Clinical evaluation of radioimmunoimaging with 131I-C0C183B2 monoclonal antibody against ovarian carcinoma by intraperitoneal injection. Forty-eight cases subjected to radioimmunoimaging (RII) by intraperitoneal injection with 131I-C0C183B2 monoclonal antibody (MAb) prepared in our laboratory were studied. Thirteen of 14 cases of proved primary ovarian carcinoma were positive. In 11 follow-up cases of ovarian carcinoma after initial surgery and chemotherapy, 5 recurrences were positive and 6 cases without recurrence were negative; all were confirmed histopathologically after a second operation. One false negative was ovarian mucinous adenocarcinoma, which also negatively stained with C0C183B2 by the peroxidase anti-peroxidase method. Twenty of 23 cases of nonepithelial or metastatic carcinoma of the ovary, benign tumors, and benign diseases were negative. The sensitivity and specificity were 94.7 and 89.7%, respectively. If patients had complications with ascites, the MAb which positively stained with the cancer cells in the ascites was chosen for RII. For follow-up cases PAP staining with the tumor tissue from the initial surgery and the MAb should be done before RII. These are the principal factors that increase the positive rate and accuracy of RII. The intraperitoneal route seems to be a valuable method for clinical staging and tumor localization as well as for follow-up use.


Ovarian cancer staging: does it require a gynecologic oncologist? Forty-seven patients with presumed Stages I-II invasive ovarian epithelial carcinoma were treated with intravenous 50 mg/m2 cis-platinum, for 2-18 cycles (median, 9), 50 mg/m2 doxorubicin for 2-14 cycles (median, 9), and/or 600 mg/m2 cyclophosphamide for 2-14 cycles (median, 6) after surgical staging by a gynecologic oncologist or a nononcologic surgeon. Mean follow-up is 6.8 years. Cumulative 5-year actuarial survival is 73 +/- 6%; 75 +/- 12% for Stage I and 71 +/- 8% for Stage II disease. When screened for poor prognosticators, only the specialty of the operating surgeon was identified (P < 0.05). Five-year actuarial survival and disease-free survival, respectively, for Stages I-II patients surgically staged by a gynecologic oncologist were 83 +/- 7% and 76 +/- 8%, compared to 59 +/- 11% (P < 0.05) and 39 +/- 11% (P < 0.03) for the group operated upon by a nononcologist.


Incomplete pregnancies and ovarian cancer risk. The role of spontaneous and voluntary abortions was assessed in a case-control study conducted in Milan, northern Italy on 953 cases of epithelial ovarian cancer (median age, 54) and 2500 control subjects (median age, 52) in hospital for acute diseases other than malignant, gynecological, or hormonal disorders. Overall the inverse relationship between total number of incomplete pregnancies and ovarian cancer risk was statistically significant, estimated relative risks (RRs) being, respectively, 0.9 (95% confidence interval (CI), 0.7-1.1) for one abortion and 0.8 (95% CI, 0.6-1.0) for two or more as compared to none. Furthermore, the protections afforded by spontaneous and voluntary abortions were well comparable (RRs 0.7 and 0.8 for > or = 2 spontaneous and voluntary abortions, respectively, versus none). While the protective effect of incomplete pregnancy was not explicable in terms of other characteristics of women nor significantly different across strata of reproductive factors or oral contraceptive use, it seemed more marked in women whose ovarian cancer occurred below age 50. Etiologically, these findings suggest that interrupted pregnancy per se and not predisposition to spontaneous abortion affects ovarian cancer risk.


Use of family history in a screening clinic for familial ovarian cancer. We have estimated the risks of ovarian and other types of cancer in first-degree relatives of women who have developed the disease (the index patients). The number of deaths from each type of cancer was determined from pedigrees taken from 391 self-referred, asymptomatic women attending a screening clinic for familial ovarian cancer. These values were compared with the expected number of deaths for women in the general population (calculated from life tables), and the relative risks were used to estimate lifetime risks. The overall relative risk were 4.5, 1.4, 1.3, and 1.1 for ovarian, stomach, breast, and endometrial cancers, respectively. The risks were invariably higher if the index patient was < 55 years old. Ovarian cancer appeared to have no clear inheritance pattern in 290 pedigrees and there was no increased risk for the first-degree relatives. Eighty-two pedigrees were compatible with a diagnosis of a multiple-site cancer family syndrome and the relative risks were 6.1, 2.8, 3.7, and 2.7 for ovarian, breast, stomach, and colorectal cancer, respectively. There was evidence of site-specific ovarian cancer in 19 families; the relative risk for the first-degree relatives was 39.1 and the lifetime risk 1 in 2. We believe that family history can be used to identify women who are at a high risk of developing ovarian and certain other types of cancer. This information can be used to counsel women attending ovarian cancer screening clinics and to maximize the usefulness of current resources.


Correlation in ages at death from familial ovarian cancer among sisters. The analysis of pedigrees taken from 97 of 1466 women attending a screening clinic for early familial ovarian cancer showed that there was a strong correlation in the ages at death from the disease among sisters (r = 0.68, confidence limits 0.51-0.82, P < 0.001), but not between mothers and daughters. This information can be used to help counsel women who are considering the appropriate time for more intensive screening or prophylactic oophorectomy.


Hypercalcemia and breast cancer related to parathormone-like secretion by liver metastases. A premenopausal woman developed hypercalcemia 30 months after treatment for infiltrating breast cancer. After bone metastases had been excluded, primary hyperparathyroidism was suspected. A parathyroid adenoma was removed and histologically confirmed. Hypercalcemia, associated with low plasma phosphate and severely depressed plasma parathormone (PTH) levels, persisted. Further investigations showed liver metastases from the primary breast cancer and also secretion of a PTH-like substance. Antitumoral treatment was effective on the liver metastases and also normalized calcemia and the PTH-like substance, demonstrating the existence of a paraneoplastic syndrome related to the secretion of a PTH-like substance by disseminated liver metastases of primary breast cancer.


Aggressive angiomyxoma of the vulva.

Aggressive angiomyxoma of the vulva. A case of aggressive angiomyxoma (AAM) of the vulva is presented. The tumor presented as a slowly growing polypoid mass in the right labium minus near the clitoris. The tumor was treated by wide local excision. The microscopic appearance was that of spindle-shaped neoplastic cells widely separated by a loose myxoid stroma rich in collagen fibers, hyaluronic acid, and prominent irregular-shaped blood vessels. Aggressive angiomyxoma of the vulva must be distinguished from the more common benign and malignant myxoid tumors including myxoma, myxoid liposarcoma, myxoid variant of malignant fibrous histiocytoma, sarcoma botryoides, nerve sheath myxoma, and other soft tissue tumors with secondary myxoid changes. Local recurrence of AAM may be avoided by wide local excision.


Inactivation of factor Va by activated protein C on selected human tumor cell lines. Previous studies have demonstrated that platelets or aortic endothelial cells provide an appropriate surface that augments the proteolytic inactivation of factor Va by activated protein C (APC). We have examined the ability of three human tumor cell lines (HepG2, CAPAN-2 and J82) to support the inactivation of human factor Va by human APC in the presence and absence of human protein S. APC-mediated factor Va inactivation on these tumor cell lines was assessed by measuring the ability of residual cell-bound factor Va to augment the proteolytic activation of prothrombin by factor Xa. Each of the tumor cell lines studied supported factor Va inactivation by APC in the presence of calcium ions. HepG2 cell monolayers supported this reaction most effectively, with CAPAN-2 and J82 cell monolayers exhibiting moderate and weak effectiveness, respectively. Although not essential for this reaction, protein S moderately enhanced the rate of factor Va inactivation by APC on these tumor cell lines. In addition, pretreatment of each tumor cell line with rabbit antihuman protein S IgG had little, if any, effect on its ability to support factor Va inactivation by APC. Our data suggest that these, and perhaps other, tumor cells can provide an appropriate phospholipid surface for promoting factor Va binding and rapid inactivation by APC.


Interferon-gamma-induced expression of tissue factor activity during human monocyte to macrophage maturation. The expression of tissue factor (TF) during differentiation of human monocytes (MO) to macrophages (MAC) in vitro is investigated in this study. In MO, TF activity can be induced by the addition of lipopolysaccharides (LPS) as detected by Northern blot analysis and measured functionally as procoagulant activity (PCA), while IFN gamma alone has only marginal stimulatory activity. During in vitro differentiation of MO into MAC, however, there is a steady increase in IFN gamma-induced PCA with a maximum on day 7. While MO during the first 2 days in culture are more responsive to LPS, IFN gamma becomes the prominent stimulus for mature MAC. The response to IFN gamma is rapid with a peak within 6-8 h and a subsequent downregulation to baseline activity within 24 h. Our results demonstrate that IFN gamma can effectively induce TF in human MAC and that its expression is developmentally regulated during MO to MAC maturation in vitro.


Imbalance between thrombin and plasmin activity in disseminated intravascular coagulation. Assessment by the thrombin-antithrombin-III complex/plasmin-alpha-2-antiplasmin complex ratio. We investigated the imbalance between thrombin and plasmin activity in vivo with various grades of severity of disseminated intravascular coagulation (DIC) in relation to the underlying diseases. Plasma thrombin-antithrombin-III complex (TAT) and plasmin-alpha 2-antiplasmin complex (PAP) levels were measured in 133 blood samples obtained from patients with DIC. The TAT/PAP ratio was higher in patients with sepsis or solid cancer than in those with hematologic malignancies. In acute promyelocytic leukemia (APL), the TAT levels were the highest, but the PAP levels were even higher and the TAT/PAP ratio was the lowest. As for the severity of DIC, in mild DIC, both thrombin and plasmin activities were increased. In moderate DIC, the TAT/PAP ratio increased, and thrombin activity was much more predominant. However, in severe DIC, the ratio decreased, and plasmin activity became excessive. In 3 patients with acute myeloblastic leukemia, APL and pancreatic cancer, respectively, the PAP level remained high during heparin therapy although the TAT level was decreased. When tranexamic acid was given, the PAP level was selectively reduced, and the TAT/PAP ratio was markedly decreased along with clinical improvement. These results indicate that monitoring of the TAT/PAP ratio may contribute to decisions regarding the institution and performance of combination therapy for DIC using anticoagulants and antifibrinolytic agents.


