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PubMed1997

Hepatitis C virus genotypes in liver transplant recipients: impact on posttransplant recurrence, infections, response to interferon-alpha therapy and outcome.

BACKGROUND: End-stage liver disease due to hepatitis C virus (HCV) is the most common indication for liver transplantation in U.S. veterans. We investigated the influence of HCV genotypes on the incidence and timing of recurrent HCV hepatitis, survival, infectious morbidity, and response to interferon-alpha therapy in this unique patient population. METHODS: HCV genotype was determined by direct sequencing of the NS5 region of HCV with type-specific primers. RESULTS: Genotype 1a (66%, 32/47) was the predominant genotype. Type 1b was found in 25% (12/47) of patients and type 2b was found in 9% (4/47). Histopathologically recurrent HCV hepatitis developed in 53% (25/47) of the patients after transplantation. This group included 45% (14/31) of the patients with type 1a, 67% (8/12) of the patients with type 1b, and 25% (1/4) of the patients with type 2b (P>0.5). The time to recurrence and the severity of HCV recurrence as defined by aminotransferase levels or Knodell scores were not different among the three genotypes. There was a trend toward a higher incidence of major infections in patients with type 1b (75%) versus type 1a (48%) and type 2b (50%) (P=0.11). The response to interferon-a therapy did not differ significantly among the genotypes. Mortality at 5 years was 16% (5/31) in patients with genotype 1a, 42% (5/12) in patients with genotype 1b, and 50% (2/4) in patients with genotype 2b (P=0.06). CONCLUSIONS: The incidence, time to recurrence, and response to interferon-alpha therapy did not differ between the various genotypes in our liver transplant recipients. However, there was a trend toward higher infectious morbidity and overall mortality in patients with genotype 1b after transplantation.

Adult↗
PubMedDate not supplied

Gastroduodenal dysmotility in patients with gallbladder carcinoma: frequency of occurrence and clinical importance.

BACKGROUND: Gastric stasis, common in patients with gall-bladder carcinoma (GBC), results from anatomical obstruction or motor abnormalities. We studied patients with GBC for antroduodenal motor dysfunction using manometry. METHODS: Forty-one patients with GBC without endoscopic gastric outlet obstruction and 10 healthy controls were evaluated using a symptom scoring system for gastric stasis, saline load test and water perfusion antroduodenal manometry. Fasting, post-prandial and post-octreotide motility were recorded and analysed on a computer using GiPC manometry software. RESULTS: Sixteen of 41 patients (39%) with GBC reported recurrent vomiting; patients with vomiting had a higher symptom score (13 [11-17] v. 6 [4-10], p<0.0001] and higher volume of aspirate on the saline load test (460 ml [210-650] v. 160 ml [70-260], p<0.0001) as compared with those without vomiting. Healthy subjects more often had spontaneous fasting migratory motor complex than patients with GBC (9/10 v. 13/41, p=0.002). The amplitudes of contractions in the antrum and duodenum were significantly lower in patients with GBC than in healthy subjects. Patients with GBC had lower fasting (157 [68-284] v. 190.5 [150-284], p=0.01) and post-prandial (200 [96-395] v. 284 [178-395], p<0.0001) antral motor indices than healthy subjects. Patients with GBC and vomiting had significantly lower contraction amplitude and motility indices than those without vomiting. Motility indices correlated inversely with the symptom score and volume of aspirate on the saline load test (Spearman correlation, p = 0.01 for all). CONCLUSION: Antroduodenal motor abnormalities are common in patients with GBC. These may explain the symptoms of gastric stasis and abnormal results of the saline load test in the absence of anatomical obstruction in such patients.

Adult↗
PubMedDate not supplied

Contemporary preoperative parameters predict cancer-free survival after radical prostatectomy: a tool to facilitate treatment decisions.

Prostate specific antigen (PSA) screening has heralded stage migration in prostate cancer toward cancers that may be readily eliminated by primary intervention. We sought to identify contemporary, preprostatectomy measures of cancer severity useful and significant for predicting postprostatectomy, recurrence-free survival. The association of baseline variables clinical variables (age, clinical stage, serum PSA, and race) and prostate biopsy parameters (Gleason score, presence of perineural invasion, number of biopsy cores with cancer, and the greatest percentage of a biopsy core occupied by cancer--GPC) with recurrence-free survival was evaluated by multivariate Cox proportional hazards regression among consecutive patients that underwent radical prostatectomy as primary therapy between 1994 and 2002. Tables were generated depicting expected 5-year recurrence-free survival after prostatectomy. From 1414 patients, 183 developed biochemical recurrence, 8 died from prostate cancer, and 31 died of all causes. Multivariable Cox regression found that clinical stage, PSA, Gleason score, and the greatest percentage of a biopsy core involved by cancer (GPC), were each significant determinants of post-prostatectomy, PSA recurrence-free survival (P < 0.05 for each). Gleason score and GPC were also significantly associated with clinical recurrence-free survival and cancer death, whereas other biopsy parameters and PSA were not. The amount of cancer in a biopsy core is a significant predictor of recurrence-free survival after prostatectomy, and is a simple clinical measure that complements baseline PSA, and Gleason score in predicting outcome. Tabulated 5-year PSA-free survival outcomes, stratified by these preoperative parameters, provide a basis for preoperative counseling of patients regarding postprostatectomy cancer control expectations.

Adenocarcinoma↗
PubMed1994

[Surgical treatment of cervix cancer. A 6-year material from a regional hospital].

The results are reported for 75 patients treated with radical hysterectomy and pelvic lymphadenectomy (Wertheim-Meigs' operation) for cervical carcinoma. There was no per- or postoperative death. Ten patients suffered immediate postoperative complications. One case of lower limb lymphoedema was observed. 17 patients (23%) had pelvic lymph node metastases. In eight patients the disease has recurred (median observation time 43 months). Overall recurrence-free survival was 89%: for patients without lymph node metastases 91%, and for patients with metastases 82%. Using a prognostic score based on stage, presence of lymph node metastases, blood or lymph vessel invasion, low differentiation, and tumour-involved resection margins; two groups could be identified, with a recurrence-free survival of 94% (score < or = 2) and 75% (score > or = 3), respectively (p < 0.02).

Adult↗
PubMed2005

AngioJet rheolytic thrombectomy versus local intrapulmonary thrombolysis in massive pulmonary embolism: a retrospective data analysis.

PURPOSE: To compare the efficacy of full-dose local intrapulmonary thrombolysis (LIT) versus AngioJet rheolytic thrombectomy (ART) in the treatment of massive pulmonary embolism. METHODS: A retrospective review was conducted of 8 consecutive patients (5 women; mean age 66.0+/-5.9 years, range 56-74) who underwent LIT with high-dose intrapulmonary urokinase (4400 IU/kg over 10 minutes followed by a 2000-IU/kg/h infusion) and a subsequent 6 consecutive patients (4 men; mean age of 59.2+/-17.0 years, range 26-69) who underwent ART plus adjunctive low-dose urokinase infusions (100,000 IU) until hemodynamic recovery was achieved. Pre and postprocedural Miller scores were calculated, and relative Miller score improvement, total urokinase doses, and duration of therapy were compared. RESULTS: Hemodynamic stability was restored in all 8 LIT patients and in 5 (83%) of the 6 ART patients; 1 (16.7%) patient died during the ART procedure due to recurrent MPE. In the LIT group, the mean Miller score prior to intervention was 17.38+/-2.67, which was reduced to 6.13+/-1.46 after the intervention (p<0.0001) compared to scores of 18.83+/-2.86 and 6.83+/-2.79, respectively, in the ART group (p<0.0001). The mean urokinase dose was 2.07+/-0.44 million IU in the LIT group versus 0.70+/-0.36 million IU in the ART group (p<0.0001). The mean duration of therapy was 11.45+/-2.94 hours in the LIT group versus 3.37+/-1.41 hours in the ART group (p<0.0001). No significant difference in relative Miller score improvement was observed. CONCLUSION: By accelerating the fragmentation of thrombus, ART plus adjunctive low-dose urokinase seems to be more rapidly effective compared to LIT. ART achieves both rapid cardiovascular relief and reduces the dose of thrombolytic agent necessary in patients with massive pulmonary embolism.

Aged↗
PubMed2003

Quality-of-life in patients with paroxysmal atrial fibrillation after catheter ablation: results of long-term follow-up.

Paroxysmal atrial fibrillation (PAF) significantly impairs patients' quality-of-life (QOL). The effect on QOL of recently developed ablation techniques with curative intention has not been studied. Thirty patients (21 men, age 54.1 +/- 9.5 years) with PAF (duration 5.6 +/- 5.2 years) who failed antiarrhythmic (3.8 +/- 1.2 trials) drug therapy underwent catheter ablation. The follow-up time was 33.9 +/- 11 months. QOL was assessed preablation, 3, 6, 9, 12, 24, and 36 months after catheter ablation. The Medical Outcomes Survey Short-Form (SF-36), scored on a 0-100 scale for each of eight domains: bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality, was used. Simultaneously, patients filled out a symptom-specific checklist (SSC) with seven clinical items scored 1-4 (1 best): dyspnea, nausea, palpitations, anxiety, syncope, presyncope, and NYHA classification. Patients with successful catheter ablation had a significant benefit in seven of eight subscales while patients with recurrence had an impact on QOL in two of eight subscales. Using SSC, a successful ablation influenced scores in all seven items while patients with recurrence had a significant change of clinical symptoms in only one item, anxiety. The subscales of the study group compared to a healthy population show higher scores after 24 months of follow-up. Patients with PAF experience a significant improvement in QOL after a successful catheter ablation. In contrast, in patients with recurrence of PAF the QOL showed improvement to a lesser extent and patients experienced ongoing symptoms.

Atrial Fibrillation↗
PubMed2006

Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score.

OBJECTIVE: To investigate the expression and potential clinical usefulness of structure-specific flap endonuclease 1 (FEN-1) in human primary prostate cancer using tissue microarray technology, as FEN-1 was recently identified to be overexpressed in CL1.1, the most aggressive clone generated from the hormone-refractory prostate cancer cell line CL1. MATERIALS AND METHODS: Immunohistochemistry was performed on tissue microarrays constructed from paraffin-embedded specimens of primary prostate cancer from 246 patients who had had a radical prostatectomy. Prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH) and normal prostate epithelium were represented on the array. FEN-1 nuclear expression was scored based on the percentage of target cells staining positively, and correlated with Gleason score, preoperative prostate-specific antigen (PSA) level and pathological stage. The time to PSA recurrence was also analysed. RESULTS: The mean expression of FEN-1 was significantly higher in cancer (36.7%) than in normal (13.2%), BPH (4.5%) and PIN (15.4%) specimens (P < 0.001). FEN-1 expression was significantly correlated with Gleason score (ó = 0.23, P = 0.002). A higher preoperative serum PSA level (P = 0.015), Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P < 0.001) and capsular involvement (P = 0.004) were associated with PSA recurrence, whereas FEN-1 expression was not. In a multivariate analysis, only Gleason score > or = 7 (P < 0.001), seminal vesicle invasion (P = 0.005) and capsular involvement (P = 0.009) were retained as independent predictors for PSA recurrence. CONCLUSIONS: FEN-1 is overexpressed in prostate cancer compared with matched normal prostate, and its expression increases with tumour dedifferentiation, as shown by increasing Gleason score. These results suggest that FEN-1 might be a potential marker for selecting patients at high risk, and a potential target for prostate cancer diagnosis and therapy.

Aged↗
PubMed2000

bcl-2 protein expression in aggressive and non-aggressive basal cell carcinomas.

bcl-2, the well known anti-apoptotic gene, cloned more than a decade ago, promotes cell viability without promoting cell proliferation. With few exceptions, high bcl-2 protein expression is associated with a favourable outcome in epithelial tumours. bcl-2 immunoreactivity in basal cell carcinomas (BCCs) is contradictory, with 67-100% immunopositivity being reported. Although BCCs are traditionally regarded as low-grade, indolent tumours, aggressive BCCs (A-BCCs) are mutilative, locally destructive tumours that often recur. bcl-2 protein expression as a predictor of BCC aggressiveness is poorly documented in the English-language literature. The bcl-2 protein immunoprofile of 50 clinically non-aggressive (NA-BCCs) and 25 clinically A-BCCs was investigated. Of the latter, 17 manifested with one, two or three recurrences. bcl-2 protein expression in each of the recurrences was also evaluated. bcl-2 expression was scored as follows: 0-5% positive cells=negative, 6-25%=1+, 26-50%=2+, 51-75%=3+, >75%=4+. "High" labeling encompassed 3+ or 4+ labeling while "low" labeling referred to 1 + or 2 + labeling. Although bcl-2 positivity was noted in all BCCs, low bcl-2 labeling was a statistically significant feature of A-BCCs (p < 0.01). High bcl-2 labeling of NA-BCCs was a reflection of the bcl-2 labeling of the dominant constituent nodular or superficial subtypes. Micronodular BCCs revealed 2+ or 3+ labeling. Initial and recurrent A-BCCs with a pure or predominantly infiltrative component, demonstrated 1+ or 2+ bcl-2 labeling. The differential bcl-2 expression in the various clinicopathological subtypes of BCCs suggests that, despite the common derivation of these tumours from a primitive basaloid stem cell and a limited potential for metastasis, they form a heterogeneous group of tumours that differ markedly in histologic and biological behaviour. While the superficial and nodular BCCs are indolent slow-growing tumours with high bcl-2 labeling, the aggressive BCCs are infiltrative, desmoplastic tumours with low bcl-2 labeling. In mixed tumours, heterogeneity of labeling is a distinctive feature and is contributed to in part by the labeling trends of the different histological subtypes. The micronodular BCC shows varied bcl-2 labeling but in combined tumours occupies a niche intermediate between the non-aggressive nodular and superficial and the aggressive infiltrative subtypes. The initial and subsequent biopsies of recurrent, adequately excised BCCs share a pure or mixed, predominantly infiltrative, stroma-rich histomorphology with low bcl-2 labeling, reflecting the immunoprofile of a more aggressive growth pattern.

Adult↗
PubMed1998

Patterns of failure following treatment for medulloblastoma: is it necessary to treat the entire posterior fossa?

PURPOSE: Craniospinal radiation (CSRT) followed by a boost to the entire posterior fossa (PF) is standard postoperative therapy for patients with medulloblastoma. A large proportion of recurrences after treatment are local, with approximately 50-70% of recurrences occurring in the PF. It is unclear, however, whether these failures are occurring in the original tumor bed or outside the tumor bed, but still within the PF. With improved diagnostic imaging, better definition of tumor volumes, and the use of three-dimensional conformal therapy (3D CRT), we may be able to restrict the boost volume to the tumor bed plus a margin without compromising local control. This retrospective study analyzes the patterns of failure within the PF in a series of patients treated with radiation therapy (RT). METHODS: From July 1986 through February 1996, 114 patients >18 months and <18 years with medulloblastoma were treated at the University of Michigan and Children's Hospital of Philadelphia, with RT following surgical resection. Of 114, 27 (24%) were found to have a recurrence and form the basis for this study. RT consisted of CSRT followed by a boost to the entire posterior fossa. Some patients received adjuvant chemotherapy. Patient's preoperative magnetic resonance imaging (MRI) and/or computerized tomography (CT) studies were used to compare the original tumor volume with the specific region of local relapse. Failure was defined as MRI or CT evidence of recurrence or positive cerebrospinal fluid cytology. Relapse was scored as local, if it was within the original tumor bed, and regional if it was outside of the tumor bed but still within the PF. RESULTS: The median age of the 27 patients who relapsed was 8.6 years. Three patients were <3 years old. Of 27, 21 had disease localized to the PF. Of 26, 22 patients received chemotherapy during their treatment regimen; 1 patient did not have information on systemic treatment. The median dose of RT to the craniospinal axis was 32.5 Gy and to the PF was 55.2 Gy. The median time to recurrence was 19.5 months. Local failure within the tumor bed as any component of first failure occurred in 52% (14 of 27) of all failures, but as the solitary site of first failure in only 2 of 27 failures. Of 14 patients who failed in the tumor bed, 11 also failed in the spine, 8 of 14 also failed within the PF but outside the tumor bed, and 7 of 14 failed in all three locations. Local failure within the PF but outside the tumor bed as any component of first failure occurred in 41% (11 of 27) of all failures, but as the solitary site of first failure in only 1 of 27 failures. Of 11 patients who failed in the PF but outside the tumor bed, 9 also failed in the spine, 8 also failed within the tumor bed, and 7 failed in the all three locations. Of the failures outside the tumor bed but still within the PF, 7 of 11 failed in the leptomeninges, 1 in the brainstem parenchyma, and 3 in the PF parenchyma. Of 7 who failed in the PF leptomeninges, 6 also failed within the spine. Failure within the spine as any component of first failure occurred in 70% (19 of 27) of all failures and as the only site of first failure in 5 of 27 patients. Of 19 patients who failed in the spine, 11 also failed in the tumor bed, 9 also failed within the PF but outside the tumor bed, and 9 failed in the all three locations. CONCLUSIONS: Leptomeningeal failure is a common component of failure and occurs in the leptomeninges of the PF, as well as the spine. Isolated tumor bed failure is a rarely observed event and occurred in only 2 of 27 failures described here. Similarly, parenchymal (nonleptomeningeal) failures in the PF but outside of the tumor bed were rare: 4 patients recurred in this manner, only 1 of whom was an isolated event without other sites of recurrence. Our data suggest that, when the entire PF is treated, very few failures develop in isolation in the PF outside the tumor bed. Further studies will be necessary to determine if RT to the tu

Adolescent↗
PubMed2001

Histopathologic analysis of angiogenic factors in localized renal cell carcinoma: the influence of neoadjuvant treatment.

BACKGROUND: This study was conducted in order to clarify whether histopathologic analysis of factor thymidine phosphorylase (TP) and Factor VIII could be a useful predictor of postoperative recurrence in localized renal cell carcinoma. Therefore, the relationship between tumor infiltrated lymphocytes (TIL) and both TP and Factor VIII was studied. METHOD: Of the 71 patients who underwent surgery, 54 patients had no neoadjuvant therapy (group 1), 10 patients were preoperatively administered IFN-gamma (group 2), and the remaining seven patients preoperatively received IFN-gamma and transarterial embolization (group 3). Both TP and Factor VIII immunostaining were performed on formalin-fixed, paraffin-embedded archival tissue from 71 renal cell carcinoma specimens, while TIL immunostaining was performed on frozen sections. Positive immunostaining was quantitatively scored by a computer-assisted digital image analysis. For TIL, positive results were semiquantitatively scored. RESULTS: A significant difference in the recurrence-free rate was recognized for Groups 1, 2 and 3 (P < 0.05). Therefore, the median TP-positive rate (PR), VIII-PR, number of microvessels and positive mean vascular area levels were investigated, between the recurrence cases (n = 6) and the recurrence-free cases (n = 11). Only the TP-PR levels showed a significant difference among them (P = 0.044). In regards to the neoadjuvant cases, a significant correlation was observed between both VIII-PR and CD4 (r = 0.815) as well as between VIII-PR and CD11b (r = 0.756). CONCLUSION: There was no clear evidence that the neoadjuvant treatment would increase the recurrence-free survival in patients with localized renal cell carcinoma. TP-PR might be a predictor of postoperative recurrence in patients with localized renal cell carcinoma.

