Impairment evaluation based on spinal range of motion in normal subjects.

Spinal range of motion is a major determinant of impairment in many disability rating schedules used today. The validity of using spinal motion as the primary variable for impairment ratings must be questioned because of the large spectrum of age-related changes in motion in a normal population. The purpose of this investigation was to test the validity of this concept by determining spinal impairment in normal subjects using one of the more popular rating systems, the American Medical Association (AMA) Guides to the Evaluation of Permanent Impairment. Ninety-five individual measurements of cervical and lumbar spine motion were performed on each of 81 healthy subjects by two examiners using the double-inclinometer method. Based on the AMA criteria, all of the normal subjects were noted to have some degree of impairment ranging from 2 to 38.5%, with a mean value of 10.8%. The level of impairment increased with age for cervical, lumbar, and total impairment percentages (p = 0.0001). The current method of impairment determination based on spinal motion may not accurately reflect impairment in many patients. Impairment may be overestimated by up to 38%. Alternate methods of impairment evaluation should be developed that are more specific for individuals with true functional impairment and that account for age-related differences in spinal motion.


Survivorship analysis of pedicular fixation systems in the treatment of degenerative disorders of the lumbar spine: a comparison of Cotrel-Dubousset instrumentation and the AO internal fixator.

We retrospectively analyzed the frequency and clinical consequences of pedicular fixation system failure in 50 patients who underwent Cotrel-Dubousset transpedicular instrumentation (CDI), and 46 patients who underwent AO internal fixator (IF) instrumentation for similar indications. After 2 years, 14 implants in the CDI group and 13 in the IF group had failed. The overall probability of implant survival was similar in both groups (CDI, 71.9% versus IF, 71.7%). However, more implant failures were associated with nonunion, loss of reduction, and nerve-root compromise in the IF group (four versus none) than in the CDI group. Implant failure usually occurred after solid fusion, and did not significantly affect the short-term clinical results. Therefore, implant failure does not a priori indicate failure of the operation.


Cervical spinal cord injury in children.

We examined 19 children under 10 years of age with cervical spinal cord injury using clinical records and radiographs. The children were divided into two groups: Eight had immediate and complete spinal cord injury, and 11 had incomplete or partial spinal cord injury. Those with complete spinal cord injury were injured in motor vehicle accidents with a proximal spinal cord injury. Eighty-eight percent had cervical spine fractures/instability with a distraction pattern of injury. Half had associated trauma. The mortality rate was 25%, and those who survived showed no neurologic improvement. Most of the children with partial spinal cord injury were injured at birth. Many had no radiographic evidence of cervical fracture. One-quarter had associated trauma. The neurologic improvement averaged 1.9 Frankel grades. Half of both groups required posterior cervical fusion, and there was a significant complication rate. Eight-eight percent developed scoliosis, and 71% developed hip subluxation.


Comparison of MRI and discography in the diagnosis of lumbar degenerative disc disease.

Recent reports have attempted to compare the relative value of discography and MRI in the evaluation of lumbar degenerative disc disease. None has compared the accuracy of the two techniques in regard to the detection of disc herniation specifically, and none has offered surgical correlation. In this prospective study, both techniques were used to evaluate 264 disc levels in 90 patients with incapacitating low back pain or radicular pain. The results showed an 86% agreement level both between tests and between the orthopaedist and radiologist on each test. Surgical findings agreed with diagnostic studies at 63 of 76 levels in 57 patients who underwent operative treatment. An analysis of the relative sensitivity and specificity of each test in the diagnosis of degeneration and herniation revealed that the greater sensitivity of MRI in the detection of herniation was the only statistically significant difference (p < 0.05).


Extraperitoneal anterolateral discectomy for lumbar disc herniation: indications, techniques, and time-related clinical results.

We analyzed 80 consecutive cases of lumbar disc herniation who underwent an extraperitoneal anterolateral discectomy according to clinical and radiologic parameters. The average follow-up period was 5 1/2 years (range, 1-10 years). The results of 71 patients (89%) were satisfactory through the mid- and long-term follow-up periods, although a very slight decrease in subjective/objective scores and ADL score was found. Satisfactory results were obtained for adolescent and younger male adults and in isolated central or centrolateral herniations with a broad base. From an analysis of the nine reoperated cases, we determined that the contraindications of this technique are a sequestrated or extruded nucleus pulposus and disc protrusion accompanied by posterior dislocation of a vertebral edge fragment. The relative indications include a small, hard posterolateral herniation located just beneath the nerve roots, double-level herniation, disc herniation accompanied by narrow spinal canal, and bulged disc in elder patients. The absolute indications for this surgery are a centrally or centrolaterally protruded disc with a relatively broad base of herniation at single-disc level that is not accompanied by spinal stenosis in adolescent and younger male adults.


Results of in situ fusion for isthmic spondylolisthesis.

Between 1976 and 1990, we treated 56 isthmic spondylolisthesis patients with an average age of 15 + 4 (range, 4 + 9 to 27 +/- 2) with in situ bilateral transverse process fusions utilizing autogenous iliac bone graft. None of the patients had a decompression or instrumentation placed. Radiographic fusion was determined from standing spot lateral radiographs and either Ferguson AP or standing AP views of the lumbosacral junction. The radiographic fusion patterns were categorized into the following four grades: (A) definitely solid (n = 28, 50%)--solid big trabeculated bilateral fusion masses; (B) possibly solid (n = 10, 18%)--unilateral large fusion mass with contralateral small fusion mass; (C) probably not solid (n = 6, 11%)--small, thin fusion masses bilaterally; (D) definitely not solid (n = 12, 21%)--graft resorption bilaterally or fusion mass with obvious bilateral pseudarthrosis. This fusion pattern is best determined by the Ferguson ("true AP") radiograph of the lumbosacral junction. Despite this surprisingly low fusion rate, overall clinical improvement was noted in > 80% of patients with preoperative symptoms of back pain, leg pain, or hamstring tightness. We recommend this critical assessment of fusion grades to determine fusion success in this patient population.


Leg-length inequality and low-back pain after Perthes' disease: a 28-47-year follow-up of 96 patients.

A follow-up of 96 patients with Perthes' disease was made 28-47 years after onset of the disease. We paid special attention to leg-length inequality and its consequences and low-back disability. Leg-length inequality was a common finding, but low-back pain was not a significant problem. Leg-length inequality and lumbar scoliosis correlated poorly with low-back disorders. Degeneration of the lumbar spine was the only factor that correlated well with low-back pain.


CT-based geometric data of human spine musculature. Part I. Japanese patients with chronic low back pain.

Mechanical factors are considered to play a dominant role in low back problems. Various spinal structures, including muscles, act in unison to resist the external load, including the body segments. An estimation of the forces in these requires a knowledge of the orientation, location, and area of cross-section of the muscles to complete the information for the formulation of a truly three-dimensional biomechanical mathematical model of the spine in the lumbar region. Computed tomography scans of 10 Japanese patients suffering from chronic low back pain were obtained to determine the geometric data of the abdominal and back muscles from the 12th thoracic vertebral to the first sacral vertebral level. The mean age +/- 1 SD of the group was 40.1 +/- 14.12 years (range, 24-70), 573 +/- 88.5 N of body weight (range, 441-705), and 1.63 +/- 0.09 m tall (range, 1.44-1.74). The geometric parameters quantified were the line of action, and the centroid and physiologic area of cross-section of each muscle as a function of the spinal level. The effective/physiological area of cross-section of each muscle changed along the length of the spine because of the change in the line of action of the muscle. The centroidal approach adopted for quantifying the lines of action of various muscles was found unsuitable for the abdominal muscles, excluding the rectus abdominis, because of the associated anatomic complexities. Alternatives are proposed to complete the data base. The application of the data for the formulation of a truly three-dimensional biomechanical model of the spine at the L3-4 level is briefly presented. Application to nonlinear optimization-based force predictions in various spinal structures is discussed.


Pullout strength comparison of two methods of orienting screw insertion in the lateral masses of the bovine cervical spine.

We undertook a biomechanical study to compare the pullout strength of 3.5-mm AO screws placed in two different orientations within the bovine cervical spine. The first set of screws were oriented obliquely and passed through the lateral mass, as recommended by the AO group. The orientation of the second set was anterior to posterior through the lateral mass, as recommended by Roy-Camille. All screw holes were drilled and tapped by a spinal surgeon experienced with both techniques. Pullout force was measured on an Instron materials testing machine using a self-centering screw-holding chuck and loading rate of 0.833 mm/sec. Although the bone strength in the Roy-Camille orientation was greater (46.7 N/mm versus 36.1 N/mm, p < 0.05), the overall mean pullout force for the AO orientation was greater (607 N versus 471 N, p < 0.025) due to the longer length of bone available for screw purchase (17.0 mm versus 10.3 mm).


Primary posterior fusion C1/2 in odontoid fractures: indications, technique, and results of transarticular screw fixation.

Odontoid fractures, especially unstable type II fractures have a poor prognosis in respect to healing. Therefore, operative stabilization (posterior fusion C1/2 or anterior screw fixation) has been suggested for the treatment of unstable type II and for some unstable type III fractures. Compared to posterior fusion C1/2, anterior screw fixation has proven to be effective; it has the advantage of leaving the motion segment C1/2 intact, therefore preserving at least some C1/2 rotation. However, in some instances, this method of stabilization is not indicated. In these cases, posterior fusion C1/2 is the treatment of choice. Primary posterior fusion C1/2 is indicated in (a) odontoid fracture associated with comminution of one or both atlanto-axial joints; (b) fracture of the odontoid associated with an unstable Jefferson fracture; (c) unstable type III odontoid fracture, when immobilization in a halo jacket or plaster cast is not suitable, as in elderly people or polytraumatized patients; (d) atypical type II fractures (comminuted or with oblique fracture in the frontal plane); (e) irreducible fracture dislocation C1/2, e.g., several-weeks-old fracture; (f) unstable type II or shallow and unstable type III odontoid fracture, when marked thoracic kyphosis is associated with limited extension of the cervical spine; (g) unstable type II or shallow type III odontoid fracture in elderly people with degenerative narrow spinal canal; (h) pathologic fracture of the odontoid. In all these instances, posterior fusion C1/2 is the treatment of choice. We prefer the transarticular screw fixation technique. Compared to other posterior fusion techniques, it has the advantage of increased stability and allows effective stabilization of C1/2 in a reduced position as well as immediate ambulation with minimal head support. This technique can also be performed when the posterior arch of the atlas is fractured or absent. Our experience of 12 acute odontoid fractures, managed by this technique, is presented. At follow-up, all C1/2 fusions were united in reduced position.


