Showing papers in "Journal of Gastroenterology and Hepatology in 1993"
TL;DR: A one‐step method which enables a quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype has been developed and should be useful for studying the epidemiology or biology of the HCV.
Abstract: Four subtypes of hepatitis C virus (HCV), Pt(I), K1(II), K2a(III) and K2b(IV), have been suggested based on the nucleotide sequences of the non-structural (NS) 5 region. A fifth subtype from Japanese patients, Tr(V), which shows a less than 68% homology in nucleotide sequence when compared with other subtypes has been identified. A one-step method which enables a quick determination of subtype using polymerase chain reaction with a mixed primer set deduced from the sequence of each subtype has been developed. Using this technique, the subtypes of 418 out of 478 Japanese patients (87.4%) were determined. The incidence of each subtype in Japan was as follows: K1(II), 307 (73.4%); K2a(III), 74 (17.7%); K2b(IV), 28 (6.7%); and Tr(V), 3 (0.7%). This one-step subtyping technique should be useful for studying the epidemiology or biology of the HCV.
160 citations
TL;DR: The identification of NO as a major inhibitory neurotransmitter to gastrointestinal smooth muscle fills an important gap in the understanding of the physiological control of motility and opens up a wide range of new experimental possibilities, which may eventually lead to the development of new drugs for motility disorders.
Abstract: Motility of the gastrointestinal tract is directly controlled by enteric inhibitory and excitatory motor neurons that innervate the layers of smooth muscle. Inhibitory motor neurons mediate receptive and accommodative relaxations and control the opening of sphincters, thus playing an important role in normal gut motility. Recent studies have demonstrated that nitric oxide (NO) is an important neurotransmitter released by inhibitory motor neurons in animal and human gut. Antagonists of nitric oxide synthase (NOS), the synthetic enzyme for NO, reduce the effectiveness of transmission from inhibitory motor neurons. Exogenous NO mimics inhibitory nerve activation, and a variety of compounds that affect the availability of endogenously produced NO modulate relaxations of gastrointestinal smooth muscle. It is clear, however, that NO is unlikely to be the only transmitter released by enteric inhibitory motor neurons: several other substances such as vasoactive intestinal polypeptide (VIP), or related peptides, and adenosine triphosphate (ATP) are also likely to contribute to nerve-mediated inhibition. The identification of NO as a major inhibitory neurotransmitter to gastrointestinal smooth muscle fills an important gap in our understanding of the physiological control of motility and opens up a wide range of new experimental possibilities. It may eventually lead to the development of new drugs for motility disorders. It should be noted, however, that NO is important in the brain, in cardiovascular control, in blood cell function and in many other organ systems, suggesting that it may be difficult to achieve specific pharmacological intervention targeted on inhibitory neurotransmission in the gut, without undesirable side effects.
103 citations
TL;DR: Calcification of the matrix confers further protection for the micro‐organisms living inside the biofilm, and hydrophobic bile salts reduce bacterial adhesion on biomaterial, suggesting that incorporation of such bile salt might prevent the formation of bacterial biofilm.
Abstract: Bacterial pathogens gain access into the biliary system by descending via the portal venous circulation or ascending through the sphincter of Oddi in duodenal-biliary reflux. Bacteria thrive as glycocalyx-enclosed microcolonies, coalescing to form an adherent biofilm. The establishment of biofilm is a key event in the formation of biliary sludge and pigment gallstones, and the blockage of biliary stents. The biofilm mode of growth is very effective because it provides bacteria with a measure of protection from antibacterial agents and phagocytic leucocytes. Calcification of the matrix confers further protection for the micro-organisms living inside the biofilm. To date, attempts to prevent blockage of biliary stent have employed physical methods by using large self-expandable stents and stents without side hole. Incorporation of antibiotics within stents has not been successful presumably because bacteria once living in their biofilm are quite resistant to antimicrobial agents. Even the most toxic bile salts have no effect on the biofilm bacteria. Yet, hydrophobic bile salts reduce bacterial adhesion on biomaterial, suggesting that incorporation of such bile salts might prevent the formation of bacterial biofilm.
79 citations
TL;DR: Chronic hepatitis B virus (HBV) infection is one of the most common persistent virus infection in man and causes significant morbidity and mortality, and therefore is important.
