Physical attractiveness: interpersonal and intrapersonal variability of assessments.

On the basis of face photographs, a team of 50 male judges assessed the physical attractiveness of 64 young women, giving them scores according to two scales (0/1 and 1-10). The attractiveness of each woman was then calculated as the mean value of assessments of all observers. The ratio of intra- to interpersonal variance of assessments was the measure of divergence of the observers' opinions (and its complement to unit was the measure of consistency). The correlation between assessments of attractiveness and measurements of the morphological features of the women was calculated as well as the correlation between the morphological features of the observers and the features of women regarded by them as the most attractive. The main conclusions are: Attractiveness is not solely a function of individual tastes. About 25 per cent of the assessments' variance can be explained by common opinion of the judges. Higher assessments of attractiveness are correlated with modal variants of morphological features of assessed women. There was no correlation between morphological features of the observers and the features of the women rated most attractive by those observers.


Changes in sibling configurations for American preschool children.

This paper uses data drawn from the 1940 through 1980 Public Use Microdata Samples of the U.S. Census of Population to document sibling configurations from the child's perspective. Changes in four aspects of siblings are examined for five cohorts of white and black preschool-aged children: number, birth order distributions, spacing intervals, and sex composition. Changes in fertility behavior of adults in the post-war era had a profound effect on the structure of sibling systems experienced by children. Successive cohorts of preschool children show a rise in number of siblings through the early post-war years before showing sharp declines in number of siblings through the 1960's and 1970's. These shifts in size of sibling sets are reflected in changes in the proportion of each cohorts who are first born and only children, both of which have increased substantially by the 1980 cohort. The 1940 and 1980 cohorts have similar proportions of children with short intervals. However, the middle cohorts show the effects of the quickened pace of fertility with substantial proportions of children with comparatively short birth intervals. Finally, substantial shifts across cohorts in several measures of sex composition of children are observed. Most significantly, there is a marked decline in the proportion of children experiencing an opposite-sex older sibling.


Organic-solvent water pollution and low birth weight in Michigan.

This pilot study explored the association between a measure of water pollution caused by benzene or chlorinated solvents and the incidence of low birth weights for white residents of Michigan counties. A positive relationship between water pollution by these contaminants and the per cent of low-weight births (less than 2,500 grams, or about 5.5 pounds) resulted despite controls for the incidence of teenaged childbearing, infrequent prenatal care, and mean household income from wages or salaries. Water pollution showed an association with the incidence of low birth weight that was as strong as that between low birth weight and low prenatal care. While correlation cannot prove causation, the finding suggests that impure water may impair fetal growth in Michigan.


Reclaiming the community: the strengths perspective and deinstitutionalization.

In the past decade, concern for the plight of severely mentally ill people has centered on such issues as mental illness among the homeless population, the burden placed on families who care for ill loved ones, and the impoverished quality of life experienced by those who attempt to survive on their own. Some have called for a rethinking of the abandonment of the asylum and a relaxation of civil commitment laws, while others have advocated for increasing community-based services that specifically target severely mentally ill people. This article discusses these issues and considers how the response to severe mental illness has overrelied on pathology-based models of helping. The strengths perspective provides an alternative. Although severe mental illness presents a formidable obstacle to the afflicted, mentally challenged individuals have strengths and abilities that can be tapped to foster their continued integration in community settings. This adjustment is best conducted through the use of naturally occurring community resources rather than specialized, segregated programs.


Corporate funding of human services agencies.

This article reviews national trends in the organization of corporate giving to human services agencies, examines how corporations make funding decisions, and reports the results of a case study of philanthropic giving among 29 companies in Cambridge, Massachusetts. The study found that most corporations use an informal rather than a formal process for making funding decisions, with many firms relying on tradition, social contacts, and intuition to guide allocations. Suggestions that social services administrators can use to enhance development planning at their agencies are provided.


Sex differences in vulnerability and maladjustment as a function of parental investment: an evolutionary approach.

Sex differences in aspects of mental health are examined as a function of uneven parental investment in children. Relative vulnerability is a new construct mediating the influence of parental investment on mental health. Couples (129) in three stages of the family life cycle are measured by scales for parental investment, relative vulnerability, anxiety, depression, and ten psychosomatic syndromes. Results show a path of positive correlations from the parent's sex to level of parental investment, to level of relative vulnerability, and to levels of anxiety and depression. Women invest more than men, and hence they are more vulnerable, anxious, and depressed. They reach the summit of their vulnerability while they have three young children. Relative vulnerability was found to have positive effects along with the negative ones and to affect women in different ways than it does men. Results are interpreted in terms of different parental strategies selected by evolution for each sex.


Enhancing the delivery of effective mental health services to children.

An increasing number of children and adolescents are in need of mental health services, although few children receive the treatment they need. Although progress in understanding and treating children's mental disorders is limited, a great deal more is known today about how to prevent mental disorders, what treatments are effective, and the importance of providing multiple services. This article presents current knowledge on assessment, treatment, and service delivery to help social workers improve the effectiveness of services for children.


Is lactation nature's contraceptive? Data from Samoa.

Data from a Samoan menstruation study suggest that lactation, even intensive on-demand lactation, does not inhibit menstruation or conception. This paper explores the applied and theoretical implications of continuing to accept lactation as a universally effective fertility control mechanism. Such thinking can have disastrous implications for family planning programs, and it keeps us from challenging long-held assumptions about lactation's role in population growth in early populations.


EAP's response to personal stress and productivity: implications for occupational social work.

Ethical and practice issues regarding the beneficiary of social work services in the workplace have been raised in the literature. However, no empirical studies could be found that specifically address these issues. This study's findings indicate that although personal stress and employee productivity are related, employee assistance program interventions improve employee productivity without reducing employee stress. Challenges and implications for occupational social work are discussed in light of the profession's person-in-environment configuration.


Violent and accidental mortality among four immigrant groups in Canada, 1970-1972.

For most people immigration to a new country such as Canada entails a positive move and an improvement in life. The many challenges associated with resettlement may, however, lead to insurmountable difficulties, stresses and conflict for a significant number of newcomers. The mortality experience of immigrants, as reflected in cause-of-death statistics, may provide indication of the extent of stress and conflict in their migration experience. This situation is most clearly exhibited in mortality from suicide, homicide, and motor vehicle accidents. In this study, hypotheses concerning immigrant mortality in Canada are developed and tested with a log-linear model for rates pertaining to rare events. Overall, the results give support for the importance of country-of-origin effects in explaining suicide propensities, but not for homicide and motor vehicle accidents mortality. Income discrepancies are a significant determinant of variability in death rates overall, but discrepancies between the immigrants in this study and the Canadian-born are not of much significance. The strongest net effect on the cause-specific death rate is associated with group membership. This effect likely reflects a number of residual unmeasured sources of variation including the influence of the immigrant ethnic community as a source of social support, and the potential confounding effects of migration selectivity.


When problems seem overwhelming: emphases in teaching, supervision, and consultation.

The intractability of many of today's problems creates unusual stress for social workers. Traditional direct practice content taught by teachers, field work instructors, agency supervisors, and consultants provides a sound foundation on which to teach and learn practice skills. However, it also is essential for teachers, instructors, supervisors, and consultants to recognize the unusually stressful nature of practice and the frequent sense of pervasive hopelessness felt by practitioners. This article focuses on the preparation of social workers for effective work in today's complex social environment and suggests five major areas that need to be emphasized in teaching, supervising, and training.


Social workers training primary care physicians: essential psychosocial principles.

The growth of primary care medicine is opening new roles for the social worker in medical education to provide instruction and to design curricula that include the psychosocial dimensions of medical practice. This article describes a family-oriented, community-based medical residency program in which the social work faculty plays a prominent role in the education of young physicians. The relevance of core social work principles to medicine and how they are introduced into the teaching and precepting of medical residents are discussed.


Caregiver support groups: factors affecting use of services.

Use of time-limited psychoeducational support groups by family caregivers to help frail elderly people in the community reflects a mixture of predisposing, enabling, and need factors. Using multivariate regression methods that control for dependent-variable censoring, the authors found that attendance in support groups by primary caregivers was greater for those who were older, who had a secondary informal caregiver involved in providing care, or who had significant health problems. Attendance was greater also for those caring for Alzheimer's victims and for those experiencing higher levels of burden in their caregiving role. In English-language groups, Mexican American caregivers showed markedly lower attendance than Anglo American caregivers, but in Spanish-language groups attendance by Mexican American caregivers was essentially the same as that of the Anglo Americans in English-language groups. Data for this study are from a federally funded support group demonstration project conducted in a southwestern metropolitan area.


[Granulocyte alkaline phosphatase activity in the chronic phase and blastic crisis of chronic myeloid leukemia. Sequential study of 43 patients].

To evaluate in a sequential fashion the activity of the leukocyte alkaline phosphatase (LAP) in the chronic phase and the blastic crisis of chronic myelogenous leukaemia (CML). This study is comprised of 43 patients diagnosed of CML according to standard criteria. The initial LAP scores were compared with those recorded in the blastic crisis, using cytochemical methods. The statistical analysis was performed with Student's test and chi-square. The LAP activity at diagnosis was low in 40 of the 43 cases (93%), the score being 0 in 20 instances. In the blastic crisis low scores were found in 27 patients (63%), while LAP activity appeared normal or increased in 16 others (37%). When the LAP scores of the two phases of the disease were compared the differences were found statistically significant (p less than 0.0001 and p less than 0.0007, respectively). These results confirm that the onset of the blastic crisis of CML is often accompanied by an increase of the LAP activity, although this last persists low in the majority of the patients.


[Low-grade non-Hodgkin's lymphomas. Study of 73 cases].

