Breathlessness and profuse haemoptysis.
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Biomedical subjects
Publications and source records attributed to R A Barker.
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A patient is reported on with a subarachnoid haemorrhage (SAH) from an aneurysm of the posterior communicating artery, who initially presented with a sentinel bleed into an arachnoid cyst and normal magnetic resonance angiography (MRA) of the intracranial vasculature which led to a delay in diagnosis. Although this is a very rare presentation of a relatively common condition, it is important to recognise the importance of intracystic haemorrhage in such circumstances as well as the limitations of MRA, as a delay in diagnosis may have serious clinical consequences.
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Grafts of embryonic ventral mesencephalic tissue placed in the striatum of 6-hydroxydopamine-lesioned rats survive, and make and receive connections to and from the host brain. The dopaminergic neurons of the graft can grow processes into the host brain, and thereby alleviate many of the behavioral deficits of this form of experimental Parkinson's disease. However, when examined some weeks after implantation, grafted substantia nigra only contains about 5% of the expected complement of dopaminergic neurons. We have examined the time course of loss of grafted neurons. We find that the majority die during the first 7 days after transplantation. However, we have shown previously that three-dimensional cultures with the same dimensions as a graft, made of identical cell suspensions, have much better dopaminergic neuronal survival. There must, therefore, be features in the environment surrounding a graft that are toxic to dopaminergic neurons. A limiting factor in the efficacy of dopaminergic grafts is the small distance over which the neurons are able to grow neurites and form connections in the host brain. We find that the growth of neurites from dopaminergic neurons into the host striatum occurs in two phases. Neurites reach their maximum length within 7 days of transplantation, and this is followed by a much slower process of branch and terminal formation. Since axon growth in the adult brain may be inhibited by a number of factors associated with reactive gliosis, we have immunostained various ages of graft for vimentin, tenascin, chondroitin sulfate proteoglycan (CS-PG) using the CS56 antibody, the DSD-1 proteoglycan, and microglia using the OX-42 antibody. We have compared this staining with that surrounding a simple stab wound. Vimentin staining was initially seen in the graft and in astrocytes immediately surrounding it. By 7 weeks staining was restricted to a ring of astrocytes surrounding the graft. Tenascin, DSD-1, and CS-PG were initially seen in and around the grafts. By 7 weeks they had disappeared from grafts, but CS-PG and tenascin persisted in small amounts around stab wounds. In general, immunostaining of these molecules persisted longer around a stab lesion than around a graft. There was also an intense local microglial reaction surrounding both grafts and stab wounds which had largely resolved by 7 weeks.
Embryonic substantia nigra cells when transplanted into the striatum can reverse many of the defects of Parkinson's disease. The efficacy of such grafts is compromised by the poor survival of grafted dopaminergic neurones; typically, 3-10% survive transplantation. We used three tissue culture models to identify stages in the procedure for the preparation and insertion of grafts which might be responsible for this cell death and to identify environments in which survival is optimised. (1) The ventral mesencephalon was dissected from the donor brain, then placed immediately into culture contained in a collagen gel. (2) The dissected tissue fragments were enzymatically dissociated, then the cells placed into monolayer culture. (3) Enzymatically dissociated tissue was packed into 0.5-mm-diameter porous tubes, to simulate the compaction of cells into a graft deposit in the host brain. Dissociation of the tissue by itself caused the death of approximately 30% of dopaminergic neurones, as judged by the difference in cell counts between the intact embryonic day 14 (E14) mesencephalon, and cells dissociated then packed into tubes. Of the dissociated neurones approximately 60% died during the first 24 h and 87% during the first 3 days in monolayer culture, while only 7% of dopaminergic neurones in three-dimensional cultures and 11% of neurones in explant cultures died over the first 3 days. Embryonic dopaminergic neurones are clearly very vulnerable to adverse conditions during the first days after their removal from the donor brain. The excellent survival of neurones in three-dimensional and explant cultures indicates that close association with other cells, which may provide greatly improved access to trophic factors, can enable the cells to survive this period of vulnerability. In contrast to its effects in monolayer cultures, bFGF had no effect on dopaminergic neuronal survival in either explant or three-dimensional cultures.