Frequency of intra-abdominal injury in cases of blunt trauma to the cervical spinal cord.

Historically, early management of the blunt trauma victim with hemodynamic instability and cervical spinal cord injury has been hampered by the physician's inability to perform an accurate physical examination. Invasive and time-consuming diagnostic tests are often run to check for the presence of occult intra-abdominal injuries. For this reason, we decided to study these patients by reviewing a clinical registry to assess the frequency of intra-abdominal injuries in cases of cervical spinal cord trauma. We hypothesized that intra-abdominal injury would occur infrequently in cases of blunt trauma to the cervical spinal cord. In fact, data from the Maryland Institute for Emergency Medical Services Systems revealed that blunt trauma victims with cervical cord injury rarely (2.6%) sustained intra-abdominal wounds. Further analysis of this population revealed that specific mechanisms of trauma and the presence of hemodynamic instability and other major injuries were factors strongly associated with occult intra-abdominal injury. In light of these findings, we have outlined a protocol for management of these patients that is geared toward more rapid stabilization of the injured spinal column.


Lumbar mobility in asymptomatic individuals.

A radiological study of angulatory and translational lumbar mobility and of lumbar scoliosis was performed on 56 persons aged 35-54 years who had no history of back pain. The measurements of mobility were based on extension-flexion views; the assessment of scoliosis was done using radiographs taken in the standing position. The results indicated that the largest range of angulatory motion occurred in the L5-S1 segment (mean, 17.3 degrees for women and 16.4 degrees for men). Five-millimeter translational motion was so common in the L3-L4 and L4-L5 segments, as was 4-mm in the L5-S1 segments, that these values cannot be considered with certainty as pathological. Ten subjects (18%) showed scoliosis of > or = 10 degrees. Although based on a small series, these results are a step toward a more objective and careful interpretation of extension-flexion and functional radiographs of low-back pain patients.


Noise pollution in the operating room: a hazard to surgeons, personnel, and patients.

Noise levels up to 118 dB--a level that is potentially damaging to the hearing--were measured in the operating room, notably during the use of high-speed gas turbine bone-cutting drills. Suction tips, which had trapped tissue "whistles" inside, yielded noise levels of up to 96 dB. Surgeons, staff, and patients should be cautioned against such noises and shielded in prolonged cases. We offer a review of acoustical criteria for various practical noises and duration of safe exposure.


Stochastic differential equation models for spatially distributed neurons and propagation of chaos for interacting systems.

Distribution or nuclear space-valued stochastic differential equations (SDEs) (diffusions as well as discontinuous equations) are discussed as stochastic models for the behavior of voltage potentials of spatially distributed neurons. A propagation of chaos result is obtained for an interacting system of Hilbert space-valued SDEs.


Modeling the variability of firing rate of retinal ganglion cells.

Impulse trains simulating the maintained discharges of retinal ganglion cells were generated by digital realizations of the integrate-and-fire model. If the mean rate were set by a "bias" level added to "noise," the variability of firing would be related to the mean firing rate as an inverse square root law; the maintained discharges of retinal ganglion cells deviate systematically from such a relationship. A more realistic relationship can be obtained if the integrate-and-fire mechanism is "leaky"; with this refinement, the integrate-and-fire model captures the essential features of the data. However, the model shows that the distribution of intervals is insensitive to that of the underlying variability. The leakage time constant, threshold, and distribution of the noise are confounded, rendering the model unspecifiable. Another aspect of variability is presented by the variance of responses to repeated discrete stimuli. The variance of response rate increases with the mean response amplitude; the nature of that relationship depends on the duration of the periods in which the response is sampled. These results have defied explanation. But if it is assumed that variability depends on mean rate in the way observed for maintained discharges, the variability of responses to abrupt changes in lighting can be predicted from the observed mean responses. The parameters that provide the best fits for the variability of responses also provide a reasonable fit to the variability of maintained discharges.


Response characteristics of the BVP neuron model to periodic pulse inputs.

The characteristics of the BVP neuron model response to periodic pulse stimuli are investigated. Temporal patterns of the output of the model are analyzed as a function of the stimulus intensity and period. The BVP model exhibits the same chaotic behavior, and a Cantor function-like graph of the response frequency (mean firing rate) as in electrophysiological experiments. This shows that the BVP model describes the complicated response characteristics of the neuron at least qualitatively.


Stochastic models of lesion induction and repair in yeast.

In the past decade several stochastic models for the effects of radiation on cell survival have been proposed. We survey them briefly and consider their possible application to some experimental results of Frankenberg-Schwager and co-authors on irradiated yeast. One possible model is a slight modification of the model proposed by Yang and Swenberg. It is shown that the modified model does not actually fit well and that the repair mechanism requires additional complications for adequate description.


DNA damage caused by ionizing radiation.

A survey is given of continuous-time Markov chain models for ionizing radiation damage to the genome of mammalian cells. In such models, immediate damage induced by the radiation is regarded as a batch-Poisson arrival process of DNA double-strand breaks (DSBs). Enzymatic modification of the immediate damage is modeled as a Markov process similar to those described by the master equation of stochastic chemical kinetics. An illustrative example is the restitution/complete-exchange model. The model postulates that, after being induced by radiation, DSBs subsequently either undergo enzymatically mediated restitution (repair) or participate pairwise in chromosome exchanges. Some of the exchanges make irremediable lesions such as dicentric chromosome aberrations. One may have rapid irradiation followed by enzymatic DSB processing or have prolonged irradiation with both DSB arrival and enzymatic DSB processing continuing throughout the irradiation period. Methods for analyzing the Markov chains include using an approximate model for expected values, the discrete-time Markov chain embedded at transitions, partial differential equations for generating functions, normal perturbation theory, singular perturbation theory with scaling, numerical computations, and certain matrix methods that combine Perron-Frobenius theory with variational estimates. Applications to experimental results on expected values, variances, and statistical distributions of DNA lesions are briefly outlined. Continuous-time Markov chains are the most systematic of those radiation damage models that treat DSB-DSB interactions within the cell nucleus as homogeneous (e.g., ignore diffusion limitations). They contain virtually all other relevant homogeneous models and semiempirical summaries as special cases, limiting cases, or approximations. However, the Markov models do not seem to be well suited for studying spatial dependence of DSB interactions, which is known to be important in some situations.


Cell survival probability under ionizing radiation.

The survival probability of a living cell exposed to ionizing radiation in an experimental setup is derived. The survival of a cell depends on the severity of the radiation damage and efficiency of the cellular repair. The formula of the survival probability is expressed as a function of dose, nonlinear rate of lesion induction, nonlinear rate of cellular repair, and a key experimental parameter--the holding time. The result is an extension of the Markovian dose-response model developed by Yang and Swenberg.


Modeling the evolution of the human mitochondrial genome.

Mitochondrial DNA data have been used extensively to study evolution and early human origins. These applications require estimates of the rate at which nucleotide substitutions occur in the DNA sequence. We consider the problem of estimating substitution rates in the presence of site-to-site rate variation. A coalescent model is presented that allows for different substitution rates for purines and pyrimidines, as well as more detailed models that allow fast and slow rates within each of the purine and pyrimidine classes. A method for estimating such rates is presented. Even for these simple models of site heterogeneity, there are, typically, insufficient data to obtain reliable estimates of site-specific substitution rates. However, estimates of the average rate across all sites appear to be relatively stable even in the presence of site heterogeneity. Simulations of models with site-to-site variation in mutation rate show that hypervariable sites can produce peaks in the pairwise difference curves that have previously been attributed to population dynamics.


Carbon monoxide poisoning: an A&E perspective.

Carbon monoxide (CO) is a colourless, odourless, tasteless and non-irritating gas and may therefore be inhaled in large quantities by the victim without his realizing it. The toxic effect of CO is not exclusively the result of the binding of haemoglobin; the primary mechanism appears to be inhibition of cellular respiration. Carboxyhaemoglobin (COHb) is excreted fairly rapidly from the body, therefore blood levels do not necessarily reflect the severity of CO poisoning. Airway support and adequate ventilation are the primary objectives of the nursing and medical team. Oxygen is the only antidote to CO. Continuous monitoring of the patient's neurological state is necessary; conscious level is the most important guide to the patient's progress. Nurses must be aware of the clinical indications and contraindications for HBO therapy to ensure that their patients receive optimal treatment.


Hearing impairment in elderly hospital residents.

Seventy per cent of the sample residents had significant hearing impairment (> or = 40 dBHL). Forty-seven per cent of the sample residents wanted further help with their hearing but this had not been offered. Screening for hearing impairment on the study wards was haphazard. Less than 10% of residents owned and used a hearing aid. The listening environment was potentially disabling on all of the wards. Nursing staff were inadequately prepared to meet the care needs of the hearing-impaired elderly hospital resident. Nursing and medical care policies are not sensitive towards the needs of the hearing-impaired elderly hospital resident. Hearing impairment is a neglected area of healthcare on long-stay wards for elderly people.


Detection and treatment of osteoporosis.

Osteoporosis is a silent disease that affects one in four women. Bone loss increases rapidly following the menopause. Osteoporosis can be easily detected and successfully monitored and treated. Prevention of osteoporosis is better than cure. Osteoporosis can be counteracted by developing a strong, healthy skeleton in early life. Bone density scanning provides a quick and accurate measurement of bone mineral density.


Developing a new uniform policy for student nurses.

It has been recognized that for many years traditional nurse uniforms are far from ideal. Inappropriate uniforms can be a contributory causative factor in back injury among nurses. Many nurses hold firmly to a traditional view of what constitutes a 'proper' nurse's uniform. Uniforms can act as a barrier and hindrance in the development of the therapeutic relationship between nurse and patient. Many colleges of nursing face amalgamation. This presents them with an opportunity to re-examine their uniform policies and rationalize the many into the one.


Role of the night nurse practitioner.

