Toxic epidermal necrolysis localized to an area of lymphoedema.

We present a man who, on two occasions, developed toxic epidermal necrolysis initially localized to an area of lymphoedema. To our knowledge, lymphoedema as a site of prediliction has not previously been reported.


Acquired tufted angioma associated with pregnancy.

Acquired tufted angioma is a distinctive condition that is different from other types of acquired vascular proliferation. Despite the progressive spread of these angiomas, they appear to be benign, and malignant change has not been encountered. We describe a case of recurrent acquired tufted angioma associated with pregnancy, an association which has not been previously recorded.


Pyoderma faciale in a patient with Crohn's disease.

We wish to report the progress of a patient with pyoderma faciale and Crohn's disease. The patient is interesting in that on two occasions the relapse in her skin condition coincided with the introduction of non-steroidal anti-inflammatory drugs. Therapy with isotretinoin was effective and well tolerated.


Distal phalangeal metastasis of a chondrosarcoma presenting initially as bilateral onycholysis.

Onycholysis is the detachment of a nail plate from its distolateral attachments. There are numerous aetiologies: congenital, traumatic, microbial, toxic, dermatological, systemic and benign or malignant tumours. We report a case with onycholysis of the ring-fingers of both hands whose symmetrical and bilateral characteristics temporarily confused the diagnosis.


Accuracy and analysis of ambulatory blood pressure monitoring data.

Two devices used to record blood pressure, the ambulatory blood pressure monitoring recorder and standard stethoscope and mercury column, were tested for accuracy against the direct intra-arterial blood pressure of patients at rest and during exercise. Recorders were found to be as accurate as mercury column measurement in patients at rest. A number of assessment techniques of ambulatory data are reviewed, including: calculation of mean or median pressures, assessment of blood pressure load, and integration of the area under the blood pressure curve over time. These have been applied during the daytime and nighttime hours. Blood pressure load and area under the blood pressure curve, using different threshold criteria for nighttime and daytime, are recommended because of their potentially closer relation to target-organ disease of hypertension than are office blood pressure readings.


Ambulatory blood pressure monitoring: a new window to decision-making in hypertension.

Ambulatory blood pressure monitoring is more physiologically valid and more reliable than office or clinic blood pressure measurement, since it provides a realtime quantitative record of the 24-h diurnal blood pressure cycle rather than a random snapshot. Its chief clinical value is the provision of accurate baselines and in making possible the individualization of patient care. It can correctly characterize episodic elevations of blood pressure and detect true as opposed to borderline hypertension. Ambulatory blood pressure monitoring may be a better predictor of target-organ damage than office blood pressure measurements.


Future uses of ambulatory blood pressure monitoring: implications for therapy.

Ambulatory blood pressure monitoring can play a significant role in evaluating the effects of treatment on the circadian cardiovascular pattern of patients with ischemic heart disease and/or congestive heart disease. In ischemic heart disease, drug therapy should be designed to reduce heart rate and blood pressure throughout the 24-hour cycle, including the early morning surge. Beta-blocking agents appear to accomplish these reductions. In congestive heart failure, some patients maintain their circadian variation while others do not, leaving them without the normal period of cardiac rest during the nighttime hours. Therapy should be designed to reduce this cardiac overload, and vasodilating agents appear to accomplish this. Ambulatory monitoring is especially useful in monitoring the effectiveness of drug interventions throughout the 24-hour cycle.


Ambulatory blood pressure monitoring: an historical perspective.

Since blood pressure was first measured more than 250 years ago, it has been assumed to be a fluctuating phenomenon, but always it has been determined by static measurements in the physician's office. In the 1940s, self-measurement at home was attempted, and two decades later the first ambulatory blood pressure recording devices were developed. These have since been improved, made more convenient, rendered automatic, and are now available for 24-h measurement during a patient's normal day. It is now increasingly recognized that such measurement is more physiologically valid and more accurate in diagnosing hypertension than clinic measurement. In addition, such monitoring may have special utility in assessing response to treatment.


The role of ambulatory blood pressure monitoring in research.

Ambulatory blood pressure monitoring has a significant research role. It documents normal daily blood pressure variations and provides data regarding the relationship between essential hypertension and the circadian cycle. It permits comparisons between normotensive and hypertensive individuals, racial groups, males and females, differing age groups, and various clinical categories. It may be a better predictor of hypertension-associated end-organ changes than clinic or office measurement. It allows quantitative analysis of the high blood pressure load over time. Ambulatory blood pressure monitoring can distinguish between borderline and true hypertension, can evaluate episodic hypertension, and can assess the effectiveness of antihypertensive drug therapy.


High resolution computed tomography in systemic sclerosis. Real diagnostic utilities in the assessment of pulmonary involvement and comparison with other modalities of lung investigation.

The real utility of high resolution computed tomography (HRCT) for early detection of lung involvement was investigated in eighteen patients affected with systemic sclerosis (SSc). The results obtained from HRCT have been compared with traditional (chest radiographs, pulmonary function tests (PFT)) and nontraditional (ventilation and perfusion scintiscan) modalities of lung investigation. A significant statistical correlation (p < 0.001) between HRCT scans and chest radiographs was observed. Moreover, HRCT was more sensitive in the detection of early pulmonary interstitial involvement and more accurate in the assessment of interstitial fibrosis in cases with severe lung involvement. A statistical correlation (P < 0.001) between HRCT and the modalities of investigation of alveolo-capillary membrane--as PFT and ventilation scintiscan--was also observed. These results indicate that in SSc HRCT may be a useful technique for assessing early pulmonary involvement and for complementing other methodologies of investigation of lung function.


Metacarpal bone mass in systemic lupus erythematosus.

We report the prevalence of metacarpal cortical thinning in systemic lupus erythematosus (SLE). Fifty-eight ambulant female patients attending a lupus clinic (mean age 32.4 years), were found to have significant thinning of metacarpal cortices (p < 0.05) when compared with 63 normal females (mean age 34.1 years). However, metacarpal bone mass was within the normal range. Measurements were made at 6 metacarpals of the 2 hands using a computer-aided technique (digitized radiogrammetry). Femoral cortical width and Singh index at the left femur, as well as the vertebral index at L3 were also recorded. The trabecular indices were in the range of normality, but the SLE group had more patients in the immediately pre-osteopenic range. Metacarpal bone loss was not related to disease duration or corticosteroid therapy. The prevalence of osteopenia in SLE is probably underestimated and the pathogenesis is likely to be multifactorial.


Systemic sclerosis in the elderly.

In our study, the characteristics of 114 patients with systemic sclerosis (SSc) are discussed with emphasis on the subgroup of cases whose onset of disease occurred above the age of 60 years. Seven out of the 9 cases showed symptoms of diffuse cutaneous systemic sclerosis with an extensive skin involvement, and 5 of these cases died within 2 years following the onset of SSc. Seven of the 9 cases showed a rapid disease course with symptoms of cardiac, pulmonary and/or renal involvement, while no secondary Sjögren's syndrome, subcutaneous calcinosis and myositis were demonstrated among these patients.


Radiographic osteoarthritis in the elderly. A cohort comparison and a longitudinal study of the "70-year old people in Göteborg".

The prevalence of radiographic osteoarthritis in hand and knee joints was studied in representative subsamples of the 75 and 79 year old population of Göteborg, Sweden. A comparison between two cohorts of 79-year-olds, revealed no significant difference between them. A longitudinal study within one of these cohorts including those aged between 75 and 79 showed a modest but not statistically significant progression of osteoarthritis in hand and knee joints. The results suggest a reduced progression of osteoarthritis after 75 years of age.


Prevention of post-menopausal bone loss with 1 alpha-hydroxy vitamin D3. A three-year prospective study.

An open and controlled prospective study was used to assess the preventive efficiency of 1 alpha-hydroxy vitamin D3 (1 alpha (OH) Vit. D3) on post-menopausal vertebral bone loss. Of the 36 patients included in the study, 25 completed two years of treatment with 1 microgram/day of 1 alpha (OH) Vit. D3 and 500 mg of calcium. The vertebral bone mineral density measured by dual photon absorptiometry did not vary in the treated group, whereas it decreased significantly in the control group at the end of the 2 years. At two years, withdrawal of treatment led to a significant bone loss, whereas bone mass remained stable in a subgroup of patients who underwent a third year of treatment with 1 alpha (OH) Vit. D3. Overall, tolerance was satisfactory. However, urinary calcium increased significantly during treatment and one third of the patients developed hypercalciuria > or = 7.5 mmoles/24 h. No variation in either serum calcium or creatinine levels was noted. These results indicate that 1 alpha (OH) Vit. D3 could be useful in preventing post-menopausal bone loss provided it was complemented by regular monitoring of urinary calcium excretion.


Renal excretion of urate by hyperuricaemic-hyperlipidemic patients.

We studied the renal urate excretory function in two groups of hyperuricaemic male patients composed of individuals with associated hyperlipidemia and hyperuricaemic-normolipidemic individuals, respectively. Both the hyperlipidemia and the hyperuricaemia were primary inasmuch as none of the patients studied was obese or had an above-normal alcohol intake or blood hypertension. The results obtained show that hyperuricaemic-hyperlipidemic patients have higher serum levels of uric acid and poorer urate excretion as reflected in smaller clearance and fractioned excretion of the metabolite than hyperuricaemic-normolipidemic patients. This, in turn, suggests the occurrence of differences in the extent of the urate handling anomalies between the two groups of patients.


Serum N terminal procollagen III fragment: a predictive marker of joint destruction in rheumatoid arthritis?

The level of the N terminal fragment of procollagen III (P3NP) levels of 100 consecutive patients affected by rheumatoid arthritis (RA) were evaluated in comparison with disease activity markers (erythrocytes sedimentation rate, C reactive protein), immunological status (rheumatoid factors, immune complexes) and joint destruction (assessed according to the Steinbrocker index). P3NP levels showed no significant relationship either to disease activity or to immunological status; however, a strong association was fond between X-ray grade and P3NP values. A two-year retrospective study of 32 patients belonging to the original 100 patient population allowed us to assign a predictive value for joint destruction to the P3NP level in the early stage of the disease.


