Mycobacterium tuberculosis infection among persons who inject drugs in San Diego, California.

BACKGROUND: Persons who inject drugs (PWID) might be at increased risk for Mycobacterium tuberculosis infection and reactivation of latent tuberculous infection (LTBI) due to their injection drug use. OBJECTIVES: To determine prevalence and correlates of M. tuberculosis infection among PWID in San Diego, California, USA. METHODS: PWID aged 18 years underwent standardized interviews and serologic testing using an interferon-gamma release assay (IGRA) for LTBI and rapid point-of-care assays for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections. Independent correlates of M. tuberculosis infection were identified using multivariable log-binomial regression. RESULTS: A total of 500 participants met the eligibility criteria. The mean age was 43.2 years (standard deviation 11.6); most subjects were White (52%) or Hispanic (30.8%), and male (75%). Overall, 86.7% reported having ever traveled to Mexico. Prevalence of M. tuberculosis infection was 23.6%; 0.8% were co-infected with HIV and 81.7% were co-infected with HCV. Almost all participants (95%) had been previously tested for M. tuberculosis; 7.6% had been previously told they were infected. M. tuberculosis infection was independently associated with being Hispanic, having longer injection histories, testing HCV-positive, and correctly reporting that people with 'sleeping' TB cannot infect others. CONCLUSIONS: Strategies are needed to increase awareness about and treatment for M. tuberculosis infection among PWID in the US/Mexico border region.

Quantification of Plasmodium malariae infection in mosquito vectors.

Plasmodium malariae occurs in various tropical regions throughout the world and causes low, yet significant, levels of morbidity in human populations. One means of studying the ecology and frequency of this parasite is by measuring sporozoite loads in the salivary glands of infected mosquitoes. An effective, species-specific test that can be used to detect the presence of sporozoites in mosquitoes is the circumsporozoite ELISA. The aim of the present study was to standardize the circumsporozoite ELISA for P.malariae, by setting quantification parameters using, as antigen, either a synthetic peptide or extracts of whole sporozoites. The standard quantification curves produced indicated that the assay had a lower threshold of sensitivity of 250 sporozoites in a 50-microl sample, equivalent to about 1250 sporozoites in a mosquito.

Quantitative determination of sporozoites and circumsporozoite antigen in mosquitoes infected with Plasmodium falciparum or P. vivax.

It is essential for malariologists and researchers to have simple and accurate means of assessing the threat of Plasmodium parasites. An attempt was therefore made to re-standardize one of the circumsporozoite (CS) ELISA that can be used to detect and quantify the circumsporozoite antigens of P. falciparum and P. vivax. A two-site, 'sandwich' ELISA based on a monoclonal antibody was used to test for the CS antigen and sporozoites of each Plasmodium species simultaneously. Using the resultant optical-density values, standard curves, that permit the number of sporozoites in an infected mosquito to be estimated from the quantification of the CS antigen, were constructed. Using these plots and the CS ELISA, the presence of just 12.5 sporozoites (i.e. 0.8 pg CS antigen) of P. falciparum, four sporozoites (3.2 pg antigen) of P. vivax-210 or 12.5 sporozoites (32.0 pg antigen) of P. vivax-247 could be demonstrated.

Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay.

To determine which species and populations of Anopheles transmit malaria in any given situation, immunological assays for malaria sporozoite antigen can replace traditional microscopical examination of freshly dissected Anopheles. We developed a wicking assay for use with mosquitoes that identifies the presence or absence of specific peptide epitopes of circumsporozoite (CS) protein of Plasmodium falciparum and two strains of Plasmodium vivax (variants 210 and 247). The resulting assay (VecTest Malaria) is a rapid, one-step procedure using a 'dipstick' test strip capable of detecting and distinguishing between P. falciparum and P. vivax infections in mosquitoes. The objective of the present study was to test the efficacy, sensitivity, stability and field-user acceptability of this wicking dipstick assay. In collaboration with 16 test centres world-wide, we evaluated more than 40 000 units of this assay, comparing it to the standard CS ELISA. The 'VecTest Malaria' was found to show 92% sensitivity and 98.1% specificity, with 97.8% accuracy overall. In accelerated storage tests, the dipsticks remained stable for > 15 weeks in dry conditions up to 45 degrees C and in humid conditions up to 37 degrees C. Evidently, this quick and easy dipstick test performs at an acceptable level of reliability and offers practical advantages for field workers needing to make rapid surveys of malaria vectors.

Career involvement and family involvement as moderators of relationships between work-family conflict and withdrawal from a profession.

