Biomedical subjects

Paul Christos

Publications and source records attributed to Paul Christos.

15 recordsLinked to original sources

PubMed2006

FDG-PET after 1 cycle of therapy predicts outcome in diffuse large cell lymphoma and classic Hodgkin disease.

BACKGROUND: Early prediction of response to therapy may offer the potential to identify patients who will benefit from standard conventional therapy. The objective of this study was to determine the predictive value of FDG-PET as an early response indicator after 1 cycle of chemotherapy for progression-free survival (PFS) in diffuse large cell lymphoma (DLCL) and classic Hodgkin disease (HD). METHODS: FDG-PET was performed before, after 1 cycle, and after completion of chemotherapy in 47 patients. The patients were followed with a median follow-up of 21 months (range, 3-47 months). PFS was compared between PET-positive and PET-negative patients after 1 cycle and after completion of therapy. RESULTS: All PET-negative patients after 1 cycle (n = 31) had sustained complete remission with a median follow-up of 28 months. Fourteen of 16 PET-positive patients after 1 cycle had refractory disease or relapsed (median PFS, 5.5 months). There were 2 false-positive results, 1 with an active infection at the biopsy site and the other in a patient who had been in remission after radiation therapy. There was good agreement between the results obtained after 1 cycle and at completion of therapy (kappa, 0.80); however, the negative predictive value was higher for FDG-PET after 1 cycle than after completion of chemotherapy (100% vs 91.4%), although not statistically different (P = .40). CONCLUSIONS: FDG-PET had a high prognostic value after 1 cycle of chemotherapy, thus it can be a valid alternative for posttreatment evaluation of DLCL and HD and may offer the potential for change in treatment paradigms.

Adolescent↗

PubMed2006

Loss of neutral endopeptidase and activation of protein kinase B (Akt) is associated with prostate cancer progression.

BACKGROUND: Neutral endopeptidase (NEP) is a cell-surface peptidase that can regulate the activation of Akt kinase through catalytic-dependent and independent mechanisms. NEP expression is absent in approximately 50% of prostate cancers. The authors investigated whether NEP loss in vivo would result in Akt phosphorylation and potentially contribute to prostate cancer progression by examining the interaction of NEP, Akt, and phosphatase and tensin homolog (PTEN) in a prostate xenograft model and in clinical specimens from patients with prostate cancer. METHODS: Using a tetracycline-repressible expression system to express NEP in a tumor animal xenograft model, the effects of NEP were tested on tumor growth, Akt phosphorylation, and PTEN expression. The clinical relevance of NEP, phosphorylated Akt, and PTEN protein expression also was investigated in 204 patients who had undergone radical prostatectomy. RESULTS: The results indicated that the induction of NEP expression inhibited established xenograft tumor growth, diminished Akt phosphorylation, and increased PTEN protein levels. In humans, prostate cancers with complete loss of NEP expression were significantly more likely to express phosphorylated Akt (P = .02). Moreover, patients who had prostate cancers with concomitant loss of NEP and expression of phosphorylated Akt had an increased, independent risk of prostate-specific antigen (PSA) recurrence (P = .03). In the study cohort, loss of PTEN protein expression did not correlated significantly with phosphorylated Akt or with patients' clinical outcome. CONCLUSIONS: The findings from this investigation demonstrated that NEP loss leads to Akt activation and contributes to the clinical progression of prostate cancer.

Animals↗

PubMed2006

Solving interpersonal problems correlates with symptom improvement in interpersonal psychotherapy: preliminary findings.

Interpersonal psychotherapy (IPT) research has addressed outcome more than mechanism. This study used the novel Interpersonal Psychotherapy Outcome Scale (IPOS) to test the theoretical axiom that symptomatic improvement in IPT reflects resolution of interpersonal problem areas. The IPOS rates change in focal interpersonal problem areas on a 5-point scale. Patients (N = 24) and therapists (N = 7) in a time-limited IPT outcome study of dysthymic disorder, and patients (N = 11) in an open trial for posttraumatic stress disorder, completed the IPOS at treatment termination. All responding dysthymic subjects (N = 24) and therapists (N = 21) reported interpersonal gains: dysthymic patients scored 4.39 (SD = 0.52) out of 5, therapists 4.27 (0.53). Posttraumatic stress disordered patients rated 4.75 (0.34). Patient and therapist IPOS ratings correlated with objectively measured symptomatic improvement with full or trend statistical significance. Despite methodological limitations, initial testing of the IPOS supports the theorized link between resolving interpersonal crises and improvement in IPT.

Attitude of Health Personnel↗

PubMed2005

Phase II trial of thalidomide for advanced and recurrent gynecologic sarcoma: a brief communication from the New York Phase II consortium.

OBJECTIVE: To define the efficacy of thalidomide on the overall survival of patients with metastatic recurrent gynecologic sarcomas. PATIENTS AND METHODS: All patients with sarcoma or carcinosarcoma of gynecologic origin and documented recurrence or persistence of disease after appropriate surgery, radiation therapy and/or chemotherapy were recruited to the study. All patients were ambulatory and had measurable disease that could be documented on CT scan. Patients were started on 200 mg/day of thalidomide orally every night and escalated by 100-200 mg every 7 to 14 days. The length of the treatment was separated into 2 cycles with the first 84 days defined as the first cycle and the next 56 days as the second cycle. Common Toxicity Criteria were used to record toxicities. Because thalidomide was postulated to induce cytostasis, the end-points were progression-free and overall survival in this mixed group of patients. RESULTS: Seventeen patients were enrolled. The drug was not well tolerated because of constipation, fatigue, worsening performance status, drowsiness and sleepiness. The total dosage of medication given to each patient ranged from 3200 mg to 40,500 mg. The maximum dosage reached in each patient ranged from 300 mg to 750 mg, with the total time of treatment ranging from 13 to 99 days. All patients had progression of disease with a median progression-free survival time of 1.84 months (CI 1.54-2.79 months) and a median overall survival of 6.64 months. DISCUSSION: Thalidomide has no activity in patients with advanced or recurrent gynecologic sarcomas and was not well-tolerated. The overall survival was <7 months. The progression-free survival was <3 months, and, since the therapy was not tolerated well, we unanimously decided to close the study at this point. Despite the poor result, we still believe in the strategy of anti-angiogenesis and will continue to pursue other potential treatment options using the same concept.

Administration, Oral↗

PubMed2005

Robotics and other devices in the treatment of patients recovering from stroke.

Stroke is the leading cause of permanent disability in the United States despite advances in prevention and novel interventional treatments. Randomized controlled studies have demonstrated the effectiveness of specialized post-stroke rehabilitation units, but administrative orders have severely limited the length of stay, so novel approaches to the treatment of recovery need to be tested in outpatients. Although the mechanisms of stroke recovery depend on multiple factors, a number of techniques that concentrate on enhanced exercise of the paralyzed limb have demonstrated effectiveness in reducing the motor impairment. For example, interactive robotic devices are new tools for therapists to deliver enhanced sensorimotor training for the paralyzed upper limb, which can potentially improve patient outcome and increase patient productivity. New data support the idea that for some post-stroke patients and for some aspects of training-induced recovery, timing of the training may be less important than the quality and intensity of the training. The positive outcome that resulted in the interactive robotic trials contrasts with the failure to find a beneficial result in trials that used a noninteractive device that delivered continuous passive motion only. New pilot data from novel devices to move the wrist demonstrate benefit and suggest that successive improvement of the function of the arm progressing to the distal muscles may eventually lead to significant disability reduction. These data from robotic trials continue to contribute to the emerging scientific basis of neuro-rehabilitation.

Clinical Trials as Topic↗

PubMed2005

Multiple re-excisions versus mastectomy in patients with persistent residual disease following breast conservation surgery.

BACKGROUND: Persistently involved margins following breast conservation surgery (BCS) create a diagnostic dilemma regarding the recommendation of further BCS or mastectomy. METHODS: A retrospective review of 276 breast cancer patients who underwent BCS and required additional surgical treatment between 1990-2002 was performed. RESULTS: For treatment of persistently involved margins, 63% of subjects underwent re-excision the first time, 49% the second time, and 37% the third time. The incidence of residual carcinoma increased linearly with the number of initially involved margins (P = .03). Ductal carcinoma-in-situ (DCIS) or infiltrating lobular carcinoma (IFLC) primary histology was associated with a higher rate of residual cancer compared to invasive ductal carcinoma (IFDC) (62% vs. 69% vs. 54%, respectively, P = .56). A trend towards an increased risk of residual cancer in primary tumors > or =2 cm versus tumors under 2 cm was also evident (63%% vs. 50%, respectively, P = .38). CONCLUSIONS: Approximately half of patients repeatedly selected BCS over mastectomy. It is important to realistically discuss the probability of definitive resection with patients who are undergoing breast conservation with re-excision.

Breast Neoplasms↗

PubMed2005

Treatment of type II endoleaks with a novel polyurethane thrombogenic foam: induction of endoleak thrombosis and elimination of intra-aneurysmal pressure in the canine model.

OBJECTIVE: The clinical significance and treatment of retrograde collateral arterial perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) have not been completely characterized. A canine abdominal aortic aneurysm model of type II endoleak with an implanted pressure transducer was used to evaluate the use of polyurethane foam to induce thrombosis of type II endoleaks. The effect on endoleak patency, intra-aneurysmal pressure, and thrombus histology was studied. METHODS: Prosthetic aneurysms with an intraluminal, solid-state, strain-gauge pressure transducer were created in the infrarenal aorta of 14 mongrel dogs. Aneurysm side-branch vessels were reimplanted into the prosthetic aneurysm of 10 animals by using a Carrel patch. Type II (retrograde) endoleaks were created by excluding the aneurysm from antegrade perfusion with an impermeable stent graft. Thrombosis of the type II endoleak was induced by implantation of polyurethane foam into the prosthetic aneurysm sac of four animals. Six animals with type II endoleaks were not treated. In four control animals, no collateral side branches were reimplanted, and therefore no endoleak was created. Intra-aneurysmal and systemic pressures were measured daily for 60 to 90 days after the implantation of the stent graft. Endoleak patency and flow were assessed during surgery and at the time of death by using angiographic imaging and duplex ultrasonography. Histologic analysis of the intra-aneurysmal thrombus was also performed. RESULTS: Intra-aneurysmal pressure values are indexed to systemic pressure and are represented as a percentage of the simultaneously obtained systemic pressure, which has a value of 1.0. All six animals with untreated type II endoleaks maintained patency of the endoleak and side-branch arteries throughout the study period. Compared with control aneurysms that had no endoleak, animals with patent type II endoleaks exhibited significantly higher intra-aneurysmal pressurization (systolic pressure: patent type II endoleak, 0.702 +/- 0.283; control, 0.172 +/- 0.091; P < .001; mean pressure: endoleak, 0.784 +/- 0.229; control, 0.137 +/- 0.102; P < .001; pulse pressure: endoleak, 0.406 +/- 0.248; control, 0.098 +/- 0.077; P < .001; P < .001 for comparison for all groups by analysis of variance). Treatment of the type II endoleak with polyurethane foam induced thrombosis of the endoleak and feeding side-branch arteries in all four animals with type II endoleaks. This resulted in intra-aneurysmal pressures statistically indistinguishable from the controls (systolic pressure, 0.183 +/- 0.08; mean pressure, 0.142 +/- 0.09; pulse pressure, 0.054 +/- 0.04; not significant). Angiography and histology documented persistent patency up to the time of death (mean, 64 days) for untreated type II endoleaks and confirmed thrombosis of polyurethane foam-treated endoleaks in all cases. CONCLUSIONS: Untreated type II endoleaks were associated with intra-aneurysmal pressures that were 70% to 80% of systemic pressure. Treatment with polyurethane foam resulted in a reduction of intra-aneurysmal pressure to a level that was indistinguishable from control aneurysms that had no endoleak. CLINICAL RELEVANCE: Endovascular repair of abdominal aortic aneurysms is dependent on the successful exclusion of the aneurysm from arterial circulation. Type II endoleaks originate from retrograde flow into the aneurysm sac. This study demonstrates the use of polyurethane foam to induce thrombosis in a canine model of a type II endoleak, thereby reducing intra-aneurysmal pressure to levels similar to levels in animals without endoleaks. This approach may be a strategy for future treatment of type II endoleaks.

Animals↗

PubMed2005

Continuous passive motion improves shoulder joint integrity following stroke.

OBJECTIVE: In a pilot study of patients with a first stroke and hemiparesis, we sought to determine whether treatment of the upper limb with continuous passive motion (CPM) that was device delivered would alter impairment, disability or the associated adverse symptoms of shoulder joint instability, pain and tone. DESIGN: Patients were randomly assigned to receive daily CPM treatments or participate in self-range of motion groups under the supervision of an occupational therapist. All patients received standard daily poststroke therapy for 3.5 h per day. A blinded evaluator at admission and discharge assessed patients using standardized scales of impairment, disability and adverse symptoms. SETTING: Specialized stroke unit of an acute rehabilitation hospital. SUBJECTS: Two hundred and eighty consecutive patients were screened and 35 of these with a first unilateral stroke, 13 +/- 6 days following the acute event, provided informed consent and were randomly assigned to CPM treatment or supervised group self-range exercise. MAIN MEASURES: Thirty-two completed the study and were evaluated using standardized measures for motor impairment (Fugl-Meyer, Motor Status Scale and Medical Research Council Motor Power), adverse symptoms (gleno-humeral stability, pain and tone), and disability (Functional Independence Measure). RESULTS: CPM-treated patients demonstrated positive trends towards improved shoulder joint stability (p = 0.06, confidence interval -0.03, 2.3) when compared with patients performing therapist-supervised self-range of motion. There were no significant differences in motor impairment, disability, pain or tone. CONCLUSIONS: Device-delivered continuous passive range of motion may offer an enhanced benefit for some adverse symptom reduction in the hemiplegic arm after stroke over traditional self-range of motion exercise.

Aged↗

PubMed2004

Robotics and other devices in the treatment of patients recovering from stroke.

Stroke is the leading cause of permanent disability in the United States despite advances in prevention and novel interventional treatments. Randomized controlled studies have demonstrated the effectiveness of specialized post-stroke rehabilitation units, but administrative orders have severely limited the length of stay, so novel approaches to the treatment of recovery need to be tested in outpatients. Although the mechanisms of stroke recovery depend on multiple factors, a number of techniques that concentrate on enhanced exercise of the paralyzed limb have demonstrated effectiveness in reducing the motor impairment. For example, interactive robotic devices are new tools for therapists to deliver enhanced sensorimotor training for the paralyzed upper limb, which can potentially improve patient outcome and increase their productivity. New data support the idea that for some post-stroke patients and for some aspects of training-induced recovery, timing of the training may be less important than the quality and intensity of the training. The positive outcome that resulted in the interactive robotic trials contrasts with the failure to find a beneficial result in trials that used a noninteractive device that delivered continuous passive motion only. New pilot data from novel devices to move the wrist demonstrate benefit and suggest that successive improvement of the function of the arm progressing to the distal muscles may eventually lead to significant disability reduction. These data from robotic trials continue to contribute to the emerging scientific basis of neuro-rehabilitation.

Equipment Design↗

PubMed2003

Nonsurgical evaluation of pathologic nipple discharge.

BACKGROUND: Nipple discharge is a common breast complaint. Because most nipple discharge is a result of benign processes, less-invasive, nonsurgical diagnostic modalities have been explored to reduce the need for surgical intervention. METHODS: Between September 1994 and December 2000, 108 female patients aged 25 to 77 years underwent duct excision for bloody or clear nipple discharge. Results of various preoperative studies were compared with surgical pathology to determine the sensitivity, specificity, positive predictive value, and negative predictive value of these tests in detecting malignant ductal pathology. RESULTS: Of the 108 surgical histopathology specimens, 90 of 108 patients were benign, 5 of 108 patients were atypical, and 13 of 108 patients were malignant. The sensitivity of mammography was 57.1%, specificity was 61.5%, positive predictive value was 16.7%, and negative predictive value was 91.4%. Hemoccult sensitivity was 50%, specificity was 0%, positive predictive value was 20%, and negative predictive value was 0%. The sensitivity of ductography was 0%, specificity was 90%, positive predictive value was 0%, and negative predictive value was 81.8%. The sensitivity of cytology was 11.1%, specificity was 96.3%, positive predictive value was 50%, and negative predictive value was 76.5%. CONCLUSIONS: Preoperative evaluations by mammography, Hemoccult, ductography, and cytology are poor predictors of histological diagnosis. These data suggest that patients with pathologic nipple discharge should undergo surgical biopsy for accurate diagnosis.

Adult↗

PubMed2003

Methylene blue dye as an alternative to isosulfan blue dye for sentinel lymph node localization.

BACKGROUND: Our study describes the use of methylene blue dye as an alternative to isosulfan blue dye to identify the sentinel lymph node (SLN). METHODS: A retrospective analysis was performed of 112 breast cancer patients (113 axillae) who underwent SLN biopsy (SLNB) with methylene blue dye and (99m)Tc-labeled sulfur colloid for SLN identification. All SLNs were submitted for intraoperative frozen section analysis, hematoxylin and eosin stain, and immunohistochemical evaluation. Patients with a pathologically negative SLN did not undergo further axillary lymph node dissection. RESULTS: Of 112 patients who underwent SLNB, the SLN was identified in 107 (95.5%); 104 (92.8%) were identified by methylene blue dye. In a subset of 99 patients with recorded isotope status in relation to blue nodes, concordant identification with both dye and isotope was observed in 94 (94.9%). Of patients with identified SLNs, 32 (29.9%) of 107 contained metastatic disease, with 31 (96.9%) of 32 identified by methylene blue dye. The SLN was the only positive node in 18 (60.0%) of 30 patients. CONCLUSIONS: SLNB with methylene blue dye is an effective alternative to isosulfan blue dye for accurately identifying SLNs in breast cancer patients.

Adult↗

PubMed2002

Analysis of nipple/areolar involvement with mastectomy: can the areola be preserved?

BACKGROUND: Skin-sparing mastectomy (SSM), which involves the resection of the nipple/areolar complex with the breast parenchyma, improves the aesthetic outcome for breast cancer patients. Most patients undergoing SSM desire reconstruction of the nipple/areolar complex for symmetry. These data explore the possibility of preserving the areola in selected mastectomy patients. METHODS: A retrospective analysis of 217 mastectomy patients was conducted to determine the frequency of malignant nipple and/or areola involvement. The association between nipple and/or areola involvement and prognostic factors, including tumor size, stage, nuclear grade, axillary nodal status, and tumor location, was evaluated. RESULTS: The overall frequency of malignant nipple involvement was 23 of 217 (10.6%). In a subgroup of patients with tumors <2 cm, peripheral tumors, and with two positive nodes or less, the incidence of nipple involvement was 6.7%. When the nipple and areolar involvement were analyzed separately, only 2 of 217 patients had involvement of the areola (0.9%). All patients with areolar involvement had stage 3 breast cancer and were located centrally in the breast. CONCLUSIONS: We conclude from these data that nipple preservation is not a reasonable option for mastectomy patients. However, preservation of the areola with mastectomy in selected patients warrants further study.

Breast Neoplasms↗

PubMed2002

Assessing the motor status score: a scale for the evaluation of upper limb motor outcomes in patients after stroke.

