Is a diagnosis of occupational post-traumatic schizophrenia possible?

We present the case of a man who became ill with schizophrenia at the age of 44 after he had been subjected to a series of investigations at his place of work. This case illustrates the issue of the development of schizophrenia as a result of trauma or stress. In our presentation we go into a detailed history of the case and the relevant legal and medical aspects, referring to the legal theory of microtrauma and the theory behind stress-vulnerability, in an attempt to contribute to the understanding of schizophrenia. We consider the legal definitions of 'occupational damage' and the 'common illness'. As to qualifying medical terms, medical science looks upon illnesses as resulting from the reciprocity between the organism and the environment. While the organism forever tends to maintain its equilibrium, environmental factors threaten to upset it. Considering mental illnesses in general and schizophrenia in particular, we discuss the theory of 'stress-vulnerability hypothesis'. We convey our opinion on how it is possible to bridge the gap between the law and medical science. Bringing together the two disciplines and their terms is not simple. The most significant question is whether vulnerability, or to be more precise, vulnerability or a genetic tendency, constitutes a natural morbidity process which is aggravated by the traumatic factor, or whether an individual who bears a 'vulnerability' is healthy until he comes into contact with the environmental factor. It is our opinion that one must not attach too much importance to this theory and must not consider it as fact, but rather confine one's judgment to cases where a latent 'vulnerability' has a clear-cut clinical expression. If we rely on a prevalent medical theory as if it were an evident reality we may miss the truth and may attach too much importance to a matter which is as yet solely theoretical. Our aim is to do justice to human beings. It is better to rely on facts than to trust the existence of latent factors which are within the bounds of theory. We also present a review of the literature about the connection between schizophrenia and trauma or unusual events of life.


Issues in the classification of mental illnesses within changing social relations.

The purpose of this article is to highlight critical issues in the onset and development of mental illnesses. Its contents critically examine the relevance of the standard psychiatric diagnostic measure (the biomedically based DSM III-R) in the classification of mental illnesses within changing social relations characteristic of the South African situation. Reference has been made to case studies whose clinical symptomatology reflects the multifaceted nature of psychological disturbance as it is manifested by people in a transitional state. Its major contribution is the proposition of a phenomenologically based dimensional approach in the conceptualization of the meaning of psychopathology as it is experienced by people in their total social context.


Bodily intrusion, drug search in the human body, human rights and the balance of interests.

This article deals with the thorny issue of official authority to search for drugs in the bodies of suspected drug offenders. Relevant Israeli cases and legislation are discussed and a draft bill proposed.


The relationship between the perception of alcohol and drug harmfulness and alcohol consumption by university students.

University students find themselves at a stage when many attitudes and habits undergo change and consolidation, and it is during this period when patterns of consumption of toxic substances are partially or definitively established. A group of 955 university students (328 medical students, 347 students of veterinary medicine, and 280 law students) were studied. Sex and religion played a decisive role in determining the relation between the use of toxic substances and the subjects' attitude toward consumption in our sample. Also, the three campuses were found to differ significantly with regard to students' assessment of harmfulness and patterns of consumption.


Drug rechallenge and patients' rights.

Challenging a hypersensitive patient with a potentially harmful drug is most important to the development of medical knowledge. However, it does not always serve the interest of the particular patient. In order to protect the interest of an individual patient, one must abstain from challenge unless it is vital to the health of the particular patient at the time and has no substitute. Patients' rights demand the establishment of limitations and guidelines for the procedure of rechallenge in all its aspects. An approach which will bring physicians closer to a solution, which will protect the patient from uncontrolled decisions and from unnecessary risks, is suggested.


New realities and old classifications: a problem in medical ethics.

Advances in research and technology are forcing us to confront hitherto unknown forms of life on both macroscopic and microscopic levels. Genetically engineered cells, human embryos growing in Petri dishes or preserved in freezers, human beings without hearts or functioning brains, these are just a few examples of the new forms of life. The challenge now is to determine what actions relative to these unfamiliar realities are morally acceptable.


A controlled auction market is a practical solution to the shortage of transplantable organs.

All attempts relying on pure altruism to meet the demand for transplantable donor organs have failed and continue to fail. The incentive of commercialization of an organ market would seem to be the only practical solution at this time. It is almost impossible to set fixed prices for such priceless items as human organs. The only fair, honest, and feasible approach is the establishment of a free and voluntary national or international auction system under the strict supervision and control of an exclusive, specially created administrative entity free of governmental or other partisan interference. The resultant flow of funds could be enormous and would enhance the welfare of all strata of society. Wealthy buyers would be removed from current waiting lists; the donor pool greatly expanded to perhaps surplus; the resultant money used to relieve the financial burdens on families involved, hospitals, insurance companies--and also used to buy organs for the indigent on waiting lists, pay for surgeries and hospitalization, and thereby increase the income and surgical experience of more surgeons. This proposed new system should include all live as well as brain-dead donors, cadavers and consenting individuals facing purposeful and pointless destruction by judicial execution.


Patients' complaints: some aspects of the evaluation of physicians' conduct by the Danish National Board of Health.

This study comprises all complaints made by patients to the Danish National Board of Health in 1984-1985. All disciplinary cases regarding physicians' conduct are evaluated by the board. A quantitative evaluation was carried out of the 1,062 complaints received by the board in the period under study. Special attention was given to some topics. It is emphasized that adverse outcome termed fortuitous has been narrowed over time, but more investigation is needed, in order to have a more objective foundation from which to determine whether an adverse outcome really is fortuitous or whether it is due to negligence. A central registration of cases of adverse outcome is suggested. The problem of allocating responsibility is very much open to debate, but more adequate case journal keeping is also mentioned. It was surprising that violations of information and consent requirements are often sanctioned very mildly, and more attention to this sphere is appropriate in order to ensure patients' rights. In this connection regular inquiries into patient satisfaction should be considered as a feedback mechanism.


Informed consent and 'wrongful birth': the Austrian Supreme Court's approach.

This article examines to what extent the Austrian Supreme Court is willing to apply the theory of informed consent and wrongful birth. In the decision at issue the judges came to the conclusion that a physician need not inform about every single risk of medical therapy. With regard to wrongful birth, the court left open for further discussion whether maintenance costs which were caused by a physician's negligent conduct are a matter of compensation.


IVF in the USA, who pays for it?

A decade has passed since the first American 'test-tube baby' was born at the Eastern Virginia Medical School in Norfolk. The announcement of this medical achievement was an excellent source of inspiration for many legal scholars to write about the problems of IVF. The Spanish, English and Swedish legislators were the first to be seduced by these scholars. They enacted very sophisticated statutes concerning fertilization and embryology. The American legislation did not seem (at first sight) to fall under the spell of lawyers. In this article, it is shown how more and more American state legislators, by enacting statutes to mandate insurers to cover IVF treatment, are indirectly regulating IVF.


A proposal to require attorney disclosure when a client communicates intent to harm.

The attorney-client privilege has been and will remain sacred. But a human life is more sacred. When a life is threatened, and the attorney has knowledge of this danger, he also has an obligation to protect the potential victim. If reasonable care under the circumstances requires him to disclose certain confidences, then an exception to the rule of privilege must be made. DR 4-101 (c)(3) should be changed to reflect this obligation.


Medical malpractice: tortious liability or no-fault insurance?

This article discusses the merits of no-fault insurance as compared to tortious liability in medical malpractice cases. The implications of adopting the Swedish model in Israel are considered.


Images of law and disorder: a survey of forensic mental health professionals in Ontario, Canada.

In this article we report on a survey that was organized to expand knowledge across a range of medicolegal issues and pragmatic applications. We wanted to provide forensic professionals with an opportunity to express their views on these various forensic trends, and on their relevance for expert identities, statuses and activities across a broad spectrum of contexts and concerns. In an exploratory framework, the intention was to operationalize many of these developments in systems, laws, ideas and practices, and to present them as structured questions for the consideration of respondents representing the full complement of mental health disciplines connected to the criminal court apparatus in one Canadian province. In what follows we set out to sketch their images of law and disorder, and their specific opinions about the role of forensic practitioners, the nature of forensic assessment and decision-making, the relationship between mental disorder and crime, the application of treatment and punishment, and the overall process of criminal court adjudication and sentencing.


The limited role of the human interferon system response to respiratory syncytial virus challenge: analysis and comparison to influenza virus challenge.

The respiratory syncytial virus (RSV)-induced production of interferon (IFN) by human macrophages and mononuclear leukocytes (MNL) and the sensitivities of RSV to subtypes of IFN-alpha were examined and compared to IFN production induced by influenza virus. Influenza virus induced high titers of total IFN bioactivity, transcription of the IFN-alpha 1 and IFN-beta gene products and production of IFN-gamma. In contrast, RSV induced minimal or no detectable total IFN activity, and the absence of IFN bioactivity could not be attributed to inhibitors of IFN activity. There was no detectable transcription of IFN-alpha or IFN-beta gene products by the cells exposed to RSV. RSV-exposed MNL did produce small amounts of IFN-gamma, consistent with prior sensitization of the cell donors to the virus, but titers were substantially lower than those induced by influenza virus. RSV showed minimal but equivalent susceptibility to several subtypes of IFN-alpha. The data raise the possibility that the IFN system has a limited direct role in early host defense against RSV infection, but results should not be extrapolated directly to in vivo events.


Intranasal infection of infant mice with Neisseria meningitidis.

In human meningococcal infection the mechanism of the transition from asymptomatic carriage to invasive disease is unknown, partly due to the lack of an effective animal model that mimics all stages of the human disease. Therefore, we have endeavoured to develop a model for the human infection by instilling a suspension of Neisseria meningitidis into the nostrils of infant mice and subsequently determining the numbers of organisms in the nasal passages, lungs, blood and brains. Intranasal (i.n.) instillation resulted in consistent nasal colonisation which usually developed into a lung infection. In many cases the lung infection preceded bacteraemia, which occasionally resulted in death of the mice. The severity of the infection and the transition to bacteraemia were enhanced by intraperitoneal (i.p.) treatment of the mice with iron dextran or human transferrin. A N. meningitidis strain that was avirulent in an i.p. infection was also avirulent following i.n. infection. The requirement for lung colonisation to precede bacteraemia and the need for i.p. injection of iron compounds limit the use of i.n. infection of the infant mouse as a model for human meningococcal disease. However, various aspects of meningococcal virulence can be examined using this model.


