Histological Inflammation Scores Research Articles

Human peripheral blood lymphocyte severe combined immunodeficiency (hu-PBL SCID) models of toxoplasmosis.

Toxoplasmosis is a potentially fatal opportunistic infection of immunocompromised hosts. Improved animal models of toxoplasmosis are needed to more nearly approximate conditions that occur in immunocompromised humans. The development of models of toxoplasmosis using human peripheral blood lymphocytes (hu-PBL) transplanted into severe combined immunodeficiency (SCID) mice is described here. Transplantation of hu-PBL into SCID mice without prior conditioning of the mice resulted in detectable differences in quantitative histological scores of brain inflammation due to Toxoplasma gondii infection, but did not alter mortality when compared to SCID mouse controls. The lack of detectable differences in survival were due to inadequate engraftment of hu-PBL, as assessed by flow cytometry. Unconditioned hu-PBL SCID mice had low titre T. gondii-specific antibody detectable after infection. When pretransplantation conditioning with irradiation and antiasialo GM 1 (n-glucolyl neuraminic acid) antibody was used, prolonged hu-PBL engraftment was observed in SCID mice, which was associated with worsened histopathology and usually impaired survival when compared with SCID mouse controls. When pretransplantation conditioning with irradiation, antiasialo GM antibody and polyethylene glycol-conjugated IL-2 was used, prolonged hu-PBL engraftment was also documented, but this did not affect survival from T. gondii infection when compared with similarly conditioned SCID mouse controls. The latter conditioning protocol resulted in hu-PBL SCID mice producing high titre T. gondii-specific antibody after infection. Conditioned hu-PBL SCID mice had evidence of increased T. gondii-induced inflammatory scores when compared with conditioned SCID mice. These models show promise for the study of the pathogenesis of toxoplasmosis and conditioned hu-PBL SCID mice may have applications for the evaluation of novel therapies for toxoplasmosis in immunocompromised humans.

Liver histology in hepatitis C: correlation with different biochemical and virological parameters

According to the German consensus statement, the indication for treatment of HCV-RNA-positive chronic hepatitis C is not derived from histopathology but from elevated aminotransferases. The indication for liver biopsy has been discussed controversely. This study aimed at investigating the correlation between different biochemical and virological parameters and histological scores of inflammation and fibrosis in chronic hepatitis C. In a retrospective study, data of 126 patients with chronic hepatitis C who had undergone liver biopsy between January 1994 and March 1998 were analyzed. Histology was interpreted according to a defined numerical score of inflammation and fibrosis by a single pathologist. Scores of fibrosis and inflammation were correlated with biochemical and virological parameters. Inflammatory grading showed a moderate but significant correlation with ALT (r = 0.33, p < 0.001), whereas staging of fibrosis did not correlate with ALT (r = 0.15). There was no association between grading or staging and HCV genotype (n = 110) or serum viral load (n = 57). Grading and staging showed a significant association with each other (p < 0.0001). Aminotransferases as "surrogate markers" reflect more or less the histological inflammatory activity but do not allow any estimation of the extent of fibrosis. Some patients may have a high inflammatory activity with low aminotransferases or high aminotransferases with low inflammatory activity. Virological parameters such as HCV genotype or viral load do not allow an estimation of histological findings. If prior to treatment of chronic hepatitis C liver biopsy is omitted and the decision for treatment depends solely on the measurement of surrogate markers, considerable misjudgement of the actual status of liver inflammation or fibrosis may result.

