Trapezial resection arthroplasty for osteoarthritis: use of abductor pollicis longus tendoplasty with interpositional material.

In this series, 45 patients had 54 trapezial resection arthroplasties for carpometacarpal osteoarthritis, with nine of the patients having bilateral arthroplasties. A major slip of the abductor pollicis longus tendon was used as a sling, with the underlying flexor carpi radialis tendon as stabilizer. Palmaris longus tendon, when present (42 cases), and absorbable gelatin sponge, when palmaris was absent (12 cases), served as interpositional material. Review was done an average of 4.3 years (range, 1 to 11 years) after the procedure. The average space maintenance of resection site was 4.4 mm. This decreased to an average of 3.5 mm on the key pinch stress maneuver. Subjectively, the patients judged their results to be good to excellent in 49 instances (91%) and fair in 5 (9%).

Triceps tendon rupture in weight lifters.

Triceps tendon avulsion injuries are rare. We report four weight lifters with triceps tendon raptures, two of whom had received local steroid injections for pain in the triceps. All four patients had taken oral anabolic steroids before injury. All patients had closed avulsion of the triceps tendon from its insertion into the olecranon. Three patients were injured while bench pressing heavy weights, and one patient was injured while swinging a baseball bat. Satisfactory results were achieved after surgical reinsertion of the tendon.

Modulation of protein kinase C activity in Plasmodium falciparum-infected erythrocytes.

Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces many morphological and biochemical changes in the host cell. Host serine/threonine protein kinases could be involved in some of these processes. The aim of this study was to determine the effect of infection on red blood cell protein kinase C (PKC) and establish the importance of this enzyme in parasite growth and sexual stage differentiation. Phorbol myristate acetate (PMA)-induced translocation of erythrocyte PKC activity is impaired in erythrocytes enriched for mature asexual stage infected cells. Western blotting shows that this is due to a relative reduction in membrane PKC protein levels rather than inhibition of enzyme activity and analysis of PKC activity isolated from whole cell lysates by DE52 chromatography suggests that total activatable PKC levels are lower in infected erythrocytes. A reduction in PMA-induced activation is also observed in PKC assays performed in situ. Downregulation of erythrocyte PKC by overnight incubation with PMA before infection causes a significant decrease in the rate of the asexual growth, suggesting that the enzyme, although lost later in infection, may be important in the earlier development of the parasite. By contrast, the lack of PKC had no effect on the production of sexual stage parasites.

Bacterial translocation to mesenteric lymph nodes is increased in cirrhotic rats with ascites.

BACKGROUND/AIMS: Cirrhotic patients are predisposed to develop spontaneous bacteremias and/or peritonitis, mainly caused by enteric bacteria. The aim of this study was to investigate if bacterial translocation, which is the passage of bacteria from the intestinal lumen to regional lymph nodes and/or the systemic circulation, is increased in a rat model of cirrhosis. METHODS: Rats were studied after 12-16 weeks of CCl4 inhalation, when samples of mesenteric lymph nodes, blood, liver, and spleen for standard bacteriologic cultures and a fragment of colon and liver for histology were obtained. Immunostaining of the cecum was performed using a polyclonal anti-Escherichia coli antibody. RESULTS: A significantly greater proportion of rats with cirrhosis and ascites (5 of 9; 56%) had positive mesenteric lymph node cultures compared with cirrhotics without ascites (0 of 9) and normal controls (0 of 12) (P < 0.01). In one cirrhotic rat, E. coli was isolated from both mesenteric lymph nodes and ascites. Rats with cirrhosis and ascites had significantly greater cecal submucosal edema and inflammation than rats with no ascites and controls. Immunoreactivity with E. coli was present in the cecal wall in 3 of 5 animals with E. coli translocation to mesenteric lymph nodes. CONCLUSIONS: In cirrhotic rats, bacterial translocation is increased after the development of ascites and may be a major factor in the development of spontaneous infections in cirrhosis.

First reported case of Aspergillus granulosus infection in a cardiac transplant patient.

We report a case of disseminated infection with Aspergillus granulosus in a cardiac transplant recipient on immunosuppressive therapy. This is the first reported case in which this organism has been described as a pathogen. This organism bears morphological features different from those of more common Aspergillus species and should be considered a potential pathogen in immunocompromised patients.

Bacterial translocation in acute and chronic portal hypertension.

