PARTIAL OCULOCUTANEOUS ALBINISM AND IMMUNODEFICIENCY SYNDROMES: TEN YEARS EXPERIENCE FROM A SINGLE CENTER IN TURKEY.

BACKGROUND AND AIM: Partial oculocutaneous albinism and immunodeficiency (OCA-ID) diseases are autosomal recessive syndromes characterized by partial hypopigmentation and recurrent infections. Moreover, some OCA-ID syndromes confer susceptibility to develop a life-threatening hyperinflammatory condition called hemophagocytic lymphohistiocytosis (HLH). We investigated the genetic, clinical and immunological characteristics of 20 OCA patients. MATERIAL AND METHODS: Herein, we present the clinical and immunological characteristics of 20 OCA patients who referred to the Department of Pediatric Immunology, Erciyes University Medical Faculty in Kayseri, Turkey between 2004 and 2014. RESULTS: Of the 20 OCA patients, 7 fulfilled diagnostic criteria for HLH, 9 showed defective functions of CD8 T cells and natural killer cells, and 8 received a definitive molecular diagnosis. Among the patients, we also report a patient diagnosed with two different genetic defects, in TYR and JAK3 genes, causing, respectively, OCA and ID. CONCLUSION: Our results illustrate the variability of clinical presentations and disease severity in OCA-ID patients, with consequent challenges in diagnosing and treating these patients.

Impact of pulmonary and extrapulmonary tuberculosis infection in kidney transplantation: a nationwide population-based study in Taiwan.

BACKGROUND: Tuberculosis (TB) has been reported to increase morbidity after kidney transplantation and pose a therapeutic challenge. However, population-based research, specifically focused on the association between kidney transplantation and subsequent pulmonary or extrapulmonary TB, is lacking. METHODS: A nationwide population-based study was conducted using Taiwan's National Health Insurance Research Database, which provided claims data belonging to kidney transplant recipients during 1997-2006. Multivariate analysis was used to identify independent risk factors for TB after kidney transplantation. Kaplan-Meier survival analysis was used to assess the outcome of patients with TB. RESULTS: Among 4554 kidney transplant recipients over the 10-year period, 109 (2.4%) patients with newly diagnosed TB were identified: 75 patients with only pulmonary involvement, and 34 with extrapulmonary spread. The incidence of kidney transplant recipients developing TB was 638 per 100,000 person-years. The independent risk factors for post-transplant TB included cyclosporine-based immunosuppressant agents during the first year after kidney transplantation (odds ratio [OR]: 1.98, P = 0.001), hepatitis C infection (OR: 1.79, P = 0.024), and chronic obstructive pulmonary disease (OR: 1.50, P = 0.041). Kidney transplant recipients who developed TB had a lower 5-year survival rate than those who did not (78.6% vs. 93.4%, P = 0.001). CONCLUSIONS: Kidney transplant recipients in Taiwan did have a high risk of TB infection, with high proportion of extrapulmonary spread. Physicians need to be vigilant in surveying for TB in kidney transplantation, especially in high-risk patients.

A randomised controlled study of risperidone and olanzapine for schizophrenic patients with neuroleptic-induced acute dystonia or parkinsonism.

The objective of this study was to compare the effects of risperidone and olanzapine in schizophrenic patients with intolerant extrapyramidal side effects (EPS) on first generation antipsychotics. We conducted an 8-week, rater-blinded, flexible dose study. Seventy patients with schizophrenia, who met the DSM-IV research criteria of having neuroleptic-induced acute dystonia or parkinsonism, were randomly assigned to risperidone or olanzapine group. The primary outcome was a comparison of the incidence of concomitant anticholinergic drugs usage between the groups to manage their acute dystonia and parkinsonism. The average doses of risperidone and olanzapine from baseline to study end point were 1.8-3.5 mg/day and 7.7-11.7 mg/day, respectively. There were no significant differences in demographic data, severity of EPS or psychotic symptoms between the groups at baseline assessment. Patients taking risperidone had significantly higher incidence of using anticholinergic drugs to manage acute dystonia or parkinsonism overall during the study (OR = 5.17, 95%CI = 1.49-17.88, P = 0.013). There was no significant between-group difference in the changing of rating scales of EPS and psychotic symptoms. The results of our study favour olanzapine as a better choice in schizophrenic patients with intolerant EPS. Double-blinded, fixed dose and different ethnical study for EPS-intolerant schizophrenic patients is needed to confirm the results of our study.

