: appearance and frequency on plain radiographs. The aims of the study were to determine the frequency of visualization of the normal transverse geniculate ligament (TGL) of the knee on lateral plain radiographs with magnetic resonance imaging (MRI) as a reference, and to determine features that make this ligament apparent on plain radiographs. 50 consecutive lateral plain radiographs and sagittal T1-weighted images of corresponding knees were evaluated prospectively. A TGL was considered visualized on plain radiographs when an opacity of soft-tissue density was apparent in the posterior part of the Hoffa's fat pad. The TGL was identified in 29 of the 50 (58%) sagittal MR images; a TGL was observed on the lateral plain radiographs of six patients (12%). Correlation with the MR images showed that, when visualized on plain radiographs, the ligament is at least 3 mm thick and completely surrounded by fat. Our study shows that the TGL is a normal variant that can be recognized frequently on lateral plain radiographs of the knee.


Macrodystrophia lipomatosa: radiographic observations. 23 cases of macrodystrophia lipomatosa (MDL) are reported showing a wide spectrum of radiographic findings. Typical findings were hypertrophy of all the mesodermal tissues of the affected digits with dramatic overgrowth of fat. Phalanges were enlarged both in length and transverse diameter, but the trabecular pattern was maintained. In one patient, the phalanges and metatarsals were elongated but thinned. In another case, all the phalanges and metatarsals of the great toe were small. The little toe was also involved in two cases. Articular surfaces were slanting. There was a high incidence of palmar and plantar involvement. In a few cases the forearm and leg were also involved. Other uncommon features observed were early maturation of epiphyseal centres of ossification of phalanges and metatarsals, syndactyly, polydactyly, brachydactyly and symphalangism. Angiography was uncharacteristic.


Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Over a 6-year period, in 1425 adult computed tomographic studies, radiological evidence of fatty infiltration of the liver (FIL) was found in 138 patients (9.7%). Patients with FIL had a mean age +/- SD of 45.9 +/- 15.7 years and 57% were males; the majority were Saudis (73%). Most patients (95%) had one or more underlying aetiological causes. Haematological and non-haematological malignancies with or without liver involvement were the most frequently encountered aetiological factors (66% of patients). FIL contributed to hepatomegaly or was associated with abnormality in one or more of the liver function tests in 30% and 39% of patients, respectively. Assessment of the various radiological patterns showed diffuse fatty changes in 68% of patients and solitary or multiple focal changes in 9% and 22%, respectively. 13 patients (9%) showed sparing of the caudate lobe within a diffuse fatty process. Patients with diffuse FIL had significantly higher values for alkaline phosphatase (p = 0.0016) and serum asparate aminotransferase (p = 0.0251) than those who had the focal pattern. FIL in 20 patients (14%) imposed a difficulty in making an appropriate diagnosis, led to inaccurate impressions, or forced unnecessary invasive or non-invasive investigations. We conclude from our large series of patients that FIL is not uncommon in hospital practice and among those at risk should always be considered as an appropriate diagnosis.


Accuracy of ultrasound and oral cholecystography in assessing the number and size of gallstones: implications for non-surgical therapy. Prior to non-surgical therapy of gallstones it is important to assess their number and size. In order to evaluate the accuracy of ultrasound (US) and oral cholecystography (OCG) in counting and measuring gallstones, a prospective blind study was conducted to compare the results of US (n = 99) and OCG (n = 36), either alone or in combination (n = 34), with the number and size of gallstones retrieved after cholecystectomy. The number of gallstones was accurately estimated by US and OCG in 74% and 69% of the cases, respectively. In assessing the presence of up to three, five or 10 gallstones both US and OCG proved reliable. In measuring the size of gallstones, there was 19% accuracy with US compared with only 3% with OCG. With an accepted measurement error of 3 mm these values increased to 80% for US and 44% for OCG. US proved more reliable than OCG in discriminating gallstones smaller or larger than 10 mm and smaller or larger than 20 mm, but with US, detection of gallstones larger than 30 mm was problematic. Both US and OCG underestimated gallstone size. The combination of both techniques did not significantly improve the assessment of either number or size of gallstones compared with the results obtained with US or OCG alone. It is concluded that (1) both US and OCG have some limitations in assessing the number and size of gallstones, (2) the combination of both examinations does not improve accuracy, and (3) patient selection for non-surgical treatment of gallstones can be started by US alone.


