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Impact of the pravastatin or atorvastatin evaluation and infection therapy-thrombolysis in myocardial infarction 22/Reversal of Atherosclerosis with Aggressive Lipid Lowering trials on trends in intensive versus moderate statin therapy in Ontario, Canada.

BACKGROUND: In March 2004, the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial demonstrated that intensive lipid-lowering therapy (atorvastatin 80 mg/d) reduced progression of coronary atherosclerosis compared with moderate lipid-lowering therapy (pravastatin 40 mg/d). The following month, the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study demonstrated the superiority of intensive (atorvastatin 80 mg/d) versus moderate (pravastatin 40 mg/d) lipid-lowering therapy for reducing death or cardiovascular events in patients suffering from an acute coronary syndrome. We sought to determine the impact of these 2 trials on trends in intensive versus moderate statin therapy in Ontario, Canada. METHODS AND RESULTS: This is a retrospective time-series analysis of statin prescribing between June 1997 and September 2004 in Ontario, Canada, for all residents age 65 years and older. The publication of the PROVE IT-TIMI 22 and REVERSAL trials was associated with a sustained and statistically significant increase in the number of prescriptions dispensed for atorvastatin 80 mg (range, 272 to 635 additional prescriptions per month), whereas the number of prescriptions filled for pravastatin 40 mg did not change. Similarly, it resulted in a temporal increase in the relative market share of atorvastatin at a dose of 80 mg versus that of atorvastatin at a dose of 40 mg. However, the proportion of simvastatin prescriptions for 80 mg relative to 40 mg did not change over time, implying a drug-specific effect rather than a class effect in prescribing practice. CONCLUSIONS: The publication of the PROVE IT-TIMI 22 and REVERSAL trials resulted in a significant sustained increase in the use of intensive compared with moderate statin therapy. This shift was evident primarily in an increased use of high-dose atorvastatin and did not appear to be generalizable to other statins.

Aged↗

Young women with symptoms of urinary tract infection. Prevalence and diagnosis of chlamydial infection and evaluation of rapid screening of bacteriuria.

OBJECTIVE: To estimate the prevalence of chlamydial infection among young women with UTI symptoms. To evaluate chlamydia diagnostics with the aid of enzyme immuno assay (EIA) on first-void urine. To evaluate rapid screening of bacteriuria, including low concentrations of common pathogens. DESIGN: EIA for detection of Chlamydia trachomatis antigen and confirmation with immunofluorescence test (DFA) in urine, cervical and urethral chlamydia culture, nitrite and granulocyte esterase test, urine sediment, chamber count, dipslide and conventional urine culture were performed. SETTING: Primary health care (PHC). PATIENTS: 217 women aged 15-35 years attending PHC for dysuria or urgency-frequency. MAIN OUTCOME MEASURES: Frequency of chlamydial infections. Sensitivity, specificity, predictive values of EIA and bacteriuria screening tests, respectively. RESULTS: The frequency of chlamydial infection was 3.7%. In spite of a high specificity of the EIA test (0.94 without DFA) the number of false positives exceeded the number of true positives. No single bacteriuria test showed sufficient diagnostic efficiency. CONCLUSIONS: Routine chlamydia testing in young women with UTI symptoms is recommended. EIA test on urine is of little use. Assessing diagnosis of UTI symptoms requires insight into the use of several rapid tests and a dialogue with the patient.

Adolescent↗

Chronic hepatitis in multiple virus infection: histopathological evaluation.

The frequency and histological pattern of multiple hepatitis virus infection was studied in 161 Italian patients who had consecutively undergone liver biopsy from 1989 to 1991. The histological features were compared with that of infection with a single virus. Thirty-nine per cent of patients had evidence of past or present multiple infection, the commonest of which was hepatitis C virus (HCV) in patients with evidence of previous infection with hepatitis B virus (HBV). In general, the severity of the histological pattern of each viral infection was maintained even when more than one virus was involved; there was neither exacerbation nor diminution of the histological changes. The delta-virus (HDV) was not associated with severe necro-inflammatory lesions, but HDV-positive patients were few in this cohort. Lymphoid follicle formation (a putative histological marker of HCV infection) was also found in a high proportion of HCV-negative patients but expressing much HBcAg or HDAg in liver tissue. Possible explanations for this finding are that follicles are relatively non-specific for HCV infection, or that these cases represent HCV infection with false-negative serology. The results of this study suggest that multiple hepatitis virus infection is common in the population investigated and that HBV and HCV co-infection cannot be reliably diagnosed histologically. Whether double infection with these viruses influences the cirrhotic evolution of the liver lesion remains unclear.

