Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration - a pilot study in vitro.

BACKGROUND: The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field. METHODS: In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds' morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 µm, 300 µm, 375 µm, 450 µm and 500 µm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63. RESULTS: All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 µm and 500 µm, a preferred box size for initial osteoblast attachment could not be found. CONCLUSIONS: These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.

Integrating asthma hazard characterization methods for consumer products.

Despite extensive study, definitive conclusions regarding the relationship between asthma and consumer products remain elusive. Uncertainties reflect the multi-faceted nature of asthma (i.e., contributions of immunologic and non-immunologic mechanisms). Many substances used in consumer products are associated with occupational asthma or asthma-like syndromes. However, risk assessment methods do not adequately predict the potential for consumer product exposures to trigger asthma and related syndromes under lower-level end-user conditions. A decision tree system is required to characterize asthma and respiratory-related hazards associated with consumer products. A system can be built to incorporate the best features of existing guidance, frameworks, and models using a weight-of-evidence (WoE) approach. With this goal in mind, we have evaluated chemical hazard characterization methods for asthma and asthma-like responses. Despite the wealth of information available, current hazard characterization methods do not definitively identify whether a particular ingredient will cause or exacerbate asthma, asthma-like responses, or sensitization of the respiratory tract at lower levels associated with consumer product use. Effective use of hierarchical lines of evidence relies on consideration of the relevance and potency of assays, organization of assays by mode of action, and better assay validation. It is anticipated that the analysis of existing methods will support the development of a refined WoE approach.

Development and clinical assessment of an artificial cornea.

Keratoprosthesis research has been a gradual, rather fragmentary process with advances being made by isolated groups of researchers. This has arisen partly because of poor funding in the area; research groups which have achieved commercial support have often had constraints upon the full disclosure of their findings. Despite these difficulties there has been real progress over the last decade by several independent groups. This article concentrates upon our own development of a hydrogel core-and-skirt keratoprosthesis, the Chirila KPro, in order to illustrate the scientific and clinical problems common to keratoprosthesis research. Pilot data from a clinical trial is presented and the priorities for future research are discussed.

Histology of the gastroesophageal junction: an autopsy study.

Current diagnostic criteria for reflux disease and Barrett's esophagus are based on the belief that the gastroesophageal junction normally contains 2 cm of cardiac mucosa composed of mucous glands devoid of parietal cells. This autopsy study disproves this belief. Even when the entire circumference of the gastroesophageal junction is examined, pure cardiac mucosa was completely absent in 56% of patients. All patients had oxyntocardiac mucosa, in which glands contained a mixture of mucous and parietal cells. Cardiac and oxyntocardiac mucosae were present only in part of the circumference of the junction in 50% of patients. The measured maximum length of cardiac plus oxyntocardiac mucosa was less than 0.5 cm in 76% of patients. There was a tendency for the presence and extent of cardiac mucosa to increase with age. Cardiac mucosa at the junction is therefore frequently absent, has considerable individual variation, is very small in extent when present, is commonly absent from some part of the circumference of the junction, and increases in prevalence and length with age. These characteristics of cardiac mucosa make it highly unlikely that it is a normal structure. We develop the hypothesis that cardiac mucosa represents an early histologic manifestation of gastroesophageal reflux.

Distribution and significance of epithelial types in columnar-lined esophagus.

An abnormal columnar-lined esophagus (CLE) is characterized by the presence of cardiac mucosa (CM) oxynto-cardiac mucosa (OCM), and intestinal metaplastic epithelium (IM) between gastric oxyntic mucosa and esophageal squamous epithelium. Thirty-two patients with CLE measuring 2-16 cm long had 5-37 biopsies per patient that showed CM, OCM, or IM for a total of 424 biopsies. Detailed mapping of the distribution of epithelial types within the CLE showed a distinct zonation of epithelial types; CM was present throughout the CLE, whereas OCM and IM tended to occur in the distal and proximal part of the CLE, respectively. All 32 patients (64 of 68 biopsies) showed IM at the most proximal level, compared with 22 of 32 patients (40 of 102 biopsies) in the most distal level biopsies. The density of goblet cells was highest in the most proximal level. The differences in prevalence and density of goblet cells between most proximal and most distal level biopsies were highly significant. These data suggest that for a given number of biopsies within the CLE, the likelihood of finding IM is greatest when the biopsies are concentrated in the most proximal area of the CLE. We suggest that glandular transformation of squamous epithelium results in CM. which evolves into OCM and IM by development of specialized parietal cells and goblet cells, respectively. The severity and nature of reflux cause these epithelial transformations in a constant and predictable manner. Recognition of these changes permits the development of morphologic definitions of reflux disease and the characterization of the sequence of epithelial changes that represent the reflux-adenocarcinoma sequence.

