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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 217 records · Page 12Linked to original sources
PubMed1997

Seroconversion to human herpesvirus 6 following liver transplantation is a marker of cytomegalovirus disease.

Human herpesvirus 6 (HHV-6) infection is common after transplantation; HHV-6 is known to interact with other viruses and induce immunosuppression. Whether HHV-6 plays a role in the occurrence of cytomegalovirus (CMV) infection after transplantation was investigated. In a cohort of 247 liver transplant recipients, HHV-6 seroconversion was identified as a significant risk factor for development of symptomatic CMV infection (P < .001), including CMV organ involvement (P < .001), even in the presence of the other significant risk factors: D+/R- CMV serologic status (P < .001) or use of OKT3 after transplantation (P = .002). Subgroup analysis indicated that HHV-6 seroconversion was significantly associated with symptomatic CMV infection in the D+/R+ but not in the D+/R- CMV serologic group (P < .001 and P = .11, respectively). These results indicate that HHV-6 seroconversion is a marker for CMV disease after transplantation and suggest that additional studies using more sensitive diagnostic techniques are warranted to determine the relationship between HHV-6 and CMV infection after transplantation.

Adult↗
PubMed1997

Efficacy of azithromycin or clarithromycin for prophylaxis of viridans group streptococcus experimental endocarditis.

The efficacy of azithromycin or clarithromycin was compared to that of amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no antibiotics or two doses of amoxicillin at 25 mg/kg of body weight, azithromycin at 10 mg/kg, clarithromycin at 10 mg/kg, clindamycin at 40 mg/kg followed by clindamycin at 20 mg/kg, or erythromycin at 10 mg/kg. Antibiotics were administered 0.5 h before and 5.5 h after intravenous infusion of 5 x 10(5) CFU of Streptococcus milleri. Forty-eight hours after bacterial inoculation, the rabbits were killed and aortic valve vegetations were aseptically removed and cultured for bacteria. Infective endocarditis occurred in 88% of untreated animals, 1% of animals receiving amoxicillin, 9% of animals receiving erythromycin, 0% of animals receiving clindamycin, 2.5% of animals receiving clarithromycin, and 1% of animals receiving azithromycin. All five regimens were more effective (P < 0.001) than no prophylaxis. Erythromycin was less effective (P < 0.05) than amoxicillin or clindamycin. Azithromycin or clarithromycin was as effective as amoxicillin, clindamycin, or erythromycin for the prevention of viridans group streptococcus experimental endocarditis in this model.

Amoxicillin↗
PubMed1997

Infections in solid-organ transplant recipients.

Solid-organ transplantation is a therapeutic option for many human diseases. Infections are a major complication of solid-organ transplantation. All candidates should undergo a thorough infectious-disease screening prior to transplantation. There are three time frames, influenced by surgical factors, the level of immunosuppression, and environmental exposures, during which infections of specific types most frequently occur posttransplantation. Most infections during the first month are related to surgical complications. Opportunistic infections typically occur from the second to the sixth month. During the late posttransplant period (beyond 6 months), transplantation recipients suffer from the same infections seen in the general community. Opportunistic bacterial infections seen in transplant recipients include those caused by Legionella spp., Nocardia spp., Salmonella spp., and Listeria monocytogenes. Cytomegalovirus is the most common cause of viral infections. Herpes simplex virus, varicella-zoster virus, Epstein-Barr virus and others are also significant pathogens. Fungal infections, caused by both yeasts and mycelial fungi, are associated with the highest mortality rates. Mycobacterial, pneumocystis, and parasitic diseases may also occur.

Antifungal Agents↗
PubMed1997

Comparison of agar dilution, broth microdilution, E-test, disk diffusion, and automated Vitek methods for testing susceptibilities of Enterococcus spp. to vancomycin.

