Mechanism(s) promoting HIV-1 infection of primary unstimulated T lymphocytes in autologous B cell/T cell co-cultures

Resting CD4(+) T cells in the lymphoid tissue (LT) are essential producers of virions at the beginning of HIV infection in vivo. We previously developed a model that allowed in vitro infection of non-prestimulated T lymphocytes in the presence of autologous B lymphocytes and complement. In this study, we try to clarify the mechanism(s) responsible for virus transmission in unstimulated autologous B cell/T cell co-cultures. Ex vivo analyses of patient plasma samples revealed that HIV was opsonized. Flow cytometry showed that opsonized virus preferentially bound to complement receptor (CR)-2 on B lymphocytes in primary B cell/T cell co-cultures. As indicated by cytokine measurements and transwell experiments, soluble factors seemed to play a minor role in enabling infection. Rather, direct interaction between B and T lymphocytes and direct binding of opsonized virus to CR2 on B cells turned out to be essential for productive infection. Antibodies blocking cell-cell adhesion inhibited p24 antigen production. An anti-CR2 antibody blocking C3d-CR2 binding also significantly reduced viral replication. Since the infection of unstimulated T cells by opsonized primary HIV isolates in the presence of B cells was highly efficient independent of the tropism of the virus, this mechanism may be critical in the pathogenesis of HIV.     

Complement receptors type 1 (CR1, CD35) and 2 (CR2, CD21) cooperate in the binding of hydrolyzed complement factor 3 (C3i) to human B lymphocytes

The C3b-binding receptor, CR1/CD35, supports CR2/CD21-mediated activation of complement by human B lymphocytes, possibly by associating with CR2 to promote or stabilize the binding of hydrolyzed C3 (C3i), the primary component of the AP convertase, C3i-Bb. To evaluate this hypothesis, we examined the uptake kinetics and binding equilibria for C3i dimer interaction with human blood cells in the absence and presence of CR1- and CR2-blocking mAb. C3i displayed dual uptake kinetics to B lymphocytes, comprising of rapid binding to CR1 and slower binding to CR2. The forward rate constants (k(1)) for CR1 and CR2, operating independently, differed ca. 9-fold (k(1)=193+/-9.4 and 22.2+/-6.0 x 10(3) M(-1)s(-1), respectively). Equilibrium binding of C3i to B lymphocytes was also complex, varying in strength by ca. 13-fold over the C3i concentration range examined. The maximum association constant (K(a, max)=109+/-27.2 x 10(7) l/mole) was ca. 9- and 6-fold greater, respectively, than those for CR1 or CR2 acting alone (K(a)=13.2+/-5.3 and 18.5+/-3.5 x 10(7) l/mole). The high avidity of the CR1-CR2 complex for C3i is consistent with its rates of C3i uptake and release being determined by CR1 and CR2, respectively.     

Grisel-Syndrom nach Anthelixplastik

Grisel??s syndrome is known as a very rare complication of ENT surgery. It is described as non-traumatic atlantoaxial rotatory subluxation, often seen after tonsillectomy or adenoidectomy in children. Therapy is staged according to the Fielding classification. We report the case of a 9-year-old female patient with Grisel??s syndrome after otoplasty. The diagnosis was confirmed by CT scan. Manual reposition was performed under general anaesthesia, followed by temporary immobilization with a Minerva orthesis     

Surgical resection and radiation therapy of desmoid tumours of the extremities: results of a supra-regional tumour centre

Purpose

Desmoid tumours of the extremity have a high recurrence rate. The purpose of this study was to analyse the outcome after resection of these tumours with special emphasis on recurrent disease and adjuvant therapeutic strategies.

Methods

In this retrospective study we evaluated prognostic factors for recurrence-free survival after surgical treatment of desmoid tumours of the extremity in 27 patients with an average age of 41 years treated from 1997 to 2009. Adjuvant radiotherapy (50–60 Gy) was given in five cases with primary and in nine patients with recurrent disease. The average follow-up was 64 months.

