Evaluation of treatment with single-dose ampicillin/sulbactam with probenecid or ceftriaxone in patients with uncomplicated gonorrhea. This study compared ampicillin/sulbactam plus probenecid with ceftriaxone for treatment of uncomplicated gonorrhea. Of the 297 men and women who were enrolled and randomized to receive either ampicillin/sulbactam (1.0 g/0.5 g) with probenecid (1 g) or ceftriaxone (0.25 g), 274 patients were evaluable. Both ampicillin/sulbactam and ceftriaxone were administered by intramuscular injections. Patients were gonococcal contacts, had positive culture results for Neisseria gonorrhoeae, or had clinical evidence of gonorrhea. Specimens for gonococcal cultures were collected from the cervix (female patients), urethra, rectum, and pharynx at pretreatment and test-of-cure visits. The presence of N. gonorrhoeae and a test-of-cure visit were required for drug efficacy analysis. Of the 274 evaluable patients, 195 (71.2%) had positive culture results for N. gonorrhoeae. Cure was achieved in 93 (94.9%) of 98 patients receiving ampicillin/sulbactam with probenecid and in 96 (99.0%) of 97 patients receiving ceftriaxone. Penicillinase-producing N. gonorrhoeae strains were found in 21 (10.8%) patients; these were eradicated by either ampicillin/sulbactam with probenecid (N = 9) or ceftriaxone (N = 12). Overall, the two drug regimens were very well tolerated and no serious adverse effects were noted. Ampicillin/sulbactam with probenecid may be useful as single-dose therapy in patients with uncomplicated genitorectal gonorrhea.


Behaviors of crack cocaine users and their impact on early syphilis intervention. The impact of crack use on syphilis intervention was investigated by reviewing records of persons diagnosed with early syphilis when voluntarily attending County Health Department clinics in Detroit, Michigan and Dallas, Texas between August 1989 and August 1990. The sample was stratified and data were analyzed using multivariate techniques. Compared with men who did not use crack, male crack users were more likely to report having four or more sexual partners during their critical period for acquiring or passing on infection (odds ratio, OR = 4.33; 95% confidence interval, CI = 2.08, 8.99). Among men, having a large number of sexual partners during this period was associated with a lower percentage of contacts being examined (OR = 11.8; 95% CI = 2.91, 47.5). Among women, having four or more sexual partners during their critical period and a lower partner examination rate were both associated with crack use; crack use was strongly associated with exchanging sex for money or drugs. We conclude that crack use has the largest impact on syphilis intervention through its association with having large numbers of sexual partners.


Compliance with antibiotic therapy for Chlamydia trachomatis and Neisseria gonorrhoeae. Control of bacterial sexually transmitted diseases (STD) depends on adequate antibiotic therapy. During a 4-week period, a survey concerning compliance was administered to all patients attending an STD clinic who were being treated with one of the standard antibiotic regimens for presumed gonococcal or chlamydial infections. Of the 497 eligible patients, 406 (81.7%) were surveyed between 24 hours and 72 hours after the end of treatment. Of those being treated with the standard 7-day regimen of tetracycline or erythromycin, 63.4% complied. Compliance was not associated with race, gender, symptoms, or antibiotic regimen. Those who were younger, were sexual contacts of an infected partner, or had gastrointestinal side effects were more likely not to comply with treatment.


[Immunohistochemical determination of antigen 19-9 (CA 19-9) in transitional carcinoma of the bladder]. Carbohydrate Antigen 19-9 (CA 19-9) histological expression in transitional cell bladder carcinoma (TCBC) was studied by means of immunohistochemistry and its findings compared with those of Tissue Polypeptidic Antigen (TPA) and Carcino Embryonic Antigen (CEA). Twenty-one TCBC of various grade and stage were analyzed by using Avidin-Biotin complex method for CA 19-9 and TPA Peroxidase-Antiperoxidase method for CEA. Grade 3 and pT1, pT2/pT3 carcinomas showed a constant staining for CA 19-9 antigen, grade 2 showed a 50% positive immunoreaction while all grade 1 cases were negative. TPA showed an inverse correlation with well differentiated carcinomas which were better and more extensively stained than anaplastic ones. CEA expression was not correlated either with grade or stage. CA 19-9 could be considered as a dedifferentiation marker in TCBC.


[Uroflowmetry in the early diagnosis of postoperative urethral stenosis]. Uroflowmetry is a widely used technique for evaluation of lower urinary tract "obstructions", and urethral strictures (US) are considered a typically late complication after endoscopic or open prostatectomy. The clinical experience of the Department of Urology of Catania University is reported. Uroflowmetry was included in routine checks of prostatic patients after operation (TUR or open surgery) and the tests were performed at 40 and 180 days post-operatively. This proved to be an effective and objective means for early diagnosis of urethral strictures.


[Diagnostic imaging of kidney carcinomas. Our experience and review of the literature]. In the image diagnosis of renal carcinoma echotomography has played an increasingly important role over the past ten years due to its simplicity and low costs. This method is responsible, above all, for the increased number of diagnosed cases of kidney carcinoma at a pre-clinical stage, the so called "incidentaloma", for which an aggressive surgical approach may be employed with good probabilities of the patient's complete recovery Having illustrated their personal experience of the diagnosis of renal carcinoma, the Authors review currently used imaging methods.


[Percutaneous use of vasoactive drugs in the diagnosis and treatment of erectile impotence]. The Authors report their experience of topical and intracavernous treatment with papaverine and phentolamine in patients with erectile dysfunction from May 1988 to March 1992. Topical application of drug cream proves efficacious both alone or combined with intracavernous injection with PGE1. Topical treatment besides may be carried out without systemic or local complications.


[Treatment of prostatic carcinoma in an advanced stage. Our experience]. The authors report the results of a retrospective study regarding 214 patients (mean age 73, smallest follow-up 6 months, greatest 70 months, average 42 months) affected by advanced prostatic cancer histologically demonstrated, observed from January 1983 to December 1990 and subject to hormonal treatment. They particular compared so-called "total androgenic suppression" (Gn-RH analogous or orchiectomy plus antiandrogen) with the "partial androgenic suppression" (Gn-RH analogous or orchiectomy). The authors report the results of the treatment regarding the subjective and the objective response, evaluated with NPCP criteria. Moreover the actuarial aspects of response and survival curves of two groups of patients are compared. The authors conclude that total compared to partial androgenic suppression does not offer significant advantages as regards to objective response and present their current treatment of advanced prostatic cancer.


[Advanced carcinoma of the prostate (stages C and D). Mortality within 12 months of the initiation of hormonal therapy]. Seventy-three patients with stage C and D prostatic carcinoma were treated with hormonotherapy. During a mean follow-up of 27 +/- 17.8 months, 30 tumour-related deaths were registered. The patients in the G3 subset suffered a 35.7% early death rate versus a 10.1% rate of G1-2 ones. This difference is significant (p = 0.0102). Nevertheless the Authors' opinion is that G3 patients should not be given a more aggressive treatment initially apart from the case of a controlled trial.


[The ultrasonographic examination in hematuria. Evaluation of its diagnostic possibilities]. Hematuria is a very frequent clinical occurrence and is connected with a number of genito-urinary diseases. Our present work is aimed at checking the usefulness of ultrasonography (US) in etiological diagnostic of hematuria. 516 patients with hematuria and 1788 controls were included in the present study. Renal and urological diseases were found in 74% of patients with hematuria and in 22.7% of those without. Their prevalence is analogous of the general population for those diseases easily detectable by US, such as cystic and heteroplastic diseases. On the contrary, no correspondence was observed for cases of inflammatory, for which echography has never been a reliable diagnostic tool. Furthermore, US sensitivity, if associated with hematuria, was 93%, specificity was 100%, diagnostic accuracy 99% and predictive value about 100%. Ultrasonography is easy to perform, well tolerated, involves low cost and may therefore be considered as the investigation technique of choice for the study of hematuria.


[Comparison of efficacy and tolerability among 3 quinolones in the treatment of lower urinary tract infections (cinoxacin versus ciprofloxacin and pefloxacin]. A clinical trial was carried out in 150 patients with lower urinary tract infections in order to compare the efficacy and tolerability of three quinolone drugs (cinoxacin, ciprofloxacin, pefloxacin). The satisfactory therapeutic efficacy of all three drugs is underlined, as is the excellent tolerability of cinoxacin.


[A case of Leydig cell tumor of the testis]. Leydig cell tumors represent about 3% of all testicular neoplasms. Actually no specific pathologic criteria has really distinguished the benign from the malignant tumors which represent about 11% of the cases. The presence of metastases is the only unequivocal criteria of malignancy. Authors present a rare Leydigoma case with gynecomastia. Clinical, diagnostical and most of all therapeutical aspects are discussed reconfirming the role of the orchifuniculectomy in T1 N0 M0 stage.


[Conservative surgical therapy in the treatment of renal carcinoma]. The authors report results in 10 patients (5 with renal neoplasms in a single kidney, 4 with healthy contralateral kidney, and one with a pathological opposite kidney following conservative surgery: 4 surgical enucleations and 6 partial nephrectomies.


[Transitional cell carcinoma of the urethra in patients after cystectomy for bladder carcinoma]. Transitional cell carcinoma of the urethra in men after radical cystectomy for bladder carcinoma have an incidence which varies from 4 to 18%. The Authors present their experience of 6 cases (6/196; 3.06%) analysing the characteristics of the urethral neoplasm and confirming the systematic cystourethrectomy when there is a urethra prostatic and bladder neck infiltration or when there is a urethral ca in situ. It also underlines the role of the clinical, radiological, cytological and urethro-endoscopical follow-up in patients who have undergone a cystoprostatovesciculectomy.


A cross-cultural study of occlusal tooth wear. Occlusal and incisal tooth wear were evaluated for the purpose of assessing their prevalence, severity and distribution in a selected Swedish high-wear patient sample and in a young adult Saudi non-patient population. Furthermore, an attempt was made to investigate, by means of a questionnaire and a clinical examination, the association of various factors with wear; any observed associations were further analyzed with reference to possible cause and effect relationships. The scales used for evaluating the severity and the progression of wear provided high inter- and intra-observer concordances. The results revealed a high wear experience in the Saudi population compared to Western equivalents. Dietary, para-functional, anamnestic, occlusal and salivary factors exhibited certain correlations with wear. Progression of tooth wear was shown to be a slow process in the Swedish sample. The common element of a harsh desert terrain in the Saudi sample may constitute the dominant passive abrasive etiological factor in this population. While progression of wear seems to be of a "linear" nature in the Saudi population, it is postulated that wear in Western populations may, in addition to a "linear" deterioration, occur in "bursts", coinciding with the presence of certain causative factors. The results from this study also indicate that the effects of excessive function, including that of wear, on certain dentoalveolar morphological features are similar in modern man and his ancestors. On the basis of the findings, not only is the multifactorial etiology of occlusal tooth wear a reality, but so too is the complex interdependence of these factors in the prevalence, severity, distribution and progression of wear.


