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Interferon monotherapy for chronic hepatitis C virus (HCV) infection leads to sustained viral eradication in a minority of patients. However, in selected groups of patients, sustained virological response is observed in as many as 50% of patients. High initial interferon dose (induction therapy) has been reported to increase the initial response rate. We have studied the effect of interferon induction therapy in patients infected with HCV genotype 2b/3a, low viral load and no cirrhosis.A total of 71 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis, with genotype 2b or 3a, viral loador = 3 million copies per ml and no cirrhosis were randomized to receive either standard interferon therapy (3 MIU interferon-alpha-2a thrice weekly) for 26 weeks or 6 MIU interferon-alpha-2a daily for 4 weeks (induction group) followed by the standard dose (3 MIU thrice weekly) for 22 weeks. Those with persistent HCV RNA at 4 weeks stopped treatment. Patients were monitored for HCV RNA during and following treatment, and data were interpreted according to intention-to-treat analysis.Viral clearance occurred more rapidly (after 4 weeks) in the induction group (33/36 = 92%) compared to the standard interferon group (21/35 = 60%) (P = 0.01). Among the initial responders, 23/33 (induction group) compared to 16/21 (standard group) were persistently HCV RNA-negative at the end of treatment. At 52 weeks (6 months' follow-up), 22/36 (61%) (induction group) compared to 10/35 (29%) (standard group) were HCV RNA-negative. Among initial responders, 22/33 (induction group) and 10/21 (standard group) achieved a sustained virological response. Among end-of-treatment responders, 22/24 (induction group) and 10/16 (standard group) were HCV RNA-negative at 6 months' follow-up (P = 0.013).In patients infected with HCV genotype 2b/3a, low viral load and without cirrhosis, IFN induction therapy increases the initial viral clearance and reduces the risk of relapse in end-of-treatment responders. A sustained virological response was achieved in 61% of the patients receiving IFN induction therapy.

BACKGROUND: Hepatitis G virus (HGV) or GBV-C is frequently detected in patients co-infected with hepatitis C virus (HCV). This study investigated host and virologic factors influencing the response to HGV/GBV-C to alpha-interferon treatment. METHODS: HGV/GBV-C was detected and quantified by nested polymerase chain reaction. The influence of variables such as liver biopsy appearance, liver function abnormalities, and response of HCV to interferon treatment was monitored. RESULTS: Fourteen of the 25 HGV/GBV-C-infected patients treated with interferon (3-6 MIU three times a week for 6 months) became non-viraemic during treatment, although all relapsed after treatment withdrawal at 6 months, with no net change in virus load between 0 and 12 months. CONCLUSIONS: Predictive factors for clearance of HGV/GBV-C viraemia by interferon were pre-treatment severity of liver disease (median Knodell score of 4, compared with 7 for non-responders; P = 0.030) and alanine aminotransferase levels (median, 114, 182 for non-responders; P = 0.039). Clearance was associated with the treatment response of HCV. Nine of 13 who cleared HGV/GBV-C also cleared HCV, compared with 3 of 11 HGV/GBV-C non-responders; P = 0.05). The shared susceptibility of HGV/GBV-C and HCV to interferon treatment suggests a link between the mechanism of clearance of the two viruses.

Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p < 0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

Background: Data on the incidence of acute pancreatitis in Norway are sparse. Danish studies have shown incidence rates increasing to about 35/100,000 (26–65% alcohol-induced), higher than found in American and British studies. Methods: We have prospectively registered all cases of acute pancreatitis during 1 year in the county of Buskerud, with a population of 224,000. Results: The incidence of acute pancreatitis was 41.5 per 100,000. The median age of the patients was 63 years (range, 21–96 years). The main etiologic factors were gallstone disease (51%) and alcohol abuse (15%), whereas 10% of the cases were classified as idiopathic. Pseudocysts or abscesses developed in 8.8%. The mortality was 6.5%. Conclusion: The incidence of acute pancreatitis in this population is comparable to what has been found elsewhere in Scandinavia, but the relative frequency of alcoholic pancreatitis is substantially less.

PURPOSE: To report a rare tumour of the eye, and to illustrate the importance of performing a fine-needle aspiration biopsy. CASE REPORT: An 80-year-old woman suffering from general malaise, dyspnea and abdominal pain was found to have multiple lung metastases, a large tumour in the upper part of the mediastinum, and a large orange-brown tumour (19 x 15 x 11 mm) situated nasally in the left eye. Fine-needle aspiration biopsy of the uveal tumour and of the goitre was performed. Cytological examination from the two sites disclosed cells compatible with a follicular thyroid carcinoma of oxyfil cell-type. RESULTS: The patient underwent a total thyroidectomy and has so far had 2 series of 131I therapy. Additionally, the eye tumour was treated locally with a 125I plaque, and three months later the tumour thickness had decreased from 11.0 to 6.4 mm. Best-corrected visual acuity is still unchanged. The patient's general state improved as her dyspnea decreased significantly. CONCLUSION: The treatment has improved the patient's quality of life, and probably prolonged her life expectancy. Fine-needle aspiration biopsy was necessary to establish the diagnosis.

