Steroid Immunosuppression Research Articles

Composite liver-small bowel allografts with preservation of donor duodenum and hepatic biliary system in children

Background/Purpose: Liver and intestinal transplantation is commonly required for children with intestinal failure who suffer concomitant total parenteral nutrition (TPN)-induced liver failure. Retrieval of such composite allografts using previously described “standard techniques” mandates reconstruction of the biliary system with a defunctionalization loop of the proximal allograft jejunum. The occasional post-transplant biliary complications have been associated with significant morbidity and mortality. Also, size matching has limited the pool of donor organs for this patient population. To improve outcome and increase the donor pool the authors have utilized a duodenal-sparing composite liver small bowel allograft technique (DLSBTx) by preserving the head of the pancreas and the pancreatic-duodenal arteries. This precludes a biliary drainage procedure.Methods: Nine children (5 girls, 4 boys), with a mean age of 1.4 years (range, 1 to 17.4 years) received a DLSBTx. In 2 patients the liver was reduced; 1 patient received the whole pancreas. The mean recipient weight at the time of transplantation was 17.4 kg (range, 6.6 to 49.8 kg). The mean age and mean weight for donors was 7.9 years (range, 3 days to 22 years) and 25 kg (range, 4 to 70 kg), respectively. All transplants were performed under tacrolimus and steroid immuno-suppression.Results: With a mean follow-up of 419 days (range, 5 to 795 days), patient and graft survival rates are 78% and 67%, respectively. One patient underwent a combined retransplantation with the standard technique 31 days after the primary allograft was destroyed by a native pancreatic fistula. Currently, all surviving recipients are at home and off TPN. DLSBTx allowed the expansion of the donor pool by transplanting 6 patients with donor to recipient weight ratio ≥1 and utilizing 2 less than 5-kg donors, including a neonatal donor. In 55% of the patients, chemical pancreatitis was observed during the early postoperative period. None of the duodenal allografts experienced signs of ischemia or leak.Conclusions: The technical advantages of this procedure include avoidance of a biliary reconstruction and simplification of the operative procedure. This, together with the feasibility of split or reduced liver grafting promises to increase the donor pool from neonates to adults.

Impact of FK506 and steroids on adaptation after intestinal resection or segmental transplantation.

Segmental small intestinal transplantation (SIT) using living related donors (LRD) is being evaluated as a therapy, clinically. Advantages of this technique include an increase in the donor pool, optimization of the timing of transplants, and potential immunologic benefits. However, the ability of a short segment of intestine to function after transplantation has not been investigated in large animal models. This study evaluates the impact of immunosuppression on the adaptive process and the ability of a transplanted segment of intestine to adapt. A pig model of segmental SIT was used. Animals were resected, leaving 150 cm of distal ileum (n = 5), resected and treated with FK506 (n = 4), or steroids (n = 4), or with FK506 + steroids (n = 7), or transplanted using a similar segment of ileum and treated with FK506 + steroid immunosuppression (n = 9). Animals undergoing resection, or resection plus steroid treatment, did well, gaining weight post-operatively (37% and 15% of preoperative weight, respectively). However, animals undergoing resection and treated with FK506 or FK506 + steroids did poorly, losing weight (-14% and -22% of preoperative weight, respectively) and showing significant impairment of intestinal adaptation, morphologically and functionally. Furthermore, FK506-treated animals developed inflammatory changes in the intestinal mucosa, mimicking rejection. Segmental SIT animals had a high rate of rejection (66%) and showed a similar impairment in adaptation. Hence, segmental SIT is a stringent physiological test of intestinal adaptation. FK506 appears to impair gut function after resection, either directly, or by interfering with the adaptive process. In this model of segmental SIT, FK506 and steroids at the doses tested did not provide adequate immunosuppression to prevent rejection and the graft did not function adequately to allow growth. Further studies are required to evaluate the mechanisms underlying these findings, and to determine if similar effects occur in humans.

