[Oncological data elements in histopathology]. / Onkologische Datenelemente in der Histopathologie.

In order to cope with increasing demands to supply information to a variety of documentation systems outside pathology, pathologists need to set standards both for the content and the use of the information they generate. Oncological datasets based on a set vocabulary are urgently required for use both in pathology and in further processing. Data elements were defined according to German pathology report guidelines for colorectal cancers in line with ISO 11179 requirements for the relations between data element concepts and value domains, as well as for further formal conditions, which can be exported in XML together with metadata information. Tests on 100 conventionally written diagnoses showed their principal usability and an increasing degree of guideline conformity in diagnoses commensurate with training time. This set of oncological data elements is a valuable checklist tool for pathologists, enabling formatted information export for further use and saving documentation effort.

Presymptomatic thyroidectomy in multiple endocrine neoplasia 2a.

AIMS: To evaluate the value of prophylactic total thyroidectomy in multiple endocrine neoplasia 2a (MEN 2a), based on results of genetic testing, in a presymptomatic early stage of the disease. METHODS: Fourteen presymptomatic patients genetically diagnosed and surgically treated at our centre. We analysed age, gender, location of the RET mutation, calcitonin tests, surgery, histologic findings, TNM classification, and postoperative follow-up. RESULTS: The 14 patients belonged to two families with MTC (MEN 2a). Median age was 16 years. The RET mutation was located in codon 618 and 634. Basal calcitonin (CT) levels were normal in all patients. Twelve had pathologic peak CT measurements. Total thyroidectomy was performed in all and associated central neck dissection in 12 patients. Pathohistologic assessment showed C-cell hyperplasia in all specimens and 11 MTCs; the median size of the tumours was 0.2 cm; two patient had lymph-node metastases. According to TNM, three had stage 0, nine had stage I, one had stage II, and one had stage III disease. Postsurgery basal and peak CT values were normal in all but one patients, indicating a biochemical curative rate of 95%. Calcitonin determination did not distinguish between MTC and C-cell hyperplasia. CONCLUSION: Prophylactic thyroidectomy based on genetic testing allows identification and treatment of patients at an early stage of the disease. Pathologic peak CT values are markers for the presence of microscopic MTC and should be considered in selecting operative procedures for these patients.

Abundant expression of AMACR in many distinct tumour types.

AIMS: Alpha-methylacyl-CoA racemase (AMACR), a mitochondrial and peroxisomal enzyme, is a valuable tool to confirm the diagnosis of prostate cancer, especially if combined with basal cell markers. To extend this diagnostic utility to other neoplasias, we comprehensively surveyed AMACR expression in human tumours. METHODS: We performed immunohistochemical analyses on tissue microarrays of AMACR expression in over 125 different human tumour types and 80 normal tissues. RESULTS: Microarray analysis revealed that tumours with prominent AMACR expression included adenocarcinomas of the prostate (72%), hepatocellular carcinomas (77%), papillary renal cell carcinomas (70%), and colorectal adenocarcinomas (71%). AMACR expression was equally frequent in colorectal adenomas and carcinomas. No significant difference in AMACR expression between untreated and hormone-refractory prostate cancers was observed. In the thyroid, AMACR expression was found in 42% of the follicular carcinomas but in only 16% of follicular adenomas. However, a more detailed analysis on a thyroid tissue microarray did not confirm a significant difference of AMACR expression in follicular adenoma and carcinomas. CONCLUSION: Taken together, the results indicate that AMACR is expressed in a wide variety of adenocarcinomas, and its diagnostic utility is restricted to specific areas.

Photocatalytic proton reduction with ruthenium and cobalt complexes immobilized on fumed reversed-phase silica.

