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R Fry

Publications and source records attributed to R Fry.

At least 19 recordsLinked to original sources
PubMed2006

Does sodium hyaluronate- and carboxymethylcellulose-based bioresorbable membrane (Seprafilm) decrease operative time for loop ileostomy closure?

BACKGROUND: Adhesions can result in serious clinical complications and make ileostomy closure, which is relatively simple procedure into a complicated and prolonged one. The use of sodium hyaluronate and carboxymethyl cellulose membrane (Seprafilm) was proven to significantly reduce the postoperative adhesions at the site of application. The aim of this study was to assess the incidence and severity of adhesions around a loop ileostomy and to analyze the length of time and morbidity for mobilization at the time of ileostomy closure with and without the use of Seprafilm. METHODS: Twenty-nine surgeons from 15 institutions participated in this multicenter prospective randomized study. 191 patients with loop ileostomy construction were randomly assigned to either receive Seprafilm under the midline incision and around the stoma (Group I), only under the midline incision (Group II), or not to receive Seprafilm (Group III). At ileostomy closure, adhesions were quantified and graded; operative morbidity was also measured. RESULTS: All 3 groups were comparable relative to gender, mean age and number of patients with prior operations (26, 25 and 19, respectively). Group II patients were significantly more likely to have pre-existing adhesions than Group III patients (30.6% vs. 14.1%, p = 0.025). At stoma mobilization, significantly more patients in Group III than in Group I had adhesions around the stoma (95.2% vs. 82.3%, p = 0.021). Mean operative times were 27, 25, and 28 minutes, respectively (p = 0.38), with significant differences among sites. There was no significant difference in the number of patients needing myotomy or enterotomy (29, 27 and 24 patients, respectively), nor in the number of postoperative complications (7, 9 and 7 patients, respectively). CONCLUSIONS: When consistently applied, Seprafilm significantly decreased adhesion formation around the stoma but not operative times without any increase in the need for myotomy or enterotomy. These findings were not seen in the overall study population possibly due to the large number of surgeons using a variety of application techniques.

Adjuvants, Immunologic↗
PubMed2005

A microscale in vitro physiological model of the liver: predictive screens for drug metabolism and enzyme induction.

In vitro models of the liver using isolated primary hepatocytes have been used as screens for measuring the metabolism, toxicity and efficacy of xenobiotics, for studying hepatocyte proliferation, and as bioartificial liver support systems. Yet, primary isolated hepatocytes rapidly lose liver specific functions when maintained under standard in vitro cell culture conditions. Many modifications to conventional culture methods have been developed to foster retention of hepatocyte function. Still, not all of the important functions -- especially the biotransformation functions of the liver -- can as yet be replicated at desired levels, prompting continued development of new culture systems. In the first part of this article, we review primary hepatocyte in vitro systems used in metabolism and enzyme induction studies. We then describe a scalable microreactor system that fosters development of 3D-perfused micro-tissue units and show that primary rat cells cultured in this system are substantially closer to native liver compared to cells cultured by other in vitro methods, as assessed by a broad spectrum of gene expression, protein expression and biochemical activity metrics. These results provide a foundation for extension of this culture model to other applications in drug discovery -- as a model to study drug-drug interactions, as a model for the assessment of acute and chronic liver toxicity arising from exposure to drugs or environmental agents; and as a disease model for the study of viral hepatitis infection and cancer metastasis.

Animals↗
PubMed2003

Age and type of procedure influence the choice of patients for laparoscopic colectomy.

