Failure after osteosynthesis of trochanteric fractures. Where is the limit of osteoporosis?

SUMMARY: The aim of this study is to identify osteoporosis values, beyond which there is a high risk of osteosynthesis failure. Bone mineral density (BMD) of 30 cadaveric femora with a pertrochanteric fracture osteotomy was correlated to the risk of cut out after osteosynthesis on a biomechanical testing approach. For a BMD less than 250 mg/cm(3), there is a high risk of fixation failure after surgical treatment of pertrochanteric fractures. This value can be regarded as a reference value for future experimental and clinical studies. INTRODUCTION: Despite continuous modification of intramedullary load carriers for the surgical stabilization of trochanteric fractures, cut out remains the most frequent complication. The aim of this experimental study was to identify threshold osteoporosis values, beyond which there is a high risk of osteosynthesis failure. METHODS: Bone mineral density (BMD) of 30 cadaveric femora was recorded for the femoral head by QCT measurement. Subsequently, a standardized osteotomy mimicking an unstable trochanteric type fracture was stabilized by intramedullary nailing. The constructs were loaded axially at a force of 2,100 N up to 20,000 cycles. Cut out at the femoral head was documented by radiograph. Statistical evaluation of the cohort group was performed by calculation of relative risk in relation to the BMD values. RESULTS: In total, there were six cases of cut out after 10,000 cycles. The incidence of cut out for BMD less than 250 mg/cm(3) was 0.55 (5 of 9) and for BMD greater than 250 mg/cm(3), it was 0.05 (1 of 21). Therefore, the relative risk of cut out for BMD <250 mg/cm(3) is 11× greater than for a BMD >250 mg/cm(3). After 20,000 cycles, an additional test caused one cut out (relative risk of cut out for a BMD <250 mg/cm(3) 5.8). CONCLUSIONS: For a BMD less than 250 mg/cm(3), there is a high risk of fixation failure after surgical treatment of pertrochanteric fractures. Although this value is based on an experimental in vitro study design with all its associated limitations, it can be regarded as a reference value for future experimental and clinical studies.

Salvage procedures for trochanteric femoral fractures after internal fixation failure: biomechanical comparison of a plate fixator and the dynamic condylar screw.

The aim of this study was the biomechanical evaluation of the reversed less invasive stabilization system (LISS) internal fixation as a joint-preserving salvage procedure for trochanteric fractures. Five LISS plates and five dynamic condylar screws (DCS) were tested using synthetic femora (Sawbones) with an osteotomy model similar to a type-A2.3 pertrochanteric fracture. The constructs were subjected to axial loading up to 1000 N for five cycles. Then, the force was continuously increased until fixation failure. For the evaluation of the biomechanical behaviour, the stiffness levels were recorded and the osteotomy gap displacement was mapped three-dimensionally. The average stiffness for the constructs with LISS plates was 412 N/mm (with a standard deviation (SD) of 103N/mm) and 572N/mm (SD of 116 N/mm) for the DCS constructs (p=0.051). Local displacement at the osteotomy gap did not yield any significant differences. The LISS constructs failed at a mean axial compression of 2103N (SD of 519N) and the DCS constructs at a mean of 2572N (SD of 372N) (p=0.14). It is concluded that the LISS plate offers a reliable fixation alternative for salvage procedures.

Induction interferon therapy in naïve patients with chronic hepatitis C: increased end-of-treatment virological responses but absence of long-term benefit.

