Teenage girls attending a Dublin sexually transmitted disease clinic: a socio-sexual and diagnostic profile.

Over a 12 month period, 32 teenage girls attended the sexually transmitted disease clinic in the Mater Misericordiae Hospital, Dublin for the first time, accounting for 17.8% of all first visits. Their mean age was 18.2 years (range 15-19 years). Twenty-four (75%) were from social class V. Five (15.6%) were abusing drugs. The mean age of first coitus was 16.1 years (range 13-19 years). The mean number of sexual partners was 1.8 (range 1-5). Four (12.5%) had been sexually abused in the past. Fourteen (43.8%) had never used contraception. Twenty-three (71.9%) were nulligravidae: 2 were diagnosed as being pregnant in the clinic. Twelve (37.5%) were unaware of cervical cytology screening. Of 29 having intercourse without condoms, none considered themselves to be at risk of contracting HIV from their present partner. A total of 26 diagnoses were made in 23 patients (71.9%). The most common diagnosis was ano-genital condylomata acuminata (6, 18.8%); Chlamydia trachomatis was located in 2 patients and Neisseria gonorrhoea in one. Mild to moderate dyskaryosis was reported in 4 cervical smears (12.5%). This data highlights the need for priority targeting of this high risk group.


Paediatric renal transplantation in Ireland: 1980-1990.

Between 1980 and 1990, 862 renal transplants were performed at our unit. Forty-six of these were given to 38 children. The mean age of the children was 8.6 years. Reflux nephropathy accounted for 39% of the primary renal diseases, followed by congenital disorders (30%), and glomerulonephritis (16%). Seventy percent of the grafts were from cadaveric donors. The one year patient survival was 90%, and the one year graft survival 61%. Seven children received a second graft with a one year graft survival of 71%.


"Avoidable mortality" as an index of health care outcome: results from the European Community Atlas of "Avoidable Death".

The history of the European Community Atlas of "Avoidable Death" is given. Data from the second Atlas are presented. For all causes of death except asthma there was a decrease in mortality in the period 1980-1984 with respect to 1974-1978. Taking the EC as a whole as the standard (100) population the standardised mortality ratio (SMR) in Ireland in the period 1980-1984 for tuberculosis was 160, for asthma 180 and maternal mortality 58. Ireland had the highest mortality for tuberculosis in both time periods. Asthma mortality increased in all countries except Scotland between 1974-1978 and 1980-1984. Ireland had one of the highest declines in maternal mortality over the two time periods. Within Ireland tuberculosis mortality was highest in the Mid-Western Health Board and lowest in the North-Western Health Board. Asthma mortality was highest in the Western Health Board and lowest in the Mid-Western Health Board. Maternal mortality was highest in the Midland Health board and lowest in the Southern Health Board.


Indomethacin and ethamsylate alone and in combination for the relief of post episiotomy pain.

In a bid to minimise dosage and possible side-effects when relieving post episiotomy pain, the NSAID Indomethacin was studied in combination with a systemic haemostat Ethamsylate which has been shown to selectively inhibit some prostaglandins. Comparative groups also took Indomethacin alone and placebo in a double blind non-crossover comparison. Efficacy was judged in terms of side-effects and assessments of pain intensity, pain relief and global assessment of pain. There was some evidence of a beneficial interaction between Indomethacin and Ethamsylate when adjustments were made for the patient's age and initial pain score. Side-effects were most common in the combination therapy group.


Clinical audit in intensive care--the Meath Intensive Care Audit.

Audit is now recognised as being an essential component of clinical practice. We report on the first year of the Meath Intensive Care Audit (MICA). This audit was instituted to investigate the activity of the unit, to assess the feasibility of continuous audit in our ICU and to provide data for future development of ICU facilities. Two hundred and fifty four patients were admitted between July 1st 1990 and June 30th 1991. The mean age at admission was 58 years and the mean length of stay 5.2 days. The mean APACHE II score was 16. Thirty four patients (13.4%) died in the ICU and 17 patients died in hospital following discharge from the unit bringing the hospital mortality rate to 20%. The audit proved feasible to implement and data collection is now accepted as a routine part of our ICU work.


The epidemiology of tuberculosis in a geographically defined area. Eastern Health Board Tuberculosis Advisory Committee.

This paper profiles the epidemiology of tuberculosis in a geographically defined area, the Eastern Health Board. In 1990, 191 new cases of the disease were notified, 15.5/100,000. One hundred and eighty five were from the indigenous population. Fifty four per cent were male. Nearly 50% of all cases occurring in females do so in those under 35 years and for males, 45% occur in those less than 45 years. One hundred and three (54%) had pulmonary tuberculosis alone and only 50 (26%) had a presumptive diagnosis. Although the lower social classes were overrepresented, cases occurred throughout all social classes and a significant proportion were either gainfully employed or in full time education. Data on BCG status was incomplete, however 28 cases were known to have had BCG at some stage of their life. Thirteen cases were also known to be HIV positive. The contact tracing process was responsible for locating 33 (17%) cases. Continuing surveillance both at national and local level is required in order to assist eradication.


The role of free radicals as mediators of endothelial cell injury in hyperhomocysteinemia.

Hyperhomocysteinemia has been suggested as a potent new risk factor for premature cardiovascular disease. Homocsyteine can induce endothelial cell injury but the mechanism is not understood. The purpose of this study was to evaluate the role of free radicals as potential causes of endothelial cell injury in a case-control study of obligate heterozygotes for cystathionine beta-synthase deficiency. Firstly, free radical production as measured by neutrophil chemiluminescence in obligate heterozygotes for cystathionine beta-synthase deficiency was compared with age- and sex-matched normal subjects. Secondly, the response of the cellular antioxidant system was examined by measuring the enzymes superoxide dismutase and glutathione peroxidase, their cofactors (selenium, copper), vitamin E and vitamin A in heterozygotes and normal subjects. Analyses of neutrophil chemiluminescence, vitamin A and E, glutathione peroxidase, selenium and copper showed no difference between heterozygotes and controls. While superoxide dismutase activity was higher in heterozygotes than normal subjects, the difference did not reach statistical significance and the hypothesis of excess free radical production as a mechanism of injury was not confirmed. However, further examination of superoxide dismutase activity in a larger number of subjects would be of interest.


The relationship between a nutritional index and acute physiology score in critical illness.

Prognostic indices derived from available physiological data (SAPS), complex nutritional and biochemical tests (PNI), grip strength and serum albumin were calculated in 16 critically ill patients receiving intravenous nutrition over a six week period. The aim was to compare these independently derived prognostic indices, to assess their response to feeding, and to determine suitability for use in Irish intensive care units. Mean SAPS (7.6 +/- 0.92), PNI (3.1 +/- 0.29), serum albumin (30.3 +/- 1.03 g/l) and grip strength (17.9 +/- 1.3%) were all suggestive of an "at risk" group. Significant associations were found between the accepted SAPS index and both PNI (r = 0.6, p < 0.001, n = 35) and grip strength (r = -0.68, p < 0.001, n = 44) but not with serum albumin. No consistent improvement was seen in response to feeding in any of the derived indices. The close correlation between prognostic indices derived from either physiological, nutritional or grip strength data in this study and the failure of prognostic indices to improve during hyperalimentation would support a common mechanism, e.g. endogenous mediators, for metabolic and physiological disturbance in critical illness. It suggests that the role of hyperalimentation is supportive rather than therapeutic and re-iterates the importance of managing underlying disease processes. Simple grip strength may be a useful alternative to complex nutritional indices.


The neuropsychological consequences of HIV infection in drug addicts.

The occurrence of neuropsychological impairment in asymptomatic, HIV-positive individuals is controversial. In the present study we compared the performance of three groups of chronic intravenous drug abusers (HIV negative, asymptomatic HIV positive, AIDS) on a battery of neuropsychological tests. While the AIDS group was significantly impaired, no difference was found between HIV negative and HIV positive asymptomatic subjects on any measure. This finding is in agreement with the results of studies of homosexual and bisexual subjects, indicating that the presence of HIV infection in the asymptomatic stage does not carry an added risk of cognitive impairment in drug addicts.


Prevention of ischemic stroke: the role of carotid endarterectomy in symptomatic patients.

Carotid endarterectomy (CE) has recently been proved to be beneficial in symptomatic patients with severe (70-99%) appropriate carotid stenosis. After discussing the historical evolution of CE as a possible preventive treatment of ischemic stroke, we review the results of North American and European trials in order to give practical information for the management of cerebrovascular patients.


Human erythrocyte contains a factor that stimulates the peptidase activities of multicatalytic proteinase complex.

A novel biological factor that stimulates the peptidase activities of multicatalytic proteinase complex (MPC) has been identified and partially purified from human erythrocytes. The stimulatory factor enhances trypsin-like, chymotrypsin-like and peptidyl-glutamyl peptide hydrolyzing activity of MPC in a dose related manner. At saturating concentration of the stimulatory factor, MPC increases the activity to a different extent (10 to 56 fold) depending on the substrate used to assay the enzyme. The stimulatory factor does not hydrolyze neither amino-blocked peptides which are used to assay MPC nor typical substrates for amino and diamino-peptidases. The stimulatory factor is characterized by a high molecular mass (300 kDa) and an extreme instability since it loses the activity at 46 degrees C in 10 min and at 4 degrees C within a week. The stimulatory activity is inactivated by incubation in acidic or alkaline media, and by treatment with protease V8, but it is relatively resistant to the action of trypsin. It has been suggested that the novel stimulatory factor herein described is a protein or a protein complex which may modulate the function and the activity of MPC by association-dissociation interaction.


Comparison of two medications in central nervous system toxoplasmosis in patients with AIDS.

We retrospectively examined 39 patients with AIDS and central nervous system toxoplasmosis in order to determine the efficacy and safety of two combinations: pyrimethamine-sulfadiazine and pyrimethamine-clindamycin. The results showed a response rate of 79% for the sulfadiazine association and a high failure rate in the clindamycin group. Side effects with sulfadiazine were slightly more frequent, but with desensitization protocols discontinuation was kept down. The combination of pyrimethamine and sulfadiazine, associated, when necessary, with desensitization schedules, was confirmed to be first choice therapy for cerebral toxoplasmosis in AIDS patients. The role of alternative regimens needs further evaluation.


