Biomedical subjects

N Mittal

Publications and source records attributed to N Mittal.

At least 19 recordsLinked to original sources

PubMed2006

Zoom endoscopic monitoring of small bowel allograft rejection.

BACKGROUND: The small bowel has been successfully transplanted in patients with irreversible intestinal failure. This report aims to describe endoscopic monitoring of small bowel rejection. METHODS: A magnification endoscope (zoom endoscope) was used in this study. In the first part of the study (October 1998 to March 2000, 271 endoscopy sessions), the specific endoscopic findings that correlated with rejection were determined. An analysis then was performed on data from the second period (March 2001 to November 2002, 499 sessions) to evaluate the zoom endoscope's accuracy in monitoring rejection. RESULTS: Specific endoscopic findings of rejection found in the first period included background erythema, villous congestion, blunted villous tip, and shortened villous height. When the rejection was successfully treated, endoscopic appearance returned to normal. On the basis of these findings, five endoscopic criteria (villous shortening, villous blunting, background erythema, villous congestion, and mucosal friability) were used to score endoscopic sessions in the second period. Endoscopic diagnosis of rejection was compared with histology. Adult patients showed a sensitivity of 45%, a specificity of 98%, a positive predictive value of 82%, and a negative predictive value of 88%. In pediatric patients, these values were, respectively, 61%, 84%, 57%, and 86%. On 59 distinct occasions (30 in period 1 and 29 in period 2) in which the results were endoscopy negative yet biopsy positive (mild) for rejection, we elected not to treat these rejections on the basis of clinical evaluation, and 58 (98%) resolved without further therapy. CONCLUSIONS: With the use of magnification, endoscopy is a useful tool for monitoring acute rejection in the small bowel allograft.

Adolescent↗

PubMed2006

Intestinal transplantation for short bowel syndrome secondary to gastroschisis.

BACKGROUND/PURPOSE: Gastroschisis is the most frequent cause of pediatric intestinal transplantation. This study reviews our experience of intestinal transplantation secondary to gastroschisis to elucidate those factors affecting the outcome of children with short bowel syndrome. METHODS: A retrospective review was performed for children who underwent intestinal transplantation for gastroschisis at the University of Miami between June 2003 and August 1994. RESULTS: Thirty-two transplants were performed in 28 children with gastroschisis during the study period. Associated intestinal anomalies were present in 22 infants (atresia [n = 14], volvulus [n = 3], and/or ischemia [n = 16]). Spontaneous prenatal closure of gastroschisis, a rare anomaly associated with bowel atresia and ischemia because of a very small abdominal defect, was seen in 9 patients. Most of the patients had a complicated course and required multiple abdominal surgeries before transplant. Fifteen (53.6%) patients are currently alive at a median follow-up of 23.5 months. Short-term survival rate has significantly improved in recent years. CONCLUSIONS: Patients with complex gastroschisis and intestinal anomalies have a significant risk for progression to short bowel syndrome. Intestinal transplantation can be a lifesaving option and provides a satisfactory outcome for children with short bowel syndrome secondary to gastroschisis.

Child↗

PubMed2005

Analysis of blood flow in the entire coronary arterial tree.

A hemodynamic analysis of coronary blood flow must be based on the measured branching pattern and vascular geometry of the coronary vasculature. We recently developed a computer reconstruction of the entire coronary arterial tree of the porcine heart based on previously measured morphometric data. In the present study, we carried out an analysis of blood flow distribution through a network of millions of vessels that includes the entire coronary arterial tree down to the first capillary branch. The pressure and flow are computed throughout the coronary arterial tree based on conservation of mass and momentum and appropriate pressure boundary conditions. We found a power law relationship between the diameter and flow of each vessel branch. The exponent is approximately 2.2, which deviates from Murray's prediction of 3.0. Furthermore, we found the total arterial equivalent resistance to be 0.93, 0.77, and 1.28 mmHg.ml(-1).s(-1).g(-1) for the right coronary artery, left anterior descending coronary artery, and left circumflex artery, respectively. The significance of the present study is that it yields a predictive model that incorporates some of the factors controlling coronary blood flow. The model of normal hearts will serve as a physiological reference state. Pathological states can then be studied in relation to changes in model parameters that alter coronary perfusion.

Animals↗

PubMed2005

A computer reconstruction of the entire coronary arterial tree based on detailed morphometric data.

