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Biomedical subjects

A M Shapiro

Publications and source records attributed to A M Shapiro.

At least 55 records · Page 3Linked to original sources
PubMed1996

Rapid resolution of chylous ascites after liver transplantation using somatostatin analog and total parenteral nutrition.

Chylous ascites is the accumulation of chylomicronrich lymphatic fluid within the peritoneal cavity. It is a rare complication of retroperitoneal surgery, and may occur spontaneously in 0.5% of patients with cirrhosis. Its management is controversial, and despite a variety of treatment options with limited efficacy, the course is usually indolent. In this article, we report a case of rapid resolution of chylous ascites after liver transplantation following 10 days of treatment using somatostatin analog (Octreotide, 100 micrograms sc. t.i.d.) and total parenteral nutrition (TPN). A 55-year-old man underwent liver transplantation for hepatitis C cirrhosis, and developed an infected chylous fistula on the 10th day. Treatment by fasting, TPN, and somatostatin analog resulted in a rapid falloff in fistula output, with complete resolution of ascites within 2 days. This is the first report, to our knowledge, of somatostatin analog and TPN used in combination for rapid and successful closure of a chylous fistula.

Ascites↗
PubMed1996

Variables in organ donors that affect the recovery of human islets of Langerhans.

In an attempt to reduce the variability in the yields of human islets isolations and to identify donor factors that were potentially deleterious, we retrospectively reviewed 153 human islets isolations in our center over a 3-year period. Isolations were performed using controlled collagenase perfusion via the duct, automated dissociation, and Ficoll purification. Factors leading to successful isolations (recovery of >100,000 islet equivalents at a purity >50%) were analyzed retrospectively using univariate and multivariate analysis. Critical factors in the multiorgan cadaveric donors that were identified using univariate analysis included donor age (P<0.01), body mass index (BMI)(P<0.01), cause of death (P<0.01), and prolonged hypotensive episodes (systolic blood pressure <90 mmHg or mean arterial pressure <60 mmHg for > 15 min) requiring high vasopressors (>15 microgram/kg/min dopamine or >5 microgram/kg/min Levophed) (P>0.01). Independent analysis of 19 donor variables using multivariate logistic stepwise regression showed six factors were statistically significant. Odds ratio (OR) showed that donor age (OR 1.1, P<0.01), local procurement team (OR 10.9, P<0.01), and high BMI (OR 1.4, P<0.01) had a positive correlation with islet recovery. In contrast, hyperglycemia (all blood glucose >10 mmol/L) (OR 0.63, P<0.01), frequency and duration of cardiac arrest (OR 0.7, P<0.01), and increased duration of cold storage before islet isolation (OR 0.83, P<0.01) had negative correlation. Using these combinations of factors, the prediction of success was 85% accurate. By donor age, success was 13% for 2.5- to 18-year-old donors (n=23), 37% for 19- to 28-year-old donors (n=30), 65% for 29- to 50-year-old donors (n=70), and 83% for 51- to 65-year-old (n=29) donors. However, when vitro function was assessed by perifusion, the insulin secretory capabilities of islets isolated from the >50-year-old donor group was significantly reduced as compared with the 2.5- to 18-year-old group (P<0.02). Multiple regression analysis using postdigestion and postpurification islet recovery as outcome variables identified BMI, procurement team, pancreas weight, and collagenase digestion time factors tht can affect the recovery of human islets. Locally procured pancreases and donors with elevated minimum blood glucose levels were identified as factors that affect the insulin secretory capabilities of the isolated islets. This review of parameters suggests an improved approach to the prediction of successful islet isolation from human pancreases. Selection of suitable pancreases for processing may improve consistency in human islet isolation and thereby decrease costs.

Adult↗
PubMed1996

Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression by measurement of inosine monophosphate dehydrogenase activity in a canine model.

The combination of pharmacokinetic and pharmacodynamic (measurement of the biological effect) monitoring of immunosuppressive drugs provides a method for the optimization of drug dosing. We chose to investigate this using mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by the inhibition of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. Using an assay developed for measurement of IMPDH activity in whole blood, the concentration required for 50% inhibition of IMPDH activity was approximately 200 mg/L (58 +/- 8.3% for whole blood [n = 6] and 55 +/- 10.0% for isolated lymphocytes). To ascertain the relationship between MPA concentration and IMPDH inhibition in vivo, dogs were administered a single dose of mycophenolate mofetil, the pro-drug of MPA, at 20 or 40 mg/kg orally. Pharmacokinetic analysis revealed that the Cmax of the 40-mg/kg group was statistically greater than that of the 20-mg/kg group (P < 0.05). There were no statistical differences in the other parameters investigated (area under the curve, beta half-life, mean residence time, volume of distribution at steady state, and clearance) between the two treatment groups. The half-life was calculated at approximately 8 hr for both dose groups. There was also substantial variability among the dogs in the absorption and clearance of MPA. An inverse relationship was found between the MPA concentration and IMPDH. Maximal inhibition of IMPDH activity of 30-40% occurs approximately 2-4 hr after dosing, followed by a gradual restoration in enzyme activity. After 24 hr, there is an increase in IMPDH activity that exceeds the pre-dosing levels in some cases by 3-fold. Evaluation of the pharmacokinetic and the pharmacodynamic responses to MPA in the canine model suggests that the drug should be administered ever 8 hr to optimize its immunosuppressive efficacy. This combined approach can be used for optimization of doses of this and other immunosuppressive drugs.