Major changes within the health service both nationally and locally demanded a closer look at the relevance of the night sister/charge nurse role. Research into particular issues such as quality of patient care, junior doctors' hours and general night administration confirm the most appropriate use of nurse practitioner skills. Careful consideration of the implications of the role and the necessary preparatory training formed a crucial part of the planning. A detailed evaluation of the new night nurse practitioner role is essential to review the effectiveness of this role and its contribution to quality patient care.


Night nurse practitioners are not 'mini-doctors'.

Nurse practitioner programmes should be negotiated between service and education. The contribution of experienced course participants should be valued through adult-centred learning strategies. The programme leader should be experienced in facilitation and have credible clinical experience; he/she will utilize the expertise of appropriately skilled lecturers. Clinical skills must be set within the context of professional accountability and within the principles of professional practice (UKCC). Assessment of practice leads to competence and theory assessments to credit rating and APL/APEL. Role development is concerned with understanding accountability and not with accepting junior doctor's tasks.


Inhibition of human immunodeficiency virus-1 proliferation by liposome-encapsulated sense DNA to the 5' tat splice acceptor site.

A liposome formulation containing a distearoylphosphatidylethanolamine analog was developed that was endocytosed by both lymphocytes and monocytes. This formulation was used to encapsulate sense and antisense 20-mer oligodeoxynucleotides to the 5' tat splice acceptor site of human immunodeficiency virus type 1. At a DNA concentration of 140 nM, the liposome-encapsulated sense DNA inhibited p24 production by as much as 84% in human peripheral blood leukocytes infected with "wild-type" virus. This treatment also reduced the number of peripheral blood leukocytes producing intracellular viral antigen by 71%. Of interest, no reduction in either parameter was observed for the antisense-containing liposomes. The results demonstrate the promise of a new liposomal delivery vehicle to inhibit human immunodeficiency virus replication by an entrapped oligodeoxynucleotide.


The use of antisense oligonucleotides to establish autocrine angiotensin growth effects in human neuroblastoma and mesangial cells.

Local renin-angiotensin systems (RAS) exist in many cell types, and angiotensin II (AII) has growth regulatory effects in some tissues. We demonstrated the presence of angiotensinogen (ANG) mRNA in cultured human mesangial cells (MC) and SHSY-5Y human neuroblastoma cells using reverse transcription and the polymerase chain reaction (RT/PCR) followed by hybridization to a human ANG-specific oligonucleotide probe. We speculated, therefore, that AII might act in an autocrine or paracrine fashion to regulate the growth of mesangial cells and neuroblastoma cells. Sense and antisense oligonucleotides were next synthesized complementary to the ANG transcription start site. Antisense but not sense oligonucleotides decreased [3H]thymidine incorporation into DNA by both MC and neuroblastoma cells. Growth of antisense oligonucleotide-treated cells was restored to control levels by the addition of AII but not by the addition of basic fibroblast growth factor. Neither oligonucleotide affected [3H]thymidine incorporation in mouse L929 cells. These data indicate that locally produced AII can act in an autocrine or paracrine fashion to alter the growth of human mesangial and neuroblastoma cells. Therefore, they suggest a role for local RAS in the pathogenesis of growth abnormalities in the cardiovascular system as well as in some forms of malignancy.


Legal implications of standard setting in nursing.

Patients are increasingly holding health professionals to account for their care. The practice of standard setting has important legal implications. Standard setting can be seen to aid the communication process in healthcare and can therefore help avoid expensive litigation. Standard setting can improve the quality of patient care. Standard documentation could be disclosed in a medical/nursing negligence case. Standards should not be automatically applied. Standard setting can be patchy, misdirected and irrelevant to actual problems. Standards can create unreal patient expectations of care. Patient care may suffer if unrealistic or unreasonable standards are in place. Standard setting can show that there is a controlled environment of care.


Managing upper airway obstruction.

A complete respiratory obstruction can lead to death in 3 minutes. The first and constant duty of the nurse aider is to check that the person is breathing by looking, listening and feeling. Partial obstruction is no less serious than complete obstruction. The nurse aider, in any situation, should assess the problem and attempt to overcome the airway obstruction using the measures described.


Cellular uptake and subcellular distribution of phosphorothioate oligonucleotides into cultured cells.

A phosphorothioate oligonucleotide that has been employed to inhibit HIV-1 viral expression in chronically infected H9 cells was examined for cellular uptake and subcellular distribution. The relationship between extracellular oligonucleotide concentration and the distribution and accumulation into subcellular organelles is important to the design, potential side effects, and understanding of a therapeutically useful antisense oligonucleotide. These studies employed uptake of both 35S- and fluorescence-labeled phosphorothioate oligonucleotides. Experiments with V79, HeLa, H9, and fresh human peripheral blood monocytes indicate that accumulations of oligonucleotide inside cells exceeds the concentration of oligonucleotide in culture media by over 100 times following 1 h of exposure at 37 degrees C. Uptake is more efficient at low concentrations, suggesting a saturable process. The total oligonucleotide that remains in cells begins to reach a plateau after 45-60 min, indicating either that efflux pathways exist or that uptake is saturable. Subcellular fractionation studies with 35S-labeled phosphorothioate demonstrate the oligonucleotide is sequestered into both the nuclei and the mitochondria of cultured HeLa cells in a time-dependent manner. The subcellular fractionation was examined with fluorescence-labeled phosphorothioate by both confocal and fluorescence microscopy, which confirmed the rate and localization of oligonucleotide into cultured cells. Finally, cellular uptake is not uniform for all cells in a nonsynchronous culture.


How to become a nurse teacher.

It may take a minimum of 4 years to become a nurse teacher. Teaching is about communicating effectively with a variety of groups. The ENB and UKCC have clear criteria that must be met. If teaching is for you, it is important to be proactive, explore alternatives and plan your way forward. The role of the teacher is open to a wide interpretation. Nurse teaching is moving towards an all-graduate profession. Your college of nursing library will have information packs and details of local courses. The college principal will be pleased to offer careers advice to prospective teachers.


Binding of antisense phosphorothioate oligonucleotides to murine lymphocytes is lineage specific and inducible.

A phosphorothioate oligonucleotide that has been employed to inhibit HIV-1 viral expression in chronically infected H9 cells was examined for its ability to associate with murine lymphoid cells. The relationship between cellular oligonucleotide concentration and the lymphoid target tissues is important to the selection of an animal model, evaluation of potential side effects, and understanding the actions of a therapeutically useful antisense oligonucleotide. Lymphoid cells were harvested from murine peripheral blood, bone marrow, thymus, lymph node, and spleen. Cell subpopulations that bind the oligonucleotide were distinguished by two-color flow cytometry employing a fluorescein-labeled anti-rev oligonucleotide and phycoerythrin-labeled antibodies to selected cell surface molecules associated with unique subpopulations of cells. Very little oligonucleotide binding was observed in peripheral blood mononuclear cells or thymic T cells, but substantial numbers of cells, primarily B cells from bone marrow and spleen, accumulated the oligonucleotide. The cell-associated oligonucleotide was increased significantly in lymphoid populations when the cells were mitogen pretreated with either concanavalin-A (ConA), a T cell mitogen, or lipopolysaccharide (LPS), a B cell mitogen. These data clearly demonstrate the ability of fluorescein-conjugated oligonucleotides to bind to unique cell populations in suspension, allowing simultaneous two-color phenotypic analysis, suggesting that fluorescein-conjugated oligonucleotides may be a useful bridge between in vitro molecular biology techniques and in vivo cell biology. In addition, these data provide optimism concerning the in vivo treatment of chronically infected HIV patients using antisense oligonucleotides.


Cellular uptake and degradation of phosphorothioate oligonucleotides by marine and freshwater ciliates.

To date, no antisense studies have been reported with either ciliated protozoa or marine organisms. This study examines the feasibility of using antisense oligonucleotides to alter gene expression in marine and freshwater ciliates. Radiolabeled, phosphorothioate-modified oligonucleotides were used to investigate whether ciliates take up and degrade oligonucleotides present in the culture medium. With all three ciliates examined, Euplotes crassus, Tetrahymena thermophila, and Oxytricha nova, the oligonucleotide in the culture medium was degraded very rapidly (> 90% in 8 h). The degradation probably occurred when the cells filtered the culture medium through the oral apparatus. Our results indicate that experiments involving the uptake of oligonucleotides from the culture medium are likely to be successful with ciliated protozoa. In studies designed to examine the uptake of fluorescent oligonucleotide by Euplotes cells, we found that dead or dying cells have a high affinity for fluorescein-labeled oligonucleotide. These results illustrate the importance of careful studies when only certain cell populations are found to have a high affinity for oligonucleotide. Although the seawater culture medium used to grow Euplotes causes some oligonucleotide to precipitate, this problem is not serious at concentrations > or = 1 microM oligonucleotide. Thus, it should be possible to use antisense oligonucleotides to manipulate gene expression in other marine organisms.


The opening of a high care hostel for problem drinkers.

This paper gives a personal and practice based account by one of the Team Leaders of the opening of a high-care hostel for problem drinkers in North London. The hostel, Rugby House, was set up to provide detoxification and assessment facilities for thirteen residents. It was part of the Rugby House Project, an alcohol agency in the voluntary sector. The paper explores the processes involved in setting up a new project; how the new paid employees turn a committee's vision into practice; how a group of individuals become a team; the importance of clarity about boundaries and underlying values and assumptions; the need for openness about negative as well as positive feelings; and the recognition that some of the experiences of staff will resonate with those of the residents for whom giving up drinking is a major life change.


The impact of intravenous drug use on mortality of young adults in Rome, Italy.

To estimate the impact of intravenous drug use (IVDU) on mortality in the general population of young adults in Rome, Italy, the Population Attributable Risk (PAR) was calculated for the overall and cause-specific mortality in the 15-34 years age group. Relative risks were derived from a previous historical cohort study on mortality among 4200 intravenous drug users (IVDUs) in Rome, in which increased mortality from cardiovascular, respiratory, and gastrointestinal diseases as well as from violence, overdose and AIDS had been observed. The prevalence of the risk factor (i.e. the proportion of IVDUs) in the general population was estimated using the 'multiplier formula' and 'capture-recapture' methods. The proportion of all deaths attributable to IVDU in the 15-34 age group in the Roman population was 16% and 9% in males and females, respectively. The cause-specific attributable proportions were 66% for endocarditis and 37% for cirrhosis in males, and 36% for endocarditis and pneumonia in females. These findings further document the relevant health consequences of IVDU on the general population of a large metropolitan area.


