Serum enolase and pyruvate kinase activities in the diagnosis of myocardial infarction.

Sequential determinations of serum enolase and pyruvate kinase (PK) activities were carried out in addition to routine enzyme assays on 191 patients admitted to a coronary care unit. The upper reference values established in 61 healthy laboratory staff members were 21 U/1 for enolase and 76 U/1 for PK. Of 99 patients with a confirmed diagnosis of myocardial infarction (MI), 97 manifested raised serum enolase during the period of observation; 85 of these patients had raised serum PK. The incidence of raised values for serum PK among patients considered not to have sustained infarction was similar to that shown by the routine enzymes, but serum enolase activity was much more frequently raised in these patients. The time-course of elevation of serum enolase and also that of PK are discussed in relation to the changes in other serum enzymes routinely measured for MI.     

Psychological support for patients undergoing breast cancer surgery: a randomised study.

OBJECTIVE--To evaluate the effect of support from a nurse specialising in breast care and a voluntary support organisation on prevalence of psychological morbidity after surgery for breast cancer. DESIGN-- Prospective randomised study. SETTING--Three teaching hospitals in Glasgow with established breast clinics. SUBJECTS--272 women aged less than 70 years undergoing surgery for breast cancer. INTERVENTIONS-- Patients were randomly allocated to receive routine care from ward staff, routine care plus support from breast care nurse, routine care plus support from voluntary organisation, or routine care plus support from nurse and organisation. MAIN OUTCOME MEASURES--Prevalence of psychological morbidity as assessed by self rating scales: 28 item general health questionnaire and its subscales, and hospital anxiety and depression scale. Measurements were made at first postoperative clinic visit and at three, six, and 12 months after surgery. RESULTS-- On each self rating scale, psychological morbidity tended to fall over the 12 month period. For each scale, scores were consistently lower in patients offered support from breast care nurse alone compared with the other groups, which were similar to each other. Differences were significant or nearly so: P values were 0.015 (28 item general health questionnaire), 0.027 (anxiety and insomnia), 0.072 (severe depression), 0.053 (somatic symptoms), 0.031 (social dysfunction), 0.093 (hospital anxiety), and 0.003 (hospital depression). CONCLUSION-- Support from breast care nurse can significantly reduce psychological morbidity, as measured by self rating scales, in women undergoing breast cancer surgery.     

Adult Hematology and Clinical Chemistry Laboratory Reference Ranges in a Zimbabwean Population

BackgroundLaboratory reference ranges used for clinical care and clinical trials in various laboratories in Zimbabwe were derived from textbooks and research studies conducted more than ten years ago. Periodic verification of these ranges is essential to track changes over time. The purpose of this study was to establish hematology and chemistry laboratory reference ranges using more rigorous methods.MethodsA community-based cross-sectional study was carried out in Harare, Chitungwiza, and Mutoko. A multistage sampling technique was used. Samples were transported from the field for analysis at the ISO15189 certified University of Zimbabwe-University of California San Francisco Central Research Laboratory. Hematology and clinical chemistry reference ranges lower and upper reference limits were estimated at the 2.5^th and 97.5^th percentiles respectively.ResultsA total of 769 adults (54% males) aged 18 to 55 years were included in the analysis. Median age was 28 [IQR: 23–35] years. Males had significantly higher red cell counts, hemoglobin, hematocrit, and mean corpuscular hemoglobin compared to females. Females had higher white cell counts, platelets, absolute neutrophil counts, and absolute lymphocyte counts compared to males. There were no gender differences in eosinophils, monocytes, and absolute basophil count. Males had significantly higher levels of urea, sodium, potassium, calcium, creatinine, amylase, total protein, albumin and liver enzymes levels compared to females. Females had higher cholesterol and lipase compared with males. There are notable differences in the white cell counts, neutrophils, cholesterol, and creatinine kinase when compared with the currently used reference ranges.ConclusionData from this study provides new country specific reference ranges which should be immediately adopted for routine clinical care and accurate monitoring of adverse events in research studies.     

COVID-19 induces a hyperactive phenotype in circulating platelets

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.

