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Biomedical subjects

R Shapiro

Publications and source records attributed to R Shapiro.

At least 91 records · Page 5Linked to original sources
PubMed1999

Infusion of donor leukocytes to induce tolerance in organ allograft recipients.

To further enhance chimerism, 229 primary allograft recipients have received perioperative intravenous infusion of a single dose of 3 to 6 X 10(8) unmodified donor bone marrow (BM) cells/kg body weight. In addition, 42 patients have been accrued in a concurrent protocol involving multiple (up to three) sequential perioperative infusions of 2 x 10(8) BM cells/kg/day from day 0-2 posttransplantation (PTx). Organ recipients (n = 133) for whom BM was not available were monitored as controls. The infusion of BM was safe and except for 50 (18%), all study patients have optimal graft function. Of the control patients, allografts in 30 (23%) have been lost during the course of follow-up. The cumulative risk of acute cellular rejection (ACR) was statistically lower in the study patients compared with that of controls. It is interesting that, 62% of BM-augmented heart recipients were free of ACR (Grade > or = 3A) in the first 6 months PTx compared to controls. The incidence of obliterative bronchiolitis was also statistically lower in study lung recipients (3.8%) compared with the contemporaneously acquired controls (31%). The levels of donor cell chimerism were at least a log higher in the peripheral blood of majority of the study patients compared with that of controls. The incidence of donor-specific hyporeactivity, as determined by one-way mixed leukocyte reaction, was also higher in those BM-augmented liver, kidney, and lung recipients that could be evaluated compared to controls.

Bone Marrow Cells↗
PubMed1999

Hamstring extensibility and transverse plane knee control relationship in athletic women.

Athletic women are at particular risk for sustaining a non-contact anterior cruciate ligament (ACL) injury. The hamstrings are vital to providing dynamic knee motion control in the sagittal and transverse planes during running stance, and some have suggested this function is enhanced when they are less extensible. This study attempted to determine the correlational relationships between hamstring extensibility and transverse plane knee kinematics and from these data to describe the dynamic transverse plane knee motion control capabilities of the hamstrings. Twenty normal athletic women (mean +/- SD; aged 21 +/- 1.6 years; height 163.3 +/- 5.7 cm; weight 60.1 +/- 3.6 kg) were evaluated for active hamstring extensibility and transverse plane knee kinematic relationships during crossover-cut stance phase. Following crossover-cut training (3 weeks) using the left (preferred) lower extremity as the stance limb, hamstring extensibility was measured. Following this, subjects were fitted with 9 retroreflective markers denoting the local segmental coordinate systems (3 markers each) of the left foot, leg and thigh. Kinematic (3-dimensional, four phase-locked cameras, 200 Hz) knee and ankle data were sampled and analyzed. Descriptive statistics and Pearson correlations between hamstring extensibility and knee and ankle kinematic variables were calculated. Statistical significance was set at P < or = 0.05 with Bonferroni adjustments. Hamstring extensibility (12 degrees +/- 8 degrees terminal extension) revealed low but significant positive correlations with tibial external rotation (6 degrees +/- 10.7 degrees) at heelstrike (19.3 degrees +/- 8.5 degrees knee flexion) (r = 0.62, P = 0.004) and tibial internal rotation (-13 degrees +/- 8.4 degrees) at peak knee flexion (57.8 degrees +/- 9.3 degrees) following heelstrike (r = 0.47, P = 0.01). Increased hamstring extensibility resulted in increased tibial external rotation at heelstrike and decreased tibial internal rotation at peak knee flexion. Increased hamstring extensibility may improve knee extensor efficiency at heelstrike by enabling greater tibial external rotation and protect the ACL at peak knee flexion by decreasing the tibial internal rotation magnitude.

Adult↗
PubMed1999

Cytomegalovirus infection of the native ureter after liver-kidney transplantation.

We report a case of invasive cytomegalovirus (CMV) infection in the native ureter of a patient 7 years after liver-kidney transplantation. Previous reports of CMV ureteritis in transplant patients have involved only the allograft ureter, usually within 3 months of transplantation. The common characteristics of these patients, the possible risk factors, and the diagnostic findings of CMV ureteritis are discussed. Combined surgical and medical intervention are required for successful treatment.

Adult↗
PubMed1999

A dentoalveolar abscess in a pediatric patient with ketoacidosis caused by occult diabetes mellitus: a case report.