Heterogeneous photocatalytic hydrogen production with a non-covalently immobilized molecular ruthenium based photosensitizer (PS) and a cobalt polypyridyl based water reducing catalyst (WRC) is reported. PS and WRC were derivatized with C18-alkyl chains and immobilized by adsorption on hydrophobic fumed silica. The resulting loaded support was suspended in water with anionic or cationic surfactants and subjected to heterogeneous photocatalytic H2 production with ascorbate as sacrificial electron donor (SED). No leaching was observed under catalytic conditions, thus catalysis was truly heterogeneous. The catalytic performance of immobilized PS and WRC clearly exceeded that of homogeneous catalysis at low concentrations. At high concentration, diffusion and light limitation lead to lower reaction rates, but the same stability as for homogeneous reactions was still achieved. WRC concentration variations indicated a relatively high stability (up to 1300 H2/Co) and mobility of amphiphilic catalysts on the hydrophobic silica surface. Comparison of fumed silica with porous and non-porous silica showed, that a high BET surface area along with a good accessibility from the reaction media are crucial for catalytic performance. Mechanistic investigations by transient absorption spectroscopy displayed reductive quenching of excited PS by ascorbate followed by on particle electron transfer to WRC as reaction pathway. Particles with additional cationic surfactants exhibited a significantly higher catalytic performance as compared to anionic surfactants. Non-covalent anchoring of correspondingly derivatized WRCs or PSs to reversed-phase silica offers a rapid and versatile transition from homogeneous to heterogeneous molecular proton reduction.

iPath - a Telemedicine Platform to Support Health Providers in Low Resource Settings.

In many developing countries there is an acute shortage of medical specialists. The specialists and services that are available are usually concentrated in cities and health workers in rural health care, who serve most of the population, are isolated from specialist support [1]. Besides, the few remaining specialist are often isolated from colleagues. With the recent development in information and communication technologies, new option for telemedicine and generally for sharing knowledge at a distance are becoming increasingly accessible to health workers also in developing countries. Since 2001 the Department of Pathology in Basel, Switzerland is operating an Internet based telemedicine platform to assist health workers in developing countries. Over 1800 consultation have been performed since. This paper will give an introduction to iPath - the telemedicine platform developed for this project - and analyse two case studies: a teledermatology project from South Africa and a telepathology project from Solomon Islands.

Elevated proinsulin levels related to islet cell antibodies in first-degree relatives of IDDM patients.

OBJECTIVE: To assess whether proinsulin levels are elevated in first-degree relatives of insulin-dependent diabetes mellitus (IDDM) patients and whether there is a relationship between proinsulin levels and the occurrence of immunological markers. RESEARCH DESIGN AND METHODS: Fasting proinsulin concentrations were measured in 85 first-degree relatives (54 siblings, 20 parents, 11 children) of IDDM patients and in 90 age- and weight-matched control subjects with no family history of diabetes mellitus. RESULTS: Fasting proinsulin levels (median, 25th, and 75th percentiles) were 8 pM (range 3.2-14 pM) in first-degree relatives and 1.7 pM (range 1.7-4 pM) in control subjects (P less than 0.0001). Proinsulin was significantly elevated in siblings (7.2 pM, range 3.8-15 pM; P less than 0.0001), parents (9.8 pM, range 6.4-13 pM; P less than 0.0001), and children (6.6 pM, range 1.8-12 pM, P = 0.04) compared with control subjects but without differences between these groups. Islet cell antibody positive (ICA+) IDDM relatives had significantly higher proinsulin levels than ICA- (16 pM; range 7.2-25 vs. 6.9 pM, range 3.1-12 pM; P = 0.02). There was no difference between individuals with and without insulin autoantibodies. No difference in proinsulin levels was observed if the relatives were subdivided according to HLA-DR sharing with the diabetic proband. CONCLUSIONS: Fasting proinsulin concentrations were raised not only in siblings but also in parents and children of IDDM patients. Because proinsulin is more elevated in ICA+ than in ICA- subjects, increased proinsulin levels could reflect minor beta-cell damage due to previous immunological attack.

The efficacy and tolerability of cyclosporine G in human kidney transplant recipients.