The reason for the increased thrombotic risk associated with SARS-CoV-2 infection remains unclear. This study reveals that disease severity is associated with increased mean platelet volume and decreased platelet:neutrophil ratio; moreover, all COVID-19 patients possess hyperactive circulating platelets, with agonist-induced ADP release 30-to-90 fold higher than controls.     

Impact of High Deductible Health Plans on Diabetes Care Quality and Outcomes: Systematic Review

ObjectiveTo provide a review of the impact of high deductible health plans (HDHPs) on the utilizations of services required for optimal management of diabetes and subsequent health outcomes.MethodsSystematic literature review of studies published between January 1, 2000, and May 7, 2021, was conducted that examined the impact of HDHP on diabetes monitoring (eg, recommended laboratory and surveillance testing), routine care (eg, ambulatory appointments), medication management (eg, medication initiation, adherence), and acute health care utilization (eg, emergency department visits, hospitalizations, incident complications).ResultsOf the 303 reviewed articles, 8 were relevant. These studies demonstrated that HDHPs lower spending at the expense of reduced high-value diabetes monitoring, routine care, and medication adherence, potentially contributing to the observed increases in acute health care utilization. Additionally, patient out-of-pocket costs for recommended screenings doubled, and total health care expenditures increased by 49.4% for HDHP enrollees compared with enrollees in traditional health plans. Reductions in disease monitoring and routine care and increases in acute health care utilization were greatest in lower-income patients. None of the studies examined the impact of HDHPs on access to diabetes self-management education, technology use, or glycemic control.ConclusionAlthough HDHPs reduce some health care utilization and costs, they appear to do so at the expense of limiting high-value care and medication adherence. Policymakers, providers, and payers should be more cognizant of the potential for negative consequences of HDHPs on patients’ health.     

Population screening for coeliac disease in primary care by district nurses using a rapid antibody test: diagnostic accuracy and feasibility study

Objective To evaluate the feasibility and diagnostic accuracy of screening for coeliac disease by rapid detection of IgA antibodies to tissue transglutaminase performed in primary care.Design District nurses screened 6 year old children using rapid antibody testing of finger prick blood. They also collected capillary blood samples for laboratory determination of IgA and IgG antibodies to endomysium and IgA antibodies to tissue transglutaminase. Children with positive rapid test results were directly sent for biopsy of the small intestine.Setting Primary care in Jász-Nagykun-Szolnok county, Hungary.Participants 2690 children (77% of 6 year olds living in the county) and 120 nurses.Main outcome measures Positivity for antibodies to endomysium or transglutaminase in the laboratory and coeliac disease confirmed at biopsy.Results 37 children (1.4%, 95% confidence interval 0.9% to 1.8%) had biopsy confirmed coeliac disease. Only five of these children had been diagnosed clinically before screening. Rapid testing had a 78.1% sensitivity (70.0% to 89.3%) and 100% specificity (88.4% to 100%) for a final diagnosis of coeliac disease by biopsy. Sensitivity was 65.1% (50.2% to 77.6%) and specificity was 100% (99.8% to 100%) compared with combined results of IgA and IgG laboratory tests. Trained laboratory workers detected 30 of the 31 newly diagnosed IgA competent patients with the rapid test kit used blindly. Median time to biopsy after a positive rapid test result was significantly shorter (20 days, range 4-148) than after a positive laboratory result (142 days, 70-256; P<0.001). Children with coeliac disease detected at screening were smaller and had worse health status than their peers but they improved on a gluten-free diet.Conclusions A simple rapid antibody test enabled primary care nurses to detect patients with coeliac disease in the community who were not picked up in clinical care. Extra training is needed to improve sensitivity.     