Adult↗
PubMed2026

Longitudinal comparison of treat-to-target states and clinical outcomes in patients with late-onset versus early-onset systemic lupus erythematosus.

OBJECTIVE: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age &#x2264;50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS: Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.

Journal Article↗
PubMed2006

Expression of the chromatin remodeling factor Rsf-1 is upregulated in ovarian carcinoma effusions and predicts poor survival.

OBJECTIVE: We recently identified Rsf-1, a chromatin remodeling gene, as a potential oncogene that is frequently amplified and overexpressed in ovarian serous carcinoma. However, its clinical role in ovarian cancer effusions is not clear. In the present study, we assessed the clinical significance of Rsf-1 overexpression in ovarian carcinoma effusions. METHODS: Formalin-fixed paraffin-embedded sections from 168 effusions (134 peritoneal, 34 pleural) were analyzed for Rsf-1 expression using immunocytochemistry. Matched primary tumors (n=48) and solid metastases (n=73) from 48 patients were additionally studied. Rsf-1 expression in tumor cells in effusions was analyzed for possible association with clinicopathologic parameters and survival. RESULTS: Rsf-1 protein expression was found in carcinoma cells in 157/168 (93%) effusions. Of these, 70 (45%) stained weakly and 87 (55%) strongly. Specimens from patients diagnosed with FIGO stage IV disease had higher staining score (extent x intensity) compared with stage III tumors (P=0.008). Rsf-1 expression level was significantly lower in primary tumors and solid metastases (P<0.001 for extent, intensity and score). Univariate survival analysis for 59 patients with post-chemotherapy recurrence effusions demonstrated a significant association between higher Rsf-1 staining and shorter overall survival (OS; P=0.009 for staining extent and intensity, P=0.02 for staining score). FIGO stage was the only clinical parameter associated with OS in this group (P=0.032). In Cox analysis, Rsf-1 expression (P=0.022 for staining extent and intensity, P=0.045 for staining score) and FIGO stage (P=0.035) were independent predictors of shorter survival. CONCLUSIONS: Rsf-1 is frequently expressed and upregulated in ovarian carcinoma cells in effusions and is a novel prognostic marker for patients with post-chemotherapy recurrent disease. The above findings support a role of Rsf-1 in mediating disease progression and aggressive clinical behavior in this subset of ovarian carcinoma patients.

Adenocarcinoma, Clear Cell↗
PubMed2006

High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence.

BACKGROUND: We wished to determine recurrences of bacterial vaginosis (BV) after treatment over the course of 12 months and to establish factors associated with recurrence. METHODS: Women with symptomatic BV (a Nugent score [NS] of 7-10 or of 4-6 with >or=3 Amsel criteria) were enrolled. BV was treated with 400 mg of oral metronidazole twice a day for 7 days. Participants completed a questionnaire and vaginal swabs were collected at 1, 3, 6, and 12 months; the study end point was an NS of 7-10. RESULTS: A total of 121 (87%) women with an NS of 7-10 and 18 (13%) with an NS of 4-6 and >or=3 Amsel criteria were enrolled; 130 (94%) returned >or=1 vaginal samples. Sixty-eight women (58% [95% confidence interval {CI}, 49%-66%]) had a recurrence of BV (NS 7-10), and 84 (69% [95% CI, 61%-77%]) had a recurrence of abnormal vaginal flora (NS 4-10) by 12 months. A past history of BV, a regular sex partner throughout the study, and female sex partners were significantly associated with recurrence of BV and abnormal vaginal flora by multivariate analysis; the use of hormonal contraception had a negative association with recurrence. CONCLUSION: Current recommended treatment is not preventing the recurrence of BV or abnormal vaginal flora in the majority of women; factors associated with recurrence support a possible role for sexual transmission in the pathogenesis of recurrent BV.

Adult↗
PubMed1994

Oral versus nebulized albuterol in the management of bronchiolitis in Egypt.

