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.     

Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer. Results of a multi-institutional cooperative trial

BACKGROUND. In 1987, a cooperative study group consisting of five institutions was formed to determine the relative benefits of magnetic resonance imaging (MRI) and endorectal (transrectal) ultrasonography in evaluating patients with clinically localized prostate cancer (stage Ta or Tb). METHODS. Over a period of 15 months, 230 patients were entered into the study and evaluated with identical imaging techniques. We compared imaging results with information obtained at the time of surgery and on pathological analysis. RESULTS. MRI correctly staged 77 percent of cases of advanced disease and 57 percent of cases of localized disease; the corresponding figures for ultrasonography were 66 and 46 percent (P not significant). These figures did not vary significantly between readers; moreover, simultaneous interpretation of MRI and ultrasound scans did not improve accuracy. In terms of detecting and localizing lesions, MRI identified only 60 percent of all malignant tumors measuring more than 5 mm on pathological analysis and ultrasonography identified only 59 percent. CONCLUSIONS. The MRI and ultrasonography equipment that is currently available is not highly accurate in staging early prostate cancer, mainly because neither technique has the ability to identify microscopic spread of disease. Further evaluation with improved equipment may improve the accuracy of these techniques.     

Surgery in the treatment of varicose veins

To identify variables which might influence the results of varicose vein surgery, a ten-year retrospective study was carried out on 612 patients undergoing varicose vein surgery. Patient symptomatology, type of venous insufficiency and operator experience were examined and correlated with the results of surgery. The female-to-male ratio was 2:1. The mean age was 47 years for women, 45 years for men. A family history of varicose veins was recorded in 74% of patients. A history of previous deep venous thrombosis was reported in 5% of cases, but in the sub-group of patients with stasis ulceration, the incidence was 9%. Cosmetic appearance was the commonest presenting complaint (54%), while ulceration was relatively infrequent (14%). There was moderate-to-marked improvement in 86% of cases at one year. This was sustained in 79% at three years, in 75% at five years and in 74% at ten years. There was no correlation between the type of venous insufficiency or the presenting complaint, and the result of surgery. Operator experience had the most significant effect on the outcome of surgery (P less than 0.001). Our findings indicate that varicose vein surgery offers most patients a satisfactory result. The only significant variable was operator experience. We strongly recommend closer supervision of junior staff performing this type of surgery, particularly as a large proportion of these patients (25% in this study) are operated on by the more junior staff.     

Effect of intranasal fluticasone proprionate on the immediate and late allergic reaction and nasal hyperreactivity in patients with a house dust mite allergy

Background Patients with perennial allergic rhinitis develop nasal symptoms not only after allergen exposure, but generally also after non-specific stimuli. Objective To evaluate the effect of 2 week's treatment with fluticasone propionate aqueous nasal spray (FPANS) on the nasal clinical response, inflammatory mediators and nasal hyperreactivity. Methods Twenty-four rhinitis patients allergic to house dust mite (HDM). participated in a douhle-blind. placebo-controlled crossover study. After 2 week's treatment with placebo or 200 μg FPANS twice daily, patients were challenged with HDM extract. Symptoms were recorded and nasal lavages were collected for up to 9.5 h after challenge. Nasal hyperreaclivity was determined by histamine challenge 24 h later. Results Because of a carry-over effect for the immediate symptom score, for this variable only the data from the first treatment period were used. FPANS treatment resulted in a significant decrease of nasal symptoms with 70%. 69% and 63% after 100. 1000 and 10000 Biological Units (BU)/mL of HDM extract respectively. Active treatment resulted in a 76% decrease of the late-phase symptoms. FPANS treatment significantly reduced albumin influx after HDM 1000 BU/mL with 62% and tended to reduce tryptase release after HDM 1000 BU ml. (P 0.0629). During the late phase FPANS treatment reduced albumin influx with 67% and eosinophil cationic protein (ECP) release with 83%. No effect of FPANS was seen on histamine levels. FPANS significantly decreased histamine-induced symptom score with 34%, secretion with 32%, and sneezes with 41%. Conclusion FPANS significantly inhibits the immediate and late allergic response, and nasal hyperreactivity, probably by suppressing mast cells and eosinophils in the nasal mucosa.     

Routes to transplant tolerance versus rejection; the role of cytokines

The alloimmune response can be divided into specific junctures where critical decisions between tolerance and immunity are made which define the outcome of the transplant. At these "decision nodes" various cytokines direct alloresponsive T cells to develop either a proinflammatory response aimed at graft destruction or an immunoregulatory response facilitating graft acceptance. This review will focus on the role of these cytokines in influencing the progression of an alloimmune response leading ultimately to either allograft survival or rejection.     

Suppression of charge movement by calcium antagonists is not related to calcium channel block

The calcium channel-inhibiting drugs nitrendipine and diltiazem represent two important classes of organic calcium antagonists. In the present study, the effect of these drugs on calcium currents and charge displacement currents in bullfrog semitendinosus muscle fibers was examined using a vaseline gap voltage clamp. Nitrendipine (10 M) reduced the quantity of charge that moved both during the ON phase (Q_ON) and the OFF phase (Q_OFF) of charge movement. This action appeared to be most selective for Q_ON. However, at this same concentration, nitrendipine had no blocking action on inward calcium currents. In contrast to these findings, diltiazem blocked calcium currents in a concentration-dependent manner, while slightly increasing the quantity of charge moved during Q_ON and Q_OFF. The enhancement of charge movement by diltiazem resulted from two actions. First, diltiazem shifted the voltage-dependence of charge movement to more negative potentials. Second, diltiazem increased the maximum amount of charge moved. (Supported by NIH NS 03178 and HL 07382.)     

Supraependymal cells in the third ventricle of the neonatal rat

Supraependymal cells in the third ventricle of neonatal male and female rats were examined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Supraependymal cells in the third ventrical of adult male rats were also studied with SEM. Many neonate supraependymal cells were round to oval in shape and exhibited varying degrees of surface irregularity. Small finger-like processes or narrow pseudopodia projected from the cell bodies over the underlying ependymal cells. Some neonatal supraependymal cells exhibited flattened cell bodies with broad pseudopodia and few surface irregularities. TEM revealed a variety of cell profiles. Prominent within the cytoplasm of many supraependymal cells were lysosomes, smooth and coated vesicles suggesting pinocytosis, subplasmalemma vacuoles, and occasional lipid droplets. The morphological characteristics of neonatal supraependymal cells suggested they were mononuclear phagocytes. Adult supraependymal cells exhibited more pleomorphic cell shapes with numerous cell processes, varying widely in size and shape, and often extending over the ventricular surface for considerable distances. These observations, in combination with previous studies by other investigators, suggest that some adult supraependymal cells may also be phagocytic in nature. The differences in morphology between adult and neonatal supraependymal phagocytes may relate to the differing third ventricle environment between adult and neonates and/or differences in the origin of the phagocytes with age.