BACKGROUND: The aim of this retrospective, case-matched controlled study was to determine the benefit of laparoscopic-assisted colectomy (LC) for the elderly (>75 years of age) and the young (<75 years of age) compared to an open colectomy (OC) control group. METHODS: A retrospective review of 39 patients older than 75 years of age and 38 patients younger than 75 years of age who underwent LC for colorectal cancer between 1991 and 1999 was performed. LC patients were matched with an open control group for procedure, age, gender, year of procedure, and surgeon. Procedures included right and left colectomy, anterior resection of the rectosigmoid, and abdominoperineal resection. Measured intraoperative variables included anesthesia time, operative time, and estimated blood loss. Postoperative parameters consisted of duration of intravenous or epidural narcotic usage, return of bowel function (RBF), length of stay, and independence at discharge. These variables were compared in the entire group of 154 patients. RESULTS: Mean ages were 81.4 and 81.8 years for LC and OC age >75 and 62.9 and 62.7 for LC and OC age <75. Mean anesthesia time and operative time were significantly longer (p < 0.05) for LC compared to OC (46.8 vs 39.3 and 159.3 vs 111.7 min, respectively) for age >75 and for age <75 (47.1 vs 40.3 and 182.8 vs 135.5 min, respectively). LC achieved faster recovery in both age groups: RBF (3.9 vs 4.9 days for age >75; 6.7 vs 7.7 days for age <75) (p < 0.05). Narcotic usage was shorter for the LC group age <75 (3.3 vs 4.4 days; p < 0.05). There was no significant difference in independence at discharge between LC and OC in either age group. Faster recovery was seen with left LC in age >75 and right LC in age <75 compared to OC. CONCLUSION: The advantages of LC over OC are the same for the elderly and the young. There may be a selective benefit of laparoscopic left colectomy in the elderly and laparoscopic right colectomy in the young.

Age Factors↗
PubMed2000

Chronic pain and health care utilization in women with a history of childhood sexual abuse.

OBJECTIVE: This cross-sectional controlled study investigated the association between chronic pain, health care utilization and a history of childhood sexual abuse. SUBJECTS: Three groups, constituting 80 women in total, were studied (1) attendees at group therapy for individuals who had experienced childhood sexual abuse (n = 26); (2) Two control groups consisting of nonabused (a) psychiatric outpatients (n = 33); and (b) nurses (n = 21). SETTING: The setting was a university affiliated community and tertiary care hospital in London. Ontario. OUTCOME MEASURES: Each subject voluntarily completed questionnaires documenting history of childhood abuse, pain, psychological symptomatology and medical and surgical history. RESULTS: Sixty-nine percent of the women who had experienced childhood sexual abuse reported a chronic painful condition lasting more than three months, compared to 43% of the combined control groups (p = .026). Women who had experienced childhood sexual abuse reported a greater number of painful body areas (p = .003), more diffuse pain and more diagnoses of fibromyalgia (p = .013). They had more surgeries (p = .037), hospitalizations (p = .0004) and family physician visits (p = .046). CONCLUSIONS: Women with a history of childhood sexual abuse reported more chronic pain symptoms and utilized more health care resources compared to nonabused control subjects. Identification of such a history in the patient experiencing persisting pain may be the first step toward a successful combination of medical and psychosocial interventions.

Adult↗
PubMed2000

Colorectal carcinomas with high microsatellite instability: defining a distinct immunologic and molecular entity with respect to prognostic markers.

Molecular analysis of hereditary nonpolyposis colorectal carcinomas (HNPCC) has identified DNA mismatch repair deficiencies with resulting microsatellite instability (MSI) as a pathway of carcinogenesis that appears to be relevant for prognosis, treatment, and possibly prevention. In this study, expression of cell cycle proteins and other known prognostic markers is correlated with the microsatellite status of colorectal cancers (CRC). One hundred consecutive cases from the CRC Registry at Thomas Jefferson University were analyzed for MSI. Immunohistochemistry was performed for the mismatch repair proteins hMLH1 and hMSH2, tumor suppressor p53, apoptosis inhibitor bcl-2, cell cycle proteins p21(WAF1/CIP1), and p27 and the proliferation markers Ki-67 and topoisomerase II. High MSI (MSI-H) is significantly correlated with loss of either hMLH1 or hMSH2, presence of bcl-2, and absence of p53. p21(WAF1/CIP1) is positive in all tumors with MSI-H. Previous findings of a lower proliferation rate were confirmed with a topoisomerase II stain. Microsatellite stable (MSS) tumors generally express both MSH2 and MLH1. Other highly significant differences are positive p53 in 56% of MSS cases and negative bcl-2 in 98% of MSS cases. p27 expression is found in approximately 50% of all CRCs irrespective of the microsatellite status. MSI-H tumors follow the mutator pathway, with loss of expression of one mismatch repair protein, wild-type p53, lower proliferation, and positivity for p21(WAF1/CIP1). MSS tumors follow the suppressor pathway, characterized by p53 overexpression, higher proliferation, and absence of bcl-2 expression; p21(WAF1/CIP1) expression can be variable. These data provide a molecular basis for the clinical observation that patients with HNPCC appear to have a more favorable prognosis. HUM PATHOL 31:1506-1514.

