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Biomedical subjects

R Sanders

Publications and source records attributed to R Sanders.

At least 73 records · Page 4Linked to original sources

Child abuse fatalities and cases of extreme concern: lessons from reviews.

OBJECTIVE: The study was commissioned by the Welsh Office to pull together lessons from all reports on cases involving either a child abuse fatality or serious child protection concern ("Part 8 Reviews") since the introduction of the Children Act 1989. METHOD: Twenty-one such reports were identified and subjected to a content analysis to extract practice issues. RESULTS: From 19 reports (excluding Reviews concerning adult sexual abusers), the authors identify seven practice themes emerging from that analysis which are related to those identified in previous studies and to six previously undertaken British overviews of child abuse fatalities. The themes are assessment, interagency communications, responsibility, number of professionals involved, role of general practitioners, insufficient training for pediatricians/radiologists, and parental choice. CONCLUSIONS: British child protection agencies are attempting to address apparently conflicting policy objectives. On the one hand they are required to ensure the protection of the most vulnerable children within the child protection system. At the same time they are also being encouraged to adopt a "lighter touch" in child protection work. The authors conclude that the seven themes may provide some indicators as to how these conflicting objectives may be reconciled.

Adult↗

Mining the Swedish clinical archives to develop pharmacogenomic tests.

Eurona Medical is a Swedish company that develops diagnostic tests to predict response to drugs or treatment. Sweden offers unparalleled retrospective clinical data resources, with epidemiological registers and collections of tissue samples built up over decades. Efficient pharmacogenomic research can be performed using these registers and sample collections in collaboration with experienced medical researchers. Eurona's tests are based on Genetic Signatures, groups of polymorphic, polygenic genomic positions linked to and therefore predictive of drug response. These are elucidated from complex data sets using unique applications of multivariate and combinatorial statistics and a multigenic approach. The company develops tests applicable to current medical practice and is preparing to launch its first within the hypertension field. Quality control (including ISO9001 certification) and clinical regulatory compliance are applied throughout all programs to produce data that can be directly translated into clinical tests.

Archives↗

The physical demands of Olympic yacht racing.

The primary purpose of this study was to quantify the up wards forces of the feet on the hiking strap and the forces in the mainsheet of four Olympic classes of racing dinghies (Europe, Laser. Finn and 470) during realistic on-water sailing in varying wind conditions. The secondary aim of the study was to measure the joint angles adopted by the sailors and boat heel angles. The tertiary aim was to identify events and sailing conditions associated with large or patterned force production. Forces in the hiking strap and mainsheet of four classes of Olympic sailing dinghies were measured on eleven New Zealand sailors during simulated on-water racing in a range of wind conditions. Up-wind hiking strap forces reached an average of 73-87% of predicted maximal voluntary contraction (pred MVC), with peak forces exceeding 100% pred MVC. Mainsheet forces reached 25-35% pred MVC, with peak forces reaching 40-50% pred MVC. Off-wind hiking strap and mainsheet forces were considerably lower than up-wind forces. Ankle and hip joint angles increased and knee joint angles decreased with increasing wind speed during up-wind sailing. Large forces occurred in the hiking strap and mainsheet when boats reached the tops of wave during up-wind sailing in high wind speeds and when a gust of wind hit the boat. During off-wind sailing large forces were observed in the mainsheet when surfing down waves. It is recommended that the intensities and joint angles found in this study be used as a basis for the development of class specific off-water physical conditioning programmes.

Biomechanical Phenomena↗

Hair removal using the ruby laser: clinical efficacy in Fitzpatrick skin types I-V and histological changes in epidermal melanocytes.

The ruby laser is effective in removing unwanted body hair. The occurrence of cutaneous side-effects such as blistering, hypopigmentation and hyperpigmentation, however, remains problematic. These side-effects are more commonly seen in patients with dark coloured skin, which partly explains the relative scarcity of information on the efficacy of ruby laser hair removal in such patients. The mechanisms of the occurrence of these side-effects are also not known. It was the aim of this study to evaluate the efficacy of ruby laser-assisted hair removal in patients with Fitzpatrick skin type V in a retrospective clinical study and to evaluate the mechanism of post-treatment pigmentary change in a prospective clinical study. The percentage reduction in hair density in patients with skin type V was assessed after a variable period following treatment with the Chromos 694 Depilation Ruby Laser, and was compared with the results of those with skin types I-IV. To study the pigmentary change and melanocyte numbers after laser irradiation, ex-vivo scalp skin and serial patient biopsies were taken and stained with S-100, dopa oxidase and Masson-Fontana methods. Laser treatment reduced melanocyte numbers as measured by DOPA stain but not by S100. Laser treatment resulted in the clearance of pigment from the epidermis on histology. Ruby laser was shown to be effective in removing unwanted hair from patients with dark coloured skin, but with a higher incidence of cutaneous side-effects. The occurrence of hypopigmentation after laser irradiation was thought to be due to the suppression of melanogenesis in the epidermis rather than to destruction of the melanocytes.

