Novel isosorbide-based substrates for human butyrylcholinesterase.

Butyrylcholinesterase [EC 3.1.1.8] present widely in mammalian tissue does not have a precisely defined biological function or known endogenous substrate. However, it plays an important role in the detoxification of certain xenobiotics and is an established vector for the systemic liberation of other drugs from their prodrugs. While investigating a series of isosorbide-based prodrugs, we discovered that BuChE catalyses the hydrolysis of esters of the simple sugar isosorbide with unusually rapidity and in some cases with remarkable regioselectivity. In this study, a series of isosorbide esters were synthesised and their rates of hydrolysis measured by HPLC following incubation in diluted plasma solution. In general, little hydrolysis of the 5-ester group could be observed but the 2-ester group was usually hydrolysed very rapidly and the hydrolysis rate exhibited an unusual dependence on the identity of the 5-group. The results indicate that while the 5-ester group is not itself hydrolysed it is important for productive binding in isosorbide diesters.

HIV testing in the setting of inpatient acute substance abuse treatment.

We examined patients' attitudes toward HIV testing in the setting of acute substance abuse treatment and determined the prevalence of offering routine on-site testing for human immunodeficiency virus (HIV) in inpatient state-funded detoxification centers in New England. Voluntary questionnaires were administered to patients (N = 66 respondents) at the only two state-funded inpatient drug detoxification treatment centers in Rhode Island, and a telephone survey of all state-funded inpatient detoxification facilities across the New England area was conducted. In New England, 17/38 (44.7%) of all state-funded inpatient detoxification facilities didnot routinely offer on-site HIV testing to clients. Of participants, 97% responded positively to the question, "Do you think HIV testing should be available to patients in drug detoxification facilities such as this one?" There were 89% who reported that they would cope "about the same" or "better" with receiving a positive HIV test result while in detoxification treatment versus elsewhere. The greatest number of participants ranked the Orasure HIV test, an assay for HIV-1 transmucosal antibody, as the test they would most prefer while in drug treatment. However, 59% of patients responded that the type of test offered would not make a difference in whether they chose testing. Most patients indicated that they would want to see a physician within a few days of a positive diagnosis of HIV infection. Despite the controversy surrounding the provision of HIV testing to patients in inpatient acute substance abuse treatment, HIV testing is desired among these patients provided that HIV clinical care is readily available.

HIV testing among young adults and older adolescents in the setting of acute substance abuse treatment.

OBJECTIVES: To examine the feasibility and acceptance of HIV testing among youth in acute substance abuse treatment. METHODS: Youth, aged 18 to 25 years old, in state-funded inpatient detoxification completed a confidential demographic/risk behavior questionnaire, and were offered a choice of no testing, serum-based testing, or oral fluid (Orasure, Epitope, Inc., Beaverton, OR, U.S.A.) HIV testing. RESULTS: In all, 74% of 204 participants accepted HIV testing. In a multivariate model, female gender (odds ratio [OR], 0.32; 95% confidence interval [CI] 0.14-0.74) and having been recently tested (OR, 0.11; 95% CI, 0.05-0.26) were independently associated with refusing testing. Recent sexual activity (OR, 5.4; 95% CI, 1.5-20.4), recent use of methamphetamines (speed) or a combination of cocaine and heroin (speedball) (OR, 3.8; 95% CI, 1.6-9.0), and a recent perceived risk for HIV (OR, 4.6; 95% CI, 1.9-10.9) were independently associated with test acceptance. Thus, 150 of 150 (100%) chose the Orasure test. Overall, 64.6% (97 of 150) of those tested received their results, but among participants requiring a follow-up appointment to learn test results, only 9.2% (8 of 87) returned. CONCLUSIONS: HIV testing is feasible and acceptable in this population. All patients preferred Orasure testing to a serum enzyme-linked immunosorbent assay (ELISA). Most youth tested in detoxification will only learn their results if they are provided during treatment. Rapid HIV testing with same-day results could improve follow-up rates.

Risk factors for syphilis among incarcerated women in Rhode Island.

Syphilis remains a significant problem in the United States. The prison environment is an ideal location to identify and treat syphilis. We undertook this study to describe the correlates and risk factors for syphilis among incarcerated women in Rhode Island. The study design was a review of all cases of syphilis identified through routine screening in the state prison and a case control study. Between 1992 and 1998, among 6,249 incarcerated women, 86 were found to have syphilis; of these, 29 were primary and secondary cases representing 49% of infectious cases of syphilis in women in the state. The prison environment offers a unique opportunity for the diagnosis and treatment of syphilis.

Laboratory testing for infection with the human immunodeficiency virus: established and novel approaches.

The enzyme-linked immunosorbent assay (ELISA) and the Western blot are the primary tests for the diagnosis and confirmation of human immunodeficiency virus (HIV) infection. The ELISA, an inexpensive screening test for antibodies to HIV-1, is both sensitive and specific. The HIV-1 Western blot is a reliable confirmatory test following a repeatedly reactive ELISA. False-positive HIV-1 results with this sequence of tests are extremely rare but can occur, and test results that are inconsistent with clinical or other laboratory information should be questioned, repeated, or supplemented. The US Food and Drug Administration has also approved rapid and more accessible testing methods. Oral mucosal transudate and urine testing are noninvasive testing methods; rapid and home sample collection kits offer easier access to testing.