Animals↗
PubMed1996

Is early response to portoenterostomy predictive of long-term outcome for patients with biliary atresia?

PURPOSE: Therapy for biliary atresia (BA) typically involves portoenterostomy (PE). In light of the development of liver transplantation (LT) as an option for therapy in infancy, the authors reviewed their experience to determine factors that might predict the requirement for LT. METHODS: Cases of BA diagnosed between September 1980 and September 1994 were reviewed. Responses to PE were rated as poor (PR; death or LT by 3 years), temporary (TR; LT > 3 years), or good (GR; anicteric). RESULTS: Twenty-nine patients were identified; 24% were native indian or Inuit. Twenty-three had PE; 11 responded. Seven (32%) became anicteric and continue to do well (GR). Four (18%) required LT after age 3 (TR). Twelve patients had PR; 3 underwent LT (average age, 1.3 years), 4 are listed for LTX, and 5 died by age 2.8 years. (Six patients did not have PE; 2 died in infancy and 4 had LT.) All transplant recipients are well. Factors associated with PR were older age at time of surgery (67 +/- 7 days v 51 +/- 4 days in the GR group), nadir of AST (273 +/- 84 U/Lv 70 +/- 26 U/L in the GR group), and number of post-PE complications (3.6 v per patient v 1 per patient in the GR group). TR was differentiated from GR by bilirubin nadir (46 +/- 10 mumol/Lv 14 +/- 3 mumol/L, respectively) and rate of bilirubin decline (2.6 +/- 1.5 mumol/L/d v 10.8 +/- 3.0 mumol/L/d, respectively). (P < .05 for all comparisons.) CONCLUSION: Outcomes are comparable to those of North American series, but the incidence is lower overall and is higher among natives. Factors that correlate with outcome include age at time of surgery, post-PE complications, postoperative decline and rate of decline of bilirubin and AST. The latter had not been reported previously and may prove useful in planning therapy for partial responders after PE.

Analysis of Variance↗
PubMed1996

Pediatric fiberoptic laser rigid bronchoscopy.

Use of the fiberoptic laser for treatment of tracheobronchial lesions in the adult is well established. However, there is a paucity of experience with the fiberoptic laser in the pediatric airway. Tracheal obstruction caused by granulation tissue or stenosis, as is often seen in children, may be effectively treated with this approach. This article documents the successful use as well as the technologic advantage of the flexible fiberoptic laser systems, primarily the potassium titanyl phosphate (KTP) laser, combined with standard pediatric rigid bronchoscopic equipment in 73 procedures involving 52 children (43 children younger than five years. with an average age of 21 months). Visualization was excellent, assisted or spontaneous ventilation was well maintained, and complications were few.

Adolescent↗
PubMed1996

Laryngotracheal reconstruction using microplates in a porcine model with subglottic stenosis.

Current techniques of laryngotracheal reconstruction require a choice between prolonged stenting (conventional technique) or short-term stenting with maintenance of sedation and paralysis until the airway has stabilized (single-stage laryngotracheal reconstruction). An alternative method is proposed using microplates to provide immediate airway stabilization without stenting. This study was designed to evaluate the long-term effects of microplate repair of stenosis of the subglottis and trachea on the growing larynx. Subglottic stenosis was produced in piglets using a transoral endoscopic technique. Eight animals underwent repair of the stenosis using an anterior cricoid split with microplate distraction and stabilization of the cricoid cartilage and first tracheal ring. The distraction was maintained and airway growth continued for the duration of this study. However, with growth of the larynx the plates migrated away from their original position. In 50% of the animals followed up for 90 days the plates migrated into the airway lumen. This study suggests that rigid distraction of the stenotic airway with microplates is a viable alternative to more traditional methods of repair. However, plate removal at some interval after surgery is required in the growing larynx in order to prevent migration of the plate into the airway.

Animals↗
PubMed1996

Tracheotomy in children with juvenile-onset recurrent respiratory papillomatosis: the Children's Hospital of Pittsburgh experience.