Is pelvic bone mineral content assessed through dual energy X-ray absorptiometry an appropriate anatomical area for bone mass estimation in women?

Bibliographic references seem very controversial regarding the most appropriate anatomical area for bone mass estimation. Since some overlapping in the different bone mass measurements among normal and osteoporotic females has been observed, we have studied the bone mineral content of the pelvic bone through DEXA, and have correlated it with the total body bone mineral content, a highly discriminating measure, in order to observe whether pelvic bone mineral may be a useful measure in bone mass assessment. Pelvic and total body bone mineral values did not decrease until menopause in 104 normal premenopausal females aged 20 to 49 years. On the other hand, these values decreased in normal postmenopausal women (n = 44) aged 50 to 65 years (p < 0.001), with a 16% pelvic bone mineral content and an 11% total body bone mineral content decrease. Osteoporotic females (n = 30), showed lower values for both levels than normal postmenopausal ones (p < 0.001), with a 54% pelvic and a 24% total decrease. A 15% overlap was observed when pelvic values between normal postmenopausal and osteoporotic females were compared. The greater percentage decrease in pelvic BMC compared to total body bone mineral content and the lower overlap observed suggest that the pelvis may be an ideal anatomical area for bone mass evaluations.


The pattern of rheumatic disorders seen amongst patients attending urban and rural clinics in west Africa.

There is a growing interest in the study of the pattern of rheumatic disorders in Africa. This has led to our studying the pattern of rheumatic disorders seen among patients attending both urban and rural clinics in West Africa. A wide spectrum of rheumatic diseases was observed among those attending both clinics. Osteoarthritis and soft tissue lesions were most commonly seen while inflammatory joint disease and connective tissue disorders were less commonly observed. We consider that these observations have significant rheumatological health care implications for West Africa and may provide useful aetiopathogenic clues.


Adult onset Still's disease: clinical features and course.

Fifteen patients with adult onset Still's disease are described, all diagnosed according to recognized criteria. Mean delay in reaching a firm diagnosis was 16 months. Besides the typical clinical picture, there was a high frequency of pruriginous rash, one instance of overlapping polymyositis and recurrent systemic manifestations in most cases. Chronic polyarticular involvement predominated, with radiological progression particularly in wrist, proximal interphalangeal and hip joints. However, functional prognosis at the end of a mean 4.8-year course was satisfactory, as also the response to treatment mainly with steroid drugs and, on occasion, with remitting agents to alleviate arthritis.


The diagnostic value of salivary fluid levels of beta 2-microglobulin, lysozyme and lactoferrin for primary Sjögren's syndrome.

In search of a simple non-invasive diagnostic test for primary Sjögren's syndrome (SS) the concentration of beta 2-microglobulin (beta 2-m), lysozyme (LZM) and lactoferrin (Lf) was measured in stimulated parotid saliva of 39 patients with primary SS, 42 patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) and in 41 normal control individuals. Salivary fluid levels of beta 2-m, LZM and Lf exceeding the mean + 2 x standard deviation of healthy control values were found in respectively 58%, 23%, and 26% of the primary SS patients and in 7%, 11% and 0% of the NON-SS patients. The results of this study indicate that due to the low sensitivity the tests are not suitable as a screening procedure for patients suspected of having primary SS. However, measurement of beta 2-m in stimulated parotid saliva may be used as an adjunctive diagnostic test for primary SS.


Is hyperlipidaemia a contributing factor to algodystrophy (reflex sympathetic dystrophy)?

To appreciate hyperlipidaemia as a contributing factor to reflex sympathetic dystrophy (RSD), we have evaluated basal lipidic values (cholesterol, HDL-cholesterol, triglycerides, apolipoproteins A1, B) and frequency of hypertriglyceridaemia (Turpin's diagnosis criteria) in 75 cases of RSD and in 75 paired controls. No difference exists in both groups with regard to frequency of hypertriglyceridaemia or basal lipidic values. These values seem independent of age, sex, duration of localization or etiology (traumatic or nontraumatic) of RSD. Hyperlipidaemia does not seem a contributing factor to RSD.


Lumbar and cervical stenosis. Frequency of the association, role of the ankylosing hyperostosis.

The authors report a study of 47 patients admitted for cervical myelopathy (N = 17) or symptomatic lumbar spinal stenosis (N = 30). Nine patients had clinical evidence of coexisting cervical myelopathy and lumbar spinal stenosis. Ten out of the 17 patients having cervical myelopathy had lumbar spinal stenosis as evidenced by sagittal tomography and/or computerized tomography. Nine out of the 30 patients admitted for symptomatic lumbar spinal stenosis had coexisting cervical canal stenosis as evidenced by sagittal tomography. Thirteen out of these 19 patients with both cervical and lumbar canal stenosis had also ankylosing spinal hyperostosis.


Prognostic significance of nailfold capillary microscopy in patients with Raynaud's phenomenon and scleroderma-pattern abnormalities. A six-year follow-up study.

The aim of this study was to assess the prognostic significance of scleroderma capillary pattern (SD-pattern) in patients with Raynaud's phenomenon. Thirty patients with a capillaroscopy examination suggestive of scleroderma (megacapillaries and/or avascularity) but without clinical criteria of scleroderma (ARA criteria) were reevaluated 6 years after the initial clinical and capillaroscopy examinations. SD-pattern abnormalities were classified according to a semiquantitative method. Eight out of the 28 evaluated patients (28%) developed a scleroderma spectrum disorder (SDS). The presence of avascularity and/or a mean of more than two megacapillaries digit greatly enhanced the percentage of evolution toward SDS (70%/88% respectively). Most of the patients with few enlarged capillaries and no capillary rarefaction at entry had primary acrocyanosis (11/15). None of them developed SDS. The microangiopathy disappeared during the follow-up period in most of these patients (14/15). These results confirm the prognostic value of SD-pattern capillary abnormalities for SDS. Primary acrocyanosis, a benign clinical entity should be considered in presence of few megacapillaries and without capillary rarefaction.


Treatment of rheumatoid arthritis with anti CD4 monoclonal antibody. Open study of 25 patients with the B-F5 clone.

Twenty-five defined severe RA patients (pts) (17 F, 8 M) were treated in an open study with a CD4 murine monoclonal antibody (Mab) (B-F5 clone, IgG1). Mab's daily dose was 10 mg (1 pt), 15 mg (2 pts), 20 mg (17 pts), 30 mg (4 pts) and 50 mg (1 pt) for 10 days. Tolerance was fair. Clinical improvement occurred during treatment period or within the first month in all but 2 patients, irrespective of Mab dosage. Improvement duration was variable (1 to 12 months), half of the patients still show signs of improvement at month 4. Biological parameters (CRP) improved parallel to the clinical. At day 180, 25% of the patients showed a reduction of 50% or more of the initial CRP values. There is no modification of RF titers, renal and hepatic parameters. Sequential evaluation showed a decrease of B, TCD3, CD4, CD8 lymphocytes and monocytes two hours after Mab infusion and return to baseline in 20 hours. Xenogenic immunization occurred in 6 patients without influence upon clinical response. These modifications are moderate and transient and do not account for the more prolonged effect in some cases, nor do they offer any prediction of further clinical response.


Human parvovirus B19 and rheumatoid arthritis.

Human parvovirus B19 infections have been linked with the development of a short-lived symmetrical polyarthritis and, rarely, a more persistent arthritis. We prospectively looked for serological evidence of recent B19 infection in 25 early synovitis patients presenting within 12 weeks of symptom onset and compared them with 21 controls seen over the same time period. None of the control patients had evidence of recent B19 infection while 3 of the early synovitis patients had raised IgM anti-B19 antibody levels. Two had a transient arthritis and 1 developed persistent seropositive rheumatoid arthritis.


Evaluation of the involvement of axial entheses and sacroiliac joints in relation to diagnosis: comparison among diffuse idiopathic skeletal hyperostostis (DISH), osteoarthrosis and ankylosing spondylitis.

Since diffuse idiopathic skeletal hyperostosis (DISH) is frequently difficult to differentiate radiologically from the axial involvement of ankylosing spondylitis and osteoarthrosis, some features of these 3 different diseases were compared. The predominantly horizontal nature of the enthesiophyte in DISH and its right preponderance in the thoracic region were demonstrated. This right preponderance was due to the presence of the thoracic aorta located in the left thoracic side. A midthoracic notch was described in DISH which seemed to be confined to noninflammatory conditions, but was not found in ankylosing spondylitis. The importance of sacroiliac computerized tomography to differentiate sacroiliac joint abnormalities associated with DISH from the sacroiliitis of spondylarthropathies was stressed.


Adolescent osteoporosis disclosing familial osteopenia.

The observations of familial juvenile osteoporosis, presumably of genetic origin are exceptional. The authors report the observation of a 16-year old adolescent suffering from osteoporosis, confirmed by histomorphometry and decrease in bone density (lumbar vertebrae 0.79 g/cm2 and femoral neck 0.88 g/cm2: LUNAR DPX). We prescribed fluorine and calcium therapy. Lumbar bone density increases by 11% and bone density of the thighbone neck by 7.6%. We cannot rule out growth as a factor in the changes observed, given that the propositus is only 16. A densitometric investigation performed in 4 of his 12 brothers shows a decrease in the lumbar bone mineral content (from 61 to 94% expressed as Z score). A genotypic origin seems to be conceivable, especially since no other cause could be considered (endocrinal, alimentary...). On the other hand, there is no argument in favour of osteogenesis imperfecta disease. The bone densitometry is a useful diagnostic means to detect familial forms of osteoporosis.


Joint manifestations of Fabry's disease.

We describe 2 patients with Fabry's disease with disabling crises of burning pain in hands and feet. These crises were accompanied by fever and an elevation of the erythrocyte sedimentation which often led to erroneous diagnosis of other rheumatic conditions. Fabry's disease should be considered on the different diagnoses of intermittent rheumatic syndromes.


Needle biopsy of joints--its contribution to the diagnosis of ochronotic arthropathy (alcaptonuria).

The authors present the case history of a 48-year-old man with ochronosis. They discuss the possibilities of articular needle biopsy in the diagnosis of this disease. The histology of the synovial membrane may help establish the diagnosis of ochronotic arthropathy.