Increased plasminogen activator inhibitor activity in survivors of myocardial infarction is associated with metabolic risk factors of atherosclerosis. To assess the relationship between the fibrinolytic system and coronary risk factors, several fibrinolytic parameters were measured in 72 male survivors of myocardial infarction and in 53 age-matched healthy controls. The coronary patients had significantly higher plasminogen activator inhibitor (PAI) activity than the control subjects, while t-PA antigen did not differ between the groups. After stratifying the coronary patients in 14 diabetic and 58 nondiabetic patients, the elevated PAI activity remained limited to the diabetic group. PAI activity correlated significantly with systolic blood pressure, blood glucose, body mass index and LDL cholesterol. In multivariate regression analysis, significant associations persisted between PAI and diabetes, body mass index and LDL cholesterol. Coronary disease had no impact on the regression model. Our results suggest that the increased PAI-1 in selected groups of coronary patients is not a consequence of coronary disease itself, but is rather related to the metabolic risk factors of atherosclerosis, especially diabetes.


Magnetic resonance imaging of retracted and nonretracted blood clots during fibrinolysis in vitro. Magnetic resonance imaging (MRI) of retracted blood clots embedded in nonretracted clots was used to follow their lysis with urokinase in a plasma milieu in vitro. The two types of clots that were imaged in the same plane differed in signal intensity on T2-weighted spin echo MR images throughout the 20-hour observation period. It was thus possible to delineate the contours of both clot types and measure their relative sizes by digital image processing. Lysis of retracted clots proceeded significantly slower than lysis of nonretracted clots. Our in vitro results suggest that MRI might prove useful in detecting thrombus retraction in vivo and in predicting the outcome of thrombolytic therapy.


Interaction of platelets with subendothelium in rats treated with PCA-4230, a new antithrombotic agent. Effect of PCA-4230 on experimental thrombosis. The effects of a new antithrombotic compound, PCA-4230, versus ticlopidine were investigated using an experimental thrombosis and vascular endothelial injury model in rats. Both PCA-4230 and ticlopidine protected rat arteries from the formation of prominent thrombi and most of microthrombi without modifying the formation of a first platelet monolayer. Neither coagulation parameters nor fibrinolysis were modified by these antithrombotic drugs. Neither PCA-4230 nor ticlopidine affected thromboxane A2 production in rats, whereas unlike PCA-4230, ticlopidine inhibited ex vivo fibrinogen binding to the fibrinogen receptor found on the platelet membrane. In conclusion, PCA-4230 and ticlopidine inhibited thrombus formation in vivo by a platelet-dependent mechanism which may be different for one or the other drug in spite of the fact that the protective effect measured in this thrombosis model is quite similar for either PCA-4230 or ticlopidine. The above-mentioned results clearly show that PCA-4230 is a new potent agent with both antivascular-damaging and antiplatelet activities, and devoid of effects on coagulation and fibrinolytic systems.


Potential influence of observer variation in thromboprophylactic trials. In order to investigate the influence of the interpretation of a postoperative venography, used as the scientific tool in a thromboprophylactic trial, twelve different evaluations of the same venography have been compared. Two hundred and nineteen patients, undergoing total hip replacement, fulfilled a randomized trial evaluating two different prophylactic regimens. Bilateral venography was performed 7-11 days after surgery, and the result of venography was defined as with or without deep venous thrombosis (DVT), irrespective of the location of a thrombus. The venograms were evaluated five times by different interpreters, and the criteria for the presence of DVT were recorded whether or not thrombi in minor veins were present. The incidences of DVT in the two prophylactic groups varied from 2.7 to 20.3% and from 13.5 to 34.2%, respectively, according to the diagnostic criteria. However, the risk reduction between the two groups was almost constant, no matter which type of evaluation was applied (7.9-15.1%), and was statistically significant at the 5% level in all but 4 of the 12 evaluations. It is concluded that despite uniformity in patient selection, the incidence of DVT is not uniform, even though it is stated that venography is used as the end point. The obvious interobserver variation did not change the conclusion when two regimens are compared in a specific randomized study.


Elastase activity in leukemic cells.

Elastase activity in leukemic cells. Elastase, a proteolytic enzyme which digests different clotting factors, has previously been isolated from monocytes, macrophages and granulocytes. In the present work, we have isolated leukemic cells from 1 patient with acute lymphoblastic leukemia (ALL) and from 6 patients with acute nonlymphoblastic leukemia. Detectable elastase activity was found in the cells from all patients with acute nonlymphoblastic leukemia and ranged from 0.016 to 0.619 mukat/l/micrograms DNA. The highest elastase activity was found in 1 patient with promyelocytic leukemia (M3), and no activity was found in the cells from the patient with ALL. It is possible that elastase-mediated proteolysis of coagulation factors is the mechanism responsible for bleeding complications which are frequent in M3.


A new marker for estimation of bloodstain age by high performance liquid chromatography. The applicability of a new marker for estimation of bloodstain age by reverse-phase high performance liquid chromatography (HPLC) is described. Using a microBondasphere C18 column with a two step linear gradient of 10.5-46.25% acetonitrile in 0.1% trifluoroacetic acid, an intriguing peak (unidentified) at a retention time of about 5 min was observed on chromatograms from human adult bloodstains and designated as 'X'. The area of this peak, which could be detected in extracts of bloodstains, but not in their fresh whole blood, increased with time. The ratios of the X area to heme area in bloodstains stored at room temperature and 4 degrees C for up to 52 weeks old linearly correlated with stain age by plotting on a double logarithmic scale. In bloodstains exposed to fluorescent light at room temperature, the regression equation calculated from the ratios (Rx) and the ages of stains in weeks (W) is ln(1000.Rx) = 1.1084 + 0.3937.ln(7.W), and the coefficient of correlation (r) is 0.9776 (n = 144, P < 0.001). When stains were stored at 37 degrees C, the ratio transformed into logarithms correlated linearly with stain age. The regression equation describing the relationship in bloodstains exposed to fluorescent light at 37 degrees C is ln(1000.Rx) = 2.4477 + 0.0866.W (r = 0.9826, n = 144, P < 0.001). The results of the present study suggest that the HPLC method may be applicable to the estimation of bloodstain age.


Experiences with single locus DNA probes in casework. DNA profiling in this laboratory has been employed primarily in cases of sexual assault and the largest category of items examined has been internal vaginal swabs. 79% of these gave a profile which was different from that of the victim. Results have been obtained from swabs taken up to 70 h after intercourse. In cases where DNA results were obtained, one or more suspects were excluded in 29% of the cases.


A new individualization marker of semen: deoxyribonuclease I (DNase I) polymorphism. We describe a method for obtaining specific and reproducible deoxyribonuclease I (DNase I) typing from liquid semen. Isoelectric focusing of the enzymes on polyacrylamide gel (IEF-PAGE, pH 3.5-5) was accomplished using a 0.5-mm thick gel. The separated isozymes were visualized by a new activity staining method, dried agarose film-overlay (DAFO). Pretreatment of semen samples with neuraminidase markedly enhanced the isozyme-band resolution and sensitivity. The method was simple and reliable, with high resolution and sensitivity. The DNase I types in semen samples were correlated with the types found in corresponding blood and urine samples. DNase I typing could therefore provide an additional discriminant characteristic in the forensic examination of semen.


Tuberculous myocarditis presenting as sudden cardiac death. A 71-year-old Chinese male presented as sudden death and autopsy revealed miliary tuberculosis with tuberculous myocarditis. Though miliary tuberculosis is not as common as in the past, it remains one of the possible causes of sudden cardiac death.


Strontium-90 as an indicator of time since death: a pilot investigation. The results of a pilot investigation are presented. The study aimed to show that the presence of radioactive strontium-90 in human bone could be used as evidence of active uptake during life. In this way the time since death of the individual could be identified as occurring before or after the date when atmospheric levels of radioactive strontium were at a peak in the early 1960s. The results of this initial investigation were encouraging but further detailed analysis is required on a substantially larger sample of material spanning a more controlled time period.


HIV-1- prevalence among drug deaths in major cities of central and northern Europe. Since 1985, a number of Institutes of Forensic Medicine in Germany have cooperated in a multicenter study, to provide a constant monitoring of HIV-1-prevalence among drug related deaths. In 1990/91, the Institutes in Copenhagen, Stockholm, Vienna and Zürich also participated in this study. HIV-1-prevalence is decreasing in the German cities, whereas the epidemiological development is not uniform in the other major cities. Regional differences are obvious. In 1991, the prevalence rates were as follows: Berlin 15% (n = 220), Hamburg 4% (n = 179), Frankfurt 17% (n = 167), Munich 9% (n = 136), Stockholm 10% (n = 79), Copenhagen 14% (n = 130), Vienna 20% (n = 56), and Zürich 23% (n = 84).


Margaret Clitherow: skeletal identification of an historical figure? This paper describes the use of physical anthropological methods of analysis in attempting to identify an historical figure in England. The historical background to the examination is detailed and reasons for the belief that the skeletal remains excavated from the site were those of a named person, Margaret Clitherow, are discussed. Analysis of age, sex and manner of death indicated that the remains were not those of Margaret Clitherow.


Anxiety in prisoners today.

Anxiety in prisoners today. Models based on modern theories of anxiety were used to develop a hypothesis concerned with the relationship of anxiety and/or the tendency to aggressive behavior and the tendency to depressive reactions in prisoners. Anxiety, aggression and depression scales were the instruments used in this study. Special emphasis was placed on the question as to whether there is a quantitative difference in anxiety and aggression in non-working as compared with working prisoners. Significant differences were found between working and non-working prisoners with regard to anxiety and depression. A difference was also calculated for the parameter of reactive aggression. In the following the far-reaching implications of these results for penological practice and perspectives for further studies are discussed.


[MRI as decisive diagnostic procedure in Perthes disease. Early diagnosis of femoral head necrosis in childhood]. In order to achieve better final results in Perthes disease, the diagnosis should be established as early and as accurately as possible. This is rarely achieved with conventional X-ray procedures. Since 1986, a total of 50 children with Perthes disease were submitted to MRI follow-up examinations employing T1 and T2-weighted coronary an sagittal sections and the results compared with the findings of conventional X-ray examinations. The authors developed their own MRI staging and typing scheme on the basis of the MRI extent of the necrosis. Catterall's group classification could not be translated to the MRI since the latter usually showed more extensive necrosis. Agreement was found only in group I. With the aid of MR imaging, it proved possible to diagnose a case of Perthes disease earlier, the total extent of the necrosis was established earlier, and also the final form of the epiphysis after completion of re-modelling was already predictable in stage II. The indication for treatment and intra-trochanteric osteotomy was established on the basis of the MR image. Further invasive investigations were not needed. In the case of Perthes disease, MRI should be given preference over other diagnostic procedures and, despite the greater expenditure of time and greater cost, should be routinely employed in this disease.