Abstract: Chronic hepatitis B virus (HBV) infection is one of the most common persistent virus infection in man. It causes significant morbidity and mortality, and therefore is important. Extensive studies on clinicopathologic studies and long-term follow up on hepatitis B surface antigen (HBsAg) carriers have largely disclosed the natural history of chronic HBV infection.
The infection easily becomes chronic when contracted in early infancy. As high as 90% of babies born to HBV carrier mothers will also become HBsAg carriers. Once chronic infection is established, it is refractory, and HBsAg carriage usually persists for life. However, the chronic infection is not monotonous, it actually evolves from an HBV replicative phase to a non-replicative phase. The host responds differently and with more complexity in different phases. The virus-host interactions, divided into three phases, virus tolerance, virus clearance and residual HBV integrated phases, result in a heterogeneous variety of hepatic lesions. The first two phases occur when HBV is actively replicating, and the last corresponds to the non-replicative phase. The high HBV level (and hence HBV gene products) renders the host's immune system tolerant to the virus, and the infected host does not exert an effort to get rid of the virus. At this stage, the liver is nearly normal, and the host is asymptomatic. However, later in the replicative phase, the HBV replication begins to wane, and the immune tolerance is no longer maintained. Hepatitis B core antigen/hepatitis B e antigen (HBcAg/HBeAg)-specific cellular immune responses result in lysis of the infected liver cells; the liver then begins to have active disease as revealed by the presence of lobular hepatitis. The asymptomatic carrier may then start to have symptoms of hepatitis. After a variable period, usually in years, the host eventually gets rid of active viral replication and only residual incomplete HBV genome integrated to host chromosomes is found. The carrier is now HBeAg negative/anti-HBe positive, serum HBV DNA decreases to very low levels, and the disease becomes qulescent at this stage.
The outcome of the host is determined by the hepatic lesions caused by HBV-host interactions mentioned above, with cirrhosis and hepatocellular carcinoma (HCC) as the major sequelae of chronic HBV infection. Although HCC is usually preceded by HBV-induced cirrhosis, this is not always the case. Cirrhosis and HCC may develop independently, with cirrhosis as the most important precipitating factor or cofactor of HCC. A significant proportion of HBsAg carriers, particularly the males, will eventually die of these sequelae.
73 citations
TL;DR: The demographic patterns and the results of studies regarding familial and environmental risk factors are described and the possibility that a H. pylori infection could lead to gastric cancer is discussed.
Abstract: This review focuses on the similarities between the epidemiology of gastric cancer and the epidemiology of Helicobacter pylori. Their demographic patterns and the results of studies regarding familial and environmental risk factors are described. The association of gastric cancer and H. pylori infection with both gastric ulcer and chronic atrophic gastritis is also characterized and the possibility that a H. pylori infection could lead to gastric cancer is discussed.
65 citations
TL;DR: In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic‐pituitary adrenal function was evaluated in patients with end‐stage liver disease awaiting transplantation.
Abstract: Patients with end-stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic-pituitary adrenal function was evaluated in patients with end-stage liver disease awaiting transplantation. The study had a prospective, open comparative design with patients restricted to those having non-alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty-one consecutive patients with end-stage, non-alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n = 8) or who were unable to complete the investigations (n = 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid-binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin-induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 micrograms tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin-induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child-Pugh scores and peak control responses to ACTH (r = -0.647, P < 0.0001) and insulin-induced hypoglycaemia (r = -0.597, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
63 citations
TL;DR: The results suggest that not only are the IFN treatment schedule and patient profile significant, but the properties of the virus also influences the response, which should be designed to maximize the benefit of IFN therapy.
Abstract: To determine how various factors influence the response to interferon (IFN) therapy, we retrospectively studied 157 consecutive Japanese patients with chronic hepatitis C who received various treatment schedules of IFN. They were divided into two groups on the bases of outcome. One group was comprised of 65 patients who achieved a sustained normalization of serum alanine aminotransferase (ALT) levels for at least 6 months after treatment, while the other group was comprised of 84 patients with persistent elevation of serum ALT levels, despite treatment. Genotyping of hepatitis C virus (HCV) was done by polymerase chain reaction (PCR) with genotype specific primers, analysing the variations in nucleotide sequence within the NS 5 region of the HCV genome, namely genotypes PT, K1, K2a and K2b. We then used a multivariate analysis to determine the factors related to mode of treatment, patient characteristics and HCV genotype in relation to the response to IFN therapy. Of the 16 factors analysed, the HCV genotype (genotype K2a or K2b, P 0.0014) and liver histology just before treatment (chronic persistent hepatitis or mild chronic aggressive hepatitis, P < 0.0324) were the most strongly correlated with a normalizing response to IFN therapy. These results suggest that not only are the IFN treatment schedule and patient profile significant, but the properties of the virus also influences the response. However, as the IFN treatment schedule is the only changeable factor, it should be designed to maximize the benefit of IFN therapy.
