Fragmented red cells are the major cause of spuriously high platelet counts in patients with fragmented red cells when counts are obtained by automated blood cell counter

Platelet counts measured by automated blood cell counter often show spuriously high values when measuring samples contain particles of equal size to platelets. The major cause of spuriously high platelet counts in samples with fragmented red cells (FRC) is thought to be the FRC themselves. We studied the correlation between FRC and spuriously high platelet counts in 40 patients demonstrating FRC on blood smears. FRC were measured by manual hemocytometry and by flow cytometry using a monoclonal antibody against glycophorin A (GPA method). There was a significant correlation between spuriously high platelet counts and FRC by manual hemocytometry (r=0.60, p<0.001) or FRC by the GPA method (r=0.45, p<0.005). These data suggest that FRC are the major cause of spuriously high platelet counts in samples with FRC.     

Molecular genetics of PKU in Eastern Europe: A nonsense mutation associated with haplotype 4 of the phenylalanine hydroxylase gene

Phenylketonuria (PKU) is a genetic disorder secondary to a deficiency of hepatic phenyalanine hydroxylase (PAH). Several mutations in thePAH gene have recently been reported, and linkage disequilibrium was observed between RFLP haplotypes and specific mutations. A new molecular lesion has been identified in exon 7 of thePAH gene in a Hungarian PKU patient by direct sequencing of PCR-amplified DNA. The C-to-T transition causes the substitution of Arg²⁴³ to a termination codon, and the mutant allele is associated with haplotype 4 of thePAH gene. The mutation is present in two of nine mutant haplotype 4 alleles among Eastern Europeans and is not present among Western Europeans and Asians. The rarity of this mutant allele and its restricted geographic distribution suggest that the mutational event occurred recently on a normal haplotype 4 background in Eastern Europe.     

Nuclear magnetic resonance studies on bacterial copolyesters of 3-hydroxybutyric acid and 3-hydroxyvaleric acid

Copolyesters of 3-hydroxybutyric acid (HB) and 3-hydroxyvaleric acid (HV), P(HB-co-HV), were isolated from Alcaligenes eutrophus and characterized by solution NMR, solid-state ¹³C CP/MAS NMR, and differential scanning calorimetry. The ¹³C CP/MAS NMR analysis was compatible with that of a random copolyester of oxy-(1-methyl-3-oxotrimethylene) ( B ) and oxy-(1-ethyl-3-oxotrimethylene) ( V ) units which adopts a regular conformation of a 2₁ -helix in the solid state throughout a wide range of compositions varying from 0 to 90 mol-% V units. The chain dynamics of P(HB-co-HV) in chloroform was studied by analysis of the ¹³C and ¹H NMR spectra. The carbon-13 spin-lattice relaxation times (T₁) and nuclear Overhauser enhancements (NOE) indicated that the copolyester molecules in chloroform are not rigid but rather flexible. The conformational preferences of the copolyester molecules were determined by analysis of the ¹H NMR spectra.     

QT interval and QT dispersion in eating disorders

BACKGROUND: Eating disorders are thought to be risk factors for cardiac sudden death secondary to arrhythmia. Results in previous studies on QT interval and QT dispersion, markers of fatal arrhythmia, have been inconsistent. METHODS: We prospectively examined 179 female eating disorder patients, being over 18 years old and diagnosed according to the DSM-IV criteria between January 1995 and December 2002, and 52 healthy women. Patients with abnormal plasma electrolytes or taking medications that might influence the electrocardiogram (ECG) were excluded from the study. QT intervals were corrected for heart rate using Bazett's formula and the nomogram method, which is more reliable at extremely low heart rates than Bazett's formula. QT dispersion was measured as the difference between the longest and shortest QT intervals. QT intervals and QT dispersion in each patient group were compared with those in the control group. RESULTS: The 164 eligible patients consisted of 43 patients with anorexia nervosa restricting type, 35 with anorexia nervosa binge eating/purging type, 63 with bulimia nervosa purging type, and 23 with bulimia nervosa non-purging type. There was no significant difference in age between eating disorder patients and controls. QT interval and QT dispersion were significantly longer in all eating disorder subtypes than in the control group. QT interval and QT dispersion were significantly correlated with the rate of body weight loss in bulimia nervosa. CONCLUSIONS: QT interval and QT dispersion were prolonged in both anorexia nervosa and bulimia nervosa. Examination of ECG in eating disorder patients without extremely low body weight also appears to be clinically important.     

Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer

Although systemic therapy is the standard treatment for metastatic prostate cancer, a randomized controlled trial showed radiotherapy to the prostate improved overall survival of metastatic prostate cancer patients with the low metastatic burden. Additionally, a randomized phase II trial showed that metastasis-directed therapy for oligo-recurrent prostate cancer improved androgen-deprivation therapy (ADT)-free survival. Therefore, administering radiotherapy to both prostate and metastatic regions might result in better outcomes. Thus, we report the treatment results of radiotherapy to both prostate and metastatic regions. Our institutional database was searched for patients who received radiotherapy to the prostate and metastatic regions. We summarized patient characteristics and treatment efficacy and performed statistical analysis to find possible prognostic factors. A total of 35 patients were included in this study. The median age was 66 years, and the median initial prostate-specific antigen (PSA) level was 32 ng/ml. The Gleason score was 7 in 10 patients, 8 in 13 patients, and 9 in 12 patients. The median radiotherapy dose was 72 Gy to the prostate and 50 Gy to the metastatic bone region. The 8-year overall survival, cause-specific survival, progression-free survival, and freedom from biochemical failure rate were 81, 85, 53, and 57%. Among the 35 patients, 12 were disease-free even after ADT was discontinued. In selected patients with metastatic prostate cancer, ADT and radiotherapy to the prostate and metastatic sites were effective. Patients with good response to ADT may benefit from radiotherapy to both prostate and metastatic regions.     

Light and electron microscopic localization of the N-terminal fragment of human pro-opiomelanocortin in the human pituitary gland and in neoplasms

Summary Immunohistochemical localization of theN-terminal fragment (1–76) (NTF) of human pro-opiomelanocortin (POMC) was studied in human adult and fetal pituitary glands, as well as in pituitary adenomas associated with Cushing's syndrome and in ectopic ACTH-producing tumors. Comparison of localization between NTF and ACTH was performed using mirror sections. Our results indicated concomitant localization of NTF and ACTH in the same cells, not only in normal adult and fetal pituitaries but also in pituitary adenomas and ectopic ACTH producing tumours. Specificity of the NTF staining was confirmed by immunoabsorption. Negative staining of the bovine pituitary gland indicated the immunohistochemical localization ofN-terminal (1–45) of human POMC as there is a known species difference in the sequence 1–45 between human and the bovineN-terminal fragment. Presence of NTF in cisterna of rough endoplasmic reticulum indicates its production by small cell carcinoma. These findings, together with the previous studies, suggest that the complete form of POMC is produced in the tumours as well as in normal pituitaries.This work was supported in part by the Grant-in-Aid for Cancer Research (58-Z) from the Ministry of Health and Welfare.Supported by NIH # 16315-04 and by a program grant from the Medical Research Center of Canada     

Hereditary pressure-sensitive neuropathy: demonstration of "tomacula" in motor nerve fibers.

By studying intramuscular nerves in 2 patients from 2 families with hereditary pressure-sensitive neuropathy (HPSN), the occurrence of abnormal thickening of myelin sheaths ("tomacula") was for the first time demonstrated in motor nerve fibers. Furthermore, the tomacula were found to line up on certain axons instead of being randomly distributed. These results indicate that the recurrent mononeuropathies of HPSN arise from an underlying asymptomatic motor and sensory polyneuropathy. It is also suggested that some signals emanating from the axons might be related to the formation of tomacula on the basis of the genetically determined myelination disorder.     

Cerebral oxygenation changes in response to post-hemodialysis standing

Journal of Artificial Organs - Few reports have examined the association between changes in cerebral oxygenation and clinical factors, including blood pressure (BP), upon standing after...     

Renal Disposition of Recombinant Human Interleukin-11 in the Isolated Perfused Rat Kidney

Purpose. To clarify the mechanism of the renal clearance of recombinant human interleukin-11 (rhIL-11), we investigated the renal disposition characteristics of rhIL-11 in the perfused rat kidney. Methods. The disposition characteristics of ¹¹¹In-labeled rhIL-11 were analyzed using a single-pass indicator dilution technique and statistical moment analysis in the perfused rat kidney under filtering and nonfiltering conditions. Results. Steady-state distribution volume (V _d ) calculated from the venous outflow patterns of rhIL-11 at the doses of 0.3 to 10 g/kidney was between 0.35 and 0.40 ml/g kidney. However, V _d at the highest dose decreased to a value almost identical to that of bovine serum albumin, suggesting that there is a reversible and saturable interaction between the capillary wall and rhIL-11 molecule. In filtering kidney, a remarkable accumulation of rhIL-11 was observed while its urinary excretion was highly restricted at all doses. In nonfiltering kidney, rhIL-11 showed a decreased but still significant renal uptake. Taken together, the marked renal uptake of rhIL-11 may be explained by both efficient tubular reabsorption and significant uptake from the capillary side. These processes were not saturable within the tested dose range. These characteristics of rhIL-11 are likely based on non-specific electrostatic interaction with the tissues due to its cationic charge in the cytokine. Conclusions. The renal disposition processes of rhIL-11 were clarified at organ level in a quantitative manner. These findings agree well with previous observations in an in vivo disposition study in mice.