A two-stage probabilistic approach to multiple-community similarity indices.

SUMMARY: A traditional approach for assessing similarity among N (N > 2) communities is to use multiple pairwise comparisons. However, pairwise similarity indices do not completely characterize multiple-community similarity because the information shared by at least three communities is ignored. We propose a new and intuitive two-stage probabilistic approach, which leads to a general framework to simultaneously compare multiple communities based on abundance data. The approach is specifically used to extend the commonly used Morisita index and NESS (normalized expected species shared) index to the case of N communities. For comparing N communities, a profile of N- 1 indices is proposed to characterize similarity of species composition across communities. Based on sample abundance data, nearly unbiased estimators of the proposed indices and their variances are obtained. These generalized NESS and Morisita indices are applied to comparison of three size classes of plant data (seedling, saplings, and trees) within old-growth and secondary rain forest plots in Costa Rica.

The rationale of fever surveillance to identify patients with severe acute respiratory syndrome in Taiwan.

STUDY OBJECTIVE: To establish a predictive scoring system and to determine its effectiveness for severe acute respiratory syndrome (SARS) cases confirmed by RT-PCR in patients with fever. METHODS: A study was conducted of 484 consecutive patients seen in the emergency department (ED) of our tertiary care center during the SARS outbreak in Taiwan. The scoring system was divided into triage and screening station stages. Data were analysed with multivariable and logistic regression analysis. RESULTS: Of 737 patients who presented to our ED for possible SARS from March to June 2003, we enrolled 484 patients with a temperature >38.0 degrees C (>100.3 degrees F) (age >18 years). Dyspnoea, diarrhoea, travel, close contact, hospital exposure, and household history were identified as predictive indicators in the triage stage. The triage score was the total of six items. With a one-point cutoff value, the sensitivity and specificity were 81.8% (18/22) and 73.6% (340/462). Leukocytosis, thrombocytopenia, lymphopenia, and CXR were identified as predictive indicators in the fever screening stage. Screening station scores (the sum of 10 items) consisted of triage scores, white blood cell count, and CXR. With a three-point cutoff value, the sensitivity and specificity were 95.5% (21/22) and 87.2% (403/462). CONCLUSIONS: Syndromic and traditional surveillance play a role in early identification of SARS in an endemic area. The SARS scoring system described is easily applicable and highly effective in screening patients during outbreaks.

Two novel mutations in the alpha-galactosidase A gene in Chinese patients with Fabry disease.

Fabry disease is an X-linked disorder caused by a deficiency of the lysosomal alpha-galactosidase A [EC 3.2.1.22]. The molecular diagnosis of Fabry disease is important for genotype/phenotype correlation, pre-natal or early diagnosis, and detection of carrier status. Although more than 200 genotypes of the alpha-galactosidase A gene have been identified, mutation data on the Chinese population is sparse. We recently identified two unrelated Chinese families with Fabry disease. Mutation analysis was performed by polymerase chain reaction (PCR) sequencing of the seven exons and adjacent introns of the alpha-galactosidase A gene. Two novel mutations were identified: in family I, a C-to-A transversion resulted in an early termination at amino acid 222 (Y222X), while in family II, an A-to-G transition resulted in a substitution of alanine for threonine at amino acid 410 (T410A). Carrier status was identified in all four females in the two families. The genotype Y222X is associated with classic Fabry disease, with unexpectedly rapid deterioration of visual acuity, while T410A is associated with a milder Fabry disease, with ventricular hypertrophy and neuropathic pain.

Waist circumference predicts insulin resistance in offspring of diabetic patients.

