Hepatic venous-portal gradient (HVPG) measurement: pearls and pitfalls

Hepatic venous pressure gradient (HVPG) is the gold-standard for measurement of portal hypertension, a common cause for life-threatening conditions such as variceal bleeding and hepatic encephalopathy. HVPG also plays a crucial role in risk stratification, treatment selection and assessment of treatment response. Thus recognition of common pitfalls and unusual hepatic venous conditions is crucial. This article aims to provide a radiographical and clinical guide to HVPG with representative clinical cases.     

Controversies in transfusion medicine. Alanine aminotransferase screening of blood donors: pro

In my opinion, independent, carefully conducted scientific studies indicate that an accurate, rapid, relatively sensitive, and inexpensive laboratory test substantially reduces the major long-term risk of blood transfusion in the United States; donor ALT has emerged as one of the most effective laboratory determinants for reducing the incidence of NANB PTH. Despite its nonspecificity and limited predictive value, ALT screening may prevent up to 30 percent of cases, one-half of which would progress to chronic liver disease and then possibly to cirrhosis and hepatocellular carcinoma. Blood donors appear to understand and accept the testing rationale as a reasonable precaution. Admittedly, ALT screening is not a perfect solution. It has not been validated by prospective studies and probably never will be. Determination of the proper cutoff value remains controversial. However, the risk of PTH progresses with increasing ALT levels, so that the real issue is not whether to test, but how best to configure the test to exclude the fewest false-positive donors while detecting the most true-positive donors. It is undesirable and expensive to discard safe units of blood, but the primary responsibility of blood collectors is to ensure an adequate supply of safe components. Some still consider the ALT assay technically too demanding for routine use. However, technical concerns regarding performance and interpretation are not insurmountable, and both quality control and proficiency testing are being addressed at the national level. The assay is capable of great precision, and a system employing a national standard and single cutoff has already been described and tested with excellent results. Circumstances have changed since donor screening with ALT was widely implemented in 1986. More thorough screening and testing have eliminated many high-risk donors. Public expectations have changed as well. While it is neither reasonable nor responsible to promise the public blood transfusions without risk, neither is it prudent to propose any major change in management of the blood supply without compelling evidence that such a change will not impair transfusion safety. It is hard to defend discontinuing the ALT screen at this time, especially when the costs of retaining it are minimal and the benefits clearly greater than those of screening for HTLV-I and for Treponema pallidum (in the United States) or HIV-2 (in West Germany). A first-generation assay specific for antibody to hepatitis C will probably be available within a year.(ABSTRACT TRUNCATED AT 400 WORDS)     

Distribution of integrins on human peripheral blood mononuclear cells

The receptors for fibronectin (FN-R) and vitronectin (VN-R) belong to a family of integral membrane glycoproteins known to be involved in cell- extracellular matrix and cell-cell interactions named integrins (FN-R = beta 1 integrin and VN-R = beta 3 integrin). Adhesion studies using FN- coated plastic dishes and highly purified subpopulations of peripheral blood mononuclear cells (PBMCs) showed a strong binding of monocytes and T lymphocytes to FN but virtually no binding of B cells to FN. Binding of monocytes and T cells to FN could be partially inhibited by a hexapeptide (GRGDSP) containing the adhesive peptide sequence Arg-Gly- Asp (RGD) as well as by an anti-FN-R antibody. The distribution of beta 1 and beta 3 integrin complexes on PBMCs was characterized by immunoprecipitation of detergent extracts of 125I-labeled cells using polyclonal antibodies against these two receptors. Two surface polypeptides corresponding to the alpha and beta chains of FN-R and VN- R were found on all three cell types. To characterize these receptors further, monoclonal antibodies (MoAbs) against the very late antigens (VLAs) 1, 3, and 5 were used for immunoprecipitation studies. Monocytes and T cells reacted with VLA 5 that was previously identified as the human FN receptor, whereas no labeling with anti-VLA 5 could be shown for B cells. When cell populations were cultured in 10% human serum for 24 hours, an increase in beta 1-integrin+ monocytes and T cells was observed. The number of beta 3-integrin+ cells remained essentially unchanged. The presence of beta 1 and beta 3 integrins on monocytes as well as on T and B lymphocytes may be of significance in the ability of these cells to interact with each other and participate in hematopoiesis and certain immune reactions.     

