Alterations in lymphocyte subsets in blood may predict resectability in carcinoma of cardia or oesophagus

Impaired immune responses in patients with carcinoma of cardia or oesophagus have previously been reported. However, we do not know whether resectability correlates with specific immunological variables. Immunological assessment was performed in 35 such cancer patients including measurement of total T cells (CD3⁺) and T cell subsets (CD4⁺ and CD8⁺), NK cells (CD16⁺) and B cells (CD19⁺) in blood. In vitro lymphocyte responses to phytohemagglutinin (PHA) separated from peripheral blood were quantitated. The numbers in peripheral blood of both total T cells (CD3³⁺) and B lymphocytes (CD19⁺) were significantly lower in the inoperable patients compared to resected patients (P < 0.01). The number of NK cells (CD16⁺) was, however, not significantly lower in the inoperable patients compared to the patients operated for cure. Lymphocyte responses to PHA in vitro were similar in resectable and non-resectable patients, but significantly lower in inoperable patients compared to the controls (P < 0.01). In conclusion, resectability in carcinoma of cardia or oesophagus is associated with changes in both T (CD3⁺) and B (CD19⁺) cell subsets.     

Moderate-to-severe pain after knee arthroscopy is relieved by intraarticular saline: a randomized controlled trial

We have previously studied intraarticular (IA) analgesics compared with saline 10 mL in 2 randomized clinical trials. The patients who were given IA saline experienced rapid pain relief. Hypothetically, saline may produce a local analgesic effect by cooling or by diluting IA algogenic substances. This randomized double-blind study compared the analgesic effect of IA saline 10 mL with saline 1 mL, which should be a pure placebo. A soft catheter was left IA in 79 patients. We included 60 patients who developed moderate-to-severe pain within 1 h after knee arthroscopy under general anesthesia. A randomized, double-blind controlled comparison of IA saline 10 mL with saline 1 mL followed. Outcome measures were pain intensity, pain relief, and analgesic consumption. Within 1 h pain intensity decreased in both groups from approximately 50 to approximately 27 on a 0-100 mm visual analog scale. Pain intensity remained low and other pain outcome measures were similar during the 36-h observation period. The patients experienced equally good pain relief after IA injection of saline 10 mL and 1 mL. Our finding of a major placebo effect may have implications for the interpretation of previously published placebo-controlled IA analgesia studies. IMPLICATIONS: In a randomized controlled trial we showed that pain after knee arthroscopy is modest and short-lived and can successfully be treated with intraarticular saline as placebo.     

A basal epithelial phenotype is more frequent in interval breast cancers compared with screen detected tumors.

Interval breast cancer reduce the effectiveness of mammography screening programs. We studied 95 interval cancers, diagnosed during 1996 to 2001 as part of the population-based Norwegian Breast Cancer Screening Program. These cases were matched on size (+/-2.0 mm) to 95 screen-detected breast cancers, and the tumors were compared by immunohistochemical methods using tissue microarrays. Patients with interval cancers were more likely to be younger [odds ratio (OR), 4.7; P = 0.0001], to have dense breasts (OR, 3.4; P = 0.004), and to have estrogen receptor-negative tumors (OR, 2.6, P = 0.01), and p53 expression was more frequent (OR, 4.0; P = 0.001). Notably, interval cancers were more likely to have a basal epithelial phenotype, in that expression of cytokeratin 5/6 (OR, 2.3; P = 0.04) and P-cadherin (OR, 2.5; P = 0.04) was more frequent in interval cases than in size-matched, screen-detected tumors. In a logistic regression model, p53 expression, age, and breast density were independent predictors of interval cancers. Our data suggest that breast cancers with a basal epithelial phenotype are more likely than nonbasal breast cancers to present between regular mammograms.     

A randomized multicenter trial of cyclosporin and prednisolone versus cyclosporin,azathioprine, and prednisolone following primary living donor renal transplantation

A total of 195 consecutive recipients of primary living donor renal transplants were randomized to receive either cyclosporin (CyA) and prednisolone (double therapy) or CyA, prednisolone, and azathioprine (triple therapy). There was no significant difference in patient or graft survival, incidence of acute rejection episodes, or major complications between the groups. The graft survival at 5 years was 71.5% in patients receiving double therapy and 71.6% in patients receiving triple therapy. In a Cox regression analysis, recipient age and occurrence of acute rejection were the only independently significant variables affecting graft survival, whereas treatment schedule did not. Renal function was stable throughout the observation period and did not differ between the double and triple therapy groups. A linear regression analysis showed that recipient age, donor age, gender, and occurrence of acute rejection significantly influenced the serum creatinine level. This and previous similar prospective studies in cadaveric renal transplantation indicate that there is no advantage of routinely adding azathioprine to a double drug regimen.     

