Long-term outcomes following infection with meticillin-resistant or meticillin-susceptible Staphylococcus aureus.

Staphylococcus aureus (SA) is becoming increasingly resistant to antibiotics in hospitals and the community. Long-term outcomes following susceptible and resistant SA infection have not been studied. We performed a retrospective matched pair analysis of all patients with positive culture for meticillin-resistant SA (MRSA) or meticillin-susceptible SA (MSSA) from any site to assess the outcomes of infection. Data were collected for length of hospitalisation and in-hospital mortality, as well as longer-term outcomes including all-cause mortality, number of rehospitalisations and subsequent cultures for SA during the year following infection. Twelve months after their initial SA infection, 42% of patients were dead. There were no differences between the groups in short-term mortality, length of hospitalisation, number of subsequent hospitalisations and cultures for SA during the year following infection. Following discharge, however, MRSA infection was associated with higher mortality than MSSA at three months (32% vs 18% P=0.02), six months (42% vs 22% P=0.002) and 12 months (51% vs 32% P=0.005). In conclusion, SA infection is associated with a high one-year all-cause mortality. Most deaths occur after discharge. The likelihood of dying during the year following infection is higher for patients with MRSA infection than for those with MSSA infection.

Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience.

We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%. Relapse was the major cause of treatment failure and occurred in 32% of patients at a median of 61 days post SCT. Five-year overall survival and leukemia-free survival (LFS) were 43% (95% CI 31-61%). All patients with favorable cytogenetics (n=6) are alive in CR. Outcomes in patients with primary refractory disease were equivalent to those with relapsed refractory AML. Blast percentage ⩽30% in the BM pre-SCT, myeloablative conditioning and acute GVHD proved to be favorable prognostic features. We could stratify patients according to age ⩾10 years and >30% blasts in BM pre-SCT. Patients with none/one of these risk factors were highly salvageable (5 years LFS 53%) whereas those with both factors had a very poor prognosis (5 years LFS 10%). This may facilitate decision making on whether it is appropriate to consider transplant in such patients.

Recipient/donor HLA and CMV matching in recipients of T-cell-depleted unrelated donor haematopoietic cell transplants.

Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1.22, 95% confidence interval (CI) 1.2-1.5, P=0.033 for 1 mismatch and RR 1.46, 95% CI 1.1-1.9, P=0.009 for >1 mismatch) and CMV mismatching (RR 1.37, 95% CI 1.2-1.6, P<0.001) were significantly associated with inferior survival. Donors aged <30 years showed a trend towards better survival. The multivariate model for mortality, combining CMV and HLA-match status, found an RR of 1.36 (95% CI 1.1-1.7, P=0.003) for HLA matched/CMV mismatched, an RR of 1.22 (95% CI 0.99-1.5, P=0.062) for HLA mismatched/CMV matched and an RR of 1.81 (95% CI 1.4-2.3, P=<0.001) for HLA/ CMV mismatched, compared with the HLA/CMV-matched recipients. These data suggest that HLA and CMV matching status should be considered when selecting unrelated donors and that CMV matching may abrogate the effect of an HLA mismatch.

Characterization of an ovarian carcinoma cell line resistant to cisplatin and flavopiridol.