Results

The five-year recurrence-free survival in patients with primary disease was 33 %. Patients with negative resection margins tended to have a better outcome than patients with positive resection margins, but the difference between both groups was not significant (56 vs 14 %, p = 0.145). In patients with positive margins, adjuvant radiotherapy did not significantly improve recurrence-free survival (40 vs 14 %, p = 0.523). Patients with local recurrence had a five-year further recurrence-free survival of 47 %. In those patients further recurrence-free survival was significantly better after adjuvant radiation (89 vs 25 %, p = 0.015). Two thirds of all patients suffered moderate or severe complications due to the treatment regimen.

Conclusions

Compared to desmoids of the trunk or the head and neck region, desmoids affecting the limbs show by far the worst outcome in terms of relapse or treatment-related morbidity. The importance of negative resection margins is still not clear. Particularly in recurrent desmoids adjuvant radiotherapy appears to reduce the further recurrence rate. Therefore, a general use of radiation should be considered for this high-risk group.     

Customised osteotomy guides and endoprosthetic reconstruction for periacetabular tumours

Purpose

We sought to analyse clinical and oncological outcomes of patients after guided resection of periacetabular tumours and endoprosthetic reconstruction of the remaining defect.

Methods

From 1988 to 2008, we treated 56 consecutive patients (mean age 52.5 years, 41.1 % women). Patients were followed up either until death or February 2011 (mean follow up 5.5 years, range 0.1–22.5, standard deviation ± 5.3). Kaplan–Meier analysis was used to estimate survival rates.

Results

Disease-specific survival was 59.9 % at five years and 49.7 % at ten and 20 years, respectively. Wide resection margins were achieved in 38 patients, whereas 11 patients underwent marginal and seven intralesional resection. Survival was significantly better in patients with wide or marginal resection than in patients with intralesional resection (p = 0.022). Survival for patients with secondary tumours was significantly worse than for patients with primary tumours (p = 0.003). In 29 patients (51.8 %), at least one reoperation was necessary, resulting in a revision-free survival of 50.5 % at five years, 41.1 % at ten years and 30.6 % at 20 years. Implant survival was 77.0 % at five years, 68.6 % at ten years and 51.8 % at 20 years. A total of 35 patients (62.5 %) experienced one or more complications after surgery. Ten of 56 patients (17.9 %) experienced local recurrence after a mean of 8.9 months. The mean postoperative Musculoskeletal Tumor Society (MSTS) score was 18.1 (60.1 %).

Conclusion

The surgical approach assessed in this study simplifies the process of tumour resection and prosthesis implantation and leads to acceptable clinical and oncological outcomes.     

The New Small Viennese Total Artificial Heart: Experimental and First Clinical Experiences

For bridging to transplantation, a new small total artificial heart (TAH) design has been developed. Function of the two membrane pumps (filling volume left: 87 ml, and right: 75 ml; four mechanical disc valves and screwed connectors) for orthotopic implantation were studied in calf experiments. A calf survival up to 180 days was achieved without problems by pumping with a rate of 117 +/- 2.4 beats/min and a cardiac output of 7.4 +/- 0.7 L/min. For bridging to transplantation, the New Small Viennese TAH was implanted into a small 45-year-old patient (height 160 cm, weight 75 kg) with end-stage coronary heart disease. The patient deteriorated suddenly [mean aortic pressure: 38 mm Hg; cardiac output (CO): 1.8-2.1 L/min; anuria and multiple organ failure] while waiting for a donor heart. Even though his pericardial space was not enlarged, no fitting problems appeared. By using pumping rates of 104.3 +/- 8.7 beats/min, a cardiac output of 5.8 +/- 0.63 L/min was achieved (free hemoglobin was 4.1 +/- 0.48 mg/dl). Even though blood circulation was reestablished, after a TAH duration of 12 days, multiple organ failure persisted, and TAH bridging had to be stopped. In November 1989, a 50-year-old deteriorating transplant candidate with idiopathic cardiomyopathy was bridged for 6 days. Adjusting the heart rate to 86.5 +/- 11.2 beats/min, a CO of 6.84 +/- 0.46 L/min was achieved (free hemoglobin was 5.9 +/- 1.7 mg/dl). Because of chronic liver dysfunction, the patient developed severe icterus while on the TAH, and it took 2 months after heart transplantation to achieve physiological bilirubin concentrations. The patient recovered fully and remains in excellent condition.     

