Lower extremity joints and their contributions to whole limb extension.

Lower extremity multi-joint strength curves tend not to evaluate individual joint contributions to endpoint force in maximum effort isometric whole limb extension. Therefore, the purpose of this study was to measure the contribution of the hip, knee, and ankle to vertical ground reaction force in maximum effort isometric whole limb extension at various postures. An effect of posture on the contributions of the hip, knee, and ankle to vertical ground reaction force was found (F(3,96) = 85.31, p < 0.0001; F(3,96) = 21.32, p < 0.0001; F(3,96) = 130.61, p < 0.0001 for the hip, knee, and ankle, respectively). The hip and knee contributed most to vertical endpoint force when the lower limb was in a flexed posture, and their contributions decreased when posture was extended. Conversely, the ankle contributed least when the limb was flexed, but its contribution increased as posture was changed from flexed to more extended. In comparison to recent research involving induced acceleration analysis, it appears that the hip, knee, and ankle utilize the same force allocation strategy in multi-joint maximum effort isometric leg extensions and activities of daily living.

Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.

OBJECTIVE: To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (AAA). METHODS: Cases and controls were recruited from a trial of screening for AAAs. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with AAA (n=678) and in controls (n=659) was examined using multivariate analyses. The association with AAA expansion (n=638) was also assessed. RESULTS: In multivariate analyses with adjustments for multiple testing, no association between either SNP and AAA presence or expansion was detected. CONCLUSION: MMP2 -1360C>T and +649C>T variants are not risk factors for AAA.

Polymorphisms of the matrix metalloproteinase 9 gene and abdominal aortic aneurysm.

BACKGROUND: Increased matrix metalloproteinase (MMP) 9 activity has been implicated in the formation of abdominal aortic aneurysm (AAA). The aim was to explore the association between potentially functional variants of the MMP-9 gene and AAA. METHODS: The -1562C > T and -1811A > T variants of the MMP-9 gene were genotyped in 678 men with an AAA (at least 30 mm in diameter) and 659 control subjects (aortic diameter 19-22 mm) recruited from a population-based trial of screening for AAA. Levels of MMP-9 were measured in a random subset of 300 cases and 84 controls. The association between genetic variants (including haplotypes) and AAA was assessed by multivariable logistic regression. RESULTS: There was no association between the MMP-9-1562C > T (odds ratio (OR) 0.70 (95 per cent confidence interval (c.i.) 0.27 to 1.82)) or -1811A > T (OR 0.71 (95 per cent c.i. 0.28 to 1.85)) genotypes, or the most common haplotype (OR 0.81 (95 per cent c.i. 0.62 to 1.05)) and AAA. The serum MMP-9 concentration was higher in cases than controls, and in minor allele carriers in cases and controls, although the differences were not statistically significant. CONCLUSION: In this study, the genetic tendency to higher levels of circulating MMP-9 was not associated with AAA.

Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.

BACKGROUND: Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (AAAs). Although this implicates inflammation as a cause of AAAs, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and AAAs. METHODS: An association study involving 677 men with screen-detected AAAs and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on AAA as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with AAAs. All analyses and haplotype estimation were performed under a generalized linear model framework. RESULTS: IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for AAA with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for AAA (OR 1.56, 95%CI: 1.02, 2.39). CONCLUSION: The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with AAA, however it is too rare to be an important cause of most AAAs. This does not support the concept that the elevated level of IL-6 reported in patients with AAAs is a primary cause of the aneurysmal process.

Trapping of cold excitons in quantum well structures with laser light.

Optical trapping and manipulation of neutral particles has led to a variety of experiments from stretching DNA-molecules to trapping and cooling of neutral atoms. An exciting recent outgrowth of the technique is an experimental implementation of atom Bose-Einstein condensation. In this Letter, we propose and demonstrate laser-induced trapping for a new system--a gas of excitons in quantum well structures. We report on the trapping of a highly degenerate Bose gas of excitons in laser-induced traps.

Esophagostomy tubes as a method of nutritional management in cats: a retrospective study.

The use of esophagostomy tubes in 60 feline patients was evaluated retrospectively. Indications for tube placement, complications associated with placement and management, duration of treatment, and change in patient body weight were evaluated. Hepatic disease was the most common indication for tube placement. A minor complication associated with the surgical technique for tube placement was observed in three cases. Inflammation or infection of the tube site, swelling of the head, or vomition of the tube were observed complications during management in 19 cases. Vomiting occurred and was a complicating factor in nine cases. The average duration of tube placement was 23 days, and most patients maintained or gained weight while being fed through their esophagostomy tubes.

Hypoadrenocorticism in a family of leonbergers.

