Improved procedures for the determination of lipid phosphorus by malachite green. We have developed two procedures for the measurement of lipid phosphorus based on interaction between phosphomolybdenum and malachite green. One method, the "micro" assay uses 50-200 microliters of HClO4 and has a sensitivity range of 0.01-1.5 micrograms phosphorus. The second method, the "macro" assay, has a sensitivity range of 0.03-5.0 micrograms phosphorus with 100-500 microliters HClO4. Both assays are very reproducible with day to day standard deviations of less than 6% between triplicates irrespective of the HClO4 content used. At different concentrations of HClO4, each method was successfully used to determine the phosphorus content in phosphatidylethanolamine and sphingomyelin standards that covered the proposed sensitivity ranges. The increased range, sensitivity and greater volumes of HClO4 permitted in the procedures represent significant improvements over existing methods.


[Circulating lupus coagulants. A paradox in vascular pathology]. Lupus anticoagulants (LA) are acquired inhibitors of coagulation related to the antiphospholipid antibodies. Paradoxically, these anticoagulants do not expose patients to the risk of hemorrhage but, on the contrary, to a thrombotic risk. The association in a patient of an antiphospholipid antibody and a clinical manifestation (thrombosis or equivalent) defines the antiphospholipid syndrome. This syndrome is termed primary or secondary according to whether it appears as an isolated disorder or is associated with an identified disease, frequently autoimmune (systemic lupus erythematous or lupus related syndrome). Clinical complications of LA are arterial or venous thrombosis at various sites. They are frequently recurrent, and deep venous thrombosis of leg, oculo-cerebral ischemic lesions and heart valve complications have all been well documented. Thrombosis of the microcirculation can cause tissue or organ disfunction, the most characteristic effect being repeated abortions. Laboratory demonstration of LA is difficult when the inhibitor is weak, and this should be completed by tests for other antiphospholipid antibodies. Clinical studies are necessary to assess the thrombotic risk of the LA in different clinical conditions and to evaluate the need and type of antithrombotic treatment. The LA are heterogeneous and only a small proportion of patients with LA will develop thrombosis. New tests capable of predicting the thrombotic risk, bases on the physiopathological mechanisms with which LA interfere in vivo, are currently being investigated.


[Surgery of aneurysms of the abdominal aorta in 1992. Lessons of a decade]. Perioperative mortality of abdominal aortic aneurysm (AAA) remains at a mean of 3% in asymptomatic cases, 6% when symptomatic and 50% when ruptured while many patients with ruptured AAA die prior to surgery. This has changed little over the last decade. The causes of this stagnation are analyzed, strategic choices as a function of clinical situations, size of aneurysm, and associated lesions exposed, and means explored to improve the prognosis. Since the perioperative mortality rate appears incompressible, an improvement in the prognosis of AAA can be obtained only by a combined medical effort. This requires the more rapid recognition of prodromal symptoms of rupture, the detection of a larger number of asymptomatic AAA and improved postoperative life expectancy, already reasonable, by more rigorous vascular and cardiologic surveillance.


[Duplex ultrasonography in the diagnosis of deep vein thrombosis of the legs. Agreement between two operators]. The operator-dependent nature of venous Duplex-ultrasonography diagnosis of deep venous thrombosis (DVT) of the leg is the principal reproach applied to it and a reason for delaying use. The aim of the present study was to evaluate concordance between two operators, with rigorous application of the same methodology of exploration of the venous axes. The study included 82 patients under hospital care, randomly selected from among those referred for the first Duplex-ultrasonography examination for DVT, and having accepted to undergo 2 consecutive explorations, one by each of the two operators. The two operators evaluated independently, for the 19 venous axes of the legs: 1: the interpretability of the examination, 2: the differential diagnosis between: absence of thrombus, presence of thrombus, nonconclusive examination, and 3: the score for the DVT extension. Evaluation of concordance of diagnosis was by Cohen's kappa coefficient, calculated on the positive diagnosis of DVT and the site of the most proximal thrombus. Extension scores were compared by calculation of the coefficient of correlation "r". Interpretability rates were 92% and 91% respectively for the two operators, 35 DVT being diagnosed in 27 patients by operator A and 36 DVT in 27 patients by operator B. The kappa coefficient for diagnosis of DVT with localization in the affected leg was 0.90 [0.81-0.98]. It was 0.89 [0.73-1] for proximal lesions, 0.86 [0.74-0.97] for the lower leg level, and 0.79 for localization of the proximal extremity of the thrombus. Extension scores evaluated by the two operators were 2.88 and 3.14 respectively, with a coefficient of correlation between the extension scores of 0.96. The 5 diagnostic divergences concerned the lower leg level; the 2 localization discordances concerned: the frontier zones leg-lower popliteal, lower femoral-upper popliteal. Good concordance between results of the two operators using Duplex-ultrasonography exploration was obtained even though the majority of the DVT were in the calf, a region known to be explored with difficulty. Overcoming the operator-dependent character of Duplex-ultrasonography by a rigorous exploratory methodology could make it the future reference examination for the diagnosis of DVT.


[Use of an active clinical maneuver for diagnosis of popliteal artery entrapment]. Overall incidence rate of popliteal artery entrapment syndrome is certainly underestimated. The aim of this work was to test and to evaluate the interest of a clinical maneuver of active and repetitive ankle extensions in upright position, for the screening, the diagnosis and the follow-up of patients with popliteal artery entrapment. During a 3 year period, this maneuver was used in 10 patients (16 popliteal artery entrapments) and in 50 age-matched controls. The results of the maneuver were compared to the results of functional vascular investigations. For all the patients the maneuver had to be stopped before 20 movements whereas it could be continued up to 50 movements for all the controls. The maneuver was easy to perform, reliable and constant in its results. The earlier the maneuver was stopped the more critical was the trouble at functional vascular investigations. We believe that this maneuver is of great help for early diagnosis of popliteal artery entrapment, assessment of its severity and follow-up treated patients. It could also help to detect athletes with asymptomatic popliteal entrapment.


[Electric stimulation of the spinal cord in arterial diseases of the legs. A multicenter study of 244 patients]. From January 1985 through January 1990, 244 patients (168 males, 76 females, mean age: 69 +/- 14 years) received epidural spinal cord stimulation for the treatment of advanced, nonreconstructable, peripheral vascular disease of the lower limbs due to atherosclerosis in 180 patients, atherosclerosis and/or diabetes in 49, and thromboangiitis obliterans in 15 patients: previous surgery included 101 bypass-grafts in 70 patients, 51% of which below the knee, and 117 sympathectomies in 113 patients as the last resource in face of distal peripheral vascular disease of the lower limbs. Mean ankle-to brachial systolic pressure ratio was .31 +/- .34 on symptomatic limbs; due to pain and advanced disease, walking capacity was assessed in only 151 patients, either on treadmill in 25, or in a metered corridor in 126; angiogram of the lower limbs was performed in every patient unless one not older than three months was readily available; pain at rest was assessed after an analogical scale; partial transcutaneous oxygen tension was measured on the dorsum of the fore-foot of 77 symptomatic limbs (mean: 13.35 +/- 14 mmHg). According to clinical and functional evaluation, 18 patients had exertional ischemia (group I), 87 had permanent ischemia with pain at rest and no tissue loss (group II), and 139 had chronic tissue loss (group III), including 93 ischemic ulcers (mean surface: 3.7 cm2, mean duration: 3.5 months) in 88 patients, 27 limited gangrene, and 24 previous limited non-healing distal amputation. After temporary spinal cord stimulation at T12-L1 level (mean duration: 9 +/- 4 days) with a percutaneous quadripolar electrode lead had allowed for selection of responders, 212 patients received an implantable neurostimulator.(ABSTRACT TRUNCATED AT 250 WORDS)


Oscillometry of radial artery in acrocyanosis and cold sensitivity. Acrocyanosis is reassessed on the basis of 34 new patients with diagnostic clinical features. The most useful tests are the skin temperature differences (STD) between wrist and end of fingers (or ankle and end of toes) and oscillometry over the radial and dorsalis pedis and posterior tibial arteries. Capillaroscopy of the conjunctival and nailfold vessels is useful in half the patients. Capillary resistance was not helpful. STD of 1.5 degrees C or more between skin of wrist or ankle and fingertip or toetip, is usually associated with more severe disease and capillary abnormalities on microscopy, and with reduced oscillometry (to 1 or less) over the radial arteries and dorsalis pedis and posterior tibial arteries. Reduced oscillometry is more associated with abnormalities than the other tests, and more than STD. The work of Mulvany and his colleagues suggests an explanation for the low oscillometry. Larger vessels than the arterioles and digital vessels can become resistance vessels in various circumstances. It is likely that the radial artery and vessels of similar diameter can temporarily act as resistance vessels in patients with acrocyanosis in a low temperature environment.


[Ambulatory and hemodynamic treatment of venous insufficiency (CHIVA cure). Study of 96 patients operated on between June 1988 and June 1990]. 96 patients were treated in two years by Ambulatory and Hemodynamic Treatment of Varicose Veins (CHIVA cure), representing 131 legs that underwent surgery. 71 patients (74%) representing 102 CHIVA cures in the long saphena territory were followed up, with a maximum of 28 months of follow-up. The CHIVA cure represents a new and interesting therapy: ambulatory, painless, it allows a very early resuming of normal life. The follow-up shows that the aesthetic and functional results are especially satisfying and seem to be steady. The CHIVA cure certainly neglects the histological and parietal aspects of venous incompetence but the treatment of the hemodynamic factor is effective. It can be applied on every type of varicose veins concerning the long saphena territory, provided that the deep venous system is normal. The interest of CHIVA cure concerning the short saphena territory remains to be demonstrated. Arteritic patients, patients with coronary arteries diseases, sportmen, young patients with a brief evolutive potential, especially women, are the best indications. The CHIVA cure is a reliable strategy in the short and medium term, offering excellent aesthetic and functional results that still have to be confirmed in the long term and or a large scale.


