Search PubMed⌕ Search

Biomedical subjects

C M Miller

Publications and source records attributed to C M Miller.

At least 91 records · Page 5Linked to original sources

Increased risk of early rejection correlates with recovery of CD3 cell count after liver transplant in patients receiving OKT3 induction.

BACKGROUND: We evaluated the utility of CD3 cell counts for monitoring OKT3 induction immunosuppression and for predicting early rejection in liver recipients. METHODS: In 32 adults in whom OKT3 and steroids were used to induce immunosuppression, CD3 cell subsets were labeled with CD3 (IgG1)-fluorescein isothiocyanate monoclonal antibody and assayed by flow cytometry before orthotopic liver transplantation and within 2-4 days, 5-7 days, and 8-10 days after transplantation. Trough OKT3 levels were measured at the same points in 10 patients. Early rejection (before postoperative [POD] day 21) was proven by elevated liver function tests and biopsy. Six patients were excluded for death, retransplantation, or early cessation of OKT3. RESULTS: Eight of 26 patients (30.8%) had early rejection and 18 (69.2%) had no early rejection. All had depletion of CD3 cells to <10.2% of baseline at POD 2-4. On POD 8-10, the mean CD3 count in rejectors was 213.31+/-184.98/mm3 vs. 22.71+/-32.42/mm3 in nonrejectors (P<0.001). By POD 8-10, five of eight (62.5%) patients who rejected had CD3 count recovery to >75% of baseline. No nonrejecting patient recovered to >26% of baseline (P<0.001). OKT3 levels did not correlate with CD3 recovery or rejection. CONCLUSIONS: The incidence of early rejection correlates strongly with recovery of CD3 counts by POD 10. Higher baseline CD3 counts do not predict early rejection.

Adult↗

Prophylactic efficacy of persistent anthelmintics against challenge with drug-resistant and susceptible Ostertagia circumcincta.

Three groups of newly-weaned Romney lambs were given either a standard oral dose of albendazole, a controlled-release capsule containing albendazole, or a standard oral dose of moxidectin. At 10, 20, 30 and 40 days after treatment, sub-groups of lambs were given 10,000 infective-stage larvae of either a drug-resistant or a drug-susceptible strain of Ostertagia circumcincta. The recommended oral dose of albendazole removed 32 per cent of the resistant strain and over 99.9 per cent of the susceptible O. circumcincta. The recommended oral dose of moxidectin removed 91 per cent of the resistant strain and over 99.9 per cent of the susceptible parasites. None of the lambs treated with controlled-release capsules was challenged at 20 or 30 days after treatment. Twenty-one days after challenge, samples of faeces were taken to determine the presence of nematode eggs and cultured to establish the proportion of eggs developing to infective-stage larvae (L3). Abomasa were recovered after slaughter and worm burdens determined. In the lambs given controlled-release capsules only the resistant parasites were able to establish, and there were significantly fewer than in the lambs treated orally with albendazole. The proportion of the eggs from resistant parasites which developed to L3 was not reduced by the presence of the capsules. Oral moxidectin provided no protection against the establishment of the resistant strain and viable L3 were recovered after challenge with resistant parasites 10 days after treatment; however, the establishment of susceptible O. circumcincta was reduced by more than 99 per cent. The establishment of the susceptible parasites in the lambs treated with moxidectin increased with time and was not significantly lower than in the other groups by 30 days after treatment.

Administration, Oral↗

Use of livers with microvesicular fat safely expands the donor pool.

