Self-reported discomfort associated with use of different nonoxynol-9 spermicides

Patients with the syndrome of chronic daily headache often report migrainous symptoms and consequently are diagnosed as having a primary headache syndrome. We report two cases of idiopathic intracranial hypertension causing chronic daily headache with migrainous features in the absence of associated papilledema.     

Pain and discomfort associated with common hospital procedures and experiences

BACKGROUND: Protein kinases play a central role in controlling diverse signal transduction pathways in all cells. The identification of the direct cellular substrates of individual protein kinases remains the key challenge in the field. RESULTS: We describe the protein engineering of v-Src to produce a kinase which preferentially uses an ATP analog, N6-(benzyl) ATP, as a substrate, rather than the natural v-Src substrate, ATP. The sidechain of a single residue (Ile338) controls specificity for N6-substituted ATP analogs in the binding pocket of v-Src. Elimination of this sidechain by mutation to glycine produces a v-Src kinase which preferentially utilizes N6-(benzyl) ATP as a phosphodonor substrate. Our engineering strategy is generally applicable to the Src family kinases: mutation of the corresponding residue (Thr339 to glycine) in the Fyn kinase confers specificity for N6-(benzyl) ATP on Fyn. CONCLUSIONS: The v-Src tyrosine kinase has been engineered to exhibit specificity for an unnatural ATP analog, N6-(benzyl) ATP, even in a cellular context where high concentrations of natural ATP are present (1-5 mM), where preferential use of the ATP analog by the mutant kinase is essential. The mutant v-Src transfers phosphate more efficiently with the designed unnatural analog than with ATP. As the identical mutation in the Src-family kinase Fyn confers on Fyn the ability to recognize the same unnatural ATP analog, our strategy is likely to be generally applicable to other protein kinases and may help to identify the direct targets of specific kinases.     

Drug inhalation therapy. Therapy for patients with respiratory disorders

We detected a high number of patients suffering from respiratory ailments which require successive hospital stays due to acute setbacks in their chronic respiratory ailments. The majority of these patients receive outpatient clinic treatment based on use of an inhaler. Given the direct relationship between the correct use of an inhaler and its effectiveness, we designed our project with the goal to discover the adroitness these patients have with an inhaler. The results of our study showed that 67% of the patients tested did not correctly use their inhaler, there by annulling or diminished the effectiveness of its use.     

Perceived exertion associated with breathing hyperoxic mixtures during submaximal work

The effect of an enriched inspired oxygen concentration on perceived exertion (RPE) was investigated while running at two submaximal treadmill loads. Twelve males (VO2 max = 49.3 ml/kg-min) worked at 50% and 80% VO2 max, breathing either air or 80% O2-20% N2 in random order using a single blind technique. Subjects were evaluated while running for 10 min and during a 20 min recovery. Heart rate (HR), ventilation (VE), respiration rate (RR), tidal volume (VT) and RPE were measured before, during and after work. Blood lactate was measured 1 min after work. Oxygen concentration did not statistically affect HR, VE, RR or VT during exercise or recovery. At both loads, RPE at the end of exercise was significantly reduced breathing the hyperoxic mixture. At 50% VO2 max, mean RPE decreased from 11.2 breathing room air to 9.6 breathing 80% O2 and, 80% VO2 max, from 13.8 to 11.7 (P less than 0.01). Blood lactates were significantly reduced breathing 80% O2; from 23.4 mg to 13.3 at 50% VO2 max and from 55.5 to 36.5 at 80% VO2 max (P less than 0.01). The RPE correlated with lactate (r=0.64) at the end of work. Results indicate that during moderate and heavy work RPE is significantly affected by the inspired O2 concentration and there is a significant relationship between RPE and blood lactate.     

Source of respiratory drive during periodic breathing in lambs

In order to investigate the mechanisms underlying periodic breathing (PB), we studied the initiation of breathing after passive hyperventilation in 14 anaesthetised 10-20 day old lambs. Eight of the lambs exhibited PB following post-hyperventilation apnea (PHA), with an epoch duration of 82.4 +/- 14.2 sec (mean +/- SEM), a cycle duration of 9.7 +/- 0.7 sec and a ratio of ventilatory duration to apnea duration (V-A ratio) of 1.24 +/- 0.32. The remaining lambs showed stable breathing patterns following PHA. The ventilatory response to isocapnic hypoxia was significantly greater in the group that had PB (-7.2 +/- 1.0 ml min-1% Sao2-1 kg-1) than in the animals that did not (-2.5 +/- 1.0 ml min-1%Sao2-1 kg-1). Using experimentally determined ventilatory response curves to O2 and CO2 we calculated that the swings in Sao2 and Paco2 during PB generated chemical drive that accounted for only 16.2% of the ventilatory oscillations observed during PB. Much of the remaining drive appeared to originate in the 'switch-on' characteristics of the respiratory controller, in lambs that exhibited periodic breathing, when breathing began after PHA ventilation jumped abruptly from zero to 55.1% of the eupneic ventilation. The magnitude of this jump in ventilation accounted for 51.9% of the amplitude of ventilatory oscillations that occur during PB. We speculate that this previously unrecognised feature of the respiratory controller, together with an elevated sensitivity to hypoxaemia, play crucial roles in generating PB in the infant.     