Overexpression of a novel endogenous NADH kinase in Aspergillus nidulans enhances growth

The complete genome sequence of the filamentous fungi Aspergillus nidulans has paved the way for fundamental research on this industrially important species. To the best of our knowledge, this is the first time a gene encoding for ATP-dependent NADH kinase (ATP:NADH 2'-phosphotransferase, EC 2.7.1.86) has been identified. The enzyme has a predicted molecular weight of 49 kDa. We characterised the role of this NADH kinase by genomic integration of the putative gene AN8837.2 under a strong constitutive promoter. The physiological effects of overexpressed NADH kinase in combination with different aeration rates were studied in well-controlled glucose batch fermentations. Metabolite profiling and metabolic network analysis with [1-(13)C] glucose were used for characterisation of the strains, and the results demonstrated that NADH kinase activity has paramount influence on growth physiology. Biomass yield on glucose and the maximum specific growth rate increased from 0.47 g/g and 0.22 h(-1) (wild type) to 0.54 g/g and 0.26 h(-1) (NADH kinase overexpressed), respectively. The results suggest that overexpression of NADH kinase improves the growth efficiency of the cell by increasing the access to NADPH. Our findings indicate that A. nidulans is not optimised for growth in nutrient-rich conditions typically found in laboratory and industrial fermentors. This conclusion may impact the design of new strains capable of generating reducing power in the form of NADPH, which is crucial for efficient production of many industrially important metabolites and enzymes.     

Neurological evaluation of chronic headache patients: is laboratory testing always necessary?

A review of records was conducted to examine the utility of doing routine laboratory testing (EEG and skull X rays) versus testing at the discretion of the attending neurologist on patients presenting for the nonpharmacological treatment of chronic headache. A total of 278 patients underwent neurological evaluation as part of a routine assessment prior to beginning self-regulatory treatment for headache. The first 112 subjects received routine laboratory tests of EEG and skull X-ray films. The second set of 166 subjects received laboratory tests only when deemed necessary by the neurologist. The rate of abnormal EEG in chronic headache sufferers was no greater than that found in the normal population, and only one or two potentially serious abnormalities were found on any laboratory test. A higher rate of abnormality was found when the CT scan was used in conjunction with clinical judgment. The majority of clients with abnormal laboratory tests (most of which were mildly abnormal) still saw substantial headache reduction with self-regulatory treatment for chronic headache. The authors suggest that routine laboratory testing may not be necessary and should be left to the discretion of a qualified neurologist.     

Evaluation of cardiac assays on a benchtop chemiluminescent enzyme immunoassay analyzer, PATHFAST

Devices for cardiac immunoassay are widely available at point of care settings. The lateral flow method is the most popular solution for ease of use. But its major shortcomings, poor assay precision, and low analytical sensitivity may lead to false negative results. Therefore, confirmatory testing by a routine lab analyzer sometimes is necessary. In the current study, we evaluated the cardiac assays troponin I, MB isoenzyme of creatine kinase, myoglobin, and N-terminal pro brain natriuretic peptide on a chemiluminescent enzyme immunoassay analyzer, PATHFAST. All of the assays demonstrated correlation coefficients higher than 0.97 against the predicate devices along with good total precision (coefficients of variation <10%), and the troponin I assay showed analytical sensitivity in conformance with the guidelines of European Society of Cardiology/American College of Cardiology and National Academy of Clinical Biochemistry. We concluded that the system was rapid and easy to use without compromising analytical performance.     

Neurological evaluation of chronic headache patients: Is laboratory testing always necessary?

A review of records was conducted to examine the utility of doing routine laboratory testing (EEG and skull X rays) versus testing at the discretion of the attending neurologist on patients presenting for the nonpharmacological treatment of chronic headache. A total of 278 patients underwent neurological evaluation as part of a routine assessment prior to beginning self-regulatory treatment for headache. The first 112 subjects received routine laboratory tests of EEG and skull X-ray films. The second set of 166 subjects received laboratory tests only when deemed necessary by the neurologist. The rate of abnormal EEG in chronic headache sufferers was no greater than that found in the normal population, and only one or two potentially serious abnormalities were found on any laboratory test. A higher rate of abnormality was found when the CT scan was used in conjunction with clinical judgment. The majority of clients with abnormal laboratory tests (most of which were mildly abnormal) still saw substantial headache reduction with self-regulatory treatment for chronic headache. The authors suggest that routine laboratory testing may not be necessary and should be left to the discretion of a qualified neurologist.This research was supported in part by grants from NINCDS, NS-15235 and NS-23440.     