Twelve consecutive first cadaveric kidney transplant recipients received cyclosporine G (CsG)(initial dose 12 mg/kg per day) as basic immunosuppressive treatment along with prednisone (initial dose 0.5 mg/kg per day) for the first three months after transplantation. Thereafter CsG was replaced by Sandimmun (cyclosporine, CsA). Evaluation of the immunosuppressive efficacy and assessment of possible side effects of CsG was made and compared with the results in 38 historical control patients starting with the same dose of CsA as part of the same immunosuppressive dosage schedule. Statistically, there was no difference in patient survival at three (91% in CsG group versus 95% in CsA group) and twelve months (91% in CsG group versus 92% in CsA group), or in graft survival at three (75% in CsG group versus 89% in CsA group) and twelve months (75% in CsG group versus 84% in the CsA group). At equivalent oral doses of CsG and CsA significantly higher blood levels of CsG were observed (2P less than 0.05). Nephrotoxicity assessed by graft biopsy could be demonstrated to a similar extent in both groups, whereas hepatotoxicity was more pronounced during CsG treatment. Sequential measurements of bilirubin revealed a significant increase in all patients but median values were significantly higher in the CsG patients. A pronounced and concordant elevation of liver enzymes occurred during CsG treatment in three out of 12 patients. Liver biopsies performed in these patients revealed histological alterations consistent with toxic liver injury. Thus, in human kidney transplant recipients CsG and CsA appeared to be equally immunosuppressive and nephrotoxic but more hepatotoxic. On the basis of this limited experience we conclude that in human kidney transplant recipients CsG has no advantage over CsA.

Immunocytochemistry of pituitary tumors.

Pituitary tumors from 376 patients were investigated, using immunocytochemical techniques at the light and electron microscopic level, and autoradiography combined with immunocytochemistry for localizing somatostatin (SRIH) receptors. Prolactinomas, growth hormone-secreting adenomas causing acromegaly, and hormonally inactive adenomas were most frequently observed (153, 86, and 90 tumors, respectively). Among the latter, we could distinguish "alpha-only adenomas," many of which were oncocytomas. At the light and electron microscopic levels, cells containing (and presumably producing) simultaneously both prolactin and growth hormone, and cells containing exclusively either prolactin or growth hormone, could be demonstrated. In addition, a highly variable number and distribution of SRIH receptors could be shown in tumors secreting prolactin, growth hormone, and in tumors not associated with symptoms caused by inappropriate hormone secretion. The systematic combination of clinical, radiological, and biological techniques has currently brought great progress in the behavior and therapeutic concepts of pituitary lesions, and promises new achievements in the near future.

Factor XII, plasma prekallikrein, alpha 2-macroglobulin and C1-inhibitor levels in renal allograft recipients during immunosuppression with cyclosporin A--sequential measurements over four months in 17 patients.

Factor XII clotting activity (F XII), plasma prekallikrein amidolytic activity (PK), alpha 2-Macroglobulin (alpha 2-M) and C1-Inhibitor (C1-Inh) antigens have been measured in 17 patients immediately before and sequentially for up to four months after kidney transplantation. Before transplantation mean F XII and PK levels were normal (99 +/- 27% and 102 +/- 21%, respectively, mean +/- S.D.) and alpha 2-M and C1-Inh levels were slightly elevated (115 +/- 55% and 129 +/- 32%, respectively, mean +/- S.D.). In the first two weeks after transplantation a significant decrease of F XII to 65 +/- 27%, of PK to 67 +/- 20% and of alpha 2-M to 88 +/- 42%, and a rise of C1-Inh to 201 +/- 44% (mean +/- S.D.) were observed (2 p less than 0.005). F XII levels four month after operation remained significantly (2 p less than 0.05) lower than preoperatively. PK and alpha 2-M values, however, were significantly higher (2 p less than 0.05) at four months as compared to the pretransplant period. Mean F XII levels in the 17 patients at various time points after transplantation correlated positively with PK, alpha 2-M and serum albumin and negatively with CyA level and dose and serum bilirubin. PK and alpha 2-M correlated positively with each other and albumin and negatively with creatinine, bilirubin and CyA (2 p less than 0.01). Whether CyA has a direct influence on production or consumption of F XII, PK, alpha 2-M and C1-Inh, or whether the changes merely reflect altered protein metabolism awaits further study.

Telepathology with an integrated services digital network--a new tool for image transfer in surgical pathology: a preliminary report.