The purpose of the study was to identify a good abdominal obesity index for insulin resistance in offspring of diabetic patients. A total of 74 non-diabetic subjects (male =36; female =38) were recruited from a diabetic family study. The waist circumference (W), waist-hip ratio (WHR) and conicity index were used as the abdominal obesity indices. The body mass index (BMI) and indices obtained from bioelectric impedance analysis (BIA) (body fat percentage, fat mass and fat mass index) were used as overall obesity indices. Fasting plasma insulin (FPI), homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda-Defronzo index from oral glucose tolerance test were chosen as the insulin sensitivity indices. We correlated obesity indices with insulin resistance indices with age and family adjusted. W was closely correlated in both sexes of subjects with Matsuda-DeFronzo index (male, r=-0.661,p<0.001; female, r=-0.419,p=0.026), FPI (male, r=0.614,p=0.001; female, r=0.503,p=0.006) and HOMA-IR (male, r=0.609,p=0.001; female, r=0.472,p=0.011). WHR and its log transformation predicted insulin resistance only in males. BMI as an overall obesity index was in good correlation with Matsuda-DeFronzo index (male, r=-0.646,p<0.001; female, r=-0.469,p=0.012), FPI (male, r=0.711,p<0.001; female, r=0.464,p=0.013) and HOMA-IR (male, r=0.708,p<0.001; female, r=0.469,p=0.012). Overall obesity indices from BIA were similar to BMI to predict insulin resistance. In conclusion, W is a good abdominal obesity predictor of insulin resistance in offspring of diabetic patients in Taiwan.

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer.

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m(-2), days 1, 8, 15) and cisplatin (90 mg m(-2), day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

Abnormal cardiovascular reflex tests are predictors of mortality in Type 2 diabetes mellitus.

AIMS: To determine whether diabetic autonomic neuropathy is an important factor contributing to mortality in Type 2 diabetes mellitus. METHODS: Between 1989 and 1993, 431 men and 181 women with Type 2 diabetes were given diabetic autonomic neuropathy cardiovascular reflex (CVR) tests. These subjects were followed for the subsequent 5--9 years to assess mortality rates. RESULTS: The prevalence rate of abnormal CVR tests was 46.1% in patients with the history of diabetes less than 5 years and up to 69.4% when the history of diabetes exceeded 20 years. During the follow-up period from 1 January 1989 to 31 December 1997 (mean 7.7 years), a total of 135 participants died. The 8-year survival rate for patients with abnormal CVR tests was 63.6% in males and 76.4% in females, compared with 80.9 and 93.3% for patients with normal CVR tests. The results were grouped as: group 1, normal CVR tests without postural hypotension (PHT); group 2, normal CVR tests with PHT; group 3, abnormal CVR tests without PHT; and group 4, abnormal CVR tests with PHT. The 8-year survival rate was 85.4% in group 1, 80.9% in group 2, 74.5% in group 3 and 61.1% in group 4. CONCLUSION: Type 2 diabetic patients with abnormal CVR tests may have increased mortality, and those combined with postural hypotension have higher mortality than those without. Abnormal CVR tests may be important predictors of mortality in Type 2 diabetes mellitus.

Comparative study of the efficacy and safety of valaciclovir versus acyclovir in the treatment of herpes zoster.

Acyclovir, a specific and selective inhibitor of the replication of Herpesviridae family, has well-documented efficacy and tolerability in the treatment of herpes zoster. Its limited oral bioavailability and short half-life, however, necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, could be rapidly converted to acyclovir after oral administration, resulting in a three- to five-fold increase in acyclovir bioavailability compared with oral acyclovir in humans. Valaciclovir allows less frequent dosing and maintains the safety profiles of the parent drug. During the period from October 1996 through May 1998, a randomized, prospective study was performed in the Kaohsiung Veterans General Hospital to compare the safety and efficacy of valaciclovir with acyclovir in the treatment of herpes zoster in Taiwanese patients. Patients presenting with herpes zoster within 72 h after the onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg valaciclovir three times daily for 7 days or acyclovir 800 mg five times daily for 7 days. Patients were followed up for 29 days beginning with the start of therapy. A total of 57 patients were enrolled and randomized to receive valaciclovir (n = 32) or acyclovir (n = 25). Five patients in the valaciclovir group and three in the acyclovir group did not complete the study. The intent-to-treat analysis (57 patients) showed that valaciclovir significantly accelerated the resolution of herpes zoster-associated pain compared with acyclovir; on day 29, the valaciclovir group was 23% superior to the acyclovir group. There was no clinically significant difference in the nature, frequency or severity of adverse events between these two groups, although one and three adverse events were reported in the acyclovir and valaciclovir group, respectively. Thus, we conclude that in the management of herpes zoster, valaciclovir accelerates the resolution of pain and offers a simpler dosing, and maintains the favorable safety profile of acyclovir.