Effects of computer reminders for influenza vaccination on morbidity during influenza epidemics.

To study the effects of computer-generated reminders for influenza vaccination of patients at high risk of pulmonary disease during the winter, we selected 4555 such patients from a population of 15,000 adults who participated in a three-year randomized trial of preventive-care reminders. The physicians who received the reminders vaccinated eligible patients twice as often as did the control physicians (P = 0.0001). There was a linear increase in the incidence of influenza in our area during the three winters under study (from 1000 to 33,451 to 71,075 cases per year), and we modeled the percentage of patients with hospitalizations, emergency room visits with chest radiography, and blood gas determinations as a logistic function of this increase. The difference in linear trends between the patients in the intervention group (whose physicians received reminders) and those in the control group was significant for emergency room visits (P less than 0.05), hospitalizations (P less than 0.01), and blood gas determinations (P less than 0.001). The most likely explanation for the difference is the greater use of influenza vaccine in the intervention group.


A high Mr factor in human blood which confers serum resistance on gonococci: some properties and synergism with CMP-NANA.

A high relative molecular mass (M(r)) component which confers serum resistance on gonococci has been purified about 300-fold from a dialysed sonicate of human blood cells. Serum resistance conferred by the high M(r) factor (RIF), like that induced by cytidine-5' monophospho-N acetyl neuraminic acid (CMP-NANA), decreased when gonococci were incubated with neuraminidase. Also, the resistance-inducing activities of both high M(r) RIF and CMP-NANA were inhibited by CMP and inactivated at pH 4.0. These activities were not additive but synergistic. Neuraminidase decreased the activity of high M(r) RIF but not CMP-NANA. In tests with 14C CMP-NANA and gonococcal lipopolysaccharide, no sialyltransferase activity was detected, even in highly active samples of high M(r) RIF under conditions in which low activities of rat liver sialyltransferase were readily detected. Conversely, rat liver sialyltransferase was neither active in the RIF assay nor able to enhance the RIF activity of CMP-NANA. Nevertheless, high M(r) RIF greatly enhanced the sialyltransferase activity of a gonococcal extract; this enhancement suggests an explanation for the synergism between CMP-NANA and high M(r) RIF in inducing serum resistance in gonococci.


Epitope analysis of an immunodominant domain on the P1 protein of Haemophilus influenzae type b using synthetic peptides and anti-idiotypic antibodies.

Synthetic peptides, anti-idiotypic antibodies (anti-Id) and human and murine monoclonal antibodies (mAbs) were used to further define a major antigenic domain on the outer membrane P1 protein (OMP) of Haemophilus influenzae type b (Hib). Synthetic peptides were elaborated from the known primary sequences of the P1 protein of prototype Hib strains MinnA (OMP subtype 1H) and 8358 (OMP subtype 6U). By peptide mapping, antibodies are categorized into three groups: A, B and C. A first epitope on the P1 from strain MinnA was identified by the reactivity of one set of murine anti-P1 mAbs with the two overlapping peptides 11H and 13H, corresponding to amino acid residues 384-412 and 400-437, respectively. On the basis of their reactivity with both peptides, these mAbs were designated as group A. Anti-Id obtained from mice immunized with two group A mAbs reacted specifically with all group A mAbs. A second epitope on the same P1 protein was identified by the reactivity of the peptide 13H with another distinct set of murine anti-P1 mAbs assigned to group B. This group of mAbs did not recognize the peptide 11H. Murine anti-Id which were prepared against one group B mAb inhibited the attachment of this mAb to outer membrane preparations, whereas the binding of the other group B mAbs was not affected, suggesting that these mAbs represent a heterologous group of mAbs. The epitope(s) recognized by two human anti-P1 mAbs was (were) distinct from the ones recognized by murine mAbs since no reactivity with the peptides was observed. Similarly, the binding of the two human mAbs to the P1 antigen was not inhibited by anti-Id raised against group A or B mAbs. Interestingly, an epitope on a different P1 protein recovered from strain 8358 was identified by the reactivity of group C murine mAbs with the peptide 13U, which occupies the same position on the P1 protein as 13H but differs from the latter by 10 amino acid residues. Our studies demonstrated the presence of several distinct surface-exposed B-cell epitopes within the antigenic domain which was defined previously on the P1 protein of Hib MinnA. Furthermore, we showed the immunodominance of this region on two different P1 proteins. None of the mAbs, however, had a bacteriolytic or protective activity against Hib strains. We suggest that the surface-exposed immunodominant region on the OMP P1 of Hib do not induce protective antibodies against Hib infection.


Binding of fibronectin and type II collagen to Staphylococcus aureus from bovine mastitis: reduction of binding after growth in milk whey.

The binding of fibronectin and type II collagen to Staphylococcus aureus strains isolated from bovine mastitis was found to be 20-80% lower for organisms grown in milk whey compared to those grown in tryptic soy broth (TSB). The reduced binding was accompanied by reduced surface hydrophobicity. The observed changes, after growth in milk whey, were not due to a mere adsorption of milk whey components. The binding of fibronectin and the degree of surface hydrophobicity of milk whey-grown bacteria became similar to that of TSB-grown bacteria after periodate treatment, whereas trypsin or papain treatments had no effect.


Statistical packages for the Macintosh.

These programs represent the entry of the Mac into major statistical computing. We believe that for the physician researcher who is not a statistician, they make the Mac the platform for data analysis. We found that statistics, research design, and data analysis seemed different and much less intimidating to us and our trainees when approached through the Mac. We have reviewed the versions of these programs available at the time of this writing, in May 1992; potential buyers should contact the software publisher for information about more recent upgrades. At this point, our recommendations would be as follows: If you are wedded to SPSS or Minitab, try the Mac versions, and you will be impressed. Otherwise, the choice is between SYSTAT, which has been around long enough to demonstrate its richness and capacity to build on its strengths, and JMP, a brash newcomer, which demonstrates that you can teach an old dog (SAS) new tricks. StatView and SuperANOVA, while endowed with intuitive, easy-to-use interfaces, lack online help--a feature we consider important in a statistics package. We anticipate that the future will lead to simplification of the SYSTAT interface and the addition of more analytic capacities to JMP--and who knows what the next generation of competitors will bring?


Enteropathogenicity of non-toxigenic Vibrio cholerae O1 for adult mice.

The enteropathogenic potential of 32 Vibrio cholerae O1 isolates that do not produce cholera toxin was examined in the orally inoculated, sealed adult mouse model. Live cultures (2 x 10(10) cfu/ml) of 7/16 clinical and 6/16 environmental isolates produced a positive intestinal fluid accumulation (FA) ratio that reached near maximum at approximately 5 h post-inoculation. Colony hybridization did not detect genes for cholera toxin, Escherichia coli heat-labile and heat-stable toxins, or shiga-like toxins. FA activity did not correlate precisely with cytotoxic activities on Chinese hamster ovary (28/32 positive), Vero (29/32) or HeLa (25/32) cells. Certain clinical and environmental isolates of non-toxigenic V. cholerae O1 appear to be enteropathogenic for the mouse, providing evidence that they may have pathogenic potential for humans through an as yet undefined mechanism(s).


Pasteurella haemolytica leukotoxin inhibits mitogen-induced bovine peripheral blood mononuclear cell proliferation in vitro.

In this study we demonstrate that partially purified Pasteurella haemolytica leukotoxin inhibits the proliferative response of bovine peripheral blood mononuclear cells (PBMC) to mitogens in vitro. Inhibition of PBMC proliferation did not appear to be due to cell death. Addition of a neutralizing anti-leukotoxin monoclonal antibody restored a normal proliferative response.


Amyloidosis and inflammatory bowel disease. A 50-year experience with 25 patients.

Amyloidosis is a rare but serious complication of inflammatory bowel disease (IBD), especially Crohn's disease (CD). It occurred in 15 of our 1709 patients with CD (0.9%) (706 with ileocolitis, 310 with colitis, and 693 with enteritis), but in only 1 of our 1341 patients with ulcerative colitis (UC) (0.07%), admitted to The Mount Sinai Hospital between 1960 and 1985. Eleven of the patients with CD who had amyloidosis had ileocolitis, 2 colitis, and 2 ileitis; these figures represent a frequency within each group of 1.6%, 0.6%, and 0.3%, respectively. Amyloidosis was thus associated 4.4 times more often with CD of the colon than with pure small bowel disease. We have added to this group of 15 patients the 5 cases of CD that were originally reported by Werther et al in 1960, plus another 4 (2 with UC and 2 with CD) who have been seen since 1985, making a total of 25 patients in this series, 22 with CD and 3 with UC. There was a striking male preponderance, 16 of 22, among patients with CD, although 2 of the 3 patients with UC were female. Amyloid disease was diagnosed at a mean age of 40 years, 15 years (range, 1-42) after the onset of CD. Six major forms of amyloidosis occurred: nephropathy, enteropathy, cardiomyopathy, hepatosplenomegaly, thyroid mass, and generalized amyloidosis. Renal disease with proteinurea and/or renal insufficiency occurred in 18 of the 22 patients with CD and in all 3 with UC. Nephropathy was by far the most common lethal manifestation of IBD-associated amyloidosis in this series. Nephrotic syndrome developed in 15 patients with CD and was accompanied by renal failure, the major contributor to mortality, in 10 of the 13 patients who died. Amyloidosis may be associated with suppurative or other extraintestinal manifestations of IBD. Fifteen of the 22 patients with CD who had amyloidosis also had suppurative complications of their bowel disease, although the other 7 had no recognizable suppuration. Extraintestinal manifestations were also common in this series, occurring in 12 of 22 patients with CD and in 2 of the 3 patients with UC; 6 of the 18 patients with nephrotic syndrome also had arthritis. However, there is no evidence that patients with IBD with amyloidosis have extraintestinal manifestations more frequently than do IBD patients without amyloidosis. Earlier reports of amyloid associated with IBD came from autopsy series. In recent years, biopsy has allowed diagnosis to be made during life.(ABSTRACT TRUNCATED AT 400 WORDS)


Central nervous system complications of thermal burns. A postmortem study of 139 patients.

