Overall results in 304 consecutive patients with acute spontaneous subarachnoid hemorrhage

The results obtained in 304 consecutive patients with spontaneous subarachnoid hemorrhage are described, the majority of whom (86%) were admitted while in acute condition. Only 46% of the patients in this series were in good condition at admission. The initial management was standardized for all patients, but the protocol of "delayed surgery" was applied to patients with subarachnoid hemorrhage from aneurysmal rupture. Two hundred and twenty-two patients (73%) had intracranial aneurysms. Of these, 20 (9%) were moribund and died shortly after admission; nine (4%) underwent emergency surgery due to the coexistence of a life-threatening cerebral hematoma; seven (3%) were operated upon within 3 days of admission; 78 (35%) died after rebleeding or after steady deterioration of the patient's condition due to vasospasm while awaiting surgery. Of the remaining 108 patients ready for delayed surgery, 12 (11%) (operation refused, elderly patients in poor general condition, spontaneous thrombosis of the aneurysm) were treated conservatively, and 96 (89%), who were in various clinical conditions, were actually operated on. Of these 96 patients, 79 (82%) exhibited excellent or good results, 5 (5%) were disabled, and 12 (12%) died. In the authors' experience, the overall management of intracranial aneurysms in unselected patients according to the protocol of delayed surgery results in significant loss of patients awaiting surgery, and good surgical results in the survivors.     

Proficiency test in clinical mammography. Results of a consecutive series of 130 volunteer Italian radiologists

PURPOSE: We evaluated the results obtained by 130 Italian radiologists undergoing a proficiency test of clinical mammography. MATERIAL AND METHODS: Radiologists were invited to report a series of 100 mammograms (two views), including 32 cancers and 78 non-cancers, with limited information regarding age, subjective symptoms, and findings at palpation. Sensitivity and specificity were then calculated. The test was validated by a panel of experts, and standards for test sufficiency were established on that basis (sensitivity > 80%, specificity > 85%). The tested radiologists differed by mammographic practice (average = 5.7 years, range 0.5-18), total number of mammograms read (average = 8,784, range 300-50,000) and per year (average = 1,535 range 300-5,000). RESULTS: Sensitivity (standard > 80%, average 81.1%, range 39-100%) and specificity (standard > 85%, average 84.0%, range 38-98%) standards were reached by 79 (60.8%) and 81 (62.3%) radiologists, respectively. Overall, only 37 (28.5%) radiologists passed the test (reached both standards). Mammographic practice (years of experience) (chi 2 for trend 5.26, p = 0.02), total mammograms read (chi 2 5.86, p = 0.05), and mammograms read per year (chi 2 8.07, p = 0.01) significantly correlated with a sufficient test. DISCUSSION: The evaluated sample is rather large but not necessarily representative of Italian radiologists. Had the sample been selected, there is no way to know if the results would have been biased towards a better or worse figure with respect to the national average. A significant correlation was found with reading experience (the best results were obtained by operators with > 10,000 films read and with > 2,000 films read/year), as which is important because most Italian radiologists reporting mammography usually read a limited number of cases. CONCLUSIONS: These results on such a wide sample of radiologists, possibly representative of the national average, are disappointing, and suggest that the average quality of mammography reporting in Italy may not be up to standards. Thus, we suggest that quality control program for clinical mammography not only test the equipment but include training and accreditation of radiologists.     

Cl- channels in basolateral TAL membranes. XIV. Kinetic properties of a basolateral MTAL Cl- channel