Bilateral pneumothorax and mediastinal emphysema in systemic lupus erythematosus.

The association of pneumothorax and mediastinal emphysema in systemic lupus erythematosus (SLE) has not been described extensively in the literature. We describe a 36 year-old man with SLE, complicated by bilateral pneumothorax, mediastinal emphysema and pneumoperitoneum. Despite the treatment received, he died of respiratory failure.


Rheumatoid arthritis associated with ankylosing spondylitis defined by scintigraphic and CT abnormalities.

Rheumatoid arthritis and ankylosing spondylitis were detected in the same patient after a long period of observation of the disease. X-ray studies demonstrated the characteristic rheumatoid arthritis changes in peripheral joints. By contrast, few X-ray changes of ankylosing spondylitis were detected, during follow-up. Diagnostic approach through scintigraphic studies disclosed a symmetric uptake of the radionuclide in sacroiliac joints, and computed tomography revealed bilateral ankylosis. The combination of these tests was useful to define the presence of axial disease. This patient was both HLA B27 and DR4 positive. Rheumatoid arthritis occurred before ankylosing spondylitis, that interestingly was defined as a late onset disease.


Characteristics associated with legal status change among psychiatric patients.

Typically research on civil commitment has simply compared voluntary and involuntary psychiatric patients and has ignored the process of legal status change. The present study examined patient characteristics associated with legal status change during different points of patients' hospital stays. Results indicated that patients with greater improvement, patients with more severe diagnoses, and non-minority patients were more likely to transition to voluntary status, but only when these transitions occurred early in the hospitalization. Later in the hospitalization, the presence of living arrangements involving family and friends was associated with higher rates of transition to voluntary status.


Suicide in a community based case management service.

Over a 9 year period, 532 people with a long term mental illness received the services of a community based case management program. Of the 532 clients, 13 committed suicide (2%). This group was compared to a control group matched for age, sex and length of stay in the program. No differences were found with regard to most socio-demographic and clinical variables investigated. However, statistically significant differences were found with regard to chronicity and number of post-admittance hospitalizations. Difficulties in establishing a working relationship were noted more often for clients who committed suicide. Some of the implications for case management programs are discussed.


Needs assessment for persons with severe mental illness: what services are needed for successful community living?

The development and implementation of effective community support systems are goals of many public mental health authorities who are attempting to shift the focus and dollars for mental health services from inpatient to community care. This article presents the results of a survey which asked 90 community mental health agency case managers to assess the community support and residential needs of over 1400 of their clients. Medication monitoring and therapy were rated high priority needs. Psychosocial treatment, day and vocational activities also ranked high. Survey responses regarding residential services indicated a need for more supported and supervised options.


Validity of case manager reports of clients' functioning in the community: independent living, income, employment, family contact, and problem behaviors.

Validity of case manager reports of client functioning in the community was assessed by examining the correspondence between case manager reports and client reports of several widely-used indicators of client well-being, including independent living, income, employment, family contact, and problem behaviors. Effects of how well case managers knew their clients and of using telephone interviews vs. self-administered questionnaires to gather case manager data were also investigated. Data were gathered from 6 case managers and 55 of their seriously mentally ill clients in a rural Wisconsin Community Support Program. Indicators of independent living and employment displayed reasonably good agreement and support the use of case manager reports in research. Indicators of income and problem behaviors produced lower levels of client-case manager agreement at least in part because client reports proved an inadequate criterion for these measures.


Family violence: contemporary research findings and practice issues.

The purpose of this paper is to describe recent empirical research findings about family violence, and to explore selected social work treatment issues in the light of these findings. The last two decades has seen a proliferation of research about family violence. Most of the early research used small clinical samples and so generalizing findings to other groups has been difficult. However, the recent research has examined a number of important psychosocial correlates of family violence using more methodologically sound methods. As a result, we now know quite a bit about how and why family violence occurs. Also, within the last decade a number of studies have explicated the kinds of treatments and approaches that are most effective in dealing with abusive people. This paper summarizes these treatment strategies.


Attitudes of African American adults toward treatment in cases of rape.

The attitudes of 155 African American adults toward the need for treatment in cases of rape were assessed. The relationship of these attitudes to sex, age, income, educational level, knowledge of the effects of rape, the influence of rape circumstances on attitudes, and expectations regarding interactions with treatment facilities and agencies were assessed. The results indicated that the ability to recognize rape in a variety of situations, perception of victim responsibility for the rape, and a knowledge of the short term reactions associated with rape had the greatest impact on respondents' attitudes toward seeking treatment. Participants generally endorsed the need for counselling following a rape and expressed positive attitudes regarding treatment outcomes.


Group treatment assignment for outpatients with schizophrenia: integrating recent clinical and research findings.

Many mental health clinics rely heavily on group treatment in the outpatient care of individuals with schizophrenia. Groups are used because they economize clinician time and provide social interaction for isolated patients. Empirical evidence suggests that groups, combined with medication, are at least as effective as other common treatments. Many group formats and techniques have been used. Choices are often based on pragmatism or inclination, rather than theory or experiment. The authors review recent findings from research on the neurobiology of schizophrenia, its natural history, and the impact of psychosocial factors in its course and treatment. From these findings, they elaborate research based principles for outpatient group therapy in schizophrenia. They describe three distinct formats for group treatment, and delineate the scope of use for each. Finally, they propose guidelines for assignment of patients to appropriate group treatments.


One-year clinical experience with FlexiGard.

In 1988, a clinical study with a new copper-containing IUD, the FlexiGard, was initiated at the Family Planning Center of the UMSD, Debrecen, Hungary. The aim of this trial was to measure the overall performance of the device with special attention to its frameless design and anchoring system. In one year (from May 1988 through May 1989), 344 FlexiGard devices were inserted in parous women during the first seven days of their menstrual cycle. This report summarizes the one-year results. By the end of the 12 -month follow-up period, 3484 woman-months of use (WMU) were accumulated. The number of women who completed the one-year follow-up period was 264. During this period, 33 cases were terminated for different reasons. The net continuation rate is 89.7 at the end of the first year of use. The device was well retained by the uterus (cumulative expulsion rate 1.5 at 12 months). The cumulative removal rate for bleeding/pain is 4.4 at 12 months and the cumulative pregnancy rate 0.6 at 12 months. The results confirm those of previously conducted multicenter studies with the device. This new generation intrauterine copper contraceptive (ICC) is well tolerated, which is attributed to its design characteristics. Besides, the device is highly effective, and its insertion is easy and safe. Removal of the ICC is equally easily accomplished.


A multicenter efficacy and safety study of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol.

The study reported herein is the primary efficacy and safety study conducted to support U.S. registration of an oral contraceptive containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol. A large multicenter study enrolled 1,221 women at 50 centers in the United Kingdom. A total of 11,656 cycles of exposure was accumulated, corresponding to approximately 879 women-years of use. Contraceptive efficacy was high; no subject conceived as a result of method failure. The product was generally well tolerated with excellent cycle control, causing fewer than 2% of the subjects to discontinue because of bleeding irregularities. The study medication demonstrated no adverse effects on cervical cytology, blood pressure, body weight or laboratory variables, while pre-existing benign breast disease generally improved. The study did not identify any medication-related adverse experiences. This study confirmed that the monophasic oral contraceptive with 150 micrograms desogestrel and 30 micrograms ethinylestradiol is a safe and effective oral contraceptive with excellent cycle control and patient acceptability.


The influence of a low-dose combined oral contraceptive on menstrual blood loss and iron status.

The influence of a low-dose combined oral contraceptive (ethinyl estradiol 30 micrograms + desogestrel 0.15 mg) on menstrual blood loss (MBL) was evaluated in 20 healthy, young women. MBL prior to commencing oral contraception was 60.2 +/- 5.6 ml (range 22-116 ml), and decreased (p < 0.001) to 36.5 +/- 5.2 ml (range 7-80 ml) and 33.7 +/- 4.1 ml (range 5-70 ml) after 3 and 6 months' oral contraceptive medication, respectively. The reduction in MBL during oral contraception was most apparent during the first two days of menstruation. Five women had an MBL > 80 ml prior to commencing oral contraceptive medication. In all of these women, MBL during the 6th menstrual period after commencing oral contraception was < 80 ml. All the women included in this study had a normal blood hemoglobin concentration, hematocrit and erythrocyte indices and there were no significant changes in these variables during the course of the study. Serum ferritin concentration prior to commencing oral contraception was 44.2 +/- 9.0 micrograms/l and was largely unchanged after 6 months' oral contraception (39.7 +/- 6.3 micrograms/l). On admission to the study, two women had a serum ferritin < 10 micrograms/l, indicative of low iron stores. Both these women had an MBL > 80 ml at the baseline assessment. Serum ferritin concentration increased during oral contraceptive medication in both women (from 8.5 micrograms/l to 12.0 micrograms/l and from 5.4 micrograms/l to 6.8 micrograms/l, respectively). The duration of menstruation (p < 0.01) and the number of women suffering from dysmenorrhea (p < 0.05) was reduced during oral contraception.


Clinical and metabolic effects of a triphasic pill containing gestodene.

The clinical and metabolic effects of a low-dose triphasic oral contraceptive containing gestodene were investigated in 42 healthy women during 6 months of treatment. No pregnancies and no severe side effects occurred during the study. The pill exerted good cycle control and the incidence of irregular bleeding was very low. As for the coagulatory system, there was an increase in prothrombin activity and in fibrinopeptide A plasma levels, and a decrease in activated partial thromboplastin time. Antithrombin III activity, fibrinogen concentration and platelets count did not change during pill intake. No significant modifications in plasma total-cholesterol, low density lipoprotein-cholesterol or in the subfraction high density lipoprotein2-cholesterol (HDL2-CH) were observed. Serum triglycerides, HDL-CH and HDL3-CH levels were significantly higher at the end of treatment. The pill did not alter fasting insulin and glucose levels or their response to an oral glucose tolerance test. These minimal effects on metabolism, combined with its high efficacy and acceptability, may suggest that this triphasic formulation with gestodene seems to be a safe and reliable contraceptive agent.


Oral contraceptives and pregnancy in relation to peptic ulcer.