The optimum pressure of oxygen for radiotherapy of a mouse tumour. Our previous studies have shown that there is more regrowth delay in mammary tumours irradiated in C3H mice after 25 Gy when breathing normobaric oxygen than in those breathing air, as might be expected. However, in both cases this radiation response was reduced in anaesthetized animals in comparison with unanaesthetized control mice, when a time interval of only 10 min was allowed after anaesthesia. After 25 min, however, the response in air returned to the control level and the oxygen group now showed significantly more radiosensitization. We have now found that when tumour-bearing mice were exposed to different pressures of oxygen for that 25-min period after the induction of anaesthesia, before the tumours were treated with 25 Gy, there was even more regrowth delay with 2 atm pressure than 1, but that there was no further advantage from using 3 atm pressure of oxygen. Our data suggest that 2 atm may be the optimal pressure to use in anaesthetized mice and there is even a small benefit from using this pressure in unanaesthetized animals for a transplanted C3H mammary tumour.


Treatment planning for 131I-mIBG radiotherapy of neural crest tumours using 124I-mIBG positron emission tomography. Patients designated to receive 131I-meta-iodobenzylguanadine (mIBG) for the treatment of neural crest tumours have been scanned with 124I-mIBG using the MUP-PET positron camera. Uptake was detected in tumour sites in lung, liver and abdomen. The tomographic images produced have allowed estimates to be made of the concentration of mIBG in both tumour and normal tissue. From these data it is possible to predict the radiation doses that would be achieved using therapy levels (up to 11 GBq) of 131I-mIBG. The levels of tumour uptake are between 0.5 and 2.0 kBq/g indicating that the radiation doses to tumour would be in the range 3 Gy to 7.5 Gy.


A pilot study of accelerated fractionation in the radiotherapy of invasive carcinoma of the bladder. 24 patients with muscle invasive carcinoma of the bladder were treated in a pilot study of twice daily fractionation at radiation doses of 1.8-2.0 Gy per fraction to total doses of 54-64 Gy to the bladder and 39.6-44 Gy to the whole pelvis. The treatment aim was to give 32 fractions in 22 days. The interfraction interval was a minimum of 6 h. The principle objective was to record acute and late tolerance, but local control and survival data is also presented. Acute radiation morbidity was scored according to the RTOG system. Grade 2 large bowel effects were seen in 52% of patients, Grade 3 effects in 26% and there was one Grade 4 and one Grade 5 effect. The mean duration of effect was 4.5 weeks although the more severe reactions were also more protracted. Grade 2 urinary effects occurred in 30% and Grade 3 in 17% of patients. The mean duration of effect was 7.2 weeks. There were no Grade 4 or 5 acute urinary effects. Late radiation morbidity was scored according to the EORTC/RTOG system and was assessable in 16 cases who survived more than 6 months. There were two cases (12%) of Grade 1 bowel toxicity, two cases of Grade 1 and three of Grade 2 urinary toxicity. There were no cases of late skin effects. Actuarial analysis at 2 years shows a local control probability of 56% and survival probability of 35%.


