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Two groups of 8 females were given either 3 X 600 mg aspirin or placebo daily for 4 days, double blind. With aspirin, slow wave sleep was significantly decreased and stage 2 sleep significantly increased. Aspirin also significantly disrupted intra-subject night-to-night continuity of several sleep stages during drug and recovery nights.
A pilot phase I study was conducted with a cyclic heptapeptide analog of alpha-melanocyte stimulating hormone (alpha-MSH). The lactam-bridged molecule, called Melanotan-II (MT-II), has the structure Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10 alpha-MSH4-10-NH2 (MT-II) and has superpotent melanotropic activity in vitro. A single-blind, alternating day (saline or MT-II), placebo-controlled trial was conducted in 3 normal male volunteers at the starting dose of 0.01 mg/kg of MT-II. Subcutaneous injections of MT-II or saline were given daily (Monday-Friday) for 2 consecutive weeks. Two subjects were escalated by 0.005 mg/kg increments to 0.03 mg/kg and one to 0.025 mg/kg. The 0.03 mg/kg dose produced Grade II somnolence and fatigue in one of two subjects (WHO standards). Mild nausea, not requiring antiemetic treatment, was reported at most MT-II dose levels. A stretching and yawning complex appeared to correlate with the onset of spontaneous, penile erections which were intermittently experienced for 1-5 hours after MT-II dosing, depending on the MT-II dose. Two subjects had increased pigmentation in the face, upper body and buttock, as measured by quantitative reflectance and by visual perception 1 week after MT-II dosing ended. These results demonstrate that MT-II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection. The recommended single MT-II dose for future Phase I studies is 0.025 mg/kg/day.
This study was done to investigate the effects of hemodilution, hyperbaric oxygenation, and magnesium sulfate on cerebral resuscitation. Sixteen mongrel dogs were anesthetized, and monitored via pulmonary artery catheter, arterial catheter and electrocardiogram. A left lateral thoracotomy was done. Ventricular fibrillation was obtained by application of a 6-volt AC current. Mechanical ventilation was stopped. Total arrest time was 12 min. All dogs were cardiac resuscitated within 6 min using internal massage, ventilation, bicarbonate, epinephrine and internal defibrillation. The animals were then randomized into three groups. Group I represented controls, and were not treated. Group II dogs received normvolemic hemodilution using hetastarch (Hespan) containing magnesium sulfate (2000 mg/l), resulting in a hematocrit of 20%-30%. Group III dogs received the above hemodilution plus compression in a hyperbaric oxygen chamber to 2 atmospheres absolute. Critical care management and hourly neurologic scoring was performed for 7 days by blinded observers. All dogs at the time of death underwent autopsies for gross study. Data analysis revealed no statistical difference among the three groups with respect to survival time, cardiac function or neurologic scoring.
Past evidence has shown that motor cortical stimulation with invasive and non-invasive brain stimulation is effective to relieve central pain. Here we aimed to study the effects of another, very safe technique of non-invasive brain stimulation--transcranial direct current stimulation (tDCS)--on pain control in patients with central pain due to traumatic spinal cord injury. Patients were randomized to receive sham or active motor tDCS (2mA, 20 min for 5 consecutive days). A blinded evaluator rated the pain using the visual analogue scale for pain, Clinician Global Impression and Patient Global Assessment. Safety was assessed with a neuropsychological battery and confounders with the evaluation of depression and anxiety changes. There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Furthermore, cognitive performance was not significantly changed throughout the trial in both treatment groups. The results of our study suggest that this new approach of cortical stimulation can be effective to control pain in patients with spinal cord lesion. We discuss potential mechanisms for pain amelioration after tDCS, such as a secondary modulation of thalamic nuclei activity.
We report a case of a 28-year-old man with acute lymphoblastic leukemia who developed rhinocerebral zygomycosis during induction chemotherapy. This life-threatening fungal infection is an infrequent cause of neutropenic fever, and is occasionally found in patients with leukemia and lymphoma, or patients with severely compromised defence mechanisms due to other diseases. It is caused by moulds belonging to the Mucoraceae family, and is characterized by local destruction of the affected organ. In our patient, the infection spread from the paranasal sinuses to the right orbit, destroyed intraorbital structures and resulted in blindness within days. Biopsy from the right maxillary sinus was performed and mucormycosis was suspected through microscopic examination. Culture of the resected specimen identified Rhizopus arrhizus as the causing agent. Treatment of zygomycosis should consist of radical surgical debridement of the infected tissue, together with intensive broad-spectrum antimycotic therapy with amphotericin B. What could be learned from this case is, that aggressive approaches to identify the cause of infection is necessary, and that aggressive treatment strategies are inevitable to overcome the infection. Furthermore, treatment of the underlying disease should be continued as soon as possible.
