Effects of IgM Allotype Suppression on Serum IgM Levels,B-1 and B-2 Cells,and Antibody Responses ir Allotype Heterozygous F1 Mice

IgM allotype heterozygous F1 mice were independently suppressed for Igh6a or Igh6b to evaluate the contribution of B-1 and B-2 cells to natural serum IgM levels and Ab responses. B-2 B cells expressing IgM of the suppressed allotype were evident in the spleens of suppressed mice 4 to 6 weeks after cessation of the suppression regimen, whereas B-1 B cells of the suppressed allotype were undetectable for up to 9 months. Although serum IgM of the suppressed allotype was initially depleted in mice suppressed for either allotype, by 7 months of age, there were detectable levels of IgM of the suppressed allotype in the serum; however, the levels were significantly below that found in nonsuppressed mice. When mice were immunized with either the T-independent or T-dependent form of phosphorylcholine, those suppressed for either allotype, and consequently depleted of B-1 B cells of that allotype, did not respond with phosphorylcholine-specific IgM of the suppressed allotype. In contrast, when mice were immunized with α1-3 dextran, the Igh6a allotype-suppressed mice were able to produce dextran-specific IgM of that allotype. These results show that allotype-bearing B-1 cells of both allotypes can be effectively suppressed by this suppression protocol and this produces long-lasting effects on B-1 cell levels and serum IgM of the suppressed allotype. These observations reflect the derivation of the majority of B-1 cells from fetal-neonatal precursors, which cannot be replaced by newly emerging B-2 cells of adult origin. Their ablation by antibody treatment results in permanent alterations to the adult B-cell repertoire.     

Dentists evaluate their patients: An empirical investigation of preferences

Dental treatment is a dyadic encounter. Yet research on the dentist-patient dyad has tended to focus on patient perceptions of dentist, to the neglect of dentist perceptions of patient. Previous theoretic and qualitative work on caregiver perceptions of patients suggested three dimensions of evaluation. Dentists (N=618) rated their patients on items taken from two prior studies. Dentists' responses were subjected to confirmatory factor analysis. The analysis substantiated the existence of three evaluative dimensions: compliance, tractability, and likability. Further analysis showed that the three dimensions formed a Guttman simplex, revealing a second-order factor of selectivity and allowing a classification of dentists on the basis of patient selectivity.This study was funded by a grant from the University of Connecticut Research Foundation.     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

A nursing challenge: adult-onset Tay-Sachs disease.

Adult-onset GM2 gangliosidosis (AOG), also labelled Adult-Onset Tay-Sachs disease, is a slowly progressing disease caused by a gradual accumulation of the GM2 ganglioside in neurons due to defective hexosaminidase A. Recent research findings and clinical experiences suggest that AOG may be more widespread than previously believed. Moreover, the diagnosis of AOG is often delayed because patients present with psychotic symptoms that mimic dementia, schizophrenia, mania, and depression. Because AOG patients typically respond poorly to psychiatric drug therapy and the symptomatology is so diverse, nurses must design and implement nursing care that ensures safety, structure, and comfort.     

A pharmacokinetic and pharmacodynamic comparison of plain and enteric-coated prednisolone tablets.

1. Eight healthy volunteers and eight patients suffering from chronic obstructive pulmonary disease (COPD) received 30 mg prednisolone as plain (P) and enteric-coated tablets (EP) in a randomised, cross-over manner. Plasma prednisolone and cortisol and blood glucose were measured over 24 h. 2. Although absorption of prednisolone was considerably slower when administered as the enteric-coated form, peak plasma drug concentrations and total AUC (0,24 h) were equivalent for the two formulations. Malabsorption of prednisolone was not observed. 3. The administration of EP was associated with significantly less adrenal suppression in volunteers than P as judged by measurement of AUC (0,24 h) values for endogenous cortisol. However, this difference did not reach statistical significance in the patient group. 4. Plasma cortisol concentrations declined more slowly following administration of the enteric-coated form to both groups. The difference in time taken (median and range) to maximum suppression of cortisol was statistically significant (P less than 0.05) between P (2.5 h; 2-4 h) and EP (4 h; 3-12 h) preparations administered to volunteers. There was a similar significant difference (P less than 0.05) between P (2.5 h; 1-4 h) and EP (7 h; 2-12 h) in the patients. 5. Plasma cortisol concentrations were significantly lower at 24 h in patients receiving the enteric-coated product in association with higher terminal prednisolone concentrations. 6. Blood glucose concentrations increased over an 8 h period in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.     