This study extended prior analyses by J. H. Greenhaus, K. M. Collins, R. Singh, and S. Parasuraman (1997) by examining relationships between 2 directions of work-family conflict (work-to-family conflict and family-to-work conflict) and withdrawal from public accounting. The sample consisted of 199 members of the American Institute of Certified Public Accountants (135 men and 64 women) who were married or in a long-term relationship and who had 1 or more children. It was found that work-to-family conflict (but not family-to-work conflict) was positively related to withdrawal intentions. In addition, relationships of work-to-family conflict with withdrawal intentions and withdrawal behavior were stronger for individuals who were relatively uninvolved in their careers than for those who were highly involved in their careers. The implications of the findings for future research are discussed.

Writing apprehension and academic procrastination among graduate students.

Academic procrastination has been associated with both fear of failure and task aversiveness. Researchers have reported that most undergraduate and graduate students delay academic tasks. Among the latter, a large proportion report procrastination in writing term papers. Such procrastination may originate from and lead to anxiety about writing so the present purpose was to investigate the relationship between scores on Daly and Miller's 1975 Writing Apprehension Test and on the two dimensions, i.e., fear of failure and task aversiveness, of Solomon and Rothblum's 1984 Procrastination Assessment Scale-Students. Participants were 135 graduate students of varied disciplinary backgrounds. Correlations between writing apprehension and academic procrastination stemmed from fear of failure (29) and task aversiveness (.41). Implications are discussed.

hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response.

Mutations in the BRCA1 (ref. 1) tumour suppressor gene are found in almost all of the families with inherited breast and ovarian cancers and about half of the families with only breast cancer. Although the biochemical function of BRCA1 is not well understood, it is important for DNA damage repair and cell-cycle checkpoint. BRCA1 exists in nuclear foci but is hyperphosphorylated and disperses after DNA damage. It is not known whether BRCA1 phosphorylation and dispersion and its function in DNA damage response are related. In yeast the DNA damage response and the replication-block checkpoint are mediated partly through the Cds1 kinase family. Here we report that the human Cds1 kinase (hCds1/Chk2) regulates BRCA1 function after DNA damage by phosphorylating serine 988 of BRCA1. We show that hCds1 and BRCA1 interact and co-localize within discrete nuclear foci but separate after gamma irradiation. Phosphorylation of BRCA1 at serine 988 is required for the release of BRCA1 from hCds1. This phosphorylation is also important for the ability of BRCA1 to restore survival after DNA damage in the BRCA1-mutated cell line HCC1937.

Clinical comparison of the SITE IRAS hand-held interferometer and Haag-Streit Lotmar visometer.

The preoperative testing of retinal acuity was evaluated using two instruments in each of 35 eyes having extracapsular cataract extraction. Retinal acuity was measured using the SITE IRAS hand-held interferometer and the Haag-Streit Lotmar visometer. The postoperative findings are given for comparisons of final acuity, prediction, and instrument evaluation. The results showed predicted acuity to be within two lines of the final acuity in 57.1% of eyes with the Haag-Streit unit and in 42.8% of eyes with the SITE instrument. The instrument differences were more in procedure than in results.

Categorization of hospital emergency services--developing valid criteria.

In a pilot project sponsored by the California State Emergency Medical Services Authority, validated, verifiable criteria were developed for the vertical categorization of hospital emergency services in 11 different groupings of medical and surgical emergencies. We describe the development of an assessment process and categorization criteria to identify the most appropriate receiving facility for interfacility transfer and, in selected instances, field triage of patients with different levels of severity of illness or injury. We propose that this facility assessment project be used in the critical care planning process for the eventual vertical categorization of hospital emergency services in California and as a template for similar projects in other states.

Outpatient termination of pregnancy: halothane or alfentanil-supplemented anaesthesia.

Inhalation anaesthesia with halothane was compared with i.v. alfentanil in 66 unpremedicated patients undergoing suction termination of pregnancy as outpatients. Blood loss was significantly greater in the halothane group with a mean loss of 213 ml, compared with a mean loss of 89.8 ml in the alfentanil group. There was a greater frequency of nausea and vomiting in the alfentanil group, but no reduction in abdominal pain or need for analgesia after operation. Positive relationships were found between blood loss and duration of anaesthesia and between blood loss and gestational age in the halothane group, but not in the alfentanil group. We conclude that alfentanil-supplemented anaesthesia is satisfactory for suction termination of pregnancy when rapid recovery is required or the duration of the procedure is likely to be long, but that halothane anaesthesia cannot be recommended, especially if the procedure is long.

Use of alfentanil in short anaesthetic procedures.

