The effect of compression rate and slope on the incidence of symptomatic Eustachian tube dysfunction leading to middle ear barotrauma: a Phase I prospective study.

Introduction: Symptomatic Eustachian tube dysfunction (ETD) and middle ear barotrauma (MEB) are the most common reported complications during hyperbaric oxygen (HBO2) treatment. There is no standardized rate of compression (ROC) reported to decrease the incidence rates of ETD and MEB during hyperbaric treatments. Few studies actually demonstrate that the ROC decreases the incidence of ETD or MEB. Methods: Our study was designed to determine an optimal hyperbaric chamber compression rate that might reduce the incidence of symptomatic ETD leading to MEB during the compression phase of treatment in a multiplace hyperbaric chamber. Data was collected prospectively over 2,807 elective patient treatments compressed using a U.S. Navy Treatment Table 9 (USN TT9) with a modified ROC. ROC was assigned using two variables, time (10 vs.15 minutes) and slope (linear vs. non-linear compression). Patients were exposed to all four compression schedules in a consecutive daily fashion. We recorded any patient requiring a stop during initial compression due to ear discomfort. Anyone requiring a stop was evaluated post treatment for MEB. Findings were compared to our standard 10-minute linear ROC. Evaluation of the tympanic membrane was accomplished using video otoscopy. Barotrauma when present was classified using both the Teed and O'Neill grading systems. Data was analyzed using basic statistical methods. Results: When comparing four different rates of compression during an elective USN TT9 in a multiplace (Class A) chamber there is a decreased incidence for symptomatic ETD when using a 15-minute linear compression schedule (p-value ⟨0.05). Conclusion: Using a 15-minute linear compression schedule is associated with less symptomatic ETD and less MEB when performing an elective 45 fsw (USN TT9) hyperbaric treatment in a Class A chamber. Asymptomatic ETD and MEB were not considered in this study.

Antipruritic effect of pretreatment with topical capsaicin 8% on histamine- and cowhage-evoked itch in healthy volunteers: a randomized, vehicle-controlled, proof-of-concept trial.

BACKGROUND: Chronic itch is difficult to treat. Low-concentration topical capsaicin (0·006-0·05%) has previously been applied in itch therapy but evidence on its efficacy is contradictory. OBJECTIVES: This vehicle-controlled, double-blinded study investigated the effect of topical capsaicin 8% after 1- and 24-h application on evoked itch, neurogenic inflammation and itch-associated dysaesthesia. METHODS: Sixteen healthy volunteers (aged 22 ± 0·5 years, nine female) were treated with capsaicin for 1 h and 24 h, and vehicle for 24 h on each volar forearm. Subsequently, histamine (1%, administered prick test lancets) and cowhage (40-45 spicules) were applied to the pretreated areas. Evoked itch and pain intensities were recorded for 10 min using a visual analogue scale (0-10 cm), while sensitivity to touch-evoked itch was evaluated using von Frey filaments before and after itch provocations. Neurogenic inflammation was assessed using perfusion imaging. RESULTS: In the vehicle areas peak itch responses to histamine and cowhage were 4·67 ± 0·58 and 5·15 ± 0·71, respectively. Capsaicin pretreatment reduced peak itch responses to histamine and cowhage after 24-h pretreatment to 1·41 ± 0·58 (P = 0·003) and 0·81 ± 0·18, (P < 0·001), respectively. Capsaicin pretreatment for 1 h reduced only cowhage-induced itch (P = 0·023). Furthermore, 24-h capsaicin pretreatment abolished punctuate hyperknesis and lowered histamine-induced neurogenic inflammation but did not affect weal reactions. CONCLUSIONS: Topical capsaicin 8% pretreatment for 24 h reduced histaminergic and nonhistaminergic itch by about 75%, while a significant reduction (≈60%) was achieved for only nonhistaminergic itch in a standard 1-h treatment. Further investigations are needed to elucidate the clinical potential of high-concentration capsaicin as an antipruritic.

Immunopathology of immune-mediated (type 1) diabetes.

Immune-mediated diabetes is established as an autoimmune disease, which most often is induced during late infancy or early childhood. Multiple genetic lesions in immune tolerance are required before autoimmunity can be sustained once induced by environmental agents, such as viruses. The diagnostic hallmarks of the disease are the islet autoantibodies, which should be made routinely available to physicians to distinguish this disease from other forms of diabetes. The ability to identify individuals with impending IMD and those at high risk of IMD lends itself to the development of clinical trials to prevent diabetes by immunologic means. We believe that this will soon be possible with the development and use of vaccines.