Endocardial resection was required in 26 patients with sustained drug-resistant ventricular tachycardia. The early mortality rate (within 30 days after operation) was 12%. Two deaths were the result of low cardiac output, and the third death was related to recurrent ventricular septal defect after septal endocardial resection. The survivors of endocardial resection were followed up from 6 to 92 months (mean 43). There were no recurrences of ventricular arrhythmias, and patients did not require antiarrhythmic drug therapy. The late mortality rate after endocardial resection was 19%. There were two late cardiac-related deaths (unrelated to arrhythmias) and three late deaths from noncardiac causes. Complete endocardial resection successfully ablates drug-resistant ventricular tachycardia, but is associated with an increased perioperative mortality rate in those patients who have severely depressed left ventricular function without a well defined left ventricular aneurysm.
Twenty to thirty percent of cases of dermatomyositis in adults are associated with malignancy. We report a case in which dermatomyositis heralded the development of a testicular germ cell tumour. Germ cell testicular tumours are treatable and our case emphasizes the importance of measuring blood levels of beta-human chorionic gonadotrophin and alpha-fetoprotein and examination of the testes in young males with indications of possible malignancy.
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Over a period of 2 months, 35 of 69 (51%) cases of juvenile diarrhoea studied in eastern Malaysia were associated with rotavirus excretion; rotavirus associated diarrhoea occurred most commonly in the 6-24 month age group. Polyacrylamide gel electrophoresis (PAGE) of genome ribonucleic acid showed that only 4 rotavirus electropherotypes could be detected. Of those, 2 predominated and 2 were detected only once each; one of these may have been a reassortment of the two predominant electropherotypes. Analysis of the clinical features of patients excreting rotavirus subgroup 1 or 2, determined by PAGE, demonstrated that rotavirus subgroup 1 was associated with more hypotonic dehydration and need for intravenous therapy: lethargy was significantly more common among those excreting rotavirus subgroup 2.
The basal ganglia are associated with motor functions of the brain, although it is becoming clear that they may subserve many nonmotor functions as well. A review of the literature reveals an association between the basal ganglia and pain, and raises the question of a new function for the basal ganglia in selective attention.
Parkinson's disease (PD) is a common condition that, in the majority of cases, is idiopathic in origin. The loss of central dopaminergic pathways is well-known and in this paper a theory is presented that this is brought about by an autoimmune process. The lack of any HLA association or familial clumping for the disease does not exclude such a theory, as a common etiological agent may exist that we do not yet recognize, e.g., infection, or drugs. Several autoantibodies and disturbances in T-cell function have been found in PD. The theory proposes that the production of autoantibodies and T-cell activation are important in the pathogenesis of idiopathic PD by an action on the substance P striatonigral pathway and its input to the dopaminergic nigrostriatal pathway. The autoimmune destruction of the substance P input leads to a secondary loss of the dopaminergic system and hence PD.
Ten patients for coronary vein grafting had induction of anesthesia with fentanyl (30 micrograms/kg), followed by enflurane-oxygen sufficient to decrease systolic blood pressure by 27% before intubation. Enflurane was continued in concentrations to maintain blood pressure below that with patients awake. All patients had preserved ventricular function and effective beta-blockade. Studies of hemodynamic functions and myocardial blood flow and oxygenation were done before induction, six times during anesthesia, and twice postoperatively. The blood pressure decrease on induction and before bypass was due to reduced cardiac index without decreased heart rate or systemic resistance. Stroke work index decreased 47% on induction and remained below awake level throughout. Coronary sinus blood flow decreased 26% after intubation and remained so before bypass. Without change in coronary resistance, coronary sinus oxygen content increased 30% on induction and stayed elevated before bypass. Normal lactate extraction continued after induction and increased before bypass; mean extraction decreased after bypass, with one or two hearts producing lactate in the first 24 postoperative hr. Fentanyl-enflurane-oxygen maintained a steady mild hemodynamic depression during the operation and soon afterward, which preserved myocardial oxygenation.