Flavopiridol, the first inhibitor of cyclin-dependent kinases to enter clinical trials, has shown promising antineoplastic activity and is currently undergoing Phase II testing. Little is known about mechanisms of resistance to this agent. In the present study, we have characterized an ovarian carcinoma cell line [OV202 high passage (hp)] that spontaneously developed drug resistance upon prolonged passage in tissue culture. Standard cytogenetic analysis and spectral karyotyping revealed that OV202 hp and the parental low passage line OV202 shared several marker chromosomes, confirming the relatedness of these cell lines. Immunoblotting demonstrated that OV202 and OV202 hp contained similar levels of a variety of polypeptides involved in cell cycle regulation, including cyclin-dependent kinases 2 and 4; cyclins A, D1, and E; and proliferating cell nuclear antigen. Despite these similarities, OV202 hp was resistant to flavopiridol and cisplatin, with increases of 5- and 3-fold, respectively, in the mean drug concentrations required to inhibit colony formation by 90%. In contrast, OV202 hp and OV202 displayed indistinguishable sensitivities to oxaliplatin, paclitaxel, topotecan, 1,3-bis(2-chloroethyl)-1-nitrosourea, etoposide, doxorubicin, vincristine, and 5-fluorouracil, suggesting that the spontaneously acquired resistance was not attributable to altered P-glycoprotein levels or a general failure to engage the cell death machinery. After incubation with cisplatin, whole cell platinum and platinum-DNA adducts measured using mass spectrometry were lower in OV202 hp cells than OV202 cells. Similarly, after flavopiridol exposure, whole cell flavopiridol concentrations measured by a newly developed high performance liquid chromatography assay were lower in OV202 hp cells. These data are consistent with the hypothesis that acquisition of spontaneous resistance to flavopiridol and cisplatin in OV202 hp cells is due, at least in part, to reduced accumulation of the respective drugs. These observations not only provide the first characterization of a flavopiridol-resistant cell line but also raise the possibility that alterations in drug accumulation might be important in determining sensitivity to this agent.

Failure of cooking to prevent shellfish-associated viral gastroenteritis.

BACKGROUND: In January 1995, Florida experienced the largest outbreak of oyster-associated gastroenteritis ever reported. METHODS: We interviewed both the cohort of persons from 38 gatherings where illness was reported and a sample of harvesters and harvest-area residents. Oysters were traced by means of tags and dealer records, and water quality measures in harvest areas were reviewed. We examined stool specimens for small round structured viruses by means of electron microscopy and amplification of RNA by reverse-transcriptase polymerase chain reaction. We also tested serum specimens for antibodies to Norwalk virus. RESULTS: Of 223 oyster eaters, 58% (129/223) became ill, compared with 3% (2/76) of non-oyster eaters (relative risk, 22; 95% confidence interval, 5.6-87.0). Most oyster eaters (67% [149/223]) ate only cooked (grilled, stewed, or fried) oysters. Oyster eaters who reported eating only thoroughly cooked oysters were as likely to become ill as those who ate raw oysters (relative risk, 0.68; 95% confidence interval, 0.45-1.0; P = .1). In 29 clusters, implicated oysters were from Apalachicola Bay, Florida. A community outbreak occurred in 2 bayside communities before the oyster harvest, leading to an increase in the reportedly common practice of overboard dumping of feces. Small round structured viruses were identified in the stool specimens of 2 harvest-area residents and 9 persons from 8 clusters. Results of water quality tests for fecal coliforms were within acceptable limits. CONCLUSIONS: This large outbreak of gastroenteritis associated with oysters may have resulted from overboard dumping of feces during a community outbreak of diarrheal illness. Our findings of acceptable water quality measures for fecal contamination and the lack of appreciable protective effect from cooking leave the consumer with no assurance of safety.

Erythema migrans-like rash illness at a camp in North Carolina: a new tick-borne disease?

BACKGROUND: Borrelia burgdorferi, the causative agent of Lyme disease, has never been isolated from a patient thought to have acquired Lyme disease in any southeastern state. OBJECTIVE: To investigate 14 cases of an erythema migrans (EM)-like rash illness that occurred during 2 summers at an outdoor camp in central North Carolina in an effort to determine the etiologic, epidemiological, and clinical aspects of this illness. METHODS: Using active surveillance, we identified cases of clinically diagnosed EM in residents and staff of the camp. We collected clinical and demographic information; history of exposure to ticks; acute and convalescent serum antibodies to B. burgdorferi, Rickettsia rickettsii, and Ehrlichia chaffeensis; and cultures for spirochetes from biopsy specimens of skin lesions. Serum samples from a group of residents and staff who did not develop rashes were tested for the same antibodies. We speciated ticks removed from people and collected from vegetation. RESULTS: We identified 14 cases of EM-like rash illness during the 2 summers. Of the 14 case-patients, 10 had associated mild systemic symptoms and 1 had documented fever. All 14 case-patients had removed attached ticks, and 8 remembered having removed a tick from the site where the rash developed a median of 12 days earlier (range, 2-21 days). One tick removed from the site where a rash later developed was identified as Amblyomma americanum, the Lone Star tick; 97% of ticks collected from vegetation and 95% of ticks removed from people were A. americanum. No spirochetes were isolated from skin biopsy specimens. Paired serum samples from 13 case-patients did not show diagnostic antibody responses to B. burgdorferi or other tick-borne pathogens. CONCLUSIONS: This investigation suggests the existence of a new tick-associated rash illness. We suspect that the disease agent is carried by A. americanum ticks. In the southern United States, EM-like rash illness should no longer be considered definitive evidence of early Lyme disease.

