Spatial and temporal patterns in antimicrobial resistance of Salmonella Typhimurium in cattle in England and Wales.

Salmonella is the second most commonly reported human foodborne pathogen in England and Wales, and antimicrobial-resistant strains of Salmonella are an increasing problem in both human and veterinary medicine. In this work we used a generalized linear spatial model to estimate the spatial and temporal patterns of antimicrobial resistance in Salmonella typhimurium in England and Wales. Of the antimicrobials considered we found a common peak in the probability that an S. typhimurium incident will show resistance to a given antimicrobial in late spring and in mid to late autumn; however, for one of the antimicrobials (streptomycin) there was a sharp drop, over the last 18 months of the period of investigation, in the probability of resistance. We also found a higher probability of resistance in North Wales which is consistent across the antimicrobials considered. This information contributes to our understanding of the epidemiology of antimicrobial resistance in Salmonella.

Poor seroprotection but allosensitization after adjuvanted pandemic influenza H1N1 vaccine in kidney transplant recipients.

BACKGROUND: Seasonal and pandemic influenza virus infections in renal transplant patients are associated with poor outcomes. During the pandemic of 2009-2010, the AS03-adjuvanted monovalent H1N1 influenza vaccine was recommended for transplant recipients, although its immunogenicity in this population was unknown. We sought to determine the safety and immunogenicity of an adjuvant-containing vaccine against pandemic influenza A H1N1 2009 (pH1N1) administered to kidney transplant recipients. METHODS: We prospectively enrolled 124 adult kidney transplant recipients in the fall of 2009 at two transplant centers. Cohort 1 (n = 42) was assessed before and after pH1N1 immunization, while Cohort 2 (n = 82) was only assessed post immunization. Humoral response was measured by the hemagglutination inhibition assay. Vaccine safety was assessed by adverse event reporting, graft function, and human leukocyte antigen (HLA) alloantibody measurements. RESULTS: Cohort 1 had a low rate of baseline seroprotection to pH1N1 (7%) and a low rate of seroprotection after immunization (31%). No patient <6 months post transplant (n = 5) achieved seroprotection. Seroprotection rate was greater in patients receiving double as compared with triple immunosuppression (80% vs. 24%, P = 0.01). In Cohort 2, post-immunization seroprotection was 35%. In both cohorts, no confirmed cases of pH1N1 infection occurred. No difference was seen in estimated glomerular filtration rate before (54.3 mL/min/1.73 m(2) ) and after (53.8 mL/min/1.73 m(2) ) immunization, and no acute rejections had occurred after immunization at last follow-up. In Cohort 1, 11.9% of patients developed new anti-HLA antibodies. CONCLUSION: An adjuvant-containing vaccine to pH1N1 provided poor seroprotection in renal transplant recipients. Receiving triple immunosuppression was associated with a poor seroresponse. Vaccination appeared safe, but some patients developed new anti-HLA antibodies post vaccination. Alternative strategies to improve vaccine responses are necessary.

Concealed pregnancy: prevalence, perinatal measures and socio-demographics.

A target group of women who concealed their pregnancy (n = 43) was compared to an aged-matched control group (n = 30) that experienced a crisis pregnancy. Comparisons were also made with a larger dataset (n = 6363) of births in University Hospital Galway (UHG) (normative group). Data was analysed using the Chi-square test and the Kolmogorov-Smirnoff two-sample test. The number of women from the target group that were from a rural background was 28 (65%), compared to 10 (33%) from the control group. The number of women from the target group that feared a negative parental reaction to the pregnancy was 34 (79%), compared to 12 (40%) from the control group. The birth weight in the target group was 4009 lower than the normative birth weight. The average age of women who concealed was 8 years lower than the normative age. The prevalence of concealed pregnancy in UHG was one in every 148 births.

The prevalence of antimicrobial-resistant Escherichia coli in sympatric wild rodents varies by season and host.