Adenoma↗
PubMed2000

Rectal cancer adjuvant therapy controversies: When? What? Why?

Although the need for adjuvant therapy in high-risk rectal cancer is widely accepted, controversies continue regarding timing, mode, and agents employed. The current recommended practice and its scientific basis are reviewed. Studies of induction therapy are discussed. Evidence of efficacy of new anticancer agents and modes of drug delivery are presented.

Chemotherapy, Adjuvant↗
PubMed1999

Infrared Emission Spectroscopic Study of the Dehydroxylation via Surface Silanol Groups of Synthetic and Natural Beidellite.

The structural changes of synthetic and natural beidellites during dehydroxylation have been studied using infrared emission spectroscopy of the OH-stretching and bending regions. The OH-stretching region is characterized by two OH-stretching modes around 3600-3615 cm-1 and around 3650 cm-1. These bands strongly decrease in intensity upon dehydroxylation up to 600 degrees C for the natural beidellite and 700-750 degrees C for the synthetic ones. The differences in bandwidth, intensity, and dehydroxylation behavior are interpreted as due to differences in crystallinity with crystallinity increasing in the order natural beidellite < synthetic beidellite BSK3 < synthetic beidellite E498. Above 400 degrees C a new band attributed to silanol groups becomes visible in all samples due to transfer of the hydroxyls from the octahedral layer to the siloxane layer before they are lost. The broad band around 3300-3400 cm-1 is assigned to both H-bonding in H2O and H-bonding to Si-O-Al linkages. The presence of two different OH groups is also reflected in the OH-bending modes around 875-895 cm-1 and 915-925 cm-1 and in the OH-libration modes around 780 and 800-820 cm-1. These bands show a decrease in intensity upon heating and dehydroxylation of the clay structure. Here again the same order can be observed for the disappearance of the bands as for the OH-stretching region. Copyright 1999 Academic Press.

Journal Article↗
PubMed1999

Five fractions of preoperative radiotherapy for selected cases of rectal carcinoma: long-term tumor control and tolerance to treatment.

BACKGROUND: Randomized Swedish studies demonstrate the efficacy of a 5-fraction course of preoperative radiotherapy for rectal carcinoma. The present study evaluates the results in a single U.S. institution over a 20-year period with a similar regimen. METHODS AND MATERIALS: During the period of 1975-1995, 83 patients received pelvic radiotherapy of 20 Gy/5 fractions, followed by immediate surgery for rectal cancer. These patients represented 21% of cases receiving preoperative treatment; the remainder received 45-50 Gy preoperatively. The 5-fraction course was used for lesions deemed readily resectable but too bulky for conservative endocavitary treatment. Since 1990, it has been our policy to administer postoperative chemotherapy to medically fit patients who prove to have pathologic Stage II or III disease. Patient characteristics including age (mean 65 years, range 23-90), gender (45% male), and location within the rectum were comparable to our previously reported cases that received 45 Gy/25 fractions preoperatively. However, the group selected for 5 fractions preoperatively had relatively fewer lesions that were tethered (20% vs. 61%), circumferential (11% vs. 20%), or near obstructing (1% vs. 16%). RESULTS: With a post treatment follow-up of 1-15 years (mean 4.7), there have been 3 local failures and 12 distant failures, with an actuarial local control of 95%, and disease-specific survival of 77% at 5 and 10 years. Grade > or = 3 perioperative or late toxicity occurred in 11 cases (13%), including 3 (3.5%) late bowel obstructions. Stage II or III disease was found in 56% of the cases, 74% of which were free of disease at last follow-up. However, patients with Stage II or III lesions that were significantly tethered or fixed had a 40% greater likelihood of recurring than similar stage lesions that were, at most, slightly tethered. Sphincter-preserving surgery was possible in 60% of the patients. In recent years, postoperative chemotherapy has been administered to 16 patients with Stage II or III disease; this has been well tolerated, with only 1 late toxicity (cystitis managed medically). When compared with a matched group of cases receiving conventionally fractionated preoperative radiation, there were no significant differences in perioperative morbidity and nonradiotherapeutic cost generating factors (length of hospital stay, duration of postoperative antibiotics, blood loss at surgery). CONCLUSION: Patients with resectable rectal cancer who received 20 Gy/5 fractions preoperative radiotherapy to the pelvis had excellent local and distant control of disease. These patients were able to undergo sphincter-preserving surgery and postoperative chemotherapy. It would be of interest to conduct a randomized trial comparing short course with longer course (45 or 50 Gy) preoperative radiotherapy for resectable T3 lesions. The results of this study suggest that, in general, differences in toxicity, local control, and disease-free survival would probably be < 10%. However, since the results of this study suggest that patients with significantly tethered lesions may be better served with the higher dose and longer duration course of radiation, clinical degree of fixation should be included as a stratification parameter, and stopping criteria should be included for tethered lesions.

