Biomedical subjects

G Motta

Publications and source records attributed to G Motta.

At least 19 recordsLinked to original sources

PubMed2006

Papillomatosis of the larynx: treatment with CO2 laser.

OBJECTIVES: We report our experience treating papillomatosis of the larynx using CO2 laser which has a lower risk of post surgical complications. Papillomatosis has a high incidence of recurrence after surgical treatment. METHODS: We treated 42 patients (10 adults and 32 children) affected by multiple papillomatosis of the larynx. Smaller papillomas were vaporized with a 7-8 Watt CO2 laser and larger papillomas were resected at the base of their implantation. A strict follow-up during the first 3 years after surgical treatment was necessary to manage recurrences with CO2 laser endoscopy. RESULTS: All patients presented with recurrences after the first surgical treatment, but within 18-60 months all patients presented a solution of their pathology. Post-operative complications were observed in patients who did not comply with the strict follow-up protocol and presented with large lesions requiring more invasive surgery. CONCLUSIONS: CO2 laser endoscopy, although it did not prevent recurrences of papillomatosis in the larynx, is a valid surgical approach in the management of this pathology.

Adolescent↗

PubMed2005

Microsurgical repair of the facial nerve.

OBJECTIVE: To report a series of 18 patients who underwent microsurgical repair of the facial nerve using different techniques and to discuss the indications and results of facial reinnervation procedures. METHODS: Eighteen patients with post-surgical facial palsy underwent facial reinnervation using different techniques.'These included classic hypoglossal-facial anastomosis in 13 cases, one-stage hemihypoglossal-intratemporal facial nerve anastomosis and translabyrinthine removal of residual intra-canalar acoustic schwannoma in 3, hemihypoglossal-facial nerve anastomosis in one, and neurotization of facial muscles through a nerve graft in one. RESULTS: The facial muscle function improved in all patients, up to grade III in 7 cases (39 %), grade IV in 9 (50 %) and grade V in 2 (11 %). The tongue atrophy was minimal in 70.5 %, moderate in 17.5 % and severe in 12 %. The outcome was better in younger patients (less than 40 years of age) and in those with a lesser grade of preoperative facial impairment. CONCLUSIONS: The classic hypoglossal-facial anastomosis is the technique of choice in most cases. The use of the intratemporal facial nerve is indicated when removal of an intra-canalar residual schwannoma must also be performed. The neurotization of the facial muscles through a nerve graft may be used when there is no distal trunk of the facial nerve available for the anastomosis.

Adult↗

PubMed2005

Evaluating the therapeutic approach in pregnancies complicated by borderline glucose intolerance: a randomized clinical trial.

AIMS: Most studies relating minor gestational metabolic alterations to macrosomia refer to glucose intolerance classified on the basis of the National Diabetes Data Group or previous World Health Organization diagnostic thresholds. Our aim was to evaluate the consequences of very mild forms of gestational glucose intolerance, defined by an elevated 50-g glucose challenge test followed by a normal oral glucose tolerance test, using the more restrictive Carpenter and Coustan's criteria (Borderline Gestational Glucose Intolerance, BGGI). METHODS: Three hundred BGGI women were randomly assigned to: Group A (standard management), Group B (dietary treatment and regular monitoring). A control group (C) was also considered. Newborns were classified as macrosomic, large (LGA), or small for gestational age (SGA). RESULTS: The three groups were similar in age, body mass index and parity. Therapy in Group B significantly improved fasting (from 4.68 +/- 0.45 to 4.28 +/- 0.45 mmol/l) and 2-h postprandial glycaemia (from 6.01 +/- 0.57 to 5.13 +/- 0.68 mmol/l). Fasting glycaemia at delivery was significantly lower in B (4.20 +/- 0.38 mmol/l) than in A (4.84 +/- 0.45 mmol/l), and was also lower than in C (4.31 +/- 0.39 mmol/l). Significantly fewer LGA babies were born to Group B (6.0%) than Group A (14.0%) and Group C (9.1%). No difference was found in the SGA rate. The neonatal Ponderal Index was higher (P = 0.030) in group A (2.73 +/- 0.35) than in C (2.64 +/- 0.30) and B (2.64 +/- 0.24). CONCLUSIONS: Even very mild alterations in glucose tolerance can result in excessive or disharmonious fetal growth, which may be prevented by simple, non-invasive therapeutic measures.