[Anorexia nervosa in boys--a case report]. In contrast to female adolescents, anorexia nervosa is rarely seen in male adolescents. In consequence, more comprehensive investigations are often carried out in the latter in a search of organic disease. A boy of thirteen-and-a-half years was referred for investigation of anorexia, loss of weight, constipation, loss of concentration and depression. Physical examination revealed bradycardia, low blood pressure, hypothermia and various endocrinological disturbances: reduced somatomedin C, tri-iodine thyronine and subnormal thyroxine levels, and delayed TSH peaking after TRH stimulation. Examination of peripheral blood revealed leukopenia with underlying hyperplastic bone marrow. A CT scan revealed widening of the ventricles of the brain, and echocardiography a mitral valve prolapse. Anorexia nervosa is accompanied by numerous pathological findings which, however, when weight is regained, return to normal without the need for further treatment. Before instituting invasive diagnostic measures in boys or male adolescents, consideration should be given to anorexia nervosa, and a psychiatric consultation sought.


[Prevention of recurrent infection of the upper and lower airways. Multicenter, open study over three months]. In a multicenter open study involving 620 patients suffering from recurrent infections of the upper and lower respiratory tract aged between 12 and 89 years, the tolerability of an oral bacterial lysate was investigated. On the basis of the nature and frequency (1.9%) of adverse effects, and an analysis of the laboratory investigations over an observation period of three months, overall tolerability was adjudged to be excellent. The frequency and severity of infections was reduced. In 75% of the cases, both physician and patient considered the augmentation of the body's defense mechanisms by immunoactivation to have been of benefit. The favourable risk-to-benefit ratio results in a high level of acceptance of immunotherapy, and 96% of the patients completed the study as planned.


[Sex-dependent differences in endogenous psychoses. A comparison between schizophrenic, schizoaffective and affective psychoses]. Sex differences in 355 patients with functional psychoses were investigated longitudinally (mean observation time more than 25 years). Using narrow criteria, 148 patients were diagnosed as having a schizophrenic disorder, 101 as having a schizoaffective and 106 as having an affective disorder. Similarities and differences between male and female patients in these three diagnostic groups were investigated and compared on four levels (premorbid and sociodemographic features, elements of course, symptomatology and the different aspects of outcome) using international standardised instruments of evaluation. A different sex distribution in the three groups was found. Female schizophrenic patients showed a better premorbid social adjustment and a better long-term psychopathological and social outcome than male patients. Differences between male and female schizoaffective patients were found only regarding premorbid personality and polarity, but not regarding symptomatology and outcome. In affective psychoses female patients showed a better social outcome than male patients, but no relevant differences regarding premorbid adjustment were found. Gender differences were found as an important variable for research in functional psychoses, but interactions with other variables have to be considered.


[Endo-neurotic depression. Necessity and irritation of a diagnostic concept]. The traditional system of diagnosis which differentiates clearly between endogenous depression on the one hand and psychogenic depression on the other, results in an dichotomy that limits our thinking and perception. This limitation is an obstacle to an open-minded realisation of the multidimensional cause-effect links underlying depressive syndromes. The historical development is outlined and the descriptive-psychiatrical and psychoanalytical-psychodynamical theoretical aspects are described. There is a definite need for an unequivocal terminology that covers both clinical observations and therapeutic assessments. The term endo-neurotic as a logical development of Weitbrecht's endo-reactive concept represents a verbal diagnostic instrument enabling the characterisation of a typical group among a multitude of "multilayered" depressions. Endogenous and neurotic factors carry the same weight in such depressions, and the phasewise course of the disease does not permit the patient to be classified as purely "somatic" or purely "mental" or "psychological". If endogenous phases having a triggering effect on depression fail to occur during psychotherapy, this may be due to minor penetration by either endogenous or psychogenic factors. A clinical case report shows how intensive psychotherapy of neurotic mechanisms increasingly improves the management of situations that were formerly critical in respect of triggering depressions. The patient feels that this is really so, and the therapist gains confidence that his therapy is progressing in the right direction. Of course such an experience cannot be proven by statistics. This highlights the well-known discrepancy between idiographic and nomothetic methods. Progress could be achieved by "cutting more finely", i. e. by a terminology that is more differentiated and eliminates the compulsion to arrive at a rough diagnosis which disregards the finer gradations of the colours that make up the entire picture. Thus the term endo-neurotic could be useful to define a certain part of the diagnostic spectrum of depression with greater clarity.


[Lesion of the brachial plexus caused by traumatic aneurysma spurium of the axillary artery--case report of two patients]. The indirect lesion of the brachial plexus by a traumatic false aneurysm of the axillary artery is a rare event. Clinical signs, diagnosis and follow-up of two patients are reported. Characteristic symptoms are persistent shoulder pain and progredient neurologic deficits with delayed onset. Examination for a jet phenomenon in the axillary region may confirm the suspected diagnosis. Colour duplex-sonography and magnetic resonance tomography are the most valid non-invasive radiological methods beside computerised tomography. Surgical treatment with resection of the aneurysm is recommended as soon as possible.


[The new euthanasia-discussion from the psychiatric viewpoint]. The practice to kill terminally ill patients on their own demand has resulted in the Netherlands in a decriminalisation of active euthanasia which thus has fundamentally changed the way to deal with dying patients. Sooner or later this development will extend to other European countries as well as to the USA. Involuntary euthanasia of severely handicapped newborn children or of demented persons is propagated by the practical ethics of P. Singer and other representatives of utilitarianistic philosophy. According to the standpoint of utilitarianism a human being should only have the right to live as long as he or she is a person, i. e. has rationality and self-consciousness. The next step toward the elimination of elderly people can easily be predicted. For economical reasons these persons may be withheld from life-saving medical treatment or may be supposed to commit suicide. A moral pressure is created to make a decision for suicide as soon as severe invalidity occurs. The consideration of such ideas shows that in today's debate on euthanasia the issue is no longer the right of a few severely and terminally ill human beings to their "own death". Instead, the right to live of a large group of handicapped and "socially useless" or "unproductive" persons is at stake. This is the danger of today's discussion of euthanasia.


Thymic pathology in primary and secondary immunodeficiencies. For the sake of clarity and in agreement with the World Health Organization immunodeficiency classification, it is important to distinguish the congenital, inherited malformative lesions called generically 'thymic dysplasia' from the secondary, acquired changes, designated under the broad term of 'severe thymic atrophy'. Thymic dysplasia represents the archetype of thymic changes in cellular immunodeficiency, since there is no example of a thymic dysplasia associated with a normal T-cell function. Thymic dysplasia is observed in several inherited diseases, the most frequent of them being severe combined immunodeficiency. More than the depletion of lymphoid cells, the lack of differentiation of the thymic epithelium, responsible for the absence of Hassal's corpuscles, is the main and constant feature of this condition. Thymic dysplasia underscores the crucial role of the thymic epithelium in the normal differentiation of the T-cell population. Severe thymic atrophy is secondary to various causes, including prolonged protein malnutrition and immunosuppressive or cytotoxic drugs, graft versus host reaction and, chiefly today, chronic viral infection, especially with HIV-1. The morphological changes are similar and are characterized by a partial lymphoid depletion, involving mainly the CD1+ population, necrosis and calcification of epithelial cells, the frequent presence of plasma cells and, more significantly, fibrohyaline changes of the basement membrane of the vessels and thymic epithelium. The severity of the atrophic changes and the immunodeficiency-related manifestations depend on the duration of the aetiological factors and, more significantly, with their early occurrence, within the first months of life. The mechanisms underlying thymic atrophy are poorly understood. A primary impairment of lymphoid cells seems at present to be the most likely hypothesis.


Parathyroid hyperplasia in tertiary hyperparathyroidism: a pathological and immunohistochemical reappraisal. Thirty-one parathyroid glands from 11 patients with tertiary hyperparathyroidism were examined histologically and immunohistochemically to characterize better the nature of the accompanying parathyroid hyperplasia. The parathyroids showed varying degrees of nodular and diffuse hyperplastic involvement as well as apparently normal background tissue. The nodules were usually multiple within any one gland and, together with diffuse hyperplastic tissue, showed a varied cyto-architectural pattern. All glands studied showed both cellular argyrophilia and parathyroid hormone immunoreactivity. The staining pattern for parathyroid hormone ranged from negative or weak to strong, and from patchy to diffuse in hyperplastic tissue from different glands and within the same gland, regardless of the cell type. Apparently normal areas usually showed only patchy weak to moderately strong parathyroid hormone positivity. From the data obtained the most striking feature of the parathyroid glands in tertiary hyperparathyroidism is their extreme variability, both morphological and functional, as indicated by parathyroid hormone immunoreactivity. Furthermore, the generally lesser degree of parathyroid hormone immunoreaction observed in apparently normal parathyroid tissue may reflect suppression of hormone synthesis, with accompanying morphological regression to normal of pre-existent diffuse hyperplasia by autonomous hyperfunctioning nodules associated with tertiary hyperparathyroidism.


