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Biomedical subjects

R Patel

Publications and source records attributed to R Patel.

At least 145 records · Page 8Linked to original sources

Clinical correlations of alpha2,6-sialyltransferase expression in colorectal cancer patients.

We have previously demonstrated a link between alpha2,6-Sialyltransferase (alpha2,6-ST; E.C. 2.4.99.1) expression and differentiation of colon tumors. So far, information is not available relative to the expression of alpha2,6-ST in tumors and the survival of patients with colorectal cancer. We have examined the expression of alpha2,6-ST in a variety of colorectal adenocarcinomas (n = 46) at different stages of differentiation (G1 to G3) by immunoperoxidase assay using monoclonal antibody (MAb) 6B9. Clinical outcome of the patients in a 5-year follow-up study has been correlated with the expression of alpha2,6-ST in tumors surgically removed from the same patients. No significant difference in the alpha2,6-ST expression was noted when age, sex, and tumor locations (colon, rectum) were included as parameters. However, 52% of the moderate (G2) and well-differentiated (G1) adenocarcinomas showed stronger alpha2,6-ST expression compared with poorly differentiated (G3) adenocarcinomas. Notably, absence to moderate levels of tumor alpha2,6-ST expression was correlated with 100% survival in patients with stage I and II tumors compared with 64% survival in patients with strong tumor alpha2,6-ST expression (p < 0.01). These studies suggest a negative correlation between the expression of alpha2,6-ST in tumors and a good clinical outcome in colorectal cancer patients.

Adenocarcinoma↗

Spondylometaphyseal dysplasia Sedaghatian type associated with lethal arrhythmia and normal intrauterine growth in three siblings.

Spondylometaphyseal dysplasia of the Sedaghatian type is a rare dysplasia, characterized by mild limb shortening, but lethal in the neonatal period. We describe three affected male siblings, the offspring of consanguineous parents. One was stillborn. Neonatal death was due to cardiac arrhythmia in two of the siblings. This report confirms the importance of cardiac pathology in this probably autosomal recessive disorder. This diagnosis should be excluded in any newborn with an arrhythmia as the clinical limb shortening may not be obvious.

Arrhythmias, Cardiac↗

Linezolid therapy of Staphylococcus aureus experimental osteomyelitis.

The in vivo activity of linezolid or cefazolin against a clinical isolate of methicillin-susceptible Staphylococcus aureus (linezolid MIC, 2 microg/ml) was studied in a rat model of experimental osteomyelitis. Sixty rats with experimental S. aureus osteomyelitis were treated for 21 days with no antimicrobial, with 25 microg of linezolid per kg of body weight administered intraperitoneally twice or three times a day, or with 50 microg of cefazolin per kg administered intramuscularly three times a day. After treatment, the animals were sacrificed and the infected tibiae were processed for quantitative bacterial cultures. The results of treatment were expressed as log(10) CFU/gram of bone and analyzed by rank sum analysis. The results of linezolid treatment were not significantly different from those of untreated controls, while cefazolin treatment was significantly more active than no treatment or linezolid treatment.

Acetamides↗

The biopesticide Paenibacillus popilliae has a vancomycin resistance gene cluster homologous to the enterococcal VanA vancomycin resistance gene cluster.

We have previously identified, in Paenibacillus popilliae, a 708-bp sequence which has homology to the sequence of the enterococcal vanA gene. We have performed further studies revealing five genes encoding homologues of VanY, VanZ, VanH, VanA, and VanX in P. popilliae. The predicted amino acid sequences are similar to those in VanA vancomycin-resistant enterococci: 61% identity for VanY, 21% for VanZ, 74% for VanH, 77% for VanA, and 79% for VanX. The genes in P. popilliae may have been a precursor to or have had ancestral genes in common with vancomycin resistance genes in enterococci. The use of P. popilliae biopesticidal preparations in agricultural practice may have an impact on bacterial resistance in human pathogens.