Estimating the trend of the epidemic of drug use in Italy, 1985-89.

We used data from different sources to estimate the extent and the trend of the epidemic of drug use in Italy in the second half of the '80s. During the study period, the number of subjects attending drug dependency units increased from 13,905 to 61,689. Mortality and morbidity indicators showed an increase in both drug related deaths (mainly from overdose) and AIDS cases reported in injecting drug users, particularly among older subjects. However, the number of young adults detected as drug users at the army recruitment remained virtually stable from 1986 on. These findings suggest that both demand and availability of treatment increased through the years 1985-89, and that clinical consequences of drug use related behaviour have become an important public health priority.


Assessment of drug involvement: applications to a sample of physicians in training.

The investigators examined survey data of lifetime and recent drug use in national samples of 2036 senior medical students and 1772 resident physicians to test whether patterns of lifetime drug use could be characterized adequately by a single underlying dimension of 'drug involvement'. The data analysis was based on a two parameter normal item response theory (IRT) model using the marginal maximum likelihood estimation method. The results showed that a single latent dimension of 'drug involvement' characterized individual drug use differences on the following measures: substances ever used, substances used in the previous year or previous month, and the sequential order of first use for each substance. The dimension was equivalent for students and resident physicians, and for both genders. Those who professed 'no religion' tended to be more drug involved. Physicians-in-training with a higher drug involvement score based on lifetime use were more likely: (a) to have used higher-ranking drugs (such as LSD and prescription opiates) in the past year; and (b) to have used a greater number of different drugs during the past month. Subjects first began to use each of the substances in a relatively invariant sequence corresponding to that predicted by the model. The implications of this model for evaluating the drug use histories of physicians-in-training, for identifying subgroups at greater risk for continued drug involvement after the beginning of medical training, and for further psychological, biological, and sociocultural research on the nature of 'drug involvement' are discussed.


Knowledge of AIDS and HIV among various groups.

To date, no cure has been found for HIV/AIDS. Prevention has therefore been the immediate principal aim and a didactic approach has been given a primary role. Studies from the USA indicate that knowledge level may be dictated by membership of particular subcultural groups and the perceived relevance of HIV/AIDS to these groups. This study investigates knowledge among four groups: homosexual; single heterosexual; IV drug users; and a 'married' group. Results indicate some gaps in knowledge and a greater knowledge base among one of the high risk groups, the homosexual group.


Socio-economic versus obstetric risk factors for drug addiction in offspring.

Two possible risk factors for drug addiction were weighed against each other: (1) perinatal factors associated with obstetric medication at time of birth; and (2) factors associated with familial socio-economic conditions at time of birth. The subjects comprised 200 amphetamine addicts and 200 opiate addicts born in Stockholm 1945-1966. In a matched case control study, addicts were compared to their siblings with regard to possible obstetric risk factors by means of conditional logistic regression controlling for socio-economic level and civil status. Administration of opiates, barbiturates and nitrous oxide to mothers during labour was associated with drug addiction in offspring, hence confirming results from earlier studies. In a cohort study the risk associated with birth at a given hospital and familial socio-economic level was analysed by means of log-linear analysis using 7100 controls from the general population. For amphetamine addicts, a low socio-economic level at time of birth might be of importance for the infant subsequently becoming an addict. This could not be demonstrated for the opiate addicts. An uneven distribution of births among the hospitals, most pronounced for the amphetamine addicts, is in agreement with the hypothesis that obstetric practices may be risk factors for adult drug addiction.


Young-adult children of alcoholic parents: protective effects of positive family functioning.

The occurrence of alcoholism is clustered within families, but the detrimental effect of a positive family history may vary with the degree of family impairment involved. In this study we assessed the effects of family history and family environment on alcohol misuse. From ongoing studies we recruited parents who had a child aged 18-30, 20 with a DSM-III-R alcohol dependence diagnosis, 20 without. The child then completed a multidimensional assessment. The young-adult participants included 20 men and 20 women (mean age = 24.8). Differences by family history were restricted to substance abuse behaviors. While a high level of alcohol problems occurred in both groups, those with an alcohol-dependent parent were more likely to be heavy drinkers and showed more symptoms of alcohol dependence. Overall psychological adjustment did not differ between the groups, however. Alcohol misuse measures did correlate moderately with symptoms of poor emotional health. The most important correlates of alcohol misuse measures in this study were exposure to parental alcoholism, abusive punishment, and psychological symptoms, with some separation of effects in the two subgroups. Psychological symptoms had a stronger relationship with misuse in subjects with social-drinking parents, while abuse was more associated in the group with an alcohol-dependent parent. These results confirm the importance of environmental interactions with familial risk. A biological vulnerability from an alcohol-dependent parent was not sufficient or necessary for the participants in this study to develop alcohol dependence as a young adult, although there was an increased risk. There appear to be strong protective effects of positive family relationships on the potential negative effects of a family history of alcoholism.


Drinking amongst medical patients: levels of risk and models of change.

Results are reported of a study in which 547 general hospital medical in-patients were screened, using a computer-administered questionnaire, for alcohol consumption, problems and concerns. Of males, 22.5% were classified as 'risk drinkers', of women 6.5%. Rates of risk were particularly high amongst younger male patients. It was concluded that certain screening questionnaire items were more useful than others in the general hospital context, and that standard questionnaires developed for other populations should not automatically be used in general hospitals. Comparisons with items relating to other health behaviours suggested that the medical profession, the general public and the patients themselves might be relatively insensitive to the risks associated with heavy drinking in comparison to those associated with smoking, weight and lack of exercise. Data from initial screening and from 75% of patients who were asked to repeat the questionnaire six months later, were used to test certain assumptions of a model of change based in part upon that of Prochaska & DiClemente (1986). Results suggested that processes of change were more complex than the model supposed.


Drinking habits and detection of heavy drinking among middle-aged women.

Little is known about alcohol consumption and the efficiency of alcohol questionnaires among women. In the present study 40-year-old (n = 90) and 45-year-old (n = 75) women participating in a health screening gave a self-report about their alcohol consumption and filled out the Malmö modified Michigan Alcoholism Screening Test (Mm-MAST) and the CAGE questionnaires. Teetotallers comprised 11% of the 40-year-old group and 8% of the 45-year-old women. CAGE, but not Mm-MAST worked with the traditional cut-off point of two recommended for men. When the criterion for heavy drinking was a self-reported consumption > or = 140 g of absolute alcohol per week or a positive (> or = 2) finding in the CAGE or > or = 4 'yes' answers in the Mm-MAST, 20% of the 40-year-old and 17% of the 45-year-old group (together 19%) proved positive. Neither of the two questionnaires nor self-report alone worked perfectly for identifying the heavy drinker group (n = 31) screened. Using the three above criteria; of the heavy drinkers 52% were detected by self-report, 55% by CAGE, and 45% by Mm-MAST. CAGE in combination with self-report detected 90% and this combination, being short and simple, can be recommended for clinical practice.


Why children start smoking cigarettes: predictors of onset.

We review findings from 27 prospective studies of the onset of cigarette smoking conducted since 1980. Almost 300 measures of predictors of smoking onset were examined, and 74% of them provided multivariate support for predictors of onset derived from theory and previous empirical findings. Expected relationships were strongly supported for (a) socioeconomic status, with students with compromised status being more likely to try smoking; (b) social bonding variables, particularly peer and school bonding, with less support for family bonding; (c) social learning variables, especially peer smoking and approval, prevalence estimates, and offers/availability, with less consistent support for parent smoking and approval; (d) refusal skills self efficacy; (e) knowledge, attitudes and intentions, with the expected stronger predictions from intentions than from attitudes than from knowledge; and (f) broad indicators of self-esteem. The few investigators who analyzed their data separately by age, gender, or ethnicity found many differences by these factors, though there were too few of them to detect any pattern with confidence. Though the 27 studies are far from perfect, we believe that they confirm the importance of many well-accepted predictors and raise some questions about others. In particular, family smoking, bonding and approval each received unexpectedly low support. It is not clear whether this lack of support reflects reality as it has always been, is due to a changing reality, reflects developmental changes, either in the age of subjects or the stage of onset, or is due to poor measurement and too few tests. Future prospective studies need to be theory-driven, use measures of known reliability and validity, report analyses of scale properties, and use statistical methods appropriate to the hypotheses or theories under study. Finally, we encourage more investigations of the potentially different predictors of transitions to experimental or regular cigarette smoking. This will require multi-wave studies and careful measurement of changes in smoking behavior.


Severity of DSM-III-R alcohol dependence: United States, 1988.

One method of subtyping alcohol dependence is according to severity. Over 4000 respondents in a US national survey who met criteria for DSM-III-R alcohol dependence were classified as mildly, moderately or severely dependent, and the characteristics of each group were examined. The proportion of males was higher in the moderate and severe groups, and the greatest proportions of cases were concentrated in the younger ages in all three groups. A clear increasing gradient from the mild to severe group was found for early age at first drink, heavy alcohol consumption, family history of alcohol problems, social pressure to reduce drinking, and helpseeking, treatment or AA for drinking. Implications for further analyses are discussed.


Pressure control in glaucoma patients after cataract surgery with intraocular lens.

In a retrospective study 97 patients with glaucoma and 16 with ocular hypertension were examined with regard to intraocular pressure (IOP) after extracapsular cataract extraction with implantation of a posterior chamber lens. During the follow-up 39 cases dropped out but 63 glaucoma patients and 11 patients with ocular hypertension were followed for three years. Compared to preoperative IOP 59% of the patients treated previously with Argon laser trabeculoplasty (ALT) had an IOP rise of > 10 mm Hg the day after surgery. The corresponding proportion among medically treated patients was 34% (P = 0.01). A pressure rise of > 10 mm Hg was less frequent among patients treated with one drug than among those treated with two or three (P = 0.05). During follow-up eight patients had a pressure rise which could not be controlled medically and they had to undergo additional ALT or surgery. All eight had been treated with ALT or with glaucoma filtering surgery prior to the cataract operation. After three years observation of 63 of the glaucoma patients, 63% were having less medical therapy than preoperatively, 30% an equal amount and 7% more; 49% (31 of 63) were still without any therapy. In the group of patients who preoperatively were only treated medically, no definite increase in therapy was needed in the long term.