Isoflurane-oxygen was given for induction and maintenance of anesthesia to ten patients having coronary artery bypass grafts. All had preserved ventricular function without hypertension or other cardiac lesions; treatment with beta-blocking drugs was maintained until the operation in all patients. Cardiac output, arterial and central pressures, coronary sinus (CS) blood flow, arterial and CS oxygen, Hb, and lactate contents were measured before, six times during, and twice after anesthesia. On induction, systolic arterial pressure was purposely reduced 33% along with systemic resistance by increasing the concentration of isoflurane; cardiac index, heart rate, and coronary flow did not change. Coronary resistance decreased 23% and CS oxygen content increased 56%; but in three of ten patients myocardial lactate production took place, evidence of global ischemia. Induction of anesthesia was not smooth in three patients. Controlled hemodynamic depression could be maintained with isoflurane-oxygen, but the frequency of myocardial lactate production before and after perfusion was greater than with other general anesthetics. Isoflurane dilated portions of the coronary bed but, because anaerobic metabolism occurred concomitantly, the theory that redistribution of flow can take place resulting in ischemic areas of ventricle is supported.
Fentanyl (mean dose 109 micrograms X kg-1) and oxygen were given to ten patients having coronary vein grafts. Serial studies were done before, during and after operation, of central and mean arterial pressures (MAP), cardiac index (CI) and coronary sinus flow (CBF) by thermodilution, myocardial oxygen consumption (MVO2) and lactate extraction (MLE). On induction CI and stroke work index decreased, but heart rate and MAP were unchanged as systemic resistance increased. Mean MAP and heart rate remained at the awake levels. Mean CBF remained unchanged along with stable MAP and coronary resistance. Oxygen content of CS blood increased on induction and remained elevated until the incision; it was above the awake level early postoperatively. MVO2 was low normal when the patients were awake and remained so. Normal MLE continued with a few exceptions. High-dose fentanyl did not uniformly abolish autonomic reflexes. Heavy premedication, complete beta adrenergic blockade and a high initial doses of fentanyl plus its continued infusion, aided in retaining a hypodynamic circulation and myocardial oxygenation.
Twenty patients about to have coronary artery bypass grafts were studied before and after 15 min of 50% nitrous oxide added to either fentanyl (75 micrograms/kg) or enflurane (0.5%) anesthesia. Arterial and central pressures and cardiac output were measured, plus coronary sinus blood flow and arterio-coronary sinus differences in oxygen, hemoglobin, and lactate contents. Fentanyl-N2O and enflurane-N2O both decreased systemic resistance, heart rate, cardiac output, and hence arterial pressure. Stroke work decreased significantly with little or no change in wedge pressure: ventricular function was impaired. Coronary flow and myocardial O2 consumption decreased with fentanyl-N2O. Oxygen extraction increased with enflurane-N2O, as did lactate contents of coronary sinus blood. Hemodynamic depression occurred from the combined effects of nitrous oxide and fentanyl or enflurane. The beta-blocked myocardia of nonstimulated coronary patients were becoming ischemic globally on 50% oxygen, after significant hypotension. From this and other evidence, we conclude that nitrous oxide may not be benign in patients with coronary arterial disease.
A signal-detection model is presented for the two-alternative forced-choice procedure that gathers simultaneous detection and identification judgments. By using vector representation, a measure of independent processing within the visual system is derived. The independence measure is applied to data on the detection and identification of stimuli that differ along the dimensions of orientation, spatial frequency, and size. Data are presented that favor the signal-detection model over a high-threshold model.
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