Autoimmune hypogonadism as part of an autoimmune polyglandular syndrome.

The most compelling case for autoimmune mediated hypogonadism occurs when ovarian failure is part of an autoimmune polyglandular syndrome (APS). In patients with the rare, recessively inherited type 1 APS (APS-1), characterized by the triad of chronic mucocutaneous moniliasis, hypoparathyroidism, and Addison's disease, primary amenorrhea (elevated pituitary gonadotropins) or oligomenorrhea and infertility are constant features. Ovarian failure is associated with autoantibodies to steroid hormone secreting cells in the adrenal cortex, Leydig cells of the testes, granulosa/thecal cells of the Graffian follicles, corpus luteum, and the syncytiotrophoblast of the placenta. These autoantibodies react with 3 P450 enzymes involved with steroidogenesis, namely, 21-hydroxylase (adrenal specific), 17 alpha-hydroxylase, and the side chain cleavage enzyme. Recently the 14 exon, APS-1 (autoimmune regulator or AIRE) gene has been cloned (chr. 21p22.3), and multiple mutants discovered. Parents who are obligatory heterozygotes for a single mutant gene lack clinical features of APS-1. They also do not develop APS-1 autoantibodies. Thus, hypogonadal patients without features of APS-1 are unlikely to have AIRE gene mutations. In the more common APS-2/3, characterized by combinations of autoimmune thyroid disease, immune mediated type 1 diabetes, vitiligo, pernicious anemia, and Addison's disease (type 2, not type 3), ovarian disease may be seen. In primary hypogonadism outside of the context of an APS, these autoantibodies are rare.

A case study in assessing an ethnically diverse community-based aging population: a multimethod approach.

Obtaining useful information to improve services for older, multi-ethnic populations requires a nontraditional approach to assessing needs that can overcome both cultural barriers and natural suspicions about research. This case study describes a multimethod needs assessment conducted in a large senior housing facility, where 58% of residents were non-English-speaking. Methods of data collection were both qualitative and quantitative. Data were gathered by focus groups, interviews, and a written survey (N = 874) on topics of need for personal care assistance, level of assistance required for instrumental activities of daily living, and mobility. Qualitative inquiry yielded information about facilities and safety, and culturally specific needs, particularly communication. The case study concludes by discussing how the research findings translated into on-site programmatic changes, and delineating the factors that contributed to the success of this approach.

Reduced epinephrine clearance and glycemic sensitivity to epinephrine in older individuals.

To test the hypothesis that glycemic sensitivity to epinephrine is reduced in older individuals and to assess the impact of a sedentary lifestyle on responses to the hormone, we performed 30-min sequential intravenous infusions of epinephrine (0, 41, 82, 164, 246, and 328 pmol. kg-1. min-1) in young (n = 10) and older (n = 23) healthy subjects. We performed these again after 12 mo of physical training, which raised peak O2 consumption from 24.4 +/- 1.0 to 30.4 +/- 1.4 ml. kg-1. min-1 (P < 0.01) in most of the older subjects (n = 21). During epinephrine infusions, plasma epinephrine concentrations were higher (P = 0.0001) in older than in young subjects (e.g., final values of 7,280 +/- 500 vs. 4,560 +/- 380 pmol/l, respectively), indicating that the clearance of epinephrine from the circulation was reduced in the older individuals. Plasma epinephrine concentration-response curves disclosed reduced glycemic sensitivity to the hormone in the older subjects (P = 0.0001), a finding plausibly attributed to increased sympathetic neural activity, as evidenced here by higher plasma norepinephrine concentrations (P = 0.0001) in the older subjects and consequent desensitization of cellular responsiveness to catecholamines. Training did not correct reduced epinephrine clearance, reduced glycemic sensitivity to epinephrine, or raised norepinephrine levels. We conclude that aging is associated with reduced clearance of epinephrine from the circulation and reduced glycemic sensitivity to epinephrine, the latter plausibly attributed to an age-associated increase in sympathetic neural norepinephrine release. These age-associated changes are not the result of a sedentary lifestyle.

Simplified measurement of norepinephrine kinetics: application to studies of aging and exercise training.