Influence of carteolol and timolol on IOP an visual fields in glaucoma: a multi-center, double-masked, prospective study.

The influences of Carteolol and Timolol eye drops on intraocular pressure (IOP) and visual fields were compared in a multi-center, double-masked, prospective study. Two-hundred and forty eyes of 120 patients were initially included in the study, and 142 eyes of 72 patients fulfilled all the criteria for final statistical analysis. Both drugs significantly reduced IOP. The visual fields in both treatment groups did not change during one year of treatment. In both groups some patients improved slightly, and others deteriorated slightly. This indicates that locally applied beta-blockers may efficiently stop further progression of visual field defects in cases with increased IOP and early visual field damage. There was no difference between Carteolol and Timolol in this regard. The side effects were minimal, and there were no differences in their frequency or intensity in the two treatment groups.


Electrophysiology in pseudohistoplasmosis and chronic idiopathic retinal vasculitis.

We used computerized electroretinography (E.R.G.) flash to study 12 patients: five pseudohistoplasmosis (P.S.H.) and seven chronic idiopathic retinal vasculitis (C.I.R.V.), compared with 12 healthy controls. We found a moderate correlation in controls between white computer averaged b-wave amplitude and b-wave obtained with other wavelengths (over 600 nm red, over 550 nm orange, and under 500 nm blue), in scotopic (white/orange r = 0.41, P < 0.05; white/red r = 0.45, P < 0.05; white/blue r = 0.48, P < 0.02) and photopic conditions (white/orange r = 0.6, P < 0.01). For P.S.H. there was a highly significant correlation between white and all wavelengths in photopic (white/orange r = 1, white/red r = 0.96, P < 0.0001) and scotopic conditions (white/orange r = 0.97, P < 0.0001; white/red r = 0.96, P < 0.0001; white/blue r = 0.96). In vasculitis, as in controls, we found no white/red correlation and only in vasculitis we could not find a scotopic white/blue correlation. We conclude that these situations are electrophysiologically different. The closer correlation in P.S.H. suggests more efficient phototransduction and in C.I.R.V. there may also be a rod-selective dysfunction.


Beta-endorphin responses to metyrapone and dexamethasone in depressed patients.

Controversy continues over the characteristics of beta-endorphin secretion in depression. Beta-endorphin plasma levels were measured in 30 drug-free male patients with a DSM-III-R major depressive disorder and 21 healthy controls. Depressed patients displayed significantly lower beta-endorphin plasma levels in baseline conditions, after the single dose metyrapone test, and after the dexamethasone suppression test. The activation of hypothalamic-pituitary-adrenal (HPA) axis in depression might be due, at least in part, to low levels of beta-endorphin. These results suggest that HPA axis dysregulation in depression may involve peptides other than ACTH.


Anticonvulsive properties of calcitonin in rats.

The effect of human calcitonin and sodium valproate (VPA) on electrically induced seizures in rats was assessed. Intraperitoneal administration of calcitonin (20 and 40 IU/kg) 60 min prior to electroshock significantly reduced the duration of the seizures and their intensity. We also found that combined treatment with calcitonin (20 and 40 IU/kg i.p.) and VPA (100 mg/kg p.o.) did not enhance the anticonvulsant activity. These findings suggest that calcitonin exerts an anticonvulsant influence on rats during electrically induced seizures.


Two different genetic markers for high and low myopia.

In myopia patients, Rh and acid phosphatase were typed in two groups: group 1 consisted of 214 patients with low myopia (-6 D or less); group 2 of 124 patients with high myopia (more than -6 D). Statistical analysis of the markers showed a good Hardy-Weinberg equilibrium for both groups. In the Rh system there was a significant difference between group 1 and the control population (p < 0.05), but not between group 2 and control (p > 0.1). In the case of ACP there was a significant difference between group 2 and the control population (p < 0.05), but not between group 1 and control (p > 0.25). We conclude that the observed association between myopia and Rh system (chromosome 1) involves low myopia, while the association between myopia and acid phosphatase (chromosome 2) involves high myopia. Further DNA research will lead to more specific results.


Changes at cholecystokinin receptors induced by long-term treatment with diazepam and haloperidol.

Fourteen days administration of haloperidol (1 mg/kg daily) prevented the motor depressant effect of caerulein (an agonist at cholecystokinin receptors, 15 micrograms/kg) and the antagonistic effect of caerulein (100 micrograms/kg) against (+)-amphetamine (5 mg/kg) induced hyperlocomotion in mice. The antiaggressive effect of caerulein (40 micrograms/kg) in saline-treated mice was replaced by increased aggressiveness after long-term haloperidol and diazepam (5 mg/kg daily) treatment. The anticonvulsant effect of caerulein (125 micrograms/kg) against picrotoxin (10 mg/kg) induced seizures was abolished after 14 days diazepam, but not after haloperidol, treatment. The above described changes in the mouse behaviour are probably related to the development of subsensitivity at CCKA receptors, whereas the CCKB receptor subtype becomes more sensitized to the action of caerulein after long-term haloperidol and diazepam treatment.


A case report of both Duane's syndrome and Rieger's anomaly in a single patient.

A young patient manifesting both Duane's syndrome and Rieger's anomaly is presented. This is believed to be the first known report of such an association. Although there is no obvious genetic correlation, the clinical implications of this finding are discussed.


Calcium antagonistic effects of carbamazepine as a mechanism of action in neuropsychiatric disorders: studies in calcium dependent model epilepsies.

Carbamazepine (CBZ) is used in neurology for the treatment of epilepsies and trigeminal neuralgia and in psychiatry for the prophylactic treatment of affective and schizoaffective psychoses. Since a common mechanism of epilepsies and affective psychoses might be increased intracellular calcium ion levels, CBZ action was analyzed in penicillin, caffeine and low Mg2+ induced model epilepsies which have been shown to be suppressed specifically by organic calcium antagonists. In CA3 and CA1 areas of hippocampal slice preparations of guinea pigs CBZ reduced paroxysmal depolarizations and extracellular field potentials (EFP) in a typical time and concentration dependent manner as it is known from calcium antagonists. Furthermore, subthreshold concentrations of the organic calcium antagonist verapamil intensified the action of CBZ. NMDA induced increases of the discharge rate of EFP were, however, unaffected by CBZ.


Presumed intraocular lymphoma in a 60-year-old man with AIDS.

A 60-year-old man with AIDS and active pulmonary tuberculosis presented with a rapidly growing chorioretinal tumor. Tuberculostatics had no effect on the tumor but radiation resulted in a quick decrease in its size. It is therefore believed to be a lymphoma. No biopsy was performed. An intraocular lymphoma in a patient with AIDS has not yet been described.


Sleep deprivation in rapid-cycling bipolar affective disorder: case report.

We describe a 4-month long hypomanic response to sleep deprivation in a patient with consistent (20-day cycles) rapid cycling. He subsequently reverted to very rapid cycling; however, sleep deprivation remained effective for each attack of depression. Sleep deprivation treatment, its immediate but short-lived beneficial effect, may have a role in the treatment of the ultra-short depressions encountered in very rapid cycling.


Effects of stimulation of putative dopamine autoreceptors on electroencephalographic power spectrum in comparison with effects produced by blockade of postsynaptic dopamine receptors in rats.

Alterations in cortical EEG activity in male rats produced by putative agonists at dopamine (DA) autoreceptors and by antagonists at postsynaptic DA receptors were compared in order to study, whether an impairment in dopaminergic neurotransmission via two different mechanisms might result in similar or different effects. Simultaneously to the EEG recordings, gross behaviour was observed. Putative agonists at DA autoreceptors (apomorphine 0.05 mg/kg, quinpirole 0.05 mg/kg, or talipexole 0.02 mg/kg s.c.) produced increases in the power in all of the frequency bands, except beta-2, with the most pronounced increase in the delta band. These EEG alterations were accompanied by hypokinesia, ptosis and yawning. In contrast, antagonists at DA receptors (haloperidol 0.1 mg/kg i.p., D2 blocker) or SCH 23390 (0.2 mg/kg i.p., D1 blocker) led to little increases in the delta band, but more pronounced increases in the alpha-2 band. Behavioural signs were hypokinesia, but little ptosis and yawning. The combination of both blockers produced, in addition, strong increases in the delta band and behavioural signs of ptosis and yawning. These results suggest that activation of putative dopamine autoreceptors produces EEG patterns and behavioural patterns different from those produced by blockade of either D1 or D2 postsynaptic dopamine receptors. In contrast, the effects following a stimulation of putative DA autoreceptors, which are expected to decrease the release of the agonist and its action at postsynaptic D1 and D2 receptors, were very similar to those found after a combined blockade of both types of postsynaptic dopamine receptors.


Synthesis of methyl alpha- and beta-N-dansyl-D-galactosaminides, probes for the combining sites of N-acetyl-D-galactosamine-specific lectins.

The synthesis of the methyl alpha- and beta-N-dansyl-D-galactosaminides is described using methyl alpha,beta-2-azido-2-deoxy-D-galactopyranoside as starting material. This was reduced to the corresponding methyl alpha,beta-2-amino-2-deoxy-D-galactopyranoside and then treated with dansyl chloride to yield a mixture of methyl alpha,beta-N-dansyl-D-galactosaminides which was separated into individual anomeric forms by flash chromatography on silica gel. Methyl alpha-N-dansyl-D-galactosaminide was used as a fluorescent indicator ligand in continuous substitution titrations to determine the association constants of nonchromophoric carbohydrates with the N-acetyl-D-galactosamine specific lectin from Erythrina corallodendron.


Effects of site-specific mutations on the enzymatic properties of a sialidase from Clostridium perfringens.