Oral health professionals are frequently asked to evaluate patients with routine odontogenic infections. These patients can sometimes present with systemic signs and symptoms, including fever, malaise, tachycardia, and dehydration. It is important for the astute clinician to understand the possible associated systemic diseases that may be contributing to odontogenic infections. We present here an interesting case of a pediatric patient with a routine canine space infection who exhibited classic clinical signs and symptoms of diabetic ketoacidosis.

Child, Preschool↗
PubMed1999

Conformational analysis of the major DNA adduct derived from the food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline.

The heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is one of a number of carcinogens found in barbecued meat and fish. It is mutagenic in bacterial and mammalian assays and induces tumors in mammals. IQ is biochemically activated to a derivative which reacts with DNA to form a major covalent adduct at carbon 8 of guanine. This adduct may deform the DNA and consequently cause a mutation, which may be responsible for initiating IQ's carcinogenicity. Atomic resolution structures of the IQ-damaged DNA are not yet available experimentally. We have carried out an extensive molecular mechanics energy minimization search to locate feasible structures for the major IQ-DNA adduct in the representative sequence d(5'-G1-G2-C3-G4-C5-C6-A7-3'). d(5'-T8-G9-G10-C11-G12-C13-C14-3') with IQ modification at G4; this contains the GGCGCC mutational hotspot sequence known as NarI. The molecular mechanics program AMBER 5.0 with the force field of Cornell et al. [(1995) J. Am. Chem. Soc. 117, 5179-5197] was employed, including explicit Na(+) counterions and an implicit treatment for solvation. However, key parameters, the partial charges, bond lengths, bond angles, and dihedral parameters of the modified residue, are not available in the AMBER database. We carefully parametrized the force field, created 800 starting conformations which uniformly sampled at 18 degrees intervals each of the three flexible torsion angles that govern the IQ-DNA orientation, and minimized their energy. A conformational mix of structural types, including major groove, minor groove, and base-displaced intercalated carcinogen positions, was generated. This mixture may be related to the diversity of mutational outcomes induced by IQ.

Chemical Phenomena↗
PubMed1999

Prevention and treatment of cytomegalovirus infection in organ transplant recipients.

Cytomegalovirus (CMV) is the most common viral pathogen in organ transplant recipients. The patients at highest risk of developing CMV disease are seronegative recipients of seropositive donors, and seropositive recipients who receive antilymphocyte agents such as OKT3 and antithymocyte globulin (ATG) for induction or for rejection. There have been many trials of CMV prevention, but they are difficult to compare with one another because of variability in definitions and end points. Two modalities that have been used to prevent CMV disease are prophylaxis and preemptive therapy. In prophylaxis all patients are given an antiviral agent in order to prevent CMV disease, while in preemptive therapy (also called targeted prophylaxis) only patients who are identified as 'high risk' are selected for treatment. Selected trials of prophylaxis and preemptive therapy in solid-organ recipients are reviewed. The factors to be considered in using one modality or the other are side effects from antivirals, cost of monitoring and antivirals, efficacy of the two modalities, and potential emergence of drug resistance. Sensitive tests that have been used for early diagnosis and monitoring of CMV are antigenemia and the polymerase chain reaction (PCR). Antigen pp65 is a lower matrix protein and can be detected in peripheral blood leukocytes. The sensitivity and specificity are high and vary from 89% to 100% and 92% to 96%, respectively. Currently, many authors believe that the antigenemia test is more useful than the PCR test. The antigenemia test is useful for viral monitoring as a guide for preemptive therapy after organ transplantation. Persistence of high counts of antigenemia may indicate inadequate antiviral therapy or emergence of resistance. Recurrence of positive antigenemia after treatment of CMV disease can be a sign of relapse. Transplant patients who develop resistance to antiviral drugs are usually seronegative recipients who receive an organ from a seropositive donor and have several courses of antivirals for CMV disease. Ganciclovir is the most frequent antiviral agent used in transplant recipients and is usually well tolerated. Resistance to ganciclovir may occur and is usually secondary to virus mutation in the UL97 gene. The availability of sensitive diagnostic tests such as pp65 antigenemia has made the early diagnosis of CMV possible in organ transplant recipients. CMV is being treated much earlier now, and progression to disseminated disease is uncommon. Prudent use of antiviral drugs will hopefully limit the problem of drug resistance.

Antiviral Agents↗
PubMed1999

Simultaneous administration of adjuvant donor bone marrow in pancreas transplant recipients.