Impact of pre-transplant co-morbidities on outcome after alemtuzumab-based reduced intensity conditioning allo-SCT in elderly patients: a British Society of Blood and Marrow Transplantation study.

The advent of reduced intensity conditioning (RIC) regimens has permitted the extension of allo-SCT to selected patients into their eighth decade but GVHD remains a major cause of morbidity and mortality. Alemtuzumab is increasingly used to reduce the risk of severe GVHD, but there are concerns that T-cell depletion may compromise outcome particularly in older patients. We therefore studied the impact of pre-transplant factors on the outcome of 187 patients with a haematological malignancy over the age of 60 transplanted using an alemtuzumab-based RIC regimen of whom co-morbidity scoring was possible in 169. Of the patients, 120 had a haematopoietic cell transplantation co-morbidity index (HCT-CI) of 0 or 1 and 49 had a score of 2 or more. The 5-year OS was 33%. In multivariable analysis, OS was determined by co-morbidity score (P=0.001) and disease status at transplant (P=0.004) but not by patient age. Non-relapse mortality was determined by co-morbidity score (P=0.001). Two-year OS for patients with a HCT-CI of 0-1 was 59 versus 6% for patients with a higher score. Alemtuzumab-based RIC allografts can be delivered safely in patients aged over 60 but co-morbidity scoring is mandatory to identify patients who will benefit.

Alpha 2-adrenergic agonists increase cellular lactate efflux.

We reported previously that genetic polymorphisms of the alpha 2-adrenergic receptor are associated with hyperinsulinemia, diabetes mellitus, and hypertension in blacks. The evolutionary driving force for maintaining such deleterious mutations in the black population is unknown. Recognizing that vascular alpha 2-adrenergic receptors mediate cold-induced vasoconstriction and that temperature maintenance is a primary thrust of cellular metabolism, we postulated that vascular alpha 2-adrenergic receptors contribute significantly to metabolic heat generation in homeotherms such as humans. Using aerobic lactate production as an indicator of thermogenesis, we measured metabolic heat production in HT29 cells that expressed the gene encoding human vascular alpha 2-adrenergic receptors. Epinephrine, an alpha 2-adrenergic receptor agonist, increased net lactate efflux from 226 +/- 20 to 280 +/- 20 nmol/min (mean +/- SE) (P = .06). Clonidine, a more specific alpha 2-adrenergic agonist, increased lactate efflux from 110 +/- 6 to 156 +/- 8 nmol/min (P < .01). Similarly, in the presence of physiological concentrations of glucose (5.5 mmol/L), insulin increased lactate production from 123 +/- 6 to 175 +/- 10 nmol/min (P < .01). Because differences in aerobic glycolysis may also explain the heat intolerance and abnormal fuel homeostasis found in genetically hypertensive rats, we also measured lactate production in cultured vascular smooth muscle cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control Wistar-Kyoto rats (WKY). Vascular smooth muscle cells from SHRSP had significantly greater lactate efflux compared with cells from normotensive WKY (296 +/- 4 versus 172 +/- 2 nmol/min, P < .001). These differences were not due to abnormalities in glucose uptake, as lactate efflux was greater in SHRSP cells compared with WKY cells when dextrose was replaced with equimolar concentrations of fructose (230 +/- 6 versus 138 +/- 2 nmol/min, P < .001). alpha 2-Adrenergic agonists increase lactate efflux in HT29 cells, and abnormalities in vascular smooth muscle lactate metabolism in genetically hypertensive rats is independent of altered glucose uptake. These data provide support for our hypothesis that balanced polymorphisms of the alpha 2-adrenergic receptor could offer protection against cold stress by increasing the thermogenic response associated with aerobic lactate production.

