Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors conducted a randomized, prospective study comparing epidural morphine with patient-controlled intravenous (iv) morphine in 30 patients recovering from total hip or total knee arthroplasty. Six, 18, and 24 hr postoperatively, patients used a 10 cm visual-analogue scale to indicate both their current degree of discomfort and the maximum discomfort they had experienced since the previous evaluation. Pain at the time of evaluation did not differ between patients receiving epidural (2.6 +/- 0.4 cm, mean +/- SEM) and patient-controlled iv morphine (3.4 +/- 0.3 cm). However, patients who received epidural morphine recalled less pain during the period preceding evaluation (4.2 +/- 0.5 cm) than did those receiving patient-controlled analgesia (5.5 +/- 0.4 cm, P less than 0.05). Patients receiving epidural morphine were more likely to require treatment for pruritus (4 of 15) than patients who received patient-controlled iv morphine (none of 15, P less than 0.05). Minimum respiratory rates were lower in patients receiving epidural morphine (15.0 +/- 0.3) than in those receiving patient-controlled analgesia (16.5 +/- 0.4, P less than 0.05), but no patients required treatment for respiratory depression. The authors conclude that epidural morphine may provide more consistent analgesia following joint replacement surgery than patient-controlled morphine; however, there is a higher incidence of side-effects with the epidural technique.
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PMID:Comparison of epidural and patient-controlled intravenous morphine following joint replacement surgery. 193 5

Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid-October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 +/- 0.15 (SEM) W kg-1 at day 2 of fasting to a stable level of 1.62 +/- 0.06 (SEM) W kg-1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 +/- 8 (SEM) nmol l-1 throughout the fasting period. Daily urinary output decreased from 236 +/- 20 (SEM) ml day-1 at day 2 to a stable value of 87 +/- 6 (SEM) ml day-1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end-product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770-1300 mosmol kg-1). Total excreted urinary nitrogen decreased by 68% from 3.7 +/- 0.7 (SEM) g day-1 to 1.2 +/- 0.4 (SEM) g day-1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post-weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress.
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PMID:Depressed metabolism and low protein catabolism in fasting grey seal pups. 236 22

The experience with 14 patients with end-stage renal disease (ESRD), 13 of them maintained on chronic hemodialysis (x 20.4 months +/- 2.9 SEM) and one following successful renal transplantation, underwent placement of a peritoneovenous shunt (PVS) for refractory ascites that had been present before insertion from two to 15 months (x 5.3 +/- 0.8 SEM). A "specific" cause for the ascites could not be identified in any of the 14 patients. The ascites was an exudate in every patient (protein content greater than 3.5 gm/dl). Twelve patients (86%) obtained significant relief of the discomfort and all effects of the ascites, and objective clinical improvement persisted for at least six months. Nine patients (75%) survived one year and six (50%) survived three or more years. Three patients (21%) had recurrence of ascites because of shunt malfunction; however, two of them were successfully treated with placement of a second shunt. Eight (57%) patients have died since the onset of their ascites (x 14.1 months +/- 3.5 SEM); one death was attributable to PVS placement, while the other seven deaths were due to complications of their ESRD. Insertion of a PVS is an effective therapeutic alternative to palliate the discomfort and ill effects of massive nephrogenic ascites that is often refractory to hemodialysis with ultrafiltration.
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PMID:Short- and long-term effectiveness, morbidity, and mortality of peritoneovenous shunt inserted to treat massive refractory ascites of nephrogenic origin analysis of 14 cases. 247 8

To determine whether pain or discomfort could be provoked by adenosine in skeletal muscle and, if so, whether it was dependent on the vasodilatation produced by adenosine, eight male volunteers were given intra-arterial bolus injections of adenosine and glyceryl trinitrate into the forearm. Local pain was assessed on a scale rate, forearm blood flow was measured by venous occlusion plethysmography, and blood was sampled simultaneously from the deep vein of the same arm. Five different doses of adenosine, ranging between the maximum tolerable and the lowest producing pain or discomfort, were given intra-arterially in random order and repeated in reverse order. Glyceryl trinitrate was given intra-arterially in increasing doses from 1 to 20 micrograms. Pain or discomfort began 12(1)(SEM) s after administration reached its maximum after 17(1) s, and disappeared after 40(2) s. Pain or discomfort appeared 8(1) s (p less than 0.001) after the first recorded increase in forearm blood flow, whereas maximum pain or discomfort preceded maximal forearm blood flow by 5(1) s (p less than 0.001). The flow remained increased after the disappearance of pain or discomfort. The effects of adenosine on pain or discomfort and vasodilatation were dose dependent. Glyceryl trinitrate provoked a similar increase in flow to that with adenosine without producing pain or discomfort. Arterial occlusion for 5 min at rest or forearm exercise with arterial occlusion increased forearm blood flow to the same extent as the maximum dose of adenosine. In addition, ischaemic work slightly increased the plasma concentration of adenosine. The pain or discomfort after ischaemic work was not considered different from the adenosine provoked pain or discomfort by four of the subjects. It is concluded that the symptoms did not appear to be dependent on vasodilatation and therefore adenosine may contribute to ischaemic pain or discomfort.
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PMID:Adenosine injection into the brachial artery produces ischaemia like pain or discomfort in the forearm. 314 48