We report a retrospective, clinicopathologic study of 139 patients who died during treatment of a severe burn. Fifty-three percent of the patients had central nervous system (CNS) complications-infections, cerebral infarcts and hemorrhages, metabolic encephalopathies, central pontine myelinolysis, and cerebral trauma. Children and adults were equally affected. Sixteen percent of the patients had a CNS infection. Candida species, Staphylococcus aureus and Pseudomonas aeruginosa caused almost 80% of them. S. aureus and candida caused cerebral microabscesses and septic infarcts. P. aeruginosa caused meningitis and infarcts due to meningitis. CNS infections arose as a result of spread from a systemic source. The major risk factors for CNS infection were an extensive burn, S. aureus endocarditis, and a burn wound infection due to candida or P. aeruginosa. Patients with burns of less than 30% of the surface area of their body, those without a systemic infection, and those in the first week after their burn were at low risk. Eighteen percent of the patients had cerebral infarcts. In almost half the patients, the infarcts were caused by septic arterial occlusions or other complications of the burn, viz, disseminated intravascular coagulation (DIC) and septic shock. In only one-third of the patients were infarcts due to atherosclerosis, atrial fibrillation, or other causes prevalent in the general population. Intracranial hemorrhages were only one-fifth as frequent as infarcts and were due to DIC and thrombocytopenia, caused by bacteremia. Diagnosis during life was difficult, because the neurologic picture of focal cerebral lesions and meningitis was indistinguishable from that of metabolic encephalopathies, and because many patients had more than 1 neurologic complication. However, our results suggest that a clinical approach that includes analysis of risk factors for CNS infection, cerebral imaging, examination of cerebrospinal fluid, and tests for DIC can lead to a neurologic and microbiologic diagnosis in most patients.


Assessment of renal osteodystrophy in hemodialysis patients.

We performed a prospective study of 30 patients undergoing chronic hemodialysis to determine which of 6 generally available diagnostic procedures provided the most useful information for the assessment of bone disease in hemodialysis patients. The 6 procedures were: routine biochemical measurements, N-terminal parathyroid hormone (N-PTH), radiographic analysis of hands and clavicles, bone density determination by dual photon absorptiometry (DPA), deferoxamine stimulation test, and iliac crest bone biopsy. Serum N-PTH was elevated in 83% of patients but was not significantly associated with abnormalities of other biochemical parameters. No significant relationship was demonstrated between biochemical data and radiographic findings or between biochemical data and bone density by DPA. All patients with abnormal DPA had an elevation of N-PTH; therefore, DPA did not reveal any unsuspected disease. Bone biopsies were done in 20 patients and findings in each were consistent with uremic osteodystrophy, including osteitis fibrosa cystica in 11 patients and aluminum-associated bone disease in 2 patients. Six patients had mixed disease, and 1 patient had osteoporosis. Despite 11 positive deferoxamine tests, bone biopsy revealed aluminum deposition in only 7 of these patients, suggesting extraosseous aluminum accumulation in the remaining 4. Evaluation of the positive and negative predictive accuracies of DPA, x-ray analysis, N-PTH levels, and aluminum bone deposition revealed that normal DPA or x-ray findings do not exclude bone disease, that N-PTH level is a good marker for secondary hyperparathyroidism, and that a negative deferoxamine test excludes aluminum-associated bone disease. Discriminant analysis also reinforced these conclusions.(ABSTRACT TRUNCATED AT 250 WORDS)


Coronary artery disease risk factors in the Johns Hopkins Lupus Cohort: prevalence, recognition by patients, and preventive practices.

Known risk factors for coronary artery disease are very common in the Hopkins Lupus Cohort, in spite of the fact that the average patients age is only 38.3 years. Three or more known risk factors were found in 53% of patients. Risk factors for CAD were common even in patients not on a regimen of prednisone therapy during their cohort follow-up. Hypercholesterolemia increased significantly with greater average prednisone dose. Despite the frequency of risk factors, patients' awareness of the risk of CAD was low, with only 16.9% of patients believing they were at high risk for developing CAD within 5 years. In general, awareness of individual risk factors was lower in black than in white patients with SLE. Preventive practices were most commonly addressed towards hypertension. Preventive practices directed against obesity, hypercholesterolemia, and smoking were underutilized. Whether these known risk factors are sufficient in and of themselves to explain the high frequency of CAD in the cohort (8%) or whether they are "enabling" factors acting upon endothelium damaged by immune-complex disease cannot be addressed by this study. However, both further investigation of these risk factors and attention to lifestyle and pharmacologic approaches to risk factor reduction are indicated by this study.


Prevalence of Clostridium botulinum type E and coexistence of C. botulinum nonproteolytic type B in the river soil of Japan.

Soil samples from 98 sites in the whole systems of four rivers in Japan were examined for the presence of Clostridium botulinum. Type E organism was prevalently shown throughout the whole river systems including upper part; detection rates of type E toxin in soil culture ranged from 33 to 82%. This type was also detected in soil of adjacent mountainous district. Type B and C toxins were detected at 7% and 9% of the sites examined, respectively. C. botulinum type E and nonproteolytic type B strains were isolated from enrichment cultures of soil samples. These results suggest that the terrestrial origin of type E organism would be considered as one of the reasons for the high incidence of this organism in the sea areas, and prove that C. botulinum nonproteolytic type B exists in the soil of Japan.


Role of the upstream region containing an intrinsic DNA curvature in the negative regulation of the phospholipase C gene of Clostridium perfringens.

The phospholipase C (alpha-toxin) gene (plc) of Clostridium perfringens was cloned into pUC19 and the effects of the upstream regions on expression of the plc gene were examined in Escherichia coli JM109. When the 0.7-kb region just upstream of the putative -35 site of the gene was deleted, production of phospholipase C increased approximately 10-fold. Northern blot hybridization analysis of the plc transcript showed that the upstream region inhibited transcription from the plc promoter. Nucleotide sequencing of this upstream region revealed that there are three periodically repeated (dA)5-6 tracts between positions -66 and -40 of the plc gene. A fragment containing this sequence showed anomalously slow electrophoretic mobility at low temperature, indicating that the region immediately upstream of the plc promoter is a locus of sequence directed DNA-bending. Nested deletions of the upstream region were created from its 5' end by exonuclease III and the effects of deletions on the expression of the plc gene were examined. When the 77-bp fragment containing the two (dA)5-6 tracts were deleted, phospholipase C production increased markedly. These results indicate that the intrinsic DNA curvature upstream of the plc promoter is involved in the negative regulation of the plc gene transcription.


Adenovirus infection and specific secretory IgA responses in the intestine of infants.

We investigated adenovirus (Ad) infection of the intestine and Ad group-specific fecal IgA antibody responses in seven infants who were followed up from birth to 16 months to seven years of age. We isolated in tissue culture from fecal samples not only enteric Ad type 41 but also other Ads (types 2, 3, 5, 6, and 12). We also detected Ad antigens in the feces by ELISA at the times of infection with even non-enteric Ads, suggesting that a large amount of antigens were produced in the intestine. We found that repeated Ad infections with different serotypes were occurring and there were good fecal IgA antibody responses at each time. The infection seemed usually mild or asymptomatic: only one out of 23 occasions of the detected infections required hospitalization.


Heat-labile toxin from Bordetella parapertussis induces contraction of smooth muscle cells in culture.

The ability of Bordetella heat-labile toxin (HLT) to contract various types of cells in culture was examined. HLT from B. parapertussis induced contraction of cultured smooth muscle cells from trachea, intestine, uterus and vas deferens as well as from aorta. The time required for contraction decreased as the dose of B. parapertussis HLT increased from 3 to 100 MID/ml. Upon exposure of cells to concentrations of toxin greater than 100 MID/ml, at least 2 hr was required for contraction. HLT from B. parapertussis did not affect cultured cardiac or skeletal muscle cells within 8 hr after the exposure to HLT (100 MID/ml). No effect on other types of primary culture cells or established cells such as Chinese hamster ovary (CHO) cells has been described. These data indicate that the primary target cells for HLT might be smooth muscle cells.


Purification and characterization of secretory proteinase of Candida albicans.

Proteolytic activity of medically important yeasts was tested in both YCB-BSA agar and medium. All of 134 strains of Candida albicans, 13 of 18 strains of Candida tropicalis and 11 of 18 strains of Candida parapsilosis had this activity, while none of 52 Candida glabrata strains or of 11 Cryptococcus neoformans strains tested had proteolytic activity. Strains of C. albicans fell into five groups based on the level and time-course of in vitro proteinase productivity. Five strains randomly selected from each group were tested for pathogenicity in mice. The strain possessing the strongest pathogenicity was used to purify proteinase. The molecular weight of the proteinase was approximately 44,000 daltons and its isoelectric point was pH 4.2. Optimal pH of the proteinase was 3.2 and the enzyme was stable below pH 7.0 and lost its activity above pH 8.0 at 37 C in a 60-min incubation. The 23 amino acid sequence of the proteinase N-terminus was determined.


Characterization of an exo-beta-D-fructosidase from Streptococcus mutans Ingbritt.

An extracellular enzyme beta-D-fructosidase was purified from the culture supernatant of Streptococcus mutans Ingbritt and characterized. The molecular weight of the enzyme was 127,000 as determined by SDS-polyacrylamide gel electrophoresis. The enzyme was specific for levan which mainly consists of beta-(2,6)-linked D-fructose and was also able to hydrolyze inulin, sucrose and raffinose at the activities of 13, 9 and 5% of that hydrolyzing levan, respectively. The pH optima for levan, inulin and sucrose were approximately 5.5, 6.0 and 5.0, respectively. The enzyme was optimally reactive at 55 C for levan. The enzyme was inhibited by Fe3+, Hg2+ and Zn2+ and not by either anionic or non-ionic detergents. Paper chromatographic analysis revealed that the enzyme attacked levan by an exo-type mechanism.


Seroepidemiology of spotted fever group rickettsiae in small field rodents in Japan.

To clarify the geographic distribution of spotted fever group (SFG) rickettsiae in Japan, small field rodents captured in endemic and nonendemic areas were screened for anti-SFG rickettsia antibodies by the immunofluorescence test. Among total 716 specimens tested, 73-75% of rodents were antibody-positive against Rickettsia japonica and/or Rickettsia montana, showing different degree of antibody-positive proportions among each species of the rodents. Interestingly, these profiles were not different in the rodents from each endemic and nonendemic areas, indicating that the SFG rickettsiae are prevailing in the wider areas where patients have not been found yet.


Immunoglobulin G Fc fragment-binding proteins in Mycoplasma salivarium cells.

