Deep venous thrombosis and pulmonary embolism in a patient with type III von Willebrand's disease, protein C and antithrombin III deficiency.
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Biomedical subjects
Publications and source records attributed to A Bloom.
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Chlorpromazine-induced liver damage is usually manifested by intrahepatic cholestasis. Hypoplastic bone marrow associated with agranulocytosis is a well-known side effect of chlorpromazine treatment. A 35-year-old woman with liver and bone marrow granulomas associated with agranulocytosis induced by chlorpromazine treatment is described.
Methicillin-resistant Staphylococcus aureus (MRSA) are now causing severe clinical infection on a worldwide basis. Pulmonary infection due to MRSA although widely reported is poorly documented. We report the predisposing factors, underlying diseases, treatment and outcome in 4 patients with pneumonia, 3 patients with empyema thoracis, 1 patient with pneumonia and empyema thoracis, 1 patient with pneumonia plus lobectomy wound infection and 2 patients with lung abscess. Vancomycin was highly effective in treatment, a finding compatible with experience treating other severe MRSA infections.
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Defective platelet thromboxane synthesis has been described in uraemia and attributed to a 'functional cyclooxygenase defect'. We have studied platelet aggregation and generation of immunoreactive thromboxane B2 (TXB2) in 11 subjects on a chronic haemodialysis programme. The platelet function abnormality of uraemia was confirmed, maximal aggregation in response to collagen (2 and 4 micrograms/ml) and sodium arachidonate (1.5 and 3.0 mM) being significantly depressed. However, increased platelet aggregation in response to sodium arachidonate 0.75 mM was noted. Due to the reduced haematocrit, the platelet concentration in platelet-rich plasma (PRP) of uraemic subjects was significantly lower than that of controls; when TXB2 generation in PRP adjusted to 200 X 10(9) platelets/l was assessed, no evidence for a defect of cyclooxygenase was found, although reduced synthesis of TXB2 in response to thrombin was noted. Furthermore, increased thromboxane generation by uraemic PRP in response to sodium arachidonate 0.75 mM was detected. We conclude that the mild platelet abnormality in uraemic subjects treated by haemodialysis is not explained by a 'functional cyclooxygenase defect', although an abnormality of thrombin-induced thromboxane synthesis may be present. Furthermore, the tendency to increased aggregation and thromboxane synthesis in response to a low concentration of arachidonic acid may contribute to the thrombotic tendency which is also described in such subjects.
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We report a patient with hemoperitoneum from rupture of intraperitoneal varices. Hemoperitoneum is rare. Nevertheless, it should be easily recognized in a patient with abdominal pain and distension, a falling hematocrit in the absence of external blood loss, and gross blood in the abdominal fluid. The syndrome is another justification for early paracentesis in patients with abdominal fluid. Mortality remains high despite surgical correction of the bleeding and reflects the severity of the underlying liver disorder.
A method is described to produce radiographs of thin sections of human teeth and periodontal structures. These high resolution contact x-rays allow for visualization of the microscopic details of the mineralized components of these tissues in a dimension heretofore not examined. Twenty-five blocks of human jaws containing teeth affected by periodontal disease were obtained from cadavers. Sagittal, transverse and cross-sectional serial slices were cut using a rotary instrument (1500 rpm) with a water-cooled 3-inch jewelers slot saw. Five hundred-micron sections were made of jaw specimens containing 2 or 3 teeth. The radiographs were taken with a Faxitron low voltage x-ray machine on Kodak-Ortho, Type 3 film. Films were exposed at a distance of 12 inches from the x-ray source at 35 kVp and 1.0 mA for 3 minutes with the specimen in direct contact with the film. Spatial representation of the internal structure of the alveolar bone was obtained using this technique and the detailed anatomy of the vascular channels within the cancellous and cortical compartments of the jaws was studied. Mineralization patterns of plaque and calculus, calcifications in the periodontal ligament, pulp calcifications, accessory root canals, caries and detailed structural changes in the enamel and cementum were also viewed on these films with the aid of microscopy. Magnifications of up to 30 times were used without excessive image distortion resulting from film grain.
