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Biomedical subjects

L Nolan

Publications and source records attributed to L Nolan.

At least 19 recordsLinked to original sources

LASIK surgery in children.

AIMS: To report success in the treatment of high myopia in children with LASIK. To report the visual results, complications and postoperative management of children with high myopia. METHODS: Six children (seven eyes) with high myopia were included in this series. Preoperative and postoperative refraction, visual acuity, and pachymetry were compared. RESULTS: Six children with high myopia ranging from -5.00DS to -16DS were treated. There were three males and three females. Five children had improved refraction and visual acuity post-LASIK. Age ranged from 2 to 12 years. Five of the children had unilateral amblyopia preoperatively. One had bilateral high myopia. CONCLUSION: High myopia in children may be treated safely and effectively with LASIK.

Child↗

ANX7, a candidate tumor suppressor gene for prostate cancer.

The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P = 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.

Annexin A7↗

ANX7 as a bio-marker in prostate and breast cancer progression.

The ANX7 gene codes for a Ca2+-activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro-arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 expression has prognostic value for predicting survival of breast cancer patients.

Animals↗

Touch-down and take-off characteristics of the long jump performance of world level above- and below-knee amputee athletes.

The aims of this study were to establish the take-off characteristics of long jump performance of disabled amputee athletes, and to establish to what extent amputee athletes conform to a model of performance defined for elite able-bodied athletes. The jumps of 8 male below-knee (trans-tibial) and 8 male above-knee (trans-femoral) amputee athletes who competed in the finals of the long jump at the 1998 World Disabled Championships were recorded in the sagittal plane on video (50 Hz). Approach speed was measured using a laser Doppler system. The best jump for each athlete was digitized, and kinematic data from the key instants of touch-down (TD), maximum knee flexion (MKF) and take-off (TO) were obtained. Amputees demonstrated a lower approach speed and jumped less far than able-bodied athletes although below-knee amputees performed better than above-knee amputees. For each amputee group there was a significant (p < 0.05) linear relationship between approach speed and distance jumped. With the exception of their slower horizontal speed and greater negative vertical speed at touch-down, below-knee amputees demonstrated characteristics of technique that were similar to elite able-bodied long jumpers. Above-knee amputees at touchdown had a more upright trunk, smaller hip and knee angles and consequently a smaller leg angle. This was attributed to the difficulty of taking off on the last stride on the prosthetic limb. Consequently, above-knee amputees were less able to gain vertical velocity during the compression (TD-MKF) phase, but were able to compensate for this by using a greater hip range of motion during the extension (MKF-TO) phase. It was concluded that below-knee amputees displayed the same basic jumping technique as elite able-bodied long jumpers, but above-knee amputees did not. These findings have implications for the training and technical preparation of amputee long jumpers.

Amputees↗

The functional demands on the intact limb during walking for active trans-femoral and trans-tibial amputees.

The aim of this study was to investigate the loading demands placed on the intact limb in terms of joint moments and power for active trans-femoral and trans-tibial amputees in comparison to a group of able-bodied subjects. Four (4) trans-tibial, 4 trans-femoral amputees and 10 able-bodied subjects walked at 1.2m.s(-1) along a walkway whilst kinematic data from both the intact and prosthetic limbs, and kinetic data from the intact limb only were collected. A Panasonic VHS video camera was used to film subjects walking in the sagittal plane with simultaneous force data collected from a Kistler force platform. The amputees were found to compensate for the functional loss of one or more joints by increasing net joint moments and power output on their intact limb compared to able-bodied subjects. At the intact limb ankle, the range of motion, peak dorsiflexor moment and power generation at toe-off increased. At the intact limb knee, power generation during stance and extensor moments and power absorption at toe-off increased. At the intact limb hip, extensor moment and power absorption during stance, and hip flexor moment and power generation at toe-off increased. These findings were partly attributed to the prostheses used but mainly to adaptation mechanisms displayed by trans-femoral and trans-tibial amputees. They have implications for the mobility of amputees and the long term health of their joints. It was recommended that prosthesis design, prosthesis fitting and training in the use of the prosthesis were all factors which could be investigated with a view to minimising intact limb loading.

Adult↗

Impact of community health workers on access, use of services, and patient knowledge and behavior.

Community health workers have been used in health centers for several decades. Known by various names (e.g., community health advisors, outreach workers, promotoras), they are trusted community members providing informal community-based health-related services and establishing vital links between health providers and the community. They perform many functions, including outreach and case finding, health education, translation, patient transportation, and case management (under the supervision of a nurse or social worker). This article, based on a study of community health worker programs at seven sites, is intended to share the lessons learned that could be helpful to other program managers and to examine the outcomes of such programs.

Community Health Centers↗

The biomechanics of soccer: a review.

