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Biomedical subjects

M Brennan

Publications and source records attributed to M Brennan.

At least 73 records · Page 4Linked to original sources
PubMed1993

Psychiatric consultation for women undergoing rehabilitation for upper-extremity lymphedema following breast cancer treatment.

Breast cancer presently affects one in nine women in the United States. Women receiving radiation and surgical resection of axial lymph nodes are at risk for development of lymphedema of the ipsilateral upper extremity. Mental health consultation and intervention can be an important part of rehabilitative efforts aimed at improving both lymphedema itself and the overall psychosocial adjustment of the patient. Such consultation begins with a careful consideration of possible psychiatric diagnosis but must necessarily depart from standard psychiatric considerations to include an assessment of psychosexual and social factors. Additionally, the consultant must gauge the degree of success the patient has had in adjustment to lifestyle changes brought on by lymphedema. This paper discusses the psychological problems posed by lymphedema and offers case examples. These cases illustrate the nature of psychiatric and psychological factors encountered in this population and the interventions that can help improve both compliance with rehabilitative efforts and psychological adjustment.

Adult↗
PubMed1993

Phase II trial of postoperative adjuvant intraperitoneal cisplatin and fluorouracil and systemic fluorouracil chemotherapy in patients with resected gastric cancer.

PURPOSE: This study was performed to assess the short- and long-term toxicities and the impact on relapse pattern and survival of postoperative intraperitoneal (IP) cisplatin and fluorouracil (FU) plus systemic intravenous (IV) FU as adjuvant therapy for gastric cancer patients who are at high risk for recurrence after potentially curative resection (T2N1-2M0 or T3-4N(any)M0). PATIENTS AND METHODS: Starting 14 to 28 days after potentially curative resection of primary gastric cancers, 35 patients were given IP cisplatin 25 mg/m2 and FU 750 mg daily for 4 days; FU 750 mg/m2 was concurrently given as a continuous 24-hour i.v. infusion. Five cycles of therapy delivered at 1-month intervals were used. RESULTS: After a median follow-up of 24 months, 51% of patients remain alive and free of disease. Sixteen patients have recurred; 13 of 16 had an intraabdominal component, whereas three had extraabdominal failure only. Two major treatment-related toxicities were noted: neutropenia and a late toxicity of peritoneal fibrosis (sclerosing encapsulating peritonitis [SEP]). There was one postoperative death. Eleven patients underwent second laparotomy: five patients had SEP, two patients had bowel obstruction from adhesions unrelated to SEP, and four patients had recurrent cancer. Potential causes of SEP included an alkaline pH of infused FU and cisplatin that possibly led to activation of cisplatin before infusion. CONCLUSION: IP cisplatin and FU and concurrent systemic FU is a tolerable adjuvant therapy in the postoperative setting for patients with resected gastric cancer. The recommended dosage schedule with this technique is cisplatin 25 mg/m2 and FU 750 mg total dose IP with FU 500 mg/m2 as a continuous 24-hour infusion daily for days 1 to 4. SEP as a late toxicity, which was observed in 15% of patients, is treatable by surgical lysis of adhesions.

Adenocarcinoma↗
PubMed1993

Carcinoma of the ampulla of Vater.

We reviewed our experience with 69 patients with carcinoma of the ampulla of Vater admitted to the Memorial Sloan-Kettering Cancer Center, New York, from October 1983 to October 1990. Of the 69 patients, 66 were explored and 55 underwent resection (83 percent resectability). The median length of survival for the 55 patients who underwent resection was 51 months, compared with eight months for the 14 patients who did not undergo resection (p = 0.000004). Of the variables evaluated, only resectability was a statistically significant predictor of survival. Positive lymph nodes in 17 of 55 patients who underwent resection were not predictive of long term survival.

Actuarial Analysis↗
PubMed1992

Primary structure of rat liver D-beta-hydroxybutyrate dehydrogenase from cDNA and protein analyses: a short-chain alcohol dehydrogenase.

