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Biomedical subjects

R Shapiro

Publications and source records attributed to R Shapiro.

At least 145 records · Page 8Linked to original sources
PubMed1997

Tacrolimus rescue therapy for renal allograft rejection--five-year experience.

Over the 5 year period from 7/14/1989 until 5/24/1994, we have attempted graft salvage with tacrolimus conversion in a total of 169 patients (median age 33 years, range 2-75 years) with ongoing rejection on baseline CsA immunosuppression after failure of high dose corticosteroids and/or antilymphocyte preparations to reverse rejection. The indications for conversion to tacrolimus were ongoing, biopsy confirmed rejection in all patients. The median interval to tacrolimus conversion was 2 months (range 2 days to 55 months; mean 4.3+/-2.6 months) after transplantation. All patients had failed high dose corticosteroid therapy and 144 (85%) of the 169 patients had received at least one course of an antilymphocyte preparation plus high dose corticosteroid therapy prior to conversion. Twenty-eight patients (17%) were dialysis-dependent at the time of conversion owing to the severity of rejection. With a mean follow-up of 30.0+/-2.4 months (median 36.5 months, range 12-62 months), 125 of 169 patients (74%) have been successfully rescued and still have functioning grafts with a mean serum creatinine (SCR) of 2.3+/-1.1 mg/dl. Of the 144 patients previously treated with antilymphocyte preparations, 117 (81%) were salvaged. Of the 28 patients on dialysis at the time of conversion to tacrolimus, 13 (46%) continue to have functioning grafts (mean SCR 2.15+/-0.37 mg/dl) at a mean follow-up of 37.3+/-16.7 months. In the 125 patients salvaged, prednisone doses have been lowered from 28.0+/-9.0 mg/d (median 32, range 4-60 mg/d) preconversion to 8.5+/-4.1 mg/d (median 12 mg/d, range 2.5-20 mg/d) postconversion. Twenty-eight patients (22.4%) are currently receiving no steroids. This 5 year experience demonstrates that tacrolimus has sustained efficacy as a rescue agent for ongoing renal allograft rejection. Based on these data, we recommend that tacrolimus be used as an alternative to the conventional drugs used for antirejection therapy in renal transplantation.

Adolescent↗
PubMed1997

Fatigue after eccentric quadriceps femoris work produces earlier gastrocnemius and delayed quadriceps femoris activation during crossover cutting among normal athletic women.

Athletic women are at greater risk of anterior cruciate ligament (ACL) injury than men. Twenty, healthy, athletic women were evaluated for the effect of preferred stance limb isokinetic quadriceps femoris and hamstring fatigue from eccentric work compared with controls on the activation onset of vastus medialis, rectus femoris, vastus lateralis, the medial hamstrings, biceps femoris, and gastrocnemius muscles. Following 3 weeks of crossover cut training, subjects were tested for fatigue effects (5 subjects/week, 3 conditions, 1 condition/day, order effect controlled) on muscle activation onsets prior to crossover cut landing heelstrike (mixed model, ANOVA, P < 0.05). Fatigue from eccentric quadriceps femoris work produced delayed vastus medialis (P = 0.03), rectus femoris (P = 0.007), and vastus lateralis (P = 0.03) activation onsets compared with control, but did not differ compared to hamstring fatigue. Neither hamstring nor quadriceps femoris fatigue produced differences (P > 0.05) in medial hamstring or biceps femoris activation onsets compared to control. Quadriceps femoris fatigue from eccentric work produced earlier gastrocnemius activation onsets (P = 0.048) than control, but did not differ for hamstring fatigue. The gastrocnemius appears to provide synergistic and compensatory dynamic knee stabilization in closed kinetic chain function during quadriceps femoris fatigue. This finding in a normal group at high risk of ACL injury while performing a maneuver with a high ACL injury risk supports gastrocnemius inclusion in knee rehabilitation and conditioning programs and suggests the need for comparative evaluations of knee injured/reconstructed subjects.

Analysis of Variance↗
PubMed1997

Cardiac operations in solid-organ transplant recipients.