Modes of Helicobacter colonization and gastric epithelial damage. A total of 144 gastric biopsies colonized by Helicobacter-like organisms were studied under light and differential interference contrast microscopy for the modes of bacterial colonization. Biopsies were also graded for the degree of epithelial damage (epithelial-damage-grade: 0 to 6, in ascending order of severity) and density of Helicobacter-like organism (Helicobacter-grade: 0 to 6, in ascending order of bacterial density). Three modes of colonization were identified: free-in-mucus, surface-adhesion and intercellular colonization. Because light microscopy cannot definitely prove the presence of intracellular colonization, bacteria located between cells and below the apical cell border were counted together as intercellular colonization. Bacteria free-in-mucus were seen in all biopsies. Surface adhesion was seen in 50-87.9% of biopsies, without obvious correlation with the epithelial-damage- and Helicobacter-grades. The incidences of intercellular and intracellular colonization were directly proportional to the epithelial-damage- and Helicobacter-grades. Free-in-mucus as the predominant mode of colonization was mainly seen in biopsies with lower (1-3) epithelial-damage- and Helicobacter-grades. Conversely, biopsies with intercellular colonization as the predominant mode of colonization were mainly cases with higher (4-6) epithelial-damage- and Helicobacter-grades. In cases showing predominantly bacteria between cells, 69.2% had a gastric ulcer whereas only 38.8% of cases showing predominantly bacteria free-in-mucus showed ulceration (P < 0.01). These results indicate that Helicobacter-like organisms can invade and penetrate between epithelial cells. When free-in-mucus, Helicobacter-like organisms are less likely to induce epithelial damage. However, the more invasive modes of colonization (intercellular) were associated with severe epithelial damage and high Helicobacter density.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidermal damage in skin of allogeneic marrow recipients: relative importance of chemotherapy, conditioning and graft v. host disease. The relative importance of previous chemotherapy, conditioning and graft v. host disease in producing the epidermal damage associated with allogeneic bone marrow transplantation was investigated by enumerating individually necrotic cells. A small number was seen in many pre-transplant biopsies and was related to the time interval between biopsy and the last dose of chemotherapy. Their presence did not predispose patients to develop graft v. host disease in the post-transplant period. In post-transplant patients without rashes the degree of epidermal damage at 14 days was similar to that seen in the pre-transplant period indicating that the effects of the conditioning regime were insignificant. In patients with rashes clinically classical of graft v. host disease, necrotic cells were increased above the pre-transplant levels even in the absence of a lymphocytic infiltrate. Lymphocytic infiltration was seen more frequently in biopsies taken later after transplantation and after the onset of the rash and was associated with the maximal amount of epidermal damage. Comparison of the degree of epidermal damage in pre- and post-transplantation specimens lacking a lymphocytic infiltrate resulted in the correct identification of the majority of patients with clinical evidence of graft v. host disease. This approach may, thus, be useful in diagnosing early graft v. host disease especially if combined with keratinocyte HLA-DR staining.


Intestinal pseudo-obstruction with deficient smooth muscle alpha-actin. We describe a 48-year-old woman with chronic constipation since early childhood who has an intestinal myopathy associated with a hitherto undescribed absence by immunostaining of smooth muscle alpha-actin confined to the intestinal circular muscle. There were no abnormalities in other contractile proteins (myosin, tropomyosin, filamin, caldesmon or desmin) and despite the abnormality of a contractile protein isoform in the circular muscle, no significant morphological changes were identified by light microscopy or ultrastructural examination. A possible developmental mechanism for the observed change is proposed. The use of specific antibodies to isoforms of contractile proteins may have potential value in the study of intestinal myopathies.


Oestrogen and progesterone receptors in screen-detected breast carcinoma: an immunohistological study using paraffin sections. The presence of oestrogen and progesterone receptors was studied in paraffin sections of 81 screen-detected breast carcinomas using the monoclonal antibodies ER-ICA and PgR-ICA (Abbott) and the immunoperoxidase technique. The immunohistological results were compared with the results of the standard dextran-coated charcoal biochemical assay in 28 tumours which were big enough to provide tumour tissue for this assay. Sixty-three cases (78%) were oestrogen receptor positive and 62 (77%) were progesterone receptor positive. There was no statistical difference between receptor positivity in palpable or impalpable, in situ or invasive tumours. In the 28 cases where the biochemical assay was carried out, the two methods gave similar results in 23 (82%) and 21 (75%) tumours for oestrogen and progesterone receptors respectively. The majority of the remaining tumours, with one exception, were positive with immunohistology and negative with biochemistry. A good correlation was also present between the mean numerical biochemical values and the semiquantitative histological scores for both receptors. It is concluded that assessment of receptor status of small screen-detected carcinomas is feasible using routinely processed paraffin sections. There is reasonably good correlation with the results obtained by the standard dextran-coated charcoal biochemical assay, but more genuine receptor positive cases are detected by immunohistology.


The histological features of splenosis.

The histological features of splenosis. This study presents a detailed histological analysis of two cases of splenosis, including one of the largest nodules to be reported. Splenosis may exhibit red and white pulp that appears histologically and immunohistochemically normal by routine methods, and a well-developed capsule and trabeculae may form. The capsule may be thicker than in the normal spleen but is otherwise indistinguishable and may contain fibrous, elastic and smooth muscle elements. These findings are in contrast to previously published works which have described poorly-developed white pulp, capsule and trabeculae in splenosis. The histological pattern may depend on the blood supply to the autotransplanted splenic tissue in the early days after implantation. The close resemblance that splenosis may show to an accessory spleen suggests that histological examination may have a limited role in the distinction between these two conditions.


The morphological spectrum of monocytoid B-cell lymphoma and its relationship to lymphomas of mucosa-associated lymphoid tissue. We report 10 cases of monocytoid B-cell lymphoma, five of which had extranodal lymphomas of mucosa-associated lymphoid tissue (MALT) type. In one patient the MALT lymphoma in the salivary gland was microscopic. In another, the small bowel lymphoma, which preceded the monocytoid B-cell lymphoma by 11 years, showed different clonal immunoglobulin gene rearrangements. Attention is drawn to the extreme degree of plasmacytic differentiation and epithelioid cell infiltration that may occur in monocytoid B-cell lymphoma. In addition to the cytological and immunophenotypic likeness of monocytoid B-cells and centrocyte-like cells, monocytoid B-cell and MALT lymphomas share a number of micro-anatomical and behavioural characteristics. These include the sharp separation of the monocytoid B-cells and plasma cells, follicular colonization and progression to high-grade lymphoma. It is suggested that the frequent association of monocytoid B-cell lymphoma with Sjögren's syndrome may be due to the fact that the salivary glands drain to cervical lymph nodes that are part of the systemic, rather than the mucosal, lymphocyte circulation pathway.


Papillary carcinoma of thyroid with exuberant nodular fasciitis-like stroma. We describe two cases of papillary carcinoma of the thyroid containing prominent nodular, fasciitis-like stroma. In one of the cases infiltration into the adjacent parathyroid gland and metastases to two cervical lymph nodes occurred. In the lymph nodes and the parathyroid gland the carcinoma grew without any fasciitis-like stroma. This unusual change in tumour stroma seems to be reactive in nature and confined only to the thyroid and adjacent soft tissues.


Evaluation of osteonectin as a diagnostic marker of osteogenic bone tumors. Osteonectin (ON), a 32,000-kd glycoprotein involved in the early steps of mineralization of skeletal tissue, is a recognized differentiation marker of normal osteogenic cells. The expression of ON was evaluated in vitro and in tissue sections by the polyclonal antibody bON II. In different cell cultures immunocytochemistry and molecular biology displayed a nonspecific reaction for the antibody, which showed itself to be useless for the in vitro identification of cells of the osteoblastic lineage. The diagnostic use of bON II antibody was investigated by immunohistochemistry on a series of osteogenic and nonosteogenic bone tumors. A strongly positive stain of the entire neoplastic component of osteosarcoma and osteoblastoma and a weaker stain of the mononuclear component of giant cell tumor and chondroblastoma were observed. On the other hand, stains for chondrosarcoma, Ewing's sarcoma, fibrosarcoma, malignant fibrous histiocytoma, and brown tumor from hyperparathyroidism were entirely negative. Our results indicate that ON may be helpful in the histologic diagnosis of bone tumors, particularly in differentiating small cell osteosarcoma from other small round cell tumors.


Contribution of immunohistochemistry, electron microscopy, and cell culture to the characterization of nonfunctioning pituitary adenomas: a study of 40 cases. We studied 40 endocrinologically inactive pituitary adenomas by immunohistochemistry, electron microscopy, and cell culture in order to determine the incidence of gonadotropic adenomas and to classify nonfunctioning adenomas. Immunohistochemical studies using a large panel of monoclonal and polyclonal antibodies identified the following nonfunctioning adenomas: 20 gonadotropic adenomas, four silent corticotropic adenomas, one plurihormonal adenoma, and 15 nonsecreting adenomas. Among nonsecreting adenomas, ultrastructural study of 13 cases identified seven null cell adenomas and six oncocytomas. Silent corticotropic adenomas were classified into subtypes I, II, and III according to Kovacs and Horvath. Most often, gonadotropic adenomas displayed a varying number of oncocytic cells, characteristic secretory granules, and a prominent Golgi apparatus. Postembedding immunoelectron microscopy was performed on eight gonadotropic or nonsecreting adenomas, but this technique did not provide any additional information. Six gonadotropic adenomas and 10 so-called nonsecreting adenomas were studied in primary cell cultures. The six gonadotropic adenomas and seven of the 10 nonsecreting adenomas released gonadotropins in the culture medium. The use of in vitro results as a supplementary diagnostic criterion allowed classification of the 40 nonfunctioning adenomas as follows: 27 gonadotropic adenomas, four silent corticotropic adenomas, one plurihormonal adenoma, and eight nonsecreting adenomas. These results demonstrate a high proportion of gonadotropic adenomas among nonfunctioning adenomas (67.5%) and the usefulness of several techniques in characterizing this type of pituitary adenoma.


Flow cytometric DNA analysis of carcinoid tumors of the ileum and appendix. Although all carcinoid tumors are considered potentially malignant, the biologic behaviors of appendiceal and ileal carcinoids are distinctly different. Appendiceal carcinoids often behave in a benign fashion, whereas ileal carcinoids pursue an aggressive course with frequent metastasis. Whether differences in DNA ploidy are related to this disparity in tumor behavior was addressed in this study. Flow cytometric DNA analyses were performed on paraffin blocks from 11 ileal and seven appendiceal carcinoid tumor cases. The mean coefficient of variation for all samples was 3.4 +/- 0.7. DNA aneuploidy was seen in two of the appendiceal cases and in six of the ileal cases. Metastases were seen in one of the appendiceal carcinoid cases, and that tumor was aneuploid. In six cases of carcinoid of the ileum, metastases were seen; of these, five tumors were aneuploid. In the ileal cases, despite the low number of cases examined, the correlation between DNA aneuploidy and metastases nearly reached statistical significance (P = .07) and showed a much stronger correlation than tumor size and metastases (P = .4). Although no statistical significance was reached in this study, the results are highly suggestive of DNA aneuploidy being an important predictor of malignant behavior in carcinoids of the ileum.


