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Biomedical subjects

C Wright

Publications and source records attributed to C Wright.

At least 127 records · Page 7Linked to original sources
PubMed1997

Autologous bone marrow purging by in situ IL-2 activation of endogenous killer cells.

The major cause of treatment failure in hematologic malignancies is the development of resistance to chemotherapeutic agents and the presence of clonogenic tumor cells in remission bone marrow. In the present study, we tested the optimal conditions for activation by interleukin-2 (IL-2) of endogenous bone marrow effector cells to develop cytotoxicity against solid tumor and leukemia cells and the effects of IL-2 treatment on eradication of malignant cells from the marrow product while preserving hematopoiesis. Normal donor bone marrow was contaminated with 10% A549 lung cancer cells, MCF-7 breast cancer, or EM2 leukemia cells, and then combined with peripheral blood-derived lymphokine-activated killer (LAK) cells which had been incubated in the presence of IL-2, 6000 IU/ml, for 5 days. Eradication (A549 and MCF-7) or >90% reduction in tumor cell number (EM2) was achieved upon exposure of the marrow to LAK cells but not to control, non-IL-2-exposed PBMC. The non-cross-resistance of chemotherapy and cell-mediated cytotoxicity were tested by using chemoresistant target cells for LAK cytotoxicity assays. Ara-C-resistant K562 cells were sensitive to LAK cytotoxicity, similar to sensitive controls. Similar effects were seen in daunomycin-resistant HL60 leukemia cells and VP-16-resistant K562 cells. The daunomycin-resistant K562 cells were also sensitive to LAK cell killing similar to sensitive controls. Activation of bone marrow mononuclear cells (BMMC) with IL-2, 6000 IU/ml for 24 h, significantly enhanced cytotoxicity against the NK-resistant, LAK-sensitive Daudi cell line. This procedure did not result in significant loss of total BMMC or hematopoietic colony-forming units. We then studied the possibility that the effector cell activity of the IL-2-activated BMMC which is diminished after removal of the IL-2 at 24 h could be recovered upon re-exposure of the marrow to IL-2. We found that the optimum conditions for preserving cytotoxicity were prolonged continuous exposures to IL-2 but that re-exposure of the 24-h IL-2-activated BMMC to IL-2 after a 1- or 2-week IL-2 withdrawal was associated with full recovery of cytotoxicity. These experiments also demonstrated that the overall recovery of viable cells from the BMMC was over 100%, possibly due to a proliferative effect of the IL-2 exposure on BMMC. These results demonstrate that the use of IL-2-activated marrow in patients with acute leukemia in remission undergoing autologous bone marrow transplantation (aBMT) may overcome the obstacles of clonogenic, drug-resistant minimal residual disease. The effector cell activity and hematopoietic capacity of the activated bone marrow product can also be maintained even if optimal clinical care requires an interruption in the in vivo exposure to IL-2. This therapeutic approach is currently being tested in acute leukemia patients undergoing IL-2-activated aBMT followed by prolonged IL-2 treatment before and after hematologic reconstitution.

Bone Marrow Purging↗
PubMed1997

Incidence and nature of feeding problems in young children referred to a paediatric HIV service in London: FEAD screening.

A detailed screening assessment was carried out on two matched groups of young children; one group was HIV-infected and the other was not. Screening included assessments of growth, development and food intake. Parents were also interviewed about their child's feeding and mealtime behaviours. Half of the HIV-infected children were reported with serious feeding problems; significantly higher than in the uninfected group. More of the children in the HIV-infected group were found to have poorer growth and developmental weaknesses than in the uninfected group. A combination of physical and psychological factors are suggested as contributing to these feeding difficulties. Early monitoring of feeding behaviours, daily routines and food intake, together with systematic growth and developmental measures are suggested as important components in the care and management of HIV-infected children.

Anthropometry↗
PubMed1997

Cellular immunotherapy and autologous transplantation for hematologic malignancy.

The success of allogeneic transplantation is in part due to the immunotherapeutic effect mediated by the graft. Autologous transplantation is hampered by the absence of this effect, leading to a higher relapse rate. We have conducted a series of studies designed to augment the immunologic activity of the graft after autologous transplant with a view towards introducing an autologous graft-versus-tumor effect that could decrease the rate of relapse after autologous transplant. These studies have included IL-2 activation of marrow followed by post-transplant infusional IL-2, the development of a novel protocol for the generation of highly efficient cytotoxic effector cells, termed cytokine-induced killer (CIK) cells, with broad and potent antitumor activity. In order to determine the potential for generating peptide-specific cytolytic T cells, studies have been conducted upon transducing antigen-presenting cells (APC) with AAV vector-mediated gene transfer, a vector capable of transducing non-proliferating target cells. Transduction of human monocytes and macrophages resulted in high expression of the transduced gene. This latter study forms the basis for determining whether genetic modification of APC can potentiate specific immune responses to tumor-specific gene products. Taken together, these strategies will hopefully increase the therapeutic efficacy of autologous transplantation.