Patients with cirrhosis are predisposed to develop spontaneous bacteremias and peritonitis, mainly by enteric bacteria. Portal hypertension, by producing congestion and edema of the bowel wall, could increase the passage of bacteria from the intestinal lumen to regional lymph nodes to the systemic circulation or to both, a process termed bacterial translocation. The aim of this study was to investigate bacterial translocation at two stages of experimental portal hypertension: (a) acute (when shunting is minimal); and (b) chronic (when shunting is extensive and mimics the portal hypertension of cirrhosis). Rats were killed 2 days (acute) or 15 days (chronic) after partial portal vein ligation or control surgeries. Samples of mesenteric lymph nodes, blood, liver and spleen for standard bacteriological cultures and a fragment of ileum for histological examination were obtained. Two days after surgery, a significantly greater proportion of rats with acute portal hypertension (12 of 13 or 92%) had positive mesenteric lymph node cultures compared with both control groups: sham-operated (4 of 13 or 31%) and inferior vena cava-ligated (3 of 10 or 33%) animals (p < 0.01). However, 15 days after surgery no differences in translocation to mesenteric lymph nodes were found between rats with chronic portal hypertension (3 of 15 or 20%) and sham-operated controls (3 of 11 or 27%). In neither the acute nor the chronic rats were bacteria isolated from blood, spleen or liver. Rats with acute portal hypertension had significantly greater mesenteric inflammation than rats with chronic portal hypertension and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Human monoclonal antibodies specific for blood group antigens demonstrate multispecific properties characteristic of natural autoantibodies.

A panel of 72 human monoclonal antibodies with specificities for blood group antigens, A, Rh D, Rh C, Rh c, Rh E, Rh e, Rh G, Jka and Jkb, has been established from the peripheral blood of deliberately immunized donors. Previous work has established that the antibodies are highly specific for their respective blood group antigens, and a number of them are in routine clinical use as blood grouping reagents. This panel was screened for reactivity against six unrelated foreign and autoantigens by ELISA, for rheumatoid factor activity by ELISA and agglutination techniques, and for reactivity with a number of different tissues by immunofluorescence. Binding of the monoclonal antibodies to unrelated exo- and autoantigens was commonly seen amongst the antibodies of the IgM class, and to a lesser degree amongst the IgG class, with reaction patterns similar to those given by natural autoantibodies. Only five of the IgM antibodies failed to demonstrate any unexpected cross-reactivities and these included 1/13 anti-D, 2/7 anti-E, 1/13 anti-c and 1/2 anti-A. We propose that rather than natural autoantibodies representing a distinct population of immunoglobulins, multispecificity (polyspecificity, or polyreactivity) may be a feature of antibodies produced in response to exogenous antigens. The implications of this for the study of autoantibodies are discussed.

Human monoclonal antibodies against blood group antigens preferentially express a VH4-21 variable region gene-associated epitope.

An anti-idiotypic antibody has been raised which recognizes human immunoglobulins with cold agglutinin activity of anti-I/i specificity. The pattern of reactivity of the antibody indicates that the structural basis for the epitope is located in the VH4-21 gene segment of the VHIV family, which is preferentially utilized by these cold reactive antibodies. Using this antibody, epitope expression was investigated in a panel of 72 human monoclonal allo-antibodies specific for human blood group antigens, as compared with a control panel of 39 randomly selected human monoclonal IgM antibodies of unknown specificities. The anti-blood group panel included 44 IgM and 28 IgG monoclonal antibodies against a variety of blood group antigens including the A antigen, Rh C, c, D, E, e, G antigens, and the Kidd antigens Jka and Jkb. The epitope was expressed by 64% (28/44) of the IgM anti-blood group antibodies and by 21% (6/28) of the IgG antibodies, but by only 7.7% (3/39) of the control IgM antibodies. These data indicate that the human alloimmune response to blood group antigens is biased in the use of VH gene families, with a preference for the VH4-21 gene segment of the VHIV family, or closely related gene segments. The fact that this mirrors the findings for the autoimmune cold agglutinins suggests a link in immunoglobulin gene usage between antibodies against structurally diverse antigens on the red cell surface.

Human monoclonal antibodies to human blood group antigens Kidd Jka and Jkb.

Three IgM human monoclonal antibodies to Jkb, and one IgM human monoclonal antibody to Jka were produced from the lymphocytes of two immunized donors. Two of the anti-Jkb monoclonal antibodies (MS-7 and MS-9) are of the IgM (kappa) isotype and one (MS-8) is an IgM(lambda). The anti-Jka monoclonal antibody (MS-15) is of the IgM(kappa) isotype. They are all specific for their respective antigens, and give positive agglutinations in saline by the immediate spin technique, even against Jk(a+b+) cells. The heterohybridomas have been shown to be suitable for bulk culture and produce levels of antibody that reach 18 micrograms/ml in the spent culture supernatant. They offer considerable advantages over currently available reagents in terms of stability, simplicity and speed of use, and will provide a reliable and unlimited supply of what are at the moment rare and unsatisfactory antibodies.

Ability of unstimulated and phorbol-ester-stimulated human blood-monocyte-derived macrophages to metabolize drugs and its implications.