Among 116 patients with biopsy-confirmed chronic hepatitis C (Riba 2 or Riba 3 positive) in a multicenter study in southern Norway on interferon, we determined hepatitis C virus genotype by restriction fragment length polymorphism (RFLP) of the 5' NCR. The RFLP method was supplemented by and compared with a serological typing method based on the detection of type-specific antibody to peptide from the NS-4 region. A total of 102/106 (96%) patient sera showed detectable type-specific antibody to NS-4 peptides and corresponded in all cases, except two, to the genotype detected by polymerase chain reaction. Combining the results from RFLP genotyping and serotyping, genotype 1 was found in 40 (35%) (27 with 1a and 10 with 1b, 3 subtypes not determined), genotype 2 in 15 (13%) (subtype 2b in 14 and 1 subtype not determined), and genotype 3 in 58 (50%) of patients. The low mean age of the patients (34 years), the low prevalence of cirrhosis (3.5%), the short duration of the disease, and a high prevalence of intravenous-drug abusers may account for the low prevalence of infection with genotype 1b (9%). The epidemiological features of hepatitis C patients are markedly different from patient groups described in southern Europe in terms of risk factors, age, and genotype distribution.

Purpose: To evaluate the visual and anatomic results of radiation therapy in ten patients with choroidal haemangiomas. Methods: Nine patients with circumscribed choroidal haemangiomas and one with diffuse choroidal haemangioma have been reviewed retrospectively. They were treated by lens-sparing external beam radiation therapy (20‐24 Gy) (9 eyes) and plaque brachytherapy (25 Gy) (1 eye), respectively. Results: The visual acuity improved by two lines or more in 8 of 10 eyes. No eyes showed deterioration of visual acuity. In all cases the retinal detachment showed complete resolution. A regression in tumour thickness was observed in all cases, and a reduction of anisometropia in cases with submacular infiltration by the tumour. During follow-up (0.4‐8.8 years) there were no signs of radiation cataract, retinopathy or optic neuropathy. Conclusions: External beam radiation (20‐25 Gy) is a reasonable alternative for treatment of symptomatic choroidal haemangiomas.

Purpose: To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), a rare paraneoplastic syndrome causing visual loss in patients with systemic carcinoma. Results: A 70-year-old woman developed visual symptoms 13 months after surgery and local irradiation therapy for uterine cancer. Following bilateral external beam irradiation supplemented with subsequent drainage of subretinal fluid in the left eye, the visual acuity improved from 0.01 to 0.15 in this eye only. The visual acuity remained at this level until she died 4 1/4 years after the onset of eye symptoms. Conclusion: This is the fourth case that survived longer than 24 months after the onset of visual symptoms of the 22 previously reported cases with BDUMP. It demonstrates that radiotherapy may have a vision-preserving effect in this group of patients. The patient also developed two different paraneoplastic phenomena ‐ a nephrotic syndrome before and BDUMP after treatment for uterine cancer.

Mastocytosis includes a range of disorders characterised by accumulation of tissue mast cells. These are derived from pluripotent haematopoietic stem cells. Recent research has improved the understanding of the mastocytosis pathogenesis. Organ manifestations and symptoms are highly variable.Two cases of systemic mast cell disease are presented.One patient had urticaria pigmentosa and systemic mast cell disease; the other had systemic mast cell disease and myelodysplastic changes in the bone marrow.The two cases illustrate different manifestations and different prognosis for various types of mastocytosis.

Preliminary results from combination therapy with interferon-alpha and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising, with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-responders or relapsers after IFN treatment.In a multicenter study we randomized 53 HCV RNA-positive patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis C, and all were recruited from a previous IFN study: 26 were previous non-responders and 27 responders with relapse. Group A received interferon-alpha2a, 4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200 mg/day, in combination with the same dose of interferon-alpha2a for 6 months. Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%), type 2 in 3 (6%), and type 3 in 26 (49%).Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of 26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In previous relapse patients sustained loss of viremia was more frequent in genotype 3 (50%) than in genotype 1 (11%) patients (P = 0.022).In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often (50%) than type-patients (11%). Previous IFN responders with relapse responded better than previous non-responders.

A project called Better cancer care in Buskerud was started in 1991 in the county of Buskerud, in Norway. The main objective was to improve the out-patient services for cancer patients at the central hospital. In this article we describe the activities at the out-patient clinic during the period 1991-1993. The clinic was staffed by two oncologists and two cancer nurses. A total of 8060 consultations were held with patients during the period. Breast cancer patients comprised the largest group (30%), followed by patients with gastrointestinal cancer (24%) or malignant lymphoma (13%). The hospital's Department of Surgery was particularly relieved to hand over the administration of chemotherapy. The number of patients who received radiotherapy at the nearest cancer centre did not increase, however, during the period. We conclude that the project in Buskerud was a success, and that most of the objectives were achieved.