We have discovered an expansive photoreceptive 'net' in the mouse inner retina, visualized by using an antiserum against melanopsin, a likely photopigment. This immunoreactivity is evident in a subset of retinal ganglion cells that morphologically resemble those that project to the suprachiasmatic nucleus (SCN), the site of the primary circadian pacemaker. Our results indicate that this bilayered photoreceptive net is anatomically distinct from the rod and cone photoreceptors of the outer retina, and suggest that it may mediate non-visual photoreceptive tasks such as the regulation of circadian rhythms.
OBJECTIVE: Body fatness is partly under hypothalamic control with effector limbs that include the endocrine system and the autonomic nervous system (ANS). In previous studies of both obese and never-obese subjects, we have shown that weight increase leads to increased sympathetic and decreased parasympathetic activity, whereas weight decrease leads to decreased sympathetic and increased parasympathetic activity. We now report on the effect of leptin, independent of weight change, on the ANS. RESEARCH METHODS AND PROCEDURES: Normal weight males (ages 20-40 years) were fed a solid food diet, measured carefully to maintain body weight, for 3 weeks, as inpatients at the Rockefeller University General Clinical Research Center. In a single-blind, 22-day, placebo/drug/placebo design, six subjects received leptin 0.3 mg/kilogram subcutaneously for 6 days. ANS measures of amount of parasympathetic control and sympathetic control of heart period (interbeat interval) were made by sequential pharmacological blockade with intravenous atropine and esmolol. Norepinephrine, dopamine, and epinephrine levels in 24-hour urine collections were also measured as well as resting metabolic rate. RESULTS: Sufficient food intake maintained constant body weight in all subjects. There was no evidence that leptin administration led to changes in energy metabolism sufficient to require additional food intake or to alter resting metabolic rate. Likewise, leptin administration did not alter autonomic activity. Parasympathetic control and sympathetic control, as well as the urinary catecholamines, were not significantly affected by leptin administration. Glucose and insulin levels were increased by food intake as expected, but leptin had no affect on these levels before or after food intake. DISCUSSION: ANS responses to changes in energy metabolism found when food intake and body weight are altered were not found in these never-obese subjects given leptin for 6 days. Although exogenous leptin administration has profound effects on food intake and energy metabolism in animals genetically deprived of leptin, we found it to have no demonstrable effect on energy metabolism in never-obese humans. The effects of longer periods of administration to obese individuals and to those who have lost weight demand additional investigation.
A 2-year-old Thoroughbred filly presented with ocular pain and epiphora of the left eye. The pupil was miotic and the cornea edematous near the ventro-temporal limbus, but did not retain any fluorescein. The topical antibiotics and atropine and diclofenac, and systemic flunixin meglumine and antibiotic therapy did not resolve the condition. A pink and fleshy infiltrate developed near the limbus indicating nonulcerative keratouveitis. The anterior uveitis deteriorated as manifested by the presence of dyscoria, hypopyon, and organized fibrin in the anterior chamber. Ocular signs were improved by topical and subconjunctival corticosteroids, but repeatedly deteriorated as the frequency of medication was reduced. The horse was seropositive to three serovars of Leptospira interrogans. The animal was diagnosed as blind on day 91 by the absence of pupillary light and menace reflexes, and donated for histopathologic diagnosis. The corneal opacity was histologically fibrotic and infiltrated predominantly by lymphocytes with Descemet's membrane partially disrupted by macrophages. The choroid was infiltrated by lymphocytes, eosinophils and basophils, and was positive to IgG and C3. There were filamentous or spiral structures positive to Warthin-Starry stain in the renal cortex. There was also polymerase chain reaction amplification of the leptospiral gene in the kidney. From these findings nonulcerative keratouveitis was believed to be caused by systemic infection with Leptospira.