An investigation into the effect of protective devices on the dose to radiosensitive organs in the head and neck. A series of experiments were performed to determine the dose reduction afforded to radiosensitive organs in the head and neck by various protective devices. These included spectacles with plastic, standard glass, photochromic and lead-glass lenses, a thyroid collar and a lead-acrylic face mask. The measurements were performed using an anthropomorphic phantom loaded with lithium fluoride thermoluminescent dosemeters, in conditions realistic of clinical practice. Irradiations were performed using scattered radiation produced by a pelvic phantom, for X-ray beams generated at 80 kVp and 110 KVp. It was found that the reduction in dose to the lens of the eye ranged between 0% and 97%, whilst the dose to the thyroid and oesophagus was reduced by between 76% and 97%, and was dependent on the protective device and tube potential employed. A reduction in brain dose of up to 81% was also measured, for the lead-acrylic face mask. Also presented is the ratio of organ dose to dose to the bridge of the nose for thyroid, oesophagus, brain and sinuses, as measured for the case of no head or neck protection.


Errors due to non-uniform distribution of fat in dual X-ray absorptiometry of the lumbar spine. Errors in spinal dual X-ray absorptiometry (DXA) were studied by analysing X-ray CT scans taken for diagnostic purposes on 20 patients representing a wide range of fat content. The mean difference between the fat thickness over the vertebral bodies and that over a background area in antero-posterior (AP) scanning was 6.7 +/- 8.1 mm for men and 13.4 +/- 4.7 mm for women. For lateral scanning the mean fat thickness difference was only 4 mm for both sexes, but the dispersion was greater, with a standard deviation of 15 mm. To relate these differences to errors in bone mineral, measurements were made of the bone mineral equivalence of fat-equivalent materials on DXA machines from three manufacturers. 10 mm of adipose tissue was equivalent to -0.043 g/cm2 of hydroxyapatite. For AP scanning a non-uniform fat distribution leads to a mean overestimate of 0.029 g/cm2 for men and 0.057 g/cm2 for women. The error exceeded 0.1 g/cm2 in 10% of slices. For lateral scanning the error exceeded 0.1 g/cm2 (about 15% of normal) in a quarter of slices.


Historical experiments predating commercially available computed tomography. Computed tomography (CT) was a revolution in radiology. Commercially available CT scanners appeared in 1972, a joint effort between the EMI Company, Atkinson Morley's Hospital, London and the Department of Health and Social Security (DHSS). The name of Sir Godfrey Hounsfield will always be associated with these developments. Like most developments in science the breakthrough came by standing on the shoulders of giants and many experiments can, with the curious wisdom of hindsight, be considered precursors to CT. Gabriel Frank's patent in 1940 showed apparatus for back-projection CT and Takahashi developed equipment in the 1940s for reconstructing from a sinogram; in both cases using an optical "computer". A medical CT scanner was reportedly constructed in 1957 in Kiev. Transmission CT was performed by Kuhl in 1965. Cormack built an experimental scanner in 1963. Oldendorf identified what was needed for successful CT as early as 1960. Throughout the 1960s a host of independent workers were busy on the mathematical problems of reconstructing from projections with both medical scanning and non-medical applications in mind. Experiments in early emission tomography influenced the development of CT. With imagination one can even see how close "classical" tomography, as started even before 1920, came to the realization of CT. The pioneering British radiographer Watson stands out from a galaxy of inventors. The lecture at Radiology and Oncology '91 in Brighton was a thumbnail sketch of the origins of radiological CT. A fuller story is told elsewhere (Webb, 1990).


Long-term follow-up of patients with hydronephrosis treated by Anderson-Hynes pyeloplasty. A series of 21 patients with hydronephrosis (mean age 37 years) underwent an Anderson-Hynes pyeloplasty; a nephrostomy catheter was not used routinely. One patient developed urinary leakage post-operatively but this ceased following insertion of a ureteric catheter. Assessment was carried out after a mean observation time of 85 months. Clinical examination, laboratory investigations, urography and renography were performed pre-operatively and at follow-up. There was no evidence of stones or stenosis in the pelvis. Patients operated upon before the age of 30 years showed improved renal function. All patients had symptoms pre-operatively but only one had symptoms post-operatively. It was concluded that the results of surgical intervention in hydronephrosis are excellent, especially in patients aged less than 30 years.