Adolescent↗

Comparison of nucleic acid hybridization and cytologic examination for detection of human papillomavirus infection, with evaluation of two commercially available hybridization kits.

Human papillomavirus (HPV) infections were detected by analyzing exfoliated cervical cells for HPV DNA by use of nucleic acid hybridization; the results were correlated with cytologic findings on Papanicolaou smears. HPV infection was diagnosed in 154 women (20%) by either morphologic evidence on cervical smears or nucleic acid hybridization. Many of these women (38%; 58/154) exhibited Papanicolaou smears with no morphologic evidence of HPV infection. In those patients with cytologic evidence of HPV infection, only 28% were positive for HPV DNA. HPV 16 and (or) 18 were the most common types (27%) detected in women with cervical intraepithelial neoplasia, whereas all HPV groups tested were equally represented in patients with normal cervical smears. We also present an assessment of 17,000 clinical specimens submitted to this laboratory for analysis of HPV DNA.

Adolescent↗

Lipoprotein-associated phospholipase A2 and its association with cardiovascular outcomes in patients with acute coronary syndromes in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is associated with the risk of cardiovascular (CV) events in population-based studies. The prognostic value of Lp-PLA2 in patients with acute coronary syndromes (ACS) has not been established. METHODS AND RESULTS: Plasma levels of Lp-PLA2 activity were measured at baseline (n=3648) and 30 days (n=3265) in patients randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d after ACS in the PROVE IT-TIMI 22 (PRavastatin Or atorVastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction) trial. The primary end point was death, myocardial infarction, unstable angina, revascularization, or stroke (mean follow-up 24 months). At baseline after ACS, the risk of recurrent CV events was similar across all quintiles of Lp-PLA2 activity (Ptrend=0.88). Overall, mean levels of Lp-PLA2 were lower at 30 days of follow-up than at baseline (35.7 versus 40.9 nmol.min(-1).mL(-1), P<0.001). In particular, treatment with atorvastatin 80 mg/d was associated with a 20% reduction in Lp-PLA2 activity (P<0.001), whereas Lp-PLA2 rose 3.6% with pravastatin 40 mg/d (P<0.001). Patients with 30-day Lp-PLA2 activity in the highest quintile were at significantly increased risk of recurrent CV events compared with those in the lowest quintile (26.4% versus 17.6%, Ptrend=0.002). After adjustment for cardiac risk factors, treatments, achieved low-density lipoprotein (LDL), and C-reactive protein, Lp-PLA2 activity in the highest quintile remained independently associated with a higher risk of recurrent CV events (adjusted hazard ratio 1.33, 95% confidence interval [CI] 1.01 to 1.74). CONCLUSIONS: Lp-PLA2 is not useful for risk stratification when measured early after ACS. At 30 days, Lp-PLA2 activity is significantly lowered with high-dose statin therapy and is associated with an increased risk of CV events independent of C-reactive protein and LDL cholesterol levels.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Schistosoma mansoni: reinfections and concomitant immunity in mice. Importance of perfusion time after challenge infection for evaluation of immunoprotection.

The concomitant immunity in the presence of repeated infections (with 15 cercariae) was studied in mice sacrificed on the 20th day after each infection. The comparison of the averages of immature worms, recovered from mice submitted to reinfection, with those of their respective controls (previously uninfected) showed a significantly lower worm recovery rate in the animals with previous infections (concomitant immunity). However, statistically significant differences could not be detected among the various groups of animals, when the mice that accumulated worms in this mature stage were perfused. The theoretical projection based on the accumulation of young worms which developed to adult ones indicates a lower recovery rate of adult worms in the animals with concomitant immunity, but this projection was not corroborated by the experimental data. The visceral hemodynamic alterations that occurred in reinfections due to the pathogeny, favouring recirculation of the recent arriving worms to the portal system, could explain the lower recovery rate of immature worms, which could remain in other organs on the occasion of perfusion of the portal system. These results suggest that special care should be taken when one wants to investigate concomitant immunity in mice based on the distinction of the immature worms from challenge infection and the mature ones from primary infection.

Animals↗

The use of induced mammary infections for evaluating dry cow treatment products. I. Development of a method.