A rigorous analysis of blood flow must be based on the branching pattern and vascular geometry of the full vascular circuit of interest. It is experimentally difficult to reconstruct the entire vascular circuit of any organ because of the enormity of the vessels. The objective of the present study was to develop a novel method for the reconstruction of the full coronary vascular tree from partial measurements. Our method includes the use of data on those parts of the tree that are measured to extrapolate the data on those parts that are missing. Specifically, a two-step approach was employed in the reconstruction of the entire coronary arterial tree down to the capillary level. Vessels > 40 microm were reconstructed from cast data while vessels < 40 microm were reconstructed from histological data. The cast data were reconstructed one-bifurcation at a time while histological data were reconstructed one-sub-tree at a time by "cutting" and "pasting" of data from measured to missing vessels. The reconstruction algorithm yielded a full arterial tree down to the first capillary bifurcation with 1.9, 2.04 and 1.15 million vessel segments for the right coronary artery (RCA), left anterior descending (LAD) and left circumflex (LCx) trees, respectively. The node-to-node connectivity along with the diameter and length of every vessel segment was determined. Once the full tree was reconstructed, we automated the assignment of order numbers, according to the diameter-defined Strahler system, to every vessel segment in the tree. Consequently, the diameters, lengths, number of vessels, segments-per-element ratio, connectivity and longitudinal matrices were determined for every order number. The present model establishes a morphological foundation for future analysis of blood flow in the coronary circulation.

Algorithms↗

PubMed2005

Transplantation for the treatment of intra-abdominal fibromatosis.

MATERIALS AND METHODS: During the last 9 years we treated 14 patients with a diagnosis of intra-abdominal fibromatosis. The 11 patients who received an intestinal allograft included isolated intestine (n = 6), liver-intestine (n = 1), intestine-kidney (n = 1), multivisceral (n = 1), multivisceral-kidney (n = 1), multivisceral-no liver (n = 1). Three patients received an intestinal autograft after partial abdominal evisceration and ex vivo tumor resection. Three patients additionally underwent an abdominal wall allograft. RESULTS: At follow-up until August 2004, all autotransplant patients are alive. Four intestinal transplant patients died within the first postoperative month. There were three graft losses. A patient who lost his graft early postoperatively was retransplanted but died of sepsis shortly there after. Two more patients lost their graft due to severe rejection and were retransplanted successfully. Two patients developed desmoid tumor recurrence in their abdominal or thoracic wall. Ten patients are alive 1 to 9 years posttransplantation. Nine have fully functioning grafts and one patient requires TPN supplementation at night due to dysmotility of her autograft. CONCLUSION: Intestinal allo-, or autotransplantation combined with transplantation of the abdominal wall can be lifesaving for patients suffering from extensive intra-abdominal fibromatosis.

Fibromatosis, Abdominal↗

PubMed2004

Trends in serum citrulline and acute rejection among recipients of small bowel transplants.

A test for detecting acute cellular rejection (ACR) of small intestinal transplants (ITx) would be a major advance. Small preliminary studies suggest that serum citrulline levels correlate with ACR. The results for a group of 26 isolated intestinal and multivisceral transplant recipients are summarized here. Serum citrulline concentrations were determined by ion exchange chromatography and compared to biopsy-based grade of ACR. Other factors considered included patient and donor age and sex, ischemia time, and serum creatinine. Straight-line fits were employed to describe how each patient's citrulline levels changed over time. Estimated times to achieve normal citrulline (>or=30 micromol/L) ranged from 1 to 730 days posttransplant for 21 patients demonstrating increasing citrulline levels over time. Using stepwise linear regression, patients' ranks for time required to achieve normal citrulline levels were the only independent predictors of both maximum ACR (P <.0001) and average ACR (P =.0059) after 14 days posttransplant. The rate and direction of change in citrulline over time may be an indicator of the risk of acute rejection. We plan to further examine the use of citrulline as a marker for rejection in larger prospective studies.

Adult↗

PubMed2004

Multivisceral transplantation for pediatric intestinal pseudo-obstruction: single center's experience of 16 cases.

Chronic intestinal pseudo-obstruction (CIPO) in children may be life-threatening due to the complications of parenteral nutrition (PN) or catheter-related sepsis. Multivisceral transplantation (MVTx) is a lifesaving option but limited experience is available. We report our experience with MVTx in pediatric CIPO patients. Sixteen children with CIPO underwent MVTx at median age of 4 years. Indications for MVTx were liver failure (n = 10), loss of venous access (n = 3), or sepsis (n = 3). Modified MVTx without the liver was performed in six patients. Induction immunosuppression included tacrolimus, steroid with adjunctive agent in period I (April 1996 to December 2000), namely, OKT3 (n = 1), mycophenolate mofetil (n = 4), or daclizumab (n = 2); and in period II (January 2001 to present), Campath 1H (n = 4) or daclizumab (n = 5). The grade of rejection was severe in 12.5% and mild to moderate in 87.5% of cases. Isolated rejection of the transplanted stomach or pancreas was not diagnosed during clinical course or on autopsy. Actuarial patient survival for 1 year/2 years for period, I and II were 57.1%/42.9% and 88.9%/77.8%. None of the long-term survivors is on PN and all tolerate enteral feedings. Pancreatic enzyme supplementation or insulin therapy is not needed in survivors. Gastric emptying was substantially affected in one case. Bladder function did not improve in those with urinary retention problems. MVTx for CIPO offers a lifesaving option with excellent function of the transplanted pancreas and stomach among survivors.