Isolation and chromosomal localization of genomic DNA sequences coding for cytoplasmic superoxide dismutase from Drosophila melanogaster.

A synthetic oligodeoxynucleotide 18-mer probe derived from the amino acid sequence of Drosophila melanogaster cytoplasmic superoxide dismutase (cSOD) was used to screen a D. melanogaster genomic library. One of the positive clones maps by in situ hybridization to position 68A8-9 on the left arm of polytene chromosome 3, the region to which cSOD mutants have previously been mapped genetically. Partial sequence analysis verifies the presence of cSOD-coding sequences in this clone and indicates that the intron structure of the Drosophila cSOD gene differs significantly from its human counterpart.

Behavioral approach to nondyskinetic dopamine antagonists: identification of seroquel.

A great need exists for antipsychotic drugs which will not induce extrapyramidal symptoms (EPS) and tardive dyskinesias (TDs). These side effects are deemed to be a consequence of nonselective blockade of nigrostriatal and mesolimbic dopamine D2 receptors. Nondyskinetic clozapine (1) is a low-potency D2 dopamine receptor antagonist which appears to act selectively in the mesolimbic area. In this work dopamine antagonism was assessed in two mouse behavioral assays: antagonism of apomorphine-induced climbing and antagonism of apomorphine-induced disruption of swimming. The potential for the liability of dyskinesias was determined in haloperidol-sensitized Cebus monkeys. Initial examination of a few close cogeners of 1 enhanced confidence in the Cebus model as a predictor of dyskinetic potential. Considering dibenzazepines, 2 was not dyskinetic whereas 2a was dyskinetic. Among dibenzodiazepines, 1 did not induce dyskinesias whereas its N-2-(2-hydroxyethoxy)ethyl analogue 3 was dyskinetic. The emergence of such distinctions presented an opportunity. Thus, aromatic and N-substituted analogues of 6-(piperazin-1-yl)-11H-dibenz[b,e]azepines and 11-(piperazin-1-yl)dibenzo[b,f][1,4]thiazepines and -oxazepines were prepared and evaluated. 11-(4-[2-(2-Hydroxyethoxy)ethyl]piperazin-1-yl)dibenzo[b,f][1,4]thiazepine (23) was found to be an apomorphine antagonist comparable to clozapine. It was essentially nondyskinetic in the Cebus model. With 23 as a platform, a number of N-substituted analogues were found to be good apomorphine antagonists but all were dyskinetic.

Substituted 3-(phenylmethyl)-1H-indole-5-carboxamides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes.

Substituted indole-5-carboxamides and indole-6-carboxamides have been found to be potent and selective antagonists of the peptidoleukotrienes. Initial derivatives of these series (4-[[5-[(cyclopentylmethyl)carbamoyl]-1-methylindol-3-yl] methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (5a) and 4-[[6-[(cyclopentylmethyl)carbamoyl]-3-methylindol-1-yl] methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (6a), respectively), when compared to the corresponding indole amides (e.g. 28 and 29), were found to be approximately 10-fold less potent in vitro and substantially less active when administered orally to guinea pigs. Efforts to improve the potency of the title series by variation of the amide, indole, or sulfonamide substituents led to compounds of comparable in vitro potency to ICI 204,219, but of somewhat lower oral activity. A trend which suggested that more lipophilic transposed amides were needed to increase oral activity was exploited with some success and has led to the discovery of 5q (4-[[5-[(2-ethylbutyl)-carbamoyl]-1-ethylindol-3-yl]methyl]- 3- methoxy-N-[(2-methylphenyl)sulfonyl]benzamide), a transposed amide with subnanomolar affinity for the leukotriene receptor and an oral ED50 of 5 mg/kg in a model of asthma in guinea pigs. In this model, ICI 204,219 was active at 0.4 mg/kg. The absolute bioavailability of 5q has been found to be 28% in the rat, as compared to 68% for ICI 204,219, with significant levels of 5q observed in the blood of rats up to 24 h postdose.

