Comparison of loracarbef (LY163892) versus amoxicillin in the treatment of bronchopneumonia and lobar pneumonia.

Loracarbef (LY163892), a carbacephem, is the first of a new class of beta-lactam compounds. A 14-day, double-blind, randomized, parallel treatment study compared loracarbef (400 mg b.i.d.; n = 169) and amoxicillin (500 mg t.i.d.; n = 167) in the treatment of lobar pneumonia and bronchopneumonia. Forty-four patients in the loracarbef group and 40 patients in the amoxicillin group were evaluable for efficacy analysis. Streptococcus pneumoniae and Haemophilus influenzae were isolated from pure or mixed cultures in 45.5% of the evaluable patients, with S. pneumoniae being isolated most frequently. Favourable clinical responses (cure or improvement) in the loracarbef-treated group (42/44; 95.5%) were similar to those in the amoxicillin-treated group (38/40; 95%). A favourable bacteriological response was observed for 36/44 (81.8%) loracarbef-treated patients compared with 28/40 (70%) amoxicillin-treated patients (p = 0.2). Adverse events were similar in both groups. Withdrawal of treatment was required in three patients in each group due to gastrointestinal events or rash/allergic exanthema. These data support the conclusion that loracarbef and amoxicillin have comparable efficacy and safety in the treatment of bronchopneumonia and lobar pneumonia caused by susceptible pathogens. However, loracarbef can be administered twice daily, offering the advantage of improved patient compliance. It is also active against beta-lactamase producing organisms.


Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.

It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001). The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.


Sudden infant death syndrome in the Tel Aviv and Petah Tikva districts.

We studied the epidemiology and incidence of the sudden infant death syndrome (SIDS) in the Tel Aviv and Petah Tikva districts during the period April 1980 to March 1983. Sixty-nine infants were diagnosed as SIDS and 38 of them had autopsies. Four cases were excluded because their autopsy revealed other diagnoses. When calculating for 24,183 live births per year during the study period, the rate of SIDS was found to be 0.47-0.90:1,000 live births. Other epidemiologic characteristics were: female:male [corrected] ratio 1:1.3; peak incidence at 2-4 months age, with 80% before age 6 months; increased incidence during the autumn and winter months (85% of SIDS cases); and highest incidence between midnight and 8:00 AM (84% of SIDS cases). None of the infants had a history of a previous apparent life-threatening event. Birthweight of infants who died of SIDS was not significantly different from that in the general population. No statistical relation to DTP (diphtheria, tetanus, pertussis) vaccination was found. Half the cases had mild respiratory illness during the week that preceded the sudden death. The incidence of parental cigarette smoking was higher than in the general population (56.5% vs. 36-53%; P less than 0.005) as well as the incidence of maternal smoking during pregnancy. We conclude that the incidence of SIDS in Israel is relatively low. The epidemiologic characteristics of SIDS in Israel are very similar to the presentation of the syndrome in other countries.


Role of the occupational health nurse in the year 2000: perspective view.

From a historical perspective, occupational health nursing practice has changed in response to historic events and societal needs. The occupational health nurse today is expected to meet a variety of challenges and assume various roles within occupational health service settings. These roles require a sophisticated knowledge base and problem solving skills which are empirically based and multidisciplinary in their approach. The occupational health nurse can effect on local and public health issues through research and influence on public values and opinion. With the increasing demand for health care cost containment, occupational health nurses must meet the challenges of today and those of the future through program planning, research, and policy making.


Industrial workers on a rotating shift pattern: adaptation and injury status.

Over 11 million Americans work some type of shift pattern. Numerous health and safety issues result when workers follow a rotating shift schedule. Over 5 million work-related injuries occur annually in the United States at a cost of almost $48 billion. Disrupted circadian rhythms and fatigue from rotating shifts have been implicated as a cause of traumatic injuries. This study revealed that factors related to circadian type, effects of the work environment, and coping styles explained over 51% of the variance in adaptation scores for this group of rotating shiftworkers. Adaptation levels were not significantly different for the injured and non-injured groups of shiftworkers. Findings of this research suggest that education on the effects of circadian rhythm disruption and more effective ways of coping may be justified. Also, additional research related to adaptation and injuries is needed.


Occupational health nurses and accident prevention: an inventory of activities in one industrial sector in Sweden.

Swedish occupational health nurses with responsibility for slaughterhouse/meat industry companies (the sector with the highest rate of occupational accidents in the country) devote only 5% of their working time, at most, to accidents and accident risks. The nurse, in comparison with the physiotherapist and safety engineer at the same Occupational Health Services (OHS) unit: works in a greater number of work environment areas; works with primary prevention and provides post-accident assistance; and works more frequently and extensively with other people. The strengths of the occupational health nurse's role are such that they can make an active contribution to the development and expansion of accident prevention activities, and promote further cooperation within OHS and between OHS and employees.


Leadership attributes identified by practicing occupational health nurses.

This study examined which theoretical approaches to leadership occupational health nurses perceive as most desirable. The trait approach dominates in North American research literature, with occupational health nurses favoring the more traditional leadership attributes of "visionary," "intellectually creative," and "strong linguistic ability." Australian occupational health nurses identified the managerial character traits of "being well informed," "good communication skills," and "objective decision maker" as most appropriate traits of good leaders. Occupational health nurses need to develop alternative leadership approaches to acquire effective political and organizational strategies in today's competitive environment.


Attitudes toward working mothers: accommodating the needs of mothers in the work force.

More women, including mothers, are part of the work force than ever before. In the workplace, barriers often exist that restrict promotion and advancement of mothers. Mothers often are penalized in attempting to meet the demands of parent and worker roles. Parenting practices have been considered primarily the domain of mothers. However, nurturing may be done effectively by fathers or other motivated adults. Policies of employers must change to accommodate needs of families. Examples of supportive practices may include flexible working hours, parental leave, and on-site child care.


Surgical correction of symphalangism with incomplete polydactylism.

Symphalangistic polydactylism is one of many congenital foot deformities. The patient may experience both functional and psychological distress with this deformity. The authors present a case of symphalangism with incomplete polydactylism and its unique surgical correction.


Inuvialuit food use and food preferences in Aklavik, Northwest Territories, Canada.

Annual frequency of use of 32 species of mammals, fish, birds and plants was examined among 36 (43% of all) Inuvialuit households in Aklavik, NWT. Degree of preference for each of 34 traditional and 12 store-bought foods was examined among 36 adults and 35 (83% of all) Inuvialuit school children ages 10-16 years, using a Likert-type scale. Traditional foods were used on average 676 +/- 464 (mean +/- S.D.) times per year, the most frequent being caribou (145, mean), beluga whale (74), hares (35), muskrat (26), whitefish (52), cisco (39), burbot (38), inconnu (37), Arctic charr (31), geese (44) ducks (19), ptamigan (18), cloudberries (22), cranberries (20) and blueberries (18). Traditional foods were well-linked, especially caribou, bannock, charr, beluga, muskrat, geese, ducks, and hare. For 31 of 34 traditional foods, there were no statistically significant differences (p < 0.05, t-test) in children's vs adult's preference ratings; however, children rated 8 of 12 store-bought foods higher (p < 0.05) than adults did. Reasons given for the selection of favourite foods included the role of caribou as the dietary staple, the food's traditional nature, its origin in nature, its association with home and childhood, as well as organoleptic and convenience considerations. Overall, traditional foods are frequently consumed and highly preferred by contemporary Inuvialuit of Aklavik.


Secular changes within Arctic and Sub-Arctic populations: a study of 632 human mandibles from the Aleutian Islands, Alaska and Greenland.

A series of 632 human mandibles was used to test temporal variations in two Aleut populations and spatial variations in four homogeneous Greenlandic Eskimo populations. Sixteen metric variables and five non-metric observations were applied to generate univariate and multivariate statistics to determine variations caused by group homogeneity (Greenland), sexual dimorphism (Aleutian and Greenland), bilateral asymmetry (Aleutian and Greenland), temporal variation (Aleutians), and spatial variation (Greenland). The following results were obtained: (1) sexual dimorphism outweighed any other investigated variation, (2) no bilateral asymmetry was found in the metric variables, (3) temporal variation (Aleutian) was more significantly expressed in the male group than in the female group (patrilocal residence?), (4) spatial variation (Greenland) was more significantly expressed in the female group (matrilocal residence?), (5) the highest biological distance within the Greenlandic isolates was found between the Northeastern and Southeastern coastal areas, (6) variations in the mandible were related to metric changes rather than to changes in the morphological configuration, and (7) changes in non-metric frequencies (i.e., for mandibular tori as observed on the west coast of Greenland) were primarily induced by phenotypical variation (masticatory stress, changes in diet, ante-mortem loss of premolars and molars) caused by an inceptive increase of exogamic tendencies. The study concludes that as a single bone the human mandible yields a considerable quantity of information applicable to biological variations and reconstructions of biological and social histories, and that this information is conveniently available within the Arctic and Sub-Arctic populations.


Some aspects of lipid metabolism and thyroid function in arctic ground squirrel, Citellus parryi during hibernation.

The increased blood levels of thyroid hormones as well as morphologic signs of high activity of thyroid gland were observed in arctic ground squirrel during hibernation. High thyroid activity could explain the characteristics of lipid metabolism observed in the studied species during hibernation-increased lipid unsaturation and decreased cholesterol/phospholipids molar ratio in plasma membranes. High blood concentrations of total lipids, cholesterol, and phospholipids in dormant animals is explained by the dissociation between thermogenic and lipotropic actions of thyroid hormones. We postulate that thyroid hormones participate in long-term regulation of body energy metabolism and of homeoviscous adaptation of membranes during hibernation.


Space or rescue blanket--a bluff?