Acute axonal idiopathic polyneuropathy: a Guillain-Barré syndrome variant?

We report 7 cases of acute polyneuropathy fitting the NINDS diagnostic criteria for GBS. Electrophysiological study and sural nerve biopsy revealed a picture of axonal polyneuropathy, without changes suggesting demyelination. We discuss whether the acute idiopathic axonal neuropathy belongs to the GBS spectrum or represents a separate clinico-pathological entity.


Linoleic acid metabolism in brain cortex of aged rats.

The linoleic acid metabolism was examined in the brain cortex of 4 month-old and 24 month-old rats. After the injection of [1-14C]-linoleate into the lateral ventricle of the brain the animals were sacrificed at 1,3 and 6 hours from the injection. The linoleate (18:2) incorporation into lipids, the presence of fatty acid peroxidation products, as well as the 18:2 transformation into elongated and desaturated derivatives were determined. Both an age-related reduction in linoleate incorporation rate into glycerophospholipids and a decrease in fatty acid turnover were found. Furthermore, in glycerophospholipids from 24 month-old rat brain cortex a higher level of hydroperoxide derivative of linoleate was found as compared to 4 month-old animals, and this damaged fatty acid is eliminated more slowly in aged rats than in adults. Finally, unlike 4 month-old animals, a stimulation of the transformation rate of linoleate into desaturation (6,9,12-C18:3) and elongation (8,11,14,C20:3) products was found in 24 month-old rat brain cortex. On the contrary, as far as arachidonic acid (one of the most important end products of the mechanism of linoleate modification) is concerned, the differences between aged and control animals were small, making it quite difficult to attribute a physiological meaning to this phenomenon.


The cerebrospinal fluid in the diagnosis of tuberculous meningoencephalitis: review of the literature.

We review the literature on the biochemical, cytological and immunological changes in the cerebrospinal fluid (CSF) in tuberculous meningoencephalitis, emphasizing the inconsistency and low specificity of the CSF findings described in classic accounts of this disease. We consider separately the possible causes of yellow or bloody fluid. The development of accurate techniques of analysis does not diminish the importance of the clinical findings and history in the early diagnosis of this disease.


Gliomatosis cerebri. Report of a case with isolated amnesic disorders.

We describe the case of a female patient with behavioral and memory disorders. A neuropsychological evaluation confirmed the absence of mental deterioration and the presence of the psychometric features of the amnesic syndrome. The clinical diagnosis was supported by MRI and histological examination.


Clinical and neuroradiological findings in a case of pure word deafness.

Pure Word Deafness is a clinical syndrome included among the aphasias and is marked by complete deafness of sudden onset with conserved ability to understand and read the written word and with no speech disorders. We report the case of 61 year old man in whom pure word deafness developed after two episodes of acute cerebral ischemia in quick succession. Neuroimaging procedures, that is: computed tomography scan, single photon emission computed tomography and magnetic resonance imaging, revealed the presence of two ischemic lesions in the temporal cortex bilaterally. Neurophysiological investigations (electroencephalogram, brainstem auditory evoked potentials and stapedial reflex) were also studied. We discuss the outcome of all these investigations in the light of the relevant published work.


MRI demonstration of the cerebellar damage in diffuse hypoxic-ischemic encephalopathy. Case report.

MRI demonstrated symmetric putaminal and cerebellar changes in a patient who survived a cardiorespiratory arrest due to acute idiopathic polyneuritis. Since similar aspects can be observed following cyanide or methanol poisoning differential diagnosis from these conditions has to rely on the combination of clinical and imaging findings.


Paroxysmal dystonia due to a lesion of the cervical cord: case report.

A 48 year old woman complained of mild weakness and paresthesias of the left limbs, followed 15 days later by episodes of paroxysmal dystonia of the left limbs occurring several times daily over 10 day period. Magnetic resonance imaging (MRI) of head and neck revealed a small area of altered signal in the T2-weighted sequences in the left posterolateral quadrant of the cord at the second cervical vertebra. An MRI scan 18 months later showed no lesion. This is the second case of paroxysmal dystonia with a single MRI lesion in the cervical region on record.


Neoadjuvant chemotherapy in the treatment of recurrent glioblastomas (GBM).

We wondered whether second line chemotherapy in recurrent GBM patients might be useful for debulking the tumor mass and improving patient performance status to prepare the way for second surgical intervention. We have treated 18 recurrent glioma patients with high dose methotrexate (HDMTX) plus 5-fluorouracil (5FU). 5 Patients were responders, 6 had stable disease, and 7 disease progression. 5 patients, 3 PRs and 2 SDs, underwent a second operation after two chemotherapy cycles. Disease progression resumed at 11.5 +/- 7 weeks in the non reoperated patients, and at 32.6 +/- 9.3 weeks in the reoperated group from initiation of neoadjuvant treatment. Survival time in reoperated patients was 82.6 weeks. Although our experience with this policy is still limited, we believe that reoperation in selected recurrent GBM patients can be worthwhile.


Autonomic nervous system function in myotonic dystrophy.

Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.


Transient topographical amnesia.

A woman experienced three isolated episodes of loss of topographical memory, without overt etiology. A rare form of selective non verbal transient amnesia, similar to the more common transient global amnesia, is postulated.


The primary antiphospholipid syndrome: case report.

Lupus anticoagulant antibodies and anticardiolipin antibodies are acquired circulating immunoglobulins that interact with phospholipids. These factors may exert anticoagulant properties in vitro and so interfere with coagulation tests that use phospholipids. These antibodies are not, however, associated with a hemorrhagic diathesis. Indeed, despite their name and their in vitro anticoagulant properties, they have been associated right from the earliest reports with systemic and cerebral thromboembolic episodes. We report the clinical and instrumental findings in a patient with ischemic stroke and anticoagulant antibodies in the serum.


Cerebral ischemia and livedo reticularis in a patient with impairment of coagulation factor VII and free protein S.

The association of ischemic cerebrovascular lesions with livedo reticularis is known as Sneddon syndrome. It affects young subjects, primarily women, and its neurological manifestations are TIAs, ischemic stroke, progressive dementia and epileptic seizures. Its etiopathogenesis has still to be clarified. Some authors have associated it with an antiphospholipid antibody syndrome. Recently it has been assumed that a defect in blood coagulation may be involved in its pathogenesis. Here we report a case in which both an increase in coagulation factor VII activity and a deficiency in free protein S were documented.


Chronic spastic atrophic hemiparesis with benign course.

We present the clinical and neuroimaging data of 4 patients (mean age: 62 years, range 54-67; mean follow-up: 19.5 years, range: 26 months-29 years) with chronic spastic atrophic hemiparesis (CSAH). Neuroimaging findings were non specific, CT scan and MRI showing white matter lesions located within the centrum semiovale in two cases, parieto-occipital lobe and pons in one case each. This study underlines that patients with CSAH may have a good long-term prognosis. MRI studies may demonstrate associated lesions within the white matter or brainstem and are advisable in all subjects with CSAH, but further studies are necessary to clarify the nature of the observed lesions.


Metachromatic leukodystrophy: on an atypical case.

We describe an atypical case of juvenile metachromatic leukodystrophy. Motor conduction velocity was still within the normal range 3 years after clinical onset, in contrast to what is commonly found in this disease. Another unusual feature is the normal level of CSF protein. These data are discussed in the light of the sural nerve biopsy findings, which revealed only slight impairment.


Veralipride-induced tardive dystonia in a patient with bipolar psychosis.

Veralipride is a benzamide derivative effective in the treatment of menopausal syndrome. Despite its antidopaminergic action, extrapyramidal side effects seem to be very uncommon. We observed a patient with bipolar psychosis, who developed segmental dystonia after taking the drug. The disorder slowly receded in 14 months, but reappeared during neuroleptic therapy a few months later. To the best of our knowledge, this is the first case of veralipride-induced tardive dystonia, and the affective disorder might have predisposed our patient to the development of this tardive side effect.


Occupational and environmental exposures and nonspecific lung disease--a review of selected studies.

Selected studies show that nonspecific lung diseases are a major occupational and environmental health hazard. Exposure to mineral dusts (such as cement and brown coal) and organic dusts (cotton, hemp and flour) as well as manganese and gaseous irritants causes significant upper respiratory tract injury. Possible additive effects of mixed exposures, combined exposure to dusts and gaseous irritants of the upper respiratory tract, individual susceptibility, and mechanisms of nonspecific respiratory effects of exposures are considered. Interpretation of the results is difficult due to uncontrolled confounding. Measures for preventing lung impairments include exposure reduction and preemployment examination of workers.


Occupational health planning in Israel: a U.S. perspective.

In order to indicate priorities for possible occupational health care planning activities, we evaluated occupational health risks, health services, and occupational research and training in Israel from the perspective of occupational medicine in the United States. We used available public information as well as data collected in a previous regional assessment of occupational health in the Negev. We estimated that each year 35% of the workforce in Israel may be exposed to high levels of noise, 4-11% to workplace toxins, and 7% to work injuries, all hazards warranting attention by health planners. Reviewing occupational health services we found that programmatic deficiencies limit the effective use of existing resources. We also evaluated the potential benefits of strengthened expert review in setting funding priorities for research and training in occupational safety and health in Israel.


Primary prevention of occupational lung disease: a view from the United States.

Occupational lung diseases are an important source of preventable morbidity and mortality in the United States. A significant proportion of lung cancer, mesothelioma, asbestosis and the other pneumoconioses, asthma, and chronic obstructive pulmonary disease, is caused by well-established occupational agents, especially among selected subgroups of the general population. Primary prevention of this set of diseases requires identification and control of workplace hazards. In the United States, data from inspections undertaken by the Occupational Safety and Health Agency, and from periodic surveys conducted by the National Institute for Occupational Safety and Health, show that respiratory toxins are commonly found in the workplace. Workplace-based education, surveillance and exposure reduction and elimination are essential components of a strategy to prevent occupational lung disorders.