Adult↗

PubMed2004

Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial.

OBJECTIVES: In order to prevent abnormalities of fetal growth still characterizing pregnancies complicated by Gestational Diabetes (GDM), in the present study we evaluated a therapeutic strategy for GDM based on ultrasound (US) measurement of fetal insulin-sensitive tissues. METHODS: All GDM women diagnosed before 28th week immediately started diet and self-monitoring of blood glucose; after 2 weeks they were randomized to conventional (C) or modified (M) management. In C the glycemic target (GT) was fixed at 90 fasting/120 post-prandial mg/dl; in M GT varied, according to US measurement of the Abdominal Circumference (AC) centile performed every 2 weeks: 80/100 if AC > or =75th, 100/140 if AC<75th. Therapy was tailored to mean fasting (FG) and postprandial glycemia (PPG). RESULTS: Globally, 229 women completed the study, 78 in C, 151 in M. Use of insulin was 16.7% in C, 30.4% in M (total groups), significantly more frequent in M than in C (59.7% vs 15.4%) when considering only women with AC > or =75th c. Mean metabolic data were similar in the 2 groups, but in M a tightly-optimized subgroup, resulting from the lowering of GT due to AC > or =75th, coexisted with a less-controlled one, whose higher GT was justified by AC<75th. Pregnancy outcome was better in M, with lower (p<0.05*) rate of LGA* (7.9% vs 17.9%), SGA (6.0% vs 9.0%) and Macrosomia* (3.3% vs 11.5%). CONCLUSIONS: Our data show the value of a flexible US-based approach to the treatment of GDM. This model does not necessarily involve a generalized aggressive treatment, allowing to concentrate therapeutical efforts on a small subgroup of women showing indirect US evidence of fetal hyperinsulinization. Such a selective approach allowed to obtain a near-normalization of fetal growth, with clear advantages on global pregnancy outcome.

Adult↗

PubMed2004

Chondrosarcoma of the epiglottis: report of a case treated with CO2 laser epiglottectomy.

Chondrosarcoma of the larynx is a rare slow-growing malignant tumour with approximately 240 cases reported in the literature: the cricoid cartilage is the most commonly affected site (72-75%), in rare case was described of epiglottis (1-2%). We report a case of a chondrosarcoma of the epiglottis treated with CO2 laser epiglottectomy. The patient was referred with dysphonia, dysphagia and halitosis that started four months before. Indirect laryngoscopy revealed a large smooth mass with a roundish appearance and a pearly-grey colour, as big as a nut, apparently arising from the laryngeal surface of the epiglottis, causing obliteration of the piriform fossa. The definitive histopathological report showed microscopically, the tumour was low-grade (grade I) chondrosarcoma. A literature review regarding chondrosarcomas of the epiglottis is presented. The diagnosis, histology and treatment of these tumours are discussed. In particular we examine the controversy of conservative surgery vs. total laryngectomy. A conservative surgical approach is typically appropriate in light of this tumour's low-aggressive nature.

Adult↗

PubMed2004

A case of highly aggressive adenoid cystic carcinoma of the external auditory canal.