A product which has been heavily promoted for a number of years is an aluminized plastic foil designed to reflect 80% of body heat. However, a large body of experience points to the following: 1. A minimal amount of heat is radiated by a clothed body. This can easily be demonstrated with a thermocamera. 2. The plastic foils is impermeable to both water and water vapour. Thus condensation is formed on the blanket's interior. This virtually eliminates the reflective properties of the aluminum foil, often after only 15-20 minutes. 3. The blanket usually works best when the wind velocity is less than 9 m/s, otherwise the wind tears it into pieces. The greater the wind velocity and amount of clothing worn, the less the effect of the blanket. 4. Water accumulation on the clothing inside the blanket rapidly conducts heat from the skin. The blanket and the aluminum then take over and conduct heat 9,300 times faster than air. 5. It is supposed to reflect radar waves. Theoretically yes, but practical tests made in lifeboats at sea have showed that it gives no help. 6. The plastic film is inflammable.


[The mechanics and function of the middle ear. Part 1: The ossicular chain and middle ear muscles].

The revelation of a sophisticated micro-mechanism within the ossicular chain--the gliding of the joints results in a characteristic change of the ossicular movement--extended our conception of the function of the ossicular chain. Contrary to our former ideas of the transmission of sound during hearing, the ossicles do not rotate around an axis, which runs through the center of mass of the malleus and anvil. The imaginary rotational axis is located outside the ossicles, resulting in a more piston-like vibration of the complete chain. The ossicular joints are rigid. This acoustic function of the ossicular chain must rigorously be separated from its behaviour at changes of static, ambient air pressure. The middle ear, working as a sensitive pressure receptor also reacts to these pressure changes with comparatively huge displacements of the drum membrane (visible in pneumatic otoscopy). Only now the malleus rotates around its axial ligaments. These movements cause a gliding motion in the malleus-incus joint, which results in a predominant up- and downward movement of the anvil; the incudo-stapedial joint glides, too, and the stapes (and the inner ear) are decoupled. This micro-mechanism explains several anatomical features of the middle ear construction, as there are the vertical alignment of the incudo-stapedial joint, the suspension of the anvil, the design of the malleus joint, etc. It also accounts for the peculiar anatomical arrangement of the middle ear muscles. Their function can be interpreted as preserving the intact cartilage of the ossicular joints.(ABSTRACT TRUNCATED AT 250 WORDS)


[Endonasal paranasal sinus surgery with the binocular magnifier].

The Keeler panoramic magnifiers can be worn in connection with a well-focussed head lamp system and permit stereoscopic surgery of the paranasal sinuses with 3 x 0 magnification. Operations under panoramic magnifier control are time-sparing and economical. Operations on the paranasal sinuses under binocular magnifiers are a useful alternative to microscopic surgery.


[Treatment and treatment results of mouth floor cancers].

The records of 68 patients with cancer of the floor of the mouth were reviewed. 56 patients underwent surgical management, 51 of them got additionally postoperative radiation. The tumour-specific five years' survival for patients with operation was 46%, 57% of treatment failures developed from local recurrence of the tumour. In 52% of all cases there was a spread to the lymphatic system in the histological evaluation. There was high incidence of false negative clinical examinations of the neck. Conservative neck dissection was the procedure of choice for clinically positive lymph nodes and for the elective management of the neck. Only advanced tumours showed involvement of the mandibular bone. Therefore a conservative management of mandibular resection was preferred. Radical tumour extirpation and histological controlling with serial sectioned specimens are methods of avoiding local tumour recurrence.


[Caries prevention in radiotherapy of the head-neck area].

Following radiotherapy of malignant head and neck tumours, tooth damage is observed in many cases, which is frequently referred to as "radiation caries". This is not the immediate result of radiation, but has a number of causes. The damage to the salivary glands caused by radiation leads to xerostomia, which affects the self-cleaning capacity in the mouth. As a result of the very painful mucositis which occurs during the course of radiotherapy as well as the restricted mastication caused by the operation, patients prefer a soft diet, which in turn promotes plaque formation. The acidogenic coating causes erosion of the enamel. If preventive measures are not taken, all of the teeth can be completely destroyed within a short time. All efforts should be made to prevent this from happening, particularly in young patients who have undergone curative radiotherapy. This should include intensive fluoride treatment and meticulous oral hygiene.


[Differential diagnosis of cervical space occupying lesion: the parapharyngeal rhabdomyoma].

A case of a parapharyngeal rhabdomyoma is presented. Only about 30 cases of this benign tumor of striated muscles are reported in the literature. Most tumors were located in the lateral cervical region. Histologically a rhabdomyoma must be distinguished from other mesenchymal tumors, especially from granular cell myoblastoma, hibernoma and reticulohistiocytoma. The value of magnetic resonance imaging in the radiological evaluation of parapharyngeal masses is emphasized. Operative resection is generally regarded as the therapy of choice. Local recurrences have been reported in some cases; malignant degeneration is not known.


[Intramuscular hemangioma of the posterior wall of the pharynx. Diagnosis and differential diagnosis].

We report on the case of a seven-year old boy who developed an enlarged swelling of the oropharynx. Clinical examination revealed a well demarcated cystic tumour. Histopathologically the diagnosis of an intramuscular haemangioma could be made because of the multitude of vascular spaces filled with erythrocytes lying between bundles of smooth muscles. Such a lesion coming from the posterior wall of the oropharynx is not described in literature. In differential diagnosis the angiosarcoma and the arteriovenous aneurysm must have been involved since there were multiple arteries and veins lying close together in couples. Moreover the adenotomia carried out one and a half year earlier prompted us to think about the possibility of a traumatic arteriovenous fistula.


[Various uncomfortable loudness thresholds, their correlation and use in general practice].

In the present study we examined the relationship of the loudness discomfort level LDL of different signals. We carried out measurements in 97 patients, all of whom suffered from a sensorineural hearing loss. The results showed almost no difference between the LDL of pure tones and narrow band noise. The LDL of broad band noise showed a good correlation to the LDL of 250 Hz. Only the LDL of monosyllables ranged at a higher SPL. For an up-to-date hearing aid fitting, all forms of LDL should be taken into consideration. This is especially necessary when using digital hearing aids.


[Nystagmus reactions after rotatory vestibular stimulation (modified Veits extended rotation method) in patients with normal equilibrium. Part II: Directional preponderance in nystagmus reactions].

Based on the absolute values of the different nystagmus reactions, measured after having used the rotational test on 70 healthy subjects, the directional preponderance (DP) was calculated in the present study according to the equation of Jongkees and Philippszoon. It could be shown that a DP of less than +/- 30% can be regarded as a normal standard only if it refers to the summarised nystagmic reaction of the per- and first postrotatory phase (Per+PI) of the test. Depending on the different parameters (frequency, amplitude or slow phase velocity of the nystagmus reactions), higher standard values have to be accepted for the different phases of the rotational test. The differentiation between healthy persons on the one hand and patients with an acute loss of vestibular function on the other can be best achieved by evaluating the nystagmographic reactions via the amplitude. Summing up, the modified rotational test also proved to be a very sensitive method in follow-up examinations of patients with vestibular lesions to differentiate between acute and compensated or regenerated stages of the disease.


[What is the value of measuring "singer's formant" in phoniatry?].

The singing formant is the product of an articulatory gesture. Devices for phonetogram measurement often claim the ability to determine it. However, they measure rather the overtone content or the noise of the voice than the formant. Moreover, the voice efficiency (ratio of the sound pressure in the frequency band 2-5 kHz to the total sound pressure), also measured by these devices, is not defined in a physical or physiological sense. Such measurement does not evaluate the efficiency of the vocal apparatus.


["Palatolaryngeal hemiplegia" in transient brain stem ischemia--a contribution to neurogenic dysphagia].

A 65-year old man suffering from dysphagia with aspiration was examined. ENT examination showed a Horner syndrome and cranial nerve palsy with paralysis of the soft palate and one vocal cord (palatolaryngeal hemiplegia, Avellis' syndrome). Pharyngeal manometry and videofluoroscopy depicted an asynergic swallowing with cricopharyngeal achalasia. CT scans of mediastinum, head, neck, and skull base showed no signs of abnormality. MR imaging of the brain stem demonstrated an enrichment of contrast medium in the dorsal region of the upper medulla oblongata in the level of the centre of the glossopharyngeal and vagus nerve. This case demonstrates an uncommon cause of dysphagia which was related to transitory brain stem ischaemia. After a period of three weeks the patients' complaints vanished as well as the clinical features. In a follow-up of MR-imaging three months later no focal enhancement of contrast medium was seen confirming the diagnosis of a brain stem ischaemic lesion.


An unusual class II molecule.

H-2O is a recently described non-polymorphic mouse MHC class II molecule. Here, Lars Karlsson and colleagues describe the discovery of the H-2Ob and H-2Oa loci and the pattern of expression of H-2O, and speculate on the possible function of this unusual molecule.


The interplay of microbes and their hosts.

Microbes and their hosts exert considerable evolutionary pressure on one another. This brief report of a recent meeting describes the strategies and tactics, and highlights some of the key molecules involved in the complex host-parasite relationship.


Intestinal gluten sensitivity: snapshots of an unusual autoimmune-like disease.

Gluten-sensitive disease is activated in genetically susceptible individuals by the ingestion of wheat protein (gluten). Breakdown in normal tolerogenic processes to dietary gluten is likely to play a primary pathogenic role. The disease is characterized by several autoimmune-type features and provides a model for studying autoimmune processes. A recent meeting emphasized the need for a clearer picture of the molecular interactions between disease triggering agents, molecules of the immune system and other products of disease susceptibility genes.


The role of CD45 in T-cell activation--resolving the paradoxes?

CD45 is one of the most abundant transmembrane glycoproteins expressed on the surface of haematopoietic cells. Despite the striking advances of the past few years in the understanding of the actions of CD45 at a molecular level, several paradoxes remain. This article argues that these paradoxes are more apparent than real, and suggests that CD45 plays a key role on the T-cell surface in regulating coupling of the antigen-receptor complex to intracellular signalling pathways.


