Interdisziplin?re Leitlinien zur Diagnostik und Therapie der extrazerebralen Amyloidosen

Ohne Zusammenfassung     

No regression of renal AL amyloid in monoclonal gammopathy after successful autologous blood stem cell transplantation and significant clinical improvement.

BACKGROUND: High-dose chemotherapy followed by autologous blood stem cell transplantation induces remission of plasma cell dyscrasia in patients with AL amyloidosis. The impact of this treatment on the glomerular amyloid mass is still unknown. METHODS: In the present study, the quantity of the renal amyloid mass before and more than 3 years after high-dose melphalan treatment and autologous blood stem cell transplantation was assessed in two patients. At the time of the second renal biopsy, both patients were in complete remission without detectable serum and urinary monoclonal IgA-lambda and a normal percentage of plasma cells in the bone marrow. RESULTS: In both patients with biopsy-proven AL amyloidosis, urinary protein excretion decreased from 7 g/24 h to <2 g/24 h more than 3 years after autologous blood stem cell transplantation. In contrast, glomerular amyloid deposits persisted, as shown in the second biopsy. CONCLUSION: Despite complete remission of the plasma cell dyscrasia and improvement of glomerular permeability, the amount of glomerular amyloid mass did not regress.     

Skeletonization of internal thoracic artery affects its innervation and reactivity.

OBJECTIVE: The studies showing the superior characteristics of ITA graft and its impact on the clinical results of coronary artery surgery were performed with ITA harvested almost exclusively as a pedicle. This study assesses the impact of ITA skeletonization on its innervation and reactivity. METHODS: Segments of skeletonized and non-skeletonized ITA were stained with antibodies against protein S-100 to look for the presence of sympathetic nerve fibers. The functional studies were performed on segments of discarded human pedicled ITA that were divided into two 3mm rings, one skeletonized and another non-skeletonized. We compared concentration-effect relationships for the contraction to norepinephrine and endothelium-dependent relaxation to acetylcholine and bradykinin, as well as endothelium-independent relaxation to sodium nitroprusside in skeletonized and non-skeletonized segments of the same ITA. RESULTS: Skeletonized ITA was devoid of protein S-100 positive nerve fibers. It contracted stronger (maximal response 37.0+/-2.04 vs. 25.4+/-1.83mN (P<0.001)) and was twice as sensitive to norepinephrine: pD(2) 6.03+/-0.10 vs. 5.70+/-0.12 (P=0.035). The endothelium-dependent relaxation responses did not differ between skeletonized and non-skeletonized ITA rings. The skeletonized ITA rings appeared over 10 times more sensitive to sodium nitroprusside: pD(2) 6.66+/-0.20 vs. 5.59+/-0.37 (P=0.012)-potency ratio 11.61. The maximal responses did not differ significantly: 112.0+/-6.71 vs. 129.4+/-16.4% (P=0.33). CONCLUSIONS: Skeletonization results in sympathectomy of ITA. It has no effect on endothelium-dependent relaxation but increases reactivity of ITA to norepinephrine. This augmented response to alpha-agonist is small, in comparison with over a ten-fold increase in sensitivity to sodium nitroprusside. Pedicled and skeletonized ITA are functionally significantly different vessels when studied in vitro.     

The influence of erythropoietin on cytokines in haemodialysis patients

Summary: In this study, the administration of erythropoietin to haemodialysis patients revealed its immunomodulating properties. to dissociate the immunological effects of erythropoietin action from its haematological effects the patients in our study were administered recombinant human erythropoietin (rhEpo) at the doses that would not affect erythropoiesis. After baseline data had been obtained, six haemodialysis patients were given rhEpo (Eprex-Cilag) at the dose 7-10 U/kg bodyweight/s.c., three times a week, for 12 weeks. All patients maintained a stable haemoglobin concentration; no blood transfusions were required. Serum levels of tumour necrosis factor (TNF), IL-2 and IL-6 levels of the study patients and the four control patients, not receiving rhEpo, were monitored every 2 weeks. the levels of IL-6 and TNF remained unchanged; however, a low serum level of IL-2, recorded before therapy, increased gradually for 10 weeks until it reached the values observed in normal healthy humans (P<0.01). After that it dropped to the initial values. During the study the red blood cell numbers did not change. This study supports the thesis that erythropoietin administered to haemodialysis patients not only corrects anaemia but also independently modulates immunological response.     

Bronchial reactivity to methacholine after combined heart-lung transplantation.