BACKGROUND: The safety of transplanting livers with moderate to severe microvesicular steatosis is unknown. Livers that appear fatty are often abandoned at the donor hospital. We have recently used frozen-section biopsy to distinguish between microvesicular and macrovesicular steatosis. We present here our single-center experience with transplantation of 40 allografts with moderate or severe microvesicular steatosis. METHODS: We reviewed our data on 426 transplants and identified 40 cases in which the donor liver contained at least 30% microvesicular steatosis. Early graft function, patient and graft survival, and donor risk factors for steatosis were examined, and results in this cohort were compared with results in all other patients who received liver transplants at our center during the same time period. We also analyzed the reliability of donor frozen-section biopsies in quantitating microsteatosis. Persistence of steatosis was assessed on the basis of 1-year follow-up biopsies. RESULTS: The incidence of primary nonfunction and poor early graft function was 5% and 10%, respectively. One-year patient and graft survival rates were 80% and 72.5%, respectively. Donor obesity and traumatic death were commonly identified risk factors for microvesicular steatosis. Frozen-section biopsy was reliable for pretransplant decision-making about the use of potential grafts, and the steatosis had disappeared from the graft at 1 year in the majority of cases. CONCLUSIONS: Livers with even severe microvesicular steatosis can be reliably used for transplantation without the fear of high rates of primary nonfunction. There was a significant incidence of poor early graft function, but this did not affect outcome. Microsteatosis is usually associated with some underlying risk factor in the donor and is reversible, as demonstrated by follow-up biopsies after transplant.

Biopsy↗

Efficacy of tacrolimus as rescue therapy for chronic rejection in orthotopic liver transplantation: a report of the U.S. Multicenter Liver Study Group.

BACKGROUND: A study was performed by 17 different U.S. liver transplantation centers to determine the safety and efficacy of conversion from cyclosporine to tacrolimus for chronic allograft rejection. METHODS: Ninety-one patients were converted to tacrolimus a mean of 319 days after liver transplantation. The indication for conversion was ongoing chronic rejection confirmed by biochemical and histologic criteria. Patients were followed for a mean of 251 days until the end of the study. RESULTS: Sixty-four patients (70.3%) were alive with their initial hepatic allograft at the conclusion of the study period and were defined as the responder group. Twenty-seven patients (29.7%) failed to respond to treatment, and 20 of them required a second liver graft. The actuarial graft survival for the total patient group was 69.9% and 48.5% at 1 and 2 years, respectively. The actuarial patient survival at 1 and 2 years was 84.4% and 81.2%, respectively. Two significant positive prognostic factors were identified. Patients with a total bilirubin of < or = 10 mg/dl at the time of conversion had a significantly better graft and patient survival than patients converted with a total bilirubin > 10 mg/dl (P=0.00002 and P=0.00125, respectively). The time between liver transplantation and conversion also affected graft and patient survival. Patients converted to tacrolimus < or = 90 days after transplantation had a 1-year actuarial graft and patient survival of 51.9% and 65.9%, respectively, compared with 73.2% and 87.7% for those converted > 90 days after transplantation. The mean total bilirubin level for the responder group was 7.1 mg/dl at the time of conversion and decreased significantly to a mean of 3.4 mg/dl at the end of the study (P=0.0018). Thirteen patients (14.3%) died during the study. Sepsis was the major contributing cause of death in most of these patients. CONCLUSIONS: Our results suggest that conversion to tacrolimus for chronic rejection after orthotopic liver transplantation represents an effective therapeutic option. Conversion to tacrolimus before development of elevated total bilirubin levels showed a significant impact on long-term outcome.

Adolescent↗

Correlation of clinical, magnetic resonance imaging, and cerebrospinal fluid findings in optic neuritis.

We found 42 of 74 patients (57%) with isolated monosymptomatic optic neuritis to have 1 to 20 brain lesions, by magnetic resonance imaging (MRI). All of the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). None of the patients had ever experienced neurologic symptoms prior to the episode of optic neuritis. During 5.6 years of follow-up, 21 patients (28%) developed definite MS on clinical grounds. Sixteen of the 21 converting patients (76%) had abnormal MRIs; the other 5 (24%) had MRIs that were normal initially (when they had optic neuritis only) and when repeated after they had developed clinical MS in 4 of the 5. Of the 53 patients who have not developed clinically definite MS, 26 (49%) have abnormal MRIs and 27 (51%) have normal MRIs. The finding of an abnormal MRI at the time of optic neuritis was significantly related to the subsequent development of MS on clinical grounds, but interpretation of the strength of that relationship must be tempered by the fact that some of the converting patients had normal MRIs and approximately half of the patients who did not develop clinical MS had abnormal MRIs. We found that abnormal IgG levels in the cerebrospinal fluid correlated more strongly than abnormal MRIs with the subsequent development of clinically definite MS.

