Effects of parathyroid hormone and serum calcium on the phenotype and function of mononuclear cells in patients with primary hyperparathyroidism

The University of Pennsylvania Smell Identification Test (UPSIT) and a smell ability questionnaire were administered to 167 Japanese volunteers ranging in age from 20 to 59 years. Of these subjects, 80 also received the T&T olfactometer threshold test. Of the latter subjects, 36 were patients tested before endoscopic nasal surgery for sinusitis and polyposis. The patients exhibited decreased smell function, as measured by the T&T olfactometer, the UPSIT, and a 30-item version of the UPSIT in which the 10 least familiar items were removed (ps < 0.001). Spearman correlations ranging from 0.53 to 0.70 were found between (i) scores on the 30- and 40-item UPSITs and (ii) the T&T detection and recognition threshold values. Significant correlations were found between scores on the smell ability questionnaire and the olfactory test measures (UPSIT30 r = 0.56; UPSIT40 r = 0.58; T&T detection r = 0.56; T&T recognition r = 0.69, p < 0.001), indicating that subjects are relatively accurate in assessing their olfactory ability. This study suggests that the 30 and 40-item UPSITs correlate well with measures derived from the T&T olfactometer, and that all three tests are sensitive to the smell loss of Japanese sinusitis/polyposis patients.     

SAMSON: a software package for the biopolymer primary structure analysis

One hundred and twenty seven patients belonging to Neurosurgery (49), Neuromedicine (48), Cardiac medicine (30) wards and Blood donors (30) as healthy controls were investigated for the prevalence of Toxoplasmosis by means of detecting specific IgM antibody against Toxoplasma gondii (T. gondii) employing Enzyme Immuno Assay (EIA). The detection rate of specific IgM antibody against T.gondii was found to be 32.7% (16/49) among Neurosurgery patients, 20.8% (10/48) among Neuromedical patients and 20% (6/30) among Cardiac medical patients. None of the voluntary blood donors tested was found to have T. gondii IgM antibody. Maximum prevalence rate was found among female patients undergoing Neurosurgery (42.3%) followed by Neuromedical patients (40%). There is an increasing rate of prevalence of Toxoplasmosis from the lower age group upto thirty years and a declining prevalence rate among the higher age groups. The present study revealed high prevalence rate of Toxoplasmosis in Neurosurgery patients (32.7%) and in particular among female (35.2%) than male (17.8%) patients.     

Prognostic role of troponin T versus troponin I in unstable angina pectoris for cardiac events with meta-analysis comparing published studies

Controversy exists as to the clinical roles and relative specificities of cardiac troponin T or I in patients with unstable angina pectoris (UAP). We measured troponin T and I levels on admission in 123 patients with UAP. Of the 107 patients with normal creatine kinase during the first 24 hours, troponin T and I were elevated in 14 and 13 patients, respectively. At 30 days, 5 of 14 patients (36%) with elevated troponin T and 3 of 93 patients (3.2%) with normal troponin T had acute myocardial infarction (odds ratio [OR], 16.7; 95% confidence interval [CI] 3.4 to 81.5; p <0.001). Of 13 patients with elevated troponin I, 5 patients (39%) and 3 of 94 patients (3.2%) with normal troponin I had acute myocardial infarction (odds ratio, 21.7; 95% CI 4.3 to 110; p <0.001). No deaths occurred within 30 days. Both markers demonstrated equivalent sensitivity (63%) and specificities (troponin T: 91%; troponin I: 92%) for myocardial infarction. Meta-analysis of 12 published troponin T and 9 troponin I studies in patients with UAP produced risk ratios of 4.2 (95% CI 2.7 to 6.4, p <0.001) for troponin I compared with 2.7 (95% CI 2.1 to 3.4, p <0.001) for troponin T. Comparison of the sensitivities and specificities of both markers using summary receiver operating characteristic curves showed no significant difference in their abilities to predict acute myocardial infarction and cardiac death. Troponin T and I show similar prognostic significance for acute myocardial infarction or death in the same patients with UAP. The 2 markers are equally sensitive and specific, as confirmed by meta-analysis, and this supports a role in risk stratification.     

