Analysis of lung damage induced by trichloroethylene inhalation in mice fed diets with low, normal, and high copper content.

Copper is both an essential nutrient required for the activity of several enzymes and a toxic element able to catalyze free radical formation. Trichloroethylene (TCE) is a xenobiotic that generates epoxidic intermediates by bioactivation through the cytochrome P-450 system. In this study, the influence of a dietary copper imbalance on the TCE-induced lung damage was investigated. Weaning mice were fed copper-deficient, copper-sufficient, and copper-excessive diets. After 4 wk, mice were exposed for 30 min to 6,500 ppm of TCE and euthanatized 48 hr later. Lung damage in the TCE-treated mice consisted of vacuolations of Clara cells and was quantitatively evaluated by counting the vacuolated cells per micrometer of basal lamina. At the ultrastructural level, vacuolations appeared as the result of hydropic swelling of the endoplasmic reticulum cisternae. The copper-deficient mice presented the highest number of vacuolated Clara cells. These mice also showed alteration of the capillary endothelium and interstitium and decreased pulmonary copper-zinc-superoxide dismutase activity. Occurrence of oxidative stress in lungs of both copper-sufficient and copper-deficient mice following TCE treatment was indicated by a decrease in reduced glutathione and an increase in its oxidized form.

Effects of dichlobenil on ultrastructural morphology and cell replication in the mouse olfactory mucosa.

The herbicide dichlobenil (2,6-dichlorobenzonitrile) is a tissue-specific inducing necrosis in the olfactory mucosa. Transmission electron microscopy showed vacuolations (1 hr) and necrosis (4 hr) in the Bowman's glands following intraperitoneal injection of dichlobenil (25 mg/kg) in C57B1 mice, whereas no lesions were noted in the olfactory neuroepithelium at these timepoints. Twenty-four hr following injection (25 mg/kg), most of the propria and the olfactory epithelium were severely damaged; the basal lamina, nerves, and blood vessels in the lamina propria, however, remained intact. Following a lower dose (12 mg/kg), the lesions were not as pronounced. The effects of dichlobenil (6, 12, and 25 mg/kg) on cell replication in the olfactory mucosa, as determined by incorporation of 3H-thymidine 3 days later, were more pronounced in the lamina propria than in the neuroepithelium and occurred at a lower dose in the lamina propria than in the neuroepithelium. Together these studies support the previous proposal that dichlobenil induces a primary damage in the Bowman's glands.

[The use of blood and blood products in total hip arthroplasty in 31 European hospitals, 1990/'91]. / Het gebruik van bloed en bloedproducten bij totale heupartroplastieken in 31 Europese ziekenhuizen, 1990/'91.

OBJECTIVE: To compare the use of blood products and artificial colloids during total hip arthroplasty in European hospitals. DESIGN: Descriptive. SETTING: Europe. METHODS: During the period October 1990-October 1991 transfusion data were obtained about patients who underwent a planned total hip replacement for the first time. The investigations were performed in 31 teaching hospitals in ten countries of the EC, as a part of the ¿Safe and good use of blood in surgery' (SANGUIS)-project. RESULTS: Red cells were ordered preoperatively in 97.4% of the 1647 cases and transfused in 81% (ranges among hospitals: 29-100). Hospitals in the Mediterranean area used more auto-transfusion than those in Central and Northern Europe. Plasma was transfused in 6% of the patients, predominantly in hospitals in southern European countries. Albumin was used especially in Central and Northern European countries. The reasons for red cell transfusion were stated in the medical records in 23% of the cases, for plasma transfusions in 7% and for albumin in 1%. Averaged transfusion-related costs were 192 ecu per patient (ranges per hospital: 60-383 ecu). CONCLUSION: Differences between European hospitals in the use of blood products for total hip arthroplasty are considerable.

Quality assurance of clinical transfusion practice by implementation of the privilege of blood prescription and computerized prospective audit of blood requests.