Patients with chronic hepatitis C respond differently when treated with interferon. We randomized 116 patients with chronic hepatitis C in order to compare two dosage regimens of recombinant interferon alpha 2a:3 MIU x 3 per week for 6 months (arm A) or 6 MIU x 3 per week for 3 months and then 3 MIU x 3 per week for 3 months (arm B). There were no significant differences concerning outcome between the two dose regimens: sustained clearance of HCV viremia 6 months after the end of treatment was obtained in 12/59 (20%) in group A compared with 18/57 (32%) in group B (p = 0.24). In patients with genotype 1a, 4/31 (13%), in genotype 1b, none of 9 (0%), 9/15 (60%) in genotype 2, and 17/58 (29%) in genotype 3, showed sustained clearance of HCV viremia 6 months after the end of treatment (p = 0.002). In a stepwise logistic regression analysis, only pretreatment viral load (p = 0.0001), genotype (p = 0.001) and age (p = 0.04) were identified as independent predictors of sustained clearance of HCV viremia. Liver histology as assessed by Knodell index was significantly improved in patients with sustained HCV RNA response 6 months after the end of treatment (5.2 +/- 2.2 vs 2.6 +/- 2.2, p0.001), but not in responders with relapse or in non-responders. In conclusion, stepwise logistic regression analysis showed that viral load, HCV genotype and age were the only independent predictors for sustained HCV RNA response.

Hepatitis C virus (HCV) has been a major cause of post transfusion hepatitis, and is still an important cause of chronic liver disease throughout the world. How to treat patients with chronic HCV infection has been brought into focus in recent years, and a substantial amount of data has been obtained about the development of hepatitis C with and without treatment. This survey considers the diagnosis of hepatitis C, and present treatment modalities and their potential. The patients most likely to respond to treatment are described, and the authors finally discuss why treatment of hepatitis C still should take place in controlled studies.

Among 116 patients with biopsy-confirmed chronic hepatitis C (Riba 2 or Riba 3 positive) in a multicenter study in southern Norway on interferon, we determined hepatitis C virus genotype by restriction fragment length polymorphism (RFLP) of the 5' NCR. The RFLP method was supplemented by and compared with a serological typing method based on the detection of type-specific antibody to peptide from the NS-4 region. A total of 102/106 (96%) patient sera showed detectable type-specific antibody to NS-4 peptides and corresponded in all cases, except two, to the genotype detected by polymerase chain reaction. Combining the results from RFLP genotyping and serotyping, genotype 1 was found in 40 (35%) (27 with 1a and 10 with 1b, 3 subtypes not determined), genotype 2 in 15 (13%) (subtype 2b in 14 and 1 subtype not determined), and genotype 3 in 58 (50%) of patients. The low mean age of the patients (34 years), the low prevalence of cirrhosis (3.5%), the short duration of the disease, and a high prevalence of intravenous-drug abusers may account for the low prevalence of infection with genotype 1b (9%). The epidemiological features of hepatitis C patients are markedly different from patient groups described in southern Europe in terms of risk factors, age, and genotype distribution.

To determine which chromosomes and chromosomal regions contain putative tumor suppressor genes important for human epithelial ovarian cancer, we performed loss of heterozygosity (LOH) studies on 37 primary epithelial ovarian tumors. Using 70 polymorphic markers, we examined all chromosome arms (excluding acrocentric arms) on all specimens. Our findings show a high frequency of LOH for the following chromosome arms: 5q (43%); 6p (62%); 6q (57%); 7p (36%); 8p (40%); 9q (54%); 13q (56%); 14q (47%); 15q (36%); 17p (81%); 17q (76%); 18q (43%); 21q (36%); and 22q (71%). When separated into low and high grade tumors, there were statistically significant differences of LOH for the following chromosome arms: 6p (29% versus 70%); 13q (0% versus 72%); 17p (33% versus 90%); and 17q (29% versus 87%). No statistically significant difference was found between different histological subtypes. The average fractional allelic loss for low grade tumors was 0.17 versus 0.40 for high grade and 0.35 for all tumors. In an effort to more specifically localize common regions of molecular genetic deletion, we examined the following chromosomes in greater detail: chromosome 13 (5 markers); chromosome 17 (8 markers); and chromosome 6 (8 polymorphic markers). No tumor showed deletion of only a portion of chromosome 13. When any informative marker for chromosome 13 showed loss, all markers showed loss. Similarly, the tumors of most patients demonstrated LOH of all informative markers that map to chromosome 17; however, regional deletion of 17p markers was observed in 3 tumors. Twelve tumors demonstrated regional deletions of portions of chromosome 6. These tumors suggest that at least 2 regions of chromosome 6 are important for ovarian epithelial carcinogenesis. One region appears to be on distal 6q and a second region is near the centromere of chromosome 6 proximal to the HLA locus.