57 citations
TL;DR: Combination antiviral chemotherapy using agents such as ganciclovir and foscarnet may offer a new approach to the management of post‐transplant recurrence of HBV.
Abstract: The authors have successfully used combination ganciclovir and foscarnet chemotherapy to control viral replication following liver transplantation in a patient with severe recurrence of hepatitis B virus (HBV) infection. The disease was characterized by extremely high viraemias, deteriorating liver function, and high levels of intra-hepatic hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg). Treatment resulted in a greater than 30-fold reduction in serum HBV DNA and HBsAg levels. Liver function tests returned to normal and the histological progression of the disease was arrested. Hepatic cytoplasmic HBsAg decreased substantially but there was little change in HBcAg, implicating HBsAg rather than HBcAg in the liver injury. Combination antiviral chemotherapy using agents such as ganciclovir and foscarnet may offer a new approach to the management of post-transplant recurrence of HBV.
52 citations
TL;DR: The results suggest the usefulness of TIMP‐1 as a tumour marker in cases of HCC where α‐fetoprotein levels are not elevated, and suggest it might also reflect hepatic inflammation.
Abstract: Serum levels of the tissue inhibitor of metalloproteinases-1 (TIMP-1) were measured in 268 patients with liver diseases by means of a one-step sandwich enzyme immunoassay. In the cases of acute hepatitis, chronic active hepatitis (CAH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC), the levels of TIMP-1 were higher than those of the control group. Tissue inhibitor of metalloproteinases-1 levels correlated with type III procollagen peptide and with type IV collagen, indicating TIMP-1 as a useful marker for hepatic fibrosis. Levels of TIMP-1 also correlated with aspartate aminotransferase and alanine aminotransferase levels and showed the highest levels in acute hepatitis. Thus, TIMP-1 might also reflect hepatic inflammation. Serum levels of alpha-fetoprotein and TIMP-1 had a significant positive correlation in patients with HCC. A cut-off level of TIMP-1 between LC and HCC was set at 440 ng/mL, having a low sensitivity and a high specificity. These results suggest the usefulness of TIMP-1 as a tumour marker in cases of HCC where alpha-fetoprotein levels are not elevated.
49 citations
TL;DR: Levels of alpha‐fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist‐II (PIVKA‐II) increased gradually without any evidence of recurrence of HCC in the liver and were useful for diagnosing the subcutaneous nodule as a metastatic HCC.
Abstract: Ultrasonically guided fine needle (21 gauge) aspiration biopsy (FNAB) was performed on a patient with a hepatocellular carcinoma (HCC) measuring 1.5 × 1.5 cm in segment VI of the liver. The tumour was located just beneath the liver surface. Subsegmentectomy of segment VI was performed. Twelve months after the biopsy and 10 months after the operation, levels of alpha-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) increased gradually without any evidence of recurrence of HCC in the liver. Thirteen months after the biopsy, the patient palpated a hard subcutaneous nodule 1.5 cm in diameter in the right lower anterior chest wall at the insertion site of the biopsy needle. A subcutaneous tumour was excised and histological examination revealed moderately differentiated HCC. The levels of AFP and PIVKA-II normalized thereafter. These tumour markers were therefore useful for diagnosing the subcutaneous nodule as a metastatic HCC. The patient is currently doing well without further recurrence of HCC or needle-tract seeding 23 months after subsegmentectomy and 11 months after excision of the subcutaneous tumour.
46 citations
TL;DR: If hepatic transplantation surivival rates were to approach 95%, the relative risk ratio between transplantation and conservative therapy would increase, and at present an 80% 1–5 year survival rate following transplantation should be expected.
Abstract: Liver transplantation is now available world-wide. It plays an important role in the treatment of irreversible acute and chronic liver disease (CLD). Selection of patients for liver transplantation is subject to many factors including economic, cultural, availability of donor organs and degree of illness. This article looks at seven general considerations for receipients of liver transplantation. As well, disease-specific criteria are investigated and include such areas as cirrhosis due to chronic hepatitis B virus (HBV), hepatitis C virus (HCV) positive cirrhosis, fulminant hepatic failure (FHF), malignancy, alcoholic liver disease (ALD), metabolic conditions and Budd–Chiari syndrome. If hepatic transplantation surivival rates were to approach 95%, the relative risk ratio between transplantation and conservative therapy would increase. At present an 80% 1–5 year survival rate following transplantation should be expected.
