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Biomedical subjects

R Page

Publications and source records attributed to R Page.

At least 37 records · Page 2Linked to original sources
PubMed1995

Autoregulatory circuits in myeloma. Tumor cell cytotoxicity mediated by soluble CD16.

BACKGROUND: Multiple myeloma remains an incurable malignancy due to marked resistance of the tumor to standard doses of chemotherapy. Treatment approaches, using chemotherapeutic dose escalation and hematopoietic stem cell support have resulted in significant augmentation of tumor mass reduction such that complete remissions are effected in approximately 50% of patients. These remissions are however, often not durable. In the setting of minimal residual disease, therefore, adjunctive immunotherapy may be useful. METHODS: Peripheral blood mononuclear cells were studied from 28 untreated patients with multiple myeloma (MM). Mononuclear cell CD16 (FcR gamma III) expression was determined by flow cytometry. The effect of lymphocyte-derived soluble CD16, isolated by affinity chromatography, on MM cell growth and differentiation was assessed. MM cell proliferation, viability, immunoglobulin production and gene expression was studied. RESULTS: Data are presented indicating that cells expressing CD16 are increased in untreated patients with IgG-secreting myeloma. The predominant phenotype of these cells is CD8+ or CD56+. These CD16+ cells can produce a soluble form of the Fc receptor (sFcR, sCD16) that can bind to surface Ig on cultured human IgG-secreting myeloma cells and effect suppression of tumor cell growth and Ig secretion. This effector function is accompanied by concomitant suppression of c-myc as well as IgH and IgL gene transcription. Finally, prolonged exposure to sCD16 causes myeloma tumor cell cytolysis. CONCLUSIONS: sCD16 and possibly other soluble FcR are candidate molecules for adjunctive immunotherapy of myeloma, once complete responses have been effected by intensive cytotoxic therapy, now possible in up to 50% of newly diagnosed patients.

Adult↗
PubMed1995

Response of guinea pigs to a vaccine containing a new adjuvant (SAF) and gram-negative bacteria.

Porphyromonas gingivalis is a gram-negative pathogen associated with severe periodontitis in man and other animals. A vaccine against P. gingivalis infection may improve resistance to such infection and disease progression in susceptible individuals. A vaccine composed of formalin-killed P. gingivalis and Syntex adjuvant formulation or saline was tested in guinea pigs. Blood was drawn before and at 2, 4, 6, 8, 24, and 27 weeks after immunization. There was no morbidity or mortality as a result of vaccination, and necropsy revealed no organ abnormalities or residual injection site granulomas. Serum immunoglobulin G (IgG) antibody titer and avidity were measured by enzyme-linked immunosorbent assay, and Western blots were done to determine the immunodominant antigens. The IgG titer increased more rapidly and reached higher values in the animals receiving SAF plus P. gingivalis vaccine than in those receiving saline plus P. gingivalis. Antibody titer decreased by 27 weeks, but avidity was twofold greater at 27 than at 8 weeks. Western blots indicated that protein and carbohydrate antigens are recognized.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1994

Aneuploid islet cell tumor with late metastasis.

An unusual case of insulin producing islet cell tumor is reported which recurred after a 16 yr interval. In most instances malignancy of islet cell tumors is impossible to assess morphologically or functionally but depends on the recognition of metastases. Nuclear DNA analysis provides significant prognostic and biological information in a number of solid human tumors. Retrospective computerized nuclear image analysis of the primary tumor in the present case showed an aneuploid DNA profile similar to that seen in the metastasis. It appears that ploidy studies may be useful in predicting malignant potential of islet cell tumors.

Adenoma, Islet Cell↗
PubMed1994

Upper lip reconstruction with a radial forearm free flap.

Although there are several methods available for lip reconstruction, the challenge for plastic surgeons is young children, in whom there is no laxity of skin. Free-tissue transfer is the method of choice in young children to avoid large unsightly scars and severe distortion of facial appearance. The radial forearm free flap is an ideal flap for lip reconstruction because it is thin and can be folded to restore both the skin and the inner lining. We present reconstruction of half the upper lip in a young girl, in whom the radial forearm free flap was folded to replace the full-thickness defect.

Animals↗
PubMed1994

Phase II trial of megestrol in the supportive care of patients receiving dose-intensive chemotherapy.