Talc pneumoconiosis: a pathologic and mineralogic study. Seventeen cases of "talc pneumoconiosis" were examined pathologically and mineralogically to ascertain whether a true talc pneumoconiosis existed and also to compare these results in primary, secondary, and tertiary exposures. Mineralogic analyses were performed on wet tissue or tissue blocks by a variety of techniques, including analytical transmission electron microscopy and x-ray diffraction. Overall, the pathologic appearance of the tissues was similar in primary, secondary, and tertiary exposures, although ferruginous bodies and foreign body giant cells were not always present in cases caused by secondary exposures. Mixed dust fibrotic lesions were found in two cases in which there were substantial quantities of quartz present. There was great variation in the minerals found within the lung tissues. Several cases showed significant quantities of mica and kaolin in addition to talc. One case consisted predominantly of mica and in fact could be regarded as "mica pneumoconiosis"; this diagnosis was correctly attributed because of the mineralogic findings. Tremolite fibers were found in only two cases. Substantial quantities of crocidolite and amosite fibers were found in one case. This study shows that "talcosis" frequently represents disease associated with a variety of minerals and that talc is a common denominator. It shows also the usefulness of lung dust mineral analysis, particularly in secondary industries, for evaluating the cause of a pathologic reaction when exposures are especially complex.


Transforming growth factor-alpha in normal and neoplastic human endocrine tissues. Transforming growth factor-alpha (TGF-alpha) is a polypeptide growth factor that binds to the epidermal growth factor receptor and is though to stimulate cell proliferation. It has been believed to play a role in tumor initiation by inducing the reversible transformed phenotype; overexpression of TGF-alpha may be important for tumor progression via autocrine stimulation and oncogene overexpression. Expression of TGF-alpha and the epidermal growth factor receptor has been documented in several nontumorous tissues and in a variety of tumors. This study used immunohistochemistry to localize TGF-alpha expression in normal and neoplastic endocrine tissues. Transforming growth factor-alpha was found in nontumorous hypothalamus, pituitary, thyroid, parathyroid, adrenal cortex and medulla, and pancreatic islets. Immunoreactivity was detected in most benign and malignant tumors of these tissues, as well as in endocrine neoplasms of the lung and gastrointestinal tract. Hypothalamic gangliocytomas, pheochromocytomas, and adrenal cortical carcinomas showed consistently greater immunoreactivity than their normal counterpart, but there was no correlation between degree of reactivity and tumor grade, stage, or hormone content. These results suggest that in endocrine tissues, TGF-alpha is unlikely to prove useful as a tumor marker but that the growth factor may play a role in both normal physiology and tumorigenesis.


Immunoreactivity with monoclonal antibody A-80 and nuclear DNA content in benign and malignant human breast disease. Immunohistochemical analysis with the monoclonal antibody (MoAb) A-80, recognizing a tumor-associated cytoplasmic mucin-type glycoprotein, and cytometric nuclear DNA assessment were performed on 314 surgical specimens of the human mammary gland. The series included 36 benign conditions, 34 epithelial hyperplasias, 40 carcinomas in situ, and 204 primary invasive carcinomas. Normal breast parenchyma, benign tumors, and other nonmalignant lesions were all of DNA diploid (euploid) type and rarely expressed the A-80 glycoprotein. Differences in MoAb A-80 immunoreactivity and nuclear DNA content were noted among subtypes of epithelial hyperplasias. Fifteen of 34 epithelial hyperplasias were of DNA aneuploid type and the majority were A-80 immunoreactive. Of these 15 immunoreactive aneuploid epithelial hyperplasias, atypical intraductal hyperplasia was the most common subgroup. None of the 19 epithelial hyperplasias of DNA euploid type immunoreacted. Most of the intraductal (33 of 40) and invasive (180 of 204) carcinomas immunostained with MoAb A-80. The majority of the A-80 immunoreactive malignant tumors were of DNA aneuploid type (26 of 33 carcinomas in situ and 108 of 180 invasive mammary carcinomas). The results suggest that expression of the A-80 glycoprotein occurs at an early stage of malignant transformation. Genetically stable (euploid) mammary tumors seem to immunoreact with MoAb A-80 less frequently than genetically unstable (aneuploid) tumor variants. Combined analysis with MoAb A-80 and of nuclear DNA content in premalignant and malignant mammary lesions could be a useful tool of differential diagnostic and prognostic value.


Mesangial deposition of type I collagen in human glomerulosclerosis. The presence of type I collagen in both diffuse and nodular diabetic glomerular lesions has been examined using immunohistochemical and electron microscopic techniques. At the ultrastructural level, banded collagen fibrils were observed in the mesangium in all cases of nodular (Kimmelstiel-Wilson) sclerosis and in 60% of the diffuse sclerotic lesions. Antibodies against type I collagen were localized in the fibrotic interstitium and the mesangium in all cases examined. Staining with type I collagen antibodies occurred in glomeruli with intact Bowman's capsules, and was predominantly localized to areas immediately adjacent to mesangial cells. In cases of focal sclerosis of nondiabetic origin, banded collagen fibrils and staining with anti-type I collagen antibody were observed in all cases in which the segmental lesion was presented in the specimen. The pattern of antibody localization in both the diabetic lesions and focal sclerosis differed from that obtained using anti-type IV (basement membrane) collagen antibodies. These results demonstrate that type I collagen is among the extracellular matrix components that comprise the sclerotic glomerular lesions of both diabetic and nondiabetic origin. Furthermore, the spatial localization of this collagen type suggests mesangial cell origin.


Tissue invasion by Pneumocystis carinii: a possible cause of cavitary pneumonia and pneumothorax. Pulmonary cavitation and pneumothorax may complicate severe cases of Pneumocystis carinii pneumonia. Both complications likely result from tissue necrosis, although how such injury occurs is unknown. To investigate mechanisms of tissue destruction in P carinii pneumonia, histochemical, immunocytochemical, and electron microscopic studies were conducted in pulmonary wedge resections or autopsy specimens from patients with the acquired immunodeficiency syndrome (n = 7) or leukemia (n = 2). Tissue invasion, defined as Pneumocystis organisms in the interstitial compartment, was present in eight of nine cases. Organisms were found in alveolar septa (eight cases), pleura (six cases), and vessel walls (two cases). All cases with tissue invasion exhibited regional necrosis as well as extensive invasion of apparently viable parenchyma. Pulmonary cavitation occurred in seven of eight cases with tissue invasion, and six of these patients developed pneumothoraces. Despite extensive tissue invasion and necrosis there was little host inflammatory or stromal response. Ultrastructurally, both the tissue-invasive and intra-alveolar organisms were predominantly of the trophozoite form; they were present in much greater numbers than suggested by routine silver stains (which detect only cysts). Immunocytochemical techniques, which detect both trophozoite and cyst forms, were much more sensitive than silver stains. These results indicate that extensive tissue invasion by P carinii can occur in severe P carinii pneumonia. We hypothesize that such invasion is an important step in the development of pulmonary necrosis, cavitation, and pneumothorax.


Retinoblastoma and p53 gene product expression in breast carcinoma: immunohistochemical analysis and clinicopathologic correlation. We examined 100 breast cancers for retinoblastoma (Rb) and p53 protein expression by immunohistochemistry using the PMG3.245 and PAb 1801 antibodies. We assessed percentages of reactive cells and their intensity, as well as staining patterns. The results were correlated with neu protein reactivity and a panel of variables, including age, tumor size and type, nuclear grade, estrogen receptor/progesterone receptor content, and lymph node status. Retinoblastoma protein negativity, either partial or complete, was noted in 47% of cases. Surprisingly, a relatively stronger Rb reaction was seen in some high nuclear grade tumors. p53 positivity was found in 23% of cases and was a significant predictor of Rb loss. p53 also was correlated with poorly differentiated (nuclear grade III) neoplasms and neu expression but not with negative ER status. Tissue distribution profiles for Rb-negative and p53-positive cells were variable in this series, with both uniform and heterogeneous patterns observed. This suggests that Rb and p53 alterations may represent early or late events in transformation. Our findings further implicate Rb and p53 derangements in mammary oncogenesis.


Distribution of the 72-kd type IV collagenase in nonneoplastic and neoplastic thyroid tissue. The 72-kd type IV collagenase (matrix metalloproteinase-2 [MMP-2]) is a neutral metalloproteinase that initiates the degradation of type IV collagen in basement membranes. Its production by tumor cells has been correlated with the invasive and metastatic potential of neoplasms. Two recently developed affinity-purified antibodies against synthetic peptides from the amino terminus (H1) and an internal domain (Ab48) of the molecule were used to investigate immunohistochemically the distribution of this enzyme in a variety of thyroid tissues. All primary carcinomas (20 papillary, seven follicular, and three medullary) as well as nine of 11 metastases were positive, with the more aggressive tumors (tall cell variant of papillary carcinomas and invasive follicular carcinomas) tending to be more reactive than the low-grade tumors (classic and microinvasive papillary carcinomas and minimally invasive follicular tumors). Negative or minimal positivity was found in six cases of normal thyroid, one goiter, and two cases of Graves' disease. Immunoreactive follicular cells were seen focally in areas of inflammation, fibrosis, and distortion of normal follicles, and in Hashimoto's thyroiditis (four cases). Five of nine adenomas showed positive cells, but this could be related to previous trauma to the area. We conclude that there is increased production of the 72-kd type IV collagenase (MMP-2) in thyroid cancer; however, this enzyme also is elevated in benign conditions that are undergoing remodeling and repair.


Desmoplastic cerebral astrocytomas of infancy: a histopathologic, immunohistochemical, ultrastructural, and molecular genetic study. The desmoplastic cerebral astrocytoma of infancy (DCAI) is a rare tumor that presents as a large hemispheric mass in infants. Despite an ominous histologic picture that may resemble a sarcoma, the tumor is astrocytic and has a good prognosis. We present two cases of DCAI, with histopathologic, immunohistochemical, ultrastructural, and molecular genetic data, and draw the following conclusions: (1) the diagnosis of DCAI requires a high index of suspicion and immunohistochemical or ultrastructural proof of astrocytic differentiation; (2) the data argue against nosologically equating these tumors with the desmoplastic infantile ganglioglioma, pleomorphic xanthoastrocytoma, or gliofibroma; (3) the components of the extensive tumor basal lamina may be elaborated by the tumor cells themselves and may contribute in an autocrine fashion to the slow growth of these lesions; and (4) if the lack of allelic loss on chromosomes 17p (including the p53 tumor suppressor gene locus) and 10 seen in our cases is found in other cases of DCAI, this may further distinguish the DCAI from other astrocytomas.