Evaluation of Immunocytochemical Staining As A Method of Improving Diagnostic Accuracy In A Routine Cytopathology Laboratory

Immunocytochemical stains in a routine cytopathology laboratory can be used to distinguish between benign and malignant cells, and to identify tumour type. In our laboratory 30 problematic cases were selected for immunocytochemical stains and the results analysed in this paper. The following markers were used: cytokeratin (CAM5.2), carcinoembryonic antigen (CEA), kappa and lambda light chains, leucocytic common antigen (LCA), chorionic gonadotrophin (hCG), prostate specific antigen (PSA), L26, UCHL1, S100-protein and vimentin. Twelve FNA (four lymph nodes, one parotid swelling, two from lungs, two from pleura and chest wall, one from lumbar region, two from soft tissue masses), and 18 effusions (12 pleural effusions, five ascitic fluids, one pericardial effusion) were investigated. We found immunocytochemical stains of value in formulating the cytological diagnosis in 11/12 of FNA and 15/18 of effusions.     

The importance of paternal care on pup survival and pup growth in Peromyscus californicus when required to work for food

We examined paternal care in the monogamous California mouse when wheel running was necessary to obtain food. Paternal and maternal care, pup survival and feeding were compared in litters with single females (Male Absent) and paired females (Male Present) under three different foraging requirements. When wheel running was required for obtaining food (Wheel Contingent), the male's presence significantly increased pup survival. There were no significant effects of the male's presence on pup survival in the No Wheel (standard laboratory housing with ad lib food) or Wheel Noncontingent (running wheel with ad lib food) groups. Males may have indirectly increased pup survival by helping generate food through wheel running and then subsequently spending less time eating than females. While females reduced the time spent in parental care as pups aged, males increased the time spent in parental care as pups aged. Thus as pups became larger and more expensive to rear, the male increased parental care. These results indicate that paternal care benefits pup survival more under conditions where the parents must forage to obtain food than when food is provided ad lib in the standard laboratory environment.     

Benign postinfection polymyositis.

Six patients developed persistent muscular cramps, aching pain, and fatigability after an influenza-like illness. Electromyography showed myopathic changes, although results of routine laboratory investigations were normal in all but one patient, whose serum creatine kinase concentration was slightly increased. All but one of the patients improved: three were asymptomatic within one to two years. The syndrome was probably a benign form of polymyositis.     

Comparison of long-term care in an acute care institution and in a long-term care institution

BACKGROUND: Acute care hospitals in Quebec are required to reserve 10% of their beds for patients receiving long-term care while awaiting transfer to a long-term care facility. It is widely believed that this is inefficient because it is more costly to provide long-term care in an acute care hospital than in one dedicated to long-term care. The purpose of this study was to compare the quality and cost of long-term care in an acute care hospital and in a long-term care facility. METHODS: A concurrent cross-sectional study was conducted of 101 patients at the acute care hospital and 102 patients at the long-term care hospital. The 2 groups were closely matched in terms of age, sex, nursing care requirements and major diagnoses. Several indicators were used to assess the quality of care: the number of medical specialist consultations, drugs, biochemical tests and radiographic examinations; the number of adverse events (reportable incidents, nosocomial infections and pressure ulcers); and anthropometric and biochemical indicators of nutritional status. Costs were determined for nursing personnel, drugs and biochemical tests. A longitudinal study was conducted of 45 patients who had been receiving long-term care at the acute care hospital for at least 5 months and were then transferred to the long-term care facility where they remained for at least 6 months. For each patient, the number of adverse events, the number of medical specialist consultations and the changes in activities of daily living status were assessed at the 2 institutions. RESULTS: In the concurrent study, no differences in the number of adverse events were observed; however, patients at the acute care hospital received more drugs (5.9 v. 4.7 for each patient, p < 0.01) and underwent more tests (299 v. 79 laboratory units/year for each patient, p < 0.001) and radiographic examinations (64 v. 46 per 1000 patient-weeks, p < 0.05). At both institutions, 36% of the patients showed anthropometric and biochemical evidence of protein-calorie undernutrition; 28% at the acute care hospital and 27% at the long-term care hospital had low serum iron and low transferrin saturation, compatible with iron deficiency. The longitudinal study showed that there were more consultations (61 v. 37 per 1000 patient-weeks, p < 0.02) and fewer pressure ulcers (18 v. 34 per 1000 patient-weeks, p < 0.05) at the acute care hospital than at the long-term care facility; other measures did not differ. The cost per patient-year was $7580 higher at the acute care hospital, attributable to the higher cost of drugs ($42), the greater use of laboratory tests ($189) and, primarily, the higher cost of nursing ($7349). For patients requiring 3.00 nursing hours/day, the acute care hospital provided more hours than the long-term care facility (3.59 v. 3.03 hours), with a higher percentage of hours from professional nurses rather than auxiliary nurses or nursing aides (62% v. 28%). The nurse staffing pattern at the acute care hospital was characteristic of university-affiliated acute care hospitals. INTERPRETATION: The long-term care provided in the acute care hospital involved a more interventionist medical approach and greater use of professional nurses (at a significantly higher cost) but without any overall difference in the quality of care.     

