Peripartum anesthetic management of a patient with brittle cornea syndrome.

Brittle cornea syndrome (BCS) is a rare autosomal recessive disease that affects the connective tissue. The syndrome is caused by genetic changes in the 4.7-Mb interval between the D16S3423 and D16S3425 markers on the 16q24 chromosome and mutations in the Zinc-Finger 469 gene (ZNF469). BCS is characterized by thin and fragile cornea that tends to perforate spontaneously or as a result of minor trauma to the eye. In addition, the patient usually suffers from hearing loss, mental retardation, hyperextensibility of skin and joints, as well as varying degrees of scoliosis. This phenotypical expression presents an interesting challenge to anesthetic care. We briefly present the perioperative management of a patient with BCS who underwent three cesarean sections.

Psoriasis and diabetes: a population-based cross-sectional study.

BACKGROUND: Previous reports have shown an association between psoriasis and the metabolic syndrome, but there are only a few studies on the association between psoriasis and diabetes. OBJECTIVES: To study the association between psoriasis and diabetes. METHODS: A cross-sectional study was performed utilizing the database of Clalit Health Services (CHS). Patients who were diagnosed with psoriasis were compared with CHS enrolees without psoriasis regarding the prevalence of diabetes. Patients with diabetes were identified using the CHS chronic diseases registry. Chi-squared tests were used to compare categorical parameters. Logistic regression models were used for multivariate analyses. RESULTS: The study included 16 851 patients with psoriasis and 74 987 subjects without psoriasis (control patients). The proportion of diabetes was significantly higher in patients above 35 years (P < 0.05). The age-adjusted proportion of diabetes was significantly higher in psoriasis patients as compared to the control group [odds ratio (OR), 1.38, P < 0.05] and was similar in men and women (OR, 1.32, 1.45, respectively). A multivariate logistic regression model showed that psoriasis was significantly associated with diabetes, independently of age and gender (OR, 1.58, P < 0.001). CONCLUSIONS: Our study supports previous reports of an association between psoriasis and diabetes. Dermatologists taking care of patients with psoriasis should be aware of this association and advise the patients to reduce additional risk factors such as smoking, hypertension or dyslipidemia.

The association between the renin-angiotensin-aldosterone system and arterial stiffness in young healthy subjects.

Aldosterone might affect arterial stiffening, in both the short- and long-term. We investigated a possible association between excess aldosterone, reflected by an increased aldosterone : renin ratio (ARR) and pulse wave velocity (PWV) in young healthy adults. In a single-centre study, 60 subjects were evaluated for lipid profile, glucose, hs-CRP, renin and aldosterone. PWV was performed as a simple non-invasive recording and computer analysis of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). The ARR was significantly, positively associated with PWV: r = 0.298, P = 0.02. ARR was not associated with anthropometric variables, blood pressure (BP), metabolic and inflammatory parameters. In conclusion, the ARR was significantly associated with PWV and may exhibit direct effects of aldosterone on the vascular wall, which are not related to changes in conventional cardiovascular risk factors.

The cumulative heat strain index--a novel approach to assess the physiological strain induced by exercise-heat stress.

The cumulative heat strain index (CHSI) is a new approach for assessing the total physiological strain experienced by subjects exposed to an exercise-heat stress. The index is based on inherent physiological logic that combines the thermoregulatory strain, which is described by the area under the hyperthermic curve, and the circulatory strain, which is characterized by heart-beat count. According to this model, the index reflects the dynamics of changes in the thermoregulatory and cardiovascular components and accounts for the complementary nature of the interaction between them. Mathematically, the index is calculated as follows: CHSI =[ sigma(0-t) hb-fc(0) x t] x l0(-3) x [ integral (0-t) Tre x dt-Tre(0) x t] (units) Where: hb=heart beats, fc(0)=initial lowest heart rate (bpm), Tre = rectal temperature (Tre(0) = baseline Tre) (degrees C) and t = time (min) from the onset of measurements. Four sets of data, from various former studies, have been used to demonstrate the index's applicability and its sensitivity to differentiate between levels of stain under various stressful conditions (e.g. clothing insulation, acclimation to heat and levels of tolerance to heat). In all cases, the index was found to be a sensitive tool for assessing the level of strain. Furthermore, the CHSI can be used to predict potential strain. The index's high sensitivity arises from its nature, which reflects miniature differences in the pattern of changes in the dynamics of physiological responses and therefore is a powerful and practical tool for evaluating even minor changes in strain.

Peripheral target contact regulates Ca2+ channels in the cell bodies of bullfrog sympathetic ganglion B-neurons.