OBJECTIVE: The effect of donor bone marrow was evaluated for its potentially favorable effect in the authors' simultaneous pancreas/kidney transplant program. METHODS: From July 1994 to January 1999, 177 pancreas transplants were performed, 151 of which were simultaneous pancreas/kidney transplants. All patients received tacrolimus, mycophenolate mofetil, and steroids for immunosuppression (azathioprine was used in the first year of the program). Fifty-three simultaneous pancreas/kidney transplant recipients received perioperative unmodified donor bone marrow, 3 to 6 x 10(8) cells/kg. RESULTS: Overall actuarial survival rates at 1 and 3 years were 98% and 95% (patient), 95% and 87% (kidney), and 86% and 80% (pancreas), respectively. In the adjuvant bone marrow group, 1- and 3-year survival rates were 96% and 91 % (patient), 95% and 87% (kidney), and 83% and 83% (pancreas), respectively. For 98 recipients who did not receive bone marrow, survival rates at 1 and 3 years were 100% and 98% (patient), 96% and 86% (kidney), and 87% and 79% (pancreas), respectively. No pancreas allografts were lost after 3 months in bone marrow recipients, and seven in the non-bone marrow recipients were lost to rejection at 0.7, 6.7, 8.8, 14.6, 24.1, 24.3, and 25.5 months. Twenty-two percent of bone marrow patients were steroid-free at 1 year, 45% at 2 years, and 67% at 3 years. Nineteen percent of the non-bone marrow recipients were steroid-free at 1 year, 38% at 2 years, and 45% (p = 0.02) at 3 years. The mean acute cellular rejection rate was 0.94+/-1.1 in the bone marrow group and 1.57+/-1.3 (p = 0.003) in the non-bone marrow group (includes borderline rejection and multiple rejections). The level of donor cell chimerism in the peripheral blood of bone marrow patients was at least two logs higher than in controls. CONCLUSION: In this series, which represents the largest experience with adjuvant bone marrow infusion in pancreas recipients, there was a higher steroid withdrawal rate (p = 0.02), fewer rejection episodes, and no pancreas graft loss after 3 months in bone marrow recipients compared with contemporaneous controls. All pancreas allografts lost to chronic rejection (n = 6) were in the non-bone marrow group. Donor bone marrow administered around the time of surgery may have a protective effect in pancreas transplantation.

Actuarial Analysis↗
PubMed1999

Case series: clonidine has no systematic effects on PR or QTc intervals in children.

This study retrospectively examined the effects of clonidine, both alone and combined with psychostimulants, on the electrocardiograms (ECGs) of children and adolescents. Two pediatric cardiologists, blinded to treatment condition, examined pre- and posttreatment ECGs in 42 subjects treated with clonidine for attention-deficit/hyperactivity or tic disorder. While ECG variability was found, it did not appear to be related to any systematic effect of clonidine, either alone or in combination with psychostimulants. These data do not rule out the possibility of rare idiosyncratic reactions to clonidine with or without psychostimulants, though none occurred in this sample.

Adolescent↗
PubMed1999

Shoulder proprioception: latent muscle reaction times.

PURPOSE: The purpose of this study was to identify electromyographic (EMG) differences in the latent muscle reaction timing (LMRT) of the rotator cuff between trained overhead throwers and control subjects in response to sudden internal rotation perturbation (P < or = 0.05). METHODS: Subjects included 15 trained overhead throwers (male intercollegiate baseball players) and 15 untrained subjects (males not active in competitive throwing sports). Subjects were tested while seated, with their dominant glenohumeral joint positioned in 90 degrees abduction/external rotation (scapular plane), their elbow flexed to 90 degrees, and their forearm placed in the perturbation device. Rotator cuff LMRT was assessed as they tried to decelerate a variably timed, sudden internal rotation force. EMG sampling (2000 Hz, 2-s duration) began immediately before perturbation. RESULTS: Trained throwers had slower infraspinatus (P = 0.011) and teres minor (P = 0.024) LMRT and decreased supraspinatus (P = 0.001) and posterior deltoid (P = 0.0001) muscle activation duration compared with control subjects. CONCLUSIONS: These results suggest that the rotator cuff muscles of trained throwers may be downregulated in response to sudden internal rotation perturbation. Although these adaptations would enable greater internal rotation velocities during overhead throwing, they may also contribute to glenohumeral joint pathology. The identification of changes in rotator cuff LMRT in response to sudden internal rotation perturbation suggests an area of acquired neuromuscular imbalance warranting consideration by those involved in the rehabilitation and conditioning of the overhead throwing athlete.