Comprehensive medical care among HIV-positive incarcerated women: the Rhode Island experience.

Our objective was to characterize the clinical presentation of human immunodeficiency virus (HIV) infection among incarcerated women in a program that provides HIV testing and primary care to all state prisoners in Rhode Island. A retrospective medical chart review on all HIV-seropositive women who were incarcerated between 1989 and 1994 and had at least two medical visits with an HIV medical care provider was used. At the Rhode Island Adult Correctional Institution (ACI), under mandatory testing laws between 1989 and 1994, 28% (172 of 623) of all women were identified with HIV infection. Of the 172 women who tested seropositive in prison, 110 were included in the study. Of the 110 women followed, 84% reported injection drug use (IDU) as their primary risk factor, and 30% reported both IDU and sex work. The median CD4 count was 596/mm3, with 60% having a CD4 count >500 cells/mm3. The most common medical conditions were vaginal candidiasis, oral candidiasis, and bronchitis. Antiretroviral therapy was well accepted and followed community standards. Continuity of medical care after release was facilitated by the same physician caring for the patient in the community setting, with 83% of women following up for HIV care after release. The medical conditions noted reflect that these women are early in the course of their HIV disease when they are initially diagnosed. This comprehensive program in Rhode Island's state prison plays a central role in the diagnosis of HIV-seropositive women and provides counseling, primary medical and gynecological care, and linkage to community resources after release.

Oral cimetidine (Tagamet) for recalcitrant, diffuse conjunctival papillomatosis.

PURPOSE: To report the efficacy of cimetidine for treatment of conjunctival papillomatosis. METHODS: An 11-year-old boy had an 8-year history of diffuse conjunctival papillomas, treated previously with standard measures of excisional biopsy and cryotherapy. He developed spontaneous conjunctival bleeding and diffuse tumor recurrence over the entire conjunctival surface. Oral cimetidine liquid (30 mg/kg/day) was prescribed. RESULTS: Within 2 months, dramatic tumor regression was noted, with nearly complete resolution by 4 months. The patient had no local or systemic side effects from the medication. CONCLUSIONS: Oral cimetidine possesses immune modulation properties and may be useful in some cases of virus-induced conjunctival papillomatosis.

Hepatitis B and C in the context of HIV disease: implications for incarcerated populations.

HIV-infected inmates are often co-infected with hepatitis B and/or hepatitis C virus. To describe the burden of HIV in the incarcerated population today, one must consider the impact of co-infection. HIV may dramatically modify the course of viral hepatitis infection, especially chronic hepatitis C. The converse is uncertain: chronic hepatitis does not seem to accelerate HIV disease progression. In this article, we offer guidelines for selecting appropriate candidates for treatment among co-infected inmates.

Legionella bozemanii pneumonia in three patients with AIDS.

Legionella bozemanii is known to cause pneumonia often in immunocompromised hosts. To our knowledge, we describe the first three cases of L. bozemanii pneumonia in patients with AIDS. At the time of presentation, these patients had varied histories, physical findings, and radiological findings. All three patients had a uniformly excellent response to treatment despite receiving different antibiotic regimens. The cases illustrate the need for thorough diagnostic workups and prompt institution of antibiotic therapy when clinical suspicion for L. bozemanii infection is high.

Hypercalcemia in an AIDS patient treated with growth hormone.

METHOD: Recombinant human growth hormone (rhGH) is a newly approved treatment for weight loss and wasting in patients with AIDS. We report a male patient with advanced AIDS who developed hypercalcemia 2 weeks after institution of rhGH therapy. RESULTS: Parathyroid hormone, parathyroid hormone-related peptide and 1,25-dihydroxyvitamin D levels were suppressed, suggesting that hypercalcemia was mediated through alternative mechanisms. The hypercalcemia responded to discontinuation of rhGH and a single dose of intravenous pamidronate disodium and has not recurred in 8 months of follow-up. CONCLUSION: We believe this to be the first reported case of rhGH-induced hypercalcemia in an HIV-infected patient.

Crohn's disease of the vulva in an 8-year-old girl.

An 8-year-old girl had Crohn's disease of the vulva 16 months before the onset of intestinal symptoms. At the time of diagnosis she had no evidence of systemic disease. Cutaneous and intestinal lesions responded rapidly to corticosteroids and metronidazole. Crohn's disease must be considered in the differential diagnosis of nontender, red, edematous plaques of the genital area.

Abdominal aortic aneurysm resection in patients more than 80 years old.