Amino Acid Sequence↗

Trovafloxacin treatment of viridans group Streptococcus experimental endocarditis.

The activity of trovafloxacin was compared with those of vancomycin and penicillin in a model of Streptococcus sanguis species group (trovafloxacin MIC, 0.125 microg/ml) and Streptococcus mitis species group (trovafloxacin MIC, 0.125 microg/ml) experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no treatment, trovafloxacin at 15 mg/kg of body weight three times a day (t.i.d.), vancomycin at 15 mg/kg twice a day, or penicillin at 1. 2 x 10(6) IU t.i.d. After 3 days of treatment, the animals were sacrificed; cardiac valve vegetations were aseptically removed and cultured quantitatively. Penicillin was as active as vancomycin as measured by in vivo clearance of bacteria. Trovafloxacin was less active (P < 0.05) than vancomycin or penicillin against S. sanguis species group infection but had similar efficacy against S. mitis species group infection. Quinolones, despite MICs in the susceptible range, may not be active for serious infections caused by some viridans group streptococci.

Animals↗

New strategies for prevention and therapy of cytomegalovirus infection and disease in solid-organ transplant recipients.

In the past three decades since the inception of human organ transplantation, cytomegalovirus (CMV) has gained increasing clinical import because it is a common pathogen in the immunocompromised transplant recipient. Patients may suffer from severe manifestations of this infection along with the threat of potential fatality. Additionally, the dynamic evolution of immunosuppressive and antiviral agents has brought forth changes in the natural history of CMV infection and disease. Transplant physicians now face the daunting task of recognizing and managing the changing spectrum of CMV infection and its consequences in the organ recipient. For the microbiology laboratory, the emphasis has been geared toward the development of more sophisticated detection assays, including methods to detect emerging antiviral resistance. The discovery of novel antiviral chemotherapy is an important theme of clinical research. Investigations have also focused on preventative measures for CMV disease in the solid-organ transplant population. In all, while much has been achieved in the overall management of CMV infection, the current understanding of CMV pathogenesis and therapy still leaves much to be learned before success can be claimed.

Antiviral Agents↗

Frequency of isolation of Staphylococcus lugdunensis among staphylococcal isolates causing endocarditis: a 20-year experience.

Eighty-nine staphylococcal isolates recovered from patients with bacterial endocarditis at the Mayo Clinic from 1980 to 1999 were studied to determine the prevalence of Staphylococcus lugdunensis among clinical isolates of staphylococci causing endocarditis. Four isolates, all from patients with native mitral valve endocarditis, were identified as S. lugdunensis.

Adult↗

Inhibiting proteasome activity causes overreplication of DNA and blocks entry into mitosis in sea urchin embryos.

The proteasome has been shown to be involved in exit from mitosis by bringing about destruction of mitotic cyclins. Here, we present evidence that the proteasome is also required for proper completion of S phase and for entry into mitosis in the sea urchin embryonic cleavage cycle. A series of structurally related peptide-aldehydes prevent nuclear envelope breakdown in their order of inhibitory efficacies against the proteasome. Their efficacies in blocking exit from S phase and exit from mitosis correlate well, indicating that the proteasome is involved at both these steps. Mitotic histone HI kinase activation and tyrosine dephosphorylation of p34(cdc2) kinase are blocked by inhibition of the proteasome, indicating that the proteasome plays an important role in the pathway that leads to embryonic p34(cdc2 )kinase activation. Arrested embryos continued to incorporate [(3)H]thymidine and characteristically developed large nuclei. Pre-mitotic arrest can be overcome by treatment with caffeine, a manoeuvre that is known to override the DNA replication checkpoint. These data demonstrate that the proteasome is involved in the control of termination of S phase and consequently in the initiation of M phase of the first embryonic cell cycle.

Animals↗

Regulation of immune activity by mild (fever-range) whole body hyperthermia: effects on epidermal Langerhans cells.