[Results of ambulatory and hemodynamic treatment of venous insufficiency (CHIVA cure)]. From January 1987 to December 1988, 100 conservative and hemodynamic treatments of superficial venous insufficiency in great saphenous vein territory, have been done on 86 patients. They were 32 men, whose mean age was 53.7 years, and 54 women, whose mean age was 44.5 years. Indication for surgery was mainly functional in 28 cases, esthetic in 26 cases, both in 25 cases and trophic problems in 21 cases. Ligation of the sapheno-femoral junction has been done in 91 cases (62 clips, 9 clips and ligations, 11 ligations, 9 sutures). Distal interruption has been done above knee in 24 cases, below knee in 50 cases, and both in 16 cases. Early postoperative complications have been one septic collection of the groin, one hematoma of the groin, one durable contusion of the saphenous nerve, and 21 superficial venous thrombosis. There were six thrombosis of excluded branches, seven subtotal thrombosis of the saphenous and height partial thrombosis of the saphenous vein. Subtotal thrombosis of the saphenous vein were due either to a mistake in position of distal ligation in three cases, either to a too large saphenous vein in four cases. Five out of height partial thrombosis occurred on saphenous veins larger than ten millimeters. Follow up was obtained, in 1990, so that all patients had at least one year of follow-up. Seven patients have been lost for follow-up. Three patients had recurrence because of failure of the clip. An additional procedure was necessary in 30 patients. Functional results were correct in 89% of patients, and esthetical results in 68% of patients.


[Chilblains].

[Chilblains]. Chilblains represents an idiopathic vascular cutaneous benign acral syndrome. Epidemiology and basic mechanisms remain hypothetic and the treatment is controversial. The patients exhibit pruritic, redness painful, burning acral patches or plaques on the toes and/or fingers. The disease is bilateral, youthful and influenced by exposure to cold. Spontaneous healing is common when spring arrives and relapse is frequent on the following winters. There is no systemic symptom and laboratory studies are normal. The physical examination is sufficient for diagnosis. Histologic examination shows vascular and perivascular capillary and venular lymphocyte infiltrates without necrosis nor leukocytoclasia. The differential diagnosis includes: lupus, cold urticaria, acrocyanosis, erythermalgia, vasculitis and the Blue Toe Syndrome. Treatment includes prophylactic measures against cold and calcium channel inhibiting drug. In more severe cases thyrocalcitonin and hemodilution might be helpful.


[Interruption of the infra-renal inferior vena cava with azygos continuation. Case report]. The authors report a case of congenital interruption of the inferior vena cava with azygos continuation with a deep venous thrombosis of the left lower extremity. It is a rare congenital abnormality which is most of the time asymptomatic. However such an abnormality may be a problem in case of cardiac catheterization or thoracic surgery.


[Acute thrombosis of the right renal vein. Two cases with coagulopathies]. We report two cases of renal vein thrombosis, unusual because of acute expression, right renal vein localization, absence of the usual renal or perirenal causes, surgical management and a never before reported etiology. In one case the thrombosis was secondary to primary antiphospholipid syndrome, in the other it was secondary to heparin associated thrombocythemia. In this case surgical management was performed during prostacyclin infusion.


[Ambulatory and hemodynamic treatment of venous insufficiency (CHIVA cure). Report of an atypical case]. After a brief introduction describing the principle, strategy and tactics of hemodynamic treatment of venous insufficiency in ambulant patients, the following atypical case is described. Ms P., aged 38 years, presented a functional symptomatology including waking at night and was obliged to get out of bed. Varices were moderately visible but she asked for treatment for esthetic reasons. A future pregnancy was discounted. Clinical examination and the pulsed ultrasound-Doppler cartogram showed incontinence of the internal perineal, opening from the genitofemoral fold and rejoining the summit of Jacomini's vein arch. The dorsal segment of Jacomini's vein was incontinent with a retrograde flux and rejoined an incontinent short saphenous continuing as a type III shunt. The cartogram obtained, the strategy decided and the intervention carried out on 19 June 1990 are illustrated by photographs. At 4 month follow up and despite the heat wave of summer 1990, all functional signs had disappeared and a sufficiently esthetic result had been obtained. Unexpectedly, the patient announced that she was pregnant.


Symmetry-breaking bifurcation: a possible mechanism for 2:1 frequency-locking in animal locomotion. The generation and control of animal locomotion is believed to involve central pattern generators - networks of neurons which are capable of producing oscillatory behavior. In the present work, the quadrupedal locomotor central pattern generator is modelled as four distinct but symmetrically coupled non-linear oscillators. We show that the typical patterns for two such networks of oscillators include 2:1 frequency-locked oscillations. These patterns, which arise through symmetry-breaking Hopf bifurcation, correspond in part to observed patterns of 2:1 frequency-locking of limb movements during electrically elicited locomotion of decerebrate and spinal quadrupeds. We briefly describe how our theoretical predictions could be tested experimentally.


A roentgenological evaluation of the relationship between segmental motion and malalignment in lateral bending. A radiographic study was undertaken to determine the relationship between static vertebral malalignment and segmental lumbar motion in lateral bending. Survey. Chiropractic college student health center and private chiropractic clinic. 249 subjects: 114 with low back pain, 29 asymptomatic with no history and 106 asymptomatic with history. Of these, 194 were freshman volunteers and 55 were new private clinic low back pain patients. None. Net lumbar segmental tilt and rotation in lateral bending: corrected and uncorrected for segmental malposition with the patient standing in the upright neutral position. There was moderate to good negative correlation of malalignment with segmental tilt motion and segmental motion asymmetry (r = -.42 to -.89, p less than .001). Correlation of malalignment with motion from the ideal neutral segmental position of perfect alignment was modest (r = .16-.42). A large variation in segmental motion was found for all segmental malalignments. This study suggests that malalignment is associated with segmental tilt motion in lateral bending, although large subject variability greatly compromises predictability on an individual basis. This study also indicates that segmental malposition may complicate the palpation of active range of motion. This is because the malalignment itself may facilitate a greater arc of segmental motion in the direction of comparative restriction in movement from the ideal neutral position to the extreme of lateral flexion.


Stability of paraspinal tissue compliance in normal subjects. The following studies were performed in order to evaluate the stability of paraspinal tissue compliance measurements. Tissue compliance is a measure of the consistency or firmness of soft tissue and is determined by a hand-held tissue compliance meter. Descriptive and blinded time course intervention measurements. All measurements were performed on subjects placed in the prone position on flat tables in a laboratory setting. Forty asymptomatic volunteer subjects. Tissue compliance measurements of the T6 and L3 paraspinal regions. Tissue compliance measurements recorded as millimeters of penetration of a metered probe. Data from this study indicate that paraspinal tissue compliance at the T6 and L3 regions does not change significantly over a 10-min interval, is not effected by the testing intervention and the number of abnormal left/right tissue compliance asymmetries is appropriate (5%) for a normal population of subjects. These findings tend to support the utility of tissue compliance as a possible tool for the evaluation of paraspinal soft tissue.


Evaluation of neck muscle strength with a modified sphygmomanometer dynamometer: reliability and validity. Determine test-retest reliability, normative data and clinical validity of isometric muscle strength testing in the neck with a modified sphygmomanometer dynamometer (MSD). Analytic survey. Paired trials of various muscle strength tests were conducted on convenience samples of normal subjects and consecutive samples of symptomatic subjects. Outpatient chiropractic research clinic. For study 2, 40 normal male subjects, average age 25 +/- 2 yr, were studied for reliability and normative data. For study 3, 24 symptomatic patients, 12 males and 12 females, average age 39 +/- 7 yr, were studied, 8 with "whiplash"-type injuries (average duration 22.5 wk) and 16 with nontraumatic chronic neck pain (average duration 110 wk). No therapeutic intervention is reported. Pressure levels generated by subjects against a modified sphygmomanometer-type dynamometer as measured in kilopascals. Study 1. Repeated paired trials of a standardized weight column (20 lbs) produced a coefficient of variation of 0.84% and virtually no difference between the means of the first vs. second trials. Study 2. High test-retest correlation coefficients were found for all ranges of motion (.79-.97). Right-to-left asymmetry in rotation and lateral flexion was within 6-8%. The flexion/extension ratio was .57:1, indicating that in normal subjects, flexion was approximately 40% lower than extension. Lower cutoffs were established as the mean--1 SD as follows (in kPa): flexion--3300, extension--5800, rotation--5200 and lateral flexion--6200. Coefficients of variation ranged from 25 to 29%. Study 3. Differences between paired trials were analyzed by intraclass coefficients, which were very high (.95-.99), and by percentages, which ranged from 4 to 10.4%, with an average of 7%, indicating a high degree of test-retest consistency. The mean values for all symptomatic subjects for flexion, extension, right rotation and right lateral bending were all well below the normal cutoff values as found in study 2. The flexion/extension ratio for whiplash subjects was 0.25:1.00, which is half of that of normal subjects. The MSD has been found to be a reliable instrument for the evaluation of isometric muscle strength in the neck in normal and symptomatic subjects. Normative values for absolute test levels, bilateral symmetry and flexion/extension ratios have been determined. A symptomatic group demonstrated significant deviations from these norms in the form of reduced strength levels and reduced flexion/extension ratios, while still maintaining very high levels of test-retest consistency and bilateral symmetry. The MSD appears very promising in the evaluation of neck-injured patients.