BACKGROUND AND AIMS: The low efficacy of interferon monotherapy and data from viral kinetic studies led us to evaluate the efficacy of interferon administered daily in chronic hepatitis C. PATIENTS AND METHODS: Thirty-eight naïve patients with chronic hepatitis C and active liver disease randomly received 3 or 5 MU IFN-alpha daily for 1 month, followed by the same dose three times a week for 11 months. Results were compared to a three-times-a-week scheme of 3 MU IFN-alpha for 1 year. RESULTS: At the end of the induction period, 27 out of 38 (71%) patients had cleared HCV-RNA with a significantly higher rate in the 5 MU than in the 3 MU group (17 out of 18 or 94% vs. 10 out of 20 or 50%, P=0.003). The end-of-treatment virological response rate was 66% (25 out of 38) in the induction groups and 40% (10 out of 25) in the control group (P=0.04). Six months after completion of therapy, the sustained response rate dropped to 29% (11 out of 38) compared to 28% (7 out of 25) in the standard regimen. CONCLUSIONS: In chronic hepatitis C, treatment with 5 or 3 MU IFN-alpha daily during the first month of a standard IFN regimen leads to significantly increased end-of-treatment virological responses, but long-term responses are similar to those of standard IFN monotherapy.

Case report: Association of giant cell arteritis and pituitary tumor. Report of two cases.

Two patients with giant cell arteritis and visual deficits were found to have pituitary tumors, which accounted for the optic findings. The various ophthalmologic abnormalities in these two conditions, which were apparently coincidentally associated in these two patients, are compared. These cases illustrate the importance of careful neuro-ophthalmologic examination and roentgenograms of the head in patients with giant cell arteritis who have visual field loss.

Intramedullary nailing of trochanteric fractures: central or caudal positioning of the load carrier? A biomechanical comparative study on cadaver bones.

BACKGROUND: Current recommendations with regard to central or caudal positioning of the femur head carrier in the management of trochanteric fractures are contradictory. METHODS: A standardised pertrochanteric osteotomy was stabilised in 15 pairs of cadaver femurs by means of intramedullary osteosynthesis (5xPFN-A-Synthes, 5xIntertan-Smith&Nephew, 5xTargon-PF-Aesculap). For each pair randomised central (group A) or caudal (group B) implantation of the femoral neck component was performed. Subsequently, the constructs were axially loaded to 2100N. In the absence of cut out after 20,000 cycles, load was increased to a maximum force of 3100N. Angular displacement was recorded based on ultrasound. Migration of the load carrier in the femoral head was monitored radiologically. FINDINGS DISPLACEMENT: No significant difference between groups (p>0.15) was found for the first 50 load cycles. A significantly greater degree of varus deformity was observed in group A (p=0.049) after 2000 load cycles and became more apparent as the number of load cycles increased (after 6000 cycles p=0.039, after 20,000 cycles p=0.034, after 22,000 cycles p=0.016). Angular displacement in the other two planes did not differ significantly across groups. CUT OUT: Migration of the load carrier in the femoral head was not significantly different for the two groups. Overall cut out occurred in 9 constructs, 3 in group A and 6 in group B. The difference in cut-out rate was not significant (p=0.213, chi-squared test). CONCLUSION: Biomechanical superiority can be shown for caudal positioning of the femoral neck load carrier in terms of reduced varus deformity. The incidence of cut out is however unaffected by the position of the load carrier.

Non-oxidative coupling of methane catalysed by supported tungsten hydride onto alumina and silica-alumina in classical and H2 permeable membrane fixed-bed reactors.

Non-oxidative coupling of methane with high selectivity into ethane (>99% among hydrocarbon) in a classical fixed-bed reactor catalysed by SiO(2)-Al(2)O(3) or gamma-Al(2)O(3) supported tungsten hydride is presented. Continuous hydrogen separation, using a Pd-Ag membrane in a fixed-bed reactor, led to methane coupling far beyond the thermodynamic equilibrium conversion.

Vasculitis of the gallbladder in a 70-year-old man with giant cell (temporal) arteritis.

A patient with giant cell (temporal) arteritis developed acute cholecystitis related to vasculitis. Histopathologically, the vasculitic lesions in the gallbladder resembled polyarteritis nodosa. In addition to demonstrating the rare occurrence of vasculitis of the gallbladder in a patient with giant cell arteritis, this case points out the inadequacies of currently used criteria to separate the various forms of arteritis.

Cellular immunity in polymyalgia rheumatica and giant cell arteritis: lack of response to muscle or artery homogenates.