We assessed simplified approaches to measurement of steady-state norepinephrine (NE) kinetics (short, nonprimed infusions of [3H]NE or of unlabeled NE and arterialized venous sampling), then reexamined the kinetic mechanism(s) of the age-associated increase in plasma NE, and tested the hypothesis that the latter is the result of a sedentary lifestyle. We studied 17 young (21-28 yr) and 21 elderly (60-76 yr) subjects and a subset (n = 8) of the latter again after 1 yr of physical training. NE appearance rates (Ra) and NE metabolic clearance rates (MCRs), calculated from arterialized venous data, were not significantly different from those calculated from arterial data, whereas those calculated from venous data were substantially (approximately 50%) higher. NE Ra and NE MCR, determined from infusions of unlabeled NE were approximately 20% higher than those determined with [3H]NE, a finding plausibly attributed to approximately 20% suppression of endogenous NE appearance. Arterialized venous plasma NE concentrations were significantly higher in the elderly as a result of significantly higher NE Ra and lower NE MCR. However, arterial NE Ra was not increased, and venous NE MCR was not decreased significantly in the elderly. In the subset of elderly subjects, 1 yr of physical training, which increased peak O2 consumption by 24%, did not decrease plasma NE or NE Ra or increase NE MCR. Therefore, 1) arterial sampling provides no practical advantage over arterialized venous sampling in the measurement of NE kinetics. 2) The use of unlabeled NE infusions to determine NE kinetics overestimates NE Ra and NE MCR by approximately 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Renin-angiotensin and autonomic mechanisms in cardiovascular homeostasis during haemorrhage in fetal and neonatal sheep.

The present study examined the roles of the renin-angiotensin and autonomic nervous systems in cardiovascular homeostasis during slow progressive haemorrhage (20% of measured blood volume over 1h) in fetal (128-132 and 143-148 days gestation) and neonatal (5-9 and 12-20 days post-natal) sheep. Basal plasma renin activity (PRA) was not significantly different in the 4 sheep groups and increased to a similar degree (approximately 2 to 3-fold) during haemorrhage. Mean arterial pressure (MAP) exhibited modest falls in response to haemorrhage in all sheep groups and while heart rate (HR) was well maintained in the fetal groups there was a tendency to bradycardia in neonates. None of these responses was significantly different in age-matched fetal sheep subjected to bilateral vago-sympathectomy, cervical cord transection or bilateral nephrectomy, with the exception of PRA in the latter group which was close to zero throughout. Treatment with the angiotensin II (AII) antagonist, (Sar1-Ala8) AII (Saralasin), significantly increased basal PRA in both fetal and neonatal sheep (approximately 5 to 7-fold). The PRA response to haemorrhage was absent in neonatal sheep treated with Saralasin but significantly increased in fetal sheep. Saralasin significantly reduced resting MAP in both sheep groups and increased the hypotensive and bradycardic effects of haemorrhage in neonatal (approximately 3 to 5-fold) but not fetal sheep. It is concluded that in the perinatal period studied, fetal and neonatal sheep are equally well able to maintain cardiovascular homeostasis in response to moderate haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Attenuated glucose recovery from hypoglycemia in the elderly.

Advanced age is a risk factor for hypoglycemia caused by sulfonylureas (and insulin) used to treat diabetes mellitus. Therefore, we hypothesized that there is an age-associated impairment of glucose counterregulation and further that this is the result of a sedentary life-style. To test these hypotheses, glycemic and neuroendocrine responses to hypoglycemia, produced by 0.05 U/kg body wt insulin i.v. were measured in nondiabetic elderly subjects (age 65.1 +/- 0.9 yr n = 23)--and in a subset (n = 11) again after 1 yr of physical training (which increased VO2 max by 5.2 +/- 0.9 ml.kg-1.min-1, P less than 0.05)--and compared with these responses in nondiabetic young subjects (23.8 +/- 0.6 yr, n = 18). Recovery from hypoglycemia was attenuated (analysis of variance P less than 0.001) in the elderly (plasma glucose recovery rate 29.4 +/- 2.2 vs. 42.7 +/- 5.0 microM/min, P less than 0.02). This attenuation was the result of a smaller counterregulatory increment in glucose production (maximum increment 13.3 +/- 1.1 vs. 17.2 +/- 1.1 mumol.kg-1.min-1; P less than 0.05) rather than a greater increment in glucose utilization in the elderly. The attenuated glucose recovery was associated with higher plasma insulin concentrations (maximum increment 1385 +/- 122 vs. 940 +/- 72 pM, P less than 0.01) and reduced glucagon responses to hypoglycemia (maximum increment 43 +/- 6 vs. 66 +/- 12 ng/L). The epinephrine, norepinephrine, cortisol, and growth hormone responses were similar, although the epinephrine response was slightly delayed and the growth hormone response appeared smaller in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma volume, osmolarity, total protein and electrolytes during treadmill running and cycle ergometer exercise.