The selectivity of protein kinase inhibitors: a further update

The specificities of 65 compounds reported to be relatively specific inhibitors of protein kinases have been profiled against a panel of 70-80 protein kinases. On the basis of this information, the effects of compounds that we have studied in cells and other data in the literature, we recommend the use of the following small-molecule inhibitors: SB 203580/SB202190 and BIRB 0796 to be used in parallel to assess the physiological roles of p38 MAPK (mitogen-activated protein kinase) isoforms, PI-103 and wortmannin to be used in parallel to inhibit phosphatidylinositol (phosphoinositide) 3-kinases, PP1 or PP2 to be used in parallel with Src-I1 (Src inhibitor-1) to inhibit Src family members; PD 184352 or PD 0325901 to inhibit MKK1 (MAPK kinase-1) or MKK1 plus MKK5, Akt-I-1/2 to inhibit the activation of PKB (protein kinase B/Akt), rapamycin to inhibit TORC1 [mTOR (mammalian target of rapamycin)-raptor (regulatory associated protein of mTOR) complex], CT 99021 to inhibit GSK3 (glycogen synthase kinase 3), BI-D1870 and SL0101 or FMK (fluoromethylketone) to be used in parallel to inhibit RSK (ribosomal S6 kinase), D4476 to inhibit CK1 (casein kinase 1), VX680 to inhibit Aurora kinases, and roscovitine as a pan-CDK (cyclin-dependent kinase) inhibitor. We have also identified harmine as a potent and specific inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) in vitro. The results have further emphasized the need for considerable caution in using small-molecule inhibitors of protein kinases to assess the physiological roles of these enzymes. Despite being used widely, many of the compounds that we analysed were too non-specific for useful conclusions to be made, other than to exclude the involvement of particular protein kinases in cellular processes.     

Clinical Outcomes and Cost Effectiveness of Accelerated Diagnostic Protocol in a Chest Pain Center Compared with Routine Care of Patients with Chest Pain

Aims

The aim of this study was to compare in patients presenting with acute chest pain the clinical outcomes and cost-effectiveness of an accelerated diagnostic protocol utilizing contemporary technology in a chest pain unit versus routine care in an internal medicine department.