Occupational cancer in Israel: an overview.

Occupational cancer is a result of exposure to carcinogens in the workplace. The critical interaction during the initiation stage of the carcinogenesis process occurs between the ultimate form of a carcinogen and the DNA, resulting in the formation of a DNA adduct or several types of gross structural alterations. Several methods have been developed by which carcinogens can be detected. These methods can be utilized for ambient monitoring of exposure and health surveillance. "Molecular epidemiology" is the combination of epidemiologic and laboratory studies, i.e., monitoring exposure by measuring the DNA adduct. Early detection of occupational cancer is difficult, due largely to the latent period which can be up to 20 years or more. For this reason it is important to develop and improve techniques for early detection of premalignant changes. Israel has numerous workers who are exposed to carcinogens, but has no special legislation concerning the use of carcinogenic substances in the workplace. However, an interministerial committee has published, and is continuing to work on, exposure and safety regulations. Medical surveillance and prevention as well as legislation are necessary to reduce morbidity and mortality from occupational cancer.


Sentinel markers for industrial disasters.

Workers, managers, and occupational health and safety inspectors can be trained to detect or recognize and promote action to correct sentinel markers for industrial disasters. A sentinel marker is defined as a pre-disaster warning sign of impending failure in prevention. Administrative sentinel markers are: a weak occupational health and safety program; lack of spontaneous access to top management; failure to accept responsibility for subcontractors; the absence of written disaster plans and drills for emergency response in the factory and the adjacent community; noninvestigation of prodromal leaks, exposures, spills or injuries; punishment of "troublesome" individuals reporting such prodromal events; nonuse or misuse of data on illness, injury and absenteeism; and suboptimal work conditions and supervision of shift workers. Information sentinel markers include absence of worker and community right-to-know programs, nonuse of data on earlier mishaps from similar technologies, and failure to provide toxicologic data to hospitals in the pre-disaster phase. Technological sentinel markers are: absence of fail-safe controls, interlocks and automated alarm systems driven by real-time monitoring. Transportation sentinel markers include suboptimal vehicle standards, and drink, drugs and fatigue in drivers. Preventive programs based on identification of all sentinel markers by workers are suggested to be more effective than selective action based on risk assessment analysis.


Regional differences in cancer incidence and mortality in Israel: possible leads to occupational causes.

Occupational causes of cancer are difficult to establish because of the long latency period and difficulty in identifying occupational linkages. This study provides a regional analysis of cancer incidence and mortality as a method of identifying localizing factors in cancer that can be followed by more specific epidemiologic investigation. In this study we analyze the regional standardized mortality ratios (SMRs) for site-specific cancers, by age, sex and continent of birth for the years 1983-86, for the Jewish population of Israel. Elevated total malignant and benign neoplasm SMRs were found in Acre (SMR 109, P < 0.05), Haifa (104, P < 0.05) and Tel Aviv (107, P < 0.001). The only other statistically significantly elevated SMRs were found in Acre for lung cancer (133, P < 0.05) and leukemia (171, P < 0.05). Age and sex-standardized incidence ratios (SIRs) by regions are also presented for the years 1980-81 for the Jewish population. Haifa had elevated SIRs for colorectal cancer (126, P < 0.001), breast cancer (118, P < 0.01) and lymphomas (126, P < 0.05). Elevated lung cancer SIRs were found in both Acre (145, P < 0.05) and Ramla (143, P < 0.05). Male to female incidence ratios (MFIRs) for ages 30+ for the Israeli Jewish population are also presented. Elevated bladder cancer MFIRs were found in the heavily industrialized Haifa region (7.69 vs. 4.62 P < 0.05). For Ramla residents, bladder and oronasopharyngeal cancer MFIRs were approximately three times the national average (not statistically significant). Ramla also had elevated MFIRs for lung cancer (14.9 vs. 3.4 nationally, P < 0.01), as did Acre (7.6 vs. 3.4 nationally, P = 0.06). These elevated MFIRs are suggestive of occupational exposure from the cement and asbestos factories in the Ramla and Acre regions. Regional analyses of cancer mortality and cancer incidence (using SMRs, SIRs and MFIRs) can serve as a basic tool for identifying sentinel markers of excess rates. Our findings indicate regions where we should undertake case-referent studies in order to identify potential risk factors and where to target possible preventive programs.


Mesothelioma mortality among former asbestos-cement workers in Israel, 1953-90.

Asbestos workers have long been recognized as a high risk group for the development of mesothelioma and other cancers. In this study we collated from a variety of sources 26 mesothelioma deaths that occurred between 1978 and 1990 among a cohort of some 4,441 former workers from an asbestos-cement plant in northern Israel. Since the expected number of deaths for this number of Israeli males in this age-group over this period is 0.12 cases, the risk of this disease was more than 223 times the national rate, age and sex adjusted [standardized mortality ratio (SMR) = 22,351, P < 0.001]. The mean years of exposure of persons who died from mesothelioma was 16.2 (SE 2.5). The mean latency period for mesothelioma cases from onset of exposure to death was 25.6 years (SE 1.3). Additional follow-up systems are needed to ensure complete reporting of asbestos-related diseases, including epidemiologic follow-up of asbestos-exposed workers after cessation of their work, with regular analysis of death and cancer registry data for high risk groups. Asbestos-related cancer is an important element in cancer epidemiology that requires further development in Israel. Studies of former workers, their families and of persons who worked or attended school adjacent to the asbestos-cement factory, as well as follow-up of other former worker groups exposed to asbestos are recommended.


Lead poisoning: I. Some clinical and toxicological observations on the effects of occupational lead exposure among firearms instructors.

Lead poisoning continues to be a common occupational disease in many countries. During the past two decades, poisoning presenting with overt clinical symptoms has become less frequent because of improvement in control of exposure, and attention has been focused on subtle biochemical and "subclinical" manifestations of lead toxicity. Firearms instructors constitute an occupational group at risk for excessive exposure to lead from the firing of arms in shooting galleries. This paper summarizes clinical and toxicological observations among lead-exposed firearms instructors and illustrates the wide spectrum of clinical and laboratory abnormalities that may occur in this occupational group. As clinical research has advanced, significant biochemical and clinical aberrations have been detected at progressively lower blood lead levels both among occupationally exposed adults and among children who are exposed to lead in the general environment. The latter is of great public health concern and has spurred efforts worldwide to reduce human exposure to lead to an absolute minimum.


A follow-up study in a lead smelter community following the introduction of an effective pollution control system.

A follow-up study using biological and environmental monitoring was performed in a lead smelter community to assess the health risk of inhabitants and to establish how long it takes after the introduction of an effective emission control system to declare a lead-contaminated area safe for normal living. In specific population groups (mothers and children) biological indicators of lead exposure and lead effect on hemoglobin synthesis were determined 2 years before and 11 consecutive years after the installation of bag filters. At the same time lead was monitored in the airborne and deposited particulates, in household dust and in soil. The results clearly show that the process of normalization is rather slow. The difference in blood lead and erythrocyte delta-aminolevulinic acid dehydratase between the exposed and control groups, even 12 years after bag filters installation, was still remarkable. It appears that soil, contaminated with lead from past exposure, is a major source of increased lead absorption in a population for many years.


Lead poisoning: II. Biological standards for occupational lead exposure--where do we stand now?

Lead poisoning is an occupational and environmental disease of great public health concern. During the past two decades major efforts have been made in many countries to minimize exposure to lead both in the occupational and general environment. Blood lead concentrations at which adverse effects can be detected have become progressively lower. Despite legislation concerning medical surveillance of lead-exposed workers and improvement in environmental control measures that took place during the 1980s, review of recent surveillance data indicates that excessive lead absorption among workers is still a problem in Israel. An approach is suggested for the reporting of surveillance data that will provide safety managers with the information necessary for introducing effective environmental control measures.


Medical findings in nickel-cadmium battery workers.

Thirty-eight workers from a factory producing nickel-cadmium and other types of batteries came to us for medical evaluation. They included 21 women and 17 men (seniority 2-20 years, age range 31-63 years), and represented a self-selected subset of 700-900 ever-employed and 200+ recently or currently employed workers in the factory. Thirty-four worked on the nickel-cadmium assembly line. Symptoms and signs included: headache in 34; weakness, fatigue and lassitude in 26; dizziness in 16; pruritus and skin eruptions in 37; gingivitis, teeth loss and caries in 34; nasal congestion, nosebleeds and anosmia in 30; cough, phlegm production, wheezing and shortness of breath in 26; "asthma" in 14; bone pain in 18; urinary frequency, beta 2 microglobulinuria and kidney stones in 17; and sterility or multiple abortions (33) in 8 of 21 women. One additional patient had died from an "amyotrophic lateral sclerosis-like syndrome", while CT scans in six workers revealed brain atrophy. One other worker had leukemia, and two had died from cancer (lung and pancreas). Those who had worked for more than 10 years had more symptoms and signs than shorter-term employees, especially neurological illness, bone pain and urinary tract problems, including beta 2 microglobulinuria. Past blood and urinary cadmium levels were in the range of 1.6-8.7 micrograms/dl and 8-306 micrograms/l, respectively. Our findings indicated that: a) health risks for workers were not confined to the nickel-cadmium assembly line or to older workers, b) hazardous exposures still existed and illness appeared in new workers after a clean-up and intervention program, and c) exposures involved increased risks for renal disease and cancers. Finally, there is a need to control exposures and determine health risks in the full cohort of those ever employed, in the workers' children, and in the surrounding environment (air, ground, water) due to the dumping of waste from the plant.


Responses of occupational physicians and laboratory staff to reports of high blood lead levels.

