Fabry disease in unselected patients with TIA or stroke: population-based study.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder frequently associated with cerebrovascular disease. In recent years, the prevalence of FD has been reported to be up to 4% in cryptogenic young stroke patients. However, there have been no population-based studies in unselected patients with transient ischaemic attack (TIA) or stroke across the full range of ages. METHODS: We determined the prevalence of FD mutations in consecutive patients from a population-based study of acute TIA or ischaemic stroke (Oxford Vascular Study). Analysis included amplifying of the α-galactosidase A gene by polymerase chain reaction, denaturing high-performance liquid chromatography (dHPLC) analysis and sequencing using standard automated sequencing protocols [Mutation Surveyor software (Softgenetics)] where the dHPLC indicated a possible mutation. RESULTS: Samples of 1046 consecutive patients (52% women; mean age 73.2 years; 15% age <60 years; 572 stroke; 474 TIA) were tested. No patient had a known gene mutation causing FD, giving an upper 95% confidence interval around the estimated frequency of 0.35% overall and 2.37% in the 154 patients aged under 60 years. However, in 5 (0.48%) samples, a known polymorphism or sequence variation in the gene was identified that can be associated with lower than normal enzyme activity in plasma without causing the full clinical manifestation of FD. CONCLUSIONS: Fabry disease is rare in an unselected group of UK patients with TIA or stroke. Larger studies in unselected younger patients with cryptogenic stroke are required to determine whether routine screening is justified in this group.

Turnover of myofibrillar proteins in cultured muscle cells from normal and dystrophic chick embryos.

Rates of protein degradation and synthesis were determined in myofibrillar and non-myofibrillar fractions and in myofibrillar subunits of cultured muscle cells from normal and dystrophic chick embryos of genetically closely related lines. Growth characteristics of normal and dystrophic cells were identical as measured by DNA, RNA and protein accumulation. Degradation rates of myofibrillar and non-myofibrillar protein determined from label-chase experiments were the same in normal and dystrophic cultures. In similar experiments in which degradation rates of eight different components of the myofibrillar fraction were measured, a spectrum of degradation rates was obtained indicating that myofibril components turn over individually or in groups, rather than as an intact unit. Myosin heavy chain was the slowest turning over component of those measured, while actin was among the most rapid. No differences were found between normals and dystrophics in the turnover of any of the components. Fractional rates of protein synthesis were also determined for the myofibrillar and non-myofibrillar fractions of cultured cells. The rates obtained with normal and dystrophic cells were indistinguishable and were the same for the myofibrillar and non-myofibrillar fractions. Initial amino acid incorporation rates into 17 separate components of the myofibrillar fractions were compared in normal and dystrophic cells. No significant differences were found.

Hemostatic changes in heart transplant recipients and their relationship to accelerated coronary sclerosis.

Hemostasis was assessed in 115 steady-state heart transplant recipients (HTRs) and compared with that of 23 age-matched healthy controls and 21 age-matched patients with ischemic heart disease (IHD). Compared with the controls, the HTRs had increased levels of fibrinogen (mean and 95% confidence limits of 4.50 [4.32-4.68] g/L versus 3.47 [3.07-3.87] g/L, P < 0.001), factor VIIC (1.16 [0.98-1.21] IU/ml versus 0.99 [0.89-1.10] IU/ml, P < 0.001), and von Willebrand factor antigen (1.72 [1.58-1.88] IU/ml versus 1.00 [0.80-1.26] IU/ml, P < 0.001). HTRs had increased antithrombin III activity (P = 0.002) and protein C activity (P = 0.002), with a decrease in total protein S levels (P < 0.001) but no change in free protein S levels. Stepwise discriminant analysis of hemostatic variables showed that fibrinogen was the best discriminator of the three groups, classifying 55.6% of HTR, 40% of IHD, and 66.7% of the controls. More marked prothrombotic changes were found in HTRs transplanted for IHD than for other causes; this reached significance for prothrombin (P = 0.048), factor IX (P = 0.003), and poor fibrinolytic activity as measured by euglobulin clot lysis time (P = 0.008). The HTRs with accelerated coronary sclerosis (ACS) tended to have the most prothrombotic changes; this reached significance with factor IX (P = 0.03). In conclusion, HTRs have perturbed hemostasis; the net effects of these changes are prothrombotic. The relationship between prothrombotic changes and ACS merits further studies.