The pharmacokinetics of alfentanil, a new and very short-acting opioid, are discussed. Its use in day-case gynaecological procedures is described, and the results of the initial study presented. Alfentanil is a valuable adjunct to anaesthesia for day-case surgery and for short, painful procedures.

Comparison of atracurium and alcuronium in day-case gynaecological surgery.

Alcuronium and atracurium were used on a randomised basis as part of the anaesthetic technique for out-patient gynaecological laparoscopy. Conditions for intubation and relaxation were similar but there was a marked decrease in the incidence of minor postoperative sequelae in the atracurium group.

Postoperative morbidity following gynaecological outpatient laparoscopy. A reappraisal of the service.

Fifty-six women having out-patient gynaecological laparoscopies were studied to determine anaesthetic problems and postoperative morbidity. It is concluded that the procedure is safe, and although the postoperative morbidity appears high it is very acceptable to the patient.

Studies of activating and nonactivating metal ion binding to yeast enolase.

Measurements of binding of certain divalent cations to yeast apoenolase were made using a pH-meter, chromatography, a divalent cation electrode, and ultrafiltration. The binding of the activating metal ions Mg2+ and Co2+ and the nonactivator Ca2+ were studied as functions of the presence or absence of substrate/product, phosphate, and fluoride or level of Tb3+. The data suggest phosphate and fluoride increase Mg2+ binding but not Ca2+ binding. Substrate/product appears to increase Ca2+ binding as well as that of Mg2+ and Co2+. In the presence of substrate, Co2+ binding was 5-6 mol/mol dimer. In the absence of substrate/product, Tb3+ reduced Co2+ binding from 4 mol/mol to 2. These data are interpreted in terms of binding to "conformational," "catalytic" (substrate/product dependent), and "inhibitory" sites. Measurements of Tb3+ fluorescence quenching by Co2+ suggested that the distance between "conformational" sites on the two subunits was large, while the distance between "conformational" and "inhibitory" sites was ca. 17 +/- 4 A. Potentiometric titrations of apoenzyme with Ca2+ and Mg2+ showed that the metal ions produced the same proton release in the presence or absence of substrate/product. If phosphate and fluoride were present, then more protons were released if Ca2+ was the titrant rather than Mg2+, suggesting a difference in ionization state in the complex with the activating metal. Electron paramagnetic resonance studies of Co2+ binding to the various sites in the enzyme are presented. The Co2+ bound to all three sites appears to be high spin, consistent with a preponderance of oxyligands in an octahedral environment. Substrate, citrate, and a strongly binding substrate analogue strongly enhance the hyperfine structure of conformational Co2+. This is interpreted as the result of a change in interaction of an axial ligand to conformational Co2+ produced by carbon-3 of substrate or analogue.

Circular dichroism (CD) studies on yeast enolase: activation by divalent cations.

The effect of divalent cations on the near ultraviolet circular dichroism (CD) spectrum of yeast enolase showed that calcium, magnesium, and nickel ions produced identical changes. This was interpreted as indicating that the cations bound to the same sites on the enzyme and produced identical changes in tertiary structure. There was no effect of magnesium ion on the far ultraviolet spectrum. Evidently magnesium ion has no effect on the secondary structure. Substrate bound to the enzyme when the above cations were present although calcium permits no enzymatic activity. The CD spectral difference produced by the substrate was nearly the reverse of that produced by the metal ions. Glycolic acid phosphate, a competitive inhibitor lacking carbon-3, produced no effect, indicating carbon-3 was necessary for the CD spectral changes. The CD and visible absorption spectra of nickel and cobalt bound to various sites on the enzyme showed that the binding sites were octahedral or distorted octahedral in coordination and that the ligands appeared to be oxyligands: water molecules, hydroxyl or carboxyl groups. Examination of the effects of substrate and two compounds thought to be "transition state analogues" showed that these perturbed the "conformational" sites of the enzyme. The "catalytic" and "inhibitory" sites did not appear to be very CD active.

Fluid loading to reduce abnormalities of fetal heart rate and maternal hypotension during epidural analgesia in labour.

Fetal heart rate (FHR) was recorded and maternal blood pressure measured in 104 patients in whom lumbar epidural analgesia was induced in labour. Fifty-one patients received an intravenous load of 11 of Hartmann's solution immediately before the epidural injection. This infusion significantly reduced the incidence of abnormalities of FHR from 34% to 12% and of maternal hypotension from 28% to 2%. We did not study mothers with pre-eclampsia and hypertension, but we conclude that there is a strong case for preloading all other mothers in whom lumbar epidural analgesia is induced in labour.