Leukocytapheresis for ulcerative colitis

Leukocytapheresis(LCAP) and Granulocytapheresis(GCAP) are classified as extracorporeal circulation therapy(ECCT). These therapies are a novel, effective way to treat patients with ulcerative colitis(UC). During 7 weeks of intensive therapy(LCAP weekly, predonisolone(PSL) 30-80 mg/day), UC patients treated with LCAP revealed significant improvements on their subjective and objective symptoms compared to patients treated with PSL intravenous administration. Moreover, LCAP has been recognized as safer than other drugs for UC. In our previous study, only 9.9% out of 1,978 LCAP sessions showed some side effects, and most were mild and temporary. Therefore, LCAP could be the first choice to treat UC patients who resist and/or reveal severe complications against ordinary drug therapies.     

Current topics on cytapheresis technologies.

Cytapheresis has been investigated recently for the treatment of autoimmune related diseases, such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis, and so on. A large number of physicians have indicated that patients with autoimmune diseases respond to cytapheresis treatment. The effective mechanism of cytapheresis for immune disorders is still controversial. However, the removal of the leukocyte including granulocyte, lymphocyte, and monocyte may play a crucial role in correcting imbalance of the immune system. A session of cytapheresis including leukocytapheresis (LCAP) and granulocytapheresis (GCAP) may not create a sufficient amount of cell removal for the human body. However, the cell removal can be a trigger of the immunomodulation as the treatment for immune disorder. Furthermore, not only cell removal but also reaction by blood contacting with medical device materials may play a role as an immunomodulation for immune disorders. This review introduces current cytapheresis technologies and attempts to elucidate the effective mechanism of cytapheresis for immune disorders, focused on LCAP and/or GCAP for RA or IBD.     

Apheresis for MPO-ANCA-associated RPGN-indications and efficacy: lessons learned from Japan nationwide survey of RPGN

A national survey concerning rapidly progressive glomerulonephritis (RPGN) was conducted in Japan between 1989 and 2000 and resulted in the registration of 715 patients with RPGN. Among the documented patients, the most frequent primary disease was primary pauci-immune crescentic glomerulonephritis (n = 283), and the second most frequent was microscopic polyangitis (n = 127). Overall, 370 patients had MPO-ANCA, and 23 patients had PR3-ANCA. We found that both renal and patient survivals were significantly worse in patients with MPO-ANCA-associated RPGN than patients with PR3-ANCA. Fifty-three patients received apheresis therapy with various combinations of immunosuppressive regimens. They had higher serum creatinine, higher CRP, and a higher frequency of complicated pulmonary involvements as compared to the controls without apheresis therapy. In dialysis-dependent patients, no additional benefit from apheresis therapy was observed. Only pulmonary renal syndrome patients with CRP > 6 mg/dl at presentation showed a slightly better prognosis (patient survival with apheresis; 66.7%, without apheresis; 56.7%). Furthermore, a rapid MPO-ANCA titer reduction was observed in patients treated with apheresis. Patients with MPO-ANCA-associated RPGN were older, and had more chronic and sclerotic lesions than patients with PR3-ANCA-associated RPGN. Based on these findings, we suggest that a lower dose of immunosuppressant should be considered in order to avoid opportunistic infection. In this situation, cytapheresis is the treatment of choice. Nevertheless, in patients with an aggressive form of RPGN with rapid deterioration of renal function like the PR3-ANCA-associated RPGN, or pulmonary renal syndrome complicated severe inflammation, or relapses with high MPO-ANCA titer, we conclude that apheresis therapy should be considered.     

Leukocyte removal filter-passed lymphocytes produce large amounts of interleukin-4 in immunotherapy for inflammatory bowel disease: role of bystander suppression.

To determine immunosuppression by leukocytapheresis, we studied the immune profiles of filter-passed lymphocytes (FPLs) in patients with ulcerative colitis. These patients were treated with a leukocytapheresis (LCAP) filter of granulocyte apheresis (GCAP) column. Cytokine profiles or FPLs and peripheral blood mononuclear cells (PBMCs) were examined using interleukin (IL)-4 and interferon-gamma (IFN-gamma) immunoassay with lectin stimulation. The IL-4 production of LCAP FPLs was significantly higher than in prefilter PBMCs and GCAP column-passed lymphocytes (median: 540 pg/ml x 10(6) cells versus 4.7 and 2.9, respectively, p = 0.001). IL-4 production in PBMCs was increased after LCAP. IFN-gamma production was not increased in the FPLs. The IL-4 immune deviation was not shown in the patients treated with GCAP. LCAP FPLs showed increased CD4+DR- cells and decreases CD4+DR+ cells in comparison to PBMCs. LCAP FPLs could produce IL-4 and may lead to bystander suppression.     