Allograft and xenograft rejection in C3H/SCID mice. A new model for the study of non-T cell graft rejection mechanisms.

Comparative cell transfer experiments have revealed that, despite their equal immune deficiency, C3H/SCID mice were markedly inferior compared with C.B-17/SCID mice in their ability to accept allogeneic and xenogeneic grafts. Allogeneic C.B-17/SCID bone marrow cells were engrafted poorly compared with syngeneic C3H/SCID when transplanted into C3H/SCID recipients, whereas cells of both strains were equally well engrafted into C.B-17/SCID mice. C.B-17/SCID mice were much more permissive for outgrowth of human Burkitt lymphoma (Raji), as well as for Epstein-Barr virus lymphoma development after transplantation of human peripheral blood lymphocytes. Human skin grafts were accepted by the C.B-17/SCID mice but were promptly rejected by the C3H/SCID mice. The resistance to human RaJi cells could be adoptively transferred by infusion of C3H/SCID splenocytes into C.B-17/SCID mice. Because the C.B-17/SCID and C3H/SCID mice equally lack both T and B lymphocytes, the latter may provide a relevant model for studies of non-T mechanisms of allograft or xenograft rejection.

Fibrinolytic activity during orthotopic liver transplantation with and without aprotinin.

Hyperfibrinolysis during orthotopic liver transplantation (OLT) has been attributed to high plasma levels of tissue plasminogen activator (t-PA). This study investigated the contribution of urokinase plasminogen activator (u-PA) to hyperfibrinolysis and the effects of high-dose perioperative aprotinin (Trasylol) on fibrinolytic activation. Plasma samples were collected before, during, and after OLT in fifty five patients receiving either high dose aprotinin or placebo in a randomized double-blind trial. t-PA antigen and u-PA antigen and activity levels were increased preoperatively compared with normal controls (P < 0.05). Hyperfibrinolysis was seen during the anhepatic phase as shown by shortened euglobulin clot lysis times (ECLT) and an increase in D-dimer titers. t-PA levels peaked on reperfusion and fell at the end of the operation, and u-PA levels did not increase during OLT, but showed a decrease at the end of the operation. With aprotinin treatment, t-PA levels were lower on graft reperfusion than the placebo group (P < 0.05), but there was no difference in u-PA antigen or activity levels between groups. Fibrinolytic inhibition during OLT by aprotinin was demonstrated by prolonged ECLT (P < 0.05), reduced D-dimer levels (P < 0.05), and an increase in antiplasmin activity (P < 0.05). This study showed that the main antifibrinolytic action of aprotinin is as an antiplasmin agent with some effect on t-PA-but not u-PA-mediated fibrinolysis.

Changes in the contact system during orthotopic liver transplantation with and without aprotinin.

The main cause of nonsurgical bleeding during orthotopic liver transplantation has been attributed to be hyperfibrinolysis due to high plasma levels of tissue plasminogen activator. The aim of this study was to investigate contact activation and its possible contribution to fibrinolysis during OLT with and without aprotinin. Aprotinin or placebo was given to 20 patients undergoing OLT as part of a randomized double-blind trial. Plasma samples were collected before, during, and after OLT. There were decreased preoperative levels of prekallikrein and factor XIIa (P < 0.05), with a trend for kallikrein and factor XIIa activity to increase during OLT peaking on reperfusion (P < 0.05). Kallikrein inhibition, C1 esterase inhibitor, and alpha-2-macroglobulin levels were normal before surgery, with low normal levels of antithrombin III and alpha-2-antiplasmin; these levels decreased during OLT with no specific change on reperfusion. In the aprotinin-treated group, kallikrein inhibition levels increased (P < 0.05) from preoperative mean (+/- SD) values of 101 +/- 47% to 154 +/- 42% and antiplasmin levels increased (P < 0.05) from 72 +/- 28% to 243 +/- 53% during the anhepatic phase, reflecting the effect of aprotinin. The antifibrinolytic effect of aprotinin was demonstrated by decreased levels of D-dimer on reperfusion (P < 0.05) and at the end of OLT (P < 0.001) in the aprotinin-treated group. We have shown that contact activation during OLT is minimal and that aprotinin does not alter the pattern of contact activation, but provides an antikallikrein effect.

