Auscultatory percussion of the urinary bladder.

A volumetric study of the bladder was done in 170 adult male patients examined by auscultatory percussion. The upper border of the urinary bladder was defined and measured in reference to the symphysis pubis to gauge urinary volume. The findings were correlated with the urinary volumes obtained after the bladder had been emptied by voiding in 90 patients without urinary tract disease and in 42 patients who required catheterization. With a bladder level less than 2 cm, none of the patients had a full bladder or a urinary volume of 250 mL. Of the 55 patients with bladder levels of 3 cm or more, 53 patients had full bladders. Catheterizations were timely and avoided frequent and unnecessary catheterization. Residual urinary volumes estimated by auscultatory percussion in 12 patients with obstructive uropathy and 26 patients studied with indwelling catheters correlated closely with the catheterized urinary volumes. Full bladders, obstructive uropathy, and malfunctioning indwelling catheters were readily detected.

Aporphines. 14 Dopaminergic and antinociceptive activity of aporphine derivatives. Synthesis of 10-hydroxyaporphines and 10-hydroxy-N-n-propylnoraporphine.

The synthesis of racemic 10-hydroxyaporphine [(+/-)-2a] and 10-hydroxy-N-n-propylnoraporphine [(+/)-2b] is described. The method involved a Reissert alkylation-Pschorr cyclization route. The dopaminergic activity of (+/-)-2b was evaluated in comparison with L-Dopa, (-)-apomorphine (1a), (+/-)-N-n-propylnorapomorphine (NPA) (1b), and (+/-)-11-hydroxy-N-n-propylnoraporphine [(+/-)-11-OH-PNA] by the behavioral model of rotational behavior in animals after unilateral lesion of the ascending DA pathways. The dopaminergic activity of NPA and 11-OH-PNA is essentially equivalent to L-Dopa and (-)-apomorphine, and both are more active than (+/-)-2b. Furthermore, (+/-)-NPA (threshold doses, 5 mug/kg) appears to be even more potent that (-)-apomorphine (threshold doses, 25 mug/kg). The duration of action of NPA and 11-OH-PNA is considerably longer than that obtained with L-Dopa. The antinociceptive activity of (+/-)-2b was evaluated by the tail-flick procedure and compared with 1a, 2b, morphine, and L-Dopa. Weak but significant antinociceptive activity was shown by (+/-)-2b and by (+/-)-1b but not by (-)-apomorphine. This effect was not antagonized by naloxone. The finding that (+/-)-2b and particularly (+/-)-11-OH-PNA are active in doses from 500 to 50 mug/kg, respectively, in causing rotational behavior further supports previous studies indicating that N-n-propyl derivatives of monohydroxylated aporphines were more active than the corresponding parent N-methyl derivatives as DA receptor agonists and that a catechol system is not an absolute requirement for dopaminergic activity in such aporphines.

Phenobarbital tolerance and physical dependence: chronically equivalent dosing model.

A rat model of phenobarbital tolerance and physical dependence has been developed based on the 'maximally tolerable, chronically equivalent' dosing paradigm. Sodium phenobarbital was administered orally twice daily for 35 days in individually adjusted doses to achieve mean daily peak CNS depression culminating in severe ataxia. Dose to dose continuity of CNS depression was maintained throughout treatment. At the time of dosing rats were mildly ataxic. Following abrupt termination of chronic treatment, an abstinence syndrome characterized by CNS hyperexcitability was observed, which demonstrates physical dependence. Signs, which included motor, autonomic, and behavioral manifestations, appeared from 12-24 h and animals recovered by 12 days. Although tolerance development was nearly complete on day 10 of treatment, the abstinence syndrome observed was more severe following 35 than after 10 days of chronic treatment. Characteristics of tolerance and physical dependence are similar to those described for other species including humans.

A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients.