Experimental infections were induced by infusing one of three different numbers of colony forming units of Staphylococcus aureus, strain 305, into 74 quarters of 17 cows, at 30, 15 or five days before drying off. The remaining 26 served as controls. A total of 73% of infused quarters were infected both at drying off and calving, although some changes in status occurred during the dry period. All control quarters were negative at drying off, but two, one in each of two lactations of the same cow, became infected during the dry period. There was no change in infection status during the dry period in 86.5% and 88.5% respectively of infused and control quarters. Disregarding dose size, 18/27, 19/24 and 17/23 quarters became infected following infusion at five, ten and 30 days before drying off. Disregarding time, significantly more infections (88%) followed infusion of a 10(-4) dilution (mean count 3215 +/- 182 S.E.) than with 10(-5) and 10(-6) dilutions combined (65%). It was concluded that a dose of S. aureus, strain 305, consisting of 0.2 mL of a 10(-4) dilution in sterile milk of a six hour milk culture would provide optimum infection levels if no antibiotic treatment were given. Wether infusion took place 30, 15 or five days before drying off appeared immaterial.

Animals↗

Chromogenic urinary tract infection medium: evaluation and introduction for routine urine culture in a large clinical microbiology laboratory.

Evaluation and introduction of a chromogenic urinary tract infection (UTI) medium for the primary culture of routine urine specimens in a very large clinical microbiology laboratory is described. A modified scheme for the direct identification of the main groups of organisms causing UTI has led to quality improvements, with enhanced discrimination of mixed cultures and in efficiencies in staffing and working time that counterbalance increases in media costs. These improvements, together with the concurrent introduction of boric acid preservative for specimens from general practice, significantly reduced the level of positive results by 4.6% (2383 specimens) over an eight-month period (P <0.001). Chromogenic medium provided a reliable alternative to CLED medium for the routine culture of urine specimens.

Bacteriological Techniques↗

Major maxillofacial infections. An evaluation of 107 cases.

A review of 107 cases of acute maxillofacial infections managed at the Royal Melbourne Hospital was undertaken, and details of the presentations, demography, management, and outcomes of these patients are presented. The results indicated that many of the patients had sought treatment from dentists in general practice, and that a significant proportion had received sub-optimal management prior to referral. Thus a review of the principles of management and guidelines for the referral of patients with maxillofacial infections is also presented.

Adolescent↗

Focal air trapping in patients with HIV infection: CT evaluation and correlation with pulmonary function test results.

OBJECTIVE: HIV-positive individuals commonly have symptoms of airway disease. We evaluated thin-section CT scans of HIV-infected individuals during inspiration and expiration for evidence of focal air trapping. We also correlated imaging findings with pulmonary function test results. SUBJECTS AND METHODS: Fifty-nine subjects, 48 of whom were HIV-positive and 11 of whom were HIV-negative, underwent thin-section CT of the thorax during inspiration and expiration. All subjects also underwent pulmonary function tests. Two radiologists, who were unaware of the subjects' HIV status and smoking history and of the results of pulmonary function tests, evaluated the CT scans for the presence and severity of focal air trapping. RESULTS: Expiratory CT revealed focal air trapping in 33 subjects: 30 were HIV-positive and three were HIV-negative (p = .0338). The mean values of forced expiratory volume in 1 sec (FEV1), forced mid expiratory flow, and diffusion capacity (DL(CO)) were significantly lower for subjects with focal air trapping (mean = 88.85, 84.52, and 80.80, respectively) than for those with normal findings on CT (mean = 100.84, 99.24, and 95.82, respectively; p = .001, p = .021, and p = .003, respectively). We found no significant differences in smoking history between HIV-positive and HIV-negative subjects. Severe air trapping on expiratory CT scans was seen in three subjects: All three had HIV infection, low CD4 counts, and abnormally decreased FEV1 and DL(CO) values. CONCLUSION: Focal air trapping was a common finding on thoracic CT scans obtained during expiration in HIV-positive subjects. In addition, focal air trapping was associated with significantly lower FEV1, forced mid expiratory flow, and DL(CO) values than those found for subjects in whom CT revealed no focal air trapping. These results suggest that small airways disease may accompany a decline in pulmonary function in HIV-positive individuals.

Adult↗

[Prevalence of Chlamydia trachomatis infection, as evaluated by molecular biology methods].