10503 Background: The IGF1 system has been implicated in sarcoma development and inhibition of IGF1R function has been shown to induce clinical responses in select sarcomas. Methods: Objectives included response rate (RR) and progression-free survival (PFS) to R1507 in patients with recurrent or refractory Ewing's (ES, 2 cohorts- primary refractory vs. others) osteo (OS), synovial (SS), rhabdomyosarcoma (RMS), and other sarcomas. Eligibility included recurrent/refractory measurable disease, age ≥ 12 yrs, life expectancy ≥ 6 weeks, Karnofsky PS ≥ 70, adequate renal, hepatic and bone marrow function. R1507 was administered i.v. at 9 mg/kg over one hour weekly. Response was assessed by WHO criteria every 6 wks X 4 and every 12 wks thereafter. A two-stage design (Green and Dahlberg) was used. The endpoint for the primary refractory ES cohort was PFS at week 18 (planned n=65). RR was the primary endpoint for the remaining cohorts (planned n=240). Results: From 12/07–12/08, 203 eligible patients from 29 centers across the US, Europe and Australia were enrolled. Age ranged from 12–85 yrs (median=27 yrs) and 126 were male. Verified histologic subtypes were ES (n=71), OS (n=43), RMS (n=28), SS (n=25), and others (n=25). 15 severe adverse events were reported in 9 patients, the most common being fatigue (n=2), thrombocytopenia (n=2), dehydration (n=2), and hyperglycemia (n=2). Clinically significant activity has been observed in ES, RMS and OS with several dramatic responses seen in ES and RMS. Independent radiologic review is currently ongoing and updated data will be presented. Conclusions: The rapid accrual amongst many centers in diverse geographical locations demonstrates the feasibility of collaborative research in sarcomas. R1507 is well tolerated and a promising new agent for the treatment of various sarcomas. SARC and Roche are collaborating in additional clinical trials to better define the role of R1507 in the treatment of selected sarcomas. [Table: see text]

Chlamydia pneumonia is now recognized as a species of the Chlamydia genus distinct from C psittaci and C trachomatis species. It is a common cause of pneumonia and other acute respiratory tract infections. We describe a patient with erythema nodosum secondary to infection with C pneumoniae. Since this agent usually causes a mild illness, with no distinct clinical findings, we recommend adding serological tests for C pneumoniae to other relevant laboratory investigations in patients with erythema nodosum.

During a three-year period 77 patients (43 men and 34 women, aged 21-82 years, mean age 62.0 years) were treated with mechanical ventilation in a medical intensive care unit. Three patients were treated twice. The most common diagnoses (in decreasing order of frequency) were acute exacerbation of chronic obstructive pulmonary disease, acute myocardial infarction, cerebrovascular trauma and chronic ischemic cardiac disease. The mean duration of ventilation was 6.4 days. 41 patients (51.3%) survived--80% of whom could be discharged to their home. Patients with chronic pulmonary disease showed the highest survival rate, those with cerebrovascular disease the lowest, with the cardiac patients in-between. It is calculated that it cost NOK 207,000 to treat each patient who survived.

The distal ileum, the segment most frequently affected by small intestinal disease, may be difficult to visualize by conventional x-ray techniques. In recent years various methods have been described for retrograde ileography during or after colonoscopy. However, these methods require special equipment and may be difficult to perform in practice. We have therefore tried out a somewhat modified technique. Patients with suspected distal ileal disease are examined on a fluoroscopy table at the x-ray department. When necessary, biopsies are taken during the introduction of the scope. With the tip of the colonoscope in the terminal ileum (or coecum) a catheter is introduced through the biopsy channel into the distal ileum. Water-soluble contrast (Mixobar) is then instilled under fluoroscopic control and films are taken in the supine, oblique and prone positions. Owing to gas already present in the ileum a double contrast effect is obtained. The ileography is completed in 5-10 minutes and entails no additional discomfort for the patient. The technique is easy to learn and requires no special equipment. It does not obviate the need for conventional small bowel enema, but may be a valuable supplement to this examination when distal ileal pathology is suspected.

Hepatic abscesses represent the most common non-enteric complication of amebic infection, and occur in 1-25% of the patients. We describe two male patients, 44 and 47 years old, who presented hepatic abscesses after travelling in endemic regions. We stress the importance of accurate and early diagnosis. Ultrasonography and computed tomography were of major importance as diagnostic tools.