We report on the results of a study comparing mianserin with amitriptyline and placebo, in outpatients with major depression (DSM-III 296.2 or 296.3). One hundred and forty-nine patients were randomized to mianserin (n = 50), amitriptyline (n = 50) or placebo (n = 49). Medication was taken in a nightly (qhs) dose. During Week 1, the maximum dose was 60 mg mianserin, 120 mg amitriptyline or two placebo capsules. Beginning at Day 7 (through Day 42) maximum dosages were 150 mg mianserin, 300 mg amitriptyline or five placebo capsules. At multiple weeks and endpoint, statistically significant reductions in the Hamilton Depression Scale (HAM-D) 17- and 21-item scores were recorded for both active drugs compared with placebo. Positive results with the HAM-D were corroborated by other measures of efficacy. There were no statistically significant differences between mianserin and amitriptyline in terms of efficacy; however, the results do suggest a more rapid therapeutic response for mianserin compared with amitriptyline, in terms of percentage of patients showing > or = 50% improvement at Weeks 2 (30% vs 23%) and 4 (61% vs 44%). The most common adverse experiences were somnolence (amitriptyline and mianserin 60%, placebo 31%) and dry mouth (amitriptyline 76%, mianserin 30% and placebo 20%). Our results indicate that mianserin is clearly superior to placebo, compares favorably with amitriptyline, and is a safe, well-tolerated, effective medication in the treatment of depressed outpatients.

Ethanol and pentobarbital: comparison of behavioral and subjective effects in sedative drug abusers.

The behavioral and subjective effects of acute oral doses of placebo, ethanol (0.5, 1.0, and 2.0 g/kg), and pentobarbital (150, 300, 600, and 750 mg/70 kg) were compared in 8 male volunteers with histories of sedative drug abuse using a double-blind, double-dummy, cross-over design. Ethanol and pentobarbital produced similar dose-related decrements in psychomotor and cognitive performance and exhibited a similar profile of effects on staff- and participant-rated measures. There was some evidence indicating that, at the highest dose, pentobarbital was perceived by participants as being more sedating than ethanol and that pentobarbital has a greater abuse liability than ethanol. In conjunction with the results of previous human laboratory studies comparing the effects of different types of sedative-hypnotic drugs, these results support a mostly barbiturate-like rather than benzodiazepine-like profile of effects for ethanol.

Modeling the growth plates in the pediatric knee: implications for anterior cruciate ligament reconstruction.

The authors develop 3-D models of the pediatric knee from magnetic resonance imaging (MRI) image files, with the goal of minimizing injury to the pediatric growth plate during surgery. Computerized tomography (CT) scans have better resolution and contrast between bone and soft tissue than MRI scans; however, surgeons rely upon MRI scans to plan knee-joint surgeries such as anterior cruciate ligament (ACL) reconstruction. Surgeons can use the virtual models to plan and verify surgical procedures such as hole drilling and ligament attachments, and to determine volume removed from a growth plate due to different drill-hole placements with various drill sizes.

Auscultatory percussion: a simple method to detect pleural effusion.

OBJECTIVE: To assess a new technique for the detection of free pleural fluid. DESIGN: 118 consecutive inpatients with radiologic evidence of free pleural fluid and a control group of 175 randomly selected inpatients were examined over a three-year period in a prospective blind study by auscultatory percussion (AP) for evidence of pleural effusion. The cutoff in the percussion note by AP is strikingly loud and sharp at the fluid level and allows precise delineation of even minimal amounts of pleural fluid. The fluid level was measured in reference to the last rib. The criterion for detection of pleural effusion by AP was a demonstrable horizontal fluid level at the sound cutoff across the posterior hemithorax above the last rib that shifted with lateral tilt. SETTING: A general medical and surgical university-affiliated teaching Veterans Affairs hospital. PATIENTS/PARTICIPANTS: All inpatients were eligible. Ready availability of examiners was essential. Rotating third- and fourth-year medical students, residents, and senior staff members participated. INTERVENTIONS: None. MAJOR RESULTS: 113 of the 118 patients with radiologic evidence of pleural effusion had a distinct horizontal fluid level above the last rib that shifted with lateral tilt (sensitivity = 95.8%). None of the 175 control patients examined at random showed evidence of pleural effusion by AP examination, which was confirmed by chest radiography (specificity = 100%). Nine of the 175 patients without radiologic evidence of pleural effusion had elevated diaphragms that simulated a fluid level in the examination by AP. Each of the nine patients, however, had no shift in the level with lateral tilt. Subpulmonic effusions were readily displaced and identified by this method of AP. CONCLUSIONS: Examination by AP is highly sensitive and specific for the detection of free pleural fluid, even in the presence of obesity, thickened pleura, lung masses, pneumonia, and associated lung disease. The examination correlates closely with standard and lateral decubitus chest radiography. Pleural effusion unsuspected by conventional means of physical examination and undetectable by standard chest radiography can readily be detected by the method of AP. The examination is easy to do and is particularly suited to enhance detection of pleural effusion. As little as 50 mL of free pleural fluid can be detected.