Adolescent↗

Hepatic angiomyolipoma: two case reports of caudate-based lesions and review of the literature.

Two case reports of hepatic angiomyolipoma, both originating in the caudate lobe, are reported with a review of the literature. The liver is the second most common site of angiomyolipoma, an uncommon benign tumor of mixed mesenchymal origin. It is commonly diagnosed following abdominal pain or as an asymptomatic mass discovered on abdominal ultrasound or computed tomography scan. Of 74 cases reported, the lesions ranged from 0.3 to 36 cm in diameter and are noted between the first and eighth decade, with predominant female predilection. The right lobe is the most common site, with lesions arising in the caudate lobe comprising only five cases. The natural history of the hepatic lesion is unknown. Malignant invasion or metastatic disease has not been documented. Hepatic and renal angiomyolipoma can occur concurrently (13 of 60 cases), although the majority are not biopsy proven. Multicentric hepatic disease occurs. The correlation between tuberous sclerosis and hepatic angiomyolipoma is not confirmed histologically and occurs rarely. These lesions have a characteristic radiographic appearance due to high fat content. Histologically, angiomyolipoma are characterized by an admixture of adipose tissue, blood vessels, and smooth muscle cells. These lesions cannot reliably be differentiated from a malignant lesion based on clinical history, radiologic examination, and/or pathologic interpretation. If clinical suspicion for malignancy is low, then careful observation with serial radiologic follow-up is performed. The treatment for a symptomatic or suspicious lesion is resection, if feasible. Liver transplantation may be considered for large or centrally located lesions not amenable to resection.

Adult↗

Retransplantation for recurrent hepatitis C.

Recurrence of hepatitis C virus (HCV) after orthotopic liver transplant (OLT) may be mild or may lead to progressive liver disease requiring retransplantation (re-OLT). Results of re-OLT for hepatitis C are not well known. We analyzed outcomes in 14 patients retransplanted for recurrent hepatitis C. All had evidence of recurrent hepatitis on multiple biopsies. Polymerase chain reaction (PCR) was performed in blood or tissue samples from 12 patients when recurrence was suspected; all 12 were positive for HCV-RNA. Explants showed chronic hepatitis with bridging necrosis in 3 patients, hepatitis with transition to cirrhosis in 2, hepatitis and cirrhosis in 3, and cirrhosis alone in 2. In 2 patients, in whom immunosuppression had been withheld for 4 to 6 weeks, there was also evidence of chronic rejection. Four died of sepsis perioperatively (median, 32.5 days; range, 9-59); pre-OLT, 3 of 4 had renal failure, and 1 had fever with no obvious source of infection. Ten patients did well early after OLT and were discharged. One patient was readmitted 6 weeks after discharge and died of cytomegalovirus (CMV) infection 127 days after re-OLT. One patient with concomitant vanishing bile duct syndrome, probably due to chronic rejection, developed recurrent hepatitis and died of progressive liver failure 161 days after re-OLT. Eight patients are well at a median of 926 days (range, 315-1930) after re-OLT. Three have evidence of mild recurrent hepatitis on liver biopsy, one is overweight with severe steatosis on biopsy, and four have no evidence of recurrent hepatitis. Retransplantation for hepatitis C should be considered a viable option for patients who develop end-stage hepatic dysfunction secondary to recurrent disease and should be performed before development of infectious complications and renal insufficiency.

Adult↗

Reassessing the role of medical therapy in the management of hepatic vein thrombosis.