Three site-specific mutations were performed in two regions of a sialidase gene from Clostridium perfringens which are known to be conserved in bacterial sialidases. The mutant enzymes were expressed in Escherichia coli and, when measured with MU-Neu5Ac as substrate, exhibited variations in enzymatic properties compared with the wild-type enzyme. The conservative substitution of Arg 37 by Lys, located in a short conserved region upstream from the four repeated sequences common in bacterial sialidase genes, was of special interest, as KM and Vmax, as well as K(i) measured with Neu5Ac2en, were dramatically changed. These data suggest that this residue may be involved in substrate binding. In addition to its low activity, this mutant enzyme has a lower temperature optimum and is active over a more limited pH range. This mutation also prevents the binding of an antibody able to inhibit the wild-type sialidase. The other mutations, located in one of the consensus sequences, were of lower influence on enzyme activity and recognition by antibodies.


Purification of the Lewis blood-group gene associated alpha-3/4-fucosyltransferase from human milk: an enzyme transferring fucose primarily to type 1 and lactose-based oligosaccharide chains.

A soluble Lewis blood-group gene associated alpha-3/4-L-fucosyltransferase has been purified from human milk by a series of steps involving hydrophobic chromatography on Phenyl Sepharose 4B, ion exchange chromatography on CM-Sephadex C-50, affinity chromatography on GDP-hexanolamine Sepharose 4B and gel filtration on Sephacryl S-200. The first step separated alpha-3-L-fucosyltransferase activity directed towards N-acetylglucosamine in Type 2 (Gal beta 1-4GlcNAc-R) acceptors from an alpha-3/4-fucosyltransferase fraction acting on both Type 1 (Gal beta 1-3GlcNAc-R) and Type 2 acceptors. Further purification of this latter fraction on CM-Sephadex and GDP-hexanolamine Sepharose gave a single peak of fucosyltransferase activity that catalysed the addition of fucose to N-acetylglucosamine in both Type 1 and Type 2 acceptors and to the O-3 position of glucose in lactose-based oligosaccharides. The enzyme preparation at this stage resembled previously described alpha-3/4-fucosyltransferase preparations purified from human milk. However, gel filtration of this preparation on Sephacryl S-200 or Sephadex G-150 separated further amounts of alpha-3-fucosyltransferase activity acting solely on Type 2 acceptors and left a residual alpha-3/4-fucosyltransferase that retained strong alpha-4 activity with the Type 1 acceptor, lacto-N-biose 1, and alpha-3 activity with 2'-fucosyllactose, but had relatively little alpha-3 activity with N-acetyllactosamine and virtually no capacity to transfer fucose to glycoproteins with N-linked oligosaccharide chains having unsubstituted terminal Type 2 structures.


Reassessment of the acceptor specificity and general properties of the Lewis blood-group gene associated alpha-3/4-fucosyltransferase purified from human milk.

The acceptor specificity and general properties of a Lewis blood-group gene associated alpha-3/4-L-fucosyltransferase isolated from human milk have been examined at the penultimate purification stage involving affinity chromatography on GDP-hexanolamine Sepharose, and after a subsequent gel filtration step on Sephacryl S-200. Both preparations transferred fucose to the O-4 position of N-acetylglucosamine in Type 1 (Gal beta 1-3GlcNAc-R) acceptors and the O-3 position of glucose in lactose-based (Gal beta 1-4Glc) oligosaccharides, and both used Type 1 sialylated compounds when the terminal N-acetylneuraminic acid was present in alpha-2,3 linkage. The striking difference between the two preparations was in their reactivity with Type 2 (Gal beta 1-4GlcNAc-R) chains; after Sephacryl S-200 chromatography the apparent KM values for the alpha-3/4- preparation with unsubstituted low-molecular-weight Type 2 oligosaccharides were considerably increased. Substitution of the terminal galactose with sialic acid in alpha-2,3 linkage decreased the KM values for low-molecular-weight oligosaccharides but no detectable incorporation of fucose was observed into N-acetyllactosamine end-groups of glycoproteins with N-linked oligosaccharide chains, irrespective of the presence of sialic acid in the terminal sequences.


Ganglioside alterations in YAC-1 cells cultivated in serum-supplemented and serum-free growth medium.

Gangliosides of the 'GM1b-pathway' (GM1b and GalNAc-GM1b) have been found to be highly expressed by the mouse T lymphoma YAC-1 grown in serum-supplemented medium, whereas GM2 and GM1 ('GM1a-pathway') occurred only in low amounts [Müthing, J., Peter-Katalinić, J., Hanisch, F.-G., Neumann, U. (1991) Glycoconjugate J 8:414-23]. Considerable differences in the ganglioside composition of YAC-1 cells grown in serum-supplemented and in well defined serum-free medium were observed. After transfer of the cells from serum-supplemented medium (RPMI 1640 with 10% fetal calf serum) to serum-free medium (RPMI 1640 with well defined supplements), GM1b and GalNAc-GM1b decreased and only low amounts of these gangliosides could be detected in serum-free growing cells. The expression of GM1a was also diminished but not as strongly as that of GM1b and GalNAc-GM1b. These growth medium mediated ganglioside alterations were reversible, and the original ganglioside expression was achieved by readaptation of serum-free growing cells to the initial serum-supplemented medium. On the other hand, a 'new' ganglioside, supposed to represent GalNAc-GD1a and not expressed by serum-supplemented growing cells, was induced during serum-free cultivation, and increased strongly after readaptation. These observations reveal that the ganglioside composition of in vitro cultivated cells can be modified by the extracellular environment due to different supplementation of the basal growth medium.


Comparison of the N-glycoloylneuraminic and N-acetylneuraminic acid content of platelets and their precursors using high performance anion exchange chromatography.

N-Acetylneuraminic acid (Neu5Ac) and N-glycoloylneuraminic acid (Neu5Gc) are distributed widely in nature. Using a Carbopac PA-1 anion exchange column, we have determined the ratios of Neu5Ac and Neu5Gc in hydrolysates of platelets and their precursors: a rat promegakaryoblastic (RPM) cell line and a human megakaryoblastic leukemia cell line (MEG-01). The ratio of Neu5Gc:Neu5Ac in cultured RPM cells is 16:1, whereas in platelet rich plasma and cultured MEG-01 cells it is 1:38 and 1:28, respectively. The nature of these sialic acids from RPM cells was verified using thin layer chromatography and liquid secondary ion mass spectrometry. The relevance of increased Neu5Gc levels in early stages of development is discussed.


1H resonance assignments, secondary structure and general topology of single-chain monellin in solution as determined by 1H 2D-NMR.

We determined the resonance assignments, secondary structure and general topology of the 11-kDa sweet protein single-chain monellin (SCM), using two-dimensional proton nuclear magnetic resonance spectroscopy (2D-NMR). SCM is a genetically engineered protein whose design is based on the crystal structure of natural, two-chain monellin (Kim et al., 1989). Analysis of the NMR spectra shows that the secondary structure of SCM consists of a five-strand anti-parallel beta-sheet and a 15-residue alpha-helix. Tertiary NOE constraints place the alpha-helix on the hydrophobic side of the beta-sheet, and indicate that the sheet is partially wrapped around the helix. The general structural features determined for SCM are similar to those of native monellin (Ogata et al., 1987). Some differences between the SCM structure in solution and the crystal structure of monellin are discussed.


Complete sequence-specific 1H NMR resonance assignment of hyperfine-shifted residues in the active site of a paramagnetic protein: application to Aplysia cyano-metmyoglobin.

Two-dimensional sequence-specific 1H NMR resonance assignment methodology (Wüthrich, 1986) has been applied for the first time to a 18-kDa paramagnetic hemoprotein (cyano-met Aplysia Mb) to identify all the hyperfine-shifted residues. The assignment was greatly facilitated by the fact that hyperfine shifts of residues impart a strong temperature dependence to the cross peaks, which aids location and identification, and provides improved spectral dispersion, particularly in the fingerprint region. 2D COSY and TOCSY were found to be surprisingly effective in locating the complete spin connectivities of all of the hyperfine-shifted residues, with the exception of the axially coordinated His95 imidazole ring, whose proton resonances were found to exhibit severe line broadening (> 400 Hz). Conventional 1D NOE and NOESY with short mixing times, combined with paramagnetic-induced relaxation effects, led to the successful assignment of even extremely broad proton signals. Three helical stretches and two loop regions were identified as the source of all hyperfine-shifted residues: the F helical residues 3-9, the E-helix residues 6-14, the G-helix residues 5-9, the FG-loop residues 1-4 and the CD-loop residues 1-4. These segments comprise all the residues that make contact with the heme and modulate the reactivity of the prosthetic group. The sequence-specific identifications of the active-site residues revealed that the solution structure of Aplysia metMbCN is fully consistent with that observed by X-ray diffraction in single crystals for a variety of other derivatives, except for the distal Arg66 (E10), which is turned into the heme pocket, as found only in the metMbF crystal structure (Bolognesi et al., 1990). The ready identification, by their temperature sensitivity, and the complete assignments of all hyperfine-shifted residues of Aplysia metMbCN demonstrate that sequence-specific assignment can be profitably applied to paramagnetic proteins, and that it should be possible to determine the solution structures of paramagnetic proteins, at least for low-spin complexes, by using NMR techniques used for diamagnetic proteins.


Gradient-tailored excitation for single-quantum NMR spectroscopy of aqueous solutions.

A novel approach to tailored selective excitation for the measurement of NMR spectra in non-deuterated aqueous solutions (WATERGATE, WATER suppression by GrAdient-Tailored Excitation) is described. The gradient echo sequence, which effectively combines one selective 180 degrees radiofrequency pulse and two field gradient pulses, achieves highly selective and effective water suppression. This technique is ideally suited for the rapid collection of multi-dimensional data since a single-scan acquisition produces a pure phase NMR spectrum with a perfectly flat baseline, at the highest possible sensitivity. Application to the fast measurement of 2D NOE data of a 2.2 mM solution of a double-stranded DNA fragment in 90% H2O at 5 degrees C is presented.


Selective in vivo and in vitro incorporation and accumulation of phenolic thioether amine into malignant melanoma and identification of a (58 kD) binding glycoprotein.