Animals↗
PubMed1997

Height and weight achievement in cleft lip and palate.

Growth was studied in 83 children with cleft lip and/or palate aged 0-4 years attending a specialist regional centre. Information was collected by a personal interview, postal questionnaire, and record review. The group as a whole grew relatively poorly in early infancy but subsequently recovered, attaining both expected weight and height by last follow up at age 25.5 months (range 3 to 47). However, the group proved heterogeneous, with children with isolated clefts of the secondary palate showing the most abnormal growth. Children with underlying syndromes were significantly more likely to be short at follow up, while type or severity of cleft was not significantly related to follow up height. Therefore, while cleft palate was associated with significant growth faltering in early infancy, rapid recovery took place following surgical repair and appears to have resulted in no residual growth deficit.

Body Height↗
PubMed1997

Analysis of myosin heavy chain mRNA expression by RT-PCR.

An assay was developed for rapid and sensitive analysis of myosin heavy chain (MHC) mRNA expression in rodent skeletal muscle. Only 2 microg of total RNA were necessary for the simultaneous analysis of relative mRNA expression of six different MHC genes. We designed synthetic DNA fragments as internal standards, which contained the relevant primer sequences for the adult MHC mRNAs type I, IIa, IIx, IIb as well as the embryonic and neonatal MHC mRNAs. A known amount of the synthetic fragment was added to each polymerase chain reaction (PCR) and yielded a product of different size than the amplified MHC mRNA fragment. The ratio of amplified MHC fragment to synthetic fragment allowed us to calculate percentages of the gene expression of the different MHC genes in a given muscle sample. Comparison with the traditional Northern blot analysis demonstrated that our reverse transcriptase-PCR-based assay was reliable, fast, and quantitative over a wide range of relative MHC mRNA expression in a spectrum of adult and neonatal rat skeletal muscles. Furthermore, the high sensitivity of the assay made it very useful when only small quantities of tissue were available. Statistical analysis of the signals for each MHC isoform across the analyzed samples showed a highly significant correlation between the PCR and the Northern signals as Pearson correlation coefficients ranged between 0.77 and 0.96 (P < 0.005). This assay has potential use in analyzing small muscle samples such as biopsies and samples from pre- and/or neonatal stages of development.

Animals↗
PubMed1997

Altered platelet function detected by flow cytometry. Effects of coronary artery disease and age.

Platelet activation state and responsiveness to physiological agonists were measured in 65 patients with documented coronary artery disease (54 male and 11 female; mean age, 58 years). Twelve patients (mean age, 52 years), selected at random from the male cohort, were compared with 12 age-matched male control subjects (mean age, 52 years) and with 10 normal, young male subjects (mean age, 25 years). Whole-blood flow cytometry was used to measure platelet activation status ex vivo and platelet responsiveness to physiological agonists in vitro. Peripheral blood samples were analyzed for bound fibrinogen and expression of P-selectin, GPIb, and GPIIb-IIIa at rest and in response to ADP (0.1 to 10 mumol/L) and thrombin (0.02 to 0.32 mu/mL). No significant differences were seen in the basal levels of fibrinogen binding between any of the groups, but P-selectin expression was significantly lower in patients compared with age-matched control subjects (P = .0005). When stimulated with agonists, patients' platelets had significantly decreased fibrinogen binding (P < .03) but no difference in P-selectin expression compared with the age-matched group. Both agonist-induced fibrinogen binding and P-selectin expression were, however, higher in the young subjects compared with either the older control group or the patients (P < .05). GPIb and GPIIb-IIIa expression were lowest in the patients with angina and highest in the young control subjects, with levels in the age-matched control subjects falling between these values. Data from the total patient cohort (n = 65) were identical to those in the smaller cohort (n = 12). In conclusion, atherosclerosis impairs platelet aggregatory responses (fibrinogen binding) over and above the decreased response seen with age. Platelet degranulation (P-selectin expression) is also impaired in patients with coronary artery disease, but only in comparison with younger subjects, not age-matched controls.