Engrafted human T and B lymphocytes form mixed follicles in lymphoid organs of human/mouse and human/rat radiation chimera.

BACKGROUND: We recently described a new approach that enables the generation of human/mouse chimera by adoptive transfer of human peripheral blood mononuclear cells into lethally irradiated normal strains of mice or rats, radioprotected with bone marrow from donors with severe combined immune deficiency. In such human/mouse chimera, a marked humoral response to recall antigens, as well as a significant primary response to keyhole limpet hemocyanin, has been generated. METHODS: In the present study, the organ distribution of the engrafted human cells in the human/mouse and human/rat chimera was investigated by immunohistochemistry. RESULTS: Our results show that the T cells seem to be distributed throughout the reticular endothelial system, almost behaving like particles without any homing specificity. The B cells, however, can barely be found in internal organs, such as the liver or the pancreas, and are concentrated in the secondary lymphoid system (e.g., spleen, lymph node, and nonencapsulated lymphoid tissue). The B cells, together with the engrafted human T cells, form mixed lymphoid follicles. CONCLUSIONS: The different homing patterns exhibited by the T and B lymphocytes indicate that the homing receptors on human B cells might be cross-reactive with their mouse counterparts, in contrast to the human T cells, which seem to be unable to interact with the mouse homing receptors. The presence of human B and T lymphocytes in close proximity to each other in the lymphoid tissues is in accordance with the ability of human/BALB radiation chimera to mount significant primary human antibody responses.

Tc-99m HIDA cholescintigraphy: the distended photon-deficient gallbladder.

Four patients with distended, photon-deficient gallbladders are presented. Markedly delayed apearance of Tc-99m HIDA in a distended gallbladder may represent chronic cholecystitis, partial obstruction of the common bile duct, or physiologic gallbladder distention. Obtaining delayed images is important in this group of patients to avoid premature diagnosis of cystic-duct obstruction. If the distended gallbladder fails to visualize within 24 hr, hydrops with cystic-duct obstruction is suggested.

Amodiaquine resistant falciparum malaria in Thailand.

Amodiaquine cured 38% (13/34) of patients with falciparum malaria in Southeast Thailand. Chloroquine cured 0% (0/13). The cure rates with amodiaquine were the same whether a 1.5 g or 2.0 g course was used. Most patients were resistant to amodiaquine at the RI level and to chloroquine at the RII level. In hospital, amodiaquine cleared parasitemia more frequently than did chloroquine. With the 2.0 g course of amodiaquine, the parasite clearance time was 77 hours; the fever clearance time of 36 hours was low and suggests that amodiaquine does not cause a drug fever. Because of resistance, chloroquine should not be used for falciparum malaria in Thailand. Routine use of amodiaquine is not indicated because more effective drugs are available.

Comparison of the Murex Candida albicans CA50 test with germ tube production for identification of C. albicans.