Efficacy of filtration leukocytapheresis on rheumatoid arthritis with vasculitis.

The present study was designed to determine the efficacy of filtration leukocytapheresis (LCAP) in the treatment of rheumatoid arthritis (RA) with vasculitis. Nine RA patients with vasculitis were studied by the Malignant RA Collaborative Group formed by 8 clinical centers. A total of 7 filtration LCAP procedures using the Cellsorba column (Asahi Medical Co., Ltd., Tokyo, Japan) were performed with 1 week intervals between treatments. During each apheresis procedure, 3,000 ml of blood was filtered and returned to the patient at a flow rate of 50 ml/min for 60 min. In addition to the amelioration of arthritis, the improvement of extraarticular symptoms associated with rheumatoid vasculitis such as polyneuritis, skin ulcers, digital gangrene and rheumatoid nodules was obtained. In contrast, no improvement was observed in interstitial pneumonia or lung fibrosis. LCAP could be an optional modality for the treatment of RA with vasculitis.     

Accuracy of bedside capillary blood glucose measurements in critically ill patients

OBJECTIVE: To compare the accuracy of fingerstick with laboratory venous plasma glucose measurements (laboratory glucose) in medical ICU patients and to determine the factors which interfere with the accuracy of fingerstick measurements. PARTICIPANTS: The study included 80 consecutive patients aged 58+/-7 years, BMI 29.5+/-9.0, and APACHE II score 15+/-6 (277 simultaneous paired measurements). MEASUREMENTS: This prospective observational study compared fingerstick measurements to simultaneously sampled laboratory glucose once a day in patients in our medical ICU (twice daily if on an insulin infusion). Data recorded included patient demographics, admission diagnoses, APACHE II score, BMI, daily hematocrit, arterial blood gasses, chemistry results, concomitant medications (including vasopressors and corticosteroids), and upper extremity edema. Accuracy was defined as the percentage of paired values not in accord (>15 mg dl(-1)/ 0.83 mmol(-1)l(-1) difference for laboratory values <75 mg dl(-1)/4.12 mmol(-1)l(-1) and >20% difference for laboratory values >or=75 mg/dl). Outliers (blood glucose difference >100 mg dl(-1)/5.56 mmol(-1) l(-1)) were excluded from the correlation and distribution analyses. RESULTS: Mean fingerstick glucose was 129+/-45 mg/dl (7.2+/-2.5 mmol/l) and mean laboratory glucose 123+/-44 mg/dl (6.8+/-2.4 mmol/l). The correlation coefficient between the two values was 0.9110 (Clinical and Laboratory Standards Institute threshold 0.9751). The mean difference (bias) between the two methods was 8.6+/-18.6 mg/dl (0.48+/-1.0 mmol/l) and limits of agreement +45.8 and -28.6 mg/dl (+2.5 and -1.6 mmol/l). Fifty-three (19%) paired measurements in 22 patients were not in accord (CLSI threshold 相似文献   

Extracorporeal fibrinogen adsorption--efficacy, selectivity and safety in healthy subjects and patients with foot ulcers.