Acoustic myography for investigating human skeletal muscle fatigue.

Sounds produced during voluntary isometric contractions of the quadriceps muscle were studied by acoustic myography (AMG) in five healthy adults. With the subject seated, isometric force, surface electromyography (EMG), and AMG were recorded over rectus femoris, and the EMG and AMG signals were integrated (IEMG and IAMG). Contractions lasting 5 s each were performed at 10, 25, 50, 60, 75, and 100% of maximum voluntary contraction (MVC) force. Fatigue was then induced by repeated voluntary contractions (10 s on, 10 s off) at 75% MVC until only 40% MVC could be sustained. After 15 min of rest, the different force levels were again tested in relation to the fresh MVC. Both before and after fatiguing activity the relationships between force and IEMG [r = 0.99 +/- 0.01 (SD), n = 10] and force and IAMG (r = 0.98 +/- 0.02) were linear. After activity, however, the slopes of the regression lines for force and IEMG increased (P less than 0.01) but those for force and IAMG remained the same (P greater than 0.05). The present results clarify the relationship between AMG and isometric force in fatigued muscle without the problem of fatigue-induced tremor, which hampered previous studies of prolonged activity. This study contributes to the validation of AMG and shows that it is a potentially useful method for noninvasive assessment of force production and fatigue. Further studies to establish the origin of AMG activity are required before AMG can be accepted for use in neuromuscular physiology or rehabilitation.

Preventing annoyance from odors in spaceflight: a method for evaluating the sensory impact of rodent housing.

For the scientific community, the ability to fly mice under weightless conditions in space offers several advantages over the use of rats. These advantages include the option of testing a range of transgenic animals, the ability to increase the number of animals that can be flown, and reduced demands on shuttle resources (food, water, animal mass) and crew time (for water refill). Mice have been flown in animal enclosure module (AEM) hardware only once [Space Shuttle Transport System (STS)-90] and were dissected early in the mission, whereas rats have been flown in the AEM on >20 missions. This has been due, in part, to concerns that strong and annoying odors from mouse urine (vs. rat urine) will interfere with crew performance in the shuttle middeck. To screen and approve mice for flight, a method was developed to evaluate the odor containment performance of AEMs housing female C57BL/6J mice compared with AEMs housing Sprague-Dawley rats across a 21-day test period. Based on the results of this test, consensus was reached that mice could fly in the AEM hardware for up to 17 days (including prelaunch and contingency) and that the AEM hardware would likely contain odors beyond this duration. Human sensory and electronic nose analysis of the AEMs postflight demonstrated their success in containing odors from mice for the mission duration of STS-108 (13 days). Although this paper focuses specifically on odor evaluations for the space shuttle, the concern is applicable to any confined, closed-system environment for human habitation.

Cognitive influences on health symptoms from acute chemical exposure.

Symptom reports, perceived adverse health effects, and public health concerns are increasingly precipitated by the perception of chemical odors. This study examined the interaction between health cognitions, odor perception, and symptom reports. A group of 180 healthy men and women were exposed to 1 of 3 ambient odors, normatively rated as healthful (methyl salicylate, or wintergreen), harmful (butanol or alcohol), and ambiguous (isobomyl acetate, or balsam), after receiving 1 of 3 odorant characterizations (harmful, healthful, and neutral). Individuals given a harmful bias reported significantly more health symptoms following exposure and more intense odor and irritation during exposure than did those given a neutral or healthful bias. The overall pattern of results suggests that many of the health-related effects of exposure to odorants are mediated not by a direct agency of odors but by cognitive variables, such as mental models of the relationship between environmental odors and health.

Acoustic myographic activity increases linearly up to maximal voluntary isometric force in the human quadriceps muscle.

