Multiple occult vascular malformations of the brain and spinal cord: MRI diagnosis

Summary We report a patient with multiple angiographically occult vascular malformations in the brain and spine. Magnetic resonance imaging showed multiple lesions in brain and spine with hypointense areas on both T1 and T2-weighted images. These hypointense areas are usually secondary to hemosiderin deposits consistent with remote bleeding in the lesions. We conclude that when magnetic resonance reveals an intraspinal lesion with signal intensity characteristics consistent with a vascular malformation, an examination of the brain should be performed to rule out associated intracranial lesions. The finding of multiple lesions in the brain with identical signal intensity characteristics reinforces the diagnosis of vascular malformation.     

Intraperitoneal infection with Salmonella abortusovis is partially controlled by a gene closely linked with the Ity gene.

The aim of the present study was to determine whether the Ity gene, which controls the resistance to S. typhimurium infection in mice, also governs the resistance to S. abortusovis, a serotype specific for goat and sheep. During either i.v. or i.p. infection, BALB/c mice (Itys) were not able to control the growth of S. abortusovis and eventually died from infection. In contrast CBA (Ityr) or (C.CB)F1 (Ityr/s) mice were able to control the growth of these bacteria. Using congenic C.D2 Ityr mice, we found that the gene controlling resistance to S. abortusovis was tightly linked to the Ity gene on chromosome 1. Furthermore, in the spleen and the liver of backcross BALB/c x (CBA x BALB/c) mice, the S. abortusovis resistance phenotype cosegregated with the two alleles of the Len-1 gene, a gene tightly linked to the Ity gene. By contrast, in these backcross mice, the level of infection of the peritoneal cavity, the site of inoculation, did not correlated with the Len-1 phenotype of the animal. These results provide evidence that after i.p. inoculation the control of S. abortusovis growth in the spleen and the liver is controlled by the Ity gene, but also suggest that additional gene(s) regulate the number of bacteria at the site of inoculation.     

Raised concentrations of glucose and adrenaline and increased in vivo platelet activation after myocardial infarction

Plasma concentration of beta thromboglobulin was used as an index of in vivo platelet activation in 36 patients after acute myocardial infarction. Twelve patients had diabetes, seven had pulmonary oedema or cardiogenic shock (pump failure) or both, and 17 had uncomplicated infarcts. On the first day of admission, concentrations of beta thromboglobulin were higher in the patients with diabetes and those with pump failure than in those with uncomplicated infarcts. Concentrations of beta thromboglobulin in the non-diabetic patients were studied by multiple regression analysis and were significantly associated with plasma concentrations of adrenaline, pump failure, and glucose but not with noradrenaline or infarct size. When all subjects were considered together, glucose, adrenaline, and pump failure were associated with the beta thromboglobulin concentration but diabetes was without significant effect. Hyperglycaemia and raised plasma adrenaline concentration after myocardial infarction may activate platelets, and this could contribute to poor outcome in such patients.     

Lesion-induced synapse reorganization in the hippocampus of cats: sprouting of entorhinal, commissural/associational, and mossy fiber projections after unilateral entorhinal cortex lesions, with comments on the normal organization of these pathways.

This study evaluates whether three forms of sprouting occur in the hippocampus of the cat following unilateral entorhinal cortex (EC) lesions: (1) sprouting of projections from the EC contralateral to the lesion; (2) sprouting of the commissural/associational system; and (3) sprouting of mossy fibers. Tract tracing techniques were used to define the normal organization of the entorhinal cortical projection system, the commissural/associational (C/A) systems, and the mossy fiber projections in normal cats. The same techniques were then used to evaluate whether there were changes in these projections in animals with long-standing unilateral EC lesions. The projections from the entorhinal cortex were evaluated autoradiographically following injections of 3H proline into the entorhinal area. The projections of the C/A system were traced using the Fink-Heimer technique after lesions of the hippocampal commissures, and by using autoradiographic techniques after injections of 3H proline into the hippocampus. The distribution of mossy fibers was evaluated using the Timm's stain. The results reveal that unilateral lesions of the EC in cats lead to the same sorts of sprouting that have been described in rats. There is: (1) an increase in the density of the crossed projection from the surviving EC to the contralateral dentate gyrus that had been deprived of its normal EC inputs; (2) an expansion of the terminal field of the C/A projection system into portions of the molecular layer of the dentate gyrus normally occupied by EC projections; and (3) an increase in supragranular mossy fibers in some animals. The mossy fiber sprouting was especially prominent when the lesions encroached upon the hippocampus. The studies also reveal additional details about the normal organization of hippocampal pathways in cats. The most important points are: (1) there is a crossed projection from the entorhinal cortex to the contralateral dentate gyrus; and (2) there is a complex laminar organization of the commissural and associational terminal fields in the molecular layer of the dentate gyrus that appears to be related to the point of origin of the projections along the septotemporal axis of the hippocampus. This heretofore unrecognized aspect of the laminar organization of C/A terminations has important implications for the temporal competition hypothesis, which has been advanced to account for the development of these afferent systems.     

The '2-week rule' for suspected breast carcinoma: a qualitative study of the views of patients and professionals.

BACKGROUND: The '2-week rule' for the referral of patients with potential cancers is an important but controversial development. AIMS: To investigate the 2-week rule for women with breast problems from the perspective of the patients and of healthcare professionals. DESIGN OF STUDY: Qualitative study using semi-structured interviews. SETTING: Patients referred to two breast care units and professionals from primary and secondary care in Teesside and Hartlepool. METHOD: Semi-structured interviews with a purposive sample of 12 patients referred under the 2-week rule and 20 professionals. RESULTS: All women experienced considerable worries in the time leading up to diagnosis. This affected relationships with others, and they used selective telling to help maintain control over their own anxiety and prevent anxiety in others. They were not aware of the 2-week rule as a new initiative, but wanted quick referral to assure them that they did not have cancer. Patients felt they needed more information about breast symptoms and the referral process. Comments about communication with professionals, both good and poor, were frequent in their accounts, which contrasted with the absence of such concerns in the accounts of the professionals. The professionals thought that the 2-week rule was advantageous in reducing anxiety, but thought that disadvantages included longer waits for patients referred outside the rule and increased pressure on hospital services. Cultural changes, including increased patient assertiveness and 'breast awareness', were considered important contextual factors. General practitioners (GPs) were concerned about missing diagnoses in patients statistically unlikely to have carcinomas. CONCLUSION: Differences in emphasis were apparent, with patients wanting to be assured that they did not have cancer, specialists concerned both about increased workload and the impact on patients with cancers, and GPs anxious about missing diagnoses. The 2-week rule compromises professional autonomy, which partially accounts for the anger directed against it. There is a need for patients to have more information, and they place great value on good communication. All patient responders experienced significant distress while waiting to be seen.     

Lack of Nonshivering Thermogenesis in Infants Anesthetized with Fentanyl and Propofol

Background: Sweating, vasoconstriction, and shivering have been observed during general anesthesia. Among these, vasoconstriction is especially important because-once triggered-it minimizes further hypothermia. Surprisingly, the core-temperature plateau associated with vasoconstriction appears to preserve core temperature better in infants and children than adults. This observation suggests that vasoconstriction in anesthetized infants may be accompanied by hypermetabolism. Consistent with this theory, unanesthetized infants rely on nonshivering thermogenesis to double heat production when vasoconstriction alone is insufficient. Accordingly, the authors tested the hypothesis that intraoperative core hypothermia triggers nonshivering thermogenesis in infants.

Methods: With Ethics Committee approval and written parental consent, the authors studied six infants undergoing abdominal surgery. All were aged 1 day to 9 months and weighed 2.4-9 kg. Anesthesia was maintained with propofol and fentanyl. The infants were mechanically ventilated and allowed to cool passively until core (distal esophageal) temperatures reached 34-34.5 degrees Celsius. Oxygen consumption-the authors' index of metabolic rate- was recorded throughout cooling. Because nonshivering thermogenesis triples circulating norepinephrine concentrations, arterial blood was analyzed for plasma catecholamines at [nearly equal] 0.5 degrees Celsius intervals. Thermoregulatory vasoconstriction was evaluated using forearm - fingertip, skin-surface gradients, with gradients exceeding 4 degrees Celsius, indicating intense vasoconstriction. The patients were subsequently rapidly rewarmed to 37 degrees Celsius. Regression analysis was used to correlate changes in oxygen consumption and plasma catecholamine concentrations with core temperature.

Results: All patients were vasoconstricted by the time core temperature reached 36 degrees Celsius. Further reduction in core temperature to 34-34.5 degrees Celsius did not increase oxygen consumption. Instead, oxygen consumption decreased linearly. Hypothermia also failed to increase plasma catecholamine concentrations.     

The influence of epitope density on the estimation of the affinity of antibody for complex antigens.

The influence of the epitope density of the antigen on antibody affinity values determined by fluid- and solid-phase immunoassays was assessed. The affinity of the interaction of a panel of monoclonal anti-DNP antibodies of different affinities (as determined by equilibrium dialysis) for DNP-protein conjugates of various hapten substitution ratios was used as the test system. The results obtained showed that the epitope density of the antigen markedly influences the observed affinity values obtained by both experimental approaches. However, the monoclonal antibodies were ranked in affinity terms by both assays in a similar order to that given by equilibrium dialysis. It is concluded that provided due care is exercised in choosing an appropriate epitope density for the test antigen, these methods can be used to provide rapid estimations of average antibody affinities.     

Stage C adenocarcinoma of the prostate. An analysis of 551 patients treated with external beam radiation

We retrospectively reviewed records of 551 patients with clinical Stage C prostatic adenocarcinoma treated with 60 to 70 Gy external beam radiation. Elective pelvic node irradiation was given to 247 patients (45%). Follow-up for all surviving patients ranged from 16 to 201 months (median, 6.5 years; mean, 7 years). The 5-, 10-, and 15-year uncorrected actuarial survival rates were 72%, 47%, and 27%, respectively. Disease-free survival rates were 59%, 46%, and 40% at the corresponding times. Actuarial local control rates were 88%, 81%, and 75% at 5, 10, and 15 years, respectively. Disease-free survival was adversely affected by high pathologic grade, disease fixed to the pelvic sidewall, invasion of the bladder, prior transurethral resection, hydronephrosis, and elevated serum levels of prostatic acid phosphatase and creatinine. Elective pelvic node irradiation did not improve the outcome. Complications of treatment were acceptable: minor anorectal and/or urinary symptoms, 11%; mild to moderate complications, 19%; serious problems requiring surgery, 3%. It is concluded that localized, high-energy external beam irradiation provides excellent local control of disease, low morbidity, and 5-, 10-, and 15-year survival rates that have not been rivaled by other treatment.     

Rapid chemical kinetic techniques for investigations of neurotransmitter receptors expressed in Xenopus oocytes

Xenopus laevis oocytes have been used extensively during the past decade to express and study neurotransmitter receptors of various origins and subunit composition and also to express and study receptors altered by site-specific mutations. Interpretations of the effects of structural differences on receptor mechanisms were, however, hampered by a lack of rapid chemical reaction techniques suitable for use with oocytes. Here we describe flow and photolysis techniques, with 2-ms and 100-μs time resolution, respectively, for studying neurotransmitter receptors in giant (≈20-μm diameter) patches of oocyte membranes, using muscle and neuronal acetylcholine receptors as examples. With these techniques, we find that the muscle receptor in BC₃H1 cells and the same receptor expressed in oocytes have comparable kinetic properties. This finding is in contrast to previous studies and raises questions regarding the interpretations of the many studies of receptors expressed in oocytes in which an insufficient time resolution was available. The results obtained indicate that the rapid reaction techniques described here, in conjunction with the oocyte expression system, will be useful in answering many outstanding questions regarding the structure and function of diverse neurotransmitter receptors.