Tyrosine-hydroxylase immunohistochemistry demonstrated that a single injection of 120 mg/kg 6-hydroxydopamine (6-OHDA) reversibly disconnected bullfrog sympathetic ganglia from their peripheral targets. This was correlated with a decrease in sympathetic outflow to the eyes and a reversible decrease in pupil diameter. 6-OHDA did not damage the cell bodies of ganglionic neurons. Calcium channel current in ganglionic B-neurons, (measured at -10 mV; holding potential -60 mnV; Ba2+ as charge carrier; IBa) was reduced. It reached a minimum of about 40% of control amplitude 7-14 days after 6-OHDA injection and recovered to 73% of control amplitude after 63 days. 6-OHDA induced loss and recovery of functional sympathetic innervation of peripheral target tissues, as determined by measurement of pupil diameter, occurred at a similar rate. Thus, pupil diameter attained mininum values 7-14 days after 6-OHDA treatment and recovered to 81% of control after 63 days. The properties of Ca2+ channels in sympathetic neurons are, therefore, determined by continuity of contact with peripheral target. 6-OHDA also decreased the peak amplitude and duration of the afterhyperpolarization (a.h.p) that follows the action potential (a.p.). The rate of recovery of a.h.p duration was more rapid than the rate of recovery of peak a.h.p. amplitude. This may reflect known differences in properties of two types of Ca2+-sensitive K currents. IC and IAHP, IC, which is responsible for the peak amplitude of the a.h.p has a low affinity for Ca2+, whereas IAHP, which determines a.h.p. duration, has higher Ca2+ affinity.

A structural mode-coupling approach to 15N NMR relaxation in proteins.

The two-body Slowly Relaxing Local Structure (SRLS) model was applied to (15)N NMR spin relaxation in proteins and compared with the commonly used original and extended model-free (MF) approaches. In MF, the dynamic modes are assumed to be decoupled, local ordering at the N-H sites is represented by generalized order parameters, and internal motions are described by effective correlation times. SRLS accounts for dynamical coupling between the global diffusion of the protein and the internal motion of the N-H bond vector. The local ordering associated with the coupling potential and the internal N-H diffusion are tensors with orientations that may be tilted relative to the global diffusion and magnetic frames. SRLS generates spectral density functions that differ from the MF formulas. The MF spectral densities can be regarded as limiting cases of the SRLS spectral density. SRLS-based model-fitting and model-selection schemes similar to the currently used MF-based ones were devised, and a correspondence between analogous SRLS and model-free parameters was established. It was found that experimental NMR data are sensitive to the presence of mixed modes. Our results showed that MF can significantly overestimate order parameters and underestimate local motion correlation times in proteins. The extent of these digressions in the derived microdynamic parameters is estimated in the various parameter ranges, and correlated with the time scale separation between local and global motions. The SRLS-based analysis was tested extensively on (15)N relaxation data from several isotropically tumbling proteins. The results of SRLS-based fitting are illustrated with RNase H from E. coli, a protein extensively studied previously with MF.

Changes in heart rate variability following acclimation to heat.

We studied the sympatho-vagal balance during acclimation to heat in eight healthy individuals. The subjects, dressed in shorts and tennis shoes, underwent a 10 d procedure of acclimation. Daily exposure lasted 115 min--5 min rest followed by 2 bouts of 50 min exercise (walking on a treadmill at a work load of approximately 350 watt) separated by 10 min rest-at 40 degrees C and 40% relative humidity. We analyzed the time and frequency domains of 256 R-R intervals, toward the end of the second bout of exercise, on the first and tenth days of acclimation. Typical changes for heat acclimation (a reduction in rectal temperature and heart rate, an increase in sweat rate) were observed. Concomitant to a decrease in the final heart rate on the tenth day, sympathetic tone increased. We suggest that, except for the chronotropic response, changes in the sympatho-vagal balance may reflect several adaptive mechanisms of the cardiovascular system. Peripheral factors rather than intrinsic cardiac factors are of relatively greater importance in the direct control of cardiac function.

[Prediction of physiological response from mathematical models].

The ability to predict the physiological responses of workers exposed to extreme environmental conditions, has been a challenge to environmental physiologists for more than 3 decades. Therefore, mathematical models have been developed to predict metabolic rate under various levels of work intensity and dynamic changes in body temperature and heart rate. Based on the effect of exercise on the cardiovascular system, a model was developed to predict mean arterial blood pressure as a function of heart rate. Physiological strain could also be estimated on the basis of thermoregulatory and cardiovascular strains. This paper summarizes knowledge accumulated during 25 years of studies in the field of mathematical modeling of physiological parameters. Besides analyzing the logic underlying each model, it explains the scientific approach in developing a model from its early concept to the model's application in the field.