Skin temperature assessment for neuromusculoskeletal abnormalities of the spinal column. A qualitative review of the scientific literature on thermographic instrumentation for detecting neuromusculoskeletal abnormalities of the spinal column was made. Electronic infrared instrumentation (telethermography), liquid crystal thermography and various hand-held devices were scrutinized in terms of reliability and comparison with other diagnostic tests (e.g., computed tomography, myelography, electromyography, magnetic resonance imaging). A Medline literature search was performed from 1966 through 1990. English language material was retrieved using the following key words: thermography and spine, spinal injuries, cervical vertebrae, thoracic vertebrae, lumbar vertebrae, sacroiliac joint, lumbosacral region, back or neck. The Index to Chiropractic Literature was also reviewed. The categories of skin temperature and thermography were scrutinized. Chapters of texts and nonpublished works were not incorporated. Studies involving the comparison of thermographic findings with those of other tests were the primary focus of the review. Case reports, as well as the use of thermography as an outcome measure, were also studied. Interexaminer reliability studies are reported. The study populations are characterized as well as binding procedures, if any. The authors' statistical work, if applicable, is presented and criticized. Relatively few reliability studies exist for thermography. Emphasis has been on validity studies that compare the results of the thermogram with other reference tests. There has been a general lack of high-quality research design (e.g., blinding) throughout the thermographic literature base. The sensitivity of the various thermographic instrumentation has shown encouraging results, although this must be tempered with the generally poor design of many studies. Specificity, in contrast, has shown mixed results. The review indicated telethermography to be a sensitive diagnostic procedure for detecting abnormalities, such as disc protrusion, of the lumbar and cervical spine. Liquid crystal thermography effectiveness is difficult to determine due to the paucity of blinded investigations, although normative data for the cervical spine and upper extremities is present. Literature on the various hand-held instruments has revealed moderate levels of examiner reliability for infrared devices, with less information available for thermocouple instruments. Normative data for hand-held instruments is absent. Continued investigation is needed in the area of thermographic research in light of the paucity of blinded and/or controlled investigations. More sensitive neurophysiological and anatomical measures must be used when comparing the results from thermography. The lack of an available gold standard for comparing thermographic findings has been problematic. Future research should focus on thermography as a noninvasive outcome measure and interpreter reliability.


Magnetic resonance imaging versus computed tomography scan: accurate diagnosis of soft tissue lesions. Due to their cost effectiveness and accessibility, computed tomography (CT) scans are being utilized when magnetic resonance imaging (MRI) appears to be the diagnostic technique of choice. Because of their availability, CT scans are still used for diagnosis of disc herniations. MRI may, however, be superior in its specificity. In taking into account the subjective complaint and orthopedic and neurological findings, a disk herniation can often be diagnosed without a CT scan or MRI. However, should the patient fail to respond to conservative care or show unusual symptoms, an MRI is indicated. This article discusses a case where MRI would be the imaging procedure of choice.


Proximal tibiofibular joint dysfunction and chronic knee and low back pain. This article reports a case of joint dysfunction of the proximal tibiofibular joint that produced knee, thigh and low back pain of 5 yr duration. An injury of a simple nature apparently caused the onset of symptoms. Manipulation of the proximal tibiofibular joint resulted in immediate and dramatic relief of symptoms. This case illustrates how a relatively minor incident can result in longstanding pain and disability. Examination and treatment procedures for the proximal tibiofibular joint dysfunction are described.


Proposal for establishing structure and process in the development of implicit chiropractic standards of care and practice guidelines. With the advent of health care's "era of accountability", the chiropractic profession is now faced with generating implicit standards and guidelines for care or having it done for us by outside agencies. Already we see chiropractic groups in individual states and provinces being pressured into naive efforts of guideline development. Current knowledge and experience are available through recent health care literature that clearly defines the structure and process of guideline development and offers suggestions on how to measure outcomes of those processes. In addition, the United States Congress has directed a new federal agency to oversee this activity and monitor outcomes of quality improvement programs. The time has come for the chiropractic profession to define its exact role in health care delivery and develop implicit standards of care and practice guidelines. This sentinel effort should be managed by a commissioned body of empaneled experts that generally represent the academic and clinical chiropractic profession. A protocol for selection of these panelists and the panel chairperson needs to be developed and memorialized. Appropriate methodology (with definitions) needs to be developed for the process of standards/guideline development. Adherence to the accepted structure and process of guideline development will ensure the continuity of this dynamic process in the coming generations. This proposal offers a preliminary definition of the structure and process, including a "seed" policy statement and decision flow chart, specific to guideline development. Once the structure and process of guideline development for chiropractic are defined, the profession can then present this product to federal and state agencies, private sector health care purchasers, patient advocacy groups and other stakeholders of chiropractic care.(ABSTRACT TRUNCATED AT 250 WORDS)


Differentiation of active and latent trigger points by thermography. This study tested whether two distinct thermographic patterns attributed to myofascial trigger points could distinguish between active and latent trigger points. A retrospective chart survey was undertaken with thermographic data divided into two groups: a) increased thermal emission only over the trigger point and b) over the area of pain referral. The criterion standard used in a blinded comparison was physical examination findings separating active from latent trigger points. All cases were drawn from a private practice referral center for thermographic evaluation of neck and low back injuries. A sample of 65 cases showing physical examination findings of trigger points was chosen from 229 consecutive motor vehicle accident case files. There was moderate agreement between the two methods of differentiating active from latent latent trigger points (Kappa = 0.44) with a specificity of 0.70 and a sensitivity of 0.74. When cases in which spinal segmental dysfunction were eliminated, the agreement increased (Kappa = 0.54) with specificity of 0.82 and sensitivity of 0.74. Thermography may be a useful tool in distinguishing active from latent trigger points, but the thermal imaging of spinal joint dysfunction may be a compounding factor.


Line drawing analyses of static cervical X ray used in chiropractic. This review article identifies the chiropractic techniques used to assess the structure of the cervical spine as seen on the static cervical radiograph. On-line search of MEDLINE, key words, radiograph and X ray in combination with cervical spine (vertebrae); the Chiropractic Research Archives Collection (CRAC); indexes published in the Journal of Chiropractic Research; conference proceedings from Annual Biomechanics Conference of the Spine, FCER sponsored conferences and Annual Upper Cervical Spine Conference; references identified from bibliographies of pertinent articles; a telephone poll of radiography/technique instructors at chiropractic colleges. Techniques that quantitatively assess relative alignment of skeletal structures or distortion of the spinal column. Techniques were grouped according to the structures analyzed and the views used. Variables and artifacts that limit the reliability or validity of static cervical X ray line drawing analysis were identified and the techniques assessed for their reported reliability and validity. Reliability studies exist showing that inter- and intraexaminer reliability are sufficient to measure lateral and rotational displacements of C1 to within +/- 1 degree. This amount of error allows objective analysis of upper cervical X rays to detect changes in the angular positional relationships of radiographic images on the order of those already seen clinically. Methods of cervical analysis that use relative angular measures of skeletal positioning are best able to control the effects of radiographic distortion. The accuracy of the analysis methods has not been ascertained to establish the extent to which angular measurement of vertebral relationships actually reflect three-dimensional movement. It is not known how much of the changes that are seen in pre/post-radiograph sets are due to positioning changes of the patient between radiographic procedure, and how much are due to actual changes of skeletal relationships brought about by adjustment.


Compression fractures in patients undergoing spinal manipulative therapy. Increasing numbers of elderly patients are currently seeking chiropractic care. One condition commonly seen in the elderly is osteoporosis of the spine, which carries with it the risk of compression fractures. We present four cases in which patients were noted to have compression fractures following chiropractic adjustments. In each of these cases, serious questions are raised concerning the relationship between the adjustment and the occurrence of fracture. What is clear is that failure to diagnose a compression fracture, together with the application of adjustment into the area of fracture, can increase symptoms and prolong disability. It is recommended that patients with osteoporosis who have suffered a fall or injury be X rayed before treatment is given. In addition, special care should be exercised in elderly patients with osteoporosis.


Digesting government's regulatory alphabet soup. The impact of the governmental regulatory acronyms implemented during this year will prove to be very similar to how implementation of the Prospective Payment System (PPS) via DRGs affected hospitals a decade ago. Those hospitals that realized the dimensional shift in their industry and made prudent business decisions and adjustments have not only survived their era of payment reform but have also flourished. Those hospitals which did not recognize the regulatory changes, or chose to ignore the changes, have not succeeded, many paying the ultimate price of business failure. The impact on physicians will be quite similar. Physicians that adopt proven, sound, business principles and accept the absolute need to be informed and pro-active, will not only succeed, but they too, will flourish. Physicians who choose otherwise, quite frankly, risk practice failure. A few years ago, the American Hospital Association published what I believe is the ultimate statement of health care regulatory bureaucracy. The publication boasted 80 pages, containing more than 2,000 entries. Its title was Acronyms and Initialisms in Health Care Administration. With the addition of the regulatory acronyms implemented during 1992, the size of that publication has probably more than doubled by now. Being able to digest this regulatory alphabet soup has its benefits; not only will physicians feel more comfortable in their knowledge of being in regulatory compliance, it may also help physicians focus on the best methods of managing their practices and ultimately, their careers.


The changing face of primary hyperparathyroidism. The introduction of multiphasic screening and the development of sensitive parathormone assays have changed the demography and clinical symptomatology of patients presenting with primary hyperparathyroidism. This retrospective review includes 158 patients operated on for primary hyperparathyroidism at the Medical College of Georgia from 1973-1987. Compared to the 46 patients managed prior to 1973, the frequency of subclinical hyperparathyroidism has increased from 46% to 64%. The median patient age has increased from 50 to 59 years. Recognition of primary hyperparathyroidism in a more geriatric population modifies indications for surgical intervention in subclinical disease. Osteoporosis, myalgias, fatigue, arthralgias, memory loss, or constipation occurred in 50% of patients. These complaints are frequent in normocalcemic elderly people. They represent disease, not normal aging. Their exacerbation by hypercalcemia should not go uncorrected if neck exploration can be tolerated by the patient.


Child abuse by scalding.

Child abuse by scalding. Physical abuse of children by burning is a serious crime that leaves the youngest of our children with permanent physical and emotional scars. The victims tends to be less than 2 years of age. Burn-abused children usually suffer from a spectrum of physical, psychologic, and nutritional neglect. Burn abuse is costly in terms of pain, suffering and health care. Up to 15% of acutely injured children seen in emergency departments, admitted or not, have been abused. Burns were involved in up to 22% of physical abuse cases. Up to 26% of pediatric burn admissions were the result of abuse. The most common form of burn abuse in children requiring hospitalization is the scald. Physicians who treat children and burn patients should have a knowledge of the literature and clinical factors associated with pediatric burn abuse.


The Human Genome Project and the social contract: a law policy approach. For the first time in history, genetics will enable science to completely identify each human as genetically unique. Will this knowledge reinforce the trend for more individual liberties or will it create a 'brave new world'? A law policy approach to the problems raised by the human genome project shows how far our democratic institutions are from being the proper forum to discuss such issues. Because of the fears and anxiety raised in the population, and also because of its wide implications on the everyday life, the human genome analysis more than any other project needs to succeed in setting up such a social assessment.