Auscultatory percussion of the chest.

In a controlled blind study 28 patients with prominent chest disease by chest X-ray each had normal or equivocal findings by conventional methods of percussion. In each case the lung abnormality was readily detected by auscultatory percussion. Lesions less than 2 cm in diameter were detected.

Auscultatory percussion of the head.

Eighty-nine consecutive patients with suspected intracranial masses were examined by auscultatory percussion in a blind study to assess the sensitivity of the procedure. Each patient underwent computed tomography (CT) of the brain as part of his medical care, and the results were compared with those of auscultatory percussion. Fifty-one of the patients had abnormal CT scans, of whom 44 (86%) had abnormal (positive) findings on auscultatory percussion; seven (13%) yielded false-negative results. Each of the patients with subdural haematomas had distinctly positive findings by auscultatory percussion. Of the 38 patients with normal CT scans, 11 had strokes with hemiparesis, and each had positive findings in the contralateral hemisphere by auscultatory percussion. The remaining 27 patients with normal CT scans were healthy; 25 had normal findings on auscultatory percussion, two (7%) gave false-positive results. Twenty subjects were studied with phonoscopy. Auscultatory percussion is easy to perform and is clinically useful.

Emergency department ultrasound in the evaluation of blunt abdominal trauma.

The main objective of this study was to compare bedside sonographic detection of hemoperitoneum with diagnostic peritoneal lavage/laparotomy in the patient with blunt abdominal trauma. A retrospective review was conducted of all blunt trauma patients that underwent emergency department (bedside) sonography to rule out intraperitoneal hemorrhage at a level I trauma center in 1991 to 1992. Patients were included in the study population only if: (1) the results of the ultrasound examination were interpreted before any other diagnostic studies, and (2) a diagnostic peritoneal lavage (DPL) or laparotomy was performed. The ultrasound examination consisted of a single right inter/subcostal longitudinal view with the patient in the trendelenburg position performed by the emergency physician or surgeon. A real-time sector scanner with a 3.5 MHz probe was used. The presence of an anechoic (black) stripe between the liver and the right kidney (Morrison's pouch) was interpreted as a positive study, and the absence of this finding was interpreted as a negative study. A positive DPL was defined as > or = 10 mL of gross blood or a blood cell count > or = 100,000/mm3 in the returned lavage fluid, and a positive laparotomy as > or = 100 mL of intraperitoneal blood. Forty-four patients met the inclusion criteria for the study. Eleven patients (24%) in this population had either a positive DPL or laparotomy. The sensitivity, specificity, and accuracy of bedside sonography in identifying intraperitoneal hemorrhage was 81.8%, 93.9%, and 90.9%, respectively. The ultrasound study provided an answer in less than 1 minute in most patients.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Aminosalicylic acid enemas in refractory distal ulcerative colitis: long-term results.