Histologic predictors of survival in acquired immunodeficiency syndrome-associated Kaposi's sarcoma. The relationship between 22 histologic variables and survival was investigated in 93 patients with acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). All the patients were homosexual men in whom KS was the initial manifestation of AIDS. All patients were followed for at least 12 months or until death. Histologic specimens of the initial KS biopsy were reviewed in a blind manner by two of the authors and were evaluated for the presence of a number of histologic features. In a univariate analysis nodular lesions of KS (upsilon patch or plaque lesions), the absence of hemosiderin, the absence of irregular vascular spaces, and the presence of spindle cell nodules were all significantly associated with increased length of survival. Two variables previously shown to be related to survival (CD4:CD8 cell ratio, initial lesion on lower extremities) were included in a multivariate analysis (Cox model) in addition to the histologic variables. Complete data were available from 85 patients. In the multivariate analysis a higher helper to suppressor T-cell ratio, initial lesion on lower extremities, presence of spindle cell nodules, and nodular histology (upsilon patch or plaque histology) were all significantly associated with increased length of survival. These data suggest that in AIDS-associated KS, as in reticuloendothelial neoplasms, histologic features may be useful in identifying prognostically different subgroups of patients.


DNA ploidy analysis of myocardial hyperplasia. A case of myocardial hyperplasia with numerous mitotic figures, caterpillar nuclei, and an abnormal DNA ploidy pattern is described in an 8-day-old full-term baby with uneventful gestation and sudden death.


[Health education and AIDS. A randomized controlled trial]. In 1987 a small health education research team in Montpellier became interested in AIDS prevention among high school students (15-19 years old). Studies at that time indicated that the majority of the youth were relatively well informed about AIDS, for example 99% of those questioned knew that the disease was transmitted by sexual intercourse or by the exchange of contaminated needles. Further studies indicated, however, that the young people did not feel that the subject concerned them personally--it was considered a problem like many others. The team decided therefore to design a programme which would involve the young people, and thus motivate them not only to question, but to look for answers and implicate themselves in the search for information. The programme design consisted in creating video workshops in selected high schools. Adults with different backgrounds were trained in video production and communication skills in order to develop sufficient staff for workshop supervision. A network of available specialists was recruited for consulting purposes and a specialized library which included audiovisual materials was created so that the young people would have sufficient resources available for their research. In order to incite the students to contemplate the subject of AIDS and all that it involves, a contest was held. The theme was simply, "AIDS" and the duration was the length of the 1988-89 school year. Eight workshops were created in eight different schools. The teams were created quite spontaneously and the dynamic of interrogation anticipated was realized. With the help of trained adult supervisors, each team started their project by designing a five minute video.(ABSTRACT TRUNCATED AT 250 WORDS)


Lead exposure in indoor firing ranges.

Lead exposure in indoor firing ranges. Higher air lead levels (time-weighted average 660, range 112-2238 micrograms/m3) were measured in firing ranges where powder charges were employed than in ranges where air guns were used (4.6, range 1.8-7.2 micrograms/m3); levels in the latter were in turn higher than those in ranges used for archery (0.11, range 0.10-0.13 micrograms/m3). Twenty-two marksmen who used powder charges had significantly increased blood lead levels during the indoor shooting season (before: median 106, range 32-176 micrograms/l; after: 138; range 69-288 micrograms/l; P = 0.0001), while 21 subjects who mainly used air guns displayed no significant increase (before: median 91, range 47-179 micrograms/l; after: 84; range 20-222 micrograms/l). Thirteen archers had significantly lower levels than the pistol shooters before the season (P = 0.006), and showed a significant decrease during the season (before: median 61, range 27-92 micrograms/l; after: 56; range 31-87 micrograms/l; P = 0.04). At the end of the indoor season, there was a significant association between weekly pistol shooting time and blood lead levels.


Comparative evaluation of urinalysis and blood analysis as means of detecting exposure to organic solvents at low concentrations. One hundred and forty-three workers exposed to one or more of toluene, xylene, ethylbenzene, styrene, n-hexane, and methanol at sub-occupational exposure limits were examined for the time-weighted average intensity of exposure by diffusive sampling, and for biological exposure indicators by means of analysis of shift-end blood for the solvent and analysis of shift-end urine for the corresponding metabolite(s). Urinalysis was also performed in 20 nonexposed control men to establish the "background level." Both solvent concentrations in blood and metabolite concentrations in urine correlated significantly with solvent concentrations in air. Comparison of blood analysis and urinalysis as regards sensitivity in identifying low solvent exposure showed that blood analysis is generally superior to urinalysis. It was also noted that estimation of exposure intensity on an individual basis is scarcely possible even with blood analysis. Solvent concentration in whole blood was the same as that in serum in the case of the aromatics, except for styrene. It was higher in blood than in serum in the case of n-hexane, and lower in the cases of styrene and methanol.


An ecologic study of skin cancer and environmental arsenic exposure. We conducted an epidemiologic study of skin cancer incidence rates for four counties in Montana. The two counties considered to be exposed to arsenic were Deer Lodge, containing the former Anaconda copper smelter, and Silver Bow, containing an open pit copper mine. Residents in these counties had potential exposure to arsenic and other heavy metals. Gallatin and Park counties served as controls. All histologically proven skin cancer cases during the period January 1980 through June 1986 were collected from pathology services and dermatologists in these four counties. In addition, all skin cancer cases from four dermatologists practicing in urban referral areas outside the counties were reviewed. Results were analyzed by individual as well as by two different definitions of anatomically distinct lesions: the National Cancer Institute (NCI) definition and the study definition. There were 1616 individuals with skin cancer in the four counties during the period under consideration, yielding 2252 (NCI definition) and 2451 (study definition) cases. The clinical features of the skin cancers in the exposed counties were not similar to those described for arsenic-related skin cancer. The age-adjusted annual skin cancer rates were higher for the two control counties as compared to either the county with the former smelter, Deer Lodge, or the county with the mine, Silver Bow. Our results cannot be explained by differences in ascertainment, latitude, or altitude. They can be partially explained by differences in both outdoor employment and medical practice. The overall skin cancer incidence rates for the exposed counties were well within the range of skin cancer rates observed for other locations in the United States.


Quantification of heat balance during work in three types of asbestos-protective clothing. Three types of protective suits for asbestos removal work were tested in a climatic chamber at two ambient temperatures, 25 degrees and 36 degrees C. Four subjects performed 50 min of bicycle exercise at 90 W dressed in shorts, socks and sneakers (NoPS). The same test was carried out with three different types of asbestos-protective suits worn on top of NoPS. Suits were made of GoreTex (GT), polypropylene (PP) and Tyvek (TYV). At 25 degrees C, responses differed very little between suits and thermal strain was small. At 36 degrees C, strain was least with NoPS. TYV resulted in significantly higher physiological and thermal strain than did PP and GT. Evaporative heat loss was maintained at a similar level with less permeable ensembles, but at the expense of increased skin wetness and sweat rate. Measured values compared favourably with calculated values for skin wetness and sweat rate according to ISO 7933, when resultant, rather than standard, basic data for insulation and evaporative resistance of ensembles were used. Results indicate that differences between suits that may be of little importance at normal room temperature become significant at higher stress levels (increased activity and/or air temperature).


Vibration syndrome among Finnish forest workers between 1972 and 1990. A longitudinal study on vibration syndrome among professional forest workers was carried out in Finland from 1972 to 1990. In the course of the follow-up the weighted vibration acceleration of chain saws decreased from about 14 to 2 m/s2. The prevalence of vibration-induced white finger (VWF) decreased gradually from 40% to 5%. Numbness occurred mainly at night, and its prevalence decreased from 78% to 28%. During part of the follow-up period (1975-1990) the complaints of hand muscle weakness decreased from 19% to 9%. Disorders of the musculoskeletal system were considered to cause more disability than VWF. The decreased vibration acceleration and the lighter weight of chain saws were considered the main reasons for the decrease in the prevalence of vibration-induced symptoms.


Prevalence of respiratory allergy in a platinum refinery. In a cross-sectional study, 65 workers in the chemical industry with exposure to platinum salts were investigated with regard to the prevalence to allergic respiratory tract diseases. A respiratory questionnaire, a skin-prick test with K2PtCl6 and environmental allergens, determination of total IgE, platinum-specific IgE and histamine release in basophilic granulocytes and lung function tests were applied before and after a Monday shift and after a Friday shift. Work-related symptoms of respiratory allergy were present in 23% of all workers, but were significantly more frequent in the most exposed group in the platinum refinery (52.4%). Of all workers, 18.7% had a positive skin-prick test with platinum salt. As compared to the other workers, the workers with work-related symptoms of respiratory allergy had significantly more positive skin-prick tests (64.3%) and a higher total IgE and platinum-specific IgE; they did not, however, show higher histamine release. In the course of the week, a significant fall in lung function, namely in FEV1 and FEF25, was recorded in the group of workers with work-related symptoms.


Chronic occupational exposure to organic solvents. XV. Glycol ether exposure during the manufacture of brakehoses. Twenty-two persons (20 men and 2 women) were examined for their external and internal exposure to the glycol ether 1-methoxypropan-2-ol (PGME) during the production, leak testing and mounting of brakehoses. For the measurement of external exposure, personal air monitoring was the method of choice. Average concentrations of PGME of 82.2 mg/m3 (22.3 ppm), 68.6 mg/m3 (18.6 ppm) and 11.3 mg/m3 (3.1 ppm) were found in the air of the brakehose production, leak test and mounting areas, respectively. For the estimation of internal exposure to PGME, this glycol ether was measured in both urine and blood. The biological samples were taken post-shift. The highest internal exposure levels were found in the brakehose production section and in the leak test area. The average post-shift concentrations for PGME in workers in the brakehose production section were 4.6 mg/l in urine and 13.5 mg/l in blood; the corresponding figures for workers in the leak test area were 4.2 mg/l in urine and 11.0 mg/l in blood. In blood and urine samples of workers engaged in the mounting area, PGME levels were below the detection limits. The elimination kinetics of PGME were also studied in three highly exposed persons, and mean excretion half-lives of PGME of approximately 4.4 h were found. On the basis of our results we made a rough calculation of a future biological tolerance value: we would except that concentrations of 38-109 mg per litre of blood and 10-31 mg per litre of urine would correspond to the German MAK value for PGME (375 mg/m3).