Histologic inflammation in the maternal and fetal compartments in a rabbit model of acute intra-amniotic infection

Objective: This study was undertaken to determine the course of acute inflammation in the maternal and fetal compartments during experimentally induced ascending intra-amniotic infection. Study Design: Forty pregnant rabbits at 70% gestation were inoculated endocervically with 105 colony-forming units of Escherichia coli. Does were killed at 0, 4, 8, 16, 24, and 30 hours after inoculation. At necropsy, blood, peritoneal fluid, amniotic fluid, and uterine tissue were cultured. Fetal brain, lung, heart, gut, and kidney were collected for histologic examination. Necrosis, infiltrates, congestion, and edema were each assessed semiquantitatively, and mean composite histologic-inflammation scores were compared with analysis of variance. Inflammation, mitotic activity, and apoptosis were evaluated in the fetal brain, and groups were compared with analysis of variance. Results: Twenty-six animals were evaluated after 14 were excluded (lack of fever or positive culture results). A significant increase in histologic inflammation score was seen in the uterus (P <.001), placenta(P =.011), and fetal lung (P =.001) but not in other fetal tissues. These changes were seen earlier in the uterus and placenta and later in the fetal lung. Mitotic activity in the fetal brain decreased significantly by 8 hours after cervical inoculation. There was no inflammation in the fetal brain, and apoptosis in the fetal brain did not increase with time. Conclusions: Histologic inflammation occurs early in both the uterus and the placenta and later in the fetal lung in the rabbit model of acute intra-amniotic infection. This contrasts with the previously reported chronic model of intra-amniotic infection in the rabbit. (Am J Obstet Gynecol 2000;183:1088-93.)

The significance of baseline serum alanine aminotransferase on pretreatment disease characteristics and response to antiviral therapy in chronic hepatitis C

We sought to determine whether pretreatment serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis C virus (HCV) correlate with demographic features and other disease characteristics and whether these values influence response to therapy. A total of 1,744 patients with HCV received either interferon alfa-2b and placebo or combination interferon alfa-2b and ribavirin for 24 or 48 weeks. Of these, 105 individuals (6%) had minimally raised serum ALT determinations at entry visit of ≤1.3 × the upper limit of normal (ULN). By analysis of variance both pretreatment histologic activity index (HAI) scores (P < .0001) and fibrosis scores (P = .003) were significantly lower among patients with baseline ALT levels ≤1.3 × ULN. Individuals with lower pretreatment ALT values were younger and weighed less than the ALT >1.3 × ULN cohort. Baseline ALT was not related to gender, race, baseline viral level, or HCV genotype. Using logistic regression analysis, the only demographic feature associated with ALT ≤1.3 × ULN was lower baseline weight and lower baseline HAI score. There was no difference in sustained response between patients with baseline ALT levels ≤1.3 × ULN and those with >1.3 × ULN, in all treatment groups (26 of 105, 24.8% for ALT ≤1.3 × ULN; 440 of 1,639, 26.8% for ALT >1.3 × ULN). We conclude that HCV patients with minimally raised ALT values (≤1.3 × ULN) weigh less, and have lower histologic inflammatory scores than patients with more conventionally elevated ALT levels. Despite these differences, these patients have a similar sustained response to antiviral therapy. (Hepatology 2000;32:400-404.)

Helicobacter pylori(HP) eradication in non-ulcer dyspepsia (NUD): A randomized, double-blind, place-bo-controlled study with a 12-month follow-up

The relationships between Hp infection and NUD are uncertain. Consequently, the clinical benefit of the eradication remains controversial. The aim of this multicenter, randomized, double-blind, placebo-controlled study was to determine the effect of Hp eradication on symptoms of dyspepsia 12 months after treatment. Methods: 253 patients with severe ulcer-like pain (grade 3 or 4 on Likert scale: from 0= none to 4= very severe) for at least 3 months, Hp infection (Clo-Testregistered with histological confirmation) and no evidence of peptic ulcer or esophagitis on upper GI endoscopy were treated. Patients were randomly allocated to a 7-day treatment of ranitidine 3OOmgx2, amoxicilline Igx2, clarithromycine 5OOmgx2 (RAe) or placebo (PLA) and were followed-up for 12 months (day 8 and months 3, 6, 9 and 12). Treatment success was defined as the reduction of at least 2 grades on Likert scale between randomization and the 12-month visit. Complete resolution of dyspeptic symptoms was defined as grade 0 on Likert scale. Presence of Hp was assessed at 3 months by l3C-urea breath-test and at 12 months by histology. Gastritis was histologically graded (Sydney System) on 2 antral and 2 corpus biopsies performed at randomization and at 12 months by an expert gastrointestinal pathologist blinded to treatment group. Results: The 2 groups were comparable. Hp eradication rates at 3 months were 70% in RAC and 9% in PLA group, and at 12 months 69% and 18% respectively. By intention to treat there was no significant difference at 12 months between the 2 groups in treatment success rates (62% RAC and 60% PLA). However, complete symptom resolution was significantly more frequent (p<0.05) in RAC group (43%) than in PLA group (31%). In RAC group, treatment success rates were 84% among patients with Hp eradication and 64% among patients with persistent infection at 12 months (p=O.04). Chronic gastritis persisted in 91% of patients in RAC group and 89% of patients in PLA group after 12 months. However, histological scores for inflammation, activity and lymphoid infiltration were significantly higher in PLA group than in RAC group. Scores for atrophy and metaplasia were similar in the 2 groups. Conclusion: Curing Hp infection in NUD patients is more likely associated with complete symptom relief at 12 months despite the large placebo effect in reducing dyspeptic symptoms severity. Moreover, chronic gastritis persisted with improvement of inflammation and activity 1 year after Hp eradication treatment.

