Acquired granular pool defect in stored platelets

Platelets stored as concentrates (PC) for 72 h at 22 degrees C develop a functional defect. Alterations in adenine nucleotides of platelets have been shown to affect platelet function. Adenine nucleotide content of platelets was measured before and after storage and a decrease of 27.1 /+- 1.7% (mean /+- SE) in ATP and 39.1 /+- 2.6% in ADP were found in 34 PC stored with final volume of 50 ml. In 11 PC with 30 ml volume. ATP and ADP decreased by 39.4 /+- 3.2% and 49.4 /+- 2.1%, respectively. The mean ATP to ADP ratio of stored platelets was significantly higher than of fresh platelets in both groups, suggesting a relatively greater decrease in granular than metabolic pool nucleotides. Levels of low affinity platelet factor 4 measured by radioimmunoassay in plasma from 0.86 /+- 0.08 microgram/ml in the fresh PC to 8.59 /+- 0.39 microgram/ml in stored PC, indicating a concomitant alpha-granular secretion. Labeling of metabolic pool with 14C-adenine revealed a mean decrease in the adenylate energy charge of 2.0 /+- 0.4% in 12 of 16 stored PC, with a lower ATP and higher hypoxanthine labeling in stored as compared to fresh platelets. These observations suggest that stored platelets develop an acquired defect in both dense and alpha granules and in their ability to maintain ATP homeostasis.     

Cortisol resistance in the New World revisited.

Insights into the molecular basis of glucocorticoid action have been obtained from the analysis of cortisol resistance. The glucocorticoid receptor (GR) in both New World primates and guinea pigs has a decreased affinity, in vivo, for cortisol; this is achieved by two distinct mechanisms. In the New World primates recent studies have identified a key role for co-chaperones. The amino acids responsible for cortisol resistance in the guinea pig GR lie not in the ligand-binding pocket but on the surface of the receptor. We hypothesize that this region might be the site of interaction between the co-chaperones and the GR, and hence that the resistance occurs through the same mechanism, albeit from opposite sides.     

Within- and between-laboratory precision in the measurement of body volume using air displacement plethysmography and its effect on body composition assessment

OBJECTIVE: To determine and compare the extent of within- and between-laboratory precision in body volume (BV) measurements using air displacement plethysmography (ADP), the BOD POD body composition system, and to interpret any such variability in terms of body composition estimates. DESIGN: Repeated test procedures of BV assessment using the BOD POD ADP were reproduced at two laboratories for the estimation of precision, both within and between laboratories. SUBJECTS: In total, 30 healthy adult volunteers, 14 men (age, 19-48 y; body mass index (BMI), 19.7-30.3 kg/m2) and 16 women (age, 19-40 y; BMI, 16.3-35.7 kg/m2), were each subjected to two test procedures at both laboratories. Two additional volunteers were independently subjected to 10 repeated test procedures at both laboratories. MEASUREMENTS: Repeated measurements of BV, uncorrected for the effects of isothermal air in the lungs and the surface area artifact, were obtained using the BOD POD ADP, with the identical protocol being faithfully applied at both laboratories. Uncorrected BV measurements were adjusted to give estimates of actual BV that were used to calculate body density (body weight (BWt)/actual BV) from which estimates of body composition were derived. The differences between repeated BV measurements or body composition estimates were used to assess within-laboratory precision (repeatability), as standard deviation (SD) and coefficient of variation; the differences between measurements reproduced at each laboratory were used to determine between-laboratory precision (reproducibility), as bias and 95% limits of agreement (from SD of the differences between laboratories). RESULTS: The extent of within-laboratory methodological precision for BV (uncorrected and actual) was variable according to subject, sample group and laboratory conditions (range of SD, 0.04-0.13 l), and was mostly due to within-individual biological variability (typically 78-99%) rather than to technical imprecision. There was a significant (P<0.05) bias between laboratories for the 10 repeats on the two independent subjects (up to 0.29 l). Although no significant bias (P=0.077) was evident for the sample group of 30 volunteers (-0.05 l), the 95% limits of agreement were considerable (-0.68 to 0.58 l). The effects of this variability in BV on body composition were relatively greater: for example, within-laboratory precision (SD) for body fat as % BWt was between 0.56 and 1.34% depending on the subject and laboratory; the bias (-0.59%) was not significant between laboratories, but there were large 95% limits of agreement (-3.67 to 2.50%). CONCLUSION: Within-laboratory precision for each BOD POD instrument was reasonably good, but was variable according to the prevailing conditions. Although the bias between the two instruments was not significant for the BV measurements, implying that they can be used interchangeably for groups of similar subjects, the relatively large 95% limits of agreement indicate that greater consideration may be needed for assessing individuals with different ADP instruments. Therefore, use of a single ADP instrument is apparently preferable when assessing individuals on a longitudinal basis.     

Detached ciliary tufts mistaken for peritoneal parasites: a warning

Detached ciliary tufts of columnar epithelial cells from the female genital tract may be mistakenly identified as protozoa when examined in wet mounts of fluid specimens in the laboratory because of their appearance and motility, although they are generally identified correctly in fixed specimens prepared for cytologic examination. A case of such mistaken identity in specimens from a gynecologic patient was documented, and the literature on ciliary tufts was reviewed. Infectious disease and gynecology consultants should be alert to the potential confusion arising from the presence of ciliary tufts in body fluids.     

Brain metastases from papillary thyroid carcinomas

Brain metastasis from papillary thyroid carcinoma (PTC) is extremely rare and carries a poor prognosis. We report nine cases (five females and four males) of brain metastasis of PTC. The age of patients ranged from 46 to 87 years old. The patients presented with nonspecific symptoms such as headaches. Brain metastasis was the first clinical presentation in three of nine patients; two of which had the aggressive tall cell variant of PTC. Six patients had prior history of PTC (four classic, one oncocytic variant, and one columnar cell variant) for 2 to 17 years with a median of 12 years. Gross total resection of brain metastasis was achieved for eight of our patients. Eight patients were treated with radioactive iodine. The median follow-up time was 12 months, ranging from 1 month to 4 years. Three patients died of their disease in 6 months, 21 months and 4 years, respectively after their first presentation of brain metastasis. It seems that these rare aggressive variants of PTC, such as tall cell variant, not only have higher propensity to develop brain metastasis, but also more frequently present with brain metastasis as their first clinical presentation than classic PTC. Furthermore, patients with PTC can develop brain metastasis even after many years.     

Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes

Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia. We studied longitudinally subjects (n = 12) with ∼30 years, disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-²H₂-glucose and compared the results with those from a nondiabetic control group (n = 8). After islet transplantation, HbA_1c was normalized, and time spent while hypoglycemic (<70 mg/dL) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent before transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, which was previously absent, was normalized after transplantation, with a similar effect seen for autonomic symptoms. Because the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results provide evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.