Desflurane-mediated sympathetic activation occurs in humans despite preventing hypotension and baroreceptor unloading

BACKGROUND: Increasing concentrations of desflurane result in progressive decreases in blood pressure (BP) and, unlike other currently marketed, potent volatile anesthetics, heightened sympathetic nervous system activity. This study aimed to determine whether baroreflex mechanisms are involved in desflurane-mediated sympathetic excitation. METHODS: Healthy volunteers were anesthetized with desflurane (n = 8) or isoflurane (n = 9). Heart rate (HR; measured by electrocardiograph), blood pressure (BP; measured by arterial catheter), and efferent sympathetic nerve activity (SNA; obtained from percutaneous recordings from the peroneal nerve) were monitored. Baroreflex sensitivity was evaluated at baseline while volunteers were conscious and during 0.5, 1, and 1.5 minimum alveolar concentration (MAC) anesthesia via bolus injections of nitroprusside (100 microg) and phenylephrine (150 microg) to decrease and increase BP. To prevent the BP decline with increasing depths of anesthesia, phenylephrine was infused to maintain mean BP at the 0.5 MAC level. RESULTS: The HR, BP, and SNA were similar between the groups at the conscious baseline measurement. Efferent SNA did not change during higher MAC of isoflurane, but it increased progressively as desflurane concentrations were increased beyond 0.5 MAC, despite maintaining BP at the 0.5 MAC value with phenylephrine infusions (P < 0.05). Cardiac baroslopes (based on changes in HR) were progressively and similarly decreased with increasing concentrations of isoflurane and desflurane (P < 0.05). Sympathetic baroslopes (based on SNA) decreased with increasing isoflurane concentrations but were maintained with increasing concentrations of desflurane; the response was significantly different between groups. CONCLUSIONS: The increase in basal levels of SNA with increasing concentrations of desflurane persisted despite "fixing" BP and thus is probably not due to hypotension and unloading of the baroreceptors. Further, the preservation of reflex increases in SNA to nitroprusside during desflurane indicates that desflurane preserves one component of the baroreflex in humans when BP is "fixed."     

Biosynthesis of progesterone derived neurosteroids by developing avian CNS: in vitro effects on the GABAA receptor complex

Although enthusiasm for measuring health-related quality of life (HRQL) in clinical trials exists, information is limited on the meaning of scores. We examined the relation between scores from the 34-item Medical Outcomes Study HIV Health Survey (MOS-HIV) and the more detailed HIV Overview of Problems-Evaluation System (HOPES) using the responses of 318 HIV-infected outpatients being treated in Los Angeles and Baltimore. With the HOPES problem statements as independent variables, statistically significant predictors of the variation in MOS-HIV scores for the Physical Function, Mental Health, and Energy/Fatigue scales were identified using stepwise regression. Approximately 60% to 70% of the variation in each of the scores was explained by five to seven different HOPES problem statements, with a single item explaining 47% to 59% of the variation. We created illustrative profiles for each of the three MOS-HIV scales using the HOPES items identified in the regressions. Independent of the scale, persons scoring in the top MOS-HIV quartile tended to report few if any problems, whereas a decline in score to the next quartile was characterized by functional difficulties (e.g., "HIV interferes with work"). The onset of specific problems might trigger further evaluation and potential intervention from health care providers to help maintain patient functioning.     

Cluster analysis and disease mapping--why, when, and how? A step by step guide

Growing public awareness of environmental hazards has led to an increased demand for public health authorities to investigate geographical clustering of diseases. Although such cluster analysis is nearly always ineffective in identifying causes of disease, it often has to be used to address public concern about environmental hazards. Interpreting the resulting data is not straightforward, however, and this paper presents a guide for the non-specialist. The pitfalls include the fact that cluster analyses are usually done post hoc, and not as a result of a prior hypothesis. This is particularly true for investigations prompted by reported clusters, which have the inherent danger of overestimating the disease rate through "boundary shrinkage" of the population from which the cases are assumed to have arisen. In disease surveillance the problem of making multiple comparisons can be overcome by testing for clustering and autocorrelation. When rates of disease are illustrated in disease maps undue focus on areas where random fluctuation is greatest can be minimised by smoothing techniques. Despite the fact that cluster analyses rarely prove fruitful in identifying causation, they may-like single case reports-have the potential to generate new knowledge.     