The Effect of Dexamethasone Treatment on Murine Colitis

Corticosteroids are used as anti-inflammatory drugs in the treatment of inflammatory bowel disease. We wanted to know whether dexamethasone (DEX) treatment could prevent dextran sulphate sodium (DSS)-induced colitis in mice. Acute colitis was induced after oral administration of 10% DSS for 2 days. Controls received normal tap water. Five days before and during DSS or tap water exposure half the group was treated with 0.06 mg/day DEX, and the other half received saline. After the mice had been killed, macroscopic observation and histologic evaluation were used to determine the degree of colonic inflammation. The macroscopic score was significantly increased in untreated DSS mice (P < 0.001). The induction of colitis was not prevented by DEX pretreatment (5.9 +/- 0.9 versus 4.2 +/- 0.6; NS). In addition, the macroscopic scores of DEX-treated controls were significantly increased (1.8 +/- 0.2 versus 0.7 +/- 0.2; P = 0.007), which suggests that DEX has a stimulating effect on colitis induction. The histology score was significantly increased in untreated DSS mice compared with controls (P = 0.016). Analogous to the macroscopic scoring results, the histology score of DEX-treated controls was significantly increased compared with untreated controls (P = 0.046). Pretreatment with dexamethasone did not prevent the induction of acute DSS colitis, reflected by both aggravated macroscopic and histologic inflammation scores.

Extraintestinal manifestations of ulcerative colitis following restorative proctocolectomy.

Rheumatological and other extraintestinal manifestations (EIM) are common in inflammatory bowel disease (IBD) but also seem to occur in patients after restorative proctocolectomy and formation of an ileo-anal pouch. The prevalence and significance of these symptoms have not been established in this clinical context. To evaluate prospectively the prevalence and associations of EIM of IBD in ulcerative colitis (UC) patients following restorative proctocolectomy (RP) and to compare the findings to those in a control group of familial adenomatous polyposis (FAP) patients who had undergone similar surgery. One hundred and twenty-three (97 UC and 26 FAP) consecutive patients with ileal pouches undergoing long-term follow-up underwent an assessment of rheumatological symptoms and signs, similarly of other EIM; each underwent pouch endoscopy and biopsy. Symptoms in the joints were reported in 30 (31%) of UC patients compared to two (8%) FAP patients (P = 0.02). Twenty-four (80%) of the affected patients had a polyarticular arthralgia affecting primarily the knees, and small joints of the hands. Clinical findings and radiological investigations were almost exclusively normal. Most patients had mild symptoms, with only 12 of the 30 reporting interference with daily life. The presence of symptoms in the joints was not associated with a positive family history for IBD or other EIM, the presence of non-rheumatological EIM or the presence of pouchitis. Histological scores of pouch inflammation did not differ between those with and without symptoms of the joints. A mild polyarticular arthralgia, similar to that associated with active IBD, is common following RP and may commence after surgery. It is not associated with the presence of pouch inflammation.