Adult↗
PubMed1997

Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer.

PURPOSE: The main objectives of this study were (a) to ascertain the feasibility and toxicity of preoperative twice-daily radiation therapy and concurrent chemotherapy, surgery, and postoperative therapy in stage IIIA (N2) non-small-cell lung cancer (NSCLC), and (b) to evaluate tumor response, resection rate, pathologic tumor downstaging, and survival. METHODS: Eligibility included biopsy-proven N2 lesion (stage IIIA) by mediastinoscopy, Karnofsky performance score > or = 70, and weight loss less than 5% in the 3 months before diagnosis. The treatment program consisted of two courses of preoperative cisplatin, vinblastine, and fluorouracil (5-FU); 42 Gy concurrent radiation at 1.5 Gy per fraction in two fractions per day; surgery on day 57; and one more course of postoperative chemotherapy and 12 to 18 Gy of concurrent twice-daily radiation. RESULTS: Forty-two patients with stage IIIA (N2) NSCLC (27 men and 15 women, age 38 to 77 years) were enrolled onto this prospective study. Forty of 42 patients tolerated the intended dose (42 Gy) of preoperative radiation and 37 of 39 resected patients received prescribed postoperative radiation. The intended dose of chemotherapy was given in 100%, 70%, and 60% of patients for the first, second, and third courses of chemotherapy. Marked dysphagia that required intravenous hydration was noted in 14% of patients (six of 42). Myelotoxicities included grade > or = 3 granulocytopenia in 23% and thrombocytopenia in 6% of 113 chemotherapy courses. Febrile neutropenia that required hospital admission was noted in 9% of 113 chemotherapy courses. Surgical resection was performed in 93% of patients. Treatment-related mortality was noted in 7% of patients. The overall survival rates by the Kaplan-Meier method were 66%, 37%, and 37% at 2,3, and 5 years, respectively, with a median follow-up time of 48 months. Pathologic examination of the surgical specimen showed a downward shift in tumor extent from stage IIIA (N2) to stage II (N1) in 33%, to stage I (NO) in 24% (10 of 42), and to stage 0 (TONO) in 9.5%, for a total of 67%. The degree of tumor downstaging was also translated into a survival benefit: 5-year survival rates from the time of surgery were 79%, 42%, and 18% for postoperative tumor stages 0 and I, II, and III, respectively (P = .04). CONCLUSION: Concurrent chemoradiotherapy using twice-daily radiation is an effective induction regimen that resulted in 67% tumor downstaging, and an encouraging 37% 5-year survival rate. The degree of tumor downstaging may be a useful intermediate end point for survival benefit in stage IIIA (N2) NSCLC.

Adult↗
PubMed1997

Preoperative predictors of operative morbidity and mortality in COPD patients undergoing bilateral lung volume reduction surgery.

Bilateral volume reduction surgery (VRS) improves lung function for selected patients with emphysema. However, predictors of outcome are not well defined. We reviewed the preoperative characteristics of the first 47 consecutive patients who underwent bilateral VRS at the Massachusetts General Hospital in order to define potential predictors of unacceptable outcome. Preoperative data included spirometry, plethysmography, diffusion of carbon monoxide (Dco), maximum inspiratory pressure (MIP), maximum expiratory pressure, resting arterial blood gases (ABG), cardiopulmonary exercise testing with ABG and lactate sampling, and radionuclide ventriculography. Prepulmonary and postpulmonary rehabilitation 6-min walk tets (6MWT), and preoperative chest CT scans were also obtained. Twenty-two subjects were male and 17 of the subjects were on the lung transplant list. Patient characteristics included age of 60.5 +/- 7.5 years, FEV1 of 0.67 +/- 0.20 L, total lung capacity of 7.56 +/- 1.7 L, Dco of 7.40 +/- 4.1 mL/min/mm Hg, and PaCO2 of 41.6 +/- 6.4 mm Hg (mean +/- SD). The FEV1, vital capacity, MIP, resting room air PaCO2, prepulmonary and postpulmonary rehabilitation 6MWT, and PaCO2 at maximum oxygen consumption correlated with length of hospitalization (p < 0.05). Based on analysis of 41 of 47 patients for whom there were complete data, the inability to walk more than 200 m on the 6MWT before or after preoperative pulmonary rehabilitation, and resting PaCO2 > or = 45 mm Hg were the best predictors of an unacceptable outcome. If either of these characteristics was present, six of 16 vs zero of 25 died (Fisher's Exact Test, p = 0.0025, one-tailed) and 11 of 16 vs four of 25 had hospital courses > 21 days (p < 0.002). Both the 6MWT < 200 m and resting PaCO2 > or = 45 mm Hg alone correlated with death (p = 0.004 and p = 0.012, respectively) and the resting PaCO2 > or = 45 mm Hg correlated with hospital days > 21 (p = 0.0002). In conclusion, the data suggest that the inability to walk at least 200 m in 6 min before or after pulmonary rehabilitation and a resting room air PaCO2 > or = 45 mm Hg are excellent preoperative predictors of unacceptable postoperative outcomes.