An evaluation was undertaken to determine the optimal method for testing the susceptibilities of 100 clinical isolates and two reference strains of Enterococcus spp. to vancomycin in vitro. Six testing methods were studied by using the following media and incubation times: agar screen with the Synergy Quad Plate (Remel, Lenexa, Kans.), an in-house-prepared brain heart infusion (BHI) agar plate, and an in-house-prepared Mueller-Hinton (MH) agar plate, all incubated for 24 or 48 h; broth microdilution (Sensititre Just One Strip; AccuMed International, Inc., West Lake, Ohio) with BHI or cation-adjusted MH broth incubated for 24 or 48 h; agar dilution with BHI or MH agar incubated for 24 or 48 h; epsilometer test (E test; AB BioDisk, Solna, Sweden) with BHI or MH agar incubated for 24 or 48 h; disk diffusion with BHI or MH agar incubated for 24 or 48 h; and the automated Vitek method with the gram-positive susceptibility Staphylococcus aureus card and R02.03 software (bioMerieux, Inc., Hazelwood, Mo.). Growth failures occurred with MH media (n = 6) but not with BHI media. One growth failure occurred with the Vitek method. Results for each testing method for each Enterococcus strain were interpreted as susceptible, intermediate, or resistant according to current National Committee for Clinical Laboratory Standards (NCCLS) criteria and compared to the vancomycin resistance genotype (i.e., vanA, vanB, vanC-1, or vanC-2/3). For all methods, extension of the incubation time from 24 h to 48 h either produced no difference in the results or gave poorer results. The following methods produced no very major or major interpretive errors: broth microdilution with BHI media incubated for 24 h, agar dilution with BHI media incubated for 24 or 48 h, and E test with BHI media incubated for 24 or 48 h. Unacceptable frequencies of very major errors (> 1%) occurred with all methods for which MH media were used. Minor interpretive errors were frequent with all methods. These minor interpretive errors also occurred most frequently with Enterococcus strains with vanC genes, which encoded low-level vancomycin resistance (MIC < or = 8 microg/ml), as opposed to Enterococcus strains which possessed vanA or vanB genes, which encoded higher-level vancomycin resistance (MIC > or = 64 microg/ml). Modification of NCCLS breakpoints, especially for motile Enterococcus spp. (E. casseliflavus, E. flavescens, and E. gallinarum), may resolve this problem; however, in the current study, one E. faecalis strain and one E. faecium strain carried only the vanC gene. The agar screen method may also require reformulation. The current agar screen plate contains 6 microg of vancomycin per ml, which may not detect all low-level resistance associated with vanC genotypes. Nevertheless, the clinical significance of this low-level vancomycin resistance remains unknown.

Agar↗
PubMed1997

Multiplex PCR detection of vanA, vanB, vanC-1, and vanC-2/3 genes in enterococci.

Vancomycin-resistant enterococci (VRE) are increasingly isolated from clinical specimens. One hundred clinical isolates of enterococci (E. casseliflavus/E. flavescens [n = 10], E. faecalis [n = 34], E. faecium [n = 43], E. avium [n = 1], E. gallinarum [n = 11], and E. raffinosus [n = 1]) were examined for the presence of vanA, vanB, vanC-1, and vanC-2/3 genes by a single multiplex PCR performed directly with colonies from blood agar plates. Six previously characterized VRE strains which carry either vanA, vanB, vanC-1, or vanC-2 genes were used as controls. To discriminate among van genes, the PCR amplicons were digested with MspI and were electrophoresed on agarose gels. Because of significant sequence homology between vanC-2 and vanC-3 genes, this assay is unable to discriminate these genes from each other; therefore, these are referred to as vanC-2/3 genes. PCR products were detected in 63 of the 100 clinical isolates. The restriction fragment length patterns were consistent with vanA for 10 strains, vanB for 30 strains, vanC-1 for 12 strains, vanC-2 for 6 strains, and vanA and vanC-1 for 1 strain. The vancomycin MICs for the isolates with restriction fragment length patterns consistent with vanA and vanB were all > and = 64 micrograms/ml. The vancomycin MICs for the isolates with restriction fragment length patterns consistent with vanC-1 or vanC-2 were 4 to 8 micrograms/ml. The vancomycin MICs for the isolates from which no PCR amplicons were produced were 2 to 4 micrograms/ml. A PCR product was produced in four isolates (vancomycin MICs, 4 to > 256 micrograms/ml) with restriction fragment length patterns differing from those for the control vanA, vanB, vanC-1, and vanC-2 isolates. DNA sequencing of these amplicons revealed that two of the four isolates had nucleic acid sequences which were closely related to the published sequence for the vanB gene and two had nucleic acid sequences which were closely related to the published sequence for the vanC-2 and vanC-3 genes. Multiplex PCR-restriction fragment length polymorphism appears to be a useful and convenient method for rapidly detecting and discriminating genotypes for vancomycin-resistant Enterococcus spp. in the clinical laboratory. In instances in which unusual restriction fragment patterns of PCR amplicons occur, DNA sequencing can be performed to discriminate van genotypes.