[Man in a hot climate--early studies of the Institute of Military Physiology].

In the 1950's many IDF soldiers were hospitalized for heat stroke--about 25% of whom died. Analyzing these cases revealed that commanders misinterpreted human ability to perform in the heat and ignored basic concepts of fluid and electrolyte balance and heat load. In the early 1960's a series of studies was conducted with regard to soldiers' performance in the heat. The first study (1959), which later became a classic, was conducted during a 21-day march from Eilat to Metula, crossing all climatic zones of Israel. The study was followed by other investigations which approached the issues of voluntary dehydration, fluid consumption vs sweat loss, salt additives, and the effect of heat load on performance. Based on these early studies, proper regulations were issued to field officers. Over the years, the lessons learned from these studies saved many lives. The number of cases of heat stroke and of other climate-related injuries was dramatically reduced, and performance was enhanced.

Backbone dynamics of escherichia coli adenylate kinase at the extreme stages of the catalytic cycle studied by (15)N NMR relaxation.

Adenylate kinase from Escherichia coli (AKeco), consisting of a single 23.6 kDa polypeptide chain folded into domains CORE, AMPbd, and LID, catalyzes the reaction AMP + ATP --> 2ADP. Domains LID and AMPbd execute large-scale movements during catalysis. Backbone dynamics of ligand-free and AP(5)A-inhibitor-bound AKeco were studied comparatively with (15)N NMR relaxation methods. Overall diffusion with correlation times of 15.05 (11.42) ns and anisotropy D(parallel)/D(perp) = 1.25 (1.10), and fast internal motions with correlation times up to 100 ps (50 ps), were determined for AKeco (AKecoAP(5)A). Fast internal motions affect 93% of the AKeco sites, with pronounced preference for domains AMPbd and LID, and 47% of the AKecoAP(5)A sites, with limited variability along the chain. The mean squared generalized order parameters, , of secondary structure elements and loops are affected by ligand binding differentially and in a domain-specific manner. Nanosecond motions predominate within AMPbd. Prominent exchange contributions, associated in particular with residue G10 of the nucleotide-binding P-loop motif, are interpreted to reflect hydrogen-bond dynamics at the inhibitor-binding site. The hypothesis of energetic counter balancing of substrate binding based on crystallographic data is strongly supported by the solution NMR results. Correlations between backbone dynamics and domain displacement are established.

Exertional heat stroke--the prevention of a medical emergency.

In most cases, exertional heat stroke (EHS) can be prevented in the military setting. The actions taken by the Israel Defense Forces (IDF) and their outcome prove this well. Unfortunately, despite the available information, there are still incidents of failure of command in conducting physical exercise, leading to EHS. In our experience, most incidences are a consequence of disregarding safety regulations. The application of simple and reasonable measures will not only prevent accidents from happening, but will also result in better trained soldiers.

Can gender differences during exercise-heat stress be assessed by the physiological strain index?

A physiological strain index (PSI) based on rectal temperature (Tre) and heart rate (HR) was recently suggested to evaluate exercise-heat stress. The purpose of this study was to evaluate PSI for gender differences under various combinations of exercise intensity and climate. Two groups of eight men each were formed according to maximal rate of O2 consumption (VO2 max). The first group of men (M) was matched to a group of nine women (W) with similar (P > 0.001) VO2 max (46.1 +/- 2.0 and 43.6 +/- 2.9 ml. kg-1. min-1, respectively). The second group of men (MF) was significantly (P < 0. 001) more fit than M or W with VO2 max of 59.1 +/- 1.8 ml. kg-1. min-1. Subjects completed a matrix of nine experimental combinations consisting of three different exercise intensities for 60 min [low, moderate, and high (300, 500, and 650 W, respectively)] each at three climates (comfortable, hot wet, and hot dry [20 degrees C 50% relative humidity (RH), 35 degrees C 70% RH, and 40 degrees C 35% RH, respectively]). No significant differences (P > 0.05) were found between matched genders (M and W) at the same exposure for sweat rate, relative VO2 max (%VO2 max), and PSI. However, MF had significantly (P < 0.05) lower strain than M and W as reflected by %VO2 max and PSI. In summary, PSI applicability was extended for exercise-heat stress and gender. This index continues to show potential for wide acceptance and application.