Tumours of the external auditory canal are extremely rare and only 20% of these are of glandular origin. The most frequent histotype is adenoid cystic carcinoma. The rarity of external auditory canal glandular tumours explains the lack of large series reported in the literature and the corresponding large number of case reports from different Authors. Adenoid cystic carcinoma, presenting in the external auditory canal, exhibits the same characteristics as those affecting the major salivary glands, this tumour has an aggressive behaviour characterized by local invasivity and with a metastatic risk of approximately 30%. A rare case of adenoid cystic carcinoma of the external ear is reported. The patient, a 75-year-old male, had right intermittent otorrhea for 6 years. On examination, a vegetating, ulcerated formation which easily bled was found protruding from the right external auditory meatus. Clinical, radiological and pathological features of the tumour are described. A subtotal petrosectomy combined with homolateral elective lymph node neck dissection was performed. Parotid gland, condyle of the mandible and VII cranial nerve were spared since these were free from disease.

Aged↗

PubMed2003

Nasal application of immunotherapy.

BACKGROUND: In patients with allergic rhinitis local nasal immunotherapy (LNIT) appears to offer considerable advantages over other hyposensitization methods. The aim of our study was to obtain further confirmation of the validity of LNIT. METHODS: A randomized, double-blind, placebo-controlled study of LNIT in patients allergic to Parietaria and Dermathophagoides was performed. Patients were evaluated, before and after treatment, with symptom and medication scores, specific nasal provocation tests, anterior rhinomanometry and mucociliary clearance time. RESULTS: Compared to placebo the clinical efficacy of LNIT was confirmed by a reduction of clinical symptoms and drug intake. In the active group the reduction of allergen-specific nasal reactivity was significant. No local or systemic side effects were observed. CONCLUSIONS: The clinical efficacy of LNIT suggests that this therapy is effective in the prophylaxis of allergic rhinitis. Finally, there is no conflict between LNIT and drug treatment.

Administration, Intranasal↗

PubMed2002

Hepatosplenic gammadelta T-cell lymphoma presenting with immune-mediated thrombocytopenia and hemolytic anemia (Evans' syndrome).

We describe an unusual case of hepatosplenic T-cell lymphoma in a 61-year-old man who presented with fever, hepatosplenomegaly, anemia, and thrombocytopenia. A spleen biopsy was consistent with T-cell lymphoma. Cytogenetic studies did not reveal chromosome abnormalities. Using the polymerase chain reaction approach, clonality of the T-cell receptor gamma-chain gene rearrangement could be demonstrated, while Southern blot analysis disclosed only a germline configuration of the T-cell receptor beta chain genes. Of interest, an immune-mediated mechanism was demonstrated and was most likely responsible for erythrocyte and platelet destruction; this is, therefore, the first report of gamma T-cell lymphoma in association with Evans' syndrome. Initial steroid treatment was efficacious in limiting autoimmunity but constitutional symptoms did not subside. Chemotherapy (MACOP-B) was successful in obtaining complete clinical remission. Finally, thrombocytopenia in gammadelta T-cell lymphoma patients should be routinely evaluated for platelet autoantibodies.

Anemia, Hemolytic↗

PubMed2001

Occult lymph node metastases in supraglottic cancers of the larynx.

Occult cervical lymph node metastases may often be associated with cancers of the supraglottic larynx. The aims of this investigation were: (1) to determine the incidence of occult lymph node metastases in patients with cancer of the larynx; (2) to assess whether the presence of such metastases was related to the extent of the primary tumor (T) and its grading (G); and (3) to discuss which therapeutic approach should be followed in treating clinically occult lymph node metastases. Our investigation included 97 patients who underwent supraglottic horizontal laryngectomy and elective cervical lymph node dissection. The incidence of occult lymph node metastases in the series considered was 27%. Based on the preoperative staging of the tumor, 14% of the cases had metastatically involved lymph nodes in the T1 tumors, 21% in the T2 tumors, 35% in the T3, and 75% in the T4. In the statistical analysis, a significant difference was shown to exist when T1 + T2 and T3 + T4 (P = 0.04) were compared. In terms of grading, occult metastases were found in 16% of the G1 tumors, 27% of the G2, and 42% of the G3. The statistical analysis demonstrated a significant difference between G1 and G3. In brief, the incidence of occult metastases was higher for the less differentiated tumors and for the ones with a higher T value; the effects of both factors are combined thereby increasing the rate of occult metastases (P = 0.05).