Analysis of Variance↗

Ruby laser-assisted hair removal reduces the coarseness of regrowing hairs: fallacy or fact?

There have been anecdotal reports that hairs that regrow after ruby laser-assisted hair removal are finer in appearance. If true, this phenomenon adds to the improved aesthetic effect of laser treatment of unwanted hair. It is the aim of this study to determine whether this phenomenon indeed occurs, and if so, assess its permanence and its mode of action. In this prospective clinical study, 71 patients with 94 treatment sites were treated with the Chromos 694 Depilation Ruby Laser. Hair diameter was measured pre-treatment, and at 3 and 7 months post-treatment. In addition, ex vivo scalp skin was used to assess if the ruby laser selectively damaged coarser hairs. Laser-treated and matched untreated skin samples were histologically assessed and the diameters of hair shafts (normal or obviously damaged) were measured. Results of this study were analysed using Kruskal-Wallis one-way analysis. There was no statistically significant difference between the hair diameter of non-lasered specimens and the hair diameter of the normal hair in lasered specimens. However, a statistically significant difference was seen between the hair diameter of non-lasered specimens and diameters of damaged hair in lasered specimens (P < 0.05). There was a statistically significant difference (P < 0.05) between pre-treatment and 3 month hair diameters, but no statistically significant difference was found between pre-treatment and 7 month hair diameters. In conclusion, ruby laser-assisted hair removal results in a temporary reduction in hair diameter of regrowing hair. This is not due to the selective targeting of larger hair follicles.

Adolescent↗

Measurement of c-myc oncogene expression provides an accurate prognostic marker for acral lentiginous melanoma.

Acral lentiginous melanoma is a particularly aggressive tumour with a worse prognosis than other varieties of primary cutaneous melanoma. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 45 patients using flow cytometry. High levels of oncoprotein were found in all tumours and exceeded that documented in other varieties of cutaneous melanoma. Survival analysis with stratification of patients according to oncogene activity provided a useful prognostic marker with shorter disease free interval (Log-Rank test, chi 2 = 16.7, P < 0.0001) and overall survival (Log-Rank test, chi 2 = 8.9, P = 0.002) in tumours with high oncoprotein levels. Multivariate analysis revealed c-myc oncogene expression to be more accurate in predicting clinical outcome than all existing clinicopathological parameters including the Breslow depth (Cox's proportional hazards model, P = 0.0011). This study provides biological evidence to explain the aggressive behaviour of acral melanoma and supports the application of oncogene measurement as an accurate prognostic marker.

Adult↗

A functional variant of lower lip reconstruction.

A functional variant of lower lip reconstruction is reported, in which a nasolabial skin flap was combined with upward transposition of the inferior part of the orbicularis oris muscle in a 'bucket-handle' fashion. The tongue was split to provide both an intraoral lining to the lip and a new vermilion.

Animals↗

Ruby laser-assisted hair removal: an ultrastructural evaluation of cutaneous damage.

Ruby laser-assisted hair removal is thought to act via selective photothermolysis of melanin in the hair follicles. Although initial clinical trials of permanent hair removal using ruby lasers are promising, the exact mechanisms of hair destruction and the potential damage to other structures of skin are not known. The aim of this study was to evaluate the cutaneous ultrastructural changes following ruby laser hair removal. Nineteen healthy Caucasian patients with dark (brown/black) hair were treated with the ruby laser and biopsies taken after 0, 2, 3, 5, 7, 14 and 21 days. Specimens were examined by light and electron microscopy. Laser-treated specimens showed widespread coagulation and charring of subcutaneous hair shafts. These obviously damaged follicles were randomly dispersed amongst intact follicles within the same treatment sites. Microscopic changes were also seen in the basal epidermis where melanin was concentrated, irrespective of any obvious macroscopic damage. A low level of inflammatory response seen up to 2 weeks after treatment always followed laser treatment. Suprabasal epidermal necrosis was only seen in patients with blister formation after treatment. Ruby laser irradiation results in selective damage to the hair follicles, with microscopic changes to the basal epidermis. The damage is probably compounded by the inflammatory response to the damaged hair. The normal appearance and distribution of collagen in the dermal layer supported the clinical evidence that laser-assisted hair removal, if performed correctly, does not lead to scar formation.