Hepatic venous outflow obstruction caused by hepatic vein thrombosis (HVT) is a manifestation of a hypercoagulable state, most commonly a myeloproliferative disorder (MPD). In the past, HVT was thought to have a poor prognosis unless treated surgically with portosystemic shunt or orthotopic liver transplantation (OLT). The aim of this study was to assess whether early diagnosis of the underlying hematologic disorder and institution of appropriate medical therapy have altered outcome. We reviewed the charts of 22 patients with HVT evaluated at our center from January 1986 to January 1995. The median age was 32 years (range, 14 to 59 years). Underlying etiologies were MPD, 13 (polycythemia vera, 8; essential thrombocythemia, 4; undefined, 1); dysfibrinogenemia, 1; anticardiolipin antibody, 1; oral contraceptive use, 3; and idiopathic, 4. All patients had ascites, hepatomegaly, and/or abdominal pain. Two underwent mesocaval shunting, and 1 had a peritoneal-venous shunt. Seven patients, including 1 with a mesocaval shunt, underwent OLT. The median duration of symptoms before transplantation was 6 months (range, 1.5 to 11 months). Six transplant patients are alive on long-term anticoagulation therapy at a mean post-OLT follow-up of 42 months (range, 2 to 77 months), without recurrence. Of 13 patients treated medically, 10 (77%) are alive at a median follow-up of 40 months (range, 17 months to 14 years 8 months), 1 has died, and 2 have been lost to follow-up. In a majority of patients, symptoms improve with prompt treatment of the underlying hematologic disorder, with a favorable long-term prognosis. Patients with decompensated liver disease can successfully undergo OLT with a low risk of recurrence on long-term oral anticoagulation.

Adolescent↗

Low-dose aspirin therapy is associated with few side effects but does not prevent hepatic artery thrombosis in liver transplant recipients.

Hepatic artery thrombosis occurs in 4% to 10% of adult patients and in up to 26% of children undergoing liver transplantation. Aspirin has been used to prevent this complication but may increase procedure-related and gastrointestinal bleeding. The aim of this study was to assess the efficacy and safety of low-dose aspirin in the prophylaxis of hepatic artery thrombosis. The histories of 529 patients who survived liver transplantation between September 1988 and December 1993 were reviewed retrospectively. The routine clinical practice followed until 1992 was to initiate oral aspirin therapy on the first postoperative day (81 mg daily in adults and 40 mg daily in children) as prophylaxis for vascular thrombosis. This was done in 354 patients. Aspirin was not administered to the remaining 175 patients. Hepatic artery thrombosis occurred in 13 patients treated with aspirin (3.7%) and in 7 patients not treated with aspirin (4.0%) (P = .85). Recipient age of younger than 2 years and low donor liver weight were the only factors that predisposed the patients to hepatic artery thrombosis. A total of 1,651 percutaneous liver biopsies were performed in this series, with 1,111 performed in patients treated with aspirin. Significant bleeding after liver biopsy occurred in 12 patients treated with aspirin (1.1%) and in 3 patients not treated with aspirin (0.6%) (P = .29). Gastrointestinal bleeding occurred in 66 patients treated with aspirin (18.9%) and in 23 patients not treated with aspirin (12.8%) (P = .08). Low-dose aspirin therapy is not shown to be effective in preventing hepatic artery thrombosis after liver transplantation. Although aspirin does not produce a statistically significant increase in the risk of bleeding after liver biopsy, there is a trend toward an increased incidence of gastrointestinal bleeding.

Adolescent↗

Assessment of liver allograft function by hyaluronic acid and endothelin levels.

BACKGROUND: Sinusoidal endothelial cells are considered the primary site of preservation-reperfusion injury occurring during cold storage and reperfusion. Hyaluronic acid (HA) and endothelin-1 (ET) are markers of endothelial cell integrity. The aim of this study was to evaluate the possible correlation between these markers and early graft function following liver transplantation. MATERIALS AND METHODS: Blood samples were collected from 85 adult orthotopic liver transplant recipients at the following time points: before surgery, just before reperfusion, first and last 20 cc of caval effluent, 30, 60, and 120 min after reperfusion, and on postoperative day (POD) 1. Levels of both HA and ET were measured by sandwich enzyme-binding assay. HA uptake was also defined for every sample as the ratio of the actual measurement to the value obtained just before reperfusion. RESULTS: Patients with severe liver disease displayed significantly higher pretransplant HA and ET levels compared with those of less advanced illness. Poor early graft function (PEGF) was defined as peak enzyme levels on the first three PODs higher than 2500 U/L and prothrombin time longer than 16 s on POD 2. Patients with PEGF (n = 9) showed significantly lower HA uptake than patients with good graft function (n = 76) at 60 and 120 min after reperfusion. There was also a significant difference in the average uptake values measured in the last 20 cc of caval effluent between the two groups. We could not find any difference in ET levels between these two groups. CONCLUSIONS: Perioperative HA uptake measurement may be an additional marker to evaluate early graft function.