Adult↗

PubMed2001

T2 tumors larger than five centimeters in diameter can be upgraded to T3 in non-small cell lung cancer.

OBJECTIVE: Among the TNM criteria, tumor size is a well-assessed factor in the prognosis of small tumors. A 3-cm cutoff point separates T1 from T2 tumors, whereas a size larger than 3 cm is not ascribed any prognostic value. Instead, N2 is considered to be the worst prognostic factor for intrathoracic extended disease. METHOD: The prognosis of 545 patients with non-small cell lung cancer larger than 3 cm in diameter (T2, T3, and T4) was studied. These tumors were completely resected by pneumonectomy (n = 126) or lobectomy (n = 411) or were partially resected (n = 8). Survivals were compared according to the following factors: tumor size (3.1-5 cm, 5.1-7 cm, >7 cm), nodal status, age, sex, histologic type, degree of pleural involvement, operative procedure, stage, and T factor. For the multivariate analysis, the Cox proportional hazard model was used with the same variables. RESULTS: The univariate analysis showed that age, sex, degree of pleural involvement, operative procedure, tumor size, nodal status, and stage were all significant prognostic factors. Further comparison of survival between different tumor sizes (< or =5 cm vs >5 cm) in the same nodal category demonstrated a significantly poor prognosis for larger tumors in N0 (P =.00374) and N2+N3 (P =.0157), but not in N1 (P =.3452). T2 tumors (n = 349) were divided, according to size, into T2a (n = 238) and T2b (n = 111), and survival was compared with those in T3 and T4. The 5-year survivals were 51.3%, 35.1%, 47.8%, and 25.3%, respectively. The difference between T2a and T2b was statistically significant (log-rank P =.0170, Breslow P =.0055). CONCLUSIONS: A tumor size of more than 5 cm in diameter was indicative of a poor prognosis in non-small cell lung cancer, because patients with T2b tumors had a significantly different survival from that of patients with T2a tumors, and the survival curve was located between those for patients with T3 and T4 tumors. Consequently, T2b might be upgraded to at least T3.

Aged↗

PubMed2001

Changes in serum interferon-gamma, interleukin-4, and interleukin-12 cytokine levels in anti-histamine type 2-treated allergic rhinitis patients.

OBJECTIVES/HYPOTHESIS: Markedly elevated immunoglobulin E (IgE) synthesis characterizes allergic diseases. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) regulate IgE synthesis. It has been shown that immunotherapy and histamine type 2 (H2) receptor antagonists induce a clinical improvement, decrease IgE antibodies, and increase T-cell subsets, which express a suppressor function. In addition, immunotherapy brings about a reduction in the amount of IL-4 in T-cell clones of allergic individuals. The purpose of this study was to investigate the profile of cytokines IFNgamma and IL-4 that occurs in vivo in anti-H2-treated patients with allergic rhinitis (AR). METHODS: Enrolled were 65 AR patients with sensitivity to a single allergen, the Parietaria, 36 of whom were randomly assigned to treatment with ranitidine at a dosage of 1 mg/kg per day intravenously for 20 days, and 29 to placebo treatment. RESULTS: A comparison of the serum cytokine values recorded before and after anti-H2 treatment showed a significant increase in INF-gamma serum level (P = .003) and a decrease in IL-4 (P = .016). Negligible variations were found in the placebo-treated group. CONCLUSION: H2 antagonists probably induce their effects by enhancing the amount of IFN-gamma and by reducing IL-4 cytokines, which, respectively, induce a decrease and an increase in the IgE synthesis.

Adolescent↗

PubMed2001

Management of chronic otitis media with effusion: the role of glutathione.