The efficacy of albuterol in the management of infants with first-time wheezing is controversial. This double-blind, placebo-controlled trial involved 128 Egyptian infants with first-time wheezing (mean age 5.9 months) who were randomly separated into four equivalent therapy groups: nebulized albuterol, nebulized saline solution, orally administered albuterol, and orally administered placebo. The nebulized therapy groups received two treatments 30 minutes apart; the oral therapy groups received one treatment. In addition, 41 infants with recurrent wheezing comprised an open-label control group who received two albuterol nebulizations. Chest radiographs, leukocyte counts, blood culture specimens, and nasal aspirate for viral antigen detection were obtained to confirm the clinical diagnosis of viral bronchiolitis. Respiratory and heart rates, clinical score, and oxygen saturation were recorded at baseline and 30 and 60 minutes after treatment. There was no difference among the four randomized groups in any of the outcomes except for an increase in heart rate of 10 beats/min in the nebulized albuterol group compared with a decrease in heart rate of 8 beats/min in the oral placebo group. No differences in the need for additional treatment were observed. Nebulized albuterol significantly improved the clinical score and reduced the respiratory rate of those with recurrent wheezing relative to those in the randomized groups. We conclude that nebulized albuterol is effective in the treatment of infants with recurrent wheezing, but there was no demonstrable efficacy of orally administered or nebulized albuterol in relieving the respiratory distress of infants with bronchiolitis in Egypt.

Administration, Oral↗
PubMed2006

An immunohistochemical scoring system of prolyl isomerase Pin1 for predicting relapse of prostate carcinoma after radical prostatectomy.

A major challenge for the management of prostate cancer (PCa) patients is to predict the clinical course of the disease after radical prostatectomy. A previous comprehensive immunohistochemical analysis using an automated image analyzer suggested that prolyl isomerase Pin1 (hence Pin1) may be a potent predictor of recurrence in PCa patients. However, a detailed pathological standard for evaluating the Pin1 immunohistochemistry in PCa has not been established yet. We here introduce a practical scoring system for Pin1 immunostaining in PCa. Using this method, the immunoreactivity of tumor cell cytoplasm and nucleus was evaluated separately and then scored for four grades (Grade=0-3). We defined the Pin1 score as the sum of both nuclear and cytoplasmic grades (Score=0-6), and the cases were then divided into either a low Pin1 score group (2) or a high Pin1 score group (3). We examined the correlation between this scoring system and postoperative PSA recurrence for 78 PCa patients. PCa patients assigned to the high Pin1 score group demonstrated PSA relapse more frequently than those assigned to the low Pin1 score group (p<0.0001). This suggests that, at the common laboratory level, our Pin1 scoring system could be a useful tool for predicting the prognosis of PCa patients after surgery.

Carcinoma↗
PubMed2001

Pretreatment clinical findings predict outcome for patients receiving preoperative radiation for rectal cancer.