While haemoconcentration due to loss of plasma volume is well established during cycling, the existence of similar changes during running remains contentious. This study compared the changes in plasma volume and associated blood indices during 60 min of running and cycling at the same relative intensity (approximately 65% VO2max), with all changes referenced to blood indices obtained after 30 min seated at rest on a cycle ergometer. Plasma osmolarity increased similarly with both forms of exercise but was less than predicted for water loss alone, such that there was a net loss of sodium during exercise and of potassium postexercise, with essentially no loss of protein. Plasma volume decreased similarly (approximately 6.5%) in both exercise trials, but while that with cycling was initiated by exercise itself and was essentially maximal within 5 min, the reduction in plasma volume in the running trial was induced by adopting the upright posture and was complete before exercise began. These data would indicate that different mechanisms are responsible for the changes in plasma volume induced by running and cycling, while the similarity of change would suggest that there is a lower limit to any reduction in plasma volume, regardless of mechanism. Furthermore, the observation that the changes in plasma volume were complete before or early in exercise, would imply that oral water ingestion during prolonged exercise, which is essential for thermoregulation, may be more concerned with homeostasis of extravascular water rather than plasma volume.

Insulin and glucagon in prevention of hypoglycemia during exercise in humans.

To assess the roles of decrements in insulin and increments in glucagon in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal young men were studied during somatostatin infusions with insulin and glucagon infused to 1) hold insulin and glucagon levels constant, 2) decrease insulin, 3) increase glucagon, and 4) decrease insulin and increase glucagon during exercise. In contrast to a comparison study (saline infusion), when insulin and glucagon were held constant, glucose production did not increase and plasma glucose decreased from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.001) initially during exercise. Notably, plasma glucose then plateaued and was 3.3 +/- 0.2 mmol/l at the end of exercise. This decrease was at most only delayed when either insulin was decreased or glucagon was increased independently. However, when insulin was decreased and glucagon was increased simultaneously, there was an initial increase in glucose production, and the glucose level was 4.5 +/- 0.2 mmol/l at 60 min, a value not different from that in the comparison study. Thus we conclude that both decrements in insulin and increments in glucagon play important roles in the prevention of hypoglycemia during exercise and do so by signaling increments in glucose production. However, since hypoglycemia did not develop during exercise when changes in insulin and glucagon were prevented, an additional counterregulatory factor, such as epinephrine, must be involved in the prevention of hypoglycemia during exercise, at least when the primary factors, insulin and glucagon, are inoperative.

Catecholamines in prevention of hypoglycemia during exercise in humans.

To assess the role of catecholamines in the prevention of hypoglycemia during moderate exercise (approximately 60% peak O2 consumption for 60 min), normal humans were studied with combined alpha- and beta-adrenergic blockade and with adrenergic blockade while changes in insulin and glucagon were prevented with the islet clamp technique (somatostatin infusion with insulin and glucagon infused at fixed rates). The results were compared with those from an islet clamp alone study. In contrast to a comparison study (saline infusion), adrenergic blockade resulted in a small initial decrease in plasma glucose during exercise, from 5.0 +/- 0.2 to 4.4 +/- 0.2 mmol/l (P less than 0.01), but the level then plateaued. There was a substantial exercise-associated decrement in plasma glucose when insulin and glucagon were held constant, i.e., from 5.5 +/- 0.2 to 3.4 +/- 0.2 mmol/l (P less than 0.0001), but the level again plateaued. However, when insulin and glucagon were held constant and catecholamine actions were blocked simultaneously, progressive hypoglycemia, to 2.6 +/- 0.6 mmol/l (P less than 0.001), developed during exercise. Hypoglycemia was the result of an absent increase in glucose production and an exaggerated initial increase in glucose utilization. Thus we conclude that sympathochromaffin activation plays a minor role when insulin and glucagon are operative, but a catecholamine, probably epinephrine, becomes critical to the prevention of hypoglycemia during exercise when changes in insulin and glucagon do not occur.

Effects of music on patient anxiety in coronary care units.

In this experimental study we examined the effects of listening to relaxation-type music on self-reported anxiety and on selected physiologic indices of relaxation in patients with suspected myocardial infarction. Seventy-five patients were randomly assigned to one of two experimental groups, one listening to music and the other to "white noise," or to a control group. The State Anxiety Inventory was administered before and after each testing session, and blood pressure, heart rate, and digital skin temperature were measured at baseline and at 10-minute intervals for the 30-minute session. There was no significant difference among the three groups for state anxiety scores or physiologic parameters. Because no differences were found, analyses were conducted of the groups combined. Significant improvement in all of the physiologic parameters was found to have occurred. This finding reinforces the need for nurses to plan care that allows for uninterrupted rest for patients in the coronary care unit.