Megestrol acetate was given daily to lung cancer patients undergoing therapy with CODE and to recurrent head and neck cancer patients receiving DEB/M in an attempt to prevent weight loss. The outcomes in this study were compared with the same outcomes in similar groups of patients treated with the same chemotherapy regimens, but in which prednisone was used as the main supportive drug along with co-trimoxazole, ketoconazole, and either cimetidine or sucralfate. Weight loss was less pronounced in the current patients than in the previous ones. Nevertheless, there were several factors that led us to conclude that megestrol is not an adequate substitute for prednisone in patients receiving this kind of chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Quality of life, appetite, and weight change in patients receiving dose-intensive chemotherapy.

Quality of life was assessed by self-report questionnaires in 30 patients receiving dose-intensive chemotherapy for either non-small-cell lung cancer (20 patients) or recurrent head and neck cancer (10 patients). Megestrol acetate was given daily to try to improve appetite and prevent the weight loss usually associated with this chemotherapy. Appetite did not change significantly overall during the first 4 weeks of chemotherapy, but it did improve in those patients still receiving chemotherapy at 8 weeks. Changes in global quality of life were significantly correlated with changes in appetite, fatigue, energy level, and physical function. Thus, these parameters may have more relevance to patients' perceptions of quality of life than does weight change, and should be used more frequently as endpoints in studies of supportive care and palliative treatment of patients with cancer.

Antineoplastic Agents↗
PubMed1994

Hemoglobin blood substitutes in extended preoperative autologous blood donation: an experimental study.

BACKGROUND: The risks of homologous blood transfusion have stimulated interest in developing possible alternatives. In this study we examined the efficacy of using a hemoglobin-derived blood substitute to augment and extend preoperative autologous blood donation. METHODS: In an ovine model, two experimental groups (n = 6 each) of animals donated either 45% or 80% or more of calculated blood volume, which was replaced with a polymerized bovine hemoglobin solution. Two control groups (n = 6 each) either did not donate or donated 45% of calculated blood volume, which was replaced with a 6% hetastarch solution. Twenty-four hours after blood donation, sheep underwent a measured surgical stress with standardized intraoperative blood loss; donated blood was reinfused. RESULTS: Extended autologous blood donation and replacement with this blood substitute were efficacious in supporting oxygen consumption; there was no systemic toxicity. After the postoperative replacement of autologous blood, animals that donated 80% or more of red cell mass exhibited overall blood conservation with a final hematocrit of 25.7% +/- 3.6%, compared with 20.5% +/- 2.0% (p < 0.05) and with 21.5% +/- 1.1% (p < 0.05) in both control groups. CONCLUSIONS: This study suggests that the benefits of a blood substitute can be combined with autologous blood donation to (1) safely increase the amount of autologous blood donated while supporting oxygen consumption, (2) avoid the need for advanced preoperative donation, and (3) decrease the need for homologous blood transfusion.

Animals↗
PubMed1993

Timing of extubation after oesophagectomy.

Ventilatory support for 24 h after surgery is standard practice in many units after oesophagectomy, especially for patients in whom respiratory problems are anticipated. Weaning difficulties may occur, however, and there is increasing evidence that mechanical ventilation is associated with alveolar trauma. A deliberate change in policy was instituted in the authors' unit in January 1990 to make early extubation mandatory in all patients undergoing elective oesophagectomy, apart from those in whom serious perioperative problems were encountered. The present study compared two sets of patients: group 1 (n = 36) underwent oesophagectomy in the year before the policy change and group 2 (n = 45) oesophagectomy in the year after. The two groups were similar in age, sex and respiratory risk factors. Early extubation was carried out in 38 patients in group 2 compared with eight in group 1 (P < 0.001). Only two patients in group 2 required prolonged ventilation compared with ten in group 1 (P < 0.005). No patient in group 2 required reventilation compared with seven in group 1 (P < 0.005), and no patient in group 2 who had undergone early extubation required delayed ventilation. The mean ventilation time and length of stay in the intensive care unit were significantly reduced following the policy change. Early extubation after elective oesophagectomy is an attainable goal and results in a significant reduction in both the morbidity rate and cost of surgery.

Aged↗
PubMed1993

Serum antibody opsonic activity against Actinobacillus actinomycetemcomitans in human periodontal diseases.

Actinobacillus actinomycetemcomitans is frequently associated with severe periodontitis. Many periodontitis patients have elevated levels of serum IgG antibodies to A. actinomycetemcomitans, but the role of these antibodies is unknown. This study evaluated the functional capacity of anti-A. actinomycetemcomitans IgG antibody to enhance phagocytosis of A. actinomycetemcomitans by polymorphonuclear leukocytes. Chemoluminescence assays were done using sera from 64 subjects, 61 of whom had severe periodontitis; results were compared with the subject's anti-A. actinomycetemcomitans IgG titer and avidity. There was a strong correlation between chemoluminescence and antibody log titer (P < .00001) and a weak correlation between chemoluminescence and antibody avidity (P < .05). The results support the hypothesis that anti-A. actinomycetemcomitans IgG antibodies are important in promoting phagocytosis and killing of A. actinomycetemcomitans. Subjects who develop high levels of highly avid antibodies against A. actinomycetemcomitans may have greater resistance to continued or repeated infection by this pathogen.