Amino Acid Sequence↗
PubMed1997

Valaciclovir for the suppression of recurrent genital HSV infection: a placebo controlled study of once daily therapy. International Valaciclovir HSV Study Group.

OBJECTIVE: To determine the efficacy and safety of once daily valaciclovir for the suppression of recurrent genital herpes simplex virus (HSV) infection in immunocompetent patients. METHODS: 382 otherwise healthy patients with a history of frequently recurring genital HSV infection (eight recurrences per year) were randomly allocated to receive either oral valaciclovir (500 mg once daily) or placebo (3:1 ratio) for 16 weeks or until the first genital HSV recurrence, whichever occurred first. Patients were clinically assessed at regular intervals and also if they experienced a recurrence. Safety was evaluated through adverse experience reporting and monitoring of haematology and biochemistry variables. On completion of the double blind phase, patients were eligible for follow up to a maximum of 48 weeks' treatment with open label valaciclovir (500 mg once daily) for further safety monitoring. The results from the double blind phase of the study are reported here. RESULTS: A significant difference was detected between valaciclovir and placebo in the time to first recurrence of genital HSV infection. The hazard ratio [95% confidence interval] for valaciclovir v placebo was 0.155 [0.112, 0.214], p < 0.0001. Valaciclovir prevented or delayed 85% of the recurrences that would have occurred with placebo. After 16 weeks (day 112) with treatment, 69% of patients receiving valaciclovir were recurrence free compared with only 9.5% of patients assigned to placebo. The safety profiles of valaciclovir and placebo were comparable, with adverse experiences being infrequent and generally mild. CONCLUSION: This study has demonstrated that once daily valaciclovir (500 mg), is highly effective and well tolerated for the suppression of recurrent genital HSV infection. Once daily dosing with valaciclovir provides a more convenient dosing regimen than the more frequent aciclovir regimens.

Acyclovir↗
PubMed1997

Valaciclovir: development, clinical utility and potential.