The elimination of fibrinogen from plasma improves plasma viscosity and whole blood viscosity. For extracorporeal adsorption of fibrinogen the pentapeptide gly-pro-arg-pro-lys was coupled to sepharose CL-4B. Columns containing 100 ml of coupled sepharose CL-4B were used to eliminate fibrinogen from the plasma of 8 healthy male subjects (mean age 27.4 +/- 4.3 years, height 180.9 +/- 8.3 cm, weight 85.1 +/- 13.6 kg). Four treatments were performed in each proband (days 1, 2, 4 and 7). Plasma fibrinogen concentration was lowered from 221.1 +/- 39.0 to 123.5 +/- 21.7 mg/dl (2275 +/- 477 ml plasma treated) by the first treatment, from 172.8 +/- 42.3 to 105.6 +/- 16.5 mg/dl (1609 +/- 761 ml) by the second, from 140.5 +/- 13.8 to 98.8 +/- 8.6 mg/dl (1224 +/- 118 ml) by the third and from 160.2 +/- 23.6 to 106.4 +/- 9.7 mg/dl (1513 +/- 521) by the fourth. Plasma viscosity was improved from 1.40 +/- 0.18 mPa s before the first treatment to 1.23 +/- 0.06 mPa s after fourth treatment, whole blood viscosity from 4.49 +/- 0.36 mPa s to 3.83 +/- 0.27 mPa s (P < 0.01). No clinical side effects and no clinically relevant change of laboratory parameters including in vitro tests on thrombocyte function were observed. Seven men and three women (48-75 years old, 9 patients suffered from diabetes mellitus, one patient from peripheral arterial occlusive disease, 5 patients were on regular hemodialysis) were treated by fibrinogen adsorption. Each column contained 135 ml of coupled sepharose CL-4B. Treatments were scheduled on day 1, 2, 4, 6, 8, 10, 13, 16, 19, 22, 25 and 28. 144 treatments with fibrinogen adsorption were performed. No clinical side effects due to the fibrinogen-adsorption procedure were observed. In these 10 patients the fibrinogen concentration before the first treatment was 473.7 +/- 183.7 mg/dl. In the first treatment session it was lowered to 241.4 +/- 125.8 mg/dl by treating 4270 +/- 1180 ml of plasma. In the following 134 treatments the pre-treatment concentration of fibrinogen was 262.6 +/- 83.4 mg/dl, the post-treatment concentration was 120.6 +/- 37.2 mg/dl. The mean volume of plasma treated was 3737 +/- 1643 ml, the mean duration of a treatment session (except the first treatment) was 143.7 +/- 63.1 min. In 7 patients a mean post-treatment fibrinogen concentration of < or = 123 mg/dl was obtained, in the other patients 133, 177 and 184 mg/dl. Yet, the decrease of fibrinogen concentration was also pronounced in these 3 patients: -82%, -67%, and -73%, respectively. Accelerated wound healing was observed in 9 of the 10 patients. In conclusion, affinity chromatography using the pentapeptide gly-pro-arg-pro-lys is an effective, selective and safe procedure to lower fibrinogen concentration in plasma thereby improving blood viscosity. It could be a therapeutic option in severe blood vessel disease where drug therapy is not sufficient and invasive procedures like bypass or angioplasty cannot be applied.     

Intravenous anti TNF-alpha antibody therapy leads to elevated triglyceride and reduced HDL-cholesterol levels in patients with rheumatoid and psoriatic arthritis

BACKGROUND & AIMS: We investigated the effect of Infliximab, an anti TNF-alpha antibody, on plasma lipids and lipoproteins in patients with rheumatoid arthritis and psoriatic arthritis. METHODS: Five male and 10 female patients with a mean age of 56.7 years were included in this study. Seven of the patients were diagnosed with rheumatoid arthritis and 8 patients with psoriatic arthritis. All patients received infusions of 3 mg/kg Infliximab (at week 0, 2 and 6). Lipids, lipoproteins and standard clinical parameters were assessed at baseline (0 week), after 2 weeks, and in 4 patients after 6 weeks. RESULTS: There was a significant increase in triglyceride levels during treatment with Infliximab (112 +/- 48 versus 133 +/- 53 mg/dl, p < 0.01). In contrast, HDL-cholesterol levels were significantly lowered (56 +/- 12 versus 50 +/- 13 mg/dl, p < 0.006) by the treatment. There was no significant difference in total cholesterol (209 +/- 25 versus 205 +/- 36 mg/dl) or in LDL-cholesterol (131 +/- 24 versus 118 +/- 43 mg/dl) before and after treatment. Similarly, lipoprotein(a) levels did not alter during treatment (median: 1.1 versus 1.4 mg/dl). CONCLUSION: This study shows that intravenous Inflixmab therapy leads to changes in plasma lipid and lipoprotein levels in patients with rheumatoid and psoriatic arthritis and may result in a more atherogenic lipid and lipoprotein profile. Although larger patient numbers need to be studied to confirm our findings, these results suggest that lipid levels should be checked and monitored in patients receiving infliximab therapy, particularly in patients with vascular disease.     

Gallbladder wall thickening in mononucleosis syndromes.