The amino acid sequence of D-beta-hydroxybutyrate dehydrogenase (BDH), a phosphatidyl-choline-dependent enzyme, has been determined for the enzyme from rat liver by a combination of nucleotide sequencing of cDNA clones and amino acid sequencing of the purified protein. This represents the first report of the primary structure of this enzyme. The largest clone contained 1435 base pairs and encoded the entire amino acid sequence of mature BDH and the leader peptide of precursor BDH. Hybridization of poly(A+) rat liver mRNA revealed two bands with estimated sizes of 3.2 and 1.7 kb. A computer-based comparison of the amino acid sequence of BDH with other reported sequences reveals a homology with the superfamily of short-chain alcohol dehydrogenases, which are distinct from the classical zinc-dependent alcohol dehydrogenases. This protein family, initially discerned from Drosophila alcohol dehydrogenase and bacterial ribitol dehydrogenase, is now known to include at least 20 enzymes catalyzing oxidations of distinct substrates.

Alcohol Dehydrogenase↗
PubMed1992

FAMTX versus etoposide, doxorubicin, and cisplatin: a random assignment trial in gastric cancer.

PURPOSE: The chemotherapy regimens of high-dose methotrexate, high-dose fluorouracil (FU), Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and leucovorin (FAMTX) and etoposide, Adriamycin, and cisplatin (EAP) have both been reported in nonrandom assignment trials to have high overall response rates and substantial complete response rates in patients with gastric cancer, as well as major toxicities of myelosuppression. Here we report a prospective, stratified, random-assignment comparison of the two combinations in previously untreated patients with advanced gastric cancer. PATIENTS AND METHODS: Sixty patients were entered onto the trial, 30 receiving EAP and 30 FAMTX. All patients had measurable or assessable tumor masses. Patient entry was stopped at the point when significant toxicity differences were seen at interim analysis. RESULTS: Response rates were similar between the two arms (FAMTX, 33% [95% confidence interval (CI), 16% to 50%]; EAP, 20% [95% Cl, 6% to 34%]). Three FAMTX and no EAP patients had complete remissions. The median survival for the two arms were similar (EAP, 6.1 months; FAMTX, 7.3 months). At 1 year, 7% of EAP and 17% of FAMTX patients were alive. EAP caused significantly more myelosuppression (leukopenia, P = .002; anemia, P = .03; thrombocytopenia, P = .0001) than did FAMTX. EAP also resulted in significantly longer hospitalizations per study month (8 v 5 days). Four EAP patients died of lethal toxicity, whereas no FAMTX patients died of treatment-related causes (P = .04). CONCLUSIONS: FAMTX is at least as active as EAP and is significantly less toxic. Although both regimens remain investigational, the toxicities of FAMTX are more manageable. Further studies involving FAMTX in both the adjuvant and advanced disease setting are underway.

Adult↗
PubMed1992

Teaching tools for the Marker Model for standards development and the Umbrella Model for quality assurance.

The learning process benefits adults more when the material is presented in the presence of "positive conditions." Teaching standards developed and QA provides ample opportunity to provide positive conditions. The Marker Model is easily adapted to all practice settings and can often be taught by using unit-specific or patient population-specific examples; however, developing these specific examples can be time-consuming. Instruction is often given to groups of nurses from different clinical areas, so unit- or patient population-specific examples are therefore inappropriate. Development of the "universal" example has also provided humor for the presentation. The Head of Household Standards model and the Quality Assurance Plan for Head of Household are applicable to almost all adults and are easily understood (see boxes). They supply further humor in their "audit" formats (Figures 3 and 4).

California↗
PubMed1991

Fibrin glue.

Fibrin glue is a topical biological adhesive, the effect of which imitates the final stages of coagulation. The glue consists of a solution of concentrated human fibrinogen which is activated by the addition of bovine thrombin and calcium chloride. The resultant clot aids haemostasis and tissue sealing and is completely absorbed during wound healing without foreign body reaction or extensive fibrosis. The fibrinogen component of fibrin glue can be produced from fresh frozen plasma obtained from single unit donations thereby reducing the risks of transfusion transmitted infections encountered by exposure to pools from large numbers of donors. Methods involving precipitation of fibrinogen by cryoprecipitation, polyethylene glycol or ammonium sulphate have been described and evaluated. The risk of transmission of infection can be further reduced by using plasma from 'accredited donors' who are plasma donors regularly tested for ALT and markers of viral infection or by use of fibrinogen prepared in advance of surgery from autologous blood. The second component, a mixture of thrombin and CaCl2, is quantitatively and qualitatively well defined and commercially available (Armour Pharmaceutical Co., Thrombinar (bovine thrombin]. Thrombin is applied to the operation site simultaneously and in equal volume to the fibrinogen but from a separate syringe. In the UK a commercial heat treated fibrin glue prepared from pooled plasma is available on a doctor/named patient basis (Tisseel, Immuno, Vienna). The haemostatic and adhesive properties of fibrin glue can be employed in virtually every surgical specialty. The usefulness of the glue is particularly well documented in the fields of cardiovascular surgery, ENT and neurosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Disorders↗
PubMed1991

Extracellular matrix mediated growth and differentiation in human pigment epithelial cell line 0041.