Valaciclovir (Valtrex, Zelitrex), the L-valine ester of aciclovir, increases aciclovir bioavailability by 3- to 5-fold over that achievable with oral aciclovir. It addresses many unmet needs of currently available anti-herpesvirus therapies. Valaciclovir extends the efficacy of aciclovir in the treatment of herpes zoster and genital HSV infections, using less frequent dose regimens but retaining the highly acceptable safety profile established for aciclovir. The potential for valaciclovir in CMV prophylaxis has now been proven, and further refining to identify the optimal dose regimen is ongoing. After oral administration, valaciclovir is rapidly absorbed and extensively converted to aciclovir and L-valine, the essential amino acid. The mode of action and spectrum of antiviral activity of valaciclovir are thus identical to aciclovir. The bioavailability of aciclovir after valaciclovir, characterised from studies in healthy adult volunteers, is similar in a wide range of patient populations, including the elderly, those with advanced HIV disease, patients with impaired liver or renal function, or undergoing bone marrow transplantation. No clinically significant drug interactions with valaciclovir have so far been identified. Dosage reductions in clinical use of valaciclovir are only necessary when renal function is severely impaired. In controlled clinical trials in herpes zoster, valaciclovir (1000 mg three times daily) is superior to aciclovir in speeding the resolution of zoster-associated pain and post-herpetic neuralgia. It is as effective as aciclovir in hastening rash healing. In patients with ophthalmic zoster, no differences were evident between valaciclovir and aciclovir treatment on zoster-associated pain or the occurrence of ocular complications. The safety profiles of valaciclovir, aciclovir and placebo were not different in this study programme. In a series of controlled, randomised trials of valaciclovir, aciclovir and placebo for the acute treatment of genital HSV infections in approximately 3000 patients, twice daily valaciclovir was proven as effective as the standard 5 times daily aciclovir regimen in resolving the clinical signs and symptoms of lesional disease. Early patient-initiated valaciclovir therapy (500 mg twice daily) of recurrent genital herpes episodes was shown significantly to increase the chance of prevention of vesicular or ulcerative lesions, a valuable clinical advantage not prospectively proven for aciclovir. When used for periods of up to one year, valaciclovir (500 mg once daily) effectively suppresses genital herpes recurrences. Long-term studies of valaciclovir for HSV suppression, evaluating doses of up to 1000 mg daily in approximately 3000 patients, about 25% of whom were HIV seropositive (CD+ > 100 cells/microl), revealed a highly acceptable clinical tolerability profile for valaciclovir that did not differ from aciclovir or placebo. There were no cases resembling thrombotic microangiopathy in these long-term studies. The aciclovir safety heritage and pharmacokinetic rationale for the development of valaciclovir have been realised through the clinical research programmes in the zoster and HSV indications. Further studies in these and related areas, including CMV prophylaxis, are in progress and aim to expand further the clinical potential of valaciclovir in the future.

Journal Article↗
PubMed1996

Risk factors of invasive Candida and non-Candida fungal infections after liver transplantation.

Fungal infections are associated with a high mortality rate after liver transplantation. To describe risk factors for fungal infections, 405 consecutive liver transplant recipients were analyzed. Forty-five patients (11%) developed invasive fungal infection. Median posttransplantation time to the first episode was 60 days. Pathogens were Candida species (spp) (n=24, 53%), Cryptococcus neoformans (n=10, 22%), Aspergillus spp (n=6, 13%), Rhizopus spp (n=l), and others (n=4). Presentations of infection included disseminated (n=9), intra-abdominal (n=9), esophageal (n=9), lung (n=8), blood (n=6), and central nervous system infections (n=3), and sinusitis with esophagitis (n=1). Eighteen patients (40%) with invasive fungal infection died, and 13 (72%) of these deaths were attributable to fungi. Mortality in the nonfungal infection group was 12%. Univariate analysis identified separate risk factors for Candida (intra-abdominal bleeding), Aspergillus (fulminant hepatitis), and cryptococcal (symptomatic cytomegalovirus infection) infections. In both univariate and multivariate analyses, a high intratransplant transfusion requirement and posttransplant bacterial infection were identified as significant risk factors for all types of fungal infection. The risk factor analysis reported here suggests that different pathogenic processes lead to Candida and non-Candida infection in liver transplant recipients. Their identification should prompt specific prophylactic measures to reduce morbidity and mortality in this population.

Analysis of Variance↗
PubMed1996

Relevance and risk factors of enterococcal bacteremia following liver transplantation.