To analyse the clinico-biologic features at diagnosis and the response to therapy and survival of a group of patients with low-grade non-Hodgkin's lymphoma (NHL). The study comprises 73 NHL patients diagnosed between 1974 and 1989 in the Covadonga Hospital and classified as low-grade in accordance with the international Working Formulation. The first-line treatment regimens used were cyclophosphamide-vincristine-prednisone (CVP), chlorambucil-prednisone (CBL-PRED), radiotherapy, and other combinations. The statistical study was performed by comparative statistics (Student's tests, chi-square), univariate analysis (Cox Mantel method) and multivariate analysis (Cox proportional risks); the BMDP pack was used for the study. The median age of the group was 63 years. Stages III and IV were seen at first in 75% of the patients, and 22% of the series had extranodal involvement. CVP was used in 69% of the cases, 7.6 received CBL-PRED, 11% were given radiotherapy, and other combinations were given to 11% of the patients. As a whole, responses were seen in 46 cases (73%), of whom complete remission (CR) was achieved in 49% and partial remission (PR) or minor responses (MR) were attained in 24% of instances. The factors influencing upon CR were: stage (p less than 0.0005), B-symptoms (p 0.004), splenomegaly (p less than 0.801), platelet count and haemoglobin rate (p less than 0.01). The total survival at 10 years was 53%, and the disease-free survival for those attaining CR was 48%, with disease-free median of 81 months. The univariate analysis was influenced in a negative fashion by the following: peripheral blood lymphocyte count below 2 x 10(9)/L, B-symptoms (p less than 0.002), bulky tumoural mass (p less than 0.007), advanced stage (p less than 0.003) and, chiefly, response to treatment (p less than 0.0001). The 10-year survival of the patients achieving CR was 86%, that of both types of response (PR and MR) was 20%, and it was 0% for the failures. 1) Patients in low stages have high possibilities of curation with radiotherapy. 2) CVP for advanced stages provides moderate percentage of response, with CR rate lower than 50%. It is necessary to select those patients with unfavourable prognostic factors in order to use aggressive treatment to achieve CR. 3) Patients attaining CR have better prognosis in spite of the frequent relapses (63% at 10 years).


[Plasma cell leukemia. Study of 6 patients].

To analyse the clinico-biological characteristics, the clinical course and the response to therapy in a group of patients with plasma cell leukaemia (PCL). Out of a total number of 107 patients diagnosed of multiple myeloma (MM) between 1983 and 1991, 6 were found to meet the criteria for PCL (prevalence: 5.6%). This was primary in 2 cases and secondary in the remaining 4. The M/F ratio was 2/1 and the median age was 63 years (range: 57-69 years). Two patients had bone pain and two others weight loss at the onset of PCL. The outstanding haematological findings were increased ESR, normocytic-normochromic anaemia and thrombocytopenia, which were present in all cases. The percentage of peripheral blood plasma cells was between 29 and 70, and the bone marrow aspirate showed plasma cell infiltration over 40% in all cases. Serum M component was found in 5 patients, with decreased values of the polyclonal immunoglobulins; the remaining patient had non-secretory MM. Renal insufficiency was present in 3 patients at diagnosis. Three of the 4 patients with secondary PCL had been previously given combination chemotherapy and the remainder had received melphalan and prednisone. The period between the diagnosis of MM and the development of PCL ranged between 1 and 21 months (median 15 months). Three patients were treated with the M-2 protocol and the others received only supportive therapy. Transient partial response could be achieved in only one case with chemotherapy. All the patients have died, the actuarial survival median being 1 month (range, 1-7 months). Three patients died of infection, 2 of renal insufficiency and one of heart failure after acute myocardial infarction. The poor prognosis of PCL was confirmed, along with the scarce response to therapy of these patients.


[Thrombin-antithrombin complexes and F1+2 prothrombin fragment in coronary revascularization surgery. Relationship with graft occlusion].

To evaluate the possible role played by activation of the coagulation system in the early occlusion of grafts in patients subjected to aortocoronary bypass. This study includes 30 patients subjected to coronary revascularization surgery. The plasma rates of thrombin-anti-thrombin complexes (TAT) and 1+2 prothrombin fragments (F1+2) were measured before and after surgery. The studies were performed by enzyme immunoassay techniques. Selective angiography was performed in every patient on the 10th day after surgery. Descriptive statistics, Student's t test and Mann-Whitney U test were used for comparison of means ans statistical analysis. Occlusive lesion was shown by angiography in 15 of the 30 patients. The TAT and F1+2 levels showed a statistically significant increase (p less than 0.001) along the postoperative period, without any correlation regarding the presence or absence of occlusion. The preoperative concentration of TAT was significantly higher in patients with thrombotic occlusion (p less than 0.05). 1) Marked activation of the coagulation system is present in patients subjected to coronary revascularization surgery. 2) The pre-operative determination of TAT may be of value for predicting early graft occlusion.


[Autoimmune hemolytic anemia. Review of 200 cases studied in a period of 20 years (1970-1989)].

To propose a new aetiologic classification of the patients suffering from autoimmune haemolytic anaemia (AIHA). Two-hundred cases of AIHA studied and followed-up between 1970 and 1989 are presented. From an aetiological and pathogenetic standpoint the disease was classified into 4 groups: (1) idiopathic, (2) secondary, (3) associated and (4) accompanying. The percentage of the different AIHA types, in accordance with the antibodies behaviour, was: (1) warm-reacting AIHA, 74.5%; (2) cold-reacting, 19%; (3) combined or mixed pattern, 6.5%. The immunoglobulins fixed on red cell surface and the specificity of the antibodies found corresponded to those reported in the literature. No treatment was needed in 27.5% of the cases. Corticosteroids were the therapy used in virtually all the cases. Corticosteroids were favourable effect could be appreciated in about 80% of the patients treated. Splenectomy had to be performed in 13.1% of the patients; 47.4% of them attained complete remission while 56.2 failed to respond. Nonsteroid immunosuppressive agents were used in 16.5% of the cases, with 50% of total or partial responses. There are striking prognostic-evolutive differences when this study is viewed from the patients or the AIHA standpoints. Thus, the mortality reached 57.5% of the cases, but in only 10% it was related with AIHA, and something similar could be said about remissions. The analysis of this series allows one to establish: (1) four aetiopathogenetic groups of AIHA; (2) a high percentage of cases related with severe underlying diseases; (3) over 50% incidence in people over 50 years of age, and (4) natural ageing of the series is appreciated after a long follow-up (1-20 years).


[Parahemophilia. Study in a family of 3 generations].

Three generations of a family with congenital deficit of factor V are reported. Those subjects showing symptoms were heterozygous. The transmission of the disease appears to be autosomal recessive. From a clinical standpoint, the patients suffered moderate haemorrhages, mostly affecting mucosae, which became severe on occasions, chiefly after labour. Isolated factor V rates did not correlate with the severity of bleeding. The different variants reported in the literature are commented. Transfusion of fresh-frozen plasma seems and adequate therapeutical approach for this disorder.


[Non-Hodgkin's lymphoma associated with human immunodeficiency virus infection in children].

A 3-year-old boy with infection by the human immunodeficiency virus (HIV) developed stage IV Burkitt's lymphoma. Complete remission was achieved with the BFM-86 protocol. One month after finishing treatment, and still in complete remission, fever appeared and seropositivity to HIV was found. The child was diagnosed of AIDS (P2-E1) and died 10 days later. Although the association of HIV infection and Burkitt's lymphoma is well known in adults, it is extremely rare in children. The routine HIV screening is suggested for children with non-Hodgkin's lymphoma.


[Resistance to antivitamins K].

Resistance to oral anticoagulant is a rare phenomenon. We report the case of a 32-year-old woman who required anticoagulation due to a deep venous thrombosis. She gradually developed resistance to acenocumarol and warfarin. Although the HPLC (high performance liquid chromatography) method proved satisfactory acenocumarol levels in plasma, therapeutic anticoagulation was not achieved. The mechanisms of resistance are discussed.


Further appraisal of APACHE II limitations and potential.

Hemodynamically unstable patients selected for invasive cardiovascular monitoring were divided into APACHE II subgroups for risk stratification to study interrelationships among monitoring, therapy, resulting cardiovascular function and outcome. When compared by regression analysis, there were no clinically relevant relationships between APACHE II scores and total intervention points (r2 = 0.02), days of invasive monitoring (r2 = 0.000001), initial cardiovascular function (r2 = 0.069) and final cardiovascular function (r2 = 0.05). Analysis of variance (ANOVA) was done between APACHE subgroups and total points (zero of 20 intragroup comparisons were different by the Scheffé test; p = 0.33), days of monitoring (zero of 20 were different; p = 0.61), initial cardiovascular function (three of 20 comparisons were different; p = 0.003) and final cardiovascular function (zero of 20 were different; p = 0.24). Opposite relationships in patients who lived and died were noted between total intervention points and APACHE II subgroups (p = 0.028, two-way ANOVA). There was an increasing number of total intervention points in patients who ultimately lived in ascending initial APACHE II subgroups. In contrast, there was a decreasing number of total intervention points in patients who ultimately died in the same APACHE II subgroups. APACHE II stratification failed to help understand the relationships among clinically important parameters. At the same time, while APACHE scores are claimed to be independent of therapy, the score seemed to be extremely sensitive to interventions, especially important in surgical populations. Should the APACHE II scores remain high in the face of continued maximal intervention, fatal outcome can be predicted. This pattern is remarkably similar across the entire initial APACHE spectrum. The predicated attributes of APACHE II scores, that is, risk stratification and independence from therapy, are neither necessary or desirable. Understanding patterns that are associated with survival or death may require alternative mathematic approaches, such as group and set theory manipulated by principles of Boolean algebra. New approaches may be more fruitful than further attempts to refine existing systems.


Combined liver and whole pancreas procurement in donors with a replaced right hepatic artery.

Aberrant donor arterial anatomy, such as a replaced right hepatic artery, is often considered a contraindication to combined liver and whole pancreas procurement for transplantation. With the increasing interest in transplantation of the pancreas and the demand for cadaver organs, methods for simultaneous procurement despite aberrant donor anatomy are essential. We describe the surgical techniques used successfully in six instances of combined liver and whole pancreas procurement in donors with a replaced right hepatic artery and suggest that a replaced right hepatic artery should not preclude simultaneous procurement in otherwise suitable donors.


Avoiding complications and decreasing costs of central venous catheter placement utilizing electrocardiographic guidance.

A technique for electrocardiographic (ECG) guided percutaneous placement of central venous catheters (CVC) was studied in a prospective, randomized manner. In 34 patients, 51 ECG guided percutaneous CVC were compared with 29 blind percutaneous CVC in 23 patients. Thirty-nine percent of CVC placements were changes over a guide wire. Ideal catheter tip location at the atriocaval junction was achieved in 96 percent of the patients in the study versus 59 percent of those in the control group (p less than 0.001). In addition, we report 25 patients with open placement of CVC using intraoperative ECG guidance and fluoroscopic confirmation. Ideal location of the catheter tip was achieved in 100 percent of these patients. ECG guided CVC placement using the technique described herein obviates the need for catheter repositioning, repeat roentgenographic studies and intraoperative fluoroscopic imaging, along with the attendant costs and radiation exposure to staff and patient. Aberrant catheter tip placement and the associated morbidity are also eliminated.