A total of 502 yeast isolates were tested with the 30-min MUREX Candida albicans CA50 (Norcross, GA) test for presumptive identification of C. albicans. The results were compared with the standard 2-h germ tube test, which was the reference standard. Of the 502 isolates, 316 were C. albicans and 186 were non-C. albicans. Identifications were based on germ tube reactions; the API20C and chlamydospore agars were used when discrepant results persisted between the germ tube and MUREX test after repeat testing of the MUREX method. A total of 16 C. albicans gave negative results on initial testing with the MUREX test but were interpreted as positive when repeated. Three germ tube negative yeasts initially tested positive with the MUREX but were negative when repeated. Two additional yeast isolates gave incorrect results with the MUREX, even with repeat testing: C. albicans and C. lusitaniae. The initial sensitivity and specificity for the MUREX C. albicans CA50 test were 94.6% and 97.8%, respectively. As an addition to the study, two fetal bovine sera were compared for production of germ tubes; fetal bovine serum and Fetal Clone II. The testing found them to be in 100% agreement.

Identification and characterization of an aadB gene cassette at a secondary site in a plasmid from Acinetobacter.

Transformation studies showed that an aminoglycoside resistance gene, aadB, is carried on a 6.0-kb plasmid (pRAY) in a clinical isolate of Acinetobacter (strain SUN). The gene was cloned and sequenced. An analysis of the DNA sequencing data showed that although the aadB gene is part of cassette, it is not associated with an integron. Rather, the aadB cassette has recombined at a secondary site downstream of putative promoters on pRAY.

Family functioning and suicidal behavior in adolescent inpatients with mood disorders.

OBJECTIVE: This study was designed to identify family and parental characteristics associated with suicidal behavior (active intent, gesture, attempt) among adolescent inpatients with mood disorders. METHOD: Subjects were 32 suicidal adolescent inpatients with mood disorders, 32 nonsuicidal adolescent inpatients with mood disorders, and 38 normal comparison adolescents. A group comparison design was used. Adolescent measures were the Family Assessment Device and two semistructured interviews (Hamilton Rating Scale for Depression, Social Adjustment Inventory for Children and Adolescents). Parent measures were the Symptom Checklist-90 and the Social Adjustment Scale-Self Report. RESULTS: Fathers of suicidal adolescents reported more depression and family unit problems than did fathers of nonsuicidal and normal comparison adolescents, even after controlling for adolescents' depression severity. Suicidal adolescents, in turn, reported less active and communicative relationships with fathers. Differences among suicidal and nonsuicidal adolescents' perceptions of general family functioning were not significant after controlling for adolescents' depression severity. CONCLUSIONS: Findings highlight the importance of treating the depressed and potentially suicidal adolescent within the family system and attending to the nature and quality of adolescents' relationships with fathers as well as with mothers. Findings also highlight interactions between suicidal adolescents' depression severity and their negative perceptions of family functioning.

Global self-worth, specific self-perceptions of competence, and depression in adolescents.

OBJECTIVE: The purpose of this research was (1) to study adolescent depression severity in relation to global self-worth and specific self-perceptions of competence, and (2) to determine whether improvement in depression during hospitalization is accompanied by improvement in global self-worth and specific self-perceptions. METHOD: A within-subject longitudinal design with cross-sectional control subjects was used. Thirty depressed adolescent inpatients participated in assessments of depression severity (Hamilton Rating Scale for Depression) and self-perceptions of global self-worth and domain-specific competencies (Self-Perception Profile for Adolescents) at hospital admission and discharge (mean hospitalization: 59 days). A demographically similar group of 30 normal comparison subjects participated in the baseline assessment. RESULTS: Global self-worth was negatively associated with inpatients' depression severity and differentiated inpatients from normal comparison subjects. Self-perceptions of specific competencies were differentially related to depression severity, with perceived social acceptance being most clearly related to depression severity. Among the subgroup of inpatients showing clear and significant improvement in depression across hospitalization, increases in global self-worth and perceived social acceptance were also evident. CONCLUSIONS: Findings underscore the importance of considering global self-worth and self-perceptions of specific competencies in developmentally significant areas when assessing and treating adolescents.

Activation of coagulation and fibrinolysis during cardiothoracic operations.