Neurourologic findings in patients with traumatic thoracolumbar vertebra junction lesions.

OBJECTIVE: To investigate neurourologic involvement in injuries to the thoracolumbar vertebra junction with magnetic resonance imaging (MRI) and electrophysiologic and urodynamic measurements and to characterize the neurogenic mechanisms of voiding dysfunctions. DESIGN: Baseline comparisons among 3 anatomic groups before neural repair. SETTING: Tertiary care center. PATIENTS: Thirty-five T11 to L2 spinal cord injury patients consecutively admitted to a rehabilitation unit. Eight patients (Group 1) had above-conus lesions without denervation and polyphasic waves revealed in the anal sphincter electromyography; 13 patients (Group 2) had conal and/or above-conus lesions and anal sphincter electromyographic abnormalities; and 14 patients (Group 3) had below-conus lesions and anal sphincter electromyographic abnormalities. MAIN OUTCOME MEASURES: Comparison of features identified on pudendal nerve terminal motor latency, urethral pressure profiles, and multichannel voiding pressure-flow study. RESULTS: The pudendal nerve terminal motor latency in Group 3, showing a significantly higher abnormal ratio (100%; p =.011, Fisher's exact test), indicated that cauda equina lesions might be the cause. Urodynamic data from Group 3 showed a significant decrease in maximal urethral closure pressure (48 +/- 17cm H2O, p =.0022, analysis of variance [ANOVA], repeated measure) and an increase in bladder capacity (429 +/- 194mL, p =.037, ANOVA, repeated measure). There were no significant changes in the other groups. CONCLUSION: Neurourologic abnormalities are less predictable with injuries to thoracolumbar junction, except in patients with cauda equina lesions.

A comparison of insulin suppression tests performed with somatostatin and octreotide with particular reference to tolerability.

To evaluate the tolerability of insulin suppression test (IST) using octreotide instead of somatostatin, we compared the steady-state plasma glucose (SSPG) values and the safety during and after the test in 17 normal volunteers. The subject received IST twice (with somatostatin or with octreotide) in random order. During the test, all subjects were infused with regular insulin and glucose simultaneously for 180 min. In addition, either somatostatin or octreotide was infused intravenously over the same period of time. Plasma glucose, insulin and C-peptide were measured. The subject response to the test was recorded during and one day after the test by a structured questionnaire. The SSPG and the steady-state plasma insulin (SSPI) values reached during IST were similar, irrespective of the use of somatostatin or octreotide. There was a positive correlation between the SSPG values obtained from both methods (r = 0.67, P = 0.003). However, the mean intra-individual coefficient of variation is 17.9% for SSPG. The SSPG levels, no matter from which method, correlated positively with the 2-h insulin after oral glucose challenge. Most adverse events (especially gastrointestinal discomfort) occurred after the test, and increased much more after using octreotide than somatostatin (P = 0.002 by chi 2 test). In conclusion, the SSPG values measured by IST using octreotide or somatostatin are similar in normal healthy subjects. Yet, the octreotide method has more adverse events after the test.

Molecular, cellular and functional characterizations of a novel ICAM-like molecule of the immunoglobulin superfamily from Leishmania mexicana amazonensis.