Adult↗
PubMed1999

A comparison of short-term group and individual therapy for sexually abused women.

OBJECTIVE: To compare the effectiveness of 10 sessions of group therapy with that of 10 sessions of individual therapy in a sample of 86 adult women seeking treatment for the effects of childhood sexual abuse. METHOD: Participants were randomly assigned to the 2 treatment modalities and tested at assessment, pretherapy following a 10-week wait condition, posttherapy, and 6-month and 12-month follow-up. RESULTS: Participants had fewer symptoms and better psychosocial functioning posttherapy and were further improved at the 6- and 12-month follow-up. Neither treatment modality was superior to the other. Approximately one-half of the sample sought further treatment during the follow-up periods. CONCLUSIONS: Improvement in symptoms and functioning was associated with short-term treatment in both modalities, but many patients remained distressed and required further treatment. Future research should investigate whether sexually abused women who meet criteria for specific diagnoses require more focused and/or longer-term therapy.

Adult↗
PubMed1998

Neonatal immunization against gonadotropin-releasing hormone (GnRH) results in diminished GnRH secretion in adulthood.

The effects of neonatal immunization against GnRH were studied in sheep after they had reached adulthood (3-4 yr) and the antibody titers had fallen to undetectable levels. The immunized animals had small gonads, and the females did not have large follicles (>3 mm) or corpora lutea in their ovaries. Compared with controls, the immunized animals had low or nondetectable levels of LH and FSH in peripheral plasma, and the immunized animals generally failed to respond to a single i.v. GnRH challenge. After ovariectomy, the control ewes, but not the immunized ewes, showed an elevation in plasma LH and FSH levels. The sampling of hypophysial portal blood, with a newly described method, showed that the secretion of GnRH was reduced in the immunized animals, but the amount of GnRH in the median eminence was similar in the control and immunized ewes. The pituitary content of LH and FSH was reduced in the immunized ewes as was messenger RNA for the gonadotropin subunits and the GnRH receptor. These data indicate that neonatal immunization does not affect the synthesis of GnRH in adulthood but reduces the secretion of GnRH, causing long-term sterility in these animals.

Animals↗
PubMed1997

Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia.