We evaluated the responses of physicians specializing in occupational health and of laboratory personnel engaged in occupational lead monitoring when periodic blood lead analysis results exceeded the Biological Exposure Index (BEI). Legally, Israeli workers must be removed from the site of occupational lead exposure after a repeat test shows "value above BEI" (VABEI). The maximum legal period between a report of VABEI and the repeat test is 14 days. Physicians have the discretion to remove workers after the first VABEI test if deemed necessary. In 1987-88, 242 of 3,776 analyses had a VABEI, 167 of which were periodic tests. The average laboratory response time between receipt of the sample and VABEI reports to occupational physicians was 13 days (SE = 0.4). Medical records of 100 workers who had 134 tests with a VABEI were available. In 35 (26.1%) of these events the physicians recommended removing the workers from the exposure source, in 55 (41.0%) events the physicians required repeat tests, and in 44 (32.9%) they neither recommended removal nor repeated the tests. The minimum time lapse between the first and repeat test was 20 days. The second test yielded 24 VABEI. Physicians recommended removing workers from the source only in 13 (54.2%) of these cases. This study suggests that the system must be improved in order to ensure the proper response to VABEI results.


Predicting increases in skin temperature using heat stress indices and relative humidity in helicopter pilots.

We used measurements of heat stress in the cockpit of Bell 206 and 212 helicopters manned by a crew of two to predict changes in the skin temperatures of 50 pilots over a 1-h ground standby period. Cockpit wet bulb globe temperatures increased from 28.1 +/- 5.6 degrees C to 32.9 +/- 3.9 degrees C over the 1-h ground standby period. Skin temperatures increased from 34.7 +/- 1.1 to 35.4 +/- 1.1 degrees C, while heart rate increased from 79.4 +/- 9.6 to 82.6 +/- 9.8 bpm. Cockpit wet bulb temperatures explained 26.9% of the variance of the increase in skin temperature (P = 0.0002). Wet bulb globe temperatures, discomfort index and dry bulb temperatures did not improve the predictive value of wet bulb temperatures alone. Relative humidity was not significantly associated with the increase in skin temperature. We conclude that wet bulb temperatures predict changes in skin temperature as well as other heat stress indices. Furthermore, despite high cockpit temperatures, pilots experienced only minimal strain during the 1-h ground standby period. Extrapolation of our results to the effects on body temperature of higher degrees of heat stress and physical activity is unwarranted and deserves further study.


Cytogenetic changes in ethylene oxide-exposed workers: a challenge to occupational medicine.

Ethylene oxide is a colorless gas that can cause neoplastic disease (leukemia, stomach cancer) in animals and humans. Its mutagenic potential is expressed by chromosome aberrations and sister chromatid exchange, as has been shown in numerous studies of groups exposed to ethylene oxide. The results of our pilot study on the effects of exposure to high levels of ethylene oxide show chromosome breakage in exposed individuals at twice the frequency of the normal population. Although these are preliminary findings, they justify urgent, specific protection from further exposure.


Residual neurobehavioral impairment in a water technician exposed to hydrazine-containing mixtures.

Residual neurobehavioral impairment in concentration, comprehension, memory, task performance and mood status persisted in a water technician with respiratory and dermal exposures to hydrazine-containing mixtures prior to treatment with steroids for concurrent thrombocytopenia. The findings call attention to the possibility that residual neurobehavioral impairment may be an effect of exposure to hydrazine mixtures.


Motion sickness-like syndrome among tank simulator drivers.

A military tank driving simulator has recently been introduced as a training aid for tank drivers in the Israel Defense Forces. Reports of nausea and vomiting among the first users of the simulator launched our investigation of the possible existence of a motion sickness-like syndrome among simulator drivers. Although the 59 subjects drove the simulator without any report of vomiting, other motion sickness-like symptoms were frequently reported. A comparison of symptoms reported after simulator and real tank driving show that dizziness, nausea, disorientation and hypersalivation were more frequently reported by simulator drivers and were of greater intensity. However, sweating and drowsiness were more prevalent among real tank drivers. The objective effect of driving the simulator was evaluated by instability and performance tests that were conducted before, during and after driving the simulator. A greater decrement in test results was observed among subjects reporting higher frequency of motion sickness-like symptoms.


Contrast sensitivity and the near point of accommodation after work with a visual display unit.

After several hours of work with a visual display unit (VDU), operators become myopic for a short time. Such transient myopia may be evaluated by measuring contrast sensitivity to a modulated grating pattern. The aim of the present study was to determine whether there are any accumulative myopic effects after 1 day of VDU work. We examined grating contrast sensitivity in a group of 13 full-time workers and in 13 office employees who used VDUs only sporadically. The results, which were compared with the near point of accommodation, clearly illustrated that there is no decrease in contrast sensitivity. In the VDU group the decrease in the near point of accommodation was uniformly distributed between zero and 1.0 diopter, whereas among the non-VDU workers 77% of the decrease was between zero and 0.25 diopter. We conclude that the myopic changes in the refractive status of operators after VDU work are not evident in a decrease in contrast sensitivity. However, in VDU workers the dynamic range of accommodation was smaller, suggesting that the visual fatigue and visual stress that developed at work hindered visual activities after work.


Prevalence of low back pain in employees of a pharmaceutical company.

The association of low back pain (LBP) with mechanical factors at the workplace is uncertain. Most of the studies on this subject did not examine multiple levels of symptoms and did not take into account both the type of work and the primary activity during work. We studied the annual prevalence, severity and duration of attacks of LBP recorded on a physician-administered questionnaire in 208 workers in a pharmaceutical factory. Symptoms were then cross-tabulated with job type, location, work requirements, gender, and years at the factory. LBP was reported by 138 (66.3%) of the workers. Although over 75% of jobs in the packing department, laboratories and offices required prolonged sitting, LBP was most prevalent among workers in the packing department, where the chairs were found to be ergonomically unfit (odds ratio 3.7, 95% confidence interval 1.5-9.1, P = 0.003). Logistic regression demonstrated a highly significant and independent association between LBP and work in the packing or production department (odds ratio 2.03), sitting or lifting (odds ratio 1.97) and 6 years seniority (odds ratio 1.64). Gender was not a significant variable. We conclude that among these pharmaceutical company employees, prolonged sitting and work in the packing or production departments were independently associated with LBP. Prospective studies are warranted to substantiate our findings.


Training in oculomotor tracking: occupational health aspects.

Smooth pursuit and optokinetic nystagmus were repeatedly examined in nine patients who sustained hemilateral brain injury. The follow-up period extended over several months of the in-hospital rehabilitation phase. Five of the patients were trained for 3-10 weeks to improve tracking responses using a biofeedback technique; the remaining four patients were not trained and served as a control group. In all patients in the first group gain responses improved and the recovery time constant increased at a rate higher than that in the untrained group. We suggest that our training procedure can be extended to other types of patients with impaired smooth pursuit tracking and may also benefit workers in need of good tracking performance.


Sleep-wake cycle in shift workers on a "clockwise" and "counter-clockwise" rotation system.

The present study investigated the effects of a 5-day rotating work schedule in the advance, or "counter-clockwise", vs. delay, or "clockwise" direction, on subjective and objective measures of sleep-wake cycles. Twenty-two workers (mean age 27.5 +/- 4.6 years) were studied in the counter-clockwise direction, and 11 workers (mean age 29.83 +/- 5.93) were studied in the clockwise direction. Each worker was studied for a complete rotation cycle (20 days). Sleep-wake cycles were measured by wrist-worn actigraphs in 1-min bins. The clockwise direction was associated with significantly earlier sleep times during the night shift, and with a better synchronization of workers' sleep-wake cycles during night and evening shifts. The present results provide support to the claim that rotating shiftworkers can better adapt to clockwise than counter-clockwise rotations.


Early detection of changes in kidney function in workers exposed to solvents and heavy metals.

Increases in urine concentration of specific proteins have been proposed as early indicators of deleterious changes in kidney function. Four urinary proteins (albumin, superoxide dismutase, transferrin and N-acetyl-beta-D-glucosaminidase) were measured in workers exposed to heavy metals and solvents. None of the workers had clinical evidence of renal disease or hypertension. Workers exposed to mercury had a significant increase in urinary transferring, superoxide dismutase levels were slightly increased in workers exposed to solvents and lead, follow-up of these workers is needed to confirm that these changes predict late clinical deterioration of kidney functions.


Noise exposure, noise annoyance and their relation to psychological distress, accident and sickness absence among blue-collar workers--the Cordis Study.

This study examined the impact of chronic industrial noise exposure on psychological distress symptoms, accident involvement and sickness absence among male and female workers. It also examined whether workers expressing high noise annoyance were more adversely affected by it. Subjects were blue-collar workers, 1,680 males and 688 females, who participated in the Cordis Study. Noise exposure levels were: low [< 75 dB(A)], moderate [75-84 dB(A)], and high [> or = 85 dB(A)]. For males, noise exposure level affected job dissatisfaction and post-work irritability, while for females it also intensified somatic complaints, anxiety and depression. All the distress symptoms were higher for females. Further analysis showed that the significant increase of symptoms with noise exposure level was only for workers reporting high annoyance. Higher noise exposure levels were associated with increased accidents and sickness absence for both sexes. Noise-annoyed males had a significantly higher percentage of accidents when exposed to moderate noise levels and a marked increase in sick leave at high noise levels. Finally, the nonauditory effects studied here were already prevalent at moderate noise exposure levels, especially among noise-annoyed workers. This indicates the importance of reducing even moderately high levels of industrial noise not usually considered harmful to hearing.


Absence from work among smokers and nonsmokers in Israeli industries--the Cordis Study.

While the negative economic effects of cigarette smoking are frequently examined in terms of the costs of health services and potential years of life lost, data on the indirect costs due to absence from work in Israel are scarce. During 1985-87, cigarette smoking habits and absence due to illness and accidents were examined in 5,826 employees (4,177 men and 1,649 women) in Israeli industry, screened in the framework of the Cordis Study. The absenteeism data related to the period 1986-87. Among men, smokers were absent an average of 2.6 days per employee more than nonsmokers (P < 0.001) over the 2-year period after adjusting for age and occupational category. Among women there was no significant difference in sickness absenteeism between smokers and nonsmokers. The excess days lost among male smokers was only partly explained by increased absence due to respiratory illness. Accident rates did not differ by smoking habits. There is a significant increase in absence due to illness among men employed in Israeli industry, which may be attributed to cigarette smoking. Since cigarette smoking continues to be a common practice, the overall costs to the economy may be considerable.