Efforts to grow differentiated pigment epithelial cells have led to a characterization of the growth kinetics of spontaneously established, continuously growing, human retinal pigment epithelial (PE) cell line 0041 on several biomatrices. These substrates were prepared from (a) placental and amniotic membrane, (b) commercially available basement membrane matrix (Matrigel), (c) dishes coated with extracellular matrix secreted by endothelial cells (ECM), (d) dishes coated with collagen IV and/or laminin, (e) dishes coated with collagen I and/or fibronectin. Our findings suggest that tissue culture plastic and dishes coated with collagen IV alone promote higher cell densities, while highest plating efficiency (24 hrs) was seen on tissue culture plastic and Matrigel. The highest degree of differentiation (epithelioid appearance, apical villi and junctional complexes) was seen in cells plated on dishes coated with collagen IV and extracellular matrix secreted by endothelial cells. Cells were epithelioid and polarized on those two substrates; they expressed fine finger-shaped villi and the highest degree of cell contact (in the form of junctions). Cells grown on Matrigel looked like fibroblasts and became deeply pigmented; however, the nature of the pigment remains to be determined. Collagen IV and ECM coated dishes, therefore, are most suitable for cultures of human PE cell line 0041 because they provide higher cell densities while retaining the differentiated state. This is the first report where an established pigmented epithelial cell line has been induced to become differentiated by use of extracellular matrices and extracellular matrix components.

Adolescent↗
PubMed1990

Prognosis of thick cutaneous melanoma of the trunk and extremity.

The records of 129 patients with thick cutaneous melanoma of the trunk or extremity treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1974 and 1984 were reviewed with the aim of defining prognostic variables. All primary lesions invaded subcutaneous fat, were Clark level V, or of a Breslow thickness of 4.0 mm or greater. Treatment in all cases was by wide excision with or without split-thickness skin graft; all patients underwent regional lymph node dissection. Overall survival rate for the group was 47% at 5 years and 36% at 10 years. Factors independently predictive of survival were pathologic negative nodes (71% at 5 years compared with 28% for pathologic positive nodes) and extremity site (58% at 5 years compared with 33% for truncal site). Patients with node-negative thick cutaneous melanoma of the extremity had a 5-year survival rate of 82%. Patients with node-positive truncal thick cutaneous melanoma had a 5-year survival rate of only 8%. There was no difference between the 5-year survival rate of patients with node-negative truncal thick cutaneous melanoma, 52%, and patients with node-positive thick cutaneous melanoma of the extremity, 42%. Nearly half of the patients with thick cutaneous melanoma of the extremity and trunk present with locoregional disease, at a stage when an aggressive surgical approach is warranted. Prognostic variables of pathologic nodal status and site identify patients at risk for early systemic failure.

Age Factors↗
PubMed1990

Is the health profile of problem drinkers different from that of other patients?

Health problems presented to the family physician over a 2-year period were compared between a group of 108 problem drinkers and a group of matched control subjects. Although the problem drinkers had a higher prevalence of many types of problems, the major differences occurred for traumatic injury, digestive disorders, and family or social dysfunction. Such problem areas could comprise a brief checklist to aid in the detection of problem-drinking patients. Information presented to the patient concerning the wide range of problems associated with their drinking may also help break through the denial so characteristic of this population.

Adult↗
PubMed1989

Changes in solubility, non-enzymatic glycation, and fluorescence of collagen in tail tendons from diabetic rats.

