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Safety and efficacy of interferon alpha-2b following prednisone withdrawal in the treatment of chronic viral hepatitis B. A case-controlled, randomised study.

The therapeutic effects of interferon alpha-2b (Intron A; Scherag) in patients with chronic active hepatitis caused by hepatitis B virus (HBV) were assessed in a randomised, case-controlled clinical trial conducted between January 1988 and June 1990. Treatment involved a short course of prednisone followed by interferon alpha-2b, initially 10 million U by subcutaneous injection, 3 times a week for 16 weeks. All patients were symptomatic, were known to have had hepatitis B surface antigen and hepatitis B e antigen (HBeAg) in their blood for at least 6 months, and had elevated serum aminotransferase activities with histological evidence of chronic active hepatitis. Patients with carcinoma, renal or haematological abnormalities or decompensated cirrhosis were excluded. In 6 of 10 patients randomised to receive interferon and 1 of 10 controls, HBeAg and HBV DNA were cleared from the blood during the 12-month study period (P < 0.05). An indeterminate response with clearance of HBV DNA but persistence of HBeAg was noted in 1 patient receiving interferon. Serum aminotransferase levels decreased only in those patients who had responded to treatment, but this did not reach statistical significance for the group as a whole. Histological studies, where available, showed decreased hepatic periportal necrosis in patients who underwent treatment. Two patients relapsed to HBeAg-positive status 2 months after their initial seroconversion; 1 became clear again during a repeat course of interferon. Side-effects of treatment were common and included fever, malaise, myalgias and myelosuppression. One patient developed hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Clinical comparisons of 1,498 chronic renal failure patients with and without tuberculosis.

OBJECTIVE: To investigate the clinical characteristics of chronic renal failure (CRF) patients suffering from tuberculosis. METHODS: Clinical materials from CRF inpatients in our department suffering from tuberculosis from 1997 to 2003 were investigated and compared with similar data from tuberculosis patients without CRF in Chongqing City (China) during the same period. RESULTS: Of the 1,498 tested CRF inpatients, 71 suffered from tuberculosis, more than half of which suffered from atypical type V tuberculosis (lesion spot uncertain). The incidence of tuberculosis in the CRF inpatients (4740/100,000) was significantly higher than that in Chongqing City (151/100,000; P<.001). We found an inverse association between renal function and tuberculosis; the worse the renal function, the higher the tuberculosis incidence. CRF patients suffering from tuberculosis had fewer positive antituberculosis-antibody and purified protein-derivative tests (12.7% and 15.5%, respectively) than did tuberculosis patients without CRF (72.1% and 58.1%, respectively; P<.05). In CRF patients with tuberculosis, the two-thirds dosage antituberculosis drug treatment was effective. Twelve cases had good outcome after a 1-year course of antituberculosis treatment and then kidney transplantation. In contrast, 4 patients who received less than half a year of antituberculosis treatment died after kidney transplantation, in association with relapsed tuberculosis. CONCLUSION: CRF patients are susceptible to tuberculosis, especially to atypical tuberculosis outside the lung. Thus, antituberculosis treatment might be necessary in CRF patients found to be suffering from chronic fevers of unknown origin. Furthermore, it appears to be safe for patients with CRF plus tuberculosis to receive kidney transplantation after 1 year of antituberculosis treatment.

Adult↗

[Detection of pulmonary tuberculosis. Special characteristics of patients detected while receiving treatment for other diseases].

Tuberculosis (TB) detection is mainly classified as being either passive case-finding, at a hospital, or positive case-finding through a mass screening. Pulmonary TB patients detected while being examined for other complaints at a hospital are classified as passive findings. It is suspected that these patients have special characteristics which separate them from patients that are detected only after the onset of TB symptoms. The aim of this study is to elucidate those special characteristics of patients where detection occurred while being examined for other diseases by comparing them with patients detected by the other means. A survey was conducted on 686 pulmonary TB patients, diagnosed between 1986 and 1988, from the area served by the Kochi Prefectural Chuo Health Center, with the following results. 1) Among the 533 patients who were detected at a hospital, and excluding those detected by mass screening, 331 patients were detected only after the onset of TB symptoms (group B), with 202 patients being treated for other diseases before being diagnosed as having TB (classified as group A). In group A, 130 patients were detected because of manifesting additional symptoms related to tuberculosis such as fever and cough (group A-1), while the remaining 72 patients were detected by chance while being examined for other diseases (group A-2). 2) The number of elderly people and relapse cases was higher in group A compared to B group and the group detected by mass screening. 3) Symptoms, the rate of tubercle bacillus positives, and the period from the onset of symptoms to diagnosis (defined delay) in group A-1, were similar to group B. In group A-2, symptoms and the rate of tubercle bacillus positives were less than those of the other groups. 4) From the above findings, it is concluded that passive case-findings should be classified into 3 distinct groups.