Presentation and course of Type 2 diabetes in youth in a large multi-ethnic city.

AIM: To review the clinical experience of children and teens diagnosed with Type 2 diabetes (T2DM) at a paediatric hospital serving a large urban multi-ethnic population. METHODS: Retrospective chart review of patients with T2DM followed in the diabetes clinic at the Hospital for Sick Children (HSC) over an 8-year period. Patients who were included were younger than 18, referred at the onset of diabetes, and where presentation and/or clinical course was 'typical' of T2DM. RESULTS: Of 1020 children with diabetes followed at HSC, 4% were identified as having T2DM in 2002. There was a sixfold increase in new cases from 1994 to 2002. The mean age at diagnosis was 13.5 +/- 2.2 years (range 8.8-17.5) with a female-to-male ratio of 1.7. Most had a first- or second-degree relative with T2DM. There was an overrepresentation of children with T2DM from Asian and African Canadian ethnic groups relative to the regional population. The majority of teens were asymptomatic at presentation, with a smaller number in diabetic ketoacidosis (DKA) at diagnosis. Mean HbA1c at diagnosis was 10 +/- 3.4%. Approximately one half of patients were initially treated by diet and exercise with many requiring intensification of therapy over a short period of time. CONCLUSIONS: We report a similar increase in T2DM incidence and clinical presentation at HSC to other clinic reports in large North American urban centres. Of note is the high prevalence of children of South/South-East Asian descent.     

Cystic spinal dysraphism of the cervical and upper thoracic region

Background Cystic dysraphic lesions of the cervical and upper thoracic region are rare and only a few series have been published about the topic. These malformations can be divided into categories that include both myelocystoceles and the so-called cervical meningoceles or myelomeningoceles.Methods A retrospective study of 18 patients was conducted.Results In 17 patients a squamous or a cicatricial epithelium of variable thickness covered the dome of the lesions, while the base was covered with full-thickness skin. In one case the skin was entirely normal. Four patients displayed associated CNS malformations and three more had systemic congenital anomalies. All patients underwent surgical exploration and the length of time between birth and surgery ranged from 6 h to 9 months. The most frequent surgical finding, seen in 14 patients, was a stalk connecting the dorsal surface of the spinal cord to the cyst. In three patients the findings were consistent with myelocystocele. Only in one case was a true meningocele found. Hydrocephalus and Chiari II malformation were not as consistently associated as in myelomeningoceles. Neurological signs and symptoms were not so marked as in myelomeningoceles and were found in the follow-up of four patients. In two of them there was a non-progressive deficit, probably expressing an imperceptible involvement of the nervous system in the first year of life. The histopathological findings were of three types: neuroglial stalks, fibrovascular stalks and myelocystoceles.Conclusions Cystic dysraphisms of the cervical and upper thoracic region differ clinically and structurally from meningomyelocele and have a more favorable outcome. We believe that these malformations have not been properly labeled and propose a classification based on the structures found inside the cyst.     

Evaluation ofin vitro drug screening leads using experimental models of human ovarian cancer

Summary Five compounds which were identified as potential new anticancer drugs inin vitro screening with the human tumor colony forming assay were selected for further evaluation usingin vitro andin vivo models of human ovarian cancer. Three of five compounds were found to inhibitin vitro colony formation of ovarian cancer cell lines derived from both untreated and combination chemotherapy refractory patients. One compound was also found to prolong survival in a human ovarian carcinoma xenograft model system. This compound, chloroquinoxaline sulfonamide, was selected for development and has shown preliminary indication of activity in phase I clinical testing.