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B Wise

Publications and source records attributed to B Wise.

At least 19 recordsLinked to original sources
PubMed1999

The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin.

Gene knockout technology has provided a powerful tool for functional analyses of genes expressed preferentially in a particular tissue. Given marked similarities between human and mouse skin, such studies with epidermally expressed genes have often provided valuable insights into human genetic skin disorders. Efficient silencing of a specified gene in a temporally regulated and epidermal-specific fashion could extend functional analyses to broadly expressed genes and increase the categories of human skin disorders to which parallels could be drawn. We have generated transgenic mice expressing Cre and a fusion protein between Cre recombinase and the tamoxifen responsive hormone-binding domain of the estrogen receptor (CreER(tam)) under the control of the human keratin 14 (K14) promoter. This promoter is strongly active in dividing cells of epidermis and some other stratified squamous epithelia. With K14-Cre, transgenic embryos recombine genetically introduced loxP sequences efficiently and selectively in the genomes of keratinocytes that reside in embryonic day 14.5 skin, tongue, and esophagus. With K14-CreER(tam), postnatal transgenic mice show no Cre activity until tamoxifen is administered. If orally administered, tamoxifen activates keratinocyte-specific CreER(tam), allowing recombination of loxP sequences in epidermis, tongue, and esophagus. If topically administered, tamoxifen allows recombination in the area of skin where tamoxifen was applied. Finally, we show that epidermal cells harboring a Cre-dependent rearranged genome persist for many months after tamoxifen application, indicating that the epidermal stem cell population has been targeted efficiently. These tools now pave the way for testing the functional role of different somatic mutations that may exist in mosaic disorders of the skin, including squamous and basal cell carcinomas.

Animals↗
PubMed1999

Long-term complete remission and immune tolerance after intensive chemotherapy for lymphoproliferative disorders complicating liver transplant.

BACKGROUND: B cell lymphoproliferative disorders (LPD) and liver rejection are major lethal complications after hepatic transplantation. Reduction in immunosuppression is the treatment for the former, but is a risk factor for the latter. METHODS: Here, we report three consecutive children with monoclonal LPD complicating orthotopic liver transplantation. All of them were treated with brief (<4 months) but intensive chemotherapy. RESULTS: These three patients have remained in complete remission for LPD for 18 months to more than 3 years. Aggressive antimicrobial prophylaxis was successful in preventing life-threatening infections. The patient who received the highest cumulative doses of chemotherapy may have also developed relative immune tolerance to the allograft. CONCLUSIONS: High-dose-intensity chemotherapy may be effective in the treatment of monoclonal LPD, as well as in the induction of immune tolerance for the prevention of allograft rejection and LPD recurrence.

Acyclovir↗
PubMed1999

Rational management of posttransplant lymphoproliferative disorder in pediatric recipients.

BACKGROUND/PURPOSE: Posttransplant lymphoproliferative disorder (PTLD) is a potentially lethal complication in the pediatric transplant patient secondary to Epstein-Barr virus (EBV) infection and potent immunosuppression. PTLD may develop in up to 10% of pediatric transplant recipients with mortality rates up to 80%. The authors report their experience with the diagnosis and efficacy of aggressive sequential management of PTLD in five patients under age 5 years. METHODS: A review of 75 pediatric liver transplant recipients on FK-506-based immunosuppression identified five biopsy-proven cases of PTLD and one probable case (8%). The probable case was a teenager, 6 months posttransplant in Spain, with mediastinal masses. No treatment or diagnosis was sought, and the patient died. The other five cases were managed with sequential therapy on an "intent-to-treat" basis with initial withdrawal of immunosuppression. If the disease progressed, patients were treated with four courses of intravenous cyclophosphamide, vincristine, Adriamycin, and intrathecal methotrexate and ara-C. RESULTS: Five children were anti-EBV titer negative at the time of transplant. Three of five received EBV-positive donor organs and two children received EBV-negative livers. Monoclonal PTLD developed between 2 and 31 months posttransplant (mean, 15.7 months). With onset of PTLD (four B cell lymphoma, one B cell leukemia) all patients had tapering or withdrawal of immunosuppression and initiation of highdose acyclovir. Two of five patients had complete remission and resumed immunosuppression. Two patients progressed and required chemotherapy. One patient with initial response relapsed 4 months later with B cell leukemia and required chemotherapy. All five patients are alive 10 to 38 months postdiagnosis (mean, 29 months). Three patients had rejection requiring resumption of FK-506 therapy. Two patients are maintained on low-dose alternate-day prednisone and no FK-506. All patients have normal liver function. Central nervous system lymphoma developed in one child with significant neurological sequelae. CONCLUSIONS: PTLD can develop in pediatric liver transplant recipients. Early withdrawal of immunosuppression and aggressive chemotherapy enabled us to achieve 100% patient and graft survival.