Acupuncture in the treatment of patients with craniomandibular disorders. Comparative, longitudinal and methodological studies. The aim of the thesis was to compare the short- and long-term effects of acupuncture and occlusal splint therapy in patients with craniomandibular disorders (CMD). One hundred and ten patients, 23 males and 87 females, participated in the study. All patients exhibited moderate or severe signs and symptoms of CMD and had had pain for more than six months. The participants were randomly assigned to three groups: acupuncture, occlusal splint therapy or control. Ten different subjective and/or clinical assessment variables were used in the evaluation of the treatment effect. Immediately after treatment, acupuncture and occlusal splint therapy had reduced the symptoms as compared with the control group which remained essentially unchanged. Acupuncture gave better subjective results than occlusal splint in the short-term. In the 12-month long-term follow-up, 57% of the patients who received acupuncture and 68% of the patients who received occlusal splints benefitted subjectively and clinically from the treatment. There were no statistically significant differences between the two groups in any of the assessment variables. Those patients who received various additional therapies following acupuncture and/or occlusal splints rarely responded favorably to additional treatment. No serious adverse events or complications were observed in the study. Acupuncture seems to have adverse events of a more general nature whereas adverse events of the occlusal splint seem to be more related to the orofacial region. The majority of the patients responded positively to the comfort of both treatment modes. In order to measure tenderness (pressure pain threshold, PPT) more objectively, the usefulness of an algometer was evaluated. A good reliability and validity was found for the algometer in recording the PPT in the masticatory muscles. The reliability was further improved by connection of a stopwatch to the algometer so that the pressure rate could be kept within acceptable limits. A moderate but statistically significant correlation was found between PPT and clinical and subjective variables. The algometer was sensitive enough to detect pre- and post-treatment changes. A statistically significant reduction in tenderness was found immediately after and at the 6-month follow-up for both treatment modes. This series of studies showed that acupuncture gave positive results similar to those of occlusal splint therapy in patients with primarily myogenic CMD symptoms over a 1-year period.


Post-treatment effects of the Herbst appliance. A radiographic, clinical and biometric investigation. The treatment effects of continuous bite jumping with the Herbst appliance in the correction of Class II malocclusions have been analysed in previous investigations. The purpose of this study was to investigate the post-treatment effects of the appliance as well as to compare various mandibular anchorage systems. The total patient sample consisted of 108 malocclusion cases treated with the Herbst appliance. The subjects in the various parts of this study were selected from the total sample according to different criteria. The study included analyses of lateral cephalometric radiographs in centric occlusion and with the mouth wide open, lateral tomograms of the temporomandibular joints, growth records and dental casts. A clinical examination of the patients and a questionnaire at the time of follow-up was also included. During Herbst appliance therapy, all subjects were treated to a Class I or overcorrected Class I relationship. During the post-treatment period of 12 months, the occlusion settled into Class I, mainly as a result of relapsing (recovering) maxillary and mandibular tooth movements. Ninety per cent of the dental changes occurred during the first 6 months post treatment. The anterior movement (proclination) of the mandibular teeth during treatment could not be prevented even if the anchorage system was increased by incorporating more dental units. In the long-term perspective (5-10 years after treatment), it was found that Herbst treatment improved the sagittal jaw base relationship but without normalising it. The sagittal dental arch relationship, on the other hand, was almost normalised. The growth period in which the subjects were treated did not seem to have any impact on the long-term result. Furthermore, Herbst appliance therapy did not seem to have any long-term adverse effects on the craniomandibular system.


Causality in medicine: towards a theory and terminology. One of the cornerstones of modern medicine is the search for what causes diseases to develop. A conception of multifactorial disease causes has emerged over the years. Theories of disease causation, however, have not quite been developed in accordance with this view. It is the purpose of this paper to provide a fundamental explication of aspects of causation relevant for discussing causes of disease. The first part of the analysis will discuss discrimination between singular and general causality. Singular causality, as in the specific patient, is a relation between a concrete sequence of causally linked events. General causation, e.g. as in disease etiology, means various categories of causal relations between event types. The paper introduces the concept of a reference case serving as a source for causal inference, reaching beyond the concept of general causality. The second part of the analysis provides exemplification of a theory of causation suitable for discussing singular causation. The chain of events that induce a disease state can be identified as effective causal complexes, each complex composed of non-redundant components, which separately contribute to the effect of the complex, without the individual component being necessary or sufficient in itself to produce the effect. In the third part of the analysis the theory is elaborated further. Causes, defined as non-redundant components, can furthermore be differentiated according to their avoidability, according to theories about human error or by the potential of eradication. Multifactorial models of disease creates a need for systematic approaches to causal factors. The paper proposes a taxonomical terminology that serves this purpose.


Selection bias in using data from one population to another: common pitfalls in the interpretation of medical literature. The prevalence, course and prognosis of diseases in patients referred to tertiary medical centers frequently differ from those treated in primary care settings. Extrapolation of findings from one population to another may therefore be unwarranted. Other factors that contribute to misinterpretation of medical literature include failure to distinguish statistical from clinical significance and advocacy of medical interventions prior to adequate clinical trials.


The importance of primary care for theoretical medicine: a commentary. Froom and Froom call attention to referral bias as a frequent cause for misinterpreting the medical literature. This is particularly a source of false certainty, and therefore false science, in U.S. practice, where referral centers are often seen as the only legitimate source of medical knowledge and where primary care is discounted as a source of scientific observations. Appreciation of the primary care setting is therefore a critical element in theoretical understanding of medical epistemology.


Meta-diagnosis: towards a hermeneutical perspective in medicine with an emphasis on alcoholism. This essay argues that making a diagnosis in medicine is essentially a hermeneutic enterprise, one in which interpretation skills play a major part in understanding a disease. The clinical encounter is an event comprised of two 'voices'; one is the voice of science which is grounded in empiricism, the other is that of human experience, which is grounded in story-telling and the interpretation of those stories. Using two 'voices', one from the Diagnostic and Statistical Manual of Mental Disorders-III-Revised, which describes 'alcohol abuse' and 'alcohol dependence', and the other, that of Claire, a character in Edward Albee's play, A Delicate Balance, who is conversing with her brother-in-law, Tobias, I apply principles from Hans-Georg Gadamer's hermeneutics to the clinical diagnostic process. The essay will demonstrate that we overlook an enormous amount of information about alcoholism by an over-reliance on 'objective data' and that our hope for understanding alcoholics is in listening to their voices, and sharing the interpretation of their experiences with them.


Why physicians should not do ethics consults. Increasing complexities facing physicians negotiating the bedside decision continue to fuel the debate over who is the appropriate party to offer ethics consults, should one be needed, during the decision-making process. Some very good arguments have been put forth on behalf of clinical ethicists as being the proper and best party to engage in ethics consultations. However, serious questions remain about the role of the clinical ethicist and his ability to provide the necessary level of objectivity called for in an ethics consult. I argue that the clinician's professional psyche, or mode of thinking as a professional, leaves him little room to maneuver as an objective and detached third party ethics consultant. Several factors are cited and discussed that greatly influence the analyses applied to a case problem by physicians. The most formidable of these factors are habits and the practice of defensive medicine. I conclude that clinical ethicists are less suited for the overall tasks required of an objective consultant in medical cases that appear to involve insurmountable ethical issues.


Justice and care: the implications of the Kohlberg-Gilligan debate for medical ethics. Carol Gilligan has identified two orientations to moral understanding; the dominant 'justice orientation' and the under-valued 'care orientation'. Based on her discernment of a 'voice of care', Gilligan challenges the adequacy of a deontological liberal framework for moral development and moral theory. This paper examines how the orientations of justice and care are played out in medical ethical theory. Specifically, I question whether the medical moral domain is adequately described by the norms of impartiality, universality, and equality that characterize the liberal ideal. My analysis of justice-oriented medical ethics, focuses on the libertarian theory of H.T. Engelhardt and the contractarian theory of R.M. Veatch. I suggest that in the work of E.D. Pellegrino and D.C. Thomasma we find not only a more authentic representation of medical morality but also a project that is compatible with the care orientation's emphasis on human need and responsiveness to particular others.


Making peace in gestational conflicts.

Making peace in gestational conflicts. Mary Anne Warren's claim that "there is room for only one person with full and equal rights inside a single human skin" ([1], p. 63) calls attention to the vast range of moral conflict engendered by assigning full basic moral rights to fetuses. Thereby, it serves as a goad to thinking about conflicts between pregnant women and their fetuses in a way that emphasizes relationships rather than rights. I sketch out what a 'care orientation' might suggest about resolving gestational conflicts. I also argue that the care orientation, with its commitment to the significance of the partial and the particular, cannot be absorbed within standard, impartialist moral theory.


Blessed are the peacemakers: commentary on making peace in gestational conflicts. The purpose of this commentary on James Nelson's article [1] is to advocate introducing the ethics of care into the arena of gestational conflict. Too often the debate gets stalled in a maternal versus fetal rights headlock. Interventionists stress fetal over maternal rights: they believe education, post-birth prosecution or pre-birth seizure of pregnant women may be permissible. In contrast to interventionists, other philosophers stress that favoring fetal rights treats women like 'fetal containers'. I question whether we should really consider issues of moral/parental obligations to children in terms of rights. Rather, the language of care should guide moral conduct vis-a-vis children/fetuses. The particularity of each woman's story--the particulars of her human relationships--inform her story. An individual's ability to care is largely a function of whether community cares for her. We must care for others to enable them to care for themselves and their loved ones--born or unborn.


Organ transplants, foreign nationals, and the free rider problem. There is strong sentiment for a policy which would exclude foreigners from access to organs from American cadaver donors. One common argument is that foreigners are 'free riders'; since they are not members of the community which gives organs, it would be unfair to allow them to receive such a scare resource. This essay examines the philosophical basis for the free rider argument, and compares that with the empirical data about organ donation in the U.S. The free rider argument ought not to be used to exclude foreign nationals because it is based on fallacious assumptions about group membership, and how the 'giving community' is defined. Polls show that even among the seventy-five per cent of Americans who support organ donation, only seventeen per cent had taken the small step of filling out donor cards. Therefore, it goes against logic to define the giving community as coextensive with American residency, while excluding foreigners who might well have become donors had they lived in countries which provided that option.