Cell proteins of Mycoplasma salivarium were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to membranes, then examined for reactivity with human IgG molecules, the Fc fragment of human IgG, and concanavalin A (ConA). Multiple protein bands bound IgG, and most of them also bound ConA. One (corresponding to a molecular mass of 90 kDa) of the IgG- and ConA-binding bands intensely interacted with the Fc fragment of IgG. The reactivity of proteins eluted from the band with the Fc fragment, tested by dot-blotting and ELISA, was inhibited (90%) by pre-incubation with IgG and to a lesser extent (50%), with IgM. Thus, M. salivarium contained a cellular protein with a molecular mass of 90 kDa, that bound the Fc fragment of human IgG.


Nucleotide sequence of the arginine deiminase gene of Mycoplasma hominis.

The arginine deiminase gene of Mycoplasma hominis was amplified by the polymerase chain reaction, and its entire nucleotide sequence was determined. This gene consists of 1227 base pairs encoding 409 amino acids, and has 35.2% guanine plus cytosine content. Nucleotide sequence homologies of the arginine deiminase gene between M. hominis and M. arginini, and between M. hominis and M. orale were 82.1 and 80.8%, respectively, suggesting that this gene is highly conserved among arginine-utilizing Mycoplasma species.


Arginine deiminase gene of an AIDS-associated mycoplasma, Mycoplasma incognitus.

Recently, we have demonstrated by molecular cloning that a strong immunosuppressive factor derived from Mycoplasma arginini is arginine deiminase. We show here that mycoplasma species identified in many of AIDS patients also bear the arginine deiminase gene. The implication of the arginine deiminase gene detected in AIDS-associated mycoplasma species is discussed.


Flow cytometric assay for estimating fungicidal activity of amphotericin B in human serum.

We describe a simple and rapid bioassay for estimating fungicidal activity of Amphotericin B in human serum using flow cytometry. The method exploits the fact that Candida albicans damaged by Amphotericin B show a decrease in size and take up propidium iodide to exhibit a red fluorescence after deoxycholate treatment. These phenomena display characteristic dose dependencies, and their assessment permits serum fungicidal activity to be broadly grouped into three categories: (1) subfungicidal; (2) fungicidal; and (3) strongly fungicidal. In normal human serum, these three categories correspond to Amphotericin B concentrations of 0 less than or equal to 0.5 micrograms/ml, 0.75-1.5 micrograms/ml, and greater than 2 micrograms/ml, respectively. Pilot analysis of serum samples obtained from four patients undergoing Amphotericin B therapy confirmed the feasibility of using the flow cytometric assay for estimating drug fungicidal activity ex vivo. The method is very simple, generates results within 5 h, and could prove useful for monitoring therapy with this effective but toxic drug.


[Influence of heavy metal ions on the electrophysical properties of Anacystis nidulans and Escherichia coli cells].

The influence of heavy metal ions (Ag+, Cu2+, Cd2+, Pb2+, Mn2+, Zn2+, Gd3+, 1 microM-1 mM) on Anacystis nidulans and Escherichia coli cells has been studied by means of electrophoresis and electro-orientation spectroscopy methods. It has been shown that changes of cell electrophoretic mobility (EM) and low-frequency (20 Hz) electro-orientation effect (EOE) observed with the increase of metal cation concentration characterize the adsorption of these ions on surface layers of cell envelopes. The degree and the character of these changes depend on cation valency and the initial value of cell EM. At the same time different changes of EM and EOE as a result of the multivalent cation adsorption allows to conclude that in that case the anisotropy of the cell surface increases. Cell damages were determined by changes in high-frequency EOE of cells which indicated the disturbance of barrier properties of their cytoplasmic membrane. Toxic effects of Ag+, Cu2+, Cd2+ ions on cells of both species and of Pb2+ on E.coli cells were observed. By toxic effects on the cytoplasmic membrane these ions could be placed in the order: for A.nidulans cells--Ag+ greater than Cu2+ greater than Cd2+; for E.coli cells Ag+ greater than Cu2+ greater than Cd2+ greater than Pb2+. Higher toxicity of heavy metals on E.coli cells seems to be connected with the more negative charge of deep layers of the cell surface.


Prevalence of infections affecting the child among pregnant women in Yaounde, Cameroon.

The prevalence of infections which have deleterious effects to either the mother or the fetus during pregnancy are unknown in Cameroon. To formulate appropriate antenatal screening policies for the Central Mother and Child Clinic in Yaounde, we tested random sera obtained from 1,014 stored samples previously obtained from pregnant women. One hundred and fifty sera were tested for the presence of the hepatitis B surface antigen (HBsAg), 544 for syphilis antibodies, 192 for antibodies to rubella and 192 for antibodies to Toxoplasma gondii. We found the HBsAg in 25.3% (38/150) of the subjects, antibodies against syphilis in 15.9% (87/544), antibodies to the rubella virus in 83.9% (161/192) and evidence of toxoplasma infection in 77.1% (148/192). Of the 38 HBsAg-positive subjects, 5.2% and 55.3% were positive for the HBe antigen and HBe antibody, respectively. We found a high prevalence for these infections in the antenatal clinical attendants. The data will be used to develop an appropriate control strategy for them.


Evidence that bismuth salts reduce invasion of epithelial cells by enteroinvasive bacteria.

The effects of sublethal concentrations of bismuth salts on bacterial invasion of mammalian cells were investigated. Pepto-Bismol, bismuth subsalicylate, and bismuth oxychloride, produced by interacting bismuth subsalicylate and simulated gastric juice, in suspension at concentrations as low as 1.4 mM significantly interfered with the invasion of RPMI-4788 cells by two different strains of Yersinia enterocolitica. Invasion of the mammalian epithelial cells by other enteric bacteria was also reduced significantly by some of these bismuth salts. Commercially obtained bismuth oxychloride, bismuth sulfide, and sodium salicylate had no affect on invasion by Y. enterocolitica. Exposure of Y. enterocolitica 8081c to Pepto-Bismol for as brief a time as 5 min was sufficient to produce the inhibitory effect. Removal of bismuth bound to bacteria by sodium potassium tartrate did not reverse the inhibition. Electron-dense deposits are observed in Y. enterocolitica 8081c exposed to bismuth subsalicylate, suggesting that interference of invasion may result from bismuth permeation of the bacterial cell wall.


[Electrophysical analysis of Escherichia coli cell damage caused by silver ions].

The influence of Ag+ (0.5-10 microM) on Escherichia coli K-12 cells was studied by electrophoresis and electro-orientation spectroscopy methods. It was shown that the pH-dependency of the cell electrokinetic potential (phosphate-citrate buffer with ion strength 0.02) practically didn't changed after Ag+ treatment, but in low-conductive media electrophoretical mobility of intact and inactivated by heat (70 degrees, 15 min) cells gradually decreased as the Ag+ concentration increased. It was due to the Ag+ adsorption on the cell surface and could not be used for the definite characterization of the cell damage. The high-frequency decrease in the cell electro-orientation spectrum shifted to the region of lower frequencies, K+ was excreted by cells, slight raise of the medium pH occurred and significant changes of cell osmotic properties were observed as a result of Ag+ action. All these changes showed the disturbance of barrier properties of the cytoplasmic membrane. Besides the damaging action of Ag+ on cell membranes increased with the decrease of pH and decreased after the addition of Mg2+, Ca2+ and Sr2+ in low concentrations.


Deposition of bismuth by Yersinia enterocolitica.

Yersinia enterocolitica 8081c cultures in exponential growth were incubated for 1 h in 0.1% microcrystalline bismuth subsalicylate (BSS) suspensions. Scanning electron microscopy (SEM) revealed microcrystals directly bound to BSS-treated bacteria. Energy dispersive spectroscopy (EDS) X-ray microanalysis of the attached microcrystals confirmed that the crystals were the microcrystalline BSS. X-ray spectra positive for bismuth were also obtained by SEM-EDS X-ray microanalysis of whole bacteria, suggesting metal incorporation into the bacteria in regions absent of bound microcrystals. Transmission electron microscopy of thin sections of embedded preparations of BSS-treated exponential-growth-phase bacteria showed electron-dense deposits in the periphery of the bacteria. Y. enterocolitica cultures that were in stationary phase at the time of incubation with microcrystalline BSS showed no evidence of the electron-dense deposits and EDS spectra were negative for bismuth. Bacteria incubated in the absence of microcrystalline BSS also lacked electron-dense deposits. Scanning transmission electron microscopy used in conjunction with EDS X-ray microanalysis to view and analyze semi-thick sections (250-300 nm) of embedded preparations of BSS-treated bacteria in exponential growth confirmed that the electron-dense deposits at the periphery of the bacteria are the sites of bismuth depositions.


Parvoviruses are inefficient in inducing interferon-beta, tumor necrosis factor-alpha, or interleukin-6 in mammalian cells.

To investigate a possible role of cytokines in parvovirus-mediated suppression of tumorigenesis, we tested in cell culture whether parvoviruses are able to induce interferon (IFN)-beta, tumor necrosis factor (TNF)-alpha or interleukin-6 (IL-6). Infection of rodent or human cells with the parvoviruses minute virus of mice (MVM), H-1 or adeno-associated virus (AAV) types 2 or 5 failed to induce expression of the luciferase or beta-galactosidase reporter genes transfected into these cells as constructs containing an IFN-beta promoter. Parvoviruses did weakly induce synthesis of TNF-alpha and of IL-6 in cell culture and could slightly enhance synthesis of these cytokines when induced by other agents. These in vitro data suggest that the rather unspecific tumor-suppressive properties of parvoviruses are unlikely to be attributable to stimulation of the synthesis of IFN, TNF or IL-6.


Experimental Yersinia enterocolitica infection in rats: analysis of the immune response to plasmid-encoded antigens of arthritis-susceptible Lewis rats and arthritis-resistant Fischer rats.

Recently, experimentally Yersinia-induced arthritis in Lewis and SHR rats has been described as a potential animal model for analyzing the pathomechanism of reactive arthritis (Toivanen et al. 1986; Hill and Yu 1987). We could confirm that Lewis but not Fischer rats develop aseptic arthritis about 2 weeks after an intravenous inoculation of Yersinia enterocolitica, serotype 0:8 (Hill and Yu 1987). Moreover, we compared the antibody response to virulence-associated Yersinia antigens (Yops) of experimentally infected Lewis rats with that of Fischer rats using an enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The ELISA results revealed a more rapid and vigorous specific IgG, IgA and IgM response for Lewis rats than for Fischer rats in the early state of infection. As demonstrated by immunoblotting, the IgG response was directed predominantly against the plasmid-encoded YopM, YopH, YopD and the V-antigen during the acute phase followed by antibodies against YopE and YadA. Although both rat strains seroconverted against this set of antigens, IgG antibodies to YadA were more prevalent and of higher titer in arthritis-susceptible rats compared to arthritis-resistant rats.