Septic arthritis of the temporomandibular joint

Septic arthritis of the temporomandibular joint (TMJ) is an uncommon disease associated with local factors such as joint involvement by rheumatoid arthritis or systemic factors such as diabetes, immunosuppression, or prolonged use of systemic steroids. 1,2

PHAEOHYPHOMYCOSIS OF THE EPIDIDYMIS CAUSED BY EXOPHIALA JEANSELMEI

The dematiaceous (dark walled) fungi are a heterogenous group of organisms that includes members of the genus Exophiala.l-* Exophiala species are ubiquitous in nature and are the most common etiological agents in phaeohyphomycosis (granulomatous infection due to dematiaceous fungiha Phaeohyphomycosis usually involves superficial and cutaneous sites but can also cause subcutaneous and systemic disease.1-3.5 Although dematiaceous fungi can infect extra cutaneous locations, to our knowledge they have not been described as a pathogen in the genitourinary ~ystem.l-~,~ We report a case of phaeohyphomycosis of the epididymis caused by Exophiala jeanselmei variant lecanii-corni following hydrocele needle aspiration which was successfully treated with epididymo-orchiectomy. CASE REPORT A 54-year-old man from Pennsylvania was referred to our institution for treatment of a right testicular abscess diagnosed on 'indium-labeled white blood cell radionuclide imaging. There was no history of immunosuppression (human immunodeficiency virus infection or steroid therapy), malignancy, diabetes mellitus, urinary tract infection or manipulation, nor were there any notable environmental or occupational exposures (farming, gardening or carpentry) to fungi. The patient had a 12-month history of a recurrent right hydrocele treated with repetitive percutaneous needle aspirations and, subsequently, epididymo-orchitis developed which was refractory to various broad-spectrum antibiotics. At presentation the patient was afebrile with no evidence of systemic disease. The genitourinary examination was unremarkable except for a fluid-filled sac surrounding a tender right testis and epididymis. Laboratory data included a normal white blood cell count and negative urine culture. Scrota1 exploration revealed a firm nodule in the epididymis surrounded by a loculated hydrocele. The right scrotal

Long-term survival and function of intrahepatic islet allografts in baboons treated with humanized anti-CD154.

Clinical islet cell transplantation has resulted in insulin independence in a limited number of cases. Rejection, recurrence of autoimmunity, and impairment of normal islet function by conventional immunosuppressive drugs, e.g., steroids, tacrolimus, and cyclosporin A, may all contribute to islet allograft loss. Furthermore, intraportal infusion of allogeneic islets results in the activation of intrahepatic macrophages and endothelial cells, followed by production of proinflammatory mediators that can contribute to islet primary nonfunction. We reasoned that the beneficial effects of anti-CD154 treatment on autoimmunity, alloreactivity, and proinflammatory events mediated by macrophages and endothelial cells made it an ideal agent for the prevention of islet allograft failure. In this study, a nonhuman primate model (Papio hamadryas) was used to assess the effect of humanized anti-CD154 (hu5c8) on allogeneic islet engraftment and function. Nonimmunosuppressed and tacrolimus-treated recipients were insulin independent posttransplant, but rejected their islet allografts in 8 days. Engraftment and insulin independence were achieved in seven of seven baboon recipients of anti-CD154 induction therapy administered on days -1, 3, and 10 relative to the islet transplant. Three of three baboons treated with 20 mg/kg anti-CD154 induction therapy experienced delayed rejection episodes, first detected by elevations in postprandial blood glucose levels, on postoperative day (POD) 31 for one and on POD 58 for the other two. Re-treatment with three doses of anti-CD154 resulted in reversal of rejection in all three animals and in a return to normoglycemia and insulin independence in two of three baboons. It was possible to reverse multiple episodes of rejection with this approach. A loss of functional islet mass, as detected by reduced first-phase insulin release in response to intravenous glucose tolerance testing, was observed after each episode of rejection. One of two baboons treated with 10 mg/kg induction therapy became insulin independent post-transplant but rejected the islet graft on POD 10; the other animal experienced a reversible rejection episode on POD 58 and remained insulin independent and normoglycemic until POD 264. Two additional baboon recipients of allogeneic islets and donor bone marrow (infused on PODs 5 and 11) were treated with induction therapy (PODs -1, 3, 10), followed by initiation of monthly maintenance therapy (for a period of 6 months) on POD 28. Rejection-free graft survival and insulin independence was maintained for 114 and 238 days, with preservation of functional islet mass observed in the absence of rejection. Prevention and reversal of rejection, in the absence of the deleterious effects associated with the use of conventional immunosuppressive drugs, make anti-CD154 a unique agent for further study in islet cell transplantation.

Simultaneous Administration of Adjuvant Donor Bone Marrow in Pancreas Transplant Recipients.

