Clonotypic polymerase chain reaction confirms minimal residual disease in CLL nodular PR: results from a sequential treatment CLL protocol.

Patient-tumor-specific oligonucleotides were generated for the detection of minimal residual disease (MRD) in a highly specific and sensitive clonotypic polymerase chain reaction (cPCR). The clone-specific region of highest diversity, CDR-III, was PCR amplified and sequenced. Nested CDR-III clonotypic primers were used in a semi-nested cPCR with a sensitivity of at least 1 in 10(5) cells. Patients with protocol-eligible Rai intermediate or high-risk chronic lymphocytic leukemia (CLL) received induction with fludarabine 25 mg/m(2) per day for 5 days every 4 weeks for 6 cycles, followed by consolidative high-dose cyclophosphamide (1.5, 2.25, or 3g/m(2)). cPCR was performed on peripheral blood and bone marrow mononuclear cells. All 5 patients achieving a clinical partial remission (PR) studied by cPCR were positive. Five patients achieved nodular PR (nPR) (residual nodules or suspicious lymphocytic infiltrates in a bone marrow biopsy as the sole suggestion of residual disease). Five of 5 patients with nPR were cPCR positive. In contrast, flow cytometry for CD5-CD19 dual staining and kappa--lambda clonal excess detected MRD in only 3 of the same 5 nPR patients, all of whom were cPCR positive, and immunohistochemistry detected MRD in only 1 of 4 assessable patients. Three of 7 CR patients evaluable by cPCR had MRD. Only 1 CR patient had MRD by flow cytometry; that patient was also cPCR positive. These data support the conclusions that nodular PR in CLL represents MRD and that clonotypic PCR detects MRD in CLL more frequently than flow cytometry or immunohistochemistry. (Blood. 2001;97:1929-1936)

Toxicological findings in a death resulting from the ingestion of trimipramine.

A fatality following ingestion of the tricyclic antidepressant trimipramine is presented. Whole blood concentrations of trimipramine and its metabolite N-desmethyltrimipramine were measured by gas-liquid chromatography and found to be 400 and 1130 ng/mL, respectively. These findings are compared to those of previous unpublished trimipramine fatalities and fatalities caused by other tricyclic antidepressants.

A fatal overdose with clomipramine.

A death attributed to self administration of toxic amounts of clomipramine is reported. Analysis of post mortem blood showed clomipramine at a concentration of 540 ng/mL and its active metabolite, N-desmethylclomipramine, at a concentration of 580 ng/mL. The corresponding concentrations of the parent compound and metabolite in the urine were only 350 ng/mL and 700 ng/mL, respectively. These blood results are construed to represent minimum lethal concentrations for the two combined compounds.

Macroamylasaemia and hepatitis in a twelve-year-old boy.

Macroamylasaemia was found in a 12-year-old boy with persistent, severe abdominal pain and mild hepatitis. No abnormality of the pancreatic or bile ducts was demonstrated. Both the symptoms and the biochemical abnormality of macroamylasaemia settled spontaneously over 10 months. Transient, asymptomatic macroamylasaemia was found in the boy's father.

Plasma and urinary luteinizing hormone levels in the diagnosis of endocrine disease.

The diagnostic value of measurements of plasma and urinary luteinizing hormone (LH) has been studied in 209 patients with endocrine disease. In 44 patients puberty was either delayed or had failed to occur. In those with chromosomal abnormalities the LH levels were often within the normal range, whereas those with a pituitary cause usually had low levels. In boys with delayed puberty plasma LH levels rose before physical changes occurred and had prognostic value. In patients with later gonadal failure, men with impotence or infertility, and women with secondary amenorrhoea LH assays proved of little value, although in one case a premature menopause was suspected and six patients with anorexia nervosa had low LH levels.Sixty patients with disorders of the hypothalamicpituitary area were studied. Levels of LH were measured and considered in relation to the other anterior pituitary hormones. Impairment of LH secretion was one of the first effects on hormone production of disease affecting this area, and this was, of course, most readily detected in postmenopausal women.The normal ranges of both plasma and urine LH are wide and there seems to be considerable day-to-day variation, especially of urinary output. Several samples should, therefore, be measured if therapeutic decisions are involved.