Algorithms↗
PubMed1998

Evaluation of the aortic root by MRI: insights from patients with homozygous familial hypercholesterolemia.

BACKGROUND: In homozygous familial hypercholesterolemia (HFH), the aortic root is prone to develop atherosclerotic plaque at an early age. However, the aortic wall and plaque have not yet been assessed in this condition by MRI. We evaluated the aortic root by use of MRI in 17 HFH patients and 12 normal control subjects in a prospective, blinded, controlled study. METHODS AND RESULTS: Morphological assessment of the aortic root was done with spin-echo and gradient-echo MRI scanning. Comparisons were made with a number of measures of disease severity, including cholesterol-year score, calcium score on electron-beam CT (EBCT), and size of Achilles tendon xanthomas. Atherosclerotic plaque, visible on fat-suppressed images but never on water-suppressed images, was present in 9 HFH patients (53%). Supravalvular aortic stenosis was present in 7 patients with HFH (41%). Maximum supravalvular aortic wall thickness was significantly greater and OD and lumen cross-sectional area (CSA) were smaller in patients than in control subjects (P=0.006, 0.0005, and 0.06, respectively). Maximum wall thickness was associated with a greater calcium score on electron-beam CT (P=0.02). Although the cumulative exposure of the aortic root to cholesterol (the cholesterol-year score) was significantly correlated with the Achilles tendon CSA and vascular calcification, this score did not correlate with the wall thickness or aortic CSA. CONCLUSIONS: This study not only demonstrates the utility of MRI for detecting and characterizing aortic root atherosclerotic plaque and supravalvular aortic stenosis in HFH patients but also suggests that the LDL receptor plays a direct or indirect role in aortic mural development and vascular growth.

Achilles Tendon↗
PubMed1998

Orthotopic liver transplantation in patients with biliary atresia and situs inversus.

Situs inversus (SI) and the polysplenia syndrome (PS) occur relatively frequently in patients with biliary atresia, the largest subgroup of pediatric liver transplantation patients. We present two cases of orthotopic liver transplantation (OLT) in pediatric patients with SI. One had SI totalis, where a normal liver was placed in the left upper quadrant (LUQ) with the right lobe overlying the vertebral column. The second had PS and isolated SI of the liver, and a living-related left-lateral-segment graft was placed in the LUQ. Although multiple, often unpredictable vascular and intestinal anomalies occur frequently in association with SI, particularly in the setting of the PS, these cases, as well as several others recently reported, reveal that these anomalies can be managed successfully by a variety of technical modifications of the standard OLT technique. Likewise, concerns about the placement of a situs solitus liver in the midline or LUQ position of a SI abdomen have proved to be unfounded.

Biliary Atresia↗
PubMed1997

Kaposi's sarcoma presenting as a protracted multisystem illness in an adolescent liver transplant recipient.

Kaposi's sarcoma (KS) is a common malignancy in patients with acquired immunodeficiency syndrome (AIDS), classically appearing as red to purple plaques containing small papules and nodules. We report our experience with an adolescent orthotopic liver transplant recipient who presented with an unusual presentation of KS. The patient had a protracted multisystem illness that began with hemolytic anemia, fevers, and fatigue and progressed to pancreatitis, sinusitis, lymphadenopathy, and mouth ulcers. The diagnosis was made by a lymph node biopsy that was performed to evaluate for Epstein-Barr virus. The classical subcutaneous nodules characteristic of KS did not become evident until shortly before the patient died. We present this case to emphasize that KS in pediatric liver transplant patients can present as a multisystem disease that progresses to disseminated organ involvement before the characteristic subcutaneous manifestations are evident.

Adolescent↗
PubMed1997

Initial experience with FK506 (tacrolimus) in pediatric renal transplant recipients.