The right to genetic information: some reflections on Dutch developments. New developments in genetics are rapidly spreading over the Western World. The standards of clinical practice differ however according to local value- and health-care systems. In this article a short survey is given of Dutch developments in this field. An effort is made to explain the philosophical and ethical background of Dutch policy by concentrating on autonomy, responsibility and the right not to know.


Right not to know or duty to know? Prenatal screening for polycystic renal disease. New dimensions in different ethical scenarios following genetic information require new medical-ethical Action Guides for physician-patient interaction. This paper discusses the ambiguity in moral choice between a "right not to know" and "a duty to know", regarding parental decision-making pro or contra selective abortion following prenatal screening for autosomal dominant polycystic kidney disease (Potter III) and related public policy issues.


Techno-thanatology: moral consequences of introducing brain criteria for death. This paper is based on the hypothesis that the effort to establish new criteria for diagnosing human death, which has been taking place over the past twenty years or more, can be viewed as a paradigm case for the impact of scientific and technological progress on morality. This impact takes the form of three tendencies within the change in morality, which may be characterized as 'denaturalization', 'functionalization' and 'homogenization'. The paper concludes with the view that these tendencies do not indicate a decline of morality, as feared by some authors, but rather a structural change.


The medical exception: physicians, euthanasia and the Dutch criminal law. The legalization of euthanasia, both in the Netherlands and in other countries is usually justified in reference to the right to autonomy of patients. Utilizing recent Dutch jurisprudence, this article intends to show that the judicial proceedings on euthanasia in the Netherlands have not so much enhanced the autonomy of patients, as the autonomy of the medical profession.


Clinical ethics in assisting euthanasia: avoiding malpractice in drug application. The debate on the ethical permissibility of euthanasia in medicine has a corollary in the ethical application of drugs. The overall moral limits of medical treatment apply evenly to the moral acceptability of the pharmacological aspect of the act of euthanasia. The pharmacological aspect of the act is of ethical importance not only for the person requesting an active ending of his or her life, but also for the grieving family.


Criteria for death: self-determination and public policy. 'Whole brain death' criteria have found support in Western cultures in regard to post-mortem organ donation and the termination of care for patients meeting these strict criteria. But they are of minimal use in Asian cultures and in the ethics of caring for the persistent vegetative patient. This paper introduces a formula for a global Uniform Determination of Death statute, based on the 'entire brain including brain stem' criteria as a default position, but allowing competent adults by means of advance directives to choose other criteria for determining death during the process of dying.


Equity and solidarity: the context of health care in The Netherlands. The current debate on health care resource allocation in the Netherlands is characterized by a social context in which two values are generally and traditionally accepted as being equally fundamental:solidarity and equity. We will present an outline of the distinctive features of the Dutch health care system, and analyze the present state of affairs in the resource allocation debate. The presuppositions of the political call for constraint and (renewed) government supervision and the role of the specific value context in recent proposals for reconstruction of the Dutch health care system will be evaluated.


The method of 'principlism': a critique of the critique. Several scholars have recently criticized the dominant emphasis upon mid-level principles in bioethics best exemplified by Beauchamp and Childress's Principles of Biomedical Ethics. In Part I of this essay, I assess the fairness and cogency of three broad criticisms raised against 'principlism' as an approach: (1) that principlism, as an exercise in applied ethics, is insufficiently attentive to the dialectical relations between ethical theory and mortal practice; (2) that principlism fails to offer a systematic account of the principles of non-maleficence, beneficence, respect for autonomy, and justice; and (3) that principlism, as a version of moral pluralism, is fatally flawed by its theoretical agnosticism. While acknowledging that Beauchamp and Childress's reliance upon Ross's version of intuitionism is problematic, I conclude that the critics of principlism have failed to make a compelling case against its theoretical or practical adequacy as an ethical approach. In Part II, I assess the moral theory developed by Bernard Gert in Mortality: A New Justification of the Moral Rules, because Gert has recommended his approach as a systematic alternative to principlism. I judge Gert's theory to be seriously incomplete and, in contrast to principlism, unable to generate coherent conclusions about cases of active euthanasia and paternalism.


Moving forward in bioethical theory: theories, cases, and specified principlism. The field of bioethics has deployed different models of justification for particular moral judgments. The best known models are those of deductivism, casuistry, and principlism (under one, rather limited interpretation). Each of these models, however, has significant difficulties that are explored in this essay. An alternative model, suggested by the work of Henry Richardson, is presented. It is argued that specified principlism is the most promising model of justification in bioethics.


Patients' duties.

Patients' duties. This paper argues that patients' duties are derivable from the idea which typically grounds the idea of patients' rights: patient autonomy. The autonomous patient, joined in partnership with the health care professional, has self-regarding obligations and obligations to others, including health care professionals. Patients' duties include, but are not limited to: a duty to be honest about why the patient seeks care; a duty to collect information on available treatments and likely side-effects; a duty for a patient who has an infectious condition to act on that information which can best prevent further transmission.


Evaluation of the critical electron dose on the contractile activity of hydrated muscle fibers in the film-sealed environmental cell. By using the film-sealed environmental cell (EC) having a liquid-injection function, we observed a contraction reaction of hydrated myofibrils isolated from crab muscle under the transmission electron microscope. Our purpose in this work was to evaluate the critical electron dose at which the hydrated fibers lose the contractile activity. The decision of whether the fibers contracted was done by the existence of contraction band after a contraction reaction. From the observations, it was concluded that its critical dose was 2 x 10(-4) C/cm2 or 12 electrons/nm2 at a protein level.


Scanning and transmission electron microscopic studies on the upper and lower surfaces of the frog skin epidermal cells. We examined the fine structure of the upper and lower surfaces of stratified squamous epithelial cells in the skin of frogs (Hyla japonica). SEM revealed the upper surface of superficial cells covered with ramified microridges (type 3). The width of the microridges was 0.20-0.24 microns. Microridges found at the cell boundary were about 0.30 microns in width and a narrow furrow was seen between the two cells. The numerous oval disk-like structures (0.23 x 0.32 microns in diameter) covered the lower surface of these superficial cells. The upper surface of cells in the 2nd layer was covered with baculiform or ramified microridges (type 2 or 3). On the cell boundary, two linear microridges (0.23-0.27 microns in width) were parallelly arranged. The width of the microridges covering the upper cell surface was 0.09-0.10 microns. Microvilli-like processes with a height of 0.32-0.37 microns were interspersed among the microridges. Their tip formed an oval plane (0.23 x 0.31 microns), which corresponded to the size of the disk-like structures on the lower surface of the superficial cells. Desmosomes were observed on the tip by TEM. These findings show that the disk-like structures on the lower surface of the superficial cells are the sites of binding with the microvilli-like processes on the upper surface of the 2nd layer cells. The disk-like structures observed in the present study seem to be equivalent to the binding site on the upper surface of the surface cell layer of mammalian stratified squamous epithelium.


Electron microscopic visualization of collagen aggregates without chemical staining. Lateral, uni-directional aggregates of collagen, segment-long-spacing crystallites (SLS), were made by dialyzing collagen solutions against acetic acid containing ATP, and were examined by transmission electron microscopes without electron staining. There detected were at least 20 dark (electron dense) cross-striations within SLS. The banding pattern was compared with the biochemical and biophysical properties of the amino acid side chains along the collagen molecule. The banding pattern of unstained SLS was mostly correlated with the intramolecular distribution of basic amino acid residues. Since basic amino acids have relatively large side chains, the distribution of mass (molecular weight of amino acids) along the molecule (local density profile) partially explained the cross-striation. Addition of fractions of molecular weight of ATP to basic residues made the local density profile much better correlate to the banding pattern. We conclude that the electron microscopic banding pattern of unstained SLS was generated by the local amount of material or local density profile along the collagen aggregates, which was enhanced by ATP bound to positively charged basic residues. The concept that the electron density correlates with the amount of material is fundamental in electron microscopy, and it has been proven with biological materials in this paper.


Effect of hydrogen peroxide on mammalian chromatin: electron microscopic studies. Chromatins purified from rat liver as well as from cultured Chinese hamster V79 cells were treated with hydrogen peroxide in presence of iron in vitro. When examined in a transmission electron microscope, chromatins from both the sources were found to lose the native morphology. There were evidences of aggregation of the chromatin fibers. This could be due to DNA-protein and DNA interstrand crosslinking induced by Fenton reaction.


Multivariate statistical analysis of electron micrographs of a mammalian transcription initiation complex. We describe the appearance of the murine ribosomal protein (rp) L32 gene transcription initiation complex as determined by electron image analysis. Using a fractionated nuclear extract enriched for transcription factors necessary for rpL32 gene transcription in vitro and a DNA fragment containing the rpL32 gene promoter, the transcription initiation complex was prepared and viewed by standard transmission electron microscopy. Image analysis demonstrated that the complex was a multilobed structure.


Effects of basic fibroblast growth factor, transforming growth factor-beta and nerve growth factor on the secretory function of the bovine corpus luteum in vitro. The effects were investigated of basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta) and nerve growth factor (NGF) on the release of progesterone and oxytocin from the bovine corpus luteum (CL) at different stages of the oestrous cycle. A microdialysis system (MDS) of CL and a cell culture system with a reduced number of endothelial cells were used. In the MDS of CL from the mid-luteal stage (days 8-12 of the oestrous cycle), infusion with bFGF (0.1, 1, 10 and 100 ng/ml), TGF-beta (0.1, 1 and 10 ng/ml) and NGF (0.1, 1, 10 and 100 ng/ml) for 30 min induced significant acute effects on the release of progesterone. Both bFGF and NGF stimulated the release of progesterone during peptide infusion, TGF-beta and also bFGF in the period thereafter. This stimulation was dose-dependent during and after the infusion only for bFGF. This response pattern was observed at all luteal stages for the three growth factors, but bFGF was more stimulatory at the early (days 5-7) and mid-luteal stages during and after peptide infusion. The release of oxytocin was stimulated by bFGF in a dose-dependent manner. At the highest dose, bFGF, TGF-beta and NGF stimulated the release of oxytocin throughout all three luteal stages. When luteal cells were cultured with growth factors, only TGF-beta showed a dose-dependent inhibition of both basal and LH-stimulated progesterone as well as oxytocin release (measured between 48 and 52 h of culture). NGF had an inhibitory effect only on the basal release of oxytocin. bFGF had no effect on the release of either hormone under continuous stimulation in cell culture. The results indicate that bFGF, TGF-beta and NGF act directly and acutely on the secretory function of bovine CL in the MDS but also have long-term effects as shown in cell culture. bFGF appears to be an important autocrine/paracrine regulator of CL function, since local expression of its mRNA, peptide synthesis and its mitogenic and non-mitogenic actions have now been confirmed. Endothelial cells from the CL have been identified as target cells for bFGF. Differences observed between the two systems might thus be attributed to the presence or absence of cell-to-cell contact and a reduced number of endothelial cells, as well as to the duration of peptide stimulation and medium changes every 24 h compared with the flow-through conditions in the MDS.