BACKGROUND: The inflammatory cells documented in chronic otitis media with effusion (OME) spontaneously release oxidants which can induce middle ear (ME) epithelial cell damage. Glutathione (GSH), a major extracellular antioxidant in humans, plays a central role in antioxidant defense. PURPOSE: To evaluate the effects of GSH treatment on chronic otitis media with effusion (OME). SUBJECTS AND INTERVENTION: Sixty children with chronic OME were enrolled, 30 of whom were randomly assigned to the treatment group and 30 to the placebo group. Patients in the treatment group received 600 mg glutathione in 4 mL saline per day subdivided into five 2-minute administrations given by nasal aerosol every 3 or 4 waking hours for 2 weeks. Patients in the control group received 4 mL saline per day following the same procedure as for GSH treatment. RESULTS: Three months after therapy improvement had occurred in 66.6% of patients in the GSH-treated group and in 8% of the control subjects (P <.01). CONCLUSION: On the basis of these results, GSH treatment could be considered for the nonsurgical management of chronic OME.

Child↗

PubMed2001

Tissue factor pathway inhibitor release induced by defibrotide and heparins.

We evaluated the release of tissue factor pathway inhibitor (TFPI) induced by defibrotide (DF), a single-stranded, negatively charged polydeoxyribonucleotide extracted from mammalian organ. Ten normal volunteers were injected with an intravenous bolus of 400 mg DF and 2,000 IU unfractionated heparin (UFH). In addition, three volunteers were also injected with an intravenous bolus of 2,000 anti-Xa U of two low-molecular-weight heparins (LMWHs), enoxaparin and nadroparin. UFH caused a 4-fold increase in plasma TFPI at 5 minutes, with a decrease that was parallel to the heparin level measured by the anti-Xa assay. However, at 80 minutes, although the plasma anti-Xa activity of UFH was almost undetectable, the level of TFPI remained 2-fold baseline. DF induced an increase of TFPI that was 2-fold higher than the baseline level, with a steady state achieved between 5 and 20 minutes. At 40 minutes, the TFPI levels returned to basal level. This pattern was not coincident with the clearance of DF and at 40 minutes, the concentration of DF was still one third of the levels at 5 minutes (25.4 +/- 4.04 microg/mL). Both of the LMWHs induced a similar TFPI peak level at 5 minutes (1.5-fold increase) and at 40 minutes the TFPI levels returned to the initial levels. At 5 minutes, both LMWHs showed a higher plasma anti-Xa activity than UFH, which was detectable even at 80 minutes. The current study demonstrated that one of the mechanisms of the antithrombotic activity of DF is mediated via TFPI. Furthermore, the release of TFPI by heparin is mediated by non-antithrombin III binding fragments. Thus, polyanionic electrolytes are capable of releasing TFPI irrespective of their antithrombin III effect.

Adult↗

PubMed2001

Plasma markers of endothelial dysfunction in pulmonary hypertension.

STUDY OBJECTIVES: To evaluate and to correlate endothelial cell dysfunction, using recently available plasma markers, with the magnitude of pulmonary artery pressure in patients with severe pulmonary hypertension (PH). DESIGN: Selected plasma markers of endothelial cell dysfunction were studied: nitric oxide (NO), thrombomodulin, tissue factor pathway inhibitor, and soluble endothelium, leukocyte, and platelet selectins (sE-, sL-, sP-selectins, respectively). SETTING: Padova University Hospital and Department of Pathology and Pharmacology, Loyola University of Chicago, Chicago, IL. PATIENTS: Fifteen patients had severe PH (four men and 11 women; mean age, 49.7 +/- 2.9 years: seven patients had primary pulmonary hypertension [PPH] and eight patients had secondary pulmonary hypertension [SPH]), and 20 patients were healthy control subjects. MEASUREMENT AND RESULTS: In patients with PH, sP- and sE-selectins were elevated, whereas sL-selectin was lower in comparison with the selectin levels in control subjects. However, the differences between patients with PH and control subjects were significant only for sL-selectin (p < 0.0001) and sE-selectin (p < 0.03). The NO level was significantly lower in patients with PH compared with the NO level in control subjects (p < 0.01). No difference in tissue factor pathway inhibitor level was noted between control subjects and patients with PH. Only a weak correlation was found between thrombomodulin plasma levels and magnitude of systolic pulmonary artery pressure (r = -0.528, p < 0.05). CONCLUSIONS: Our data are in keeping with the evidence for significant endothelial cell dysfunction in patients with PH and the need for chronic anticoagulation believed to increase survival in these patients. In addition, these data seem to suggest a need for newer agents that are able to increase the antithrombotic endothelial function.