PURPOSE: To investigate whether a combined examination with MRI enteroclysis and MRI colonography is practicable and would provide additional findings in the regions seen with ileo-colonoscopy in the work-up of patients with Crohn's disease. MATERIAL AND METHODS: Twenty-five consecutive patients with Crohn's disease (CD) (age range 19 to 42 years, mean age 29.2 years, gender ratio male:female 8:17) were retrospectively studied. All patients underwent conventional ileo-colonoscopy as a standard of reference followed by a combined examination of MRI enteroclysis and MRI colonography at 1.5T within 15 days. Two blinded radiologists evaluated the MRI examinations and compared them with the colonoscopic results. RESULTS: The MRI examination detected 31 inflamed bowel segments in 25 patients. In comparison to colonoscopy, 5 additional, endoscopically inaccessible lesions were found by MRI and only 2 lesions were missed by MRI. Compared to colonoscopy, MRI found 7 of 10 fistulas detected by colonoscopy, and 3 otherwise indiscernible abscesses. The detection of inflamed bowel segments by means of MRI (endoscopy) revealed a sensitivity of 88.8 % (100 %), specificity of 80 % (100 %) and an overall accuracy of 96 % (100 %). CONCLUSION: This study provides strong evidence that the combination of MRI enteroclysis and MRI colonography is practicable and supplies additional results regarding the regions which are not seen with ileo-colonoscopy in the work-up of patients with Crohn's disease.
BACKGROUND AND STUDY AIMS: Patients with spondyloarthropathies are often found to have signs of small-bowel inflammation when examined by ileocolonoscopy. Because capsule endoscopy has been found to be superior to other endoscopic and radiological modalities in the detection of small-bowel inflammation, we aimed to compare the diagnostic yield of capsule endoscopy with that of ileocolonoscopy in the detection of small-bowel lesions in patients with spondyloarthropathies. PATIENTS AND METHODS: Twenty patients with documented seronegative peripheral arthritis, ankylosing spondylitis, or sacroiliitis, who had not taken nonsteroidal anti-inflammatory drugs (NSAIDs) in the preceding 2 months, participated in the study. The patients underwent capsule endoscopy, followed by ileocolonoscopy within 7 days, with blinded assessment of both examinations. Biopsies were taken when indicated and adverse events were monitored. Patients completed a questionnaire on their satisfaction with the two procedures. RESULTS: A total of 20 patients (11 men, 9 women; mean age 41+/-13 years) with seronegative inflammatory spondyloarthropathies but without abdominal complaints completed the study. No adverse effects were reported and all the capsules were excreted. Of these 20 patients, 11 (55%) had a normal small bowel on both examinations. Significant small-bowel findings (erythema, mucosal breaks, aphthous or linear ulcers, erosions) were detected by capsule endoscopy in six patients (30%) and by ileocolonoscopy in only one patient. In addition, capsule endoscopy detected significant upper gastrointestinal pathology in 40% of patients. The patients preferred capsule endoscopy to ileocolonoscopy. CONCLUSIONS: Capsule endoscopy detected more small-bowel lesions than ileocolonoscopy, and provided additional potentially relevant information on upper gastrointestinal pathology in patients with spondyloarthropathies.
Based on animal experiments it has been proposed that antihypertensive agents may differentially influence albuminuria through their divergent effects on glomerular haemodynamics or glomerular sieving properties and may beneficially influence the progression of diabetic nephropathy even without an effect on blood pressure. However, to date this hypothesis has not been tested in normotensive patients with diabetic nephropathy. The main aim of this study was therefore to investigate the effects of the administration of two antihypertensive agents on albuminuria during rest and exercise. The study consisted of 3 x 3 randomised, cross-over periods with five days double blind administration of enalapril (E: 2.5 mg bid), nitrendipine (N: 5 mg bid) and placebo (P) on 18 Type 1 normotensive (blood pressure < 140/90 mmHg) diabetic patients with incipient diabetic nephropathy (albuminuria 30-300 mg/24 h, normal glomerular filtration rate, diabetes duration > 6 years and presence of diabetic reinopathy. The aim of this study was to investigate the effect of enalapril and nitrendipine on blood pressure values and albuminuria during exercise challenge (bicycle ergometry: 20 min at 75 W and 20 min at 100 W) in comparison to the placebo. Albumin excretion rates during pre-exercise rest (mean +/- SD; E: 6.2 +/- 6.0; N: 7.1 +/- 8.0; P: 7.7 +/- 7.0 mg/mmol creatinine) and during exercise (E: 8.7 +/- 9.4; N: 8.2 +/- 8.2; P: 11.1 +/- 11.4 mg/mmol creatinine) were comparable between the drugs and not significantly different after administration of placebo. Blood pressure values were significantly different between the medications (systolic blood pressure: p = 0.0269; diastolic blood pressure: p = 0.0021, ANOVA for repeated measurements). There were no significant correlations between blood pressure values and albuminuria at any time. In normotensive patients with incipient diabetic nephropathy low-dose administration of enalapril, nitrendipine and placebo does not result in clear cut differences in albuminuria.
