Biomedical subjects
Publications and source records attributed to R Page.
The administration of antibiotics in otitis media alters the natural course of the disease process. If the antibiotics used are inappropriate, or if dosage or duration of treatment is inadequate, an imminent intracranial complication may be masked. A case of latent mastoiditis presenting with Pott's puffy tumour is described.
OBJECTIVE: We wished to assess the contributions of insulin secretion, insulin sensitivity and glucose-mediated glucose disposal to glucose tolerance in subjects exposed to chronic glucocorticoid excess. DESIGN: Patients with Cushing's disease were subjected to a frequently sampled intravenous glucose tolerance test before and at least 3 months after curative surgery and compared to a control group. PATIENTS: Seven patients with clinical and biochemically proven pituitary dependent Cushing's disease and 10 healthy control subjects were studied. MEASUREMENTS: Paired glucose and insulin plasma profiles were analysed by the Minimal Model method of Bergman, which provided simultaneous estimates of the glucose decay rate, insulin secretion, insulin sensitivity and glucose-mediated and non-insulin-mediated glucose disposal. Data were evaluated by non-parametric statistical analysis and reported as median and interquartile ranges. RESULTS: Basal glucose, insulin, C-peptide and glucagon levels were significantly raised preoperatively and fell towards normal post-operatively. Glucose tolerance assessed as glucose decay rate was reduced significantly preoperatively (pre: 1.3 (0.8-2.0) vs post: 1.6 (1.5-2.6) per min x 10(2), P less than 0.05). First phase insulin release was similar in the Cushing's disease and control subjects. In contrast, second phase insulin release was significantly greater preoperatively and remained high post-operatively compared to control subjects (pre: 18.8 (16.7-23.6) vs post: 16.7 (8.5-18.8) vs control 11.1 (4.5-15.4) mU/g/min2 x 10(-2), P less than 0.002). Median insulin sensitivity was reduced by 60% preoperatively in the Cushing's disease subjects compared to the post-operative Cushing's disease and control subjects (pre: 2.1 (1.3-4.2) vs post: 5.0 (3.2-7.3) vs control 5.1 (2.2-7.2) per min/mU/l x 10(4)). Median glucose-mediated glucose disposal was reduced by 40% in the pre and post-operative Cushing's disease subjects compared to the control group (pre: 1.1 (0.6-2.1) vs post: 1.1 (0.6-2.1) vs control 1.9 (1.4-2.6) per min x 10(2)), but this was not statistically significant. However, non-insulin-mediated glucose disposal was significantly reduced in the preoperative Cushing's disease subjects (pre: 0.55 (0.08-1.59) vs control 1.43 (0.94-2.27) per min x 10(2), P less than 0.05). In the Cushing's disease subjects, glucose tolerance correlated with both insulin sensitivity (rs = 0.84, P less than 0.01) and non-insulin-mediated glucose disposal (rs = 0.56, P less than 0.05). The fractional clearance rate of insulin was unaltered by Cushing's disease. CONCLUSIONS: Cushing's disease subjects are characterized by impaired glucose tolerance due to both reduced insulin sensitivity and non-insulin-mediated glucose disposal, in the presence of enhanced insulin secretion.
The effect of the non-steroidal anti-inflammatory drug, naproxen, in reducing periodontal disease activity was assessed in 15 patients with rapidly progressive periodontitis. All patients in this double-blind study were treated with scaling and root planing. Thereafter, 7 patients receiving 500 mg naproxen b.i.d. for 3 months, and 8 patients received placebo. Disease activity was assessed in three ways. First, alveolar bone height was determined using standardized radiography. Second, alterations in alveolar bone metabolism were assessed using 99m-Tc-methylene diphosphonate uptake prior to dosing and 3 months later. Finally, bone loss or gain was detected using digital subtraction radiography. In this study, conventional subtraction images were processed to isolate the area of change and superimpose the change on the original radiograph. This allowed determination of both the direction and location of osseous changes. There was significantly less bone loss as determined by analysis of bone height during the 3-month study in the naproxen-treated patients when compared to the placebo-treated patients (p less than 0.001). Radiopharmaceutical uptake was significantly reduced in the alveolar bone in patients receiving naproxen (p less than 0.03), whereas no significant change was observed in the placebo-treated patients. Furthermore, the subtraction radiographs showed a significant increase in the proportion of teeth demonstrating bone gain in the naproxen-treated group. These findings indicate that naproxen may be a useful adjunct to scaling and root planing in patients with rapidly progressive periodontitis.