BACKGROUND: During open cardiac operations using cardiopulmonary bypass, there is activation of coagulation and fibrinolysis. We assessed the separate contributions of the surgical procedure itself and cardiopulmonary bypass to this, by studying sequential samples from patients undergoing routine open cardiac operations or thoracic operations without cardiopulmonary bypass. METHODS: Activation of coagulation and the extent of fibrinolysis were measured from sequential samples obtained before the operation to 48 hours after the operation for 7 thoracic patients and 8 cardiac patients. RESULTS: In the thoracic group operation length was shorter (p = 0.002), and there was no significant increase in thrombin-antithrombin III complexes or D-dimers until 24 hours postoperatively. In contrast, there was a highly significant increase in thrombin-antithrombin III complexes (p = 0.0043) and D-dimer levels (p = 0.009) during cardiopulmonary bypass. The increase in fibrinolytic activity was caused by an increase in tissue plasminogen activator (p = 0.013). At 48 hours postoperatively, the cardiac patients had a more hypercoagulable state than thoracic patients with significantly higher levels of thrombin-antithrombin III complexes (p = 0.041) and plasminogen activator inhibitor-1 activity (p = 0.0033). CONCLUSIONS: This study suggests the major activation of coagulation and fibrinolysis seen during cardiac operations is caused by the use of cardiopulmonary bypass.

Parents' marital functioning and adolescent psychopathology.

Parents' marital functioning and adolescent psychopathology were investigated in 2 studies. The first study compared parents' marital satisfaction, conflict over childrearing, affective communication, and traditional role orientation in matched samples of psychiatric inpatient and control-group adolescents. The second study examined associations between specific dimensions of marital functioning and adolescent depression severity, suicidal ideation, and social adjustment in a larger sample of adolescent inpatients. In Study 1, parents of inpatients reported less marital satisfaction and more conflicts over childrearing than parents of control-group adolescents. In Study 2, marital conflicts over childrearing were associated with a less active or involved father-adolescent relationship and more severe school behavior and spare time problems. Marital functioning was not associated with depression severity or suicidal ideation.

Comparison of a 9-phenanthrene methanol (WR33063), a 4-quinoline methanol (WR30090), and quinine for falciparum malaria in Thailand.

Quinine was compared with a 9-phenanthrene methanol (WR33063) and a 4-quinoline methanol (WR30090) for the treatment of 207 patients with falciparum malaria in Southeast Thailand. Quinine eradicated parasitaemia (average 70 hours) more rapidly than either WR30090 (72 hours) or WR33063 (77 hours). But WR33063 had a higher cure rate (92%) than WR30090 (86%) or quinine (85%). The mean duration of fever and of parasitaemia were combined with the failure rate to form an arbitrary efficacy index. Using this concept WR33063 was the most effective drug. The recrudescence rate correlated with the degree and duration of parasitaemia and with the duration of fever. WR33063 was the least toxic drug. Side effects associated with WR30090 appeared to be headache, backache and urticaria. Quinine was the most toxic drug. All 3 drugs were inconvenient in having to be administered every 8 hours for 6 days. One patient did not respond to oral quinine but did respond to an intravenous quinine infusion (IVQ). A "Medication Ward Round" was perfected during the study and comprised sequential history, drug administration, physical examination, dose notation and patient observation. Falciparum nephrosis was diagnosed in one patient.

Giant serpentine aneurysm. Report of two cases.

The authors describe two cases of giant middle cerebral artery aneurysms presenting as mass lesions. Angiograms in each case revealed a distinctive serpentine vascular channel surrounded by an avascular area causing a "mass effect." Both lesions were resected in toto with excellent clinical results. Similar lesions in the literature are noted and the pathophysiology and origin of this group of aneurysms are discussed.

Extradural spinal involvement by gout. Case report.

A case of extradural gouty tophus in the lumbar region in a teen-age girl is presented as an addition to the differential diagnosis of erosive lesions of the spinal canal.

Intradural epithelial cyst at the craniovertebral junction. Case report.

A case of an intradural epithelial cyst at the craniovertebral junction is reported in a 37-year-old man. The classification of these rare lesions is discussed.