PURPOSE: The efficacy and safety of the new immunosuppressant agent, FK506 (tacrolimus), was assessed in pediatric renal transplant recipients over a mean 12-month follow-up period. METHODS: Twenty pediatric renal transplant recipients received oral FK506 therapy (0.3 mg/kg/d) in combination with azathioprine (1 to 2 mg/kg/d) and low-dose prednisone as primary therapy (n = 11) or were converted from cyclosporine-based therapy (n = 9) for complications including cyclosporine toxicity (n = 2), acute refractory rejection (n = 4), and chronic rejection (n = 3). Patients were then followed-up prospectively to evaluate effectiveness of therapy and complications. RESULTS: In the primary treatment group, 45% of patients had one or more rejection episodes. Two required OKT3 therapy (18%) for persistent rejection, with one (9%) graft loss at 3 months. All other episodes were treated effectively with FK506 dose adjustment and steroid pulses. Patient and graft survival was 100% and 91%, respectively, at 12 months mean follow-up. In the FK506 conversion group, two teenage girls with intractable acne and hirsutism were converted with complete resolution and no change in renal function. Four patients were converted for acute rejection: two who did not respond to steroid pulse and two who did not respond to both steroids and OKT3. All four grafts were salvaged (mean follow-up, 12 months; mean Creatinine [Cr], 1.1). Three patients were converted for biopsy-proven chronic rejection at 3, 10, and 12 years after transplant (mean Cr, 2.4) with two of three of patients stable with functioning grafts at 1 year after conversion. Complications of FK506 therapy included temporary insulin-dependent diabetes mellitus (10%), neurological complications (25%), renal toxicity (15%), and hypertension (85%). There were no cases of gastrointestinal toxicity, hepatic dysfunction, lymphoproliferative disorders, or life threatening viral infection. All symptoms of toxicity responded to dose adjustment. No patient required conversion from FK506 to other agents. CONCLUSION: This early experience indicates that FK506 in combination with low-dose steroids and azathioprine appears to provide safe and effective immunosuppression in the pediatric age group as a primary agent and may salvage grafts in patients with refractory steroid and OKT3 resistant rejection. Graft and patient survival is comparable to that seen with conventional cyclosporine-based immunosuppression.

Adolescent↗
PubMed1997

Steroid withdrawal in tacrolimus (FK506)-treated pediatric liver transplant recipients.

PURPOSE: The use of steroids in pediatric transplant recipients is associated with significant adverse side effects. The authors examined the feasibility of steroid withdrawal in patients who underwent immunosuppression with tacrolimus (FK506; FK). METHODS: All pediatric liver transplant recipients on FK greater than 6 months were evaluated for steroid withdrawal. FK was administered 0.3 mg/kg/d in two divided doses. Steroids were tapered as tolerated with goals of 0.2 to 0.3 mg/kg/d at 6 weeks, 0.2 to 0.3 mg/kg every other day at 3 months, and complete withdrawal after 6 months. Steroid bolus and taper were instituted for enzyme elevation or rejection during biopsy. RESULTS: Twenty-nine patients underwent evaluation for steroid withdrawal. Five patients could not be placed on FK506 monotherapy (chronic, recurrent rejection or LPD). The remaining 24 had steroids withdrawn. Tweleve (50%) had no sequelae and continue on FK monotherapy (mean, 22 months off steroids). The other 12 required intermittent steroid therapy for presumed or biopsy-proven rejection (n = 7), graft dysfunction (FK toxicity, n = 2), lymphoproliferative disease necessitating reduction in FK (n = 2) or exacerbations of asthma (n = 1). Five of these 12 patients are now on FK monotherapy (mean, 6 months) for a total of 17 of the 24 (71%) currently off steroids. CONCLUSION: FK monotherapy can be successfully used to withdraw steroid therapy in the majority of pediatric liver transplant recipients with few sequelae.

Graft Rejection↗
PubMed1997

Evaluation of neurotoxicity in pediatric renal transplant recipients treated with tacrolimus (FK506).