Colloid osmotic pressure in plasma (IIp) and in subcutaneous interstitial fluid (IIi) (wick technique), plasma volume (PV) and interstitial fluid volume (IFV) were measured in 12 patients with hepatic cirrhosis and fluid retention. The value of IIp (mean +/- SD) was 21.4 +/- 4.2 mmHg (28.6 +/- 3.4 mmHg in normal subjects (p less than 0.01)), mean IIi was 8.6 +/- 2.2 mmHg (15.8 +/- 2.7 mmHg in normal subjects (p less than 0.01)) and mean transcapillary colloid osmotic gradient (IIp-IIi) was 12.7 +/- 3.8 mmHg compared to 12.8 +/- 2.7 mmHg in normal subjects (p greater than 0.1). Mean PV was increased by 21% compared to normal values (p less than 0.01) and IFV increased by 43% (p less than 0.01). The study demonstrates that reduction in IIp in hepatic cirrhosis is accompanied by a decrease of IIi in subcutaneous tissue resulting in unchanged transcapillary colloid osmotic gradient. The reduction in IIi can partly be explained by simple dilution and partly by a decrease in interstitial protein mass. The wash-down of interstitial proteins in non-splanchnic tissues reduces the tendency to oedema and hypovolaemia.

Incorporation of 14C-acetate into digitonin-precipitable sterols and of 3H-leucine into proteins was examined in per- or post-operative liver biopsies from morbidly obese patients subjected to either gastric or jejunoileal bypass operations. Biopsies obtained from non-obese patients without liver disease served as controls. Incorporation of precursors into sterols and proteins in peroperative biopsies from obese patients (mean weight, 131 kg) did not differ from that of control subjects (mean weight, 64 kg). However, biopsies obtained from eight patients 11-53 months after jejunoileal bypass (mean weight loss, 32% of initial weight) showed an eightfold increased 14C incorporation into sterols, whereas incorporation of 3H-leucine into proteins did not differ from that of the control group. The results in postoperative biopsies (3-12 months) from 9 patients subjected to gastric bypass (mean weight loss, 25% of initial weight) did not differ significantly from those in 15 controls. The markedly stimulated biosynthesis of sterols in patients with jejunoileal bypass might reflect increased faecal excretion of cholesterol and bile acids, causing reduced feedback control mediated by bile acids and cholesterol.

A 46 year old woman had a history of chronic relapsing pancreatitis of 17 years duration and a 1 year history of symptoms pertaining to the CNS: sleepiness, tiredness, giddiness, reduced memory and ability to concentrate, aphasia and a pressure in the head, nausea, and vomiting. The patient became comatous during two prolonged attacks which were preceded by abdominal pain and were accompanied by focal convulsions. During the final stage, but in the absence of coma, markedly increased CSF and plasma amino acid levels were found, mainly of citrulline and arginine (6 to 19 times mean control level), but also more moderate increase of other amino acid levels.

Two hundred patients with different liver diseases were observed during a period of 6-8 years. The diagnosis at the first hospitalization was based on morphological criteria (and, in some cases, additional clinical information). In 162 of the cases an initial 'specific' diagnosis could be made. By the time of the follow-up study the diagnosis was confirmed in 73% of them. In 22 of 38 patients who were initially unclassifiable, the diagnosis was made definite by the follow-up study. Eighty-five patients were hospitalized for re-examination 6-8 years after the initial study. Several of the liver diseases initially had quite typical patterns of clinical chemical data. Allocation by discriminant analysis was therefore in good agreement with the morphological classification. The follow-up study showed that several patients with initially atypical patterns of clinical chemical results had their diagnosis changed. In 35 patients with the final diagnosis of chronic active hepatitis (CAH) or primary biliary cirrhosis (PBC), laboratory data from the last hospitalization were used for discriminant analysis with teaching data from the initial study. Ninety-seven per cent were correctly allocated, and we conclude that these patients retain recognizable patterns of laboratory results for several years, even when given immunosuppressive treatment. The potential clinical usefulness of discriminant analysis of laboratory data for differential diagnosis was evaluated by a prospective study of 65 patients with the morphological diagnosis of CAH or PBC. Correspondence with the morphological classification system was found in almost 90% of the cases.

Sequential quantitative determinations of lipoprotein-X (LP-X), measurements of plasma lipids, initial rate of cholesterol esterification, and liver function tests were performed after experimental cholestasis in 6 dogs. In 3 animals ligation and transsection of the common bile duct were combined with cholecystectomy. In 2 other dogs a similar operation, but without removal of the gallbladder, was carried out. In the bile-duct-obstructed and cholecystectomized dogs, LP-X appeared 11-21 hours after operation, and in dogs with preserved gallbladder 32 hours after operation. During the observation periods (6-41 days), the LP-X levels were much higher in the cholecystectomized dogs than in the ones with preserved gallbladders. In most of the bile-duct-obstructed dogs the curves of LP-X concentrations in plasma were bi-phasic. The first peak after 1 to 5 days was followed by a fall, and 10 to 14 days after operation another rise was observed. Concomitant with the changes in the level of LP-X, fluctuations in the levels of phospholipids and free cholesterol occurred. An inverse relationship between LP-X and the activity of lechithin: cholesterol acyltransferase was found.