Should physicians be bayesian agents?

Should physicians be bayesian agents? Because physicians use scientific inference for the generalizations of individual observations and the application of general knowledge to particular situations, the Bayesian probability solution to the problem of induction has been proposed and frequently utilized. Several problems with the Bayesian approach are introduced and discussed. These include: subjectivity, the favoring of a weak hypothesis, the problem of the false hypothesis, the old evidence/new theory problem and the observation that physicians are not currently Bayesians. To the complaint that the prior probability is subjective, Bayesians reply that there will be ultimate convergence, but the rebuttal to this is that there will not be uniform convergence. Secondly, since the Bayesian scheme favors a weak hypothesis, theories turn out to be a gratuitous risk. The problem with the false hypothesis comes out in the denominator of the theorem, revealing that a factor which is not a theory at all is being considered in the reasoning. On the old evidence/new theory problem old evidence cannot confirm a new theory so that the posterior probability will equal the prior probability. Finally, empiric studies have shown that current physicians are not Bayesians. But on consideration of Bayesian inference as a system of inference, it can be reasoned that physicians should be Bayesians. However, the problem of physicians' and patients' own subjectivity continue to plague this system of medical decision making.


T cell receptor repertoire of gamma delta cells generated from the 14-day embryonic mouse thymus. Whole, undisrupted 14 day mouse fetal thymus lobes cultured in the presence of 10 U/ml IL-2 generate a heterogeneous population of gamma delta-expressing T cells. Phenotypic analysis has shown that the majority of gamma delta T cells in such cultures stain with the anti-V gamma 3-specific mAb 536. To investigate the V gamma T-cell receptor diversity of cultured fetal thymocytes, cDNA was prepared and amplified using the polymerase chain reaction. The DNA fragments obtained were subsequently cloned and sequenced and compared with those obtained from fresh and organ-cultured 14 day fetal thymus lobes. Results obtained tend to support a positive selection model of gamma delta T cell differentiation.


Immunomodulatory properties of cyclic hexapeptide oxytocin antagonists. The thymic repertoire of neuroendocrine 'self' antigens has been previously described on the basis of the intrathymic expression of neurohypophysial (NHP)- and tachykinin-related peptide signals and receptors. According to that model, the cryptocrine signalling between thymic epithelial/nurse cells and thymocytes through NHP-related signals and receptors constitutes one accessory pathway in the process of T-cell differentiation and/or activation. A pharmacological manipulation of that novel type of cell-to-cell signalling was tested by the investigation of the immunomodulatory properties of novel cyclic hexapeptide oxytocin (OT) antagonists (MSD Research Laboratories). These compounds were found to significantly inhibit the productions of cytokines (mainly IL-1 beta and IL-6) elicited by anti-CD3 treatment of human whole blood cell cultures. Cytokine productions were more significantly reduced by OT antagonists in whole blood cell cultures derived from female volunteers than in those obtained from male donors, suggesting an influence of the gonadal steroid environment on the expression of NHP peptide receptors by immune cells. These observations support the concept of novel immunomodulating approaches through immune-specific neuropeptide antagonists, as well as the pharmacological value of such strategies in selective immunotherapy.


Conditioning of Nude bone marrow increases in vitro migration to thymus supernatant. The thymus must be continuously seeded by cells termed prothymocytes in order to maintain normal T-cell development (Scollay et al. 1986). Using parabiotic studies, the source of prothymocytes appears to be either from the fetal liver or the adult bone marrow (Roderwald et al. 1992). The ability of the body to distinguish self from non-self and mount a functionally mature immune response is dependent upon the intrathymic education of these cells. Therefore, it is apparent that successful migration of prothymocytes into the thymus is an inescapable event in the development and maintenance of the immune system. Utilization of the athymic Nude mouse is a valuable asset in the elucidation of the mechanisms influencing the migration of bone marrow cells into the thymus. Its aberration enables investigators to examine the effect of thymic factors on cells previously devoid of thymic influence. In an attempt to understand the migration of normal prothymocytes into the thymus, we analyzed the in vitro migration of athymic bone marrow cells towards newborn thymus supernatant. Adult athymic murine bone marrow cells were incubated in either thymus supernatant or media and allowed to migrate toward one or the other. Similar control experiments were performed using CBA adult mice. Results indicate that athymic bone marrow migration towards both supernatant and media can be restored to control levels after incubation in thymus supernatant.


Age-dependent induction of thymic lymphomas by N-propyl-N-nitrosourea in the F344/DuCrj rat. N-Propyl-N-nitrosourea (PNU) is one of the most potent thymic-lymphomagenic agents in rats. Our previous experiments strongly suggested that leukemogenic viruses were not the cause of thymic lymphomas in rats and that target cells of PNU exist in the thymus but not in the bone marrow. On the other hand, the role of retrovirus in lymphomagenesis is undeniable in mice. Therefore, chemically induced rat thymic lymphoma provides a good model to analyse lymphomagenesis without viral implications. In the present experiment 1, we investigated the relationship between the age of animal at commencement of PNU treatment and the incidence of thymic lymphomas. Incidences of thymic lymphomas were 100, 100, 80 and 18, and average latent periods were 15.1, 18.7, 25.4 and 27.3 weeks after the start of PNU-treatment, in 5-, 10-, 20- and 40-week-old groups, respectively. In experiment 2, rats were sacrificed postnatally at 5, 10, 20, 30 and 40 weeks each, and thymus weight, number of thymocytes in the thymus, frequency of mitosis, and percentage of OX-7 (Thy 1.1), OX-8 (CD8), or W3/25 (CD4) positive cells, were examined cytologically. Thymus weight, number of cells in the thymus and mitotic index were maximum at 10 weeks old, and thereafter decreased gradually. No marked changes were observed in the ratio of each cell-surface marker positive cell. These results indicate that induction of thymic lymphomas by PNU is very closely related with the total number of mitotic cells in the thymus. Thus, chemical induction of rat thymic lymphoma reflects an age-dependent function of the thymus.


V(D)J recombination gets a break.

V(D)J recombination gets a break. The diversity of immunoglobulins and T cell receptors is largely due to the assembly of functional genes from separate segments. The mechanism by which these gene fragments are joined is starting to be deciphered, with broken DNA molecules that may be intermediates in the reaction providing a new clue.


Activation of V(D)J recombination by RAG1 and RAG2. V(D)J recombination is normally limited to lymphoid cells, but expression of the RAG1 and RAG2 genes allows other cell types to carry out this reaction. The products of these recently discovered genes may form part of the recombination machinery, and are a focal point for lymphoid development.


Creation of immunoglobulin diversity by intrachromosomal gene conversion. Not all vertebrates create an immunoglobulin repertoire through the recombination of individual members of variable (V), diversity (D) and joining (J) gene segment families. In chickens, for example, a diverse set of immunoglobulins is created by intrachromosomal gene conversion of the single variable gene segments of the immunoglobulin heavy and light chain genes. Recent evidence from other species such as the rabbit suggests that gene conversion may be a more widespread mechanism for the creation of immunologic diversity than previously supposed.


Chromatin diminution in nematode development. Chromatin diminution in Parascaris and Ascaris represents the classical case of a developmentally programmed genome rearrangement. The process is very specific with respect to ontogenetic timing and chromosomal localization, and involves chromosomal breakage, new telomere formation and DNA degradation. Recent evidence from Ascaris lumbricoides var. suum suggests that chromatin diminution might have a function in gene regulation.


Mating-type gene switching in Saccharomyces cerevisiae. The study of yeast mating-type (MAT) gene switching has provided insights into several aspects of the regulation of gene expression. MAT switching is accomplished by a highly programmed site-specific homologous recombination event in which mating-type-specific sequences at MAT are replaced by alternative DNA sequences copied from one of two unexpressed donors. The mating-type system has also provided an opportunity to study both the genetic regulation of gene silencing by alterations in chromatin structure, and the basis of preferential recombination between a recipient of genetic information and one of several possible donors.


Antigenic variation in African trypanosomes. African trypanosomes evade the humoral immune response by periodically changing the antigenic identity of their variant cell-surface glycoprotein (VSG) coat. Antigenic variation relies on DNA rearrangement events that can translocate a silent VSG gene to a telomerically located VSG gene expression site. Antigenic switches can also be brought about by the differential transcriptional control of the expression sites, only one of which is transcribed at any time.


Cutaneous findings associated with HIV disease including AIDS: experience from Sub Saharan Africa. Cutaneous manifestations are common in patients with HIV infection and tend to be more frequent as immunodeficiency progresses. In the initial stage of HIV infection a transient maculopapular-rash may appear. During the otherwise asymptomatic phase that follows, patients may develop seborrhoeic dermatitis, persistent genital ulcer disease, pruritic papular eruption and/or a variety of scaling dermatoses. The most frequent skin tumour associated with HIV disease is Kaposi's sarcoma. Skin manifestations of adverse reactions to a variety of drugs occur more frequently in patients with HIV disease than in immunocompetent patients. In general most skin diseases that occur in association with HIV disease respond well to standard treatment regimens. However relapses, and/or recurrences are frequent in this group of patients.


An approach to the patient with skin disease. We practise an integrated approach to the management of skin diseases, leprosy and sexually transmitted diseases because the latter diseases are still stigmatized and patients are unwilling to attend clinics so labelled. When approached by a patient with skin disease it is advisable to see the patient promptly, because any further delay encourages the use of assorted remedies which may lead to undesirable complications, physically, emotionally and financially. Since there is no health insurance scheme, it is also prudent to manage the patient as much as possible without admission to hospital and with minimal laboratory investigations, to save cost, so that the patient still has sufficient money to buy the required drugs. Family health workers treat patients at the primary health care (PHC) level. At this level, patients are managed by the use of specially prepared standing orders (SO), where checklists and flow charts are grouped by problems or complaints, to facilitate usage by an individual with minimal training in morphology. The SO presents, so far as is possible, the best treatment available for each condition, but which cannot be misused by the primary health care personnel. Before discussing the management of individual diseases, it is important for the reader to appreciate the milieu in which we practise which determines our approach to the patient with skin disease. Some of its features will be highlighted before the management of individual disorders is discussed.