We describe a low-cost telepathology system working via a commercial integrated services digital network (ISDN) and consisting of modular software and hardware elements. The main elements are Apple Macintosh workstations; a software program for the simultaneous transfer of pictures, voice, and data; and procedures for image processing and general administration of all the information generated. Additionally, the system allows remote control of any peripheral instruments by a "picture-instrument manager." The transfer rate is currently 64 kbit/s; it will be extended to 128 kbit/s (ISDN basic rate) in the near future and to 2 Mbit/s (ISDN primary rate) in the next 2 years. The system was tested by the regional hospital in Samedan, Switzerland, and the Department of Pathology, University of Basel, Basel, Switzerland, a distance of 250 km, by offering a remote frozen section service to the regional hospital in 16 cases. Fifty-four to 58 seconds were needed for the transfer of a diagnostic 8-bit grey-level image containing 341 (median value) +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit color image containing 165 (median value) +/- 16.9 (standard error) kbytes (n = 3). The time required for a diagnostic session was between 25 and 35 minutes.

Long distance image transfer: first results of its use in histopathological diagnosis.

Histopathological images were transferred by use of normal telephone lines between three pathology institutes located in three different cities in the FRG. Images were digitized using a colour TV camera and stored in a special computerized image transmission system. The stored image was transferred and visualized on a (receiver) colour TV screen after dialing the telephone number connected to the receiver image transmission system. An additional telephone dialogue was activated by use of a normal acoustic telephone, and the diagnostic difficulties of the underlying image were discussed. Diagnostic assistance was possible in all transferred cases as well as histopathological diagnosis. Resolution of the images was set at 512 x 512 pixel x 8 bit. Image transfer time was 3.2 min on average. The differences between the original and transferred image were measured by "retransfer" of the original image and by subtracting the two images from each other. No major transfer errors could be measured.

The expression of subunits of human chorionic gonadotropin (hCG) by nontrophoblastic, nonendocrine, and endocrine tumors.

The value of the subunits of human chorionic gonadotropin (hCG) as tumor markers is controversial. The production of hCG-alpha and hCG-beta by 214 nontrophoblastic exocrine and by 416 endocrine tumors was analyzed by using immunocytochemical technics. hCG-alpha immunoreactivity was found in 131 of 416 endocrine and in 8 of 214 nonendocrine tumors. hCG-beta could not be visualized specifically with the use of two polyclonal antisera and one monoclonal antibody. The authors conclude that (1) hCG-alpha is neither a tissue nor a tumor-specific marker; (2) hCG-alpha is produced by a variable proportion (21-55%) of endocrine tumors arising in various organs but not by ileal carcinoids, paragangliomas, pheochromocytomas, nor Merkel cell tumors; (3) hCG-alpha is a marker of malignancy only in pancreatic endocrine tumors; and (4) hCG-beta is rarely, if ever, produced by tumors.

Telepathology: frozen section diagnosis at a distance.

Telepathology may be used to provide a frozen section service to hospitals without a department or institute of pathology. We have developed a telepathology system using the commercially available Integrated Services Digital Network (ISDN). The main software and hardware elements of our system are: Apple Macintosh workstations, a program for simultaneous transfer of image, voice and data, and a data bank for storage of patients' data and microscopic images. A picture instrument manager (PIM) makes remote control of microscopes or other instruments possible. The system connects the Department of Pathology of the University of Basel with the Regional Hospital of Samedan, 250 km away, and the Regional Hospital of Burgdorf, 100 km away. During a period of 20 months, frozen sections with the hospitals in Samedan and Burgdorf were performed in 53 patients. Between 54 and 58 s were required for the transfer of a diagnostic 8-bit grey level image containing 341 +/- 26.1 (standard error) kbytes (n = 13) or a diagnostic 24-bit colour image containing 165 +/- 16.9 kbytes (n = 40). Frozen section diagnosis was completed in 20-40 min. True-positive diagnoses of malignant tumours were achieved in 85.7% of cases (sensitivity = 0.857). No false-positive diagnosis was made. In 3 of the 53 cases telepathological diagnosis was not possible for technical reasons.

Parathyroidectomy in primary hyperparathyroidism: preoperative localization and routine biopsy of unaltered glands are not necessary.