A pseudo-outbreak of Aureobasidium species lower respiratory tract infections caused by reuse of single-use stopcocks during bronchoscopy.

OBJECTIVE: To investigate and control an apparent outbreak of lower respiratory tract infections due to Aureobasidium species. DESIGN: Outbreak investigation. SETTING: University-affiliated medical center. PATIENTS: Nine patients who underwent bronchoscopy between June and August 1998. RESULTS: Ten bronchoalveolar lavage (BAL) fluid cultures from nine patients grew Aureobasidium species during the outbreak period; whereas, respiratory specimens from only two patients grew Aureobasidium species during the preceding 6 years. No patient was judged to have true infection due to Aureobasidium species either before or after bronchoscopy. Nine of the 10 bronchoscopies that yielded Aureobasidium species were performed in the outpatient bronchoscopy suite. The Aureobasidium isolates were not associated with any one bronchoscope. Observation of bronchoscopy procedure revealed that plastic stopcocks labeled for single use were reused on different patients during BAL. There was no record of how many times each stopcock was being reused. After each use, the stopcocks were placed in an automated disinfection machine designed for bronchoscopes. Culture of the stopcocks after they had been "disinfected" yielded a heavy growth of Aureobasidium species, while culture of fluid from the automated disinfection machine was negative. Reuse of the stopcocks was halted, and, during the following 6-month period, Aureobasidium species were not isolated from any BAL specimen. CONCLUSIONS: Reuse of medical equipment labeled for single use is potentially hazardous, especially if no quality control system is in place to monitor sterility and function after reprocessing.

The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs.

OBJECTIVE: To determine mortality, morbidity, and costs attributable to surgical-site infections (SSIs) in the 1990s. DESIGN: A matched follow-up study of a cohort of patients with SSI, matched one-to-one with patients without SSI. SETTING: A 415-bed community hospital. STUDY POPULATION: 255 pairs of patients with and without SSI were matched on age, procedure, National Nosocomial Infection Surveillance System risk index, date of surgery, and surgeon. OUTCOME MEASURES: Mortality, excess length of hospitalization, and extra direct costs attributable to SSI; relative risk for intensive care unit (ICU) admission and for readmission to the hospital. RESULTS: Of the 255 pairs, 20 infected patients (7.8%) and 9 uninfected patients (3.5%) died during the postoperative hospitalization (relative risk [RR], 2.2; 95% confidence interval [CI95], 1.1-4.5). Seventy-four infected patients (29%) and 46 uninfected patients (18%) required ICU admission (RR, 1.6; CI95, 1.3-2.0). The median length of hospitalization was 11 days for infected patients and 6 days for uninfected patients. The extra hospital stay attributable to SSI was 6.5 days (CI95, 5-8 days). The median direct costs of hospitalization were $7,531 for infected patients and $3,844 for uninfected patients. The excess direct costs attributable to SSI were $3,089 (CI95, $2,139-$4,163). Among the 229 pairs who survived the initial hospitalization, 94 infected patients (41%) and 17 uninfected patients (7%) required readmission to the hospital within 30 days of discharge (RR, 5.5; CI95, 4.0-7.7). When the second hospitalization was included, the total excess hospitalization and direct costs attributable to SSI were 12 days and $5,038, respectively. CONCLUSIONS: In the 1990s, patients who develop SSI have longer and costlier hospitalizations than patients who do not develop such infections. They are twice as likely to die, 60% more likely to spend time in an ICU, and more than five times more likely to be readmitted to the hospital. Programs that reduce the incidence of SSI can substantially decrease morbidity and mortality and reduce the economic burden for patients and hospitals.