Peripheral blood lymphocyte functions were evaluated in 20 patients with active polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA) by determining the percent of E-rosette-forming cells and by measuring the uptake of tritiated thymidine by peripheral blood lymphocytes after exposure to common infectious antigens and to homogenates of homologous and heterologous artery, muscle, and elastin. Although lymphocytes from patients with PMR and/or GCA were stimulated slightly by artery and muscle homogenates, no differences in lymphocyte responses were found when the results were compared with 22 normal controls and 16 patients with rheumatoid arthritis. The hypothesis that GCA results from a cellular immune reaction to normal or diseased arterial wall antigens is not supported by these studies.

Multiple myeloma and acute leukemia.

A patient suffering from multiple myeloma without treatment with cytoxic drugs or irradiation, died within 4 months, from acute leukemia. The appearance of acute leukemia in a patient with multiple myeloma without previous treatment is very unusual. The relation of these two conditions is briefly discussed.

The role of the hepatitis delta virus in acute hepatitis and in chronic liver disease in Greece.

HDV infection has been documented in Greece for more than 3 decades. Its epidemiology appears to be changing over the years with a decrease in the general Greek population and an invasion of the delta virus in the community of drug addicts. For the time being HDV infection has a low endemicity in the general greek population, it has been detected with high endemicity in a rural community and it is spreading epidemically in the new, increasing population of Greek drug addicts. Chronic HDV infection has been detected constantly over 20 years with a higher frequency in HBsAg positive chronic liver disease (19.5-33.5%) than in asymptomatic HBsAg carriers with normal liver enzymes (5.9-9.2%). However, in the community of Archangelos, where HDV infection is highly endemic, and probably also all over Greece, the total number of chronic HDV carriers with minimal or no liver disease appears to be higher than those with severe liver damage. HDV infection plays a significant role in terms of morbidity and mortality from acute and chronic liver disease in Greece but the situation would have been much worse if chronic HDV infection was invariably associated with severe liver damage.

Expression of pre-S gene-encoded proteins in liver and serum during chronic hepatitis B virus infection in comparison to other markers of active virus replication.

Pre-S gene-encoded proteins of the hepatitis B virus (HBV) were studied in the liver by immunofluorescence and in serum by radioimmunoassay in 30 patients with chronic HBV infection. The results were compared with molecular hybridization analysis of HBV-DNA in liver and serum, with serum hepatitis B e antigen/antibody (HBeAg/anti-HBe) status and with underlying liver histology. Pre-S peptides were detected in the serum of 11 patients, 10 of whom were positive for serum HBV-DNA and/or liver hepatitis B core antigen. Only 4 of these patients were HBeAg positive. The prevalence of serum pre-S among HBV replicating carriers was 59% (10/17) compared to only 8% (1/13) among those with non-replicating virus (P less than 0.01). All patients with circulating pre-S peptides had active liver disease. Anti-pre-S was detected in the serum of only 4 patients, 3 with integrated HBV-DNA. In contrast to serum findings, pre-S peptides were detected in the liver of all patients with histochemically demonstrable hepatitis B surface antigen (HBsAg), regardless of HBV replicative status. HBsAg carriers with integrated HBV-DNA had abundant cytoplasmic pre-S1 and pre-S2 localized in numerous ground-glass hepatocytes. It is concluded that pre-S peptides are usually displayed in the liver simultaneously with histochemically detectable HBsAg; they are secreted in the serum in association with high HBV replication and release of HBV particles, but in the absence of episomal HBV replication, pre-S peptides seem to be largely retained within hepatocytic membranes.

Interferon alfa-2b treatment of HBeAg negative/serum HBV DNA positive chronic active hepatitis type B.