Adult↗

Selective modulation of T cell memory markers CD62L and CD44 on murine draining lymph node cells following allergen and irritant treatment.

Naive and activated T cells are known to express different adhesion molecules and are thought to exhibit different migratory patterns that result from their expression of discrete adhesion molecules. Two adhesion molecules that have been associated with differentiating naive and activated/memory T cells are CD62L (L-selectin) and CD44 (H-CAM). It has been demonstrated previously that naive T cells express a CD62LhiCD44lo phenotype, whereas memory T cells exhibit a CD62LloCD44hi phenotype. The purpose of the present investigation was to determine whether chemical allergens, in contrast to irritants, would induce a CD62LloCD44hi phenotype on CD4 and/or CD8 T cells isolated from draining lymph nodes (DLN) of treated mice. Mice were treated on the ears for 3 consecutive days with concentrations of allergens or irritants which caused an increase in the number of DLN cells. The DLN were excised 72 hr following the final chemical treatment and cells prepared for analysis by flow cytometry. In mice treated with the allergen trinitrochlorobenzene an increase in the percentage of CD4+ cells expressing CD62LloCD44(hi) was observed compared to cells isolated from mice treated with the irritant benzalkonium chloride or vehicle treated mice. Mice treated with dintrochlorobenzene had an increase in the percentage of CD4+ cells expressing CD62LloCD44(hi) that was dose dependent and peaked at 72 hr following the final allergen treatment. Concomitant with changes on CD4+ cells, increases in the percentage of CD8+ cells expressing CD62LloCD44hi were observed with allergens, but not with irritants. Increases in the percentage of CD4+ and CD8+ cells expressing CD62LloCD44(hi) were observed with other allergens including oxazolone and alpha-hexylcinnamaldehyde, but not the irritant sodium lauryl sulfate. These data demonstrate that allergens, but not irritants, cause a selective and reproducible increase in the percentage of CD4+ and CD8+ cells expressing the T cell activation/memory phenotype CD62LloCD44hi. Analysis of T cell activation/memory markers may be useful in differentiating allergen and irritant responses in the draining lymph nodes of chemically treated mice.

Allergens↗

The death rate of Ostertagia circumcincta and Trichostrongylus colubriformis in lactating ewes: implications for anthelmintic resistance.

Lactating adult Romney ewes were infected, 4 weeks post-lambing, with benzimidazole (bz) resistant strains of Ostertagia circumcincta and Trichostrongylus colubriformis. Commencing 4 weeks after the initial infection the ewes were subjected to challenge 3 times weekly with 5000 L3 of bz-susceptible strains of both parasite species. At weekly intervals over the following 6 weeks, groups of ewes were drenched with a bz anthelmintic (oxfendazole) to remove bz-susceptible parasites and slaughtered to determine adult worm burdens of the bz-resistant parasites. The O. circumcincta infection declined exponentially with a mean daily death rate of 10.6% day-1 and no worms were recovered after 4 weeks or more of challenge. The T. colubriformis infection did not decline significantly over the 6 weeks of continuous challenge, indicating that the death rate could not be distinguished from zero. The upper 95% confidence limit for the death rate of T. colubriformis was 4.9%. The implications of these death rates on selection for drug resistance following ewe drenching during the post-partum period are discussed with selection pressure likely to be greater for T. colubriformis than for O. circumcincta.

Animals↗

Operator interactions by the Bacillus subtilis arginine repressor/activator, AhrC: novel positioning and DNA-mediated assembly of a transcriptional activator at catabolic sites.