Renal carcinoma in patients undergoing nephrectomy: analysis of survival and prognostic factors. A series of 155 patients who underwent nephrectomy for renal carcinoma between 1965 and 1985 at Manchester Royal Infirmary were analysed for survival in relationship to presenting features, surgical staging and histopathology. Univariate and multivariate analyses were carried out. Five-year survival estimates for stage 1 disease were 81%, for stage 2 disease 65%, for stage 3 disease 39% and for stage 4 disease 6%. An erythrocyte sedimentation rate (ESR) greater than 30 mm/h was associated with worse survival and a history of hypertension was associated with better survival. Renal vein invasion alone was related to worse survival. Perinephric fat invasion was also associated with worse survival and this association in the multivariate analysis was more significant than expected, suggesting that the principles of radical surgery should be observed. The presence of granular cells as opposed to clear cells worsened survival. Patients with papillary tumours had a better survival than those with solid tumours.


Blood transfusion and survival following surgery for renal carcinoma. The effect of peri-operative blood transfusion on survival after surgery for renal carcinoma was studied in 201 patients. In addition to blood transfusion, several other factors were included in a multivariate analysis. Using Cox's proportional hazards model, transfusion of more than 4 units of blood was found to be an independent prognostic factor in addition to tumour stage, erythrocyte sedimentation rate and macrohaematuria.


Ureteric complications of renal transplantation. Of 507 consecutive recipients of renal allografts, 45 developed a urological complication. In 39 patients (7.7%) ureteric problems were implicated and these comprised 30 cases of obstruction and 9 cases of ureteric necrosis presenting as urinary leakage. In 7 patients ureteric obstruction resolved following a period of nephrostomy decompression; 10 patients were reconstructed surgically and this was successful in 8, with 2 patients requiring further surgical procedures. Ten patients were successfully treated by percutaneous stenting after dilatation of the stricture. Stenting failed in 4 patients and in 1 patient caused rupture of a calix. All 10 stents have now been removed and there is no recurrence of stricture (follow-up 32.0 +/- 8.6 months). Of the remaining 3 grafts, 2 were removed and the other graft had percutaneous removal of a ureteric calculus. The 1-year survival rate of allografts in the ureteric complication group was 84.6%; in the recipients without a urological complication it was 81%. It was concluded that an active approach to ureteric problems following renal transplantation results in the rescue of the majority of allografts.


Voiding dysfunction and urodynamic findings in patients with cervical spondylotic spinal stenosis compared with severity of the disease. A group of 30 consecutive patients (26 men and 4 women, mean age 51 years), with clinically and radiologically verified cervical spondylosis causing radiculopathy and/or myelopathy, were questioned about voiding symptoms, examined urodynamically and subjected to tests of tibial somatosensory evoked potentials (SEP). Seventeen patients (61%) complained of irritative bladder symptoms and detrusor hyperactivity was demonstrated urodynamically in 13 (46%). Three (11%) experienced difficulty in emptying the bladder, and all of these had a hypotonic detrusor. The bladder was insensitive to cold in 36%, this and SEP abnormalities being more common in the patients with clinically severe myelopathy, whereas detrusor hyperactivity was found equally in all patients. Urodynamic investigation seems to provide additional information on the severity of the disease and is therefore recommended for wider use in these patients.


Acute urinary retention. Comparison of suprapubic and urethral catheterisation. A total of 86 consecutive patients who presented to the accident and emergency department with acute urinary retention due to prostatomegaly required catheterisation; 56 received suprapubic catheters and 30 were catheterised urethrally. Both groups were followed up for 3 years. Of the 30 patients catheterised urethrally, 12 (40%) developed urinary tract infections compared with 10 (18%) urinary tract infections in the 56 patients catheterised suprapubically. Five patients (17%) in the urethral group developed urethral strictures with no strictures in the suprapubic group. Two patients catheterised urethrally developed epididymo-orchitis and 1 developed septicaemia. None of the patients with suprapubic catheters developed these complications. Furthermore, 16 patients catheterised suprapubically underwent successful trial clamping of their catheter, whereas 7 patients required recatheterisation following removal of their urethral catheters. We recommend that the use of suprapubic catheters should become the preferred initial treatment for acute urinary retention.