Effects of tri-iodothyronine and insulin-like growth factor-I (IGF-I) on alkaline phosphatase activity, [3H]thymidine incorporation and IGF-I receptor mRNA in cultured rat epiphyseal chondrocytes. The effects of tri-iodothyronine (T3) and insulin-like growth factor-I (IGF-I) on [3H]thymidine incorporation, alkaline phosphatase (ALP) activity and IGF-I receptor mRNA levels were studied in rat epiphyseal chondrocytes cultured in monolayer. Chondrocytes from enzymatically digested rat tibia epiphyseal growth plates were seeded in monolayer culture and precultured for 7-14 days in Ham's F-12 medium supplemented with 10% (v/v) newborn calf serum and 1% (v/v) of a serum substitute. After preculture the medium was changed to Ham's F-12 medium containing 1% (v/v) serum from hypophysectomized rats, and the effects of T3 and/or IGF-I on DNA synthesis ([3H]thymidine incorporation), ALP activity (a late marker of differentiated epiphyseal chondrocytes) and IGF-I receptor mRNA levels were studied. ALP activity was increased by T3 in a dose-dependent manner with a maximal response at 10 micrograms T3/l (678 +/- 86% compared with control culture). The increase in ALP activity was accompanied by a concomitant decrease in [3H]thymidine incorporation (52 +/- 14% compared with control culture). Human GH (hGH; 50 micrograms/l) and IGF-I (25 micrograms/l) had no stimulatory effect on ALP activity. However IGF-I (10 micrograms/l) exerted an inhibition on the T3 (10 micrograms/l)-induced increase in ALP activity (64 +/- 9% compared with T3-treated culture). T3 (3 micrograms/l) inhibited the increase in [3H]thymidine incorporation caused by 25 micrograms IGF-I/l (51 +/- 13% compared with IGF-I-treated culture). Furthermore, IGF-I receptor mRNA levels were increased by 10 micrograms T3/l (137 +/- 4.2% compared with control culture) while no effect of hGH (50 micrograms/l) or IGF-I (25 micrograms/l) was demonstrated. Both T3 and IGF-I were shown to interact with epiphyseal chondrocytes and both substances seemed to affect cell proliferation and maturation and therefore longitudinal bone growth. Furthermore, the results indicated that IGF-I is important for proliferation of the cells while T3 initiates the terminal differentiation of epiphyseal chondrocytes.


Glycyrrhizin induces mineralocorticoid activity through alterations in cortisol metabolism in the human kidney. It has been suggested that the mineralocorticoid action of glycyrrhizin is caused by a defect in the conversion of cortisol to cortisone through inhibition of the enzyme 11 beta-dehydrogenase (11 beta-DH). We investigated the functional significance of the inhibition of this enzyme as a mechanism of the mineralocorticoid action of glycyrrhizin. Eighteen healthy volunteers were divided into three groups of six and treated as follows: (1) 225 mg glycyrrhizin/day, (2) 0.1 mg 9 alpha-fluorocortisol (FC)/day and (3) 225 mg glycyrrhizin and 1.5 mg dexamethasone/day, all of which were given for 7 days. The administration of glycyrrhizin or FC induced a similar mineralocorticoid effect; specifically, suppression of plasma renin activity, hypokalaemia and kaliuresis. During the concomitant administration of glycyrrhizin and dexamethasone, however, these mineralocorticoid effects were significantly attenuated. During the administration of glycyrrhizin, urinary excretion of cortisol increased without change in the plasma levels of cortisol, while both plasma level and urinary excretion of cortisone decreased. Changes in cortisol metabolism were not observed during the administration of FC. These results demonstrated the functional significance of the inhibition of 11 beta-DH in the mineralocorticoid activity of glycyrrhizin in man.


Carbachol increases intracellular free calcium concentrations in human granulosa-lutein cells. We investigated whether the stimulation of human granulosa-lutein cells with muscarinic and nicotinic receptor agonists can cause increases in intracellular free calcium (Ca2+), using Fura-2 microfluorimetry. The addition of carbachol (a non-selective muscarinic and nicotinic receptor agonist) to cultured human granulosa-lutein cells increased intracellular free Ca2+ levels. Concentrations as low as 10 nmol/l were effective. In contrast, nicotine did not evoke elevations of intracellular free Ca2+. Basal Ca2+ levels ranged around 70-140 nmol/l and maximal, carbachol-induced peaks reached 1.1 mumol/l. The carbachol-induced Ca2+ signal was abolished after preincubation of the cells with the muscarinic receptor antagonists quinuclidinyl benzilate or atropine, but it was not affected by removal of extracellular Ca2+. Further evidence for the involvement of intracellular Ca2+ stores is provided by experiments in the absence of extracellular Ca2+. While thapsigargin (a blocker of ATP-driven Ca2+ uptake by intracellular stores) and ionomycin (an ionophore by which Ca2+ is released from intracellular stores) evoked small Ca2+ transients, cells pretreated with these agents did not respond to carbachol any more. These data suggest the presence of a functional muscarinic receptor on human granulosa-lutein cells and imply the involvement of intracellular Ca2+ stores during the cellular response. These results also suggest the participation of the nervous system, acting through muscarinic receptors, in the control of the function of human granulosa-lutein cells.


Influence of ovarian steroids on myometrial sensitivity and tolerance to relaxin in the rat in vivo: lack of cross-tolerance between relaxin, salbutamol and cromakalim. The influence of oestradiol benzoate and progesterone on uterine sensitivity and development of tolerance to relaxin was investigated in bilaterally ovariectomized non-pregnant rats in vivo. Bolus doses of relaxin (2-20 micrograms/kg i.v.) produced rapid and reversible inhibition of uterine contractions in a dose-dependent manner. Treatment with oestradiol benzoate or oestradiol benzoate plus progesterone significantly increased uterine sensitivity to relaxin over 48 h by 2.4- to 8.5-fold. Tolerance to relaxin developed during continuous infusion of the hormone at 20 micrograms/kg per h for 40 h. A 7.8- to 17.4-fold reduction in sensitivity to relaxin was observed in relaxin-infused rats, whereas no change in sensitivity was observed in saline-infused rats. Infusion of relaxin at 50 micrograms/kg per h for 40 h produced a 131.8-fold reduction in uterine sensitivity to relaxin. The uterus remained tolerant to relaxin for up to 24 h after cessation of infusion. Treatment with oestradiol benzoate and/or progesterone did not influence the extent of tolerance development, but a more rapid recovery of uterine sensitivity to relaxin was observed in rats treated with oestradiol benzoate plus progesterone. Cross-tolerance with other uterine relaxant drugs was measured to investigate possible common mechanisms of action and sites of tolerance between relaxin and a beta-adrenoceptor agonist (salbutamol) and potassium channel openers (cromakalim and minoxidil sulphate). No cross-tolerance was observed between relaxin and salbutamol, or relaxin and cromakalim or minoxidil sulphate. Cross-tolerance between cromakalim and minoxidil sulphate was seen.


Interaction between myometrial relaxants and oxytocin: a comparison between relaxin, cromakalim and salbutamol. The influence of treatment with oestradiol on the effects of the uterine relaxants, relaxin, salbutamol (an agonist at beta 2-adrenoceptors) and cromakalim (a potassium channel opener) and their interactions with the uterine stimulant oxytocin were investigated in vivo in the ovariectomized rat. Oestradiol benzoate (0.4 micrograms/kg per day) significantly increased sensitivity to cromakalim as an inhibitor of spontaneous uterine contractions compared with vehicle-treated rats by approximately threefold. The same dose of oestradiol benzoate had no effect on uterine sensitivity to salbutamol. Previous studies have shown that this dose of oestradiol benzoate produces a twofold increase in uterine sensitivity to relaxin as an inhibitor of spontaneous contractions. Oestradiol influenced the ability of relaxin to inhibit oxytocin-stimulated uterine contractions. In corn oil-treated rats, uterine responses to relaxin were markedly reduced during oxytocin infusion compared with responses to relaxin before oxytocin; the maximum obtainable response to relaxin was less than 50% inhibition. In oestradiol-treated rats, uterine sensitivity to relaxin during oxytocin infusion was similar to that observed against spontaneous contractions. Cromakalim was able to inhibit uterine contractions during oxytocin infusion in both corn oil- and oestradiol-treated rats, uterine sensitivity to cromakalim being similar in the absence and presence of oxytocin for both hormone treatment groups. Salbutamol was also able to inhibit uterine contractions during oxytocin infusion in both corn oil- and oestradiol-treated rats. Oestradiol treatment increased the potency of salbutamol as an inhibitor of oxytocin-stimulated uterine contractions compared with corn oil treatment by 3.5-fold. The interaction of oestradiol and relaxin during late pregnancy may be important for attenuation of the myometrial response to stimulants.


Relationship between the resting metabolic rate and hepatic metabolism in rats: effect of hyperthyroidism and fasting for 24 hours. We have examined the relationship between the changes in resting metabolic rate (RMR) and those in hepatic metabolism induced by hyperthyroidism and fasting for 24 h. We found that hyperthyroidism induced a significant increase in RMR, while fasting for 24 h reduced RMR in euthyroid but not in hyperthyroid rats. We have also measured oxygen consumption in isolated hepatocytes from euthyroid and hyperthyroid rats, fed or fasted for 24 h. Hyperthyroidism induced an increase in oxygen consumption in rat liver cells; fasting for 24 h increased respiratory rates in isolated liver cells from euthyroid but not from hyperthyroid rats. The findings showed that hyperthyroidism and fasting for 24 h have opposite effects on RMR but similar effects on hepatic metabolism. The results also indicated that the increase in RMR found in hyperthyroid rats is partly due to an increase in hepatic metabolism, while no correlation exists between variations in resting and hepatic metabolism induced by 24-h fasting.