Enhancement of true-positive rates for nonpalpable carcinoma of the breast through mammographic selection.

A retrospective review of 332 needle localization biopsies for nonpalpable mammographic abnormalities was performed. Twenty-one invasive and 12 noninvasive carcinomas were identified in this population, for a true positive biopsy rate of 10 percent. A review of all needle localization mammograms performed on these patients by a radiologist specializing in mammography identified 225 mammograms with a low probability of malignancy. In this group, there were four in situ and six invasive carcinomas (true positive biopsy rate of 4 percent). In the remaining 107 mammograms with a high probability of malignancy, there were eight in situ and 15 invasive carcinomas (true positive biopsy rate of 21.4 percent). In the low probability group, fine needle aspiration or excisional biopsy were recommended for six of the ten neoplasms and follow-up mammograms at three to six months for the remaining four (two in situ and two invasive carcinomas). Using selectivity, 225 biopsies could have been avoided at a savings of $97,368 (Canadian dollars) in fees for physicians alone while still identifying 29 of 33 neoplasms (87 percent of all neoplasms) and possibly delaying diagnosis for three to six months or longer in four of 33 neoplasms (13 percent, two in situ and two invasive) for which follow-up mammograms were recommended.


The results of autopsy of patients with surgical diseases of the digestive tract.

The results of autopsy of 77 patients who died because of surgical disease of the digestive tract were compared with antemortem findings. An analysis was performed to identify missed diagnoses and incorrect therapy. Primary diagnoses had not been frequently missed, but many complications of the primary disorder or treatment had been overlooked. Many patients died because of septic conditions. Error in treatment, with an adverse impact on the course of the disease as assessed by the postmortem examination, occurred in 9 percent of the patients. The most common error had been failure to reoperate upon patients with an intra-abdominal complication. Unexpected death was significantly associated with incorrect diagnosis; failed or inadequate diagnostic methods were significantly associated with treatment failure (chi-square tests). The autopsy remains a valuable procedure in clinical operation. Selection of patients for autopsy, as indicated by decreasing autopsy rates, is not justified.


Surgical management and prevention of vaginal vault prolapse.

From 1984 to 1988, we corrected and prevented the prolapse of the vaginal vault of patients who wanted to maintain a satisfactory sexual function. This was done by adopting two different surgical techniques. The first, generally favored technique, was performed upon 179 patients and consisted of a colposuspension to the sacrospinous ligaments. The second technique, a colposacropexis, was performed upon 71 patients, in which abdominal associated pathologic changes required an abdominal surgical approach. Colposacropexis was performed, whenever possible, directly to the anterior longitudinal vertebral ligament or using synthetic materials (Mersilene [polyester fiber], Teflon [polytetrafluoroethylene] and Gore-Tex [expanded, reinforced polytetrafluoroethylene]). Both colposacropexis and vaginal suspension to sacrospinous ligaments have had comparable results in vaginal accommodation and long term fixation. Vaginal approach has a lower incidence of operative complications than the abdominal approach and seems to ensure a lower risk of recurrent cystocele, even if simple and asymptomatic.


Surgical treatment for cholelithiasis.

In a retrospective study, the results of 1,631 consecutive operations for cholelithiasis were analyzed. With an overall mortality rate of 0.18 percent and a reoperation rate of 1.3 percent, conventional cholecystectomy proved to be a safe method. Mortality proved to be age dependent, with a zero mortality rate for patients less than 60 years of age. Choledochotomy had a 13-fold greater mortality rate than simple cholecystectomy (0.92 versus 0.07 percent). For acute cholecystitis, we observed an unusual zero mortality rate, whereas the mortality rate in chronic cholecystitis was 0.2 percent. All three patients who died had an accompanying cirrhosis of the liver. Morbidity, defined as reoperation during the same period of hospitalization, was mainly the result of retained stones after choledochotomy; endoscopic papillotomy was the treatment of choice. Cholecystectomy remains the "gold standard" in the treatment of cholelithiasis.


Poor predictive value of hematocrit and hemodynamic parameters for erythrocyte deficits after extensive elective vascular operations.

Fluid resuscitation and transfusion therapy are particularly critical in patients undergoing extensive vascular operations because of diffuse atherosclerosis and the risk of perioperative myocardial infarction. Sophisticated perioperative monitoring has reduced the mortality rate substantially, but indications for transfusion remain controversial. We determined erythrocyte volume, (EV), total blood volume (TBV) and plasma volume (PV) preoperatively and 18 to 24 hours postoperatively in 41 elderly patients (68.8 +/- 1.3 years) undergoing elective vascular operations (30 abdominal aortic aneurysmorrhaphy, ten aortofemoral bypass and one carotid endarterectomy). EV was measured using 51chromium-labeled autologous erythrocytes; TBV and PV were calculated from EV and total body hematocrit (peripheral venous hematocrit [HCT] x 0.89). Ideal blood volumes were calculated from nomograms based on body surface area and gender. Relationships between body volumes (percentage of ideal), simultaneously measured peripheral venous HCT and hemodynamic parameters heart rate, mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index and systemic vascular resistance index were studied by stepwise regression. In 24 patients, blood volumes and hemodynamic parameters were also measured in the recovery room. HCT significantly correlated with EV at all three time periods (p less than 0.001), but the ability of HCT to predict EV in an individual patient was relatively poor (r = 0.50 preoperatively; r = 0.54 in recovery room and r = 0.66 24 hour postoperatively). By 24 hours postoperatively, EV had decreased to 78.3 +/- 2.4 percent of ideal EV (range of 47 to 112 percent). However, only two patients had HCT less than 30 despite the fact that 13 of 41 patients had an EV deficit of greater than 30 percent. No patient had a HCT of less than 25 percent. Hemodynamic parameters did not contribute to the prediction of EV, PV or TBV at any time. Two patients had myocardial infarctions postoperatively associated with 24 hour EV deficits of 18.5 and 29.6 percent. One patient died of a pulmonary embolus. Because of these findings, the concept of a "transfusion trigger" must be viewed with caution, since many patients undergoing vascular operations will have considerable EV deficits despite an "acceptable" HCT.


Role of three hour roentgenogram of the chest in penetrating and nonpenetrating injuries of the chest.

The current study examined whether a three hour roentgenogram of the chest was as reliable as the six hour roentgenogram of the chest in detecting delayed complications (that is, pneumothorax and hemothorax) of penetrating and nonpenetrating trauma to the chest. The 285 patients in the study were placed into three groups: those stabbed in either the chest or back; those sustaining multiple fractures of the ribs, and those with gunshot wounds to the chest or back. All the patients selected for study by three and six hour films of the chest were asymptomatic on admission and no pneumothorax or hemothorax was seen on initial anteroposterior and lateral roentgenograms of the chest. None of the patients included in the study required immediate operation. Twelve patients (4 percent) had delayed pneumothoraces on the three hour roentgenogram of the chest. Nine of these 12 (75 percent) required thoracostomy tube drainage, while the remaining three patients were managed with needle aspiration. No additional patients had complications on the six hour roentgenogram of the chest. Computed tomographic (CT) scan discovered five additional patients (2 percent) with pneumothoraces not visualized by the three or six hour films. Seventeen patients (6 percent) had delayed pneumothoraces despite negative admission roentgenograms of the chest and lack of symptoms. Twelve of the 17 (71 percent) were discovered on three hour roentgenogram of the chest, while an additional five of 17 (29 percent) were only seen by CT scan. Three hour roentgenograms of the chest are as reliable as six hour roentgenograms of the chest in visualizing the development of delayed complications of penetrating and nonpenetrating thoracic trauma. The CT scan is more effective than the roentgenogram of the chest in visualizing small pneumothoraces, but its use as a screening tool for detection of delayed complications of trauma to the chest pneumothoraces is probably cost-prohibitive.


Factors influencing the outcome of a no incision endoscopic urethropexy.

A urethropexy without incision has been used in 108 women with a minimum of one year follow-up evaluation. Most of the patients (81 percent) experienced postoperative urinary retention, with the mean period of retention being 22 days. The cure rate was 81.5 percent. The technique was successful in women with grade I stress urinary incontinence (97 percent), but not as effective in women with high grade stress incontinence (45.5 percent in women with grade III stress urinary incontinence). The success rate, therefore, correlated significantly with the grade of incontinence (p less than 0.001). It is noteworthy that there were no failures in 36 women who were premenopausal and the cure rate of 72 percent in the postmenopausal group represented a significant reduction (p less than 0.001). The approach without incision is often effective in patients who have failed previous anti-incontinence procedures, with a cure rate of 82 percent in 22 women in this category, but most patients with a successful outcome in the more complex instances of stress urinary incontinence were also noted to be premenopausal. These data suggest that the success of the repair is dependent on the strength and integrity of the vaginal mucosa. When using the no incision technique, it is advisable to avoid the use of foreign body material in the suprapubic stab sites because of the high incidence of infection and tender nodules.


Surgical curability and prognosis for standard versus extended resection for T1 carcinoma of the pancreas.

The prognosis of 185 patients who underwent surgical resection of small carcinomas of less than 2.0 centimeters (T1) of the pancreas in whom either standard or extended resection was used was analyzed. Pancreatic resection was performed upon 98.3 percent of the patients who were more than 49 years old. The location of the tumor was the head of the pancreas in 83.4 percent of the patients, the body of the pancreas in 13.2 percent and the tail of the pancreas in 3.3 percent. Tumor staging revealed 42.9 percent in stage I and the remainder in advanced stage, that is 33.1 percent stage II, 18.8 percent stage III and 5.1 percent stage IV. When standard resection was performed, surgical cure rates were more than 80 percent in stage I, II and III, but in stage IV, it was only 16.6 percent. After extended resection, the surgical cure rates increased even in stage IV (100 percent). There were no significant differences in the overall postoperative cumulative survival rates between standard and extended operation. In stage II, however, a significant better survival rate was observed after extended resection than after standard resection.


A new technique of side to side caval anastomosis during orthotopic hepatic transplantation without inferior vena caval occlusion.

An original technique of OLT with preservation of the entire IVC of the recipient and side to side caval anastomosis is described. The procedure has permitted the avoidance of retrocaval dissection and temporary vena caval occlusion. The caval outflow was respected during the anhepatic phase. The technique, requiring only one caval anastomosis, has reduced the duration of the anhepatic phase and the need for venous bypass.


Nutritional support for acute pancreatitis.