Intestinal permeability and contractility in murine colitis.

We developed an in vitro organ bath method to measure permeability and contractility simultaneously in murine intestinal segments. To investigate whether permeability and contractility are correlated and influenced by mucosal damage owing to inflammation, BALB/c mice were exposed to a 10% dextran sulphate sodium (DSS) solution for 8 days to induce colitis. The effect of pharmacologically induced smooth muscle relaxation and contraction on permeability was tested in vitro. Regional permeability differences were observed in both control and 10% DSS-treated mice. Distal colon segments were less permeable to 3H-mannitol and 14C-PEG 400 molecules compared with proximal colon and ileum. Intestinal permeability in control vs. 10% DSS mice was not altered, although histologic inflammation score and IFN-gamma pro-inflammatory cytokine levels were significantly increased in proximal and distal colon. IL-1beta levels were enhanced in these proximal and distal segments, but not significantly different from controls. Any effect of pharmacologically induced contractility on intestinal permeability could not be observed. In conclusion, intestinal permeability and contractility are not correlated in this model of experimentally induced colitis in mice. Although simultaneous measurement in a physiological set-up is possible, this method has to be further validated.

Therapy of hepatitis C: interferon alfa-2a trials.

Interferon alfa-2a resembles other recombinant alpha interferons in structure and pharmacology. Studies delineating its efficacy suggest that after 6 to 12 months of therapy, sustained biochemical responses occur in 4% to 49% of patients, providing adequate doses (> or = 3 million units three times weekly) are used. Overall, a dose-response curve is evident in regard to biochemical responses, decrease in histological scores for inflammation, and virological responses (percent negative serum hepatitis C virus [HCV] RNA) after treatment. Differences in response rates between studies probably reflect patient selection and particularly the percent of patients with established cirrhosis, because these patients respond less well than those with earlier histological stages of disease. A variety of regimens of interferon alfa-2a have been used, including use of higher doses, longer periods of treatment, induction using higher doses initially, and intermittent pulse therapy. Both longer periods of therapy and induction dosing show strong but not significant trends toward improvement in response rates, which reach significance when the two strategies are combined. Outcome is not significantly improved by escalating doses during therapy when inadequate responses are seen, or by pulse therapy. The side effect profile of interferon alfa-2a is similar to that of other interferons. Long-term follow-up studies have demonstrated that 90% of patients with a sustained biochemical response at 6 months after therapy maintain the response, and 95% remain negative for HCV RNA in serum. Challenges for the future include better delineation of the advantages of induction dosing, the optimal duration of therapy, and further understanding of the frequent discordance between HCV RNA data and aminotransferase levels. This latter finding suggests that use of both parameters is necessary to evaluate fully responses to therapy.

Implications of Helicobacter pylori serological titer for the histological severity of antral gastritis.

We attempted to determine whether the serological titer of anti-Helicobacter pylori (HP) immunoglobulin (IgG) would be capable of predicting the presence of ulcer, or would correlate with the histological grading of gastritis in patients with dyspepsia. One hundred eighty-three dyspeptic patients were prospectively included in the study after panendoscopy. Each patient underwent blood sampling for anti-HP IgG titer, and antral biopsy for both a rapid urease test (CLO) and histology. The severity of antral gastritis was semi-quantitated for acute and chronic inflammation scores (range 0-3). The HP findings were positive in 157 patients (85.5%), and their histological inflammation scores and serological titer were higher than those of HP-negative patients (P < 0.05). Based on the endoscopic findings, these 157 patients were classified into ulcer (n = 109) and non-ulcer dyspepsia (n = 48) subgroups. The mean chronic inflammation score in the ulcer subgroup was higher than that in the non-ulcer dyspepsia subgroup (1.77 vs. 1.28, P < 0.001). However, on the basis of only the titer itself, there was no cut-off value for serological titer to predict the presence or absence of ulcer in HP-infected patients. As the scores for either acute or chronic inflammation increased, the mean serological titer rose (acute inflammation score 0-3: 0.63, 0.78, 0.93, 1.39; chronic inflammation score 0-3: 0.18, 0.56, 0.88, 0.91). The titer of HP serology does not provide a method for predicting the presence of ulcer in patients with HP infection, but may indirectly offer evidence of the severity of histological changes.