Adolescent↗
PubMed1999

The epidermotropic mycosis fungoides associated alpha1beta1 integrin (VLA-1, CD49a/CD29) is primarily a collagen IV receptor on malignant T cells.

Several of the beta1 integrin receptors [very late antigen (VLA) molecules] for extracellular matrix (ECM) proteins are expressed by malignant T cells in cutaneous T-cell lymphoma (CTCL). We evaluated the function of VLA-1, a beta1 integrin specifically expressed in epidermotropic mycosis fungoides (MF), in CD4+ leukemic T cells Jurkat line). We found that Jurkat cells adhere significantly to collagens only after their activation with phorbol 12-myristate 13-acetate (PMA). However, the adhesion to collagen IV (but not to collagen I) of Jurkat cells selected for expressing increased levels of VLA-1 (with unchanged levels of VLA-2, the second collagen integrin receptor) was significantly enhanced relative to that of "VLA-1 low" cells. Monoclonal antibody (mAb) 1B3.1, directed against the collagen binding domain of VLA-1, inhibited adhesion to collagen IV and to collagen I by 36.67%+/-5.25% and 18%+/-4.32%, respectively (p<0.05), whereas the inhibition by anti-VLA-2 mAb PIE6 was comparable on both collagens (25%+/-7.48% and 36.3%+/-0.94%, respectively; p<0.09). Immuno-histochemical studies of skin biopsies from 10 untreated MF patients showed that in all cases at least 10% of the lymphocytes residing in the epidermis are VLA-1+VLA-2-. While not directly applicable to MF, the demonstrated functions of VLA-1 in leukemic Jurkat cells, together with its expression in MF skin, suggest a role for VLA-1 integrins in epidermotropism in a small proportion of leukemic MF cells.

Antigens, CD↗
PubMed1999

mAngiogenin-3, a target gene of oncoprotein E2a-Pbx1, encodes a new angiogenic member of the angiogenin family.

Angiogenins are proteins in the pancreatic ribonuclease superfamily that utilize their ribonuclease activity to induce formation of new blood vessels. Recently we identified a new member of the angiogenin gene family, mouse angiogenin-3, by virtue of its transcriptional activation in NIH3T3 fibroblasts coincident with transformation by the chimeric leukemia oncogene, E2a-Pbx1. Here we have isolated the cDNA encoding mouse angiogenin-3 and used it to produce the protein in E. coli. We demonstrate that mouse angiogenin-3 is a ribonuclease whose activity and specificity towards tRNA and dinucleotide substrates differ from those of mouse angiogenin or of mouse angiogenin-related protein, a non-angiogenic factor. Mouse angiogenin-3 induced angiogenesis in both the chicken embryo chorioallantoic membrane assay and the rat cremaster muscle. Electron microscopy revealed that endothelial cells within vessels induced by both mouse angiogenin-3 and mouse angiogenin contain fenestrations similar to those observed in endothelial cells from neovasculature induced by vascular endothelial growth factor and basic fibroblast growth factor. Mouse angiogenin-3 also induced other molecular events typical of rapidly proliferating endothelial cells, such as increases in rough endoplasmic reticulum, polysomes, and mitochondria.

3T3 Cells↗
PubMed1999

Salmonella Thompson associated with improper handling of roast beef at a restaurant in Sioux Falls, South Dakota.

In October 1996, we investigated an outbreak of Salmonella serotype Thompson infections associated with Restaurant A in Sioux Falls, South Dakota, and conducted two cohort studies among persons who ate at luncheons catered by Restaurant A. Fifty-two Salmonella Thompson infections were identified between 29 September and 14 October 1996. Infections occurred among employees and patrons at Restaurant A and among attendees at three luncheons catered by the restaurant on 7 October. Roast beef cooked at Restaurant A was the only food item significantly associated with illness. Cooking times and storage temperatures for roast beef were inadequate to prevent multiplication of Salmonella, and the chefs were unaware of proper cooking and storage temperatures. We conclude that improper handling of roast beef probably caused this outbreak of Salmonella Thompson infections. Better knowledge of food safety practices by the cooking staff at Restaurant A, through required food safety education, might have prevented the outbreak.

Adolescent↗
PubMed1999

Outcome of kidney transplantation under tacrolimus-based immunosuppression in elderly patients.