Guidelines, algorithms and recommendations have been issued in the attempt to ensure appropriateness of transfusion practice, but the results are less than satisfactory, mainly due to the difficulty to turn paper procedures into actual practice. In our hospital we have tried to overcome this difficulty through the implementation of a quality assurance programme which includes giving the privilege of nonurgent blood prescription to a limited number of physicians and a computerized prospective audit of blood requests. The latter is performed through verification of the compliance of blood requests, which are designed to include a patient's laboratory and clinical data, with hospital guidelines for the proper use of blood. In the 12 months since implementation of the computerized prospective audit the transfusion service has evaluated 7884 requests. Of these, 63.4% (n = 4998) were for red blood cells, 21.1% (n = 1664) for platelets and 15.5% (n = 1222) for fresh frozen plasma. The prospective audit showed that 96.8% and 98.1% of requests for red units and platelets were appropriate, respectively. Conversely, approximately 27% of plasma requests did not comply with guidelines, mainly because the evidence of coagulopathy was missing. However, inappropriateness of plasma requests for elective general surgery decreased from 39% at the onset of the programme to 14% in the last trimester considered. Moreover, the evaluation by retrospective audit of the proportion of patients transfused with both red blood cells and plasma in the perioperative period out of those transfused with red blood cells only, as an indicator of unwanted reconstitution of whole blood, showed that this proportion decreased from 47.6% (320/672) in the 12 months before implementation of computerized audit to 37.8% (244/646) in the following 12 months (difference = -9.8%, 95% confidence interval of the difference from -4.5% to -15.1%; P < 0.005 by chi 2 test). Our initial experience, together with the present system, shows that (1) the restriction of nonurgent blood prescription to a group of clinicians more educated in transfusion medicine than average clinicians practicing in a large multispecialty hospital is feasible; (2) prospective audit is a useful tool for assuring the quality of blood requesting.

Prospective evaluation of posttransfusion hepatitis.

The incidence of posttransfusion hepatitis (PTH) was determined prospectively at our institution. An active surveillance program of transfused surgical patients was set up; alanine aminotransferase (ALT) levels were determined before transfusion and at monthly intervals for 6 months after transfusion. Patients with confirmed ALT values greater than 2.5 times the upper reference values were referred to the out-patient clinics for diagnosis. Of 4051 surgical patients who underwent transfusion between January 1986 and December 1989, 2459 (60.7%) were enrolled in the surveillance program, and 1018 (25.1%) completed the follow-up; 238 patients received autologous blood only and were used as controls. No PTH was observed in the control patients, and the incidence of the disease in patients receiving homologous blood was 10.97 percent in 1986, 6.58 percent in 1987, 5.55 percent in 1988, and 4.29 percent in 1989; the decreasing trend is significant (p = 0.018).

Damage and repair of mouse bronchial epithelium following acute inhalation of trichloroethylene.

The time-course of damage and repair in the bronchial epithelium of the mouse was studied morphometrically after a single inhalation of trichloroethylene (TCE). Mice were exposed for 30 min to 500, 1000, 2000, 3500, or 7000 ppm of TCE under controlled conditions and sacrificed after 2 and 24 h, and 2, 5, and 7 days. At all TCE concentrations, the damage consisted of dilation of endoplasmic reticulum and was selective for nonciliated cells throughout the bronchial tree. Damage was quantitatively evaluated by counting the percentage of vacuolated cells. Injury was maximal 24 h after exposure and was significantly (p less than 0.05) higher in bronchi with a diameter smaller than 0.4 mm (67.0% +/- 8.5%) in comparison with larger bronchi (34.0% +/- 13.2%). Cell turnover was studied by autoradiography after [3H]thymidine injection. Following TCE inhalation, the percentage of [3H]thymidine labeled cells, which in the controls was virtually zero, increased to a maximum of 13.5% +/- 6.8% (average at all doses) 48 h after treatment and then rapidly decreased to baseline values at 7 days (0.2% +/- 0.1%). Repair of some cells occurred after 24 h, and at 48 h the percentage of vacuolated cells decreased and became significantly related (p less than 0.01) to the administered TCE dose (2.4% +/- 1.4% and 21.2% +/- 6.0% average in the 500 and 7000 ppm groups, respectively). Repair of bronchial epithelium took place by both recovery of less damaged cells and proliferation of residual nonciliated cells, leading to restoration of the normal ratio between ciliated and nonciliated cells.

Prevalence of hepatitis C virus antibodies in Italian blood donors. The Italian Cooperative Group.

11,117 blood donors from 24 blood transfusion services evenly distributed throughout the various Italian regions were tested for the presence of hepatitis C virus (HCV) antibodies in the serum and serum alanine aminotransferase (ALT) level. The results are as follows: (1) anti-HCV seroprevalence in Italy was 0.87% with a difference between Northern and Southern regions (0.68 vs. 1.37%) and between younger and older subjects (0.62 vs. 1.21%); (2) prevalence of elevated ALT levels was 4.74% without a North-South effect (except than for markedly elevated ALT levels); (3) anti-HCV seroprevalence was higher in subjects with elevated ALT (5.0%), with a North-South effect (2.2 vs. 9.9%) and particularly high (19.2%) in subjects with markedly elevated ALT; (4) ALT levels were elevated in 26.2% of anti-HCV positive subjects, with a North-South effect (14 vs. 40.5%).