The current review has summarized current data relevant to the nutritional support of patients with acute pancreatitis. Selection of the most appropriate form of nutritional support for patients with acute pancreatitis is intimately linked to a thorough understanding of the effects of various forms of enteral and parenteral nutrition on physiologic exocrine secretory mechanisms. Two basic concepts have emerged from the multiple studies that have addressed these issues to date: 1, enteral feeds should have low fat composition and be delivered distal to the ligament of Treitz to minimize exocrine pancreatic secretion and 2, parenteral substrate infusions, alone or in combinations similar to those administered during TPN, do not stimulate exocrine pancreatic secretion. From a practical standpoint, most patients with acute pancreatitis are diagnosed by nonoperative means and will manifest some degree of paralytic ileus during the early phase of the disease. Therefore, jejunal feeds are usually not a therapeutic option early in the course of this disease. On the basis of the clinical studies reviewed herein we propose general guidelines for the nutritional support of patients with acute pancreatitis: 1, most patients with mild uncomplicated pancreatitis (one to two prognostic signs) do not benefit from nutritional support; 2, nutritional support should begin early in the course of patients with moderate to severe disease (as soon as hemodynamic and cardiorespiratory stability permit); 3, initial nutritional support should be through the parenteral route and include fat emulsion in amounts sufficient to prevent essential fatty acid deficiency (no objective data exist to recommend specific amino acid formulations); 4, patients requiring operation for diagnosis or complications of the disease should have a feeding jejunostomy placed at the time of operation for subsequent enteral nutrition using a low fat formula, such as Precision HN (Sandoz, 1.3 percent calories as fat), Criticare HN (Mead Johnson, 3 percent calories as fat) or Vivonex High Nitrogen (Norwich Eaton, 0.87 percent calories as fat), and 5, oral feedings should be low fat in composition and should be reinstituted using traditional clinical criteria, including the symptoms of the patient, physical examination and computed tomographic appearance of the pancreas (clinicians should bear in mind the well documented exocrine stimulatory effects of even low fat oral feeds and the risks of early refeeding). These general guidelines must be individualized to incorporate what is perhaps the most important clinical variable--the premorbid nutritional state of the patient.(ABSTRACT TRUNCATED AT 400 WORDS)


The bacterial factor in hemorrhagic shock.

After a century of research on hemorrhagic shock, traumatic shock, septic shock and burn shock, it is known that all of the states lead to cellular injury and death through the same common pathways. Methods for blocking these pathways may ameliorate all of these conditions.


Extra-cranial bleeding and other symptoms due to low dose aspirin and low intensity oral anticoagulation.

Data from the early stages of the thrombosis prevention trial (TPT) have been used to establish and quantify the risk of extracranial bleeding due to low dose aspirin (75 mg) and low intensity oral anticoagulation with warfarin (international normalised ratio, INR, 1.5) singly or in combination, in men aged between 45 and 69 who are at high risk of ischaemic heart disease (IHD). The design of the trial is factorial, the four treatments being combined low dose aspirin and low intensity anticoagulation (WA), low intensity anticoagulation alone (W), low dose aspirin alone (A) and double placebo treatment (P). The trial is being carried out through the Medical Research Council's General Practice Research Framework, with participating practices throughout the United Kingdom. Results are based on the first 3,667 men entered. The risk of major gastrointestinal bleeding due to active treatment is probably about 1 in 500 man-years of treatment, there currently being no difference between the three active regimes (WA, W, A). Intermediate and minor bleeding episodes occur more frequently with WA than with W or A on their own, the excess being mainly due to minor nose bleeds and bruises. In turn, both W and A on their own cause more such minor episodes than placebo treatment, P. There is no evidence that any of the three active regimens increases the risk of peptic ulceration, nor do they increase reports of indigestion. Aspirin increases reports of constipation and reduces reports of blurred vision. Minor bleeding occurs less frequently in smokers than in non-smokers but is not influenced by age. The antithrombotic regimes used are feasible and acceptable.


Granulocyte elastase, tumor necrosis factor-alpha and urokinase levels as prognostic markers in severe infection.

We have examined the prognostic value of the levels in the blood of granulocyte elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) complex, tumor necrosis factor-alpha (TNF-alpha) and urokinase-type plasminogen activator (u-PA) in 35 patients with severe infection upon admission to an Intensive Care Unit. Fourteen patients died. No differences for E-alpha 1-PI complex were found between survivors and nonsurvivors, but in all patients the levels on admission were eight-fold higher than the reference value. TNF-alpha levels, measured by immunoassay, on admission were four times higher in the nonsurvivors than in the survivors (p = 0.0003) and correlated with the severity of the disease (APACHE II score, r = 0.43, p less than 0.05). TNF-alpha was not detectable by bioassay. Total u-PA antigen (u-PA Ag), plasmin-activatable single-chain u-PA (scu-PA) and inactive, nonactivatable u-PA (u-PA#) were on admission all two-fold higher in the nonsurvivors (p = 0.0006, 0.003 and 0.0003, respectively), while normal in the survivors. In both, survivors and nonsurvivors, the ratio between scu-PA and u-PA Ag was significantly decreased (p less than 0.001, compared to a reference group of healthy volunteers), indicative for enhanced conversion of scu-PA to active two-chain u-PA (tcu-PA) and inactive u-PA# during severe infectious disease. tcu-PA was detected in nine of the 35 patients, while virtually undetectable in controls. scu-PA correlated with the Child-Pugh score on admission (r = 0.42, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Pronounced effects of the combination of a new thromboxane antagonist (GR32191) and heparin on bleeding time in man.

Potential pharmacokinetic and pharmacodynamic interactions between two oral doses of GR32191 (40 and 80 mg), a new thromboxane antagonist, and heparin (5,000 IU bolus + 1,000 IU/h for 3 h) were studied in eighteen healthy male volunteers using two separate double-blind, randomised, placebo-controlled, cross-over studies. Mean (range) bleeding time values were 8.4 min (7.5-9.7) during heparin/placebo, 12.1 min (9.2-18.6) (GR32191/placebo) and 16.3 min (11.5-21.4) (GR32191/heparin) in the 40 mg study, while these values were 8.7 min (5.5-15.5), 16.0 min (9.3 - greater than 36.0) and 23.8 min (10.7 - greater than 36.0), respectively in the 80 mg study. Compared to screening values, the combination of 80 mg of GR32191 and heparin had a greater effect on the bleeding time than the sum of the prolongations after the separate treatments (p = 0.05). In the 40 mg study this was not the case. Pharmacokinetics of heparin (as assessed by plasma anti-Xa and antithrombin activity) and GR32191 were unaltered during co-administration of the two drugs. GR32191 did not influence the effects of heparin on APTT. Heparin slightly diminished the inhibition of collagen induced platelet aggregation by 80 mg of GR32191 and the U-46619 (thromboxane A2-mimetic) induced platelet aggregation remained unchanged. Overall fibrinolytic activity (as evaluated by the fibrin plate test) was similar during all three treatments in the study with 80 mg. The combination of 80 mg of GR32191 and heparin caused a prolongation of the bleeding time which was more than expected on the basis of their individual effects.


Diurnal rhythm in anticoagulant effect of heparin during a low dose constant rate infusion. A study in healthy volunteers.

The objective of the study was to investigate possible diurnal rhythms in coagulation tests during a continuous intravenous infusion of unfractionated heparin. Six volunteers participated in the study, which was divided in a treatment (500 U heparin/h for 30 h) and a control experiment. Under basal conditions, no rhythm was found in coagulation tests. During heparin treatment, APTT, thrombin clotting time and anti-Xa activity showed a greater anticoagulant effect at night, with a striking decrease in the morning. In a search for the explanation of this phenomenon we looked for diurnal variations in the urinary excretion of heparin, in the plasma concentrations of antithrombin III and platelet factor 4, and in the effect of heparin added to the plasma samples in vitro. None of these studies provided the explanation.


Clearance of recombinant tissue factor pathway inhibitor (TFPI) in rabbits.

The pharmacokinetics of recombinant tissue factor pathway inhibitor (TFPI) after an intravenous bolus injection was studied in rabbits. Clearance of TFPI was followed by measurement of the radioactivity of the 125I-labelled compound in the whole plasma or the trichloroacetic acid precipitate and by quantitation of the functional TFPI activity of the unlabelled compound using a tissue factor-induced coagulation assay. When iodinated TFPI was used, the ratios of the trichloroacetic acid precipitable counts vs. that of the whole plasma was about 1 in the first 10 min after TFPI injection, but this ratio gradually decreased to less than 0.5 after 2 h. This result suggested that the iodinated TFPI in the plasma was partially degraded after prolonged circulation in the animal. When unlabelled TFPI was used, the clearance of TFPI activity from the plasma exhibited bi-exponential elimination kinetics with a rapid alpha phase half-life (t1/2 alpha) of 2.3 min, and a terminal beta phase half-life (t1/2 beta) of 79 min. The plasma clearance was 4.2 ml kg-1 min-1. The tissue distribution of intravenously administered 125I-TFPI in the rabbit was studied using whole-body autoradiography. At 3 min after dosing, significant levels of TFPI were apparent in the liver, kidney, and other highly blood perfused tissues. Significant levels of 125I-TFPI-derived radioactivity were also apparent in the liver and kidney at 30 min after intravenous administration. The localization within the liver demonstrated a mottled appearance, suggesting regions of higher uptake within the liver. In the kidney, the outer cortex consistently revealed the highest activity.


The influence of infusions of 1-desamino-8-D-arginine vasopressin (DDAVP) in vivo on thrombin generation in vitro.

To investigate the effect of increasing FVIII:C in-vivo on coagulation ex-vivo, DDAVP was infused over 15 min in 10 volunteers and in-vitro thrombin generation measured. FVIII:C rose from 0.42 and 0.43 IU/ml before DDAVP to 1.38, 1.73 and 1.78 IU/ml at 15, 30 and 60 min respectively (p less than 0.001). A computer-assisted thrombin generation test was performed in defibrinated plasma using chromogenic substrate, S2238. Time to reach 50% maximal thrombin activity (T50/s) and lag phase of thrombin generation (lag/s) were measured. Lag shortened from 75 and 60 s before to 45 s during and after infusion (p less than 0.001). T50 shortened from 78.5 and 76.0 to 62.5, 60.0 and 58.5 s at times 15 (p less than 0.01), 30 (p less than 0.001) and 60 (p less than 0.001) min. FVIII:C correlated inversely with lag and T50 (r = -0.847, p less than 0.001, r = -0.826, p less than 0.001, n = 10) respectively. These findings show that acute elevations of FVIII:C in-vivo accelerate in-vitro thrombin production. This work suggests that elevated FVIII:C levels in-vivo may be important in thrombo-occlusive disease.


