Participation of the anterior hypothalamus in the baroreceptor reflex

1. On the basis of discrete electrical stimulation in the pre-optic region and anterior hypothalamus of anaesthetized cats, a depressor area has been defined, stimulation of which elicits a fall of arterial blood pressure of 30-50 mm Hg and a bradycardia of some 25%, caused by inhibition of sympathetic vasomotor tone and by vagal activation respectively. These are accompanied by a reduction in rate and depth of respiration.2. The depressor area, from which this pattern of response is elicited, lies ventral and caudal to the anterior commissure, and extends caudally in the dorsal hypothalamus, dorsal to the fornix.3. The pattern of response elicited from identified points in the depressor area was shown to be indistinguishable from that to baroreceptor afferent stimulation.4. A lesion destroying the hypothalamic depressor area bilaterally reduced the response to baroreceptor afferent stimulation. Lesions in the medullary depressor area which spared a large part of the nucleus of the tractus solitarius also reduced, but did not abolish, the baroreceptor reflex response. The two lesions combined abolished the reflex.5. It is concluded that the whole brain-stem depressor area, from the hypothalamus through the mid-brain to the medulla, constitutes a functional unit which integrates the response to baroreceptor afferent stimulation.     

Ultimate tensile strength of dentin: Evidence for a damage mechanics approach to dentin failure

Dentin structure and properties are known to vary with orientation and location. The present study explored the variation in the ultimate tensile strength (UTS) of dentin with location in the tooth. Hourglass specimens were prepared from dentin located in the center, under cusps, and in the cervical regions of human molar teeth. These were tested in tension at various distances from the pulp. Median tensile strengths ranged from 44.4 MPa in the inner dentin near the pulp, to 97.8 MPa near the dentino-enamel junction (DEJ). This increase in the median UTS with distance from the pulp to the DEJ was statistically significant (P <.001). Of particular importance was the observation that the UTS measurements followed a Weibull probability distribution, with a Weibull modulus of about 4.5. The Weibull behavior of the UTS data strongly suggests that the large variances in fracture strength data result from a distribution of preexisting defects in the dentin. These findings justify a damage-mechanics approach to studies of dentin failure.     

The pontomedullary area integrating the defence reaction in the cat and its influence on muscle blood flow

1. In anaesthetized cats the effects were investigated of electrical stimulation of regions in the caudal mesencephalon, pons and medulla on muscle blood flow, skin blood flow and arterial blood pressure.2. It was found that within the dorsal part of the well known pressor area there is a narrow strip, 2.5 mm lateral from the mid line, starting ventral to the inferior colliculus and ending in the medulla close to the floor of the IV ventricle, from which vasodilatation in skeletal muscles is selectively obtained. This strip is quite separate from the more ventral, efferent pathway for active vasodilatation running from the hypothalamic and rostral mesencephalic ;defence centre'.3. As in the case of the hypothalamic and rostral mesencephalic ;defence centre', the muscle vasodilatation obtained from the caudal strip is accompanied not only by a rise of arterial blood pressure, but also by tachycardia, vasoconstriction in the skin, pupillary dilatation and piloerection.4. Stimulation, restricted to the caudal strip, via implanted electrodes in unanaesthetized animals, produced a behavioural response resembling the defence reaction. The strip, therefore, is probably a caudal extension of the ;defence centre'.5. Unlike the vasodilatation elicited from the more rostral part of the ;defence centre' in the hypothalamus and mesencephalon, the muscle vasodilatation obtained on stimulation of the caudal strip was resistant to atropine, but was blocked by guanethidine.6. It is suggested that during naturally occurring defence reactions in the normal animal the ponto-medullary area is activated together with the hypothalamo-mesencephalic area, inhibition of vasoconstrictor tone then accompanying activation of the vasodilator nerve fibres in skeletal muscle.     

COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity

BackgroundThe novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients.MethodsData were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test.ResultsSixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored.ConclusionsSevere disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.     

Reproductive tract immune cells from pregnant women or those using depot medroxyprogesterone acetate show no excess susceptibility to HIV-1: Results of an ex vivo fusion assay

IntroductionEx vivo fusion assays offer an efficient method for studying HIV-1 entry associated with contraceptive use and pregnancy outside of cohort studies of HIV-1 incidence.MethodsWe measured ex vivo HIV-1 fusion to cervical or endometrial immune cells from three groups of women: pregnant, non-pregnant not using hormonal or intrauterine contraception, and using depot medroxyprogesterone acetate (DMPA).Results and conclusionsThere was no excess susceptibility to HIV-1 fusion of cells from pregnant women or DMPA users compared to controls. Although the number of target cells in endometrium was higher in DMPA users compared to controls, HIV-1 fusion was lower.ImplicationsIn ex vivo assays, HIV-1 showed no enhanced fusion to cervical immune cells from pregnant women or DMPA users compared to controls, and lower fusion to endometrial immune cells from DMPA users. This assay is useful for studying hormonal and contraceptive effects on HIV-1 entry into reproductive tract immune cells.     

