Beta-cell secretory defect caused by mutations in glucokinase gene.
Explore the source record for details and available documents.
Diabetes Mellitus, Type 2↗
Biomedical subjects
R Page
Publications and source records attributed to R Page.
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↗
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↗
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↗
Opsonic antibody activity against Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.
Actinobacillus actinomycetemcomitans has been closely associated with early-onset, severe periodontitis, and such patients often have serum immunoglobulin G (IgG) antibodies reactive with antigens of this gram-negative pathogen. We examined the functionality and potential importance of these antibodies. The opsonic activity against A. actinomycetemcomitans of sera from 30 patients with rapidly progressive periodontitis (RPP) and from 28 periodontally normal subjects was tested by using polymorphonuclear leukocyte (PMN) chemiluminescence and bactericidal assays. Peak chemiluminescence values correlated strongly with killing observed in the PMN-dependent bactericidal assay (r = 0.88; P < 0.001). Neither the mean IgG titer nor the mean peak chemiluminescence differed significantly between the two groups. However, when the relationship between chemiluminescence and titer was examined, regression analysis showed that antibodies present in low-titer normal sera were significantly more effective at opsonizing A. actinomycetemcomitans than antibodies present in low-titer RPP patient sera (P = 0.04). Thus, periodontally normal individuals may be better able than RPP patients to clear A. actinomycetemcomitans in early stages of colonization, and anti-A. actinomycetemcomitans antibodies in RPP patients may be relatively ineffective in preventing infection by this organism.
Adult↗
Cutaneous mastocytosis in a dog.
Explore the source record for details and available documents.
Animals↗
Brief intensive chemotherapy for metastatic non-small-cell lung cancer: a phase II study of the weekly CODE regimen.
Fifty-three patients, 17 with stage IIIB and 36 with stage IV non-small-cell lung cancer, were given CODE (cisplatin, vincristine, doxorubicin, and etoposide) plus antibiotic prophylaxis and an antiemetic regimen in an intensive chemotherapy program emphasizing weekly treatment and a planned brief duration (9-12 weeks); for 45 of these patients, the CODE program also included antifungal prophylaxis and supportive corticosteroids. Of the total study population, 33 patients (62%) responded to treatment, including five (9%) with complete response. The median survival for the entire group was 42 weeks (55 weeks for those with stage IIIB and 39 weeks for those with stage IV). More than 40% were alive at 1 year. Comparison of granulocyte counts of patients receiving prednisone with those of the subgroup to whom no corticosteroids were given showed less granulocytopenia for those receiving prednisone. Use of prednisone thus allowed improved delivery of myelosuppressive drugs. CODE was halted in nine patients because of disease progression. Although more constitutional side effects are associated with weekly chemotherapy than with standard chemotherapy, only 12 of the remaining 44 patients (27%) failed to receive at least 9 weeks of treatment. Serious toxicity was uncommon: There were no treatment-related deaths and only three episodes of neutropenia with fever. CODE is a novel treatment for non-small-cell lung cancer that this pilot study provided entirely in an outpatient setting over a 9-12 week period with an acceptable incidence of toxicity and a promising level of efficacy. Additional testing and comparison with other regimens or supportive care alone are warranted.
Adenocarcinoma↗
Acoustic neuroma (schwannoma) surgery 1978-1990.
A series of 151 patients with 154 acoustic schwannomas have been operated upon in Manchester Royal Infirmary by a joint Otological and Neurosurgical team, employing either the translabyrinthine or the suboccipital approach. The perioperative mortality rate was 3 per cent. Anatomical preservation of the facial nerve was achieved in 89 per cent of tumour removals and a good to normal functional result in 79 per cent of cases. Attempts at hearing preservation have been unsuccessful, largely because of the small number of patients in the series in whom useful hearing was present preoperatively. Complications included major brain stem ischaemia (1.2 per cent), CSF fistula (5 per cent) and facial dysaesthesia (7 per cent). The incidence of mortality and morbidity is directly related to tumour size and to the experience of the surgeons. A number of patients experienced an unusual type of post-operative dreamlike state which appeared to be a form of hypnagogic hallucination, and the possible neurophysiological mechanism responsible for this phenomenon is discussed. The continuing failure to attain the ideal of early diagnosis is lamented, and the importance of a flexible bidisciplinary surgical approach emphasized.
Adolescent↗
Latent mastoiditis: no room for complacency.
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.
Adult↗
Insulin secretion, insulin sensitivity and glucose-mediated glucose disposal in Cushing's disease: a minimal model analysis.
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.
Adult↗
Use of digital radiography to demonstrate the potential of naproxen as an adjunct in the treatment of rapidly progressive periodontitis.
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.
Adolescent↗
Intensive weekly chemotherapy for the treatment of extensive-stage small-cell lung cancer.
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.
Adult↗
Panel discusses future of periodontal diagnostics.
Explore the source record for details and available documents.
Humans↗
Vasculitis related to hepatitis B vaccine.
Explore the source record for details and available documents.
Female↗
Changes associated with metastasis in B16-F1 melanoma cells surviving heat.
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.
Cell Survival↗
Human recombinant interleukin-2 induces maturation and activation signals for feline eosinophils in vivo.
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.
Animals↗
[Thrombocytopenic thrombotic purpura occurring in spite of antiaggregant treatment using ticlopidine].
Explore the source record for details and available documents.
Aged↗
Hard-shell cardiotomy reservoir for reinfusion of shed mediastinal blood.
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.
Blood Transfusion, Autologous↗