Specific binding sites for 125I-labelled epidermal growth factor in the ovine corpus luteum and human placenta. Specific, high-affinity binding sites for radiolabelled mouse epidermal growth factor (mEGF) were demonstrated in homogenates and membranes of ovine corpora lutea. Subcellular fractionation on sucrose density gradients demonstrated that luteal EGF receptors were associated with fractions enriched in cell surface-membrane markers. Binding of 125I-labelled mEGF to ovine luteal EGF receptors was dependent on the pH, temperature and duration of incubation, and on the concentration of metal ions present in the incubation medium. Unlabelled mEGF and human EGF (urogastrone) competed for the binding of radiolabelled mEGF to ovine luteal homogenates at low doses (half-maximal inhibition of binding (IC50) at 2-3 nmol/l). Transforming growth factor-alpha also competed for mEGF-binding sites (IC50, 4-10 nmol/l), but a range of peptides, growth factors and protein hormones were ineffective at much higher concentrations. Concave Scatchard plots for 125I-labelled EGF binding and Hill coefficients of < 1 for displacement radiolabelled EGF suggested negative co-operativity of binding sites, and dilution at equilibrium accelerated the rate of dissociation of 125I-labelled EGF from human placental (but not from ovine luteal) receptors. Specific EGF-binding sites were also demonstrated in rat and rabbit placental homogenates, and in luteal homogenates of the pig. Luteal concentrations of EGF receptors appeared to be reduced significantly during early pregnancy in both the pig and sheep.


11 beta-Hydroxysteroid dehydrogenase in the rat ovary: high expression in the oocyte. The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the conversion of physiological glucocorticoids to inactive products, thus modifying the access of glucocorticoids to glucocorticoid and mineralocorticoid receptors. Glucocorticoids may affect ovarian function both indirectly and via binding to ovarian receptors. We have demonstrated 11 beta-HSD bioactivity and mRNA expression in rat ovary in vitro. The enzyme was localized to oocytes and luteal bodies immunohistochemically using two antibodies raised against purified rat liver 11 beta-HSD. These data are supported by in-situ hybridization studies, which also localized 11 beta-HSD mRNA expression to oocytes and luteal bodies. The results suggest that 11 beta-HSD may modulate the effects of glucocorticoid on ovarian function.


Growth hormone promotes early initiation of hepatocyte growth factor gene expression in the liver of hypophysectomized rats after partial hepatectomy. GH accelerates hepatic regeneration in the rat. Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, is considered to be a major regulator of hepatic regeneration. In the present study, the effects of GH and insulin-like growth factor-I (IGF-I) on HGF gene expression in regenerating rat liver was investigated. In hypophysectomized rats treated with GH, hepatic HGF mRNA levels were increased 3 h after partial hepatectomy and reached peak levels after 5 h. In rats with intact pituitaries and in hypophysectomized rats not given GH treatment, HGF mRNA levels in liver were unchanged during the first 5 h following hepatectomy and reached peak levels after 10-18 h. DNA synthesis in the liver of GH-treated rats increased from low levels 10 h after hepatectomy to peak levels after 18 h. In rats without GH treatment the synthesis of DNA was still low 18 h after hepatectomy and was increased after 26 h. Treatment of hypophysectomized rats with IGF-I promoted increases in hepatic HGF mRNA levels and DNA synthesis 3.5 h and 15 h after hepatectomy respectively. HGF mRNA levels were constantly lower after sham-hepatectomy than after partial hepatectomy. In summary, in hypophysectomized rats the responses of hepatic HGF gene expression and DNA synthesis to partial hepatectomy were both accelerated by treatment with GH or IGF-I.


Activation of the hypothalamo-pituitary-adrenocortical axis in the conscious rabbit by the pyrogen polyinosinic:polycytidylic acid is dependent on corticotrophin-releasing factor-41. The pyrogenic interferon inducer polyinosinic:polycytidylic acid (Poly I:C) was shown to activate the rabbit hypothalamo-pituitary-adrenocortical (HPA) axis in vivo. The immunoreactive cortisol response to Poly I:C (2.5 micrograms/kg) was shown to have a corticotrophin-releasing factor-41 (CRF-41)-dependent component which was abolished by peripheral immunoneutralization using an anti-CRF-41 monoclonal antibody (KCHMB001; 2.5 mg/kg i.v.). Peripheral administration of the arginine vasopressin (AVP) V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin; 225 nmol/kg i.v.) had no effect on the response of immunoreactive cortisol to Poly I:C, suggesting that AVP was not involved in activation of the HPA axis. Poly I:C increased both body temperature and circulating immunoreactive prostaglandin E2; these responses were abolished by the cyclo-oxygenase inhibitor ketoprofen (3 mg/kg s.c.). The immunoreactive cortisol response to Poly I:C, however, remained after the administration of ketoprofen, indicating a prostaglandin (PG)-independent component. The immunoreactive cortisol levels in control, saline vehicle-treated, animals were reduced by both the CRF-41 receptor antagonist (alpha-helical CRF (9-41); 6.25 nmol/kg i.v.) and ketoprofen (3 mg/kg s.c.) indicating that this basal state is dependent on both CRF-41 and PGs.


Epidermal growth factor concentrations in pig tissues and body fluids measured using a homologous radioimmunoassay. A homologous radioimmunoassay for the measurement of epidermal growth factor (EGF) levels in pig tissues and body fluids has been developed using an antiserum to recombinant porcine EGF. The assay is highly specific, showing no cross-reactivity with a variety of other polypeptides including the structurally related protein, transforming growth factor-alpha. Furthermore, < 1% cross-reactivity was observed with mouse EGF emphasizing the necessity for homologous assays for EGF measurement. Immunoreactive EGF was present in extracts of pig kidney and pancreas (3.44 +/- 0.43 and 0.76 +/- 0.13 (S.E.M.) pmol/g wet weight respectively), but was not detected in extracts of submaxillary gland or liver. Although immunoreactive EGF was not detectable in uterine, allantoic or ovarian follicular fluids, colostrum contained EGF at biologically active concentrations (0.84 +/- 0.15 nmol/l). Immunoreactive EGF was also present in pig urine, with similar concentrations in samples from male or female animals. In addition, pig urine inhibited the binding of 125I-labelled EGF to 3T3 fibroblasts and stimulated DNA synthesis in quiescent monolayers of these cells, indicating that the immunoreactive material in urine is biologically active. Quantitative comparisons of the data presented here with that published previously indicate considerable species variation in the EGF levels of various tissues and body fluids.


Salivary insulin-like growth factor-I originates from local synthesis. Insulin-like growth factor-I (IGF-I) is a GH-dependent growth factor found in its highest concentrations in plasma. It is also measurable in saliva. The origins of salivary IGF-I concentrations were studied. Intracardial administration of Sprague-Dawley rats with 125I-labelled IGF-I and subsequent analysis of plasma and saliva samples by exclusion gel chromatography and SDS-PAGE, followed by autoradiography, demonstrated the apparent inability of IGF-I to cross from the plasma pool through to saliva. 125I-Labelled IGF-I was not chromatographed immediately before injection, resulting in administration of free iodide along with the iodinated peptide. This free iodide was demonstrable in saliva, indicating that movement of substances from plasma to saliva was measurable using the levels of 125I activity administered. Free iodide in saliva was not contributed to by 125I-labelled IGF-I degradation since 125I-labelled IGF-I was shown to be stable in saliva over 24 h. These data indicated that IGF-I in saliva is produced locally. Identification of a 4.7 kb IGF-I mRNA transcript in rat parotid salivary gland was consistent with IGF-I synthesis within that tissue.


Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor. The infusion of low doses of epidermal growth factor (EGF) into lactating ewes stimulates water intake and urine volume. The plasma concentrations and daily output of various electrolytes in milk and urine are also affected. We have investigated this further by recording the effects of EGF infusion on fluid balance, electrolyte profiles and plasma concentrations of glucose and parathyroid hormone (PTH) in non-pregnant, non-lactating ewes. Twenty-four animals (n = 8 per group) received infusions of 100 ml saline/day into the jugular vein for 10 days (days 1-10) followed by EGF at a dose rate of either 1 (low dose), 5 (medium dose) or 10 (high dose) micrograms/kg liveweight per day in 100 ml saline for 5 days (days 11-15). All ewes then received an infusion of 100 ml saline/day for 10 days (days 16-25). Most plasma and urine samples had undetectable concentrations of EGF-immunoreactive material during the periods of saline infusion. During EGF infusion, the highest amounts of EGF infusate excreted in urine were 1.6, 5.9 and 5.6% for ewes in low, medium and high dose groups respectively. Water intake increased by 17% (0.5 kg), 88% (2.5 kg) and 89% (2.3 kg) and urine volume increased by 29% (0.5 kg), 108% (2.2 kg) and 134% (2.1 kg) for the three groups respectively. Fluid balance and feed intake were not affected by EGF infusion, but the output of faecal dry matter was reduced in ewes receiving the two higher doses of EGF. All levels of EGF resulted in hypocalcaemia, increased plasma PTH concentrations and hypermagnesaemia. There was no effect of EGF on plasma concentrations of K+ and glucose or on daily urinary excretion of K+ and Mg2+. The only response to the low dose was a reduced plasma concentration of Na+ and an increased daily urinary urate excretion. The two higher doses increased the daily urinary excretion of Na+, PO4(3-) and urate, but had no effect on the respective concentrations in plasma. Urinary Ca2+ excretion was reduced only during infusion of the medium dose of EGF. The responses of most variables were similar during infusion of the medium and high doses of EGF. All three doses of EGF induced polydipsic and diuretic responses in ewes, and infusions of 5-10 micrograms EGF/kg liveweight per day affected renal excretion of Ca2+, Na+ and PO4(3-). We interpret the responses of the kidney and plasma PTH concentrations as a means of maintaining the homeostasis of plasma profiles of electrolytes.