The increase in acid-insoluble collagen (AIC) from tail tendons of streptozotocin-diabetic rats was measured and compared with that for control rats. AIC increased from 10% initially to 75% after 12 weeks of diabetes. It then increased slowly to 85% after 45 weeks. AIC for control rats was constant for the first 12 weeks and then increased slowly to 40% after 45 weeks. These data are consistent with an increase in the number of acid-stable cross-links in the collagen due to diabetes. The quantity of collagen solubilized by pepsin at 4 degrees C was unaltered due to diabetes, strong evidence that formation of diabetes-induced cross-links between helical regions of collagen molecules cannot explain the increase in AIC observed. Non-enzymatic glycation (NEG) increased linearly over 45 weeks, but the rate of NEG was much slower than the rate of increase in AIC observed for diabetics. The level of NEG for diabetics was about three times that for controls at a given time, but there was still less than 1 mol of glucose detected/mol of collagen at near maximum acid insolubility. Fluorescence associated with tail tendons was measured to test the hypothesis that fluorescent cross-links form as a consequence of NEG and result in decreased collagen solubility. Fluorescence (lambda ex 370; lambda em 430) increased slowly with age but was similar for control and diabetic tendons of the same age. Fluorescence was not increased in AIC compared with acid-soluble collagen derived from a given tendon sample. NEG of collagen reached near-diabetic levels in non-diabetic rats whose growth was inhibited by restricted feeding, but there was no associated increase in AIC. These data suggest that NEG and the subsequent formation of fluorescent cross-links do not contribute significantly to the rapid increase in AIC in the streptozotocin-rat model of diabetes.

Aging↗
PubMed1989

Changes in the cross-linking of collagen from rat tail tendons due to diabetes.

The acid solubility of Type I collagen from rat tail tendons decreases due to diabetes. This finding has been taken as evidence that collagen from diabetics may be more cross-linked than normal. We compared CNBr peptide maps prepared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis for [3H] NaBH4-reduced tail tendons from streptozotocin-diabetic rats with maps from age-matched control rats. At least through 30 weeks of diabetes, the distribution of mass of both cross-linked and uncross-linked CNBr peptides was identical in diabetic and control tendons. Therefore, the number of cross-linked peptides did not increase due to diabetes. We analyzed the 3H-cross-linking compounds present on the CNBr peptides and found that the 3H content of peptides cross-linked in control tendons through the bivalent, reduced cross-links hydroxylysinonorleucine and lysinonorleucine was diminished on corresponding peptides from diabetic tendons as a function of duration of diabetes. The cross-linked peptides, however, persisted. Therefore, we conclude that a larger fraction of these bivalent cross-links is found in an unknown, non-reducible form in tendons from diabetic compared with control rats. This resembles a phenomenon normally associated with maturation and/or aging where the non-reducible form of the cross-links is acid-stable. An increase in the fraction of the cross-links that is non-reducible and acid-stable would explain, at least in part, the decrease in acid solubility of the collagen. Non-enzymatic glycation (NEG) was not very specific, since most CNBr peptides bound some glucose. However, peptides from the alpha 2-chain seemed to be preferential targets for NEG. While NEG clearly increased due to diabetes, we found no evidence that increased NEG led to an increased number of cross-links in tail tendon collagen from streptozotocin diabetic rats.

Animals↗
PubMed1989

Fibronectin does not enhance epidermal growth factor-mediated acceleration of corneal epithelial wound closure.

Concomitant use of epidermal growth factor and fibronectin for the treatment of corneal epithelial wounds has a putative advantage of promoting complementary aspects of wound healing: epidermal growth factor enhances mitosis, while fibronectin increases cell-to-substrate adhesiveness and possibly cell motility. To determine if the combination of epidermal growth factor and fibronectin is synergistic in accelerating the speed of corneal epithelial wound coverage, epithelial wound closure rates were compared in serum-free rat corneal organ cultures among epidermal growth factor alone, fibronectin alone, their combination, and drug-free controls. Epidermal growth factor (50 to 1000 ng/mL) significantly increased the rate of wound closure over that of the drug-free controls, while fibronectin (50 to 100 micrograms/mL) had not significant effect. Wound closure rates with combined epidermal growth factor and fibronectin were no faster than with epidermal growth factor alone. The results indicate that fibronectin does not accelerate the rate of corneal epithelial migration when used alone or in combination with epidermal growth factor. This may reflect that the major role of fibronectin may be in the enhancement of cell-to-substrate adhesion and not of migration per se.

Animals↗