There is evidence in the scientific literature that peptic ulceration occurs less frequently during pregnancy than at other times. This encouraged us to examine the pattern of hospitalisation for peptic ulcer in the Oxford-Family Planning Association contraceptive study. In total, 175 women in the study had been hospitalised for peptic ulcer; 105 had duodenal disease, 55 had gastric disease and 22 had disease of unspecified site (some had disease at more than one location). Hospitalisation for peptic ulcer increased with age, parity and cigarette smoking. In addition, hospitalisation was at a low rate during pregnancy and was not seen at all during the 12 months following delivery. There was no relationship between hospitalisation for peptic ulcer and total duration of oral contraceptive use. Likewise, there was no significant relationship with recency of oral contraceptive use, but the lowest rate of hospitalisation was in current users of the pill.


Use of a monophasic, low-dose oral contraceptive in relation to mental functioning.

The objective of the study was to evaluate the effect of Minulet, a new low-dose oral contraceptive on mood in two groups and to compare the effect with a control group of women not taking oral contraceptives (OC). The women participating were between 16 and 45 years of age. They completed the Amsterdam Mood Questionnaire (AMQ) and the Sickness Impact Profile (SIP) three times. They were filled in before treatment started, after taking Minulet for one month and then again after three months. The questionnaires were filled in by a group of 200 women who had not taken OC before (starters), and by a second group of 370 women who were already taking OC (switchers). A group of 140 women who did not use any OC during the study served as a control group. These women also filled in the same questionnaires, both at the start, and after one and three months. As far as the AMQ was concerned, the switchers appeared in the initial measurement to have significantly higher scores (that is to say, a worse mood) for "tiredness", "depression", "moodiness", "anxiety" and "anger", than those of the starters and the control group. Moreover, the switchers had reduced scores (that is to say, an improved mood) on the AMQ-scales during their use of Minulet compared to their initial use of oral contraceptives. The scores of the starters and the control group on the AMQ-scales remained unchanged on all three measurements. It can be concluded from this that these groups felt as well as they did before.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of oral contraceptives on integrated secretion of gonadotropins.

The mechanism of action of various oral contraceptives has not yet been satisfactorily resolved, as to how gonadotropins affect ovarian function. Alterations of the pulsatile release of LH might be a common denominator. As methodological difficulties for the evaluation of LH pulse pattern with low basal levels exist, we elected to determine the area under the curve (AUC) for LH and FSH for 6 hours before and during treatment with oral contraceptives. LH and FSH were determined every 15 min for 6 hours on day 4 and day 20 of a control cycle and a treatment cycle in 22 women with ovulatory cycles. They received either a combined preparation containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, a sequential preparation containing 50 micrograms of ethinyl estradiol and 125 g of desogestrel or only 125 micrograms desogestrel. There was no difference between the sum of LH pulses on day 4 and day 20 of the control cycle. The AUC for FSH was lower on day 20. When the combined preparation was taken, FSH was suppressed on day 4, and FSH and LH on day 20 of treatment. The degree of suppression was even more pronounced when the sequential OC was taken. Ethinyl estradiol alone was as effective as the combination with desogestrel. Desogestrel alone inhibited ovulation without affecting serum LH and FSH in a comparable manner, suggesting a direct effect on the ovary. The determination of the AUC seems to be a sensitive tool for the evaluation of OC-induced changes in gonadotropin output.


Microbiological studies in mid-trimester abortion with Emcredil versus normal saline.

In 40 mid-trimester abortion seekers, in whom abortion was induced by extra-amniotic normal saline or Emcredil, microbiological studies were carried out before induction and at 24 hours. It was observed that there was no difference in the isolation of organisms from vagina and cervix of these subjects between 0 hours and 24 hours. Thus, this study shows that leaving the catheter in the extra-amniotic space until it is expelled spontaneously does not increase the risk of ascending infection. At the same time, leaving the catheter in-situ until it is expelled spontaneously reduces the induction-abortion interval appreciably.


Evaluation of four different contraceptive vaginal rings: steroid serum levels, luteal activity, bleeding control and lipid profiles.

Four different models of contraceptive vaginal rings were tested during three cycles for luteal activity, bleeding control, plasma lipoproteins and serum levels of the contraceptive steroids. Two progestins, levonorgestrel acetate (LNGA) and ST 1435, alone or in combination with ethynyl-estradiol (EE) were tested. The rings released 100 ug/day of the progestins and 30 ug/day of EE. Luteal activity was detected among users of the progestin-only rings: 4 of 8 cycles with ST 1435 and 2 of 10 with LNGA. Only one of the 18 cycles studied with the two combined rings showed luteal activity, but the measurement of contraceptive steroid in plasma suggested that this subject delayed reinsertion of the ring for about one week in that particular cycle. Breakthrough bleeding was observed in 12 of 30 cycles of use of the progestin-only rings, and in only 2 of 27 cycles with the combined models. No significant changes in total cholesterol or its HDL-fraction were observed. However, the only reduction observed in HDL-cholesterol was among users of the LNGA-only ring. It is concluded that the two combined CVR models offer good possibilities of high effectiveness and bleeding control and merit further development.


Determination of carcinogenic potency of alkytoxynol-741 (AP-741) by rat peritoneal cell cultures.

The carcinogenic potency of AP-741 was tested in rats using the Nashed method of rat peritoneal cell short-term carcinogenic test. N-methyl-N-nitro-N'-nitrosoguanidian (MNNG) was used as positive control; saline and nonoxynol-9 (NP-9) were used as negative control. Two doses of AP-741 (4 mg/kg and 40 mg/kg equivalent to 4 and 40 times human doses) were tested. The result showed that no colonies of more than 9 cells were seen in the saline and NP-9 groups, and the two dose groups of AP-741. However, 12 +/- 8.3 colonies (9-29 cell/colony) and 4.5 +/- 4.2 colonies (30-300 cell/colony) were seen in the MNNG group. According to the Nashed criterion, we can say MNNG has potential carcinogenesis, while AP-741 does not have any potential carcinogenesis and its use as a vaginal contraceptive drug is safe.


High-performance computing, high-speed networks, and configurable computing environments: progress toward fully distributed computing.

The next several years will see the maturing of a collection of technologies that will enable fully and transparently distributed computing environments. Networks will be used to configure independent computing, storage, and I/O elements into "virtual systems" that are optimal for solving a particular problem. This environment will make the most powerful computing systems those that are logically assembled from network-based components and will also make those systems available to a widespread audience. Anticipating that the necessary technology and communications infrastructure will be available in the next 3 to 5 years, we are developing and demonstrating prototype applications that test and exercise the currently available elements of this configurable environment. The Lawrence Berkeley Laboratory (LBL) Information and Computing Sciences and Research Medicine Divisions have collaborated with the Pittsburgh Supercomputer Center to demonstrate one distributed application that illuminates the issues and potential of using networks to configure virtual systems. This application allows the interactive visualization of large three-dimensional (3D) scalar fields (voxel data sets) by using a network-based configuration of heterogeneous supercomputers and workstations. The specific test case is visualization of 3D magnetic resonance imaging (MRI) data. The virtual system architecture consists of a Connection Machine-2 (CM-2) that performs surface reconstruction from the voxel data, a Cray Y-MP that renders the resulting geometric data into an image, and a workstation that provides the display of the image and the user interface for specifying the parameters for the geometry generation and 3D viewing. These three elements are configured into a virtual system by using several different network technologies. This paper reviews the current status of the software, hardware, and communications technologies that are needed to enable this configurable environment. These interdependent technologies include: (1) user interface and application program construction methodologies, (2) the interprocess communication (IPC) mechanisms used to connect the software modules of the application, (3) the network protocols and interface hardware used by the IPC for communicating between modules running on separate and independent computing system elements, (4) the telecommunications infrastructure that provides the low-level data transfer functions for the networks that connect the geographically distributed elements used by the application, and (5) the nature of the functional elements that will be connected to form virtual systems.


Visualization of bioelectric phenomena.

Biomedical investigators are currently able to acquire and analyze physiological and anatomical data from three-dimensional structures in the body. Often, multiple kinds of data can be recorded simultaneously. The usefulness of this information, either for exploratory viewing or for presentation to others, is limited by the lack of techniques to display it in intuitive, accessible formats. Unfortunately, the complexity of scientific visualization techniques and the inflexibility of commercial packages deter investigators from using sophisticated visualization methods that could provide them added insight into the mechanisms of the phenomena under study. Also, the sheer volume of such data is a problem. High-performance computing resources are often required for storage and processing, in addition to visualization. This chapter describes a novel, language-based interface that allows scientists with basic programming skills to classify and render multivariate volumetric data with a modest investment in software training. The interface facilitates data exploration by enabling experimentation with various algorithms to compute opacity and color from volumetric data. The value of the system is demonstrated using data from cardiac mapping studies, in which multiple electrodes are placed in an on the heart to measure the cardiac electrical activity intrinsic to the heart and its response to external stimulation.


Impact of massively parallel computation on protein structure determination.

For the past two decades, an important paradigm in protein chemistry has been the assertion that a biologically active protein is at thermodynamic equilibrium and therefore adopts its minimum free energy structure. Although some evidence now suggests that not all proteins conform to this notion, it is true often enough to remain an important guiding principle in structure determination, whether by direct computation or by the computationally assisted approaches of diffraction and resonance. Among the difficulties in predicting structure from sequence are the lack of a useful potential function incorporating the influence of solvent and the inability to sample the phase space efficiently or even to determine whether a free energy minimum is, in fact, the global minimum. These problems are general. Although they are greatly mitigated by experimental information, they become increasingly severe as empirical constraints are reduced. We review the difficulties involved in the general problem of protein structure prediction and discuss the impact of increased computer power in the context of new approaches to solvation and parallel algorithm design. A general focus of our discussion is the need to understand the theoretical basis for effective theories and to accommodate in numerical methods the interplay of different temporal and spatial scales.


High-performance computing in radiation cancer treatment.

