Use of monoclonal antibodies to identify cerebrospinal fluid lymphoblasts in children with acute lymphoblastic leukemia

The identification of small numbers of leukemic cells in the cerebrospinal fluid (CSF) presents a diagnostic problem in the treatment of children with acute lymphoblastic leukemia (ALL). We adapted a latex sphere rosetting technique to allow us to identify simultaneously cell surface markers and cell morphology in 199 CSF samples from 34 patients and 14 control subjects. In patients without leukemic meningitis, the majority of CSF lymphocytes (69%) were found to be mature T cells positive for OKT11. A much smaller number of cells (8%) were found to be B cells positive for la. In these children, only 3% of CSF lymphoid cells expressed the common acute lymphoblastic leukemia antigen (CALLA). Similar results were found in the control subjects. By contrast, 28 CSF samples from nine children with varying numbers of CSF lymphoblasts had much greater proportions of CALLA- and la-positive CSF cells (24% to 96%). Leukemic meningitis was present in one of these patients and later developed in four others. However, three patients with small numbers of lymphoblasts present but with low proportions of CALLA-positive CSF cells (less than 5%) subsequently had normal CSF examinations. We found the use of this rosetting technique valuable in providing information complementary to that obtained from cell morphology alone about the possible malignant nature of small numbers of lymphoblast-like CSF cells seen on cytocentrifuge preparations in children with ALL.     

Electrophoretic analysis of red blood cells in polycythaemia

In contrast with previously published observations, this study has found no increase in the net negative surface charge of the red blood cells (RBC) from patients with various forms of polycythaemia when compared with normal subjects. Two sub-populations of RBCs with different electrophoretic mobilities (EPM), termed fast and slow, were present in samples from both patients and normal individuals. Frequently, the slow cell population in RBCs from patients with polycythaemia, particularly the apparent polycythaemia sub-group, was of a lower EPM and contained more cells than the corresponding population in normal subjects. The membrane-bound sialic acid content of RBCs from patients with primary proliferative polycythaemia, associated with iron deficient RBC changes, was increased if the results were expressed per unit volume of RBCs and decreased if the sialic acid concentration was presented per number of RBCs. These results imply that differences in surface charge of RBCs are of no value in discriminating between primary and secondary polycythaemia.     

Canagliflozin and cardiovascular and renal events in type 2 diabetes

Review of: Neal B, Perkovic V, Mahaffey K, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644–657.

The report combines the data from two trials, CANVAS and CANVAS-Renal, which were designed to evaluate the safety and effect of canagliflozin, an SGLT-2 inhibitor, on the appearance of cardiovascular and renal events in patients with type 2 diabetes. Enrollees were patients with type 2 diabetes of at least 30 years of age, with a glycated hemoglobin of > or equal to 7.0% and < or equal to 10.5%. Patients either had to have preexisting cardiovascular disease or to be at elevated risk for cardiovascular disease, and to have an estimated glomerular filtration rate (eGFR) of >30 ml/min. Patients were randomized to canagliflozin at doses of either 100 mg or 300 mg or matching placebo in CANVAS, and to canagliflozin 100 mg with a possible increase to 300 mg, or placebo, in CANVAS-Renal. Physicians were instructed to continue appropriate diabetic management and other therapies in accordance with the best practices in their community. There was a significant 14% reduction in the combined endpoint of cardiovascular events of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in the canagliflozin treated patients. There was also a pattern of improvement in markers of renal disease, including the change in the level and nature of albuminuria, a 40% decrease in the glomerular filtration rate, the need for renal replacement therapy, or death from renal causes. This study expands the scope of SGLT-2 inhibitor therapy to prevent cardiovascular disease in diabetic patients beyond those with preexisting cardiovascular disease studied in the previous empagliflozin study, raising the question as to whether SGLT-2 inhibitor therapy should be considered appropriate for most, if not all, type 2 diabetes patients, not only to control hyperglycemia but also to reduce cardiovascular and renal events.     

Measurements of pulmonary mechanics prior to the elective extubation of neonates

We measured total respiratory system compliance (CRS) and resistance (RRS) by the passive expiratory flow technique prior to the elective extubation of 61 neonates with a history of respiratory distress syndrome. Successful trials of extubation were characterized by a higher mean value of CRS when compared to trials that led to reintubation (1.52 vs. 1.10 mL/cm H2O, P = 0.004). Low values of CRS (0.9 mL/cm H2O or less) were invariably associated with extubation failure, whereas high values of CRS (1.3 mL/cm H2O or greater) were associated with extubation success in 94% of patients. A higher mean value of RRS was recorded in the group of infants who failed extubation when compared to those who were successful (0.22 vs. 0.17 cm H2O/mL/s, P = 0.042). We propose that measurements of pulmonary mechanics, particularly CRS, may be useful in identifying infants who will be at risk for extubation failure.     

Prevalence of Hypertension in Patients with Type II Diabetes in Referral versus Primary Care Clinics

We compared the prevalence of hypertension in patients with non–insulin-dependent diabetes mellitus (NIDDM) in referral and primary care practices using definitions of The Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V), while controlling for other risk factors such as hypertension, obesity, smoking, and age. Patients (n = 1443) were enrolled consecutively from a large referral practice at the Jackson Diabetes Center and four primary care clinics in the vicinity. Blood pressures were measured at three clinic visits after a 5-min rest in a sitting position using a standard clinical sphygmomanometer. Charts were reviewed to determine diabetes duration, insulin usage, height, weight, smoking history, use of antihypertensive and oral hypoglycemic medications, socioeconomic status, and race. Patients were classified as hypertensive based on JNC-V definitions or if they were on antihypertensive medication. Hypertension was termed uncontrolled if blood pressure was JNC-V Stage 2 or higher while on antihypertensive medication.

Seventy-eight percent of referral clinic and 55% of primary care clinic patients had either JNC-V State 1 or higher hypertension or were on antihypertensive medication. Actual blood pressures indicated that more patients had JNC-V Stage 1 (mild) or higher hypertension in referral compared to primary care clinics (62% versus 48% p = 0.01) but fewer had JNC-V Stage 2 or higher (moderate-severe) hypertension (12% versus 19% p = 0.002). Patients seen in the referral clinic were significantly more likely to have greater age, greater duration of diabetes, higher insulin dosage, longer smoking history, antihypertensive medication, and live outside the metropolitan area. By logistic regression, the odds of hypertension were significantly increased with age (OR 1.51/decade), BMI greater than 27 (OR 2.17), diabetes duration (OR 1.04/year), and insulin dosage (OR 1.74/U/kg). Current smoking and attending a referral clinic were not significantly related. The odds of moderate-severe hypertension were significantly increased with age (OR 1.23/decade), decreased by attending a referral clinic (OR 0.45), and not significantly related to other confounders in the model.

The prevalence of hypertension among patients with NIDDM was higher in referral than primary care clinics. The higher prevalence in the referral practice can be accounted for by the greater severity of associated risk factors in the referral practice patients; however, most patients will be diagnosed and treated for hypertension prior to referral. More patients in the referral practice were on hypertensive medication, which lowered the stage or severity of hypertension but still not to the normal range. The results suggest that the primary detection of hypertension in patients with type II diabetes resides with the primary care physician. Management of hypertension will require both a delineation and acceptance of responsibilities between the primary care physician and diabetes specialists.