Hypoadrenocorticism was diagnosed in four related leonbergers. Two of the four dogs also had low-resting serum thyroxine (T4) levels and signs consistent with hypothyroidism. The familial association of the affected dogs and the presence of coexisting thyroid dysfunction are similar to what is seen in human type II polyglandular autoimmune syndrome.

Autologous bone marrow transplantation in multiple myeloma: identification of prognostic factors.

Multiple myeloma remains a universally fatal malignancy with a median survival time not exceeding 3 years. A clinical trial was undertaken to determine feasibility and efficacy of marrow-ablative chemoradiotherapy supported by unpurged autologous bone marrow (ABMT) and to define prognostic variables. Total body irradiation and either melphalan or thiotepa were administered to 55 patients (median age 53 years; range 20 to 66 years). The group of 21 patients with resistance to standard melphalan-prednisone and to continuous infusions of vincristine and Adriamycin with high dose dexamethasone (VAD) included 7 with primary unresponsive disease and 14 with resistant relapse; among the 34 patients achieving remission with the VAD regimen, 14 were in first and 20 in a subsequent remission. Marked cytoreduction by greater than or equal to 75% was observed among all 21 patients with refractory myeloma, whereas further cytoreduction of this magnitude was noted in only 56% of the 34 patients already in remission after VAD. Five of the 6 early deaths among all 55 patients occurred in the 14 patients with resistant relapse, none of whom achieved complete remission and who, as a group, had median durations of relapse-free and overall survival of only 8 and 7 months, respectively. Among the 41 remaining patients, there was only one early death, and 27% achieved complete remission including a 36% incidence among the 14 patients treated in first remission; their projected 4-year survival rate was 82% regardless of their disease status (first or later remission or primary resistance). When information about sensitivity to prior therapy is unavailable, the presence before ABMT of both high beta-2-microglobulin levels (greater than 3 mg/L) and non-IgG isotype helped identify 9 among the 55 patients with a very poor prognosis: all 8 responders relapsed within 9 months, and 8 patients died within 15 months. By contrast, a 4-year projected survival rate of over 70% for the other patients (about 80% of this series) justifies further investigation of this novel treatment approach in comparison with standard dose regimens. Our results indicate that marrow-ablative therapy cannot be recommended for myeloma patients with resistant relapse or those with a combination of risk factors (advanced tumor burden, absence of IgG isotype). The apparent lack of an adverse effect of even marked plasmacytosis in autografts (up to 30%) emphasizes the need for better cytoreduction rather than bone marrow purging.

High-dose melphalan and granulocyte-macrophage colony-stimulating factor for refractory multiple myeloma.

High-dose melphalan has induced remissions in about 40% of patients with refractory myeloma, but the mortality has been high, at about 20%, due to complications of prolonged granulocytopenia. In an attempt to stimulate earlier granulocyte recovery, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously to 23 patients with refractory myeloma who had been treated with melphalan at a high dose of 100 mg/m2. Thirty-nine percent of patients achieved marked tumor cytoreduction by at least 75%, 2 died within 2 months from infectious complications during severe neutropenia; and median durations of relapse-free and overall survival were 7 and 10+ months, respectively. The nine patients presenting with both advanced age over 50 years and a long history of prior therapy of over 1 year required significantly longer median times of 31 days for granulocytes and of 63 days for platelets to reach safe levels of at least 500/microL and 50,000/microL, respectively, than the 14 remaining patients who had none or only one of these adverse features (21 and 26 days, respectively). In a historic control of 43 patients treated previously with high-dose melphalan but without GM-CSF, hematologic recovery to the aforementioned levels of granulocytes and platelets proceeded over almost 5 weeks, regardless of age and prior treatment exposure. Thus GM-CSF seems to hasten marrow recovery, especially in patients with adequate normal marrow stem-cell reserve as defined by younger age or less prior therapy. While not shortening the duration of neutropenia, GM-CSF dose increments (from 0.25 to 0.5 to 0.75 mg/m2) increased the incidence of severe toxicity from 0% to almost 40%, especially among older patients. These results support the usefulness of low-dose GM-CSF (0.25 mg/m2) in stimulating marrow recovery in selected patients with adequate marrow reserve treated with high-dose melphalan for refractory multiple myeloma.

High serum levels of lactic dehydrogenase identify a high-grade lymphoma-like myeloma.