A molecule with two immunoglobulin (Ig) domains cloned from Leishmania mexicana amazonensis was characterized to have a sequence homology to the Ig domains of an ICAM-like molecule telencephalin, cloned from the brain of mammals, as well as to the variable domains of human immunoglobulin lambda light chain. The molecule therefore appears to be an ICAM-like molecule as well as a member of the immunoglobulin superfamily. We thus named it ICAM-L for Leishmania ICAM. The gene was coamplified with the ribonucleotide reductase M(2) subunit gene responsible for hydroxyurea resistance from hydroxyurea (Hu)-resistant Leishmania variants. As expected, an increase of the ICAM-L protein as well as an increase of the specific ICAM-L transcript of 2.1 kb was detected in the Hu-resistant variants with increasing doses of the drug used for resistance selection. Structurally, ICAM-L is more similar to the secretory adhesive molecules, such as 1Bgp and the link protein of the immunoglobulin superfamily, in that it lacks a transmembrane region and a GPI anchor sequence. Although ICAM-L was mainly localized in the nucleus of the parasite by confocal microscopy, however, detailed studies by electron microscopy and FACS analysis indicated that the protein was also localized on the surface of the parasite. The surface localization of the protein was furthered strengthened by the observations that anti-ICAM-L or ICAM-L itself can significantly block the binding of the parasite to macrophages. The blocking of the attachment of parasite to macrophages may indicate that ICAM-L functions as an intercellular adhesive molecule.

Treatment and outcome of Taiwanese patients with 6-pyruvoyltetrahydropterin synthase gene mutations.

Ten cases of tetrahydrobiopterin (BH4) deficiency were identified in 1,337,490 newborns screened in a Chinese population in Taiwan. The high incidence of BH4 deficiency in the Taiwanese population may be explained by a founder effect, since all of the patients revealed 6-pyruvoyltetrahydropterin synthase gene mutations, and grouping N52S and P87S mutations together constituted 88.9% of the disease alleles. BH4 supplementation with restriction of high-protein foods gave control of plasma phenylalanine within normal range, and levodopa itself prevented seizure. However, the average intelligence quotient (IQ) score of these patients was only 76 +/- 14 (56-98). Statistically, the age of starting medication, including 5-hydroxytryptophan (5-HTP), was inversely correlated to IQ scores of these patients. We suggest the combination of BH4, levodopa and 5-HTP as the standard protocol to commence the treatment of BH4 deficiency as early as possible, although prenatal brain damage could have existed.

Ethambutol retinal toxicity: an electrophysiologic study.

BACKGROUND AND PURPOSE: In animal studies, ethambutol (EMB) has been shown to be toxic to cone pedicles and to cause their degeneration in the retinas of fish. The purpose of this study was to determine whether EMB is toxic to retinas in humans. METHODS: Twenty-seven patients with EMB-induced optic neuropathy and 20 normal control subjects were included in this study. The following details were recorded: age, sex, and systemic condition of the patients, daily dosage of EMB, duration of EMB treatment, visual function at the time of electrophysiologic investigation, time from the onset of blurred vision to the discontinuation of EMB treatment (symptom duration), and time from termination of EMB treatment until electrophysiologic investigation. RESULTS: The electroretinograms were normal in 25 patients. Twelve patients had normal electro-oculogram (EOG) findings in both eyes and the remaining 15 patients had abnormal EOG findings in at least one eye. Ten eyes showed supranormal EOG (light/dark (L/D)) ratios of more than 2.33, and 13 eyes had decreased L/D ratios (< 1.65). The symptom duration was shorter in the supranormal EOG group. CONCLUSIONS: The results suggest that a supranormal EOG may be indicative of an early toxic state during EMB therapy and that EMB may cause dysfunction of the retinal pigment epithelium.

Glucose-6-phosphatase gene mutations in Taiwan Chinese patients with glycogen storage disease type Ia.

Glycogen storage disease type Ia (GSD Ia) is caused by a deficiency of glucose-6-phosphatase (G6Pase) activity. Eighteen GSD Ia families were studied for G6Pase gene mutations. Thirty-two mutations were found in 36 GSD Ia chromosomes: 16 were 727 G-->T (44.44%); 13 were R83H (327 G-->T; 36.11%); 1 was 341delG; 1 was 933insAA; and 1 was 793 G-->T. The 727 G-->T and R83H mutations together accounted for 80.56% (29/36) of the GSD Ia chromosomes. These two mutations were easily examined by polymerase chain reaction-based methods, and the prenatal diagnosis of a non-affected fetus was successfully made. The 727 G-->T mutation is the predominant mutation in Japanese GSD Ia patients, but is rarely seen in Western counties. The 727 G-->T mutation is also the most prevalent mutation in Taiwan Chinese, although the incidence is not as high as in Japan.