PURPOSE: We used sonography to measure gallbladder wall thickness in patients with mononucleosis syndromes and then evaluated laboratory data, spleen size, and clinical evolution to assess any relationship between gallbladder wall thickening (GBWT) and the severity of disease. METHODS: We retrospectively reviewed the medical records, sonograms, and sonographic reports of 39 patients who were diagnosed with mononucleosis syndromes on the basis of fever, tonsillopharyngitis, cervical adenopathy, hepatosplenomegaly, and lymphocytosis with atypical lymphocytes. All 39 were included in the study. The gallbladder wall thickness in each patient was sonographically determined. GBWT was defined as a wall thickness exceeding 3 mm. We assessed the laboratory data and clinical evolution in each patient, and the differences between patients with and without GBWT were statistically analyzed. RESULTS: Six patients (15%) had GBWT. The mean atypical lymphocyte count +/- standard deviation (SD) in the patients with GBWT (1,830/microl +/- 1,000/microl) was significantly higher than that in patients without GBWT (1,140/microl +/- 660/microl; p < 0.05). The mean total serum protein and serum albumin levels in the patients with GBWT (6.6 mg/dl +/- 0.7 mg/dl and 3.7 mg/dl +/- 0.5 mg/dl, respectively) were significantly lower than those in patients without GBWT (7.3 mg/dl +/- 0.4 mg/dl and 4.1 mg/dl +/- 0.3 mg/dl, respectively; p < 0.05). The duration of hospitalization in the patients with GBWT (14 +/- 8.5 days) was significantly higher than that in patients without GBWT (8 +/- 3.5 days; p < 0.05). CONCLUSIONS: GBWT in mononucleosis syndromes may be a sign of the severity of the illness and when present indicates the need to carefully monitor the clinical course.     

Substrate cycling between gluconeogenesis and glycolysis in euthyroid, hypothyroid, and hyperthyroid man.

Substrate, or futile cycles, have been hypothesized to be under hormonal control, and important in metabolic regulation and thermogenesis. To define the role of thyroid hormones in the regulation of substrate cycling in glycolysis and gluconeogenesis, we measured rates of cycling in normal (n = 4), hypothyroid (n = 5), and hyperthyroid (n = 5) subjects employing a stable isotope turnover technique. Glucose labeled with deuterium at different positions (2-D1-, 3-D1-, and 6,6-D2-glucose) was given as a primed-constant infusion in tracer doses, and arterialized plasma samples were obtained and analyzed by gas-chromatography mass-spectrometry for the steady state enrichment of glucose that was labeled at the various positions. The rate of appearance (Ra) was then calculated for each isotopic tracer. The difference between the Ra determined by 2-D1-glucose (Ra2) and the Ra determined by 3-D1-glucose (Ra3) represents the substrate cycling rate (SCR) between glucose and glucose-6-phosphate. The difference between the Ra determined by 3-D1-glucose (Ra3) and the Ra determined by 6,6-D2-glucose (Ra6) represents the SCR between fructose-6-phosphate and fructose-1,6-diphosphate. The difference between Ra2 and Ra6 represents the combined SCR of both cycles. In normal subjects (serum thyroxine [T4] = 8.4 +/- 1.2 microgram/dl (all expressions, mean +/- SD), n = 4), the rates of appearance for Ra2, Ra3, and Ra6 were 3.23 +/- 0.56, 2.64 +/- 0.50, and 2.00 +/- 0.27 mg/kg X min, respectively, whereas those in the hypothyroid subjects (T4 = 1.0 +/- 0.8 microgram/dl; n = 5) were 1.77 +/- 0.56 (P less than 0.01), 1.52, 1.57 +/- 0.31 (P less than 0.05) mg/kg X min, respectively. Conversely, the rates of appearance for Ra2 and Ra6 in the hyperthyroid subjects (T4 = 23.9 +/- 3.6 micrograms/dl) were 3.94 +/- 0.43 (P less than 0.05) and 2.54 +/- 0.22 (P less than 0.02), respectively, compared with the normal subjects. On the basis of these data, we noted that the normal subjects had a combined SCR of 1.23 +/- 0.35 mg/kg X min. In contrast, the hypothyroid patients had a significantly decreased combined SCR, 0.20 +/- 0.54 mg/kg X min (P less than 0.02). The hyperthyroid patients had a combined SCR of 1.39 +/- 0.23 mg/kg X min (P less than NS). To determine whether these cycles responded to thyroid hormone treatment, these same hypothyroid subjects were acutely treated for 1 wk with parenteral 50 micrograms/d sodium L-triiodothyronine and chronically with 100-150 micrograms/d L-thyroxine. After 7 d, their mean oxygen consumption rate and carbon dioxide production rate increased significantly from 102+/-13 micromol/kg.min, to 147+/-34 micromol/kg.min (P<0.05), and from 76+/-13 micromol/kg.min to 111+/-19 micromol/kg.min (P<0.05), respectively. The combined SCR (Ra(2)--Ra(6) remained unchanged at 0.07+/-0.37 mg/kg.min. However, after 6 mo of oral L-thyroxine therapy (T(4)=9.5+/-1.4 microgram/kl) the treated hypothyroid patients had increased their combined SCR (Ra(2)--Ra(6)) to 0.86 +/-0.23 mg/kg.min (P<0.02), a value not significantly different from the combined SCR of normal subjects. We conclude that substrate cycling between glucose and glucose-6-phosphate and between fructose-6-phosphate and fructose-1,6-diphosphate occurs in man and is affected by thyroid hormone. Substrate cycles may represent a mechanism by which thyroid hormone alters the sensitivity of certain reactions to metabolic signals.     

