Diabetic ketoacidosis associated with cocaine use

BACKGROUND: Multiple risk factors for diabetic ketoacidosis (DKA) have been described, including omission of insulin therapy and clinical conditions known to increase counterregulatory hormones. Recently, substance abuse has been identified in patients with DKA. We observed many cases of DKA in cocaine users, although the association between cocaine use and DKA has not been well described in the medical literature. METHODS: We performed a retrospective case-control study of admissions for DKA in cocaine users and non-user controls in an urban teaching hospital from January 1, 1985, to December 31, 1994. RESULTS: We identified 720 adult admissions for DKA. Twenty-seven cocaine users accounted for 102 admissions (14% of all DKA admissions). The users were compared with 85 nonuser controls who had 154 DKA admissions. Cocaine users had more admissions for DKA (mean, 3.78 vs 1.81; P = .03). Cocaine users were less likely than controls to have an intercurrent illness identified as a precipitating factor for DKA (14.7% vs 33.1%; P<.001) and were more likely to have missed taking insulin prior to admission (45.1% vs 24.7%; P<.001). Although cocaine users had higher serum glucose levels on admission (32.9 mmol/L [593.4 mg/dL] vs 29.5 mmol/L [531.1 mg/dL]; P =.03), no differences in intensity of illness or treatment outcome were detected. CONCLUSIONS: In this preliminary study, cocaine use was found in a significant number of adults admitted with DKA and was associated with more frequent omission of insulin therapy and the absence of precipitating systemic illness. Either because of its association with insulin therapy omission or its effects on counterregulatory hormones, cocaine use should be considered a risk factor for DKA, particularly in patients with multiple admissions.     

The clinical and diagnostic characteristics of perforations in acutely bleeding gastroduodenal ulcers

Over the period 1982-1996 a total of 8822 patients with ulcerorrhagias were treated in a clinical setting. In 122 (1.4%) patients different variants of association of perforation of the bleeding ulcers (PBU) were recordable. Features of development, course, diagnosis and treatment of PBU patients were studied. Two variants of PBU development were identified: concurrently emerging perforation with ulcer bleeding--in 34 (27.9%) patients; when perforation of the ulcer emerged in 88 (72.1%) in--patients one to seven days following a bleeding event, presenting in 48 (54.5%) with bleeding recurrence, and in 40 (45.5%) patients without the above recurrence against the background of varying degrees gravity of loss of blood. As to PBU localization, 92 (75.4%) patients had the same site (in the stomach--18 subjects, pyloroduodenal region--74 ones), 30 (24.6%) patients developed simultaneously one perforating gastric or duodenal ulcer and some other ulcer bleeding. Analysis of symptoms in PBU and in 474 patients presenting with perforating ulcers without bleeding revealed varying degrees atypicalness of PBU course depending on variants of combination. A symptom complex of lesser PBU sign has been singled out, an algorithm proposed for procedures that might be helpful in making early diagnosis and planning surgical treatment to be done in a timely fashion. The suggested approach enabled the postoperative mortality to be reduced 3.5-fold (from 25% to as low as 7.1%).     

Comparing self-reported cocaine use with repeated urine tests in outpatient cocaine abusers.

Sixty-one participants in outpatient therapy for cocaine dependence provided urine samples and self-reports of cocaine use 3 times a week for 4 weeks. Participants later gave a retrospective self-report of cocaine use for the month on the Addiction Severity Index (ASI). Comparisons with urine test values revealed substantial underreporting of cocaine use on both measures, and results from the 2 forms of self-report were only imperfectly correlated. More participants admitted to at least 1 cocaine use episode on the ASI than on the repeated self-reports, but the repeated reports provided a more accurate index of the relative frequency of cocaine use during the month. Self-reports can enhance cocaine use detection when urines are infrequently collected and can help determine whether consecutive positive urine samples represent elevated metabolite levels from a single drug use episode. However, self-reports cannot substitute for regular urine sampling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sulpiride in the management of gastroduodenal ulcers. A comparative double-blind study