A modular neural network approach to fault diagnosis

Certain real-world applications present serious challenges to conventional neural-network design procedures. Blindly trying to train huge networks may lead to unsatisfactory results and wrong conclusions about the type of problems that can be tackled using that technology. In this paper a modular solution to power systems alarm handling and fault diagnosis is described that overcomes the limitations of "toy" alternatives constrained to small and fixed-topology electrical networks. In contrast to monolithic diagnosis systems, the neural-network-based approach presented here accomplishes the scalability and dynamic adaptability requirements of the application. Mapping the power grid onto a set of interconnected modules that model the functional behavior of electrical equipment provides the flexibility and speed demanded by the problem. After a preliminary generation of candidate fault locations, competition among hypotheses results in a fully justified diagnosis that may include simultaneous faults. The way in which the neural system is conceived allows for a natural parallel implementation.     

Hybrid genetic optimization and statistical model based approachfor the classification of shadow shapes in sonar imagery

We present an original statistical classification method using a deformable template model to separate natural objects from man-made objects in an image provided by a high resolution sonar. A prior knowledge of the manufactured object shadow shape is captured by a prototype template, along with a set of admissible linear transformations, to take into account the shape variability. Then, the classification problem is defined as a two-step process: 1) the detection problem of a region of interest in the input image is stated as the minimization of a cost function; and 2) the value of this function at convergence allows one to determine whether the desired object is present or not in the sonar image. The energy minimization problem is tackled using relaxation techniques. In this context, we compare the results obtained with a deterministic relaxation technique and two stochastic relaxation methods: simulated annealing and a hybrid genetic algorithm. This latter method has been successfully tested on real and synthetic sonar images, yielding very promising results     

Building the IBM 4758 secure coprocessor

Meeting the challenge of building a user-configurable secure coprocessor provided several lessons in hardware and software development and continues to spur further research. In developing the 4758, we met our major research security goals and provided the following features: (1) a lifetime-secure tamper-responding device, rather than one that is secure only between resets that deployment-specific security officers perform; (2) a secure booting process in which each layer progressively validates the next less-trusted layer, with hardware restricting access to its secrets before passing control to that layer; (3) an actual manufacturable product - a nontrivial accomplishment considering that we designed the device so that it does not have a personality until configured in the field; (4) the first FIPS 140-1 Level 4 validation, arguably the only general-purpose computational platform validated at this level so far; and (5) a multipurpose programmable device based on a 99-MHz 486 CPU internal environment, with a real operating system, a C language development environment and relatively high-speed cryptography     

The early detection of colorectal cancer

A review of the American Cancer Society's statistics for colorectal cancer indicates that there has been little improvements in the survival rate for this disease in the past 25 years. Although there have been advances in surgical techniques, radiation therapy, and chemotherapy, the key to improved survival rates is earlier diagnosis. A significant percentage of patients continues to present with regional or distal metastasis at the time of their initial diagnosis. Both proctosigmoidoscopy and guaiac impregnated filter slide paper methods have been productive in diagnosing this disease at an earlier stage. The "Hemoccult" test, however, is inexpensive, can be used on a routine basis, is easier for patients to perform themselves, and is aesthetically pleasing. It represents a significant cost savings compared to proctosigmoidoscopy and should be advocated for routine use in all patients over 40 years of age. Although there continues to be a role for local and regional mass screening programs, significant improvements in colorectal survival rates cannot be expected until routine application of this type of screening is practiced.     

Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide

A healthy adolescent boy was treated on two occasions for an overdose of chlorpropamide (Diabinese). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an "insulin antagonist." The administration of diazoxide was effective in our patient, substantially reducing the plasma insulin level; this agent may be the "insulin-antagonist" of choice for use in sulfonylurea-induced hypoglycemia.     

Micropuncture studies of glucose transport in the dog: mechanism of renal glycosuria

Clearance and micropuncture studies were performed in 23 dogs without glucose loading to examine the tubule mechanism of renal glycosuria. Studies were carried out in three groups of animals before and after 10% extracellular volume expansion, and administration of maleic acid in low dose at 150 mumol/kg and in high dose at 300 mumol/kg. Specific hexokinase methods were used for the determination of glucose in tubule fluid and urine. Under control conditios, glucose reabsorption occurred predominantly in the proximal tubule. In all three groups, proximal tubule reabsorption of both sodium and glucose was inhibited in the second phase, showing a good correlation between the two. In contrast, fractional urinary glucose excretion remained unchanged after volume expansion and low-dose maleic acid, indicating reabsorption of virtually all the increased glucose load at a further "distal" site. On the other hand, significant glycosuria developed after high-dose maleic acid that was a result of reduced glucose reabsorption in the distal nephron, in addition to the proximal effect. It was concluded that distal glucose transport plays a significant role in regulating urinary glucose excretion and maintains renal thershold for glucose,