Exertional heat stroke: a case series.

UNLABELLED: Exertional heat stroke (EHS) is a state of extreme hyperthermia that occurs when excess heat that is generated by muscular exercise exceeds the body's ability to dissipate it at the same rate. EHS is thought to coincide with previously healthy, highly motivated, and relatively untrained individuals exerting in hot environments for long periods. PURPOSE: To establish this notion, the present study was aimed to follow the trends in the incidence of EHS in the period 1988-1996. METHODS: During these years, 150 cases of male soldiers (age = 20+/-3 yr) were reported to our institute as suffering from heat illnesses. According to the files, 82 cases were definitely diagnosed as EHS. RESULTS: More than 50% of the cases occurred during the first 6 months in service. Most of the cases occurred during the summer season (June-September), but 30% of the cases occurred during the spring. EHS was not related to time in the day. Many cases occurred during the night or early morning, even under mild heat load. Forty percent of the cases occurred during very short activities, and about 60% occurred already during the first 2 h of exercise. The results were discussed in view of the regulations which prevail in the Israeli army. CONCLUSIONS: It seems that almost all EHS cases occurred when regulations were not strictly followed.

[Physiological aspects of women in combat].

Since military service is physically demanding, soldiers must maintain high levels of physical fitness for optimal performance of their duties. Women are at a physiological disadvantage when competing against men: they have a smaller muscle mass, more body fat, lower red blood cell counts, lower hemoglobin levels and smaller cardiac outputs. Women are slower and weaker than men and more prone to exercise-induced skeletal injuries. Fewer women than men meet the standards of physically demanding jobs. Therefore integrating women into physically demanding military-oriented jobs requires redesigning or modifying the tasks (different pace, mechanical aids, teamwork). While physical training can increase the physical capacity of women, training cannot completely eliminate gender differences. Thus the data presented do not imply that women cannot be integrated into combat units, but highlight gender-related differences which might have an effect on the ability of women to compete equally with men at the same task.

How significant is magnesium in thermoregulation?

Nine apparently healthy male subjects, mean age 22.8 yr, SD 4.1, free from disease, medication or addiction who gave informed consent, underwent acclimation process in a heat chamber; exposed during 2 h daily for 10 consecutive days to a temperature of 40 degrees C and 40% relative humidity while walking on a treadmill elevated by 3 degrees at a speed of 5 km/h (VO2 1.2 1.min-1). Serum, mononuclear and erythrocyte magnesium (S-Mg, M-Mg and E-Mg, respectively) were monitored on day 1, 5 and 10 before and after the heat exposure. S-Mg decreased while M-Mg increased after the heat exposures, suggesting a shift of S-Mg to mononuclear cells. The decrease of S-Mg was sustained at the end of the acclimation process. E-Mg increased up to day 5 and decreased gradually approximating the baseline by day 10. Mg appears to play a significant role in heat acclimation.

Acclimatization strategies--preparing for exercise in the heat.

More than 200 years ago, in 1768, Lind in his monograph: "An assay on diseases incidental to Europeans in hot climate" pointed out that habituation to hot climates reduced the danger to health. Two centuries later, Lind and Bass in a classical study which was carried out under hot/dry climatic conditions (49 degrees C and 20% rh) demonstrated that the adaptation to heat may be described as the series of physiological adjustments that occur when a person who is accustomed of living in a cool environment is transferred to a hot climate. This adaptation is a process which is fully achieved after 10 to 14 days of exposure to heat, but two thirds or even 75% of the adaptation is obtained already within 5 days (1). According to this study improved tolerance to heat is related to typical physiological changes: heightened sweating response, lowered heart rate, and lowered rectal temperature during exercise in the heat.

Heat intolerance induced by antidepressants.

A case in which prescription medications induced heat intolerance which led to heat stroke is presented. A subject who suffered from depression and was treated with fluoxetine HCL (prozac) and lithium carbonate was engaged in mild intermittent work for 4 hours under hot/dry climatic conditions (Ta = 37 degrees C, rh = 15%). The subject lost consciousness, was hyperthermic and suffered from disseminated intravascular coagulation. A year later residual cerebellar symptoms were still evident and severe atrophy of the cerebellar tissue was demonstrated in a CT scan. It is suggested that drug-induced heat intolerance was the predisposing factor that reduced the patient ability to sustain exercise-heat stress, and under the favorable environmental circumstances led to excessive heat accumulation which ultimately caused heat stroke. This is the first description, to our knowledge, of heat intolerance of a patient treated by a combination of fluoxetine and lithium carbonate.