AIMS: To investigate the prevalence and temporal patterns of antimicrobial resistance in wild rodents with no apparent exposure to antimicrobials. METHODS AND RESULTS: Two sympatric populations of bank voles and wood mice were trapped and individually monitored over a 2- year period for faecal carriage of antimicrobial-resistant Escherichia coli. High prevalences of ampicillin-, chloramphenicol-, tetracycline- and trimethoprim-resistant E. coli were observed. A markedly higher prevalence of antimicrobial-resistant E. coli was found in wood mice than in bank voles, with the prevalence in both increasing over time. Superimposed on this trend was a seasonal cycle with a peak prevalence of resistant E. coli in mice in early- to mid-summer and in voles in late summer and early autumn. CONCLUSIONS: These sympatric rodent species had no obvious contact with antimicrobials, and the difference in resistance profiles between rodent species and seasons suggests that factors present in their environment are unlikely to be drivers of such resistance. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that rodents may represent a reservoir of antimicrobial-resistant bacteria, transmissible to livestock and man. Furthermore, such findings have implications for human and veterinary medicine regarding antimicrobial usage and subsequent selection of antimicrobial-resistant organisms.

Serum amyloid A and plasma fibrinogen concentrations in horses following emergency exploratory celiotomy.

BACKGROUND: Acute-phase proteins may help assess the nature and severity of lesions and outcome in horses undergoing colic surgery. OBJECTIVES: To compare serum amyloid A and plasma fibrinogen concentrations ([SAA] and [fibrinogen]) in the immediate post-operative period after exploratory celiotomy and determine their value in assessment of post-operative complications and survival to discharge. STUDY DESIGN: Observational study. METHODS: This study included horses over 1 year of age undergoing exploratory celiotomy. Surgical procedures, lesions, post-operative care, complications and survival to discharge were recorded. [SAA] and [fibrinogen] were measured prior to surgery and 5 days post-operatively. Statistical analyses included Yate's Chi-square test, linear mixed effects model, Mann-Whitney U test and logistic regression. RESULTS: Of 300 horses, 52.0% developed post-operative complications and 83.7% survived to discharge, with significantly reduced chance of survival in horses that developed post-operative complications (P<0.01). Median [SAA] at days 1, 2, 3, 4 and 5 and median [fibrinogen] at days 3, 4 and 5 were significantly different between horses that did and did not develop post-operative complications (P<0.05). Median [SAA] at days 1, 4 and 5 were significantly different between horses that did and did not survive to discharge (P<0.05). Logistic regression revealed post-operative complications to be associated with strangulating lesions (OR 2.35, 95% confidence interval [CI] 1.41-3.91, P≤0.001) and higher [fibrinogen] at admission (OR 1.21, 95% CI 1.00-1.45, P<0.05), and survival to discharge to be associated with lower [SAA] at 5 days post-operatively (OR 0.965, 95% CI 0.94-0.99, P = 0.002). MAIN LIMITATIONS: A large variety of lesions and complications prevented detailed analysis of associations between inflammatory markers, lesions and complications. CONCLUSIONS: Horses that develop post-operative complications have acute-phase responses of greater magnitudes and durations compared with those that do not develop complications. This is also seen in horses that do not survive to discharge. Measuring [SAA] daily and [fibrinogen] at admission, may help predict the development of post-operative complications.

Identification of performance problems in a commercial human immunodeficiency virus type 1 enzyme immunoassay by multiuser external quality control monitoring and real-time data analysis.

