Long-term follow-up of Perthes' disease treated nonoperatively

Forty-six patients with Perthes disease treated nonoperatively were reviewed 10 to 43 years later. The median follow-up was 17 years. The patients were analyzed according to sex, age of onset, quantity of head involvement, type of treatment, duration of treatment, functional end result based on the Harris hip scale, and anatomic end result based on Mose templete evaluation. Most patients were treated with an ischial weight-bearing brace. The anatomic results of this treatment tended to be poor, probably worse than no treatment at all. In general, poor results were correlated with late onset, greater quantity of head involvement, and lateral subluxation of the femoral head. As reported in other series, the anatomic results did not correlate well with the functional results, only two patients having Harris hip scales below 70.     

Technical basis for EPA's proposed regulation on the cleanup of sites contaminated with radioactivity

The U.S. Environmental Protection Agency is proposing a regulation for the protection of the public from radioactive contamination at sites that are to be cleaned up and released for public use. The rule will apply to sites under the control of Federal agencies, and will impose limits on radiation doses to individuals living or working on a site following cleanup; it will thereby provide site owners and managers with uniform, consistent cleanup criteria for planning and carrying out remediation. This paper presents an overview of EPA's approach to assessing some of the beneficial and adverse effects associated with various possible values for the annual dose limit. In particular, it discusses the method developed to determine how the choice of cleanup criterion affects (1) the time-integrated potential numbers of non-fatal and fatal radiogenic cancers averted among future populations, (2) the occurrence of radiogenic cancers among remediation workers and the public caused by the cleanup process itself, and (3) the volumes of contaminated soil that may require remediation. The analytic methods described here were used to provide input data and assumptions for the Regulatory Impact Analysis (RIA) that supports the proposed regulation; the RIA also considered non-radiological benefits and costs (i.e., public health, economic, and ecological) of the standards.     

Cellular and molecular basis of estrogen's neuroprotection. Potential relevance for Alzheimer's disease

Alzheimer's disease (AD) is one of the most common types of dementia among the aged population, with a higher prevalence in women. The reason for this latter observation remained unsolved for years, but recent studies have provided evidence that a lack of circulating estrogen in postmenopausal women could be a relevant factor. Moreover, follow-up studies among postmenopausal women who had received estrogen-replacement therapy (ERT), suggested that they had a markedly reduced risk of developing AD. In addition, studies among older women who already had AD indeed confirmed that a decrease in estrogen levels was likely to be an important factor in triggering the pathogenesis of the disease. In this review article, we will discuss the evidence suggesting that estrogen may have a protective role against AD, mainly through its action as: a trophic factor for cholinergic neurons, a modulator for the expression of apolipoprotein E (ApoE) in the brain, an antioxidant compound decreasing the neuronal damage caused by oxidative stress, and a promoter of the physiological nonamyloidogenic processing of the amyloid precursor protein (APP), decreasing the production of the amyloid-beta-peptide (A beta), a key factor in the pathogenesis of AD.     

Early synaptogenesis in vitro: role of axon target distance

In contrast to some previous reports suggesting a delay in synapse formation in vitro, we found that under ideal conditions, most hippocampal and hypothalamic rat neurons were synaptically coupled after 3 or 4 days in vitro. Synaptophysin immunocytochemistry revealed strongly stained presynaptic boutons by 3 days in vitro. Studies with time-lapse laser confocal imaging of FM1-43 revealed that axonal boutons were recycling their synaptic vesicles, an indication of synapse formation, as early as 3 days after plating. To test the hypothesis that neurite outgrowth was enhanced in high-density cultures, thereby increasing the probability of synapse formation, neurons were transfected with the jellyfish green fluorescent protein (GFP) gene. After 2 days in high-density cultures, green fluorescent neurites were about three times longer than in sister neurons plated in low-density cultures. Even in single dishes, GFP-transfected cells in contact with other neurons had neurites that were at least three times longer and grew faster than more isolated cells. Neurons grew longer neurites (+51%) when growing on surface membranes of heat-killed neurons than on polylysine, underlining the importance of plasma membrane contact. Calcium imaging with fura-2 and whole cell recording showed that both GABA and glutamate presynaptic release occurred after 3 or 4 days in vitro in high-density cultures but was absent in low-density cultures at this time. Together, these morphological, cytochemical, and physiological data suggest that the distance an axon must grow to find a postsynaptic partner plays a substantial role in the timing of synapse formation. Although other factors in vitro may also play a role, the distance to a postsynaptic target, which defines the interval during which an axon grows to its target, can probably account for much of the difference in timing of synapse formation previously reported in vitro. A short intercell distance may increase the concentration of limited amounts of trophic factors available to a nearby cell, and once contact is made, a neuronal membrane provides a superior substrate for neuritic elongation.     