A model of cortically induced synchronization in the lateral geniculate nucleus of the cat: a role for low-threshold calcium channels.

Recently Sillito et al. (Nature 1994;369:479-82) discovered correlations in the spike trains of a relatively distant pair of cat lateral geniculate nucleus cells when simultaneously stimulated by a drifting grating; no such correlation occurs when the visual cortex is removed. In a further analysis of the data, we have found that short, high-frequency bursts contribute substantially to the synchronization and we hypothesize that the origin of the bursts is the low-threshold calcium spike. Guided by this hypothesis, our model of the corticogeniculate pathway and early visual system reproduces the experimental data in nearly every detail, as well as making predictions about cortical activity during the synchronizing process. We also discuss the possible behavioral relevance of correlations in the geniculo-cortical loop as well as other neural systems.

Rapid, high-resolution high-performance liquid chromatographic analysis of antibiotics.

A HPLC column devised for high separation speed combined with highly practical operating features has been found useful for separating antibiotics. Important characteristics involved compromises in packing particle size, column configuration and support-stationary phase combinations. We determined that these columns are useful for rapid, high-resolution separations with unmodified state-of-the-art HPLC equipment without the extra-column band-broadening effects typical of so-called "fast" HPLC columns. The proposed columns feature efficient sterically-protected monofunctional silane stationary phases that provide good separation reproducibility and high column stability. The combination of these unique bonded silanes and a highly purified, less-acidic silica support give superior peak shapes for antibiotic compounds. The proposed column configuration can halve separation times and double peak heights without loss in resolution, compared to widely used analytical columns. Increased mobile phase flow-rates permit even faster separations of antibiotics with only modest loss in resolution and peak heights for trace analyses in biological systems.

Neural assemblies: technical issues, analysis, and modeling.

Neurons often work together to compute and process information, and neural assemblies arise from synaptic interactions and neural circuits. One way to study neural assemblies is to simultaneously record from several or many neurons and study the statistical relations among their spike trains. From this analysis researchers can try to understand the nature of the assemblies, which can also lead to attempts at modeling the underlying mechanisms. In this review we discuss three important parts of this process: (1) technical issues related to simultaneously recording more than one single unit, (2) ways of analyzing the data and (3) recent models offering hypothetical mechanisms of neural assemblies, especially models which incorporate feedback.

Steaming oysters does not prevent Norwalk-like gastroenteritis.

OBJECTIVES: To determine whether steaming oysters prevents gastroenteritis caused by small round structured (Norwalk-like) viruses and to identify risk factors for illness. METHODS: The authors interviewed all 48 people who ate oysters at two church suppers that were followed by outbreaks of gastroenteritis from a Norwalk-like virus. Data were collected on demographics, clinical illness, number of oysters eaten, and the extent to which they were cooked. RESULTS: Among the 48 persons, the attack rate was 56%. The risk of illness increased with the number of oysters eaten (chi-square for trend = 5.7, P = 0.02). There was no decrease in attack rates among persons who ate oysters that were better done (chi-square for trend = 1.1, P = 0.29). CONCLUSIONS: In these outbreaks, the risk of illness increased with the number of oysters eaten. Steaming oysters did not appear to prevent illness, suggesting that steaming may not be adequate to inactivate small round structured viruses. Public health messages that have emphasized the role of raw shellfish in the transmission of enteric viruses should be altered to increase the public's awareness that eating steamed oysters may also pose health risks.

Clinician judgement as a tool for targeting HIV counseling and testing in North Carolina state mental hospitals, 1994.