Although conferring a grave prognosis in patients with malignant lymphoma, high levels of serum lactic dehydrogenase (LDH) are usually not seen in patients with multiple myeloma, a more indolent tumor composed mainly of B cells in their terminal stage of differentiation. Thus, only 2 of 118 patients in earlier phases of myeloma showed marked LDH elevations to more than 500 U/L, whereas such abnormalities were present in 12 of 64 patients with advanced disease progressing despite treatment with vincristine, doxorubicin (Adriamycin), dexamethasone (VAD) (median LDH level, 700 U/L). High LDH levels were associated with high serum levels of beta-2-microglobulin, hypercalcemia, extraosseous disease features, a short preceding clinical course as well as a short subsequent survival time. A poor prognosis was also noted in patients with lower LDH in whom marked increments were induced by high-dose chemotherapy; thus, LDH elevations to greater than 300 U/L present before or found after high-dose cytotoxic therapy were observed in about 50% of patients with VAD-resistant myeloma and define a new clinical entity with features of extraosseous disease and an unusually aggressive course ("high-grade myeloma"). The shorter survival of newly diagnosed patients with high-normal compared with those with low-normal LDH levels (less than 200 U/L), regardless of tumor mass, suggests the presence in some patients of a tumor subpopulation with high LDH production that escapes growth control with standard treatment. Staging of multiple myeloma should therefore include measurements of serum LDH levels in addition to beta-2-microglobulin analysis and tumor mass estimation.

Prognostic factors with high-dose melphalan for refractory multiple myeloma.

High doses of melphalan (HDM) and dexamethasone were administered to 43 patients with advanced multiple myeloma, 36 of whom were refractory to both standard melphalan-prednisone and vincristine-adriamycin-dexamethasone (VAD). Forty-four percent responded with greater than 75% reduction in calculated tumor mass, including three patients who achieved a complete remission. The response rate to HDM was 56% in 18 relapsing patients and 50% in 12 patients with less than 12 months of primary drug resistance, but it was only 23% among the remaining 13 unresponsive patients. A high early mortality rate of 30% was confined to 26 patients with either poor performance (Zubrod greater than 1) or impaired renal function (creatinine greater than 1.4 mg%). When this toxic treatment was given to the 21 patients with good performance (Zubrod less than 2) whose disease lacked high serum lactic dehydrogenase (less than or equal to 500 U/L) as a recently recognized feature of high-grade myeloma, a superior median survival of 18 months was obtained as opposed to only 3 months for the 22 remaining patients (P less than .001). Thus, when employed in a timely fashion, HDM overcomes resistance to standard chemotherapy and VAD and benefits selected patients with advanced myeloma.

Application of biosafety principles in blood establishments.

In light of increasing public and employee concern over potential infectious hazards associated with blood and other body fluids, several government agencies (the Food and Drug Administration, the Centers for Disease Control, the Occupational Safety and Health Administration, the Environmental Protection Agency, the Health Care Financing Administration and the National Heart, Lung and Blood Institute) cosponsored a Biosafety Workshop in April 1988. The objective of the workshop was to identify appropriate biosafety practices and standard control procedures to protect workers involved in the collection, storage, and transportation of human blood donations with the least possible disruption of the nation's blood supply. Speakers focused on human immunodeficiency virus (HIV) and hepatitis B virus (HBV); however, the safety principles discussed were considered equally applicable to other known (e.g., non-A, non-B hepatitis and human T-lymphotropic virus type I (HTLV-1) blood-transmitted infections. The resulting consensus included the need for blood establishments to develop and apply thoughtful biosafety programs to address staff training, accident prevention, HBV vaccination, handling spills, managing contaminated waste and transporting blood specimens. There was lack of agreement, however, on the usefulness of gloves during the phlebotomy of healthy blood donors.

Chromatographic removal of hepatitis B virus from a factor IX concentrate. Experimental studies in chimpanzees.

Non-A, non-B hepatitis virus can be removed from a factor IX concentrate by a hydrophobic chromatographic step added to the ordinary fractionation process. The efficacy of this procedure for removal of hepatitis B virus (HBV) was evaluated in chimpanzees. A well-defined hepatitis B virus (HBV) inoculum was added to a factor IX preparation and this preparation was subjected to chromatography with octanohydrazide-Sepharose 4B at a high salt concentration and then injected intravenously into two chimpanzees. A control chimpanzee was inoculated with the part of the factor IX/HBV preparation that had not been chromatographed. The two chimpanzees that received the treated material remained free of any serologic or biochemical evidence of hepatitis B infection during a 12-month follow-up, whereas the control chimpanzee had hepatitis B. After a later HBV challenge, the two healthy animals also had hepatitis B. The hydrophobic binding procedure seems to be useful for the adsorption of viral agents in blood components.

Prognostic implications of tumor cell DNA and RNA content in multiple myeloma.

Flow cytometric studies of bone marrow DNA and RNA content were conducted in 71 previously untreated patients with multiple myeloma. There was a progressive increase in response rate with rising plasma cell RNA content. The DNA-derived ploidy level also affected chemotherapy sensitivity: only one of 11 patients with either hypodiploidy or biclonal DNA stemlines responded. DNA-RNA-defined marrow plasmacytosis was the only tumor mass-related variable adversely affecting remission induction. Survival was longer in patients with low tumor burden and favorable DNA features. The availability of objective and quantitative pretreatment variables associated with both initial response and survival should permit a risk-based selection of patients for novel treatment approaches.