The presence of severe and mild neurotoxicity in our pediatric renal transplant recipients treated with tacrolimus was determined by chart review (severe neurotoxicity) and patient survey (mild neurotoxicity). 14 patients were studied (mean age 15 yr, 5 month, +/- 4.4 yr). 1 patient experienced seizures, felt to be related to malignant hypertension. No other episode of severe neurotoxicity was documented. Most patients (12/14) reported at least one mild neurologic symptom, and half stated their symptoms were present at least 'most of the time'. The most frequent complaints were myalgias (7/14, 50%) and tremors (7/14, 50%) followed by fatigue (5/14, 38%). Severe neurotoxicity may be relatively infrequent in pediatric renal transplant patients treated with tacrolimus. Milder neurologic complaints may be commonly seen in this population, but in general are not severe enough to cause discontinuation of tacrolimus.

Adolescent↗
PubMed1996

Liver transplantation in infants younger than 1 year of age.

OBJECTIVE: The authors report on experience with liver transplantation for infants younger than 1 year of age. SUMMARY BACKGROUND DATA: Over the last 15 years, orthotopic liver transplant has become the only lifesaving procedure available for infants with end-stage liver disease. Many transplant centers initially required infants to reach a specific weight or age to minimize morbidity and mortality. Size-appropriate infant donors also were uncommon. As a result, many children, in the first few years of life, died of their disease. The availability of reduced-size cadaveric and living-related liver transplants has offered the ability to transplant the young infant with liver failure. METHODS: The authors instituted a program to aggressively transplant infants with liver failure in the first year of life using both cadaveric and living-related liver donors. RESULTS: Between June 1991 and January 1995, 13 infants were transplanted for rapidly progressive liver failure. Infant age ranged from 4 to 11 months (mean, 7.5 months). The cause of liver failure included biliary atresia (11), alpha 1-antitrypsin deficiency (1), and liver failure secondary to echovirus 7 (1). The United Network for Organ Sharing status at the time of transplant ranged from status 4, intensive care unit bound (4 patients); status 3, hospitalized (4 patients); or status 2, failing at home (5 patients). Six patients (46%) received cadaveric whole organ (2) or segmental transplants (4). Seven patients (54%) received left lateral segment living-related transplants from parental donors. After operation, patients received cyclosporine or FK506-based immunosuppression. Three patients (23%) required four retransplants (two cadaveric for primary nonfunction; one living-related for graft thrombosis in the face of fungal infection and bile leak). Postoperative complications included primary nonfunction (15%), rejection (85%), graft vascular thrombosis (15%, two of three revascularized successfully), bacterial and fungal infections (77%), and viral infections (46%). Epstein-Barr virus-associated lymphoproliferative developed in two patients (15%). Intestinal perforation requiring reoperation developed in two patients (15%). Bile leaks requiring reoperation or transhepatic stinting or both developed in three patients (23%). Two patients died in the perioperative period (< 1 month) from a combination of primary nonfunction or graft thrombosis and sepsis. Overall survival was 85%, ranging from 11.0 months to 4.5 years. CONCLUSIONS: Orthotopic liver transplantation in infants younger than 1 year of age poses significant challenges from technical and infectious complications. Despite these barriers, overall patient survival is comparable to that of older children and adults.

Biliary Atresia↗
PubMed1995

Proximal renal tubular acidosis secondary to FK506 in pediatric liver transplant patients.

We hereby report our experience with an index case of a pediatric liver transplant patient in whom FK506 administration was associated with the development of proximal renal tubular acidosis (RTA), as well the prevalence of acidosis and renal dysfunction in all pediatric liver transplant patients in our institution followed long term during a 6-year period. Data were grouped according to immunosuppressant regime: cyclosporine (CsA) only, FK506 only, or CsA with conversion to FK506. A 23-month-old female treated with FK506 after orthotopic liver transplantation (OLT) performed 15 months earlier presented with a 1-wk history of fever, watery diarrhea and metabolic acidosis. Although the acidosis did not improve following correction of her hydration status, administration of oral bicarbonate was effective. Discontinuation of this therapy resulted in acidosis. Since other indirect measurements of renal tubular function were normal, the patient was judged to have an isolated proximal RTA. In our group of pediatric liver transplant patients converted from CsA to FK506, FK506 administration was associated with a decline in serum bicarbonate (19 +/- 1 vs. 16 +/- 1 mEq/l, p < 0.02); neither blood urea nitrogen nor serum creatinine differed between the two groups. The number of rejection episodes/patient/month was comparable, allowing clinically relevant comparison of relative drug nephrotoxicities. We conclude that proximal RTA may be a relatively common treatable complication of FK506 administration in children.