The regimen of cisplatin, vincristine, doxorubicin, and etoposide (CODE) was designed to double the dose intensity of these drugs in comparison with a standard regimen (alternating cyclophosphamide, doxorubicin, and vincristine [CAV] and etoposide-cisplatin [EP]) for extensive-stage small-cell lung cancer (SCLC). The dose intensity was increased by more frequent treatments rather than by increasing the dose size. The structure of this outpatient protocol includes weekly administration of chemotherapy, alternation of myelosuppressive and nonmyelosuppressive treatments, supportive corticosteroids, gastroprotective agents, and prophylactic antibiotics. Although the duration of chemotherapy was brief (9 to 12 weeks), the total cumulative doses of drugs delivered were similar to the standard regimen. Patients with no residual disease outside the chest after chemotherapy received thoracic irradiation, and patients with complete responses (CRs) received prophylactic cranial irradiation. Eligible extensive-stage SCLC patients were ambulatory, younger than 66 years of age, and free of brain metastasis. Forty-eight extensive-stage SCLC patients were treated. Forty-five (94%) responded to chemotherapy, with 19 (40%) attaining CR. After consolidative thoracic irradiation, the CR rate was 56%. The median time to progression was 43 weeks, and the median survival was 61 weeks. The 2-year survival rate was 30%. The most common site of first relapse was brain (38%). Although two patients (4%) died of toxicity, overall toxicity was acceptable for an outpatient regimen. We conclude that the CODE regimen reliably produces palliative remissions for selected extensive-stage SCLC patients, and it may be associated with durable remissions for some patients. The results of this pilot study are sufficiently promising to justify a phase III trial of CODE versus standard (alternating CAV and EP) chemotherapy.
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Metastasis to distant sites is mediated by various receptors on the surface of tumor cells. B16-F1 melanomas surviving 43.5 degrees C heat in vitro for 15 minutes and cultured for 10 days bind significantly increased amounts of the basement membrane protein laminin. Motility of heat-resistant B16-F1 cells in vitro toward the chemoattractant laminin is significantly increased. The increased expression of putative laminin receptors may be associated with increased metastasis of melanomas after subcurative hyperthermia.
Immunotherapy, with interleukin-2 (IL-2) or IL-2 plus lymphokine-activated killer (LAK) cells, has been used to treat cancer and acquired immunodeficiency syndrome (AIDS) in man. Similarities between feline leukemia virus (FeLV) infection in the cat and human immunodeficiency virus (HIV) infection in man have prompted immunotherapeutic studies in the cat. To develop baseline data on hematological responses to infused IL-2, cats were given daily (1-14 days) i.v. injections of 5 x 10(4) U/kg of recombinant human IL-2 (rHulL-2). Complete blood cell (CBC) counts were done weekly. Red blood cell (RBC), neutrophil, and lymphocyte numbers did not change appreciably over the course of the study. In contrast, rHulL-2 caused an eosinophilia in all but the 1 day treatment group. Treatment for 3 days generated a transient eosinophilia on day 7 that returned to baseline by 3 weeks. Five day and 7 day treatments generated an eosinophilia by day 7 that peaked on day 14 and returned to normal values by day 28. Treatment of cats for 14 days did not increase the magnitude or duration of the eosinophilia beyond the 5 or 7 day treatments. Bone marrow (BM) biopsies from rHulL-2-treated cats revealed a marked selective hyperplasia of eosinophil precursors. In the 5 day treatment group, all maturation stages of eosinophils were elevated by week 1 of treatment. By week 2, the early stages had returned to normal, whereas the late stage cells remained elevated, suggesting an ordered maturation response. Numbers of all eosinophil precursors approximated pretreatment numbers by weeks 3-4. Thus the BM hyperplasia preceded the blood eosinophilia by 1 week, suggesting that an enhanced maturation response of BM eosinophil precursors is a major contributor to the rHulL-2-induced blood eosinophilia. In addition to a maturation signal, rHulL-2 induces a potent activation signal for eosinophils as measured by a decrease in density and an increase in longevity in culture. The significance of the activated eosinophil in the therapeutic or toxicologic response to rHulL-2 infusion is discussed.