The role of G-proteins versus protein tyrosine kinases in the regulation of lymphocyte activation.

The relative roles of G-proteins and protein tyrosine kinases (PTKs) in the regulation of antigen receptor-mediated signalling in B and T cells is controversial. As they, and the biochemical events they control, are potential targets for intervention in various immune dysfunctions, the resolution of the controversy is of great interest. Here, Margaret Harnett and Kevin Rigley provide a timely assessment of current understanding, and propose a model for the interaction of G-proteins and PTKs in antigen receptor-mediated signalling.


The cognitive paradigm and the immunological homunculus.

In last month's issue of Immunology Today, Irun Cohen discussed the inadequacies of the clonal selection paradigm and proposed a cognitive paradigm in which preformed internal images guide and restrict the process of clonal activation. Here he clarifies the nature of these internal images, during on concrete examples from the image of infection and the image of self, the immunological homunculus.


GM-CSF, IL-3 and IL-5: cross-competition on human haemopoietic cells.

The biological properties of GM-CSF, IL-3 and IL-5 are multiple; initially described as haemopoietic growth factors, they also regulate inflammation, allergic reactions and cell adherence. The receptors for these three cytokines share a common component which may play a key role in their biological activity. This review describes the potential roles of GM-CSF, IL-3 and IL-5 in inflammation and discusses approaches to modulate their function.


Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: a new view.

This new view of the immunoreactivity of the normal brain is based on three key components. First, there is an active and highly-regulated communication between the brain and the central immune organs. Secondly, the connection from the brain to the draining nodes is much larger than previously appreciated. And third, the blood-brain barrier, by virtue of its selective permeability properties, contributes to the regulation of immunoregulatory cells and molecules in the brain cell microenvironment.


Nicotinic receptor-associated 43K protein and progressive stabilization of the postsynaptic membrane.

An extrinsic membrane protein of apparent molecular mass 43 kDa is specifically localized in postsynaptic membranes closely associated with the nicotinic acetylcholine receptor (AChR). Since its discovery in 1977, biochemical and morphological studies have combined to provide relatively clear pictures of 43K protein structure and subcellular compartmentalization. Nevertheless, despite these advances, the precise function of this synapse-specific protein remains unclear. Data gathered in recent years indicate that the postsynaptic apparatus develops through the incremental agglomeration of receptor microaggregates; evidence derived from a number of sources points to a role for 43K protein in certain underlying reactions. In this paper, I review 43K protein structural and anatomical data and analyze evidence for its role in the organization and maintenance of the postsynaptic membrane. Finally, I offer a model presenting a view of the role of 43K protein in the ontogeny of the motor endplate.


Thymopoietin, a thymic polypeptide, potently interacts at muscle and neuronal nicotinic alpha-bungarotoxin receptors.

Current studies suggest that several distinct populations of nicotinic acetylcholine (ACh) receptors exist. One of these is the muscle-type nicotinic receptors with which neuromuscular nicotinic receptor ligands and the snake toxin alpha-bungarotoxin interact. alpha-Bungarotoxin potently binds to these nicotinic receptors and blocks their function, two characteristics that have made the alpha-toxin a very useful probe for the characterization of these sites. In neuronal tissues, several populations of nicotinic receptors have been identified which, although they share a nicotinic pharmacology, have unique characteristics. The alpha-bungarotoxin-insensitive neuronal nicotinic receptors, which may be involved in mediating neuronal excitability, bind nicotinic agonists with high affinity but do not interact with alpha-bungarotoxin. Subtypes of these alpha-toxin-insensitive receptors appear to exist, as evidenced by findings that some are inhibited by neuronal bungarotoxin whereas others are not. In addition to the alpha-bungarotoxin-insensitive sites, alpha-bungarotoxin-sensitive neuronal nicotinic receptors are also present in neuronal tissues. These latter receptors bind alpha-bungarotoxin with high affinity and nicotinic agonists with an affinity in the microM range. The function of the nicotinic alpha-bungarotoxin receptors are as yet uncertain. Thymopoietin, a polypeptide linked to immune function, appears to interact specifically with nicotinic receptor populations that bind alpha-bungarotoxin. Thus, in muscle tissue where alpha-bungarotoxin both binds to the receptor and blocks activity, thymopoietin also potently binds to the receptor and inhibits nicotinic receptors-mediated function. In neuronal tissues, thymopoietin interacts only with the nicotinic alpha-bungarotoxin site and not the alpha-bungarotoxin-insensitive neuronal nicotinic receptor population. These observations that thymopoietin potently and specifically interacts with nicotinic alpha-bungarotoxin-sensitive receptors in neuronal and muscle tissue, together with findings that thymopoietin is an endogenously occurring agent, could suggest that this immune-related polypeptide represents a ligand for the alpha-bungarotoxin receptors. The function of thymopoietin at the alpha-bungarotoxin receptor is as yet uncertain; however, a potential trophic, as well as other roles are suggested.


Structures of the 4-cyano and 4-methylamidate analogs of tiazofurin.

4-Cyanotiazofurin [2-(beta-D-ribofuranosyl)thiazole-4-carbonitrile, (1)], C9H10N2O4S, M(r) = 242.3, monoclinic, P2(1), a = 7.329(1), b = 8.295 (1), c = 8.697(1) A, beta = 90.90 (1) degree, V = 528.7(1) A3, Z = 2, Dx = 1.52 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 27.2 cm-1, F(000) = 252, T = 293 K, R = 0.0487 for all 1171 unique reflections. 4-Methylamidatetiazofurin [methyl 2-(beta-D-ribofuranosyl)thiazole-4-carboximidate, (2)], C10H14N2O5S, M(r) = 274.3, orthorhombic, P2(1)2(1)2(1), a = 8.596(1), b = 11.060(1), c = 26.064(1) A, V = 2478.1(2) A3, Z = 8, Dx = 1.47 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 24.5 cm-1, F(000) = 1152, T = 293 K, R = 0.0374 for all 2902 unique reflections. Compound (2) crystallizes with two crystallographic unique structures in the asymmetric unit [(2a) and (2b)]. All three structures show a close contact between the thiazole sulfur and the pentose oxygen O(1'). S...O(1') distances are 2.936 (3) A in (1), 2.773 (2) A in (2a) and 2.878 (2) A in (2b), resulting from C-glycosidic torsion angles of 34.5 (4), 15.6 (3) and 27.2 (3) degrees respectively. This interesting feature is conserved in the crystal structures of other thiazole nucleosides [Burling & Goldstein (1992).


Molecular biology of Alzheimer's amyloid--Dutch variant.

Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) (or familial cerebral amyloid angiopathy) and familial Alzheimer's disease (FAD) share several properties. Both are autosomal dominant forms of cerebral amyloidosis characterized by beta-amyloid (A beta) deposition. In HCHWA-D the A beta is predominantly found in blood vessels and in early parenchymal plaques, whereas in AD parenchymal A beta deposits in the form of senile plaques and neurofibrillary tangles are a more prominent finding. Point mutations in the amyloid precursor protein (APP) have recently been described, in both conditions. A G to C transversion at codon 618 (extracellular portion of APP695), producing a single amino acid substitution of glutamine instead of glutamine acid, occurs in HCHWA-D; whereas mutations at codon 642 in the intramembrane region of APP695 (phenylalanine, isoleucine, or glycine instead of valine) are associated with early onset FAD. This suggests that the site of particular mutations in the APP gene and the type of amino acid substitution in the APP holoprotein are more important in determining clinicopathological phenotype and age at which A beta is deposited. Thus FAD and HCHWA-D can be regarded as two sides of the same coin.


Vitamin neurotoxicity.

Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the brain or CSF, recommended in certain disease states, is hazardous and best avoided. The lack of controlled trials prevents us from defining the lowest human neurotoxic dose of any vitamin. Large differences in individual susceptibility to vitamin neurotoxicity probably exist, and ordinary vitamin doses may harm occasional patients with genetic disorders.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of nefiracetam, DM-9384 on amnesia and decrease in choline acetyltransferase activity induced by cycloheximide.

The effects of nefiracetam, [N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide, DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre-training administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. It protected against CXM-induced inhibition of choline acetyltransferase activity in the cerebral cortex. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with AChergic neuronal system and enhancing protein synthesis in the brain.


Effects of nefiracetam, a novel pyrrolidone derivative, on brain monoamine metabolisms in mice.

The effects of acute and chronic administration of nefiracetam, a pyrrolidone derivative, on monoaminergic neurotransmitter systems in the mouse hippocampus, frontal cortex, hypothalamus, and striatum were studied. The levels of monoamines and of their metabolites were measured by high performance liquid chromatography with electrochemical detection on the first, 7th, and 14th days after nefiracetam was given. The neurochemical effects of nefiracetam were compared with those of oxiracetam and indeloxazine. Acute administration of nefiracetam (10 mg/kg, po) and oxiracetam (10 mg/kg, po) had no effect on the levels of noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT), or on the levels of their metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in any of the regions examined. In contrast, a single dose of indeloxazine (10 mg/kg, po) decreased the levels of MHPG, DOPAC, and 5-HIAA in all regions examined. After chronic administration of nefiracetam (10 mg/kg, po, once daily), the levels of MHPG, DOPAC, and 5-HIAA were higher than control in all regions on the 14th day only. Oxiracetam (10 mg/kg, po, once daily) similarly increased the levels of MHPG, DOPAC, and 5-HIAA in the hippocampus, frontal cortex, and striatum, but not in the hypothalamus. Conversely, indeloxazine (10 mg/kg, po, once daily) decreased the levels of MHPG and 5-HIAA in all regions and the levels of DOPAC and HVA in the hippocampus and striatum as measured on the 7th and 14th days. These results show that nefiracetam has a delayed effect on brain monoaminergic metabolism, and that its effects are similar to those of oxiracetam, but clearly different from those of indeloxazine.