BACKGROUND: An assessment was made of operative risk and outcome after parathyroidectomy for primary hyperparathyroidism. METHODS: A retrospective study was conducted in a single center university hospital in Switzerland. The 173 patients (130 women and 43 men) ranged from 17 to 89 years of age (mean, 62.0 years). No routine preoperative localization methods were used for primary neck exploration. Parathyroidectomy was performed under general anesthesia. No routine use was made of intraoperative biopsy of glands whose macroscopic appearance was normal. The 173 patients underwent 179 operations (170 primary and 9 secondary interventions). Resection of a single gland was performed in 127 cases (73.4%) and of two glands in 36 cases (20.8%). Subtotal parathyroidectomy (3 1/2 glands) was performed in 10 cases (5.8%). RESULTS: Of 170 patients with primary intervention, 164 (96.5%) were normocalcemic after operation. Six of 170 patients (3.5%) underwent early reexploration. Three additional patients underwent late secondary procedures. These nine secondary operations were successful in seven patients (78%). At follow-up (mean, 24.7 months after operation) normocalcemia was noted in 163 of 171 patients (95.3%). Persistent and recurrent hyperparathyroidism occurred in 1.2% and 3.5% of patients, respectively. Permanent postoperative hypoparathyroidism was noted in 4% (six of seven patients underwent a subtotal parathyroidectomy for multiglandular hyperplasia). Operative morbidity and mortality were 2.3% and 0.6%, respectively. CONCLUSIONS: Our surgical strategy for treatment of primary hyperparathyroidism has proved to be safe with a favorable outcome in more than 95% of patients. This was possible without the routine use of preoperative localization studies and intraoperative biopsy of macroscopically normal glands. Routine biopsy of normal-appearing glands seems to be unnecessary and may increase the risk of hypoparathyroidism.

Insulitis and diabetes are preceded by a decrease in beta cell volume in diabetes-prone BB rats.

Immunocytochemistry combined with morphometry was used to test the hypothesis that insulitis and diabetes are preceded by quantitative changes in the pancreas of diabetes-prone BB (DPBB) rats. Diabetes-resistant BB (DRBB) rats of the w-subline served as controls. In the first part of the study rats aged 15, 30, 45, and 60 days were studied. At 60 days preceding both insulitis and onset of diabetes, the DPBB rats demonstrated lower volumes of the entire pancreas, the parenchyma, the endocrine pancreas, and beta, A, and D cells. Body weights of the DPBB rats were lower than the DRBB rats from 15 days of age on. In the second part of the study, DP and DRBB rats were coreared by a foster mother to obtain weight-matched animals. Morphometric analysis at 70 days of age revealed a reduction in both the beta cell volume density and volume whereas no differences were seen in other pancreatic parameters. These results indicate that the appearance of insulitis and the later onset of insulin-dependent diabetes are preceded by a reduction in beta cell volume.

Analysis of proliferative activity using Ki-67 on cervical precancerous lesions and the relationship to p53 expression.

Neoplastic cell growth rate and the p53 expression have been recently analysed in invasive cervical carcinoma. Samples of 20 specimens with normal cervical epithelium and 73 specimens of dysplasia and carcinoma in situ (CIS) were immunostained with monoclonal antibodies to p53 and Ki-67 to examine the interrelationship between p53, Ki-67 and HPV status in cervical intraepithelial neoplasm. The presence of HPV was assessed by in situ DNA hybridization. Of dysplasias and CIS 79% were HPV positive. The growth rate of neoplastic cells was significantly correlated to the histological grade and the HPV status. The highest proliferation was found in poorly differentiated HPV 16/18 positive precancerous lesions. The analysis of the p53 expression showed no difference between various histological grades. However, the p53 oncoprotein was expressed significantly lower in HPV 16/18 positive neoplasms. The assessment of neoplastic cell growth rate offers a potentially valuable approach to predicting biological behaviour in intraepithelial neoplasms.

Vascular changes in the human endometrium following the administration of the progesterone antagonist RU 486.

Eleven healthy women were assigned to one of two groups. They received 50 mg RU 486 orally per day either on cycle days 7 to 10 (preovulatory group n = 5) or on cycle days 20 to 23 (postovulatory group, n = 6). An endometrial biopsy was taken on the fourth day of the RU-treatment in the preovulatory group and on the second (n = 2) or fourth (n = 4) treatment day in the postovulatory group. Biopsies from 34 untreated women representing matched samples from early and mid preovulatory phase (n = 10) and mid and late postovulatory phase (n = 24) were used as control. The ultrastructure of the endometrial capillaries was investigated by morphometric methods. The administration of RU 486 during the preovulatory phase did not modify the vascular structure. However, when given in the postovulatory phase, necrosis occurred in the capillary endothelial cells with and without regressive changes of the adjacent stroma. The area and diameter of the capillary lumen and the area of the adventitia was smaller than in the control material (p less than 0.01). The result of the study suggests that RU 486, when administered in the postovulatory phase, directly affects the capillary vessels of the endometrium.