Motor neuron disease with neurofibrillary tangles in a non-Guamanian patient

Neurofibrillary tangles are described in Guamanian and post-encephalitic forms of motor neuron discase (MND) but not in sporadic MND. We report the neuropathological findings in a 79-year-old man who died after a 1-year history of MND without extrapyramidal features or dementia. There was no family history of neurological disease and he had not visited Guam. The spinal cord showed loss of anterior horn cells, and skeletal muscle typical changes of denervation. The brain appeared macroscopically normal but histology revealed many neurofibrillary tangles, particularly in medial temporal lobe structures, insula, nucleus basalis, hippocampus, oculomotor nucleus, raphe nuclei and locus ceruleus. Neurofibrillary tangles were not seen in the primary motor cortex, which appeared histologically unremarkable. Occasional tangles were present in the substantia nigra and pontine nuclei. None were seen in the cerebellum, medulla or spinal cord. The tangles were argyrophilic, and, in sections stained with thioflavin-S, both the intracellular and the extracellular tangles fluoresced strongly under ultraviolet light. The intracellular neurofibrillary tangles reacted strongly with an antibody to tau protein, and only occasional tangles showed weak ubiquitin immunoreactivity. Scattered neuropil threads were present in the cortex in the areas of neurofibrillary tangle formation. No plaques were present in any part of the brain and no A4/ protein immunoreactivity was detected. Ultrastructural examination revealed Alzheimer-type neurofibrillary tangles composed of paired helical filaments. The present findings further extend the spectrum of diverse neurological disorders associated with neurofibrillary tangles.     

Identifying patients at low risk of death from cardiac failure after operation for postinfarct ventricular tachycardia

BACKGROUND: In unselected patients, cardiac failure accounted for most deaths after antiarrhythmic operation (ER) for postinfarction ventricular tachycardia (VT). This study aimed to determine whether patients at low risk of this outcome could be predicted from a retrospective analysis of variables from 100 consecutive ER patients. METHODS: Thirteen variables suggested by other researchers as predictive of outcome were analyzed. At the time of study, ER was the only therapy available for drug refractory VT. RESULTS: Only emergency ER, wall motion score less than 3 and Killip classification were significantly related to death from cardiac failure. The lack of correlation between emergency ER and variables of ER timing, VT less than 24 hours of ER or VT type implies that the need for emergency ER is also related to ventricular dysfunction. Multivariate analysis identified a group at particularly low risk of death with a specificity of 95%. CONCLUSIONS: Patients at low risk of death after ER can be identified prospectively. In the implantable cardioverter defibrillator era, elective ER is best reserved for such patients. Emergency ER may still be justified in younger patients without comorbidity who will die of VT without it.     

The vagaries of self-reports of physical activity: a problem revisited and addressed in a study of exercise promotion in the over 65s in general practice.

BACKGROUND: The assessment of levels of physical activity relies upon suitable measurement tools. OBJECTIVE: We aimed to investigate whether a practice nurse, using a motivational interview technique, could encourage older patients to increase their physical activity. METHODS: Health and well-being were monitored at baseline and 8 weeks following intervention. Physical activity levels were ascertained using both a self-report measure and ambulatory heart-rate monitoring. RESULTS: Whilst patients reported higher levels of physical activity at follow-up, this finding was not confirmed by the heart-rate data. CONCLUSION: The study concludes that patients tend to overestimate the amount of physical activity undertaken and that ambulatory heart-rate monitoring may be more useful for verifying actual behaviour.     

'Culture-negative' prosthetic valve endocarditis. Hazards of postoperative steroid therapy for unexplained fever

Two patients had prolonged unexplained fever along with multiple negative blood cultures after cardiac valve replacement surgery. Following the administration of corticosteroids for presumed postpericardiotomy syndrome, both patients improved symptomatically and defervesced, only to have positive blood cultures for Staphylococcus epidermidis shortly thereafter. The theoretical and practical risks of the empiric use of anti-inflammatory agents for unexplained post-operative fever are reviewed. "Culture-negative" prosthetic valvular infection due to prior antibiotic prophylaxis or therapy must be strongly considered in the evaluation of such unexplained fever.     

Chronic toxicity of dietary disodium arsenate heptahydrate to juvenile rainbow trout (Oncorhynchus mykiss)

Juvenile rainbow trout were fed semi-purified diets containing graded levels of disodium arsenate heptahydrate (DSA) for 12–24 weeks under standard laboratory conditions to define the maximum acceptable toxicant concentration (MATC) and to correlate signs of toxicity with diet and tissue arsenic concentrations. The MATC for DSA was between 13 and 33 g As/g diet or 0.281–0.525 mg As/kg body weight/day. The most sensitive and reliable indicator of chronic dietary DSA toxicity in rainbow trout was chronic inflammation of the gallbladder wall. Chronic inflammatory changes in the sub-epithelial tissues of the gallbladder wall were evident in 71% of rainbow trout exposed to 33 g As/g diet for 24 weeks, and 100% of rainbow trout exposed to 65 g As/g diet for 24 weeks or 49 g As/g diet for 12 weeks. No fish exposed to 13 g As/g diet or less for up to 24 weeks showed any demonstrable gallbladder lesions or any other ill effect of arsenic exposure. Other signs of chronic dietary DSA toxicity to rainbow trout included decreased growth rate, mild to moderate anemia, and, at higher levels of exposure, active feed refusal leading to decreased feed consumption. Mild nephrocalcinosis was noted in one experiment where kidney arsenic residues exceeded 14 g As/g tissue dry weight.Supported by the Natural Sciences and Engineering Research Council of Canada and the Ontario Ministry of Agriculture and FoodPortions of this material were presented at the 29th Annual Meeting of the Canadian Federation of Biological Societies, June 16–20, 1986, Guelph, Ontario, and the 14th Annual Aquatic Toxicity Workshop, November 2–4, 1987, Toronto, Ontario, Canada