The pharmacokinetics and protein-binding of orally administered prednisolone have been studied in seven patients with chronic liver disease and portosystemic shunts. The peak prednisolone serum concentration and the time of peak prednisolone concentration were similar to those found in normal subjects, indicating that there is no clinically significant first-pass metabolism of prednisolone. The elimination half-time and the extent of bioavailability of total prednisolone tended to be lower in the patients, and the extent of free, unbound prednisolone higher, but the differences were not statistically significant. The patients had a significantly lower serum protein-binding of prednisolone than the controls. Despite the decreased protein-binding in the patients, however, the results indicate that changes occur in the pharmacokinetics of prednisolone that tend to reduce the bioavailability of free, biologically active prednisolone towards that seen in healthy subjects. Reduction of the prednisolone dose is therefore not indicated in patients with portosystemic shunt and chronic liver disease, even in the presence of hypoalbuminemia.

Four patients with Felty's syndrome developed massive upper gastrointestinal bleeding due to oesophageal varices. The underlying hepatic pathology in all 4 was nodular regenerative hyperplasia. This appears to be a difficult histological diagnosis to make, having been initially reported as normal on percutaneous biopsy or as fibrosis or cirrhosis on wedge biopsy. This series brings the total number of cases reported in the English literature of this association to 12, suggesting a definite symptom complex. The portal hypertension seems to be due to a combination of increased splenic blood flow and postsinusoidal resistance. The clinical importance of this syndrome is that the appropriate therapy for bleeding oesophageal varices appears to be shunt procedure such as a splenorenal shunt with splenectomy, which should be well tolerated.

Incorporation of 14C-acetate into 3-beta-OH sterols and of 3H-leucine into proteins was examined in liver biopsies from patients with liver disorders. Biopsies obtained from patients in whom no liver disease was found served as controls. Reduced 14C-acetate incorporation into sterols was found in biopsies from patients with chronic active hepatitis and primary biliary cirrhosis. Stimulated incorporation of 3H-leucine into proteins was demonstrated in patients with alcoholic liver cirrhosis and in patients with ulcerative colitis associated with liver disease. No correlation could be established between serum proteins and lipids, respectively, on the one hand, and between incorporation of precursors into proteins and sterols, on the other. 'Incorporation parameters' were also inferior to conventional liver tests when used in the differential diagnosis between different liver disorders by discriminant analysis. Our findings may suggest, however, that hepatic sterol synthesis is frequently decreased in patients with chronic active hepatitis and primary biliary cirrhosis.

Hepatic copper content, measured by neutron activation analysis, has been studied in 70 patients during a median observation period of 3 years. In 15 patients with chronic active hepatitis the median hepatic copper content was 39 μg/g dry weight at the start and 28 μg/g dry weight at the end of the observation period, during which the clinical condition was improved in most patients. The hepatic copper content did not change significantly (41 versus 54 μg/g dry weight) in 28 patients with hepatobiliary disorders associated with inflammatory bowel disease. In 27 patients with primary biliary cirrhosis the median hepatic copper concentration was initially 176 μg/g dry weight, and at the follow-up 186 μg/g dry weight. Serum ceruloplasmin was elevated in most of the patients with hepatobiliary disorders associated with inflammatory bowel disease and in all the patients with primary biliary cirrhosis and remained at high levels throughout the observation period. In primary biliary cirrhosis the hepatic copper ...

Two hundred patients with liver disease were re-studied after six to eight years. The initial routine diagnosis (mainly based on morphological criteria) was confirmed in almost 80% of cases of chronic liver disease. In chronic active hepatitis, agreement was found in 86%. An alternative classification based on cluster analysis of clinical chemical results from the first admission was also to a great extent confirmed by the follow-up study. Discriminant analysis of clinical chemical data correctly allocated 94% of patients with alcoholic cirrhosis (who had low haptoglobin and albumin) into groups with different prognosis. Clinical chemical results differed between verified and non-verified cases of primary biliary cirrhosis. By retrospective examination , we found that 15 of 16 patients with this disease or chronic active hepatitis who were initially misclassified by biopsy findings could be correctly diagnosed by discriminant analysis of clinical chemical results.

Four female and five male patients (mean age 26 years) with hyperlipoproteinaemia type II A were treated with an anion exchange gel (Secholex) 9 g/day for 3 months and 15 g/day for 9 months. After these 12 months clofibrate 1.5 g/day was added to the therapy in 6 patients, whereas 2 patients continued with the resin alone for another 6 months, and one was withdrawn from the trial because of pregnancy. During the first year plasma cholesterol decreased averagely 18% from a mean pretreatment value of 461 mg/100 ml. Dosis of 9 g/day seemed to be as efficient as 15 g/day. When clofibrate was added, a further decrease of plasma cholesterol by 6% was observed, and the levels of triglycerides were reduced. Significantly increased concentrations of bile acids and a rise in the glycine/taurine ratio in duodenal aspirate were caused by the resin. On combined treatment the concentration of bile acids decreased to the pretreatment values, whereas the glycine/taurine ratio remained unchanged. During the trial slight transient changes in serum folic acid, fasting insulin, calcium, alkaline phosphatases, and vitamin B 12-absorption occurred. No changes in serum vitamin A, vitamin-K-dependent clotting factors, serum gastrin, gastric acid output, the absorption of glucose and iron, and faecal excretion of fat were observed. Serum insulin 30 and 60 minutes after an oral glucose loading decreased in the patients on combined treatment, whereas the insulin response remained normal in patients taking Secholex alone. Liver function tests and creatinine were unchanged during the trial. Apart from transient abdominal discomfort in two patients, no side-effects were discovered. The patients found the gel palatable.