TL;DR: It is concluded that the differential regulation of the two ferritin subunits in response to different stimuli and in different tissues occurs at the level of alteration in mRNA concentration.
Abstract: Iron overload, such as occurs in the genetic disease haemochromatosis, leads to synthesis of ferritin containing an increased proportion of L subunits. Inflammation also leads to clinically important increases in ferritin synthesis but the predominant subunit involved is unclear. Elevation of serum ferritin concentration during the acute phase response confounds its use as an indicator of body iron stores and identification of the major subunit involved may allow distinction of the ferritin associated with inflammation from that synthesized during iron overload. The present study examined H and L ferritin subunit mRNA levels in rats with: (i) longstanding iron overload, both parenteral and oral, in which changes should be maximal and stable; and (ii) inflammation of 24 and 48 h duration. A two-fold increase in L mRNA level was found in both groups of iron loaded animals while H mRNA level was unchanged. This finding would account for the observed preponderance of L subunits in ferritin during iron overload. During the course of inflammation there was a progressive decrease in L mRNA level in the liver but not the spleen. H mRNA relative to total RNA level was unchanged in both liver and spleen. It is concluded that the differential regulation of the two ferritin subunits in response to different stimuli and in different tissues occurs at the level of alteration in mRNA concentration.
TL;DR: The aim of this article is to review three basic issues of malnutrition in end-stage liver disease: what are the dominant pathophysiological factors which cause wasting and malnutrition to develop;What are the most reliable methods of assessing the nutritional status of cirrhotic patients; and what is the prognostic influence of malnutrition once it does develop.
Abstract: Malnutrition is a common development in end-stage liver disease. Its progression is insidious and its presentation is much less dramatic than other complications of cirrhosis. In the past, many hepatologists have regarded it as part and parcel of the disease and this may explain why there have been limited attempts to define its exact contribution to patient outcome or to evaluate methods of reversing its progress. Despite more intensive research of late, many fundamental questions still remain unanswered. These questions include: (i) what are the dominant pathophysiological factors which cause wasting and malnutrition to develop; (ii) what are the most reliable methods of assessing the nutritional status of cirrhotic patients; and (iii) what is the prognostic influence of malnutrition once it does develop? The aim of this article is to review these three basic issues.
TL;DR: As the pathogenetic mechanisms of inflammatory bowel disease are further elucidated, new forms of treatment will be developed, with studies looking at such agents as immunoglobulin G, eicosapentaenoic acid and a new specific inhibitor of 5-lipoxygenase.
Abstract: The aetiology of ulcerative colitis and Crohn's disease remains unknown. While this remains so, treatment must be directed towards pathogenetic mechanisms. Corticosteroids, sulphasalazine and the new salicylates, the immunosuppressants azathioprine, 6-MP and, more recently, cyclosporin and metronidazole have become the accepted and standard forms of treatment. The importance of maintaining nutritional status is often overlooked but must be considered in every patient. Recognition of the occurrence of disease in all age groups, and in particular in children and adolescents, is also important, as is an appreciation of the special problems involved. The possibility of surgery at some stage of the disease should be raised with the patient. As the pathogenetic mechanisms of inflammatory bowel disease are further elucidated, new forms of treatment will be developed. This is already happening, with studies looking at such agents as immunoglobulin G, eicosapentaenoic acid and a new specific inhibitor of 5-lipoxygenase. These offer hope of more potent drugs with low side-effect profiles that may complement or replace the currently available agents used in the management of inflammatory bowel disease.
Journal Article•
TL;DR: In order to explore multiple risk factors of hepatocellular carcinoma (HCC), a total of 13 737 male adult residents in 12 townships were studied for an average follow‐up period of 5.2 years.
TL;DR: Results indicate that in the Kure district in Japan, where HDV infection of persons infected with HBV is about 6%, such superinfection increases the risk of LC and HCC.
