Complex-dependent inhibition of factor VIIa by antithrombin III and heparin

The regulation of the factor VIIa-tissue factor complex is essential for control of the hemostatic response. However, the role of the inhibitor antithrombin III in the regulation of factor VIIa has remained in question. The inhibition of factor VIIa activity by antithrombin III and heparin in the presence and absence of tissue factor was evaluated using the fluorescent substrate m-LGR-nds. Our data show that the activity of recombinant human factor VIIa is inhibited by antithrombin III in the presence of heparin at a rate of 1.7 x 10(2) M-1 s-1. In the presence of tissue factor, the rate constant for this reaction increases to 5.6 x 10(3) M-1 s-1. A 1:1 stoichiometric complex between factor VIIa and antithrombin III, with an apparent molecular weight of 110,000, was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A heterogeneous mixture of factor VIIa products with molecular weights between 50,000 and 80,000, most likely representing proteolytically degraded factor VIIa-antithrombin III complexes, was also observed.     

Systemic candidiasis in the newborn. Report of 3 cases

In two related studies, a pictorial sorting task served as the means of measuring conceptual development in LD and normal boys. The studies found no differences in the bases on which groups were formed (perceptible attributes, function, or nominal class membership) or in the manner in which groups were structured (thematically, in complexive groups or superordinate groups). Furthermore, parallel developmental trends were found in both LD and normal subjects groups. These findings are not consistent with early studies of concept formation in brain-damaged subjects, most of whom were retarded. Subjects in the present studies were selected on the basis of clinical diagnosis of LD and average IQ. The findings of the present studies suggest that generalizations about conceptual abilities of LD children of normal intelligence should not be based on early studies of the effects of brain damage.     

Massive pulmonary hemorrhage in newborn infants successfully treated with high frequency oscillatory ventilation

The micellization process of bovine rod outer segment (ROS) membranes is investigated utilizing a series of neutral detergents. It is found that when alkyl(thio)glucosides with an appropriate hydrophillic-lipophilic balance (e.g. octylthioglucoside) are used in combination with a divalent cation, rhodopsin is selectively extracted from ROS membranes at a specific detergent-to-membrane ratio. This allows remarkable purification of rhodopsin by a single-step solubilization, because the residual membranes are heavily aggregated in the presence of divalent cation and are therefore easily sedimented by low-speed centrifugation. The absorption spectrum of the supernatant reproducibly exhibits an A280/A500 value of 1.6, an excellent value that could rarely be obtained by chromatographic purification. The degree of purification also depends on the type of divalent cation included in the solubilization solution; specific binding of IIB-series cations (Zn2+ and Cd2+) to ROS membranes is suggested to play an important role in the solubilization process. The present result represents a unique example of selective solubilization of a specific membrane protein from highly aggregated membranes.     

Amyloid goiter. Report of two cases

Congenital pedicle abnormalities are rare. Unilateral aplastic and hypoplastic lumbar pedicles have been reported, but these were usually discovered incidentally and did not need surgical treatment. We present a case of absence of both pedicles and the neural arch of L2, with associated kyphoscoliosis with neurological involvement, that needed a two-stage corrective surgery. An L1-L4 fusion was achieved with relief of the symptoms.     

Granulomas and cholestatic--hepatocellular injury associated with phenylbutazone. Report of two cases

A combined cholestatic-hepatocellular injury and noncaseating granulomas occurred in two patients 1 and 4 weeks after phenylbutazone therapy. Both patients were jaundiced, one had a macular rash, and both had peripheral blood eosinophilia. Symptoms and signs subsided, and abnormal findings from tests of hepatic function rapidly returned to normal following withdrawal of the drug. Sections of liver biopsy specimens 6 months later showed no granulomas or other pathologic changes. Previously reported cases are reviewed.     

Persistent hypoglossal artery associated with aneurysms. Report of two cases

The approach to management of idiopathic thrombocytopenic purpura (ITP) during pregnancy remains controversial--particularly regarding the method of delivery. Regardless of the maternal platelet count, we believe that these patients should be delivered by elective cesarean section at term because of the continued presence of maternal antiplatelet IgG antibodies, which cross the placenta. Despite the method of treatment used to increase maternal platelets, immunologic factors are significnat for neonatal involvement and should be considered in the management of these patients. The single largest factor responsible for reported neonatal losses has been intracranial hemorrhage secondary to thrombocytopenia and birth injury. Two patients with ITP are presented with data to substantiate our position on the method of delivery. The infants were transiently thrombocytopenic following delivery (despite adequate maternal levels of platelets).     