Methods and Results

Hospital and 90-day course were prospectively studied in 585 consecutive low-moderate risk acute chest pain patients, of whom 304 were investigated in a designated chest pain center using a pre-specified accelerated diagnostic protocol, while 281 underwent routine care in an internal medicine ward. Hospitalization was longer in the routine care compared with the accelerated diagnostic protocol group (p<0.001). During hospitalization, 298 accelerated diagnostic protocol patients (98%) vs. 57 (20%) routine care patients underwent non-invasive testing, (p<0.001). Throughout the 90-day follow-up, diagnostic imaging testing was performed in 125 (44%) and 26 (9%) patients in the routine care and accelerated diagnostic protocol patients, respectively (p<0.001). Ultimately, most patients in both groups had non-invasive imaging testing. Accelerated diagnostic protocol patients compared with those receiving routine care was associated with a lower incidence of readmissions for chest pain [8 (3%) vs. 24 (9%), p<0.01], and acute coronary syndromes [1 (0.3%) vs. 9 (3.2%), p<0.01], during the follow-up period. The accelerated diagnostic protocol remained a predictor of lower acute coronary syndromes and readmissions after propensity score analysis [OR = 0.28 (CI 95% 0.14–0.59)]. Cost per patient was similar in both groups [($2510 vs. $2703 for the accelerated diagnostic protocol and routine care group, respectively, (p = 0.9)].

Conclusion

An accelerated diagnostic protocol is clinically superior and as cost effective as routine in acute chest pain patients, and may save time and resources.     

Early Indicators of Fatal Leptospirosis during the 2010 Epidemic in Puerto Rico

Background

Leptospirosis is a potentially fatal bacterial zoonosis that is endemic throughout the tropics and may be misdiagnosed as dengue. Delayed hospital admission of leptospirosis patients is associated with increased mortality.

Methodology/Principal Findings

During a concurrent dengue/leptospirosis epidemic in Puerto Rico in 2010, suspected dengue patients that tested dengue-negative were tested for leptospirosis. Fatal and non-fatal hospitalized leptospirosis patients were matched 1:1–3 by age. Records from all medical visits were evaluated for factors associated with fatal outcome. Among 175 leptospirosis patients identified (4.7 per 100,000 residents), 26 (15%) were fatal. Most patients were older males and had illness onset during the rainy season. Fatal case patients first sought medical care earlier than non-fatal control patients (2.5 vs. 5 days post-illness onset [DPO], p < 0.01), but less frequently first sought care at a hospital (52.4% vs. 92.2%, p < 0.01). Although fatal cases were more often diagnosed with leptospirosis at first medical visit (43.9% vs. 9.6%, p = 0.01), they were admitted to the hospital no earlier than non-fatal controls (4.5 vs. 6 DPO, p = 0.31). Cases less often developed fever (p = 0.03), but more often developed jaundice, edema, leg pain, hemoptysis, and had a seizure (p ≤ 0.03). Multivariable analysis of laboratory values from first medical visit associated with fatal outcome included increased white blood cell (WBC) count with increased creatinine (p = 0.001), and decreased bicarbonate with either increased WBC count, increased creatinine, or decreased platelet count (p < 0.001).

Conclusions/Significance

Patients with fatal leptospirosis sought care earlier, but were not admitted for care any earlier than non-fatal patients. Combinations of routine laboratory values predictive of fatal outcome should be considered in admission decision-making for patients with suspected leptospirosis.     

Programmatic evaluation of a combined antigen and antibody test for rapid HIV diagnosis in a community and sexual health clinic screening programme

Background

A substantial proportion of HIV-infected individuals in the UK are unaware of their status and late presentations continue, especially in low prevalence areas. Fourth generation antigen/antibody rapid test kits could facilitate earlier diagnosis of HIV in non-clinical settings but lack data on performance under programmatic conditions.

Methods and Findings

We evaluated the performance of Determine HIV-1/2 Ag/Ab Combo Test (Determine Combo), a rapid test with indicators for both HIV antibodies and p24 antigen, in participants recruited from community outreach and hospital-based sexual health clinics. HIV infection was confirmed using laboratory enzyme-linked immunosorbent assay (EIA), Line Immuno Assay (LIA) and quantitative polymerase chain reaction (PCR). In total, 953 people underwent HIV testing. HIV antibody (Ab) prevalence was 1.8% (17/953). Four false positive rapid tests were identified: two antibody and two p24 antigen (Ag) reactions. Of participants diagnosed as HIV Ab positive, 2/17 (12%) were recent seroconverters based on clinical history and HIV antibody avidity test results. However, none of these were detected by the p24 antigen component of the rapid test kit. There were no other true positive p24 Ag tests.