To analyze the clinical characteristics of and identify specific risk factors for enterococcal bacteremia following liver transplantation, we performed a study in 405 consecutive liver transplantation recipients prophylaxed with a selective bowel decontamination regimen. Seventy enterococcal bacteremias in 52 patients were identified. Enterococcus faecalis (50) outnumbered Enterococcus faecium isolates (18), and 49% of enterococcal bacteremias were polymicrobial. Biliary tree complications were present in 34% of enterococcal bacteremias. Of the 15 deaths (29%) among the patients with enterococcal bacteremia, 4 were directly associated with enterococcal bacteremia. In a multivariate analysis, Roux-en-Y choledochojejunostomy (P=0.005), a cytomegalovirus-seropositive donor (P=0.013), prolonged transplantation time (P=0.02), and biliary stricturing (P=0.016) were identified as significant risk factors. Other risk factors identified in a univariate analysis included primary sclerosing cholangitis (P=0.009) and symptomatic cytomegalovirus infection (P=0.008). Enterococcal bacteremia is a frequent infectious complication in liver transplantation recipients receiving selective bowel decontamination. Its association with cytomegalovirus and biliary tree abnormalities suggest specific areas for prophylactic intervention.

Anastomosis, Roux-en-Y↗
PubMed1996

Relationships between beta-amyloid (A beta) deposits and blood vessels in patients with sporadic and familial Alzheimer's disease.

The density of diffuse, primitive and classic beta-amyloid (A beta) deposits was studied in relation to the incidence of blood vessels in the superior frontal gyrus of nine cases of sporadic Alzheimer's disease (SAD), two cases of familial Alzheimer's disease (FAD) with amyloid precursor protein (APP) mutations (APP717, Val --> Ile), and eight cases of FAD not linked to chromosomes 21, 14 or 1. Stepwise multiple regression was used to determine for each patient whether variations in the density of A beta deposits along the cortex were significantly correlated with the incidence of blood vessels. In the majority of FAD and SAD cases, the density of the diffuse and primitive type A beta deposits was not related to blood vessels. However, the incidence of the larger diameter (> 10 microns) blood vessels was positively correlated with the density of the classic A beta deposits in eight (89%) SAD and two (20%) FAD cases. The data suggest that the densities of vessels and deposits were not significantly correlated between cases but only within cases, suggesting a strictly local effect. In addition, the spatial association between classic A beta deposits and blood vessels may be more apparent in SAD compared with FAD cases.

Aged↗
PubMed1996

Formation of chimeric DNA primer extension products by template switching onto an annealed downstream oligonucleotide.

Oligodeoxynucleotide sequences are described that anneal to a template downstream of a priming site. During polymerase-catalyzed extension of the primer, the extending primer shifts from the original template to a segment of the annealed oligonucleotide that acts as an alternative template. The resulting chimeric extended primer has one segment that is complementary to the template and a second segment that is complementary to the oligonucleotide. The influence of the sequence elements of the oligonucleotide and the reaction conditions on template switching have been explored. The sequence requirements for template switching are compared to those for transposon excision.

Base Sequence↗
PubMed1996

Effect of prolonged blood contact time on deposition of cellular and amorphous material on teflon-coated guidewires: a scanning electron microscopy study.

Prolonged contact of blood with guidewires and catheters has been implicated in leading to thromboembolic complications during cardiac catheterization. To study the effect of exposure time on blood product deposition on Teflon-coated guidewires, 35 patients undergoing routine coronary arteriography were randomly assigned to three time groups with exposure of the guidewire to blood of 3, 5, and 10 min, respectively. The exposed wires were examined by scanning electron microscopy, and the micrographs were graded by a pathologist "blinded" as to the exposure time. Deposition of cellular and amorphous material on the guidewire surface and interstices was graded using an arbitrary scale of 1-10 (1, least amount; 10, abundant amount of material). All patients received low-dose systemic administration of heparin (2,500 units) at the beginning of the procedure. The overall activated clotting time (ACT) was 147 +/- 39 sec (mean +/- SD) prior to heparin dose. The mean ACT after low-dose systemic heparin, measured at sheath removal immediately after exposure of the wire to blood had been completed, rose to 241 +/- 79 sec (P < 0.0001). The deposition of cellular and amorphous material on the surface and grooves of the wire was not significantly different at 3, 5, and 10 min. Thus, in this study, Teflon-coated guidewires showed no increase in cellular or amorphous deposits from 3 min to 10 min of blood-wire contact time in the presence of low-dose heparinization.