Sickness absence in 21 industrial plants in Israel (1986-87)--the Cordis Study.

A population of 6,016 men and women working in 21 factories in Israel was screened for cardiovascular risk factors in the course of the Cordis Study. Sickness absence was analyzed to obtain overall indices and distributions by disease groups. Factors such as sex, age, and type of occupation were introduced. Most indices were higher for women than for men, for older workers than for younger, and for blue-collar than for white-collar jobs. Loss of scheduled workdays was estimated at 5%; at this rate, loss of revenue for the manufacturing industries (excepting diamonds) may amount to as much as half a billion dollars.


A pilot occupational health service for small enterprises: first year experience--the Givat Shaul project.

An experimental Occupational Health and Safety Center was established as a pilot project for Israel in the Givat Shaul industrial area of Jerusalem. The center provides occupational health services to those working in its vicinity and is particularly oriented to employees of small enterprises (i.e., fewer than 20 employees). In addition to the routine occupational health services supplied by each occupational health clinic in Israel, the Center's staff also performs safety and hygiene inspections at workplaces, and provides social care services for the working population of the area. This paper summarizes the first year of the project's activities, particularly those of the clinical staff and the safety technician. Projected future activities are also outlined. The effectiveness of this project is currently under study and will be finally evaluated by an independent Hebrew University research team. If their evaluation shows the project to have been successful, establishment of similar centers in other parts of the country will be considered.


Realizing the potential of social work in occupational health.

Potential problems in occupational health that are suitable for social work intervention are illustrated by data obtained in a study of textile industry workers. Significant differences were observed between groups of workers (newly hired, veteran, and currently unemployed) on self-rated health, frequency of health problems that interfere in role function, smoking, and frequency of alcohol consumption. In addition, health behaviors varied by sex, age, educational achievement and ethnic origin among newly hired workers. These results indicate the need to identify target groups of workers when designing and implementing health prevention/health promotion programs. A model of social work practice in occupational health is presented based on different types of health behavior (preventive health behavior, illness behavior, sick role behavior and rehabilitation) and intervention modes in social work practice (individual treatment, group work, family therapy and policy and program planning).


Findings in pre-employment examinations.

Results of comprehensive pre-employment examinations of about 8,600 persons were analyzed. The most frequent findings are those related to the more prevalent risk factors and morbidity (of adults) in industrialized countries. Of special interest were the associations found between low level of education (or socioeconomic status), exposure to various occupational hazards, and poor life-style habits. These findings attest to the need for providing preventive follow-up (intervention) services to complement any large-scale screening program. Such services could be developed, relatively simply, based on existing occupational medicine units. The advantages and pitfalls of utilizing multiphasic screening technology in general and in occupational health settings are discussed.


Exposure of workers to toxic substances and physical hazards: the law in theory and practice.

Israel has an enviable legal framework to protect the worker from exposure to dangerous substances at the workplace: a duty of the employer to inform the worker of exposure to dangerous substances; a duty of the employer and the occupational doctor to report exposure, disease and death to the factory inspectorate; and a comprehensive network of occupational doctors in place to find early symptoms of exposure in order to prevent disease. Unfortunately this framework has not been effective enough. In some instances--the Isabest factory in Naharia and the Tadiran factory in Ekron--the system has failed miserably.


Genetics and the moral mission of health insurance.

Deciding whether genetic differences among individuals are morally relevant to health insurance requires us to ask, What kind of good is health care? and, What principles should govern its distribution? There are good reasons to doubt that "actuarial fairness" is an adequate description of genuine fairness in health insurance.


Acral lentiginous melanoma: case studies from Kauai.

Cutaneous malignant is generally regarded as a skin cancer of Caucasians. However, one subtype, acral lentiginous melanoma (ALM), has an equal distribution among all ethnic groups and is the variant most common in non-Caucasians. In its early stage it is difficult to recognize and, unless diagnosed early, has a very poor prognosis. Herein, we present 3 cases of ALM seen on Kauai in 1990.


Race, ethnicity and birth-weight: Hawaii 1983 to 1986.

A study of racial/ethnic-specific mean infant birth-weights reported on 1968 to 1972 live birth-weight certificates for Oahu, Hawaii is reviewed here. The 1983 to 1986 data confirm those earlier results: (a) The Hawaiian group is significantly heavier in mean birth-weights than other cohorts during the preterm period (33 to 36 weeks gestational age); (b) statistically significant differences also were present in mean birth-weights for the term and post-term periods (37 to 45 weeks gestational age); and (c) the ranking of cohorts from heaviest to lightest in mean birth-weights is Caucasian, Hawaiian, Japanese and Filipino respectively. The data raises 2 questions: (1) Which birth-weight standards are most applicable for Asian and Pacific Islanders; and (2) what are the implications of the race/ethnic-specific mean birth-weight differences relative to mortality, morbidity and developmental outcome?


Physician-hospital networking: avoiding a shotgun wedding.

The erosion of the traditional market is forcing hospitals and physicians to reevaluate their historical relationships. One method for addressing the potential conflicts created by current pressures is the formation of physician-hospital networks. These entities are formed and function on the basis of mutual interests and responsiveness to change.


Organization of marketing in U.S. hospitals: an empirical investigation.

In this article the results of an empirical investigation of the marketing function in U.S. hospitals are reported. The relationship between hospital marketing orientation and hospital performance is examined. Results of the study indicate that substantial evidence exists to conclude that marketing is effective in the health care industry. Marketing failures in hospitals seem to be related to inappropriate marketing organization and inadequate top management support.


Insurance for the insurers. The use of genetic tests.

Genetic testing raises concerns that individuals will be denied health insurance (and thus, effectively, access to health care), or that employers will screen to eliminate potentially costly workers. Although we as a society do not yet concur on the degree to which private businesses have a responsibility to promote social justice, several different policy alternatives might allow us to weigh the interests of insurers, as businesses, against the interests of citizens in a responsible manner.


Demand/capacity management in health care: an application of yield management.

Although the concepts of yield management have been applied successfully to many services such as hotels and airlines, the concepts have not expanded much further. Some segments of health care appear to be logical candidates to apply and benefit from the concepts, and this article addresses that application by examining the implementation of yield management in a health care facility. Not only is the implementation described, but the issues surrounding that implementation are discussed.


Quality of health care and financial performance: is there a link?

The relation between operating margin and quality of care is investigated by using survey and financial data for 82 small and medium-sized hospitals. A positive relation between the variables is found, and implications of that relationship are discussed.


Strategies for small community hospitals operating in the shadow of a medical center.

Small community hospitals compete with medical centers. This article presents select descriptive information and strategy considerations that are based on experiences within an 82-hospital system.


Denials of staff privileges face increased antitrust scrutiny.

Recent court decisions and statements by federal antitrust officials indicate that hospitals may face increasing scrutiny of their staff privileges decisions. In view of these developments, hospitals must be prepared to defend their decisions from antitrust challenges and should structure their actions to satisfy the remaining defenses to antitrust claims.


New directions for hospital strategic management: the market for efficient care.

An analysis of current trends in the health care industry points to buyers seeking high quality, yet efficient, care as an emerging market segment. To target this market segment, hospitals must be prepared to market the efficient physicians. In the coming years, hospitals that can identify and market their best practicing providers will achieve a competitive advantage.


Viewpoint: managerial imperatives.

The development of an institutional culture cannot be left to chance. One must articulate the desirable managerial variables that will establish the mores of and for the institution. When these are known and become the basis for the actions and activities of those who are part of the institution, the operational results will be satisfactory and desirable.


HCMR interview: Pat N. Groner. Interview by Montague Brown.

Pat N. Groner, President Emeritus, Baptist Health Care, Pensacola, Florida, is a man of ideas and action. Pat has ably led his hospital, was founder of the Hospital Research and Development Institute and Voluntary Hospitals of America, and is now a leader in higher education. Whenever and wherever Pat sees an opportunity to improve things, he jumps in with a hundred ideas, most of them real winners. He engages others and fights for constructive change. For all who seek models for the full life well lived, look at Pat Groner.


[Oral nickel provocation and a nickel-free diet. Indications and practical implementation].

In spite of some unsolved questions, an influence of orally ingested nickel on some forms of chronic eczema is generally accepted. In cases of chronic relapsing dermatitis with typical location, positive nickel patch test and positive oral nickel challenge, a nickel-restricted diet may be recommended for a limited period of time. Regional nutritional habits should be considered in the design of diets. Indications, practice and evaluation criteria for oral nickel challenge and nickel-reduced diets are described.


[The effect of neuropeptides on wound healing in vitro and in vivo].

Neuropeptides constitute the largest family of extracellular messengers and have a long phylogenetic history. They and their receptors have been detected in normal human skin and related epithelial tissues. They act as neurotransmitters, hormones and paracrine factors. In skin they are involved in innervation, secretory gland function, growth control, and the regulation of blood flow. They are of remarkable interest in normal and disturbed wound healing, on three major levels: regulation of blood flow, modulation of inflammation, and trophism. Both neuropeptides and their antagonists are of potential interest as therapeutic agents. Their basic activities include immunomodulation, inhibition of inflammation, histamine release and stimulation of blood flow.


[Polymorphous photodermatitis. Morphology and temporal course].

From 1985 to 1990 we saw 318 patients with polymorphous light eruption (PLE). Papular (47.4%) and papular-vesicular (27.2%) skin lesions were predominant. A monomorphous picture was seen in 31%. The first lesions appeared within a median period of 19 h after sun exposure, and in 38% of cases within 5 h. In most patients (78.7%) the skin eruptions faded within 1 week of appearance (median 4 days). There seems to be a correlation between the course of light exposure and the resulting clinical morphology. Terminological and methodical problems in the classification of PLE are discussed.


[Practical use of the TDF factor in radiotherapy of basalioma and squamous cell carcinoma].