Inflammation of the skin and systemic fever, both of which occur with injury or infection, include a hyperthermic component that many believe constitutes a physiological stress. Such increases in local or systemic body temperature may also have a regulatory effect on immune function. Langerhans cells (LCs), the dendritic cells of the skin, continuously monitor the extracellular matrix of the skin by taking up particles and microbes that they then carry to draining lymph nodes for presentation to T lymphocytes. We hypothesize that the thermal element of inflammation and/or fever may help regulate the activation and migration of LCs out of the epidermis. To test this hypothesis, Balb/ c mice were exposed to a mild (39.8 degrees C +/- 0.2 degrees C), long-duration (6 hours) whole body hyperthermia (WBH) treatment, which mimics the thermal component of fever. The number of LCs and their morphology were analyzed at various time points up to 7 days after the initiation of WBH. The LCs of the ear epidermis were visualized using a fluorescein isothiocyanate-conjugated antibody specific for the major histocompatibility complex (MHC) class II molecule and confocal microscopy. Although MHC class II staining was diffuse on the surface of the LC body and dendritic extensions of both WBH and control samples, the WBH-treated LCs exhibited a more punctate morphology with fewer dendritic processes compared with control LCs. A significant decrease in the number of LCs was also observed 1 to 5 days after WBH treatment. Furthermore, in vitro heating of Balb/c ear skin cultures at 40 degrees C for 6 to 8 hours enhanced the numbers of viable LCs that migrated into the culture wells. These results suggest that WBH treatment stimulates epidermal LCs in the absence of foreign antigen.

Animals↗

Monitoring skeletal response to treatment which site to measure in the femur?

In the past it was usual to interpret bone mineral density (BMD) scans of the femur using the femoral neck, trochanter, or Ward's triangle sites. Recently, a study by the International Committee for Standards in Bone Measurement recommended that the total hip should be the preferred site for the interpretation of femur BMD, and another study described a new central hip site that may offer improved precision. This article compares the longitudinal sensitivities of the different femur BMD sites for monitoring patient response to treatment. The study population was 152 postmenopausal women enrolled in a trial of a bisphosphonate therapy. Spine and hip BMD scans were performed at 0, 1, and 2 yr. The mean percentage change at 2 yr was calculated for six sites in the hip, and the spine was also included for comparison. Treatment effect was defined as the difference in the BMD change between the treated and placebo groups. Although the data analysis incorporated a term for a calibration change caused by a repair of the dual X-ray absorptiometry scanner, the effect of this event on the estimation of treatment effect was negligible. Longitudinal sensitivity was derived by dividing the treatment effect by the root mean square error (RMSE) of the statistical model. Results (and standard errors) normalized to the ratio of treatment effect: RMSE for femoral neck BMD were as follows: femoral neck: 1.00; trochanter: 1.33 (0.38); intertrochanteric: 0.84 (0.41); total hip: 1.20 (0.38); Ward's triangle: 1.03 (0.27); central hip: 1.09 (0.30); spine: 2.08 (0. 45). At none of the femur sites was the change in BMD large enough to allow monitoring of response to treatment in individual patients. However, for studies involving the follow-up of a group of subjects, the longitudinal sensitivities of the different femur sites were equal within the statistical errors of the study. In particular, total hip BMD appears to be as effective as femoral neck BMD for detecting response to treatment in the femur in the setting of a clinical trial or similar research study.

Absorptiometry, Photon↗

Amphotericin B colloidal dispersion.