Endothelium, Vascular↗

PubMed2001

[Microlaryngoscopy treatment of laryngeal dysplasia with CO2 laser].

Classification of laryngeal dysplasia, the most appropriate treatments and criteria for evaluation of the results is still a highly controversial issue. The objectives of the present study on the treatment of laryngeal dysplasia lesions are to: 1) evaluate the relative incidence of the various forms of dysplasia in relation to grading of the histopathological findings; 2) establish the prognosis for the various forms of dysplasia considered; 3) determine the results achieved by the author's treatment protocol according to the characteristics of the dysplasia; 4) critically evaluate the classifications of laryngeal dysplasia found in the literature in view of the results of the present study. The study involved 141 patients with vocal cord dysplasia (134 men, 7 women; mean age: 56.2 years) who had come under observation at the E.N.T. Dept. of the University of Naples "Federico II" between January 1981 and April 1998. In all cases the dysplasia was removed by CO2 laser microlaryngoscopy. Of the 141 patients 89 (63.2%) showed mild dysplasia, 14 (9.9%) moderate dysplasia, 20 (14.2%) severe dysplasia and 18 (12.7%) in situ carcinoma. The five-year survival rate showed an overall actuarial survival of 89.1% for all patients while the corrected actuarial survival was 98.5% and local disease control was 86.1%. In 17 cases (12%) the dysplasia lesion recurred, in 11 (7.8%) an infiltrating carcinoma arose. Recurrences in the dysplasia were encountered in 9% of the patients with mild lesions, 7.1% of those with moderate dysplasia, 15% of the subjects with the severe form and in 27.7% of those with in situ carcinoma. An infiltrating carcinoma arose in 5.6% of the cases of mild lesion, in 7.1% of the medium dysplasias, 5% of the severe forms and in 22.2% of those with in situ carcinoma. The recurrences and infiltrating carcinomas were successfully treated with endoscopic CO2 laser surgery. Only three cases (2.1%) required radical surgery (total laryngectomy): these were patients who had not quit smoking and who had not adhered to the planned follow-up. One of the latter patients died with widespread metastases of the laryngeal cancer. The significantly higher incidence of dysplasia recurrences (P = 0.028) and infiltrating carcinomas (P = 0.015) in those patients with in situ carcinoma shows that, when preparing classification and determining prognosis, these pathologies should be considered separately. Moreover, they require a particularly precise follow-up. In conclusion, the following observations can be drawn from the study: mild and moderate dysplasias are more frequent as compared to severe dysplasia and carcinoma in situ; carcinoma in situ should be distinguished for classification and prognosis from dysplasias, considering their different clinical course and evolution; CO2 laser surgery in these forms is a valid therapeutic approach for its precision, the achievable results, the reduced discomfort to patients and for its evident cost-effectiveness.

Adult↗

PubMed2001

Assembly of high molecular weight kininogen and activation of prekallikrein on cell matrix.

