Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis, for extracorporeal hemorheotherapy. Safety and efficacy of Rheopheresis for wound healing and skin oxygenation were investigated in patients with ischemic diabetic foot syndrome. Eight patients with type 2 diabetes mellitus and non-healing foot ulcers caused by severe ischemic diabetic foot syndrome were treated by a series of seven Rheopheresis sessions in a time span of 11 weeks. Wound healing had not been detectable under conditions of standardized wound care during at least 2 months. Wound status was classified by its morphology, severity and location, according to the criteria of Wagner. Transcutaneous oxygen pressure (tcPO2), laser Doppler flowmetry and vital capillary microscopy were repeatedly performed to monitor the effects of the Rheopheresis treatment series on microcirculation and skin blood flow. Laboratory parameters of blood rheology, endothelial function and inflammatory state were measured in addition to safety parameters. In four patients (baseline Wagner stage 2), Rheopheresis accelerated wound healing of foot ulcers and was associated with an improvement of Wagner stage and a pronounced increase in tcPO2. In two patients (baseline Wagner stage 2), wound healing was unchanged but mean tcPO2 increased, allowing successful minor amputation. Values of tcPO2 remained stable and enhanced for the 3 months follow-up period. In two patients (baseline Wagner stage 4 or 5), no improvements in foot lesions were observed within the treatment period. As an adjunct therapeutic option, Rheopheresis may preserve a functional lower extremity, delay amputation or reduce the extent of amputation.
1. Neurovascular inflammation is impaired in patients suffering from diabetic neuropathy. The aim of our study was to evaluate the distribution of nutritive and total skin blood flow in diabetic patients with and without neuropathy after neurovascular stimulation with acetylcholine. 2. Twenty patients with Type I diabetes, 10 with and 10 without neuropathy, and 10 age-matched non-diabetic control subjects, underwent microvascular investigations before and after neurovascular stimulation by intracutaneous application of acetylcholine. The capillary blood cell velocity in the nailfold of the hallux was measured by videophotometric capillaroscopy, and the total skin microcirculation in the same area by laser Doppler flowmetry. 3. The increase in total skin blood flow was significantly impaired in the group of neuropathic diabetic patients compared with the non-neuropathic diabetic patients (17.5 +/- 8.3 versus 51.0 +/- 16.2; P < 0.05) and the non-diabetic subjects (17.5 +/- 8.3 versus 67.8 +/- 19.7; P < 0.01). The increase in capillary blood flow was not significantly impaired in Type I diabetes patients with neuropathy. 4. The ratio between capillary blood flow and total skin perfusion decreased significantly in the control group (from 0.82 +/- 0.15 to 0.47 +/- 0.11; P < 0.05) and in the Type I diabetes patients without neuropathy (from 0.79 +/- 0.12 to 0.43 +/- 0.12; P < 0.05), whereas the decrease in the neuropathic group was statistically insignificant (from 1.05 +/- 0.19 to 0.72 +/- 0.16). 5. Diminished total skin perfusion in the foot after intracutaneous stimulation with acetylcholine in Type I diabetes patients is associated with diabetic neuropathy, indicating a disturbance in the neurovascular reflex arc. This impaired neurovascular response is caused by a diminished total and subpapillary blood flow and not by a diminished nutritive capillary flow. There is no evidence of a diminished nutritive capillary blood flow during neurogenic inflammation in Type I diabetes patients suffering from diabetic neuropathy.
In a randomized, open-label, controlled cross-over trial, 107 patients with type 1 diabetes were treated with either regular human insulin or insulin lispro, a rapid-acting insulin analogue. After a lead-in period of 2 to 4 weeks, the patients were randomized to receive intensified insulin treatment with one of the insulins. NPH-human insulin was used for basal substitution in both groups. The crossover took place after 3 months of treatment. Efficacy and safety of the drugs were established by the assessment of hemoglobin A1c, pretest blood glucose, 1 and 2-hour postprandial glucose excursions, number of hypoglycemic episodes, daily insulin doses, body weight, insulin antibodies, and the number and severity of adverse events. A questionnaire comprised of four primary domains was used to measure some quality of life aspects of the patients. Both treatment regimens were well tolerated. While no differences were seen in the hemoglobin A1c values, there was a trend for a decrease in the pretest blood glucose levels and significant decreases of the 1 and 2-hour postprandial glucose excursions in the patients treated with insulin lispro. The number of hypoglycemic episodes was also significantly lower in the insulin lispro treatment period. The evaluation of the quality of life questionnaire revealed an improvement in the patients treatment satisfaction for the insulin lispro group. During treatment with insulin lispro, the basal insulin doses increased slightly. However, the total daily insulin doses decreased to a greater extent with insulin lispro as compared to regular human insulin. Human insulin-specific antibody binding values at endpoint were not different for the two treatments. In conclusion, intensive insulin treatment with insulin lispro therapy results in improved postprandial glycemic control and HbA1c levels at least equal to the treatment with regular human insulin but with less hypoglycemia and more treatment satisfaction for the patient.