Continuous subcutaneous lisuride infusion in OPCA.

Four patients with sporadic olivopontocerebellar atrophy (OPCA) and severe signs of Parkinsonism received continuous subcutaneous lisuride infusion via a small external pump. All 4 patients benefitted from this treatment: 3 showed an overall improvement in motor performance, in 1 patient mainly dysphagia and dysarthria improved. Therapeutic benefit lasted for at least 6 months of follow up. With a daily dose of 1.0 mg subcutaneous lisuride, treatment limitations were reached in the form of dysphagia, probably due to oropharyngeal dystonia. Subcutaneous lisuride infusion should be taken into consideration in OPCA patients with signs of Parkinsonism if oral dopaminergic treatment has failed earlier on.


MRI white matter hyperintensity in neuroleptic malignant syndrome (NMS)--a clue to pathogenesis?

The case of a young female patient with neuroleptic malignant syndrome (NMS) and extended MRI white matter hyperintensity in the left parietal and both occipital lobes is reported. MRI lesions resembled findings in hypertensive encephalopathy, they were not readily compatible with CNS vasculitis. Venous sinus thrombosis could be ruled out. Vascular encephalopathy with transient white matter edema and a small residual left parietal lesion is suggested. Neurochemical implications are discussed with particular reference to a possible involvement of excitatory amino acids in NMS pathogenesis.


[Left ventricular hypertrophy: physiopathological signs using a hemodynamic and cardio-autonomic approach].

The presence of left ventricular hypertrophy (LVH) in either hypertensives -H- or in normotensives -N-, suggests that not only blood pressure is determining this anatomic change, but various factors, as neural or endocrine ones, could be involved in its genesis. In order to evaluate the role of sympathetic dys-reactivity on LVH, we studied three groups of subjects: a) 12 -H- (SBP 159+/-9; DBP 99.6+/-7; FC 80+/-7) with LVH, diagnosed by echocardiogram. b) 12 -N- (SBP 138.2+/-8; DBP 83+/-2; FC 75.6+/-4) with LVH. c) 12 -N- (SBP 136.6+/-11; DBP 81.8+/-5; FC 76.3+/-5) without LVH. Using computer interfaced equipment, we measured beat to beat, hemodynamic and extra-cardiovascular autonomic functions, during a session of stressors (Mental Arithmetic, Color Word Stroop, Cold Pressure and Handgrip Tests), preceded and followed by 10' of observation. Among the various considered indexes, we evaluated the Percentual Total Activity Index (PTAI), as percentual total activity change + percentual total recovery change. Our findings point out that the PTAI of N with LVH is significantly higher for SCL, PHT, HR, SV, CO, TPR than either in H with LVH or N without LVH. These data seem to demonstrate a prolonged reactivity in N without LVH and are according to the hypothesis that LVH could also be supported by a hyper-adrenergic state with sympathetic dys-reactivity, independently from high blood pressure values.


[Usefulness of the prevention of oxygen radical damage in the critical patient using the parenteral administration of reduced glutathione in high doses].

A hyperproduction of Oxygen Free Radicals (FRO) is frequently observed during stress, anoxia, hyperbarism and may worsen the clinical conditions of intensive care patients. The hyperproduction of FRO may be reduced by antioxidants. The glutathione (GSH) is frequently associated with organic antioxidant protective systems. Forty patients receiving a continuous infusion of 70 mg/Kg/die of GSH were compared with forty patients not receiving GSH; the patients in both groups were randomized for age, sex, and pathology. Some parameters which are indirect indexes of FRO hyperproduction were chosen: ethane in the expired air, plasma malondialdehyde, fibrinopeptide A and C5 activated complement fraction, also the erythrocyte membrane deformability was investigated. The results obtained in the group receiving GSH were compared with the control group and a significative difference was found indicating a reduced FRO production. These interesting results need more trials in order to confirm a real GSH involvement in the antioxidant organic protection. In any case the supplementation with antioxidants in the therapy of intensive care patients can be regarded as an interesting means to improve their clinical conditions.


Protein kinase C-dependent phosphorylation regulates osteoclast calcium-sensing.

Osteoclasts display a membrane Ca(2+)-sensing mechanism capable of detecting the extracellular calcium concentration ([Ca2+]o), and to induce increase of [Ca2+]i and inhibition of bone resorption. The ultimate result of the stimulation of such sensing is probably the activation of protein kinase C (PKC). To demonstrate whether PKC plays a role in the control of the osteoclast activity, we treated rabbit single osteoclasts with agents known to activate or to inhibit the enzyme. We measured [Ca2+]i in single fura 2-loaded single cells and found that activation of PKC by phorbol esters doubled the [Ca2+]o-induced [Ca2+]i elevation, whereas inhibition of the enzyme by H7, staurosporine or sphingosine, completely blocked the ability of the cell to respond to elevated [Ca2+]i. By contrast, a control inactive agent, 4Aphorbol, failed to modify the cellular response to elevated [Ca2+]o. We conclude that PKC plays a synergistic role in the regulation of osteoclast Ca(2+)-sensing. Since we have previously demonstrated that activation of PKA up-regulates the Ca(2+)-sensing as well, we hypothesize that such mechanism is positively fed-back by both PKA and PKC-dependent threonine/serine phosphorylations.


Functional and biochemical characterization of osteoclast-like cells derived from giant cell tumours of bone.

Cells harvested from human giant cell tumours of bone were characterized on the basis of morphological features, proliferative capacity, total(AP) and tartrate resistant acid phosphatase (TRAP) activity, and hormonal response. Culture were formed by mononucleated and multinucleated cells. Mononucleated cells showed fibroblastic morphology, whereas multinucleated cells showed osteoclastic phenotype. We conclude that in these cultures mature osteoclasts and their mononuclear precursors are present.


Integrin expression and adhesion property of osteoclast-like cells from giant cell tumours of bone.

Cells cultured from human giant cell tumours of bone were used to study interactions with different extracellular matrix proteins as Collagen, Fibronectin, Osteocalcin, Thrombospondin and Bone Sialoprotein II. Cells were capable of recognizing these substrata; beta 3 integrin subunit was distributed in focal adhesions, together with beta 1 on BSPII, FN, and in presence of serum, whereas and presented a diffuse organization onto the other substrate. beta 1 alone was expressed over collagen coated coverslips.


Serum levels of soluble interleukin-2 receptor (sIL-2R) in B-chronic lymphocytic leukemia.

By using an enzyme-linked immunosorbent assay, the levels of the soluble form of the interleukin-2 receptor (sIL-2R) were evaluated in the peripheral blood of 20 patients with cell chronic lymphocytic leukemia in different stages of disease and in supernatants obtained from enriched B cell suspensions. In either all serum samples or in one out of three supernatants, elevated levels of sIL-2R were found. This could indicate that the B leukemic cells release sIL-2R which in turn, for its potential capacity of binding circulating IL-2, could contribute to the abnormal immunoregulation which characterizes B-CLL. This finding, which needs further investigation, could have prognostic significance.


[Correlations between karyotype and phenotype in structural and numerical abnormalities of chromosome 18].

Five cases with different abnormalities of chromosome 18 are described: one case with trisomy 18, two cases with ring 18, one case with partial trisomy 18q and one case with a mosaic 18p-/iso 18q. The karyotypes of the parents were normal. Cytogenetic analysis was performed on PHA stimulated blood lymphocytes. GTG, QFQ, MTX banding techniques were used. Karyotype-phenotype correlations are made. All patients present mental retardation, hypotonia and facial dismorphisms. The different degree of mental retardation and the clinical signs are in relation to the different size of deletions or trisomies of the short or long arm of chromosome 18. In the case with mosaicism 18p-/iso18q the phenotype is determined from the chromosomal abnormality more frequent in the cells (18p-).


[Plasma levels of lipids and apoprotein in a group of middle-school students 11-14 years of age: preliminary data].

Plasma lipids and apoprotein A and B levels were measured in 63 children, of both sexes, in the age range 11-14 years. The children have been subjected to a blood drawing after a 12 hour fast at least. Statistical analysis proves that total cholesterol (TC) is positively correlated with triglycerides (TG), HDL cholesterol (HDL) with apolipoproteins A (Apo A), apolipoproteins A (Apo A) with apoproteins B (Apo B). In the end we confirm the utility of determining plasma lipids and apoproteins to estimate lipidic risk for atherosclerosis in pediatric age.


[Evoked oto-acoustic emissions in retrocochlear deafness].

In order to give a contribution to the genesis of the EOAEs, we have recorded the echoes in 6 subjects affected with unilateral acoustic neuroma, surgically proven (I. group); 11 subjects with sensorineural hearing loss with electrophysiological or balance signs of retrocochlear impairment (II. group) and 10 normally hearing young subjects as control group. In this study EOAEs have been recorded in response respectively to 3 ms 1000 Hz tone-burst and to 200-5000 filtered click, both sending with 2048 stimuli, at a repetition rate of 21 pps and different stimulus intensities ranging from 40 db SPL to saturation threshold in 10 db steps. The results have shown that the EOAEs were present in half of the tested patients in response to the clicks in both I. and II. group and in all the ears to the tone-burst although the 1.0 KHz audiometric threshold mean were > 65 db HL in I. group and in a third of the subjects in the II. group. The properties of EOAEs (detection and saturation threshold, dynamic range and duration) depended on the degree of hearing loss. These results suggest that acoustic tumor could determine a wallerian degeneration of the external fibers of the VIII nerve and consequently a dysfunction of the correspondent external hair cells of the cochlea, while in the II. group a contemporary or secondary involvement of the cochlear structures is possible.


Long-term sensitization training in Aplysia leads to an increase in calreticulin, a major presynaptic calcium-binding protein.