Internal exposure to organic substances in a municipal waste incinerator. Fifty-three persons occupied in a municipal waste incinerator were examined with respect to their internal exposure to organic substances which may be produced during pyrolysis of organic matter. For this purpose the levels of benzene in blood, polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) in plasma, and mono- (MCPs), di- (DCPs), tri- (TCPs), tetra- (TCEPs) and pentachlorophenol (PCP) and hydroxypyrene in urine were determined. For control purposes, 431 men and women were examined. Significantly higher values for the workers were found for the excretion of hydroxypyrene [median (m): 0.24 vs 0.11 microgram/l; non-smokers], 2,4/2,5-DCP (m: 10.5 vs 3.9 micrograms/l) and 2,4,5-TCP (m: 1.2 vs 0.8 micrograms/l) and for the HCB level in plasma (m: 4.4 vs 2.8 micrograms/l). For the concentrations of 4-MCP and 2,3,4,6/2,3,5,6-TECP, the controls had significantly higher concentrations in urine than did the workers in the incineration plant (m: 4-MCP 1.7 vs 1.2; 2,3,4,6/2,3,5,6-TECP: 1.2 vs 0.3 micrograms/l). No significant differences between workers and controls were detected with respect to benzene in blood (m: 0.20 vs 0.28 microgram/l; non-smokers), 2,4,6-TCP and PCPs in urine (m: 0.85 vs 0.60 and 2.2 vs 2.2 micrograms/l) or the levels of PCB congeners in plasma (m: sigma 138, 153, 180: 5.6 vs 4.1 micrograms/l). The elevated levels of hydroxypyrene, 2,4/2,5-DCP, 2,4,5-TCP and HCB in biological material may be related to the incineration of the waste. These elevations, however, are very small and are of interest more from the environmental than from the occupational point of view.


Aspects of granulocyte function in workers professionally exposed to pesticides. Granulocyte function in 92 workers from a chemical plant for the production of pesticides was tested by means of the nitro-blue tetrazolium test (spontaneous and stimulated) and the phagocytosis test. Two opposite types of change were identified, namely increased and reduced functional activity. No reliable correlation between the studied parameters and length of service was found. In comparison with the routine hematological methods, the identified functional changes in polymorphonuclear neutrophil granulocytes serve as an early indicator of an impact on the leukocytes. The applied methods are accessible and may be used as an objective means of studying the dynamics of the unfavorable effect of zineb and of identifying groups at increased toxicological risk.


Medical wastage in shipyard welders: a forty-year historical cohort study. A 40-year historical cohort study of medical wastage among about 550 shipyard welders and 1100 controls (shipwrights and engine fitters), all employed at the same shipyard, was carried out. The welders left their job 20% more often than the controls; the excess considerably increased with duration of employment. Wastage was particularly due to respiratory, cardiovascular, locomotor and mental disorders. Both welders and controls contributed considerably (about 20%) to permanent work disability. Medical wastage among welders because of respiratory diseases was more than four times higher than among controls, which could not be explained by differential smoking habits alone. The study raises concern about locomotor health hazards for shipyard workers. Moreover, it underscores the need to reduce the large excess risk of respiratory diseases among shipyard welders. The same may be true for welders in other large metal construction plants, e.g. in boiler production.


Effects of noise on mental performance with regard to subjective noise sensitivity. Objective and subjective effects of moderate levels of recorded traffic noise [Leq = 55 dB(A) and 75 dB(A)] on mental performance were studied in a laboratory setting. A total of 45 subjects (23 males and 22 females) were investigated with respect to subjective noise sensitivity (SNS). Four cognitive tasks were applied involving different psychological functions: Short-Term Memory (STM), Search and Memory 5 (SAM 5) (vigilance), Hidden Figures (HF) (spatial reasoning) and Mental Arithmetic (MA) (parallel processing). Three groups of 15 subjects were defined according to their scores on Weinstein's Noise Sensitivity Scale as tolerant, moderately sensitive or highly sensitive to noise. A similar level of performance was observed in the three groups under quiet conditions [30 dB(A) Leq], but under noisy conditions significant differences (P < 0.05) were seen between them on the STM (words) and MA (total results) tasks, and the lowest performance accuracy was demonstrated by the noise-sensitive subjects. SNS was the primary factor responsible for these differences. There were no significant differences between the groups in respect of the SAM 5 and HF tasks, under either quiet or noisy conditions. Annoyance while performing tasks under noisy conditions was regularly and significantly higher among subjects judged to be noise sensitive on Weinstein's scale, as compared with those judged to have low or moderate SNS.


Chromosome and sister-chromatid exchange analysis in peripheral lymphocytes, and mutagenicity of urine in anesthesiology personnel. Genotoxic effects of occupational exposure to anesthetic gases (halothane and nitrous oxide) were studied in 24 persons working at departments of anesthesiology and resuscitation (14 anesthesiologists and 10 anesthesiologic nurses). Frequencies of chromosomal aberrations were determined in 48-h cultures, and sister-chromatid exchanges (SCEs) in 72-h cultures of peripheral lymphocytes. In parallel, the mutagenetic potential of urine was tested using Ames tester Salmonella typhimurium strains TA98 and TA100 in both the presence and the absence of a metabolic activation system. The control group consisted of 30 healthy blood donors from the Clinic of Hematology and Blood Transfusion. Halothane concentrations in the working environment of operating rooms were determined using gas-liquid chromatography. Halothane exposure levels were far above the maximum allowable concentration in most countries, ranging between 9 and 490 mg.m-3. Cytogenetic analysis of peripheral lymphocytes revealed significantly increased frequencies of aberrant cells (ABCs) and SCEs in the exposed group as compared with the controls (3.84% vs 1.87% ABCs, 8.69 +/- 1.30 vs 7.86 +/- 1.07 SCEs per cell). Results of the urine mutagenicity test were negative.


Upper airway obstruction and the Robin sequence. Both the etiology of Robin sequence and the mechanisms of upper airway obstruction are heterogeneous. As a result, generalizations about the care of newborns with the combination of micrognathia, cleft palate, and airway obstruction cannot be made. Management of the airway obstruction should be based on the results of direct endoscopic observation of the site of obstruction and not on the presumptive diagnosis of glossoptosis. It should not be assumed that "catch-up growth" of the mandible will occur and lead to spontaneous resolution of either the airway obstruction or the micrognathia. The presentation of the child with Pierre Robin sequence should not be the end of the diagnostic search, but rather the beginning.


Pharyngeal flap surgery: postoperative complications. Using a protocol specifically designed to decrease the risk factors for postoperative morbidity and upper airway obstruction, we have essentially eliminated major complications after pharyngeal flap surgery while maintaining excellent speech results. The protocol includes inserting a short pharyngeal flap into a tissue "sandwich" and keeping an NP tube in place for 48 hours postoperatively. The complications reduced by use of this protocol include apnea and other upper respiratory complications, as well as bleeding. In addition, postoperative discomfort is decreased with the current protocol. Using this approach, pharyngeal flap surgery is highly effective in improving speech and is associated with low morbidity.


Flexible bronchoscopy in infants.

Flexible bronchoscopy in infants. Flexible bronchoscopy is a useful diagnostic and sometimes therapeutic tool in small or premature infants, just as it is in older children. Special diligence is required to monitor the child before, during, and after the procedure, and to choose the appropriate instrument. Procedures must be completed rapidly, because most premature infants will be essentially apneic during the time the tip of a flexible bronchoscope is below the glottis. For some procedures, a rigid instrument may be a better choice, although for the majority of diagnostic procedures, flexible instruments are entirely satisfactory.


The effect of gastroesophageal reflux on the pediatric airway. The child with airway signs and symptoms that may be associated with GER presents diagnostic challenges. A high index of suspicion may be needed to make the diagnosis of GER, because no one test gives consistently definitive results. Specialists from multiple disciplines, including otolaryngology, gastroenterology, pulmonology, pediatrics, critical care, anesthesiology, and pediatric surgery may ultimately need to work together to arrive at the correct diagnosis and implement appropriate therapy.


Autoperfusion balloon catheter for complicated coronary angioplasty: a prospective study with retrospective controls. Prolonged angioplasty balloon inflation with an autoperfusion balloon for failed conventional coronary angioplasty, was compared with emergency surgery for this condition. Restenosis was assessed 6 weeks after successful intervention with the autoperfusion balloon. Forty consecutive patients with persistent acute occlusion and/or severe intimal dissection during conventional angioplasty, were treated with the autoperfusion balloon. They were candidates for emergency surgery if it failed. Total inflation time was significantly longer (p < 0.001) with the autoperfusion balloon (27.5; 10-180 min) than with the standard balloon (10; 1-20 min) (median; range). The number of inflations was significantly lower (p < 0.001) with the autoperfusion balloon (2; 1-5 times) than with the standard balloon (5; 2-14 times) (median; range). Two patients died, one before surgery could be performed. The autoperfusion balloon was successful in 26 patients (65%). After 6 weeks, 16 (62%) were asymptomatic without anti-anginal medication, 24 underwent repeat angiography, 10 (42%) had restenosis, 7 (27%) underwent elective bypass surgery. Emergency surgery remained necessary in 13 patients (33%), 9 received arterial grafts. In 31 retrospective controls, who had undergone immediate surgery for the same indication, only venous grafts could be used. Thus, prolonged autoperfusion balloon inflation was successful in 65% of the cases of failed, conventional angioplasty. The angiographic restenosis rate after 6 weeks was 42%. If emergency surgery remained necessary, the autoperfusion balloon facilitated the use of arterial bypass grafts.