Quality assessment of transfusion practice in elective surgery.

A program of quality assurance (QA) was adopted to improve blood transfusion practice in elective surgery at a large urban hospital. For this purpose, a cooperative multidisciplinary group was formed, key indicators were identified, and an organization was set up. Data collected by this organization in the 1-year period needed for implementation of the program indicated that blood misuse was common practice. In fact, overrequest, overtransfusion, excessive reconstitution of whole blood (i.e., concurrent transfusion of red cells and fresh-frozen plasma), and underuse of predeposit were found in all ten surgical departments of the hospital. In a pilot study, data were collected from one surgical department during and after the implementation phase of the QA program; comparison of these data showed a postimplementation reduction of about two thirds in overtransfusion, whereas overrequest, reconstitution of whole blood, and predeposit rates remained unchanged. These results prompted continuation of the program in order to reach a definitive evaluation of its effectiveness.

Autologous blood predeposit for elective surgery: a program for better use and conservation of blood.

We report the results of a pilot study on predeposit autotransfusion for elective surgery. In 2 years 319 U, each consisting of 350 ml of blood, were donated by 206 patients. Each patient gave 1, 2, or 3 U according to hematocrit levels within 10 days of undergoing surgery on the gastrointestinal tract, lung, liver, kidney, brain, thyroid, arteries, or breast. A hemoglobin drop of about 0.8 gm/dl occurred after each blood donation. A total of 259 autologous and 128 homologous U were transfused to 166 patients during surgery or within postoperative day 4; 40 patients required no blood transfusion. About 70% of patients did not need homologous blood products in addition to autologous units. The most active team of surgeons and anesthesiologists covered about 40% of the patients' blood needs during the study period with autologous units. No patient experienced untoward reactions before, during, or after surgery. Surgeons' and anesthesiologists' responses to the program improved during the study as soon as the advantages of the procedure became clearer. However, gentle pressure from the Transfusion Center was essential for the program's expansion. The patients' acceptance was excellent. We conclude that predeposit autotransfusion is a safe and feasible procedure for transfusion treatment in elective surgery.

Relacion entre sindrome de Down, edad materna y presencia de translocaciones cromosomicas. / Relation of Down's syndrome, maternal age and chromosomic translocations presence

Se realizaron estudios citogeneticos en 28 ninos con sindrome de Down de la Escuela de Ensenanza Especial "Fernando Centeno Guell", hijos de madres con edades entre los 16 y 30 anos, con el objeto de determinar el porcentaje de translocaciones presentes en la muestra. Se encontraron 2 ninos con translocaciones de un cromosoma 21 u, otro del grupo G (7,1 por ciento) y um nino con translocaciones de un cromosoma 21 a um cromosoma del grupo D (3.6 por ciento), los tres con un numero cromosomico de 46. No se encontraron alteraciones cromosomicas en ambos padres de los ninos con translocaciones, ya que rehusaron el estudio a pesar de amplia informacion. Consideramos de interes comunicar esos hallazgos preliminares, con el fin de motivar la extension de programas prevetivos similares a poblaciones de alto riesgo

Functional study of lipids of PNH red cell membranes: susceptibility of liposomes to reactive lysis.

Lipids extracted with chloroform-methanol from red blood cell membranes of 7 PNH and 13 control subjects were used for the preparation of liposomes, which were then examined with the reactive lysis test. PNH liposomes lysed to a higher extent than control liposomes as indicated by the higher dilution of the limiting complement reagent that was necessary to lyse 50% of the PNH liposomes. A similar finding was also observed with liposomes made of lipids from AET-treated red cells. The enhanced reactive lysis can be attributed to the polar lipid fraction, as indicated by the increased lysis of hybrid liposomes prepared from this polar lipids extracted from PNH erythrocyte membrane and lipids extracted from normal erythrocyte membrane. The increased susceptibility to reactive lysis does not seem to be specific of PNH liposomes, since it was also observed with liposomes prepared from lipids of red cells from beta-thalassemia major and autoimmune hemolytic disease.