In vivo detection by microscopic chromocystoscopy of concurrent urothelial atypia in superficial bladder cancer. Microendoscopic observation of methylene blue-stained urothelial surfaces, so-called microscopic chromocystoscopy (MCC), was undertaken in 65 patients with superficial bladder cancer (Ta and T1) and its effectiveness in detecting concurrent urothelial dysplasia or carcinoma in situ was studied. A total of 166 biopsy samples were taken from 75 stained and 91 non-stained portions. Of 75 methylene blue-stained areas, 21 were judged to be abnormal (MCC-positive) by microscopic observation. Fourteen of these 21 MCC-positive areas (67%) were proven to be abnormal histologically, while 7 of 54 MCC-negative portions (13%) were histologically abnormal. Only 4 of 91 biopsies (4%) from non-stained mucosa were proven to have urothelial atypia. In per patient figures, 1 or more concurrent field changes were detected in 15 of 65 cases (23%). MCC contributed to the diagnosis in 10 of these 15 patients.


Initial combination chemotherapy with cisplatin, methotrexate and vinblastine in locally advanced transitional cell carcinoma--response rate and pitfalls. MRC Subgroup in Advanced Bladder Cancer (on behalf of the MRC Urological Working Party). A total of 51 patients with locally advanced transitional cell carcinoma of the bladder were entered into a phase II study to evaluate the effect of initial cisplatin (100 mg/m2, Day 2) combined with methotrexate (30 mg/m2, Days 1 and 8) and vinblastine (4 mg/m2, Days 1 and 8). Of 44 evaluable patients, 25 (57%) achieved an objective response of their primary bladder tumour (complete response (CR): 4 patients; partial response (PR): 21 patients); 30 of the 36 patients with micturition disturbances obtained relief. Toxicity was acceptable, but dose modifications due to haematological or renal toxicity were required in 153 of the 690 drug courses. Non-protocol dose modifications were performed 45 times. The experience gained in this trial emphasises the need for improved co-operation between urologists, radiologists and clinical oncologists in such multicentre phase II studies. Difficulties were observed in adhering to dose modification rules, assessing pre-treatment tumour size (due to variation in quality of measure and in timing relative to initial transurethral resection (TUR)) and defining response to chemotherapy (due to failure to perform mandatory investigations at the right time). This study also illustrates that the accepted criteria for assessing response in the primary bladder tumour are difficult to apply in practice and that the results of any study using this indicator lesion require caution in their interpretation.


Intravesical instillation of beta-interferon in the treatment of bladder cancer. A total of 36 patients with single superficial bladder cancer TNM stage Ta-T1/G2 was studied over a 24-month period before entering the study to evaluate the efficacy and tolerance of high doses of beta-interferon (beta-INF); 24 patients had a primary tumour (group 1) and 12 had had more than 3 recurrences (group 2). They received 8 intravesical doses of beta-INF, 50,000,000 IU in 50 ml sterile water, at weekly intervals, 15 days after transurethral resection of the bladder (TURB). Efficacy was estimated by simple recurrence rate and by the person-years method. The recurrence rate was 25% in group 1 with a mean follow-up of 21.6 months. Comparison with the recurrence rate of a historical control group treated only by TUR showed that there was a slight statistically significant difference. Group 2 had a recurrence rate of 100% in the period before beta-INF (follow-up 24 months) and 91% after INF administration (mean follow-up 20.5 months). Patients were questioned about side effects before and after each treatment; tolerance of the drug was excellent. The results suggest that beta-interferon could be safely used as a prophylactic agent against the recurrence of primary superficial bladder cancer. Its efficacy seems comparable to that obtained with other current chemoprophylactic agents.