In 1989 a consortium of the Radiation Oncology and Computer Science Departments at the University of North Carolina, BellSouth Corporation, GTE, and the MCNC was formed in response to the high-speed network initiative proposed by the National Science Foundation and the Defense Advanced Research Projects Agency. One of the purposes of this effort has been to demonstrate that applications exist that require gigabit per second networks. Our consortium, known as VISTAnet, proposed to use real-time radiation therapy treatment planning as the application that would require the use of a gigabit network. The plan was to develop a system that could rapidly calculate and display a three-dimensional radiation dose distribution for any configuration of radiation beams. The gigabit network would be used to tie the dose calculations done with the Cray Y-MP at the Research Triangle to the graphics engine at the Department of Computer Science (Pixel-Planes 5) and the medical workstation at Radiation Oncology. The system would then provide the radiation physician with the capability of considering hundreds of potential treatment plans, instead of the usual two or three, with the goal of arriving at a highly optimized plan within a few minutes.


An anatomical heart model with applications to myocardial activation and ventricular mechanics.

A three-dimensional finite element model of the mechanical and electrical behavior of the heart is being developed in a collaboration among Auckland University, New Zealand; the University of California at San Diego, U.S.; and McGill University, Canada. The equations of continuum mechanics from the theory of finite deformation elasticity are formulated in a prolate spheroidal coordinate system and solved using a combination of Galerkin and collocation techniques. The finite element basis functions used for the dependent and independent variables range from linear Lagrange to cubic Hermite, depending on the degree of spatial variation and continuity required for each variable. Orthotropic constitutive equations derived from biaxial testing of myocardial sheets are defined with respect to the microstructural axes of the tissue at the Gaussian quadrature points of the model. In particular, we define the muscle fiber orientation and the newly identified myocardial sheet axis orientation throughout the myocardium using finite element fields with nodal parameters fitted by least-squares to comprehensive measurements of these variables. Electrical activation of the model is achieved by solving the FitzHugh-Nagumo equations with collocation at fixed material points of the anatomical finite element model. Electrical propagation relies on an orthotropic conductivity tensor defined with respect to the local material axes. The mechanical constitutive laws for the Galerkin continuum mechanics model are (1) an orthotropic "pole-zero" law for the passive mechanical properties of myocardium and (2) a Wiener cascade model of the active mechanical properties of the muscle fibers. This chapter concentrates on two aspects of the model: first, grid generation, including both the generation of nodal coordinates for the finite element mesh and the generation of orthotropic material axes at each computational point, and, second, the formulation of constitutive laws suitable for numerically intensive finite element computations. Extensions to this model and applications to the mechanical and electrical function of the heart are described in Chapter 16 by McCulloch and co-workers.


Large-scale finite element analysis of the beating heart.

The regional mechanics of the beating heart are directly related to factors such as ventricular pumping performance, coronary blood flow, myocardial energetics and oxygen consumption, vulnerability to ischemia and injury, hypertrophy and remodeling, and arrhythmogenesis. Important characteristics include: the complex three-dimensional geometry and fibrous architecture; the nonlinear, nonhomogeneous, anisotropic material properties of the myocardium; the hierarchical collagen connective tissue matrix; the time- and history-dependent active tension development of the cardiac muscle cells; and the three-dimensional anisotropic patterns of cardiac impulse propagation. To model these features realistically requires large-scale computational analysis with sophisticated numerical methods. As described in the chapter by Dr. Hunter and colleagues, an accurate three-dimensional finite element model has been developed to describe the geometry, fiber architecture, and extracellular matrix structure of the heart. The model is based on extensive anatomical measurements in the left and right ventricles (LV and RV) of the canine heart. In this chapter, we illustrate some new approaches to the special problems of large-scale finite element modeling in biomechanics using examples from the analysis of stress and electrical activation in the heart. Prospects for further progress--particularly in coupled problems such as cardiac electromechanics--are examined in light of new developments in high-performance computing.


Cardiac fluid dynamics.

The heart is modeled as a system of elastic and/or contractile fibers immersed in a viscous incompressible fluid. Simulated heart walls and valves are constructed by arranging the fibers according to an idealized version of the actual distribution of muscle fibers in the heart walls and collagen fibers in the valve leaflets. Then the combined motion of the fluid-fiber system is predicted through the numerical solution of its coupled equations of motion. Fluid equations are solved by a finite difference method on a fixed, regular computational lattice. Fiber points move freely through this lattice without being constrained to lie at the lattice intersections. Communication between fibers and fluid involves interpolation of the fluid velocity to the fiber points and the spreading of the fiber forces to the computational lattice of the fluid. Both of these operations make use of a smoothed approximation to the Dirac delta function. The entire method is suitable for implementation on vector, parallel, or parallel-vector hardware. Applications include the investigation of normal cardiac function, the simulation of disease processes affecting the mechanical function of the heart or its valves, and the computer-assisted design of prosthetic cardiac valves.


Bone remodeling around total hip implants.

This chapter reviews the research in the computer simulation of bone remodeling caused by hip implants and also attempts to give nonmedical personnel a basic introduction to total hip arthroplasty and implant-induced bone resorption. First, a short discussion of the hip arthroplasty procedure and the results of follow-up studies are presented to motivate the study of hip prostheses. Current implant materials and technologies and future trends in implant design are reviewed. A description of what are believed to be the mechanisms of bone resorption due to femoral implantation is presented. Different mathematical theories of bone remodeling and their application to the problem of implant analysis are presented, and recent advances in the finite element modeling of bone resorption and implant micromotion are discussed.


Nonpustular palmoplantar psoriasis.

Nonpustular palmoplantar psoriasis can be disabling in causing painful fissuring and scaling. Preventive measures in avoiding friction and irritants can reduce the morbidity of this variant. Lubricants, anthralin, and corticosteroids form the mainstay of therapy in mild and moderate psoriasis of the palms and soles. Topical PUVA therapy and use of cytotoxic agents should be reserved for refractory cases.


Symptomatic zinc deficiency in a one-year-old child precipitated by changing from formula to cow's milk.

The case of a one-year-old girl with symptomatic zinc deficiency is presented. She had been misdiagnosed as having impetigo and/or candidiasis and had been treated with topical antifungal agents and both oral and topical antibiotic agents without success during the four months before she presented. Zinc replacement led to rapid improvement. Her nutritional history suggests that weaning from formula to cow's milk precipitated her eruption. The clinical findings, differential diagnosis, and treatment of zinc deficiency are reviewed.


Psoriasiform eruption from intramuscular botulinum A toxin.

Botulinum A toxin is used intramuscularly in the treatment of spastic neuromuscular disorders, strabismus, and laryngeal dystonia. The toxin has recently been reported as being useful for the cosmetic removal of glabellar furrows. The clinical effect of the toxin lasts four months or longer. Systemic side effects are rare and usually transient. We report the case of a psoriasiform eruption temporally related to the injection of botulinum A toxin into the medial rectus muscle to treat an ocular motility disorder. To our knowledge, this is the first case of a psoriasiform dermatitis caused by this agent.


Large erythematous patch as the presenting manifestation of meningococcemia.

Meningococcemia commonly presents with a petechial rash and a transient macular or papular rash is sometimes present. This report describes a patient with meningococcemia who presented with an atypical erythematous patch over the right hemithorax, petechial rash, and a normal platelet count. The patient was treated with broad-spectrum antibiotics and his condition rapidly improved. He was discharged showing complete resolution of his rash with no neurologic sequelae.


Cutaneous blastomycosis.

We report on a patient with cutaneous blastomycosis and no evidence of systemic involvement. This diagnosis was made on the basis of clinical findings and confirmed by histologic examination and results of culture. The primary lesion in blastomycosis is almost always pulmonary. However, occasionally, as in our patient, the pulmonic focus resolves spontaneously before the patient presents. Disseminated lesions occur most often in the skin, followed by bone, genitourinary tract, and central nervous system. Our patient had an excellent response to ketoconazole without adverse effects.


Specificity of insulin binding by plasma and nuclear membrane receptors in Tetrahymena: similarities and dissimilarities at the two levels.

The plasma membrane and nuclear envelope of Tetrahymena are equally able to bind insulin both specifically and otherwise. Primary interaction with exogenous insulin (imprinting) accounted for an increase in the specificity of binding which became even more pronounced in the distant offspring generations of the imprinted cells. Virgin Tetrahymena cells not imprinted with insulin showed a greater specificity of insulin binding at the nuclear than at the plasma membrane level. This difference became equalized under the influence of imprinting with exogenous insulin which increased the specificity of binding at the plasma membrane level.


Influence of chromosome condensation and preparative chromosome methods on chromatid volume.

Human metaphase chromosomes 1 and 2 were examined by electron microscopy. Volumetric determinations were calculated on non-treated isolated chromosomes and spread metaphases treated with ammoniacal silver carbonate (ASC). Chromatid volume increased from early-metaphase to late-metaphase and this increase was statistically significant. A similar relationship was found when chromosomes with differentially condensed sister chromatids were studied. The more condensed chromatid volume was greater than its less condensed sister chromatid. ASC treatment produced structural changes in chromosomes which caused an increase of volume in relation to the isolated chromosomes.


The preservation of mitochondrial functions in extracellular environments.

Mitochondria are labile objects when isolated from mammalian organs and may undergo rapid changes (aging) in vitro. This work attempts to examine conditions which retard such changes. Isolated rat heart mitochondria were incubated for 180 min in the presence of various substances whose properties might influence the aging process as expressed by changes in oxygen consumption rates. It was found that retardation was greatest with substances which potentially influence reactions involving fatty acids. This effect is discussed in terms of various mechanisms of mitochondrial aging.


Cytological aberrations in maize populations exhibiting unusual recombinational behaviour.

Earlier studies identified higher recombinational activity and increased somatic instability at various loci in the F1 and F2 progeny of particular stocks of a maize inbred line, A188. Hypothesizing that this may reflect a genome-wide perturbation of chromosome structure which would be detectable cytologically, aberrant meiotic behaviour in these stocks was investigated. Microsporocytes from a population of F2 plants derived from these stocks displayed the following aberrations: varying frequencies of metaphase and anaphase laggards, 'stickiness' at anaphase I resulting in chromosome bridges from pole to pole, acentric fragments and a spontaneous translocation of the NOR on chromosome 6. The frequencies of metaphase I and anaphase I abnormalities in these stocks were higher to a statistically significant extent than in control F2 populations, suggesting that these aberrations may be related to the unusual genetic behaviour of these stocks.


