Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.     

Safety and immunogenicity of Salmonella typhi Ty21a vaccine in young Thai children.

Salmonella typhi Ty21a vaccine in a liquid formulation was evaluated in 634 Thai children 2 to 6 years of age. The seroconversion rate was 69% for those who received vaccine versus 14% for those who received placebo (P < 0.005). The immune responses among vaccine recipients ranged from 60% in 3-year-olds to 81% for 6-year-olds.     

A comparison of three diuretic regimens in heart failure

Abstract. Eight patients with mild heart failure were treated in random order for 1 week with 2 mg bumethanide at 0800 and 1200 (treatment I) h, 1 mg bumethanide at 0800, 1200, 1800, 2200 (treatment 2) and 5 mg bendroflumethiazide at 0800 and 1800 (treatment 3) h. The 'quality of life' did not differ significantly between the three treatment periods. At the presumed trough of the diuretic effect the circulating blood volume was largest during treatment 1; it was 6.3% smaller during treatment 2 ( P< 0.02) and 6.7%) lower during treatment 3 (P<0.05). In comparison with treatment 1, the maximal increase in rate-pressure product during physical exercise was 24.6% higher in treatment 3. Compared with treatment 1 the area under the curve (AUC) for plasma lactate during physical exercise was 14% lower during treatment 2 (P<0.05) and 18% lower during treatment 3 (P<0.01). These findings suggest that the type of program for diuretic therapy influences the magnitude of inevitable diurnal fluctuations in body fluids, the ability of the heart to work and the ability of the body to adjust to the oxygen demand.     

Effect of hydrocortisone succinate on growth of Chlamydia pneumoniae in vitro.

We examined the effect of hydrocortisone succinate on the growth of three isolates of Chlamydia pneumoniae in vitro. There was a significant increase in the number of inclusions seen in two of the C. pneumoniae strains in the presence of hydrocortisone. There was no significant increase in the number of inclusions with various concentrations of hydrocortisone over time. The addition of hydrocortisone did not affect the in vitro activities of azithromycin, erythromycin, and doxycycline against C. pneumoniae.     

Binding of host collectins to the pathogenic yeast Cryptococcus neoformans: human surfactant protein D acts as an agglutinin for acapsular yeast cells.

Cryptococcus neoformans is an opportunistic pathogen in AIDS patients causing disseminated disease and lethal meningitis after inhalation of acapsular or sparsely encapsulated yeast cells. In this study we have investigated whether a recently described family of primitive opsonins, termed collectins, contribute to innate resistance against C. neoformans. The pulmonary surfactant proteins SP-A and SP-D as well as the serum collectins mannose-binding protein and CL-43 bound in a calcium-dependent manner to acapsular C. neoformans in vitro. Binding was concentration dependent and abolished by competition with defined mono- and oligosaccharides. In contrast, no binding of the collectins was observed with the encapsulated form of the yeast. Furthermore, binding of purified collectin SP-D, but not SP-A, mannose-binding protein, or CL-43, led to a concentration-dependent agglutination of acapsular C. neoformans. These data indicate that collectins recognize carbohydrate structures in the cell wall of an initial infectious form of C. neoformans and may play a role in early antifungal defenses in the lung.     

Die Indikation für Veneninterponate bei der mikrochirurgischen Rekonstruktion komplexer Defekte der unteren Extremität nach Tumor und Trauma

Reconstructive microsurgery has become a routine procedure in plastic surgery. Success rates in major centers range between 95 and 98%. In selected “high risk” cases, vein grafts are required to facilitate microsurgical anastomoses, as in complex defects of the lower leg, post ischemic syndrome (PIS) or following major tumor resections. The indications and results of vein grafts or A-V loops are demonstrated in these three groups. 25 patients with defects of the lower leg were operated using vein interposition grafts. Ten A-V loops were created prior to flap transfer. Three flaps had to be revised, only one flap was lost due to recurrent arterial thromboembolism from an injured proximal segment. Data show that vein grafts are clinically reliable and may be used without hesitation in appropriate clinical situations.