[Degradation of endo- and exogenous albumin in normal and starved rats]. A rate of degradation of homologous exogenous 14C-albumin proved to be higher 3-fold as compared with that of endogenous 14C-albumin, while the albuminolysis rate was additionally increased in starvation. Evaluation of 14C- and 3H-labels demonstrated that the protein hydrolysis occurred mainly in liver tissue, kidney and intestinal membrane and its rate was elevated in starvation. Dissimilar secretion of exo- and endogenous albumins into small intestine lumen was detected. Removal of albumins was found to depend on augmentation in the proteolytic potential and on reconstructive activity of secondary lysosomes.


[Mechanisms of anticoagulant effect of chitosan sulfuric acid ester]. Anticoagulation effect of chitosan sulfate ester and some mechanisms of its influence on hemostasis were studied in vitro. The chitosan sulfate ester catalyzed more effectively inactivation of the enzymes involved in the inner pathway of blood coagulation affecting only slightly the activity of outer pathway factors. The ester, similarly to heparin, inhibited blood coagulation mainly via accelerated thrombin inactivation by means of blood plasma antithrombin III. Inhibition of the enzyme coagulation activity using heparin cofactor II occurred only at high concentrations of chitosan sulfate ester in blood plasma. Besides, the ester decreased the thrombin catalytic activity in reactions with natural and synthetic peptide substrates. Thus, anticoagulation effect of chitosan sulfate ester is similar to that of heparin.


[Assessment of vitamin B2, B6, and PP supply from data on excretion of vitamins and their metabolites in alimentary iron and riboflavin deficiency]. Alimentary deficiency in riboflavin and/or iron in rats involved distinct decrease in excretion of 4-pyridoxylic acid and 1-N-methyl nicotinamide--the metabolites considered as the indices of vitamins B6 and PP consumption. The effect observed appears to occur due to a decrease in activity of some iron- and flavin-containing enzymes participating in the metabolism of pyridoxine and niacin. Addition to the diet of the deficient component normalized these patterns. Use of the data on excretion of 4-pyridoxylic acid and 1-N-methyl nicotinamide as criteria of consumption of pyridoxine and niacin is discussed.


[Activity of menadione reductase and level of cytochrome B5 and P-450 in liver with varying supplies of vitamin K and administration of pelentan to rats]. Content of cytochromes b5 and P-450 as well as activity of soluble menadione reductase were estimated in liver microsomes of rats deprived of vitamin K or maintained both on a diet containing excess of vicasol or antivitamin K-pelentan. Deficiency of vitamin K led to an increase in the specific activity of menadione reductase and in content of the cytochrome P-450. Administration of antivitamin K did not alter these parameters but caused an increase in the content of cytochrome b5, which was not changed in vitamin K deficiency. Dissimilar effects of alimentary deficiency in vitamin K and of pelentan administration suggest that administration of antivitamins K (although it allowed to discover alterations developed via the system of vitamin K-dependent carboxylation) could not be completely identified with alimentary vitamin K deficiency.


[The effect of oxythiamine on tumor growth and certain biochemical and genetic characteristics of normal and tumor cells]. The effect of oxythiamine (400 mg/kg) on chromosomal structure of Ehrlich ascites carcinoma cells (EAC, hyperdiploid strain) and bone marrow cells was studied in intact AF mice. The influence of the antivitamin on the rate of tumor growth was investigated in tumor-bearing mice. Oxythiamine decreased transketolase activity in hepatocytes and tumoral cells and markedly inhibited tumor growth. Amount of chromosomes was unaltered both in tumor cells and in bone marrow cells, which could be manifested as increased content of cells with impairment of chromosomal set calculated per a cell. However, the oxythiamine-induced impairment of chromosomal integrity was less distinct as compared with the effect of such mutagens as urethane and cyclophosphamide; hence, the antivitamin might be used in the courses of combined chemotherapy.


[Status of oxidative phosphorylation in brain mitochondria during its toxic and traumatic edema-swelling]. A rate of oxidative reactions was decreased in brain mitochondria under conditions of toxic edema and within 1 day after traumatic impairment of brain tissue. Oxidative phosphorylation in mitochondria was normalized within 4 days after trauma. These alterations appear to depend on inhibition of oxidative enzymes in the respiration chain.


[Use of o-phenylenediamine in determining the activity of L-lysine- alpha-oxidase and concentration of L-lysine]. A spectrophotometric procedure for estimation of L-lysine-alpha-oxidase activity involved measurement of optical density in samples after reaction of the H2O2 formed with o-phenylene diamine. Suitable values of pH, o-phenylene diamine concentration and time of incubation were chosen. The procedure developed was distinctly dissimilar as compared with the methods currently widely used. Advantages of the new method are due to its sensitivity, reproducibility, accessibility, relative safety and short time of the reaction performance. The procedure may be used for estimation of L-lysine content in various biological materials.


[Status of carbohydrate metabolism in the rat brain during alcohol withdrawal syndrome]. Periodically repeating alterations of carbohydrate metabolism were found in rat brain tissue under conditions of experimental alcohol withdrawal syndrome. Along with the maximal external manifestations of the withdrawal, a significantly higher glucose levels in all brain formations were observed, which was decreased within 3 days. Activity of the glycolytic enzymes was altered differentially in various brain structures.


[Use of vitamins in allergic illnesses in children]. Therapeutic efficacy of vitamins B6, P and E was studied in children with allergic diseases. Bronchial asthma and atopic dermatitis were treated more effectively if maximal doses of vitamin B6 were used. Quercetin was found to be useful for treatment of children with pollinosis in order to correct impairments in metabolism of lymphocyte membrane lipids. Only slight efficacy of vitamin E was detected in atopic dermatitis of children.


[Free radical reactions and cancer].

[Free radical reactions and cancer]. Activities of superoxide dismutase (SOD) and catalase as well as content of malonyl dialdehyde (MDA) were estimated in the blood of patients with tumor of gastrointestinal tract. In the early stage of development of tumor SOD activity and concentration of MDA in whole blood was decreased while catalase activity was increased significantly. In the cases of metastases spreading and cachexia both SOD and catalase activities were greatly decreased; the content of MDA was increased.


[Vitamin E and its synthetic analogs in experimental cardiovascular pathology]. Oxidative metabolism and the antioxidant system were studied in the myocardium of rats with various experimental impairments of heart tissue. Vitamin E and its synthetic derivatives proved to be effective in correction of the deteriorations observed.


[Metabolism of vitamins B1 and PP and their use in oncological practice]. Blood of patients with gastric tumor was studied after their admission to the hospital and after the chemotherapeutic course. Formation of the tumor was accompanied by development of hypovitaminoses B1 and PP. The vitamin deficiency was more distinct after treatment of the patients with cyclophosphan: content of thiamine diphosphate (TDP) was decreased by 40%; NAD+NADP, by 30% and NADH+NADPH, by 20%. In mice with Ehrlich ascites carcinoma, activity of transketolase in erythrocytes was decreased by 48%, content of TDP, by 61% and that of NADPH, by 27%. The administration of cyclophosphan increased further thiamine deficiency in the tumor-bearing mice. Simultaneous administration of thiamine and cyclophosphan abolished the cytostatic toxic effect but did not affect their antitumoral properties. Under these conditions treatment with vitamins B1 and PP complex was undesirable due to malignization. The vitamins B1 and PP did not stimulate the tumor growth, partially restored impaired metabolism of the vitamins and may be included separately into combined multidrug oncotherapeutics.


Pocket computers in anesthesiology.

Pocket computers in anesthesiology. Pocket computers are a new technology in academic anesthesia practice. These computers are inexpensive, portable, easy to use and can store large amounts of data, but the limited ability to program them and the length of time necessary to enter data can be disadvantages.


[The effect of a soy protein isolate and sources of polyunsaturated omega-3 fatty acids in an anti-atherosclerotic diet on the lipid spectrum of blood serum and immunological indicators in patients with ischemic heart disease and hypertension]. Blood serum lipid spectra and immunologic spectra were studied in patients with ischemic heart disease and hypertension maintained on antiatherosclerotic diet containing either soy bean protein isolates or ichthyenic oil. The ichthyenic oil-containing diet decreased distinctly the level of cholesterol, triglycerides and the atherogenicity coefficient simultaneously with an increase of cholesterol content in high density lipoproteins in blood of 37 patients with these diseases. The diet with soy bean protein isolates exhibited less pronounced effects on lipid metabolism patterns in blood serum as compared with the ichthyenic oil-containing diet; however, the former diet contributed to normalization of the immunologic reactions in patients with ischemic heart disease and hypertension.


[The effect of unilateral nephrectomy on vitamin D metabolism in pregnant rats]. Unilateral nephrectomy causes a decrease in provision of vitamin D dihydro derivatives in pregnant rats, which correlated with the development of hypocalcemia and hypophosphatemia as well as with an increased content of parathyroid hormone. Fetuses of these females contained less amount of mineral components and active metabolites of vitamin D. Neonates, being born by these females with the nephrectomy, had vitamin D deficiency, which was manifested as a decrease in content of active vitamin D metabolites and minerals as well as an increase in activity of alkaline phosphatase and in the content of parathyroid hormone.


[Dynamics and factors regulating the intensity of free radical processes during experimental supravesical block]. Two phase alterations of induced chemoluminescence were detected in kidney homogenates and blood plasma after unilateral ureteral occlusion in rats. A high correlation was observed between the rates of free radical oxidation in the blocked kidney tissue and blood plasma. Hemodynamic alterations in the kidney, accumulation of activated phagocytes in the interstitial space and elevation of medium-weight molecules were mainly responsible for the regulation of lipid peroxidation rates.


Chlamydia trachomatis antigen prevalence among pregnant women in West Virginia. During 1990, more than 2,100 women who received prenatal care at one of four clinics which serve 11 West Virginia counties, were screened for chlamydial antigen. Overall, 5.6 percent of the women screened had positive antigen tests and 90 percent of these individuals were under the age of 25. The prevalence of chlamydia was different at three geographic sites with the highest rate of positive antigen test being 9.4 percent at one site. These findings led to a careful analysis of the prevalence of this disease among women who lived in rural areas versus those who lived in urban areas. This detailed analysis involved only patients seen in the Grafton and Morgantown clinics, and revealed a tendency for most positive antigen tests to occur among women with urban addresses. Our study indicates that a substantial chlamydial problem exists among pregnant women of young age. Although screening all pregnant women for chlamydia may not be cost effective, knowing which individuals are at highest risk may help target limited screening for these patients.