Screening for fibrin specific monoclonal antibodies: the development of a new procedure.

The acquisition of monoclonal antibodies specific for human fibrin has been impaired by the similarity in chemical composition between fibrinogen and fibrin and the conformational difference between immobilised and soluble fibrinogen. Five monoclonal antibodies (mabs) with a known affinity for fibrin have been subjected to screening procedures which involved the presentation of different forms of both fibrinogen and fibrin to the test mabs. It was observed by scanning electron microscopy that dried fibrin (denoted fibrin D), immobilised on the wells of PVC plates was morphologically similar to the fibrin found in human clots whereas PVC-immobilised fibrin monolayers (fibrin M) and a homogenised form of fibrin (fibrin FF) presented two very different morphological appearances. It was shown that lack of cross reactivity of a mab with an antigen (e.g. fibrinogen) was validly demonstrated only when both mab and antigen were present in the soluble state. These findings have allowed the generation of a screening procedure which involves the use of fibrin D on PVC plates in conjunction with whole human plasma incubated with the test antibody. This screening procedure has been validated using two mabs, one of which has an exclusive fibrin affinity while the other has a broad spectrum crossreactivity with both fibrinogen and fibrin. This procedure would ensure the acquisition of all the five fibrin-specific mabs used in this study while other less reliable screening procedures might not.


Reactivated recombinant plasminogen activator inhibitor-1 (rPAI-1) effectively prevents thrombolysis in vivo.

The effects of human recombinant plasminogen activator inhibitor (rPAI-1) on thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) were studied in a rabbit model of jugular vein thrombosis. Two functionally distinct rPAI-1 preparations were used in these experiments, including latent rPAI-1 (approximately 2 units of t-PA neutralizing activity per micrograms protein) and reactivated rPAI-1 (approximately 150 units/micrograms). Simultaneous intravenous infusion over 4 h of 1.7 mg/kg of reactivated rPAI-1 (inhibitory capacity approximately 0.5 mg/kg rt-PA) with 0.5 mg/kg of rt-PA completely prevented lysis of a jugular venous thrombus, whereas an equivalent amount of latent PAI-1 did not significantly influence clot lysis. These findings demonstrate that reactivated human rPAI-1 efficiently neutralizes thrombolysis with rt-PA in vivo. Since previous studies have suggested that elevated endogenous levels of PAI-1 do not attenuate the thrombolytic potency of rt-PA in the endotoxin-treated model, we compared the stability of complexes formed by 125I-rt-PA with reactivated human rPAI-1 and with rabbit PAI-1 in vitro. Our findings indicate that both forms of PAI-1 form SDS-stable complexes following incubation with 125I-rt-PA. Thus, it seems likely that elevated levels of active PAI-1 can negate the thrombolytic effects of rt-PA in vivo and argues against the possibility that t-PA can dissociate from PAI-1 and have its activity restored in the presence of a thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of thrombin inhibitors on tissue plasminogen activator induced thrombolysis in a rat model.

Successful coronary thrombolysis depends on rapidly restoring blood flow and maintaining patency of the infarct-related artery. Although widely used as an adjunct to lytic therapy, heparin is limited in its ability to produce these effects. Since the limitations of heparin may reflect its inability to inactivate clot-bound thrombin, we developed a rat model of tissue plasminogen activator (t-PA) induced thrombolysis to compare doses of heparin, hirudin, hirulog (a synthetic hirudin-derived peptide), and D-Phe-Pro-ArgCH2Cl (PPACK) that produced a 4-fold prolongation of the baseline activated partial thromboplastin time (APTT) with saline in terms of their ability to accelerate thrombolysis and to prevent reocclusion. A thrombus rich in red cells and fibrin was formed in the distal aorta by applying an external constrictor after denuding the endothelium with a balloon catheter. Thrombolysis was induced with t-PA (1 mg/kg bolus, followed by 1 mg kg-1 h-1 over 30 min) and the rats were then randomized to receive a concomitant 80 min infusion of a thrombin inhibitor or saline. By continuously monitoring blood flow and pre- and post-stenotic blood pressures, the time to clot lysis, and the number of reocclusions were determined. Compared to saline, heparin had no significant effect on these variables.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of fibrinolytic activity in-vivo by dexamethasone is counterbalanced by an inhibition of platelet aggregation.

Dexamethasone decreases the fibrinolytic activity in cultured medium of several cell types by an induction of PAI-1 synthesis. As a result of this enhanced PAI-1 synthesis a prothrombotic state is expected in patients treated with dexamethasone. However, such a prothrombotic state is not reported as a major adverse effect. We have studied the effects of dexamethasone (dose range: 0.1-3.0 mg/kg) on the fibrinolytic system of rats after a 5 day pretreatment period. It appeared that dexamethasone dose dependently decreased the fibrinolytic activity (a dose of 1 mg/kg showed a reduction of about 40%). This reduced fibrinolytic activity could be functionally translated into an increased thrombus size as measured with a venous thrombosis model: thrombus size was increased by 50% with 1 mg/kg dexamethasone. No effects could be measured on the coagulation system, but it appeared that ex-vivo measured platelet aggregation was dose dependently inhibited by dexamethasone treatment. This effect resulted in-vivo in prolonged obstruction times as measured with a modified aorta-loop model. These results indicate that the expected prothrombotic state due to a diminished fibrinolytic activity caused by dexamethasone is counterbalanced by an inhibition of platelet aggregation.


Thromboembolic disease--critical evaluation of laboratory investigation.

Previous studies of patients with thromboembolic disease have revealed an association either with hereditary anticoagulant protein deficiencies or with defects in the fibrinolytic system. To obtain a more comprehensive picture and to investigate which analyses are useful in the evaluation of such patients, we have performed an extensive laboratory investigation in 439 individuals with thromboembolic disease. Anticoagulant protein deficiencies were found in 24 patients. Deficiencies of protein C (n = 10) and protein S (n = 9) were most common followed by deficiencies of antithrombin III (n = 3) and plasminogen (n = 2). Six of the nine protein S deficient patients demonstrated a selective deficiency of free protein S with normal total protein S concentrations. To diagnose protein C and S deficiencies among the 201 patients receiving oral vitamin K antagonists, the concentrations of protein C and S were compared with the mean concentration of several other vitamin K-dependent proteins. One protein C and three protein S deficiencies were identified among the treated patients. The number of protein C deficiencies found in this group was significantly lower than the number found among untreated patients. Although fewer protein S deficiencies were also identified among the treated patients, than in the untreated group, the difference was not statistically significant. The results suggest that protein C deficiencies went undetected in the treated group and that oral anticoagulant therapy should be discontinued before efforts to diagnose protein C deficiency are made. We found no cases with heparin cofactor II deficiency. Lupus anticoagulant was present in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


Coagulation factor IXa binding to activated platelets and platelet-derived microparticles: a flow cytometric study.

Factor IX plays a central role in blood coagulation, since it can be activated by either XIa (intrinsic pathway) or tissue factor-VIIa (extrinsic pathway). Activated factor IX (IXa), in a surface-bound complex with factor VIIIa, then activates factor X. Platelets provide the catalytic surface upon which this Xase complex is assembled in vivo. We have used flow cytometry to examine binding of factor IXa to thrombin-activated platelets in the absence of added VIIIa. Platelet-bound IXa and platelet protein GPIb were detected by indirect immunofluorescence staining followed by two-color flow cytometric analysis. Microparticles were identified by their light scattering characteristics. Two binding sites for factor IXa were detected. The high affinity binding site saturated at about 10 nM, with a Kd of 1.6 nM. A second binding curve, with a Kd of about 100 nM, was observed at higher concentrations of IXa. The high affinity factor IXa binding sites comprise about 7% of the total factor IXa binding. Binding to both sites was dependent on the presence of calcium. Thus, we conclude that factor IXa, in addition to its high affinity binding, has a calcium-dependent low affinity association with activated platelets and microparticles. Sims et al, have shown that binding sites for a different coagulation factor, factor Va, are concentrated on microparticles relative to platelet membrane proteins, such as GPIb. GPIb is distributed on platelets and microparticle in proportion to plasma membrane surface.(ABSTRACT TRUNCATED AT 250 WORDS)


ADP receptor induced activation of guanine nucleotide binding proteins in rat platelet membranes--an effect selectively blocked by the thienopyridine clopidogrel.

The thienopyridine clopidogrel, a potent analog of ticlopidine, is a powerful inhibitor of ADP induced platelet aggregation and ADP induced inhibition of cyclic AMP accumulation in intact platelets but not of ADP induced shape change. We have recently demonstrated that ADP stimulates the binding of GTP gamma S to GTP binding proteins (G proteins) in human platelet membranes. We now studied the effects of clopidogrel, a specific inhibitor of ADP induced platelet aggregation on the stimulation of GTP gamma S binding to rat platelet membranes by ADP. Using the non hydrolyzable stable analog of ADP, 2MeSADP, we demonstrate that 2MeSADP stimulates the binding of [35S]GTP gamma S to rat platelet membranes in a concentration dependent manner, that this effect is inhibited by the specific ADP receptor antagonist Sp-ATP alpha S and that clopidogrel completely and selectively blocks the stimulation by 2MeSADP of [35S]GTP gamma S binding to platelet membranes of treated rats. We conclude that: i) rat platelet membranes possess an ADP receptor coupled to unidentified G protein(s) and ii) the thienopyridine clopidogrel impairs the interaction of the ADP receptor with its G protein by an irreversible modification the ADP receptor itself or its putative G protein.


Modulation of aflatoxin B1 biotransformation in rabbit pulmonary and hepatic microsomes.

Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin that requires activation to the corresponding 8,9-epoxide for activity. In addition to being present in foodstuffs, AFB1 can contaminate respirable grain dusts and thus the respiratory system is a potential target for carcinogenesis. In the present study, we have investigated the role of polycyclic aromatic hydrocarbon-inducible forms of cytochrome P-450 in the pulmonary and hepatic microsomal activation ([3H]AFB1-DNA binding) and detoxification ([3H]AFM1 and [3H]AFQ1 formation) of [3H]AFB1. In rabbit lung microsomes, the apparent Vmax for [3H]AFM1 formation was increased significantly when values were expressed per mg microsomal protein or per nmol P-450 present. In liver microsomes, the apparent Vmax for DNA binding and [3H]AFM1 formation were increased by beta-naphthoflavone (BNF) treatment (to 2.3 and 3.3 times control, respectively) when expressed per mg protein, but when expressed per nmol P-450, only AFM1 formation was significantly increased. The apparent Km values for both these reactions were unaffected. The apparent Vmax for [3H]AFQ1 formation was not affected by BNF treatment, but the apparent Km was increased to 4.5 times control. Boiling of microsomes or omitting the NADPH-generating system decreased DNA binding, AFM1 formation and AFQ1 formation by 89-97%, while addition of 1.0 mM SKF-525A inhibited these reactions by 46-57%. Addition of 1.0 mM alpha-naphthoflavone (ANF) had no effect on the biotransformation of [3H]AFB1 in lung microsomes of control rabbits, but significantly decreased AFM1 formation (by 31%) in lung microsomes from BNF-treated animals (other reactions were unaffected). In liver microsomes from BNF treated rabbits, 1.0 mM ANF inhibited DNA binding of [3H]AFB1 by 68%, while there was no effect in control microsomes. ANF significantly inhibited AFM1 formation in liver microsomes from both control and BNF-treated animals (by 87-97% and 67-78% at 1.0 mM and 2.0 microM, respectively), but had no effect on AFQ1 formation in liver microsomes from animals in either treatment group. These results indicate an important role for the 1A subclass of P-450 isozymes in the biotransformation of AFB1 to AFM1 in rabbit lung and liver, and a minor role in AFB1 activation in liver.


Antioxidant-dependent inhibition of diquat-induced toxicity in vivo.

The abilities of two experimental antioxidants (U-74006F and U-78517G), as well as the model antioxidant, diphenyl-p-phenylenediamine (DPPD), to protect against diquat-induced toxicity in male Fischer-344 rats were examined. Both experimental compounds afforded near complete protection against diquat-induced hepatotoxicity, as measured by clinical chemistry and histopathological indices. When observed, diquat-induced nephrotoxicity was also inhibited. Minimal protection was afforded by the model compound, DPPD. In follow-up studies with U-78517G, no effect on diquat-induced biliary excretion of oxidized glutathione was observed, suggesting that a shift in the thiol:disulfide ratio is not responsible for diquat-induced hepatotoxicity. These data are consistent with those from previous in vitro studies in our laboratory and are in agreement with studies by others which suggest that lipid peroxidation is an important event in diquat-induced hepatotoxicity in vivo. The antioxidant effects were largely route-independent as either oral pre-treatment alone (200 mg/kg, 24 h before diquat), intravenous pre-treatment alone (6 mg/kg, 5 min before diquat) or the combination of both treatments produced a similar degree of protection. While pre-treatment with antioxidants was quite effective, no significant U-78517G-dependent inhibition of toxicity was observed when administration was delayed by as little as 10 min post diquat. These latter data suggest that initiation of diquat-induced hepatotoxicity is rapid and that these compounds would therefore be unlikely to have clinical utility in the treatment of diquat intoxication.


High carbonyl reductase activity in adrenal gland and ovary emphasizes its role in carbonyl compound detoxication.

Carbonyl reduction has been studied in liver, kidney, adrenal gland and ovary of female Wistar and Sprague-Dawley rats as well as of female NMRI mice by using metyrapone as a substrate and by means of direct HPLC analysis of the reduced alcohol metabolite metyrapol. Carbonyl reducing activities were found in all tissues examined so far, with that in rat ovary and adrenal gland cytosol exceeding the liver cytosolic specific activity severalfold: 15-fold and 12-fold in the Wistar strain; 12-fold and 7-fold in the Sprague-Dawley strain, respectively. In general, Wistar rat enzyme activities were about four times higher than those of Sprague-Dawley rats in all fractions, which indicates an interesting genetic difference between the two rat strains. Due to the sensitivity towards the diagnostic inhibitor quercitrin, carbonyl reductase (EC 1.1.1.184) seems to be mainly responsible for metyrapone reduction in rat and mouse adrenal gland and ovary cytosol. However, sensitivity towards dicoumarol in microsomal fractions of mouse tissues points to the involvement of further carbonyl reducing enzymes. Western blot experiments revealed immunological differences between metyrapone reductase from liver microsomes and respective enzymes of all other tissues. In conclusion, the difference in tissue and intracellular distribution suggests that several enzymes are involved in carbonyl reduction of metyrapone and the intracellular multiplicity of the enzymes may have some relation to their significance in carbonyl compound detoxification. These results support the hypothesis that carbonyl reductases, besides their participation in the metabolism of physiologically occurring substances, provide the enzymatic basis for the detoxification of xenobiotic carbonyl compounds in adrenal gland and ovary which have escaped their metabolic conversion by the liver.


Differences between rats and mice in the immunosuppressive activity of 2-methoxyethanol and 2-methoxyacetic acid.

Previous studies from this laboratory have demonstrated that 2-methoxyethanol (ME) and its principal metabolite 2-methoxyacetic acid (MAA) are immunosuppressive in young adult male Fischer 344 rats. In the present study, the immunosuppressive potential of ME and MAA was evaluated in young adult female Fischer 344 rats and C57BL/6J mice. Rats and mice were dosed by gavage with either ME or MAA in water, at dosages ranging from 50-400 mg/kg/day, for 10 consecutive days. Rats and mice were examined for alterations in body, spleen and thymus weights and mitogen-induced proliferation of splenic lymphocytes in vitro; separate groups were employed for the antibody plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS). Rats dosed at 100-400 mg/kg/day ME and rats dosed at 50-400 mg/kg/day MAA had decreased thymus weights in the absence of decreased body or spleen weights. Lymphoproliferative (LP) responses to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and Salmonella typhimurium mitogen (STM) were all reduced in rats treated with all dosages of ME. Rats treated with MAA displayed similar reductions in these LP responses except that the responses to PWM and STM in rats dosed at 50 mg/kg/day were not reduced. In contrast to the effects of ME and MAA on these end points in the rat, no thymic involution or suppression of LP responses were observed in mice dosed at 50-400 mg/kg/day. The PFC response to TNP-LPS was suppressed in rats dosed with either ME or MAA at dosages of 100-400 mg/kg/day. ME and MAA, however, failed to suppress the PFC response in mice immunized with TNP-LPS. These results indicate that unlike Fischer 344 rats, C57BL/6J mice are insensitive to the immunosuppressive effects of ME and MAA at the dosages employed in this study. Whether the different sensitivities of these two rodent species to ME- and MAA-induced immunosuppression are due to immunologic, pharmacokinetic or metabolic differences within each species remains to be determined.


D-penicillamine and prussian blue as antidotes against thallium intoxication in rats.

D-penicillamine (DP) and prussian blue (PB), given alone and in combination, were evaluated in rats as treatments against acute thallotoxicosis. Animals were poisoned by intraperitoneal (i.p.) injection of thallium(I) acetate at different doses (16, 30, 40, 50 and 70 mg/kg). Later (24 h), treatments were administered until day 5, as follows: D-penicillamine (DP), 25 mg/kg, i.p. route, twice daily; prussian blue (PB), 50 mg/kg, oral route, twice daily. LD50 values were estimated for each treatment with the following results: control, 32 mg/kg; DP, 27 mg/kg; PB, 42 mg/kg; PB + DP, 64 mg/kg. Thallium content was analyzed in six body organs and eight brain regions after treatments. PB administration induced significant elimination of thallium from all tissues. DP treatment diminished thallium content in body organs, but increased it in brain regions, indicating a redistributive effect of DP. DP + PB treatment decreased thallium content in all body organs and brain regions. Renal thallium content in the DP + PB group was significantly lower than that of PB alone group, suggesting accelerated urinary excretion of thallium as a result of DP action. Results indicate that DP administered alone may be dangerous because of its redistributive effect, but given in combination with PB may be useful as treatment against thallium poisoning.


Role of para-hydroxylation in phensuximide-induced urotoxicity in the Fischer 344 rat.

Phensuximide (PSX) is an antiepileptic agent which has been shown to induce hemorrhagic cystitis and mild nephrotoxicity following repeated administration in man or rats or when acutely administered to phenobarbital-pretreated rats. The purpose of this study was to explore the role of para-hydroxylation of the phenyl group of PSX in PSX-induced urotoxicity. Two PSX derivatives, 2-(4-fluorophenyl)-N-methylsuccinimide (FMPS) and N-methyl-2-(4-methylphenyl)succinimide (MMPS), were synthesized and evaluated for urotoxic potential. Male Fischer 344 rats (four rats/group) were administered intraperitoneally (i.p.) a succinimide (0.4 or 1.0 mmol/kg) or vehicle and renal function monitored for 48 h. In a separate experiment, rats were pretreated with phenobarbital (75 mg/kg/day; 3 days, i.p.) prior to succinimide or succinimide vehicle. In non-phenobarbital pretreated rats, acute FMPS or MMPS treatment had little effect on renal function or morphology at the doses tested. Hematuria (+) was noted in the FMPS (1.0 mmol/kg) group on post-treatment day 2. However, in the phenobarbital-pretreated rats, FMPS (0.4 or 1.0 mmol/kg) induced marked hematuria (++) and increased proteinuria while having little or no effect on other renal functional parameters or renal morphology. At killing, bladders of treated rats were distended with bloody urine and exhibited hemorrhagic areas within the bladder wall. In phenobarbital-pretreated rats, MMPS administration had little effect on any renal functional parameter measured or urological morphology. These results suggest that para-hydroxylation does not contribute to the hemorrhagic cystitis induced by PSX.


Cadmium exposure inhibits the prolactin secretory response to thyrotrophin releasing hormone (TRH) in vitro.

In vitro dose response (0.1-100 microM) and time course studies were performed on anterior pituitary cells isolated from female Sprague-Dawley rats in the diestrous stage of the estrous cycle. All doses of TRH produced a significant increase in prolactin release by 5 min which was sustained for 30 min. Pretreatment with 25 or 50 microM Cd for 2 or 4 h produced a significant decrease in prolactin secretion during Cd exposure and in the prolactin secretory response to 1 microM TRH. These results suggest that Cd pretreatment alters the subsequent ability of the lactotrophs to respond to the physiological secretagogue TRH. This alteration does not appear to be due to a rebound phenomenon since basal prolactin release was the same in Cd-pretreated and control cells once the metal was removed. These results suggest that Cd pretreatment produces a significant decrease in prolactin release from the anterior pituitary lactotrophs in response to subsequent TRH stimulation in vitro.