Adolescent↗

[Chronic cryptogenic pneumonia].

We report a case of a 72 year old man with the appropriate criteria for the recently identified chronic cryptogenic pneumonia: dyspnoea, cough, low general state, fever, raised sedimentation rate, localised opacities on the chest x-ray; no cause has been identified; the patient will improve on steroid therapy even though antibiotics are without effect, but relapses on stopping the steroids. A lung biopsy shows a predominant intra-alveolar fibrosis. A definitive cure can be obtained by 12 weeks of steroid therapy.

Aged↗

Infective endocarditis in a community hospital.

Recent reviews from major university centers of infective endocarditis have stressed an increase in unusual infections owing to virulent pathogens. This article compares the 40 episodes of infective endocarditis at a community hospital complex with the recent literature. It was observed that the majority of infecting microorganisms were penicillin-susceptible streptococci similar to those seen in the early antibiotic era. An older patient population was encountered, but overall mortality was low. Streptococcus bovis was a frequent cause of both natural and prosthetic valve infections. Symptoms lasting longer than two months were associated with vegetations demonstrated by echocardiography and high morbidity. Clinical features in this series that significantly correlated with a poor prognosis were height of fever at admission, the failure of fever to resolve within one week of appropriate therapy, the degree of peripheral leukocytosis, gross hematuria, and CNS signs. Conservative parenteral treatment closely monitored by serum bactericidal levels was employed. No relapses occurred among patients surviving initial therapy.

Aged↗

[Atopic dermatitis].

Atopic dermatitis (AD) is a multifactorial skin disease with a chronic or a chronic-relapsing course which often starts during infancy. The persistence rate of AD after the puberty is certainly higher than mostly assumed. 60% of the patients also develop respiratory atopies as hay fever or bronchial asthma. The etiology of this distressing skin condition is still obscure, but an immunological disturbance of the T-cell immune response is most probably implicated in its pathogenesis. The demonstration of IgE-bearing epidermal Langerhans cells with high-affinity receptors for IgE opens up new perspectives in its pathophysiology. As no efficient treatment of AD is known and a symptomatic treatment, local with emolients, corticosteroids and/or disinfectants as well as internal with antihistamines, is often difficult and unsatisfactory, prevention is of particular importance. The efficacy of prolonged breast-feeding, a strict prohibition of cow milk, egg, fish--during the first six months of life--and of keeping pets as well as a consequent treatment against house-dust mites can reduce the incidence of AD in 'at risk' children with a family history of atopy. Besides symptomatic treatment a substitution of essential fatty acids, a UV therapy and a climate therapy are other possible approaches in the management of such patients.

Adolescent↗

Immunomagnetic CD4+ and CD8+ cell depletion for patients at high risk for severe acute GVHD.

Acute GVHD remains a major problem in allogeneic BMT, in particular when donors other than HLA-identical siblings are used. To determine the efficacy of an immunomagnetic method for depletion of CD4+ and CD8+ lymphocytes from the marrow graft, a series of 15 patients was studied. Thirteen patients had matched unrelated donors, and two patients had related donors. Cyclosporine was used as GVHD prophylaxis in combination with CD4+ and CD8+ depletion, which removed 94.1 +/- 3.2%, 97.0 +/- 5.1%, and 96.7 +/- 3.1% of CD3+, CD4+ and CD8+ cells, respectively. All patients engrafted promptly with AGC > 500/mm3 after a median of 16 days post-BMT. Acute GVHD grade II-IV developed in 0/2 related transplants and 4/13 MUD transplants; only one patient had grade III-IV acute GVHD. No late graft failure was observed. Three patients relapsed; two had advanced disease at the time of BMT. Seven patients are alive and in CCR after a median of 497 days; actuarial survival is 39% at 24 months. The fever syndrome observed with selective CD8+ cell depletion was not seen with the combined CD4+ and CD8+ cell depletion. Immunomagnetic CD4+ and CD8+ cell depletion of marrow grafts, in combination with in vivo cyclosporine, is a simple, reproducible and effective method to decrease the incidence and severity of acute GVHD in patients at high risk for this complication after allogeneic BMT.