Glutamine peptide-supplemented long-term total parenteral nutrition: effects on intracellular and extracellular amino acid patterns, nitrogen economy, and tissue morphology in growing rats.

Glutamine (GLN) is a nonessential amino acid that is not included in current regimens for parenteral nutrition because of its chemical instability. This study tested the hypothesis that GLN supplementation during long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a growing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:carbohydrate = 1.1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocaloric, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and alanyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in which extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histologic sections of liver and small-bowel mucosa (light and scanning electron microscopy) were evaluated. Hepatic intracellular GLN concentrations were significantly lower, in animals receiving GLN-free TPN (11.7 +/- 1.6 nmol/mg fat-free dry and solid tissue mass, n = 9) compared with both GLN-supplemented TPN (16.0 +/- 3.0, n = 7) and enteral feeding (18.2 +/- 1.8, n = 6) (p < .001). Corresponding results were found for intracellular GLN concentrations in skeletal muscle (TPN standard 12.5 +/- 3.1, TPN GLN 14.7 +/- 3.1, enteral control 17.3 +/- 2.3, p < .05), intestinal mucosa, and spleen as well as for plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Intralipid-based short-term total parenteral nutrition does not impair small intestinal mucosa-related cellular immune reactivity in the healthy rat.

BACKGROUND: The lipid component of total parenteral nutrition (TPN) has reportedly been associated with trophic effects on the intestinal mucosa and suppressive effects on the immune system. METHODS: We have challenged these hypotheses using a 7-day TPN rodent model comparing the effects of isocaloric, isonitrogenous lipid-based (TPN-lipid, 50% of calories as long-chain triacylglycerol) and carbohydrate-based TPN (TPN-CH, 100% of calories as carbohydrates) on mucosal morphology and immune function. Enterally fed animals were included to establish a baseline for immunologic read-outs. The study was performed in healthy, metabolically stable animals to avoid interference by septic or trauma-related stress factors. RESULTS: Both TPN regimens resulted in a significantly smaller weight gain (TPN-lipid, 29.8 +/- 4.0 g; TPN-CH, 30.3 +/- 4.4 g) compared with enterally fed reference animals (49.2 +/- 3.2 g; p = .007), with no difference in nitrogen balance between the TPN groups. Mucosal sucrase activity was significantly lower in both TPN groups (TPN-lipid, 8.8 +/- 1.0 x 10(-7) katal per gram (kat/g) of protein; CH: 11.9 +/- 1.6 x 10(-7) kat/g of protein) compared with enteral feeding (17.4 +/- 0.9 x 10(-7) kat/g of protein; ANOVA: p = .0007). Morphometric analysis of the small intestine revealed no differences between the two TPN groups although a significantly depressed villus height in the TPN-lipid group could be observed in comparison to enterally fed reference rats (TPN-lipid, 0.47 +/- 0.02; TPN-CH, 0.50 +/- 0.01; enteral, 0.56 +/- 0.02 mm; ANOVA: p = .0298). Light and electron microscopy revealed a normal surface architecture in all three groups of rats. Cellular immune reactivity was evaluated using a novel specific immunization protocol: animals were immunized against OVA 4 weeks before TPN. OVA-induced lymphoproliferative responses and phenotypic data from draining popliteal and mesenteric lymph nodes were evaluated after the different regimens. Results did not differ among the three groups. CONCLUSIONS: In healthy rodents, short-term lipid-based and carbohydrate-based TPN regimens lead to limited mucosal atrophy with preserved surface architecture compared with enteral feeding. However, peripheral and mesenteric cellular immune responsiveness after both TPN regimens remained comparable to enterally fed reference animals. Therefore, mesenteric and systemic cellular immune reactivity does not appear to be impaired by lipid-based or carbohydrate-based TPN.

von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients.

In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment.