Search PubMed⌕ Search

Biomedical subjects

P Perkins

Publications and source records attributed to P Perkins.

At least 19 recordsLinked to original sources
PubMed2001

Phase II study of the cyclin-dependent kinase inhibitor flavopiridol administered to patients with advanced gastric carcinoma.

PURPOSE: Flavopiridol is the first cyclin-dependent kinase inhibitor to enter clinical trials. Activity in gastric cancer xenografts and in a patient with gastric cancer on the phase I trial led to this phase II study of flavopiridol in patients with metastatic gastric cancer. PATIENTS AND METHODS: Sixteen patients were entered onto the study, and 14 were assessable for response. Flavopiridol was administered initially at a dose of 50 mg/m(2)/d by continuous infusion for 72 hours every 2 weeks. Assessment of plasma pharmacokinetics was performed in all patients. Peripheral mononuclear cells were collected throughout the 72-hour infusion for determinants of apoptosis. RESULTS: There were no major objective responses (exact confidence interval 0% to 23%). One patient achieved a minor response in his liver metastases, though the primary progressed. Other patients exhibited histologic and radiographic evidence of tumor necrosis. Common toxicities included fatigue in 93% of patients (grade 3 or 4 in 27%) and diarrhea in 73% of patients (grade 3 or 4 in 20%). Five patients (33%) developed venous thromboses at the central catheter tip. The studies performed on peripheral mononuclear cells indicated no induction of apoptosis. CONCLUSION: Flavopiridol administered as a single agent for 72 hours every 14 days is inactive in the treatment of gastric cancer. The drug also induced an unexpected higher incidence of vascular thrombosis and fatigue than was anticipated from the phase I trials. Future development of flavopiridol will depend on other doses and schedules in combination with chemotherapy.

Adenocarcinoma↗
PubMed2000

The outcome of knee synovitis in early arthritis provides guidelines for management.

The aim of the study was to examine the clinical outcome of patients presenting to an early arthritis clinic with synovitis of the knee. The patients were assessed at presentation for evidence and pattern of joint inflammation. These patients were then reassessed at 3, 6 and 12 months and thereafter annually to determine clinical outcome. One thousand six hundred and thirty-three consecutive referrals were examined, 903 of whom had early synovitis. One hundred and thirty had knee synovitis at presentation, of whom 73 fulfilled ACR criteria for rheumatoid arthritis (RA) during the study. All 73 presented with a symmetrical polyarthritis that included the small joints and had persistent disease at 1 year. Of the remaining 57 patients, 61% of those presenting with an oligoarthritis and 33% with a polyarthritis (including knee synovitis) were in remission at 1 year. None of those presenting as a monoarthritis of the knee had inflammation at 1 year or fulfilled ACR criteria for RA at any time. It was concluded that patients presenting with knee synovitis in the absence of a small joint polyarthritis usually have a benign course following standard therapy. No patient who presented with monoarthritis developed RA. Knee synovitis as part of a polyarthritis (even when not fulfilling ACR criteria) probably justifies disease-modifying antirheumatic drug at presentation.

Antirheumatic Agents↗
PubMed1999

Gout.

Explore the source record for details and available documents.

Acute Disease↗
PubMed1998

Prognostic biomarker study in pathologically staged N1 non-small cell lung cancer.

PURPOSE: The prognostic influence of 6 biomarkers correlated to histologic subtypes of non-small cell lung cancer (NSCLC) on loco-regional control, overall survival, disease-free survival (DFS), and distant disease control (DDC) rates, all measured at 5 years, were examined. MATERIALS & METHODS: Cell blocks from the primary tumors of 137 patients with pathologically staged N1 NSCLC at MDACC were analyzed by 6-biomarker status correlated to histological subtypes and their outcomes. RESULTS: The ranges of biomarker values were as follows: apoptotic index, 0.2-2.8%; mitotic index, 0-1.8%; the proportion of cells in S+G2M, 3-36%; p53 status, 0-100%; Ki-67, 0-9.3%; DNA index, 1.0-2.74. Subtypes of 137 cases from the postoperative pathology specimen showed that 74 patients had squamous carcinoma and 63 patients had adenocarcinoma. Mean and median lengths of follow-up were 4.21 years and 2.43 years, respectively. Patients with squamous cell carcinoma (SCC) had a better 5-year survival (p = 0.006), DFS (p = 0.002), and distant metastasis control (p = 0.002) than patients with adenocarcinoma (AC). Among patients with AC, the DNA index was a significant predictor of 5-year DFS (p = 0.02), DDC rate (p = 0.04), and local-regional control (p < 0.05). Higher apoptosis (p = 0.03) and mitosis indices (p = 0.03) were also univariate predictors of increased distant disease among patients with AC. Multivariate analysis of patients with AC revealed that the DNA index and Ki-67 were the only significant independent predictors of distant metastasis (p < 0.04 and p < 0.02, respectively) and DFS (p < 0.04 for both). Among patients with SCC, univariate analysis showed that S+G2M proportion (p < 0.05) and Ki-67 levels (p < 0.02) were significant predictors for local-regional control; for SC, multivariate analysis showed that only mitosis was a significant predictor in this case for overall survival (p < 0.04). CONCLUSION: Spontaneous apoptotic index and Ki-67 were significantly higher in SC than in AC. Patients with SC had less distant metastasis better DFS and overall survival than those with AC. Multivariate analysis revealed that DNA index and Ki-67 status were significant predictors for DDC and DFS in patients with AC, but only mitotic index was a significant predictor of overall survival for patients with SCC.

Adenocarcinoma↗
PubMed1998

Cutaneous ulcers of refractory adult dermatomyositis responsive to intravenous immunoglobulin.

We report the case of a woman from the Bahamas who presented with many of the classic manifestations of dermatomyositis. She responded well to initial therapy, which included oral corticosteroids, low-dosage methotrexate, and hydroxychloroquine. The cutaneous component of her disease flared dramatically months later, and progressed despite aggressive therapy with the higher dosages of the same medications. Therapy with intravenous immunoglobulin (IVIG) was initiated and the patient stopped forming new cutaneous ulcers within 1 to 2 weeks. Theories about the mechanism of action of IVIG, and practical guidelines for its use in treating patients with dermatomyositis, are briefly reviewed.

Dermatologic Agents↗
PubMed1997

Carcinoid tumors of the lung and family history of cancer.

Family history of cancer has been described among patients with lung neoplasms. Carcinoid tumors, originally thought to be slow growing and nonmetastatic, have not historically been included in these studies. In some instances these tumors have demonstrated aggressive metastatic potential. A medical record review of 86 patients with histopathologically confirmed carcinoid tumors of the lung, treated at the University of Texas M.D. Anderson Cancer Center between 1959 and 1994, was conducted to describe family history of cancer. Family history of cancer was recorded in 74 (86%) of the medical records and 32 (43%) reported first-degree relatives with cancer. Five-year survival for patients with affected relatives was 45% and 73% for patients without affected relatives (p = .23). Among 67 patients without metastatic disease at diagnosis, the risk of distant metastasis by 5 years was 40% among patients with a positive family history of cancer compared to 6% of the patients without affected relatives (p = .03), (rate ratio 5.01). These results suggest that genetic susceptibility may affect the metastatic potential of some carcinoid tumors.

Carcinoid Tumor↗
PubMed1997

Pretreatment characteristics of carcinoid tumors of the lung which predict aggressive behavior.

Carcinoid tumors of the lung are uncommon and usually have a favorable outcome after resection. However, some patients have aggressive tumors that cannot be completely resected or have unfavorable outcomes after resection. A retrospective study was conducted to identify factors that predict outcome. Records of all previously untreated patients treated at the University of Texas M. D. Anderson Cancer Center (UTMDACC) between 1959 and 1994, with histologically confirmed carcinoid tumors of the lung, were reviewed. Histologic specimens were reclassified by contemporary criteria. Five-year survival for 79 patients without distant metastasis who had tumors with clinically aggressive features at diagnosis (defined as extension to the carina, involvement of regional lymph nodes, and/or vascular invasion) was 50.9% as compared with 76.9% (p = 0.01) for patients without these features. Five-year survival was 38.7% for patients with "atypical" histopathology as compared with 78.9% for patients with "typical" histopathology. Patients with aggressive tumors were more likely to have atypical tumors [odds ratio (OR) 11.73, p < 0.001]. However, 17.5% of the patients with clinically aggressive carcinoid tumors had tumors that were classified as typical. Carcinoid tumors of the lung that exhibit aggressive behavior may not have atypical histopathologic features. Clinical features that suggest aggressive behavior and unfavorable outcome warrant further investigation.

Adolescent↗
PubMed1997

Incidence and prevalence of dementia in a multiethnic cohort of municipal retirees.

BACKGROUND: Multiethnic population-based studies of dementia are lacking in the literature; therefore, we conducted a study to determine the incidence and prevalence of dementia among, black, white, and Hispanic municipal retirees age 50 and older. METHODS: In 1991, city of Houston municipal workers who retired between 1980 and 1984 received in-home screening for cognitive impairment using the Mini-Mental State Examination and were referred for comprehensive neurologic evaluation if indicated. Families of deceased retirees were interviewed, medical records were reviewed, and death certificates were obtained to determine case status of the retiree. Study participation was 90%. RESULTS: Crude prevalence of dementia, among retirees age 60 and older, was 2.65 per 100 population. Age-adjusted to the 1970 US population, age 60 to 80, the prevalence was 1.85 per 100 population. Age-adjusted prevalence of dementia was similar among Hispanic and black men, 4.75 and 4.80 respectively, and lowest among white men, 2.42 per 100 population. Forty-three percent of the prevalent cases (30% of the incidence cases) were not previously diagnosed. The cumulative incidence of dementia calculated to age 80 was 39% for Hispanic men, 28% for black men, and 14% for white men. Fifty-five percent of the incidence cases were diagnosed as having ischemic vascular dementia (IVD), 20% as having probable or possible Alzheimer's dementia (AD), and 25% as having unspecified dementia. CONCLUSIONS: Risk of dementia by age 80 was more pronounced for Hispanic and black men compared with white men. IVD was the predominant cause of dementia among both black and white men. Grouping Hispanics with whites may mask differences when studying dementia.

Aged↗
PubMed1997

The acute phase and function in early rheumatoid arthritis. C-reactive protein levels correlate with functional outcome.

OBJECTIVE: To discover whether normalization of C-reactive protein (CRP) in patients with rheumatoid arthritis (RA) results in stabilization of their functional state, and whether a measure of disease activity can be used as a predictor of functional outcome. To examine the relationship between change of CRP and Health Assessment Questionnaire (HAQ) over a 24 mo period to define the sensitivity of HAQ to change. METHODS: A prospective study of 109 consecutive patients who fulfilled the American College of Rheumatology criteria for RA and had elevated CRP before steroid or 2nd line therapy. A full clinical assessment including HAQ was performed at presentation and at 3, 6, 12, and 24 mo. On the basis of the change in CRP at 6 mo, patients were divided into 3 groups: (1) CRP suppression to normal, (2) 50% reduction in CRP, and (3) less than 50% CRP change. RESULTS: The 3 groups were clinically and immunologically similar at onset. At 6 mo the median HAQ fell to 5 (lower to upper quartiles 7.5 to 19) in Group 1 (CRP normalized, n = 34), 6 (3.75 to 10) in Group 2 (CRP reduced by 50%, n = 30), and 12 (6 to 18) in Group 3 (less than 50% CRP change, n = 44), p < 0.005 for Groups 1 and 2 versus Group 3. At 12 and 24 mo HAQ remained significantly lower in Groups 1 and 2 compared with Group 3. In Group 1, patients either maintained a normal CRP (n = 28) or their CRP became elevated (n = 6). Only in those patients in whom a re-elevation of the CRP occurred was deterioration in HAQ subsequently seen. CONCLUSION: Suppression of elevated CRP in patients with active RA is associated with improvement in functional score, whereas persistent elevation of CRP is associated with functional deterioration. Once abnormal CRP is suppressed, no functional deterioration is likely to occur without re-elevation in CRP. Therefore, elevated CRP provides a convenient short term correlation with functional outcome and can be used as a guide for therapy. A HAQ score is a sensitive indicator of change in early disease.

Analysis of Variance↗
PubMed1996

Apoptosis and mitosis as prognostic factors in pathologically staged N1 nonsmall cell lung cancer.

PURPOSE: This study aimed to established whether spontaneous apoptosis or mitosis has prognostic value among patients with pathologically staged N1 nonsmall cell lung carcinoma (NSCLC) treated with surgical resection with or without adjuvant therapy. METHODS AND MATERIALS: Material from 173 patients who had resections between 1970 and 1988 was analyzed for apoptosis and mitosis. There were 128 men and 45 women, with a median age of 61 years. There were 86 squamous cell carcinomas (SQ), 73 adenocarcinomas (AC), 3 large-cell carcinomas (LC), 6 SQ-AC, and 5 unclassified. Patients were observed from 2 to 209 months (median 27). Actuarial methods were used to assess survival and freedom from distant metastasis. RESULTS: In NSCLC, apoptosis was found to range from 0.2% to 2.8% (median 1.0%) and mitosis from 0 to 1.8% (median 0.4%). Tumors having higher levels of apoptosis also had higher levels of mitosis (p = 0.001). The values of neither apoptosis nor mitosis depended on size, location, differentiation of tumors, age, performance status, or weight loss of patients. However, the values of apoptosis depended on tumor histology in that high values (greater than or equal to the median) were more frequent in SQ (49%) than in AC/LC (29%) (p = 0.01). The overall survival for NSCLC patients, which was 33% at 5 years, did not depend on the level of either apoptosis or mitosis. The 5-year survival of patients having SQ was higher (43%) than that of patients having AC/LC (21%) (p = 0.03). Patients with high apoptosis showed significantly better 5-year overall (p = 0.008) and DMF (p = 0.0012) survivals in the SQ group compared to the AC/LC group. High mitosis compared to low mitosis was a significantly better predictor for 5-year survival (62% vs. 29%, respectively) (p = 0.035) in the SQ. However, high mitosis was a significantly worse 5-year DMF survival predictor compared to low mitosis: 13% vs. 56%, respectively (p = 0.05) in AC/LC. In the multivariate models for AC/LC, mitosis remained a significant predictor of 5-year distant metastasis (p = 0.025) controlling for treatment groups (p = 0.042), whereas apoptosis was an independently significant predictor of 5-year distant metastasis (p = 0.010). CONCLUSION: Squamous cell histology predicted significantly better 5-year overall and DMF survivals compared to AC/LC. Apoptosis was correlated with mitosis. Although apoptosis or mitosis did not predict survival or DM, high apoptosis or mitosis predicted significantly better survival in SQ and significantly worse survival in AC/LC with regard to overall and DMF survivals. In the multivariate models for AC/LC, apoptosis alone or mitosis with variable treatment was a significant predictor of 5-year distant metastasis. Thus, pretreatment levels of apoptosis or mitosis might be useful for predicting treatment outcome of SQ and AC/LC subsets of NSCLC when analyzed separately and for predicting metastatic incidence of AC/LC.

Adenocarcinoma↗
PubMed1996

Breast cancer. Is ethnicity an independent prognostic factor for survival?

BACKGROUND: A survival difference between white and black females has been reported after diagnosis and treatment for breast carcinoma. Although multivariate analyses demonstrate that the survival difference is less or nonexistent when additional prognostic factors are considered, study results have been inconsistent. The objective of this study was to examine further the role of ethnicity as an independent prognostic factor for breast carcinoma survival among white and black females treated over a 30-year period. METHODS: Among 3382 eligible white and black females who registered at M. D. Anderson Cancer Center (MDACC) from 1958 to 1987, ethnicity, age, socioeconomic status (SES), stage of disease, and treatment were examined. Data were obtained from the hospital tumor registry and survival was compared using actuarial life tables and multivariate Cox regression analyses. RESULTS: Univariate analyses demonstrated that the survival difference between white and black females was significant, with black females having a 1.63 times higher risk of mortality at 5 years compared with white females (confidence interval (CI), 1.47-1.82), with ethnicity a significant predictor of survival (P < 0.001). After controlling for SES, stage, and treatment, the relative risk was 1.12 (CI, 1.00-1.25) and ethnicity was no longer a strong predictor of survival (P = 0.048). CONCLUSIONS: In this hospital population, the white and black female survival difference, which was highly significant when only univariate analyses were considered, became marginally significant after controlling for other prognostic factors.

Black or African American↗
PubMed1996

Mechanisms of cell death after pancreatic duct obstruction in the opossum and the rat.

BACKGROUND & AIMS: Mechanisms of cell death in human and experimental pancreatitis remain poorly understood. The aim of this study was to determine the mechanisms of cell death, apoptosis vs. necrosis, in models of pancreatitis induced by pancreatic duct ligation in the opossum and rat. METHODS: Morphological changes were shown by light and electron microscopy, chromatin condensation and DNA breaks were assessed using Hoechst 33258 staining and DNA nickend labeling, and DNA fragmentation was characterized b gel electrophoresis. RESULTS: Cells with morphology of both necrosis and apoptosis were found in pancreata from duct-ligated animals; however, the apoptosis-necrosis ratio was different for the opossum and the rat. Both apoptotic and necrotic cells stained for breaks in DNA, suggesting that both apoptosis and necrosis are associated with DNA fragmentation and that DNA end labeling cannot specifically detect apoptotic cells. No significant oligonucleosomal DNA fragmentation was found in pancreas from duct-ligated animals, although the endonuclease responsible for oligonucleosomal DNA fragmentation was present in pancreatic nuclei. CONCLUSIONS: Duct ligation resulted predominantly in apoptosis in the rat and necrosis in the opossum. The differences in types of cell death in the two models may result from differences in inflammatory cell infiltration.

Animals↗
PubMed1996

Clinical associations of dual-energy X-ray absorptiometry measurement of hand bone mass in rheumatoid arthritis.

Hand bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA) has potential as a marker of progression in early rheumatoid arthritis (RA). We examined a DXA methodology and studied in a cross-sectional manner 202 patients with RA. Hand BMD correlated inversely with age and was higher in males. Hand BMD correlated with lumbar and femoral sites. In females, BMD of the hand correlated positively with grip strength and negatively with disability. Those with higher C-reactive protein (CRP) had significantly lower hand BMD than those with normal CRP. In patients with a normal CRP, the hand BMD:lumbar BMD ratios were significantly higher in patients with longer disease duration. Hand BMD correlates with measures of disease activity, functional capacity and also with lumbar and femoral BMD. Hand bone loss occurs in early disease, in the absence of detectable systemic disease, and before lumbar BMD loss. It has the potential to be an outcome measure in early disease.

Absorptiometry, Photon↗
PubMed1996

Spindle cell hemangioendothelioma. An analysis of 78 cases with reassessment of its pathogenesis and biologic behavior.

Seventy-eight cases of spindle cell hemangioendothelioma (SCH) were studied to reevaluate its pathogenesis and determine its long-term behavior. Most of the original findings were confirmed by this study. The tumor occurred at all ages (8-78 years; median, 32 years; mean, 34 years). Males and females were equally affected. The tumor developed as a superficially located mass of the distal extremities (upper, 32 cases; lower, 30 cases). Four patients (5%) also had Maffucci's syndrome. The lesions were circumscribed red-brown masses occasionally containing phleboliths that consisted of cavernous blood spaces alternating with cellular areas consisting of collapsed vascular spaces separated by spindled fibroblastic cells. Often the endothelium lining the collapsed blood spaces appeared epithelioid with cytoplasmic vacuolization. The spindled fibroblastic cells lacked significant atypia and had at most a low level of mitotic activity. As a significant departure from what was originally reported, more than half of these cases (58%) were partially or completely intravascular. The vein containing the tumor often had an irregularly attenuated wall with small intimal herniations and intimal papillae traversing the lumen. Similar intimal changes in adjacent vessels suggest that SCH grows as a multifocal or contiguous process within vessels. Follow-up information was obtained in 40 cases, ranging from 1 month to 40 years (mean, 5.4 years). Despite conservative excisions in most patients (simple excision, 83%; wide local excision, 13%; amputation, 2%), prognosis was excellent. Fifty-eight percent experienced recurrences, but no patient developed metastasis and no patient died of the direct effects of the tumor, although one patient with Maffucci's syndrome developed a concurrent angiosarcoma. We conclude that SCH is a primary benign vascular neoplasm or malformation similar to angiomatosis in which alterations in blood flow might explain some of the secondary features. Areas of diminished blood flow result in vascular collapse with formation of the "cellular" zones, and areas of vascular engorgement with stasis promote thrombosis and organization. Local "recurrences" probably represent contiguous spread along or multifocal involvement of a vessel. Because there is no evidence that this lesion has metastatic potential, we suggest that the lesion be designated spindle cell hemangioma for solitary lesions and spindle cell hemangiomatosis for multifocal lesions.

Adolescent↗
PubMed1995

Limited-stage small-cell lung cancer: patient survival after combined chemotherapy and radiation therapy with and without treatment protocols.

PURPOSE: To compare survival of patients who undergo treatment in protocols versus survival of patients not in protocols. MATERIALS AND METHODS: Records of 81 adult patients with small-cell lung cancer who underwent chemotherapy and radiation therapy in 1987-1992 were reviewed retrospectively. Forty-one patients were in a protocol; 40 patients were not. Patient demographics and prognostic factors were not statistically significantly different. RESULTS: Median overall survival was 16.7 months in the nonprotocol group versus 29.0 months in the protocol group (P = .0023). Median disease-specific survival was 18.3 months in the nonprotocol group versus 27.1 months in the protocol group (P = .0176). Survival was not statistically significantly influenced by Karnofsky performance status, weight loss, or thoracic radiation dose. CONCLUSION: There was a highly statistically significant difference in survival outcome in the nonprotocol group versus the protocol group (P = .0023). Differences in chemotherapy-radiation therapy timing and other treatment-related factors may have contributed substantially to the improved survival in the protocol group.

Adult↗