In this trial, we examined the role of 4-g 5-aminosalicylic acid (5-ASA) enema in the long-term management of patients with previously refractory distal ulcerative colitis. Of 20 such patients treated with nightly 5-ASA enemas, 16 improved symptomatically, with 15 achieving clinical remission and 14 achieving sigmoidoscopic remission within 3 to 5 wk. An attempt was made to maintain clinical remission with 5-ASA enemas in these 16 by successively decreasing the frequency of administration to every other night and then every third night, as long as remission was maintained. Relapses were treated by reinstituting nightly 5-ASA enema administration followed by another attempt at tapering the frequency of administration. Follow-up has ranged from 5 to 16 months. Nine patients were rapidly tapered to every third night administration, but six relapsed. Of these six, four were brought into remission with reinitiation of nightly enemas and tapered to every three nights, whereas one ultimately required enemas every two nights for control and one required enemas nightly (with mild symptoms). Six other patients relapsed when the enemas were tapered to every two nights, and after retreatment on a nightly regimen, four could be maintained on an every third night regimen while two have required every second night administration. One patient has required nightly administration from the outset. Currently, one patient is off all medication, while eight are on an every third night, three are on an every second night, and three are on a nightly schedule. We conclude that in patients with distal ulcerative colitis refractory to conventional therapy but responsive to 5-ASA enemas, relapse is common as the frequency of 5-ASA enema administration is decreased, although some patients may be maintained on a less than nightly schedule. The optimal maintenance regimen remains to be determined.

Small bowel injuries: mechanisms, patterns, and outcome.

OBJECTIVES: To determine the relationship between mechanism of injury (MI), operative management (OM), and outcome for traumatic jejunal and ileal wounds using an aggressive diagnostic, therapeutic, and support protocol. METHODS: Medical records for patients discharged with small bowel injuries from the Trauma Service between 1988 and 1992 were reviewed. The MI, presence of shock, method of diagnosis, OM, morbidity, and mortality were analyzed. RESULTS: Seventy patients had jejunal and/or ileal injuries. Blunt mechanisms caused injury in 33%, whereas the rest were penetrating wounds. Twenty-one diagnostic peritoneal lavages facilitated diagnosis (71% positive by tap). Ninety-six percent of the patients were explored within 3 hours of admission. Multiple perforations of jejunum were the most common injury of the small bowel. Using the Organ Injury Scale, grade III and IV wounds were statistically more common with penetrating injuries. Most of the injuries were managed with resection and stapled anastomosis, even in the presence of shock. CONCLUSIONS: There is a significant difference in MI and OM for small bowel wounds. Resection and stapled anastomosis is safe even in the presence of shock. Mortality and morbidity are related to associated injuries.

Building a team on a medical floor.

The article describes a case in which dysfunctional teamwork was threatening patient care on medical units. Various team-building techniques were used by trained facilitators. Survey results showed that the interventions resulted in improved communication, morale, and working relationships.

Sulfasalazine-induced abnormal sperm penetration assay reversed on changing to 5-aminosalicylic acid enemas.

Sulfasalazine, a drug used in the treatment of inflammatory bowel disease, has been associated with male infertility, an effect attributed to sulfapyridine rather than to 5-aminosalicylic acid (5-ASA), the presumed therapeutically active component of sulfasalazine. Recently, the sperm penetration assay (SPA) has been found to be an accurate method of quantitating male fertilization potential. We report the case of a man with ulcerative colitis in whom infertility and a markedly abnormal SPA were demonstrated while he was taking sulfasalazine. Shortly after discontinuing sulfasalazine and initiating treatment with 5-ASA enemas, his SPA became normal and his wife became pregnant. The SPA is a useful screening test for sulfasalazine-induced male infertility. On the other hand, 5-ASA enemas do not appear to be associated with an abnormal SPA.

Tolerance and physical dependence to a short-acting benzodiazepine, midazolam.