Palmitate oxidation by in vivo and in vitro grown Mycobacterium lepraemurium.

Oxidation of palmitate by Mycobacterium lepraemurium isolated from C3H mice lepromata (in vivo) and also grown on Ogawa egg-yolk medium (in vitro) was investigated. Palmitate was found to be oxidized, after a lag period of about 8 h, by both the in vivo and in vitro grown bacilli. Cell-free extracts prepared from in vivo and in vitro grown cells catalysed an active oxidation of palmitate after a lag period of 3-4 h. The amount of ATP increased, with the increase in time during oxidation of palmitate by the cell-free extracts. The generation of ATP was strongly inhibited by the inhibitors rotenone, antimycin A and cyanide as well as by the uncouplers 2,4-dinitrophenol and 2,6-dibromophenol. These results indicated that oxidation of palmitate by the in vivo and in vitro grown M. lepraemurium is mediated through the respiratory chain using oxygen as the terminal electron acceptor.


Protein phosphorylation and the regulation of basal body microtubule organizing centres in Tetrahymena.

Previous work suggests that changes in the phosphorylation state of some centrosomal proteins regulate centrosomal activity. The hypothesis that changes in the phosphorylation state of one or more basal body microtubule organizing centre (MTOC) components regulate its ability to nucleate cilia assembly in Tetrahymena thermophila was tested. The MPM-2 antibody, which recognizes phosphorylated epitopes in MTOCs in a variety of organisms, was used to probe immunoblots of cytoskeletal frameworks prepared from starved Tetrahymena, from starved deciliated Tetrahymena, and from a starved deciliated mutant Tetrahymena which failed to initiate ciliogenesis following deciliation. The MPM-2 antibody recognized an identical array of proteins in all blots. These results suggest that, unlike centrosomes, basal body MTOC activity is not regulated by changes in the phosphorylation state of component proteins.


Characterization of yeast artificial chromosomes containing interleukin genes on human chromosome 5.

To understand better the organization and linkage of the interleukin genes, IL4 and IL5, we prepared long-range restriction maps of five yeast artificial chromosomes (YACs) containing IL5. We determined that IL4 and IL5 are within 100-170 kb, and that the regions surrounding these genes contain several GC-rich areas. Fluorescence in situ chromosomal analysis demonstrated that three of the five YAC clones contain non-contiguous genomic sequences originating from multiple human chromosomes.


The gene for leukocyte antigen-related tyrosine phosphatase (LAR) is localized to human chromosome 1p32, a region frequently deleted in tumors of neuroectodermal origin.

In situ hybridization was employed to localize a cDNA probe from the human protein tyrosine phosphatase gene LAR to human metaphase chromosomes. LAR, a putative tumor suppressor gene, has been localized to 1p32, a chromosomal region that is frequently found deleted in human neuroblastoma and pheochromocytoma.


The gene for receptor-like protein tyrosine phosphatase (PTPRB) is assigned to chromosome 12q15-->q21.

Using a cDNA probe, the gene encoding the human receptor-like protein tyrosine phosphatase (PTPRB) was localized by an in situ hybridization to chromosome 12q15----q21.


The human gene for oxytocin-neurophysin I (OXT) is physically mapped to chromosome 20p13 by in situ hybridization.

Two posterior pituitary hormones oxytocin and arginine-vasopressin control the important activities of water excretion, parturition and lactation. Both these hormones are synthesized as inactive precursors in the hypothalamus along with their carrier proteins neurophysin I and neurophysin II respectively and are activated upon transport to posterior pituitary. Human genes for both oxytocin-neurophysin I (OXT) and arginine-vasopressin-neurophysin II (ARVP) are cloned and found to be linked on chromosome 20 separated by approximately 12 kb of intergenic sequences. Though OXT is not yet associated with any disease, ARVP is linked to the autosomal dominant disease neurohypophyseal diabetes insipidus (AD-NDI). We have mapped regionally the OXT locus to chromosome 20p13 by both radioactive (ISH) and fluorescence in situ hybridization (FISH).


Chromosomal location of the human transketolase gene.

The gene encoding the human transketolase enzyme (TKT) was localized by fluorescence in situ hybridization to normal and FRA3B human chromosomes. Southern blot analysis of a series of human x mouse and human x hamster hybrid cell lines confirmed this localisation. TKT maps to 3p14 and distal to FRA3B, localizing TKT to 3p14.3.


Comparative gene mapping in the species Muntiacus muntjac.

An extreme case of chromosomal evolution is presented by the two muntjac species Muntiacus muntjac (Indian muntjac, 2n = 6 [females], 7 [males]) and M. reevesi (Chinese muntjac, 2n = 46). Despite disparate karyotypes, these phenotypically similar species produce viable hybrid offspring, indicating a high degree of DNA-level conservation and genetic relatedness. As a first step toward development of a comparative gene map, several Indian muntjac homologs of known human type I anchor loci were mapped. Using flow-sorted, chromosome-specific Southern hybridization techniques, homologs of the protein kinase C beta polypeptide (PRKCB1) and the DNA repair genes ERCC2 and XRCC1 have been assigned to Indian muntjac chromosome 2. The male-specific ZFY gene was presumptively mapped to Indian muntjac chromosome Y2. Ultimate generation of a comparative physical map of both Indian and Chinese muntjac chromosomes will prove invaluable in the study of mammalian karyotype evolution.


Location of the mouse complement factor H gene (cfh) by FISH analysis and replication R-banding.

A technique for replication R- and G-banding of mouse lymphocyte chromosomes was developed, and the replication R-banding pattern was analyzed. Optimal banding patterns were obtained with thymidine- and BrdU-treatment of lymphocytes in the same cell cycle. This produced replication R-band patterns that were the complete reverse of the G-band patterns on all chromosomes. Replication R-banding methods can be used in conjunction with nonisotopic, fluorescence in situ hybridization (FISH) to localize cloned probes to specific chromosomal bands on mouse chromosomes. with these methods the mouse complement factor H gene (cfh) was localized to the terminal portion of the F region of Chromosome 1. Q-banding patterns were also obtained by the replication R-banding method and may be useful for rapid identification of each chromosome.


Chromosomal localization of the ovine beta-casein gene by non-isotopic in situ hybridization and R-banding.

The ovine beta-casein gene (CNS2) has been mapped to a specific chromosome band using nonradioactive in situ hybridization and simultaneous fluorescent R-banding. The probe pTZ-E4 was a fragment of the ovine beta-casein gene inserted in the plasmid pTZ18R and labeled with biotin-11-dUTP. It hybridized to band q32 of ovine chromosome 4. The discrepancy between this result and the previous localization of this gene on cattle chromosome 6 may be explained by the very great similarity of the banding patterns of ovine and bovine chromosomes 4 and 6.


Fertility of male and female mice heterozygous for the reciprocal translocation T(7;17)3BKM.

The present paper describes the fertility of male and female mice heterozygous for the reciprocal translocation T(7;17)3BKM. This translocation was induced by gamma rays in the spermatozoa of an irradiated parent. It is characterized by "asymmetrical" localization of the breakpoints, distally in Chromosome 7 (7F5) and proximally in Chromosome 17 (17B1). The data presented here relate only those matings in which, for both partners, heterozygosity or normality could be confirmed cytogenetically. The results indicate that both male and female translocation heterozygotes are fertile, their mean litter size being reduced to about 50% of that of normal littermates. This leads to the conclusion that the multivalents mainly undergo either alternate or adjacent-1 2:2 segregation. No viable tertiary trisomics were observed among the progeny of the translocation carriers. Analysis of the frequency of the different types of multivalents in diakinesis-metaphase I spermatocytes showed a significant predominance of chain-type figures (CIV and CIII+I), with chains of four elements (CIV) being more frequent than other configurations. This demonstrates that the small marker chromosome remains attached by one of its segments to the tetravalent.


Case reports on psychosomatic eye disorders.

Symptoms of headache, floaters, blurred vision, eye strain may be respectable outward manifestations of secret fears or failure to adjust to life events. The work in this hospital of Mr W.S. Inman, ophthalmologist and psychoanalyst, has largely been forgotten. I will present case histories to show that the approach 'Let's have a chat about your problem' can reveal deep underlying tensions. The description of these by the patient, for the first time, to a neutral listener is usually curative. It takes longer than a detachment operation and can be more difficult than cataract surgery but the end result is a very grateful patient whose symptoms have been cured--by talking. We can easily dismiss these patients with 'Your problem is not ocular'. By spending time listening and being unafraid of their muddled lives, their confused sexuality and inadequate personal relationships, we can reach a wider range of patients to help, as Inman taught our predecessors. I find it rewarding.


Pigment-containing cells in extraocular tissues of the primate.

In the present study pigment-containing (PC) cells, localized in extraocular tissues of man and the cynomolgus monkey, were investigated to establish their localization, nature and relationships with the autonomic nervous system. In the orbit of man as well as the cynomolgus monkey three localizations of PC cells were detected: (1) Tenon's capsule along the ciliary arteries at the level of the entrance of the arteries into the eyeball, (2) Tenon's capsule along the ciliary nerves at the level of the entrance into the eyeball, and (3) the sclera around the ciliary arteries and nerves. Moreover in the orbit of the cynomolgus monkey PC cells were found along and around the accessory lateral rectus muscle. Histological, histochemical and electron microscopical studies led to the conclusions that PC cells are similar in nature to melanocytes and do not have neuronal properties. In contrast to the melanocytes in the anterior segment of the eye in both man and monkey, melanocytes in the extraocular tissues are not innervated either adrenergically or cholinergically.


Magnetic resonance imaging and computed tomography in the detection and localization of intraocular foreign bodies.