Our previous in vivo studies indicated that a phenolic thioether amine (PTEA), 4-S-cysteaminylphenol (CAP), selectively disintegrates melanocytes of black hair and skin, and inhibits the growth of murine and human malignant melanomas. To elucidate the mechanism of the in vivo melanocytotoxicity and anti-melanoma effect, this study examined the selectivity and specificity of PTEA incorporation into malignant melanoma cells using [14C]4(2)-S-CAP, and then identified a PTEA-binding protein through a ligand binding assay using [125I]-labelled cell lysates. Whole body autoradiography showed that [14C]4-S-CAP is selectively incorporated and accumulated into the eye and tumours of a B16 melanoma-bearing mouse. SK MEL 23 human melanoma cells also showed a steady accumulation of [14C]4-S-CAP (threefold at least up to 5 min) and of [14C]2-S-CAP (sevenfold up to 20 min), compared with that of HeLa cells and fibroblasts, which plateau at 5 min. Chromatography of 4-S-CAP on an affinity column (both CH- and CNBr-activated Sepharose 4B) identified a 58 kD protein in melanoma cells, which was present at very low levels in HeLa cells; this 58 kD protein was retained by both 4-S- and 2-S-CAP affinity columns, but not by columns of a phenolic thioether (cysteinylphenol: CP) or a phenolic thioether amide (N-acetyl-4-S-CAP), and could be retrieved by either 4-S or 2-S-CAP but not by CP and N-acetyl-4-S-CAP. This protein was glycosylated, and contained mannose residues.(ABSTRACT TRUNCATED AT 250 WORDS)


Bromodeoxyuridine hypersensitivity of metastatic melanoma cells.

A model system for testing the efficacy of chemotherapy protocols for metastatic melanoma was established using cell cultures from two brain and three lymph node metastases of melanoma from five different patients. Continuously growing cultures which were positive for tyrosinase activity were analysed regarding their proliferation rate by continuous bromodeoxyuridine (BrdU) labelling and subsequent Hoechst-33258/ethidium bromide flow cytometry. Melanoma cell cultures exhibit a strong sensitivity to BrdU: at 5% oxygen, 50% growth inhibition is attained with 360 +/- 130 microM BrdU (range: 130-520; n = 11) vs 650 +/- 50 microM BrdU (n = 3) for diploid human fibroblasts and 570 +/- 20 microM BrdU (n = 6) for human lymphoid cell lines. Moreover, BrdU sensitivity of melanoma cells is clearly oxygen dependent: 50% growth inhibition at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs 360 +/- 130 microM BrdU for 5% oxygen. The cell cycle kinetic mechanism of BrdU-induced growth inhibition is accumulation of cells in the first cycle G2 phase. On the basis of these results we suggest testing BrdU in chemotherapy protocols for the treatment of metastatic melanoma.


Improving the prognostic value of DNA flow cytometry in metastatic melanoma by combining ploidy and S-phase fraction.

The prognostic value of cellular DNA content of melanoma metastases was investigated in tumours from 114 consecutive patients referred to the Helsinki University Central Hospital Melanoma Team. Thirty-six percent of the tumours were diploid and 64% aneuploid. For 91 patients the S-phase fraction was calculable. Tumour ploidy and S-phase fraction (SPF) were shown by multivariate Cox model analysis to be independent prognostic variables and major determinants of survival after first recurrence. Patients with either aneuploid or low SPF tumours survived longer than did those with diploid or high SPF tumours. By combining DNA ploidy and SPF, three types of DNA histograms could be defined, associated with favourable, intermediate and poor prognosis. Patients with aneuploid, low SPF metastases showed a median survival of 57 months, whereas the high-risk group with diploid, high SPF metastases survived only 13 months. When ploidy, SPF, age, sex, TNM stage and duration of disease-free survival were analysed as covariates the division of flow cytometry histograms into these three types resulted in the most significant prognostic factor (p < 0.001) in the Cox multivariate analysis.


Local control of subcutaneous murine melanoma xenografts in nude mice by neutron capture therapy.

The systemic administration of enriched [10B]D,L-p-boronophenylalanine results in the selective uptake of boron by Harding-Passey melanoma xenografts in the nude mouse model. The boron-10 located in the tumour cells acts as a radiation sensitizer for thermal neutron irradiation. The nude mouse model can be successfully used to demonstrate that regression and local control of melanoma can be achieved by neutron capture therapy. Control is a manifestation of the high linear energy transfer radiation released after neutron capture by boron-10, and does not result from an equal fluence of neutrons alone. Histological examination of remnant tumour beds 300 days after treatment shows the presence of isolated melanoma cells. However, these cells are few in number and appear incapable of division.


Treatment of recurrent in transit metastases from cutaneous melanoma by isolation perfusion in extracorporeal circulation with interleukin-2 and lymphokine activated killer cells. A pilot study.

Chemoresistant melanoma cells are known to be susceptible in vitro to lymphokine activated killer (LAK) cells. To obtain a high LAK/tumour cell ratio in vivo and avoid systemic toxicity due to interleukin-2 (IL-2), we used IL-2 plus LAK cells in the treatment of in transit melanoma metastases of the limbs by isolation perfusion (IP). In vivo immunological modifications induced by this immunotherapeutic approach were also analysed. Six patients previously treated with IP in extracorporeal circulation with tumour cytotoxic drugs and presently relapsing or not responding, were submitted to locoregional adoptive therapy consisting of 5 days systemic administration of IL-2 (Proleukin, EuroCetus) (9-12 x 10(6) IU/m2/day c.i.). Autologous LAK cells were derived from leukapheresis and subsequent in vitro stimulation with IL-2; LAK cells were then given along with IL-2 (120-2400 IU/ml of perfusion priming) to the affected limb by IP. In addition, 7-16 x 10(9) LAK cells were administered by systemic infusion the day after together with IL-2 (9-12 x 10(6) IU/m2/day) by c.i. for 5 days. All patients concluded the treatment without major toxicity. The analysis of circulating lymphocytes obtained from extracorporeal circuit at different times revealed rapid disappearance of LAK cells, suggesting their extravasation and/or endothelial adhesion in perfused tissues. Clinical responses included four partial and one complete response; another patient had stable disease. All patients are presently alive. Follow-up after IP ranges from 8 to 22 months.


Elective lymph node dissection in stage I malignant melanoma: a meta-analysis.

The role of elective lymph node dissection (ELND) in stage I melanoma has been a controversial issue for decades. Numerous studies have been conducted to try to establish the benefit of ELND versus wide local excision (WLE). The majority of these studies suggest no significant difference in survival, although some investigations have shown ELND to be of benefit in intermediate thickness (0.76-3.99 mm) melanomas. In order to resolve this ongoing controversy, a meta-analysis was undertaken to review and analyse the results of previous reports. There was a total of 10,132 patients of whom 3,409 in 15 studies underwent ELND for all melanoma patients and 3,618 patients of whom 1,336 in eight studies had ELND for intermediate thickness (0.76-3.99) melanomas. No significant 5-year survival was present in all patients treated with ELND (p > 0.05, confidence intervals -0.0780, 0.0788), however, a significant 5-year survival was found in the intermediate thickness subgroup (p < 0.0001, confidence intervals -0.02, 0.22). Therefore, ELND may be valuable for improving the prognosis of patients with intermediate thickness melanomas.


The export of hazardous industries to newly industrialized countries.

The majority of investment in manufacturing industries in the newly industrialized countries come from foreign companies or investors. This vital source of new jobs and capital for the development of infrastructure brings with it some very significant longterm costs in environmental remediation and workers' compensation insurance that are seldom discussed with candor. These costs may be considered a necessary step on the road to industrialization by many developing countries. But the longterm costs may be high enough to sustain the relative poverty of the country. Moreover, the absence of value added in the process of manufacturing may insure the continued economic dependence on foreign interests. The inadequacy of international environmental law is of concern to a few important organizations. But the extent of environmental degradation in many newly industrialized countries warrants far more effort at regulation and enforcement. Likewise, the high levels of worker fatalities and injuries in developing countries remind us of the need for international cooperation and health and safety program development.


Non specific environmental factors and asthma development.

Environmental pollutants seem to be responsible for dramatical increase of allergic disorders that have been observed lately. The best documented environmental factors facilitating allergy development are: ozone, diesel-exhaust particulate matter and tobacco smoke. Formaldehyde and SO2 seem to be also very important but still are not sufficiently documented. Mechanisms involved in allergy promotion include: better penetration of allergens across respiratory mucosa or direct modulation of immunological response.


On the examination of the pulmonary toxicity of mordenite in rats.

Mordenite, a fibrous-granular type of zeolites, was examined in CFY rats in long term in vivo experiments. After single intratracheal treatment, the lungs, cervical and hilar lymph nodes of the animals were processed at the end of the 1st, 3rd and 6th month and also the 1st year by routine histology, enzyme histochemistry and electron microscopy. After observing the effect of mordenite, dust-storing macrophage foci developed in the interstitium, showing minimal fibrotic tendency by the end of the 1st year. Electron microscopic examinations showed that the dust introduced was stored in the macrophages without structural changes. Energy dispersive X-ray microanalysis indicated that in intracellularly stored dust, the ratio of the two main elements: aluminium and silicon changed in favour of aluminium as compared to the original dust sample. This phenomenon was assessed as an increase in intracellular aluminium concentration, which inhibited fibrosis, exerting an antagonistic effect on silicon.


Effect of isoniazid or phenobarbital pretreatment on the metabolism of dihalomethanes to carbon monoxide.

An oral dose of 6.2 mmoles of diachloromethane (DCM), bromochloromethane (BCM) or dibromomethane (DBM) per kg body mass yielded a maximum carboxyhemoglobin (COHb) level of about 9% (at 6 hr), 11% (at 8 hr) and 22% (at 12 hr), respectively. Pretreatment of rats with isoniazid, 4 x 0.36 mmol/kg i.p., produced significant enhancements of the COHb formation; the values were 18.0 +/- 0.8% COHb after DCM, 24.1 +/- 0.8% COHb after BCM, and 39.0 +/- 1.3% COHb after DBM. Prior administration of phenobarbital, 4 x 0.31 mmol/kg i.p., caused no appreciable alterations in the COHb levels after DCM and slight but significant increases after BCM as well as after DBM. The data indicate that the oxidative metabolism of dihalomethanes to carbon monoxide is mainly catalyzed by cytochrome P-450 IIE1 and that the DCM-evoked COHb formation seems to be a method of testing whether a chemical is an inducer of this form of cytochrome P-450 in vivo.


Effect of low dose ionizing irradiation on rat metabolism.