Effect of abdominal vagotomy on interleukin-1 induced nitric oxide release in the paraventricular nucleus in conscious rats

The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis.

Threshold effect of liver iron content on hepatic inflammation and fibrosis in hepatitis B and C

Background/Aims: In hepatitis C, iron depletion may improve serum aminotransferases and the response to interferon, but it is not known whether inflammation and fibrosis correlate with hepatic iron content. Our aim was to establish whether hepatic from content correlates with histological and serum indices of hepatic inflammation and fibrosis in hepatitis B and C. Methods: Total hepatic iron was measured using computerized histomorphometry, and hepatic inflammation and fibrosis using a modified Knodell score, on histological slides from 31 patients with chronic hepatitis B and 38 with hepatitis C. Results: Total hepatic iron was similar in the hepatitis B and C groups (0.82±1.72% and 0.56±1.12%; mean±SD). No iron was detectable in 11 patients with hepatitis B and 13 with hepatitis C. Alanine aminotransferase (85.96±67.1 vs 44.2±39.7 p<0.05), aspartate aminotransferase (93.8±75.6 vs 47±33.5 IU/ml p<0.05) and histological inflammatory score (9.33±3.51 vs 7.79±3.3 p=0.07) were increased in those with stainable hepatic iron compared to those without. However, where iron was present, no association was found between the amount of hepatic iron and inflammatory or fibrosis scores. In hepatitis C, fibrosis was minimal in 77% of patients if iron was absent vs 24% with iron present, while marked fibrosis was present in 56% with iron vs 15% without iron ( p<0.01, Fisher's exact test). Conclusion: Hepatic iron is associated with increased hepatic inflammation in chronic hepatitis B and hepatitis C and with high fibrosis scores in hepatitis C. There is a threshold effect, and once present, increasing iron does not correlate with increasing inflammation or fibrosis.

Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat.

FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.

Pathogenicity of the Streptococcus milleri group in pulmonary infections--effect on phagocytic killing by human polymorphonuclear neutrophils.

The pathogenicity of Streptococcus constellatus in pulmonary infections was investigated in mice in correlation with the phagocytic killing of the microorganisms by human polymorphonuclear neutrophils (PMNs). The histological inflammation score of the lungs in mice inoculated intratracheally with 10(8) cfu/mouse of the virulent strain S. constellatus RZYK001 obtained from bronchoalveolar fluid of a patient with pneumonia, was significantly higher than in mice inoculated with the avirulent strains S. constellatus RT4303 and RT6002 obtained from saliva of healthy adults (p < 0.001). The bactericidal activity of human PMNs against Staphylococcus aureus ATCC 25923 was not inhibited at all by the culture filtrate of the virulent strain, but the killing index against RZYK001 was 36.4% after 90-min incubation whereas that against RT4303 and RT6002 was 94.7% and 99.4%, respectively (p < 0.001). Therefore, these results suggest a possible pathogenic mechanism of S. constellatus apparently mediated by a structural component of the organisms so that a virulent strain is less likely to be killed than an avirulent one, predisposing it to survive in the infection sites.

The effect of chlorpromazine on endotoxin-induced uveitis in the Lewis rat.

Chlorpromazine (CPZ) has been used extensively in the treatment of psychiatric disorders, and has recently been shown to possess systemic anti-inflammatory properties as well. To investigate the potential effects of CPZ on ocular inflammation, we evaluated its action on endotoxin-induced uveitis (EIU) in Lewis rats. At three different dosage levels, CPZ produced highly significant reductions in the mean aqueous aspirate inflammatory cell counts and histological inflammatory scores as compared to controls treated with vehicle only. Analysis of aqueous fluid demonstrated a similar decrease in protein concentration and phospholipase A2 (PLA-2) activity in the treated animals. The ability of CPZ to inhibit the development of EIU may be related to its properties as a calcium channel blocker and inhibitor of the enzyme phospholipase A2.