Amphotericin B colloidal dispersion (ABCD) is a colloidal dispersion of a stable complex of amphotericin B with cholesteryl sulphate in a 1:1 proportion, forming uniform disk-shaped particles. ABCD is associated with less nephrotoxicity than conventional amphotericin B deoxycholate. Infusion-related adverse events are more frequent in patients receiving ABCD than in patients receiving liposomal amphotericin B or amphotericin B deoxycholate. ABCD has been shown in a randomised, double-blind study, to be an effective alternative to amphotericin B deoxycholate for empirical treatment of patients with fever and neutropenia. ABCD is active in the treatment of invasive Candida spp. and Aspergillus spp. infections in immunocompromised hosts, however most of the data supporting its use for these types of infections is derived from non-comparative open-label clinical trials of patient refractory to or intolerant of conventional antifungal therapy. ABCD is approved by the US FDA for the treatment of invasive aspergillosis in patients where renal impairment of unacceptable toxicity precludes the use of amphotericin B deoxycholate in effective doses, and in patients with invasive aspergillosis where prior amphotericin B deoxycholate therapy has failed. Two other lipid formulations of amphotericin B, amphotericin B lipid complex and liposomal amphotericin B, are available and, like ABCD, are associated with reduced nephrotoxicity as compared to amphotericin B deoxycholate. The role of ABCD in comparison with these other lipid formulations of amphotericin B is discussed herein. High cost remains an issue with all lipid formulations of amphotericin B.

Amphotericin B↗

Ciprofloxacin inhibition of experimental fracture healing.

BACKGROUND: Fluoroquinolones, such as ciprofloxacin, have an adverse effect on growing cartilage and endochondral ossification in children. This study was carried out to determine whether ciprofloxacin also has an adverse effect on the healing of experimental fractures. METHODS: Sixty male 300-gram Wistar rats were divided equally into three groups, which received ciprofloxacin, cefazolin, or no treatment for three weeks, beginning seven days after production of a closed, nondisplaced, bilateral femoral fracture. The serum concentrations of the ciprofloxacin and the cefazolin were 2.4 and 146 micrograms per milliliter, respectively. Radiographic, histological, and biomechanical studies were used to evaluate fracture-healing. RESULTS: Radiographs revealed significantly more advanced healing of the control fractures compared with the fractures in the ciprofloxacin-treated group (average stage, 2.1 compared with 1.5, p = 0.01). The cefazolin-treated group was not different from the controls with respect to radiographic healing (average stage, 1.8 compared with 2.1, p = 0.18). Torsional strength-testing of fracture callus exposed to ciprofloxacin revealed a 16 percent decrease in strength compared with the controls (284 compared with 338 newton-millimeters, p = 0.04) and a 49 percent decrease in stiffness (twenty compared with thirty-nine newton-millimeters per degree, p = 0.001). The biomechanical strength in the cefazolin-treated group was not different from that of the controls. Fracture calluses in the animals treated with ciprofloxacin showed abnormalities in cartilage morphology and endochondral bone formation and a significant decrease in the number of chondrocytes compared with the controls (0.77 x 10(4) compared with 1.3 x 10(4) cells per square millimeter, p = 0.004). CONCLUSIONS: These data suggest that experimental fractures exposed to therapeutic concentrations of ciprofloxacin in serum demonstrate diminished healing during the early stages of fracture repair. The administration of ciprofloxacin during early fracture repair may compromise the clinical course of fracture-healing.

Animals↗

Excellent tolerance of rituximab when given after mitoxantrone/cyclophosphamide: an effective and safe combination for indolent non-Hodgkin's lymphoma.

Treatment for extensive indolent lymphoma should provide optimization of efficacy while avoiding excessive toxicity. Rituximab may be an ideal agent to combine with chemotherapy because of its lack of classical myelotoxicity. In this study, 27 patients with a variety of histologies of indolent B-cell non-Hodgkin's lymphoma have been treated utilizing a novel three-drug combination. Nine patients had relapsed disease and 18 were previously untreated. Patients first received cyclophosphamide 800 mg/m(2) and mitoxantrone 8 mg/m(2) i.v. on day 1, every 3 weeks for 2 cycles. Subsequently, patients received rituximab 375 mg/m(2) followed by mitoxantrone 8 mg/m2 every 2 weeks for 4 cycles. This regimen and, in particular, the rituximab infusion were extremely well tolerated. Only two of 27 patients experienced a grade 1/2, infusion-related reaction during the first rituximab infusion. Grade 4 neutropenia was noted at some point in 16 patients who were then offered granulocyte-macrophage colony-stimulating factor support for improvement of neutropenia. No infections were noted. Alopecia was minimal. Of 27 patients, 19 achieved a complete response (CR), one achieved an unconfirmed CR (CRu), and five patients achieved a partial response, for an overall response rate of 92.5%. Molecular remissions were noted in seven of 12 tested patients in CR. We concluded that the cyclophosphamide/mitoxantrone/rituximab (CyMiR) regimen is effective and extremely well tolerated. Furthermore, rituximab infusion-associated morbidity is markedly reduced.