Biopsy↗

Is Dupuytren's disease caused by an imbalance between proliferation and cell death?

Dupuytren's contracture shares certain properties with malignant tumours, characterized by proliferation and lack of apoptosis, which may be induced by the c-myc oncogene. Because of these similarities, the relationship between the c-myc oncogene expression, bcl-2 oncogene (anti-apoptotic gene) and proliferation was investigated in Dupuytren's disease. Proliferation was assessed by immunohistochemical staining of the mib-1 antibody. Results were compared with those from fibrosarcoma specimens, representing a related malignant tumour. Non-diseased fascia from Dupuytren patients and flexor retinaculum from patients undergoing carpal tunnel release without Dupuytren's disease were used as controls. Expression of c-myc was elevated in primary Dupuytren's disease and fibrosarcoma specimens, whilst recurrent Dupuytren's disease, non-diseased Dupuytren fascia and flexor retinaculum exhibited significantly lower levels. Neither bcl-2 nor mib-1 were detected in Dupuytren's disease, non-diseased fascia or flexor retinaculum, in contrast to fibrosarcoma. The imbalance between proliferation and apoptosis, producing malignant growth was thus confirmed for fibrosarcoma, but not for Dupuytren's disease.

Adult↗

The effect of ruby laser light on ex vivo hair follicles: clinical implications.

Several clinical studies on the efficacy of ruby laser-assisted hair removal have reported that regrowth of hair after treatment is common. One of the reasons for the regrowth of hair is the incomplete destruction of germinative hair cells due to the insufficient penetration of the ruby laser in the skin. It was the aim of this study to estimate the extent of damage to the hair follicles after one ruby laser treatment and to determine whether the ruby laser destroyed the bulbs and the bulge regions of hair follicles. The extent of laser damage in hair shafts was determined by serial examination of six specimens of ex vivo scalp skin lasered with the Chromos 694 Depilation Ruby Laser at 14 J per square centimeter and 20 J per square centimeter. Another nine specimens of ex vivo scalp skin were similarly lasered, and monoclonal antibody LP2K was used to identify the bulge regions of the hair follicles using the immunoperoxidase technique. Damage to the bulge region was assessed from consecutive specimens, which were stained with hematoxylin-eosin stain. The mean depth of laser damage sustained by hair follicles was 1.34 mm (14 J per square centimeter) and 1.49 mm (20 J per square centimeter) underneath the skin surface. Most of the laser damage involved the bulge regions but fell short of the hair bulbs. The laser damage did not seem to extend far enough down the hair shafts to result in permanent hair destruction. The clinical implications of this finding are discussed.

Hair Follicle↗

A staged protocol for soft tissue management in the treatment of complex pilon fractures.