Surgical treatment in tetralogy of Fallot diagnosed by echocardiography. The purpose of this paper is to present the authors' 3-yr experience of echocardiographic examination of patients with the clinical diagnosis of tetralogy of Fallot, and their evaluation for surgical treatment without prior cardiac catheterization. Among the patients with the clinical diagnosis of tetralogy of Fallot 227 had a definite diagnosis made by M-mode, two-dimensional, Doppler and contrast echocardiography. For the diagnosis of tetralogy of Fallot, ventricular septal defect, pulmonary stenosis, and overriding of the aorta were considered to be fundamental. Ventricular septal defect could be seen easily in the subaortic region by two-dimensional echocardiography. However, in some patients whose ventricular septal defect was not seen clearly, peripheral vein contrast echocardiography was performed. The diameters of pulmonary artery, and main branches at a few millimeters distal to their origin were measured. These parameters were correlated with the aortic diameter for evaluation as to whether they were able to accept the total cardiac output. In patients whose left ventricular end-diastolic dimension was small, shunt operation was preferred. In 115 patients the pediatric cardiologist performing the echocardiography thought that cardiac catheterization was necessary. In these cases the reliability of echocardiography in detecting important cardiac abnormalities was evaluated. Detection of ventricular septal defect, presence of pulmonary valve, detection of stenosis on the pulmonary bifurcation and/or main branches revealed a high sensitivity. Two-hundred-and-one patients diagnosed by echocardiography underwent total correction. In all cases except one the preoperative diagnosis was confirmed by surgery.(ABSTRACT TRUNCATED AT 250 WORDS)


Myocardial vitamin E is consumed during cardiopulmonary bypass: indirect evidence of free radical generation in human ischemic heart. Although a role for free radicals in myocardial damage during cardiopulmonary bypass for open heart surgery has been postulated, direct evidence of free radical production as well as consumption of tissue antioxidants such as vitamin E is still lacking. Twenty patients (age 26-66 yr, mean 48) undergoing elective open heart surgery with moderate hypothermia, and cold crystalloid cardioplegia, were studied. Cardiopulmonary bypass time was 61.4 +/- 31.2 min. The specimens of atrial tissue collection before and after cardiopulmonary bypass, were immediately frozen in liquid nitrogen. Mean vitamin E atrial content, measured by reverse phase HPLC, was 355 +/- 249 pmol/mg of dry weight basally, 135 +/- 85 pmol/mg (p < 0.05) at the end of the ischemic period and 405 +/- 288 pmol/mg after the reperfusion period (p < 0.01). Microscopic examination of right atrial biopsies ruled out differences in fibrosis or cellular damage as the cause of vitamin E changes. Although a great basal variability in atrial vitamin E content was observed, which was independent of age, sex and clinical status, a reproducible and substantial decrease in atrial vitamin E content after cardiopulmonary bypass occurred (mean reduction 45 +/- 17% and 55 +/- 22%, respectively, after ischemia and after reperfusion). This was directly related to the aorta cross-clamping duration and partially to the minimum temperature achieved. In conclusion, apart from the great variability observed in basal vitamin E tissue content, vitamin E was always reduced during cardiopulmonary bypass, suggesting an oxidative stress on the myocardium during open heart surgery.


Microalbuminuria and other cardiovascular risk factors in nondiabetic subjects. The association between urinary albumin:creatinine ratio and other cardiovascular risk factors such as age, blood pressure, obesity, glycemic indices, insulin and lipid profile was examined in a population in a Chinese community consisting of 795 men (mean age 35.8 +/- 8.8 yr) and 538 women (mean age 37.9 +/- 8.9 yr) with a normal glucose tolerance defined by WHO criteria. Men with a urinary albumin:creatinine ratio above the 90th percentile had higher systolic and diastolic blood pressures, fasting plasma glucose, 2-h glucose after a 75 g oral glucose load, and fasting serum insulin. Women with high urinary albumin:creatinine values had higher systolic and diastolic blood pressures, body mass index, waist-hip ratio, fasting insulin and triglycerides. Multivariate analysis showed that only systolic blood pressure and fasting glucose in men, and diastolic blood pressure and fasting insulin in women, independently contributed to urinary albumin:creatinine. When the effect of blood pressure was eliminated by excluding subjects with systolic blood pressure > 140 and diastolic > 90 mm Hg, only fasting insulin was associated with urinary albumin:creatinine in women. No associations were found for men. We conclude that microalbuminuria may be a marker for cardiovascular disease only because of its association with blood pressure in men, while in women, there is an additional independent association with fasting serum insulin.


Early diastolic left ventricular function as a marker of acute cardiac rejection: a prospective serial echocardiographic study. Changes in left ventricular early diastolic time intervals are sensitive indicators of incipient left ventricular dysfunction. We tested the hypothesis that acute rejection in cardiac transplant recipients is associated with alteration of early diastolic myocardial function, as expressed by the time interval Te, a parameter derived from digitized M-mode echocardiograms. Te is defined as the time interval between maximal posterior wall contraction and the point of peak posterior wall endocardium retraction velocity, as determined by the nadir of the computed first derivative curve. In transplant patients without rejection (group A, n = 48), Te was prolonged compared to healthy individuals (group C, n = 35) (79.0 +/- 12.5 ms vs 64.0 +/- 7.9 ms; p < 0.0001). During acute rejection (group B, n = 18) transplant patients had significantly longer mean Te values compared to transplant patients without rejection (group A) (97.8 +/- 17.9 ms vs 79.0 +/- 12.5 ms; p < 0.0001). Longitudinal studies in individual patients (group D, n = 18) demonstrated that rejection is associated with prolongation of Te (94.5 +/- 16.0 ms during rejection vs 79.0 +/- 10.3 ms before rejection; p < 0.0002) and that Te returns to individual baseline values in response to treatment (79.2 +/- 9.4 ms after therapy vs 79.0 +/- 10.3 ms before rejection; NS). In a prospective study, Te changes in transplant patients (group E, n = 96) were correlated with myocardial biopsy results. Sixty-one biopsies showed acute rejection, and 115 biopsies were negative.(ABSTRACT TRUNCATED AT 250 WORDS)


Accuracy of percussion of the left cardiac border. The purpose of this study was to determine the accuracy of percussion of the left cardiac border. Sixty-six adult patients were studied. The left cardiac border as determined by percussion and marked with a calibrated lead marker was compared with that obtained by a chest X-ray. The error in locating the left cardiac border by percussion ranged from underestimating by 5.0 cm to overestimating by 5.5 cm. The mean absolute error was 1.6 cm (SD = 1.6 cm). In 74% (49/66) and 85% (56/66) of the patients the percussed border was within 1.0 and 2.0 cm, respectively, of that established by X-ray. In 24 of the 66 cases, a second examiner also independently percussed the left cardiac border. The differences between the location determined by the two observers ranged from 0 to 4 cm with a mean difference of 1.2 cm (SD = 1.0 cm). Percussion can accurately locate the left cardiac border in the adult patient and is a reproducible technique.


Anatomical origin of pressure-related ventricular ectopic rhythms. In order to determine the origin of pressure-related ectopic rhythms, the main arteries were clamped in 11 anesthetized dogs, or the arteries or veins were transfused, while on or off metaraminol. The epicardial right atrial electrogram, the intracavity electrograms and the pressure of the two ventricles were recorded. Sinus rhythm was associated with 64/64 (100%) of the control periods off metaraminol, but only 19/50 (38%) of the clamping of the main arteries (P << 0.0005). In 14/27 aortic clampings ectopic beats appeared from the left ventricle and in 13/27 from the right one. In 4/23 clampings of the pulmonary artery ectopic beats appeared from the left ventricle and in 15/23 from the right one (P < 0.05). Sinus rhythm was associated with significantly lower left ventricular systolic pressure than any ventricular arrhythmia. The left ventricular systolic pressure associated with ectopic rhythms from the left ventricle was significantly (P < 0.005) higher than that associated with those from the right ventricle. The right ventricular systolic pressure during sinus rhythm was significantly (P < 0.005) lower than that during ectopic rhythm from any ventricle. It is concluded that a rise in the pressure of one ventricle tends to cause ventricular ectopic rhythms originating predominantly, but not exclusively, from this ventricle. The origin of ventricular ectopic rhythms from the right ventricle does not preclude that the arrhythmia may respond favorably to lowering of the systemic pressure.


Assessment of spatial and temporal velocity profiles distal of normally functioning Björk-Shiley prosthesis by the Doppler method. By Doppler echocardiography, the performance of heart valve prostheses is assessed with the aid of maximal transprosthetic velocities, which, however, may not be representative for the full spatial velocity profile in the vicinity of mechanical valve substitutes due to flow separation by the open occluder. The purpose of this study was to determine characteristics of velocity profiles downstream of a normally functioning Björk-Shiley prosthesis. In a pulsatile flow apparatus, different flow rates of 6.3 and 8.4 l/min were delivered. Using a spatially and temporally resolving ultrasonic Doppler method, velocity profiles 20 and 30 mm distal from the prosthesis were registered and displayed in a three-dimensional grid. The spatial velocity profile was found to deviate substantially from a flat profile at these transducer positions at the two flow conditions. Distal to the minor orifice, velocities measured only 70 and 80% of those downstream of the major orifice. In between, a region of relatively slow moving flow was present. The shape of the profiles remained essentially unchanged during acceleration and deceleration of flow. Thus, spatially resolved velocity profiles downstream of mechanical prostheses can be registered by an ultrasonic Doppler device. These findings may be useful for the detection of beginning malfunction both in the experimental and the clinical setting.


Blood pressure changes during pregnancy in Nigerian women. The purpose of this longitudinal study was to determine the pattern of blood pressure during pregnancy in Nigerian women. The blood pressure of 189 women from early pregnancy and up to term, during labor and 24 h after delivery were monitored. The mean systolic, diastolic and mean arterial blood pressure were computed and the blood pressure readings were correlated with parity and selected anthropometric and socioeconomic variables. The results showed a decline in blood pressure levels during the mid-trimester of pregnancy with a progressive increase towards term. The highest blood pressures were recorded during the third stage of labor. The mean (+/- 2 SD) of blood pressure was 130/80 mmHg. There was no significant correlation of blood pressure with parity but there was a significant positive correlation with maternal age and Quetelex index after 30 weeks of gestation. As compared to Caucasian women, Nigerian women showed higher levels of diastolic blood pressures. We conclude that: (1) the higher incidence of gestational hypertension in African women may be due to higher levels of resting baseline blood pressures in the women, and (2) pregnant women in our population with persistent elevation of blood pressures above 130/80 mmHg should be closely monitored.


Assessment of cardiac adrenergic supply in mitral valve prolapse using m-[123I]iodobenzylguanidine scintigraphy. Presynaptic as well as postsynaptic adrenergic regulation abnormalities are reported in symptomatic patients with mitral valve prolapse. This study was undertaken to evaluate presynaptic sympathetic supply by m-[123I]iodobenzylguanidine scintigraphy in 17 preselected patients with mitral valve prolapse and symptoms suggestive of hyperadrenergic dysautonomia as compared to normal scintigraphic findings. Mitral valve prolapse was echocardiographically proven within the left parasternal long axis view. Percentual activity of m-[123I]iodobenzylguanidine in 33 sectors of all oblique slices along the short axis was calculated relative to the maximal uptake, set at 100%. In general, no significant differences of mean values of sectoral quantitative uptake of m-[123I]iodobenzylguanidine were detectable between patients and the control group. Only in two sectors of the basal anterolateral region P values < 0.01 were present. Thus, using m-[123I]iodobenzylguanidine scintigraphy as marker of cardiac adrenergic supply, no evidence of altered presynaptic hyperadrenergic supply was present in patients with mitral valve prolapse. These findings suggest postsynaptic regulation abnormalities to be preponderant in this condition.