This review considers the biomechanical factors that are relevant to success in the game of soccer. Three broad areas are covered: (1) the technical performance of soccer skills; (2) the equipment used in playing the game; and (3) the causative mechanisms of specific soccer injuries. Kicking is the most widely studied soccer skill. Although there are many types of kick, the variant most widely reported in the literature is the maximum velocity instep kick of a stationary ball. In contrast, several other skills, such as throwing-in and goalkeeping, have received little attention; some, for example passing and trapping the ball, tackling, falling behaviour, jumping, running, sprinting, starting, stopping and changing direction, have not been the subject of any detailed biomechanical investigation. The items of equipment reviewed are boots, the ball, artificial and natural turf surfaces and shin guards. Little of the research conducted by equipment manufacturers is in the public domain; this part of the review therefore concentrates on the mechanical responses of equipment, player-equipment interaction, and the effects of equipment on player performance and protection. Although the equipment has mechanical characteristics that can be reasonably well quantified, the player-equipment interaction is more difficult to establish; this makes its efficacy for performance or protection difficult to predict. Some soccer injuries may be attributable to the equipment used. The soccer boot has a poor protective capability, but careful design can have a minor influence on reducing the severity of ankle inversion injuries. Performance requirements limit the scope for reducing these injuries; alternative methods for providing ankle stability are necessary. Artificial surfaces result in injury profiles different from those on natural turf pitches. There is a tendency for fewer serious injuries, but more minor injuries, on artificial turf than on natural turf pitches. Players adapt to surface types over a period of several games. Therefore, changing from one surface to another is a major aetiological factor in surface-related injuries. Heading the ball could lead to long-term brain damage. Simulation studies suggest the importance of ball mass, ball speed and player mass in affecting the severity of impact. Careful instruction and skill development, together with the correct equipment, is necessary for young players. Most applications of biomechanical techniques to soccer have been descriptive experimental studies. Biomechanical modelling techniques have helped in the understanding of the underlying mechanisms of performance, although their use has been limited. It is concluded that there are still many features of the game of soccer that are amenable to biomechanical treatment, and many opportunities for biomechanists to make a contribution to the science of soccer.

Athletic Injuries↗

Analysis of the effect of prior therapy on progenitor cell yield: use of a chemotherapy scoring system.

A quantitative analysis of peripheral blood stem cell (PBSC) yield, measuring absolute numbers of CD34+ cells x 10(6)/kg and CFU-C x 10(4)/kg was performed in 74 consecutive patients. The interval or 'gap' from the end of previous chemotherapy to the date of priming was recorded in weeks. Geometric mean CD34 and CFU-C values were significantly higher in patients with a score of < or = 60 compared to those with score > 60 (P = 0.003 and 0.02, respectively) and a significant difference in CD34 values was also found when scores of < or = 38 were compared with scores > 38 (P = 0.003), with the difference in CFU-C values approaching significance (P = 0.08). Patients exposed to toxicity factor 4 drugs had significant lowering of both CD34 and CFU-C values (P < 0.001 and P = 0.038) and this emerged as the only independent factor when analysed using linear regression. No significant difference in the geometric mean CD34 or CFU-C values of patients was found in any of the gap categories analysed. Prior exposure to toxicity factor 4 drugs had a significant adverse effect on stem cell yield and should be avoided or minimized prior to stem cell harvesting.

Adolescent↗

Can quantitative 99mTc-MDP bone scans be used to predict longitudinal growth of epiphyseal plate allografts after microvascular transplantation? An experimental study.

Allograft and autograft microvascular proximal tibial epiphyseal plate transplants were performed in female New Zealand White (NZW) rabbits to quantify the growth rate and total growth potential of immunosuppressed and nonimmunosuppressed rabbits. The purpose of this experiment is to examine whether the 99mTc-MDP radionuclide uptake of the transplanted epiphyseal plate at 1 week postoperatively, done to assess anastomotic patency of the transplant, could also serve as a predictor of eventual longitudinal growth of the transplant or replant. All transplants and replants demonstrating positive 99mTc-MDP uptake in the proximal tibial epiphyseal plate at 1 week showed continued longitudinal growth. The precise amount of 99mTc-MDP uptake, however, did not correlate with the amount of growth at 3 and 5 weeks follow-up.

Animals↗

Microvascular transplantation of physeal allografts.