BACKGROUND: The success of solid organ transplantation has resulted in an increasing pool of patients that subsequently require cardiac surgical procedures, yet the perioperative management of these patients is not well documented. We report a single institutional experience with the management techniques used and the outcomes of the cardiac surgical procedures performed in solid organ transplant recipients with functioning allografts. METHODS: Sixty-four patients underwent 66 cardiac procedures broken down as follows: coronary artery bypass grafting, 30; single or combined valve replacement-repair, 24; combined coronary artery bypass grafting and valve repair, 3; aortic repair, 4; pericardiectomy, 3; transmyocardial laser revascularization, 1; and native cardiectomy, 1. Patients consisted of 40 kidney, 16 liver, 5 heart, 2 lung, and 1 liver and kidney transplant recipients. The mean interval from the time of transplantation to the cardiac operation was 53 months (range, 1 day to 220 months). Forty-six male and 18 female patients in New York Heart Association functional class III or IV had a mean age of 53 years (range, 19 to 77 years); 50% (32/64) were diabetic, and 97% (62/64) were hypertensive. Immunosuppressive therapy, cardiopulmonary bypass, and medical management were similar in all patients. RESULTS: There were two (3%) perioperative deaths, one of which was caused by an arrhythmia-induced cardiac arrest, and there were seven (11%) late deaths from non-cardiac-related causes. Major complications included 12 infections (19%), ten mediastinal reexplorations for the control of bleeding (16%), and nine others (15%). Sixteen of the 64 (25%) transplant recipients had chronic renal failure (serum creatinine levels, > 3 mg/dL), including 13 of 40 (33%) kidney transplant patients. Acute renal failure developed postoperatively in 7 (54%) of these 13 patients; the grafts failed permanently in 3 (23%). Three patients (5%), 2 kidney transplant recipients and 1 lung transplant recipient, experienced transient acute rejection. Fifty of the 55 surviving patients are alive and well (New York Heart Association functional class I or II) without recurrent cardiac disease at a mean follow-up period of 22 months. CONCLUSIONS: Although the short-term morbidity was significant, the low mortality and low incidence of permanent graft dysfunction indicate that solid organ transplant recipients can safely and effectively undergo subsequent cardiac surgical procedures.

Adult↗
PubMed1997

Word-stem completion priming for perceptually and conceptually encoded words in patients with Alzheimer's disease.

This study examined whether the frequently reported word-stem completion priming deficit of Alzheimer's disease (AD) patients could be characterized as either a semantic encoding deficit or a conceptual priming deficit. AD patients and normal elderly control subjects studied words in two conditions: (1) reading visually presented words aloud, which maximizes perceptual encoding of seen words, and (2) generating words aloud from definitions, which maximizes conceptual encoding of words not seen but retrieved on the basis of semantic context. Recognition accuracy was greater for words that were generated at study, and word-stem completion priming was greater for words that were read at study. For the AD patients, recognition accuracy was impaired and word-stem completion priming was intact for words encoded in both conditions. The findings are discussed in terms of discrepant results about word-stem completion priming in AD.

Aged↗
PubMed1997

A molecular mechanics and dynamics study of the minor adduct between DNA and the carcinogen 2-(acetylamino)fluorene (dG-N2-AAF).

Experimental studies involving the carcinogenic aromatic amine 2-(acetylamino)fluorene (AAF) have afforded two acetylated DNA adducts, the major one bound to C8 of guanine and a minor adduct bound to N2 of guanine. The minor adduct may be important in carcinogenesis because it persists, while the major adduct is rapidly repaired. Primer extension studies of the minor adduct have indicated that it blocks DNA synthesis, with some bypass and misincorporation of adenine opposite the lesion [Shibutani, S., and Grollman, A.P. (1993) Chem. Res. Toxicol. 6, 819-824]. No experimental structural information is available for this adduct. Extensive minimized potential energy searches involving thousands of trials and molecular dynamics simulations were used to study the conformation of this adduct in three sequences: I, d(C1-G2-C3-[AAF]G4-C5-G6-C7).d(G8-C9-G10-C11-G12-C13-G14+ ++); II, the sequence of Shibutani and Grollman, d(C1-T2-A3-[AAF]G4-T5-C6-A7).d(T8-G9-A10-C11-T12-A13-G14); and III, which is the same as II but with a mismatched adenine in position 11, opposite the lesion. AAF was located in the minor groove in the low-energy structures of all sequences. In the lowest energy form of the C3-[AAF]G4-C5 sequence I, the fluorenyl rings point in the 3' direction along the modified strand and the acetyl in the 5' direction. These orientations are reversed in the second lowest energy structure of this sequence, and the energy of this structure is 1.4 kcal/mol higher. Watson Crick hydrogen bonding is intact in both structures. In the two lowest energy structures of the A3-[AAF]G4-T5 sequence II, the AAF is also located in the minor groove with Watson-Crick hydrogen bonding intact. However, in the lowest energy form, the fluorenyl rings point in the 5' direction and the acetyl in the 3' direction. The energy of the structure with opposite orientation is 5.1 kcal/mol higher. In sequence III with adenine mismatched to the modified guanine, the lowest energy form also had the fluorenyl rings oriented 5' in the minor groove with intact Watson-Crick base pairing. However, the mispaired adenine adopts a syn orientation with Hoogsteen pairing to the modified guanine. These results suggest that the orientation of the AAF in the minor groove may be DNA sequence dependent. Mobile aspects of favored structures derived from molecular dynamics simulations with explicit solvent and salt support the essentially undistorting nature of this lesion, which is in harmony with its persistence in mammalian systems.