Molecular epidemiology of tuberculosis: toy or tool? A review of the literature and examples from Central Europe

Genotyping has become an indispensable tool in medical microbiology and epidemiology. One of the first targets has been Mycobacterium tuberculosis. Over the past 15 years approximately 900 pertinent publications have substantiated the value of the genotyping approach for tuberculosis control. New insights into the understanding of the natural history of tuberculosis, especially regarding the frequencies of reactivation, reinfection or multiple infection entailed adaptations of pathophysiological concepts. However, assessment of recent transmission, outbreak analysis, and detection of laboratory contamination still form the genuine scope of genotyping. Detection of unsuspected clusters of cases can provide clues to search for further, undetected cases. Uncovering false positive cultures spares the risks and costs of unnecessary treatment and may reveal systematic laboratory weaknesses. Several European countries already profit from nationwide prospective fingerprinting. After providing genotyping results to public health officials, these were able to document epidemiological links for substantially more tuberculosis patients. On a global scale, strain families and particular strains have been identified, characterised and traced in their spread. The importation of Beijing-genotype multidrug-resistant M. tuberculosis into Central European countries will be described here as an example. The goal for further developments is the ability to compare isolates for epidemiological purposes in a single step that also comprises species determination, drug resistance testing and detection of pathogenicity factors.     

Periprothetische Frakturen bei Hüftendoprothese

The number of periprosthetic fractures following hip replacement is increasing due to longer life expectancy and the rising number of joint replacements. The main causes of periprosthetic fractures include trauma, implant specific factors or loosening of the endoprosthesis. When planning therapy, surgeons should consider specific and general implant- and patient-related risk factors to ensure the best possible treatment. Established classification systems can facilitate preoperative planning. At present, the Vancouver classification system probably comes closest to the ideal, as it considers fracture configuration, stability of the implant and quality of the bone stock. Depending on these factors, therapeutic options include conservative treatment, fracture stabilisation or replacement of the endoprosthesis. The problems associated with periprosthetic fractures of varying etiology and the available treatment options are discussed against the background of the established classification systems.     

Timing for implantation and transplantation in mechanical bridge to transplantation

The implantation of a mechanical blood pump in a deteriorating candidate for heart transplantation is indicated in general if the cardiac index is less than 1.9 L/min/m2 despite maximal inotropic support. Deterioration of end organ function may be taken as a second factor indicating the need for mechanical support as patients with acute onset of shock may react differently from patients with chronic deterioration. Preoperative need for dialysis largely reduces the chances of long-term survival. The time on support should be long enough to normalize or at least improve secondarily damaged organ systems, but with time infectious and thromboembolic complications will increase. So optimal periods for artificial heart support range between two days and four weeks. Age less than 40 years is a positive predictor for outcome in TAH bridging. The general guidelines, however, do not preclude a favourable outcome in complicated cases, as we show in our own series.     

Recombinant versus plasma-derived hepatitis B vaccine: comparison of immunogenicity in medical students.

A group of 92 medical students were immunized with a commercial recombinant hepatitis B vaccine (Engerix B). Antibody responses were determined and compared with those to plasma-derived Pasteur vaccine, obtained in 1986. Antibody concentrations were significantly higher in the group given recombinant vaccine, therefore this vaccine has superior immunogenicity and probably confers extended duration of protection.