Long-term memory for sensitization in Aplysia requires new protein and RNA synthesis. Here, we identify a late protein as calreticulin, the major Ca(2+)-binding protein of the lumen of the endoplasmic reticulum. An antiserum against Aplysia calreticulin reveals an enrichment of calreticulin immunoreactivity in presynaptic varicosities. Quantitative S1 nuclease analysis indicates that the steady-state level of calreticulin mRNA in Aplysia sensory neurons increases during the maintenance phase of long-term sensitization. The finding that this mRNA increases in expression late, some time after training, is consistent with the idea that long-term neuromodulatory changes underlying sensitization may depend on a cascade of gene expression in which the induction of early regulatory genes leads to the expression of late effector genes.


Formation of the Drosophila larval photoreceptor organ and its neuronal differentiation require continuous Krüppel gene activity.

The Drosophila segmentation gene Krüppel (Kr) is redeployed to play a critical role for the establishment of the larval visual system. Using reporter gene expression conducted by a specific Kr cis-acting element, we were able to trace back the origin of the larval photoreceptor organ, the Bolwig organ, to a single progenitor neuron and to examine Kr function in Bolwig organ development when Kr+ activity is absent from embryos due to specific mutations or reduced by neuron-specific and temporally restricted Kr antisense RNA expression. Our results show that Kr is required for neurons to differentiate into Bolwig organs, for fasciculation of the Bolwig nerve, and for this nerve to follow a specific pathway toward the synaptic targets in the larval brain. The transcription factor encoded by Kr is likely to regulate surface molecules necessary for neuronal cell adhesion and recognition in the developing larval visual system.


Changes in neurotrophin responsiveness during the development of cerebellar granule neurons.

Neurotrophins and their receptors are widespread in the developing and mature CNS. Identifying the differentiation state of neurotrophin-responsive cells provides a basis for understanding the developmental functions of these factors. Studies using dissociated and organotypic cultures of rat cerebellum demonstrated that the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) affect developing granule cells at distinct stages in differentiation. While early granule neurons in the external germinal layer responded to BDNF, more mature granule cells responded to NT-3. BDNF, but not NT-3, enhanced survival of granule cells in cultures of embryonic cerebella. Thus, BDNF and NT-3 have distinct sequential functions that are likely to be critical in the development of the cerebellum. BDNF may promote the initial commitment, while NT-3 may direct the subsequent maturation of granule cells.


NGF and other growth factors induce an association between ERK1 and the NGF receptor, gp140prototrk.

As detected by coimmunoprecipitation from PC12 cells, NGF induces rapid association between ERK1 (a growth factor-activated serine/threonine protein kinase) and gp140prototrk NGF receptors. In contrast, no such association is found with the closely related ERK2. Anti-trk immunocomplexes generated from NGF-treated cells also contain protein kinase activity that shares many properties with soluble ERK1. The association of both ERK1 protein and ERK-like kinase activity with gp140prototrk is maximal by 5 min of NGF treatment, persists for approximately 1 hr, and subsequently declines by 18 hr. Treatment with either basic fibroblast growth factor, epidermal growth factor, or orthovanadate also leads to association of ERK1 with gp140prototrk without tyrosine phosphorylation of the latter. The interaction between ERK1 and gp140prototrk may prove relevant to the NGF mechanism.


Neurotrophin expression in rat hippocampal slices: a stimulus paradigm inducing LTP in CA1 evokes increases in BDNF and NT-3 mRNAs.

We report that stimulation inducing long-term potentiation (LTP) in the CA1 pyramidal cell layer of the hippocampus evokes significant increases in both BDNF and NT-3 mRNAs in CA1 neurons. No changes in BDNF or NT-3 mRNA levels were seen in the nonstimulated regions of the pyramidal cell layer or the dentate. No change was seen in the levels of NGF mRNA at the time point examined. These results suggest that relatively normal levels of activity may regulate region-specific neurotrophin levels in the hippocampus. Given that known effects of NGF (and presumably of BDNF and NT-3) include elevation of neurotransmitter levels, elevation of sodium channels, and promotion of axonal terminal sprouting, activity-associated changes in neurotrophin levels may play a role in regulating neural connections in the adult as well as the developing nervous system.


Retrovirally introduced antisense integrin RNA inhibits neuroblast migration in vivo.

We used retrovirus-mediated gene transfer to ask whether integrins are involved in the development of neuroblasts in the chicken optic tectum. Vectors were constructed with the E. coli lacZ gene in the sense orientation and beta 1 integrin sequences in the antisense orientation. Tests in culture showed that the progeny of cells infected by these vectors were identifiable by expression of LacZ and had reduced levels of beta 1 integrins on their surfaces. We then injected these vectors into optic tecta on E3, at the height of neuronal production. Clones of LacZ-positive cells were analyzed 3-9 days later, as they migrated along radial glia to form the tectal plate. Antisense sequences had little effect on the proliferation of progenitors, or on the radial stacking of their progeny in the ventricular zone (E6). However, many antisense-bearing cells accumulated in the ventricular zone and failed to migrate into the tectal plate (E7.5 and E9). At later stages (E12), few antisense-bearing cells could be found. Thus, integrin appears to be required in the migratory process, and cells that fail to engage in integrin-mediated interactions may die.


Synapsin I partially dissociates from synaptic vesicles during exocytosis induced by electrical stimulation.

The distribution of the synaptic vesicle-associated phosphoprotein synapsin I after electrical stimulation of the frog neuromuscular junction was investigated by immunogold labeling and compared with the distribution of the integral synaptic vesicle protein synaptophysin. In resting terminals both proteins were localized exclusively on synaptic vesicles. In stimulated terminals they appeared also in the axolemma and its infoldings, which however exhibited a lower synapsin I/synaptophysin ratio with respect to synaptic vesicles at rest. The value of this ratio was intermediate in synaptic vesicles of stimulated terminals, and an increased synapsin I labeling of the cytomatrix was observed. These results indicate that synapsin I undergoes partial dissociation from and reassociation with synaptic vesicles, following physiological stimulation, and are consistent with the proposed modulatory role of the protein in neurotransmitter release.


Topographic mapping and source localization of the pattern onset visual evoked magnetic response.

The topography of the visual evoked magnetic response (VEMR) to a pattern onset stimulus was investigated using 4 check sizes and 3 contrast levels. The pattern onset response consists of three early components within the first 200ms, CIm, CIIm and CIIIm. The CIIm is usually of high amplitude and is very consistent in latency within a subject. Half field (HF) stimuli produce their strongest response over the contralateral hemisphere; the RHF stimulus exhibiting a lower positivity (outgoing field) and an upper negativity (ingoing field), rotated towards the midline. LHF stimulation produced the opposite response, a lower negative and an upper positive. Larger check sizes produce a single area of ingoing and outgoing field while smaller checks produce on area of ingoing and outgoing field over each hemisphere. Latency did not appear to vary with change in contrast but amplitudes increased with increasing contrast. A more detailed topographic study incorporating source localisation procedures suggested a source for CIIm-4cm below the scalp, close to the midline with current flowing towards the lateral surface. Similar depth and position estimates but with opposite polarity were obtained for the pattern shift P100m previously. Hence, the P100m and the CIIm may originate in similar areas of visual cortex but reveal different aspects of visual processing.


Topographical changes in the ongoing EEG related to the difficulty of mental tasks.

An experiment was carried out to investigate the hypothesis that task difficulty is reflected in changes in the topographical distribution of the ongoing EEG. Subjects had to perform three different tasks at two difficulty levels each; the Sternberg memory scanning task in an auditory and in a visual mode and a task whose performance required mainly visual scanning. Task difficulty was verified by the measurement of response times. Using a commercial Brain Electrical Activity Mapping device, EEG was recorded from 19 scalp electrodes while the subjects performed the tasks. Spectral matrices of the EEG were calculated to investigate spatial relationships in the EEG. Compared to the lower level, higher task difficulty resulted in EEG changes that led to the identification of two factors. One was the reduction of parietal and occipital alpha activity due to the amount of visual scanning and the other an increase of theta activity in the left frontal electrodes which may be associated with the amount of general mental processing.


The scalp distribution of the fractal dimension of the EEG and its variation with mental tasks.

The insights gained by the concept of deterministic chaos for the EEG is that this seemingly disordered process may be governed by relatively few simple laws which could be determined. One of the quantitative measures of a complex dynamical system is that of its dimension. The term 'dimension' refers to the ability of a space to contain a set of points. We estimated the correlational dimension of the EEG and compared the outcome to traditional Fourier analyses. In addition, we tested the hypothesis that the EEG can be described as filtered noise. Data from 15 electrode sites and 31 subjects are reported in the present study. We have utilized a variety of tasks that cut across sensory modalities including touch, vision, and imagery which reflect neuropsychological processes that differentially engage areas of the cortex in the first part of the study. In the second part, the differences between the perception of an object and the imagination of the same object were evaluated. The outcome shows variations between scalp sites for all measures and also variations between tasks in terms of dimensionality of the EEG. The hypothesis of a higher dimensionality ("complexity") of imagery compared to actual perceptual processing was confirmed. A statistical comparison between the maps generated by means of the various measures shows that different informations are extracted when using the different measures. There is also statistical evidence that the EEG cannot completely be described by the model of filtered noise.


Clinical significance of focal topographic changes in the electroencephalogram (EEG) and evoked potentials (EP) of psychiatric patients.

The relationship between psychiatric symptoms that respond to anticonvulsants and epileptic activity is still debated. Evidence linking electroencephalographic changes to treatment response is scarce and controversial, partly because of the poor scalp representation of limbic electrical activity. We studied the clinical relevance of focal topographic changes in the resting EEG, the visual evoked potential and the P300 response in 90 psychiatric patients, by evaluating response to anticonvulsants and development of neurological complications. The group with focal changes was compared to a group with epileptiform activity but no focal changes and a group with normal or diffusely altered EEG. Focal EEG and EP changes predicted good response to anticonvulsants, while the presence of epileptiform activity did not. Clinical seizures developed only in patients with focal changes and no anticonvulsants medication. Structural abnormalities and selective neuropsychological deficits were seen only in the focal group. There was an association of symptom type and the site of focus. We concluded that focal EEG and EP changes in psychiatric patients have important theoretical as well as practical implications.