Gene expression (collagenase, tissue inhibitor of metalloproteinases, complement, and HLA-DR) in rheumatoid arthritis and osteoarthritis synovium. Quantitative analysis and effect of intraarticular corticosteroids.

In situ hybridization was used to localize and quantify gene expression in rheumatoid arthritis (RA) and osteoarthritis (OA) synovial tissue. Collagenase, tissue inhibitor of metalloproteinases (TIMP), HLA-DR, and complement (C2 and C3) gene expression was studied in synovial tissue from 23 patients with RA, OA, or other inflammatory arthropathies. Gene expression was highly compartmentalized: Collagenase, TIMP, and C2 messenger RNA (mRNA) were localized primarily to the synovial lining layer; HLA-DR mRNA was prominent in the lining and in some sublining lymphoid aggregates; the C3 probe hybridized only to sublining lymphoid aggregates. Relative mRNA levels were quantified using computer-assisted image analysis. There was significantly more collagenase, C2, C3, and HLA-DR mRNA in RA compared with OA patients. However, TIMP mRNA levels were similar in RA and OA. Expression of collagenase, TIMP, C2, C3, and HLA-DR genes correlated with the degree of synovial inflammation. The effect of intraarticular corticosteroid injection on synovial tissue gene expression was studied using serial percutaneous synovial biopsy samples from the knees of 3 RA patients. Joints were biopsied, injected with triamcinolone, and rebiopsied 1-2 weeks later. Histologic inflammation scores were lower in posttreatment synovia. Collagenase and TIMP mRNA, although abundant in presteroid samples, were nearly undetectable in post-steroid tissues. HLA-DR mRNA levels also were significantly decreased. C2 and C3 hybridization significantly decreased in 2 of 3 patients and 1 of 3 patients, respectively. Hence, clinical response to intraarticular steroid therapy was accompanied by histologic improvement and decreased expression of genes that play a role in articular destruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Interferon alpha-2b treatment of chronic posttransfusion non-A, non-B/C hepatitis: Long-term outcome and effect of increased interferon doses in non-responders

The biochemical and histological long-term outcome of interferon alpha-2b treatment for chronic posttransfusion non-A, non-B/C hepatitis was evaluated in a randomized study. 4/19 treated patients had a sustained response with normal serum alanine aminotransferases (s-ALAT) levels during follow-up, at present for 18-20 months after the end of interferon treatment. None of 11 responders with biochemical relapse normalized their s-ALAT levels during 1 year follow-up after treatment. Histological changes were assessed by a scoring system. The scores for portal inflammation, piecemeal necrosis and fibrosis were essentially unchanged in all treated patients between biopsies taken at the end of treatment and 1 year later. Six non-responders to 3 million units (MU) alpha-2b interferon thrice weekly (t.i.w.) were given 6 MU t.i.w. for at least 8 weeks. None normalized the s-ALAT levels during treatment with the higher dose, instead the side effects were much more pronounced, an obstacle to the usefulness of higher interferon doses. The biochemical non-responders had higher pretreatment histologic inflammation scores indicating a more severe infection. They also had a higher body weight and seemed to have prominent macrovesicular steatosis more often than responders, a finding that could contribute to raised aminotransferases, thereby in some of the non-responders, masking a positive biochemical effect of interferon treatment.

Quantitation of arthritis by 99mTc-uptake measurements in the mouse knee-joint: correlation with histological joint inflammation scores.

A method is described to detect and to quantitate inflammation in knee-joints of mice. Approximately 10 muCi 99mTechnetium pertechnetate (99mTc) is injected subcutaneously in the neck region and the accumulation of the short-lived isotope in the knee-joint is detected by external gamma counting. 99mTc-uptake values correlate well with histological grading of joint inflammation at various intervals after induction of the inflammation. The method can be used to detect changes in activity of unilateral as well as bilateral joint inflammation using either the ratio of 99mTc uptake in the right knee versus that in the left knee or absolute 99mTc-uptake values.