OBJECTIVE: To determine whether open reduction and internal fixation of intra-articular pilon fractures using a staged treatment protocol results in minimal surgical wound complications. DESIGN: Retrospective. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Between January 1991 and December 1996, 226 pilon fractures (AO types 43A-C) were treated, of which 108 were AO type 43C. Fifty-six fractures were included in a retrospective analysis of a treatment protocol. Injuries were divided into Group I, thirty-four closed fractures, and Group II, twenty-two open fractures (three Gustilo Type 1, six Type II, eight Type IIIA, and five Type IIIB). METHODS: The protocol consisted of immediate (within twenty-four hours) open reduction and internal fixation of the fibula when fractured, using a one-third tubular or 3.5-millimeter dynamic compression plate and application of an external fixator spanning the ankle joint. Patients with isolated injuries were discharged after initial stabilization and readmitted for the definitive reconstruction. Polytrauma patients remained hospitalized and were observed. Formal open reconstruction of the articular surface by plating was performed when soft tissue swelling had subsided. Complications were defined as wound problems requiring hospitalization. All affected limbs were then evaluated via chart and radiograph review, patient interviews, and physical examination until surgical wound healing was complete, for a minimum of twelve months. RESULTS: Group 1 (closed pilon): Follow-up was possible in twenty-nine out of thirty fractures (97 percent). Average time from external fixation to open reduction was 12.7 days. All wounds healed. None exhibited wound dehiscence or full-thickness tissue necrosis requiring secondary soft tissue coverage postoperatively. Seventeen percent (five out of twenty-nine patients) had partial-thickness skin necrosis. All were treated with local wound care and oral antibiotics and healed uneventfully. There was one late complication (3.4 percent), a chronic draining sinus secondary to osteomyelitis, which resolved after fracture healing and metal removal. Group II (open pilon): Follow-up was possible in seventeen patients with nineteen fractures (86 percent). Average time from external fixation to formal reconstruction was fourteen days (range 4 to 31 days). By definition, all Gustilo Type IIIB fractures required flap coverage for the injury. Two patients experienced partial-thickness wound necrosis. These were treated with local wound care and antibiotics. All surgical wounds healed. There were two complications (10.5 percent), both deep infections. One Type I open fracture developed wound dehiscence and osteomyelitis requiring multiple debridements, intravenous antibiotics, subsequent removal of hardware, and re-application of an external fixator to cure the infection. One Type IIIA open fracture of the distal tibia and calcaneus developed osteomyelitis and required a below-knee amputation. CONCLUSION: Based on our data, it appears that the historically high rates of infection associated with open reduction and internal fixation of pilon fractures may be due to attempts at immediate fixation through swollen, compromised soft tissues. When a staged procedure is performed with initial restoration of fibula length and tibial external fixation, soft tissue stabilization is possible. Once soft tissue swelling has significantly diminished, anatomic reduction and internal fixation can then be performed semi-electively with only minimal wound problems. This is evidenced by the lack of skin grafts, rotation flaps, or free tissue transfers in our series. This technique appears to be effective in closed and open fractures alike.

Adult↗

Ruby laser-assisted hair removal success in relation to anatomic factors and melanin content of hair follicles.

Ruby laser-assisted hair removal is thought to work via selective photothermolysis, which relies on light reaching the deeper layers of skin, and the absorption of light by the target chromophore, melanin. It is therefore possible that efficacy of treatment is affected by anatomic factors that determine the amount of light reaching the hair bulbs (i.e., skin color, depth of intracutaneous hair, epidermal thickness and dermal density) and the melanin content of hair. To examine this hypothesis, a prospective study was performed. Forty-eight volunteers were treated with the Chromos 694 Depilation Ruby Laser at a single standard fluence of 11 J/cm2. Treatment efficacy was determined by measuring hair density at 3 and 7 months after treatment. Epidermal depth and dermal density were measured from 2-mm biopsies taken before treatment, and the intracutaneous hair length was determined from plucked hair. Skin color was assessed using a spectrophotometer, and melanin content of dissolved hair was assessed using spectrophotometry. Efficacy of treatment for each patient was compared with the patient's age, intracutaneous hair length, epidermal depth, dermal density, skin color, and total melanin content and relative eumelanin content of hair. No correlation was found between the efficacy of treatment and age and the various anatomic factors. Patients with higher eumelanin content in their hair had better long-term results (Spearman rank test, p = 0.00219). The results suggested that the efficacy of treatment did not depend solely on the amount of laser light penetrating the skin but correlated well with the eumelanin content of hair. The clinical implication of this finding is discussed.

Adolescent↗

Efficient in vivo targeting of malignant melanoma by single-chain Fv antibody fragments.

Single-chain antibody fragments (scFvs) have superior pharmacokinetic and biodistribution characteristics compared with larger antibody fragments when used for radioimaging of human tumours. An scFv specific for malignant melanoma (B4 scFv) was tested in a mouse xenograft model for human melanoma and compared with the monoclonal antibody (MAb) LHM2. LHM2 is specific for the high molecular weight proteoglycan melanoma-associated antigen (HMW-MAA), while B4 scFv binds a novel melanoma-specific antigen. The B4 scFv was cleared rapidly from the circulation (t(1/2)alpha = 7 min) compared with LHM2 MAb (t(1/2)alpha = 37 min). However, the B4 scFv had an unusually long t(1/2)beta (437 min compared with 384 min for LHM2 MAb). Biodistribution studies showed that B4 accumulated specifically in the tumour grafts. Although non-specific accumulation in the liver, lung, spleen and blood was lower than with LHM2, non-specific accumulation of B4 in the kidney was higher. Despite this, the overall targeting efficiency in this study, as determined by tumour:normal tissue ratios, showed that B4 was superior to whole antibody. Immunoscintigraphy images showed good correlation with the biodistribution data for B4 and LHM2. This study represents the first use of an anti-melanoma scFv in vivo.