91 Purpose: The effect of donor bone marrow was evaluated for its potential favorable effect in our simultaneous pancreas/kidney (SPK) transplant program over a 4 year period. Methods: From July 1994 through August 1998, 164 pancreas transplants were performed, 140 of which were SPK. All patients received tacrolimus, mycophenolate mofetil and steroids for immunosuppression (azathioprine was used in the first year of the program). Fifty-three SPK patients received perioperative unmodified donor bone marrow (BM), 3-6 × 106 cells per kg. Results: Overall actuarial survival at 1 and 3 years was 98% and 97% (patient), 96% and 89% (kidney) and 86% and 82% (pancreas), respectively. In the adjuvant donor bone marrow group 1 and 3 year survival was 96% and 93% (patient) and 83% and 83% (pancreas), respectively. Three deaths were unrelated to BM and occurred 6 months to 3 years in patients with early graft losses. For 87 non-BM recipients, survival at 1 and 3 years was 100% and 100% (patient) and 88% and 80% (pancreas), respectively. No pancreas grafts were lost after 3 months in the BM recipients, and 3 in the non-BM recipients were lost to rejection at 10, 22 and 26 months, respectively. Fifty-seven percent of BM patients were off steroids at one year, 65% at 2 years and 83% at 3 years, respectively: 52% of the non-BM patients were steroid-free at one year, 53% at 2 years and 62% (p< 0.007) at 3 years, respectively. The mean acute cellular rejection rate was 67% in the BM group and 83% in the non-BM patients (includes borderline rejection and multiple rejections). The level of donor cell chimerism in the peripheral blood of BM patients was at least two log higher than in the controls. Conclusion: In this series, which represents the largest experience with adjuvant BM infusion in pancreas recipients, there was a higher steroid withdrawal rate (p< 0.007), fewer rejection episodes, and no pancreas graft loss after 3 months in BM recipients compared to contemporaneous controls. Donor bone marrow administered perioperatively may have a protective effect in pancreas transplantation.

MANAGEMENT OF PEDIATRIC HEART TRANSPLANT RECIPIENTS WITHOUT MAINTENANCE CORTICOSTEROIDS: A 10 YEAR EXPERIENCE

832 Although corticosteroids are widely used as immunosuppressants (IS), there is ongoing controversary regarding their optimal use in pediatric solid organ transplantation. Purpose: To report a single center experience of pediatric heart transplant recipients without maintenance steroid IS. Data was obtained by review of all patients transplanted since 1988 over 4 years old at transplant. Patient age, survival, current medications, biopsy results, and details of all episodes of graft rejection were analyzed. There were 42 patients (26 males). Six were excluded from analysis (3 followed elsewhere, 3 perioperative deaths), leaving 36 patients who had 38 transplants. Median age at transplant (all 38 grafts) was 10.6 yrs (3.8-22.6yrs) with median follow up of 2.8 yrs (0.04-10.5yrs). Endomyocardial biopsies (EMB) were done by protocol at 1, 3 and 12 months post-transplant and yearly thereafter, or at the time of suspected rejection. All patients received 10 mg/kg × 6 doses of methylprenisolone as part of routine induction and then steroids were discontinued. Rejection was treated with bolus steroids alone (34%), steroids and anti-T cell antibodies (37%), steroids and methotrexate (14.5%), and increased basal IS without steroids (14.5%). Results: There were 190 EMB (5.0±2.4 per graft): 34 Grade 0, 42 - 1A, 62 - 1B, 9 - II, 16 - IIIA, 19 - IIIB, 2 - IV, 3 "no" and 3 "mild" rejection (prior to ISHLT grading). There were 103 episodes of acute rejection (2.7 per graft): 51 early (<3 months), and 52 late. Diagnosis was by clinical criteria and/or echo in 63% and by EMB in 37%. Median time to first rejection was 34 days (5 days-5.1 yrs). Four patients had no rejection. Only 3/36 (8.3%) patients received maintenance steroids for a prolonged period of time: 6 mo (deceased), 10 mo (discontinued), and 2 yrs (retransplanted). Graft coronary artery disease was present in 10/38 grafts (26%). Diagnosis was by angiography (4) and intravascular ultrasound (3) at a mean follow up in 7 grafts of 4.5 yrs (1.5-10.5 yrs). Remaining 3 were noted by pathology. Two patients (6%) were successfully retransplanted at 5 and 5.6 yrs. Two patients (6%) died due to rejection (9 mo, 4.5 yrs). Graft survival at 1 and 5 yrs was 97% and 92% with overall patient survival rates at 1 and 5 yrs of 97% and 94%. Current immunosuppression in the 34 survivors is CyA/Aza in 19, CyA/MMF in 6, and FK506/MMF in 9. Conclusion: Pediatric heart transplant recipients can be successfully managed without steroid IS without an increase in rate of rejection, graft failure, graft coronary artery disease, or mortality.