Inflammatory pseudotumor of the liver. Report of two cases

Hypersensitivity reactions from trimethoprim/sulfamethoxazole are likely caused by a reactive nitroso intermediate formed from sulfamethoxazole hydroxylamine. This pilot study tested whether cimetidine inhibits the urinary excretion of sulfamethoxazole hydroxylamine. Ten outpatients infected with human immunodeficiency virus (HIV) and currently receiving trimethoprim/sulfamethoxazole prophylaxis were randomly selected from 59 eligible patients. Five received cimetidine 800 mg twice daily for 1 week and five served as controls. Two spot urine samples one week apart were obtained after a trimethoprim/sulfamethoxazole dose for all patients. Patients taking cimetidine had a significant decrease in excretion of sulfamethoxazole hydroxylamine relative to total excreted drug in the two urine samples compared with control patients. Cimetidine likely caused this decrease in sulfamethoxazole hydroxylamine excretion through inhibition of CYP3A4. Because of potential differences between HIV-infected patients and healthy subjects in oxidative metabolism, future studies of inhibitors of sulfamethoxazole hydroxylamine formation should be conducted in the HIV population.     

Post-traumatic flank hernias. Report of two cases

Dissecting aneurysms of the hepatic artery are extremely rare. We report herein the case of a 51-year-old man with massive hepatic metastases from rectal carcinoma, who was found incidentally to have a left hepatic artery aneurysm by a preoperative angiography. After replacing the left hepatic artery with a 2-cm segment of long saphenous vein, an extended right lobectomy with partial resection of the left lateral segment for multiple metastases was successfully performed. To prevent thrombus formation at the anastomosis, the Pringle maneuver was not used during dissection of the hepatic parenchyma. Histological examination of the resected specimen showed a dissecting aneurysm of the left hepatic artery, but there were no findings to suggest the etiology of this disease. The patient is currently alive 13 months after his operation without any evidence of further recurrence of the carcinoma. To the best our knowledge, 12 case reports of this anomaly have been documented, but only one of these describes a successful operation. The clinical features and etiology of the hepatic artery aneurysm that develops independent of other vascular diseases are discussed following this case report.     

Giant-cell arteritis of the uterus. Report of two cases

Two cases of giant-cell arteritis of uterus were found incidentally in association with uterine prolapse. One similar case has been reported in the literature. Microscopic examination disclosed fragmentation of the elastic laminae of the myometrial arteries with a giant-cell and mononuclear infiltrate. The relationship between giant-cell arteritis of the uterus, temporal arteritis, and polymyalgia rheumatica is discussed in view of similar cases reported in the literature.     

Metastatic carcinoma to the mandible. Report of two cases

Two cases of rare metastases from malignant neoplasms to the posterior mandible in young adults are reported. Multiple imaging modalities were necessary to identify the many metastases and, in one case, the suspected primary site. Many of the radiographic images are presented for that case.     

Osteopetrosis and total hip arthroplasty. Report of two cases

In a 47-year-old male cadaver the splenic artery traveled partially through the substance of the pancreas. Additionally, the pancreas was apparently large and had an unusual shape; the neck of the organ could not be differentiated; the uncinate processus was absent; two pancreatic ducts were present. The probable reason for this combined anomaly was abnormal fusion of the ventral and dorsal pancreatic buds due to different levels of origin.     

Spontaneous drainage of syringomyelia. Report of two cases

Two cases are reported of Arnold-Chiari type I malformation associated with syringomyelia, in which magnetic resonance (MR) imaging revealed spontaneous decompression of the syrinx. In one case axial MR imaging sections showed a communication between the syrinx and the spinal subarachnoid space, which supports the hypothesis that fissuring of the cord parenchyma is instrumental in the spontaneous resolution of syringomyelia. The MR imaging changes were not accompanied by variations in the patients' clinical course.     

