Opposite sorting of tissue factor in human umbilical vein endothelial cells and Madin-Darby canine kidney epithelial cells

Tissue factor (TF) is a 48-kD transmembrane glycoprotein that triggers the extrinsic pathway of blood coagulation by interacting with the plasma coagulation factor VII (FVII). TF is also a true receptor in that a cellular signal is generated when activated FVII (FVIIa) binds to TF. For both of these functions, the cellular surface distribution of TF is important, since FVII is primarily available on the apical side of vascular endothelial cells and on the basolateral side of epithelial cells lining the internal and external surfaces. We show that in endothelial cells, TF (both antigen and procoagulant activity) is sorted to the apical surface, whereas in wild-type and stably transfected Madin-Darby canine kidney epithelial cells (MDCK), which form tight junctions and express TF constitutively, TF antigen is on the basolateral surface. No significant clotting activity is detectable on this surface. Truncated TF (cytoplasmic tail residues 246 to 263 deleted) is sorted as wild-type in MDCK cells.     

Naturally occurring anticoagulants and bone marrow transplantation: plasma protein C predicts the development of venocclusive disease of the liver

Venocclusive disease (VOD) of the liver is the major dose-limiting complication of pretransplant regimens for bone marrow transplantation. Recent reports from different groups point to the involvement of the hemostatic mechanism in the development of VOD. We measured the naturally occurring anticoagulants protein C, antithrombin III, and protein S in 45 patients undergoing bone marrow transplantation for hematologic malignancies before cytoreductive therapy and after transplant. The aim of this prospective study was both to evaluate the status of the naturally occurring anticoagulant pathway in patients who develop VOD compared with patients who do not, and to find a predictive marker of VOD. In transplant patients, protein C decreased from before cytoreductive therapy to posttransplant, whereas protein S and antithrombin III did not. In a multivariate analysis, protein C was the only variable that could independently discriminate between VOD and non- VOD patients at all times. Discriminant function analysis established that low protein C levels before cytoreductive therapy predicted the occurrence of VOD with good sensitivity and specificity.     

Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study

IntroductionAdrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase.MethodsWe prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 μg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests.ResultsPatients with low (<250 nM) Δ cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar.ConclusionsEven though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.     

Crossmatch-compatible platelets improve corrected count increments in patients who are refractory to randomly selected platelets

BACKGROUND: HLA-matched platelets and crossmatch-compatible platelets are used to support thrombocytopenic patients who are refractory to randomly selected platelets. Data supporting the effectiveness of crossmatch-compatible platelets are limited, being essentially restricted to the subset of refractory patients previously shown to be alloimmunized. The authors' hospital does not test for alloimmunization. To determine the effectiveness of crossmatch- compatible platelets in an unselected group of refractory patients, the use of such platelets for all patients who are refractory to random- donor platelets was reviewed. STUDY DESIGN AND METHODS: All patients who received crossmatch-compatible platelets between January 1991 and May 1994 were retrospectively reviewed. All study patients were refractory to random-donor platelets, having two consecutive corrected count increments (CCIs) of < 10,000. A solid-phase red cell adherence method was used for platelet crossmatching, and CCI was used to monitor the effectiveness of each platelet transfusion. RESULTS: A total of 475 crossmatch-compatible platelet components were administered to 66 evaluable patients who were refractory to random-donor platelets. A significant improvement was found in the mean CCI when crossmatch- compatible platelets were compared with randomly selected platelets (p < 0.0001): an increase of 8000 +/? 6100 (mean +/? SD). In 59 percent (39/ 66) of the patients, the mean CCI improved to at least 7,500 and in 41 percent (27/66) to at least 10,000. If the 10 patients for whom crossmatch-compatible platelets were not identified are included, the mean CCI in 51 percent (37/76) of the refractory patients improved to at least 7,500; in 36 percent (27/76), it improved to at least 10,000. The effectiveness of crossmatch-compatible platelets did not decline with continued use. CONCLUSION: Crossmatch-compatible platelet components significantly improve the mean CCI for approximately one- half of patients who are refractory to random-donor platelets, even when the patients are not preselected for having alloimmunization to explain their refractory state.     