The Motor Status Scale (MSS) measures shoulder, elbow (maximum score = 40), wrist, hand, and finger movements (maximum score = 42), and expands the measurement of upper extremity impairment and disability provided by the Fugl-Meyer (FM) score. This work examines the interrater reliability and criterion validity of the MSS performed in patients admitted to a rehabilitation hospital 21 +/- 4 days after stroke. Using the MSS and the FM, 7 occupational therapists masked to each other's judgments, evaluated 12 consecutive patients with stroke. Two therapists evaluated 6 additional patients on consecutive days. Intraclass correlation coefficients were significant for each group of raters for the shoulder/elbow and for the wrist/band (P < 0.0001); test-retest measures were also significant for the shoulder/elbow (Pearson correlation coefficient r = 0.99, P < 0.004) and for the wrist/hand (Pearson correlation coefficient r = 0.99, P < 0.003). The internal item consistency for the overall MSS was significant (Cronbach alpha = 0.98, P < 0.0001). Finally the correlation between the MSS and the FM (R2 = 0.964) was significant (P < 0.0001). The MSS affords a reliable and valid assessment of upper limb impairment and disability following stroke.

Disability Evaluation↗

PubMedDate not supplied

Economic consequences of renal dysfunction among cardiopulmonary bypass surgery patients: a hospital-based perspective.

BACKGROUND: Renal dysfunction is common after cardiopulmonary bypass procedures and is associated with higher mortality rates and longer lengths of stay. However, less is known about the actual cost of care for these patients. We sought to quantify the hospital costs attributed to renal dysfunction in cardiopulmonary bypass patients at a large academic referral center. METHODS: All patients undergoing cardiopulmonary bypass procedures were identified through administrative databases for a 3-year study period. Renal failure was defined using laboratory values from the hospitalization. Total direct costs and costs by hospital department were determined using the hospital cost-accounting system. A multivariate linear model was developed to determine total direct hospital costs after cardiopulmonary bypass procedures after adjusting for relevant clinical and demographic variables. RESULTS: Nine percent of the study population developed new-onset renal dysfunction, and 18% of patients overall undergoing cardiopulmonary bypass experienced renal dysfunction during the hospitalization. Direct costs were 42% higher for patients with renal dysfunction, an average of 5807 US dollars per case. Higher costs were noted in intensive care unit use and pharmacy, laboratory, and radiology services. CONCLUSIONS: Renal dysfunction increases the direct hospital costs of care, even after adjustment for age, sex, race, and comorbidities. Nationwide, we estimate that renal dysfunction may add up to 643 million US dollars in hospital costs for caring for cardiopulmonary bypass patients. Interventions designed to reduce the incidence and severity of renal dysfunction may significantly reduce hospital costs for these patients.

Aged↗

PubMedDate not supplied

Bone marrow micrometastases and adjuvant treatment of breast cancer.

The immunohistochemical detection of epithelially derived cells in the bone marrow of patients with primary breast cancer has been shown to be associated with increased risk of distant relapse as well as higher rates of cancer-related death. Despite the correlation between bone marrow micrometastases and poor outcome in breast cancer patients, bone marrow status does not yet have an established role in patient management. In this prospective study, adjuvant therapy recommendations for 43 patients with stage I, II, or III breast cancer treated with lumpectomy or mastectomy, sentinel lymph node biopsy and/or axillary dissection, and intraoperative bone marrow aspiration were recorded. Recommendations were made by a multidisciplinary tumor board both blinded and unblinded to the results of the bone marrow aspiration. In our study, 10 of the 43 breast cancer patients were found to have bone marrow micrometastases. Four of these patients (40%) had axillary lymph node metastases. When blinded to the results of the bone marrow aspiration, the tumor board recommended adjuvant chemotherapy for these four node-positive patients, as well as two node-negative patients. When unblinded to the results of the bone marrow aspiration, the tumor board did not change its recommendations for any of these six patients. The remaining four node-negative, bone marrow-positive patients were not advised to have adjuvant chemotherapy by the tumor board when blinded to bone marrow status. However, once the tumor board was informed of the presence of bone marrow micrometastases, adjuvant chemotherapy was recommended for all of these patients. The results of this pilot study indicate that the presence of bone marrow micrometastases in breast cancer patients with stage I, II, or III disease does influence recommendations for adjuvant chemotherapy, particularly in patients with node-negative disease.

Adult↗