Heart disease in women.

Heart disease in women. Heart disease is a significant problem in women. Age, smoking, and hyperlipidemia are potent risk factors, as is the presence of diabetes. Hypertension is less of a risk factor in women than men. Diagnosis of coronary artery disease is most difficult in women, especially using non-invasive techniques, because of a lower prevalence of disease. Thrombolytic therapy may be associated with more bleeding in older, smaller women. Angioplasty and surgical bypass may be more difficult because of smaller coronary artery size in women. Exercise, aspirin, and estrogens appear to decrease the incidence and mortality of heart disease in women, but concern has been raised that the use of resources for the study, prevention and treatment of heart disease has a gender bias, with men receiving more than their fair share.


[Dependence of the initial stages of the pentose phosphate cycle on vitamin C metabolism in connective tissue pathology]. Correlation between rates of oxidative and non-oxidative steps of the pentose phosphate pathway and vitamin C concentration was studied in experimental diffuse impairment of connective tissue. As compared with transketolase, activity of glucose-6-phosphate dehydrogenase was more closely dependent on concentration of ascorbic acid. Content of vitamin C was considerably altered in tissues thus demonstrating profound deterioration of vitamin C metabolism under these conditions. Simultaneous impairment of the pentose phosphate pathway primary steps and of vitamin C metabolism appear to be responsible for initiation of the diffuse injury of the connective tissue.


The ideological and technological shaping of motherhood. Women's medical care, especially the care of birthing women, is increasingly based on technological innovations. While the use of electronic fetal monitoring, in vitro fertilization and cesarean section have benefited some women, the expanding use of medical technology distances women and their physicians. The problem is compounded because the application of medical technology is often clouded by a gender based ideology that defines women as mere reproductive beings. Forgotten is the recognition that the "facts" and interpretations generated by medical advance are subject to the same ideological bias as traditional beliefs and understandings about women. Forgotten is the women, the person, in the body. By seeing, hearing, touching and talking with women, physicians, not technological feats, provide a foundation for women's health based on the mutual interaction, understanding and respect between women and their physicians.


Effects of a combination of evening primrose oil (gamma linolenic acid) and fish oil (eicosapentaenoic + docahexaenoic acid) versus magnesium, and versus placebo in preventing pre-eclampsia. In a placebo controlled, partially double-blinded, clinical trial, a combination of evening primrose oil and fish oil was compared to Magnesium Oxide, and to a Placebo in preventing Pre-Eclampsia of Pregnancy. All were given as nutritional supplements for six months to a group of primiparous and multiparous pregnant women. Some of these women had personal or family histories of hypertension (21%). Only those patients who received prenatal care at the Central Maternity Hospital for Luanda were included in the study. Compared to the Placebo group (29%), the group receiving the mixture of evening primrose oil and fish oil containing Gamma-linolenic acid (GLA), Eicosapentaenoic acid (EPA), and Docosahexaenoic acid (DHA) had a significantly lower incidence of edema (13%, p = 0.004). The group receiving Magnesium Oxide had statistically significant fewer subjects who developed hypertension of pregnancy. There were 3 cases of eclampsia, all in the Placebo group.


Positive-spillover effects from job to home: a closer look. What is the association between subjective experiences in two roles, employee and mother, and women's psychological distress? Previous research indicated that employed mothers with troubled mother-child relationships reported high levels of psychological distress, unless they were in rewarding jobs. In this paper, using data from the same sample of 228 employed mothers, we explored further the above finding by addressing two related questions: (1) which job rewards mitigate the relationship between parent-role quality and psychological distress?; and (2) which parental concerns are buffered by these stress mitigators? The main finding was that having a rewarding job per se did not automatically serve as a parent-stress mitigator. Although several job-reward factors (e.g., Helping Others at Work, Challenge), were associated with reports of low distress, Challenge was the only job-reward factor that mitigated parental stress. Thus, the previously reported positive-spillover effect from work to home was attributable to the presence of rewards from challenging work. However, Challenge buffers only particular parent concerns. For employed mothers, a job high in rewards from Challenge mitigates the distress associated with Disaffection (not Burden or Safety) in their relationships with their children.


[Increase in the level of luminol-dependent chemoluminescence in mouse blood under the effect of certain synthetic peptides]. Synthetically produced peptides increased the luminol-dependent chemoluminescence of mice whole blood during phagocytosis. Using some peptides it is possible to cause an increase in the antimicrobial peroxidase system activity of neutrophils very rapidly (within seconds).


Maternal demographic, situational and psychosocial factors and their relationship to enrollment in prenatal care: a review of the literature. Whether or not a woman enrolls in prenatal care in a timely fashion is a major predictor of pregnancy outcome. In this review, we consider maternal demographic, situational and psychosocial factors which have been studied with relation to enrollment in prenatal care. Paying increased attention to some situational barriers such as problems with child care or transportation, and a number of psychosocial factors such as unplanned pregnancy and negative feelings about medical care, holds promise in achieving improved utilization of prenatal care.


[Status of the monooxygenase enzyme system in rat and rabbit organs in sugar diabetes and upon insulin administration]. Content of cytochromes P450 and b5, activities of amidopyrine-N-demethylase, alanine- and p-nitrophenol hydroxylases, NADPH-cytochrome c reductase were studied in the liver, kidney, small intestine and lung tissues of rats and rabbits in insulin-dependent hypoglycemia and alloxan diabetes. The diabetes and hypoglycemia caused dissimilar alterations in activity of alanine- and p-nitrophenol hydroxylases, thus indicating their dependence on blood sugar levels. The activity of monooxygenase enzymes studied was altered similarly in rabbit liver and other tissues, while the enzymatic activity was distinctly differentiated in rat tissues. Specific properties of cytochromes P450 isozyme spectra appear to be responsible for these alterations detected.


Women and mental health: two traditions of feminist research. Gender differences in mental health have been the focus of much research and debate in several academic disciplines. This paper reviews the literature regarding the socio-cultural dimensions of women's mental health in the United States. Feminist scholarship on mental health has followed two lines of inquiry. The first, a social causation approach, examines the features of women's lives that enhance or undermine well-being. The social constructionist perspective involves critical analyses of methodology and conceptions of mental health and illness. This body of literature suggests that the findings of gender differences in mental health are artifactual and focuses on the sexism of psychiatry. Although these bodies of work have remained largely distinct and have been criticized as contradictory, both are important ingredients of a general feminist perspective on mental health. Feminist therapy is used as a model for a synthesis of approaches.


Health value and gender in predicting health protective behavior. This research analyzes the influence of selected social psychological factors (health locus of control and health value), social support factors (influence of parents and peers, organizational involvement, and reliance on others during stressful times), and health-specific factors (recent health crisis and self-assessment of health status) on participation in health protective behaviors by males and females. While much research has focused on identifying determinative factors (often with inconsistent findings), little research has been directed to understanding if and how predictive factors vary by gender. Data for the research were obtained from personal interviews with 167 undergraduate college students collected during the fall semester of their freshman year and again during their sophomore year. Female students averaged statistically significant more health protective behaviors than did male students, and increased involvement in HPBs from their freshman to sophomore years (while male students' participation declined). Among the factors studied, peer practices (collected in time 2) is a statistically significant predictor for both males and females. Value placed on health predicts for females but not males, while grade point average predicts for males but not females. Overall, females and high GPA males are most likely to engage in HPBs.


Health status and health care utilization among New York City home attendants: an illustration of the needs of working poor, immigrant women. In this paper, the health needs and health care utilization patterns of home attendants and their families have been studied as an illustration of those likely to be found among working poor, immigrant women and their children. Despite tremendous growth in the number of immigrants, studies to date provide only limited information regarding the specific health needs and patterns of health care utilization among such women and their children. As part of a longitudinal study on the impact of insurance on health status and health care utilization, 387 female, immigrant home attendants were interviewed. Data were also gathered on 355 of their minor children. These women and children were found to be less likely than other Americans to make use of basic health services, despite the fact that they are more likely to indicate fair or poor health status. This is true even in comparison to poor or uninsured Americans. Immigrant attendants in fair or poor health report an average annual visit rate of 4.1 ambulatory care visits for themselves and 2.2 for their children, as compared to 8.4 for poor adults and 4.4 for poor children in national samples. These findings illustrate the likelihood that poor, immigrant women make limited use of American medical care, and face barriers to health care that appear even greater than those faced by the uninsured and the poor.


In vitro assessment of cytotoxicity and biotransformation of propranolol in Cunninghamella echinulata. 1. Biotransformation studies with five concentrations of racemic propranolol were conducted using the filamentous fungus Cunninghamella echinulata ATCC 9244. 2. The rate of formation and subsequent disappearance of a new major metabolite, 8-hydroxypropranolol, was dose-dependent. Desisopropylpropranolol and 4-hydroxypropranolol were also formed. 4-Hydroxypropranolol was the major fungal metabolite in earlier studies. 3. Propranolol exerted a dose-dependent response on biotransformation, fungal growth, dextrose utilization, ammonia formation and incubation broth pH. Determination of dextrose utilization and incubation broth pH would provide reliable, cost-effective and convenient alternative methods for cytotoxicological evaluation.


The metabolism of acitretin and isoacitretin in the in situ isolated perfused rat liver. 1. The metabolism of acitretin and its 13-cis isomer, isoacitretin, has been investigated in the in situ isolated perfused rat liver in order to differentiate the action of the liver from that of the gut on the metabolism of these isomers. 2. Acitretin undergoes alpha-oxidation, chain shortening O-demethylation, and glucuronidation in the perfused rat liver. 3. Isoacitretin undergoes glucuronidation as the major, almost exclusive, route of metabolism in the perfused rat liver. 4. The difference in the hepatic metabolism of the cis and trans isomers of this retinoid may explain the differences in their pharmacokinetics, and may help in understanding the pharmacokinetics of related retinoids.


Mercapturic acid formation from 2-aminopyrazine in rats. 1. The compound 2-aminopyrazine was given by oral gavage to normal rats and their urine collected. 2. A mercapturic acid containing the 2-aminopyrazine moiety was isolated from this urine. This represents the first example of this type of a metabolite from a pyrazine.