The operation of combined heart-lung transplantation results in acute denervation of the heart, lungs, and airways below the level of the trachea. The bronchoconstrictor response to inhaled methacholine of 12 recipients of heart-lung transplants was compared with that of 12 recipients of heart transplants having similar medication and 12 normal subjects. The median dose of methacholine that produced a reduction of at least 20% in the FEV1 (PC20) for the recipients of heart-lung transplants (8 mg/ml) was significantly lower than that for the recipients of heart transplants (64 mg/ml) and normal subjects (greater than 64 mg/ml). The increased airway reactivity may be related to the effects of chronic pulmonary denervation or subclinical inflammation in the airways. The effect of denervation on the response to full inspiration during bronchoconstriction was studied in six patients with heart-lung transplants by means of partial and maximal forced expiratory manoeuvres. Four showed bronchodilation after a deep breath, indicating that this response can occur after extrinsic pulmonary denervation in man. The patients with heart-lung transplants described a "tight" sensation in the anterior chest during bronchoconstriction, indicating that this sensation is not dependent on pulmonary innervation.     

Near-ultraviolet light perceived by the retina generates the signal suppressing melatonin synthesis in the chick pineal gland-an involvement of NMDA glutamate receptors

Exposure of dark-adapted chicks to near ultraviolet (UV-A) light significantly decreased melatonin (MEL) content and the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in MEL production) in the pineal glands. Significant reduction in MEL level and AA-NAT activity was also found in pineals of animals whose heads were covered with black opaque tape, an observation suggesting that in the chicken UV-A light perceived by the eyes alone is capable of affecting MEL synthesis in the pineal gland. Covering the chick's eyes, in addition to the head, totally blocked the studied UV-A action. Although SCH 23390 (a selective D1-dopamine receptor antagonist), injected directly into both eyes at a dose of 10 nmol/eye, prevented the decline in pineal AA-NAT activity produced by retinal illumination with white light, the drug did not modify the UV-A light-evoked decrease in the enzyme activity. MK-801 (a selective antagonist of NMDA glutamate receptors; 1 nmol/eye) abolished the suppressive action of UV-A light on pineal AA-NAT activity, but it was inactive in the case of white light. Intraocularly injected sulpiride and CNQX (selective antagonists of D2-dopamine and AMPA/kainite glutamate receptors, respectively) had no effect on the actions of both UV-A and white light (acting on the eyes only) on pineal AA-NAT activity. It is concluded that in the chick retinally perceived UV-A light generates a signal which suppresses MEL production in the pineal gland. At the level of the retina, such signal does not involve dopamine, but is dependent on the stimulation of NMDA glutamate receptors.     

The effect of carbon dioxide in the airways and alveoli on ventilation; a vagal reflex studied in the dog

1. The inhalation of CO(2) produces a tachypnoea only in the presence of intact vagus nerves; the present study was designed to examine the mechanism of this phenomenon in the dog.2. Closed-chest cardiopulmonary bypass was established in dogs weighing 16-24 kg, anaesthetized with chloralose. When the ;bypass' was established pulmonary blood flow ceased, P(A, CO2) was reduced and the respiratory rate slowed. 3-10% CO(2) in O(2) could then be inhaled without change in the level of P(a, CO2) set at the oxygenator.3. The addition of CO(2) in these concentrations to the inspired oxygen resulted in an increase in respiratory frequency, maximal at the first breath and sustained for the 1 min period of exposure. The increase in respiratory frequency was due to a shortening of expiratory duration. Inspiratory duration did not change. The response was absent after vagotomy.4. Inert gases in O(2), given as a control, had no effect on breathing.5. The effect of raising P(a, CO2) (by increasing the concentration of CO(2) in the gas equilibrating the blood in the oxygenator), was primarily to increase tidal volume.6. The ventilatory effect of inspiring CO(2)/O(2) mixtures was shown to be additive to the effect of raising P(a, CO2).7. These experiments show that an afferent vagal reflex originating from the lungs causes tachypnoea, when a dog, on ;bypass', inhales low concentrations of CO(2) in O(2).     

Increase of interleukin 6 and decrease of interleukin 2 production during the ageing process are influenced by the health status

The ageing process is accompanied by the disregulation of interleukin 2 (IL2) and interleukin 6 (IL6) production. In our paper, we asked whether the age between 60 and 70 years is a turning point for the disregulation of both IL2 and IL6 production. Fifty volunteers 60–70 years old, 25 aged 36–59, and 50 of 20–35 years old were enrolled into the study. Their health status was graded according to the criteria of the Senieur Protocol (SP) as ‘healthy' and ‘almost-healthy'. The cytokines level was determined in the sera of the volunteers. Moreover, the spontaneous release of IL6 by peripheral blood mononuclear cells (PBMC) and the activity of the IL6 gene in non-stimulated PBMC were also analysed. Cytokine levels were measured by biological assays, mRNA for IL6 was detected by RT-PCR method. The results showed that the production of IL2 is not disregulated in the ‘healthy' people until the age of 60–70. People not fulfilling all SP criteria are characterised by a lower level of IL2 in the sera. The overproduction of IL6 into the sera and supernatants from non-stimulated PBMC and PBL as well as the activation of IL6 gene start between the ages 36 and 59 and is more pronounced in the ‘almost-healthy'.