Sounds produced during voluntary isometric contractions of the quadriceps muscle were recorded by acoustic myography (AMG) in seven healthy adults. With the subject seated, surface AMG and electromyography (EMG) were recorded over rectus femoris (RF) during isometric contractions, at different levels of maximum voluntary force. The AMG and EMG signals were amplified and integrated (IAMG and IEMG). The relationships between force and IAMG (r = 0.98 +/- 0.01, mean +/- 1 SD) and force and IEMG (r = 0.99 +/- 0) were linear in all subjects. The results for EMG confirm previous reports but those for AMG differ from the relationships reported for other muscles. Physiological and technical explanations are proposed for these differences and the necessity for further validation of the AMG technique is stressed.

Acoustic myography of the human quadriceps muscle during intermittent fatiguing activity.

Integrated acoustic myography (IAMG) and electromyography (IEMG) were recorded over rectus femoris (RF) in six healthy subjects during a series of intermittent isometric contractions of quadriceps. Contractions were held for 10 sec with 10 sec rest between each, commencing at 75% maximum voluntary contraction (MVC) force and continuing to 40% MVC. The IAMG activity initially decreased (75%-60% MVC) in a linear relationship (r = 0.9) with fatigue (i.e. force loss) but then plateaued and increased once force fell below 52% MVC. The AMG/force relationship for the whole fatiguing protocol (i.e. 75%-40% MVC) was quadratic (r = 0.87). The IEMG also showed a quadratic relationship with force (r = 0.85) but activity initially increased before decreasing. The results of the present study quantify the relationship between AMG and force in quadriceps during fatigue from intermittent contractions commencing at 75% MVC. The findings confirm previous observations that AMG decreases with fatigue during strong contractions but the quadratic relationship found in the present study differs to that for other muscles during sustained contractions. The results also suggest that simultaneous recordings of AMG and EMG may help distinguish central and peripheral fatigue. Acoustic myography may therefore be a useful non-invasive monitor of force during early fatiguing activity using the present protocol but the need to study AMG during fatigue of different muscles and force levels is stressed.

Immunity after treatment of human schistosomiasis mansoni. I. Study design, pretreatment observations and the results of treatment.

This paper describes the design of a study on immunity to reinfection after treatment of children with Schistosoma mansoni infections, the initial observations on transmission that led to the selection of the study population, the effects of treatment, and the results of immunological tests carried out before and at five weeks after treatment. Iietune village in Machakos District, Kenya, was selected on the basis of high prevalence and intensities of infection in a small preliminary survey, a stable population living in a small area amenable to detailed study, and a lack of previous intervention in the area. Subsequent observations over a pretreatment period of one year confirmed that prevalence and intensities of infection among children attending the local primary school were high. This was associated with extensive contact of members of the community with water-bodies shown to contain large numbers of infected snails. Analysis of pretreatment intensities of infection and water contact patterns in the schoolchildren allowed the selection of 129 children showing a broad scatter between: (a) high intensity, low water contact, and predicted to be non-immune, and (b) low intensity, high water contact, and predicted to be immune. These children were treated with oxamniquine, 30 mg/kg in divided doses. Five weeks after treatment, 70% of children showed apparent complete cure, and the over-all reduction in geometric mean egg output was 98.9%. Since these children represented only a small proportion of the whole community, there was no obvious reduction in transmission, as reflected by snail infection rates, during the following five-month period. Thus, we are in a position to determine whether successfully treated children do or do not become reinfected in a high transmission environment in which it will be possible to make direct estimates of exposure. Immunological tests carried out immediately before treatment were consistent with a pattern of high exposure leading to the early expression of immune responses in most infected children. Eosinophil levels were elevated in 61% of the children, all of whom showed detectable levels of antibodies against adult worm and egg antigens, as measured by ELISA. In addition, all patients showed antibodies capable of mediating eosinophil-dependent killing of schistosomula. At five weeks after treatment, eosinophil counts and anti-adult worm antibody levels had risen, whereas anti-egg antibodies remained grossly unchanged. The wide variation in the levels of responses shown by different individuals will allow us to test whether such responses are associated with resistance to reinfection during the follow-up period.

Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment.

Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man.

Evidence for predisposition of individual patients to reinfection with Schistosoma mansoni after treatment.

Statistical analysis of the relationship between intensities of infection before treatment and during reinfection after treatment in a sample of 119 Kenyan schoolchildren demonstrated a positive association, indicating that the individuals differed consistently in their tendency to become infected. This association was stronger in young children but the trend was detectable in older individuals. Possible reasons for this variation and for its apparently greater influence in younger age groups are discussed.