2-Acetylaminofluorene↗
PubMed1997

Acquired von Willebrand disease in a patient with angiodysplasia resulting from immune-mediated clearance of von Willebrand factor.

A patient with a severe bleeding tendency due to acquired von Willebrand disease (VWD) is presented. Although no underlying disorder has emerged during 6 years of follow-up, an immune-mediated mechanism was responsible for acquired VWD in this patient as demonstrated by detection of von Willebrand factor (VWF)/anti-VWF complexes in the patient's plasma and their removal by protein A-sepharose beads and resumption of normal haemostasis with correction of VWF antigen, VWF activity and VWF multimeric pattern after treatment of the patient with high-dose gammaglobulin. Detection of anti-VWF antibodies in the patient's plasma had a significant impact on the choice of therapeutic intervention to control bleeding.

Angiodysplasia↗
PubMed1997

Effect of mechanical ventilation strategy on dissemination of intratracheally instilled Escherichia coli in dogs.

OBJECTIVE: To test the effect of different mechanical ventilation strategies on dissemination of intratracheally instilled Escherichia coli in dogs and to determine the extent and distribution of lung damage. DESIGN: Prospective, randomized study. SETTING: Experimental animal laboratory. SUBJECTS: Eighteen anesthetized and paralyzed dogs. INTERVENTIONS: We studied the effect of three ventilatory strategies based on two variables: transpulmonary pressure and positive end-expiratory pressure (PEEP). Group 1 animals (n = 6) were ventilated with a PEEP of 3 cm H2O and a tidal volume of 15 mL/kg, which generated an end-inspiratory transpulmonary pressure of < or = 15 cm H2O. In group 2(n = 6), tidal volume was adjusted to generate a transpulmonary pressure of 35 cm H2O and PEEP was set to 3 cm H2O. In group 3(n = 6), tidal volume was also adjusted to yield a transpulmonary pressure of 35 cm H2O but PEEP was set to 10 cm H2O. In each group, we instilled approximately 10(8) colony-forming units of E. coli into the trachea of the dogs and ventilated them with the chosen tidal volume and PEEP for 6 hrs afterward. MEASUREMENTS AND MAIN RESULTS: We measured the pressure-volume relationship (pressure-volume curve) of the respiratory system before and 6 hrs after bacterial instillation. We obtained blood cultures before and 0.5, 1,2,3,4,5, and 6 hrs after bacterial instillation. After 6 hrs, the lungs were removed for histologic (histologic score) and gravimetric (wet-to-dry weight ratio, WW/DW) analysis. During the experiment 0, 5, and 1 dogs developed positive blood cultures in groups 1, 2, and 3, respectively. The number of dogs that developed bacteremia in group 2 was significantly greater than in the other two groups (p < .05). In group 1, pressure-volume curves demonstrated a lower inflection point which was greater than the end-inspiratory transpulmonary pressure suggesting that low transpulmonary pressure/low PEEP strategy ventilated aerated regions without expanding atelectatic areas. In group 2, pressure-volume curves demonstrated both a lower inflection point and an upper deflection point which were spanned by the tidal volume, suggesting that high transpulmonary pressure/low PEEP strategy might have caused both overdistention and cyclic closure and reopening. In group 3, pressure-volume curves demonstrated only a upper deflection point which was less than the maximal alveolar tidal pressure. At the end of the experimental protocol, group 2 manifested the most lung injury as assessed by gravimetric and histologic indices of lung injury. WW/DW of group 2(13.1 +/- 1.0 (SD); p < .05) was greater than groups 1 and 3(7.5 +/- 1.2 and 8.6 +/- 1.0, respectively). Similarly, the overall weighted histologic injury score for group 2 (1.19 +/- 0.26; p < .02) was greater than for groups 1 and 3 (0.82 +/- 0.20 and 0.88 +/- 0.22, respectively). For groups 2 and 3, the overall weighted histologic injury scores of the dependent regions were greater than the nondependent regions (p < .004). CONCLUSIONS: We conclude that the ventilatory strategy most likely to overdistend the lungs while allowing repetitive opening and closure of alveoli (group 2) facilitated bacterial translocation from the alveoli to the bloodstream and increased lung injury, as determined by histologic and gravimetric analysis. PEEP ameliorated these effects, despite lung overdistention, but increased histologic and gravimetric indices of lung injury in dependent as compared with the nondependent regions.