The authors undertook a retrospective search of intestinal parasite laboratory records obtained from 200 consecutive-day pairs of stool specimens to compare prevalence estimates from the first and second stool examinations. The laboratory results had previously been recorded as part of a screening program offered to Southeast Asian refugees arriving in Montréal, Québec, Canada, between July 1982 and February 1983. No statistically significant differences in either overall prevalences or parasite-specific prevalences were observed. This suggests that, at least in some population-based situations, single stool examinations provide estimates of intestinal parasite prevalence which are as valid as those from the routine examination of two consecutive-day specimens. Blinded studies must be undertaken to accurately assess the true value of multiple specimen submission in epidemiologic studies.
Whether anesthetized patients register emotionally charged information remains controversial. We tested this possibility using subanesthetic concentrations of propofol or desflurane. Twenty-two volunteers (selected for hypnosis susceptibility) received propofol and desflurane (on separate occasions, and in a random order) at a concentration 1.5-2 times each individual's minimum alveolar anesthetic concentration (MAC)-awake (or equivalent for propofol). We gave vecuronium, intubated the trachea of each volunteer, controlled ventilation, and then presented a neutral (control) drama or a "crisis" drama stating that the oxygen delivery system had failed, assigning crisis and control dramas in a blinded, randomized, and balanced manner. One day later, interviewers blinded to the assigned drama conducted a 2-h structured interview (including hypnosis) to determine whether the contents of the interviews after crisis and control dramas differed. In addition, messages permitting subsequent assessment of learning of matter-of-fact information (Trivial Pursuit-type question task and a behavior task) were presented at the anesthetic concentration just sufficient to prevent response to command in each volunteer. No analyses of the tasks involving matter-of-fact information revealed learning except one which correlated hypnosis susceptibility with behavior task performance. Both propofol and desflurane suppressed memory of the crisis. Consistent with previous findings for isoflurane and nitrous oxide, propofol and desflurane suppressed learning of matter-of-fact information at concentrations just above MAC-awake, except that volunteers' susceptibility to hypnosis correlated with performance of a behavior suggested during anesthesia. Propofol and desflurane suppressed learning of emotionally charged information at anesthetic concentrations 1.5-2 times MAC-awake (less than MAC), a different result from that previously reported for ether.
BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) increases production and release of neutrophil precursors and activates multiple functions of circulating polymorphonuclear neutrophils (PMNs). G-CSF has therapeutic effects in many experimental models of sepsis; its actions with superimposed reperfusion insults are unknown. In traumatic conditions, G-CSF could exacerbate unregulated, PMN-dependent injury to otherwise normal host tissue or, it could partially reverse trauma-induced immune suppression, which may improve long-term outcome. This study tested whether stimulating PMN proliferation and function with G-CSF during recovery from trauma+sepsis potentiated reperfusion injury or whether it improved host defense. METHODS: Anesthetized swine were subjected to cecal ligation and incision, 35% hemorrhage, and 1 hr of hypotension. Resuscitation consisted of intravenous G-CSF (5 microg/kg) or placebo followed by shed blood and 40 mL/kg of lactated Ringer's solution. The control group received laparotomy only. G-CSF or placebo was given daily. Animals were killed at 4 days. Observers, blind to the protocol, graded autopsy samples for localization of infection and quality of abscess wall formation. Data included complete blood count, granulocyte oxidative burst after phorbol myristate acetate stimulation in vitro (GO2B), bronchoalveolar lavage (BAL) cell count, BAL noncellular protein, lipopolysaccharide-stimulated tumor necrosis factor production in whole blood in vitro (lipopolysaccharide-tumor necrosis factor), and lung tissue myeloperoxidase (MPO). RESULTS: Neutrophilia and localization of infection, were significantly improved by G-CSF. Variables altered by G-CSF, though not significantly, showed GO2B potential increased by 50%, lipopolysaccharide-tumor necrosis factor decreased by 50%, and improved survival versus placebo (100% vs. 70%). G-CSF did not increase lung MPO, BAL cell count, or BAL protein. Both arterial and venous O2 saturations were unaltered. CONCLUSIONS: Our data show that G-CSF initiated at the time of resuscitation reduced the sequelae of posttrauma sepsis by increasing PMN proliferation and function without potentiating PMN-mediated lung reperfusion injury.