Metabolism of antipyrine and sulphadimidine in dwarf goats: effects of the enzyme-inducing agents phenobarbital, troleandomycin and rifampicin. 1. Antipyrine (AP) and sulphadimidine (SDD) plasma elimination and metabolite formation were studied in dwarf goats before and after treatment with phenobarbital (PB), triacetyloleandomycin (TAO), and rifampicin (RIF). 2. PB treatment significantly increased AP plasma clearance in both male and female goats. With SDD, only male goats were studied, which showed a significant increase of SDD plasma clearance following PB treatment. 3. After PB treatment, partial clearance values of four AP metabolites, 3-hydroxymethylantipyrine (HMA), norantipyrine (NORA), 4-hydroxyantipyrine (OHA) and 4,4'-dihydroxyantipyrine (DOHA), were significantly increased. This induction effect was different for the individual metabolites and also showed sex-dependency. 4. In PB-induced male goats the formation of the hydroxylated SDD metabolites, 6-hydroxymethyl-SDD and 5-hydroxy-SDD, was significantly increased. 5. After TAO treatment, female goats showed a slightly reduced AP plasma clearance and a decreased partial clearance of two AP metabolites, HMA and DOHA. There was no effect on SDD plasma elimination or metabolite excretion. 6. In male goats, RIF had no effect on plasma elimination of AP and SDD. With SDD, it decreased the urinary excretion of the unchanged drug and its N4-acetylated metabolite. 7. Induction/inhibition studies of drug metabolism in food-producing animal species are desirable to gain more insight into the regulation of enzymes involved in the metabolism of xenobiotics.


Comparative biodisposition and metabolism of 14C-(+/-)-fenfluramine in mouse, rat, dog and man. 1. The comparative metabolism of fenfluramine was investigated in mouse, rat, dog and man following a single oral dose of 14C-(+/-)-fenfluramine hydrochloride (1 mg/kg), and also in rat after eight consecutive 12-h subcutaneous doses (24 mg/kg). 2. Main route of excretion of radioactivity in all species and at all doses was into urine (> 80%), with only minor amounts of radioactivity found in faeces. 3. From all species examined a total of 11 metabolites were observed in urine and plasma by t.l.c. and h.p.l.c. analysis and no metabolite was present in the plasma which was not present in urine. 4. All species dealkylate fenfluramine to the active metabolite norfenfluramine, to a relative greater or lesser extent, with plasma metabolic ratios (norfenfluramine/fenfluramine) showing inter-animal variation (rat >> dog >> mouse = man). 5. These differences are due to the efficient deamination of both compounds to polar inactive metabolites in man, with less dealkylation and lower plasma levels of norfenfluramine compared with the other species studied. 6. In conclusion, major species differences in the metabolism of (+/-)-fenfluramine, both qualitative and quantitative were observed, and no one species had a similar metabolic profile to that found in man.


Disposition and pharmacology of propofol glucuronide administered intravenously to animals. 1. Propofol glucuronide (PG) is the major human metabolite of the i.v. anaesthetic propofol, 2,6-diisopropylphenol. 2. Bolus i.v. doses of 14C-PG (1 mg/kg) to rat and dog were eliminated in urine (40 and 66% respectively) and faeces (48 and 19%); 25 and 48% of the dose were excreted unchanged in urine. 3. In dog, PG was distributed from plasma (t 1/2 4 min) into a volume equivalent to extracellular water and eliminated with t 1/2 80 min. Total body clearance was 1.8 ml/min per kg, and renal clearance about 20% GFR. In rat, plasma 14C concentrations were about one-tenth those in dog, thus PG levels were not quantified. 4. Propofol was not detected in the plasma showing that PG is hydrolytically stable. Enterohepatic circulation of PG occurred in rat and to a lesser extent in dog. Metabolites, mainly side-chain hydroxylation products, were evident in both species from 4 h after dosing. 5. Bolus i.v. doses of PG (200 mg/kg) showed no hypnotic activity in mice.


Metabolism of 2,4,5,2',4',5'-hexachlorobiphenyl with liver microsomes of phenobarbital-treated dog; the possible formation of PCB 2,3-arene oxide intermediate. 1. Metabolism of 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) was investigated in vitro using liver microsomes of one male beagle dog after phenobarbital treatment. 2. Three major metabolites were isolated and identified as 3-hydroxy-2,4,5,2',4',5'-HCB, 2-hydroxy-4,5,2',4',5'-pentachlorobiphenyl (PenCB), and 2-hydroxy-3,4,5,2',4',5'-HCB, by comparison of g.l.c.-mass spectrometry and 1H-n.m.r. data with those of authentic samples. 3. 2-Hydroxy-3,4,5,2',4',5'-HCB was found as a metabolite of 2,4,5,2',4',5'-HCB for the first time using dog liver microsomes. Present result indicate that this metabolite and the dechlorinated PenCB are derived from a metabolic intermediate, namely, 2,3-epoxy-2,4,5,2',4',5'-HCB. 2,3-Epoxide formation is a new metabolic pathway of PCB.


Enantioselective metabolism of cumene.

Enantioselective metabolism of cumene. 1. The enantioselective metabolism of cumene (isopropylbenzene) was studied in intact rabbits. 2. Of the total 2-phenyl-1-propanol formed metabolically, 90.3% was shown by h.p.l.c. to be (R)-(+)-2-phenyl-1-propanol. The corresponding values for (S)-(+)-2-phenylpropanoic acid and (R)-(-)-2-hydroxy-2-phenylpropanoic acid were 99.0 and 81.0%, respectively. 3. These results imply that firstly, preferential omega-hydroxylation occurs at the pro-S methyl group and secondly, the oxidation is followed by stereochemical inversion of (R)-(-)-2-phenylpropanol to the corresponding (S)-(+)-acid.


The formation of proximate carcinogens from three polycyclic aromatic compounds by human liver microsomes. 1. The metabolism of 3H-benzo[a]pyrene (BP), 3H-7-methylbenz[c]acridine (7MBAC) and 3H-dibenz[a,j]acridine (DBAJAC) have been studied in human liver microsomes from 13 subjects. 2. When the metabolism of these carcinogens to more polar ethyl acetate-soluble metabolites were compared, the activities towards the nitrogenous carcinogens were twice that determined for BP. 3. The specific rates of formation of the three proximate carcinogens, BP-7,8-dihydrodiol, 7MBAC-3,4-dihydrodiol and DBAJAC-3,4-dihydrodiol per nmol cytochrome P-450 for 12 subjects were positively correlated. 4. These dihydrodiols constituted 5.9 +/- 0.7% (mean +/- SEM), 57.8 +/- 2.6% and 3.0 +/- 0.4% of the total metabolites identified by cochromatography with standards, 7MBAC, DBAJAC and BP respectively.


Comparison of pulmonary and hepatic glucuronidation and sulphation of ethanol in rat and rabbit in vitro. 1. Pulmonary and hepatic UDP-glucuronyltransferase and sulphotransferase activities in subcellular fractions from rats and rabbits were determined, comparing ethanol with known substrates for these enzymes. 2. No ethyl glucuronide formation was detected with either hepatic or pulmonary microsomal incubations. 3. Chromatographic, autoradiographic and scintillation counting analysis indicated that ethanol is sulphated by rat and rabbit pulmonary cytosol, although this activity was approx. 2-6% of that in liver. 4. Rat hepatic and pulmonary sulphotransferase activities with beta-naphthol were approx. 13 and 60 times higher than with ethanol, respectively. 5. Rabbit hepatic and pulmonary sulphotransferase activities with both substrates were higher than those in rat.


Microsomal formation of a pyrrolic alcohol glutathione conjugate of the pyrrolizidine alkaloid senecionine. 1. Pyrrolizidine alkaloids (PAs) are metabolized primarily to putative dehydroalkaloid (PA pyrrole) metabolites and to PA N-oxide by rat liver microsomal monooxygenases. 2. The dehydroalkaloids are highly reactive and either bind covalentely to tissue nucleophiles or are hydrolysed to the more stable pyrrole, (R,S)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), and the corresponding necic acid. 3. Addition of glutathione (GSH 1 mM) to incubation mixtures containing rat liver microsomes and the PA senecionine (SN), resulted in the formation of a conjugate of DHP with GSH. 5. The mass spectrum of this DHP-GSH conjugate was identical to that of the chemically-synthesized dehydroretronecine (the R enantiomer of the racemic DHP) and GSH. 6. Only negligible amounts of DHP-GSH conjugate were formed when DHP itself was incubated with GSH at physiological pH. 7. These findings provide strong evidence for the microsomal conversion of SN to a highly reactive metabolite, presumably dehydrosenecionine, which then reacts with GSH to form the DHP-GSH conjugate. 8. It is likely that a similar mechanism is responsible in vivo for the formation of GSH conjugates of DHP from SN and other PAs.


Effects of oxygen concentration on the metabolism of anisole homologues by rat liver microsomes. 1. The effects of oxygen concentration were studied on the metabolic pathways of anisole homologues (anisole, phenetole and isopropoxybenzene) catalysed by liver microsomes from phenobarbital-treated rats. 2. With increase of oxygen concentration, the rate of anisole o-hydroxylation reached a plateau at about 35 microM O2, while the rates of O-demethylation and aromatic p-hydroxylation were still increasing at 223 microM O2 (air). 3. The rates of all three metabolic reactions of phenetole reached plateau levels at about 80 microM O2. 4. The rates of all three metabolic reactions of iso-propoxybenzene were still increasing as 223 microM O2 (air). 5. The ratio of aromatic p-hydroxylation or O-dealkylation to aromatic o-hydroxylation decreased in anisole metabolism, and showed no uniform change in phenetole and isopropoxybenzene metabolism with decreasing oxygen concentration. 6. The ratio of aromatic p-hydroxylation to O-dealkylation was essentially constant over the range of oxygen concentration studied in anisole and phenetole metabolism, while in iso-propoxybenzene metabolism the ratio was different between higher and lower oxygen concentrations than 60 microM. 7. This series of compounds with increasing chain length did not show homologous changes in rates of product formation or O2 dependent of product formation.