A randomized controlled trial of recombinant interferon alfa-2b has been initiated in patients with chronic active hepatitis who were negative for serum hepatitis B e antigen but positive for serum hepatitis B virus DNA and hepatitis B core antigen expression in the liver. Twenty-five patients received interferon alfa-2b 3 million units thrice weekly for 14-16 weeks and 25 served as untreated controls. Seventeen patients in the treatment and 18 in the control group have already completed a 12-month period of observation. Interferon alfa-2b was well tolerated by all patients. At the end of therapy, complete responses, defined as disappearance of hepatitis B virus DNA from serum and return of alanine aminotransferase to normal, were observed in 10 (59%) of the 17 treated patients compared to none in the control group (p less than 0.01). Twelve months after the onset of interferon alfa-2b therapy, 11 (65%) of the 17 treated patients were complete responders compared to 2 (11%) of 18 in the control group (p less than 0.01). Fifty per cent (4/8) of complete responders to interferon alfa-2b therapy, followed for 16-24 months, experienced reactivations of hepatitis B virus replication with reappearance of serum hepatitis B virus DNA and a return of serum alanine aminotransferase activity. The response to interferon alfa-2b therapy appeared to be independent of pre-treatment serum alanine aminotransferase and hepatitis B virus DNA levels.

Effect of IgG and C-reactive protein on complement depletion by monosodium urate crystals.

Complement activity in normal human serum was rapidly depleted by the addition of monosodium urate crystals (MSUC), while the same MSUC preparation had little effect on complement activity in 4 of 8 sera from patients with common variable immunodeficiency (CVID). The degree of complement depletion in the CVID sera correlated with their C-reactive protein (CRP) concentrations but not with their concentrations of IgG. MSUC-induced complement depletion in the 4 poorly reactive sera was partially restored by addition of CRP or by normalizing the IgG concentration, but not by addition of IgM or IgA. It is proposed that CRP, an acute phase protein, may play a role in the pathogenesis of gouty arthritis attacks occurring in some patients following surgery or acute physical illness.

Yersinia enterocolitica endocarditis: case report and literature review.

Endocarditis is a rare manifestation of Yersinia enterocolitica infection. The case of a 45-year-old man who presented with high fever and in whom prosthetic valve Yersinia enterocolitica endocarditis was diagnosed is described. The patient was successfully treated with ceftriaxone plus tobramycin, as proved by negative cultures of the prosthesis removed at the end of therapy. Including the patient reported, only 12 cases of Yersinia enterocolitica endocarditis have been published to date, two of which describe prosthetic cardiac valve endocarditis. The clinical characteristics do not distinguish septicemia from involvement limited to the cardiac valves. Diagnosis, however, has been improved by progress in echocardiography. Prognosis is grave but can be ameliorated if appropriate antimicrobial agents are administered, i.e. the combination of a third-generation cephalosporin plus an aminoglycoside. Fluroquinolones may also constitute an attractive therapeutic alternative.

Circulating immune complexes in giant cell arteritis and polymyalgia rheumatica.

Sera from 74 patients with polymyalgia rheumatica or giant cell arteritis or both were tested for immune complexes by using the Raji cell radioimmunoassay. Levels in patients with active disease were higher than in patients whose disease had become inactive. There was no difference in levels of immune complex-like materials between patients with polymyalgia rheumatica alone and those with giant cell arteritis. Density gradient analysis of one serum showed immune complex-like materials mainly in the 19S region. Immune complexes may be important in the pathogenesis of these conditions.

Local hyperhidrosis.

A case of local hyperhidrosis at the ulnar aspect of the left forearm-carpal region with exacerbation, especially during summer, is presented. The sweat function is normal on the remainder of the body. This case is rare, and few similar cases are known in the literature. The possible pathogenetic mechanisms are discussed.

Biochemical and virological outcome of patients with chronic hepatitis C treated with interferon alfa-2b for 6 or 12 months: a 4-year follow-up of 211 patients.