OBJECTIVE: To compare the evolution of Alzheimer disease (AD), vascular dementia (VaD), and mixed dementia by cognitive domain. SETTING: The University of Western Ontario Dementia Study, which is a registry of cases of dementia seen for secondary and tertiary assessment in a university memory disorders clinica with extensive follow-up data and histopathological confirmation of clinical diagnoses. PATIENTS: One hundred twenty-nine patients with definite or probable AD, 12 patients with definite or probable VaD, and 36 patients with definite or probable mixed dementia. METHODS: Patients were grouped as having an early, moderate, or advanced stage of disease according to the extended scale for dementia (ESD). The ESD was subdivided into cognitive domains, and the domain scores were compared for each stage of disease by diagnostic category with the use of a 2-way analysis of variance with repeated measures. RESULTS: As expected, the scores in all domains decreased significantly with increasing severity. There was a significant difference in the decline in memory among the diagnostic groups (P = .02) that was mostly attributable to the difference between AD and mixed dementia (P = .03), with the difference between AD and VaD only approaching significance (P = .06). There was a similar finding for praxis. The interaction between diagnosis (AD and VaD) and severity was significant only for memory (P = .02), showing a less severe memory deficit at onset but a proportionately more rapid progression in VaD and arithmetic ability (AD and mixed dementia [P = .03]). CONCLUSIONS: Alzheimer disease, VaD, and mixed dementia evolve similarly as assessed using cognitive domains obtained by subdivision of the ESD in a patient population derived from a memory clinic and by analyzing VaD as a single entity. Only memory impairment evolves differently between AD and VaD, with this depending on the severity. Memory is more severely impaired in the early stage of AD; however, with increasing severity of dementia, memory impairment in VaD accelerates and catches up with AD at the level of moderate impairment. The differences between AD and mixed dementia are greater than those between mixed dementia and VaD, suggesting an important role for the ischemic component of mixed dementia. Simple neuropsychological tools (eg, the ESD) may be incapable of distinguishing between AD and VaD, and more focused instruments may be required. Inherent bias in case selection may prevent extrapolation of these results to VaD in general, but the neuropsychological criteria for VaD may need to vary, depending on the severity.

Alzheimer Disease↗
PubMed1997

Preoperative staging of irradiated rectal cancers using digital rectal examination, computed tomography, endorectal ultrasound, and magnetic resonance imaging does not accurately predict T0,N0 pathology.

PURPOSE: The postradiation preoperative staging results of 25 patients with rectal cancer who were found to have Stage T0,N0 lesions after surgery were examined. Our aim was to assess the ability of preoperative staging following radiation therapy to predict the absence of disease. METHODS: From 1983 to 1994, 25 patients treated with preoperative radiation therapy for biopsy-proven rectal cancer were found to have no pathologic evidence of disease in the resected specimen (T0,N0). The preoperative postradiation disease staging results of these patients were compared with the postoperative pathologic findings. Each patient received 4,500 to 5,580 cGy during a five-week to six-week period, and four patients had preoperative chemotherapy. Surgical resection was performed six to eight weeks after completion of radiation therapy. All 25 patients were staged by digital rectal examination before surgery. In addition, 13 patients were assessed using computed tomography, 6 by endorectal ultrasound, and 1 by magnetic resonance imaging. RESULTS: Most irradiated lesions were overstaged by radiologic assessment and physical examination. No technique could reliably distinguish between postradiation fibrosis and residual cancer. The negative predictive value for digital rectal examination was 24 percent. Computed tomography accurately staged 23 percent of lesions, and endorectal ultrasound predicted 17 percent of lesions correctly. The single patient evaluated by magnetic resonance imaging was overstaged and thought to have a T2 lesion. CONCLUSIONS: Our ability to assess local eradication of rectal cancer following radiation therapy remains poor. Conventional imaging and clinical examination techniques are unable to safely predict which patients do not require surgical excision following curative radiation therapy for rectal cancer.

Adenocarcinoma↗
PubMed1996

Carcinoma of the rectum. Possible cellular predictors of metastatic potential and response to radiation therapy.

