A multiparametric index of platelet in vitro aggregation in cerebrovascular disease

148 patients with various forms of cerebrovascular disease (CVD) were studied by means of a multiparametric analysis ofin vitro platelet aggregation, based on the following six parameters: ADP and epinephrine primary and secondary aggregation thresholds and percent maximum aggregation induced by optimal concentrations of ADP and epinephrine. These patients were assigned to four study groups, according to clinical diagnosis supported by CT scan, of transient ischemic attack and reversible neurological deficit (TIA-RIND), or completed stroke, in the presence or absence respectively of antiplatelet medical treatment at the time of the study. A statistically significant increase of thein vitro platelet aggregation was found in 44.4% of the untreated TIA-RIND patients and in 33.9% of the untreated stroke patients. However this last group showed a higher percentage of very marked hyperaggregation. Differences between the two treated study groups and controls were not signicant. No difference was found in collagen-and ristocetin-induced aggregation between the patient groups and the controls.

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Sommario 148 pazienti con varie forme di malattia cerebrovascolare, sono stati studiati con analisi multiparametriche dell'aggregazione piastrinica in vitro sulla base dei seguenti sei parametri: le soglie di aggregazione primaria e secondaria e l'aggregazione massima percentuale indotta da ADP ed Epinefrina. Questi pazienti sono stati suddivisi in 4 gruppi di studio in accordo con la diagnosi clinica confortata dai dati della TAC e cioè: TIA, RIND, o rammollimento in presenza o in assenza rispettivamente di un trattamento antiaggregante nel momento dello studio. è stato trovato un aumento statisticamente significativo dell'aggregazione in vitro delle piastrine nel 44.4% dei casi TIA, RIND non trattati e nel 33,9% dei casi di rammollimento non trattati. Quest'ultimo gruppo, però, ha dimostrato una più alta percentuale di iperaggregazione molto marcata. Le differenze tra i 2 gruppi di studio trattati con antiaggreganti e i controlli non erano significative. Inoltre nessuna differenza è stata riscontrata tra i gruppi e i controlli nell'aggregazione indotta da collageno e ristocetina.

     

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.     

A model for sustainable short-term international medical trips.

The health status of many people in developing countries is often dismal compared with the norms in industrialized countries. Increasingly, medical practitioners in the United States and other industrialized countries have become interested in global health issues, an interest that often takes the form of short-term international medical trips. We discuss several ethical issues associated with participation in such trips and use our experiences in developing the Children's Health International Medical Project of Seattle (CHIMPS) to outline and illustrate a set of 7 guiding principles for making these trips. CHIMPS is a resident-run, faculty-supported international medical program founded in 2002 by pediatric residents at the University of Washington in Seattle. Members of CHIMPS work with a rural community in El Salvador to support ongoing public health interventions there and provide sustainable medical care in collaboration with the community and a local nongovernmental organization. The 7 principles developed as a result of this work-mission, collaboration, education, service, teamwork, sustainability, and evaluation-can be used as a model for health practitioners as they develop or select international medical trips. The importance of partnering with the community and working within the existing medical and public health infrastructure is emphasized. Many of the challenges of doing international medical work can be overcome when efforts are guided by a few specific principles, such as those we have outlined.     

Fertilization and early embrology: Monozygotic twinning in the human is associated with the zona pellucida architecture

Six cases of identical twin pregnancies which occurred in 2163cycles of in-vitro fertilization during a 3 year period arereported. Monozygosity was confirmed when the number of fetusesexceeded the number of embryos replaced (n = 4) or when twoconcepti were observed in a single amniotic sac (n = 2). Eachof the reported pregnancies resulted from replacement of embryoseither with naturally thin zonae pellucida or embryos whosezonae had been breached during micromanipulation for assistedfertilization (subzonal sperminsertion) or assisted hatching.That such cases exclusively gave rise to monozygosity suggestsa link between the physical state of the zona pellucida, hatching,and generation of identical twins.     