HIV infection increasingly affects populations that may not appear at high risk based on the use of some traditional targeting strategies. To shed some light on how to more sensitively/effectively identify people who need routine HIV testing and counseling, the objective of this study is to determine the prevalence of HIV infection in North Carolina state mental hospitals and to evaluate clinician judgment as a tool for targeting HIV counseling and testing. The design used is a blinded seroprevalence study. The study population includes all patients admitted to North Carolina state mental hospitals between March 1st and May 31st, 1994. The main outcome measures are the HIV seroprevalence, demographic and diagnostic features, and clinician assessment of the likelihood of HIV infection. The results of the study find that of 2159 study subjects, 35 persons (1.6%) were infected with HIV; of these, 14 (40%) were not previously known to be infected. All 35 HIV infections occurred in persons aged 13-59 years. Within this age group, infection rates were significantly higher for Blacks, males, persons who had a diagnosis of organic brain disease, and persons who had multiple psychiatric diagnoses. However, testing strategies that targeted any of the higher risk groups were insensitive. The rate of HIV infection for persons judged by the admitting clinician to have a high or intermediate likelihood of HIV infection was 26.4 times higher than the rate for those judged to have a low likelihood of infection (2.1 vs. 0.1%, 95% confidence intervals: 3.5-201.3). Of the 14 previously undiagnosed HIV-infected persons, 13 were judged by clinicians to have a high or intermediate likelihood of HIV infection. Moreover, 1258 persons were correctly assessed to have a low likelihood of infection. Conclusions from this study are that an HIV counseling and testing strategy targeting persons (in this setting aged 13-59 years) who were judged by clinicians to have a high or intermediate likelihood of infection, would have identified more than 90% of previously undetected infections while substantially reducing the number of negative HIV tests performed.

Relationship between insulin secretion and oxygen tension in hybrid diffusion chambers.

Oxygen tension is of potential importance in hybrid diffusion chambers, where both islet density and the site chosen for implantation can significantly affect the pO2 within the chambers. To investigate this, isolated islets were incubated at oxygen tensions of 38 mmHg ("low") and 154 mmHg ("ambient"). The mean (+/- SD) ratio between insulin secretion at low and at ambient oxygen tensions was 0.92 +/- 0.27 (n = 10) for porcine islets and 0.80 +/- 0.08 (n = 5) for canine islets. The pO2 was then determined in vivo in cylindrical diffusion chambers (inner diameter 4.5 mm) fabricated from acrylic copolymer, seeded with isolated porcine islets at densities of 0, 15, 30, and 45 islets/mm3, and implanted intraperitoneally in rats. The pO2 levels inside the chambers after 2 weeks were 57 +/- 6 (n = 12), 39 +/- 5 (n = 6), 38 +/- 6 (n = 6), and 43 +/- 3 (n = 6) mmHg, respectively. After 6 weeks, the results were 51 +/- 3 (n = 6), 26 +/- 8 (n = 3), 29 +/- 12 (n = 3), and 40 +/- 5 (n = 3) mmHg, respectively. In comparison, similar chambers containing 10 islets/mm3 cultured for 1 week at ambient oxygen had a pO2 of 120 +/- 9 (n = 4) mmHg immediately underneath the membrane and 67 +/- 7 (n = 4) mmHg at the axial center.(ABSTRACT TRUNCATED AT 250 WORDS)

The in vitro effects of EDTA-tris, EDTA-tris-lysozyme, and antimicrobial agents on equine genital isolants of Pseudomonas aeruginosa.

Five isolants of Pseudomonas aeruginosa collected from clinical cases of equine genital infection and one standard strain of P. aeruginosa were exposed to various concentrations of ethylene-diaminetetraacetic acid (EDTA) and tris (hydroxymethyl) aminomethane (tris buffer pH 8) and EDTA-tris lysozyme. Colony forming units of the isolants and minimal inhibitory concentrations for 11 antimicrobial agents were determined with each isolant before and after exposure to the EDTA solutions. Decreased cellular viability was found with all six isolants after exposure to the EDTA-tris solutions. Reversal of antimicrobial resistance was variable and unpredictable. These effects were not enhanced by the addition of lysozyme. The results suggest that EDTA-tris could be a useful adjunct in treating equine genital infections caused by Pseudomonas aeruginosa.