Child↗

PubMed2004

Immunoenzymatic and morphological detection of epithelial cell apoptotic stages in gastrointestinal allografts from multivisceral transplant patients.

Acute allograft rejection (AR) is a major contributor to morbidity and mortality among patients who undergo multivisceral transplantation. Critical to the assessment of AR is detection of apoptosis in the glandular epithelium of the gastrointestinal allograft. We utilized the TUNEL stain (TdT-mediated biotin 16-dUTP nick-end labeling) to test whether this method improved detection of apoptosis compared to standard slide evaluation. TUNEL and H&E stains were performed on paraffin-embedded tissue sections to estimate the number of apoptotic bodies per 10 high power fields, as determined by independent pathologists in blinded fashion. Both methodologies showed similar numbers and distributions of apoptotic foci present among the epithelial cells. There was a correlation between the number of apoptosis and the grade of rejection (P <.001). This is the first use of the TUNEL stain in gastrointestinal allograft biopsies to our knowledge. The similarity in pattern and sensitivity of TUNEL with standard morphology confirms that biopsy assessment with routine H&E staining allows an accurate appraisal of epithelial cell apoptosis. Therefore, current staining protocols for endoscopically derived mucosal biopsies of gastrointestinal allografts are sufficiently accurate to enumerate the critical feature of epithelial apoptosis as a determinant of the grade of acute rejection.

Apoptosis↗

PubMed2004

Lymphoplasmacytic hyperplasia (possibly pre-PTLD) has varied expression and appearance in intestinal transplant recipients receiving Campath immunosuppression.

Posttransplant lymphoproliferative disorders (PTLD) are a frequent complication in bowel transplant recipients. Histological changes in PTLD range from expansile lymphoplasmacytic (LP) hyperplasia to frank lymphoma. Small bowel allograft biopsies obtained in the first 250 days posttransplant were retrospectively graded after patients had received induction immunosuppression with either anti-CD52 (Campath) or anti-CD25 (Zenapax) monoclonal antibodies. The biopsies were analyzed with respect to the onset intensity of lymphoplasmacytic infiltrates and presence of in situ EBV hybridization (EBER) positivity. We observed that lymphoplasmacytic infiltrates were a frequent change in all bowel transplant patients over the examined period. Campath-treated patients developed earlier LP infiltrates of mild to moderate intensity between day 1 and 100 posttransplant, thereafter decreasing to mild. No EBER positivity was detected in this group. Zenapax-treated patients presented with LP infiltrates later of mild to moderate intensity through day 100 posttransplant. However, more persistent and intense LP infiltrates was observed after day 101 in this group, including a case of lymphoma and two cases of EBER positivity. We conclude that Campath immunosuppression results in an earlier appearance of LP lesions that are generally less intense than those evident with Zenapax. We attribute these findings to the more profound immunodeficiency and cell targeting following Campath treatment.

Alemtuzumab↗

PubMed2004

Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation.

Campath-1H, an anti-CD52 antibody, is being used at our institution as immunosuppression in multivisceral and intestinal transplantation. We reviewed the pathologic findings of 1696 small bowel allograft biopsies obtained in the first 250 days posttransplant from 78 patients who underwent isolated intestinal or multivisceral transplantation and received induction immunosuppression with Campath (n = 30) or Zenapax (n = 57). We found an overall reduced incidence of acute cellular rejection (ACR) in patients receiving Campath (19.1%) compared with those on Zenapax (32.8%). The majority of Campath patients showed no rejection or was indeterminate for rejection over the period of measurement. The frequencies of mild and moderate ACR were approximately twice and three times more common, respectively, in Zenapax-treated patients. The mean grade of ACR in Campath patients compared with Zenapax patients was significantly lower (P <.01) during the first 6 weeks posttransplant. Thereafter, the grade of rejection in both patient groups showed fluctuation, with Zenapax patients sometimes having lower values (eg, at 2 to 4 months) than Campath patients. Patient and graft survival was not significantly different between the two groups. These data suggest that the incidence of ACR is significantly reduced with Campath during the first 2 months posttransplant, when compared with Zenapax. However, the incidence and intensity of ACR following this initial time period shows vacillation with both types of immunosuppression.