Abstract: To investigate the effect of hepatitis delta virus (HDV) superinfection on the long-term outcome of Japanese subjects with chronic hepatitis B virus (HBV) infection, we examined the presence of antibodies to hepatitis delta antigen (anti-HD) in serial serum samples collected from 1127 subjects with chronic HBV infection. The subjects were followed for at least 36 months (mean: 121.3 months) between 1973 and 1991. Among 69 cases where anti-HD was detected, eight (12%) developed liver cirrhosis (LC) and six (9%) developed hepatocellular carcinoma (HCC). However, among 1058 cases without anti-HD, there were 43 patients (4%) who developed LC and 29 (3%) who developed HCC. The prevalence of LC and HCC was significantly higher among the cases with anti-HD than those without anti-HD. The proportion of LC and HCC per 1000 person years was 10.46 and 7.84, respectively among cases with anti-HD, and 4.05 and 2.73 among those without anti-HD, respectively. The overall relative risk of LC and HCC was 2.58 and 2.87, respectively; 95% confidence interval (CI): LC, 1.14-5.13; HCC, 1.03-6.23. These results indicate that in the Kure district in Japan, where HDV infection of persons infected with HBV is about 6%, such superinfection increases the risk of LC and HCC.
TL;DR: In this paper, a total of 13 737 male adult residents in 12 townships were studied for an average follow-up period of 5.2 years, and Cox's proportional hazards models were used to analyse multiple risk factors of hepatocellular carcinoma.
Abstract: In order to explore multiple risk factors of hepatocellular carcinoma (HCC), a total of 13 737 male adult residents in 12 townships were studied for an average follow-up period of 5.2 years. Sociodemographic characteristics, history of cigarette smoking and alcohol drinking, dietary habits, as well as personal and familial history of chronic liver diseases were obtained through standardized interviews based on structured questionnaires at the recruitment. Blood samples were also collected from 9688 (71%) study subjects and examined for the hepatitis B surface antigen (HBsAg). A total of 60 new HCC cases occurred giving an incidence rate of 83.3 per 100 000 person-years. Cox's proportional hazards models were used to analyse multiple risk factors of HCC. In addition the HBsAg carrier status which showed a multivariate-adjusted relative risk of 17.0, cumulative cigarette smoking, alcohol drinking quantity, vegetarian habit and low vegetable consumption were associated with the development of HCC. The multivariate-adjusted relative risk was 1.8 for those who smoked 26 or more pack-years of cigarettes compared with non-smokers, 3.1 for those who drank alcohol 50 mL or more per day compared with those who were non-drinkers or drank less than 50 mL per day, 2.5 for vegetarians compared with non-vegetarians, as well as 4.6 and 2.6, respectively, for those who had a weekly vegetable consumption frequency of less than two meals and two to five meals compared with those who had a frequency of six or more meals.
TL;DR: Although a review of the literature shows this tumour to be rare and difficult to differentiate from a malignant lesion pre‐operatively, the pre‐operative diagnosis of angiomyolipoma is considered feasible when the characteristic findings are present.
Abstract: An asymptomatic patient with pre-operatively diagnosed solitary angiomyolipoma is reported. The tumour was a well defined, fat density mass on computerized tomography (CT) and magnetic resonance imaging (MRI), and a hyperechoic nodule with a sharp margin on ultrasonography (US). The lesion was hypervascular on arteriography and CT during hepatic angiography. Chemical shift MRI confirmed the fat component within the lesion. Although a review of the literature shows this tumour to be rare and difficult to differentiate from a malignant lesion pre-operatively, the pre-operative diagnosis of angiomyolipoma is considered feasible when the characteristic findings as described here are present.
TL;DR: It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.
Abstract: This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.
TL;DR: The therapeutic options for relief of cholestatic pruritus are summarized in Table 2 and Ursodeoxycholic acid and methotrexate have an advantage in not only relievingPruritus but also potentially retarding disease progression in PBC and PSC, respectively.
Abstract: The pathogenesis of pruritus of cholestasis remains unclear. Bile salts do not appear to be the sole prurogens in cholestasis. Histaminergic pathways may be involved, and central opiate receptor processes seem much more important than has previously been recognized. The therapeutic options for relief of cholestatic pruritus are summarized in Table 2. Resins such as cholestyramine are the first line of therapy. In cases where cholestyramine has failed, rifampicin and antihistamines may be beneficial. Opiate antagonists hold great potential if opioid withdrawal-like syndromes can be avoided. Ursodeoxycholic acid and methotrexate have an advantage in not only relieving pruritus but also potentially retarding disease progression in PBC and PSC, respectively, although this remains to be proved. Other agents such as EPO and SAMe remain experimental and require further study to clarify their effectiveness before they can be recommended.