The binding of 1-anilino-8-naphthalenesulfonate, heparin, salicylate and caprylate by human antithrombin III

The binding of 1-anilino-8-naphthalenesulfonate to human antithrombin III was studied by fluorescence enhancement of the fluorophor and fluorescence quenching of the protein emission. Two molecules of 1-anilino-8-naphthalenesulfonate were found to bind per antithrombin molecule with an average dissociation constant of 4.4-10(-5) M. The binding of heparin to antithrombin was studied by ultraviolet difference spectroscopy. The stoichiometry of the heparin binding indicated 1.8 binding sites with an average dissociation constant of 4.3 - 10(-6) M. Further the fluorometric competition experiments with 1-anilino-8-naphthalenesulfonate, heparin, salicylate and caprylate indicated two different classes of anion binding sites on the antithrombin molecule.     

Heparin, low molecular weight heparin, heparinoid, and antithrombin III therapy of disseminated intravascular coagulation

OBJECTIVE: To determine features of fractures in young children that would be helpful in distinguishing child abuse from unintentional injuries. DESIGN: Case series. SETTING: Pediatric Services of Yale-New Haven (Conn) Hospital (a tertiary care center). PATIENTS: Consecutive children who were less than 3 years of age and who were examined for a fracture from January 1979 through December 1983 were identified from the daily logs of the emergency department or the hospital's child abuse registry. OUTCOME MEASURE: Each case was rated, by means of predefined criteria and a consensus of two clinicians and two pediatric radiologists, on a seven-point scale from "definite child abuse" to "definite unintentional injury." A middle rating of "unknown" was used if there was not enough information to reach a consensus. RESULTS: Of the 253 fractures in 215 children that were identified, we categorized 24.2% as abuse, 8.4% as unknown, and 67.4% as unintentional injuries. Fractures that were considered likely due to abuse were (1) fractures in children whose caretakers reported either a change in the child's behavior, but no accidental event, or a minor fall, but the injury was more severe than expected; (2) fractures of the radius/ulna, tibia/fibula, or femur in children less than 1 year of age; or (3) midshaft or metaphyseal fractures of the humerus. Linear fractures of the parietal bone were the most common skull fractures, whether due to abuse or unintentional injuries. CONCLUSION: In young children with fractures, child abuse is common. By comparing fractures due to abuse and those due to unintentional injuries, we obtained empiric evidence to help clinicians and radiologists correctly examine children with such serious injuries.     

Orbital involvement by plasmacytoma. Report of two cases

Two patients with orbital involvement of plasma cell myeloma are presented. The first patient presented an isolated plasmacytoma in the orbit; the second patient had generalized plasma cell myeloma. In both cases X-rays and computed tomographic scanning gave valuable information and biopsy confirmed the diagnosis.     

Antenatal thalamic lesions in the newborn: two anatomoclinical cases

We report two cases of antenatal bilateral thalamic lesions constituted by neuronal loss, gliosis and mineralized glial or neuronal cells. No etiology could be found. Neuroradiological findings were poorly correlated with histological changes. These cases are compared with the few previously reported cases of the same condition. We strongly recommend extensive etiological investigation as recurrence occurred in one family.     

Breast hamartoma with invasive ductal carcinoma. Report of two cases and review of the literature

Two cases of well-defined masses also containing clinical and radiographical abnormalities suggestive of malignancy, subsequently found to be invasive ductal carcinomas in breast hamartomas are described. The patients were 53 and 78 years old. Both presented with a generally soft palpable breast lump, containing a firm area which in one case invaded and ulcerated the skin. Mammography demonstrated two typical hamartomas: one containing a spiculated opacity, the other irregular opacities with suspicious calcifications, suggesting the presence of carcinomas in these benign lesions. The cut surface of these well-circumscribed masses measured 5 cm and 7 cm. The microscopic appearance was characteristic of breast hamartoma (sharp circumscribed "pseudocapsule" surrounding breast fibrocystic changes with variable amounts of adipose tissue) with the firm area in each case corresponding to invasive ductal carcinoma. In one case the invasive ductal carcinoma was confined to the hamartoma, whereas in the other malignant tumor, cells extended beyond the surrounding breast tissue and infiltrated the skin. These findings raise the question of secondary involvement of a hamartoma by invasive carcinoma. Breast hamartomas are probably underrecognized lesions. In our view, these findings do not justify a more aggressive approach towards the management of breast hamartomas.