Animals↗
PubMed1997

Congenital intractable diarrhea of infancy in Iraqi Jews.

We report on five patients who presented with intractable diarrhea starting during the first days of life. The patients belonged to four families of Iraqi Jewish origin. Autosomal recessive inheritance is suggested by parental consanguinity in three families and recurrence in another sib in one family. The patients were all born after uneventful pregnancy and labor, with birth weight in the normal range. There were no dysmorphic features. Three patients were breast fed. Diarrhea started between the first and eighth day of life. Diarrhea was of the secretory type. No pathogen was cultured from the stool. Jejunal biopsies performed on all patients ranged from normal to severe partial villous atrophy. The patients received different drug regimens with no beneficial effect and all are dependent on TPN. These findings and the common ethnic origin of the patients suggest that these patients have the same syndrome of congenital intractable diarrhea. No similar cases are known in other ethnic groups in Israel, suggesting a possibility of high gene frequency among the Jews of Iraqi origin.

Adrenal Glands↗
PubMed1997

The effect of quadriceps femoris, hamstring, and placebo eccentric fatigue on knee and ankle dynamics during crossover cutting.

This study attempted to determine the effect of eccentric quadriceps femoris, hamstring, and placebo fatigue on stance limb dynamics during the plant-and-cut phase of a crossover cut. Twenty female college students (task trained) were tested. Hamstring fatigue resulted in decreased peak impact knee flexion moments (p < or = .01), increased internal tibial rotation at peak knee flexion (p < or = .05), and decreased peak ankle dorisflexion (p < or = .05). Quadriceps fatigue resulted in increased peak ankle dorsiflexion moments (p < .01), decreased peak posterior braking forces (p < or .01), decreased peak knee extension moments (p < or = .01), delayed peak knee flexion (p < or = .01), delayed peak propulsive forces (p < .01), and delayed subtalar peak inversion moments (p < or = .05). Fatigue of either muscle group produced earlier peak ankle plantar flexion moments (p < = .05) and decreased peak propulsive knee flexion moments (p < or = .05). Variables requiring further study (p < or = .1) provide discussion data. Soleus, gastrocnemius, tibialis anterior, and deep posterior compartment calf muscles serve as dynamic impact force attenuators, compensating for fatigued proximal muscles.

Adult↗
PubMed1997

Significance of tubulitis in chronic allograft nephropathy: a clinicopathologic study.

Tubulitis is the principal lesion used for the diagnosis of acute rejection (AR) in the Banff schema for renal allograft pathology. It is considered to be reliable for assessing AR early after transplantation. However, its significance in biopsies with concurrent changes of chronic allograft nephropathy (CAN) is less well understood. To address this issue we studied seventeen allograft biopsies taken 9-108 (median 39) months post-transplant from 17 patients. All specimens were scored for AR and CAN using Banff criteria. Medical records were reviewed to determine the clinical course of the patients. Five biopsies showed t1 changes, whereas nine biopsies graded as t2, and three biopsies as t3. The CAN scores varied from cg0, ci1, ct1, cv1, to cg1, ci3, ct3, cv3. A response to increased immunosuppression, defined as a fall in the serum creatinine of at least 20% compared to the peak value, was observed in 7/17 (41%) cases. The responsive cases included 2/5, 4/9, and 1/3 cases respectively with t1, t2, and t3 tubulitis. The mean +/- SD CAN scores in these three groups were 8.4 +/- 1.8, 6.5 +/- 1.4, and 7.0 +/- 1.4, respectively. We conclude that the presence of coexisting tubulitis and CAN in renal allograft biopsies may indicate reversible acute rejection. In this study, clinical response was observed in 7/17 (41%) patients. Patients with therapeutically responsive rejection could not be differentiated from refractory cases by serum creatinine, tubulitis grade, per cent glomerulosclerosis and sum scores for AR or CAN. Hence a trial of anti-rejection therapy may be warranted pre-emptively in all such cases.

Adult↗