We have previously reported the initial characterization of a catabolic operator site (O[rocA]) for the Bacillus subtilis arginine repressor/activator protein AhrC. Here, we present the characterization by gel retardation and DNase I footprinting of both O(rocA) and a second catabolic operator site, O(rocD). Both operator sites encompass a single recognition site, an ARG box, located immediately upstream of the transcriptional start points, a unique positioning for a transcriptional activator protein. Although there is considerable sequence homology between the two catabolic operator sites, they vary significantly, around twofold, in their apparent affinities for the protein (K'd approximately 90 nM for O[rocA] and approximtaely 190nM for O[rocD]). This difference may result from the lower match to the ARG box consensus of the O(rocD) site. Both catabolic operators show evidence for co-operative binding with respect to protein concentration. Determination of the sequences of two AhrC catabolic operator sites, in combination with the three such biosynthetic sites, has allowed the derivation of an improved B. subtilis ARG box consensus sequence, CATGAATAAAAATg/tCAAg/t. This is not identical to the Escherichia coli consensus operator for the AhrC homologue, ArgR, which may explain the only partial cross-functioning of these proteins in vivo. The O(rocA) site is adjacent to a sharp, stable bend located 5' to the catabolic operator. Circular permutation analysis has been used to determine the relative angle of bend (approximately 50 degrees), its location and the effect of adding magnesium ions and/or AhrC protein. Protein binding increases the relative bend angle to approximately 85 degrees. Bending is shown to be associated with a number of A-tracts in the upstream sequence. However, altering the phasing of the A-tracts has little effect on the affinity for AhrC. Truncation and competition experiments have been used to investigate the possible role of sequences flanking the operator on affinity. Very surprisingly, the affinity of the O(rocA) site appears to increase in the presence of excess, specific competitor fragment, i.e. the system shows anti-competitive effects. Competition is restored at high molar excesses of specific fragment over the protein. We propose a novel model for the assembly of a higher affinity form of AhrC at operator sites that is consistent with both the apparent co-operativity of binding and the anti-competitive effects. These data suggest that the molecular interactions occurring between the prokaryotic arginine-regulatory proteins and their operators may be more complex than is generally appreciated.

Arginine↗

Deoxyribonucleic acid ploidy enhances the cytological prediction of recurrent transitional cell carcinoma of the bladder.

PURPOSE: We determined whether deoxyribonucleic acid (DNA) ploidy analysis by image analysis cytometry enhances the cytological diagnosis of recurrent transitional cell carcinoma of the bladder. MATERIALS AND METHODS: A retrospective study was performed during a 5-year period to evaluate the cytological diagnosis and DNA ploidy analysis of 469 patients with previously diagnosed superficial transitional cell carcinoma. Cytological and DNA ploidy analysis was performed on 1,034 urine and bladder wash specimens, and the patients were monitored with cystoscopy and biopsies as clinically indicated. Cytology results were classified as normal, atypical, dysplastic or cancerous, and DNA ploidy was defined as normal if the diploid index was 1.2 or less, the S phase+G2M fraction was less than 21% or if there were 3% or less hyperploid cells, or abnormal if there was an increased S phase+G2M fraction, an aneuploid peak on the histogram or tetraploidy or hyperploidy was present. RESULTS: The majority of patients (85 of 88, 97%) with a cytological diagnosis of cancer had an abnormal DNA ploidy, and in 60 of 85 of these patients (71%) recurrence was diagnosed within 6 months. Only 5 of 284 specimens (2%) with normal cytology had abnormal DNA ploidy and 1 of these 5 (20%) heralded transitional cell carcinoma recurrence. However, in 145 patients with atypical cytological findings 29 (20%) with abnormal DNA ploidy had a recurrence, compared to 20 of 391 (5%) with normal DNA ploidy (p < 0.0001). Similarly, in 101 patients with dysplastic cytological findings 39 (39%) with abnormal DNA ploidy had transitional cell carcinoma recurrence compared to 4 of 25 with normal ploidy (p = 0.033). CONCLUSIONS: Abnormal DNA ploidy determined by image analysis significantly enhances the detection of bladder tumor recurrence in patients with atypical or dysplastic cytology but not in those with normal cytology or frank carcinoma on cytological findings.

Adult↗

Effluent levels of thrombomodulin predict early graft function in clinical liver transplantation.