Cytoplasmic immunoglobulin content in multiple myeloma.

Bone marrow cells of 82 patients with multiple myeloma were subjected to flow cytometric analysis of DNA and cytoplasmic immunoglobulin (CIg) content using propidium iodide and direct immunofluorescence assays. Except for two patients with nonsecretory myeloma, there was conformity in the immunoglobulin type derived from immunoelectrophoresis and plasma cell CIg staining. One patient with nonsecretory myeloma exhibited monotypic CIg staining, while the second showed no reaction. In eight patients with IgG lambda myeloma, the same tumor cells contained both lambda and kappa light chains, suggesting the productive rearrangement of both light chain genes. 14 patients with previously unrecognized plasma cells of low RNA content, all of whom were resistant to chemotherapy, were identified by CIg staining. By revealing previously unrecognized plasma cells with low RNA content, CIg analysis identified more patients with treatment-refractory myeloma.

Serologic markers of hepatitis A and B in the population of Bali, Indonesia.

A total of 343 sera from Balinese subjects in different age groups and geographic locations were tested by radioimmunoassay (RIA) for serum antibodies to hepatitis B surface antigen (anti-HBs) and hepatitis B core antigen (anti-HBc); most sera were also tested for hepatitis B surface antigen (HBsAg), and for antibody to hepatitis A virus (anti-HAV). One hundred percent of the adult population was found to have anti-HAV, with antibody acquisition beginning in early childhood and reaching a level of 95% by the age of 10 years. Antibodies to hepatitis B virus were also frequent in young children, rapidly peaking to near 80% in older children and adolescents, then declining to a plateau that fluctuated between 40% and 60% throughout adult life. Overall, anti-HBc (49%) was detected slightly more often than anti-HBs (45%), but the relative frequencies of the 2 antibodies varied considerably from group to group. Despite these high antibody prevalences, HBsAg was detected in only 1.5% of the general population, and in no woman of child-bearing age. In utero infection is thus far less likely to account for the early acquisition of antibody to hepatitis B virus than inapparent percutaneous transmission occurring under conditions of close personal contact.

Community-acquired non-A, non-B hepatitis: clinical characteristics and chronicity.

The characteristics of 86 patients with acute non-A, non-B hepatitis were compared to 23 patients with acute hepatitis A and 76 with acute hepatitis B by medical record reviews of patients seen at 5 hospitals in Baltimore, Maryland, as part of case-control study of viral hepatitis. Results of serum aminotransferase levels, bilirubin, albumin, and prothrombin times alone could not distinguish the type of viral hepatitis because of extensive overlap. The alanine aminotransferase range for non-A, non-B hepatitis was 56 to 1819 IU/liters, for hepatitis A 250 to 1995 IU/liters, and for hepatitis B 203 to 2120 IU/liters. The ranges of aspartate aminotransferase and bilirubin for the types of hepatitis also overlapped. Fewer patients with non-A, non-B hepatitis or hepatitis A had a prolonged prothrombin time compared to patients with hepatitis B. Hepatic encephalopathy was seen only in two patients with hepatitis B. Forty-two percent of non-A, non-B hepatitis patients followed for 6 months or longer continued to have elevated alanine aminotransferase levels. Chronic alanine aminotransferase elevation was independent of the source of infection: transfusion, parenteral drug use, or all other sources. Prolonged follow-up is necessary to evaluate chronicity in patients with non-A, non-B hepatitis.

Concomitant hepatitis B surface antigen and antibody in thirteen patients.

Both hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) were found in 13 patients. Nine patients had HBsAg subtype ad, and 7 had anti-HBs monotypic subtype anti-y. Nine patients had HBsAg before detectable levels of anti-HBs were present. Of the 6 patients whose serum contained subtypes of both HBsAg and anti-HBs, 4 had HBsAg before development of the monotypic antibody. All patients have remained positive for HBsAg and anti-HBs (mean duration, 55.5 weeks). Nine patients were positive for HBeAg, and 7 had renal disease. Six of these seven patients are on hemodialysis. Because of the differing subtype specificities of the circulating HBsAg and anti-HBs, we conclude that HBsAg and anti-HBs occur concomitantly. The presence of HBeAg, which indicates infectivity, is common in our study group, suggesting that these patients are a reservoir for transmission of hepatitis-B-virus infection. Therefore, the presence of anti-HBs alone does not indicate a noninfectious serum. Concomitant HBsAg and anti-HBs seems to be particularly common in patients with renal disease who are on hemodialysis.