Dopamine clearance in critically ill infants and children: effect of age and organ system dysfunction

To learn if there are age-related differences in the pharmacokinetic behavior of dopamine, plasma dopamine clearance was determined in 27 acutely ill infants and children who were receiving a continuous intravenous infusion of the drug. Steady-state clearance was calculated from dopamine concentration in arterial blood. Dopamine clearance was 60.7 +/- 28.1 ml/kg/min. The age of the patient exerted an effect on clearance of dopamine (r = -0.63; p less than 0.05), and dopamine clearance was nearly twice as rapid in children younger than 2 years as it was in older children (82.3 +/- 27.7 ml/kg/min versus 45.9 +/- 17.0 mg/kg/min). Conjugated bilirubin exerted an age-independent effect on clearance of dopamine; clearance was 44.8 +/- 28.6 ml/kg/min in children with abnormal conjugated bilirubin (greater than or equal to 0.9 mg/dl) and 70.1 +/- 2.56 ml/kg/min in children with normal conjugated bilirubin (less than 0.9 mg/dl). Clearance was lowest (29.8 +/- 5.7 ml/kg/min) in the four children who had both hepatic and renal dysfunction. Age is an important determinant of dopamine clearance, explaining in part the clinical observation that infants and young children require higher infusion rates.     

Therapeutic cytapheresis for inflammatory bowel disease.

Cytapheresis therapy has recently been investigated as a treatment for several diseases, especially autoimmune related diseases such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. The removal of leukocyte components has been performed by the centrifugal method; however, using fiber technology or column technology, leukocyte components can be removed simply, and these technologies are more effective than the centrifugal method in removing numbers of cells. Each of 3 types of leukocytapheresis methods removes a different kind of cell in its therapeutic principle. Thus, if we understand what kind of cells should be removed, we can choose the best method for removing leukocytes. For this reason, the authors propose an international standard for unifying names. The therapy that makes use of a centrifuge to selectively remove about 40% of neutrophils and more than 60% of lymphocytes may be called a lymphocyte removal therapy, lymphocytapheresis (LCA). Using cellulose acetate beads in a G-1 granulocyte removal column, granulocytes and monocytes are removed but not lymphocytes, so we suggest calling this granulocytapheresis (GCAP). In addition, using a leukocyte removal filter, the Cellsorba leukocyte removal filter, 99% of both granulocytes and monocytes and about 70% of lymphocytes are removed. We propose calling this leukocytapheresis (LCAP). In the near future, we hope that we will be able to select one of these methods for cytapheresis for each disease pathogenesis or cellular immune abnormality. Presently, a lot of research is on-going to analyze how cytapheresis is effective for the immune related diseases. The mechanism of cytapheresis will be clarified by investigators. We strongly believe that cytapheresis therapies offer good news to those patients suffering from incurable diseases as well as their physicians.     

Postprandial exercise in type I diabetic patients on multiple daily insulin injection regimen

This study shows the influence on plasma glucose concentrations of 45 min of mild exercise (48 +/- 4% of maximum aerobic capacity) performed 180 min after breakfast and 195 min after a subcutaneous injection of regular insulin by six type I (insulin-dependent) diabetic patients on a three-daily insulin injection regimen (regular insulin before breakfast and lunch, regular + intermediate insulin before supper). It has been observed that such exercise does not induce a large plasma glucose decrease. Actually, plasma glucose concentrations were 99 +/- 18 mg/dl before exercise, reached a nadir of 78 +/- 17 mg/dl at 35 min, and were 81 +/- 15 mg/dl at the end of exercise. During the control study at rest, in the same 45-min time interval, plasma glucose decreased from 146 +/- 31 to 128 +/- 31 mg/dl. In the exercise study, one patient began exercising while hypoglycemic, and another patient developed asymptomatic hypoglycemia during exercise. In the control study at rest, one patient showed hypoglycemic glucose concentrations. Throughout the exercise study, plasma free-insulin concentrations decreased (from 32 +/- 5 to 20 +/- 4 microU/ml) as a result of the pharmacokinetics of subcutaneously injected insulin.     