Laparoscopic ligation of internal spermatic vein. Laparoscopic procedures have long been a standard form of treatment for gynaecological disorders but have only recently shown promise in the evaluation and treatment of urogenital diseases, such as pelvic lymphadenectomy. We performed laparoscopic ligation of the bilateral internal spermatic veins in 15 male pigs. The average operative time was 20 min and operative morbidity was minimal, comprising mild subcutaneous emphysema around the trocars. Engorgement of the spermatic vein proximal to the endoclip site was noted. There was no operative mortality. Laparoscopic ligation of the internal spermatic veins seems to be a feasible method for the treatment of varicoceles, especially bilateral lesions.


Urine transparency as an index of absence of infection. A visual assessment of the clarity of urine was used as an exclusion test to indicate the absence of infection; verified by dipslide culture, it was applied to 363 urine samples collected from patients attending 2 adult nephrology clinics over a period of 6 months. The crimped aluminium bowl used for collection of samples assisted the assessment of clarity. The sensitivity of the method compared with dipslide culture was 73%, with specificity and efficiecy both 58%. The predictive value of a negative test (clarity) was 97% with a false negative rate of 3%, enabling this simple examination to be used as an exclusion test for further testing. In simple terms, a clear urine is unlikely to be infected. It is also an advantage to have an immediate indicator of the absence of infection available at the clinic. Analysis of only those urines assessed as cloudy could result in financial savings and, from the clinics, a 56% reduction in workload.


Current management of duplex-system ureteroceles: experience with 41 patients. Experience is described of 41 infants and children with duplex-system ureteroceles, 25 presenting clinically and 16 by prenatal ultrasonography. Bladder outflow obstruction was rare but lower polar vesicoureteric reflux (VUR), usually of lesser grades, was common. Upper polar function, as assessed by 99mTc-DMSA, was negligible in children with truly ectopic ureteroceles but well preserved in those where the lesion lay wholly intravesically. Lower polar function was good, even in the presence of secondary obstruction, except in 2 infants with major VUR. Twenty-three patients were treated by upper polar nephrectomy plus aspiration of the ureterocele; 2 subsequently required ureterocele excision. Histology of excised specimens indicated that a more conservative approach would not have been rewarded. Where upper polar function was good, conservation was maintained in 3 cases by pyelopyelostomy and in 5 more by excision of the ureterocele plus bipolar ureteric reimplantation. Other operative strategies were employed in 2 cases. Finally, a defined group of 8 children was managed expectantly without untoward results. It was concluded that the variable anatomy and function associated with duplex-system ureteroceles require a flexibile approach to treatment, including, possibly, no treatment at all.


Monitoring and cerebral protection during carotid endarterectomy. Two recently published multicentre trials have confirmed the overall benefit of carotid endarterectomy in symptomatic patients with severe carotid artery disease. The key to improving further the long-term advantages of carotid endarterectomy, however, remains the continued reduction of the initial operative risk. While the principal responsibility for this continues to be borne by the surgeon, specifically in reducing technical error, the time is perhaps approaching when he or she might also be able to apply some of the recent advances in cerebrovascular research to reduce operative morbidity still further in the future. This article summarizes the aetiology and pathophysiology of operation-related neurological deficits and reviews current approaches towards intraoperative monitoring, cerebral protection and assessment of quality control.


Chest physiotherapy for the surgical patient. This article reviews the evidence that chest physiotherapy is effective in the prevention and treatment of pulmonary complications after major abdominal and thoracic surgery. There is some evidence that regular chest physiotherapy significantly decreases the incidence of pulmonary complications, although the mechanism of this effect is uncertain. It is not known whether chest physiotherapy is effective in the treatment of postoperative pulmonary complications after they have developed.