Aged↗
PubMed1996

Surface adsorption and fibrinogen interactions with hirudin-thrombin complex.

This study describes the protein interaction properties of hirudin-thrombin complex adsorbed onto a surface. Hirudin-thrombin complex, preadsorbed thrombin bound with hirudin, and thrombin were coated onto the surfaces of glass beads. The activity of the thrombin component adsorbed onto the surface, and hence the ability of hirudin to bind and inactivate thrombin, was determined by measuring the activity of thrombin to cleave fibrinogen to generate fibrin and to cleave a chromogenic substrate, S-2238. Pure thrombin adsorbed on the surface (without hirudin) retained its activity to cleave fibrinogen and cleave S-2238. Hirudin-thrombin complex adsorbed on the surface did not stimulate the activation of fibrinogen, nor did it cleave S-2238.

Biocompatible Materials↗
PubMed1996

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder.

Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease. We therefore conducted a risk factor analysis of variables that might predict the development of PTLD. Specifically, since EBV may cause both PTLD and the development of monoclonal proteins (M protein), we sought to determine if the development of an M protein preceded and therefore might serve as a predictive marker of subsequent PTLD. Before and after liver transplantation, 201 patients were evaluated for the presence of urine and serum M proteins. Patients were followed to monitor the development of PTLD for a mean of 1,733 days. PTLD developed in seven patients (3.5%), three (43%) of whom died from disseminated PTLD. PTLD was classified as polymorphous in six patients and monomorphous in one patient. Fifty-seven patients (28%) developed an M protein after transplantation: five of seven patients (71%) with PTLD and 52/194 (27%) of patients without PTLD. Multivariate risk factor analysis for the development of an M protein after transplantation identified cytomegalovirus (CMV) donor seropositivity (P = 0.0002) and postoperative symptomatic CMV infection (P = 0.019) as risk factors. Whereas EBV serostatus of either the donor or recipient was not found to be a risk factor for the occurrence of either an M protein or PTLD, the development of a serum immunoglobulin M (IgM) M protein (P = 0.04) and of any urine M protein (P = 0.01) was identified by univariate analysis as being associated with the development of PTLD. Further studies are needed to determine the predictive value of M proteins as a marker for PTLD. Until such time, the development of serum or urine M protein should heighten the suspicion of developing PTLD.

Adolescent↗
PubMed1996

Effects of cisapride on salivary production in normal subjects.

Cisapride improves reflux esophagitis and enhances esophageal acid clearance. To test the effect of cisapride an salivary production, we enrolled 14 healthy volunteers in a double-blind, randomized, placebo-controlled study. Subjects received cisapride, 10mg per os four times a day, or placebo for three days. Saliva, collected during fasted and fed states, was analyzed for volume and buffer capacity. Buffer capacity was expressed as the volume of 0.01 N HCl needed to titrate 1 ml of saliva to pH 6.1. Both volume and buffer capacity significantly increased during the fed state as compared to the fasted on both cisapride and placebo. Cisapride significantly enhanced the postprandial salivary volume and buffer capacity compared to placebo: 29.6 +/- 11.3 ml vs 22.9 +/- 9.5 ml and 1.07 +/- 0.31 vs 0.89 +/- 0.28, respectively (P< 0.0001). Cisapride's enhancement of salivary flow rate and buffer capacity in the fed state may be another mechanism by which it exerts its beneficial effect in patients with reflux esophagitis.

Adult↗