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We conducted a prospective, randomized, controlled trial comparing homologous blood consumption between groups of patients receiving conventional mediastinal drainage (group 1) or reinfusion of shed mediastinal blood (group 2) using hard-shell cardiotomy reservoir. One hundred consecutive patients who had elective coronary artery or valvular operations were studied. The two groups were comparable with regard to age, sex, weight, preoperative and postoperative hemoglobin levels, and surgical procedure. Group 2 patients had their shed mediastinal blood reinfused for up to 18 hours postoperatively; otherwise, the two groups were treated identically. For groups 1 and 2, average mediastinal blood losses were 705 +/- 522 and 822 +/- 445 mL and homologous blood consumption was 3.83 +/- 2.58 and 3.15 +/- 2.05 U, respectively (neither measure was significantly different). However, if blood losses exceeded 500 mL, there was a statistically significant reduction in homologous blood requirements in group 2 as compared with matched controls in group 1. This difference was most significant in patients with the greatest mediastinal losses.
1. The northern leopard frog, Rana pipiens, pipiens, in contrast to the southern leopard frog, Rana pipiens, berlandieri, did not demonstrate any significant H+ excretion across its integument even during a challenge of chronic metabolic acidosis. Likewise, no increase in the number of H+ secreting mitochondria-rich cells were observed in the northern frogs. 2. Under normal acid-base conditions in the southern frogs, H+ excretion was found to be dependent on mucosal sodium concentrations, whereas during chronic metabolic acidosis, H+ excretion was independent of mucosal sodium concentrations, but was amiloride sensitive. 3. High salinity adapted southern frogs, under normal and acidotic conditions, had enhanced H+ excretion rates as compared to the control non-salt adapted frogs. 4. Blood analyses demonstrated that significant acid-base changes were the result of systemic acidosis and not due to salt adaptations. Blood Na+ and K+ concentrations were also efficiently maintained during salt adaptations or chronic metabolic acidosis. 5. The results suggest that H+ excretion in epithelia can be influenced by the sodium transport state of the cell and the systemic acid-base profile. Models are proposed explaining these relationships.
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Recent studies of laboratory-provoked asthma have suggested that asthma is an inflammatory disease of lower airways. The purpose of this study was to measure the systemic elaboration of 2 bronchoconstrictive inflammatory mediators during naturally acquired acute asthma utilizing a prospective, serial-sampling protocol. Plasma levels of 13,14-dihydro-15-keto-PGF2 alpha and histamine were measured by radioimmunoassay and radioenzymatic assay, respectively, in 23 children with acute asthma. Mean PG metabolite and histamine values (pg/ml) before (167 +/- 72, 1,029 +/- 378) and 10 to 90 min after (377 +/- 145, 1,000 +/- 489) initial therapy were significantly higher than those of the same children after resolution of asthma (2.9 +/- 0.2, 260 +/- 42) and those of normal children (4.3 +/- 0.9, 240 +/- 14). Peak PG metabolite levels were significantly higher in children who presented with PEFR values (% predicted) less than 40% (1,234 +/- 432) compared with those who presented with greater than 40% (404 +/- 296), and in children with post-therapy improvement in PEFR of less than 20% (1,281 +/- 470) compared with those with greater than 20% (365 +/- 226). Histamine levels were significantly higher in children with post-therapy improvement in PEFR of less than 20% (2,560 +/- 1,600) compared with those with greater than 20% (475 +/- 100), and in hospitalized (3,915 +/- 1,910) compared with nonhospitalized (408 +/- 130) children. Significant differences were not observed on the basis of corticosteroid dependence, allergic disposition, or type of initial therapy. These data suggest a role for histamine and PGF2 alpha in the pathogenesis of airway inflammation in acute asthma.
Two cases of primary intracranial choriocarcinoma are reported. One patient died with raised intracranial pressure and pulmonary metastases whereas the second patient, who was diagnosed early, has remained well a year after chemotherapy. Human chorionic gonadotrophin level estimation in serum and cerebrospinal fluid is a useful marker in suspected cases, and chemotherapy following biopsy appears to be the treatment of choice.
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A cross-sectional study was conducted on functional status of adults visiting primary care practices. Limitations in physical and mental function were assessed independently in 28 practices by patients (N = 1,227) and physicians (N = 47) using a simple global index of disability. Results indicated 12% of patients rated their physical limitations as major and 8% rated major emotional limitations during the past month. Comparable assessments by physicians were 5% and 4%, respectively. Differences between patients and physicians were statistically significant and are demonstrated to be clinically relevant. Patients' functional limitations were associated with increased utilization of ambulatory care, older age, lower level of education, unemployment, and a primary diagnosis of a chronic condition. We conclude that functional status can be routinely recorded in medical practice to help describe severity, predict utilization, and improve the physician-patient relationship.