Pediatric cardiology from its beginnings to the century that approaches]

Activation of the T-cell receptor (TCR) results in recruitment of tyrosine kinases and changes of tyrosine phosphorylation levels. We quantitatively analyzed protein phosphorylation of resting and TCR stimulated T cells for healthy donors and immunocompromised patients using two-colour flow cytometry. Stimulation of T cells of healthy persons by OKT3 antibody led to a biphasic increase of phosphotyrosine levels with the first peak after 15 s and the absolute maximum occurring after 3-5 min. Levels remained high up to 30 min and returned to baseline levels afterwards. Compared to healthy blood donors, the phosphotyrosine baseline levels were 20-30% increased in patients after bone marrow transplantation (BMT). Using OKT3 to stimulate T cells of BMT patients led to strong increases in phosphotyrosine levels comparable to those of controls. In contrast, the response of T cells of human immunodeficiency virus-infected patients with acquired immune deficiency syndrome was severely impaired (P = 0.01). In conclusion, this flow cytometric methodology enables analyses of changes in cellular phosphotyrosine levels following TCR stimulation. The increased baseline levels in BMT patients and the observed unresponsiveness of T cells in AIDS patients could be of interest for the study of predictors of graft-versus-host reactivity and the clinical analysis of immune functions in AIDS patients, respectively.     

In vivo relevance of CD30 in atopic dermatitis

CD30 expression was evaluated by immunohistochemistry in lesional skin biopsies of eight patients with active atopic dermatitis (AD) and three patients with allergic contact (nickel-induced) dermatitis (ACD). CD30 expression was also assessed in a large panel of CD4+ and CD8+ T-cell clones generated from the skin biopsies of four patients with AD. Finally, the levels of soluble CD30 (sCD30) were measured in the serum of 41 patients with AD, 19 patients with ACD, and 60 healthy controls. In all specimens of lesional AD skin, where the great majority of infiltrating cells were CD4+ T cells, remarkable numbers of cells were CD30+, whereas virtually no CD30+ cells were found in the skin of patients with ACD. In CD4+ T-cell clones generated from the lesional AD skin, most of which produced both interleukin (IL)-4 and interferon-gamma (IFN-gamma) (Th0-like cells) or IL-4 and IL-5, but not IFN-gamma (Th2-like cells), CD30 expression directly correlated with the ability to produce IL-4 and IL-5, but was inversely related to IFN-gamma production. High levels of sCD30 (correlated with disease activity: r = 0.618) were detected in the serum of most AD patients, whereas there was no increase of sCD30 levels in the serum of patients with ACD. These data support the view that Th0/Th2-type responses predominate in the skin of patients with AD and suggest that the presence of CD30+ T cells in tissues and/or increased levels of sCD30 in biologic fluids are indicative of Th2-dominated responses.     

Magnetic resonance imaging of lower extremity muscles and isokinetic strength in foot dorsiflexors in patients with prior polio

The thigh and lower leg of six patients with prior polio were examined using magnetic resonance imaging (MRI), and the strength of their weak foot dorsiflexors was measured isokinetically. Spinecho images of the lower extremities were visually evaluated on a semi-quantitative four-point scale, and T1 and T2 relaxation times of the lower leg anterior compartment were analysed. There were prominent MRI signs of randomly distributed muscle degeneration. The high signal intensity changes in the affected muscles on T1-weighted images and T1 and T2 values indicated replacement of muscle fibres with fat and the accumulation of tissue water, respectively. MRI findings were compared with isokinetic strength in foot dorsiflexor muscles. Foot dorsiflexor peak torque values at 30 deg/s ranged from 6 to 29 Nm. There was no significant correlation between MRI visual scoring, T1 and T2 relaxation times and peak torque values at 30 deg/s. However, the most severe MRI changes with visual scoring and T2 relaxation times were observed in the patients with the most pronounced muscle weakness.     

Circulating skin-homing T cells in atopic dermatitis. Selective up-regulation of HLA-DR, interleukin-2R, and CD30 and decrease after combined UV-A and UV-B phototherapy

BACKGROUND: As the cutaneous lymphocyte-associated antigen appears to detect circulating T cells that migrate to the skin in atopic dermatitis but not T cells that migrate to mucosal sites in allergic asthma and rhinitis, we investigated T-cell activation markers and CD30 on the cutaneous lymphocyte-associated antigen-positive circulating T-cell subset in atopic dermatitis to see whether these markers are different from those in normal controls and related to disease activity. DESIGN: Open study. SETTING: University referral center. PATIENTS: Twelve patients with atopic dermatitis and 12 healthy controls. INTERVENTION: Combined UV-A and UV-B treatment for 2 months. MAIN OUTCOMES MEASURES: Percentage of circulating cutaneous lymphocyte-associated antigen-positive T cells that express HLA-DR, interleukin-2 receptor, CD69, CD71, and CD30 (triple-color flow cytometric analysis). Clinical score, Dermatology Life Quality Index, pruritus score, and consumption of topical corticosteroids were determined. RESULTS: Increased relative numbers of cutaneous lymphocyte-associated antigen-positive T cells expressing HLA-DR, interleukin-2 receptor, and CD30 were found in patients with atopic dermatitis before treatment. Treatment with UV-A and UV-B was associated with clinical improvement and a decrease of levels of HLA-DR, interleukin-2 receptor, and CD30 in cutaneous lymphocyte-associated antigen-positive T cells. HLA-DR on cutaneous lymphocyte-associated antigen-positive T cells correlated significantly with the clinical score. CONCLUSION: Expression of HLA-DR and interleukin-2 receptor is a sensitive marker of disease activity in atopic dermatitis. Apart from giving information on disease activity in atopic dermatitis, the availability of skin-seeking T cells in the blood offers the opportunity to obtain further information on T cells that may have effector function in the skin.     

Magnetic resonance imaging of the wrist in defining remission of rheumatoid arthritis

OBJECTIVE: To assess the efficacy of magnetic resonance imaging (MRI) in objectively defining a state of remission in rheumatoid arthritis (RA) after treatment. METHODS: Ten patients with RA involving the wrist were evaluated before treatment with methotrexate and hydroxychloroquine, and then mean 14 mo later with a followup evaluation. Clinical variables, laboratory measurements, and MRI using various techniques (T1 weighted image, T2 weighted image, fat suppression T2 weighted image, postcontrast T1 weighted image, postcontrast dynamic image, postcontrast 3 dimensional image) were observed. Remission was defined by ACR criteria. MRI changes were observed using 3 variables: extent of synovial proliferation; extent of bone marrow edema; and development of new erosion. In 6 of 10 patients, synovial signal intensity time curve changes at 30 s (E30 ratio) were determined for quantitative assessment of synovitis. RESULTS: Four patients achieved remission and 6 did not. All patients in remission showed decrease in extent of synovial proliferation and bone marrow edema with no newly developed erosion after treatment, compared to baseline. Five of 6 patients in nonremission showed newly developed erosions with variable changes in extent of synovial proliferation and bone marrow edema. E30 ratio was determined in 3 patients in the remission group and 3 in the nonremission group, with 48% reduction in the former compared to 9% reduction in the latter. CONCLUSION: MRI is feasible for objectively defining remission and assessing the therapeutic effect of antirheumatic drugs; utility of MRI measures in clinical remission criteria remains to be verified.     

Efficacy of dose-intensified MEC (methotrexate, epirubicin and cisplatin) chemotherapy for advanced urothelial carcinoma: a prospective randomized trial comparing MEC and M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin). Japanese Urothelial Cancer Research Group

BACKGROUND: To evaluate the antitumor activity in patients with T3b, T4 or metastatic urothelial carcinoma treated with MEC or M-VAC chemotherapy, by performing a multi-center randomized prospective study. METHODS: From 1991 to 1995, 89 patients with T3b, T4 or metastatic urothelial carcinoma were randomly allocated to a methotrexate, epirubicin and cisplatin chemotherapy group (arm 1: S-MEC therapy; n = 29), a dose-intensified MEC therapy combined with G-CSF group (arm 2: I-MEC therapy; n = 30) or a methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy (arm 3: M-VAC therapy; n = 30). At the registration center, the patients were stratified into previously untreated patients and patients with recurrence after radical operation and then randomly allocated to the treatment groups. In each arm, two or more courses of chemotherapy (4-week cycles) were performed. RESULTS: Of the 88 eligible patients, four treated with S-MEC therapy and two treated with I-MEC therapy showed CR. The response rates (CR + PR) were 52% (15/29) with S-MEC therapy, 76% (22/29) with I-MEC therapy and 47% (14/30) with M-VAC therapy. The response rate with I-MEC therapy was significantly higher than that with M-VAC therapy (P = 0.02). Although the incidence of leukopenia was low with I-MEC therapy, the incidence of thrombocytopenia was high with this therapy. CONCLUSION: MEC therapy used in this study is promising in terms of the antitumor effects.     

T cells from patients with Hodgkin's disease have a defective T-cell receptor zeta chain expression that is reversible by T-cell stimulation with CD3 and CD28

To investigate the mechanisms underlying the deficiency of T lymphocytes from patients with Hodgkin's disease, we investigated the expression of the T-cell receptor (TCR) zeta chain in patients with Hodgkin's disease. By flow cytometry using an anti-zeta chain monoclonal antibody, peripheral blood T lymphocytes from patients with untreated Hodgkin's disease were shown to express decreased levels of the TCR zeta chain. After stimulation by combined CD3 and CD28 cross-linking, T cells from Hodgkin's disease patients upregulated zeta chain protein expression to normal values within 48 hours and achieved a cytolytic potential and levels of interleukin (IL)-2 secretion that were not different from T cells obtained from healthy controls. These results show that downregulation of the TCR zeta chain in Hodgkin's T lymphocytes is a reversible event. Costimulation of CD3 and CD28 is a novel approach for overcoming the T-cell deficiency in Hodgkin's disease and might be exploited clinically. As upregulation of the zeta chain can also be achieved using bispecific monoclonal antibodies (BI-MoAbs) with specificity for tumor antigens and CD3 and CD28, respectively, an immunotherapy with CD3/CD30 and CD28/CD30 Bi-MoAbs may overcome and should therefore, not be jeopardized by the inherent T-cell deficiency in patients with Hodgkin's disease.     

Carcinoma of the tonsillar fossa: prognostic factors and long-term therapy outcome

PURPOSE: To identify prognostic parameters and evaluate the therapeutic outcomes for patients with carcinoma of the tonsillar fossa treated with three treatment modalities. METHODS AND MATERIALS: The results of therapy are reported in 384 patients with histologically proven epidermoid carcinoma of the tonsillar fossa; 154 were treated with irradiation alone (55-70 Gy), 144 with preoperative radiation therapy (20-40 Gy), and 86 with postoperative irradiation (50-60 Gy). The operation in all but four patients in the last two groups consisted of an en bloc radical tonsillectomy with ipsilateral lymph node dissection. RESULTS: Treatment modality and total irradiation doses had no impact on survival. Actuarial 10-year disease-free survival rates were 65% for patients with T1 tumors, 60% for T2, 60% for T3, and 30% for T4 disease. Patients with no cervical lymphadenopathy or with a small metastatic lymph node (N1) had better disease-free survival (60% and 70%, respectively) at 5 years than those with large or fixed lymph nodes (30%). Primary tumor recurrence (local, marginal) rates in the T1, T2, and T3 groups were 20-25% in patients treated with irradiation and surgery and 31% for those treated with irradiation alone (difference not statistically significant). In patients with T4 disease treated with surgery and postoperative irradiation, the local failure rate was 32% compared with 86% with low-dose preoperative irradiation and 47% with irradiation alone (p = 0.03). The overall recurrence rates in the neck were 10% for N0 patients, 25% for N1 and N2, and 35-40% for patients with N3 cervical lymph nodes, without significant differences among the various treatment groups. The incidence of contralateral neck recurrences was 8% with the various treatment modalities. On multivariate analysis the only significant factors for local tumor control and disease-free survival were T and N stage (p = 0.04-0.001). Fatal complications were noted in 7 of 144 (5%) patients treated with preoperative irradiation and surgery, 2 of 86 (2%) of those receiving postoperative irradiation, and 2 of 154 (1.3%) patients treated with radiation therapy alone. Other moderate or severe nonfatal sequelae were noted in 30% of the patients treated with preoperative irradiation and surgery, in 53% treated with postoperative irradiation, and in 19% receiving radiation therapy alone. CONCLUSION: Primary tumor and neck node stage are the only significant prognostic factors influencing locoregional tumor control and disease-free survival. Treatment modality had no significant impact on outcome. Radiation therapy remains the treatment of choice for patients with stage T1-T2 carcinoma of the tonsillar fossa. In patients with T3-T4 tumors and good general condition, combination surgery and postoperative irradiation offers better tumor control than single-modality and preoperative irradiation procedures, but with greater morbidity.     

Differential proliferative and interleukin-10 responses to fractionated filarial antigens: preferential recognition by patients with chronic lymphatic dysfunction

To characterize filarial antigens that may be associated with the development of chronic lymphatic dysfunction in persons with lymphatic filariasis, T cell responsiveness to Brugia pahangi adult worm extracts and SDS-PAGE antigen fractions were examined among Haitians from an area in which Wuchereria bancrofti is endemic. Greater T cell proliferation and interleukin-10 (IL-10) production were observed in amicrofilaremic patients with hydrocele or elephantiasis than in amicrofilaremic or microfilaremic asymptomatic persons. Antigen fractions that stimulated the highest proliferative responses (in the 25-49 kDa range) and IL-10 production were not identical. Further separation of an immunodominant 30- to 38-kDa fraction by ion exchange high-pressure liquid chromatography identified several subfractions, including a 32-kDa protein band, that elicited T cell responses from patients with elephantiasis or hydrocele. By immunoblot, these patients also had markedly greater humoral reactivity to parasite antigens of approximately 52, 43, 32, and 30 kDa.     

Electrocardiographic and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 +/- 114 vs 443 +/- 54 ms [mean +/- SD], P < 0.01), a larger precordial QT dispersion (50 +/- 74 vs 27 +/- 26 ms, P < 0.05), and a lower T wave amplitude (0.12 +/- 0.21 vs 0.24 +/- 0.16 mV, P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 +/- 26 vs 489 +/- 74 ms, P < 0.001), a larger QT dispersion in precordial (82 +/- 7 vs 54 +/- 52 ms, P < 0.01) and extremity leads (163 +/- 0 vs 40 +/- 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.     

Persistence of porcine reproductive and respiratory syndrome virus in intensive farrow-to-finish pig herds

We analyzed signal-averaged electrocardiograms (ECG) obtained in 50 patients with recent myocardial infarction (RMI: 25 anterior and 25 inferior) and 20 normal subjects to determine the relationship between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size. We examined (1) the root mean square voltage (RMS10-40, microV), (2) the integration (A10-40, microV.msec) at 10-msec intervals over the first 40 msec of the signal-averaged QRS complex, and (3) the intervals (T) of the magnitude of the signal-averaged ECG achieved at 10-microV intervals over the first 40 microV (T10-40, msec). The mean RMS10-40 (p < 0.01) and A10-40 (A10, p < 0.05; A20-40, p < 0.01) were significantly lower and the T10-40 (p < 0.01) was significantly longer in RMI patients than in normal subjects. The RMS10-40 (p < 0.01) and A10-40 (p < 0.05) were significantly lower and the T10-40 (T10.20, p < 0.01; T30.40, p < 0.05) was significantly longer in patients with anterior RMI patients than in patients with inferior RMI. The A30 was correlated with the ejection fraction and total creatine kinase (CK) release in all patients (r = 0.73, and -0.78, respectively, p < 0.001). These results suggest that the A30 may be an important predictor of ventricular dysfunction and infarct size in patients with RMI.     

Local expansion of allergen-specific CD30+Th2-type gamma delta T cells in bronchial asthma

BACKGROUND: T lymphocytes infiltrating airways during the allergic immune response play a fundamental role in recruiting other specialized cells, such as eosinophils, by secreting interleukin 5 (IL-5), and promoting local and systemic IgE synthesis by producing IL-4. Whether these presumed allergen-specific T cells are of mucosal or systemic origin is still a matter of conjecture. MATERIALS AND METHODS: Immunophenotype, IL-4 production, and in vitro proliferative response to specific or unrelated allergens were analyzed in the bronchoalveolar lavage (BAL) fluid lymphocyte suspensions obtained from untreated patients with allergic asthma. Healthy subjects and patients affected by pulmonary sarcoidosis, a granulomatous lung disease characterized by infiltrating Th1 CD4+ lymphocytes, served as controls. RESULTS: The proportions of gamma delta T lymphocytes, mostly CD4+ or CD4- (-)CD8-, was higher in asthmatic subjects than in controls (p < 0.05). Most BAL gamma delta CD4+ lymphocytes of asthmatic patients displayed the T cell receptor (TCR)-gamma delta V delta 1 chain. While CD30 antigen coexpression on the surface of BAL alpha beta(+) T lymphocytes was low (ranging from 5 to 12%), about half of pulmonary gamma delta T cells coexpressed it. These cells produced IL-4 and negligible amounts of interferon-gamma (IFN gamma), and proliferated in vitro in response to purified specific but not unrelated allergens. In contrast, control or sarcoidosis gamma delta T cells never displayed the CD30 surface molecule or produced significant quantities of IL-4. CONCLUSIONS: These findings not only confirm our previous hypothesis that the allergen-specific Th2-type lymphocytes found in the lungs of asthmatic patients are gamma delta T cells belonging to airway mucosal immunocytes, but also strongly support the notion that asthma is a local rather than a systemic disease.     

Association of Ureaplasma urealyticum biovars with clinical outcome for neonates, obstetric patients, and gynecological patients with pelvic inflammatory disease

In this prospective study, the prevalence of the two Ureaplasma urealyticum biovars, parvo and T960, was determined in pregnant women and in gynecological patients colonized by ureaplasmas. Furthermore, we investigated the association of these biovars with gynecological complications and adverse pregnancy outcome. Isolates of U. urealyticum from 254 women were biotyped by a PCR method recently developed. The parvo biovar was found in 81% (206 of 254) of the patients, and the T960 biovar was found in 30% (76 of 254) of the patients; 6% (14 of 254) of the women were coinfected. Identical biovars were detected in mothers and their infants. Serial isolations or cultures from different sampling sites of the same individual revealed the same biovar. T960 was dominant in patients with pelvic inflammatory disease (57%) and patients who had had a miscarriage (42%), showed a higher rate of tetracycline resistance than did parvo isolates (55 versus 18%), and seemed to have more adverse effects on pregnancy outcome with regard to birth weight (2,500 versus 1,720 g), gestational age (35 versus 30 weeks), and preterm delivery (35 versus 77%).     

Lif, the lysostaphin immunity factor, complements FemB in staphylococcal peptidoglycan interpeptide bridge formation

We conducted serial studies on peripheral blood lymphocytes from four patients with acute Coxiella burnetii infection. These studies revealed that the proportion of gammadelta T cells in these patients significantly increased after the onset of disease (mean, 16%; range, 13%-30%) as compared with that in five healthy controls (mean, 4%; range, 0.5%-7%; P < .0055) and that in five controls with pneumonia (mean, 2%; range, 1%-3%; P < .0014). Most of the gammadelta T cells from these patients expressed the Vgamma9 Vdelta2 gene product. During the acute phase of disease, most gammadelta T cells expressed the activation marker human leukocyte antigen DR but not CD25. During this phase, gammadelta T cell activation was higher than alphabeta T cell activation. Our findings indicate that gammadelta T cells are predominantly involved in the acute immune response to C. burnetii.     