Platelet aggregation and thromboxane synthesis and platelet sensitivity to the antiaggregatory action of prostaglandin I2 were studied serially in a subject suffering from adult hemolytic-uremic syndrome. Platelet aggregation in vitro was defective during the acute phase of the disease and recovered during the convalescent phase. Defective aggregation was not associated with a failure of thromboxane synthesis although it was related to an intrinsic platelet defect rather than an inhibitor in the plasma. The platelets were insensitive to prostaglandin I2, even in the recovery phase of the disease. Furthermore, plasma from the patient rendered normal platelets insensitive to prostaglandin I2 and more sensitive to aggregating agents. It is concluded that the platelet abnormality in hemolytic-uremic syndrome is complex and it combines both an intrinsic platelet abnormality and a plasma component.
Restriction mapping of the globin genes from a homozygous delta beta thalassemia patient from Israel indicates that at least a 10-kilobase deletion is present extending 3' from within the large intervening sequence (IVS 2) of the delta globin gene and including the entire beta globin gene. Unique bands are seen when cellular DNA from this patient is digested with a variety of restriction endonucleases and hybridized with a probe specific for the delta IVS 2. Extensive analysis of the Israeli delta beta thalassemia DNA as well as material from an Italian delta beta thalassemia homozygote with enzymes which cleave more frequently in delta IVS 2 has localized the 5' end of the deletion to a 107-base pair region within delta IVS 2. This region contains a unique repetitive sequence (TG)4 which has been reported to be a specific recognition signal for recombination and may be involved in the formation of these mutant genes. Two homozygous delta(0) thalassemia DNA samples from Japan were also analyzed for gene rearrangements or other changes by restriction enzyme mapping. No changes from normal were seen using 14 different enzymes indicating the absence of large deletions in the region around the delta globin gene. More specifically, both the 5' and 3' splice junctions of the IVS 2 appear to be normal from hybridization of restriction fragments generated by HphI and AluI, respectively, with a delta IVS 2 specific probe. We have also shown that point mutations which could lead to termination codons are not present at codons 35, 37, 43, 61, and 121, since restriction enzymes which recognize these sites produce normal patterns. The delta(0) thalassemia phenotype in these two subjects is most likely due to a point mutation either at one of the other 24 potential termination codons not accessible to restriction analysis or to other single nucleotide changes which could either decrease delta globin gene transcription or lead to abnormal processing or transport of delta globin mRNA.
Hemoglobin Miyada, an anti-Lepore hemoglobin, represents the protein product of a nonhomologous crossover between beta and delta genes. The mutant globin is beta-like from the N terminus to amino acid 12, and delta-like from amino acid 22 through the C terminus, thus predicting a crossover site in the first coding region of the gene. DNA analysis, using multiple restriction endonucleases and hybridization to delta and beta globin gene-specific probes, confirms that the beta delta hybrid gene 1) is located on a single chromosomal fragment between normal delta and beta genes, and 2) has 5' beta promoter sequences, delta IVS 1 and 2, and 3' coding and flanking sequences.
Gel filtration (sepharose 2B CL) patterns of factor VIII coagulant antigen (VIIIC:Ag) and factor VIII related antigen (VIIIR:Ag) were obtained using normal plasma and plasma from patients with von Willebrand's disease. The latter group consisted of five individuals with normal mobility of factor VIIIR:Ag on cross-immunoelectrophoresis (Type I) and five others with abnormal (increased) mobility (Type II). Results showed that the elution of VIIIC:Ag was delayed in those subjects whose ratio of VIIIR:Ag to VIIIC:Ag was reduced. It has previously been reported that VIIIR:Ag exerts a stabilizing influence on the coagulant activity of factor VIII (VIII:C); our data suggests that when VIIIR:Ag is deficient, abnormal (low molecular weight) forms of VIIIC:Ag circulate.
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