Sulpiride (Dogmatil) is a new type of drug acting on the hypothalamus resulting in a physiological increase in amplitude and frequency of gastric motor activity, reduction of signs of abnormal activity and pyloric spasm and an increase in the rate of gastric emptying. Gastric secretion is for all practical purposes unchanged, either in quantity or in acid content. The effects of Sulpiride on the duodenum are similar through some hypotony may be seen. The motor effects of Sulpiride do not relate to its effectiveness in treatment of gastroduodenal ulceration and experiments have shown that this activity can be explained by the reduction of capillary vaso-constriction in local blood circulation at the site of experimentally-induced ulcers, producing a vaso-dilatation assisting healing. This study objectively evaluates the activity of Sulpiride in gastro-duodenal ulcers. 64 patients were studied under strict criteria and acute hemorragic, multiple or abnormally situated ulcers as well as those associated with other infections were eliminated. The dosage was uniform, two ampoules daily of 100 mgs i.m. of Sulpiride or placebo for 12 days, followed by 3 capsules daily of 50 mgs of Sulpiride or placebo for 48 days. No other treatment was given and no dietery restrictions were imposed, though alcohol and Aspirin and similar drugs were restricted. Of the 64 patients, 26 (18 men, 8 women, aged from 21 to 80 years) had gastric ulcers, 14 were treated with Sulpiride, 12 with placebo. 38 cases (29 men and 9 women, aged between 21 and 70 years) had duodenal ulcers, 18 were treated with Sulpiride, 20 with placebo. Full clinical, biological, radiological and endoscopic tests were carried out and a full questionnaire was completed. Results: Highly significant differences in favour of Sulpiride were shown in both gastric and duodenal ulcer cases, maximum from the 20th day than less significative radiological results appeared. Similar remarks apply to endoscopic results. Sulpiride was extremely well tolerated, though amenorrhea (1) or galactorrhea (2) were noted without causing inconvenience to the patient. The author believes that the clinical effectiveness of Sulpiride in the treatment of gastro-duodenal ulcers is incontestable showing maximum results in ambulatory patients from the 20th day. A large number of patients would probably have produced statistically significant differences in radiological and endoscopic evidence of healing.     

Severe rhabdomyolysis with renal failure after intranasal cocaine use

Torsion of a long bone is the twist along its longitudinal axis; torsion of the radius is defined by the angle between the proximal and distal metaphyses in the transverse plane. Measurement of the radial torsion angle provides a means of detection and quantification of malrotation after a fracture. The purpose of the current study was to develop and standardize a technique for the measurement of torsion of the radius. Axial computerized tomographic images of thirty-nine pairs of dry cadaver specimens of normal radii, and an additional four pairs of radii with a unilateral deformity of the distal metaphysis that was consistent with a previous fracture, were studied and a measurement protocol was established. The radial torsion angle was measured by three independent observers on two separate occasions. Reproducibility of the technique was determined with use of the intraclass correlation coefficient to express both interobserver and intraobserver reliability. Consistency of measurements between observers and by the same observer was high, with intraclass correlation coefficients ranging from 0.87 to 0.94. The mean torsion angle for the eighty-two normal radii in the study was 32.6 degrees (95 per cent confidence interval of the mean, 30.3 to 34.9 degrees; range, 1.4 to 58.8 degrees). There were small variations in torsion angle between the two radii of each normal pair (mean side-to-side difference, 4.9 degrees; 95 per cent confidence interval of the mean, 3.5 to 6.3 degrees). The mean torsion angle of the four radii with a malunited fracture was 10.4 degrees (95 per cent confidence interval of the mean, 5.7 to 15.1 degrees), and the mean side-to-side difference in the pairs containing these radii was 24.1 degrees (95 per cent confidence interval of the mean, 8.5 to 39.6 degrees; p < 0.0001 compared with the normal radii).     

Assessment of cocaine use with quantitative urinalysis and estimation of new uses

Qualitative urinalysis methods of monitoring cocaine use may over-detect frequency of use, possibly decreasing the ability of clinical trials to detect effective treatments. Quantitative urinalysis and newly developed criteria for identifying new cocaine use were evaluated as alternative measures of cocaine use. Urine specimens collected in a cocaine dosing study in non-treatment-seeking subjects (n = 5) and a cocaine treatment trial (n = 37) were analyzed for the cocaine metabolite, benzoylecgonine, with qualitative and quantitative methods. Pharmacokinetic criteria ('New Use' rules) were applied to quantitative data to identify occasions of new cocaine use. Results were compared to known cocaine administrations in the laboratory study and to self-reported drug use and qualitative urinalysis for subjects in the clinical trial. New Use criteria correctly identified cocaine administrations in the cocaine dosing study in all but a small number of specimens. In the clinical trial, quantitative urinalysis and estimated New Uses provided more information about patterns and frequency of use than qualitative urinalysis in the different treatment conditions in the clinical trial. Interpretation of quantitative urinalysis with New Use rules appears to be a useful method for monitoring treatment outcome and may be more accurate than traditional qualitative urinalysis in estimating frequency of cocaine use.     

The late results of the surgical treatment of perforated gastroduodenal ulcers in young people

The article is devoted to surgical treatment of perforating gastroduodenal ulcers. An investigation of remote results of palliative and radical interventions for the perforation of the stomach and duodenum in patients of young age has shown that recurrent ulcers after suturing the perforation take place in 67.2% of the people operated upon against 21% of those subjected to bilateral truncal subdiaphragmatic vagotomy with pyloroplasty. A conclusion is made that for perforating ulcers it is expedient to perform radical operative interventions as a bilateral truncal subdiaphragmatic vagotomy with pyloroplasty.     