For X-ray therapy, the relation between single doses, number of fractions and duration of therapy have been combined in the TDF (time, dose, fraction) factor by Orton and Ellis. This factor seems to be well suited to evaluation of the X-ray therapy of basal cell carcinomas and squamous cell carcinomas of the skin. A simplified TDF formula is presented, together with some methods of calculation. Furthermore, tables are presented containing TDF values for frequently applied single doses and for two to five fractions per week. In addition, some hints are given on the use of the decay factor of Orton and Ellis to compensate for the loss of X-ray effectiveness if therapy has been interrupted.


[Cytologic aspects of the differential diagnosis of basalioma].

Basal cell carcinoma is a common cancer of the skin with characteristic histological features. A total of 200 skin lesions suggestive of basal cell carcinoma were compared by cytology and histology correlated, 2 cases were false-negative, and 4 cases false-positive. In 6 cases the material was non-diagnostic. The characteristic cytologic feature of basal cell carcinoma allowed differentiation from other tumors of the skin. If the technique and preparation are adequate, cytology is highly diagnostic for basal cell carcinomas.


[Considerations of the pathogenesis of parakeratosis variegata based on morphologic and molecular genetic findings].

We report on a 63-year-old woman who had been suffering from generalized parakeratosis variegata since she was 7 years old. Increased tightness of the skin was the only clinical symptom. On the whole integument except for the face, we found a fine network of hyper- and depigmentation and telangiectasias. The skin surface was dry and atrophic with fine lamellar scaling. Histological, immunohistological and ultrastructural findings indicated early infiltration by a cutaneous T-cell lymphoma. However, PCR analysis of the T-cell receptor gamma-chain genes revealed multiple amplification products favouring a polyclonal T-cell proliferation. In light of the clinical history over a period of 56 years, we consider parakeratosis variegata to be a benign, chronic inflammatory condition, as is confirmed by the results of PCR analysis in this patient.


[Detection of the Köbner phenomenon of the skeleton of patients with psoriasis].

Psoriasis is a humorally controlled systemic disease. The degree of "eruptive strength" of manifestation results from hereditary factors (disposition) and environmental factors (provocation). We were able to demonstrate that the well-known Köbner phenomenon of the skin also occurs on the skeleton of patients suffering from psoriasis. We analysed 83 patients in whom bone scans were carried out. Our results indicate that provocation factors such as bacterial foci and/or trauma correlate with a significantly higher number of pathological scintigraphic findings, ranging up to "hot spots". Furthermore, not only did bone fractures remained scintigraphically positive for an unusually long time, traumas of the end phalanx could be demonstrated in 70% of psoriatic patients compared with 21% of a control group. Obviously, one factor alone or a combination of factors triggers the involvement of the skeleton as a "deep Köbner phenomenon". In psoriatic patients the response of bone metabolism to disturbance differs from that of non-psoriatic patients in that there is a long-lasting dysregulation. This explains the high correlation between skin and skeletal manifestation in psoriatics. Therefore the manifestation of psoriatic disease is due not to a single-stranded linear causal interrelation but to a multicausal "network pathogenesis". Bone scintigraphy is the diagnostic method of choice in patients with psoriatic osteoarthropathy and allows an objective evaluation of therapeutic success.


[Chronic urticaria in enterobiasis vermicularis (oxyuriasis)].

We report on a patient with chronic urticaria associated with enterobiasis vermicularis (oxyuriasis). The current distribution of Enterobius vermicularis and its importance concerning chronic urticaria of endogenous origin is evaluated and discussed.


[Cutaneous angiosarcoma after telecobalt irradiation].

Cutaneous angiosarcomas are rare neoplasms. They occur most frequently on areas of skin exposed to sunlight in the elderly, or in long-standing lymphoedema (Stewart-Treves syndrome). Radiation is an important aetiological factor. With only 1 exception, the 34 published cases of cutaneous angiosarcoma on the trunk were caused by irradiation of internal tumours, occurring between 4 and 50 years after the irradiation treatment. The prognosis quoad vitam is poor. The tumours should be removed surgically. When they are inoperable, irradiation is an alternative therapeutic option. The aim of this paper is to show the histological differential diagnosis of cutaneous angiosarcomas and to demonstrate problems with the treatment.


[Painful cutis marmorata teleangiectatica congenita].

A 39-year-old woman with cutis marmorata telangiectatica congenita (CMTC) on the back presented with a 5-year history of pain in the involved area which initially occurred only on touch and cold exposure but was ultimately virtually constant. Histological examination of a skin biopsy specimen revealed an increased number of nerve fibres. The phlebectatic subcutaneous veins were demonstrable by NIR (near infrared) venoscopy.


Historical perspective: a forward look, a backward look.

This paper summarizes how the problems of fallout, genetics, radioactive waste, and regulatory control of radiation were perceived by Dunning, Straub, Taylor, and others in 1955 at the inaugural meeting of the Health Physics Society. It was stated that health physicists had a great opportunity to resolve these problems and to avoid past mistakes. Throughout the 1950s, health physicists made major contributions to elucidating the fallout problem and contributed to its resolution, and it can be considered a success story. Waste disposal is not considered to be a success to date. A major difference has been the lack of political will to grapple with a perceived "no win" situation. The evolution of radiation limits is briefly traced over the past 37 y from voluntary standards to rigorously enforced regulations demanded by society. This paper speculates that the changing international scene makes the United States the pre-eminent nuclear power which will challenge future health physicists to maintain a balance between the control of radioactive material and its peaceful applications.


Assessment of potential doses at the Maralinga and Emu test sites.

An assessment has been undertaken of potential doses to future aboriginal inhabitants of the Maralinga and Emu areas of South Australia, where nuclear weapons tests in the 1950s and 1960s have resulted in residual radioactive contamination. Radioactive material due to this program of tests and other experiments is still detectable several tens of kilometers from some of the test sites. Continued occupancy by individuals following an Aboriginal lifestyle could give rise to annual effective dose equivalents of several mSv within contours enclosing areas of several hundred square kilometers. The most significant dose pathways are calculated to be the inhalation of resuspended activity and ingestion of soil by infants. An analysis of the effects of uncertainties in the dose calculation has indicated the uncertainty distribution on predicted doses from the inhalation pathway.


Inhalation doses for aboriginal people reoccupying former nuclear weapons testing ranges in South Australia.

The Australian Government plans to rehabilitate the former nuclear weapons testing ranges at Maralinga and Emu in South Australia and to allow access to the areas for the Pitjantjatjara (Aboriginal) people who are the traditional owners of the land. The major radiological hazard posed by reoccupation of the ranges arises from inhalation of residual plutonium. The committed effective dose that these people might receive from inhalation on reoccupation of the lands is computed for a range of sites. The estimated doses for permanent occupancy range up to 300 mSv y-1 indicating the need for substantial rehabilitation before these areas are suitable for unrestricted access.


Radiological implications of inhaled 239Pu and 241Am in dusts at the former nuclear test site in Maralinga.

The biokinetics of 239Pu and 241Am present in three dust samples obtained from Maralinga were investigated after their deposition in the rat lung. Results were used as an experimental basis for assessing the radiological implications for human exposure. The transfer rates of these actinides to blood in the various dusts differed by 50-fold. The most transportable forms were compatible with a material that had 25% class W and 75% class Y characteristics. The doses per unit intake for adults, children, and infants exposed to an aerosol of 5 microns AMAD were calculated to be, respectively, 0.059, 0.076, and 0.140 mSv Bq-1. The corresponding doses for the least transportable forms were the same as those calculated for a class Y compound, namely 0.036, 0.049, and 0.096 mSv Bq-1. The behavior of the actinides in humans was predicted by combining the transfer rates to blood with mechanical clearance data obtained after volunteers had inhaled 85Sr or 88Y labeled fused aluminosilicate particles. The results suggested that monitoring of 241Am in the chest could be used to advantage for assessing intakes incurred by workers involved with any further decontamination procedures but would be of little practical value for assessing inadvertent public exposure. The paper includes comments on the relevance of the 1990 ICRP recommendations and the proposed new dosimetric model for the respiratory tract.


14C release from a Soviet-designed pressurized water reactor nuclear power plant.

The Paks Nuclear Power Plant in Hungary runs with four pressurized water reactors, each of 440-MWe capacity. Sampling systems have been developed and used to determine the 14C of various chemical forms (14CO2, 14CO, 14CnHm) in the airborne releases. The average normalized yearly discharge rates for the time period 1988-1991 are equal to 0.77 TBq GWe-1 y-1 for hydrocarbons and 0.05 TBq GWe-1 y-1 for CO2. The contribution of 14CO was less than 0.5% of the total emission. The 14C discharge rate is estimated to be four times higher than the corresponding mean data of Western European pressurized water reactors. The calculated effective dose equivalent to individuals living in the vicinity of the power plant, due to 14C release, was 0.64 microSv in 1991 while the effective dose equivalent due to the natural 14C level was 15 microSv y-1. The long-term global impact of the 14C release in the operational period of the plant (1982-1991) was 1,270 man-Sv. The 14C excess in the environmental air has been measured since 1989 by taking biweekly samples at a distance of 1.7 km from the nuclear power plant. The long-term average of radiocarbon excess coming from the power plant was 2 mBq m-3. The local 14C deposition was followed by tree ring analysis, too. No 14C increase higher than the uncertainty of the measurement (four per thousand = 0.17 mBq m-3) was observed.


Meteorological observations at Hiroshima on days with weather similar to that of the atomic bombing.

An attempt to explain discrepancies between measured neutron-induced radioactivities (i.e., 152Eu, 60Co) and calculated yields based on the Dosimetry System 1986 was made by considering moist air densities at different altitudes over Hiroshima, Japan. The investigation checked the validity of moist air density estimates used in the Dosimetry System 1986 computer codes. Meteorological observations were conducted to obtain atmospheric temperature and pressure profiles for the Hiroshima area. By coupling these observations with surface measurements taken on 6 August 1945 at Ebayama Park (3.6 km from the hypocenter), estimates of temperature, pressure, and humidity at the time of detonation were derived. This allowed the calculation of densities for dry air, moist air, and water vapor. The results proved similar to the Dosimetry System 1986 estimates. Water vapor density calculations showed the largest difference (at most 7%). These results imply that the 152Eu yield contradiction in the Dosimetry System 1986 calculations vs. real measurements for large ground distances (> 900 m) is not the result of an erroneous estimate of moist air density in Hiroshima.