Long-term followup of all patients with muscle invasive (stages T2, T3 and T4) bladder carcinoma in a geographical region

PURPOSE: We studied the relationship between long-term survival and treatment of stages T2, T3 and T4 bladder carcinoma in an unselected patient population. MATERIALS AND METHODS: A total of 680 patients with the initial diagnosis of bladder carcinoma in 1987 to 1988 in Western Sweden was prospectively registered and followed until 1994. Of these patients 107 had stage T2 to T3 and 41 had stage T4 disease. RESULTS: Of the patients with stage T2 to T3 disease 30 (mean age 66) underwent radical cystectomy, 33 (mean age 75) full dose radiotherapy and 44 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). The 5-year crude survival rates were 33, 15 and 14%, respectively. Of the patients with stage T4 disease 6 (mean age 61) underwent radical cystectomy, 9 (mean age 73) full dose radiotherapy and 26 (mean age 81) nonradical therapy (mainly transurethral resection of the bladder). All except 1 patient died of disease within 4 years. CONCLUSIONS: More than 60% of the patients in the cohort were considered unsuitable for radical cystectomy and their survival was poor, whether treated with full dose radiotherapy or transurethral resection of the bladder alone.     

Alpha-interferon treatment of chronic hepatitis C after bone marrow transplantation for homozygous beta-thalassemia

The standard modality of the treatment for the patients with T4 esophageal cancer, whose prognosis still remains quite poor, is not established yet. Salvage surgery for the T4 esophageal cancer following downstaging by neoadjuvant chemo-radiotherapy has become to be available. During the period from 1992 to 96, 30 patients with the suspected T4 esophageal cancer underwent chemoradiotherapy, which consisted of two courses of CDDP/5-FU with-sequential or concurrent 50-60Gy radiotherapy. Among them eleven patients became to be resectable by means of thoracotomy and laparotomy and pathological CRs were obtained in either primary lesions or lymph nodes. The longest survival term following surgery is 36 months. Three patients died of cancer recurrence including the organ metastasis and one died from pyothorax without cancer due to severe immunosuppression attributable to chemoradiation. Our results warrants further studies of neoadjuvant chemoradiotherapy for the patients with T4 esophageal cancer.     

Five-year followup of a prospective trial of radical cystectomy and neoadjuvant chemotherapy: Nordic Cystectomy Trial I. The Nordic Cooperative Bladder Cancer Study Group

PURPOSE: Chemotherapy is widely used in patients with locally advanced bladder cancer but until now there has been no conclusive evidence that this therapy improves survival. The Nordic Cooperative Bladder Cancer Study Group conducted a randomized phase III study to assess the possible benefit of neoadjuvant chemotherapy in patients with bladder cancer undergoing radical cystectomy after short-term radiotherapy. MATERIALS AND METHODS: Our trial included 325 patients with locally advanced stage T1 grade 3 or stages T2 to T4aNXM0 bladder cancer allocated randomly into a chemotherapy or no chemotherapy group (control). The chemotherapy schedule consisted of 2 cycles of 70 mg./m.2 cisplatin and 30 mg./m.2 doxorubicin with a 3-week interval between the cycles. RESULTS: After 5 years the overall survival rate was 59% in the chemotherapy group and 51% in the control group (p = 0.1). The corresponding cancer specific survival rate was 64 and 54%, respectively. In regard to treatment, no difference was observed for stages T1 and T2 disease, while there was a 15% difference in overall survival for patients with stages T3 to T4a disease (p = 0.03). In a multivariate analysis only chemotherapy and T category emerged as independent prognostic factors. The relative death risk for patients who received chemotherapy was 0.69 (95% confidence interval 0.49 to 0.98) compared to the control group after adjustment for the other tested factors. CONCLUSIONS: Neoadjuvant chemotherapy seems to improve long-term survival after cystectomy in patients with stages T3 to T4a bladder carcinoma, while no survival benefit was found for stages T1 to T2 disease.