Clinical experience with desferrioxamine in dialysis patients with aluminium toxicity

A desferrioxamine (DFO) infusion test, using a DFO dose of 36.9 +/- 11.2 mg/kg (mean +/- SD), was performed in 50 consecutive dialysis patients undergoing diagnostic bone biopsy. In 30 patients whose bones stained positively for aluminium the serum aluminium level increased by an average of 373 +/- 250.4 ng/ml. The increase in 20 aluminium-negative patients was 231 +/- 179.2 ng/ml (p less than 0.05). Aluminium-positive patients had lower levels of immunoreactive parathyroid hormone (336 +/- 442 muleq/ml) than aluminium-negative patients (1278 +/- 1400 muleq/ml; p less than 0.05). A change in serum aluminium level of greater than 200 ng/ml after the administration of DFO was 73 percent sensitive and 50 percent specific, and had a positive predictive value of 69 percent for detecting positive bone aluminium staining. The combination of a baseline immunoreactive parathyroid hormone level less than 200 muleq/ml and a change in serum aluminium of greater than 200 ng/ml after DFO was 90 percent specific and had a positive predictive value of 85 percent. In the second phase of our study, 28 dialysis patients with aluminium toxicity received long-term therapy (11.0 +/- 4.3 months) with DFO at an average starting dose of 41.7 +/- 17.1 mg/kg, administered once weekly. The four deaths which occurred during this treatment involved the only patients who had advanced dialysis dementia. Seven patients with less severe neurological symptoms responded favourably. Fractures decreased from 1.7 fractures/patient/year to 0.1 fracture/patient/year. Muscular strength and overall functional class were improved or stable in 25 patients; myalgias and arthralgias were also stable or improved in 19 patients. After 5-7 months of treatment, serum aluminium levels decreased from 401 +/- 262 ng/ml to 245 +/- 217 ng/ml (p less than 0.01); erythrocyte mean corpuscular volume increased from 86.3 +/- 10.91 fl to 94.1 +/- 9.23 fl (p less than 0.02); and serum calcium decreased from 10.4 +/- 0.94 mg/dl to 9.9 +/- 0.70 mg/dl (p less than 0.02). Serum immunoreactive parathyroid hormone levels remained stable in 25 patients, but severe hyperparathyroidism developed rapidly in three patients. Eight patients with transfusional iron overload had no change in serum ferritin levels. Iron depletion developed in six patients, with a decrease in serum ferritin from 251 +/- 229.8 micrograms/l to 45 +/- 29.3 micrograms/l, and they required parenteral iron supplementation. Significant side-effects occurring during long-term DFO administration were hypotension (11 patients), gastrointestinal upset (seven patients), porphyria cutaneous tarda-like lesions (three patients), and transient visual disturbance (one patient). There was a decrease in stainable bone aluminium in all nine patients with paired bone biopsy specimens (pre- and post-DFO).(ABSTRACT TRUNCATED AT 400 WORDS)     

Perioperative control of blood glucose in diabetic patients: a two-step protocol

Perioperative control of blood glucose in patients with diabetes has been difficult due to frequent occurrence of hypoglycemia or hyperglycemia. We developed a two-step protocol for management of insulin-treated patients during general anesthesia. Regular insulin was given intravenously before anesthetic induction according to the step I formula (initial): initial blood glucose - 150/10 = U. Regular insulin was then given during surgery according to the step II formula (hourly): blood glucose 150-250 mg/dl = 2 U; blood glucose greater than 250 mg/dl = 4 U. Fluid replacement of 5% dextrose with lactated Ringer's solution, 3 ml/kg estimated ideal body weight, was given hourly and additional lactated Ringer's solution was given as indicated. Thirty patients received preoperative (long- or intermediate-acting) insulin and were managed by the two-step protocol. Ten patients received preoperative (long- or intermediate-acting) insulin and were managed by a standard method used in the same institution. Thirty patients did not receive preoperative insulin and were managed by the two-step protocol. All patients underwent retinal surgery under general anesthesia. In comparing the two groups pretreated with insulin, patients treated by the standard method had significantly higher (mean) blood glucose levels (360.2 +/- 100.4 mg/dl) than those treated with the two-step protocol (181.2 +/- 50.8 mg/dl) (P = 0.0001) at the end of surgery. Of the two-step protocol patients, those pretreated with one-half the usual morning dose of long- or intermediate-acting insulin had lower (mean) blood glucose levels (225 +/- 87 mg/dl) than patients not pretreated (310 +/- 130.8 mg/dl) (P = 0.0069) the morning after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Complement activation in septic shock patients