Actinobacillus Infections↗
PubMed1993

Necrotizing infundibulo-hypophysitis: a unique syndrome of diabetes insipidus and hypopituitarism.

Clinical, radiological, histological, and anatomical features in 2 patients with necrotizing infundibulo-hypophysitis are reported. The patients presented with a combination of diabetes insipidus and hypopituitarism. Each was found to have a sellar mass lesion with an abnormally thickened enlarged pituitary stalk that intensively enhanced on contrast magnetic resonance imaging. They were suspected to have pituitary tumors with suprasellar extension. However, tissue obtained at transphenoidal surgery revealed necrosis, fibrosis, and chronic inflammation; there was no evidence of infiltrative, infective, or neoplastic disease processes. Postoperatively, they continued to have diabetes insipidus and hypopituitarism despite radiological improvement and steroid therapy. Several clinical and anatomical features distinguish these 2 cases from classical lymphocytic hypophysitis, the most common entity in the differential diagnosis. Specifically, diabetes insipidus has not been observed preoperatively in 30 cases of lymphocytic hypophysitis, but was present in the 2 cases reported. Histological evidence of tissue necrosis present in these 2 cases is not a feature of lymphocytic hypophysitis. Pituitary stalk involvement on magnetic resonance imaging or computed tomographic scan present in these 2 cases is highly unusual in lymphocytic hypophysitis. Finally, 29 of 30 cases of lymphocytic hypophysitis were females, whereas the 2 cases reported are men. On the basis of these disparate findings, we suggest that these 2 cases represent a unique syndrome, which may be recognized clinically and radiologically.

Adult↗
PubMed1992

Cobalamin deficiency associated with methylmalonic acidemia in a cat.

A 9-month-old sexually intact male longhair cat was examined because of lethargy, anorexia, cold intolerance, and failure to thrive since acquisition at an early age. Clinical signs of disease were less pronounced when the cat was fed a low-protein diet. Anemia, hypoglycemia, low total CO2 content, and hyperammonemia were detected. The cat was euthanatized. Urine obtained immediately before euthanasia contained a large amount of methylmalonic acid. Total serum cobalamin concentration was low. Hepatic methylmalonic-CoA mutase activity, with and without the addition of coenzyme adenosylcobalamin, was consistent with a cobalamin deficiency. Methylmalonic acidemia secondary to a putative defect in cobalamin absorption was diagnosed.

Absorption↗
PubMed1992

Missense glucokinase mutation in maturity-onset diabetes of the young and mutation screening in late-onset diabetes.

We describe a codon 299 mutation in the glucokinase gene in a British pedigree with maturity-onset diabetes of the young (MODY) resulting in a substitution of glycine to arginine. One out of fifty patients diagnosed with classical late-onset type 2 diabetes mellitus was also found to have this mutation. All nine relatives of this patient who have inherited the mutation have type 2 diabetes, although six others without the mutation are also present with diabetes. The discovery that glucokinase mutations can cause MODY and was also found in ten affected members of a pedigree with type 2 diabetes in which MODY had not previously been considered indicates that diagnosis based on molecular pathology will be helpful in understanding the aetiology of type 2 diabetes.

Adolescent↗
PubMed1992

Transoesophageal pulsed wave Doppler measurement of cardiac output during major vascular surgery: comparison with the thermodilution technique.

We measured cardiac output in 12 patients undergoing elective abdominal vascular surgery at specific times during the procedure with simultaneous thermodilution and transoesophageal pulsed Doppler echocardiographic techniques. No patient had clinical evidence of valvular heart disease before surgery. Five patients had echocardiographic evidence of mitral regurgitation on colour-coded Doppler. Using Bland and Altman analysis to compare the cardiac output measurement by the two techniques, the Doppler method overestimated the cardiac output (bias = 0.86 litre min-1) compared with the thermodilution technique and there were wide limits of agreement between the two techniques (+2.4 to -4.1 litre min-1). However, in the seven patients with no evidence of mitral regurgitation, closer agreement (bias 0.14 litre min-1) and narrower limits (+1.6 to -1.3 litre min-1) were observed. We conclude that, in patients with competent mitral valves, transoesophageal echocardiograph may provide accurate determination of cardiac output.

Aorta↗