In June 2005, a pilot program was implemented in Canadian laboratories to monitor the performance of the Abbott human immunodeficiency virus types 1 and 2 (HIV-1/2) gO enzyme immunoassay (EIA). Two different external quality control (QC) reagents and a "real-time" software analysis program were evaluated. In November 2005, higher-than-expected calibrator rate values in these kits were first reported at the Ontario Ministry of Health (Etobicoke), followed by the Alberta Provincial Public Health Laboratory (Edmonton and Calgary) and others. These aberrations were easily and readily tracked in "real time" using the external QC reagents and the software program. These high calibrator values were confirmed in Delkenheim, Germany, by Abbott, and a manufacturing change was initiated beginning with lot 38299LU00, which was distributed to laboratories in Canada in April 2006. However, widespread reports of calibrator failure by laboratories outside Canada were made in March 2006. In April 2006, Abbott Diagnostics initiated a level III investigation to identify the root cause, which was prolonged storage, under uncontrolled storage conditions, of the raw material used in the manufacture of the matrix cells. To the best of our knowledge, this is the first example of a program in Canada for serological testing that combines a common external QC reagent and a "real-time" software program to allow laboratories to monitor kit performance. In this case, external QC monitoring helped identify and confirm performance problems in the Abbott HIV-1/2 gO EIA kit, further highlighting the benefit of implementing such a program in a national or multilaboratory setting for laboratories performing diagnostic and clinical monitoring testing.

Comparison of high-field and low-field magnetic resonance images of cadaver limbs of horses.

Eleven limbs taken postmortem from 10 lame horses were examined by MRI in a low-field 0.27T system designed for standing horses and a high-field 1.5T system used to examine anaesthetised horses. Nine limbs were examined in the foot/pastern region and two in the fetlock region, and the results were compared with gross pathological examinations and histological examinations of selected tissues. The appearance of normal tissues was similar between the two systems, but the anatomical arrangement of the structures was different due to differences in positioning, and a magic angle artefact was observed at different sites in some imaging sequences. Articular cartilage could be differentiated into two articular surfaces in most joints in the high-field images but could generally be separated only at the joint margins in the low-field images. Abnormalities of tendon, ligament and bone detected by gross examination were detected by both forms of MRI, but some details were clearer on the high-field images. Articular cartilage found to be normal on pathological examination was also classified as normal on MRI, but lesions in articular cartilage detected on pathological examination were identified only by high-field MRI. An abnormality was detected on MRI of all the limbs that had abnormal navicular flexor fibrocartilage on pathological examination.

Deep erosions of the palmar aspect of the navicular bone diagnosed by standing magnetic resonance imaging.

REASONS FOR PERFORMING STUDY: Erosion of the palmar (flexor) aspect of the navicular bone is difficult to diagnose with conventional imaging techniques. OBJECTIVES: To review the clinical, magnetic resonance (MR) and pathological features of deep erosions of the palmar aspect of the navicular bone. METHODS: Cases of deep erosions of the palmar aspect of the navicular bone, diagnosed by standing low field MR imaging, were selected. Clinical details, results of diagnostic procedures, MR features and pathological findings were reviewed. RESULTS: Deep erosions of the palmar aspect of the navicular bone were diagnosed in 16 mature horses, 6 of which were bilaterally lame. Sudden onset of lameness was recorded in 63%. Radiography prior to MR imaging showed equivocal changes in 7 horses. The MR features consisted of focal areas of intermediate or high signal intensity on T1-, T2*- and T2-weighted images and STIR images affecting the dorsal aspect of the deep digital flexor tendon, the fibrocartilage of the palmar aspect, subchondral compact bone and medulla of the navicular bone. On follow-up, 7/16 horses (44%) had been subjected to euthanasia and only one was being worked at its previous level. Erosions of the palmar aspect of the navicular bone were confirmed post mortem in 2 horses. Histologically, the lesions were characterised by localised degeneration of fibrocartilage with underlying focal osteonecrosis and fibroplasia. The adjacent deep digital flexor tendon showed fibril formation and fibrocartilaginous metaplasia. CONCLUSIONS: Deep erosions of the palmar aspect of the navicular bone are more easily diagnosed by standing low field MR imaging than by conventional radiography. The lesions involve degeneration of the palmar fibrocartilage with underlying osteonecrosis and fibroplasia affecting the subchondral compact bone and medulla, and carry a poor prognosis for return to performance. POTENTIAL RELEVANCE: Diagnosis of shallow erosive lesions of the palmar fibrocartilage may allow therapeutic intervention earlier in the disease process, thereby preventing progression to deep erosive lesions.