LANSOPRAZOLE PLUS CLARITHROMYCIN: EVALUATION OF A NEW DUAL THERAPY FOR Helicobacter pylori ERADICATION

SUMMARY The aim of this pilot study was to evaluate the efficacy and safety of lansoprazole plus clarithromycin for eradication of Helicobacter pylori. A total of 26 patients with H. pylori infection were randomised to receive clarithromycin, 500 mg t.i.d. for 14 days, plus either lansoprazole, 30 mg o.m., (group L30, n=13) or lansoprazole, 30 mg b.i.d., (group L60, n=13). H. pylori status was determined pre-treatment and four to six weeks after completion of the study medication by histology and ¹³C-urea breath test. Two patients were unable to complete the course of medication. Of the remaining 24 patients, 14 (58%) successfully eradicated H. pylori — 8/12 (67%) patients in group L30 and 6/12 (50%) in group L60. Side-effects were experienced by 17/26 (65%) of patients, most commonly a taste disturbance. The results from this pilot study suggest that dual therapy with lansoprazole plus clarithromycin is only a moderately effective regimen for eradicating H. pylori.     

COR TRIATRIATUM: UNUSUAL CAUSE OF TRANSIENT ISCHAEMIC ATTACKS IN A 67-YEAR-OLD MAN

SUMMARY Cor triatriatum is a rare congenital cardiac malformation, and in its most common form is characterised by a membrane that separates the left atrium into a proximal and distal chamber. First manifestation in adulthood has been reported previously, but at 67 years of age this patient is one of the oldest to present for the first time. It was diagnosed after a probable TIA, episodic vertigo and central retinal artery occlusion. The value of echocardiography in patients with neurological disease of presumed embolic origin is demonstrated here.     

Pigment gallstone composition in cirrhotic and noncirrhotic subjects

The composition of pigment gallstones from patients with and without cirrhosis was compared. Carbonate-containing pigment stones were distinguished from noncarbonate stones by infrared spectroscopy. Calcium was the major cation of each stone group. The major anion in noncarbonate pigment stones was bilirubinate or phosphate, but was carbonate in carbonate stones. The composition of pigment stones from cirrhotic and noncirrhotic patients was similar except that significantly less carbonate was present in carbonate stones, and less pigment (bilirubinate) was present in noncarbonate stones from noncirrhotics. These data suggest that irrespective of the presence of cirrhosis, the formation of noncarbonate pigment stones involves the selective precipitation of calcium bilirubinate and phosphate, whereas carbonate stone formation involves the selective precipitation of calcium carbonate.     

Seroprevalence of cytomegalovirus among pregnant women attending Murtala Mohammed Specialist Hospital Kano,Nigeria

Background

Primary Cytomegalovirus (CMV) infection during pregnancy is a frequent and serious threat to the fetus. As there is no vaccine alternative measures are needed to prevent congenital CMV infection.

Objective

This study determined CMV Immunoglobulin G (IgG) antibody among pregnant women in order to ascertain the immune status of mothers to guide policy makers.

Methods

A semi-structured questionnaire was initially administered to obtain information on demographic details, stage of pregnancy and risk factors. Blood was collected by venipuncture from 180 women attending the antenatal clinic in Murtala Mohammed Specialist Hospital Kano, Kano State, Nigeria. Sera samples were screened using CMV IgG ELISA kit (Dialab, Austria).

Results

Out of 180 pregnant women, 164 (91.1%) were seropositive. Based on stages of pregnancy 6/6(100%), 52/60(86.7%) and 106/114(93.0%) were seropositive among women in the first, second and third trimesters respectively.

Conclusion

Seroprevalence of pregnant women to CMV Ig G is high, hence the need for CMV - IgM screening to know the extent of active infection. There is also need for public enlightenment on the methods of transmission, effective prevention and control strategies.