Effect of intrauterine exposure to cocaine on acetylcholinesterase in primary cultures of fetal mouse brain cells.

The effect of in utero exposure to cocaine on the developmental pattern of acetylcholinesterase (AChE), a major regulator of the central nervous system neurotransmitter acetylcholine, was studied in fetal brain cell cultures collected from mice on gestational day 15 after maternal exposure to cocaine from gestational days 6-14. A significant decrease in total and specific activity (expressed per mg of protein) of acetylcholinesterase was seen throughout the culture period in the cells grown from the cocaine-exposed animals as compared to controls (p less than .002). Similarly, the total protein content of the brain cells grown from the cocaine-exposed animals was significantly decreased as compared to controls (p less than .03). Utilizing AChE as a biochemical marker, these studies have shown that in utero exposure to cocaine has an adverse effect on the normal developmental pattern of the production of acetylcholinesterase in cholinergic neurons in the fetal mouse brain.


Behavioral effects of lead in monkeys tested during infancy and adulthood.

A total of 12 monkeys (Macaca fascicularis) were dosed orally from birth with 0 or 2000 micrograms/kg/day of lead as lead acetate. Blood lead concentrations of treated monkeys peaked at an average of 115 micrograms/dl by 100 days of age and decreased to a steady state level of 33 micrograms/dl after withdrawal of infant formula at 270 days of age. At 5-6 months of age, they were tested on a nonspatial discrimination reversal paradigm. At 2.5-3.0 years of age, they were tested on a series of nonspatial discrimination reversal problems, including irrelevant cues. As adults, performance was assessed on a differential reinforcement of low rate (DRL) schedule of reinforcement, a spatial delayed alternation task, and during training on a visual discrimination task for a visual psychophysics experiment. There were no or marginal deficits on the discrimination reversal task during infancy. Although lead-treated monkeys were impaired on this task as juveniles, they were less impaired than would have been predicted based on their history of blood lead concentrations. Treated monkeys exhibited decreased interresponse times and a greater ratio of responses per reinforcement on the DRL schedule compared to controls. Four of five treated monkeys were unable to learn the visual discrimination task without a remedial training procedure in which the relevant visual stimuli were arranged to appear as if they were on the response buttons. Treated monkeys were unimpaired on the delayed spatial alternation task. The results are interpreted as suggestive of an interaction between the behavioral history of the monkeys as infants with the results of later behavioral testing.


Modulation of glial cell differentiation by exposure to lead and cadmium.

The influence of the neurotoxic agents lead and cadmium on human glioma cells (86HG-39, 87HG-31, 88HG-14, and A172) and rat glioma cells (F98 and RG2) was investigated in vitro by means of immunocytochemistry and growth data. Both heavy metals increased the growth rate, decreased the expression of differentiation markers (glial fibrillary acidic protein, S100 protein), and increased the expression of the malignancy marker transferrin receptor. The results indicate a decrease in the level of differentiation and impairment of glial cell function. Consequently, the neurotoxicity of Pb and Cd may be attributed to direct action not only on neurons but also on glial cells necessary for neuronal function. Possible molecular mechanisms are discussed.


Euthanasia by decapitation: evidence that this technique produces prompt, painless unconsciousness in laboratory rodents.

Rapid euthanasia of laboratory rodents without the use of anesthesia is a necessary research technique whenever there is the likelihood of anesthesia or stress interfering with the chemistry of the tissues under investigation. Decapitation has long been the procedure of choice under such circumstances. Recently, however, the American Veterinary Medical Association (AVMA) panel on euthanasia recommended that decapitation be avoided on the grounds that the decapitated head may be conscious and suffering for as much as 15 seconds. The panel further recommended that if decapitation was scientifically necessary, the decapitated head be immediately immersed in liquid nitrogen. These AVMA guidelines now enjoy regulatory status; the recommendation that decapitation be avoided has thus caused considerable difficulty for all research requiring rapid, anesthesia-free collection of tissues. The scientific validity of these recommendations is consequently a matter of great practical as well as theoretical importance. The decision to discourage decapitation appears to have been based on a single literature report claiming that the EEG of the decapitated head revealed conscious suffering for more than 10 seconds (Mikeska and Klemm 1976). This review carefully examines the scientific literature on this subject. It is concluded that the report by Mikeska and Klemm of EEG activation in the decapitated head is correct, but that this phenomenon is also seen when the decapitated head is under deep anesthesia, and in normal brains under ether anesthesia or during REM sleep. Hence these findings do not demonstrate either consciousness or the perception of pain.(ABSTRACT TRUNCATED AT 250 WORDS)


Recommendations for the use of folic acid to reduce the number of cases of spina bifida and other neural tube defects.

Spina bifida and anencephaly are common and serious birth defects. Available evidence indicates that 0.4 mg (400 micrograms) per day of folic acid, one of the B vitamins, will reduce the number of cases of neural tube defects (NTDs). In order to reduce the frequency of NTDs and their resulting disability, the United States Public Health Service recommends that: All women of childbearing age in the United States who are capable of becoming pregnant should consume 0.4 mg of folic acid per day for the purpose of reducing their risk of having a pregnancy affected with spina bifida or other NTDs. Because the effects of higher intakes are not well known but include complicating the diagnosis of vitamin B12 deficiency, care should be taken to keep total folate consumption at less than 1 mg per day, except under the supervision of a physician. Women who have had a prior NTD-affected pregnancy are at high risk of having a subsequent affected pregnancy. When these women are planning to become pregnant, they should consult their physicians for advice.


Safety-belt use and motor-vehicle-related injuries--Navajo Nation, 1988-1991.

Injuries are the second leading cause of death among American Indians and Alaskan Natives; during 1986-1988, injuries accounted for 22% of all deaths (1). The risk for motor-vehicle-related injury deaths is nearly threefold higher among American Indians and Alaskan Natives than among the total U.S. population (age-adjusted death rates: 57.5 per 100,000 versus 19.5 per 100,000) (1-3). For residents of many rural, western, Indian reservations, age-adjusted motor-vehicle-related death rates are substantially higher; in particular, the rates for Navajos* are fivefold greater than for the total U.S. population (97.9 per 100,000 versus 19.5 per 100,000) (1) and almost three times the rate for all New Mexico residents (35.2 per 100,000) (4). To increase safety-belt use by front-seat occupants and thereby reduce motor-vehicle-related injuries, the Navajo Area Indian HealtH Service (IHS) Office of Environmental Health and Engineering, the Navajo Department of Highway Safety, and the Navajo Nation implemented a primary enforcement safety-belt use law and educational campaign. This report summarizes results of their effort.


Effects of postnatal aluminum exposure on choline acetyltransferase activity and learning abilities in the rat.

Young rats were treated by gastric intubation with aluminum lactate (0, 100, and 200 mg Al/kg/day) from postnatal days 5 to 14 to determine the treatment's influence on brain choline acetyltransferase activity and learning abilities. The results indicated that aluminum concentrations in the cerebral areas increased in parallel to plasma aluminum at the dose of 200 mg. In the same case, choline acetyltransferase activity was reduced. At postnatal days 50 and 100, the treated rats did not show alterations in their learning abilities in the 2 tests which are based on different motivations (avoidance of an aversive light or alimentary motivation) and different ways of achievement (pressing on a lever or running in a maze). A low reduction in the general activity, particularly in the radial maze test, was only observed in rats treated with 200 mg Al/kg/day.


Neurotoxicity of acrylamide and 2,5-hexanedione in rats evaluated using a functional observational battery and pathological examination.

The clinical effects of two neurotoxicants, acrylamide and 2,5-hexanedione, were compared in rats using a functional observational battery (FOB), which includes a series of home cage and open-field observations, sensorimotor measurements, and physiological parameters. Neurotoxicity was assessed weekly in adult male Long-Evans rats after initiation of IP administration of 9 doses of acrylamide (12, 15, or 50 mg/kg given 3 times a week) and 28 doses of 2,5-hexanedione (150, 225, and 350 mg/kg given daily). Using the FOB, it was possible to detect differences in neurotoxic effects of these two chemicals. Acrylamide significantly affected home cage posture, foot splay and time on the rotarod, whereas 2,5-hexanedione altered hindlimb grip strength and the approach response. Both compounds caused changes in ability to walk, right, and maintain agility on a rotarod within 21 days from initiation of toxicant administration. In addition, both compounds caused dose-dependent decreases in weight gain. Neuropathic changes were detectable at the highest dosages at 21 days in acrylamide-treated rats and at 28 days in rats treated with 2,5-hexanedione. Administration of acrylamide also decreased activities of neural esterases. This study indicated that the FOB could be used to detect evidence of neurotoxicity in rats treated with acrylamide and 2,5-hexanedione, with alterations evident even before pathological changes were induced by 2,5-hexanedione.


Increased HIV/AIDS mortality among residents aged 25-44 years--Baltimore, Maryland, 1987-1989.

From 1987 through 1989, overall mortality among Baltimore residents aged 25-44 years increased from 380.7 deaths per 100,000 residents to 452.6 deaths per 100,000, reflecting the substantial impact of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). To better characterize this increase in mortality, the Baltimore City Health Department analyzed information on death certificates from the Baltimore City Bureau of Vital Statistics for persons aged 25-44 years for 1987-1989. This report summarizes the analysis and characterizes HIV-infection/AIDS-related deaths among residents of Baltimore in this age group.(ABSTRACT TRUNCATED AT 250 WORDS)


Carboxyhemoglobin and brain blood flow in humans.

It has been shown that with increased carboxyhemoglobin (COHb) and associated decrease in blood oxygen-carrying capacity, a compensatory increase in brain-blood flow (BBF) develops. The BBF response in humans has been shown to be quite variable. Two experiments were conducted in which humans were exposed to sufficient carbon monoxide (CO) to produce COHb levels up to 18.4%. BBF was measured by the method of impedance plethysmography. The first was a pilot study in which BBF in 14 men was studied after transient exposure to various concentrations of CO in air. BBF increased as a function of COHb but not to the same extent (or at all) in some subjects. In a confirmatory experiment with 12 men, BBF was measured once per h during a 4-h experiment. All 12 subjects received CO. The variation of the BBF response among subjects was large and statistically significant whereas the variation over time was not significant. Thus it appears that the magnitude of the BBF response is unique for a given subject and differs across subjects. These results may help predict CO-induced behavioral decrements in future studies if subjects whose BBF response to COHb is small or absent are also more susceptible to impairment by acute CO exposure.