Lineage extinction and replacement in dengue type 1 virus populations are due to stochastic events rather than to natural selection

Between 1996 and 1998, two clades (B and C; genotype I) of dengue virus type 1 (DENV-1) appeared in Myanmar (Burma) that were new to that location. Between 1998 and 2000, a third clade (A; genotype III) of DENV-1, which had been circulating at that locality for at least 25 years, became extinct. These changes preceded the largest outbreak of dengue recorded in Myanmar, in 2001, in which more than 95% of viruses recovered from patients were DENV-1, but where the incidence of severe disease was much less than in previous years. Phylogenetic analyses of viral genomes indicated that the two new clades of DENV-1 did not arise from the, now extinct, clade A viruses nor was the extinction of this clade due to differences in the fitness of the viral populations. Since the extinction occurred during an inter-epidemic period, we suggest that it was due to a stochastic event attributable to the low rate of virus transmission in this interval.     

Effect of leukocyte hydrolases on bacteria

Leukocyte extracts, trypsin, and lysozyme are all capable of releasing the bulk of the LPS from S. typhi, S. typhimurium, and E. coli. Bacteria which have been killed by heat, ultraviolet irradiation, or by a variety of metabolic inhibitors and antibiotics which affect protein, DNA, RNA, and cell wall synthesis no longer yield soluble LPS following treatment with the releasing agents. On the other hand, bacteria which are resistant to certain of the antibiotics yield nearly the full amount of soluble LPS following treatment, suggesting that certain heatlabile endogenous metabolic pathways collaborate with the releasing agents in the release of LPS from the bacteria. It is suggested that some of the beneficial effects of antibiotics on infections with gram-negative bacteria may be the prevention of massive release of endotoxin by leukocyte enzymes in inflammatory sites.     

Utilization of the 2017 diagnostic criteria for hEDS by the Toronto GoodHope Ehlers–Danlos syndrome clinic: A retrospective review

The new 2017 diagnostic criteria for hypermobile Ehlers–Danlos Syndrome (hEDS) provide a framework for diagnosing hEDS but are more stringent than the previous Villefranche criteria. Our clinical experience at the GoodHope EDS clinic was that the 2017 criteria left many highly symptomatic patients without a diagnosis of hEDS. We conducted a retrospective cohort study to confirm our clinic experience and assess the accuracy of the 2017 diagnostic criteria for hEDS in patients who had a previous hEDS diagnosis based on the Villefranche criteria. Our study found that 15% (n = 20 of 131) of patients with a prior diagnosis of hEDS met the 2017 diagnostic criteria, and many of the traits used to distinguish hEDS were not significantly more frequent in patients who met 2017 criteria versus those who did not. In both groups objective systemic manifestations were found less frequently than subjective systemic manifestations. Beighton score (BS) as assessed by primary care practitioner was found to be higher than assessment by EDS practitioner in 81% (n = 74 of 91) of cases. Generalized joint hypermobility was confirmed in only 46% (n = 51 of 111) of patients who had a previous diagnosis of hEDS. Higher BS did not correlate with increased number of systemic manifestations in our cohort. Common comorbidities of hEDS were found with similar frequency in those who met 2017 criteria and those who did not. Based on our cohort, the 2017 hEDS diagnostic criteria require refinement to improve its diagnostic accuracy.     

Ultrastructural Changes Suggestive of Focal Segmental Glomerulosclerosis in Atypical Minimal Change Nephrotic Syndrome

In an attempt to recognize early stages of focal segmental glomerulosclerosis (FSGS) in patients with a clinical course suggesting a diagnosis other than minimal change disease (MCD) and normal histology, or minor, nondiagnostic changes on light microscopy (LM), we used a protocol for systematic and extensive electron microscopy (EM) examination of kidney biopsies obtained from such patients. By this method ultrastructural pathology was found in 8 patients. These changes were localized, involving only portions of single glomerular segments. The findings included mild to moderate increase of the mesangial matrix, focal wrinkling of the capillary basement membrane, and early obliteration of the normal architecture of individual capillary loops, as well as electron-dense deposits in a mesangial and subendothelial distribution. Of these 8 patients, 2 are at present in remission without therapy (in 1, following therapy with cyclophosphamide); 3 are in remission on steroid therapy; 1 developed massive proteinuria during pregnancy, after a spontaneous remission lasting almost 2 years; 1 patient advanced to terminal renal failure 3 1/2 years after biopsy; and 1 died of sepsis 1 month after biopsy. We believe that the ultrastructural changes found may represent early or mild FSGS and that the protocol described can add valuable information in clinically worrisome patients in whom renal histology appears normal.