Immunity after treatment of human schistosomiasis mansoni. II. Identification of resistant individuals, and analysis of their immune responses.

Intensities of re-infection were monitored at three-monthly intervals after treatment of Schistosoma mansoni infections in a group of 119 Kenyan schoolchildren, whose levels of water contact were also observed. 22 children showed high reinfection intensities (greater than 100 eggs per gram of faeces) by 12 months after treatment, and were considered to be susceptible. Out of 70 children who showed low reinfection intensities during the same period (less than 30 eggs per gram), 35 showed high levels both of total water contact and of contact with sites containing infected snails. In these children, the relative lack of reinfection could not be attributed to a lack of exposure, and they were classified as resistant to reinfection. Comparison of the two groups, resistant and susceptible, revealed no difference in pretreatment intensities of infection. However, there was a marked difference in age, the mean age of the resistant group being two years greater than that of the susceptible group, within a restricted starting age range. These findings indicated that resistance was an acquired and age-dependent phenomenon, not obviously related to previous egg-induced pathology. Studies of immune responses revealed no clearcut correlate of resistance, but there were interesting differences between the two groups. Whereas anti-egg antigen responses declined after treatment to a greater extent in the resistant than in the susceptible group, antibodies mediating eosinophil-dependent killing of schistosomula rose markedly in both groups, strongly suggesting that the resistant children were being exposed to cercariae. Anti-adult worm antibodies rose sharply in both groups immediately after treatment, and thereafter declined to pretreatment levels. Although some individual children showed high levels of IgE anti-schistosomulum antibodies, there were no significant differences between the two groups. Since all children showed detectable levels of antibodies mediating eosinophil-dependent killing of schistosomula, the possibility was considered that such antibodies might be a necessary, but not a limiting, factor in immunity. Instead, the functional state of the effector cells mediating antibody-dependent killing might be limiting. Eosinophil levels, measured as an indirect estimate of eosinophil functional activity, did not differ between the two groups. There were, however, marked differences between different individuals in their capacity to produce eosinophil-stimulating monocyte mediators, and although this cannot yet be related to resistance, this aspect is worth further study.(ABSTRACT TRUNCATED AT 400 WORDS)

Preliminary evaluation of a hydrogel core-and-skirt keratoprosthesis in the rabbit cornea.

BACKGROUND: We developed a core-and-skirt keratoprosthesis, with both components made from poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels. The identical chemical nature of both spongy skirt and transparent core assures a permanent union between them. We have previously shown that PHEMA sponges, within a certain range of pore size, can support cellular invasion and neovascularization when implanted into the rabbit cornea. The present study is the first to evaluate the behavior of the whole prosthesis after implantation into the rabbit cornea. METHODS: Hydrogel keratoprostheses were inserted intrastromally into the corneas of seven rabbits and histologically examined by light microscopy in five eyes enucleated at 8, 12, and 14 weeks. RESULTS: None of the implants extruded over this period. Both clinical and histopathologic examination showed that the keratoprostheses were well tolerated by the host tissue. The porous skirt was fully integrated into the stroma by fibrovascular invasion, and no capsule formed around the implants. Stromal melting anterior to the implant occurred in two cases, but this did not affect the fixation of the keratoprostheses. CONCLUSIONS: This study indicates that our keratoprosthesis can prevent extrusion in the short term when inserted into an intrastromal pocket of the rabbit eye.

Clinical results of implantation of the Chirila keratoprosthesis in rabbits.

AIMS/BACKGROUND: An ideal keratoprosthesis (KPro) would closely resemble a donor corneal button in terms of its surgical handling, optics, and capacity to heal with host tissue in order to avoid many of the complications associated with the KPros which are currently in clinical use. This study was carried out to assess the long term clinical outcomes on implantation of the core and skirt poly(2-hydroxyethyl methacrylate) KPro in animals. METHODS: 20 KPros were made and implanted as full thickness corneal replacements into rabbits and followed for up to 21 months to date. RESULTS: 80% of the prostheses have been retained, with a low incidence of complications such as cataract, glaucoma, and retroprosthetic membrane formation which are frequently associated with KPro surgery. CONCLUSIONS: KPros of this type may offer promise in the treatment of patients for whom penetrating keratoplasty with donor material carries a poor prognosis. Refinement of the KPro and further animal trials, including implantation into abnormal corneas, are however mandatory before human implantation could be planned.