Evaluation of foot pain in the standing horse by magnetic resonance imaging.

The records of 41 horses with previously undiagnosed foot pain that had been examined by standing magnetic resonance imaging were reviewed and follow-up information was obtained from their owners two years after the examination. A range of soft tissue and osseous abnormalities were identified, with multiple lesions frequently occurring. Deep digital flexor tendonitis was recorded in 12 of the horses, and distension of the distal interphalangeal joint was identified in 15, but it was not always associated with lameness; in contrast, distension of the navicular bursa was always associated with lameness in the seven affected horses. Navicular bone lesions were identified in 13 of the horses, often in the absence of radiographic changes. Follow-up information was obtained for 35 of the horses, 27 of which were alive; of these, 16 had returned to their previous level of performance. Of the five horses with navicular bursal changes, four had been euthanased owing to lameness and the other had returned to work at a reduced level.

Magic angle effect on low field magnetic resonance images in the superficial digital flexor tendon in the equine proximal pastern region.

Recognition of artefacts is an essential component of the accurate interpretation of diagnostic images. This study aimed to investigate the presence of magic angle effect in the superficial digital flexor tendon (SDFT) in the equine proximal pastern region. The proximal pastern of four cadaver limbs was imaged using a 0.27 Tesla magnet with high-resolution sequences that are commonly utilised in clinical equine practice. The limbs were imaged in a neutral position and positions that simulated the horse 'leaning in', 'leaning out' and having internal and external rotation of the distal limb. Signal intensity changes in the SDFT were described and compared. The simulated 'leaning in' and external rotation positions resulted in increased signal intensity in the axial and middle thirds of the lateral half of the SDFT on sequences with short echo times. The simulated 'leaning out' and internal rotation positions resulted in increased signal intensity in the axial and middle thirds of the medial half of the SDFT on sequences with short echo times. These signal intensity changes did not occur or were only mild and inconsistent on T2 fast spin echo sequences with longer echo times. The increases in signal intensity in the SDFT are consistent with a position-induced magic angle artefact that has been noted in clinical cases. Attention to positioning of the equine distal limb is essential during clinical imaging; radiologists should be aware of position-induced artefacts to ensure accurate image interpretation.

Technical innovation changes standard radiographic protocols in veterinary medicine: is it necessary to obtain two dorsoproximal-palmarodistal oblique views of the equine foot when using computerised radiography systems?

Since the 1950s, veterinary practitioners have included two separate dorsoproximal-palmarodistal oblique (DPr-PaDiO) radiographs as part of a standard series of the equine foot. One image is obtained to visualise the distal phalanx and the other to visualise the navicular bone. However, rapid development of computed radiography and digital radiography and their post-processing capabilities could mean that this practice is no longer required. The aim of this study was to determine differences in perceived image quality between DPr-PaDiO radiographs that were acquired with a computerised radiography system with exposures, centring and collimation recommended for the navicular bone versus images acquired for the distal phalanx but were subsequently manipulated post-acquisition to highlight the navicular bone. Thirty images were presented to four clinicians for quality assessment and graded using a 1-3 scale (1=textbook quality, 2=diagnostic quality, 3=non-diagnostic image). No significant difference in diagnostic quality was found between the original navicular bone images and the manipulated distal phalanx images. This finding suggests that a single DPr-PaDiO image of the distal phalanx is sufficient for an equine foot radiographic series, with appropriate post-processing and manipulation. This change in protocol will result in reduced radiographic study time and decreased patient/personnel radiation exposure.

Idiopathic Fibrosis of the Tunica Muscularis of the Large Intestine in Five Horses with Colic.

Histological evidence of fibrosis affecting the outer layer of the large intestinal tunica muscularis was identified in five of 32 horses affected by colic. In three cases, foci of pale eosinophilia and vacuolation of myocytes were observed. These findings are suggestive of a degenerative and fibrotic abnormality in the outer layer of the tunica muscularis of the large intestinal smooth muscle of some horses with colic.