Acute Disease↗

Classical Hodgkin's disease. Clinical impact of the immunophenotype.

Antibodies against CD15, -30, and -20 are often used to support morphological diagnosis of Hodgkin's Disease (HD). The classical HD, i.e., the non-lymphocyte-predominance types, are CD15+, CD30+, and CD20- in general. However, the results for CD15 are less clear-cut in many studies, showing up to 40% of classical HD that lack positivity for this maker. Little is currently known about the relevance of antigen expression in relation to clinical outcome in HD. Therefore, the three markers were analyzed in 1751 cases from the German Hodgkin Study Group, using micro-wave epitope retrieval to optimize staining sensitivity. Eighty-three percent of the cases showed a classical immunophenotype (CD15+, CD30+, CD20-), twelve percent lacked CD15 positivity (CD15-, CD30+, CD20-), and five percent showed other combinations. For 1286 cases, clinical follow-up was available, which revealed significant differences for freedom from treatment failure (P = 0.0022) and overall survival (P = 0.0001) between cases with classical immunophenotype and CD15 negativity (CD30+, CD20-). Multivariate Cox regression using the three markers, age, sex, histology, stage, B-symptoms (fever, sweats, weight loss > 10% of body weight), hemoglobin, and erythrocyte sedimentation rate as factors showed that lack of CD15 expression in classical HD is an independent negative prognostic factor for relapses (P = 0.022) and survival (P = 0.0035). In conclusion, immunohistochemistry is able to identify classical HD cases with unfavorable clinical outcome.

Adolescent↗

Post-remission intensive consolidation with high-dose cytarabine-based chemotherapy and granulocyte colony-stimulatory factor in adults with acute myelogenous leukemia: a preliminary report.

BACKGROUND: Modern induction chemotherapy produce 60% to 80% complete remission in adults with newly diagnosed acute myelogenous leukemia (AML). A major challenge is to eradicate subclinical disease in remission and prevent leukemic relapse. Intensive post-remission chemotherapy was proved of comparable disease-free survival as BMT. METHODS: From February 1992 to to March 1995, twelve patients with AML, aged 15 to 57 y/o, received intensive consolidation chemotherapy immediately after the first complete remission. The chemotherapy included either 4 courses of high dose Arac (HiDAC), 3 gm/m2 q12h x3 days, or 2 courses of HiDAC (4 days) plus mitoxantrone for 3 days and etoposide for 7 days (HiDAC-3-7). Granulocyte colony-stimulating factor (G-CSF) used used 24 hours after chemotherapy until absolute neutrophile count greater than 500/mm3. RESULTS: Totally 24 courses of high dose chemotherapy were given. The median duration of severe neutropenia (absolute neutrophile count < or = 500/mm3) was 12 days, thrombocytopenia (< or = 50,000/mm3) 18 days, fever > or = 38 degrees C 6 days, and from severe neutropenia (absolute neutrophile count < or = 500/mm3) was 12 days, thrombocytopenia (< or = 50,000/mm3) 18 days, fever > or = 38 degrees C 6 days, and from severe neutropenia (< or = 500/mm3) to infection 4 days. Infection was the most frequent complication during HiDAC treatment. No toxic death was noted. After a median follow-up of 16 months, early relapse was noted in 3 patients (2, 4, and 5 months, respectively), and late relapse in two patients (11 and 20 months, respectively). Seven patients remained in complete remission status after a median follow-up of 14+ months (7+ to 37+ months). CONCLUSIONS: Intensive consolidation chemotherapy is well tolerable and may prolong remission duration when used in the early post-remission phase of AML.

Adolescent↗

Interferon beta-1b is effective in Japanese RRMS patients: a randomized, multicenter study.

OBJECTIVE: To assess the efficacy of interferon beta-1b (IFNB-1b) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: The effects of IFNB in RRMS have been assessed in study populations comprised predominantly of white patients. MS in Japanese patients is different from that in white patients in that there are two different presentations--classic MS (C-MS) and optic-spinal MS (OS-MS)--and chronic progressive forms are infrequent. METHODS: A total of 205 Japanese patients with RRMS were randomized to receive 50 microg or 250 microg (1.6 or 8.0 MIU) IFNB-1b administered SC every other day for up to 2 years. The primary endpoint was annual relapse rate. Secondary endpoints included further relapse-related and MRI outcome measures, as well as changes in Expanded Disability Status Scale and Neurologic Rating Scale. Efficacy was assessed in 188 patients, and safety was assessed in 192 patients. Supplemental ad hoc subgroup analyses were also performed for patients with OS-MS and those with C-MS. RESULTS: Annual relapse rates were 0.763 in the 250 microg group and 1.069 in the 50 microg group, a relative reduction of 28.6% (p = 0.047). Results for all secondary endpoints favored 250 microg IFNB-1b. Subgroup analyses suggested that the magnitude and direction of treatment effect in patients with OS-MS and C-MS was similar, albeit not significant due to small sample size. CONCLUSIONS: Interferon beta-1b (IFNB-1b) 250 microg significantly reduced relapse rates and change in MRI lesion area in Japanese patients with relapsing-remitting multiple sclerosis, and seemed to be comparably effective in optic-spinal multiple sclerosis (MS) and classic MS. The response to treatment with IFNB-1b in Japanese patients with MS suggests that a common pathogenesis and underlying genetic characteristics are shared with white patients.