Solutions containing 5,5-diphenyl[4-14C]hydantoin (15 micrograms/ml) or pheno[2-14C]barbital (20 micrograms/ml) were incubated for 0.5-6 h with monolayers of unstimulated and phorbol-ester-stimulated human blood-monocyte-derived macrophages and suspensions of K562 cells. The incubated solutions were centrifuged and the cell-free supernatants subjected to chromatography on Q-Sepharose Fast Flow anion exchange resin. The interaction with unstimulated macrophages but not with K562 cells resulted in a time-dependent conversion of the original radioactive drug molecules to molecules with a larger negative charge in the case of diphenylhydantoin and a smaller negative charge in the case of phenobarbital. These conversions were prevented by 20 mM tetrahydrofurane and partially inhibited by 300 U/ml superoxide dismutase (SOD) and, therefore, appeared to depend on cytochrome-P-450-mediated reactions and to some extent also on superoxide anion radicals. Macrophages which were stimulated by 20 nM phorbol myristate acetate metabolized both drugs at much faster rates than unstimulated macrophages. Since this increased metabolism was abolished in the presence of SOD, it appeared to be entirely dependent on superoxide anion radicals. These data provide biochemical evidence that unstimulated human monocyte-derived macrophages have a substantial capacity to metabolize certain xenobiotics and that stimulated macrophages have an even greater capacity to do so. This property of macrophages may have considerable biological significance and be important in the pathogenesis both of drug-induced tissue damage and of malignant disease.

Human monoclonal antibodies to C, c, E, e and G antigens of the Rh system.

A panel of heterohybridomas secreting human IgG and IgM monoclonal antibodies to the C, c, G, E, and e antigens of the Rh system has been established. Both classes of antibody have been shown to react with red blood cells carrying their respective antigens; those of the IgM class being able to directly agglutinate unmodified red blood cells in saline. The heterohybridomas have been shown to be suitable for bulk culture and produce levels of antibody in the range of 15-73 micrograms/ml in the spent culture supernatant.

Differences in the nature and kinetics of the ethanol-related circulating cytotoxic proteins in normal subjects and patients with alcohol-induced cirrhosis.

The kinetics and nature of the nondialyzable cytotoxic activity which appeared in the serum after the consumption of 1.2 g ethyl alcohol per kilogram body weight over 45 min was studied in six healthy volunteers and eight patients with histologically proven alcohol-related cirrhosis of the liver. Whereas the cytotoxic activity in the dialyzed serum showed a single peak with a maximum value 8 hr after the start of ethanol consumption in the healthy volunteers, it showed two peaks with maximum values at 2 and 8 hr in the patients with cirrhosis. Studies of the fractions obtained by Sephacryl-S-300 gel filtration of the 2-hr postalcohol serum samples revealed substantial cytotoxic activity in the fractions containing both the albumin peak and the IgG peak in the patients with cirrhosis and only in the fractions containing the albumin peak in the healthy volunteers. Experiments with pure IgG preparations obtained from prealcohol and 2-hr postalcohol sera by chromatography on Q-Sepharose Fast Flow anion-exchange resin showed considerable cytotoxic activity in the preparations from the patients with cirrhosis and little or no cytotoxic activity in those from the healthy volunteers. Thus, the early peak of the biphasic serum cytotoxicity curve seen after ethanol consumption by patients with cirrhosis appeared to be caused by the development of a substantial cytotoxic activity in the IgG molecules during the first 2 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde-modified serum proteins inhibit mitogen-stimulated human lymphocyte transformation.

Sera obtained from healthy volunteers immediately before and 8 h after the rapid consumption of 1.2 g ethanol/kg body weight were dialysed against RPMI 1640 and added ab initio to microcultures of normal human lymphocytes containing 1-3 micrograms phytohaemagglutinin (PHA)/ml or 2-8 micrograms pokeweed mitogen (PWM)/ml. When compared with the pre-alcohol sera, the post-alcohol sera inhibited lymphocyte transformation after 48 h incubation with either mitogen. In other experiments, acetaldehyde-albumin complexes were generated by reacting solutions of human serum albumin with 45-720 microM acetaldehyde, and the same quantity of either unmodified albumin or acetaldehyde-modified albumin was included in freshly-prepared lymphocyte microcultures containing 3 micrograms PHA/ml or 8 micrograms PWM/ml. When compared with unmodified albumin, acetaldehyde-modified albumin inhibited lymphocyte transformation after 48 h of culture with either mitogen. The inhibition of lymphocyte transformation caused by post-alcohol sera and acetaldehyde-modified albumin was partially corrected after treatment of the proteins with 1.55 mM sodium borohydride at a pH of 9.5. The data indicate that post-alcohol sera contain a non-dialysable activity which inhibits mitogen-stimulated lymphocyte transformation in vitro and that at least part of this activity may reside in acetaldehyde-modified serum albumin.