TL;DR: The results suggest that eliminating free radicals is one of the protective mechanisms of PQQ and its derivatives against CCl4‐induced liver injury.
Abstract: Pyrroloquinoline quinone (PQQ) and its derivative, oxazo pyrroloquinoline (OPQ-G), protected rats from experimental liver injury induced by carbon tetrachloride (CCl4) in vivo. This effect was observed after an intraperitoneal injection of 5 mg/kg PQQ or OPQ-G, which was given twice, 10 min and 1 h before CCl4 administration. Pyrroloquinoline quinone protected primary cultured rat hepatocytes from CCl4 toxicity in vitro. This protection was most effective at a concentration of 3 mumol/L PQQ. Pyrroloquinoline quinone derivatives (oxazo pyrroloquinoline, methyl-thioethyl oxazo pyrroloquinoline and PQQ-allylester) also protected the hepatocytes from CCl4 toxicity. Pyrroloquinoline quinone and its derivatives inhibited the lucigenin-enhanced chemiluminescence from isolated hepatocytes initiated by CCl4. These results suggest that eliminating free radicals is one of the protective mechanisms of PQQ and its derivatives against CCl4-induced liver injury.
TL;DR: The amount ofHCV RNA in serum samples obtained from 85 patients with chronic hepatitis type C was determined and there was as much as a 100 000‐fold difference in the levels of HCV RNA from patient to patient.
Abstract: A method that allows the quantitation of hepatitis C virus (HCV) RNA is described. The RNA was extracted from serum samples and reverse transcribed. Target cDNA was then co-amplified by nested polymerase chain reaction with a known amount of competitive template at various concentrations. Since this internal control DNA uses the same primers as those of the target and is distinguishable from the target cDNA after amplification by size, the initial concentration of the target could be estimated by comparing the intensity of the two bands of amplified DNA fragments. That is, if the starting amount of the cDNA and the competitive template are equal, the intensity of the two bands should also be equal. Using this method the amount of HCV RNA in serum samples obtained from 85 patients with chronic hepatitis type C was determined. There was as much as a 100 000-fold difference in the levels of HCV RNA from patient to patient. A rapid decrease of HCV RNA in a patient treated with interferon is also described.
TL;DR: The results suggest that although IL‐8 may be involved in the inflammatory process in inflammatory bowel disease, it is a poor marker of disease activity.
Abstract: To investigate the relationship between serum concentrations of interleukin-8 (IL-8) and disease activity in inflammatory bowel disease, serum IL-8 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in 93 patients. Interleukin-8 levels were compared with plasma interleukin-6 (IL-6) levels in 80 of these patients. Interleukin-8 levels were also measured in ten patients with active Crohn's disease, before and after treatment with a defined formula polymeric diet. Of these patients, 70 out of 93 IL-8 concentrations were below the detection limit of the assay. Levels were higher in patients with active ulcerative colitis (median < 20 pg/mL, 75th centile value = 190) compared with inactive disease (median and 75th centile value < 20; P < 0.05). Interleukin-8 concentrations correlated with a combined score for disease severity and extent (P = 0.01). Thirty-eight per cent (8/20) of patients with active Crohn's disease also had high levels of IL-8 but there was no significant difference between active and inactive disease. There was no correlation between serum IL-8 and plasma IL-6; on the contrary, very few patients had raised blood levels of both cytokines. In the diet treated group, serum IL-8 fell significantly after treatment (median = 37 pg/mL, range < 20-4615 before treatment, median < 20, range < 20-104 after treatment; P = 0.03). The results suggest that although IL-8 may be involved in the inflammatory process in inflammatory bowel disease, it is a poor marker of disease activity.
TL;DR: The diagnosis and management of patients who have dyspepsia of unknown cause is critically reviewed.
Abstract: In clinical practice, gastroenterologists commonly encounter patients with chronic symptoms that appear to arise from the proximal gastrointestinal tract; yet, after initial evaluation, the majority of these patients do not have peptic ulceration or any other structural or biochemical explanation for their symptoms. This article will critically review the diagnosis and management of patients who have dyspepsia of unknown cause.
TL;DR: A cross‐sectional profile on 53 adults who have survived beyond 2 years following liver transplantation was developed, finding that there has only been one case of internal malignancy (lymphoma) although 19 patients attend regular dermatological review for skin cancer surveillance.