Improvement in anesthetic and surgical techniques has prompted a more aggressive approach to repair of abdominal aortic aneurysms in patients more than 80 years old. In order to determine if surgical treatment is justified, all of the patients who were more than 80 years old admitted to the hospital during the ten year period from 1974 to 1983 with the diagnosis of abdominal aortic aneurysm were reviewed. A total of 90 patients were available for analysis. The mortality of the 18 patients treated conservatively for ruptured aortic aneurysms was 100 per cent. Ten of the 27 patients operated upon for a ruptured aneurysm died yielding a mortality of 37 per cent. Eleven patients with symptomatic aneurysms had urgent repair with a mortality of 27 per cent. Only one of the 34 patients undergoing elective aneurysm repair died. There was no difference in the size of aneurysms among the groups. Although the ruptured aneurysms required more blood (10.2 +/- 3.7 units), there was no difference between the other two groups (symptomatic 4.5 +/- 3.1 units, elective 4.6 +/- 2.8 units). There was significantly fewer myocardial and renal complications in the elective group, although the sole death in this group was from myocardial infarction. Based upon these observations, we recommend aggressive elective therapy for selected patients who are more than 80 years of age with asymptomatic abdominal aortic aneurysms. Although the mortality is higher in those patients with symptomatic or ruptured aneurysms, it is not formidable, and therefore, repair should not be ruled out on the basis of age alone.

Accuracy of carotid Doppler peak frequency analysis: results determined by receiver operating characteristic curves and likelihood ratios.

To determine the accuracy of peak Doppler frequency measurements in the diagnosis of extracranial carotid arterial disease and to apply the results to the assessment of the individual patient, 397 studies of continuous-wave Doppler frequency analysis were compared with the results of arteriography. The diagnostic accuracy of the measurement of peak frequency was determined in two ways. First, receiver operator characteristic curves were calculated for different threshold levels of peak frequency. The results showed that the measurement of the peak frequency can be related in only an approximate way to the severity of the arteriographic stenosis because of the uncertainty of the probe-to-vessel angle. Nevertheless, the overall maximum diagnostic accuracy was approximately 91% (Kappa = 0.82 +/- 0.05). Second, likelihood ratios were calculated to take into account the degree of abnormality of the peak frequency measurements. The probability of carotid disease increased as the peak frequency increased, giving likelihood ratio ranges from 0.03 to 25.71. To be able to apply the peak frequency measurements to the assessment of the individual patient in the vascular laboratory, our results were used to construct tables that show the posttest probability of carotid disease based on the clinically estimated pretest probability of disease and the measured peak frequency. It is concluded that the measurement of peak Doppler frequency is an adjunct in the diagnosis of carotid artery disease.

Percutaneous transluminal dilatation of peripheral arteries: an analysis of factors predicting early success.

Four hundred ninety-five patients undergoing peripheral arterial percutaneous transluminal dilatation (TLD) with the Gruntzig balloon catheter were studied prospectively to determine which factors could be used to predict a successful result from the procedure. Ten variables were recorded before the TLD. The procedure was considered a success at follow-up if both the clinical grade and the objective vascular laboratory results improved. The results of a logistic discriminant function analysis showed that three variables were associated with success of a TLD at 3 months: the site of the TLD, the severity of the lesion (i.e., stenosis or occlusion), and the runoff. With these results, logistic regression analysis was used to estimate the chances of a successful result for all combinations of these significant variables. It is concluded that the early result of a TLD is determined by the site of the TLD, the severity of the lesion, and the runoff. A table of the estimated chances of success for any combination of these variables has been constructed and accurately describes our patient population.

Limitations in the accuracy of peak frequency measurements in the diagnosis of carotid disease.

Peak Doppler frequency is an index of the severity of carotid stenosis. Variability in this measurement is examined through in vitro and clinical studies. In vitro studies, using a carotid flow model, show that observers locate a stenosis and interpret the peak frequency differently, and each observer uses a different probe-vessel angle. Clinical studies support these findings. Comparison of 304 carotid Doppler studies with arteriograms demonstrates 90% overall clinical accuracy. Each observer has a consistent range of peak frequency measurements, yet the description of a discrete percent stenosis is limited by observer variability.

Computer-assisted handwriting instruction and visual/kinaesthetic feedback processes.

An evaluation of computer-assisted handwriting exercises which offer significant advantages over more conventional teaching techniques is described. Handwriting is considered as a skill that must be regulated by processes which at first are externally controlled but which become internalized as the learner becomes more proficient at the skill. Handwriting samples of lower-case alphanumeric characters were obtained from nine mentally retarded school children. After a training program spread over a period of four weeks (approximately 5 hours in total), the greatest improvement in handwriting ability occurred where the constraints of the computer-assisted handwriting exercises encouraged students to gradually transfer control of letter formation from computer-mediated cues to more internal ones. These results are discussed in terms of control functions and the acquisition of skilled behavior.

Computer-assisted teaching of sight-word recognition for mentally retarded school children.

A computer-assisted training program used to teach a sight vocabulary to mildly mentally retarded school children was described and evaluated. The training program was designed to supplement conventional methods of teaching by using aspects of computer technology to implement various learning principles that would otherwise be difficult to employ. Eight children were taught associations between the written and spoken versions of words by a "talking" computer. These children increased their sight vocabularies by an average of 128 percent; a comparison group had a 34 percent increase. Furthermore, this increase remained constant for over 23 weeks following the completion of the nonintensive 4-week training program.