Do low field magnetic resonance imaging abnormalities correlate with macroscopical and histological changes within the equine deep digital flexor tendon?

Correlating magnetic resonance (MR) imaging and histopathological findings is essential to validate low field MR imaging in lame horses. This study aimed to compare signal changes in the deep digital flexor tendon (DDFT) of the distal limb on low field MR imaging with macroscopical and histological findings. Cadaver limbs from lame horses with DDFT lesions were selected. The DDFT MR imaging findings and histopathological results were graded, and macroscopical abnormalities were recorded. There was a strong correlation between MR imaging and histopathology grades (rs = 0.76, p < 0.001) in the foot. There was moderate agreement (Kappa statistic 0.52) between the MR and histopathology grades; agreement was superior further proximal in the foot. The presence and severity of pathology in the DDFT are well represented by the presence and severity of MR imaging signal changes. The study supports the use of low field MR imaging for diagnosis of equine distal limb DDFT lesions.

Effect of N-butylscopolammonium bromide on equine ileal smooth muscle activity in an ex vivo model.

REASONS FOR PERFORMING STUDY: N-butylscopolammonium bromide (NBB) is an anticholinergic agent used to treat spasmodic colic in horses. Intestinal smooth muscle spasm also occurs in horses with intraluminal intestinal obstructions, such as ileal impactions. The antispasmodic effects of NBB may be useful in managing ileal impactions, but the effects of NBB on equine ileal smooth muscle are unknown. OBJECTIVES: To investigate the effects of NBB on spontaneous and induced contraction of the equine ileum in an ex vivo model. STUDY DESIGN: Ex vivo biomechanical study assessing contractile properties in isolate equine ileal smooth muscle with and without exposure to NBB. METHODS: Ileal tissue was collected from 6 healthy horses after euthanasia, and isolated circular and longitudinal smooth muscle strips were connected to isometric force transducers in organ baths. After equilibration, the effect of NBB (1 nmol/l to 100 µmol/l) on spontaneous and carbachol-induced contraction was determined and compared with responses in control tissue. RESULTS: At ≥30 µmol/l, NBB inhibited spontaneous contractions in all muscle strips that exhibited spontaneous activity. N-butylscopolammonium bromide pre-treatment inhibited carbachol-induced contraction in circular (NBB-treated half maximal effective concentration [EC50] 0.530 × 10(-8) mol/l vs. control EC50 41.57 × 10(-8) mol/l) and longitudinal muscle strips (NBB-treated EC50 0.243 × 10(-8) mol/l vs. control EC50 90.84 × 10(-8) mol/l). Abolition of carbachol-induced contraction with NBB was observed at lower concentrations in circular than longitudinal muscle strips. Pretreatment with NBB significantly inhibited carbachol-induced contractions; NBB-treated tissue required greater carbachol concentrations to produce sustained contractions than control muscle strips. Histamine-evoked contraction was not affected by NBB. CONCLUSIONS: N-butylscopolammonium bromide inhibits spontaneous and cholinergically mediated contraction in equine ileal smooth muscle strips ex vivo. Thus, NBB might reduce intestinal spasm in equine ileal impactions and could be useful for medical management of these cases, although further study is needed to confirm these effects in vivo.

Hairy leukoplakia-like lesions following bone-marrow transplantation.

Hairy leukoplakia (HL) also occurs in immunosuppressed post-bone-marrow transplantation patients, and in the presence or absence of Epstein-Barr virus. It may not always be diagnostic of HIV positivity. However, HIV status should still be determined in patients with HL.

Antiviral effect of double and triple drug combinations amongst HIV-infected adults: lessons from the implementation of viral load-driven antiretroviral therapy.