To compare two interferon (IFN) schedules for the treatment of chronic hepatitis C, we followed 211 patients who received 3 million units IFN-alpha2b thrice weekly for either 6 months (group 1; 85 patients) or 12 months (group 2; 126 patients), with a median follow-up of 3.4 (0.1-8.4) and 4.2 (0.7-8.7) years, respectively. The biochemical and virological responses at the end of treatment were 34.1% and 16.5% versus 62.7% and 41.2% for the 6- and the 12-month regimens, respectively. Late biochemical responses (after the third month of treatment) occurred in 30.6% of responding patients, and they were not particularly associated with an adverse long-term treatment outcome. In a multivariate analysis, patients with a primary response were significantly more frequently infected with a non-1b HCV genotype (relative risk [RR]: 14.4), had been treated for 12 months (RR: 6.0), and had an early stage of liver fibrosis (RR: 5.2). Baseline serum HCV-RNA and ferritin levels also bore a significant, though weaker, association with a primary response. Using a set of pretreatment variables in a model of discriminant analysis, we could correctly predict the long-term virological outcome in 86.6% of the individual cases. At the end of follow-up, a biochemical and virological sustained response was observed in 14.1% and 11.8% versus 40.5% and 31% of groups 1 and 2, respectively. Significant predictors of a virological sustained response were a virological primary response (RR: 41.2) and the pretreatment level of serum HCV-RNA (RR: 10.3 per each 10(6)-Eq/mL decrease). Patients with a "good treatment profile," including an early stage of liver fibrosis, a non-1b genotype and serum HCV-RNA <0.35 x 10(6) Eq/mL, had a 66.7% rate of observed virological SR, compared with a zero response for those with the opposite, a "bad treatment profile." We conclude that a 12-month IFN treatment, along with a non-1b genotype and the absence of advanced stage of fibrosis, are the main determinants for the induction of a virological primary response in chronic hepatitis C. Such response, along with a low pretreatment serum HCV-RNA level, are the main predictors for a 4-year virological response to IFN.

Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis B.

We evaluated the safety and efficacy of long-term lamivudine monotherapy in a group of 25 patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Lamivudine was administered in a daily dose of 150 mg for a mean of 26 +/- 7 months and was well tolerated. No patient lost hepatitis B surface antigen (HBsAg). The rate of initial biochemical response increased from 88% at 6 months to 96% at 12 months of therapy, but it progressively decreased thereafter; the biochemical remission rate was 68% at 18 months, 59. 5% at 24 months, and 42.5% at >/=30 months. Alanine transaminase (ALT) increased to higher than the baseline levels in 8 of the 11 patients with a biochemical breakthrough reaching acute hepatitis levels in 6 of them. Acute icteric hepatitis developed in one patient. The virologic remission rate assessed by a sensitive quantitative polymerase chain reaction (PCR) assay was 68% at both 6 and 12 months, decreasing thereafter to 52% at 18 months and to 41. 6% at both 24 and >/=30 months. Virologic breakthroughs were always persistent and preceded ALT elevations by a median of 4 (3-24) months. YMDD mutants were detected in all patients with a virologic breakthrough. In conclusion, in patients with HBeAg-negative chronic hepatitis B, long-term lamivudine therapy is safe and is associated with high biochemical and virologic response rates at the end of the first year. However, response rates tend to decrease with time and breakthroughs due to YMDD mutants accumulate. ALT activity during breakthroughs often exceeds the baseline and may reach even acute hepatitis levels.

Base changes at positions 1014 and 578 of delta virus RNA in Greek isolates maintain base pair in rod conformation with efficient RNA editing.

Analysis of delta hepatitis virus (HDV) genomic RNA, derived from Greek patients from an area where HDV infection is associated with low pathogenicity, is described. In all isolates sequenced, which included 18/18 HDV cDNA clones derived from 6 different patients, irrespective of pathogenicity, a base change (T-->C) was found in position 1014. No significant differences in editing efficiency were found between isolates from inactive and active forms of the disease, although L-antigen was present in low to undetectable levels in the serum of 5/6 patients. An additional mutation was identified at position 578 (A-->G), which reestablishes the canonical base pair G/C with the mutated 1014 when the genome adopts the "rod-like" conformation. This finding supports the presence of this genome conformation in vivo and the requirement for the Watson-Crick base pair 1014/578. A mutation, found at amino acid position 170 (serine-->asparagine), appears to segregate with patients with inactive disease.