To evaluate the status of the complement system and to determine the effects of corticosteroids on complement component levels in septic shock, C3, C4, and Factor B were measured in 42 patients with severe late septic shock. Serum levels of C4 and Factor B correlated with C3 levels (r = 0.48 and 0.64, respectively; p less than .01) in patients in shock for more than 4 h, but only Factor B correlated with C3 (r = 0.85; p less than .01) in patients in shock for 4 h or less. C3 and Factor B levels were significantly (p less than .05) lower in patients who died (12,174 +/- 1,524 CH50 U/ml and 14 +/- 1 mg/dl, respectively) than in patients who survived (18,418 +/- 2,833 CH50 U/ml and 21 +/- 2 mg/dl, respectively). Corticosteroids did not alter complement component levels. The alternative pathway appears to be activated early in septic shock, whereas the classical pathway is activated later. C3 and Factor B levels may predict survival of patients in septic shock. In this study, corticosteroids did not change the complement component levels of patients in late severe septic shock.     

Impact of transfer from animal-source insulins to biosynthetic human insulin (rDNA E coli) in patients with diabetes mellitus.

Six hundred forty-eight patients (50.5% men; 49.5% women) with diabetes mellitus on animal-source insulin therapy for at least five years were studied. In this patient population, approximately 68.7% had Type I insulin-dependent diabetes mellitus and 31.3% had Type II noninsulin-dependent diabetes mellitus, nonetheless requiring insulin therapy. Patients were voluntarily transferred from animal-source insulin to biosynthetic human insulin derived by recombinant DNA technology from genetically altered Escherichia coli [human insulin (rDNAE coli)] and were monitored regularly thereafter. At a mean interval of 14 months after transfer to human insulin (rDNAE coli), these patients had gained 0.8 kg in body weight (P less than 0.01). There was a significant decline in systolic (P less than 0.01) but not in diastolic blood pressure. Insulin requirements while on animal-source insulin averaged 47.6 +/- 22.9 U/day (mean +/- SD); this requirement was not significantly different after transfer to human insulin (rDNAE coli) (47.0 +/- 21.2 U/day). The distribution of regular and modified insulin types prescribed did not change after patients were transferred from animal-source insulin to human insulin (rDNAE coli). However, a significant increase in the number of insulin injections from 1.79 +/- 0.59 to 1.96 +/- 0.61 injections/day was observed (P less than 0.001). Fasting glucose levels declined significantly from 202 +/- 87 mg/dl on animal-source insulin to 178 +/- 66 mg/dl on human insulin (rDNAE coli) (P less than 0.001). Postprandial glucose levels (at two hours) also declined from 227 +/- 83 mg/dl to 212 +/- 80 mg/dl. Glycosylated hemoglobin (HbA1c) decreased from 9.57 +/- 2.01% while taking animal insulin to 8.97 +/- 2.00% on human insulin (rDNAE coli) (P less than 0.001) Serum cholesterol and triglyceride levels insulin (rDNAE coli). Serum high-density lipoprotein cholesterol (HDL-cholesterol) levels increased from 54.2 +/- 15.1 mg/dl on animal insulin to 57.2 +/- 15.5 mg/dl on human insulin (rDNAE coli) (P less than 0.001). These data demonstrate that transfer of patients from animal-source insulins to human insulin (rDNAE coli) was associated with: (1) an improvement in glycemic control parameters; (2) a slight increase in the number of insulin injections in some patients, but no overall alteration in insulin requirements; and (3) no adverse trends in indicators of cardiovascular risks, such as serum lipids. Indeed, overall cardiovascular risk may have declined not only as a result of improvement in glycemic control, but also owing to a reduction in systolic blood pressure and an elevation in HDL-cholesterol levels.     