Hypertension in thoracic transplant recipients.

There are many mechanisms underlying the hypertension which occurs after thoracic transplantation. Previous disease, effects of cyclosporin, tacrolimus and steroid immunosuppression and cardiac denervation are major contributory factors. Abnormal sodium and water balance is an important common mediating factor. A new approach is clearly needed for classifying the severity of hypertension in these patients taking into account day-night variation and total blood pressure (BP) load. This would allow improved strategies for investigation and treatment. The evidence suggests that ambulatory BP measurements should be included in the assessment of initial severity of post-transplant hypertension as well as response to treatment. Further studies are needed to look at the effects of raised clinic and 24-h ambulatory BP and its treatment on longer term morbidity and mortality in thoracic transplant patients.

Epithelial regeneration and preservation of tracheal cartilage after tracheal replacement with cryopreserved allograft in the rat

Objective: We investigated the origin of the epithelium in transplanted cryopreserved tracheal allografts in rats and tried to clarify the mechanism by which immunogenicity is reduced in this procedure. Methods: Tracheal transplantation was performed with PVG rats (allele at the RT1 locus: c) used as donors and ACI rats (allele at the RT1 locus: a) as recipients. After resection of a 5-ring segment of the cervical trachea of an ACI rat, the trachea was reconstructed with the cryopreserved tracheal segment of a PVG rat ( n = 6). No immunosuppressive agents or steroids were given. Histologic changes were determined and immunohistochemical staining was performed to investigate major histocompatibility complex class I antigens of the transplanted tracheal segment. Results: Two months after tracheal transplantation, 6 surviving ACI rats were killed. Histologically, the epithelium and tracheal cartilage of the transplanted cryopreserved segment displayed normal structure. Immunohistochemical staining showed that the major histocompatibility complex class I antigen of the ACI rat was expressed in the epithelium of the transplanted segment and that the class I antigen of the PVG rat was expressed in the cartilage of the transplanted segment. Conclusions: After transplantation of the cryopreserved trachea, the epithelium of the transplanted cryopreserved segment originated from the recipient epithelium whereas the cartilage retained the structure of the donor trachea. We hypothesize that transplantation of a cryopreserved trachea leads to the growth of the recipient's epithelium over the donor trachea, thereby reducing the antigenicity of the transplant. (J Thorac Cardiovasc Surg 1998;116:624-7)

Experience with Neoral versus Sandimmune in primary liver transplant recipients

Abstract We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 ± 1.9 days in the Neoral group vs 7.8 ± 4.9 days in the Sandimmune group (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13 %) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60%) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early post-transplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplanta-tion, and similar liver, renal, and marrow function up to 1 year posttransplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24% in these 59 patients compared to our historical experience of 70 % using Sandimmune.

The Necessity for Steroid Induction or Long-Term Maintenance After Liver Transplantation: The Argument Against

HE question to be debated is whether our traditional reliance on steroids is relevant in the 1990s, given the new immunosuppressive modalities now available to us. The immunosuppressive properties of steroids are certainly of historic importance in the success of solid organ transplantation. As early as 1951, the efficacy of steroid immunosuppression in prolonging survival of rabbit skin homografts was demonstrated, 1 and the early success of human renal allografts was also clearly dependent on steroid therapy. However, in the modern era of improved immunosuppressive choices, it is now necessary to critically assess the balance between the immunosuppressive benefits of steroid therapy and their side effects, many of which carry significant morbidity, particularly with longterm use. Steroids exert their immunosuppressive effect by inhibition of cytokine expression. 2 This is particularly important in the direct blockade of IL1 and IL6 release from antigen presenting cells, which prevents optimal T helper cell stimulation. Steroids have also been shown to inhibit IL2, IL3, TNFa, and interferon-g, a mechanism which requires costimulation and affects activated T cells. Counterbalancing these beneficial immunosuppressive properties are the well described adverse effects of steroids, the most important of which are osteoporosis, hypertension, glucose intolerance, hyperlipidemia, obesity, and growth stunting. 3 The morbidity associated with

Living related liver transplants in children confer reduced need for pulse steroid immunosuppression

Living related liver transplants in children confer reduced need for pulse steroid immunosuppression

Incidental detection of calcified dialysis graft on Tc-99m MDP bone scan.