Underground air returns as active transportation pathways for radon gas entry into homes.

Levels of elevated 222Rn in homes can fail to correlate with measured radium concentrations in soils and surrounding rocks for reasons which can include water sources, building materials, and unusual variations in climate or building construction. Several homes were identified in the Phoenix, AZ metropolitan area with soil radium concentrations of < 0.074 Bq g-1 (2.0 pCi g-1) which had elevated radon concentrations unexplained by geological sources alone. Continuous monitoring of eight houses under different conditions of cooling system usage revealed a definite role of the underground air returns as active transport pathways contributing to the enhancement of the indoor concentration of 222Rn in six of the houses. The ratio of indoor 222Rn concentrations on days when the cooling system was operated continuously compared to days the system was off ranged from essentially one up to a factor exceeding 10.


Mitigation of elevated indoor radon gas resulting from underground air return usage.

Underground air returns have been found to be active transportation pathways for radon gas entry into homes. Several homes for which underground air returns were contributing to elevated indoor 222Rn concentrations were evaluated for possible mitigation. Two houses with such problems were successfully mitigated by inserting flexible ducts into the returns. In one of these houses, the initial mitigation attempt resulted in an exacerbation of the problem due to leakage of the ducting. This was solved by re-sleeving the returns using a stronger material. Mitigation of elevated indoor radon gas caused by use of underground air returns by inserting flexible ducts is not possible for all situations, especially those for which the returns are small, filled with debris, misaligned, or inaccessible.


Characterization of radioactive petroleum piping scale with an evaluation of subsequent land contamination.

Scale formation in oilfield piping and equipment has been a problem for petroleum companies. In the past, scale waste from cleaning of piping and equipment has been considered nonhazardous. Naturally occurring radioactive material in the form of 226Ra and, to a lesser degree, 228Ra with their associated decay products have recently been discovered in the scale. Due to the lower abundance and short half-life, 228Ra is not addressed in this paper. 226Ra, an alpha emitter, is a potential internal hazard to workers from the inhalation and ingestion of the dust produced during descaling or pipe cleaning operations. Along with this, a higher-than-normal background gamma exposure rate is seen where the pipe cleaning was routinely done. An evaluation of the radiation hazards associated with a retired pipe cleaning field was performed. Gamma exposure rates, 226Ra concentration, and 226Ra leachability were examined using scale containing soil from the field. Radon emanation from the soil was also determined.


The self-defining critical group and its application to a measured check of the derived limit for 125I in drinking water.

Using a series of daily measurements of 125I in the drinking water of North Surrey, England, from November 1988 through May 1990, the accumulated activities in the thyroids of adults drinking such water were calculated on the assumption that the fraction of ingested iodine taken up by the thyroid was f = 0.3 and the tap water consumption was C = 600 L y-1. These figures were compared with measured values of 125I activities in 42 thyroids taken at necropsy from residents in the North Surrey area who were dying during this same time period. Eight thyroids (19%) had measured activities greater than predicted, so they were named the self-defining critical group. After comparing the thyroid with the drinking water activity, the current generalized derived limit for 125I in the drinking water may be too high by a factor of 2. The reason for this appears to be the use of f = 0.3 which is the mean value for the "normal" population. Models involving critical groups should use values of parameters different from the mean. In the present case, making f = 0.6 would remove the discrepancy between measurement and prediction and would be in reasonable accord with measured distributions of f.


Dosimetry study of an accidental overexposure to 192Ir gamma rays.

Localized irradiation of the skin and subcutaneous tissues with large single doses of gamma rays can induce delayed effects characterized by fibrosis that invades the irradiated tissues. The skin surface dose and the depth of penetration of 192Ir gamma rays, measured in phantoms and in frozen thighs of sacrificed pigs after acute single doses of irradiation and different skin-to-source distances, are reported in this note. Correlations between the dosimetry and the evolution of the lesions are considered.


Pleural mesothelioma in the rat following exposure to 239PuO2.

Pleural mesothelioma was an infrequent observation following deposition of 239PuO2 in the lung or pleural cavity. Only five tumors were found in 2,105 rats exposed to 239PuO2 aerosols in the present study, while four tumors were found in 527 rats that inhaled 239PuO2 in previously published lifespan studies. Risk of pleural mesothelioma was not significantly increased by intrapleural injection of 30 kBq 239PuO2. In contrast, a much higher incidence of peritoneal mesothelioma was seen following intraperitoneal injection of 239PuO2 due to aggregation of 239PuO2 particles on mesothelial surfaces. It was concluded that the lack of 239PuO2 aggregation on pleural surfaces is responsible for small numbers of pleural mesothelioma observed following deposition of 239PuO2.


Photoneutron fields in medical accelerator rooms with primary barriers constructed of concrete and metals.

This study investigates the photoneutron field found in medical accelerator rooms with primary barriers constructed of metal slabs plus concrete. An increased neutron dose equivalent was observed for barriers containing lead or steel as compared to barriers fabricated entirely of concrete. The effect of the beam's size and distance from the primary barriers on the neutron dose was evaluated and the portion of the neutron dose due to the metal slabs was determined.


A thermoluminescent dosimetry intercomparison in operational power station fields.

A dosimetry intercomparison was held among the five agencies in Canada that are recognized by the Atomic Energy Control Board as competent to perform external dosimetry. Exposures of thermoluminescent dosimeter badges were made under operational conditions to radiation fields in Candu nuclear generating stations. Details of the method are described including the large, block-type phantoms (with a rotating front face so that all badges were equally exposed) and a small device to measure the depth-dose distribution. Thirty-six exposures (or "runs") were made, exposing 522 badges for periods of 1 h-2 d. Normalization between the runs was based on the absorbed dose at 1,000 mg cm-2 for each run, as measured by the depth-dose device. Using this method, the average relative readings for the five participants ranged from 1.01-1.40 (dimensionless).


Miles Technicon H.2 automated hematology analyzer.

Automated hematology analyzers are used in all large hospitals and most commercial laboratories, as well as in most smaller hospitals and laboratories, to perform complete blood counts (including white blood cell, red blood cell, and platelet counts; hemoglobin concentration; and RBC indices) and white blood cell differential counts. Our objectives in this study are to provide user guidance for selecting, purchasing, and using an automated hematology analyzer, as well as to present an overview of the technology used in an automated five-part differential unit. Specifications for additional automated units are available in ECRI's Clinical Laboratory Product Comparison System. We evaluated the Miles Technicon H.2 unit and rated it Acceptable. The information in this Single Product Evaluation is also useful for purchasing other models; our criteria will guide users in assessing components, and our findings and discussions on some aspects of automated hematology testing are common to many available systems. We caution readers not to base purchasing decisions on our rating of the Miles unit alone, but on a thorough understanding of the issues surrounding automated hematology analyzers, which can be gained only by reading this report in its entirety. The willingness of manufacturers to cooperate in our studies and the knowledge they gain through participating lead to the development of better products. Readers should refer to the Guidance Section, "Selecting and Purchasing an Automated Hematology Analyzer," where we discuss factors such as standardization, training, human factors, manufacturer support, patient population, and special features that the laboratory must consider before obtaining any automated unit; we also provide an in-depth review of cost issues, including life-cycle cost analyses, acquisition methods and costs of hardware and supplies, and we describe the Hemacost and Hemexmpt cost worksheets for use with our PresValu and PSV Manager CAHDModel software. Readers should also review the Clinical and Technical Overview and the articles "Miles Technicon H.2 Reports" and "Developing the Evaluation Reference Method."


Final CLIA regulations. Clinical Laboratory Improvement Amendments.

One clinical pathologist has noted that the broad scope of CLIA means "that every testing situation in the hospital, whether in or out of the laboratory, could now be a liability for ... hospital administration." Portions of CLIA became effective September 1, 1992; thus, it is important that all appropriate personnel are aware of the requirements of CLIA and that all ancillary testing sites are accounted for. CLIA will require unprecedented coordination and cooperation between the clinical laboratory and ancillary sites. Also, clinical laboratories must comply with the sometimes more stringent state regulations and requirements of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and CAP. JCAHO, for example, has regulations specific to blood glucose monitors--regulations that demand a high level of QC, proficiency testing, and documentation. In contrast, CLIA categorizes blood glucose monitoring as a waived test. (This classification has been widely criticized by laboratory organizations, which argue that an erroneous result from a blood glucose monitor could be deadly for the patient.


Donating and selling used medical equipment. International Medical Device Group.

This position paper was issued by the International Medical Device Group (IMDG) in June 1992. The group includes representatives from Finland, France, Germany, Hungary, Italy, Norway, Sweden, the United Kingdom, and the United States. ECRI is the United States representative and a founding member of IMDG.


Laser technology planning.

Lasers continue to be a highly useful and important surgical tool, and, in today's competitive healthcare environment, they are also an effective marketing tool. The public perceives lasers to be "high-tech" instruments, associating them with excellence of care. And the availability of state-of-the-art equipment such as lasers is often critical to medical staff recruitment. However, lasers are not universal surgical tools, as some proponents suggest. They are costly, and other less expensive technologies are acceptable and sometimes more desirable for certain procedures. Also, marketing reasons alone cannot justify laser acquisition. Faced with new, more restrictive federal regulations for Medicare reimbursement of capital expenses, hospitals need effective technology planning more than ever, particularly when planning for such "high-ticket" items as lasers. They can no longer afford to acquire lasers based on the perceptions of the public or the demands of one or even a few physicians; poor planning in the past has caused many new lasers to collect dust from low utilization. (ECRI's 1991 user survey on general-purpose surgical lasers found that, on average, hospitals use lasers in less than 5% of their total surgical procedures.) Hospitals need to approach the acquisition of laser technology cautiously to ensure that the appropriate equipment is obtained, that it will be well utilized for procedures in which it offers a demonstrable improvement over alternative technologies, and that it will also conform to the overall strategic plan of the institution. The purpose of this article is to provide guidance on the technology acquisition process, whether a hospital is acquiring its first laser or has a well-established laser program.(ABSTRACT TRUNCATED AT 250 WORDS)


Laser use and safety.