Despite the risk of airway obstruction, tracheotomy has been viewed with trepidation in the management of recurrent respiratory papillomatosis (RRP). The literature suggests that the injury associated with the tracheotomy site may initiate the progression of disease to the distal airway. Alternatively, patients who require tracheotomy for RRP may be predisposed to distal spread because of more aggressive disease. In an effort to clarify this issue, we reviewed the Children's Hospital of Pittsburgh experience with 35 patients with RRP between 1984 and 1994; 13 patients received tracheotomies. Tracheotomy patients presented at a younger age with more widespread disease, often involving the distal airway prior to tracheotomy. Although distal spread occurred in 50% of patients, it was generally limited to the tracheotomy site. Overall, outcome in the tracheotomy group was satisfactory. Complications related to the tracheotomy were rare. We conclude that tracheotomy is an appropriate option for significantly airway compromise in patients with RRP.

Child↗
PubMed1995

Head and neck manifestations of Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome is a congenital disorder manifested by organomegaly, omphalocele, hypoglycemia, and macroglossia. We have found a significant number of these children to be at risk for upper airway obstruction during infancy or childhood. In this review of 13 children, 2 required tracheotomy during infancy for cor pulmonale caused by macroglossia. Seven of nine children older than 1 year required tonsillectomy and adenoidectomy to relieve upper airway obstruction. Although macroglossia can be a cause of airway obstruction in infants with Beckwith-Wiedemann syndrome, we have found that airway obstruction during childhood is related to tonsillar and adenoidal hypertrophy and not to macroglossia. Anterior tongue reduction is reserved for the correction of malocclusion, articulation errors, or cosmesis, whereas tonsillectomy and adenoidectomy may be curative of obstructive symptoms.

Adenoidectomy↗
PubMed1995

Otitis media reassessed. Up-to-date answers to some basic questions.

For children with acute otitis media, appropriate antibiotic therapy provides a modest improvement over the high rate of spontaneous recovery and, more importantly, has greatly reduced the incidence of serious complications. Prophylaxis with antibiotics is beneficial for patients with recurrent episodes. Otitis media with effusion also has a high rate of spontaneous resolution, and many physicians have adopted a "wait and see" approach to this problem. Modification of risk factors may be helpful. Antibiotic therapy is recommended for infants who have otitis media with effusion (since they cannot relate symptoms); patients with a coexisting purulent infection of the upper respiratory tract; patients who have significant hearing loss, vertigo, or structural changes in the tympanic membrane; and patients who have had effusion for more than 2 to 3 months. Referral to an otolaryngologist should be considered if medical therapy for recurrent acute otitis media or chronic otitis media with effusion has failed or been poorly tolerated, or if complications are present.

Acute Disease↗
PubMed1994

Forgetting of verbatim information in discourse.

In three experiments, the causes of forgetting of verbatim information in discourse were investigated. In Experiment 1, we tested the view that the surface form of a sentence decays when linguistic elements are integrated into larger discourse structures. Contrary to such a view, the results showed that when text could be integrated, both content and verbatim memory improved. In Experiment 2, we examined the possibility that task instructions could influence the level of memory for exact wording and content. The results showed that although task did influence the amount of verbatim memory, it did not affect memory for content. Experiment 3 was an investigation of the degree to which subjects would spontaneously encode surface information on the basis of the social interactiveness of the sentences. Past research has shown that verbatim memory for insults, jokes, and other personal utterances is quite good. In this experiment, identical sentences were tested in texts that had high versus low interactiveness. Verbatim memory was much higher for the same sentences in the highly interactive context. A pragmatic account of verbatim memory is given to explain how content and instructions influence the encoding of surface form.

Communication↗
PubMed1993

Stimulation of kappa light-chain gene rearrangement by the immunoglobulin mu heavy chain in a pre-B-cell line.

B-lymphocyte development exhibits a characteristic order of immunoglobulin gene rearrangements. Previous work has led to the hypothesis that expression of the immunoglobulin mu heavy chain induces rearrangement activity at the kappa light-chain locus. To examine this issue in more detail, we isolated five matched pairs of mu- and endogenously rearranged mu+ cell lines from the Abelson murine leukemia virus-transformed pro-B-cell line K.40. In four of the five mu+ cell lines, substantial expression of mu protein on the cell surface was observed, and this correlated with an enhanced frequency of kappa immunoglobulin gene rearrangement compared with that in the matched mu- cell lines. This increased kappa gene rearrangement frequency was not due to a general increase in the amount of V(D)J recombinase activity in the mu+ cells. Consistently, introduction of a functionally rearranged mu gene into one of the mu- pre-B-cell lines resulted in a fivefold increase in kappa gene rearrangements. In three of the four clonally matched pairs with increased kappa gene rearrangements, the increase in rearrangement frequency was not accompanied by a significant increase in germ line transcripts from the C kappa locus. However, in the fourth pair, K.40D, we observed an increase in germ line transcription of the kappa locus after expression of mu protein encoded by either an endogenously rearranged or a transfected functional heavy-chain allele. In these cells, the amount of the germ line C kappa transcript correlated with the measured frequency of rearranged kappa genes. These results support a regulated model of B-cell development in which mu protein expression in some way targets the V(D)J recombinase to the kappa gene locus.

Alleles↗