We compared growth in vascularised allograft transplants, autografts and in non-operated physes in rabbits immunosuppressed with cyclosporin A and in non-immunosuppressed animals. Molecular haplotyping was undertaken before operation to ensure allogenicity. Postoperative bone scans and fluorochrome labelling were used to confirm physeal vascularity. The animals were killed at three or five weeks. Proximal tibial physeal autografts, with or without cyclosporin A, or allografts with cyclosporin A, grew at similar rates to the physes of non-operated rabbits. All the operated physes grew at rates significantly greater than their contralateral controls. 99mTc-MDP bone scans accurately predicted the viability of the epiphyseal plate. Quantitative histomorphological analysis of the heights of the physeal proliferative and hypertrophic zones showed that successful physeal transplants have a normal appearance, but when unsuccessful have thickened hypertrophic zones compatible with physeal ischaemia. We discuss the significance of these results in relation to the transplantation of physes in children.

Analysis of Variance↗

Short-term response of epiphyseal plate cell populations following selective devascularization and microsurgical revascularization.

The distal femoral epiphyseal plates of 21 8-week-old New Zealand white rabbits were totally or partially (nutrient artery only) devascularized, or devascularized and then microsurgically revascularized. Sacrifice was at 24, 48 or 72 hours postoperatively. The heights of the proliferative and hypertrophic zones of the epiphyseal plates operated upon were compared with the contralateral control epiphyseal plates for both the central and the peripheral regions of the epiphyseal plate. Neither extent of devascularization nor revascularization had a significant effect on the height of the proliferative zone of chondrocytes at any of the follow-up intervals. Selective devascularization of the nutrient artery led to a significant increase in height of the central region of the hypertrophic zone of chondrocytes at 48 and 72 hours. Microsurgical revascularization did not lead to a significant change in the height of either the central or the peripheral regions of the hypertrophic zone of chondrocytes at any of the follow-up intervals. This study is another 'building block' experiment toward vascularized epiphyseal plate transplantation in humans.

Animals↗

Distribution of epitopes within the amino acid sequence of the Epstein-Barr virus major envelope glycoprotein, gp340, recognized by hyperimmune rabbit sera.

Epstein-Barr virus (EBV) is a major human pathogen for which the development of an effective vaccine remains an important goal. Rabbits were immunized with one of a set of 10 fusion proteins representing protein fragments from the EBV receptor-binding ligand and candidate subunit vaccine gp340. Sera from recipients of fragments from the amino-terminal half of the polypeptide chain bound gp340 in Western blot assays and ELISA but were not virus-neutralizing. The fine epitope specificity of these sera, and of EBV-neutralizing rabbit sera raised against whole EBV and gp340-containing immune-stimulating complexes, were assessed in a peptide ELISA. All but two of these sera bound peptides located between positions 236 and 327 in the 907 amino acids of the gp340 polypeptide chain. Among these it was possible to identify regions containing candidate virus-neutralizing B cell epitopes. The use of a gp340 fusion protein affinity column to isolate antibodies from EBV-neutralizing rabbit sera specific for this region suggests the presence of both continuous and discontinuous B cell epitopes with potential roles in EBV neutralization.

Amino Acid Sequence↗

A positive step.

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Critical Care↗

Investigation into the immunological effects of miltefosine, a new anticancer agent under development.

Miltefosine is the prototype of alkylphosphocholines, a new class of anticancer agents related to alkyl-lysophospholipids. These agents were considered to possess potent immunomodulatory properties. Miltefosine was highly active against the human KB tumour xenograft in nude mice, leading to growth inhibition as well as regression of large established tumours, which suggested that its mode of action was not mediated by the T cell system. In vivo natural killer cell activity was measured by chromium release of YAC-1 cells using spleen cells from treated animals as effector cells. Miltefosine had no significant effect on YAC-1 cytolysis. Similarly, the compound did not induce cytotoxic spleen cells against KB target cells. The results were identical when spleen cells from tumour-bearing animals were used. Humoral antibody production in rats following sheep red blood cell immunization was not changed by miltefosine pretreatment. Finally, the in vitro phagocytic activity of mouse bone marrow macrophages was not stimulated but rather inhibited in a dose-dependent manner. In conclusion, there is no experimental evidence that the miltefosine action is mediated by the host immune system and no major immunotoxicity was observed.

Animals↗

Monocyte esterase deficiency in malignant neoplasia.

A survey of the incidence of monocyte esterase deficiency in 4000 inpatients (including 808 with malignant neoplastic disease) and 474 normal controls was performed using an automated esterase method. A highly significant excess of patients with malignant disease and the deficiency was evident when compared with normal controls or all other patients. Within the group of patients with malignant disease the demonstrable excess occurred in B chronic lymphocytic leukaemia, non-Hodgkin's and Hodgkin's lymphoma, and carcinoma of the gastrointestinal tract. There was also a significant excess of patients with the deficiency attending the renal unit, both among patients who had had renal transplants and those who had not. A familial incidence of monocyte esterase deficiency was found in 19 (35%) of first degree relatives of those patients in whom family studies were done. It is suggested that the reason for the increased prevalence of the anomaly in these disorders might be that the diminution of esterase activity has a role in their development.

Esterases↗