Conclusion

These data lend support to an increasing body of evidence suggesting that 4th generation rapid HIV tests have little additional benefit over 3rd generation HIV kits for routine screening in low prevalence settings and have high rates of false positives. In order to optimally combine community-based case-finding among hard-to-reach groups with reliable and early diagnosis 3rd generation kits should be primarily used with laboratory testing of individuals thought to be at risk of acute HIV infection. A more reliable point of care diagnostic is required for the accurate detection of acute HIV infection under programmatic conditions.     

Inhibition of macrophage activation by isoquinolinesulfonamides, phenothiazines, and a napthalenesulfonamide

The influence of isoquinolinesulfonamides (H-7 and H-8), phenothiazines(trifluoperazine and fluphenazine), and a naphthalenesulfonamide (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on stimulated superoxide anion production and phosphatidyl inositol (PI) cycle activity was investigated in the guinea pig alveolar macrophage. All five drugs were able to inhibit superoxide anion production stimulated by n-formyl-nel-leu-phe (FNLP), leukotriene B4 (LTB4), and phorbol-12,13-dibutyrate (PDB). The order of potency was trifluoperazine greater than or equal to fluphenazine greater than H-7 = W-7 greater than H-8. The dose response curves could be shifted to less efficacy by increasing extracellular calcium. By itself, W-7 markedly stimulated 45Ca+2 efflux, fluphenazine and trifluoperazine slightly stimulated 45Ca+2 efflux, while H-7 and H-8 had no effect on 45Ca+2 efflux from macrophages preloaded with 45Ca+2. Consistent with these results, W-7 markedly stimulated PI cycle activity, fluphenazine and trifluoperazine slightly stimulated PI cycle activity, while H-7 and H-8 had no significant effects on PI cycle activity. In addition, W-7 by itself was able to stimulate a weak and short-lived "burst" of superoxide anion production. In order to evaluate whether a site of action of the inhibitors was at protein kinase C and whether protein kinase C was involved in terminating the normally short-lived FNLP- and LTB4-stimulated macrophage activation, fluphenazine and H-7 were used to evaluate the duration of FNLP- and LTB4-stimulated PI cycle activity, at concentrations of the inhibitors that significantly blocked stimulated superoxide anion production. In all cases, FNLP and LTB4 still stimulated PI cycle activity, which still terminated even though protein kinase C was inhibited. These results suggest that all five drugs block protein kinase C, but H-7 was the most specific in its action at protein kinase C, while the phenothiazines and W-7 have multiple sites of action. In addition, these results suggest that protein kinase C may not function to cause the termination of FNLP- and LTB4-stimulated PI cycle activity and subsequent superoxide anion production.     

Bacteriuria testing by the ATP method as an integral part in the diagnosis and therapy of urinary tract infection (UTI)

Rapid tests for bacteriuria have the highest value, if the test result is available while the patient is with the doctor. At the bacteriological laboratory rapid testing of samples obtained by mail may be cost-effective but is of little clinical value. In a previous study performed at a health care centre using conventional urine culture as a reference the ATP test came out as the most reliable one among several rapid bacteriuria tests. The present study was performed to see how the ATP test could be fitted into the routine of the health care centre. Female patients with UTI symptoms were asked to deliver a urine sample to the health care centre laboratory and to wait for the result before seeing the doctor. After having the symptoms confirmed the doctor based the diagnosis on the ATP value. A low ATP value ruled out UTI and a high ATP value confirmed UTI. In patients with an intermediary ATP value (10–50 nmol/I) a positive nitrite test was used to confirm UTI. Only those patients with intermediary ATP values and negative nitrite test had to wait for conventional urine culture. Thus in most patients the decision on antibiotic therapy or not was based on clinical symptoms and ATP results only. Antibiotics (trimethoprim) were given as single dose or as a conventional 7-day regime in a double-blind comparison. The correlation between the ATP method and conventional culture was good. Although results of the present study are promising the ATP test as performed is too complicated to become widely accepted at health care centres. However, the dipstick version of the ATP test at present being developed will make the method ideally suited for rapid bacteriuria testing at health care centres and similar doctor's surgery situations.