BACKGROUND: To determine the prevalence of Chlamydia trachomatis infection in our area by molecular methods. METHODS: We describe the combined results of three studies carried out in the city of Barcelona including a total of 408 women considered to be at high risk for acquiring a sexually transmitted disease (STD). The first study was performed in 94 women attended at a public STD clinic located downtown, the second in 112 women attended at the Hospital Clinic and the third in 202 women attended at Hospital Vall d'Hebron (both third-level hospitals). In the first and third study endocervical exudate was tested with a PCR technique, and in the second study LCR was performed in 20-ml urine samples. RESULTS: Chlamydia trachomatis was detected in 1 woman in the first study, in no women in the second and in 3 women in the third. The prevalence of Chlamydia trachomatis infection detected in the three studies using molecular biology techniques was 1.06%, 0% and 1.48% respectively, giving an overall prevalence of 0.98%. CONCLUSION: The prevalence of Chlamydia trachomatis infection in our geographic area is surprisingly low.

Adult↗

Endoscopic evaluation of infected pancreatic necrosis.

The most severe form of acute pancreatitis is characterized by necrosis of the pancreatic parenchyma and/or peripancreatic tissue. Secondary infection of this necrotic tissue carries a high mortality because there is little limitation to the spread of this infection in the retroperitoneum. Improvements in the management of infected pancreatic necrosis have been achieved by techniques that allow complete removal of the infected debris. Problems still remain in identifying the extent of necrosis and removing all of it. Intraoperative endoscopy can be used to evaluate tracking of the infected process to other areas of the retroperitoneum. Direct visualization of the path that the necrotizing process has taken to areas of the retroperitoneum that are difficult to reach allows the dissection to be limited if there is no necrosis or expansion to remove all necrotic material completely. The endoscope can also be used to remove necrotic material either by irrigation or by direct debridement. The methodology of this technique is described.

Abdomen↗

The evaluation of infection and pulmonary maturity in women with premature rupture of the membranes.

Although the etiology of PROM is multifactorial, increasing evidence regarding clinical risk factors, membrane histology, membrane culture, and amniotic fluid microbiology shows a strong association with infection. Recent studies suggest an association between genital tract infection, preterm labor (PTL), and preterm premature rupture of the membranes (pPROM). If correct, this information may be used to target areas for prevention, as well as to develop management protocols. This article reviews both the diagnostic tests for the causes associated with pPROM and the evaluation of intraamniotic infection and pulmonary maturity in patients with pPROM.

Female↗

Cinoxacin in the treatment of acute urinary tract infections: an evaluation of efficacy and a comparison of dosage schedules.

Fifty-one women with acute urinary tract infections have been treated with cinoxacin, a new synthetic compound that is similar chemically and in antimicrobial activity to nalidixic acid. Urine cultures were made before treatment was started, midway through the 7 to 10-day course of therapy, 1 week after therapy and 4 to 6 weeks after therapy, if possible. Pre-treatment , mid-therapy and post-therapy evaluations of renal and liver function along with a complete blood count were done. All patients were believed to have lower urinary tract infections. Urine cultures in 48 of the 51 patients (94 per cent) became sterile during therapy and 47 patients (92 per cent) maintained sterile urine 1 week after therapy. Of those patients undergoing followup cultures 4 to 6 weeks after therapy 72 per cent had sterile urine. No significant hematological, renal, hepatic or gastroenterologic toxicity was noted. Cinoxacin seems to be a safe and useful drug in the treatment of urinary tract infections caused by the common gram-negative organisms and there does not seem to be any difference in efficacy between the dosage schedules tested.

Acute Disease↗

The use of induced mammary infections for evaluating dry cow treatment products. II. Trial of a proposed method to compare three levels of novobiocin.

Infections were induced at the end of lactation in all udder quarters of 19 cows by the infusion of 0.2 mL of a 10(-4) dilution in milk of a six hour milk culture of Staphylococcus aureus, strain 305 (A.T.C.C No. 29740). Two right or two left udder quarters were infected at 15 days and the opposite two five days before the last milking of lactation. Following the last milking all four udder quarters of eight cows were treated with 400 mg novobiocin in 10 mL of 2% aluminum monosterate in peanut oil, gelled. All udder quarters of eight other cows were treated with 50 mg novobiocin in the same vehicle and the udder quarters of three cows were treated with the vehicle only. At calving, eight of 32 quarters treated with 400 mg novobiocin were still infected, as were 18 of 32 treated with 50 mg of novobiocin and all those quarters treated with vehicle only. Results were identical from udder quarters infected 15 and five days before drying off. No significant differences were found between quarters in milk yield on the last day of lactation, nor the length of the dry period. An increasing number of udder quarters were infected at calving with increase in lactation age of the cow, although the small number of cows would not allow a firm conclusion. A significant difference in results was found between front and hind udder quarters, only five of 32 front quarters were infected at calving as compared to 21 to 32 hind quarters. The method proposed was found to give essentially the same results as those from a large field trial using the same antibiotic. It should therefore be useful in evaluation trials of new antibiotic products for dry cow treatment.