A 48-year-old woman with a renal transplant and a history of immunosuppressive steroid use presented with a history of persistent hip pain. She was referred for radionuclide bone scan to evaluate the presence of avascular necrosis. No evidence of avascular necrosis was seen; however, incidental uptake of Tc-99m MDP was seen in a heavily calcified, nonfunctioning, synthetic dialysis access graft in the left groin.

Impairment of fibrinolytic potential in long-term steroid treatment after heart transplantation.

Thrombotic complications constitute an important risk in transplant recipients, in whom a hypercoagulable state and hypofibrinolysis have been associated with immunosuppressive treatment, especially with cyclosporine. In no case have clotting and fibrinolytic abnormalities been correlated with steroid immunosuppression, even though steroids were always administered. Previous studies found a relationship between hypercorticism and hypofibrinolysis both in Cushing's disease and after renal transplantation. The aim of this investigation was to compare fibrinolytic potential using the venous occlusion test in two similar groups of heart transplant patients treated with or without steroids. Euglobulin lysis time, tissue-type plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) activities, and antigens were determined before and after the venous occlusion test. A reduced fibrinolytic potential (significant prolongation of lysis time) due to a significant increase in PAI-1 activity and antigen levels was found in heart transplant patients treated with steroids, as compared with patients without steroid treatment and control subjects. The prevalence of reduced fibrinolytic potential was 69.2% (18 cases) in the steroid-treated group and 34.8% (8 cases) in the non-steroid-treated group. In every case, the impaired fibrinolytic potential was due to high basal PAI-1 levels. Our results are compatible with the presence of a hypofibrinolytic state secondary to long-term steroid treatment. In heart transplant recipients, steroid-induced hypofibrinolysis may constitute a further risk factor for thrombotic disease.

Steroid withdrawal in kidney transplant recipients: is it a safe option?

The long‐term side effects of lifelong steroid immunosuppression are well documented, therefore, steroid withdrawal (SW) if safe would clearly be of benefit. From 1987‐1996, 470 kidney transplants were performed at our institution. During this time period, steroid withdrawal was offered to a select group of patients (n=43) who were at least 1 year post transplant (27.6±12.0 months, 15‐64 months), had stable graft function and had experienced only mild episodes of rejection in the postoperative period. Informed consent was obtained from all participants. Twenty‐five patients were male and 18 were female. The mean age at time of transplantation was 42.4±14.1 years (17‐65 years). There were 28 cadaveric renal transplants (CRT), 10 living related kidney transplants (LRT) and 5 simultaneous kidney‐pancreas transplants (SPK). Maintenance immunosuppression in all patients consisted of CSA 3‐5 mg/kg, and AZA 1‐2 mg/kg. Twenty‐nine patients (67%) have remained off steroids with good renal function for 13‐ 59 months (38.3±11.0). Steroids were restarted in 14/43 (32%) patients 1‐ 36 months post SW (13.3±11.0 months). Eight of these 14 patients had a rise in creatinine and biopsy proven rejection, 5 of whom responded to reinstitution of steroid immunosuppression, and have stable renal function (CR=2.0±0.4) 41‐53 months (45+4.0 months) post SW. Three (7%) patients lost their allograft. One was a SPK recipient who retained good pancreatic function and subsequently received a successful 2nd kidney transplant. The other 2 patients died awaiting retransplantation. Steroids were recommenced in 6/14 patients who did not develop rejection for inability to tolerate CSA/AZA (2), anxiety (2) or recurrent disease (2). In the majority of our patients, (93%) SW did not result in immunologic graft loss. A graft loss of 7% (3) is not significantly different from the expected graft loss in a kidney transplant recipient population over a time period of 9 years. Therefore, we feel that with careful monitoring steroid withdrawal can be safely accomplished in select patients.

Slipped capital femoral epiphysis associated with renal failure osteodystrophy.

A retrospective institutional and literature review of 31 children (20 boys and 11 girls) with 58 renal failure-associated slipped capital femoral epiphyses (RFASCFEs) was performed. The average age at diagnosis of renal failure was 8.9 years, and for RFASCFE 11.5 years, with a linear correlation between these two ages. All patients had secondary hyperparathyroidism at diagnosis of the RFASCFE. The median height and weight were below the 5th percentile. The RFASCFEs were stable and bilateral in 95% of the children. Slip magnitude was mild in 53%, moderate in 8%, and severe in 39%. Avascular necrosis was associated with steroid immunosuppression in children with renal transplants. All children were treated with medical management; surgery was used in an additional 29 hips. If correction of secondary hyperparathyroidism is not achieved within 2 months, RFASCFEs are likely to progress and surgical stabilization is recommended.