BACKGROUND: Preoperative radiation therapy can markedly improve local control of rectal carcinoma. However, some tumors do not respond well to moderate doses of preoperative radiation and would be better served by more aggressive preoperative treatment (e.g., chemoradiotherapy). Cellular predictors of responsiveness to radiation can help to select lesions for more aggressive treatment. In addition, there is a need for cellular predictors of metastatic potential. This is particularly important in the setting of preoperative radiation-downstaging by preoperative treatment can obscure the true pathologic stage of a tumor and confound the usual selection criteria for postoperative chemotherapy. PURPOSE: This study was undertaken to determine if proliferating cell nuclear antigen (PCNA), p53, DNA ploidy, and S-phase fraction are associated with response to radiation and/or risk for distant metastatic disease and to determine if these cellular markers are best evaluated from preradiation biopsy specimen or the larger (but possibly altered) final surgical specimen. MATERIALS AND METHODS: Archival specimens from 23 cases of ultrasound T3 or T4 rectal carcinoma treated preoperatively with radiation therapy were reviewed. Eligible lesions had preradiation biopsy specimens of sufficient size for flow cytometric review of archival tissue. Factors considered included PCNA positivity, presence of mutant nuclear p53, more than 30 percent tumor cells in S-phase, and presence of aneuploidy. RESULTS: With a median follow-up of three years, overall freedom from relapse was 83 percent, with all but one failure being extrapelvic. PCNA positivity in the preradiation specimen was significantly (P = 0.025) associated with a greater risk of tumor recurrence. In addition, there was a trend to greater likelihood of "probable downstaging" (defined as surgical T stage less than preradiation ultrasound T stage) for lesions that were PCNA-negative or lesions with normal p53. Biomarkers measured in the postradiation surgical specimen were not associated with either freedom from relapse or response to radiation. Radiation treatment appeared to produce false-negatives in the final specimen. Thus, there were significantly more specimens converting from PCNA-positive to PCNA-negative after preoperative radiation than would be expected solely on the basis of sampling errors (P = 0.004). Similar results were found for abnormal p53 findings (P = 0.02). CONCLUSIONS: Prospective studies of biomarkers should be based on pretreatment specimens if preoperative radiation is given. For carcinoma of the rectum, PCNA and p53 may be useful predictors of both metastatic potential and responsiveness to radiation.

Adenocarcinoma↗
PubMed1995

Adjuvant radiation therapy for rectal carcinoma: predictors of outcome.

PURPOSE: To review predictors of outcome, including sequencing of modalities and pretreatment findings for adjuvantly treated rectal cancer. METHODS AND MATERIALS: From 1975 through 1990, 307 patients with adenocarcinoma of the rectum underwent adjuvant radiation therapy. In 251 cases the radiation therapy was administered preoperatively, either 40-50 Gy (median dose 45 Gy) followed in 6-7 weeks by surgery (210 cases), or 20 Gy in five fractions immediately prior to surgery (41 cases). In 56 cases, patients were referred postoperatively for radiation (median dose 50 Gy). Adjuvant chemotherapy was never given concurrently with the preoperative radiation (RT), although 43 of the cases (including 14 of the preoperative RT cases) received postoperative chemotherapy. RESULTS: Multivariate analysis (Cox model) indicated that significant predictors of better overall freedom from disease were preoperative rather than postoperative RT (p < 0.001), low surgical stage (p < 0.0001), specialist surgeon (p = 0.007), low or moderate histologic grade (p = 0.026), and proximal lesion (p = 0.033). The significant predictors for better local control included use of preoperative RT (p < 0.001), low or moderate grade (p = 0.001), and low surgical stage (p = 0.015). The 5-year local control and freedom from disease for the preoperative RT patients were 90% +/- 2% and 73% +/- 3%, respectively. The selected cases that received the short course of 20 Gy preoperatively did well. Although 24 out of 41 patients proved to have Astler Coller B2 or C disease, local control at last follow-up was 39 out of 41 (95%). A second multivariate analysis of pretreatment factors was performed on the preoperative RT cases. The significant factors for both local control and overall freedom from disease were noncircumferential vs. circumferential tumor, proximal vs. distal lesion, and background of the surgeon. Additional negative factors on univariate analysis (although not achieving independent significance on multivariate analysis) included the finding of near-obstructing lesions and elevated carcinoembryonic antigen (CEA). Grade > or = 3 sequelae occurred in 8% of cases (including 3% bowel obstruction). The only significant factor for complications was background of the surgeon (4% for colorectal specialists vs. 12% for nonspecialists, p = 0.015). CONCLUSIONS: Significant factors for better tumor control included preoperative as opposed to postoperative RT and the experience of the surgeon. In selected cases, excellent results can be obtained with a short course of preoperative radiation. Concurrent chemotherapy need not be given routinely with preoperative radiation. Subgroups of preoperative RT cases at risk for distant metastases (who might benefit from postoperative chemotherapy), and at high risk for local failure (for whom concurrent preoperative chemotherapy and radiation might be considered), are identified.

Adenocarcinoma↗