Thie biological effect of low dose radiation is little known. In the current study male Wistar rats were exposed monthly to a 60Co-source low dose whole body irradiation (0.25 Gy, per 18 months; total dose: 4.5 Gy). The glutathione disulphide (GSSH): total glutathione (GSH) ratio, the concentration of thiobarbituric acid-reactive substances and the activities of glutathione peroxidase and glutathione transferase in: small intestine, spleen, kidney, soleus muscle, and liver were analysed. Low dose irradiation is accompanied by distinct peroxidative changes in organs, observed in the small intestine, the spleen and in the kidneys. The current study suggests that the measurement of glutathione status and thiobarbituric acid-reactive substances can be proposed as sensitive parameters for low dose radiation induced changes.


Physiological reaction to workload in women performing manual or mental work.

The aim of our study was to evaluate the reaction of the circulatory system on work with various levels of physical and mental load. The examinations were carried out at a department store in two groups of women: 20 cashiers (mental work) and 53 saleswomen (physical work). There were no statistically significant differences in age, duration of employment or physical fitness between those groups. Work at this department store was performed on a two-shift system with irregular rotations. The psychic load was evaluated as a relation between subjective estimation of work demands and the ability to cope with them. Physical effort was measured as an energy expenditure during work. Cardiovascular reaction was expressed by heart rate during work, leisure time and sleep estimated according to the 24-hour Holter monitoring method. No statistically significant differences in heart rate were found to exist between cashiers and saleswomen. This, taking into account the much higher energy expenditure in saleswomen, suggests that mental effort is likely to affect heart rate. In fact, mean values of subjective assessment of work demands in cashiers were much higher (5.1) than in saleswomen (4.4), unlike the evaluation of the ability to cope with them, which points to the occurrence of a significant psychic load in the work of cashiers. A lower difference between maximum and minimum frequencies of heart rate in cashiers in comparison with saleswomen confirmed this observation, although it might have resulted from different levels of physical activity during work.(ABSTRACT TRUNCATED AT 250 WORDS)


The statokinesiometry in evaluation of the balance system in persons with chronic carbon disulphide intoxication.

In the group of 37 patients with chronic carbon disulphide (CS2) intoxication manifested by encephalopathy, polyneuropathy or psycho-organic syndrome and complaining for vertigo, a statokinesiometric test was performed with open and closed eyes, and with visual stimulation. Basic test parameters of stabilograms and statokinesiograms were compared with standard values of the control group. Results of the test were additionally verified by electronystagmography with the recording of spontaneous, positional, optokinetic and post-rotatory nystagmus as well as the eye-tracking test. The statokinesiometry revealed postural stability disorder in 72.9% of patients. Balance disorders detected by means of this test showed high compatibility with results of electronystagmography which confirmed damage of the central part of vestibular system due to CS2 intoxication.


Educational attainment and the risk of non-insulin-dependent diabetes or coronary heart disease in Japanese-American men.

Japanese-American men have higher rates of non-insulin-dependent diabetes mellitus and coronary heart disease than same-aged men in Japan. Associations of educational attainment with either non-insulin-dependent diabetes mellitus or coronary heart disease were examined in a sample of 229 second-generation Japanese-American men (aged 45 to 74 years) living in King County, Washington (1984 through 1985). Men with a terminal school education showed higher frequencies of both disease compared to men with any college education and to men with high school educations. Occupation, income, diet, physical activity, weight, insulin, lipids, and lipoproteins were examined to determine whether they could account for the observed associations of educational attainment with disease. Logistic regression analysis indicates that the association of educational attainment with risk of coronary heart disease is explained, in part, by the larger average body mass index, higher total and VLDL triglyceride, and lower HDL and HDL-2 cholesterol observed in men with technical school educations compared to the other men. The association of educational attainment with risk of non-insulin-dependent diabetes is not explained by any of the factors examined. The findings suggest that attainment of a college education ameliorates some of the negative effects of westernization on the health of Japanese-American men.


Social inequality of stroke mortality among US black populations, 1968 to 1987.

Though the rate of stroke mortality in the United States has been declining for all race-sex-specific groups, rates for blacks are among the highest in the world. Studies of the geographic and social variation of stroke mortality between populations have focused solely on either trends or social determinants, but not on both. In addition, conclusions have concentrated on the comparison of whites to nonwhites. The purpose of this study was to investigate the variation in stroke mortality trends, from 1968 to 1987, between US black populations categorized by the socioeconomic structure of the state economic area. The educational achievement profile of the population (percentage of the state economic area that had not completed high school) was used as an indicator of socioeconomic development. This aggregate study assessed whether (1) an inverse relationship existed between stroke mortality and educational achievement category, and (2) levels and trends of stroke mortality by educational achievement category varied from 1968 to 1987, for each age-gender-specific group (35 to 64, 65 to 74, and 75 to 84 years). Results showed an inverse relationship between educational achievement level of communities and stroke mortality, as well as a rank-ordering in level of educational achievement for all age-gender-specific groups. The absolute difference in rates among educational achievement levels clearly converged over time, with greater convergence in the period 1968 to 1978 than 1979 to 1987. The percent declines were similar across education categories. Results suggest that geographic inequalities in stroke mortality, in relation to socioeconomic structure, have converged over time.(ABSTRACT TRUNCATED AT 250 WORDS)


Cross-cultural studies in Alzheimer's disease.

The search for risk factors for Alzheimer's disease would be greatly enhanced by identification of populations with significantly different prevalence rates, particularly if these populations consisted of ethnic groups now living in different environments and cultures. Evidence is presented that two such groups are worthy of further study: subjects of African origin living in Africa and in the West and Native Americans living on and off reserves.


Correlates of HIV risk behaviors in black and white San Francisco heterosexuals: the population-based AIDS in multiethnic neighborhoods (AMEN) study.

This study, the first random household probability sample of unmarried adults in an HIV epicenter, examined the prevalence and correlates of HIV risk behaviors among sexually active unmarried heterosexual white and black adults (n = 848) in San Francisco, California. Racial or gender differences were found in the HIV risk factors among the men and women in our sample. More whites (17% men, 15% women) than blacks (12% men, 5% women) reported they had ever used injection drugs. White women were more likely to report that they had a sexual partner who used injection drugs (17%) than white men (11%), black women (5%), or black men (4%). Also, men were more likely than women to have had two or more sexual partners in the past year without using condoms: 43% of white men compared to 34% of white women and 40% of black men compared to 24% of black women. Among all ethnic and gender groups, more than half of those at sexual risk for HIV infection reported never using condoms. Of those at risk, more black women (75%) than white women (53%) reported they never used condoms with their sexual partners within the past year. However, only slightly more black men (62%) than white men (60%) at sexual risk for HIV reported they never used condoms with their sexual partners during the past year. High levels of HIV risk behaviors were associated with low income, not having a primary sexual partner, less enjoyment of condoms, and greater barriers to using condoms. The results support the need for major intervention programs and social marketing campaigns to promote the use of condoms by enhancing enjoyment of and reducing barriers to condom use, especially among sexual partners of black women.


Predicting intentions to use condoms among African-American adolescents: the theory of planned behavior as a model of HIV risk-associated behavior.

The relation of attitudes, subjective norms, and perceived behavioral control to intentions to use condoms was examined among 179 adolescents who completed a confidential self-administered questionnaire prior to participating in a minority youth health conference. Approximately 72% of the adolescents were African Americans. Hierarchical multiple regression analyses revealed that attitudes and subjective norms predicted intentions to use condoms and that, consistent with the theory of planned behavior, perceived behavioral control added a significant increment to the squared multiple correlation. Although adolescents' perceptions of their friends' approval of condom use was unrelated to their condom-use intentions, adolescents' behavioral beliefs about the effects of condoms on sexual enjoyment, normative beliefs regarding partners' and mothers' approval, and control beliefs regarding technical skill at using condoms were associated with such intentions. These results suggest the utility of the theory of planned behavior as a model of condom use among adolescents. Implications for HIV risk-reduction interventions are discussed.


Cultural, gender, and psychosocial influences on HIV-related behavior of African-American female adolescents: implications for the development of tailored prevention programs.

This paper presents epidemiologic data describing the risk of HIV/AIDS and sexually transmitted diseases for African-American female adolescents relative to their white peers. Diverse cultural, psychosocial, and gender influences affect behavior; these should be considered in the development and implementation of culturally sensitive HIV prevention interventions tailored toward African-American female adolescents. These influences include sex-role socialization issues, the African-American family; issues related to racial identity; communication styles common among African-American youth; normative influences in adolescent heterosexual relationships; and factors affecting feelings of self-efficacy, empowerment, and gender rules in the African-American female adolescent. Strategies for incorporating cultural, psychosocial, and gender influences into the development of HIV risk-reduction interventions are suggested. Culturally specific interventions tailored toward this population may be more effective at motivating the adoption and maintenance of HIV-preventive behaviors.


'Many are called...': participation by minority leaders in an AIDS intervention in San Francisco.

Though the AIDS epidemic has posed a significant threat to minority people, especially African Americans and Latinos, minority community response to the epidemic has lagged significantly behind the organized efforts initiated by the European-American gay community. To test the efficacy of an educational intervention in increasing the involvement of minority leaders in AIDS-related efforts, we identified and recruited 166 African-American and Latino leaders to participate in a randomized controlled trial. This report describes the identification and recruitment of leaders to the study. Overall, participation was low. Rates of participation were not associated with race but were significantly associated with category of leadership--that is, whether the individual was a religious leader, an agency director, an elected official, or an informal leader, with religious leaders least likely and agency directors most likely to participate. We discuss the implications of these findings for improving epidemic response in minority communities.


Oxytalan fibres in proliferative vitreoretinopathy.

The distribution of elastic and related fibres was studied in 29 fibrocellular membranes associated with proliferative vitreoretinopathy using histochemical, immunohistochemical and ultrastructural techniques. Ten subretinal and ten epiretinal membranes were subjected to light microscopical investigation, whilst the remaining nine membranes were examined by transmission electron microscopy. Oxytalan fibres, an elastic fibre precursor that is found in a variety of normal and pathological connective-tissue matrices, were identified in all of the specimens. Mature elastic fibres were not observed in any of the 29 membranes. The demonstration that oxytalan connective-tissue fibres contribute to the infrastructure of PVR membranes adds further evidence to the suggestion that this proliferative tissue might be the result of a repair mechanism.