Verbal versus non-verbal visual evoked potentials: Kanji versus line drawings.

Cortical areas related to perception of verbal and non-verbal stimuli were studied using VEPs. Kanji characters, line drawings (LD), or a blank were displayed. Verbal VEPs were obtained by subtracting the blank-VEPs from the Kanji-VEPs, and non-verbal VEPs by subtracting the blank-VEPs from the LD-VEPs. Both the verbal and non-verbal VEPs showed a negative peak (100-300 msec) focally over bilateral occipital, posterior temporal and parietal areas, and a positive peak diffusely over frontal halves. Differences between the non-verbal from the verbal VEPs showed an initial peak (100-200 msec) focally over bilateral occipital and posterior temporal areas, followed by a peak (200-300 msec) focally over bilateral posterior temporal areas. The frontal areas diffusely showed peaks at 100-200, 200-300 and 300-400 msec. Left-right asymmetries of both the verbal and non-verbal VEPs showed peaks between 100 and 300 msec over posterior temporal, parietal, and occipital areas. Left-right asymmetries of the subtraction to the non-verbal from the verbal VEPs showed a peak (100 msec) over occipital and parietal areas, and a broader peak over posterior temporal area (100-200 msec). Bilateral occipital, posterior temporal, and parietal areas are focally activated by the two perceptions (100-300 msec), while frontal areas are activated diffusely. Further, different processes may be focally involved between the hemispheres over occipital (100-200 msec) and posterior temporal (100-200 and 200-300 msec) regions. Initial left-right asymmetries of the subtracted VEP between the two perception would occur over occipital and parietal areas (100 msec) and last for 200 msec over posterior temporal area.


Principal components and multidimensional scaling of auditory and visual event-related potential topography.

Principal components analysis and metric multidimensional scaling were used to assess auditory and visual event-related potential topography in healthy late-middle-aged and elderly adults (n = 20). Binaurally elicited auditory evoked potentials and full-field checkerboard pattern reversal visual event-related potentials were recorded from 28 scalp sites. The zero-lag, cross-correlations of all waveforms for 300 msec post-stimulus epochs were obtained and separate analyses of the auditory and visual data were performed. Ultimately, three of the four dimensions identified in the principal components and multidimensional scaling solutions were similar and represented electrode site differences in (1) the anterior-posterior plane; (2) laterality; and, (3) the proximal-distal relation to midline. The remaining multidimensional scaling axis appeared to reflect effects specific to the modality of stimulation. Under auditory stimulation, the temporal and central-parietal sites were distinct from other scalp regions, whereas under visual stimulation, the occipital and frontal sites were distinctive. Although the results of the principal component analyses were conceptually similar to the multidimensional scaling outcomes, there were consistent differences between them. The findings provide empirical support for the validity of these multivariate methods in topographic analysis.


Topographic mapping of somatosensory evoked potentials helps identify motor cortex more quickly in the operating room.

Median nerve somatosensory evoked potentials were recorded from exposed cerebral cortex during craniotomies. This technique is valuable when knowledge of the motor cortex location can influence surgical decisions about resection limits or biopsy sites. Two different recording techniques were compared: strips of electrodes and arrays of electrodes. The arrays recorded electrical potentials suitable for topographic mapping. We found that motor cortex could be identified more quickly when using the topographic mapping of SEPs from arrays. We conclude that topographic mapping of SEP from sensorimotor regions during craniotomies works well in general and can be done more quickly than the traditional electrode strip technique.


Pelvic blood flow following aortobifemoral bypass with proximal end-to-side anastomosis.

Nine patients with end-to-side aortobifemoral bypasses were studied in the first year after surgery using color duplex imaging to determine the source of pelvic blood flow. No patient had clinical evidence of postoperative pelvic ischemia. Six of nine patients were found to have occluded distal aortas by duplex studies performed at a mean of 4.4 months postoperatively (range 0.8-8.2 months). Of those six patients, postoperative duplex examination demonstrated two with no common or external iliac blood flow, two with bilateral retrograde external iliac flow, and two with unilateral retrograde external iliac flow. Of the three patients with patent distal aortas, two had no demonstrable external iliac blood flow, while the third had continued antegrade flow through one external iliac and retrograde flow through the other. Analysis of preoperative arteriograms failed to reveal accurate predictors of postoperative distal aortic patency or retrograde iliac blood flow. Despite the preoperative assumption that prograde common iliac artery blood was required to prevent pelvic ischemia, distal aortic patency was maintained in only three of nine patients. In the six patients with prograde iliac blood flow, no ischemic symptoms were present, including two patients with complete absence of antegrade aortic or retrograde external iliac blood flow. Our observations indicate that assumptions which underlie the decision to perform end-to-side aortic anastomoses are often not borne out in the months following aortobifemoral bypass.


Characterization of an elastase from aneurysmal aorta which degrades intact aortic elastin.

Accumulating evidence suggests that abdominal aortic aneurysms (AAA) are due to a pathologic process which results in the destruction of aortic elastin and other matrix components. In this study, protein extractions were performed on both aneurysmal and normal aorta. Extracts were applied to frozen section of normal aorta either alone or in combination with 10 mM ethylenediaminetetraacetic acid, recombinant tissue inhibitor of metalloproteases, 10 mM zinc, and 5 mM phenylmethylsulfonyl fluoride, under conditions where calcium was removed from the buffer. After incubation, the sections were stained for elastin and evaluated by computerized morphometry. Aneurysm extracts, only in the presence of calcium, showed significant elastolytic activity characterized by destruction of intact elastic lamellae that was inhibited by ethylenediaminetetraacetic acid, the recombinant metalloprotease inhibitor, and zinc. Phenylmethylsulfonyl fluoride showed no inhibitory activity. Healthy aortic extract showed no elastolytic activity. This inhibitory profile is consistent with a metalloenzyme. We conclude that aneurysmal aorta contains elastolytic activity that is secondary to a metalloenzyme which is not present in normal aorta. This activity may play a role in the destruction of the elastin matrix that is seen in AAA's.


The effect of diabetes on the proliferation of aortic endothelial cells.

Diabetic vascular disease is more severe, diffuse, and accelerated when compared to nondiabetic vascular disease. Endothelial cell injury or alteration in endothelial cell function is hypothesized to be the initial cellular event in the pathophysiology of diabetic vascular disease. We examined the effect of insulin-treated and untreated alloxan diabetes on the proliferation of rabbit aortic endothelial cells in vitro by growing thoracic aortic endothelial cells from alloxan diabetic rabbits in serum obtained from alloxan diabetic rabbits. Diabetes adversely affected the proliferation of aortic endothelial cells; the most significant decrease in cell proliferation was noted in untreated diabetic cells. Crossover studies between endothelial cells and serum from different groups revealed that diabetes slows endothelial proliferation by not only a serum effect but also an intrinsic cellular effect. These observations suggest that diabetes adversely affects the proliferation of aortic endothelial cells by changing cell and serum functions.


Laser Doppler flowmetry in lower extremity ischemia: application and interpretation.

The present study was undertaken in order to develop numerical criteria for the parameters of laser Doppler flowmetry-skin blood flow velocity and pulse wave amplitude in the evaluation of lower extremity ischemia. Fifty limbs of young healthy volunteers were examined in order to obtain baseline normal values. Patient population was divided into moderately ischemic (52 limbs) and severely ischemic (22 limbs), based on patients' complaints, physical examination, ankle-brachial indices, pulse volume recordings and arteriographies. Univariate comparison between the three groups of skin blood flow velocity and pulse wave amplitude at each time point were done by analysis of variance. Power of discrimination between degrees of ischemia was evaluated by computing sensitivity and specificity, based on skin blood flow velocity and pulse wave amplitude values at time points best for predicting the severity of disease by multiple regression analysis. Using cutoff points of < 31 for skin blood flow velocity and < 9 for pulse wave amplitude, a 96% sensitivity and 96% specificity were obtained in separating normal from ischemic limbs. Cutoff points of < 9 for skin blood flow velocity and < 4 for pulse wave amplitude discriminated with a 100% sensitivity and specificity between the moderately and severely ischemic limbs. We propose the use of laser Doppler flowmetry with local heating and reactive hyperemia, and the cutoff points stated above as an additional tool to evaluate lower extremity ischemia through assessment of cutaneous microcirculation.


Vascular access for hemodialysis: pathologic features of surgically excised ePTFE grafts.

We analyzed 52 surgically excised ePTFE grafts used as secondary vascular access in chronic hemodialysis patients, structurally and histopathologically. Pseudoaneurysm formation at the site of repeated venipuncture was the main cause of surgical removal later than two years after implantation. Repeated needle punctures, twice per treatment, two or three times a week may result in a perigraft fibrous tissue capsule directly above areas where the graft was punctured. The delicate microporous structure of the graft wall was shown to be disrupted by needle punctures. The needle puncture sites were filled by surrounding connective tissue, and in one case, capillary formation was observed within the puncture sites. Examination by both light and scanning electron microscopy demonstrated identical patterns of pseudointima on the luminal surface. A thin pannus of endothelium-like cells, confined to the vicinity of the anastomoses, was noted in only four cases. On other areas of the luminal surface without endothelium, a red coagulum incorporating blood cells and fibrin was observed. Histological evidence of acute infection was absent in 61% of the cases and only 27% were considered to be clinically infected. Careful needle puncture technique, systematic rotation of puncture sites, and the use of rigorous aseptic technique are essential in preserving the long-term structural integrity of the vascular access, despite the good mechanical properties and reasonable good resistance to infection of ePTFE grafts.


A case of popliteal cystic degeneration with pathological considerations.