Ectopic respiratory epithelium associated with multiple malformations

We report a patient with unique cutaneous plaques of ectopic respiratory epithelium. The epithelium was located superficially as raised erythematous plaques on the right lateral surface of the neck with some viscous secretion. Underlying branchial cysts or sinuses were excluded. The occurrence of ectopic respiratory epithelium was associated with congenital deafness and a hare-lip in our patient, suggesting multiple malformation during early embryonic development.     

Chest discomfort associated with liposomal amphotericin B: report of three cases and review of the literature

Liposomal formulations of amphotericin B are designed to maintain therapeutic efficacy of amphotericin B deoxycholate while reducing its associated toxicities. In three patients chest discomfort occurred during planned 1-hour infusions of liposomal amphotericin B (AmBisome) 3 mg/kg/day during an open-label trial. The first patient experienced chest tightness and difficulty breathing and the second had dyspnea and acute hypoxia, both within 10 minutes of the start of the infusion. The third patient complained of chest pain 5 minutes after the start of two infusions. All symptoms resolved on terminating therapy. Two patients were later rechallenged with slower infusions and tolerated the drug well. A review of the English-language literature revealed only two other case reports of infusion-related chest or pulmonary reactions with the drug, although similar reactions were noted in several reports of clinical trials. Further review of the literature revealed reports of chest and pulmonary adverse events with other liposomal formulations of amphotericin B, liposomal daunorubicin, liposomal doxorubicin, and liposomes. The pathophysiology of such reactions remains unclear, and premedication with diphenhydramine did not completely prevent this reaction in one of our patients. We recommend infusing liposomal amphotericin B over at least 2 hours with careful monitoring for adverse reactions.     

Expiratory flow limitation during spontaneous breathing: comparison of patients with restrictive and obstructive respiratory disorders

BACKGROUND AND STUDY OBJECTIVES: Comparison of tidal and forced expiratory flow-volume (V-V) curves has inherent technical problems in the characterization of expiratory flow limitation. In addition, patients with neuromuscular disorders may be unable to perform forced expiratory maneuvers because of muscle weakness or poor coordination. A recently developed simple, noninvasive technique that avoids these problems was used to detect expiratory flow limitation at rest in 19 seated patients with restrictive respiratory (13 with musculoskeletal) disorders (RD) and 20 with chronic obstructive airway disease (COAD). SETTING: A large rehabilitation hospital for the care of patients with chronic musculoskeletal and respiratory disorders. INTERVENTIONS AND MEASUREMENTS: The method consisted of applying negative pressure of about 5 cm H2O at the airway opening during expiration and comparing the ensuing V-V curve to the preceding tidal V-V curve. RESULTS: While nine patients with COAD demonstrated flow limitation, only one patient with RD did so. Patients with expiratory flow limitation exhibited various contours of the control tidal expiratory V-V curve. Thus, inspection of the tidal V-V curve is not a reliable means of detecting expiratory flow limitation. CONCLUSIONS: We conclude that expiratory flow limitation during resting breathing is common in patients with COAD but not in patients with RD.     

Leptin attenuates respiratory complications associated with the obese phenotype

A profile of respiratory complications has been associated with the onset and development of obesity in humans. Similar phenotypes have been routinely demonstrated in genetic animal models of obesity such as the ob mouse (C57BL/6J-Lepob). The objective of the present study was to test the hypothesis that a constellation of respiratory complications are attenuated with leptin (i.e., protein product of the ob gene) replacement. Daily leptin administration during a 6-wk period was conducted to control body weight of mutant ob mice similar to genotypic control groups. During the treatment period, repeated baseline ventilatory measurements were assessed by using whole body plethysmography while quasistatic pressure-volume curves were performed to further explore the role of leptin in improving lung mechanics. Diaphragmatic myosin heavy chain (MHC) isoform phenotype was examined to determine proportional changes in MHC composition. In room air, breathing frequency and minute ventilation were significantly (P < 0.01) different among ob treatment groups, suggesting that leptin opposed the development of a rapid breathing pattern observed in vehicle-treated ob mice. Quasistatic deflation curves indicated that the lung volume of leptin-treated ob mice was significantly (P < 0.05) greater relative to vehicle-treated ob mice at airway pressures between 0 and 30 cmH2O. Diaphragm MHC composition of leptin-treated ob mice was restored significantly (P < 0.05) to resemble the control phenotype. In this genetic mouse model of obesity, the results suggested that respiratory complications associated with the obese phenotype, including rapid breathing pattern at baseline, diminished lung compliance, and abnormal respiratory muscle adaptations, are attenuated with prolonged leptin treatment.     