Effect of different sealers on thermoplasticized Gutta-percha root canal obturations. The objective of this study was to test the hypothesis that the apical seal provided by thermoplasticized root canal obturations depends on the film thickness of the sealer used. The root canals of 120 maxillary cuspid teeth were instrumented and divided into six equal groups of 20 teeth. A thermoplasticized gutta-percha root canal obturator was used to make an impression of the lubricated canal and coated with a sealer cement before reseating. Five different sealer cements of known film thickness were studied. They were, in the decreasing order of film thickness, Roth's Type I Cement, Seal-apex, Lee Endofil, AH26, and Ketac-Cem. The control group that received no sealer was prepared as recommended by the manufacturer. The degree of microleakage was based on the depth of dye penetration from the apical end measured by two independent examiners. The data collected were analyzed by analysis of variance and Weibull distribution. Analysis of variance shows that the control group exhibited significantly higher dye penetration depth (p < 0.05) while there were no significant differences among the other five groups. Analysis by Weibull distribution function shows that Lee Endofil and AH26 exhibited a higher percentage of lower linear dye penetration values compared with other groups.


Intracanal placement of Ca(OH)2: a comparison of techniques. Ten extracted human maxillary first molars were selected with a variety of root curvatures. The distofacial roots were resected and the mesiofacial canals were instrumented to a size #25 K file. Three techniques were used to introduce Ca(OH)2 paste into the instrumented canals. These techniques were evaluated for their ability to carry the Ca(OH)2 to working length and also to produce a dense fill. The Lentulo spiral was most effective in carrying the paste to working length. The Lentulo spiral also produced the highest quality fill. The Calasept injection system followed by a #25 finger plugger was the second most effective technique. Counterclockwise rotation of a #25 K file was the least effective of the techniques tested.


Effects of Nd:YAG laser on apical seal of teeth after apicoectomy and retrofill. The application of Nd:YAG laser to tooth surface can change its surface permeability. The purpose of this study was to investigate the effects of Nd:YAG laser on the permeability of dentin following apicoectomy and retrofill. Sixty single-rooted teeth were randomly assigned to six groups of 10 teeth each. The six groups were arranged in three pairs, experimental and control groups. The canals of teeth in pairs 1 and 2 were cleaned, shaped, obturated, and their apical 2 mm were resected. A class I preparation was prepared and filled with amalgam in each tooth in pair 1. The apical 2 mm of each tooth in pair 3 was removed, and a class I preparation was prepared and filled with amalgam. The apical surface of resected roots in half of the samples in each pair was lased twice by using Nd:YAG laser. The duration of lasing and the number of pulses were recorded for each tooth. After application of nail polish to the unoperated surface of each tooth, the teeth were placed in 0.5% methylene blue dye for 48 h. The amount of dye penetration in sagittal sections of each tooth was measured. The amount of dye penetration was significantly lower in lased roots than in nonlased ones (p < 0.05). Based on our results, it appears that application of Nd:YAG laser reduces the permeability of resected roots.


Evaluation of internal sealing ability of three materials. Thirty-six maxillary central incisors were prepared in a manner similar to nonvital bleaching procedures. They were examined with respect to the degree of procion green dye penetration of dentin with and without heating. Cavit, IRM, and zinc phosphate cement were used to evaluate their sealing ability. Cavit and IRM provided better internal sealing of the dentin than did zinc phosphate cement.


Torsional testing of Canal Master U hand instruments. Ten each of size 25, 30, 35, 40, and 45 Canal Master U hand instruments were tested for torsional failure and revolutions to failure. In addition, the point at which separation occurred was measured on the instrument shaft. An Instron 1125 machine was used for all torsion testing. The mean torque failure value for size 25 and 35 Canal Master U instruments exceeded the ADA specification No. 28 minimum values while sizes 30, 40, and 45 were below the ADA minimum average values. All Canal Master U averages for revolutions to failure exceeded the ADA minimums. Although size 25 was above the minimum average, due to a wide range of values, 5 of the 10 were below the ADA specification No. 28 values. The point of instrument separation was 0.325 to 1.575 mm behind the cutting head. Due to the structural design differences of endodontic files versus Canal Master U, it is suggested that an additional category of ADA specification be introduced for Canal Master endodontic instruments.


The mental foramen: 3. Size and position on panoramic radiographs. Panoramic radiographs were made of 75 dry, adult human mandibles. The size and position of the mental foramen in relation to the second premolar was determined. The mental foramen on panographic radiographs was slightly larger than reported on periapical radiographs. The average position of the foramen was mesial and below the radiographic apex of the tooth. Panoramic radiography may account for a distal shift of the foramen and a 23% increase in size of the mandibles examined.


Long-term evaluation of surgically placed amalgam fillings. The coauthors of this article had developed the clinical impression that whereas surgically placed amalgam fillings are successful on a short-term basis, the long-term prognosis for these cases may not be nearly as favorable. In order to test this hypothesis, as many patients as could be contacted, either directly or indirectly, who had been treated before 1981 were evaluated. Excluded from this study were cases for which failure could be attributed to any reason other than failure from the amalgam reverse filling. Therefore, all cases included had to demonstrate periapical healing prior to ultimate breakdown. On this basis, 60 of 104 teeth (57.7%) were considered to be successful and 44 teeth (42.3%) were determined to be failures.


Periodontal changes following coronal/root perforation and formocresol pulpotomy. A clinical case report is presented which describes the sequelae of an iatrogenic lateral crown/root perforation and a formocresol pulpotomy. The post-operative course of the initial therapy included significant hard and soft tissue destruction and eventual tooth loss. The possible implication of the role of formocresol is discussed.


The Epping jaundice outbreak: a 24 year follow up. The aim was to trace 84 cases of jaundice that occurred following accidental ingestion of methylene dianiline (MDA) in Epping in 1965, and to look at long term health effects. The original case notes of the cases were used to identify the patients. Subsequent tracing procedures included local general practitioners, the Central NHS Registry, electoral rolls, and company records. This was a community based survey. The health status of 68 (81%) of the group was established with 18 deaths. Of the 50 cases known to be alive, 58% completed a health questionnaire. The causes of death were unremarkable except for one case of carcinoma of the biliary tract. Two surviving cases had suffered retinal pathology. Four other surviving cases had had a further, perhaps unrelated, episode of jaundice. Although the dose and route of administration in the epidemic differed from occupational exposure, this follow up study a generation on provides little, if any, evidence of long term health sequelae. Nevertheless, in the absence of well documented exposure and health effects data, such accidental poisonings with proven animal carcinogens warrant long term follow up. The identified cohort will be the subject of further study.


Auditing and improving notification and chemoprophylaxis in bacterial meningitis. The aim was to audit, against agreed standards, the control of bacterial meningitis, in particular completeness of notification and appropriateness of distribution of chemoprophylaxis to contacts; and to implement appropriate changes and monitor their impact. The first phase involved determination, for the years 1983 and 1984, of completeness of notification by comparison with a comprehensive case register. Information about chemoprophylaxis was obtained from case notes, questionnaires to general practitioners and other records. The second phase involved introducing a programme of clinician education in the hospital with the poorest observed notification performance and re-examining performance during 1988. Districtwide education regarding chemoprophylaxis was undertaken and the situation re-examined in 1988. The study took place in Mid Glamorgan Health Authority (population 536,000), with four acute hospitals. Consisted of all the residents of Mid Glamorgan Health Authority. During the first phase of the audit only 28 out of 79 cases of bacterial meningitis were notified (35%). Performance in one hospital was significantly worse than in the other three. Chemoprophylaxis was distributed to 20 out of 26 (77%) cases of meningococcal meningitis but inappropriate drugs were used in four cases and prophylaxis was distributed more widely than is recommended in 10 cases. In the phase 2 re-examination, a significant improvement in notification was observed in the hospital where special measures were taken, with no change in a "control" hospital. Chemoprophylaxis improved throughout the District, although rifampicin continued to be distributed too widely. As a result of this audit, measurable improvements in both infectious disease notification and chemoprophylaxis practice were obtained by the education of clinicians. The study provides a good example of a completed audit cycle in public health medicine.


Bacteriological survey of tuberculous lymphadenitis in southeast England, 1981-1989. The aim was to detect any changing trends in the nature and incidence of tuberculous lymphadenitis in southeast England and to determine whether there is any evidence for an increase in this disease that could be related to HIV infection. Mycobacteria isolated from patients with lymphadenitis in the years 1981 to 1989 were identified. Information was available on the age, sex, and ethnic origin of the patients and the anatomical site from which the mycobacterium was isolated. The Public Health Laboratory Service Regional Tuberculosis Centre at Dulwich, which receives over 95% of mycobacteria isolated in southeast England. From 1980 to 1989, cultures were received from 1817 patients with mycobacterial lymphadenitis: 1677 were M tuberculosis, 25 M bovis, 21 M africanum, and 94 were other (environmental) species. In comparison with a survey conducted in the same region in 1973-80, the number of ethnic Indian subcontinent patients with lymphadenitis due to M tuberculosis had dropped by 30% and the number of European patients had dropped by 43% and showed a continuing decline and a shift towards an older age group. By contrast, there was a 20% increase in the number of cases due to environmental mycobacteria. The number of species causing such infections had increased and a greater proportion of patients were adults. Three patients infected by environmental mycobacteria were known to be HIV positive. The incidence of lymphadentis due to M tuberculosis is declining but cases due to environmental mycobacteria are increasing, with a greater diversity of species and more adult patients. There is no conclusive evidence for an impact of HIV infection on the incidence and nature of mycobacterial lymphadenopathy in southeast England, but this cannot be ruled out.


The Thule episode epidemiological follow up after the crash of a B-52 bomber in Greenland: registry linkage, mortality, hospital admissions. The aim was to explore the pattern of disease in staff associated with a bomber that crashed in 1968 when carrying nuclear bombs. The database was constructed from staff files of Danish workers employed from 1 April 1963 to 1 July 1971. Comparison was made between subsequent mortality and hospital admissions of workers employed during the clean up of the crashed bomber, and those employed outside this period. The study involved workers employed at Thule US air base in Greenland. During 1963-1971, 4322 staff were employed at the air base. Of these, 4265 (98.7%) were identified in 1987, among whom 1202 workers were employed during the clean up period. No differences were found in total mortality, or mortality from cancer, heart disease, or accidents, after allowing for differences in age, marital status, or length of employment, between those employed during the clean up period and those employed at other times. Similarly, no difference in hospital admissions between the two groups was found. No harmful effects on health due to the crash were found, as measured by mortality and hospital admissions.