Metabolism of the anti-psoriatic agent 5-methoxypsoralen in humans: comparison with rat and dog. 1. Single oral doses of 14C-5-methoxypsoralen (5-MOP) to human subjects (50 mg), rats (1 mg/kg) and dogs (1 mg/kg) were fairly well absorbed but subjected to extensive first-pass metabolism, at least in rat and human. Means of 62, 51 and 40% dose in urine and 31, 38 and 48% dose in faeces, were excreted by humans (during 5 days), rats (3 days) and dogs (1 day), respectively. In dogs, faecal 14C was probably derived, in part, from biliary excreted material. 2. Total 14C in human plasma reached peak concentrations after 2 h (mean 235 ng 5-MOP equivalent/ml) and declined relatively slowly, to about 60% of this value within 24 h. Unchanged 5-MOP was not detected in plasma using h.p.l.c. (< 5 ng/ml). 3. Tissue concentrations of 14C were generally greater in dogs than rats and reached peak levels at 1 h in dogs but at 24 h in rats. Apart from liver and bile, dog tissue 14C concentrations were lower than those in the corresponding plasma, whereas in rat they were lower only until the time of peak concentrations, after which they were generally greater. 4. 5-MOP was extensively metabolized in all three species. The major 14C-components in human and dog urine were glucuronic acid conjugates, mainly of an arylacetic acid and arylalcohols, resulting from initial oxidative metabolism of the furan ring of 5-MOP. In rat, these metabolites were excreted mainly unconjugated. An unusual metabolite was formed by reduction of the lactone moiety of 5-MOP, probably by the gut flora, giving rise to an arylpropionic acid, excreted as a glucuronic acid conjugate in the urine of all three species. 5. Unchanged drug was a very minor component of human and rat plasma, but a major component of dog plasma. In all three species, circulating 14C-metabolites were similar to those in the urine but were present mainly unconjugated. On the basis of these data, the metabolic fate of 5-MOP in humans was more similar to that in dog than to that in rat, although humans appeared to metabolize 5-MOP more rapidly than did dog.


[The overall toxic situation today. Thoughts on the WHO report, "Diet, nutrition and the prevention of chronic diseases."]. In the 1950s to '70s, food additives and contaminants were considered important risk factors for cancer and other chronic diseases. Opinion leaders like F. Eichholtz and W. Kollath in Germany and R. Carson and J.J. Delaney in the United States maintained that the exclusion of man-made chemicals from the food supply would decisively contribute to better health. In contrast to these views, world-wide scientific opinion now emphasizes the role of personal lifestyle, e.g., over-nutrition, unbalanced diets, smoking, and excessive alcohol consumption in the causation of chronic diseases. Dietary guidelines now recommended for the prevention of cancer are largely identical with those recommended for the prevention of cardiovascular disease. Indications are that oxidative damage to DNA contributes importantly to both these diseases. In research the role of antioxidants and other protective substances in foods receives as much attention today as man-made carcinogens received in the past. Media reporting and nutrition counseling have taken very little notice of these fundamental changes in scientific opinion.


[Influence of an activator of protein kinase C (TPA) and a calcium-mobilizing agonist (A 23187) on zinc metabolism in the rat]. The influence of 12-O-Tetradecanoylphorbol-13-acetate, an activator of proteinkinase C and A 23187, a calcium ionophore increasing cytosolic free calcium concentration on zinc metabolism was investigated in a study with 24 eight-week old rats. Twenty-four hours before killing, the rats (235 g body weight, 8 per group) were either injected intraperitoneally with TPA (1.6 x 10(-7) mol/kg body weight) or A 23187 (1.6 x 10(-6) mol/kg body weight). Control rats received the solvent dimethylsulfoxide. The application of TPA and A 23187 provoked a marked decline in feed intake accompanied by a reduction in body weight and liver mass. Serum concentrations of zinc were reduced significantly after A 23187 injections. TPA and A 23187 increased liver zinc levels by 20 and 30% respectively, if based on fresh and dry weight. The injections, however, did not alter total liver zinc. Liver metallothionein (MT) concentration was elevated 2.4-fold after TPA administration. The increase in response to A 23187 was only 1.5-fold and not significant. Mucosa MT levels were not altered. Serum activity of alkaline phosphatase was significantly reduced (TPA: -23%, A 23187: -31%). There was no change in serum glucose after injections. However, serum creatinine and urea were increased in response to A 23187. In conclusion, TPA and A 23187 had an effect on zinc metabolism of the rat, most marked in the case of MT induction in the liver. There is evidence that the reduced feed intake caused by TPA and A 23187 resulted in effects indistinguishable from those caused by fasting. Further experiments are needed to clarify whether proteinkinase C and cytosolic free calcium are directly involved in the regulation of zinc metabolism.


Assessment of the iodine status in children aged 2-3 years. In 22 healthy toddlers (age: 2.5 +/- 0.06 years; from families living in Dortmund, FRG) measurements of iodine and creatinine concentrations were carried out in spontaneous urine samples collected in the afternoon (U1), as well as during the night (U2). Median iodine-creatinine ratios found in the "afternoon specimens" U1 were significantly elevated (p < 0.05) compared to U2 (181.3 vs. 119.5 micrograms/g). Higher values in U1 than in U2 were also obtained when total daily iodine excretion (under the assumption of an average creatinine excretion of 15 mg/kg/d for infants) was calculated and the corresponding data were related to body surface area (BSA). The results of the specimens collected during the night were (after expressing as iodine-creatinine ratio as well as after correcting for BSA) comparable with the excretion data of accurately timed 24-h urine collections obtained in a separate group of toddlers (n = 23) of nearly the same age. When the iodine-creatinine ratios established by the WHO--after standardizing with BSA--were taken as criteria for iodine deficiency, then in both study groups (spontaneous urine samples at night (U2) and timed 24-h urine collections) about half of the infants would fall in the deficiency state II with an elevated risk for iodine-deficiency goiter. It is suggested that the nutritional status of iodine can be reliably monitored (in infants) by determining iodine and creatinine concentrations in overnight urine samples and relating the data to BSA.


Bioavailabilities of calcium, phosphorus and magnesium from whey mineral complex in growing male rats. The bioavailabilities of Ca, P and Mg from whey mineral complex (WMC) were studied from the viewpoint of the mineral balance and bone properties in growing male rats and compared with bovine bone ash (BBA) and CaCO3. Ca source showed no significant effect on feed intake, body weight gain or feed efficiency (p < 0.05). When the dietary Ca level was 0.3%, the dry weight of the femur in rats fed WMC was significantly higher than that in rats fed BBA. The femur P content of rats fed 0.3% Ca as WMC was significantly higher than that of rats fed BBA or CaCo3. The breaking energy of the femur from rats fed WMC was significantly higher than that from rats fed BBA at a Ca level of 0.2% or 0.3%. There was the same tendency in bone densities as was observed in breaking properties. There was no significant difference in quantitative values for Ca balance among three groups of rats, whereas those rats fed WMC had a significantly higher P retention than other groups. Ca bioavailability from WMC and the effect on the utilization of P and Mg were discussed.


[Hot weather damage of wheat gluten: determination of the intermediate lysine degradation in chicks using isotope techniques (14C-U-L-lysine oxidation]. The aim of our experiments was to identify a restricted lysine bioavailability after heating of wheat gluten by estimating a reduced metabolic 14C-lysine degradation. In two trials, male broiler chickens were fed with six diets based on wheat and wheat gluten (gluten untreated or heated), but differing in lysine content according to lysine supplementation. In trial 1 animals were fed restrictively, in trial 2 they were fed ad libitum. For estimation of metabolic lysine degradation all animals received an additional i.v. injection of 14C-U-L-lysine 3 weeks posthatching, followed by hourly collection of 14CO2 up to 3 h after injection. There were no differences between groups receiving untreated or heated gluten concerning weight gain and N-balance if the lysine supplementation was medium or high. When applying a lysine supply close to the requirement level or above the requirement the lysine degradation to 14CO2 (% of the dose) and the specific radioactivity of CO2 in animals receiving heated gluten was significantly lower compared to the corresponding group with untreated gluten. It can be concluded that reduced bioavailability of lysine due to heat treatment of gluten might be indicated by means of weight gain or N-balance only at lysine supply levels below the requirement. In contrast, measurements of lysine degradation by means of 14CO2-excretion after i.v. lysine injection indicate the heat-damaging effect, especially at lysine levels close to the requirement.


[Synchronized coronary venous retroperfusion: protection from ischemia in coronary angioplasty (PTCA)]. The potentially ischemia-protective effect of ECG-synchronized coronary venous retroperfusion (SRP) with arterial blood via the coronary sinus (CS) was assessed in 26 patients (56 +/- 10 years, 22 male, 4 female) in the clinical scenario of PTCA of a proximal LAD stenosis. In six additional patients the SRP procedure failed due to anatomical or technical reasons. In an intraindividual comparison at least two standardized balloon inflations for 60 seconds at 6-8 atm were performed in randomized order with and without continuous SRP at a flow rate of 200 +/- 46 ml/min. Under both conditions echocardiographic regional wall motion, ST depression in leads V1-6, hemodynamic parameters and symptoms expressed in a pain score were continuously monitored during angioplasty. This study revealed that the echocardiographic regional wall motion score in the perfusion territory of the dilated artery increased from 1.65 +/- 1.81 at baseline to 5.65 +/- 2.88 (p < 0.001) during a one minute dilatation without SRP. With SRP-support the regional wall motion at 1 minute angioplasty was significantly improved to 3.55 +/- 2.80 (p < 0.025). Moreover, the ischemic ECG-changes were markedly less pronounced, whereas the subjective perception of anginal pain was not different as a function of SRP-support. Thus, the simultaneous coronary venous retroperfusion with arterial blood has ischemia-protective potential in elective PTCA of a proximal LAD stenosis and may reduce ischemic dysfunction with prolonged balloon inflations.