A nosocomial outbreak of Branhamella catarrhalis confirmed by restriction endonuclease analysis.

An outbreak of respiratory illness due to Branhamella catarrhalis occurred in the intermediate care unit of a Veterans Administration hospital and involved patients and staff members. Four patients had pneumonia and four had bronchitis. Infected patients were placed in a cohort separated from noninfected patients and were treated. Pharyngeal culture was used to survey prevalence in staff and all other patients on the unit; three of 18 staff members and two of 19 asymptomatic patients were positive for B. catarrhalis. A case-control study showed that respiratory therapy, steroid use, and location within the unit were significant risk factors for B. catarrhalis infection or colonization. Strains from five patients and two staff members had identical bacterial restriction endonuclease digestion patterns with three different enzymes; these patterns were distinct from those of control strains. This study is the first to document an outbreak of B. catarrhalis infection confirmed with a typing system and thus establishes B. catarrhalis as a nosocomial pathogen.

Circulating cytotoxic protein generated after ethanol consumption: identification and mechanism of reaction with cells.

Serum obtained from healthy volunteers 6-7 h after consumption of 60-95 g of ethanol contained cytotoxic activity against mouse A9 cells and all of six human cell lines tested. Affinity chromatography of such sera demonstrated that at least some of the cytotoxic molecules consisted of altered albumin. Complexes formed by the reaction of 14C-acetaldehyde with 125I-labelled human serum albumin in vitro were also cytotoxic. After treatment with a reducing agent, sodium borohydride, the cytotoxicity of both post-alcohol serum and the acetaldehyde-albumin complexes fell sharply, suggesting that the cytotoxic activity resided in the unstable Schiff bases formed during the first stage of reaction between the acetaldehyde and proteins. A detailed analysis of the reaction between the double-labelled acetaldehyde-albumin complexes and K562 cells revealed that the cytotoxic activity resulted from the release of acetaldehyde from such complexes and the preferential binding of the free acetaldehyde to the target cells.

The capacity of macrophages from different murine tissues to metabolise ethanol and generate an ethanol-dependent non-dialysable cytotoxic activity in vitro.

Tissue macrophages obtained from liver, bone marrow, spleen and thymus of C57 BL/6 mice closely resembled blood-monocyte-derived human macrophages in three characteristics. These were: the rate of metabolism of ethanol to acetate, the biochemical pathways involved in ethanol metabolism and the ability to generate an ethanol-dependent non-dialysable cytotoxic activity in vitro. The metabolism of ethanol by all four types of murine tissue macrophage was only slightly suppressed by pyrazole, 4-iodopyrazole and 3-amino-1,2,4-triazole, which are known to inhibit alcohol dehydrogenase (ADH), pi ADH and catalase respectively. By contrast, ethanol metabolism by these cells was strongly suppressed by three inhibitors of the cytochrome P-450-dependent microsomal ethanol-oxidising system--namely, carbon monoxide, metyrapone and tetrahydrofurane.

Cytotoxic protein molecules generated as a consequence of ethanol metabolism in vitro and in vivo.

A non-dialysable cytotoxic activity developed in the supernatants of human blood-monocyte-derived macrophages cultured in the presence of ethanol and in the serum of three healthy volunteers who drank 500-700 ml wine over 20-35 min. On 'Sephacryl S-300' gel filtration of the culture supernatants and the serum samples from the subjects who took alcohol, the cytotoxic activity eluted together with albumin molecules. Studies of human serum and of various commercially purchased human serum protein fractions treated with carbon-14-labelled acetaldehyde and non-radioactive acetaldehyde, respectively, provided strong circumstantial evidence that the cytotoxic proteins were albumin molecules that had become complexed with acetaldehyde generated by the metabolism of ethanol. The cytotoxic activity developing in vivo was greatest 6-10 h after the consumption of ethanol started, when blood alcohol levels were normal or only slightly high. The appearance of a circulating long-acting cytotoxic macromolecule after the ingestion of ethanol may be of considerable importance in clarifying the mechanisms underlying ethanol-induced tissue damage.

Hospital-acquired gangrenous mucormycosis.

A post-operative diabetic patient who had been treated for Serratia marcescens bacterial sepsis developed recurrent thrombosis of the left femoral artery following intra-arterial instrumentation. Pathological examination of arterial thrombus ultimately demonstrated invasive mucormycosis of the femoral artery and cultures of this material grew Rhizopus oryzae. The occurrence of cutaneous and subcutaneous mucormycosis is reviewed, as well as recently recognized nosocomial risk factors for mucormycosis, such as elasticized bandages and wound dressings.