Synergistic action of calcium ionophore A23187 and phorbol ester TPA on B-chronic lymphocytic leukemia cells

The peripheral blood mononuclear cells from 16 patients with B-chronic lymphocytic leukemia (B-CLL, n = 13), B-prolymphocytic leukemia (B-PLL, n = 2) or hairy cell leukemia (n = 1) were incubated in the presence of the phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore A23187. A synergy between these inducers was found with respect to morphological changes and B cell proliferation and differentiation. A23187 used alone did not activate the cells. B-CLL cells treated with the double stimulus acquired a plasmacytoid morphology, showed significantly higher incorporation of 3H-thymidine and 3H-uridine, and produced significantly higher amounts of monoclonal immunoglobulin compared with the same cells exposed to either of the inducers alone. These results indicate that phorbol ester and calcium ionophore act synergistically on B-CLL cells to induce proliferation and differentiation. B-PLL cells responded more vigorously to the signals provided by TPA and A23187. Previous studies showed that TPA and A23187 can mimic the two physiological second messengers diacylglycerol and inositol trisphosphate in the transduction of signals leading to cell activation, proliferation, and differentiation in normal B cells. The present findings suggest that the capacity of B- CLL and B-PLL cells to differentiate in response to signals of the second messenger pathway is intact.     

Soluble interleukin-2 receptors in serum and urine of patients with chancroid and their response to therapy

To investigate cell-mediated immune response in chancroid, soluble interleukin-2 receptor levels in serum and urine samples of healthy individuals and patients were measured by an enzyme-linked immunosorbent assay. Increased levels both in serum and in urine were observed in cases of Haemophilus ducreyi infection. In patients showing a prolonged incubation period, urine levels exceeded serum values. Therapy led to a reduction of elevated interleukin-2 receptor levels in serum and in urine.     

Structural abnormalities and persistent complaints after an ankle sprain are not associated: an observational case control study in primary care

Background

Persistent complaints are very common after a lateral ankle sprain.

Aim

To investigate possible associations between structural abnormalities on radiography and MRI, and persistent complaints after a lateral ankle sprain.

Design and setting

Observational case control study on primary care patients in general practice.

Method

Patients were selected who had visited their GP with an ankle sprain 6–12 months before the study; all received a standardised questionnaire, underwent a physical examination, and radiography and MRI of the ankle. Patients with and without persistent complaints were compared regarding structural abnormalities found on radiography and MRI; analyses were adjusted for age, sex, and body mass index.

Results

Of the 206 included patients, 98 had persistent complaints and 108 did not. No significant differences were found in structural abnormalities between patients with and without persistent complaints. In both groups, however, many structural abnormalities were found on radiography in the talocrural joint (47.2% osteophytes and 45.1% osteoarthritis) and the talonavicular joint (36.5% sclerosis). On MRI, a high prevalence was found of bone oedema (33.8%) and osteophytes (39.5) in the talocrural joint; osteophytes (54.4%), sclerosis (47.2%), and osteoarthritis (55.4%, Kellgren and Lawrence grade >1) in the talonavicular joint, as well as ligament damage (16.4%) in the anterior talofibular ligament.

Conclusion

The prevalence of structural abnormalities is high on radiography and MRI in patients presenting in general practice with a previous ankle sprain. There is no difference in structural abnormalities, however, between patients with and without persistent complaints. Using imaging only will not lead to diagnosis of the explicit reason for the persistent complaint.