OBJECTIVE: To study the antiviral effect and predictors of response to two- and three-drug regimens amongst antiretroviral-naive individuals using an intent-to-treat analysis. MAIN OUTCOME MEASURE: Suppression of plasma viral load to < 500 copies/ml. PATIENTS: A total of 420 (264 double drug, 156 triple drug) individuals in a province-wide treatment programme were studied. RESULTS: A decrease in plasma viral load to < 500 copies/ml was documented in 197 (47%) subjects. This was independently associated with a lower baseline plasma viral load (odds ratio, 3.67; 95% confidence interval, 2.13-6.30) and initiation onto a three-drug regimen (odds ratio, 3.86; 95% confidence interval, 2.24-6.66). Median plasma viral load failed to reach < 500 copies/ml and in fact rebounded in the two-drug group. In contrast, 91 (58%) subjects receiving three drugs reached < 500 copies/ml during the study period. CONCLUSION: These results support the use of powerful triple drug regimens as initial therapy in HIV-infected individuals.

Use of pooling and outpatient laboratory specimens in an anonymous seroprevalence survey of HIV infection in British Columbia, Canada.

OBJECTIVE: To conduct an anonymous HIV seroprevalence survey to establish a baseline estimate of HIV seroprevalence in a general population; to evaluate serum pooling and alternative testing strategies as cost-saving measures. DESIGN: Prospective anonymous HIV seroprevalence study using outpatient laboratory specimens. SETTING: Two large non-hospital-associated outpatient chemistry testing laboratories in the major population centers in British Columbia, Canada. PATIENTS AND SERA: Leftover sera received for chemistry screen testing in outpatient laboratories were provided to the study after chemistry testing was completed. Those from patients aged < 15 and > or = 55 years were excluded. METHODS: Patient identifiers were erased from samples. Sera were pooled 10:1 and tested by viral lysate enzyme-linked immunosorbent assay (ELISA). Sera from HIV-positive pools were tested individually. All individual HIV-positive specimens were retested for verification of positivity using a recombinant protein ELISA. MAIN OUTCOME MEASURES: HIV seroprevalence rates were stratified by sex, age group, and geographic area; and costs of pooling and alternative algorithm strategy were compared with those of conventional methods. RESULTS: A total of 80,238 sera were collected from 66,658 individuals (53% women, 47% men). Of these, 276 men (88.3 per 10,000) and 24 women (6.8 per 10,000) were HIV-seropositive. The highest rates were in those aged 30-34 years, for both men and women. Using pooling and non-Western blot verification saved US$2.07 per specimen, or 80% of the cost for conventional testing. CONCLUSIONS: The anonymous outpatient laboratory setting is practicable to obtain a reasonable estimate of HIV seroprevalence rates in a general population. Such studies can be made cost-effective by pooling sera and using alternative confirmatory strategies.

Full suppression of viral load is needed to achieve an optimal CD4 cell count response among patients on triple drug antiretroviral therapy.

OBJECTIVE: To characterize the relationship between plasma viral load (pVL) suppression and triple drug antiretroviral therapy, and the accompanying changes in CD4 cell counts. METHOD: Retrospective study of 465 participants in a HIV/AIDS Treatment Program who initiated triple drug therapy between August 1996 and May 1998. Participants were divided into three groups according to their pVL response: (i) non-responders (NR; n = 112) exhibited pVL persistently > 500 copies/ml over the study period; (ii) partial responders (PR; n = 100) achieved a pVL < 100 copies/ml at least once and subsequently rebounded to > 500 copies/ml; and (iii) full responders (FR; n = 253) achieved a pVL < 500 copies/ml and sustained this level for the remainder of the study period. For each group, the accompanying changes in absolute and fractional CD4 cell counts were evaluated. RESULTS: The median net change in pVL per person from baseline to the end of the observation period was -0.37, -2.27, and -2.56 log10 copies/ml for NR, PR and FR, respectively. During weeks 68-83, the median CD4 cell count (x 10(6) cells/l) was 150 [interquartile range (IQR) 90-370], 380 (IQR 300-480) and 525 (IQR 305-705) for NR, PR and FR, respectively. Median changes in CD4 cells (x 10(6) cells/l) were -20 (IQR -90 to 40), 150 (IQR 30-250) and 240 (IQR 110-365) for NR, PR, and FR, respectively. The net percentage change in CD4 cells per person was 0% (IQR -34-31), 54% (IQR 6-160), and 83% (IQR 39-173) for NR, PR, and FR, respectively. By weeks 68-83, the median fractional CD4 cells was 0.16 (IQR 0.07-0.22), 0.22 (IQR 0.15-0.28), and 0.26 (IQR 0.17-0.34) for NR, PR and FR respectively. CONCLUSIONS: An optimal CD4 cell count response appears to be coupled with continued pVL suppression. Our data indicate that maximal suppression of viral replication should remain the primary goal of therapy.