Adventitial cystic degeneration of the popliteal artery is seldom encountered; only 39 cases have been reported up to now in Japan. The pathogenesis of this disease remains controversial, and the authors describe a case in which the pathological findings differed from cases reported in the previous literature. The subject was a 74-year-old man admitted to our hospital complaining of intermittent claudication. The characteristic findings of cystic degeneration of the popliteal artery were uncovered by contrast-enhanced computed tomography (CT) and duplex sonography. The contrast-enhanced CT showed a low-density area and duplex sonography revealed a multi-lobulated low-echoic lesion. The Doppler signal of the low-echoic lesion could not be detected. While some cysts were found in the adventitia, they were mainly located in the media. The media also showed a remarkable decrease of smooth muscle cells and a prominent mucinous degeneration that had occurred circumferentially. These findings suggest that the medial degeneration noted had occurred prior to cystic formation. Because of this and other findings, we recommend the use of the term cystic degeneration of the popliteal artery in addition to the term cystic adventitial disease of the popliteal artery.


Radial artery collateral aneurysm: a rare entity resulting from an unusual etiology.

Atherosclerotic occlusive disease of the upper extremity can be a challenging and complex problem for the vascular surgeon. Due to the variety of pathologies that can affect the upper extremity, an accurate diagnosis may be difficult to obtain. We describe the case of a 52-year-old white man who presents with a pulsatile mass on the volar aspect of the right wrist. Arteriography of the aortic arch and right upper extremity revealed an 80% atherosclerotic stenosis at the origin of the right subclavian artery, as well as occlusion of the superficial radial artery. The occlusion resulted in the formation of an aneurysmal collateral, which communicated with the superficial palmar arch. A right carotid-subclavian bypass was necessary to prevent further embolic phenomena. The radial artery aneurysm was treated by resection and primary repair.


Successful percutaneous balloon catheter treatment of renal artery occlusion and anuria.

Progressive renal failure may be due to renal artery stenosis and occlusion. Gradual occlusion of the renal arteries may allow the development of collateral arterial supply sufficient to avoid dialysis. Even when dialysis is required, significant viable renal parenchyma may still be present to allow escape from dialysis following revascularization of one or both kidneys. The chance of success in such cases is thought to be better if the patient still produces a significant amount of urine. We report here a patient who was completely anuric for five days and in whom excellent renal function returned after balloon angioplasty of one of two occluded renal arteries.


Delayed rupture of an internal iliac artery aneurysm following proximal ligation for abdominal aortic aneurysm repair.

This is a report of a patient presenting with a contained rupture of an internal iliac aneurysm following proximal ligation after abdominal aortic aneurysm repair three years earlier. The patient presented with a large pelvic mass with symptoms of urgency, frequency, dysuria, tenesmus and fevers associated with anemia. Following evacuation of the aneurysm and direct suture ligation of the distal branches of the internal iliac artery, the patient's aortic graft was covered with omentum which also filled the pelvic cavity. The importance of proximal and distal control of aneurysms and/or the importance of complete luminal control of internal iliac artery aneurysms is emphasized by this case.


A simple technique of renal transplant preservation during aortic reconstruction.

Various methods of insuring renal transplant perfusion during aortic reconstruction have been described but these are often complex and troublesome. Although short periods of warm ischemia are probably well tolerated, reinstitution of pulsatile flow is more desirable. A simple method of rapidly restoring renal perfusion during aortic reconstruction is described.


Portal hypertension and bleeding esophageal varices.

Bleeding from esophageal varices exacts a high mortality and extraordinary societal costs. Prophylaxis--medication, sclerotherapy, or shunt surgery to prevent an initial bleeding episode--is ineffective. In patients who have bled from varices, endoscopic injection sclerotherapy can control acute bleeding in more than 90% of patients. Because recurrent bleeding frequently occurs and survival without definitive therapy is dismal, selection of a permanently effective treatment is mandatory once variceal bleeding has been controlled. Long-term injection sclerotherapy can be performed in compliant patients; it is relatively safe but is associated with a 30-50% rebleeding rate. Beta-blockers significantly reduce portal pressure and recurrent bleeding but have not been shown to diminish mortality from BEV. Portal decompressive surgery permanently halts bleeding in more than 90% of patients; the risk of operative mortality is high in decompensated cirrhotics, and long-term complications of encephalopathy and accelerated liver failure may limit indications for shunt surgery to good-risk cirrhotics who are not liver transplant candidates. Devascularization procedures have a low operative mortality and encephalopathy rate but unacceptably high rates of recurrent bleeding. Liver transplantation is curative therapy for bleeding esophageal varices and the associated underlying hepatic dysfunction; cost and availability of donor organs generally limit its use in this setting to variceal bleeders with end-stage liver disease not associated with active alcoholism.


Respiratory disease in non-smoking Western Australian goldminers.

Respiratory symptoms, spirometry, and transfer factor were measured in 208 non-smoking Western Australian underground goldminers (mean age 32) to identify the presence of respiratory abnormalities resulting from underground work. These subjects were part of a larger group of 771 subjects attending for statutory periodic chest x ray examinations in the industry. They had worked underground for a median of three years. The prevalence odds ratios of bronchitis, dyspnoea, wheeze, and asthma all tended to be related to duration of underground employment, even after adjusting for age, those for wheeze and asthma reaching statistical significance. After adjusting for age and height the duration of employment also had a significant effect on TL/VA but not on FEV1, FVC, or TL. These changes are consistent with the presence of airway narrowing and non-specific lung fibrosis or emphysema in non-smoking underground goldminers.


Agglutination of lung surfactant with glucan.

Respirable cotton dust, implicated in the pathogenesis of byssinosis, contains a number of bioactive compounds. These include lipopolysaccharide (LPS), tannins, bacterial peptides, byssinosin, iacinilene C, and 1,3-beta-D-glucan. The exact aetiological agent of byssinosis in such dust has not been definitively identified nor has its mechanism of action on lower lung surfaces been determined. In the present study 1,3-beta-D-glucan, Enterobacter agglomerans LPS, and ovine pulmonary surfactant were mixed in varying combinations. After incubation, their characteristics were determined by sucrose density centrifugation, TLC, and carbohydrate analysis. Precipitates were found in mixtures containing surfactant-glucan and surfactant-glucan-LPS, but not in surfactant-LPS. Precipitates were not seen in the surfactant, LPS, and glucan controls. The formation of a precipitate did not increase the density of the surfactant glucan mixture when compared by density gradient centrifugation with the surfactant control. The interaction between surfactant and glucan was analysed by molecular modelling. The energy of a surfactant-glucan complex (60.07 kcal/mol) was calculated to be much lower than the sum of glucan (47.09 kcal/mol) and surfactant (30.98 kcal/mol) when added separately. The results indicate that 1,3-beta-D-glucan does interact with surfactant and this complex may play a part in the pathogenesis of byssinosis by altering lung physiology maintained by pulmonary surfactant.


Evaluation of exposure to polycyclic aromatic hydrocarbons in a coke production and a graphite electrode manufacturing plant: assessment of urinary excretion of 1-hydroxypyrene as a biological indicator of exposure.

Characterisation of the airborne concentration of 13 polycyclic aromatic hydrocarbons (PAHs) at various workplaces in a graphite electrode and a coke production plant. Validation of the urinary excretion of 1-hydroxypyrene (hydroxypyrene) as a biological marker of exposure to PAH. Cross sectional study of workers exposed to PAHs (106 in the graphite electrode producing plant and 16 in the coke works). Personal air sampling during at least six hours per workshift using a glass fibre filter and a Chromosorb 102 solid sorbent tube and analysis of PAHs by high performance liquid chromatography (HPLC) and spectrofluorometric detection (SFD). Collection of spot urine samples before and after the shift and analysis of 1-hydroxypyrene by HPLC and SFD. The workers most exposed to PAHs were those occupied at the topside area of the coke oven plant and those working in the blending and impregnation areas of the graphite electrode producing plant (mean airborne concentration of total PAHs: 199 and 223 micrograms/m3 respectively). Except for naphthalene and perylene, the relative proportion of the different PAHs did not differ between the plants. Pyrene concentration in air was highly correlated with the total airborne PAH concentration (r = 0.83, p < 0.0001) and the correlation coefficients between hydroxypyrene concentration in postshift urine samples and pyrene or total PAHs in air were 0.67 (p < 0.0001) and 0.72 (p < 0.0001) respectively. Excretion of hydroxypyrene doubled when the exposure to pyrene in air increased 10-fold. The half life for the urinary excretion of hydroxypyrene was around 18 hours (95% confidence interval 16.1-19.8). Smoking habits only explained 2.3% of the variance in hydroxypyrene excretion compared with 45% for the pyrene concentration in air. The determination of the urinary excretion of hydroxypyrene in postshift urine samples can be used as a suitable biomarker to assess individual exposure to PAHs in coke ovens and in graphite electrode manufacturing plants.


Allergy to methyltetrahydrophthalic anhydride in epoxy resin workers.

One hundred and forty four current and 26 former workers in a plant producing barrels for rocket guns from an epoxy resin containing methyltetrahydrophthalic anhydride (MTHPA; time weighted average air concentration up to 150 micrograms/m3) were studied. They showed higher frequencies of work related symptoms from the eyes (31 v 0%; p < 0.001), nose (53 v 9%; p < 0.001), pharynx (26 v 6%; p < 0.01), and asthma (11 v 0%; p < 0.05) than 33 controls. Also they had higher rates of positive skin prick test to a conjugate of MTHPA and human serum albumin (16 v 0%; p < 0.01), and more had specific IgE and IgG serum antibodies (18 v 0%; p < 0.01 and 12 v 0%; p < 0.05 respectively). There were statistically significant exposure-response relations between exposure and symptoms from eyes and upper airways, dry cough, positive skin prick test, and specific IgE and IgG antibodies. There was a non-significant difference in reaction to metacholine between exposed workers and non-smoking controls. In workers with and without specific IgE antibodies, differences existed in frequency of nasal secretion (54 v 23%; p < 0.05) and dry cough (38 v 12%; p < 0.05). Workers with specific IgG had more dry cough (38 v 12%; p < 0.05), but less symptoms of non-specific bronchial hyperreactivity (0 v 26%; p < 0.05). Atopic workers sneezed more than non-atopic workers (65 v 30%; p < 0.01). In a prospective study five sensitised workers who left the factory became less reactive to metacholine, and became symptom free. In 41 workers who stayed, there was no improvement, despite a 10-fold reduction in exposure. The results show the extreme sensitising properties of MTHPA.