Abstract: Although hepatic transplantation is now a well-accepted treatment modality for end-stage liver diseases there are little detailed data on the clinical profile of patients who survive beyond 1 year following transplantation. The aim of this study was to develop a cross-sectional profile on 53 adults who have survived beyond 2 years following liver transplantation. These patients have been followed for a mean of 43.5 months (range 24–84) since the time of transplant. Nineteen patients had persisting liver enzyme abnormalities, 11 due to chronic viral hepatitis (seven hepatitis C virus, three hepatitis B virus), four due to biliary disease. Two had post severe rejection, one steatosis secondary to obesity while in one the aetiology was unclear. Nineteen (36%) of patients required anti-hypertensive medications. The median doses of Prednisone, Cyclosporin and Imuran were 7.5, 300 and 50 mg daily, respectively. The mean serum creatinine was 117 ± 27 μmol/L. However 22 (41%) had an elevated serum creatinine (> 120 μmol/L) but in only seven was the serum creatinine > 150 μmol/L. Fourteen (26%) of patients were obese (body mass index > 30) whilst 46% had a higher than recommended serum cholesterol (mean level 5.6 ± 1.5 μmol/L). There has only been one case of internal malignancy (lymphoma) although 19 patients attend regular dermatological review for skin cancer surveillance. Forty-eight patients had a Karnofsky Score > 80.
In conclusion, the vast majority of these patients have excellent clinical function but some caution is required with respect to renal function, hypertension, obesity and mild hypercholesterolaemia. Persisting liver abnormalities in 37% of patients highlight the need for continued close monitoring in the long term.
TL;DR: Liver disease does not feature among these common manifestations of SLE, and it was stated that clinically important liver disease was negligible, which would now appear to be an oversimplification.
Abstract: Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease associated with the development of auto-antibodies to a variety of self-antigens, particularly nuclear antigens. It is likely there are several different factors which induce the disease by impairing normal immune regulatory processes and breaking self-tolerance. In some individuals genetic predisposition may be very strong. In other cases environmental triggers such as viral infections may play the most important role. It is likely that the induction and mainienance of pathogenic autoantibodies is a ‘multi-hit’ process. The clinical manifestations of SLE are diverse and it may be difficult to establish a firm diagnosis in some patients. In 1982, the American Rheumatism Association published revised criteria for the classification of SLE and these have been widely accepted.’ For diagnosis of SLE, patients should have four or more of the following: malar rash, discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, pleuritis or pericarditis, renal disorder, seizures or psychosis, haematological disorder, immunological disorder or positive antinuclear antibody. These criteria have been particularly useful for standardizing patients entered in clinical studies. When used for individual diagnostic purposes however, they lack sensitivity for recognizing milder cases of SLE. Liver disease does not feature among these common manifestations of SLE. In classical descriptions of SLE, it was stated that clinically important liver disease was negligible. This statement would now appear to be an oversimplification. Mild liver dysfunction is not uncommon in typical cases of SLE. A few cases develop severe immunologically mediated liver disease and overlap with autoimmune chronic active hepatitis (AICAH). In addition, patients with active SLE seem particularly susceptible to drug-induced hepatic damage. Liver disease can also develop secondary to vascular occlusion related to the hypercoagulable states that occur in SLE. LIVER INVOLVEMENT COMMONLY OBSERVED I N SYSTEMIC LUPUS ERYTHEMATOSUS
TL;DR: This new approach revives controversies concerning cholecystectomy; namely indication, use of intra‐operative cholangiography, ductal calculi and pregnancy, and there are new issues to consider, including use of a Veress needle for pneumoperitoneum, type of trocars, cardiovascular responses to pneumoper Tone, and so on.
Abstract: In 1989 a new trend occurred in the surgical treatment of a diseased gall-bladder, laparoscopic cholecystectomy (LC). Laparoscopic surgery is now accepted world-wide as the choice of treatment with the advantages of less pain, good cosmesis, short hospital stay and early recovery. It is also a curative procedure for cholelithiasis as well as a cholecystectomy. The rate of conversion to open surgery is about 5% and the rates of bile duct injury are 0.1-0.6%. This new approach revives controversies concerning cholecystectomy; namely indication, use of intra-operative cholangiography, ductal calculi and pregnancy. There are new issues to consider, including use of a Veress needle for pneumoperitoneum, type of trocars, cardiovascular responses to pneumoperitoneum using carbon dioxide and so on. With increasing use, these difficulties will be overcome. Advances in technology are expected to make even more new types of surgery possible, even perhaps extending into robotic surgery.