Investigations determined if extracellular matrix of endothelial cells (EC) is a platform for HK assembly and PK activation. In buffers containing bovine serum albumin, biotin-HK binding to ECV304 cells or their matrix requires > or = 50 microM added Zn2+. Ortho-phenanthroline or a HK domain 5 peptide blocks HK binding. Binding to umbilical vein EC or matrix, but not ECV304 cells or matrix, is mediated by cytokeratin 1. Biotin-HK binds to ECV304 cells or matrix with a Kd of 15.8 or 9.0 nM and a Bmax of 2.6 x 10(7) or 2.4 x 10(7) sites/cell, respectively. PK activation on ECV304 cells or matrix is blocked by antipain or SBTI and corn trypsin inhibitor partially inhibits kallikrein formation. PK activation occurs on ECV304 cells or matrix prepared without serum or in human factor XII deficient serum, indicating that the PK activator is not factor XIIa. EC matrix promotes plasminogen activation after the assembly of HK, PK and pro-urokinase. These studies indicate that matrix of various EC has the ability to assemble HK allowing for PK activation and subsequent activities.

Amino Acid Sequence↗

PubMed2000

The International Association for the Study of Lung Cancer (IASLC) worldwide educational program on lung cancer: a keynote address presented by the president of the IASLC.

BACKGROUND: In this keynote address presented at the American Cancer Society International Conference on Prevention and Early Diagnosis of Lung Cancer, Varese, Italy, in 1998, the genesis and the activities of the International Association for the Study of Lung Cancer (IASLC) are outlined. IASLC is devoted institutionally to promoting education and international cooperation in the entire field of lung carcinoma knowledge, from basic research to advanced strategies in treatment. From its foundation in 1974 by an international group of specialists from all medical branches concerned with lung carcinoma, the IASLC organized 8 world conferences and over 60 international workshops or symposia on lung carcinoma. Moreover, in recent years, IASLC has been instrumental in setting up postgraduate medical programs in countries that have limited resources and an increasing incidence of lung carcinoma.

Congresses as Topic↗

PubMed2000

Tissue factor pathway inhibitor levels in patients with homocystinuria.

Thrombotic events are a well-recognized complication of homocystinuria. However, the mechanisms involved in the atherogenic and thrombotic effects of homocyst(e)ine remain incompletely understood. The objective of this study was to determine the role of endothelial cell activation/damage as indicated by levels of thrombomodulin, tissue factor and tissue factor pathway inhibitor, and factor VII activity in patients with homocystinuria. Six patients with homocystinuria, nonresponsive to pyridoxine, treated only with trimethylglycine (betaine) were injected with a bolus of 20 IU/kg body weight of unfractionated commercial heparin to induce the release of tissue factor pathway inhibitor from the vascular endothelium. Tissue factor, thrombomodulin, and factor VII activity were measured by enzyme-linked immunosorbent assay and clotting assay before heparin administration. Tissue factor pathway inhibitor antigen and activity were measured before and 5 minutes after the bolus of heparin. Levels of homocyst(e)ine were elevated (patients: 144.2+/-19.2 micromol/L; controls: 10.2+/-0.9 micromol/L); however, levels of thrombomodulin, tissue factor, and tissue factor pathway inhibitor antigen were not statistically different from the control group. In contrast, tissue factor pathway inhibitor activity showed a significantly increased level (patients: 2.09+/-0.34 U/L; controls: 1.14+/-0.20 U/L; p<0.05) that was correlated with homocyst(e)ine. Factor VII activity was significantly decreased (patients: 64.7+/-5.1%; controls: 91.4+/-4.7%; p<0.05) and inversely correlated with homocyst(e)ine. After heparin the patients released higher amounts of tissue factor pathway inhibitor antigen and activity compared with the control group; however, the difference was not statistically significant. Although not treated with antithrombotic drugs, none of the patients had any thromboembolic complications after starting betaine. In addition to betaine treatment, the enhanced factor pathway inhibitor antigen activity observed in this small series of patients suggests that factor pathway inhibitor antigen may play an additional, as yet unexplained, role in this genetic disorder.

Adult↗