Nucleotide pyrophosphatase and phosphodiesterase I activities were determined in sera from 126 patients with different types of liver disease and in two additional groups of patients with intra- and extrahepatic cholestasis, respectively. Both activities probably represent the same enzyme, and were positively correlated with alkaline phosphatase, lipoprotein X, and several other tests reflecting cholestasis. Also, we found by discriminant analysis that tests for cholestasis frequently replaced the results of both enzymes. In some groups of liver disease, nucleotide pyrophosphatase and phosphodiesterase I were correlated with the concentrations of prealbumin and albumin. The sensitivity of phosphodiesterase I (and nucleotide phosphatase) is rather low when compared with alkaline phosphatase, and we do not recommend it for use in the clinical routine. Nevertheless, it appears to be of potential value for studies on classification of liver diseases, adding information to a panel of 20 commonly used "liver tests" by appearing in some of the best four test-sets for distinguishing between groups of liver disease by discriminant analysis.

A method for quantitation of the abnormal lipoprotein of cholestasis, LP-X, is described. After incubation of the serum with labelled free cholesterol, LP-X is separated from the normally occurring lipoproteins by electrophoresis in agar. By liquid scintillation counting the percentage of free cholesterol present in LP-X is determined. From the serum level of free cholesterol, the amount of free cholesterol in LP-X is calculated. The composition of lipids and proteins in LP-X has previously been found to be fairly constant, and from its content of free cholesterol the amount of LP-X may be calculated.

Quantitative determination of the abnormal plasma lipoprotein of cholestasis LP-X has been performed in 81 LP-X positive patients with different liver disorders. Great variations in the plasma concentration of LP-X were demonstrated both in the 45 patients with intrahepatic cholestasis (acute hepatitis, toxic hepatitis, primary biliary cirrhosis and cholangitis) and in the 36 patients with extrahepatic cholestasis (extrahepatic biliary obstruction by tumours and choledocholithiasis). The plasma concentratkons of LP-X in the patients with extrahepatic cholestasis (median 158 mg/100 ml) were significantly (psmaller than 0.001) higher than in the patients with intraphepatic cholestasis (median 25 mg/100 ml) was exceeded by 42% of the patients with extrahepatic biliary obstruction, and 33% of the patients with extrahepatic biliary obstruction, had LP-X LEVELS ABOVE 400 MG/100ML. The plasma concentration of LP-X was significantly correlated to the plasma activity of alkaline phosphatases and serum bilirubin, but seemed to be superior to these two parameters in the differentiation between intrahepatic and extrahepatic cholestasis. Plasma levels of LP-X above 400 mg/100 ml are highly indicative of extrahepatic biliary obstruction.

Increased liver copper concentration and raised serum ceruloplasmin were demonstrated in primary biliary cirrhosis and disorders of the biliary tract, and occasionally in chronic active hepatitis and cirrhosis of the liver. Eight of 13 patients with primary biliary cirrhosis had liver copper content as high as seen in patients with hepatolenticular degeneration (is greater than 250 mjg/g dry weight). Normal liver content was found in patients with acute hepatitis, steatosis of the liver, hepatic amuloidosis, haemochromatosis, and Gilbert's syndrome. The urinary copper excretion was increased (is greater than 75 mjg/24 h) in half the patients with primary biliary cirrhosis and occasionally in the other patient groups. Serum ceruloplasmin was raised in more than half of all patients, and none had levels below the reference range. Raised heaptic copper content did not always coincide with enhanced urinary copper excretion, but was significantly correlated with this parameter and also with ceruloplasmin, alkaline phosphatases, and vitamin-K-dependent clotting factors, but not with ALAT. Combination of laboratory data, as found in typical cases of hepatolenticular degeneration, was not observed in this study, including 66 patients.

Determinations of serum lecithin : cholesterol acyl transferase (LCAT) and the “abnormal serum lipoprotein of cholestasis” (LP-X) have been carried out in 52 patients with different liver disorders and in 20 normal subjects. In acute hepatitis reduced LCAT activity was demonstrated in both LP-X positive and LP-X negative patients. In primary biliary cirrhosis and large bile duct obstruction the presence of LP-X was associated with reduced, normal or increased LCAT activity. Thus this study could reveal no specific LCAT/LP-X pattern in liver diseases, nor were we able to differentiate between intra- and extrahepatic cholestasis on the basis of these two tests. Possible relationships between LP-X and LCAT are discussed and mechanisms for the formation of LP-X in liver- and bile duct diseases are considered.