Previous estimates of PRL pharmacokinetics have been made using radioiodinated human PRL (hPRL) infusions or by measuring serum PRL disappearance following prolactinoma resection. The recent purification of hPRL in significant quantities made it possible to measure the clearance and volume of distribution directly. Studies were also carried out to determine absorption and clearance after im injection. In five normal men whose endogenous PRL secretion was suppressed by dopamine, a loading dose of hPRL (70-90 micrograms) followed by a constant infusion (1.39-2.9 ng/min) produced steady state serum PRL levels of 15.2-25.4 ng/mL by 30-60 min. The calculated mean volume of distribution was 7.3 +/- 2.9 (+/- SD) L. The calculated MCR was 71 +/- 19 mL/min X m2, and the calculated production rate was 802 +/- 377 micrograms/24 h X m2. The plasma disappearance half-life following discontinuation of the infusion was 37 +/- 10 min. The PRL infusate consisted primarily (75.6%) of a 22.5 K dalton species, probably PRL monomer, a component eluting at 45K daltons (16.1% of the total radioimmunoreactivity), probably dimer, and a small amount of a larger mol wt species. Serum obtained during dopamine infusion but before hPRL infusion contained 68.1% of the 22.5K, 7.2% of the 45K, and 24.7% of the larger mol wt moieties. During hPRL infusion in two men there was a relative decrease in the proportion of PRL monomer to 55% and 69% and a relative increase in the PRL dimer to 33% and 18%, respectively. hPRL was injected im in doses of 1, 2, 4, and 8 micrograms/kg without prior dopamine infusion. No significant changes in serum PRL levels occurred after the 1 and 2 micrograms/kg doses (n = 5). After the 4 micrograms/kg dose (n = 8), mean serum PRL levels rose from 10.0 +/- 1.8 (+/- SEM) ng/mL to peak levels of 13.1 +/- 1.8 ng/mL (P less than 0.01). After the 8 micrograms/kg dose (n = 7), PRL levels rose from 9.3 +/- 1.6 to 16.5 +/- 1.8 ng/mL (P less than 0.01). The PRL rise began between 60 and 80 min after injection; peak levels occurred at 160-180 min. In two men given 8 micrograms/kg who were sampled for an additional 3 h, PRL levels peaked at 200-220 min and began to fall by 220-240 min, but had not returned to baseline by 6 h. There were no side-effects of PRL administration, although the 8 micrograms/kg dose caused transient local discomfort.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetic studies of highly purified human prolactin in normal human subjects. 359 9

Alteration in visceral sensation locally at the site of presumed symptom origin in the gastrointestinal tract has been proposed as an important etiopathological mechanism in the so-called functional bowel disorders. Patients presenting with one functional gastrointestinal syndrome, however, frequently have additional symptoms referable to other parts of the gut, suggesting that enhanced visceral nociception may be a panintestinal phenomenon. We measured the sensory thresholds for initial perception (IP), desire to defecate (DD), and urgency (U) in response to rectal balloon distension, and the thresholds for initial perception and for discomfort in response to esophageal balloon distension in 12 patients with irritable bowel syndrome (IBS) and 10 patients with functional dyspepsia (FD), in comparison with healthy controls. As expected, IBS patients exhibited lower rectal sensory thresholds than controls (P < 0.0001), but in addition had significantly lower sensory thresholds for both perception and discomfort evoked by balloon distension of the esophagus (mean +/- SEM: 8.8 +/- 1.3 ml vs 12.1 +/- 1.5 ml (P < 0.05) and 12.2 +/- 1.4 ml vs 16.4 +/- 1.4 ml (P < 0.02) respectively. Patients with FD showed similarly enhanced esophageal sensitivity, with thresholds for perception and discomfort of 8.1 +/- 0.9 ml (P < 0.02), and 10.1 +/- 1.0 ml (p < 0.001), respectively, but were also found to have sensory thresholds for rectal distension similar to those observed in the IBS group, significantly lower than in controls: IP 45.0 +/- 17.6 vs 59.3 +/- 1.5 ml (P < 0.001), DD 98.0 +/- 17.9 vs 298.7 +/- 9.0 ml (P < 0.0001), U 177.2 +/- 25.4 vs 415.1 +/- 12.6 ml (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. 764 57