Direct relationship between mononuclear leukocyte and lung beta-adrenergic receptors and apparent reciprocal regulation of extravascular, but not intravascular, alpha- and beta-adrenergic receptors by the sympathochromaffin system in humans.

To examine putative relationships between adrenergic receptors on accessible circulating cells and relatively inaccessible extravascular catecholamine target tissues, we measured mononuclear leukocyte (MNL) and lung beta-adrenergic receptors and platelet and lung alpha-adrenergic receptors in tissues obtained from 15 patients undergoing pulmonary resection. Plasma catecholamine concentrations were measured concurrently to explore potential regulatory relationships between the activity of the sympathochromaffin system and both intravascular and extravascular adrenergic receptors. MNL and lung membrane beta-adrenergic receptor densities were correlated highly (r = 0.845, P less than 0.001). Platelet alpha 2-adrenergic receptor and lung alpha 1-adrenergic receptor densities were not. Lung alpha 1-adrenergic receptor densities were positively related to plasma norepinephrine (r = 0.840, P less than 0.01) and epinephrine (r = 0.860, P less than 0.01) concentrations; in contrast, lung beta-adrenergic receptor densities were not positively related to plasma catecholamine concentrations (they tended to be inversely related to plasma norepinephrine and epinephrine [r = -0.698, P less than 0.05] levels). This apparent reciprocal regulation of alpha- and beta-adrenergic receptors by the sympathochromaffin system was only demonstrable with adrenergic receptor measurements in the extravascular catecholamine target tissue. Neither MNL beta-adrenergic receptor nor platelet alpha-adrenergic receptor densities were correlated with plasma catecholamine levels. Thus, although measurements of beta-adrenergic receptors on circulating mononuclear leukocytes can be used as indices of extravascular target tissue beta-adrenergic receptor densities (at least in lung and heart), it would appear that extravascular tissues should be used to study adrenergic receptor regulation by endogenous catecholamines in humans. These data provide further support for the concept of up regulation, as well as down regulation, of some adrenergic receptor populations during short-term activation of the sympathochromaffin system in humans.

Glucagon, not insulin, may play a secondary role in defense against hypoglycemia during exercise.

The sympathochromaffin system, probably sympathetic neural norepinephrine, plays a primary role in the prevention of hypoglycemia during exercise in humans. Our previous data indicated that changes in pancreatic islet hormones are not normally critical but decrements in insulin, increments in glucagon, or both become critical when catecholamine actions are blocked pharmacologically. To distinguish between the role of insulin and that of glucagon in this secondary line of defense against hypoglycemia during exercise in humans, glucoregulation during moderate exercise (approximately 55% of maximum O2 consumption over 60 min) was studied in people who could not decrease insulin but could increase glucagon, i.e., patients with insulin-dependent diabetes mellitus (IDDM). While receiving constant intravenous infusions of regular insulin, in individualized doses shown to result in stable plasma glucose concentrations of approximately 95 mg/dl before exercise, patients with IDDM were studied under two conditions: 1) a control study (n = 13) and 2) an adrenergic blockade study (propranolol infusion, n = 8). In the control study, mean plasma glucose concentrations did not change (from 95 +/- 2 to 100 +/- 11 mg/dl) during exercise despite constant plasma free insulin levels. In the adrenergic blockade study plasma glucose declined (from 96 +/- 2 to 74 +/- 7 mg/dl, P less than 0.01) but stabilized; hypoglycemia did not occur. Exercise-associated increments in plasma glucagon were comparable in the two studies. These data confirm that decrements in insulin are not critical to the prevention of hypoglycemia during moderate exercise in humans and indicate that compensation for deficient catecholamine action does not require decrements in insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronotropic actions of cholecystokinin octapeptide on the rat heart.

Cholecystokinin octapeptide (CCK-8) administered i.v. to urethane-anaesthetized rats or added to the perfusion stream of isolated rat hearts produced an immediate bradycardia. The size of this response was dose-related. Studies in vivo and in vitro using atropine and propranolol indicated that the response to CCK-8 was largely due to a direct action of the peptide on the heart. N-carbobenzoxy-tryptophan (CBZ-Trp), a cholecystokinin receptor antagonist, abolished the response of the isolated heart to CCK-8. Gastrin I did not produce bradycardia. The receptors on rat heart were similar to the classes of cholecystokinin receptors found in brain and exocrine pancreas in that CCK-8 rather than cholecystokinin tetrapeptide (CCK-4) was the preferred agonist.