Kidney transplantation has become a reasonable treatment option for selected patients aged 60 years or older, and a number of different immunosuppressive drug protocols have been described. This article concerns 230 recipients who were aged 60 years or older and who were undergoing kidney-only transplantation at the University of Pittsburgh between January 1990 and April 1997. All recipients were treated with a tacrolimus-based immunosuppression regimen. The median follow-up was 31.5 months (range, 1-86). The 1-, 3-, and 5-year actuarial patient survival rates were 90%, 83%, and 76%, respectively. There were 42 (19%) deaths, cardiovascular disease (50%) and infection (38%) being the main causes. Death with a functioning kidney occurred in 28 (67%) patients. The 1-, 3-, and 5-year actuarial graft survival rates were 84%, 74%, and 64%, respectively. The delayed graft function rate was 33%. Rejection was seen in 57 (25%) elderly patients. The mean serum creatinine was 2.6 +/- 2.7 mg/dL and the serum urea nitrogen was 35 +/- 22 mg/dL. The mean tacrolimus level was 8.5 +/- 3.8 ng/mL. These results suggest that renal transplantation in older recipients under tacrolimus-based immunosuppression is associated with reasonable outcomes, and can be offered to appropriately selected patients.

Actuarial Analysis↗
PubMed1999

Simultaneous pancreas-kidney transplantation at the University of Pittsburgh.

Analysis of the SPK program at the University of Pittsburgh has led to a number of observations: 1. Under tacrolimus-based immunosuppression, without antibody induction, it has been possible to achieve (a) One- and 3-year actuarial patient survival rates of 98% and 95% (b) One- and 3-year actuarial kidney survival rates of 95% and 87% (c) One- and 3-year actuarial pancreas survival rates of 86% and 80% 2. Steroid withdrawal has been achieved in over half of the successfully transplanted recipients, with excellent outcomes and a low rate (4.7%) of subsequent rejection. 3. Bone marrow augmentation has been associated with (a) less rejection (b) less pancreatic graft loss to rejection (c) an increased ability to withdraw steroids 4. Rejection has been associated with a rising serum lipase. 5. Renal allograft rejection in SPK patients with elevated serum lipase levels has been seen in the setting of normal renal function. 6. Enteric drainage has been associated with a reasonably low complication rate. 7. SPK transplantation is a successful therapeutic option in selected type I diabetics with end-stage renal disease.

Adult↗
PubMed1999

Crossover cutting during hamstring fatigue produces transverse plane knee control deficits.

OBJECTIVE: To assess the effects of eccentric work-induced hamstring fatigue on sagittal and transverse plane (axial) knee and ankle biodynamics and kinetics during a running crossover cut directional change (functional pivot shift). DESIGN AND SETTING: A pretest-posttest, single-group intervention experimental design was employed. All data were collected in a biodynamics laboratory. SUBJECTS: Twenty healthy athletic females were trained for 3 weeks in crossover cutting before testing. MEASUREMENTS: Data were sampled during 3 unfatigued and 3 fatigued (20% eccentric isokinetic knee-flexor torque reduction) crossover cut trials. Three-dimensional kinematic and ground reaction-force data were sampled at 200 Hz and 1000 Hz, respectively, and joint moment estimates were calculated. Data were standardized to initial force-plate heelstrike for comparisons of mean differences between conditions using paired t tests with Bonferroni adjustments. Pearson product-moment correlations compared kinematic and eccentric hamstring-torque relationships. RESULTS: During internal rotation phase 1, between heelstrike and impact absorption, mean internal rotation velocity increased by 21.2 degrees /s +/- 114 degrees /s. During internal rotation phase II, mean peak transverse plane knee rotation during propulsion decreased by 3.1 degrees +/- 9 degrees . During internal rotation phase II, mean peak ankle plantar flexor moment onsets occurred 12.7 +/- 53 milliseconds earlier, and this activation demonstrated a moderately positive relationship with the onset of mean peak knee internal rotation during propulsion and a weak negative relationship with mean peak hamstring torque/lean body weight. CONCLUSIONS: The increased knee internal rotation velocity during phase I indicates transverse plane dynamic knee-control deficits during hamstring fatigue. Earlier peak ankle plantar-flexor moments and decreased internal rotation during phase II in the presence of hamstring fatigue may represent compensatory attempts at dynamic knee stabilization from the posterior lower leg musculature during the pivot shift portion of the crossover cut. The weak relationship between decreased hamstring torque/lean body weight and delayed knee internal rotation during propulsion further supports greater dependence on ankle plantar flexors for dynamic knee stabilization compensation.

Journal Article↗