A de novo intragenic deletion of the potential EGF domain of the factor IX gene in a family with severe hemophilia B

We have studied a family of three patients who were severely afflicted with hemophilia B without inhibitor for their factor IX genes through the use of factor IX cDNA and genomic DNA probes. The patients had detectable (30% of normal) factor IX antigen. DNA hybridization analysis demonstrated that these patients had a partial intragenic deletion in their factor IX gene. This 2.8-kb deletion included exon d and the surrounding sequences. This exon codes for the amino acid sequence from No. 47 through 84 of the factor IX protein and contains its first potential EGF domain; the de novo occurrence of the mutation in the grandfather's germ cells was established by linkage analysis. This specific gene has been named F IXStrasbourg.     

The ultrastructural localization of immunoglobulins in human b cells of immunoproliferative diseases

The cellular distribution of immunoglobulins in human malignant and normal B cells was investigated by immunoelectron microscopy by direct incubation of fixed cells with electron microscopy by direct incubation of fixed cells with peroxidase-coupled antibody. These conjugates penetrated into the cell, resulting in the simultaneous detection of surface and cytoplasmic immunoglobulins. The latter were seen as specific intracisternal staining of the perinuclear space and endoplasmic reticulum and occasionally of the Golgi complex. Plasma cells were frequently characterized by a heterogeneity of reactivity of the endoplasmic reticulum. Minute amounts of cytoplasmic immunoglobulin were demonstrated in cells without developed secretory organelles, such as lymphoma cells and lymphocytes from chronic lymphocytic leukemia (CLL). The method allowed us to define several subsets of cells according to the expression of surface and cytoplasmic immunoglobulins and thus to determine the stage of maturation of cells involved in monoclonal proliferation.     

In vitro effects of argon laser radiation the human healthy and atherosclerotic aorta

Argon laser exposures in vitro were done on human aortas. The laser energy applied on a fresh aorta section (A) was from 100mw to 1000mw. A second aorta section (B), formalin fixed, was irradiated under saline solution by a fiberoptic system. Laser energy was from 400mw to 720mw. The time exposures were all different in both sections. A and B histologic findings of thermal damage were similar Three zones of tissue injury were observed: I) crater because of tissue vaporization; II) coagulative necrosis surrounding it; and III) multiple vacuoles in the adjacent tissue produced by acoustic or shock injury. Tissue damage was related directly with total energy delivered: less than or equal to 500mw showed inner vascular wall necrosis, and at greater than or equal to 720mw it was perforated. Atherosclerotic tissue was more resistant to laser thermal injury than normal tissue. We could not find time relation with thermal damage. This preliminary information is an early step for the possible use of Argon laser on cardiovascular area.     

High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) [see comments]

Resistance to activated protein C (APC) is a common inherited risk factor for venous thrombosis, which is associated with a mutation in coagulation factor V (factor V Leiden). We investigated the risk of venous thrombosis in individuals homozygous for this abnormality. We determined the factor V Leiden genotype in 471 consecutive patients aged less than 70 years with a first objectively confirmed deep-vein thrombosis and in 474 healthy controls. We found 85 heterozygous and seven homozygous individuals among the cases with thrombosis and 14 heterozygous individuals among the control subjects. The expected number of homozygous individuals among the controls was calculated from Hardy-Weinberg equilibrium and estimated at 0.107 (allele frequency, 1.5%). Whereas the relative risk was increased sevenfold for heterozygous individuals, it was increased 80-fold for homozygous individuals. These patients experienced their thrombosis at a much younger age (31 v 44 years). The homozygous individuals were predominantly women, most likely due to the effect of oral contraceptives. Because of the increased risk of thrombosis with age, the absolute risk becomes most pronounced in older patients, both for heterozygous and homozygous individuals. For the homozygous individuals, the absolute risk may become several percentage points per year. This implies that most individuals homozygous for factor V Leiden will experience at least one thrombotic event in their lifetime.     

De novo subgaleal abscess

The authors report a case of spontaneous subgaleal abscess formation in a 62-year-old woman without antecedent trauma or injury. She presented with occipital scalp pain and swelling which rapidly became generalized two days following recovery from an upper respiratory infection. Diagnosis was based on radiological examination and aspiration of the subgaleal space, which yielded a purulent exudate with a pure growth of Streptococcus pyogenes. Initial management with incision, drainage and parenteral antimicrobial therapy was not successful. Operative exploration of the subgaleal space revealed extensive necrosis of the galea aponeurotica, and bone curettings revealed microscopic evidence compatible with osteomyelitis. Management with debridement and excision of all necrotic tissue plus prolonged parenteral antimicrobials was successful. Subgaleal abscess formation without an overlying wound or previous trauma has not been reported previously.     