This Guidance Article is an update of an article published in a special issue of Health Devices entitled "Lasers in Medicine--An Introduction" (13[8], June 1984). Although surgical lasers have a good overall safety record, they do expose patients, physicians, and other clinical staff to serious risks. Laser hazards can cause injury, disability, or even death: hospital staff have been burned by misdirected laser beams, technicians and maintenance personnel have received eye injuries while working on lasers and have been exposed to hazardous chemicals while changing laser dyes, and patients have died from injuries resulting from fires ignited by laser energy. Laser accidents most commonly result from misdirection of the laser beam. Direct or reflected radiation can burn skin, hair, or, more seriously, the cornea or retina, causing permanent damage. Misdirected laser energy can also cause ignition of surgical drapes, tracheal tubes, or the patient's hair. Also, a frequent by-product of laser-tissue interactions is laser plume, or smoke. Its acrid smell and particulate matter irritate the eyes, nose, and lungs and cause nausea; it is also a suspected vector for transmitting infectious materials, such as the human papilloma virus (HPV) associated with condyloma (a wartlike lesion) and cervical cancer. The risks are not limited to patients and those directly involved in using and maintaining lasers. Many laser procedures are performed in areas outside the controlled environment of the surgical suite; patients in a waiting area or even passersby could conceivably walk into an accessible laser treatment room, such as a doctor's office, and inadvertently be exposed to a direct or reflected beam.(ABSTRACT TRUNCATED AT 250 WORDS)


Xintec Optica 120 Nd:YAG surgical laser.

This update to our recent Evaluation "Surgical Lasers" (Health Devices 20[7-8], July-August 1991) provides information about the Xintec Optica 120 Nd:YAG surgical laser, which was not available at the time of our original study and which has several unique features. Xintec also offers a 50 W, 120 VAC version of this laser, the Optica 60, which we did not evaluate; the manufacturer states that these models share many of the same features. The criteria and test methods used to evaluate the Optica 120 can be found on pages 252 to 260 in the 1991 issue. Below, we briefly describe the unit in the Characteristics section, and we provide an overall rating for the unit, as well as an individual rating for each major test, in the Significant Test Results and Ratings section. Under each of these tests, we report on features that are unique to this laser or that surpassed our criteria and would likely be considered by hospitals during the selection process. We also report on limitations and deficiencies that failed to meet our criteria, that are hazardous, or that played a significant role in our rating for both the test category and the unit, as well as any modifications that the manufacturer has made to the unit to address our concerns. Some reliability problems that we encountered during testing are also discussed to provide users with some indication of the laser's performance and service requirements; however, this information was not used in determining the unit's rating. Also see the "Laser Technology Planning" and "Laser Use and Safety" Guidance Articles in this issue.


Manufacturers' support policies.

Choosing an effective plan for supporting a medical device is critical to its safe use, cost-effectiveness, and longevity. Hospitals can choose from a variety of support providers, including manufacturers, third-party service vendors, or hospital clinical engineering (CE) departments. However, if the hospital plans to use a third-party service vendor or its own CE department to provide support, the manufacturer's cooperation or assistance will still be needed to implement the support plan effectively. Over the years, ECRI has received many comments from hospitals about the way in which manufacturers respond to their equipment support needs. We have learned that some manufacturers are not willing to assist third-party service vendors or in-house service programs or do not always deliver the support they promise. Also, hospitals do not always consider their support needs before purchase, when they have the most leverage to negotiate flexible support arrangements. To help foster better equipment support and customer satisfaction, we polled manufacturers that have participated in recent Health Devices Evaluations to obtain detailed information about their policies toward manufacturers' contract, third-party, and in-house support. Ready access to this information will help hospitals evaluate whether manufacturers' support policies will meet their needs, and it will allow them to minimize problems by working with the manufacturer to negotiate optimal support arrangements during the purchase process. In this article, we briefly discuss the factors to consider when evaluating support alternatives and manufacturers' support policies. We also present the questions posed to each manufacturer on our Manufacturers' Support Policies Questionnaire, along with a summary of the responses that we received for each question.(ABSTRACT TRUNCATED AT 250 WORDS)


IV free-flow--still a cause for alarm.

A nurse's aide, in transferring a mother in labor to the delivery room, turned off the infusion pump delivering Pitocin, a drug administered intravenously to accelerate contractions. The aide removed the infusion set from the pump without first closing the manual clamp on the line. A free-flow infusion occurred, and the mother received nearly 35 times the prescribed amount of drug. The infant suffered organ damage and pneumonia and died four days later. Free-flow infusions can have tragic consequences when a potent drug is involved. Although other causes of overinfusion and free-flow exist, such incidents are typically associated with removing a disposable intravenous (IV) infusion set from an infusion device without first closing the manual clamp. We first raised this issue in our 1982 Evaluation "Infusion Controllers" and have emphatically and repeatedly addressed it in Health Devices and other ECRI publications. Yet, hospitals continue to report free-flow infusions, a problem that can be addressed by both hospitals and device manufacturers. In this article, we describe the causes of free-flow--both user error and device design; report numerous incidents, some resulting in death; and provide recommendations for reducing the likelihood that such problems will continue to occur.


A bifunctional HBED-derivative for labeling of antibodies with 67Ga, 111In and 59Fe. Comparative biodistribution with 111In-DPTA and 131I-labeled antibodies in mice bearing antibody internalizing and non-internalizing tumors.

To investigate whether bifunctional ligands containing chelating structures other than EDTA and DTPA and metallic radiotracers other than 111In will reduce the non-specific radioactivity uptake in the liver during immunoscintigraphy, we synthetized an isothiocyanato-substituted phenolic polyaminocarboxylic acid (HBED-CI) for labeling of MAbs with 67Ga, 111In and 59Fe. Biodistribution of HBED-CI-labeled MAbs was compared to that of 131I and 111In-DTPA labeled MAbs in nude mice bearing tumors, which differ with regard to intracellular internalization and catabolism of the corresponding MAb-antigen complex. In the liver a continuous radioactivity excretion for 67Ga-HBED-CI-labeled MAbs was observed with kinetics that parallel 131I clearance after administration of 131I-MAbs, while 111In-HBED-CI-labeling led to a constant 111In liver level quite similar to that of 111In-DTPA-MAbs. In tumors, 67Ga-HBED-CI-MAb uptake again paralleled that of 131I-MAbs, showing continuous accumulation in tumor tissues when internalization of the MAb-antigen complex was not involved. A much lower uptake, which peaked between 24 and 48 h, was found in the case of MAb-antigen internalization. 111In of 111In-HBED-CI- and 111In-DTPA-labeled MAbs continuously accumulated in both types of tumors. Compared with 111In-DTPA-MAbs, an improvement in tumor-to-liver ratios, due to the reduced liver radioactivity associated with 67Ga-HBED-CI-labeled MAbs, could only be obtained with non-internalizing tumors. The time course of radioactivity distribution in the liver and in MAb-internalizing tumors after administration of 67Ga-HBED-CI-, 111In-HBED-CI- and 111In-DTPA-labeled MAbs further indicates a dominating influence of the metallic radiotracer rather than the ligand on retention or excretion of radioactivity in MAb-catabolizing tissues.


Attachment of 99mTc to lipid vesicles containing the lipophilic chelate dipalmitoylphosphatidylethanolamine-DTTA.

The binding of 99mTc to negatively-charged and neutral unilamellar lipid vesicles was investigated in the absence and presence of the ligand diethylenetriaminepentaacetic acid (DTPA) covalently attached to the headgroup of phosphatidylethanolamine at the surface of the membrane. Even in the absence of DTPA on the membrane surface, 99mTc reduced by Sn bound to the membrane surface but rapidly dissociated from the vesicles in the presence of plasma in vitro. When DTPA was present on the membrane surface, dissociation of 99mTc from the vesicle surface in plasma was much reduced. The dissociation of 99mTc from the surface of negatively-charged vesicles was less than for neutral vesicles in the absence of ligand but was markedly greater than for vesicles containing the ligand DTPA, suggesting that the binding of 99mTc to vesicles with surface-attached DTPA could not be explained solely on the basis of the negative charge provided by the DTPA. In vitro experiments using 14C-labeled lipids as well as in vivo imaging studies indicated that dissociation of 99mTc from the surface of the vesicle did not arise predominantly because of lipid exchange with plasma components or due to cleavage of Tc-DTPA from the vesicle surface. For vesicles with surface-attached DTPA, 99mTc dissociation from the vesicle surface in plasma was further reduced by addition of the antioxidant ascorbate.


Evaluation of S-[11C]citalopram as a radioligand for in vivo labelling of 5-hydroxytryptamine uptake sites.

The biologically active S-enantiomer of [N-methyl-11C]citalopram was evaluated as a radioligand for in vivo labelling of the 5-hydroxytryptamine uptake site in brain, using ex vivo tissue counting in rats and positron emission tomography in man. In rats, the maximal signal for total versus non-specific binding was approx. 2 at 60-120 min after radioligand injection. Subsequent studies in man failed to identify a specific signal over a 90 min scanning period, due to prolonged retention of non-specific label.


Ligands and tracers for PET studies of the 5-HT system--current status.

The status of the radiochemical development and biological evaluation of radioligands and tracers for PET studies of the serotonergic system is reviewed, indicating those agents with present value and those with future potential. Practical recommendations are given for the preparation of two useful radioligands for PET studies of central 5-HT2 receptors, namely [18F]setoperone and [18F]altanserin. Though, it has not proved possible to recommend tracers or radioligands for the study of other aspects of serotonergic system, prospects for future radiochemical development are indicated, especially for developing radioligands for the 5-HT re-uptake site, and for the 5-HT1 and 5-HT3 receptors.