Exercise Test↗
PubMed1997

A prospective comparative study of moderate versus high protein intake for critically ill patients with acute renal failure.

Critically ill patients with acute renal failure are traditionally treated with low-protein diets to help control uremia. This dietary approach may be deleterious to the patient's nutritional status and unnecessary, especially if continuous renal placement therapies (CRRT) are used. However, the optimal amount of protein supplementation during CRRT is unknown. In patients receiving CRRT, a high protein intake may result in a positive nitrogen balance in the absence of uncontrolled uremia. Accordingly, we studied nitrogen metabolism in two consecutive cohorts of acute renal failure patients receiving equal amounts of calories but variable amounts of nitrogen. One group received protein according to the preferences of the attending clinician, the other a high and fixed amount of protein (2.5 g/kg/day). Patients treated according to attending clinician preferences received significantly less dietary protein (1.2 g/kg/day vs. 2.5 g/kg/day; p < 0.0001) and had a negative mean nitrogen balance of -5.5 g/day. Patients receiving a high and fixed amount of protein had a less negative mean nitrogen balance (-1.92 g/day). Such patients were more likely to experience a positive nitrogen balance during any 24-h period (53.6% vs. 36.7%; p < 0.05). They also required more aggressive hemofiltration to maintain control of uremia (mean ultradiafiltrate volume: 2145 mL/h vs. 1658 mL/h; p < 0.0001) and had a significantly higher but still acceptable mean plasma urea level (26.6 mmol/L vs. 18 mmol/L; p < 0.0001). Survival was not significantly different in the two groups (37.5% vs. 31.3%). We conclude that a high-protein diet can be safely administered to critically ill patients with acute renal failure receiving continuous renal replacement therapy. Such a high protein intake improves nitrogen balance when compared to moderate protein intake. A low protein intake is unnecessary in patients treated with CRRT.

Acute Kidney Injury↗
PubMed1997

Sirenomelia, limb reduction defects, cardiovascular malformation, renal agenesis in an infant born to a diabetic mother.

The clinical features of a fetus with sirenomelia, limb reduction defects, cardiovascular malformation and renal agenesis are reported. The mother of the child suffers from insulin dependent diabetes. The limb, cardiac and renal abnormalities are well recognized sequelae of diabetic pregnancies. The association of sirenomelia and maternal diabetes is somewhat controversial. The link between caudal regression syndrome, sirenomelia and maternal diabetes will be discussed.

Cardiovascular System↗
PubMed1996

Tenuous link between ischaemic threshold and both ambulatory ischaemia and symptom status over time in stable angina: a 5-year follow-up study.

This study evaluates changes in ischaemic threshold over a 5-year period in patients with stable angina pectoris, who did not suffer any intervening cardiac event. Changes in ischaemic threshold are related to alterations in symptomatic status and ambulatory ischaemia. Over long-term follow-up, there is a significant fall in ischaemic threshold in such patients (mean heart rate at onset of ischaemia fell from 104 +/- 17.8 to 97 +/- 17.4 bpm: P < 0.001), but this is not matched by a worsening of either symptoms or ischaemia during daily life. In the 68% of patients that had a reduction in ischaemic threshold of > or = 5 bpm, 68% had either definite reduction or no change in symptoms and 84% had either reduction, abolition or no change in transient ischaemic activity. The dissociation between ischaemic threshold, ambulatory ischaemia and symptoms has implications for long-term monitoring and management of the patient with stable angina.

Adult↗
PubMed1996

Primary tracheal non-Hodgkin's lymphoma. A case report and review of the literature.