Midazolam is a new ultra short-acting benzodiazepine whose physical dependence properties have not been well characterized. Our laboratory has demonstrated previously that physical dependence to the long-acting chlordiazepoxide in the rat is inducible by a single intoxicating dose, whereas maximal dependence required chronically equivalent maximally tolerable dosing b.i.d. for 5 weeks. Based on the methods developed in our laboratory to quantify benzodiazepine intoxication and withdrawal, Trs were designed to evaluate midazolam's capacity to induce dependence in the rat after definable acute (120 mg/kg p.o.), sub-acute (120 mg/kg q.i.d. x 3 days) and chronic (120-180 mg/kg bid. x 5 weeks) dosing that was near maximally tolerable. A single dose of midazolam failed to produce withdrawal signs. Tolerance and dependence increased as a function of midazolam dose and duration of Tr.

Evaluation of the abuse potential of methocarbamol.

The subjective and behavioral effects of p.o. administered methocarbamol, lorazepam and placebo were studied in a nonresidential group of adult male volunteers with histories of recreational substance abuse including sedative/hypnotics. In the first phase of the investigation, a dose run-up of methocarbamol (up to 12 g) was conducted in six subjects to determine appropriate doses. In the second phase, a randomized block cross-over study using 14 subjects was conducted. The following drug conditions were tested in the cross-over phase: placebo, lorazepam 1, 2 and 4 mg, and methocarbamol 2.25, 4.5 and 9 g. Drug conditions were tested under double-blind conditions. Psychomotor and cognitive performance measures and subject- and observer-rated behavioral responses were measured daily before dosing and for 5.5 hr after drug administration. The results showed that both lorazepam and methocarbamol produced statistically significant dose-related increases in subjects' ratings of drug effect and liking, although only lorazepam increased morphine-benzedrine group (MGB) scale scores. Methocarbamol also increased ratings on measures indicating the emergence of dysphoric and other side effects at high doses. Both drugs impaired psychomotor and cognitive performance, with lorazepam generally producing greater effects than methocarbamol. The results indicate that methocarbamol, at doses well above those used therapeutically, has some potential to be abused by persons with histories of sedative/hypnotic abuse; however, this potential for abuse is probably decreased by the accompanying side effects at high doses and is probably less than that of lorazepam.

Subjective and behavioral effects of diphenhydramine, lorazepam and methocarbamol: evaluation of abuse liability.

The effects of orally administered placebo, diphenhydramine, lorazepam, methocarbamol and placebo were studied in volunteers with histories of recreational substance abuse including sedative/hypnotics. Placebo, diphenhydramine (100, 200 and 400 mg), lorazepam (1 and 4 mg) and methocarbamol (2.25 and 9 g) were tested in a randomized, double-blind crossover study using 14 subjects. Psychomotor and cognitive performance and subject- and observer-rated responses were measured daily before and for 5.5 hr after drug administration. The results showed that each of the drugs exhibited a different profile of effects on the test battery. Lorazepam produced significant increases in subjects' ratings of drug effect and liking, increases in measures of sedation and impairment of psychomotor performance. Methocarbamol also produced significant increases in subjects' ratings of drug effect and liking and measures of sedation, but it produced only minor impairment of psychomotor and cognitive performance. Diphenhydramine increased subjects' and observers' ratings of drug effect and measures of sedation, but it produced less psychomotor performance impairment and liking than lorazepam. Diphenhydramine produced the most side effects. The present study clearly differentiated the behavioral and subjective profiles of diphenhydramine, lorazepam and methocarbamol. Consistent with its recognized low abuse liability, diphenhydramine produced fewer increases in measures of positive mood and more adverse effects. The considerable overlap in subjective effect measures of positive mood make further differentiation with respect to abuse liability difficult.

The effect of high pressure on microporous membrane oxygenator failure.