Contrast-enhanced MR imaging of diffuse and focal splenic disease with use of magnetic starch microspheres

The diagnostic value of magnetic starch microspheres (MSM), a new superparamagnetic contrast agent, was studied in experimental models of diffuse and focal splenic disease in rats by means of ex vivo relaxometry and in vivo magnetic resonance (MR) imaging. Owing to small differences in unenhanced T1 and T2 values between diffuse lymphoma and normal spleen, MR imaging failed to distinguish tumor-bearing animals from control animals by signal-to-noise ratios (SNRs) obtained with T1- and T2-weighted spin-echo sequences. One hour after injection of 20 μmol/kg MSM, lymphomatous spleen showed significantly (P <.001) reduced enhancement relative to normal splenic tissue. As a result, animals with diffuse lymphoma (SNR: 10.3 ± 1.7) could be easily differentiated from control animals (SNR: 5.5 ± 0.6) on T2-weighted (TR msec/TE msec = 2,000/45) images. In focal splenic disease, MSM produced normal enhancement of nontumorous splenic tissue, whereas relaxation times of tumors were not different before and after contrast agent injection. On T2-weighted images (2,000/45), the tumor-spleen contrast-to-noise ratio increased from (4.8 ± 1.6 to 21.8 ± 1.9 +354%), improving conspicuity of splenic tumors. The results show that MSM-enhanced MR imaging improves the detection of diffuse and focal splenic disease.     

Protection by natural human immunoglobulin M antibody to meningococcal serogroup B capsular polysaccharide in the infant rat protection assay is independent of complement-mediated bacterial lysis

Neisseria meningitidis, an important cause of bacterial meningitis and septicemia worldwide, is associated with high mortality and serious sequelae. Natural immunity against meningococcal disease develops with age, but the specificity and functional activity of natural antibodies associated with protection are poorly understood. We addressed this question by using a selected subset of prevaccination sera (n = 26) with convergent or discrepant serum bactericidal activity (SBA) and infant rat protective activity (IRPA) against the serogroup B meningococcal strain 44/76-SL (B:15:P1.7,16) from Icelandic teenagers. The sera were analyzed by opsonophagocytic activity (OPA) assay, immunoblotting, immunoglobulin G (IgG) quantitation against live meningococcal cells by flow cytometry, and enzyme immunosorbent assay (EIA). High levels of SBA and OPA were reflected in distinct IgG binding to major outer membrane proteins and/or lipopolysaccharide in immunoblots. However, we could not detect any specific antibody patterns on blots that could explain IRPA. Only IgM antibody to group B capsular polysaccharide (B-PS), measured by EIA, correlated positively (r = 0.76, P < 0.001) with IRPA. Normal human sera (NHS; n = 20) from healthy Finnish children of different ages (7, 14, and 24 months and 10 years) supported this finding and showed an age-related increase in IRPA that coincided with the acquisition of B-PS specific IgM antibody. The protection was independent of complement-mediated bacterial lysis, as detected by the inability of NHS to augment SBA in the presence of human or infant rat complement and the equal protective activity of NHS in rat strains with fully functional or C6-deficient complement.     

A DNA vaccine directed against a rainbow trout rhabdovirus induces early protection against a nodavirus challenge in turbot

A DNA vaccine encoding the envelope glycoprotein from a fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), has previously been shown to induce both early and long time protection against the virus in rainbow trout. Challenge experiments have revealed that the immunity established shortly after vaccination is cross-protective against heterologous fish rhabdoviruses. In this study, we show that the DNA vaccine encoding the VHSV glycoprotein also induces early protection against a non-enveloped, positive-sense RNA virus belonging to the Nodavirus family, the Atlantic halibut nodavirus (AHNV). In a vaccine efficacy test using juvenile turbot as model fish, the fish injected with the VHSV vaccine were completely protected against a nodavirus challenge performed 8 days post vaccination, while the cumulative mortality in the control group reached 54%. A DNA vaccine carrying the gene encoding the capsid protein of AHNV revealed no protective properties against the nodavirus challenge. Histological examination of muscle tissue sections from the vaccine injection site showed that the DNA vaccine against VHSV triggered a pronounced inflammatory response in turbot similar to what has earlier been observed in rainbow trout.     

Goodpasture's syndrome: A report of seven patients including long-term follow-up of three who received a kidney transplant

Seven patients with Goodpasture's syndrome are presented. Bilateral nephrectomy was performed in five patients, and postnephrectomy pulmonary hemorrhage occurred in three. Three nephrectomized patients underwent a successful renal transplant, renal transplantation being postponed until circulating antiglomerular basement membrane antibody had disappeared. The argument is made that pretransplant bilateral nephrectomy in patients with Goodpasture's syndrome is indicated.