Alemtuzumab↗

PubMed2004

Neurodevelopmental outcomes of infant intestinal transplant recipients.

Little is known about the impact of intestinal transplantation on development of the infant brain. In this study we report four neurodevelopmental studies on children receiving either liver or intestinal/multivisceral transplants. Our preliminary investigation examined the pretransplant status of 27 infants, who were either liver or intestinal/multivisceral candidates, using the Bayley Scales of Infant Development. A second study examined 23 infants after liver or intestinal/multivisceral transplant. A third study included pre- and posttransplant evaluations on 5 multivisceral infant transplants. In the fourth study, 10 children were tested several years after intestinal/multivisceral transplantation. Some children are able to achieve a normal development. However, even several years posttransplant most children can still experience significant cognitive delays. Children receiving a transplant during infancy may also suffer severe motor delays. Infants undergoing intestinal/multivisceral transplantation show significantly more cognitive delays than those undergoing single-organ liver transplantation. In addition, multivisceral transplanted infants are more likely to continue to be severely developmentally delayed at the time of hospital discharge. With improved survival rates for infant transplants, both cognitive and motor development must be evaluated to determine the need for early intervention. In addition, educating families on the importance of compliance with intervention services outside the hospital is essential to maximize long-term neurodevelopmental outcomes for these infants.

Aging↗

PubMed2003

Sclerosing mesenteritis in small bowel transplantation: possible manifestation of acute vascular rejection.

BACKGROUND: Acute rejection of human small bowel allografts is characterized by clinical symptoms combined with characteristic morphologic alterations. The typical geographic distribution of acute rejection in the bowel is involvement of the intestinal parenchyma, which can be transmural, particularly when the rejection is more severe. However, little is known concerning the potential for donor-derived soft tissue adjacent to the bowel to become involved by the host alloimmune response. METHODS: We describe a male patient who, several weeks after combined small bowel and liver transplantation, demonstrated sclerosing mesenteritis with vasculitis and acute rejection of the bowel. RESULTS: The vascular lesions in the mesentery demonstrated increased IgG deposition and the patient developed an alloantibody to the donor. CONCLUSIONS: The changes described herein may represent a novel presentation of acute vascular rejection.

Acute Disease↗

PubMed2003

Bacterial infections after intestine and multivisceral transplantation.

BACKGROUND: The frequency of bacterial infections (BI) in intestinal transplant (IT) patients is high with sepsis being the leading cause of death after this procedure. We herein report our experience with major BI to ascertain the incidence, microbiological and clinical factors, risk factors and outcome. MATERIALS AND METHODS: 124 patients (72 children and 52 adults) received 135 grafts: namely, 39 isolated intestine, 33 liver-intestine and 63 multivisceral. Only major BI were considered, namely, those associated with serious morbidity/mortality requiring specific therapy. Patient data were retrieved from computerized databases, flow-charts, and medical records. RESULTS: 92.7% patients showed BI. There were 327 episodes, representing 2.6 episodes/patient (2.8/patients with infection): 193 episodes of bacteremia (1.7/patient with BI) including 29.5% due to catheter related sepsis, 16.5% from abdominal source, 5.7% from respiratory origin and 4.1% from the wound. The organ locations includes 46 respiratory infections, 33 intraabdominal abscesses or infected fluid collections, 8 diffuse peritonitis, 34 wound infections and other miscellaneous sites: empyema, soft tissue infections, cholangitis em leader etc. Median time of infection was nine days after surgery (mean 22+/-3 days), with 67.7% patients having at least one BI before the end of the first month. Infection was present in 76.2% of the 63 deceased patients. An infectious episode during month 1, a clinically manifest abdominal infection and a positive intraabdominal culture had negative impacts on patient survival. CONCLUSIONS: BI are common and early complications after IT. The high rate of bacteremia, line sepsis and abdominal and respiratory infections reflect the recipient's condition, with chronic deterioration superimposed with the effects of prolonged abdominal visceral surgery.

Adult↗

PubMed2003

Intestinal transplantation: advances in immunosuppression and surgical techniques.

Campath-1H is being used as induction immunosuppression for intestinal/multivisceral transplantation. Patient and graft survival in this preliminary experience is similar to previous studies but there has been a significant decrease in the incidence and severity of acute rejections without increase of opportunistic infections. Collage of the abdominal wall (transplantation of a composite graft of the abdominal wall) can provide biologic coverage of the newly transplanted abdominal organs if necessary. Partial abdominal exenteration, ex vivo resection, and intestinal autotransplantation may be useful in removing otherwise unresectable lesions of the root of the mesentery.

Graft Rejection↗

PubMed2003