Changes in pulmonary permeability provide a partial measure of the clinical impact of biocompatible oxygenator use during cardiopulmonary bypass surgery. Previous research has shown that the clearance rate of 99mTc-labelled diethylene triamine penta-acetic acid (99mTc-DTPA) aerosol from the lungs is increased following cardiopulmonary bypass, resulting from an increase in pulmonary permeability. The aerosol clearance rate has been shown to return to normal after a period of 7 days. A blind trial was set up to assess the clinical impact of a biocompatible, Trillium-coated oxygenator compared with a standard oxygenator. In a group of 25 patients 99mTc-DTPA aerosol studies were carried out prior to cardiopulmonary bypass surgery for mitral valve surgery. Repeat studies were undertaken 3-4 h and 24-28 h after surgery. Analysis of the rates of pulmonary clearance reproduced the trends seen in earlier research. There was however no statistically significant difference in the variation of serial clearance times between the groups of patients undergoing surgery using the Trillium-coated oxygenators and those using the standard oxygenators.
BACKGROUND: Helicobacter pylori eradication fails in about 25-30% of children, particularly because of the occurrence of resistance to antibiotics and side-effects. AIM: To determine whether adding the Lactobacillus reuteri to an anti-H. pylori regimen could help to prevent or minimize the gastrointestinal side-effects burden in children. METHODS: Forty H. pylori-positive children (21 males; median age: 12.3 years) were consecutively treated with 10-day sequential therapy [omeprazole + amoxycillin for 5 days, and omeprazole + clarithromycin + tinidazole for other 5 days] and blindly randomized to receive either L. reuteri ATCC 55730 (10(8) CFU) or placebo. All children completed the Gastrointestinal Symptom Rating Scale (GSRS) at entry, during and after treatment. H. pylori status was assessed after 8 weeks by (13)C-urea breath test. RESULTS: Overall, in all probiotic supplemented children when compared with those receiving placebo there was a significant reduction of GSRS score during eradication therapy (4.1 +/- 2 vs. 6.2 +/- 3; P < 0.01) and at the end of follow-up (3.2 +/- 2 vs. 5.8 +/- 3.4; P < 0.009). Overall, children receiving L. reuteri report less symptoms than those receiving placebo. CONCLUSION: L. reuteri is capable of reducing frequency and intensity of antibiotic-associated side-effects during eradication therapy for H. pylori.
A double-blind comparison of the effect of Ketogan (ketobemidone and A-29, an anticholinergic and spasmolytic agent) and morphine + scopolamine as premedication was performed in 113 women admitted for abortion and in 114 women admitted for gynaecological dilatation and curettage. Anaesthesia was thiopentone and nitrous oxide and oxygen, occasionally supplemented with enflurane. It was found that 1 ml morphine + scopolamine (10 mg + 0.4 mg) was more sedative than 1 ml ketogan (ketobemidone 5 mg + A-29 25 mg). After ketogan there was less nausea and dryness of the mouth before induction of anaesthesia than after morphine + scopolamine. Ketogan had the same tranquillizing effect but less hypnotic effect preoperatively than morphine + scopolamine. During the 3-h postoperative observation period the patients premedicated with ketogan woke up significantly sooner and had more pain than those given morphine + scopolamine. More patients required postoperative antiemetics in the ketogan-premedicated group than in the morphine + scopolamine-premedicated group.
During a 12-month period, 19,457 blood cultures were collected. Yeasts were isolated from 193 cultures derived from 76 cancer patients. Candida albicans or Candida tropicalis accounted for 79% of isolates. Of the three methods compared, the radiometric method required 2.9 days to become positive, "blind" subculture required 2.6 days, and Gram stains required 1 day. However, the radiometric method was clearly superior in detecting positive cultures, since 73% of all cultures were first detected radiometrically, 22% were detected by subculture, and only 5% were detected by Gram stain. Although 93% of the isolates were detected by aerobic culture, five (7%) isolates were obtained only from anaerobic cultures. Seven days of incubation appear to be sufficient for the radiometric detection of yeasts.