Symptomatology of children in contact with sea water contaminated with sewage. The aim was to determine whether or not there was a measurable risk of ill health associated with contact with sea water for children between the ages of 6 and 11 years old. This was a prospective survey carried out on Blackpool beach. Parents of children between the ages of 6 and 11 years were interviewed over a seven week period during July, August, and September, 1990. Respondents were followed up 10-14 d after the original interview by either telephone or post. Water samples were collected on each day of the survey. 939 interviews with parents or guardians were completed on the beach; 857 (91.9%) of these persons agreed to a follow up interview. The results of this study are based on 703 cases of matched data, of good quality, collected for each child on the beach and during a follow up interview. Non-compliance with the European Community microbiological imperative standards for recreational waters at Blackpool Tower and South Pier sampling sites, respectively, ranged between: 6% and 7% for total coliforms; 13% and 25% for faecal coliforms; 69% and 80% for faecal streptococci (Guide standard); 50% and 67% for salmonellae and 73% and 88% for enteroviruses. There was a significant overall increase in the mean number of symptoms reported for each child (p < 0.001). However, the prevalence of certain symptoms increased significantly only in those children who had been in contact with the water on the day of the beach interview. These symptoms included vomiting (p < 0.0009), diarrhoea (p < 0.0001), itchy skin (p < 0.0009), fever (p < 0.0013), lack of energy (p < 0.0007), and loss of appetite (p < 0.0227). None of the other variables investigated could account for the significant increase in the reported symptom experience of those children in contact with sea water contaminated with sewage. Children who come into contact with contaminated sea water are likely to develop symptoms as a result.


The Small Area Health Statistics Unit: a national facility for investigating health around point sources of environmental pollution in the United Kingdom. The Small Area Health Statistics Unit (SAHSU) was established at the London School of Hygiene and Tropical Medicine in response to a recommendation of the enquiry into the increased incidence of childhood leukaemia near Sellafield, the nuclear reprocessing plant in West Cumbria. The aim of this paper was to describe the Unit's methods for the investigation of health around point sources of environmental pollution in the United Kingdom. Routine data currently including deaths and cancer registrations are held in a large national database which uses a post code based retrieval system to locate cases geographically and link them to the underlying census enumeration districts, and hence to their populations at risk. Main outcome measures were comparison of observed/expected ratios (based on national rates) within bands delineated by concentric circles around point sources of environmental pollution located anywhere in Britain. The system is illustrated by a study of mortality from mesothelioma and asbestosis near the Plymouth naval dockyards during 1981-87. Within a 3 km radius of the docks the mortality rate for mesothelioma was higher than the national rate by a factor of 8.4, and that for asbestosis was higher by a factor of 13.6. SAHSU is a new national facility which is rapidly able to provide rates of mortality and cancer incidence for arbitrary circles drawn around any point in Britain. The example around Plymouth of mesothelioma and asbestosis demonstrates the ability of the system to detect an unusual excess of disease in a small locality, although in this case the findings are likely to be related to occupational rather than environmental exposure.


Screening infants for hearing loss--an economic evaluation. The aim was to carry out an economic evaluation of the programme implemented in one district health authority for the screening of infants for hearing loss. The approach taken was a cost-effectiveness analysis using the methodology of decision analysis to model the options appraised: (1) the conventional screening policy was for a health visitor and colleague to screen at 8-9 months, and at 10 months for each child to be seen again by a clinical medical officer for a developmental assessment plus hearing screen if necessary; (2) the alternative policy was for screening to take place at 10 months only if concern is expressed (or if there is a clinical indication) at the developmental assessment; the introduction of a "clue list" was considered; (3) the third option was no screening. The annual expected cost per unit output was pounds 20.57 for the conventional screening policy, between pounds 11.13 and pounds 11.23 for the alternative policy, and pounds 11.27 for the third option of no screening. Introducing the "clue list" under the alternative screening policy is likely to raise the cost per unit output, but the effects are uncertain. The results suggest that the alternative screening policy is more cost-effective than the conventional policy, but has little advantage over not screening at all. The effects of introducing a clue list need further investigation.


Factors influencing childhood immunisation in an urban area of Brazil. The aim was to examine the factors associated with incomplete vaccination in an urban area in Sao Paulo, Brazil; and to explore whether differences in vaccine coverage in the catchment area of health centres remain after the demographic constitution of the population in these areas is controlled for. The children were selected as controls for a case-control study. 455 children were selected at random (but age matched) from the health centre registries. Data was collected from the health centre records and from home interviews. All children were registered in FAISA, a municipal health service comprising a large network of health centres and hospitals. FAISA's services are free at the point of delivery, and over 85% of the city's children are registered. Participants were selected to represent, except in their age distribution, all children registered in the municipal health service. Information was collected on subjects' vaccine history, year of birth, sex, birth order and birth weight, and health centre of registration; their mothers' age, education, and marital status; and the family's income per capita and history of migration. Analysis was undertaken to identify risk factors for vaccination and whether the differential coverage in health centres' catchment areas remained after demographic characteristics of the population were controlled for. The high coverage for DPT and polio vaccines suggests that low overall coverage was not simply a result of mothers failing to bring children for vaccination. The variable that best predicted vaccine coverage was year of birth. Children born to immigrant mothers or into large families had lower vaccine uptake. The characteristics of children and their mothers did not account for the variation in vaccination coverage in catchment areas of different health centres. It is likely that in this area vaccination completeness was associated mainly with the health centre's ability to deliver vaccination to the target population.


A case-control evaluation of the effect of breast cancer screening in the United Kingdom trial of early detection of breast cancer. The aim was to assess the extent to which selection bias affects a case-control study of breast cancer screening in which attenders and non-attenders for screening are compared. There were two retrospective case-control studies, one estimating the risk of death from breast cancer in women in the screening district relative to those in the comparison district (study A), the second estimating the relative risk for women who had ever been screened compared with women who had never been screened in the screening district alone (study B). For cases and controls in study B, the women's screening history was summarised for the time period from date of entry to diagnosis of the case, or the equivalent time from date of entry for the matched controls. For cases detected by screening, the screen at which cancer was detected was included in the screening history. Cases were deaths from breast cancer in women with disease diagnosed after entry to the trial, up to 31 December 1986 or a maximum of seven years from date of entry, in one of the screening districts (Guildford) and one of the comparison districts (Stoke) participating in the UK Trial of Early Detection of Breast Cancer: study A: 198 deaths in Guildford and Stoke; study B: 51 deaths in Guildford only. There were five age matched controls for each case, with length of follow up at least as great as the time from entry to death of the case. The estimate of the risk of death from breast cancer in the screening district relative to the comparison district from study A was 0.76, thus implying a reduction of 24% in the screening district, similar to that obtained from a cohort analysis of data from the two districts. In contrast, the relative risk in study B for ever v never screened women was 0.51, which, taking the 72% compliance into account, would result in a relative risk of 0.65 for the screening district if there were no selection bias. The risk of breast cancer mortality in the never screened relative to the comparison district was 1.13, despite the fact that incidence rates in the two populations were similar. This suggested that cancers in the never screened group had a particularly poor prognosis, contributing to selection bias. The possible existence of selection bias should lead to caution in interpretation of the results of case-control studies of the effect of breast cancer screening on mortality.


Influence of rural environment on diagnosis, treatment, and prognosis of colorectal cancer. Several studies have shown that residential location (urban or rural) influences the incidence of colorectal cancer. The aim was to investigate the influence of rural environment on colorectal cancer history and survival in a well defined population. Patients with colorectal cancer diagnosed in the department of Calvados (France) were classified by place of residence (urban/rural) and information on clinical symptoms, tumour extension, treatment, and survival was collected. The study was population based, in the department of Calvados in France. During 1978-1984, 1445 colorectal cancers were collected by the Digestive Tract Cancer Registry of Calvados, 1047 with an urban place of residence (544 males and 503 females) and 284 with a rural place of residence (134 males and 150 females). In both sexes, rural patients with colorectal cancers were treated less frequently in a specialised health care centre (40.0%) than patients from an urban population (53.4%). The difference was mainly but not entirely explained by distance from the specialised health care centre. In females in the rural population, cancers were diagnosed more frequently at the stage of severe clinical symptoms (22.1%) and metastases (18.8%) than they were in the urban population (15.5% and 12.3%). In addition among females a rural environment appeared to confer a worse prognosis (relative risk = 1.3). Our findings suggest an inequality between rural and urban populations, especially for women. The loneliness of rural women leads to a delay in diagnosis and worse survival. In health education campaigns on colorectal cancer, efforts must be made to provide medical information to rural women in order to reduce the delay in diagnosis and improve survival.


Coefficients of relationship by isonymy among registrations for five common cancers in Scottish males. The aim was to assess the relative importance of genetic factors in carcinoma of the stomach, colon, rectum, prostate, and bladder in Scottish males. Cancer cases and controls were compared in terms of the coefficient of relationship by isonymy (Ri). Surname distributions for cancer cases were derived from the Scottish Cancer Register for the years 1959-85. Control distributions were derived from all births, marriages and deaths in Scotland for 1976. Analysis was carried out on a total of 60,933 cancer registrations and 101,836 births, marriages, and deaths over the 12 local government regions of Scotland. Comparisons of Ri within and between regions indicated that inherited susceptibility was of greatest importance in carcinoma of the prostate and colon, of intermediate importance in carcinoma of the rectum and stomach, and of minimal importance in carcinoma of the bladder. Familial aggregation of cancers was most pronounced in Highland, Tayside, and Borders Regions. For Highland, this appeared to be the result of region-specific familial influences, while Tayside and the Borders shared genetic factors contributing to cancer aetiology with neighbouring regions in south east Scotland. Surname analysis is a simple but useful tool for studying population genetic structure and its relationship to disease incidence.