Elevated blood lead levels in adults--United States, second quarter, 1992.

In the United States, more than 95% of elevated blood lead levels (BLLs) in adults result from workplace exposure (1). Beginning with this issue of MMWR, CDC's National Institute for Occupational Safety and Health (NIOSH) will report on a quarterly basis summary results of state-based surveillance programs for elevated BLLs (greater than or equal to 25 micrograms/dL) among adults (Table 1). In addition to the 18 states with blood lead surveillance programs previously reported (2), three other states maintain such activities, including Arizona (physician reporting of BLLs greater than or equal to 25 micrograms/dL, all ages), Florida (laboratory reporting of BLLs greater than or equal to 10 micrograms/dL, all ages), and Nebraska (laboratory reporting of BLLs greater than or equal to 10 micrograms/dL, all ages).(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of prenatal alcohol exposure on behavioral and neuroanatomical components of olfaction.

Prenatal alcohol exposure is associated with deficits in odor-associative learning in very young rat pups. One alternative explanation for these findings is that rather than a learning deficit per se, alcohol-exposed pups may display a sensory deficit. The present study was designed to examine the effects of prenatal alcohol exposure on behavioral and neuroanatomical components involved in olfaction. The subjects in this study were pups exposed to 35% ethanol-derived calorie (EDC) liquid diet from gestation days (GD) 6-20. Two control groups were included, a 0% EDC pair-fed and an ad lib lab chow group. In Experiment 1, respiratory response to a novel odor was examined in pups tested at either 3, 4, or 10 days of age. The 35% EDC offspring clearly detected the odor. Furthermore, there was an apparent alcohol-related development delay in respiratory rate as shown by a lower baseline respiratory rate at PN 3 relative to controls which was no longer apparent by PN 4. Experiment 2 examined the volume of two neuroanatomical structures involved in olfaction, the main olfactory bulb (MOB) and the vomeronasal organ (VNO) in 3-day-old pups. Prenatal alcohol exposure was associated with a decreased volume of the MOB although the VNO was unaffected.


Mifepristone (RU 486) compared with high-dose estrogen and progestogen for emergency postcoital contraception.

Mifepristone (RU 486) is a synthetic steroid with potent antiprogestational and antiglucocorticoid properties that provides an effective medical method of inducing abortion in early pregnancy. Since progesterone is essential for implantation, we tested the use of mifepristone for emergency postcoital contraception. We studied 800 women and adolescents requesting emergency postcoital contraception who had had unprotected intercourse within the preceding 72 hours. A total of 398 women and adolescents were randomly assigned to treatment with 100 micrograms of ethinyl estradiol and 1 mg of norgestrel, each given twice 12 hours apart (standard therapy), and 402 women and adolescents were randomly assigned to receive 600 mg of mifepristone. None of the women and adolescents who received mifepristone became pregnant, as compared with four of those who received standard therapy; the difference in failure rates between the two regimens was not statistically significant. The number of pregnancies in each group was significantly lower than the number expected according to calculations based on the day of the cycle during which intercourse had taken place (P less than 0.001). In many subjects the stage of the cycle as calculated by menstrual history was inconsistent with measurements of plasma progesterone or urinary pregnanediol excretion. The subjects treated with mifepristone reported less nausea (40 percent vs. 60 percent) and vomiting (3 percent vs. 17 percent) on the day of treatment, as well as lower rates of other side effects, than the subjects treated with the standard regimen, but they were more likely to have a delay in the onset of the next menstrual period (42 percent vs. 13 percent). Mifepristone is a highly effective postcoital contraceptive agent that, if used more widely, could help reduce the number of unplanned and unwanted pregnancies.


High-dose epinephrine in adult cardiac arrest.

Recent studies suggest that doses of epinephrine of 0.1 mg per kilogram of body weight or higher may improve myocardial and cerebral blood flow as well as survival in cardiac arrest. Such studies have called into question the traditional dose of epinephrine (0.007 to 0.014 mg per kilogram) recommended for advanced cardiac life support. We randomly assigned 650 patients who had had cardiac arrest either in or outside the hospital to receive up to five doses of high-dose (7 mg) or standard-dose (1 mg) epinephrine at five-minute intervals according to standard protocols for advanced cardiac life support. Patients who collapsed outside the hospital received no advanced-life-support measures other than defibrillation before reaching the hospital. There was no significant difference between the high-dose group (n = 317) and the standard-dose group (n = 333) in the proportions of patients who survived for one hour (18 percent vs. 23 percent, respectively) or who survived until hospital discharge (3 percent vs. 5 percent). Among the survivors, there was no significant difference in the proportions who remained in the best category of cerebral performance (90 percent vs. 94 percent) and no significant difference in the median Mini-Mental State score (36 vs. 37). The exploration of clinically important subgroups, including those with out-of-hospital arrest (n = 335) and those with in-hospital arrest (n = 315), failed to identify any patients who appeared to benefit from high-dose epinephrine and suggested that some patients may have worse outcomes after high-dose epinephrine. High-dose epinephrine was not found to improve survival or neurologic outcomes in adult victims of cardiac arrest.


A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital. The Multicenter High-Dose Epinephrine Study Group.

Experimental and uncontrolled clinical evidence suggests that intravenous epinephrine in doses higher than currently recommended may improve outcome after cardiac arrest. We conducted a prospective, multicenter study comparing standard-dose epinephrine with high-dose epinephrine in the management of cardiac arrest outside the hospital. Adult patients were enrolled in the study if they remained in ventricular fibrillation, or if they had asystole or electromechanical dissociation, at the time the first drug was to be administered to treat the cardiac arrest. Patients were randomly assigned to receive either 0.02 mg of epinephrine per kilogram of body weight (standard-dose group, 632 patients) or 0.2 mg per kilogram (high-dose group, 648 patients), both given intravenously. In the standard-dose group 190 patients (30 percent) had a return of spontaneous circulation, as compared with 217 patients (33 percent) in the high-dose group; 136 patients (22 percent) in the standard-dose group and 145 patients (22 percent) in the high-dose group survived to be admitted to the hospital. Twenty-six patients (4 percent) in the standard-dose group and 31 (5 percent) in the high-dose group survived to discharge from the hospital. Ninety-two percent of the patients discharged in the standard-dose group and 94 percent in the high-dose group were conscious at the time of hospital discharge. None of the differences in outcome between the groups were statistically significant. In this study, we were unable to demonstrate any difference in the overall rate of return of spontaneous circulation, survival to hospital admission, survival to hospital discharge, or neurologic outcome between patients treated with a standard dose of epinephrine and those treated with a high dose.


A controlled trial of scheduled replacement of central venous and pulmonary-artery catheters.

The incidence of infection increases with the prolonged use of central vascular catheters, but it is unclear whether changing catheters every three days, as some recommend, will reduce the rate of infection, It is also unclear whether it is safer to change a catheter over a guide wire or insert it at a new site. We conducted a controlled trial in adult patients in intensive care units who required central venous or pulmonary-artery catheters for more than three days. Patients were assigned randomly to undergo one of four methods of catheter exchange: replacement every three days either by insertion at a new site (group 1) or by exchange over a guide wire (group 2), or replacement when clinically indicated either by insertion at a new site (group 3) or by exchange over a guide wire (group 4). Of the 160 patients, 5 percent had catheter-related bloodstream infections, 16 percent had catheters that became colonized, and 9 percent had major mechanical complications. The incidence rates (per 1000 days of catheter use) of bloodstream infection were 3 in group 1, 6 in group 2, 2 in group 3, and 3 in group 4; the incidence rates of mechanical complications were 14, 4, 8, and 3, respectively. Patients randomly assigned to guide-wire-assisted exchange were more likely to have bloodstream infection after the first three days of catheterization (6 percent vs. 0, P = 0.06). Insertions at new sites were associated with more mechanical complications (5 percent vs. 1 percent, P = 0.005). Routine replacement of central vascular catheters every three days does not prevent infection. Exchanging catheters with the use of a guide wire increases the risk of bloodstream infection, but replacement involving insertion of catheters at new sites increases the risk of mechanical complications.


[Psychiatric nursing. Delirium: dilemma or not?].

Delirium patients were often admitted to a psychiatric hospital in the past. This practise has to stop. Delirium is an illness which is caused by an organic factor, and in some cases, such as delirium tremens, there is a 5% mortality rate. If the causative factor is identified and rectified, and effective sedation is administered, the delirium patient should not be a problem for nursing staff to handle. A few simple, practical guidelines followed by the nursing staff can help the delirium patient recover within a week.


Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.

The three-domain structure of porphobilinogen deaminase, a key enzyme in the biosynthetic pathway of tetrapyrroles, has been defined by X-ray analysis at 1.9 A resolution. Two of the domains structurally resemble the transferrins and periplasmic binding proteins. The dipyrromethane cofactor is covalently linked to domain 3 but is bound by extensive salt-bridges and hydrogen-bonds within the cleft between domains 1 and 2, at a position corresponding to the binding sites for small-molecule ligands in the analogous proteins. The X-ray structure and results from site-directed mutagenesis provide evidence for a single catalytic site. Interdomain flexibility may aid elongation of the polypyrrole product in the active-site cleft of the enzyme.


Enhancements in biologically effective ultraviolet radiation following volcanic eruptions.

Aerosols injected into the stratosphere by large volcanic eruptions may induce ozone destruction through processes including heterogeneous chemical reactions. The effect of ozone reductions on surface ultraviolet irradiation is not obvious, however, because aerosols also increase the reflection of sunlight. Here we use a radiative transfer model to estimate the changes in biologically effective ultraviolet radiation (UV-BE) at the Earth's surface produced by the El Chichón (1982) and Mount Pinatubo (1991) eruptions. We find that in both cases surface UV-BE intensity can increase because the effect of ozone depletion outweighs the increased scattering.


The genomic mutation rate for fitness in Drosophila.