Acute thrombocytopenic purpura in relation to the use of drugs

The relation of acute thrombocytopenic purpura (TP) to the use of drugs was investigated in a case-control study conducted in eastern Massachusetts, Rhode Island, and the Philadelphia region; 62 cases over the age of 16 years with acute onset and with a rapid recovery were compared with 2,625 hospital controls. After control for confounding by multiple logistic regression, use of the following drugs in the week before the onset of symptoms was significantly associated: trimethoprim/sulfamethoxazole (relative risk [RR] estimate, 124), quinidine/quinine (101), dipyridamole (14), sulfonylureas (4.8), and salicylates (2.6). The overall annual incidence of acute TP was estimated to be 18 cases per million population. The excess risks for the associated drugs were estimated to be 38 cases per million users of trimethoprim/sulfamethoxazole per week, 26 per million for quinidine/quinine, 3.9 per million for dipyridamole, 1.2 per million for sulfonylureas, and 0.4 per million for salicylates. Associations with sulfonamides, quinidine/quinine, sulfonylureas, and salicylates have been previously reported, but the present study has provided the first quantitative measures of the risk. The association with dipyridamole was unexpected. In general, despite large RRs, the incidence rates attributable to the drugs at issue (excess risks) were low, suggesting that TP is not an important consideration in the use of the various drugs.     

Successful donor cell engraftment in a recipient of bone marrow from a cadaveric donor

A 12-year-old male with acute lymphocytic leukemia received donor bone marrow from his histocompatible father whose marrow was harvested 40 minutes postmortem after he suffered a myocardial infarction. The marrow was stored in liquid nitrogen for 17 days prior to infusion into the recipient. Trypan blue viability was greater than 99% for the fresh marrow. Progenitor cell assays revealed that 20% of the CFU-MIX, 16% of the BFU-E, 10% of the CFU-E, and 17% of the CFU-GM were spared during the cryopreservation period. Posttransplantation, the recipient had a leukocyte count greater than 10(3)/microL by day 26. Southern blotting analysis documented the donor origin of the peripheral blood mononuclear cells and granulocytes isolated 46 days posttransplantation. Unfortunately, the patient died of complications relating to graft-v-host disease 67 days following transplantation. This case demonstrates the feasibility of cadaveric marrow as a source of donor cells and is the first reported case of documented leukocyte engraftment in a recipient of cadaveric marrow.     

Proarrhythmic and antiarrhythmic effects of intravenous prostacyclin in man

Prostacyclin (PGI2) has been shown to reduce the occurrenceof experimental ventricular arrhythmias. To assess potentialbeneficial effects in man, the electrophysiological action ofPG12 was studied in 16 non medicated patients. The protocolused in incremental pacing and programmed stimulation in theright atrium and ventricle. This protocol and measurement ofeffective refractory periods (ERP) were performed before andduring the injection of 2.5, 5 and 10 ng kg^–1 min^–1of PGI2. The atrial functional refractory period decreased significantly(P<0.05); PGI2 had no influence on the occurrence of induciblenon-sustained (NS) atrial tachycardias and was responsible forthe occurrence of 2 non-sustained atrial tachycardias in 8 patientswith inducible atrial echo beats under basal conditions. Thirteenpatients did not have inducible ventricular tachycardia ( VT)under basal conditions. Non-sustained VT was induced after PGI2in 4 of them but in only 1 of them after the administrationof propranolol. Three patients had inducible VT under basalconditions (1 non-sustained, 2 sustained VT). PG12 did not preventthe occurrence of VT (1 non-sustained, 1 sustained VT), exceptin 1 patient with ischaemic-related VT, who had non-sustainedVT after PGI2. In conclusion, PGI2 does not seem to have a cardiacantiarrhythmic effect and may increase the atrial and ventricularrepetitive response. This effect could be related to an increaseof adrenergic tone.     

Reproducibility of the index of orthognathic functional treatment need scores derived from plaster study casts and their three-dimensional digital equivalents: a pilot study

Objective: To determine the reproducibility of Index of Orthognathic Functional Treatment Need (IOFTN) scores derived from plaster casts and their three-dimensional (3D) digital equivalents.

Design: Pilot study, prospective analytical.

Setting: UK hospital orthodontic department.

Participants: Thirty casts and their digital equivalents, representing the pre-treatment malocclusions of patients requiring orthodontic-orthognathic surgical treatment, were scored by four clinicians using IOFTN.

Methods: Casts were scanned using a 3Shape digital scanner and 3D models produced using OrthoAnalyzer^TM (3Shape Ltd, Copenhagen, Denmark). Examiners independently determined the IOFTN scores for the casts and digital models, to test their inter- and intra-operator reliability using weighted Kappa scores.

Results: Intra-operator agreement with IOFTN major categories (1–5: treatment need) was very good for plaster casts (0.83–0.98) and good-very good for digital models (0.78–0.83). Inter-operator agreement was moderate-very good for casts (0.58–0.82) and good-very good for digital models (0.65–0.92). Intra-operator agreement with IOFTN sub-categories (1–14: feature of malocclusion) was good-very good for casts (0.70–0.97) and digital models (0.80–0.94). Inter-operator agreement was moderate-good for casts (0.53–0.77); and moderate-very good for the digital models (0.58–0.90).

Conclusions: Digital models are an acceptable alternative to plaster casts for examining the malocclusion of patients requiring combined orthodontic-orthognathic surgical treatment and determining treatment need.