The causes of early postoperative complications in the surgical treatment of hemorrhaging gastroduodenal ulcers

Based on the material of 1201 patients who had been operated on for complicated gastroduodenal ulcers, the causes are analyzed of the early postoperative complications (EPC) development. The EPCs were encountered in 15.5%. The most important risk factors identified in the study included peptic ulcer complications, the degree of severity of ulcer bleeding, time for the surgical intervention to be done, the technique employed, with the effects thereof having been studied on the EPC occurrence. Stenosis presenting with penetration and gigantic ulcers was found out to have the most apparent impact on the origination of EPC.     

Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine

The human dopamine D4 receptor (D4R) has received considerable attention because of its high affinity for the atypical antipsychotic clozapine and the unusually polymorphic nature of its gene. To clarify the in vivo role of the D4R, we produced and analyzed mutant mice (D4R-/-) lacking this protein. Although less active in open field tests, D4R-/- mice outperformed wild-type mice on the rotarod and displayed locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Biochemical analyses revealed that dopamine synthesis and its conversion to DOPAC were elevated in the dorsal striatum from D4R-/- mice. Based on these findings, we propose that the D4R modulates normal, coordinated and drug-stimulated motor behaviors as well as the activity of nigrostriatal dopamine neurons.     

Generalization of D-, L- and DL-chlorpheniramine and zolantidine to the discriminative stimulus effects of cocaine and methamphetamine

We recently demonstrated that some H-antagonists have cocaine or methamphetamine-like discriminative stimulus effects. In the present study, the effects of optical isomers of chlorpheniramine (D-, L- and DL-forms) on the discriminative stimulus effects of cocaine and methamphetamine were examined in rats trained to discriminate between cocaine (10.0 mg/kg) or methamphetamine (1.0 mg/kg) and saline, to determine whether these effects of H1-antagonists are mediated by the blockade of H-receptors. In generalization tests with optical isomers of chlorpheniramine, the D-, L- and DL-forms all completely generalized to the discriminative stimulus effects of cocaine, but did not generalize to those of methamphetamine. Dose-generalization by the optical isomers of chlorpheniramine to the discriminative stimulus effects of cocaine did not correlate with the H-antagonistic potency of these drugs. These results suggest that all of the optical isomers of chlorpheniramine have cocaine-like discriminative stimulus effects, but that these effects are not mediated by H1-receptor blockade. On the other hand, the H2-antagonist, zolantidine, generalized to the discriminative stimulus effects of methamphetamine, but not to those of cocaine, suggesting that zolantidine may have methamphetamine-like discriminative stimulus effects. In the present study, GBR12909 (dopamine uptake inhibitor) completely generalized to the discriminative stimulus effects of cocaine, but not to those of methamphetamine, whereas apomorphine (dopamine receptor agonist) generalized more potently to the discriminative stimulus effects of methamphetamine than to those of cocaine. These findings imply that although the dopaminergic system plays an important role in the discriminative stimulus effects of both cocaine and methamphetamine, there may be differences between their effects.     

The validity of self-reported cocaine use in two groups of cocaine abusers.

To evaluate the validity of 2 self-report methods for estimating cocaine use, Timeline Follow-Back (TLFB) and weekly calendar reports from 65 patients with a cocaine use disorder were compared with urine drug test results. The TLFB showed fair to moderate validity, and the weekly calendar showed moderate to high validity in measuring the frequency of cocaine use. Similar results were obtained when the self-report measures were used to time specific cocaine use episodes. In addition to evidence for superiority of the weekly calendar, the validity of self-reports was inversely related to the percentage of positive urine test results. Furthermore, there was some evidence that validity increased as the time window over which the comparisons were drawn increased. Given the central role of self-reports in the clinical and research evaluation of drug use, factors affecting their validity warrant further investigation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association of road-traffic accidents with benzodiazepine use