The mutation rate per genome for local affecting fitness is crucial in theories of the evolution of sex and recombination and of outbreeding mechanisms. Mutational variation in fitness may also be important in the evolution of mate choice in animals. No information is available on the rate at which spontaneous mutations with small effects on fitness arise, although viability (probability of survival to adulthood) has been studied in Drosophila melanogaster. These experiments involved the accumulation of spontaneous mutations in the virtual absence of natural selection, in a set of independently maintained lines with a common origin. The rates of decline in mean and increase in variance among lines permit estimation of limits to the mean number of new mutations arising per generation (U) and the average homozygous effect of a new mutation of minor effect(s). For the second chromosome of D. melanogaster, the value of U is at least 0.17 (ref. 7), and (1-h)s is less than 0.02, where hs is the average decline in fitness of heterozygotes. As the second chromosome is about 40% of the genome, these data indicate a mutation rate per haploid genome of at least 0.42 for viability. Here we present similar data on the effects of homozygous spontaneous mutations on a measure of fitness in D. melanogaster.


Antisense c-myb oligonucleotides inhibit intimal arterial smooth muscle cell accumulation in vivo.

Synthetic antisense oligonucleotides have been used to dissect gene function in vitro. Technical difficulties prevented the use of this approach for investigating the effect of gene products in vivo. Here we report the use of local delivery of antisense c-myb oligonucleotide to suppress intimal accumulation of rat carotid arterial smooth muscle cells. Our results suggest that antisense oligonucleotides can be used to define the in vivo biological role of specific macromolecules in the blood vessel wall and could potentially serve as a new class of therapeutic agents for cardiovascular disorders.


Expression cloning of a human DNA repair gene involved in xeroderma pigmentosum group C.

Xeroderma pigmentosum (XP) is a rare human autosomal recessive disease characterized by solar sensitivity, high predisposition for developing cancers on areas exposed to sunlight, and, in some cases, neurological abnormalities. XP cells are defective in DNA repair, and complementation of this defect has been used to identify eight genetic groups (A-G and variant). We have developed a simple, highly efficient complementary DNA expression system for use in human cells. Here we use this system to isolate a cDNA clone that restores the ultraviolet sensitivity and unscheduled DNA synthesis of XP-C cells to normal levels. The XP-C complementing clone XPCC encodes a highly hydrophilic protein which is composed of a predicted 823 amino acids and shares limited homology with the product of the yeast DNA repair gene RAD4. The XPCC transcript is undetectable by northern blotting in most XP-C cell lines examined.


Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor.

A critical point during mammalian pregnancy is the implantation of the blastocyst when the embryo attaches to the wall of the uterus. The autonomously developing preimplantation embryo then becomes dependent on the maternal environment for its continued development. Little is known about the regulation of implantation, except that a complex interaction between peptide and steroid hormones synchronizes the preparation of the uterus for implantation with the development of the embryo. Whether the implantation event is under maternal or embryonic control is also unclear (reviewed in refs 1, 2). We have previously shown that a cytokine, leukaemia inhibitory factor (LIF), is expressed in the uterine endometrial glands specifically on the fourth day of pregnancy. This burst of expression is under maternal control and always precedes implantation of the blastocyst. Here we report that transient expression of LIF in mice is essential for implantation. Females lacking a functional LIF gene are fertile, but their blastocysts fail to implant and do not develop. The blastocysts, however, are viable and, when transferred to wild-type pseudopregnant recipients, they can implant and develop to term.


Reagents for the site-specific cleavage of megabase DNA.

The physical mapping of chromosomes will be facilitated by methods of breaking large DNA into manageable fragments, or cutting uniquely at genetic markers of interest. Key issues in the design of sequence-specific DNA cleaving reagents are the specificity of binding, the number of different sequences that can be targeted and the cleavage yield.


Isoprenylation in regulation of signal transduction by G-protein-coupled receptor kinases.

Rhodopsin kinase and beta-adrenergic receptor kinase (beta ARK) are related members of a serine/threonine kinase family that specifically initiate deactivation of G-protein-coupled receptors. After stimulus-mediated receptor activation, these cytoplasmic kinases translocate to the plasma membrane. Here we show that the molecular basis for this event involves a class of unsaturated lipids called isoprenoids. Covalent modification in vivo of rhodopsin kinase by a 15-C (farnesyl) isoprenoid enables the kinase to anchor to photon-activated rhodopsin. Mutations that alter or eliminate the isoprenoid, fully disable light-specific Rhodopsin kinase translocation. Other receptor kinases (such as beta ARK), which lack an intrinsic lipid, are activated on exposure to brain beta gamma subunits of the signal-transducing G proteins, the gamma subunit of which bears a 20-C (geranylgeranyl) isoprenoid. Using chimaeric beta ARKs that undergo isoprenylation in vitro, we demonstrate that membrane association and activation of these kinases can occur in the absence of beta gamma. These results indicate that rhodopsin kinase (by means of an integral isoprenoid) and beta ARK (through its association with beta gamma) both rely on the function of isoprenyl moieties for their translocation and activity, illustrating distinct, though related, modes of biological regulation of receptor function.


Association between GTPase activators for Rho and Ras families.

The ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion. The cycling of these proteins between GTP-bound and GDP-bound states is partially controlled by GTPase activating proteins (GAPs) which stimulate the intrinsic GTP-hydrolysing activity of specific GTPases. The ras GTPase-activating protein (Ras-GAP) forms a complex with a second protein, p190 (M(r) 190,000), in growth-factor stimulated and tyrosine-kinase transformed cells. At its carboxy-terminal end, p190 contains a region that is conserved in the breakpoint cluster region, n-chimaerin, and Rho-GAP. Each of these three proteins exhibits GAP activity for at least one member of the rho family of small GTPases. We have tested recombinant p190 protein for GAP activity on GTPases of the ras, rho and rab families, and show here that p190 can function as a GAP specifically for members of the rho family. Consequently, the formation of a complex between Ras-GAP and p190 in growth-factor stimulated cells may allow the coupling of signalling pathways that involve ras and rho GTPases.


Loss of gene function through rapid mitotic cycles in the Drosophila embryo.

The early developmental period in Drosophila is characterized by rapid mitotic divisions, when the body pattern becomes organized by a cascade of segmentation gene activity. During this process localized expression of the gap gene knirps (kni) is required to establish abdomen segmentation. The knirps-related gene (knrl) encodes a kni-homologous nuclear hormone receptor-like protein and shares the spatial patterns of kni expression. The two genes differ with respect to the size of their transcription units; kni contains 1 kilobase and knrl 19 kilobases of intron sequences. The consequence of this difference in intron size is that knrl cannot substitute for kni segmentation function, although it gains this ability when expressed from an intronless transgene. Here we show that the length of mitotic cycles provides a physiological barrier to transcript size, and is therefore a significant factor in controlling developmental gene activity during short 'phenocritical' periods. The required coordination of cycle length and gene size provides severe constraints towards the evolution of rapid development.


Structure of the pancreatic lipase-procolipase complex.

Interfacial adsorption of pancreatic lipase is strongly dependent on the physical chemical properties of the lipid surface. These properties are affected by amphiphiles such as phospholipids and bile salts. In the presence of such amphiphiles, lipase binding to the interface requires a protein cofactor, colipase. We obtained crystals of the pancreatic lipase-procolipase complex and solved the structure at 3.04 A resolution. Here we describe the structure of procolipase, which essentially consists of three 'fingers' and is topologically comparable to snake toxins. The tips of the fingers contain most of the hydrophobic amino acids and presumably form the interfacial binding site. Lipase binding occurs at the opposite side to this site and involves polar interactions. Determination of the three-dimensional structure of pancreatic lipase has revealed the presence of two domains: an amino-terminal domain, at residues 1-336 containing the active site and a carboxy-terminal domain at residues 337-449 (ref. 6). Procolipase binds exclusively to the C-terminal domain of lipase. No conformational change in the lipase molecule is induced by the binding of procolipase.


Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours.

Ewing's sarcoma and related subtypes of primitive neuroectodermal tumours share a recurrent and specific t(11;22) (q24;q12) chromosome translocation, the breakpoints of which have recently been cloned. Phylogenetically conserved restriction fragments in the vicinity of EWSR1 and EWSR2, the genomic regions where the breakpoints of chromosome 22 and chromosome 11 are, respectively, have allowed identification of transcribed sequences from these regions and has indicated that a hybrid transcript might be generated by the translocation. Here we use these fragments to screen human complementary DNA libraries to show that the translocation alters the open reading frame of an expressed gene on chromosome 22 gene by substituting a sequence encoding a putative RNA-binding domain for that of the DNA-binding domain of the human homologue of murine Fli-1.


[The phenomenon of hearing: an interdisciplinary discussion. II].

This part of the paper deals with the neurophysiological background of speech analysis and hearing of music. Single vowel- and consonant-detector cells could be clearly separated at the colliculus and geniculate level (Kallert, Keidel). Musical stimulation is decoded at three levels: hair cells, geniculate, and auditory cortex. Human cortical evoked potentials represent rhythm, consonance, and (as DC-shift) the emotional content of music. Marked harmonics, even of single hair-cell vibrations and in single units of medial geniculate in combination with clock-cell networks, are the physiological basis of "harmony" in music. Dissonant stimuli are detectable at the cortical level in man (Finkenzeller, Keidel).


[Urination problems following total hip arthroplasty: insertion or not of an indwelling catheter?].

To assess the frequency of urine retention and of urinary tract infection after total hip replacement in order to: to minimize morbidity due to urine retention and urinary tract infection after total hip replacement; to limit the discomfort to the patient; to decrease the work load of the nursing staff, if possible. University Hospital Rotterdam. Prospective, randomized. In 61 patients after 63 total hip replacements the use of an indwelling catheter for 48 hours (group 1) was compared with catheterisation on indication only (group 2). Urine retention was less in group 1 than in group 2, 12/39 (31%) versus 15/24 (63%). In the subgroup males no difference was found between both groups. Urine retention was more frequent in elderly people. No other risk factors could be demonstrated. The number of patients with bacteriuria greater than 10(5) CFU/ml in group 1, 11/39 (28%) did not differ from group 2, 9/24 (38%). On the basis of these study results we recommend: In females: to use an indwelling catheter for 48 hours after total hip replacement; In males: to discuss this choice with the patient, because use of an indwelling catheter appears not to decrease the frequency of urine retention. The risk of discomfort caused by catheterisation and urine retention still exists. An indwelling catheter can, without increasing the risk of significant bacteriuria, eliminate this discomfort in the first 48 hours after operation.