Animals↗

99mTechnetium-ciprofloxacin scintigraphy for the evaluation of spinal infections: a preliminary report.

UNLABELLED: Currently available laboratory and imaging tests have limitations diagnosing and following patients with spinal infections. We evaluated 17 Technetium-99m labeled ciprofloxacin scintigraphy studies in 11 patients who had the diagnosis of a spinal infection based on the Centers for Disease Control and Prevention criteria. Three of the 17 studies were performed in three patients within 2 months from the onset of the symptoms. All of these three studies showed increased uptake of the radiopharmaceutical in the area of the spinal infection. Fourteen studies were performed during the followup period (from 210 to 690 days after the onset of symptoms) in nine patients with spinal infections. Ten of the 14 studies performed in five patients with an active spine infection showed positive results while the patients had evidence for active spinal infection at the time of the testing. Four studies were performed during the followup period in four patients who at the time of the nuclear imaging testing had no symptoms, signs, or laboratory or other imaging evidence for active infection. All four studies showed negative results. The results of this preliminary study show that scintigraphy with 99mTc-ciprofloxacin may be useful in the diagnosis of active spinal infections. LEVEL OF EVIDENCE: Diagnostic study, level II-1 (Testing of previously developed diagnostic criteria on consecutive patients [with universally applied reference "gold" standard]). Please see Guidelines for Authors for a complete description of levels of evidence.

Bacterial Infections↗

Cellular response in Salmonella typhimurium-infected mice: evaluation of Salmonella receptors of B lymphocytes.

The cellular response in the course of experimental infection with Salmonella typhimurium was studied in mice. T cells were detected by the presence of theta-antigen, B cells by the binding of fluorescent immunoglobulins, and cells with receptors by labeled Salmonella binding. Lymphocytes were from spleen and lymph nodes. Results have been divided into three groups: group A, including mice with slight symptomatology; group B, including those with serious infection symptomatology; and group C, including mice that died in the course of the experiment. In spleen and lymph nodes of group A mice, an increase in the percentage of T and B lymphocytes was observed. This increase reached a peak 10 days after experimental infection. In lymph nodes, the B-cell percentage was equal to the percentage of T cells, whereas in spleen lymphocytes the B-cell percentage was higher. In spleens of group B mice we observed the same response as in mice of group A, whereas in lymph nodes there was a low response of T and B lymphocytes. In group C mice, there was no significant response of T and B lymphocytes in either spleen or lymph nodes. In B lymphocytes prepared from spleens of surviving mice, a small number of Salmonella receptors was detected: 200 bacterial cells per 10(9) lymphocytes.

Animals↗

The hepatitis B virus-trimera mouse: a model for human HBV infection and evaluation of anti-HBV therapeutic agents.

Previous studies have demonstrated the feasibility of implantation of human blood cells or tissues in lethally irradiated mice or rats, radioprotected with SCID mouse bone marrow cells: The Trimera system. In the present study, we describe the development of a mouse Trimera model for human hepatitis B virus (HBV) infection. In this model, viremia is induced by transplantation of ex vivo HBV-infected human liver fragments. Engraftment of the human liver fragments, evaluated by hematoxylin-eosin staining and human serum albumin mRNA expression, was observed in 85% of the transplanted animals 1 month postimplantation. Viremia levels were determined in these mice by measuring serum HBV DNA using polymerase chain reaction (PCR), followed by dot-blot hybridization. HBV DNA is first detected 8 days after liver transplantation. Viremia attains a peak between days 18 and 25 when HBV infection is observed in 85% of the transplanted animals. The HBV-Trimera model was used to evaluate the therapeutic effects of human polyclonal anti-HBs antibodies (Hepatect) and of two reverse-transcriptase inhibitors, lamivudine (3TC) and beta-L-5-fluoro-2',3'-dideoxycytidine (beta-L-5FddC). Treatment of HBV-Trimera mice with these drugs effectively reduced both the percentage of infected animals and the viral load in their sera. Treatment cessation resulted in rebound of viral load, indicating HBV replication upon drug withdrawal. These results show that the HBV-Trimera model represents a novel experimental tool for simulating human HBV infection and evaluating potential anti-HBV therapeutic agents.

Animals↗