Adolescent↗

Cytokines and tumor vaccination.

Patients with locally advanced stages of renal cell carcinoma are at high risk of relapse or progress even after initial radical surgery. Based on the proven efficacy of adoptive and active immunotherapeutic approaches of metastatic renal cell carcinoma, a phase II trial was started in 1989 using autologous, Newcastle disease virus modified and lethally irradiated tumor cell vaccines in combination with low-dose recombinant interleukin-2 (1.8 million U) and recombinant interferon-alpha 2a (1.0 million U) for a surgical adjuvant treatment. Patients were vaccinated (subcutaneous injection) once a week for 8-10 weeks and the treatment was started about 4-10 weeks after surgery. Up to now more than 208 patients with locally advanced renal cell carcinoma (stages pT2-3a, N1-2, M0; pT3b-4, N0-2, M0) were vaccinated after initial radical surgery (tumor nephrectomy with lymph node dissection and ipsilateral adrenalectomy and if necessary in combination with en bloc removal of venous extensions). We overview a follow-up of 203 evaluable patients with a median disease-free survival of 21 months (range of 2-64 months). During this observation period 18 relapses (8.9%) were diagnosed with 3 local relapses (1.5%), 10 lymph node metastases (5%) and/or distant organ metastases in 9 cases (4.5%). These progressive patients' disease was treated by surgery and/or combined immunochemotherapy. Toxicity encountered on this tumor cell vaccination was mild (WHO grade 1) and was characterized by flu-like symptoms and fever up to 38.8 degree Celsius for some hours beginning at 4 hours after the vaccine/cytokine application. Occasionally a transient local inflammation at the site of injection was observed. The comparison of the risk-factor-adapted group of adjuvant treated renal cell carcinoma patients (locally advanced stages) with historical data gave evidence for an improvement in disease-free survival on vaccination treatment. Although this was not a prospective randomized trial, we can summarize that the surgical adjuvant treatment of autologous tumor vaccines in combination with low-dose cytokines may improve relapse-free and overall survival in patients with locally advanced renal cell cancer.

Adult↗

Fever of unknown origin: a review of 20 patients with adult-onset Still's disease.

In this study we aimed to investigate the findings in patients with adult-onset Still's disease (AOSD) admitted with fever of unknown origin (FUO) during the last 18 years in our unit, in order to discover the ratio of such patients to all patients with FUO during the same period, and to determine the clinical features of AOSD in FUO. The number and the aetiologies of the patients with FUO diagnosed between 1984 and 2001, and the clinical features of those with AOSD, were taken from the patient files. The diagnosis of AOSD was reanalysed according to the diagnostic criteria of Cush et al. [11]. The presumed diagnoses before a diagnosis of AOSD was established were also noted. The chi(2) and Fisher's exact tests were used for statistical analysis. We studied 130 patients with a diagnosis of FUO, 36 (28%) of whom had collagen vascular diseases. Of these 36 patients, 20 (56%, 12 female, 8 male, mean age 34 years, range 16-65) had AOSD. Clinical and laboratory findings were as follows: fever (100%), arthralgia (90%), rash (85%), sore throat (75%), arthritis (65%), myalgia (60%), splenomegaly (40%), hepatomegaly (25%), lymphadenopathy (15%), anaemia (65%), neutrophilic leukocytosis (90%), increased erythrocyte sedimentation rate (100%), elevated transaminase levels (65%), a negative RF (100%), and a negative FANA (80%). Antibiotics had been prescribed in 18 (90%) of cases. The presumed infectious diagnoses were streptococcal tonsillitis/pharyngitis (50%), infective endocarditis (four patients), sepsis (two patients) and acute bacterial meningitis (two patients). The presumed non-infectious diagnoses were acute rheumatic fever (three patients), seronegative rheumatoid arthritis (two patients) and polymyositis (two patients). Sixteen patients were followed for a mean duration of 30 months (range 2-59). A remission was obtained with indomethacin in three cases (19%), and with prednisolone in the remainder. Relapse was detected in three cases (19%). AOSD is one of the most frequent aetiologies of FUO. During the diagnostic course of a patient with FUO, a maculopapular rash and/or arthralgia and/or sore throat should raise the suspicion of AOSD. Because the disease has heterogeneous clinical findings, certain bacterial infections (e.g. streptococcal pharyngitis and sepsis) are generally considered and the prescribing of antibiotics is common.