BACKGROUND: Psychomotor studies suggest that commonly prescribed psychoactive drugs impair driving skills. We have examined the association between the use of psychoactive drugs and road-traffic accidents. METHODS: We used dispensed prescribing as a measure of exposure in a within-person case-crossover study of drivers aged 18 years and over, resident in Tayside, UK, who experienced a first road-traffic accident between Aug 1, 1992, and June 30, 1995, and had used a psychoactive drug (tricyclic antidepressant, benzodiazepine, selective serotonin-reuptake inhibitor, or other psychoactive drug [mainly major tranquillisers]) between Aug 1, 1992, and the date of the accident. For each driver, the risks of having a road-traffic accident while exposed and not exposed to a drug were compared. FINDINGS: 19386 drivers were involved in a first road-traffic accident during the study period. 1731 were users of any study drug. On the day of the accident, 189 individuals were taking tricyclic antidepressants (within-patient exposure odds ratio for an accident 0.93 [95% CI 0.72-1.21]), 84 selective serotonin-reuptake inhibitors (0.85 [0.55-1.33]), 235 benzodiazepines (1.62 [1.24-2.12]), and 47 other psychoactive drugs (0.88 [0.62-1.25]). The risk associated with benzodiazepine use decreased with increasing driver's age and was greater when the breath test for alcohol was positive. A dose-response relation was evident with benzodiazepines. The increased risk with benzodiazepines was significant for long-half-life drugs, used as anxiolytics, and for short-half-life hypnotics (all zopiclone). INTERPRETATION: Users of anxiolytic benzodiazepines and zopiclone were at increased risk of experiencing a road-traffic accident. Users of anxiolytic benzodiazepines and zopiclone should be advised not to drive.     

Intermittent cocaine use associated with recurrent dissection of the thoracic and abdominal aorta

Acute aortic dissection has been reported with the use of cocaine. We report a case of intermittent cocaine use spanning nearly 5 years and leading to recurrent dissection and extension of the false lumen. The patient repeatedly declined surgical correction. Management involved aggressive pharmacologic blood pressure control, close monitoring, and encouragement to enter drug rehabilitation.     

Cocaine use is associated with increased craving in outpatient cocaine abusers

Continuous treatment with transdermal nitroglycerin leads to tolerance development within the first day of application. Effective long-term therapy can be provided by interval treatment with nightly patch removal, but even during the hours of intermittent patch application there is rapid attenuation of initial effects. To assess whether an unattenuated antiischemic and antianginal efficacy during the hours of intermittent dosing can be maintained, a modified drug-release profile with increasing plasma concentrations was evaluated using a double-blind, placebo-controlled crossover protocol. Eleven patients with documented coronary artery disease received, in a randomized order, a total of four low-dose nitroglycerin patches (5 mg/24 h each) or placebo, respectively, at intervals of 3 hours. After a treatment interval of 12 hours, all patches were removed for an equally long patch-free interval prior to renewed application of one patch the next morning. At a comparable workload, reductions of ST-segment depression of 65%, 63%, and 56% were found at 2.5 hours, 8 hours, and 12 hours after application of the first patch on day 1, respectively (all significant vs. placebo; 2.5 hours vs. 12 hours, n.s.). On day 2, the comparable reduction of 63% at 2.5 hours after renewed application indicates prevention of tolerance development during subchronic treatment. Effects on exercise capacity and angina pectoris paralleled those on exercise-induced ST-segment depression. Plasma concentrations of nitroglycerin increased from 223 pg/mL to 558 and 803 pg/mL on day 1 and amounted to 205 ng/mL at 2.5 hours on day 2. Thus, interval therapy with increasing nitroglycerin concentrations provides unattenuated antiischemic and antianginal efficacy during the hours of treatment and circumvention of early tolerance during subchronic application. This modified pharmacokinetic profile can be regarded as a model for an improved dosage regimen in nitrate interval therapy.     

The association between maternal cocaine use and placenta previa

We compared various diagnostic tests for their abilities to detect Mycobacterium ulcerans infection in specimens from patients with clinically active disease. Specimens from 10 patients from the area of Zangnanado (Department of Zou, Benin) with advanced, ulcerated active M. ulcerans infections were studied by direct smear, histopathology, culture, PCR, and oligonucleotide-specific capture plate hybridization (OSCPH). A total of 27 specimens, including 12 swabs of exudate collected before debridement and 15 fragments of tissue obtained during debridement, were submitted to bacteriologic and histopathologic analysis. The histopathologic evaluation of tissues from all six patients so tested revealed changes typical of those caused by M. ulcerans infection. Five specimens were contaminated, and M. ulcerans was cultivated on L?wenstein-Jensen medium from 12 of the remaining 22 (54.5%) specimens. Detection of mycobacteria was performed by PCR, and M. ulcerans was detected by OSCPH with a new probe (5'-CACGGGATTCATGTCCTGT-3') reacting with M. ulcerans and Mycobacterium marinum. In 10 of 22 (45.5%) specimens, M. ulcerans was identified by PCR-OSCPH. There was no statistically significant difference between the detection of M. ulcerans by culture and by PCR-OSCPH (P > 0.05). This is the first demonstration of an amplification system (PCR-OSCPH) with a sensitivity similar to that of culture for the direct and rapid recognition of M. ulcerans in clinical specimens. This system is capable of identifying M. ulcerans, even in paucibacillary lesions. Our findings suggest that PCR-OSCPH should be used in the quest for the elusive environmental reservoir(s) of M. ulcerans.