Forty-three patients were examined with computed tomography of the liver and liver biopsies with measurement of hepatic copper content. All recorded liver attenuation values were within normal range, even in patients with markedly elevated hepatic copper content. No statistically significant correlation between the liver attenuation values and the copper concentrations in liver tissue was demonstrated. At present, therefore, computed tomography has no place in monitoring the development of copper accumulation.

In a controlled clinical trial 208 patients with myocardial infarction were randomised into two groups. The patients in group A were given anticoagulant treatment for 3 months, the patients in group B for 12 months. All the patients were under 70 years of age and had not previously had a myocardial infarction. 10 patients were withdrawn from the investigation for different reasons, leaving 101 patients in group A and 97 in group B. The comparability between the two groups was found to be good. The intensity of the treatment was moderate. The average mean prothrombin-proconvertin value per week was 24·8% in both groups in the first 3 months, and 22·4% in group B during the whole 12 months. In group A 9 patients had 11 reinfarctions, 4 sudden deaths occurred, and the mortality was 6·9%. In group B there were 5 reinfarctions, 7 sudden deaths, and a mortality of 8·3%. There were 3 extracardiac thromboembolic episodes in group A and none in group B. None of these episodes proved fatal. 1 patient died of subarachnoidal haemorrhage. No statistically significant difference between the groups with regard to death-rate or reinfarction-rate could be demonstrated. There was no difference in the results between patients over and under 60 years of age. The investigation supports the opinion that following myocardial infarction there is no indication for anticoagulant therapy beyond the first 3 months with moderate intensity of treatment as used in this study.

After incubation whole plasma and low density lipoproteins (LDL) taken before and 10 min after intravenous administration of heparin, from a patient with primary biliary cirrhosis and a patient with familial lecithin:cholesterol acyltransferase (LCAT) deficiency, have been tested for the presence of lipoprotein X (LP-X) by agar gel electrophoresis. LP-X was present in preheparin whole plasma and LDL. No precipitation lines on the cathodal side of the wells, indicating the absence of LP-X, were seen after electrophoresis of postheparin plasma and LDL. Immunodiffusion revealed the presence of apo-beta-lipoproteins and LP-X in preheparin as well as postheparin LDL. After gel filtration three subfractions and similar patterns were observed in the preheparin and postheparin LDL. Electronmicroscopical examination of the intermediate subfractions showed LP-X-like particles in preheparin and postheparin samples. These observations indicate a changed electrophoretic mobility in agar gel of postheparin LP-X, giving a false negative LP-X test by the conventional agar gel electrophoresis.

A training program was started in nine patients with chronic active hepatitis in clinical remission while receiving immunosuppressive therapy. The patients were examined before and after a training period of 4-5 weeks and 10-12 weeks, respectively. The calculated oxygen consumption increased by 19% and 29%, and the estimated work load capacity improved. No change occurred in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatases, gamma-glutamyl-transpeptidase, serum bilirubin, or prealbumin, whereas creatine kinase and lactate dehydrogenase increased significantly. The clinical condition did not worsen in any patient, and most of the patients felt that their physical performance capacity had improved. We conclude that long-term regular physical training is well tolerated by patients with chronic active hepatitis in clinical remission and that training leads to improvement in the oxygen consumption and the estimated work load capacity in such patients.

Since opinions differ about the effect of physical activity in chronic liver disease, we performed a submaximal ergometric exercise test in 17 patients with chronic active hepatitis in clinical remission while receiving immunosuppressive therapy and in 5 patients with portacaval shunts. The calculated oxygen consumption was low in most patients. Blood samples were drawn before the exercise and 4 h, 24 h, and 48 h after. No changes occurred in serum ALAT, ASAT, ALP, CK, GT, or prealbumin. The clinical condition was not influenced by the exercise test. We conclude that moderate physical activity, at least of short duration, is well tolerated by patients with chronic active hepatitis.

In a 5-year period 48 (14%) of 336 patients with ulcerative colitis were found to have hepatobiliary disease. The bile ducts were examined in 35 of these patients, and optimal visualization of both intra- and extra-hepatic bile ducts was obtained in 26. Duct changes compatible with sclerosing cholangitis were found in 14 patients. This finding of sclerosing cholangitis in 4% of all patients admitted with ulcerative colitis by far exceeds previous estimations on the incidence of sclerosing cholangitis in ulcerative colitis. The entire colon was usually affected, and the symptoms of the bowel disease were most often mild or moderate. The age at the onset of the colitis was usually below 20 years in patients with combined ulcerative colitis and hepatobiliary disease. In most patients the hepatobiliary disease gave no symptoms. Biochemical data and the histological findings in the liver biopsies did not distinguish between patients with hepatobiliary disease with and without sclerosing cholangitis. Our follow-up study has so far shown that most patients with sclerosing cholangitis remain asymptomatic for a considerable period of time.