Echocardiographic indexes of rejection in pediatric cardiac transplant recipients managed without maintenance steroid immunosuppression

In this investigation, of the parameters evaluated, we demonstrated that Doppler flow velocity patterns through the mitral valve may be useful for detecting cardiac allograft rejection in children. However, the findings in our investigation compared with results reported by others suggest that the use of noninvasive indexes for detection of cardiac rejection may be more discriminating in pediatric patients not receiving steroid immunosuppression therapy.

Severe community-acquired pneumonia in the elderly: epidemiology and prognosis. Study Group for Severe Community-Acquired Pneumonia.

Ninety-five patients with severe community-acquired pneumonia (SCAP) who were > or = 65 years of age were studied prospectively. A definite pathogen was identified in 37 cases (38.9%) and was most commonly Streptococcus pneumoniae, Haemophilus influenzae, or another gram-negative bacillus. The overall death rate was 40%. Eighty-three patients required mechanical ventilation and 40 needed vasoactive drugs. Multivariate analysis showed that the risk of death was higher in cases involving rapid radiological spread (relative risk [RR] = 6.99; 95% confidence interval (95% CI) = 1.54-31.70), shock (RR = 6.70; 95% CI = 2.13-21.02), previous steroid treatment or immunosuppression (RR = 5.50; 95% CI = 0.77-39.10), acute renal failure (RR = 3.88; 95% CI = 1.30-11.59), or an APACHE II score of > 22 on admission (RR = 2.25; 95% CI = 0.73-6.95). We conclude that SCAP in elderly patients is associated with high mortality, but it is inappropriate to withhold intensive care on account of age. The presence of complications and the severity of illness at initial presentation were the major variables affecting outcome. Except for immunosuppression, comorbidities did not seem to influence outcome. Finally, our data reinforce the current American Thoracic Society guidelines concerning therapy for patients with SCAP.

The effect of (steroid) immunosuppression on skeletal muscle glycogen metabolism in patients after kidney transplantation.

To examine the mechanisms by which immunosuppression by steroids impairs glycogen synthesis in human skeletal muscle, we measured glycogen synthase protein content and activity in muscle samples from 14 patients receiving corticosteroid therapy after kidney transplantation and in 20 healthy control subjects. A percutaneous muscle sample was taken before and at the end of a euglycemic hyperinsulinemic insulin clamp. Insulin-stimulated glucose disposal was reduced by 33% in kidney transplant patients compared with healthy controls (33.8 +/- 4.2 vs. 50.5 +/- 2.7 mumol (kg LBM)-1 min-1; P<0.01), primarily due to a decrease in nonoxidative glucose metabolism (14.2 +/- 3.3 vs. 32.3 +/- 2.7 mumol (kg LBM)-1 min-1; P<0.001). Glycogen synthase activity measured at both 0.1 mmol/L (17.6 +/- 2.6 vs. 24.0 +/- 2.2 nmol min-1 mg protein-1; P<0.05), and at 10 mmol/L glucose 6-phosphate (24.1 +/- 3.5 vs. 33.7 +- 2.4 nmol min-1 mg protein-1; P<0.05) and glycogen synthase protein concentrations (8.8 +/- 1.8 vs. 18.9 +/- 1.9 relative units per ng DNA; P<0.01) were lower in kidney transplant patients compared with controls. Glycogen synthase protein correlated with nonoxidative glucose metabolism (r=0.42; P=0.04). Alpha-actinin (used as a control of general protein degradation) was lower in kidney transplant patients compared with controls (4.4 +/- 0.8 vs. 9.6 +/- 1.1 cpm/ng DNA; P<0.01). In conclusion, corticosteroids cause insulin resistance, which correlates with impaired activation of glycogen synthase and decreased enzyme protein content. The decrease in glycogen synthase protein may reflect increased degradation rather than a defect in translation.

Mixed connective tissue disease. Progress of diagnosis and treatment. Treatment. 2. Commencing time and usage of Adrenocortical steroid medicine and immunosuppressant.

MCTDは予後が比較的良好な疾患単位と考えられていた.たしかに全身性エリテマトーデス(SLE),および多発性筋炎(PM)様の症状は副腎皮質ステロイド薬(GC)に反応する.しかし皮膚硬化,肺線維症などの強皮症(PSS)様症状やRaynaud現象はかかる治療に抵抗性である.また,肺高血圧症例の予後は悪く,その早期診断法・治療法の開発が望まれている.