[Acute and long-term results of coronary Excimer laser angioplasty]. Laser and catheter technology have been considerably improved within the first 2 years of the clinical use of coronary excimer laser angioplasty. Furthermore, patient selection has changed due to increasing operator experience. We report on the acute- and long-term results achieved in 163 patients in three subgroups with different system parameters and catheter technology. In the initial series 1 (N:60) a prototype catheter with a diameter of 1.4 mm was used. In series 2 and 3, we employed improved transmission devices with 1.3, 1.5 or 1.8 mm. In series 3 the pulsewidth was increased from 60 ns to 115 ns. The target vessel was the LAD in 68%, the LCX in 10%, and the RCA in 21%. According to the AHA/ACC Lesion classification there were 13% type A, 26% type B1, 55% type B2, and 5% type C lesions. Stand-alone laser angioplasty was performed in 23/60 (38%), 24/40 (60%), and 34/64 (53%) in series 1, 2, and 3, respectively. Additional balloon angioplasty was necessary in 32, 11, and 21 interventions. Failure of laser angioplasty occurred in five patients of series 1 and 2, and nine patients of series 3. Frequently observed complications included coronary spasm in 18 to 32%, dissections in 16% to 33%, and vessel closure in 18 to 27%. Myocardial infarction occurred in three patients in the first and one patient of the second and third series. There was one in-hospital death in series 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)


[Chronic coronary artery occlusion--age, morphology and chance of reopening. An attempt to define indications]. In chronic coronary occlusions the rate of successful reopening seems to be improved with the help of new techniques; the chance of success can be judged by the age of occlusion. Frequently this age cannot be fixed exactly. The purpose of the study was therefore to find out, whether the chance of reopening can be judged by morphology. 60 patients in whom the occlusions could not be passed with a conventional wire were treated with the ROTACS system. Cine angios were reviewed carefully, morphological details in at least two projections were evaluated in graphic representations and correlated with the acute success rate and the estimated age of occlusion. Morphological parameters associated with a higher rate of success (type A) were: 1) a clearcut proximal stump with 2) no sidebranches at the site of occlusion, 3) no bridging collaterals and 4) only a slight filling of the distal vessel. Parameters with a low success rate (type B) were: 1) no proximal stump, 2) sidebranches at the site of occlusion, 3) bridging collaterals and 4) a very good distal filling. 48/60 (80%) of occlusions could be classified in type A or type B. The success rate was 17/21 (81%) (type A) versus 5/27 (18.5%) (type B) (p < 0.0002). The estimated age of type B occlusions was significantly higher than in type A: median 8 versus median 4 months (p < 0.002). It is concluded that the rate of success in reopening chronic coronary occlusions can be judged in the majority of patients using morphological parameters.


[Ventricular late potentials in athletes]. Ventricular late potentials detected by signal averaging have a high predictive value for the origin of malignant ventricular tachyarrhythmias in patients with coronary artery disease. We examined 35 male sportsmen aged from 22 to 33 years. Clinical examination, ECG at rest, echocardiography and signal averaging were performed. In nine of the 35 sportsmen (26%) ventricular late potentials were detected. In a control group of 20 nonsportsmen none had late potentials. The nine sportsmen with late potentials all had electrocardiographical and echocardiographical signs of left-ventricular hypertrophy. Of the 26 sportsmen without ventricular late potentials five had left-ventricular hypertrophy. Ventricular late potentials are not rare in sportsmen. They seem always to appear together with left-ventricular hypertrophy.


[Prospective long-term ECG study of 100 patients surviving sudden cardiac death]. One hundred survivors of sudden death were randomized to four groups and treated with Amiodarone, Propafenone and Metoprolol, or were supplied with an automatic implantable cardioverter/defibrillator (AICD, control group). Prospective Holter-monitoring showed that the prognostic significance of the complexity and frequency of ventricular ectopic activity in survivors of sudden cardiac death is relative to the chosen prophylactic antiarrhythmic treatment: Findings in the control group confirm the classical notion that frequent and complex ventricular ectopic activity is predictive for recurrent life-threatening ventricular tachyarrhythmias (relapse) (> or = 25 VES/h, p < 0.05; Lown IVb, just short of statistical significance). Therapy with Amiodarone reduced frequent and complex ventricular ectopic activity as well as the 2-year relapse rate, which was significantly lower than in the control group (AICD: 36%, Amiodarone 12%, p = 0.03). Under Metoprolol the frequency and complexity of ectopic ventricular activity increased, yet the relapse rate was reduced (12%, p = 0.03). Under Propafenone, especially, those patients who showed low frequencies of ventricular ectopic activity were at high risk; the 2-year relapse rate was 28%.


[Acoustic quantification--a new online procedure for automatic recording of left ventricular areas and area changes in the echocardiogram]. Initial experiences were obtained with a new technique for automatic quantification of left ventricular areas and area changes in two-dimensional (2D) echocardiograms (acoustic quantification, AQ). AQ is based on integrated back-scatter-analysis in real-time. Practicality and reliability of AQ were studied in 50 non-selected patients. AQ measurements of left-ventricular (LV) cavities were compared with off-line measurements which were obtained by analysis of videotaped images. Thirty-two (64%) and 39 (78%) patients could be studied by AQ from parasternal and apical views, respectively. LV areas measured from parasternal views or apical views showed a good correlation with corresponding values obtained by off-line analysis (r = 0.78 to 0.91). In addition, LV fractional area changes measured by AQ showed an excellent correlation with off-line measurements (parasternal: r = 0.86; apical: r = 0.84). During infusion of dobutamine (n = 3; 5, 10, 20 micrograms/kg/min, 10 min each dose), reduction of LV cavity areas could be continuously monitored and quantified by AQ for each cardiac cycle. In five of six patients who underwent transesophageal echocardiography, AQ could easily detect LV contours in the transgastric short axis view. Although AQ is not practicable in all patients, this new technique appears to be a promising and reliable approach for real-time, automatic boundary detection in 2D echocardiograms.


[Doppler echocardiography measurement of diastolic filling parameters in acute changes of pre- and afterload in healthy probands]. For a more precise understanding of the net effects of acute alterations of pre- and afterload on left-ventricular filling, loading conditions were altered in normal subjects. The specific purpose of this study was to investigate if Dopplerechocardiographically derived transmitral flow patterns are able to differentiate the manner of loading condition. In 24 normal subjects (13 female, 11 male, mean age 44.1 +/- 11.5 years) the following Doppler variables were analyzed at baseline, after rapid infusion of volume (preload increase), nitroglycerine (preload decrease), isometric exercise (afterload increase) and converting enzyme inhibitor (afterload decrease): peak and integrated early (E, Ei) and late (A, Ai) diastolic flow velocities, their ratios (E/A, Ei/Ai), the percentage of atrial contribution (ACON) and the times of acceleration (Az) and deceleration (Dz) of early filling. Preload reduction as well as afterload increase led to a similar filling pattern with a significant decrease (p < 0.05 from baseline) of E and Ei, increase of A and Ai, and, consequently, a reduction of E/A and Ei/Ai. The atrial contribution to filling increased during both alterations; Az and Dz were reduced. Following the increase of preload, only the increase of E and Ei was statistically significant, while afterload reduction showed no significant differences. Different loading conditions alter Doppler-derived diastolic filling patterns. But the transmitral flow profile is not specific enough to differentiate in which manner loading conditions have been altered.


[Differences in the non-invasive assessment of left ventricular filling in patients with dilated cardiomyopathy using Doppler echocardiography and radionuclide angiography]. Doppler echocardiography and radionuclide angiography were shown to provide valuable tools with comparable functional parameters for the noninvasive assessment of left ventricular (LV) diastolic function in patients with coronary artery disease or LV hypertrophy. In order to examine the influence of an impaired systolic function on both methods, we studied LV filling simultaneously by Doppler echocardiography and radionuclide angiography in 47 patients with idiopathic dilated cardiomyopathy and stable sinus rhythm. The Doppler echocardiographic peak velocities (VE, VA) and radionuclide angiographic peak filling rates (PFRFF, PFRA) normalized to either left ventricular enddiastolic volume or stroke volume were measured and systolic function was assessed by obtaining the ejection fraction (EF) with the radionuclide angiography. Patients were divided into two groups with moderately (group 1: EF > or = 35%) or severely impaired (group 2: EF < 35%) systolic function. In group 2 the PFRFF (1.8 +/- 0.5 vs. 3.3 +/- 0.8 SV/s; p < 0.01) and PFRA (1.2 +/- 0.6 vs. 2.5 +/- 1.0 SV/s; p < 0.01) were both lower than in group 1, as was the Doppler echocardiographic VA (0.44 +/- 0.20 vs. 0.63 +/- 0.17 m/s; p < 0.01). However, VE was increased with reduced systolic function (0.75 +/- 0.20 vs. 0.53 +/- 0.16 m/s; p < 0.01). No relation was found between PFRFF and VE and only a weak relation between the atrial filling parameters of Doppler echocardiography and radionuclide angiography. The peak filling rates were closely correlated with the systolic function (PFRFF:r = 0.86; p < 0.001) and were reduced with an impaired systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)


[Risk stratification and long-term therapy with amiodarone in patients with idiopathic dilated cardiomyopathy]. Patients with cardiomyopathy are known to suffer from a high prevalence of tachyarrhythmic complications and sudden cardiac death. In a prospective study, 30 patients (25 men, 5 women, mean age: 52 +/- 12 years) with dilated cardiomyopathy underwent 48-h-Holter monitoring and programmed electrical stimulation and, independent from the results of the diagnostic work-up, were then randomized either to amiodarone or to a conventional or no antiarrhythmic therapy. At baseline, frequent ventricular arrhythmias (> 30 ventricular premature beats/h) were observed in 15/30 patients (50%), 13 patients (43%) had repetitive ventricular arrhythmias, additionally. Four patients suffered spontaneous sustained tachyarrhythmias. During programmed electrical stimulation, sustained monomorphic ventricular tachycardia was induced in 3/3 patients with and in 1/25 patients (4%) without a history of sustained tachycardia. Sustained monomorphic ventricular tachycardia was induced with one to two extrastimuli; three extrastimuli only increased the incidence of inducible ventricular fibrillation (8 patients, 28%). During a mean follow-up of 28 +/- 6 months 10/30 patients (33%) died for cardiac reasons (sudden cardiac death: 4/10 patients). Cardiac death was most likely in patients with a left-ventricular ejection fraction < 35% (5/18 patients, 28% versus 1/12 patients with ejection fraction > 35%, 8%) and further increased in the presence of reduced exercise tolerance and frequent and repetitive ventricular arrhythmias (4/7 patients, 57%). In the amiodarone group 4/15 patients died (27%, sudden cardiac death: one patient), while in patients not treated by amiodarone 8/15 patients died (54%; sudden cardiac death: three patients). Amiodarone therapy was well tolerated in all but one patient.


[Early radiological assessment of spinal injuries. Indication for additional imaging procedures]. The question of the best radiological diagnostic pathway to explore the acute spinal trauma is discussed. the current state of knowledge is given, based on bibliography and the authors experience. Standard-radiography allows fast orientation. CT ist the best procedure for high resolution imaging of bony structures and MRI is best suited for soft tissue and medullar lesions. Ligamentous lesions are still explored with functional X-ray studies, but ligament rupture can be visualized directly by MRI. Standard-radiography must precede all further studies. In patients without neurological deficit: CT is indicated if standard radiography suspects a bony lesion. MRI is indicated, if there is a discrepancy between a normal radiography and severe complaints of the patient. functional radiographies are indicated if ligamentous damage is suspected, but MRI can directly visualize ligament rupture. In patients with a radicular lesion, CT is indicated. In patients with a medullar or central radicular lesion, MRI or Myelo-CT are indicated.