Spatial patterns of human water contact and Schistosoma mansoni transmission and infection in four rural areas in Machakos District, Kenya.

This paper presents the results of microgeographical studies of human water contact behavior and Schistosoma mansoni transmission levels and intensity of infection in four rural areas in Machakos District, Kenya. The relationship between intensity of infection (geometric mean egg counts) in 3502 persons aggregated in 120 household clusters and eight independent variables was investigated using straight and stepwise linear regression and mapping techniques. Results indicate that the two water contact variables, mean frequency per person and mean duration per person, as well as mean number of sites used per person, a transmission index and mean distance to the most frequently used site were the strongest predictors of geometric mean egg counts. All three distance variables were usually negatively associated with infection although intensity of infection and water contact declined relatively slowly with distance from the streams. This pattern appears to be owing to a combination of the relatively short distances, a general lack of safe alternative water sources and the use of more distant water contact sites both inside and outside the study area during periods of drought. The study of snail-to-man transmission identified number of infected snails as the major transmission variable and number of contacts as the major predictor variable. Mapping of total egg counts at the household cluster level and total number of infected snails revealed spatial association with transmission sites. All results varied considerably between study areas, owing to differences in exposure levels, transmission patterns and environmental factors. Findings are discussed in relation to the epidemiology and control of schistosomiasis and suggestions are made for further spatial studies.

The distribution and characteristics of neck-arm pain in patients with and without a neurological deficit.

Neck and referred arm pain may arise from either somatic or neural tissues. Clinicians use the subjective nature of a patient's pain to aid the differentiation of the origin of the referred pain but little evidence has been presented to support the reliability of this practice. For this reason, 42 subjects with neck-arm pain were studied. They were subgrouped according to their neurological status in order to investigate whether differences existed between the groups in the descriptive nature and distribution of pain. Subjects with and without neurological signs were found to have no significant differences in the pain characteristics of area, region of greatest intensity, quality, depth and pain localization (p> .05).

The use of Fourier transform infrared spectrometry for monitoring the retention of polymers in the vitreous humour.

A frequent cause of the failure of various materials tested as artificial vitreous substitutes is their short retention in the vitreous humour of the eye. Previous techniques to monitor the residence time of the vitreous substitutes have been traditionally complicated and usually involved the chemical modification of the test fluids. Fourier transform infrared (FTIR) spectrometry is used in this study to determine the rate of disappearance of a crosslinked poly(1-vinyl-2-pyrrolidinone) (PVP) hydrogel after injection into the vitreous humour of rabbits. The fluid removed from the eye at various postoperative intervals of time (1 day, 1 week, and 1 month) was placed on a horizontal attenuated reflectance (ATR) unit, and the infrared spectrum from 700 to 3000 cm-1 was obtained directly. The absorption band at 1295 cm-1 due to C-N stretching vibration does not overlap with bands of any other species (natural vitreous, blood) present in the test fluid. By estimating the intensity of this band, it was found that about 80% of the injected polymer was removed from the vitreous cavity within 1 month. This study shows that (1) FTIR spectrometry is a convenient method to assess the residence time of foreign materials in the vitreous humour, and (2) the PVP gel is unsuitable in this current form as a permanent vitreous substitute, regardless of the pathways of its removal, such as phagocytosis of fragments produced by the injection process, or enzymatic biodegradation.

Dupuytren's disease of the wrist.

The authors present the case of a 47-year-old female who presents with bilateral Dupuytren's disease of the wrist. To date, three English language papers reporting on the occurrence of Dupuytren's disease at the wrist have been presented. These reports represent cases in males with unilateral involvement of their wrists where there has been primary Dupuytren's disease of the palm apparently spreading to the wrist in continuity. Our case demonstrates isolated bilateral Dupuytren's disease of the wrist in a female. The authors feel that this clinical presentation is rare and that consideration should be given to the diagnosis of Dupuytren's disease when there is a painful lesion of the soft tissues adjacent to the wrist. The presence of bilateral lesions at the wrist should further heighten the suspicion of Dupuytren's disease even in the absence of associated disease in the palm or fingers. A discussion of the previous reports is included.