The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension.
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PMID:Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia? 767 80

Recent objective studies demonstrate relatively low hours of nightly use during nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). Patients frequently complain of dyspnea or discomfort during CPAP use, especially during expiration (against the continuous pressure), which may be a reason for the low hours of use. We hypothesized that with decreased expiratory pressure, hours of nightly use would increase. Therefore, we randomized 83 OSA patients to receive either continuous or bilevel positive airway pressure when expiratory pressure is lower. To document objectively the effective use of either therapy, we built and installed elapsed-time and mask pressure sensors in the patients' positive airway pressure units. A total of 62 patients were evaluable and followed for 1 yr. Of these, 26 received bilevel and 36 CPAP pressures. The machine timers measured accumulated "machine-on" time, and the mask pressure sensor recorded the total time in which the mask pressure was within 2 cm H2O of the effective pressure (pressure shown to eliminate 95% of the obstructive apneas during a full night of polysomnography). The mean machine timer hours of CPAP were 5.0 +/- 0.19 SEM and 4.9 +/- 0.23 SEM during bilevel therapy (p NS) over a 12-mo period. The pressures required during CPAP or bilevel therapy were not different between high and low hourly users. Effective use, the percentage of time that the machine was running and the prescribed pressure was being delivered, was 80% in CPAP and 82% in the bilevel users (p NS). Both groups had equal complaints with regard to mask discomfort, machine noise, and nasal stuffiness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Continuous versus bilevel positive airway pressure for obstructive sleep apnea. 784 4

Gallium nitrate is a potent antiresorptive drug that has been extensively tested in patients with accelerated bone turnover. We have evaluated the effects of this new agent in a pilot multicenter trial of 49 patients with advanced Paget's disease of bone. Patients were randomized to receive 0.05, 0.25, or 0.5 mg/kg.day gallium nitrate administered by sc injection in two 14-day cycles. Serum alkaline phosphatase, fasting 2-h urinary hydroxyproline and N- telopeptide collagen cross-links excretion, and quality of life were assessed every 2 weeks for 12 weeks. The group mean alkaline phosphatase activity at baseline was 854 +/- 100 (+/- SEM) IU/L. The mean changes from baseline to week 12 in serum alkaline phosphatase were +0.5%, -24%, and -31%, respectively, for the three doses tested. The differences for each of the higher dose levels (0.25 and 0.5 mg/kg.day) was statistically significant (P < or = 0.05), and nearly half of the patients treated with the 0.5 mg/kg.day dose achieved a 50% or more reduction in enzyme activity. The nadir value in hydroxyproline excretion occurred at 10 weeks, with mean changes of +9%, -10%, and -17% for the 0.05, 0.25, and 0.5 mg/kg.day doses, respectively; the difference was significant only at the 0.5 mg/kg.day level (P < 0.01). Urinary collagen cross-link excretion showed a significant decrease at the 0.25 and 0.5 mg/kg.day doses. We also observed a definite, but nonsignificant, trend for improved quality of life in patients treated at the highest drug dose. Minor discomfort at the injection site was frequently reported, but did not lead to interruption of therapy. Our results in these patients who had received moderate to extensive prior therapies with other drugs show that cyclical, low dose, sc administration of gallium nitrate is safe and effective for treating patients with advanced Paget's disease of bone.
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PMID:A multicenter trial of low dose gallium nitrate in patients with advanced Paget's disease of bone. 785 26

We examined the effect of inspiratory flow rate (IFR) on respiratory sensation during mechanical ventilation in 10 normal subjects. We adjusted the ventilator tidal volume (VT), frequency, and IFR until subjects indicated that they were maximally comfortable ("comfort IFR"). Subjects then rated breathing discomfort on a visual analog scale (VAS) while IFR was varied among four levels: 70%, 100%, 200%, and 300% of the comfort IFR. When compared with VAS ratings at the comfort IFR (4.4 +/- 1.2, mean +/- SEM), VAS ratings were significantly greater at the lowest (i.e., 70% comfort; 12.1 +/- 2.1) and highest (300% comfort; 8.2 +/- 0.9) IFR; there was no difference in ratings between the comfort IFR and 200% comfort IFR. At the lowest IFR, the breathing discomfort arose in the chest and had an air hunger-like quality; at high IFR, the discomfort arose in the upper airway. In the second portion of the study, subjects used open magnitude estimation to rate breaths of five different sizes at three different IFR (70%, 100%, and 200% of comfort rate). Neither the exponent nor intercept for VT perception differed among the three IFR. Our results demonstrate that although IFR does not alter magnitude estimation of breath size, deviations of IFR from that desired by the subject may greatly affect respiratory comfort.
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PMID:Effect of inspiratory flow rate on respiratory sensation and pattern of breathing. 788 66


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