BACKGROUND: Primary tracheobronchial non-Hodgkin's lymphoma (NHL) is an uncommon occurrence. The authors report a patient who presented with primary tracheal NHL, the sixth such patient described in the literature. METHODS: Using a MEDLINE search, 41 additional patients presenting with symptomatic primary or secondary tracheobronchial NHL were identified. The characteristics, management, and outcome of these patients are described. RESULTS: Patients with NHL of the upper respiratory tract present with dyspnea, wheezing, and cough, and frequently are misdiagnosed as having asthma. The majority of patients have additional sites of intrathoracic disease with tracheobronchial involvement occurring in the setting of advanced or relapsed NHL. Low grade histology is seen most commonly in patients with primary tracheal NHL. Several patients demonstrate the typical histologic features of mucosa-associated lymphoid tissue. Surgery, chemotherapy, and radiation therapy have been used alone or in combination for treatment. The outcome of these patients does not appear different from that observed in patients with lymphomas of similar histology and stage that do not involve the tracheobronchial tree. CONCLUSIONS: Thoracic surgeons, pulmonologists, and oncologists should recognize that NHL can rarely be confined to the trachea or bronchi. NHL should be considered in the differential diagnosis of airway obstruction, because it represents a highly treatable malignancy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Fetal hepatic necrosis following blood sampling from the intrahepatic vein.

Previous reports have suggested that fetal blood sampling from the intrahepatic vein is not associated with significant fetal hepatic injury. We report a case of fetal liver necrosis occurring 24 h following blood sampling from the intrahepatic vein of a fetus with severe growth retardation at 34 weeks. The placenta was in a posterior position, precluding either blood sampling from the placental insertion or placental biopsy. Fetal death occurred in utero within 24 h of the procedure, which was carried out by an experienced operator. At post-mortem the liver appeared normally formed, but the right lobe was diffusely congested, with a well-defined demarcation line between the right and left lobes. Liver histology revealed extensive recent haemorrhagic necrosis of the right lobe.

Adult↗
PubMed1996

The Generalized Self-Efficacy Scale in people with arthritis.

OBJECTIVE: To examine the comprehensibility, reliability, and validity of a trait measure, the Generalized Self-Efficacy Scale (GSES), among people with arthritis. The scale is designed to measure perceived coping ability across a wide range of demanding situations. METHODS: Four studies were conducted. Study 1 tested the comprehensibility of the GSES. Studies 2, 3, and 4 tested the reliability and validity of the modified scale. Data were collected through self-administered questionnaires. Reliability and structure of the GSES were examined using standard item analysis, internal consistency (Cronbach's alpha), test-retest reliability, and factor analyses. Concurrent and predictive validity were examined in relation to demographic, physical, psychological, and social dimensions. RESULTS: The GSES assessed a unitary concept. Higher generalized self-efficacy was associated with greater psychological well-being, both cross-sectionally and longitudinally. The GSES was independent of age and physical health status. CONCLUSIONS: The GSES is a reliable and valid measure for use among community-based samples of people with arthritis and may be a useful indicator of general adaptational outcomes.

Adaptation, Psychological↗
PubMed1996

Omeprazole produces parietal cell hypertrophy and hyperplasia in humans.

While there is evidence that omeprazole may induce changes in parietal cells, the effect of acid suppression on parietal cells in humans is poorly documented. This study was undertaken to evaluate the effects of omeprazole in human parietal cells over time. The light microscopic morphology of parietal cells in gastric biopsies from 17 patients on omeprazole were compared with those from 13 patients on ranitidine and 20 patients on no acid-lowering medication. Light microscopic and ultrastructural morphology of parietal cells was also evaluated in an additional 14 patients before and after omeprazole administration. Objective measurements of parietal cell height, mass and number were analyzed using analyses of variance. Electron microscopy was used to evaluate parietal cell enlargement. Twenty-five of 31 biopsies from patients on omeprazole, 1 of 13 from patients on ranitidine, and 0 of 20 from patients on neither drug showed parietal cell enlargement. Parietal cell height, mass, and number were increased in omeprazole-treated patients compared with ranitidine-treated patients and those on neither drug, and with the group also evaluated prior to beginning omeprazole treatment. Parietal cell height and mass were increased in patients on omeprazole longer than 12 months compared with biopsies from patients on the drug for less than 12 months. Resin-embedded sections and electron microscopy showed enlarged parietal cells with prominence of cytoplasmic tubulovesicles with sparse secretory canaliculi. Parietal cell hypertrophy and hyperplasia develops in patients on chronic omeprazole therapy; this can be recognized on routine examination of histologic sections. These morphologic changes increase with duration of therapy.

Adolescent↗