[Interobserver variation in the application of 2 disability scales in heart patients].

To examine the use of the Rankin scale for the assessment of disability in patients with ischaemic heart disease. University Hospital Utrecht. Prospective interobserver study. Fifty-two outpatients with heart disease (previous myocardial infarction, angina or both) were separately interviewed by four physicians (residents or specialists), viz., two cardiologists and two neurologists. The degree of disability was recorded by each observer on two different scales: the modified Rankin scale, a six-point scale developed from a neurological background, and the four-point scale developed by the New York Heart Association (NYHA). The agreement rates for the observers (23 in all) were corrected for chance (kappa-statistics; maximum 1.0). Total agreement on both scales was found for six of the participating 51 patients and for 10 and 11 patients when the Rankin scale and the NYHA scale were considered separately. Kappa values were 0.21 for the Rankin scale and 0.24 for the NYHA scale. The weighted kappa values were 0.56 and 0.47, respectively. The agreement among neurologists and cardiologists was comparable. The agreement rates of cardiologists and neurologists in the use of the Rankin scale and the NYHA scale in outpatients with heart disease are at best satisfactory. The good results of an earlier study with the Rankin scale in stroke patients were not achieved. This study indicates that the Rankin scale may be useful for the assessment of disability from heart disease particularly in patients with neurological disease, but there is room for further improvement.


[Alpha-interferon antiviral treatment in 100 patients with chronic hepatitis B].

In a retrospective study we investigated the antiviral effect of alpha-interferon in 100 patients with chronic hepatitis B who were treated in controlled trials conducted in Rotterdam (1985-1990). The aim of the treatment was to induce viral latency as indicated by HBeAg seroconversion. Alpha-interferon was administered in a dose of 5 mega-units per day subcutaneously. Sixty-two patients received alpha-interferon for 16 weeks combined with a second antiviral agent (acyclovir or descyclovir) while the other 38 patients were treated with alpha-interferon monotherapy during 20 to 34 weeks. Follow-up continued until 1 year after the start of therapy. Thirty-eight per cent of the patients exhibited an HBeAg seroconversion and 9% exhibited an HBsAg seroconversion indicating a complete eradication of the virus. After 1 year transaminase levels were normalised in 70% of the patients with HBeAg seroconversion compared with 22% in those without seroconversion (p less than 0.05). The combination therapy for 16 weeks and the alpha-interferon monotherapy of longer duration resulted in HBeAg seroconversion rates of 29% and 53%, respectively (p less than 0.05). The predominant adverse effects were fatigue, flue-like illness and leukopenia. Serious side effects such as seizures, psychosis and peripheral neuropathy occurred in seven patients. Side effects led to a dose reduction in 26% of the patients. Alpha-interferon is effective in terminating the virus replication in chronic hepatitis B. However, both the common mild and the uncommon major side effects necessitate intensive patient monitoring during alpha-interferon treatment.


[Estimation of the potential number of donor organs in 1988 and 1989 in 13 hospitals with a major neurosurgical department].

In the Netherlands the supply of donor organs for transplantation still fails to meet demand. This study deals with the total number of donors and donor organs available in the 13 Dutch hospitals with a large neurosurgical department. The number of kidneys that could have been donated was twice as large, hearts and livers five times as large, and pancreas 35 times as large as the numbers actually donated (in absolute numbers for 1988 and 1989 respectively 631 and 642 (kidneys), 173 and 204 (livers), 154 and 178 (hearts) and 239 and 285 (pancreata). Refusal by the potential donor's family was the main reason for not donating organs.


[Subfascial lipoma of the forehead].

Three patients with subfascial lipoma of the forehead are presented. These deeply placed lipomas are seen in up to fifty percent of the lipomas of the scalp. A characteristic feature is the intact skin line pattern over the tumour. Surgical treatment involves incision of the aponeurosis of the M. occipitofrontalis.


[Gilles-de-la-Tourette syndrome].

Gilles de la Tourette's syndrome, a combination of multiple chronic tics and vocalizations, usually first occurring during childhood, is described in its history, symptomatology, genetics, etiology and therapy. Traditionally TS has been viewed either as an organic or as a psychogenic disorder. We propose an integrative concept combining both aspects. During a vulnerable phase in childhood a hypersensitivity of dopamine 2-receptors, induced by gene defects or perinatal trauma, leads to a lack of suppression of subcortical programs which discharge as tics. Tics are modified by multiple psychological contents (aggressive or sexual impulses, imitation of others) which tend to become independent of their origin. Severity of tics in the course of the illness is often dependent on the emotional status of the patient. Recent research focuses on the search for a major gene locus and the relationship between dopamine-receptor hypersensibility and the disturbances of other neurotransmitter systems (norepinephrine, serotonin, endorphin).


[Occupationally-induced carpal tunnel syndrome].

In Western Europe the Carpal-tunnel syndrome (CTS) is rarely regarded as a work injury, but in the USA this syndrome is usually considered to be work-related compression of a peripheral nerve, and the labour unions are already concerned about it. The median nerve can be squeezed by the flexor tendons of the index and middle fingers. These tendons pass dorsally from the median nerve through the carpal canal, where the nerve is subject to pressure when the tendons stretch whilst the wrist is flexed. Measurements in the carpal canal confirm this mechanism and show that, whilst grasping with the muscle-strength necessary for many jobs, the pressure for the median nerve can rise as high as 450 mm Hg, if the wrist is in volar flexion. Among my own patients, 51% of the men and 28% of the women with CTS reported a clear connection between the onset of symptoms and an unfamiliar use of the hands. All these different activities had in common grasping with a volar flexed wrist. A dorsal splint was constructed, with a double joint that permits dorsal and lateral movements of the hand, but blocks flexion. Of 58 patients who carried on their working activities wearing this splint, 52 answered a questionnaire. Of the 42 patients without a prior CTS operation, 32 had remained perfectly well with the splint, 3 not at all. Two of the 10 patients with prior CTS operation reported no benefit. 13 of the 58 patients had a further operation following splint-treatment. It is concluded that proper design of the workplace and instruction of the workers could prevent many cases of work-related CTS.


[Clinical and neurophysiologic markers of epilepsy with frontal lobe seizures in a series of patients diagnosed by video-EEG-telemetry].

The general and ictal clinical features, including EEG findings, of 20 consecutive patients with frontal lobe epilepsy are presented. Diagnosis in all cases was based on video-EEG telemetry using strict criteria. Among the ictal motor phenomena, turning movements, dystonic, choreic and ballistic features prevailed. Ten patients vocalised during their seizures but loss of consciousness was rare, even if there was pronounced motor involvement. The duration of attacks generally was short, not exceeding 60 seconds in 18 patients, in whom sudden onset and cessation of seizures was noted. Ten patients showed inter-ictal epileptiform EEG activity and 19 had ictal abnormalities. The short duration and ictal clinical course may be helpful in differentiating frontal seizures from pseudoseizures.


[Transcranial magnetic stimulation of patients with a single epileptic seizure].

Transcranial magnetic stimulation (TMS) was performed in 21 patients who had had loss of consciousness of unknown origin, in order to find out whether TMS could help in finding the cause of unconsciousness and to estimate the risk of provoking a seizure in patients who had single fits in the past. Furthermore, EEG recordings with hyperventilation, photostimulation, 24-hour EEG and sleep-deprivation EEG's were carried out as well as CCT or NMR investigation. In 15 patients the loss of consciousness was judged to be due to an epileptic seizure. None of the 21 patients had epileptic potentials in EEG recordings or showed an epileptic seizure during or after TMS, hyperventilation or photostimulation. One patient developed spike-wave activity in the sleep-deprivation EEG, another in the 24-hour EEG. On the basis of our results and previous reports, TMS does not seem to be helpful in the diagnosis of loss of consciousness of unknown origin. However, TMS can be used more liberally than hitherto in the study of motor pathways, in cases with a history of single epileptic seizures.


[Simultaneous occurrence of sarcoidosis and MS or sarcoidosis within the clinical picture of multiple sclerosis?].

Twelve years following the diagnosis of a histologically proved Sarcoidosis, a patient developed a central paresis of one lower limb. Two years later, tetraparesis, bladder dysfunction, ataxia and an internuclear bilateral ophthalmoplegia occurred. In CSF oligoclonal IgG without dysfunction of the blood brain barrier was found. On the basis of these data multiple sclerosis was diagnosed.


[Cerebral multisystem atrophy in a patient with depressive hallucinatory syndrome. A case report].

In a female patient, aged 47 years at the beginning, the successive appearance of extrapyramidal signs preceded by depression, paranoid-hallucinatory psychosis, autonomic and cerebellar dysfunction was followed up over a period of 8 years. Autopsy revealed--in accordance with the clinical symptomatology--both olivo-ponto-cerebellar atrophy and a striatonigral degeneration. As a rule these changes are accompanied by dementia. The reported case is unusual in having first presented with severe depression and paranoid-hallucinatory symptoms.


Increased age affects properties characterizing behavioral plasticity in freely behaving Aplysia.

In the marine mollusc Aplysia, in vitro studies showed that the gill withdrawal reflex (GWR) and its neuronal substrates were altered by age. In contrast, age minimally affected the gill respiratory pumping movements (GPM) and its neuronal substrates. Based on the respective properties of the GWR- and GPM-pathways in vitro, we proposed that the more pronounced the effect of age, the greater the expression of plasticity in a pathway. This conclusion may hold for in vitro preparations, but it remained to be demonstrated in intact animals. Based on this conclusion, the GWR should exhibit greater plasticity than the GPM in intact animals. Using freely behaving Aplysia, we tested for plasticity of the GWR and the GPM in three age groups (young, mature, and old). The tests for behavioral plasticity were: Graded responses to varying stimulus strength, response decrement (or habituation) to repetitive stimulation, enhanced response to dishabituating stimuli, and the effect of the GWR stimulus on the GPM and the GPM stimulus on the GWR. The GWR in mature animals exhibited all four properties, but in old animals, graded responses and habituation were significantly altered and in young animals habituation and dishabituation were absent. The GPM exhibited fewer of the properties than the GWR, only graded responses and response decrement, both of which were generally the same in the three groups. We found that behavioral plasticity and age-induced plasticity are related in freely behaving animals and are consistent with in vitro findings. The effect of age on properties characterizing plasticity at both the behavioral and pathway levels is discussed.