High pressure effects on reflexes in isolated spinal cords of newborn rats.

High pressure induces hyperexcitability and convulsions in both intact and decerebrated animals. However, pressure suppresses synaptic transmission in isolated invertebrate preparations. We examined the effect of high pressure on monosynaptic (MSR) and polysynaptic (PSR) reflexes in isolated spinal cords of newborn rats. Reflex activity was recorded extracellularly from the cut ends of the lumbar ventral roots L3-L5 following stimulation of the corresponding dorsal roots. Increasing the stimulus frequency from 0.1 to 2.0 Hz reduced the amplitude of both reflexes by 75%. High pressure (10.1 MPa helium) did not affect this phenomenon. Pressure had no effect on MSR amplitude, but increased PSR amplitude by 30%. For MSR, pressure increased the latency by 25%, duration by 20%, and rise time by 25%. Pressure abolished the moderate (119 +/- 4.5%, mean +/- SEM) posttetanic potentiation observed at 0.1 MPa. For the curve relating MSR amplitude to [Ca2+]o, high pressure produced a slight rightward shift of 0.25 mM without affecting its saturation level. These data suggest that the response of vertebrate central synapses to pressure may be different from previously described invertebrate synapses. Alternatively, if synaptic potentials are reduced at high pressure, other processes that determine excitability must be invoked to account for the relatively stabile reflex response.


Paradoxical air embolism in pigs with a patent foramen ovale.

Recent studies have indicated that divers with a patent foramen ovale (PFO) are at risk of developing some forms of decompression sickness. Thus, the objective of the present study was to investigate if the occurrence of paradoxical air embolism (PAE) was enhanced in pigs with a PFO compared to the occurrence in pigs without such a defect. Out of 54 pigs, 18 had a PFO (group PFO), and the other 36 composed the controls (group C). The pigs were anesthetized, mechanically ventilated, and received venous air infusion at four different rates (0.050, 0.075, 0.100, and 0.200 ml.kg-1.min-1). PAE was monitored by use of a transesophageal echocardiographic probe to detect if any arterial air bubbles were present in the left atrium or the aorta. We found that PAE appeared at a lower infusion rate in group PFO than in group C. When PAE occurred, the mean pulmonary arterial pressure and the mean arterial pressure were significantly higher in pigs with a PFO than in the control pigs. Finally, the infused air volume per kilogram of body weight in group PFO was significantly lower than that observed in group C. The results demonstrated that the risk of PAE occurring in mechanically ventilated pigs with a PFO was greater compared to the risk observed in pigs without a PFO.


[Hypospadias--current surgical procedures].

The treatment of hypospadias has developed over the years from a disabling intervention to a surgical procedure devised with due consideration for the needs of paediatric patient. The operation is timed to fit in with the child's psychological development, being performed early in life before it becomes too traumatic for the child. Resection of the chordee and creation of the neourethra in a single session is increasingly superseding the two-stage procedure usual earlier, especially for distal and medial hypospadias. However, when the surgeon is sufficiently experienced even proximal hypospadias can be corrected in a single session, for example by a combination of a Thiersch and a free island flap or by free bladder mucosal flaps or grafts. The use of suitably fine instruments and suture material should be a matter of course, as should the use of magnifying lenses. Urinary diversion is still obligatory in most centres, and, like the sort of dressing used, it depends on the individual experience and judgement of the surgeon. The incidence of postoperative complications should be below 10% regardless of the degree of hypospadias.


[Chromosome abnormalities in hypospadias? An analysis of 131 patients].

We performed chromosome studies in 131 patients presenting with hypospadias, with the aim of detecting any causal connections between chromosomal abnormalities and the induction of hypospadias. Autosomal abnormalities were revealed in 6 and sex chromosomal abnormalities in 10 patients. Although a significant causal relationship between the occurrence of hypospadias and chromosomal abnormalities was seen in this study in only two cases of mixed gonadal dysgenesis (45,X/46,XY and streak gonad), the high incidence of chromosomal abnormalities observed (12.2%) seems noteworthy compared with the incidence of only 0.61% in the normal male population.


[Prognostic parameters of scar progression, new scar formation and maturation in primary vesico-ureteral-renal reflux].

We analysed the data recorded for 901 children (1357 kidneys) treated for primary vesicoureteral reflux between 1973 and 1988 at our institution. The retrospective study showed a rate of 7.3% for new renal scarring and progression; analysis by reflux grade revealed progression and new scarring in reflux, 10.9% of cases with grade IV and 16.5% of cases with grade V whereas low grades (I and II) were followed by no scarring at all. A close correlation of new scarring with urinary tract infection and bladder function was demonstrated. Spontaneous resolution of reflux was observed in 33.6% of all patients and in only 2.6% of patients with grade V reflux, as against a 85.5% resolution rate in patients with grade I or II reflux. A different sex distribution was revealed in the age group under 1 year, in which 80% of the patients were boys and the resolution rate was higher than in any other age group.


[Reflux nephropathy: decreased renal function and osteodystrophy].

In the early stages of chronic renal failure in childhood renal osteodystrophy is a therapeutic challenge, since in childhood it is mainly growth that is affected. The clinical appearance, pathophysiology and therapy are discussed with reference to an actual case of reflux nephropathy in a child.


[ESWL in hemophilia B].

One of the most dramatic dangers in treating nephrolithiasis by ESWL is the development of intra- and perirenal bleeding, which requires therapeutic intervention. Even in patients whose blood parameters suggest they are healthy, hematomas are found in up to 80%. Therefore, ESWL must be regarded as contraindicated in patients with blood disorders. A case of a patient suffering from hemophilia B and from a large renal pelvic stone is reported, whom we treated by ESWL twice after sufficient substitution. X-ray revealed that the patient was stone-free on the 25th day after the first ESWL session. ESWL. A review of the literature is presented.


[Is down-staging of advanced bladder cancer by neoadjuvant chemotherapy possible?--MVEC protocol].

In 22 patients with advanced transitional cell carcinoma of the bladder, neoadjuvant chemotherapy according to the MVEC regimen was given. Subsequent radical cystectomy showed down-staging in 7 patients (32%). The preoperative clinical staging revealed regression of the bladder cancer in 77% of all cases. Down-grading was seen in only 2 patients. Because of the discrepancy between preoperative clinical staging and the histopathological staging after radical cystectomy, invasive tumour surgery is necessary even when clinical staging has not revealed a tumour after chemotherapy.


[Polychemotherapy in advanced bladder cancer. Practicality and clinical results].

From 1987 to 1990 a consecutive series of 172 patients were treated for advanced bladder cancer, in our clinic, 48 of whom underwent radical cystectomy. In 80 of the remaining 124 patients polychemotherapy was not possible, because of impaired renal function, poor performance status, cardiovascular disease, second malignancy or other problems. There were 11 patients who refused further treatment and 13 patients with tumor restricted to the pelvis who underwent radiochemotherapy. Thus, 20 patients received polychemotherapy with either methotrexate, vinblastine, Adriamycin and cisplatin (M-VAC) or cisplatin, methotrexate and vinblastine (CMV). In 90% of the M-VAC cycles and 34% of the CMV cycles dose reduction was necessary. Median survival was 10 months. We achieved 2 complete responses lasting 6 months and 19 months and 4 partial responses. The authors conclude that patients who cannot undergo radical surgery for bladder cancer are not good candidates for polychemotherapy either. Only patients with measurable remission of the tumour have a longer survival. New regimens with lower toxicity, and especially with lower renal toxicity, must be developed.


Microscopic and ultrastructural studies of necrotizing hepatopancreatitis in Pacific white shrimp (Penaeus vannamei) cultured in Texas.

Granulomatous hepatopancreatitis of unknown etiology has been considered an important disease of Texas shrimp mariculture since 1985. Samples of Pacific white shrimp (Penaeus vannamei) were collected during 1986, 1987, and 1990 from three farms and an experimental mariculture facility with histories of production loss and increased mortality rates. Histologic and ultrastructural examination of shrimp from the four sites demonstrated two morphologically distinct, Gram-negative, double-enveloped, intracytoplasmic bacteria in necrotic hepatopancreatic epithelium. The more numerous small, pleomorphic rod as well as the helical organism are both taxonomically unclassifiable. The helical organism lacked ultrastructural characteristics of previously described helical or spiral bacteria. The relationship between the two organisms is unknown, but the pleomorphic rod is thought to play a major role in the disease. The role of a bacterial agent(s) in subsequent disease episodes is suggested by the observation that the use of oxytetracycline-medicated feed resulted in increased production and survival. Hepatopancreatic tubular epithelial necrosis and shrimp mortality correlated directly with the extent of infection by the small pleomorphic rod. Individual discrete bacteria were identified microscopically by Steiner and Steiner's method. Three major developmental stages of the disease were characterized based on the extent and number of hepatopancreatic tubular epithelial cells containing bacteria, the degree of tubular interstitial inflammation, and the extent and chronicity of tubular necrosis. Additional studies are needed to clarify the roles of the different bacteria identified and the potential role of environmental factors on the disease process.


Age-related changes in thyroid structure and function in Sprague-Dawley rats.

Investigation of thyroid glands from 500 male and 500 female Sprague-Dawley rats, at time points of 8, 17, 30, 56, and 108 weeks of toxicity studies conducted at the Huntingdon Research Centre between 1981 and 1984, revealed age-related structural and functional changes that have previously not been well documented. The number of ultimobranchial cysts decreased with age, while area(s) of C-cell hyperplasia appeared with age. Beginning at 56 weeks, some of the thyroid follicles were hyperdistended with colloid, had irregular lumens, and were lined by flattened epithelium. These follicles had clumped, granular, and stratified colloid. Follicular tumors were found in 8% of the males and 6% of the females at 108 weeks. There was an increase in absolute thyroid weights (males from 21.8 +/- 4.0 g to 46.5 +/- 19.05 g, females from 17.2 +/- 4.53 g to 41.7 +/- 26.92 g) and body weights (males from 382.0 +/- 70.6 g to 806.0 +/- 120.7 g, females from 220.0 +/- 21.0 g to 495.0 +/- 127.3 g) with age in both sexes, but the relative thyroid weights were not significantly affected. Negative allometry was observed. With an increase in the age of the rats, there was a decrease in the height of the follicular epithelium and an increase in the internal follicular diameter and the total number of follicles. No prediction for sex could be detected. Serum T3 and T4 concentrations were constant until 56 weeks of age, but at 108 weeks, the values were markedly reduced (in males, serum T3 concentration decreased from 91.60 +/- 13.970 ng/100 ml to 32.90 +/- 10.878 ng/100 ml, and in females, from 90.80 +/- 11.338 ng/100 ml to 48.10 +/- 8.875 ng/100 ml; in males, serum T4 concentration decreased from 5.94 +/- 0.679 microgram/100 ml to 3.04 +/- 0.604 microgram/100 ml, and in females, from 4.59 +/- 0.717 microgram/100 ml to 2.77 +/- 0.786 microgram/100 ml). The data suggest that the thyroid function of Sprague-Dawley rats reduces as the rats age.