Carnitine transport defect presenting with hyperammonemia: report of one case.

Carnitine (beta-hydroxy-gamma-trimethylaminobutyric acid) is involved in the transport of long-chain fatty acids into the mitochondrial matrix and removal of potentially toxic acylcarnitine esters. Carnitine transport defect is a very rare metabolic disease. A 7-month-old female infant was found to have consciousness disturbance, hyperammonemia, hepatomegaly and elevated transaminases. Both the concentrations of free carnitine and acylcarnitines in her blood were very low. The diagnosis of carnitine transport defect was confirmed by assays of carnitine uptake and transport in skin fibroblasts. She responded dramatically to carnitine therapy, and there was no hyperammonemia attack for more than 3 years. Her cardiac function also remained normal.

Optimal debulking surgery is an independent prognostic factor in patients with FIGO IIIC primary epithelial ovarian carcinoma.

BACKGROUND: Ovarian cancer is a well-known disease with a poor prognosis. Due to the relatively small number of cases in Taiwan, the outcome and prognostic factors of patients with primary epithelial ovarian carcinoma are unknown. METHODS: We retrospectively studied patients with proven surgical and pathologic (Federation Internationale de Gynecologie et d'Obstetrique) FIGO IIIC primary epithelial ovarian carcinoma. All patients underwent standard staging surgery, including washing cytology, total abdominal hysterectomy, bilateral salpingo-oophorectomy, retroperitoneal lymphadenectomy, infracolic omentectomy and excisional biopsy of all suspicious lesions followed by adjuvant chemotherapy with four to 12 courses of cyclophosphamide, epirubicin and cisplatin (CEP) or cyclophosphamide, adriamycin and cisplatin (CAP) intravenously, every three weeks. To avoid the coeffects of chemotherapy and surgical procedures upon the outcome, patients who received paclitaxel-based regimens or underwent incomplete surgery were excluded. Ninety-eight patients from 1990 to 1996 were identified. RESULTS: The mean follow-up time was 28.7 months, ranging from 5.4 months to 105.9 months. The cumulative five-year disease-free survival rate for all patients was 31.6%. Optimal debulking surgery was completed in 41.8% of patients, which contributed to long-term patient survival (54% vs 16%, p < 0.0001), compared to patients without optimal debulking surgery. Optimal debulking surgery was the only statistically significant independent prognostic factor for five-year disease-free survival using multivariate analysis. CONCLUSIONS: To improve survival of patients with FIGO stage IIIC epithelial ovarian carcinoma, optimal debulking surgery should be performed as the initial form of surgical intervention.

TNP-470 inhibits intraabdominal adhesion formation.

BACKGROUND/PURPOSE: Angiogenesis plays an integral role in wound healing and tissue remodeling. The authors hypothesized that inhibition of angiogenesis would reduce intraabdominal adhesion formation. METHODS: In 98 C57BL6/J mice, a 2-cm midline laparotomy was performed and a 5 mm2 SILASTIC (Dow Corning, Midland, MI) patch fixed to the right side of the peritoneum. Mice were injected with normal saline (n = 54) or TNP-470, an inhibitor of angiogenesis (n = 44; 30 mg/kg every other day over 6 days before surgery until 10 days after surgery). Animals were killed on postoperative days 10, 15, 35, and 55. Adhesions to the SILASTIC (Dow Corning) patch were scored based on their extent, type, and tenacity. Angiogenesis was quantified digitally as the area of vascularized peritoneum over the patch. RESULTS: At day 10, when TNP-470 was stopped, the percentage of vascularized peritoneum over the patch was less in treatment animals than in controls (P = .004). At day 35, the patch in treatment animals was completely covered by vascularized peritoneum, similar to controls. Adhesions in TNP-470 animals were reduced at day 10 compared with controls (P<.05) and remained reduced off treatment at day 55. CONCLUSIONS: Angiogenesis appears to play an important role in the development of intraabdominal adhesions, because the extent of early neovascularization correlates with adhesion formation. Perioperative treatment with TNP-470, a potent endothelial cell inhibitor, reduced vessel ingrowth over the patch and was associated with a sustained reduction in adhesion formation.