Thrombomodulin is a surface protein on vascular endothelial cells that serves as a binding site for thrombin and plays an important role as an anticoagulant factor. We correlated plasma thrombomodulin levels with early graft function after liver transplant in 58 recipients. Blood samples were collected at the following time points: before surgery, just before reperfusion, 30, 60, 120 min after reperfusion, and post-operative day 1. The first and last 20 cc of caval effluent were also collected. Plasma thrombomodulin levels were measured by a sandwich enzyme-binding assay in the blood samples; tissue expression was determined by immunohistochemistry. Poor early graft function was defined as peak aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2500 U/l during the first 3 post-operative days and prothrombin time >16 s on post-operative day 2. Thrombomodulin levels in the first 20 cc of caval effluent ranged from 1.33 to 91 FU/ml and showed a significant positive correlation with ischemic time, intra-operative blood transfusion requirement, and early graft function. In grafts with high effluent thrombomodulin (>20 FU/ml, n=12), the incidence of poor early graft function and primary nonfunction was 66.7% and 25.0%, respectively; in grafts with low effluent thrombomodulin (<20 FU/ml, n=46), graft function was not impaired. By immunohistochemistry, thrombomodulin was detected in large vessels of every donor liver. Sinusoidal cells, however, showed positive staining only in livers with poor early graft function. Effluent thrombomodulin levels reflect the extent of preservation injury and might be a useful marker for predicting graft function after liver transplantation.

Adult↗

The lived experience of relapsing multiple sclerosis: a phenomenological study.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that is well known but poorly understood by the medical and nursing community as well as the general public. The myriad neurological symptoms result from an autoimmune attack on the insulating myelin of the nerves which cause a disruption of nerve impulses in the brain and spinal cord. MS most often affects young adults and may be broadly categorized as either a relapsing or a chronic progressive disease course. Until recently, research has focused on the progressive form of MS though it accounts for less than half of the cases. People who are diagnosed with relapsing MS are cared for in the same way as those with the debilitating progressive form. Relapsing MS affects individuals periodically with exacerbations from which they often recover completely, whereas chronic MS results in a progressive functional deterioration. People with relapsing MS are not given a realistic prediction of what to expect in their future nor are they left with any hope for normalcy in their lives. The purpose of this study was to provide a description of the lived experience of people who have relapsing MS. To answer the question, "What is the lived experience of people with relapsing multiple sclerosis?" this study was conducted using hermeneutic phenomenology. A sample of 10 patients with relapsing MS was interviewed over a seven month period. Interviews began with the question, "What is it like for you living with multiple sclerosis?" The interviews were tape recorded and transcribed verbatim. Data were analyzed using the Colaizzi method of hermeneutic phenomenology. Themes that emerged from the data were combined and abstracted into twelve dimensions that described the lived experience of people with relapsing MS. Participants' social networks served as either positive or negative influences in their adjustment process and led to conflicts for some. Coping with recurrent symptoms and social situations related to the MS was facilitated by maintaining control and a sense of hope. Most expressed a sense of relief with diagnosis because they had secretly feared their symptoms were a result of a fatal illness or psychological instability. Uncertainty surfaced as a major theme due to the unpredictability of relapsing MS. Participants also experienced fear and loss. Getting to know MS was an integral part of the experience often made difficult by concealment of facts. Participants experienced acts of revealing and concealing throughout their illness process and often attempted to conceal their illness from a society that did not understand. Nurses should be aware of the relapsing MS experience when providing care and teaching to patients and families with MS. The nurse should also reflect on the importance of maintaining hope and open communication.

Activities of Daily Living↗

Adult presentation of Caroli's syndrome treated with orthotopic liver transplantation.

When Caroli's disease, defined as a congenital dilation and ectasia of segmental intrahepatic bile ducts in the absence of other histological abnormalities, is associated with periportal fibrosis, it is termed Caroli's syndrome. We describe the case of a 35-yr-old woman with Caroli's syndrome without clinical manifestation of portal hypertension despite diffuse involvement of the liver who was successfully treated with orthotopic liver transplantation after recurrent nearly fatal episodes of cholangitis.

Adult↗