Adult↗

Nasal toxicity of cocaine: a hypercoagulable effect?

Nasal insufflation of cocaine injures the nasal mucosa and can perforate the septum. Cocaine-induced vasoconstriction resulting in ischemia is one of the methods that may be responsible for this damage. We are determining whether cocaine also produces a hypercoagulable state that may compound factors which have been previously established to cause damage to the nasal mucosa and septum. This study uses Modified Recalcification Time (MRT), a test developed in our laboratory that has the ability to measure the overall coagulation process. Our study revealed no connection between cocaine and enhanced platelet function or monocyte-released tissue factor. The coagulation process was unaffected by the addition of the drug, so we conclude that cocaine does not cause a hypercoagulable state and cannot assist in the explanation regarding the ischemic changes of the nasal septum.

Blood Coagulation↗

Complications from Sinus of Valsalva aneurysm--a case of stable ischemia from compression of the left main stem and one of surgical recurrence.

Two cases of Sinus of Valsalva aneurysm with unusual complications are presented. Left main stem compression from an expanding Sinus of Valsalva aneurysm usually carries a poor prognosis and aggressive surgical management has been proposed. We describe a case with stable myocardial ischemia over four months from left main stem compression. Surgical repair of Sinus of Valsalva aneurysm is usually curative, but our second case demonstrates the pitfalls of inadequate surgical management.

Adult↗

Right coronary artery occlusion caused by blunt trauma.

We describe the diagnostic and management dilemmas faced in the case of a thirty-year-old woman without a prior cardiac history, who after a motor vehicle accident, was found to have persistent EKG changes in the inferior leads consistent with an acute injury pattern. The patient was ultimately thought to have trauma and subsequent occlusion of the right coronary artery.

Accidents, Traffic↗

Quantification of DNA using the luminescent oxygen channeling assay.

BACKGROUND: Simplified and cost-effective methods for the detection and quantification of nucleic acid targets are still a challenge in molecular diagnostics. METHODS: Luminescent oxygen channeling assay (LOCI(TM)) latex particles can be conjugated to synthetic oligodeoxynucleotides and hybridized, via linking probes, to different DNA targets. These oligomer-conjugated LOCI particles survive thermocycling in a PCR reaction and allow quantified detection of DNA targets in both real-time and endpoint formats. The endpoint DNA quantification format utilized two sensitizer bead types that are sensitive to separate illumination wavelengths. These two bead types were uniquely annealed to target or control amplicons, and separate illuminations generated time-resolved chemiluminescence, which distinguished the two amplicon types. RESULTS: In the endpoint method, ratios of the two signals allowed determination of the target DNA concentration over a three-log range. The real-time format allowed quantification of the DNA target over a six-log range with a linear relationship between threshold cycle and log of the number of DNA targets. CONCLUSIONS: This is the first report of the use of an oligomer-labeled latex particle assay capable of producing DNA quantification and sequence-specific chemiluminescent signals in a homogeneous format. It is also the first report of the generation of two signals from a LOCI assay. The methods described here have been shown to be easily adaptable to new DNA targets because of the generic nature of the oligomer-labeled LOCI particles.

Chlamydia trachomatis↗