Trichloroethene levels in human blood and exhaled breath from controlled inhalation exposure

The organic constituents of exhaled human breath are representative of bloodborne concentrations through gas exchange in the blood/breath interface in the lungs. The presence of specific compounds can be an indicator of recent exposure or represent a biological response of the subject. For volatile organic compounds, sampling and analysis of breath is preferred to direct measurement from blood samples because breath collection is noninvasive, potentially infectious waste is avoided, the sample supply is essentially limitless, and the measurement of gas-phase analytes is much simpler in a gas matrix rather than in a complex biological tissue such as blood. However, to assess the distribution of a contaminant in the body requires a reasonable estimate of the blood level. We have investigated the use of noninvasive breath measurements as a surrogate for blood measurements for (high) occupational levels of trichloroethene in a controlled exposure experiment. Subjects were placed in an exposure chamber for 24 hr; they were exposed to 100 parts per million by volume trichloroethene for the initial 4 hr and to purified air for the remaining 20 hr. Matched breath and blood samples were collected periodically during the experiment. We modeled the resulting concentration data with respect to their time course and assessed the blood/breath relationship during the exposure (uptake) period and during the postexposure (elimination) period. Estimates for peak blood levels, compartmental distribution, and time constants were calculated from breath data and compared to direct blood measurements to assess the validity of the breath measurement methodology. Blood/breath partition coefficients were studied during both uptake and elimination. At equilibrium conditions at the end of the exposure, we could predict actual blood levels using breath elimination curve calculations and a literature value partition coefficient with a mean ratio of calculated:measured of 0.98 and standard error (SE) = 0.12 across all subjects. blood/breath comparisons at equilibrium resulted in calculated in vivo partition coefficients with a mean of 10.8 and SE = 0.60 across all subjects and experiments and 9.69 with SE = 0.93 for elimination-only experiments. We found that about 78% of trichloroethene entering the body during inhalation exposure is metabolized, stored, or excreted through routes other than exhalation.     

Innervation of the equine mature and immature proximal sesamoid bone by calcitonin gene-related peptide and substance P-containing nerves

OBJECTIVE: To localize and determine relative frequency of occurrence of calcitonin gene-related peptide (CGRP) and substance P (SP) fibers in the proximal sesamoid bones (PSB) and adjacent structures in sound horses. SAMPLE POPULATION: 4 foals and 3 adult horses. PROCEDURE: Medial PSB and adjacent ligaments of both forelimbs were collected, flushed, and fixed in buffered 4% formalin. The left PSB were cut into 5 longitudinal, sagittally oriented slabs, and the right PSB were cut into 5 transverse slabs. After decalcification in EDTA, slices were transferred to a 30% sucrose solution, deep frozen, sectioned (80 microm), and stored in Tris-buffered saline solution for free-floating immunocytochemical processing, staining of which was performed by use of the peroxidase-antiperoxidase method with polyclonal rabbit antibodies against CGRP and SP. Sections were examined by light microscopy. RESULTS: Calcitonin gene-related peptide and SP fibers were present throughout the PSB; in ligaments, they were concentrated at the attachment sites. Presentation of the fibers, the innervation pattern, and intensity in the bones of horses differed from that in foals, in which the fibers were more delicate and frequency of occurrence was lower. In horses, innervation with CGRP and SP fibers was more dense in the periphery of the bone, whereas in foals, local difference in innervation of the bone was not evident. With the exception of the intersesamoidean ligament, ligaments were more richly innervated than was bone. CONCLUSION: Presence of the nociceptive peptides CGRP and SP indicated that the PSB and, more practically, the adjacent ligaments are sensitive structures.     

Indications for laparoscopic colorectal surgery. Results from the Medical Centre Alkmaar, The Netherlands

The Boyden chamber method showed that the invasiveness to reconstituted blood vessel endothelium of metastatic gynecologic cancer cell lines of the uterine cervix (MS751 and ME-180), endometrium (AN3 CA), and ovary (SK-OV-3 and PA-1) was significantly higher than of primary cancer cell lines of the cervix (HeLa and C-33 A), endometrium (Ishikawa, HEC-1-A and HHUA), and ovary (MCAS and Caov-3), and that the invasiveness was inhibited by estradiol or progestin in the metastatic cells but not in the primary cells. These results suggest that metastatic cancer cells by themselves increase the potential of blood vessel invasion, which can be inhibited by estrogen and progestin administration.