BACKGROUND: As a sole modality, preoperative radiation for rectal carcinoma achieves a local control comparable to that of postoperative radiation plus chemotherapy. Although the addition of chemotherapy to preoperative treatment improves the pathologic complete response rate, there is also a substantial increase in acute and perioperative morbidity. Identification of subsets of patients who are at low or high risk for recurrence can help to optimize treatment. METHODS: During the period 1977-95, 384 patients received preoperative radiation therapy for localized adenocarcinoma of the rectum. Ages ranged from 19 to 97 years (mean 64.4), and there were 171 females. Preoperative treatment consisted of conventionally fractionated radiation to 3600-5040 cGy (median 4500 cGy) 6-8 weeks before surgery in 293 cases or low doses of <3000 cGy (median 2000 cGy) immediately before surgery in 91 cases. Concurrent preoperative chemotherapy was given to only 14 cases in this study period. Postoperative chemotherapy was delivered to 55 cases. RESULTS: Overall 93 patients have experienced recurrence (including 36 local failures). Local failures were scored if they occurred at any time, not just as first site of failure. For the group as a whole, the actuarial (Kaplan-Meier) freedom from relapse (FFR) and local control (LC) were 74% and 90% respectively at 5 years. Univariate analysis of clinical characteristics demonstrated a significant (p < 0.05) adverse effect on both LC and FFR for the following four clinical factors: (1) location <5 cm from the verge, (2) circumferential lesion, (3) near obstruction, (4) tethered or fixed tumor. Size, grade, age, gender, ultrasound stage, CEA, radiation dose, and the use of chemotherapy were not associated with outcome. Background of the surgeon was significantly associated with outcome, colorectal specialists achieving better results than nonspecialist surgeons. We assigned a clinical score of 0 to 2 on the basis of how many of the above four adverse clinical factors were present: 0 for none, 1 for one or two, 2 for three or four. This sorted outcome highly significantly (p < or = 0.002, Tarone Ware), with 5-year LC/FFR of 98%/85% (score 0), 90%/72% (score 1), and 74%/58% (score 2). The scoring system sorts the data for both subgroups of surgeons; however, there are substantial differences in LC on the basis of the surgeon's experience. For colorectal specialists (251 cases), the 5-year LC is 100%, 94%, and 78% for scores of 0, 1, and 2, respectively (p = 0.004). For the more mixed group of nonspecialist surgeons (133 cases), LC is 98%, 80%, and 65% for scores of 0, 1, and 2 (p = 0.008). In multivariate analysis, the clinical score and surgeon's background retained independent predictive value, even when pathologic stage was included. CONCLUSIONS: For many patients with rectal cancer, adjuvant treatment can be administered in a well-tolerated sequential fashion-moderate doses of preoperative radiation followed by surgery followed by postoperative chemotherapy to address the risk of occult metastatic disease. A clinical scoring system has been presented here that would suggest that the local control is excellent for lesions with a score of 0 or (if the surgeon is experienced) 1, and therefore sequential treatment could be considered. Cases with a clinical score of 2 should be strongly considered for protocols evaluating more aggressive preoperative treatment, such as combined modality preoperative treatment.

Adenocarcinoma↗
PubMedDate not supplied

Should patients with a pre-operative prostate-specific antigen greater than 15 ng/ml be offered radical prostatectomy?

BACKGROUND: Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) >15 ng/ml who undergo radical retropubic prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option of surgery. AIM: To assess the outcome of patients who underwent RRP with a pre-operative PSA >15 ng/ml. METHODS: Thirty-four patients, mean pre-operative PSA: 25.46 ng/ml (15.03-76.6) and mean Gleason score: 6.4 (5-9) were assessed. RESULTS: Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30-106). Mean PSA: 18.8 ng/ml (15.03-25.84). Mean Gleason score: 6.1 (5-7). Clinical stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow up of 66 months (36-98). Mean PSA: 28.9 ng/ml (15.28-76.6). Mean Gleason score: 6.7 (5-9). Clinical stage: T1c in 25%. Eleven patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2). CONCLUSION: RRP seems feasible in patients whose pre-operative PSA is between 15 and 25 ng/ml with stage T1c, Gleason score < or = 7 and negative lymph node frozen section.

Adenocarcinoma↗
PubMed2001

Improved prediction of the number of residue contacts in proteins by recurrent neural networks.

Knowing the number of residue contacts in a protein is crucial for deriving constraints useful in modeling protein folding, protein structure, and/or scoring remote homology searches. Here we use an ensemble of bi-directional recurrent neural network architectures and evolutionary information to improve the state-of-the-art in contact prediction using a large corpus of curated data. The ensemble is used to discriminate between two different states of residue contacts, characterized by a contact number higher or lower than the average value of the residue distribution. The ensemble achieves performances ranging from 70.1% to 73.1% depending on the radius adopted to discriminate contacts (6Ato 12A). These performances represent gains of 15% to 20% over the base line statistical predictors always assigning an aminoacid to the most numerous state, 3% to 7% better than any previous method. Combination of different radius predictors further improves the performance. SERVER: http://promoter.ics.uci.edu/BRNN-PRED/.

Amino Acid Sequence↗