TL;DR: Genital ulcers caused by venereal diseases due to frequent sexual contact with multiple partners, and use of unsterilized needles in ear‐piercing or tattooing play important roles in the high prevalence of HDV infection in prostitutes.
Abstract: Two hundred and sixty-three adult licensed, 233 adult and 157 teenage unlicensed prostitutes from Taiwan were studied for prevalence and risk factors of hepatitis D virus (HDV) infection. The hepatitis B carrier rate among the three groups was 21, 15 and 20%, respectively, not significantly different from that of the general population in this area. However, the prevalence of HDV infection among carrier prostitutes was 55, 36 and 16%, respectively, much higher than that in general hepatitis B carriers. Univariate analysis revealed that the history of conducting paid sex for more than 12 months (P < 0.03), ear-piercing (P < 0.02), tattooing (P < 0.02), and gonorrhoea or syphilis (P < 0.005) were significant factors associated with HDV infection among these subjects. Multivariate analysis revealed that the history of ear-piercing and venereal diseases (P < 0.001) were still significant. In summary, genital ulcers caused by venereal diseases due to frequent sexual contact with multiple partners, and use of unsterilized needles in ear-piercing or tattooing play important roles in the high prevalence of HDV infection in prostitutes.
TL;DR: UDCA is safe and effective in the treatment of Chinese PBC patients in stages I—III and the Mayo clinical risk score improved significantly after long‐term UDCA treatment.
Abstract: In order to evaluate the efficacy of ursodeoxycholic acid (UDCA) in the treatment of Chinese patients with primary biliary cirrhosis, a short-term, randomized, double-blind controlled, cross-over study was done with long-term follow up. In the first part of the study, 12 patients were randomly chosen to receive either UDCA 600 mg/day for 3 months followed by a placebo for 3 months or a placebo for 3 months followed by UDCA for 3 months. The clinical symptoms of pruritus improved when the patients were receiving UDCA but became worse when receiving a placebo. Mean serum levels of alkaline phosphatase (ALPase), gamma-glutamyl transferase (gamma-GT), total bilirubin, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase all decreased below the baseline values when receiving UDCA treatment and all increased above the baseline values when receiving the placebo. The difference was statistically significant. In the second part of the study, 19 patients received long-term UDCA treatment (mean 20 months). The clinical symptoms of pruritus improved in 90% of the pruritic patients. Serum levels of ALPase, gamma-GT and ALT fell significantly from the pretreatment values, 6, 12 and from the mean 20 months after UDCA treatment. Serum levels of total bilirubin fell significantly 6 and 12 months after UDCA treatment but did not reach statistical significance at the last follow up. No patient lost antimitochondrial antibody and elevated immunoglobulin levels did not improve significantly, but the Mayo clinical risk score improved significantly after long-term UDCA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: The remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.
Abstract: Over the past 15-20 years, research has progressively focused on the mucosal T cell as the central factor in the initiation of physiological or pathological changes, first in the growth and maturation of the early (postnatal) intestine, and second in adult-type enteropathies resulting from sensitivity to either food or pathogen-derived antigens. T cell-mediated events may be measured, for example, in terms of specific immunopathologic patterns of change and injury, such as type 1 (lymphocyte infiltration), type 2 (crypt hyperplasia) and type 3 (flat-destructive), which can be recognized and quantitated microscopically; by determination of lymphocyte reactivity through secretion of interleukin-2 receptors (IL-2R) into plasma or expression by mucosal lymphocytes; by quantitation of lymphocyte subsets emigrating into inflamed tissues by immunoperoxidase-labelled monoclonal antibodies; or by the determination of T cell receptor polymorphisms. Alterations in intestinal growth, structure and function at weaning are likely to be T cell-mediated as they are analogous to the same type 1/2 lesions that reflect modulation of adult mucosal architecture in food and parasite-induced hypersensitivity reactions. Enteropathies associated with HIV infection and T cell deficiency display a milder degree of villous flattening and impaired crypt hyperplasia than that typical of gluten-sensitivity, suggesting a reversion to lesser degrees of mucosal pathology (type 1/2). Clearly more information will accrue; meanwhile the remarks in this brief survey should provide a firm basis whereby clinician and scientist can meet, and together recognize and further dissect the modulatory effect of T lymphocytes on mucosal structure and function.