BACKGROUND: This article reports studies on the kinetics of chloride (Cl-) conductance in Cl- channels fused into bilayers from basolaterally enriched vesicles from rabbit outer medulla. A considerable body of evidence indicates that these channels represent rbClC-Ka, a 77 kDa kidney-specific protein of the ClC family of Cl- channels. rbClC-Ka, a candidate channel for mediating net Cl- absorption in the medullary thick ascending limb (MTAL), has been cloned from rabbit outer medulla and localized by immunofluorescence to basolateral membranes of the MTAL. Thus, this is the first account, to our knowledge, of the kinetics of ion permeation through a renal Cl- channel mediating net basolateral Cl- absorption in the thick ascending limb of Henle (TALH), and this channel may represent rbClC-Ka. METHODS: The electrophysiological properties of these channels were studied by fusing basolaterally enriched MTAL vesicles into planar bilayer membranes. RESULTS: Cl- conductance through these channels was concentration dependent and saturable. The relationship between gCl (pS) and symmetrical aqueous Cl- concentrations could be expressed in terms of the Michaelis equation with a limiting conductance (GClmax, pS) of 114 pS at infinitely high aqueous Cl- concentrations and a K1/2 of 163 mM Cl-. A log-log plot of the conductance-Cl- concentration relations, in the nonsaturating Cl- concentration range, had a slope of 0.91, that is, virtually unity. The relatively impermeant anion I- produced a voltage-dependent conductance blockade that could be overcome at high electric field strengths. CONCLUSIONS: The experimental data described earlier here fulfill the traditional criteria for a first-order process with a single Cl- ion occupying these channels at a given time. Although the channels may contain multiple ion binding sites, the latter function, in integral kinetic terms, as a single rate-limiting locus.     

A comparison of skinfold anthropometry and dual-energy X-ray absorptiometry for the evaluation of body fat in cirrhotic patients

BACKGROUND AND AIMS: Skinfold anthropometry has been used to evaluate the nutritional status in cirrhosis. Such estimates are based on the calculations which derive from healthy subjects and may not apply to cirrhotic patients. We aimed to calculate the limits of agreement between Skinfold anthropometry (SA) and dual-energy X-ray absorptiometry (DXA) in estimating body fat in cirrhotics. METHODS: Forty cirrhotic patients were studied by both methods. The limits of agreement were estimated by the Bland and Altman method. RESULTS: Percentage body fat was similar when measured by DXA and SA (29.6 +/- 9.2 vs 28.9 +/- 7.5 %). Body fat mass was also similar (20.3 +/- 8.4 vs 20.3 +/- 7.7 kg). The limits of agreement between DXA and SA measurements were -7.04 (95%CI: -9.55 to -5.2) +8.56 (95%CI: +10.7 to +6.4.) in the assessment of percentage body fat and -5.32 (95%CI: -6.77 to -3.87) +5.24 (95%CI: +3.79 to +6.69) in the assessment of fat mass. CONCLUSION: Percentage body fat can be evaluated by SA or DXA with a difference of less then 5% in the majority of cirrhotic patients without overt fluid retention. This result is important when considering the large applicability of SA.     

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

The present study investigated the effects of dietary oltipraz on cigarette smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats were exposed daily to sidestream cigarette smoke in a whole- body exposure chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained on control diet while another group received the same diet supplemented with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz, starting 1 week prior to initiation of smoke exposure until the end of the experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated 32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5 predominated in both the lung and the heart while adduct nos 3 and 2 predominated in the trachea and bladder, respectively. Quantitative analysis revealed that the total adduct level was the highest in lungs (270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48 adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides) and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz treatment reduced the adduct levels in lungs and bladder by >60%, while the reduction in lungs in the low-dose group was approximately 35%. In trachea, the effect of low and high dietary oltipraz on smoke DNA adduction was equivocal, while smoke-related DNA adducts in the heart were minimally inhibited by high-dose oltipraz. In a repeat experiment that employed a 3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to inhibit the formation of DNA adducts in rat lungs and trachea by 80 and 65%, respectively. These data clearly demonstrate a high efficacy of oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts in the target tissues.      

Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.      

Membrane‐based therapeutic plasma exchange (mTPE): Technical and clinical experience

Therapeutic plasma exchange (TPE) has long been utilized to manage a variety of immune‐mediated diseases. The basic principle relies on removal of circulating pathogenic substances from the bloodstream. Methods of plasma separation include centrifuge (cTPE) and membrane (mTPE). Although mTPE has existed for a few decades, recent advances in developing highly permeable filters that are compatible with currently existing dialysis machines has opened a new frontier. Published data in the area of technical and clinical experience with mTPE is lacking. We report our single center experience of 998 inpatient mTPE treatments performed in 237 patients at a large tertiary care academic center. The most common treatment indication was neurologic. We found a very low incidence of patient‐reported complications. Filter clotting without the use of anticoagulation occurred in 7.7% of treatments. Laboratory parameters that significantly changed during the course of therapy included serum potassium, platelet count, and partial thromboplastin time. We found that mTPE can be safely and efficiently performed as an alternative to cTPE, and suggest an individualized approach when prescribing this therapy.