The antiviral effect of ritonavir and saquinavir in combination amongst HIV-infected adults: results from a community-based study.

OBJECTIVE: To characterize the antiviral effect and predictors of response to ritonavir and saquinavir-based antiretroviral combination therapy. DESIGN: Intent-to-treat analysis with suppression of plasma viral load to levels below 2.7 log10 copies/ml as the main outcome measure. PATIENTS: All adult HIV-positive individuals in the province of British Columbia who started taking ritonavir and saquinavir (each at 600 mg twice daily) in combination from 1 September 1996 to 28 February 1997, with a minimum of two plasma viral load measurements, one at baseline and one after the initiation of therapy. RESULTS: A total of 58 participants were prescribed ritonavir and saquinavir. The median plasma viral load at entry was 4.80 log10 copies/ml (interquartile range, 4.51-5.15 log10 copies/ml). A total of 29 (50%) subjects demonstrated a decrease in plasma viral load to levels below 2.7 log10 copies/ml. This level of suppression was associated with higher baseline CD4 cell counts (P=0.022) and no prior exposure to protease inhibitors (P=0.001). After controlling for baseline CD4 cell count and plasma viral load, participants naive to protease inhibitors were almost seven times (odds ratio, 6.99; 95% confidence interval, 1.85-26.39; P=0.004) more likely to suppress their plasma viral load to below 2.7 log10 copies/ml than those who had previously used protease inhibitors. CONCLUSION: Our analysis demonstrates that a ritonavir and saquinavir-based combination can produce a substantial decrease in plasma viral load with half of the participants decreasing their plasma viral load to below the limit of quantification of the assay. This response, however, is seriously compromised by prior exposure to protease inhibitors.

Serological responses to cytomegalovirus during renal transplant rejection.

We studied the role played by CMV in kidney transplant rejection by recording serological responses to CMV replication in cadaver graft recipients and recording clinical graft rejection by monitoring acute changes in renal function and the appearance of antidonor lymphocyte antibody (anti-Dab). If CMV plays a significant role in rejection, clinical rejection should correlate with CMV activity; if CMV does not play a role, clinical rejection would be likely to correlate with anti-Dab but not necessarily with CMV activity. We selected retrospectively 18 rejectors and 18 nonrejectors by clinical criteria and assayed for anti-Dab (by fluorescence-activated flow cytometry) and CMV antibody (by complement fixation and Western blot for IgG and IgM) over a 3-6-month period after transplantation. Primary CMV infection occurred in 8 of 12 (67%) CMV seronegative graft recipients and reactivation or reinfection occurred in 16 of 24 (67%); 12 of 14 (86%) rejectors developed anti-Dab compared with 2 of 18 (11%) nonrejectors (P less than 0.00001). Active CMV infection occurred in 11 of 18 (61.1%) rejectors and 13 of 18 (72.2%) nonrejectors (P = 0.36), and in 8 of 15 (53.3%) of those who developed anti-Dab and 12 of 17 (70.6%) of those who did not (P = 0.26). The results show no evidence to link CMV activity with kidney graft rejection.