In this experimental study, various foreign bodies were inserted into fresh bovine eyes, in different localizations. Twenty-one magnetic and non-magnetic foreign bodies, dimensions of which varied from 1.5 x 1.5 x 2 mm to 3.5 x 6 x 7 mm, were tried to detect by computed tomography (CT) and magnetic resonance imaging (MRI) scanning. In addition, further dissections were applied to check the ocular damage attributable to movement of the foreign bodies. Ferromagnetic foreign bodies have been shown to move in the eye and the risk of torsional forces being applied to the ferromagnetic foreign body seemed to cause intraocular complications during MRI scanning. All of the foreign bodies that were implanted in bovine eyes were recognized on CT scanning, except intraocular lenses. As a general rule, metallic foreign bodies produced beam-hardening artifacts, but these artifacts did not cause any problem in detecting the localizations of foreign bodies.


Long-term follow-up of central serous retinopathy in 150 patients.

To study the evolution of the retinal pigment epithelial lesions in the central serous retinopathy, the authors studied 150 patients with ages between 20 and 49 years at the first examination, during periods varying between 6 months and 14 years. It was found a greater incidence of the disease in the males (83.3%); bilaterality in 23.3%; only one point of leakage in 62.7%; 3 different types of diffusion (inkblot 71.4%; mushroom 23.8%; with serous pigment epithelial detachment 4.9%). The final visual acuity was < 20/40 in a quarter of the cases and the frequency of the recurrences was 30%. The laser treatment did not influence the recurrences. In 50 patients with a follow-up superior to 3 years, 8 (16%) developed lesions similar to those described as diffuse retinal pigment epitheliopathy with visual field defects and subnormal EOG. Actuarial calculus suggests that 50% of the patients may get the most severe and extensive form of the disease after 12 years of evolution. The results allow to conclude that the diffuse retinal pigment epitheliopathy is only the terminal state of the most severe cases of central serous retinopathy.


Serum levels of antioxidants and age-related macular degeneration.

A number of reports have suggested that oxidative damage in the retina may contribute to the pathogenesis of Age-related macular degeneration (AMD). The present study was designed to investigate the hypothesis that serum levels of the antioxidants, Vitamin E and selenium are related to the pathogenesis of AMD. Fasting bloods were obtained from 80 patients with AMD and 86 controls. Assays for serum levels of Vitamin E, selenium, cholesterol and triglycerides were performed. Assessment of patients and controls was based upon eye examination, fundus photography and medical history. No significant difference was found in serum levels of Vitamin E between subjects and controls, however, there was a borderline association between AMD and both serum selenium levels and current smoking status. The results suggest that if oxidative damage is a factor in the pathogenesis of AMD, it is not reflected in serum levels of Vitamin E; further studies are required to clarify the possible relationship between serum selenium levels, smoking and AMD.


Cocaine and development: mechanisms of fetal toxicity and neonatal consequences of prenatal cocaine exposure.

As cocaine use during pregnancy has become increasingly recognized, there also has been increased concern about the toxic and teratogenic properties of cocaine on the fetus. A significant literature exists describing the adverse fetal and neonatal outcomes associated with in utero cocaine exposure. However, specific causality by cocaine on outcome in the human is difficult to ascertain because of multiple confounding variables associated with substance abuse including social factors and polydrug use as well as difficulty in confirming timing, dose and frequency of cocaine exposure. Most literature suggests that prenatal cocaine exposure is associated with developmental risk to the fetus. What is currently unknown is the extent of risk, the additive and/or synergistic factors contributing to cocaine's toxicity and the reversibility of the injury. In this paper we review the pharmacologic properties of cocaine as related to a model of mechanisms for developmental injury secondary to cocaine exposure and the published literature on the adverse fetal and neonatal outcomes associated with cocaine use during pregnancy. Specific attention has been focused on the structural, neurobehavioral and respiratory control teratogenesis.


Effect of the maternity ward system on the lactation success of low-income urban Mexican women.

We compared the lactation performance of 165 healthy mothers who planned to breastfeed and gave birth by vaginal delivery, without complications to a healthy infant in either a nursery (NUR) (n = 58) or a rooming-in hospital where formula supplementation was not allowed. In the rooming-in hospital, women were randomly assigned to a group that received breastfeeding guidance during the hospital stay (RIBFG) (n = 53) or to a control group (RI) (n = 54). Women were interviewed in the hospital and at 8, 70 and 135 days post-partum (pp). The groups were similar in socio-economic, demographic, anthropometric, previous breastfeeding experience and prenatal care variables. Non-parametric survival analyses adjusting for potential confounding factors show that breastfeeding guidance had a positive impact (P < or = 0.05) on breastfeeding duration among primiparous women who delivered in the rooming-in hospital. Among primiparae, the RI and RIBFG groups had higher (P < or = 0.05) full breastfeeding rates than the NUR group in the short term. In the longer term, only the difference between the RIBFG and the NUR group remained statistically significant. The maternity ward system did not have a statistically significant effect on the lactation performance of multiparae.


Feeding preterm infants a formula containing C20 and C22 fatty acids simulates plasma phospholipid fatty acid composition of infants fed human milk.

Thirty-four premature infants weighing less than 1500 grams at birth were fed preterm formula (formula), preterm infant formula manufactured to contain a balance of C20 and C22 omega 6 and omega 3 fatty acids within the range characteristic of human milk (LCPE-formula) or their mothers' expressed breast milk (EBM). Blood samples were obtained during the first week of life and after 28 days of feeding to determine the effect of feeding C20 and C22 omega 6 and omega 3 fatty acids on plasma lipids. Fatty acid analyses of red blood cell phospholipids indicated few differences between dietary treatment and age. Fatty acid content of plasma cholesterol esters indicated a high plasma cholesterol linoleate level for infants fed formula and a reduced content of C20 and C22 omega 6 and omega 3 fatty acids. For infants fed the modified formula (LCPE-formula) the levels of 20:4 omega 6, 20:5 omega 3 and 22:6 omega 3 were higher than observed for the formula group and similar to those observed for infants fed EBM. By the fifth week of life, feeding the modified formula resulted in plasma phospholipid levels of C20 and C22 omega 6 and omega 3 fatty acids similar to levels of C20 and C22 omega 6 and omega 3 fatty acids found in infants fed EBM and significantly higher than levels characteristic of infants fed formula. It is concluded that infants fed LCPE-formula illustrate an overall balance between C20 and C22 omega 6 to omega 3 fatty acids in the plasma similar to that characteristic of infants fed human milk.


Recovery of tracheal epithelium following high frequency ventilation at low inspired humidity.

We used scanning electron microscopy (SEM) and light microscopy (LM) to study the recovery of tracheal epithelium in newborn lambs damaged by high frequency flow interrupted ventilation (HFFIV) at low inspired humidity (30%). Newborn lambs were mechanically ventilated for 6 h, allowed to recover and subsequently killed at 2, 7 or 14 days. The recovery of the trachea above and below the tip of the endotracheal tube (ETT) was studied at these time periods and compared to a control non-intubated group and a group killed immediately after 6 h of ventilation. Above and below the ETT, SEM and LM revealed deciliation to be greatest 2 days after ventilation. The damaged tracheal mucosa had converted to non-ciliated epidermoid squamous metaplastic cells. Recovery was not complete by 14 days, although the squamous cells had already differentiated into goblet and ciliated columnar epithelial cells. No difference was seen in the rate of recovery of the tracheal mucosa above or below the tip of the ETT.


How should parents be informed about major procedures? An exploratory trial in the neonatal period.

The current doctrine of informed consent in medical practice may require the provision of more information than is understandable or desired by some parents. We conducted an exploratory trial comparing: (1) detailed risk/benefit disclosure provided both verbally and in writing and (2) flexible disclosure consisting of a brief verbal description supplemented with detailed verbal and written disclosure if desired by the mother. Information about mechanical ventilation was presented to 26 mothers of newborns at risk for respiratory failure. Of the 13 mothers in the flexible disclosure group, seven (54%) desired only brief verbal disclosure. Despite poor recall of information, most mothers were satisfied with the information provided. There was no evidence that the detailed disclosure group had greater maternal satisfaction or less maternal anxiety. Flexible disclosure as evaluated in this study had no important disadvantages relative to detailed disclosure. Methods of providing information to better meet the wants and needs of parents deserve further study.


[Control of isometric muscle contraction in muscle hypotonia of central origin: EMG mapping analysis].

Electromyographic and mechanographic investigations in patients with muscular hypotonia, which is, for instance, a side-effect after stereotactic treatment of tremor syndromes, permit the presumption that in this sensomotor open-loop situation the decreased muscular resistance to stretching during isometric contraction (initial stiffness) is caused by changes of muscular innervation pattern. Probably, the innervation pattern during tonic activity is changed by a shift of a more tonic motoneurone behaviour to motoneurone activities with predominantly phasic characteristics. In 17 controls and 4 patients with muscular hypotonia caused by stereotactic lesions of VIM area (treatment of tremor syndromes) the EMG of right and left side forearm flexors (especially the activity of the M. biceps brachii) was investigated by a sophisticated, topographically oriented 16-channel-surface-EMG-technique ("EMG-Mapping") during slight isometric contraction. EMG-Maps of forearm flexors (especially of M. biceps brachii) in patients with centrally evoked muscular hypotonia demonstrate that in these open-loop conditions the motor control is changed. For this the reason could be a shift of the activated motor units from a predominantly static to a more phasic functional behaviour. The latest results on muscular activation processes in cats support this presumption.


[Jaw opening reflex: a new electrophysiologic method for objective assessment of trigeminal sensory disorders. I. Method and normal values].

Retrospective analysis of trigeminal nerve evoked potentials in 40 consecutive patients, most of them with traumatic nerve lesions, showed that in 12 cases no trigeminal nerve SEP were obtainable, and 11 of the remaining 28 patients had normal trigeminal nerve SEP. Therefore the jaw-opening reflex was investigated as a potential tool for electrophysiologic analysis of facial sensory disturbances. The jaw-opening reflex was investigated in 60 healthy subjects (31 female, 29 male) aged 23-82 years. It was elicited by electrical 0.1 ms square wave pulses delivered to the lower and upper lips and to the infraorbital region on either side at a rate below 1 per 5s. The EMG responses were recorded from the bilateral masseter and temporalis muscles at a moderate voluntary activation. Under these conditions, the jaw-opening reflex reveals itself as two inhibitory pauses of the ongoing EMG on both sides, the onset latency of the first EMG-suppression being 10-15 ms, and of the second 35-50 ms. Particular attention was paid to the stimulus strength at threshold (TR) to evoke the jaw-opening reflex. We found that the jaw-opening reflex was constantly evoked by weak stimuli applied to the 2nd and 3rd trigeminal branches. Bilateral reflex responses with unilateral stimulation were a regular finding. The reflex responses increase with increasing stimulus strength (Fig. 1). Moderate to forcible activation of the jaw closing muscles is a prerequisite for optimum recordings of the jaw-opening reflex (Fig. 2).(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical application of quantitative evaluation of horizontal pursuit movements of the eye].