The crucial diagnostic tool for decision-making in diabetic foot syndrome was MRI, which normally shows osteomyelitis with high sensitivity and specificity. In patients with Charcot-neuro-osteoarthropathy, the bone marrow oedema of the involved parts of the skeleton might misleadingly suggest the diagnosis of osteomyelitis. If amputation is inevitable in severe abscess formation combined with instability and perforation of the dislocated and destroyed bones in Charcot-neuro-osteoarthropathy, these patients might benefit from a foot amputation according to the technique Syme described. For this procedure the blood supply of the posterior tibial artery is essential. All these patients were able to walk without support. The material presented helps to generate hypotheses for further prospective studies.
The postprandial insulin requirements after three mixed meals of equal carbohydrate and energy content were assessed in 10 type-1 and 12 type-2 diabetics by a glucose-controlled insulin infusion system. These were compared with the glycemic response to the same meals of 10 healthy individuals (glycemic index). In type-1 diabetics, we found the highest insulin requirements after consumption of a continental breakfast (low fibre, low protein, high fat). Ten percent less insulin was infused after milk (low fat, high protein) and 30% less after an English breakfast (high fibre, high protein). Type-2 diabetics showed no significant differences in insulin requirements between the three test meals. The glycemic response in healthy individuals had no relation to these insulin requirements. Continental and English breakfast had a similar glycemic effect, whereas milk produced only 30% of the blood glucose response observed after the continental breakfast. These results indicate that neither the carbohydrate content (exchange lists) nor the glycemic index enable prediction of postprandial insulin requirements in insulin-deficient diabetes. For this purpose, we propose the insulin-need index, elaborated by testing whole meals in closed-loop experiments with type-1 diabetics.
Contrast-enhanced three-dimensional MR angiography is superior to DSA in revealing patent vessel segments of the foot in diabetic patients with severe arterial occlusive disease. Contrast-enhanced three-dimensional MR angiography should be part of the diagnostic algorithm for patients in whom pedal bypass grafting is a therapeutic option.
Indoor air pollutants may cause inflammatory changes of the airways and adjacent pulmonary tissue. After phagocytosis of inhaled particles alveolar macrophages (AM) release chemotactic mediators capable of attracting inflammatory cells into the lung tissue. To evaluate these mechanisms further peripheral blood mononuclear cells (PBMNC) and human AM (freshly recovered from the lower respiratory tract) were exposed to the indoor particles Soot FR 101 and Printex 90, the asbestos fiber Chrysotile B, and titanium dioxide (TiO2) at concentrations of 10 or 50 microg/10(6) cells for up to 8 h. The migration of granulocytes into the conditioned supernatants of AM and PBMNC was quantified by chemotaxis assay in a Boyden chamber. Granulocyte migration increased by 42.3 +/- 25.8% (Chrysotile B), 64. 6 +/- 18.3% (FR 101), 74.2 +/- 16.5% (P 90), and 86.7 +/- 25.6% (TiO2) in AM-conditioned supernatants (p < 0.05). Qualitative, Interleukin (IL)-8 specific reverse transcriptase-polymerase chain reaction was performed after exposure of AM or PBMNC to Chrysotile B, FR 101, P 90, and TiO2 at concentrations of 10 and 50 microg/10(6) cells for 90 min. Each of the tested particles caused an increase in IL-8-specific mRNA expression of AM or PBMNC after particle exposure compared with the unexposed control. To find out if IL-8, the most powerful granulocyte chemokine, is involved, supernatants were preincubated with anti-IL-8. Granulocyte migration decreased by up to 35 +/- 15% (50 ng/ml anti-IL-8) and 41.5 +/- 16% (100 ng/ml anti-IL-8) (p < 0.0625) in AM-conditioned supernatants. Pretreatment of the granulocytes with human IL-8 decreased by up to 59 +/- 18% (10 ng/ml) (p < 0.0625) in AM-conditioned supernatants. Similar reaction patterns were observed using anti-IL-8-pretreated supernatants of particle-exposed PBMNC. In conclusion, indoor air pollutants may promote inflammatory changes in the lung via IL-8 release by alveolar macrophages.
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