A retrospective study to determine the relationship between early microporous membrane oxygenator (MMO) failure and blood pressure at the MMO outlet (Pmo) was conducted using data collected with 19 dogs (22 +/- 1 kg, mean +/- SEM) undergoing routine normothermic cardiopulmonary bypass. Because gas flow was maintained at a high level, it could not be used to control CO2 exchange. Instead, blood PCO2 was controlled by adding CO2 to the sweep gas. Blood PO2 was controlled as suggested by the manufacturer, by adjusting the %O2 in the gas phase (g). Blood flow was 2575 +/- 54 ml/min; Pmo ranged from 173 to 790 mm Hg; and hematocrit was 33 +/- 1%. O2 exchange was calculated from blood gas parameters. Changes in the diffusion potential of O2 (delta PO2) and CO2 (delta PCO2) and MMO performance (P, taken as oxygen exchange normalized to a diffusion potential of 100 mm Hg) indicated MMO failure. Initial values, taken within 60 min of bypass initiation, were compared to final values taken at 226 +/- 9 min of bypass. Despite higher final delta PO2 (411 +/- 9 vs. 538 +/- 19 mm Hg, p less than 0.0001 paired t-test) and delta PCO2 (18.6 +/- 2.4 vs. 30.5 +/- 4.7 mm Hg, p less than 0.0017), arterial blood PO2 decreased (159 +/- 15 to 89 +/- 6 mm Hg, p less than 0.0005) and PCO2 increased (36.4 +/- 1.5 to 46.1 +/- 3.0 mm Hg, p less than 0.0039), and the performance decreased [24.5 +/- 1.1 to 20.1 +/- 0.7 (ml/min)/(100 mm Hg), p less than 0.0001].(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of sucrose feeding on alpha 1-adrenergic responses in rat liver.

A sustained increase in sympathetic nervous system (SNS) activity was induced by substituting a 10% sucrose solution for the drinking water of rats fed laboratory chow ad libitum. The effects of increased SNS activity on alpha 1-adrenergic processes in liver were examined by evaluating three alpha 1-responses, namely, phenylephrine-stimulated ouabain-sensitive 86Rb+ uptake, 45Ca2+ efflux, and glucose release. Sucrose feeding abolished phenylephrine stimulation of ouabain-sensitive 86Rb+ uptake and 45Ca2+ efflux and induced a three- to fourfold reduction in the ability of phenylephrine to stimulate glucose release from liver slices. Pretreatment with 6-hydroxydopamine markedly reduced liver norepinephrine content. When 6-hydroxydopamine was used to prevent the sucrose-induced increase in SNS activity, the changes in 86Rb+ uptake, 45Ca2+ efflux, and glucose release that otherwise followed sucrose feeding were not observed. Sucrose feeding did not alter binding of the alpha 1-antagonist [3H]prazosin to liver cell membrane alpha 1-receptors or displacement of [3H]prazosin by the alpha-agonist epinephrine. These observations suggest that sustained increases in SNS activity may have profound effects on liver alpha 1-adrenergic events that occur subsequent to hormone-receptor interaction.

Pharmacologic characterization of acute chlordiazepoxide dependence in the rat.

A single intoxicating dose of chlordiazepoxide HCl (p.o.) in the rat can induce quantifiable manifestations of physical dependence. Dependence was revealed by antagonist precipitation (Ro 15-1788, CGS-8216) as well as spontaneous emergence of neurobehavioral signs of withdrawal observed by multiple raters blind to treatments. Ro 15-1788 was 45% more effective than CGS-8216 in both reversing chlordiazepoxide intoxication and expressing withdrawal signs. The severity of Ro 15-1788-precipitated withdrawal varied with chlordiazepoxide dose, Ro 15-1788 dose and the agonist-antagonist dose interval. Maximal precipitated dependence was evoked 3 days after chlordiazepoxide HCl (450 mg/kg) by Ro 15-1788 (25 mg/kg i.p.). The precipitated syndrome consisted of tail erection, reduced motor activity, high step, curled claw, arched back, muscle hypertonus and piloerection. Ro 15-1788-precipitated dependence emerged between 28 and 52 hr, peaked at 76 hr and disappeared by 124 hr. Spontaneous withdrawal had emerged from 100 to 124 hr and then faded gradually. The neurobehavioral expression of central nervous system depression and its reversal were necessary but not sufficient conditions for the induction and expression of acute chlordiazepoxide dependence. These results suggest caution in reviving acute benzodiazepine-overdosed patients to avoid iatrogenic withdrawal analogous to naloxone for opiates.