Reduced incidence of radiocontrast-induced nephropathy in ICU patients under theophylline prophylaxis: a prospective comparison to series of patients at similar risk

OBJECTIVE: To investigate whether the adenosine-antagonist theophylline reduces the incidence of contrast-induced nephropathy (CIN). DESIGN AND SETTING: Prospective, comparison to series of patients at similar risk of CIN in a university hospital medical ICU. PATIENTS: 78 ICU patients with at least one risk factor for CIN undergoing 150 consecutive contrast examinations. INTERVENTIONS: Administration of 200 mg theophylline/70 kg BW intravenously 30 min before that of 100 ml or more low-osmolarity contrast medium (CM). MEASUREMENTS AND RESULTS: Concentrations of serum creatinine and blood urea nitrogen (BUN), urine volume, fluid balance, and the incidence of CIN [increase in creatinine > or =20.5 mg/dl (= 44.2 micromol/l) within 48 h] were monitored for 48 h. Despite the large number of risk factors (6.8 per patient) including a high dose of CM (169.4 ml), impaired renal function (51%), diabetes (38%), aminoglycosides (61%), vancomycin (53%), catecholamines (52%), creatinine concentrations were not increased 24 h (1.40+/-0.92 mg/dl) or 48 h (1.38+/-0.88 mg/dl) after CM [1.47+/-1.0 mg/dl (= 130+/-88 micromol/l)] vs. baseline. The fluid balance was not different before (+3 ml/h) and after CM (-9 ml/h). The urine volume slightly increased after CM and theophylline (184 ml/h vs. 164 ml/h). Only three patients (2%) developed CIN. The incidence was significantly lower than that of 14% (78/565) in the control series with patients at comparable risk of CIN (p < 0.0001). CONCLUSIONS: Using a theophylline prophylaxis the incidence of CIN in patients with increased risk of CIN is as low as 2%.     

The beneficial effects of lymphocytapheresis for treatment of nephrotic syndrome.

A considerable permeability factor (or factors) derived from circulating T cells has a crucial role in proteinuria of nephrotic syndrome (NS). We attempted to remove pathogenic T cells through lymphocytapheresis (LCAP) in 6 patients with primary NS, 2 patients with minimal change nephrotic syndrome (MCNS), 2 patients with focal segmental glomerulosclerosis (FSGS), 1 patient with membranous nephropathy (MN), and 1 patient with MN and FSGS using Cellsorba (Asahi Medical Co., Osaka, Japan). LCAP was performed 2 times in 2 consecutive weeks and was followed with corticosteroid therapy with or without cyclosporine A in 5 patients. Two patients with MCNS, 1 with FSGS, and 1 with MN and FSGS showed a dramatic decrease of proteinuria (-30% and -94%) in their urine protein/creatinine ratio. Three out of 4 patients had a complete or partial remission (proteinuria <1g/day) within 8 weeks following immunosuppressive therapy. During the LCAP, T cells, especially activated T cells, decreased significantly in the response group. The other 2 patients, 1 with FSGS and 1 with MN, however, had no response to LCAP and following immunosuppressive therapy or low-density lipoprotein apheresis and suffered from end-stage renal failure or death by pneumonia. These results suggested that LCAP might have a beneficial effect on the treatment of NS, especially MCNS and in some patients with FSGS, despite varying responses to LCAP and concomitant immunosuppressive therapy.     

Bedside capillary glucose monitoring in the general hospital

We assessed the accuracy and reliability of capillary glucose monitoring (CGM) for 20 hospitalized patients as an alternative to repeated venipunctures for laboratory blood glucose (LBG) determination. A total of 330 pairs of observations was obtained. Pearson correlation between patient estimates using Chemstrip bG and the laboratory glucose-oxidase method was 0.87. The mean LBG determination was 197 +/- 5 mg/dl compared with 176.4 +/- 4.3 mg/dl for patient CGM estimates. The mean deviation was 17.6 +/- 2.9 mg/dl or 8.9%, which is well within the 20% range that is generally accepted as sufficiently accurate. Certain individual patients may require relatively more instruction and supervision to reliably carry out these measurements. These patients may represent 10-25% of all diabetic patients. Neither age nor years of schooling is a useful index to identify these patients. Therefore, we suggest as a routine that 10 or more CGM be checked against simultaneous LBG to confirm accuracy before relying on bedside CGM estimates alone in managing the hospitalized patient. Patients who can carry out CGM accurately may be managed with CGM alone.