Animals↗

Reliability of coated wire defibrillation leads.

A higher rate of complications and need for reoperation has been identified with epicardial and endocardial defibrillator systems. Improved reliability may be achieved with alternate designs that use coated wire and coated coil conductors. Six-year reliability in the 98% range is reported for one bipolar design, the Sulzer Intermedics Intervene lead.

Coated Materials, Biocompatible↗

Reporting basal cell carcinoma: a survey of the attitudes of histopathologists.

AIMS: To investigate the histopathological reporting of basal cell carcinoma. METHODS: Methods of classification and attitudes to excision margins were ascertained from histopathologists in 130 centres; 82 replies were obtained (63% response rate). RESULTS: 24% of those replying did not use any classification system for basal cell carcinoma. The remainder (76%) used a wide variety of different classification systems. A small number (9%) of those questioned felt reporting on completeness of excision was not important. The majority of histopathologists considered the excision margin was worth reporting but there were differences in methods of processing and reporting biopsies. CONCLUSIONS: There is considerable variation in histopathological reporting of basal cell carcinoma. There is a need for uniformity of histopathological reporting to allow both improved management decisions and comparative audit of this extremely common skin cancer.

Attitude of Health Personnel↗

Intracellular and extracellular, ionized and total magnesium in pre-eclampsia and uncomplicated pregnancy.

Magnesium (Mg) and calcium (CA) concentrations in women with pre-eclampsia, women with an uncomplicated pregnancy and non-pregnant women were compared. Ionized serum magnesium and calcium concentrations and intracellular magnesium concentrations were measured in 15 pregnant women with severe pre-eclampsia, 34 uncomplicated pregnant women early, at midterm and preterm in their pregnancy and 24 non-pregnant women. The ionized calcium concentration did not chance during normal pregnancy or during pre-eclampsia relative to non-pregnant women. In contrast, elevated total and ionized magnesium serum concentrations were found in women with severe pre-eclampsia (total Mg = 0.85+/-0.11 mM, ionized Mg = 0.61+/-0.06 mM) relative to uncomplicated pregnant women (total Mg = 0.72+/-0.06 mM, ionized Mg = 0.53+/-0.03 mM). Total magnesium in pre-eclamptic women were similar to non-pregnant women. Intracellular ionized and total magnesium concentrations in mononuclear blood cells and erythrocytes were similar in pre-eclamptic women and women with uncomplicated pregnancy. Serum magnesium concentrations are elevated in severe pre-eclamptic women relative to women with uncomplicated pregnancy and are related to birth weight and gestational age at delivery. There may be a causal relationship since magnesium is involved in blood pressure regulation through an intracellular inhibition of NO synthase in endothelial cells.

Calcium↗

Serum ionized magnesium: comparison of results obtained with three ion-selective analyzers.

In a two-center (Academic Medical Center, The Netherlands, and National Institutes of Health, USA) study, we compared ionized magnesium (iMg2+) results in serum determined with the AVL 988/4, KONE Microlyte 6 and NOVA CRT, which are the currently available analyzers equipped with a magnesium ion-selective electrode. The comparison was performed with frozen serum samples from normal individuals and patients. Imprecision and reference intervals were established. We found the best agreement between the KONE(x) and AVL(y) magnesium ion-selective electrodes (y= 0.972x-0.013; n=138) with samples from patients. With samples from normals, all three analyzers reported significantly different results (p<0.05). Best precision was found using the NOVA; coefficients of variation established at three levels were all < 4.0%. Coefficients of variation for the AVL and KONE were <5% at normal and high iMg2+, but 10.7 and 9.4%, respectively, at iMg2+ approximately 0.30 mmol/l. The reference intervals (mean+/-standard deviation) based on measurements in fresh serum samples were different for each analyzer: 0.55-0.63 mmol/l for AVL, 0.470.57 mmol/l for KONE and 0.43-0.55 mmol/l for NOVA. Thus, significant differences among the ionized magnesium concentration obtained with the three analyzers, limit comparison of results in clinical practice, and need to be resolved (e.g. by improvement of specificity and standardization of calibrators).

Adult↗