Organic brain damage and occupational solvent exposure.

Three hundred and nine men with organic dementia, cerebral atrophy, or psycho-organic syndrome admitted for five nights or more to one of 18 Quebec hospitals were individually matched with patients admitted (1) with some other psychiatric diagnosis and (2) to a general hospital. Lifetime occupational histories were obtained by telephone. Occupational exposure to solvents was assessed blind to type of case by (1) individual ratings and (2) a job exposure matrix; men who worked in moderate or high solvent concentrations for at least 10 years were considered exposed. With the psychiatric referent series, an odds ratio of 1.4 (90% CI 1.0-2.0) was calculated by individual exposure ratings and 1.4 (90% CI 0.9-2.2) by job matrix. Increased risk was mainly in those with organic dementia or cerebral atrophy and an alcohol related diagnosis. The same pattern of risk was found against the general hospital referents. Adjustment for possible confounders did not alter the risk estimates appreciably. Also, lifetime job histories, compared in selected case-referent pairs, gave similar evidence of increased risk (odds ratio 2.3; 90% CI 1.0-5.5). It is concluded that the combined effect of occupational solvent exposure and alcohol intake is probably an important cause of organic brain damage.


Chronic neurobehavioural effects of elemental mercury in dentists.

Neurobehavioural tests were performed by 98 dentists (mean age 32, range 24-49) exposed to elemental mercury vapour and 54 controls (mean age 34, range 23-50) with no history of occupational exposure to mercury. The dentists were exposed to an average personal air concentration time weighted average (TWA) of 0.014 (range 0.0007-0.042) mg/m3 for a mean period of 5.5 (range 0.7-24) years and had a mean blood mercury concentration of 9.8 (range 0.6-57) micrograms/l. In neurobehavioural tests measuring motor speed (finger tapping), visual scanning (trail making), visuomotor coordination and concentration (digit symbol), verbal memory (digit span, logical memory delayed recall), visual memory (visual reproduction, immediate and delayed recall), and visuomotor coordination speed (bender-gestalt time), the performance of the dentists was significantly worse than that of the controls. The dentists scored 3.9 to 38.9% (mean 13.9%) worse in these tests. In trail making, digit span, logical memory delayed recall, visual reproduction delayed recall, and bender-gestalt time test scores were more than 10% poorer. In each of the tests in which significant differences were found and in the block design time, the performance decreased as the exposed dose (product of the TWA of air mercury concentrations and the years of exposure) increased. These results raise the question as to whether the current threshold limit value of 0.050 mg/m3 (TWA) provides adequate protection against adverse effects of mercury.


A case-control study of motor neurone disease: its relation to heritability, and occupational exposures, particularly to solvents.

Motor neurone disease (MND) was studied in relation to various determinants in a case-control study covering nine counties in southern Sweden. A questionnaire about occupational exposures, medical history, lifestyle factors etc was given to all cases in the age range 45-79 and to a random sample of 500 population controls in the same age range. The questionnaires were answered by 92 cases and 372 controls, a response rate of 85% and 75% respectively. Among men high Mantel-Haenszel odds ratios (MHORs) were obtained for electricity work (MHOR = 6.7, 95% confidence interval (95% CI) 1.0-32.1), welding (MHOR = 3.7, 95% CI 1.1-13.0), and impregnating agents (MHOR = 3.5, 95% CI 0.9-13.1). Heritability with regard to a neurodegenerative disease or thyroid disease seemed to predispose to a risk of developing MND (OR = 2.1, 95% CI 1.0-4.3). The highest OR was found for the combination of such heritability, exposure to solvents, and male sex (OR = 15.6, 95% CI 2.8-87.0), a combination that occurred for seven cases and three controls. Hereditary factors and external exposures had a different distribution among cases with the spinal type of MND than among cases with involvement of the pyramidal tract or bulbar paresis also.


Menstrual function in workers exposed to toluene.

Rates of menstrual disorders were studied in 231 female production workers with high exposure to toluene (mean 88 (range 50-150 ppm) in a factory manufacturing audio speakers and compared with a control group of 58 female production workers in other departments in the same factory who had little or no exposure to toluene (0-25 ppm). An external community control group of 187 working class women under routine care at public maternal and child health centres were also studied. Detailed menstrual and reproductive histories were obtained by personal interview using a structured questionnaire. The rates for dysfunctional uterine bleeding (cycle irregularity and prolonged or heavy menstrual bleeding) were similar in all groups. Dysmenorrhoea seemed to occur more often in the women highly exposed to toluene compared with women at maternal and child health centres, but not compared with factory controls with low exposure to toluene. There was no evidence that dysfunctional uterine bleeding was likely to result from exposure to toluene. It is uncertain whether dysmenorrhoea was associated specifically with exposure to toluene, as other behavioural and work related factors may also result in dysmenorrhoea.


Risk of spontaneous abortion in workers exposed to toluene.

Rates of spontaneous abortions were determined using a reproductive questionnaire administered by personal interview to 55 married women with 105 pregnancies. They were employed in an audio speaker factory and were exposed to high concentrations of toluene (mean 88, range 50-150 ppm). These rates of spontaneous abortion were compared with those among 31 women (68 pregnancies) who worked in other departments in the same factory and had little or no exposure to toluene (0-25 ppm), as well as with a community control group of women who underwent routine antenatal and postnatal care at public maternal health clinics (190 women with 444 pregnancies). Significantly higher rates for spontaneous abortions were noted in the group with high exposure to toluene (12.4 per 100 pregnancies) compared with those in the internal control group (2.9 per 100 pregnancies) and in the external control group (4.5 per 100 pregnancies). Among the exposed women, significant differences were also noted in the rates of spontaneous abortion before employment (2.9 per 100 pregnancies) and after employment in the factory (12.6 per 100 pregnancies). Almost all the women were nonsmokers and did not drink; other known risk factors such as maternal age at pregnancy, order of gravidity, and race were not likely to explain the results. Thus, specific exposure to toluene seems to be associated with a risk of foetal loss.


Spinal cord compression: prognosis and implications for treatment fractionation.

A review of 158 cases of metastatic extradural spinal cord compression referred to three radiotherapy departments shows that the median survival time is less than 3 months, that recovery of motor and sphincter function is uncommon, and that low fraction (2-5) regimens have a similar clinical outcome to more protracted regimens.


Neutropenic sepsis complicating treatment of solid tumours, lymphoma and myeloma.

Ninety-three episodes of fever or infection while neutropenic (defined as neutrophil count < 2.0 x 10(9)/l) occurred in 76 patients treated for solid tumours, lymphoma and myeloma over a 4-year period. Most followed the first (39%) or second (18%) cycle of chemotherapy. The neutrophil count at onset of sepsis was < 0.5 x 10(9)/l in 69%. Pathogens were isolated in 32 episodes (34%) and a clinical focus detected in a further 19 (20%). Gram negative bacteria accounted for 51% of pathogens; 49% of bacteria were isolated from blood, 65% of them were Gram negative. The initial antibiotic regimen was cefuroxime with gentamicin or tobramycin in 76 episodes. Fever or infection resolved on first line antibiotics in 78%. The mean duration of antibiotic therapy was 7.6 days. Antibiotic therapy was changed following urine culture in 1.5% of 66 episodes and following chest radiography in 5.8% of 69 episodes, where these tests were performed. Nine (9.6%) patients died from infection, all of whom were receiving second line salvage chemotherapy. Three other patients died of progressive malignancy with sepsis present. In six major diagnostic groups, 56 episodes of infection or fever complicated 4% of chemotherapy cycles.


Usefulness of immunoscintigraphy in the follow-up of surgically treated gastrointestinal carcinomas using 111In-labelled anti-CEA monoclonal antibodies.

Twenty-five patients treated surgically for gastrointestinal carcinomas (16 rectum-sigmoid colon, 6 colon, 3 stomach) were investigated by immunoscintigraphy (IS) using 111In-labelled anti-CEA antibody (mouse monoclonal F023C5) F(ab')2 fragments in order to visualize questionable abdominopelvic recurrences (excluding the liver). Fifteen (60%) patients showed a rise in serum CEA levels above 5 ng/ml. Planar scans and emission computed tomographic (ECT) imaging were carried out without reference to the results of computed tomographic (CT) scans and gastrointestinal endoscopic examinations done 1-2 weeks before IS. Final diagnoses were based on biopsies and autopsies (13 cases) or on follow-up findings over at least 2 years (12 cases). Sixteen patients had a final diagnosis of recurrent malignant disease in the extrahepatic abdomen or pelvis. Of these, six were correctly diagnosed by both IS and conventional diagnostic procedures, six by IS only and two by conventional methods only. Two tumour recurrences remained undetected by both diagnostic approaches. However, five tumour recurrences were detected by IS more than 4 months earlier than by any other diagnostic procedures performed during clinical follow-up. Of the nine disease-free patients (disregarding the liver) three were correctly identified by both IS and the other diagnostic methods, four by IS only and two by conventional diagnostic procedures only. Overall sensitivity (75%) and specificity (89%) of 111In-IS were higher than figures obtained using CT scanning and endoscopy (50% and 78% respectively). True positive IS was observed in 6/15 (40%) CEA seropositive patients and in 6/10 (60%) CEA seronegative patients.(ABSTRACT TRUNCATED AT 250 WORDS)