Economic impact associated with respiratory disease in beef cattle

This experiment sought to ascertain whether overt gaze (i.e., directed attention) would influence attentional performance in Huntington's disease (HD), via the use of a vibrotactile choice reaction time procedure involving biased probabilities of event occurrence. Subjects looked (i.e., direct gaze) either at the hand receiving the most (expected) vibrations, or the hand less often stimulated (the unexpected), for both crossed and uncrossed arm postures. Patients with HD showed performance advantages when directing attention (i.e., gaze) at the responding hand, especially for expected events. Patients with HD, however, were not sensitive to distributions of event probability in the uncrossed arm posture, nor when looking away from the responding hand. With the crossed arm posture, and when directing attention at the expected side, patients with HD became more sensitive to distributions of event probability. In HD, there may be a disruption of fronto-striatal circuitry on both cortical and subcortical levels which may account for impairments both in holding and shifting attention.     

Override of spontaneous respiratory pattern generator reduces cardiovascular parasympathetic influence

We investigated the effects of voluntary control of breathing on autonomic function in cardiovascular regulation. Variability in heart rate was compared between 5 min of spontaneous and controlled breathing. During controlled breathing, for 5 min, subjects voluntarily reproduced their own spontaneous breathing pattern (both rate and volume on a breath-by-breath basis). With the use of this experimental design, we could unmask the effects of voluntary override of the spontaneous respiratory pattern generator on autonomic function in cardiovascular regulation without the confounding effects of altered respiratory pattern. Results from 10 subjects showed that during voluntary control of breathing, mean values of heart rate and blood pressure increased, whereas fractal and spectral powers in heart rate in the respiratory frequency region decreased. End-tidal PCO2 was similar during spontaneous and controlled breathing. These results indicate that the act of voluntary control of breathing decreases the influence of the vagal component, which is the principal parasympathetic influence in cardiovascular regulation.     

Role of vagal afferents in the ventilatory response to naloxone during loaded breathing in the rabbit

We report here, a patient of systemic lupus erythematosus (SLE) with severe fibrinoid necrosis in the afferent arteriole of the glomerulus, in whom antiphospholipid antibody might have contributed to the pathogenesis. A 24-year-old female who was suffering from severe anemia with fragmented red blood cells, acute renal failure and thrombocytopenia, was admitted to our hospital. Further examinations revealed findings compatible with active lupus nephritis. Moreover, she was found to be positive for antiphospholipid antibody, and anticardiolipin antibody, as well as for lupus anticoagulant and syphilis test. Intensive treatment by methylprednisolone pulse therapy, hemodialysis, and double filtration plasmapheresis were performed. However, 13 days after admission she died suddenly because of intracranial hemorrhage. Pathological investigation of renal tissue revealed severe fibrinoid necrosis of the arterioles mainly in the glomerular afferent arteriole associated with diffuse proliferative lupus nephritis. In this case, hemolytic uremic syndrome (HUS) was associated with SLE. Antiphospholipid antibody was considered to be not only an accelerator in the arterial lesions of HUS, but also an initiator of HUS itself.     

Determination of l-menthol in pharmaceutical products by high performance liquid chromatography with polarized photometric detection

PURPOSE: An immortalized human corneal epithelial cell line (HCE) was tested as a screening tool for prediction of topical ocular irritation/toxicity by pharmaceuticals METHODS: Effects of various drugs, excipients and cyclodextrins (CDs) on viability of HCE cells were evaluated using two in vitro cytotoxicity tests, 3-(4,5-dimethlthiazol-2-yl)-205-diphenyl tetrazolium bromide (MTT) dye reduction assay and propidium iodide assay. RESULTS: Mitochondrion-based MTT test was a more sensitive indicator of cytotoxicity than the plasma membrane-based propidium iodide test. The tests revealed following cytotoxic rankings for ophthalmic drugs: dipivefrin > timolol > pilocarpine approximately equal to dexamethasone; for excipients: benzalkonium chloride (BAC) > sodium edetate (NA2 EDTA)>polyvinyl alcohol (PVA) > methylparaben; and for CDs :alpha- CD > dimethyl beta-cyclodextrin (DM-beta-CD) > sulfobutyl ether beta-cyclodextrin ((SBE)7m-beta-CD approximately equal to hydroxypropyl-beta-cyclodextrin (HP-beta-CD) > lambda CD. In consideration of the in vivo clinical situation, the short exposure time (5 min) is more relevant even though toxic effects of some test substances were seen only after longer exposure time (30 and 60 min). CONCLUSIONS: Immortalized HCE cells are a promising tool for rapid cytotoxicity assays of ocular medications. The cell line is potentially useful in predicting the in vivo coreal toxicity of ocularly applied compounds.     

Severe adult respiratory distress syndrome associated with transfusion of antileukocyte antibodies

The use of blood products is common in the period after cardiopulmonary bypass. A rare cause of adult respiratory distress syndrome is a reaction to antileukocyte antibodies. The plasma transfused may contain a potent leukocyte antibody that may cause severe problems in the intensive care unit.