Horizontal smooth pursuit eye movements were quantitatively evaluated in forty patients with various neurological diseases (chronic alcoholism, acusticusneurinom and multiple sclerosis) as well as in twenty-four healthy subjects. Different frequency sinusoidal targets with an amplitude of 20 degrees were used. The quantitative analysis was possible after calculating the pursuit value as the difference between the saccadic part and the maximal amplitude of the recorded eye movement. Maximal and minimal P-values of 0.5, 0.7 and 0.9 Hz were chosen in the discriminant analyses. It is suggested that these parameters are very helpful in distinguishing between the groups of patients and the group of subjects.


[Neurophysiologic monitoring in neurosurgical vascular operations: specific technical requirements and their conversion].

Several authors have presented evidence for a strict relation between regional cerebral blood flow and EEG. Therefore the EEG can serve as an adequate physiological parameter when monitoring cerebral function in the operating room. However, to exploit the inherent information as far as possible, both multichannel EEG and somatosensory evoked potentials should be recorded simultaneously. In the present article we describe a monitoring system which is capable to handle this task under the conditions of an operating room. In the first step some numerically simple algorithms are applied to detect gross artifacts. In the subsequent processing stage an analysis procedure is performed which is robust with respect to the remaining more subtile artifacts. In addition the raw signals are continually displayed on a monitor to allow for a visual evaluation of the EEG. The results of a trend analysis procedure are presented on the same graphical display by means of a compact topographical scheme. The system has been running under routine conditions for approximately two years now.


[Topography of early cortical median nerve somatosensory evoked potentials: results for routine use of the method].

The results from a topographic analysis of the early median nerve SEPs allowed to design a method for recording and analysing the SEPs in the routine laboratory. The detailed analysis of the topography of 50 normal subjects revealed: 1. An inter- and intraindividual variability of the location of the maximal amplitudes, 2. A significantly longer latency of the cortical potentials after left side stimulation, 3. A significantly higher amplitude of N20 after left side stimulation and 4. A significantly higher amplitude of the later potentials P25 and N30 after right side stimulation. It was shown that a 4-channel recording from the neck at C7 with a Fz-reference as well as from stimulus contralateral F3, CP3 and P3 or F4, CP4 and P4 with an stimulus contralateral earlobe reference provides all necessary parameters in comparison to an 20-channel recording. The definition of normal values has to take into account these results. Absolute maximum values were taken instead of the standard deviation because all amplitude values were proven to be not distributed normally. In 7 out of 30 MCA-stroke patients pathological SEP amplitudes were obtained using the 4-channel montage, whereas the 1-channel recording from CP3 and CP4 with a Fz-reference revealed normal amplitudes.


[Quality of day time sleep in the multiple sleep latency tests in patients with narcolepsy, obstructive sleep apnea and psychogenic hypersomnia].

The multiple sleep latency test (MSLT) has proved to be a useful diagnostical tool for patients complaining of excessive daytime sleepiness (EDS). The intention of the present study was to investigate the structure of MSLT naps and in particular sleep spindle and k-complex density in three different groups of EDS patients. MSLT was performed at 8 a.m., 10 a.m. 12 a.m., 2. p.m. and 4 p.m.. Each recording lasted 20 minutes and was not stopped even if sleep occurred before 20 min. Sleep was scored visually. Spindle and k-complex density was determined per minute of S2 sleep. Statistical analysis used ANOVA. Each of the three groups consisted of 15 patients. Diagnosis of narcolepsy, sleep apnea, of EDS due to a psychiatric disorder has been confirmed subsequently. There were 5 female and 10 male narcoleptics (mean age: 43.9 +/- 10.9 years), 2 female and 13 male obstructive sleep apnea patients (mean age: 53.9 +/- 10.9 years) and 7 female and 8 male patients complaining of EDS, in whom a psychiatric disorder was diagnosed (mean age: 38.8 +/- 13.8 years). Narcoleptics sent more than half of the recording time of 100 min asleep (52.9%). Apnea patients slept 41.3% and psychogenic EDS patients 22.7%. The proportion of sleep stages 1 and 2 in narcoleptics (S2/S1 = 1:1) was clearly different from the other two (apnea patients: S2/S1 = 4:1; psychogenic EDS patients: S2/S1 = 3:1). 18.5% of the naps contained stage REM and during the afternoon naps 0.9% of S3 in the narcoleptics. Neither REM nor S3 was observed in the others.(ABSTRACT TRUNCATED AT 250 WORDS)


[Periodic discharges of sleep spindles with placebo and zopiclone].

According to our experiences (parietal) sleep spindles often show a periodical appearance. Successive sleep spindles in series have a distance of about four seconds. In 95% the duration of such series of sleep spindles is not longer than 40 s, so that there appears no more than ten successive periodical sleep spindles. In the present study ten subjects aged between 57 and 77 years were given Placebo and 7.5 mg Zopiclone. Under the effect of verum we found a doubling of sleep spindle series. However, the distance between the periodical spindles and the length of the spindle series remained unchanged. The variance in the ability to generate sleep spindle series was very high across subjects. One subject for example produced only one sleep spindle series in the Placebo-night (three under verum) and another subject on the other hand 95 (under verum 130). The results of the present study well corresponding to the results of a former investigation comparing Placebo, Pentobarbital, Methaqualon, Carbromal, Flunitrazepam, Triazolam and Lormetazepam.


[Computer-assisted analysis of the electroencephalogram with a theta ground rhythm variant].

From 8 men and 12 women with a slow posterior rhythm on the one hand and from 7 male and 5 female healthy volunteers with a regular alpha-EEG on the other closed-eye-EEGs were registered at 8:00 a.m., 12:00 noon, 4:00 p.m., and 8:00 p.m. and recorded on tape for computer processing. Simultaneously each time the body temperature was measured. In 11 of the 20 patients the slow posterior rhythm shows a right-sided accentuation, in 6 a left-sided. Besides the activity of all frequency-bands favours occipital and occipital-central the right hemisphere. The control group shows only an insignificant right-sided accentuation of alpha-power and alpha-peak-power. The alpha-peak-frequency of the 20 patients is slower than in the controls, the body temperature on the contrary is higher. The physiological circadian shift of the alpha-peak-frequency and of the body temperature does not come up to a similar extent as in the controls. Striking slight is the circadian shift of the frequency of the slow posterior rhythm. Furthermore the day-time related shifts of the alpha-power and of the beta-power take other courses than in the controls. And the maxima of the alpha-power and of the alpha-peak-power are mostly located parietal instead of occipital. All in all the slow posterior rhythm seems to be connected with far-reaching peculiarities of the cerebral function.


The relationship between mind, brain, and seizures.

The medical model of epilepsy suggests that seizures arise at random or in response to precise physiological events. Little weight is given to the part that ongoing brain activity may play in either precipitating or inhibiting seizures. In the focal epilepsies, the presence of damaged neurons that fire in the epileptic mode continuously and are called pacemaker cells has been demonstrated in both animal models and human epilepsy. If these pacemaker cells are firing all the time, why then do seizures arise only spasmodically? Behavior can be thought of as changes in the excitation and inhibition of populations of neurons. Therefore, it is likely that these excitatory and inhibitory waves will either increase or decrease the likelihood of seizures arising. The conditioning of the neurons to fire in volleys in a biofeedback paradigm, the conditioning of seizures in a classic Pavlovian sense, and the occurrence of seizures in response to behavioral changes has been shown in animal models of epilepsy and in humans. There is now evidence that children can both inhibit and generate their own seizures spontaneously. Many adult patients have behavioral strategies that they use either to inhibit or to stop the spreading seizures. In patients who have difficulties in coping with the stresses in their life, the voluntary generation of seizures may come to form a response to difficult situations. Thus, any complete epilepsy program must consider the patient, the behavior, and the relationship between seizures and behavior.


Cognitive correlates of interictal discharges.

Interictal discharges can occur silently without apparent simultaneous clinical manifestations. Nevertheless, formal testing during electroencephalographic (EEG) recording may demonstrate transitory cognitive impairment (TCI). The probability of demonstrating TCI is related to the nature of the test employed and the type of epileptiform discharge. Difficult tasks are more useful to detect TCI, and working memory and language tests may be particularly sensitive. Generalized 3-Hz spike-wave bursts lasting at least 3 s are most likely to produce demonstrable TCI, but they can also be found during briefer and even focal discharges. The latter exhibit some specificity: left-sided focal spiking more frequently produces errors in verbal tasks, whereas right-sided discharges are more often accompanied by impairment in handling nonverbal material. TCI may adversely affect the patient's psychosocial functioning in daily life, as has been shown by some studies pointing out an impairment of educational skill in epileptic children and of driving performance in motorists. Our study on benign childhood epilepsy with Rolandic spikes also detected TCI in the majority of the patients. Nevertheless, it is not possible to claim that everyone with subclinical EEG discharges has TCI that adversely affects their psychosocial functioning. It may be possible to treat TCI by antiepileptic drugs.


Everyday memory failures in people with epilepsy.

In a series of studies, we have explored the nature of memory problems experienced by people with epilepsy. By means of a questionnaire, the first study surveyed everyday memory failures experienced by 742 people with epilepsy. Findings revealed a high level of failures that were associated with later age of onset of seizures and raised levels of anxiety and depression. A second smaller prospective study confirmed these findings and suggested that patients with epilepsy had underestimated the frequency of memory complaints when assessed retrospectively. The third study investigated the relationship between self-reported memory failures and neuropsychological test performance. A measure of verbal recall was the best predictor of reported memory failures. Again, older age of onset and mood were found to be pertinent variables in relation to memory complaints.