In situ versus reversed femoropopliteal vein grafts: long-term follow-up of a prospective, randomized trial. In a prospective, randomized trial, 226 patients undergoing femoropopliteal bypass for lower limb ischaemia were allocated to reversed (123 patients) or in situ (103) techniques. The groups were comparable for age, sex, incidence of diabetes, and indications for surgery. Eleven veins were rejected at operation, nine in the reversed group and two in the in situ group, leaving 114 reversed and 101 in situ grafts for study. Cumulative patency rates were not significantly different between reversed and in situ grafts at any time up to 6 years after operation, with primary patency rates at 1, 3 and 5 years of 84.8, 69.5 and 62.4 per cent for reversed grafts and 79.9, 71.2 and 63.5 per cent for in situ grafts. Small vein grafts (< 4 mm in diameter) were associated with patency rates at 1, 3 and 5 years of 63.5, 46.7 and 36.0 per cent compared with 93.9, 82.5 and 75.9 per cent for vein grafts > or = 4 mm in diameter (P < 0.002, log rank test). The patency rates of small veins employed in situ and reversed were similar. The in situ technique confers neither short- nor long-term advantage over reversed vein grafting for femoropopliteal bypass.


Success rates for rehabilitation of vascular amputees: implications for preoperative assessment and amputation level. All lower limb amputations performed during 1986 and 1988 in eight hospitals in the south-east region were assessed. Of 440 amputations for vascular disease, 193 were above-knee, 193 below-knee, 15 Gritti-Stokes, 15 through-knee and 24 bilateral. Of the 440 patients, 75 died in hospital, 113 were considered unsuitable for a prosthesis and 252 (57 per cent) were referred for prostheses. Rehabilitation questionnaires were sent to 179 patients (41 per cent), as a further 54 had died and 19 had become known non-wearers before the study commenced. The response rate was 81 per cent; 102 patients completed the questionnaire, 21 were reported dead, and 22 were non-wearers. Of a maximum rehabilitation score of 12, 52 patients scored 6 or more (consistent with mobility on their artificial limb around the home), and 21 scored 9 or more (a standard accepted as successful rehabilitation). It is concluded that 10-15 per cent of amputees achieve mobility around the home on their prosthesis. Only 5 per cent, however, rehabilitate well and become independent of their wheelchair. When amputation is inevitable, more consideration should be given to surgery that optimizes wheelchair rehabilitation.


Systemic cytokine response after major surgery. The systemic cytokine response to major surgical trauma was studied in 20 patients undergoing elective aortic surgery and five patients after inguinal hernia repair. Tumour necrosis factor alpha and interferon gamma were not detected in these patients. An early and short-lived interleukin 1 beta (IL-1 beta) response to major surgery was detected only by intensive sampling in the perioperative period. The IL-1 beta peak preceded a more marked interleukin 6 (IL-6) response that peaked 4-48 h after surgery. IL-6 levels had fallen sharply by 48-72 h in all patients who had an uneventful postoperative course. The IL-6 peaks were significantly lower after hernia surgery than after major aortic operations (P < 0.001); IL-1 beta was not detected in any samples. Three patients undergoing aortic surgery developed unexpected major postoperative complications. IL-6 levels in this group were significantly higher than those of the other patients undergoing aortic surgery within 6-8 h of skin incision, and remained elevated for longer. These rises in plasma IL-6 levels preceded the clinical onset of major complications by 12-48 h. The systemic IL-1 beta and IL-6 response to surgical trauma increased with the severity of the surgical insult. An early, exaggerated IL-6 response was associated with the subsequent clinical development of major complications.


Continuing experience with transaxillary excision of the first rib for thoracic outlet syndrome. The results of transaxillary excision of the first rib for thoracic outlet syndrome are reported. During a 3-year period, 40 transaxillary rib resections were performed on 32 patients. The symptoms in 33 limbs were completely relieved and in a further four symptoms were improved. These results confirm that transaxillary excision of the first rib is the operation of choice in the management of thoracic outlet syndrome.