Clonal B cell populations in a minority of patients with Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is a risk factor for thyroid lymphoma, and clonal B cell populations in HT support this link. The literature on B cell clonality in HT is controversial. AIMS: To identify clonal B cell populations in HT and to assess their usefulness in differentiating HT from mucosa associated lymphoid tissue (MALT) lymphoma and predicting future development of lymphoma. METHODS: DNA from formalin fixed, paraffin wax embedded blocks of thyroid specimens from 10 patients with HT and two thyroid MALT lymphomas was analysed for B cell clonality by seminested polymerase chain reaction (PCR) using FRIII/LJH and FRIII/VLJH primers to amplify the IgH gene VDJ region. In one case, PCR products were sequenced. Immunohistochemistry was performed by labelled streptavidin-biotin technique using antibodies to: CD45, CD45RO, CD3, CD20, and cytokeratin. RESULTS: The histopathological and clinical findings were characteristic of HT. Clonal bands were seen in three and a polyclonal smear pattern was seen in seven cases. The clonal bands in HT were associated with a background smear, and could not be reproduced from other blocks from the same case or from deeper sections of the same block. The clonal bands in thyroid lymphomas were not associated with a background smear and were reproducible. None of the patients with clonal B cells has developed malignant lymphoma during a follow up of 10-13 years. CONCLUSIONS: B cell clonal bands in HT have different features from those in lymphoma (non-pure and non-reproducible) and do not predict future development of lymphoma.

A cardiovascular risk factor reduction clinic.

OBJECTIVE: To describe a cohort of patients referred to a cardiovascular risk factor reduction unit (CRFRU). DESIGN: Prospective cohort study. SETTING: Out-patients referred to a specialty clinic in a tertiary care hospital. PATIENTS: Seven hundred and four consecutive male and female patients with one or more cardiovascular risk factors, of whom 388 were reassessed after one year. INTERVENTIONS: Standard risk factors were measured in all participants. The probability of coronary artery disease (CAD) was assessed according to the Framingham equation and results were compared with data from the Saskatchewan Heart Health Survey for the general population of Saskatchewan. Patients received dietary and fitness advice, as well as drug therapy when indicated. For follow-up studies, the change in probability of CAD and selected variables after one year were measured. MAIN RESULTS: Patients referred to the CRFRU were at considerably higher risk for CAD than the general population. One hundred and sixty-eight of 235 men and 77 of 153 women seen in follow-up had a reduced risk score. Those who improved had a favourable change in systolic blood pressure and in their lipid profile, as well as greater weight loss. CONCLUSIONS: A CRFRU is feasible and appears to reduce risk in a considerable proportion of patients.

Disposition of lorazepam in diabetes: differences between patients treated with beef/pork and human insulins.

The pharmacokinetics of lorazepam was examined in 10 male patients with insulin-dependent diabetes mellitus before and following treatment with neomycin and cholestyramine. Neomycin and cholestyramine were given in an attempt to block the enterohepatic circulation of lorazepam and so to permit an in vivo estimate of hepatic glucuronidation. The volume of distribution and clearance of free lorazepam in diabetic patients were not significantly different from the corresponding estimates in 14 normal controls. Neomycin and cholestyramine increased the clearance of lorazepam by 63% consistent with their effect in non-diabetic controls. However, patients on beef/pork insulin exhibited a greater than normal increase on this interupting regimen (125%), and had a significantly greater neomycin/cholestyramine cycling-interrupted clearance of lorazepam than either normal controls or patients on human insulin (15.4 vs. 6.96 and 7.87 ml.min-1.kg-1). The clearance was correlated positively and significantly with HbA1c and glycated proteins (fructosamine), but only in patients on human insulin. Thus, the pharmacokinetics of lorazepam was not altered in patients with insulin-dependent diabetes mellitus. However, it is possible that there are differences in the rate and extent of hepatic glucuronidation and enterohepatic circulation of lorazepam between patients treated with beef/pork and human insulins and between diabetics treated with beef/pork insulin and non-diabetic controls.