Adolescent↗

High-intensity intravenous cyclophosphamide and cisplatin, interim surgical debulking, and intraperitoneal cisplatin in advanced ovarian carcinoma: a pilot trial with ten-year follow-up.

PURPOSE: This trial was undertaken to study the effect of intensified intravenous cyclophosphamide/cisplatin and interim surgical debulking, followed by intraperitoneal cisplatin on surgically defined complete remission rate and survival in advanced ovarian cancer. PATIENTS AND METHODS: Forty patients with stage IIB through IV ovarian cancer were entered and 36 were evaluable for response and survival and approximately 10 years. Following a first laparotomy for diagnosis and debulking, the patients received two cycles, spaced 28 days apart, of intravenous cisplatin 30-40 mg/m2/day with hypertonic saline for 4 to 5 days and cyclophosphamide 200 mg/m2/day for 5 days. A second laparotomy was done to further debulk remaining cancer and to place an intraperitoneal catheter. Four cycles of intraperitoneal cisplatin at 50 or 100 mg/m2 were administered 21 days apart and followed by a third laparotomy to define response and plan any further therapy. RESULTS: The surgically confirmed complete response rate was 47% and median survival is 68.3 months for this group. Ten of the 17 patients (58.8%) relapsed following complete response at a median of 19.5 months (range, 5-98). Both aggressive chemotherapy and surgery seemed to play a role in inducing this high complete response rate. Traditional prognostic factors, including stage and diameter of largest residual disease, had little apparent effect on likelihood of complete response or survival, whereas tumor grade had a more significant effect on survival. Nadir fever was experienced by 33% of patients but peripheral neuropathy was dose limiting. CONCLUSION: In the context of recent data failing to support any clinical benefit to modest increases in dose escalations of cisplatin or carboplatin, in this trial the high complete response rate suggests that the multimodality approach (i.e., interval surgical debulking and intraperitoneal cisplatin) is worthy of further study. The high relapse rate among complete responders and the unacceptable neurotoxicity also suggest that modifications could improve the results. The use of newer agents and further intensification (substituting carboplatin for cisplatin and the use of paclitaxel) with stem cell support are two examples.

Antineoplastic Combined Chemotherapy Protocols↗

Trimethoprim-sulphamethoxazole in the treatment of enteric fever.

Twenty-three patients with typhoid fever diagnosed by blood culture were treated with co-trimoxazole (trimethoprim/sulphamethoxazole, 1 :5) at a dosage of 10 mg trimethoprim/kg/day in two divided daily doses for 10 days. Twenty-two patients responded, the mean period to defervescence being three days and to relief of toxaemia being 1-7 days. Another nineteen patients with similarly proven typhoid were treated with chloramphenicol (100 mg/kg/day) in four divided daily doses for 10 days. Eighteen patients responded, defervescence occurring in an average of 4-1 days and relief of toxaemia in a mean of 2-6 days. None of the patients included in the study developed complications, relapses or became a convalescent carrier during the period of observation.

Child↗

[Study of 728 cases of children with acute articular rheumatism, divided into 2 similar groups observed at an interval of 10 years].

A group of 364 children treated for acute rheumatic fever between 1955 and 1961 was compared with a similar group of 364 cases matched for age between 1965 and 1972, treated in the same fashion. In the second group an increase was found in the percentage of first attacks compared with relapses, indicating an improvement from prophylaxis. Cardiac involvement on admission, in first attacks, is equally common in both groups but more severe in the first group: in relapses, the severity of cardiac involvement increases with the number of previous attacks. The course of the carditis with corticosteroid treatment is the same in both groups. The reduced severity of the cardiac involvement in first attacks in the recent group suggests a role played by earlier diagnosis, antibiotic therapy previous to hospitalization, or variations in the epidemic nature of the disease.

Adolescent↗