Acidosis, Renal Tubular↗
PubMed1995

Codependency in nurses. How it affects your organization.

Codependence in a staff nurse affects both direct patient care and relationships with coworkers, physicians, and supervisors. Codependent behaviors negatively impact the nurse's sphere of influence. The nurse manager's codependency has the same impact, but the sphere of influence is larger and thus, the potential for harm is greater. Codependent behaviors enacted at different levels of an organization can disrupt an entire institution or profession. The author describes how nurses' practices are affected by codependent behaviors and identifies ways in which those behaviors can be modified by good management.

Adult↗
PubMed1994

Recombinant human growth hormone.

Recombinant human growth hormone was initially used as replacement therapy in children with short stature. As rhGH has become more readily available, it has been tested in a variety of other individuals who have delayed growth. Children with ESRD experience significant problems with delayed growth, thus replacement therapy with rhGH has been used in this population. resulting in improved growth velocity. The clinical significance of improved height may have a positive impact on the psychological well being of these children.

Child↗
PubMed1992

Atypical thrombotic and septic complications of totally implantable venous access devices in patients with cystic fibrosis.

The use of vascular access systems in patients with cystic fibrosis (CF) is well accepted, with lower overall complications and maintenance costs than percutaneous silastic catheters. We report our 6 year experience with 22 infusaports in 15 CF patients. Our patients had indwelling catheters for an average of 539 days per catheter (range, 14-2,224 days). These infusaports were used for home antibiotic therapy, blood sampling, and total parenteral nutrition. The overall complication rate was relatively low, 1 in every 1,483 catheter days. Infectious complications were extremely infrequent at a rate of 1 in 5,929 catheter days. The rate of mechanical complications was 1 in 1,976 catheter days. However, superior vena caval syndrome or deep venous thrombosis was associated with 3 of 22 catheters (13.6%). Due to this high incidence of major thrombotic events with the attendant risk of pulmonary embolism, all patients with CF using infusaports and without evidence of liver disease or bleeding problems receive aspirin prophylaxis.

Adolescent↗
PubMed1991

Urge incontinence and stress incontinence.

Urinary incontinence remains a common problem that adversely affects the quality of life of millions of women. In detrusor instability, treatment measures often lack efficacy or are accompanied by unacceptable side effects. In this review, standard treatments are discussed, together with recent pharmacologic advances and the introduction of newer techniques including maximal electrical stimulation. The nonsurgical treatment options currently available for genuine stress incontinence are considered in the light of recent advances.

Female↗
PubMed1989

Conformational and steric aspects of phenylethanolamine and phenylethylamine analogues as substrates or inhibitors of phenylethanolamine N-methyltransferase.

The conformational and steric aspects of binding to phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) for phenylethanolamine substrates and phenylethylamine inhibitors were probed with three conformationally defined analogues (11, 12, and 13) of phenylethylamine (1) and phenylethanolamine (6) containing the benzobicyclo[3.2.1]octane skeleton. The 2-aminotetralin (2AT) moiety in conformationally defined analogues 11, 12, and 13 exists in a half-chair conformation with an equatorial amino group. Although conformationally restricted phenylethylamine analogue 2AT (3, Ki = 6.8 microM) and conformationally restricted phenylethanolamine analogues (cis)- and (trans)-2-amino-1-tetralol (9, Km = 22 microM; Vmax = 0.15; 100 X Vmax/Km = 0.68; 10, Ki = 9.4 microM) are good ligands for PNMT, none of the analogues 11, 12, and 13 showed activity as a substrate of PNMT. The fact that 11 (Ki = 206 microM) is more potent than analogues 4 (Ki = 1296 microM) and 5 (Ki = 479 microM), with a half-boat 2AT moiety, suggests that PNMT preferentially binds the half-chair conformation of 2AT at the active site. This is consistent with previous findings that a fully extended conformation for the aminoethyl side chain of phenylethylamine inhibitors is optimal for PNMT binding. The reduced activity of 11, 12 (Ki = 1246 microM), and 13 (Ki = 3000 microM), compared with 2AT and (cis)- and (trans)-2-amino-1-tetralol (9 and 10) is consistent with a negative steric interference from the extra ethano bridge in 11, 12, and 13. The results from 11, 12, and 13, combined with previous findings, suggest that PNMT interacts better with relatively planar ligands.

2-Hydroxyphenethylamine↗