Brain lesions of naturally occurring pregnancy toxemia of sheep.

The neuropathology and biochemical features of 17 sheep with clinical signs and gross necropsy features of naturally occurring pregnancy toxemia were retrospectively evaluated. The sheep ranged in age from 3 to 6 years and were of seven different breeds and three breed crosses. Thirteen sheep (case Nos. 1-4, 6-9, 11-14, 16) showed astrocytic nuclear swelling, hypertrophy and proliferation, and cerebrocortical neuronal necrosis. Seven of these sheep had Purkinje cell necrosis (case Nos. 2, 3, 6, 11, 12, 14, 16), and seven had vacuolation of cerebral and cerebellar sub-cortical white matter (case Nos. 1-4, 9, 12, 13). The neuropathologic features were similar to those of naturally occurring hypoglycemia of human beings and experimentally induced hypoglycemia of primates and the rat. The lesions seen in the sheep studied may have been caused by cerebral hypoglycemia, but data for blood or cerebral glucose concentrations were not available.


Carbonic anhydrase localization in normal and osteochondrotic joint cartilage of growing pigs.

The histochemical localization of carbonic anhydrase in the normal and osteochondrotic epiphyseal growth cartilage from 15 growing pigs (6 to 18 weeks old) was studied. All animals were clinically normal. The entire thickness of the articular-epiphyseal cartilage complex from the femoral condyles was fixed in 2% glutaraldehyde and embedded in a water-soluble glycolmethacrylate. Sections (1-2 microns) were incubated on the surface of a medium containing cobalt, phosphate, and bicarbonate. A black precipitate formed at sites of enzymatic activity. This method shows the activity of all different isoenzymes of carbonic anhydrase. The specificity was checked by adding the carbonic anhydrase inhibitor acetazolamide to the incubation medium. Osteochondrosis in the epiphyseal growth cartilage was characterized by chondronecrotic areas in resting, proliferative, hypertrophic, and calcifying regions. When the hypertrophic and calcifying regions were involved, insufficient cartilage calcification and focally impaired ossification were seen. The chondronecrotic areas were surrounded by groups of morphologically viable cells, or so-called "clusters." Carbonic anhydrase was present in chondrocytes of hypertrophic and calcifying regions of the normal growth cartilage and in osteoclasts and erythrocytes. No evidence of carbonic anhydrase activity was found in the articular cartilage or in the resting region of normal growth cartilage in any of the pigs. No enzyme activity was found in the osteochondrotic cartilage, either in clusters or dead cells. The lack of carbonic anhydrase in the osteochondrotic cartilage demonstrated in this study may result in an inability to produce the alkaline matrix necessary for calcification and could be one reason for the insufficient calcification typical of this cartilage.


A retrospective clinicopathologic study of 212 dogs with cutaneous hemangiomas and hemangiosarcomas.

The relationship between skin pigmentation and piliation and the development of hemangiomas and hemangiosarcomas in the dermis and subcutaneous tissue was studied in 212 dogs. These 212 dogs had a combined total of 306 tumors; 38 of these 212 dogs had two or more of the same tumor in a different location or a combination of hemangioma and hemangiosarcoma. The average age of the dogs at the time of excision of these tumors was greater than 10 years. There was no sex predilection for the presence or absence of tumors. Cutaneous hemangiomas (73%) were more common than cutaneous hemangiosarcomas (27%). Hemangiomas had no predilection for dermis (51%) or subcutaneous tissue (47%), but hemangiosarcomas had a marked predilection for dermis (73%) over subcutaneous tissue (7%). Dogs with short hair coats and lightly pigmented skin had more hemangiomas and hemangiosarcomas of the dermis (65%) than did dogs with variable length hair coats and pigmentation (28%). Dogs with short hair coats and lightly pigmented skin had fewer hemangiomas and hemangiosarcomas of the subcutaneous tissue (10%) than did dogs with variable length hair coats and pigmentation (22%). Dogs with short hair coats and lightly pigmented skin also had more hemangiomas and hemangiosarcomas of ventral glabrous skin (65%) than did dogs with variable length hair coats and pigmentation (22%). In addition, there was no predilection of subcutaneous hemangiosarcoma for haired (33%) versus glabrous (33%) skin, but dermal hemangiosarcoma had a marked predilection for the glabrous skin (63%) when compared with haired skin (10%). The increased incidence of dermal hemangiomas and hemangiosarcomas in ventral glabrous skin suggests an association between solar radiation and the biologic properties of glabrous skin in the genesis of these tumors.


Cutaneous vascular neoplasia in 15 cats: clinical, morphologic, and immunohistochemical studies.

Seven cases of cutaneous hemangioma and nine of cutaneous hemangiosarcoma were diagnosed from biopsy specimens of 15 Domestic Shorthairs of 5,091 cats that were examined by necropsy or biopsy during the 5-year period from 1 January 1986 through 31 December 1990. All but three cats were male. Tumor cells of both hemangiomas and hemangiosarcomas were immunoreactive for factor VIII-related antigen and for vimentin by the avidin biotin peroxidase complex method. In cats with a median age of 10 years, hemangiomas occurred in skin with pigmented hair in six of seven cases without apparent site predilection. These solitary tumors did not recur after excision although one cat (No. 3) subsequently developed cutaneous hemangiosarcoma at another site. Seven of nine hemangiosarcomas occurred in dermis and subcutis of the head, usually on the pinna. All five hemangiosarcomas of the head, for which cutaneous pigmentation could be determined, occurred in unpigmented skin. Cats with hemangiosarcoma had a median age of 12.5 years at the time of diagnosis. Metastasis has not been documented, but hemangiosarcoma has recurred, from 1 month to 2 years after excision, in 6/7 cats that were studied.


A pathologic and bacteriologic study on otitis media in swine.

A pathologic and bacteriologic study on otitis media in swine was performed on 237 swine, ranging in age from 1 day to 1 year. These 237 swine from eight selected farms were slaughtered due to unfavorable prognosis associated with clinical signs of illness. One hundred sixty-three (68.8%) of the 237 swine were found to be affected with otitis, though only a few swine showed clinical signs characteristic of the disease. One hundred fifty-one (63.7%), 53 (22.4%), and 39 (16.5%) had lesions in the middle, external, and internal ear, respectively. Of the 151 cases with otitis media, bilateral and unilateral infection accounted for 114 (75.5%) and 37 (24.5%), respectively. Only 5/53 swine with otitis externa and 6/39 swine with otitis interna failed to show otitis media. All swine with infection in the tympanic cavity had inflammatory lesions in the auditory tube. Examination of the swine grouped by age revealed that, regardless of age, incidence of otitis media was 50-70%. In swine younger than 1 month old, otitis media tended to center on the auditory tube, where a mild infiltration of neutrophils into the mucous membrane was frequent. Thereafter, otitis media increased in degree and extent with age. Forty (26.5%) of the 151 swine affected with otitis media were accompanied by a substantial amount of inflammatory exudate in the tympanic cavity and bulla. Purulent exudate was found in 20/40 (50%) swine. Severe otitis media prevailed in swine between 1 and 4 months of age, showing inspissation of a suppurative exudate in the tympanic cavity and lysis of the underlying osseous wall of the tympanic bulla with subsequent fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of humoral hypercalcemia of malignancy on the parathyroid gland in nude mice.

The ultrastructure of parathyroid chief cells was examined from four groups of nude mice (NIH:Swiss) with different serum calcium concentrations. The groups consisted of eight male mice with hypercalcemia induced by transplantable canine adenocarcinoma (CAC-8), eight female mice with hypercalcemia induced by infusion of parathyroid hormone-related protein, ten male control mice, and six male mice fed a low calcium (0.01%) diet. Hypercalcemia induced by malignancy or parathyroid hormone-related protein infusion was associated with low serum phosphorus concentration, a decrease in the number of secretory and prosecretory granules in the parathyroid chief cells, and an increase in the cytoplasmic area of chief cells. Prominent myelinlike membranous whorls were present in the cytoplasm of chief cells of tumor-bearing and parathyroid hormone-related protein-infused hypercalcemic mice. Mice fed a low calcium diet had decreases in the number of secretory granules and cell area but increases in the number of prosecretory granules compared with control mice. The number of mitochondria and the nuclear area of chief cells were similar in all four groups. The prominent membranous whorls and increased cytoplasmic area of chief cells from these hypercalcemic mice mark these cells as distinctly different from the parathyroid chief cells of other species with hypercalcemia.


Stillbirth/perinatal weak calf syndrome: preliminary pathological, microbiological and biochemical findings.

Microbiological, biochemical and pathological data collected from 293 calves which were either stillborn, or born alive and either failed to breathe or failed to breathe for more than about 10 minutes are presented. No bacteria were recovered from 96 of the calves (32.7 per cent), and bacteria which were considered significant were isolated from only four (1.4 per cent). Evidence of leptospiral infection was found in 75 calves (25.5 per cent). Of 64 calves examined for bovine virus diarrhoea (BVD) and infectious bovine rhinotracheitis (IBR) antigens, two were positive for BVD virus and none for IBR virus. The mean (+/- sd) liver vitamin E and kidney selenium concentrations, determined in 148 of the calves, were 2.0 +/- 0.76 micrograms/g wet matter and 0.47 +/- 0.17 micrograms/g wet matter, respectively. The thyroid iodine concentration in 15 of 71 calves (21 per cent) was less than 300 micrograms/g wet matter and the mean (+/- sd) thyroid weight of 266 of the calves was 18.5 +/- 11.6 g. Evidence of severe trauma was found in 19 of the calves (6.5 per cent). Histological findings included thyroid epithelial hyperplasia, hepatic haemosiderosis, erythrophagocytosis in the spleen, perivascular haemorrhage in brain and adrenal glands, and accumulation of leucocytes in blood vessels.