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Biomedical subjects

R Sanders

Publications and source records attributed to R Sanders.

At least 37 records · Page 2Linked to original sources

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↗

Plastic surgery.

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Guided Tissue Regeneration↗

Cellular proliferation characteristics do not account for the behaviour of horrifying basal cell carcinoma. A comparison of the growth fraction of horrifying and non horrifying tumours.

This study compared the clinical features, histological subtype, growth fraction (by Ki67 immunohistochemistry) and proliferation pattern of 22 clinically defined horrifying basal cell carcinoma compared to 81 non horrifying lesions. Late presentation was associated with half of the horrifying tumours. The other half developed horrifying tumours despite early intervention. The horrifying tumours exhibited a variety of histological growth patterns. A total of 50% were infiltrative, 23% nodular and 18% micronodular. There was no difference in the growth fraction or proliferation pattern between horrifying and non horrifying tumours of similar growth pattern (P = ns), although infiltrative tumours in either group exhibited a significantly higher growth fraction than nodular tumours (P < 0.01). This suggests that there is no intrinsic biological difference between horrifying and non horrifying tumours to account for their behaviour. We conclude that late presentation, failed or inadequate early management especially of infiltrative tumours (and other subtypes) determines the development of horrifying tumours.

Adult↗

The clinical significance of c-myc oncogene expression in melanomas of the scalp.

Melanomas of the scalp are rare and have a poorer prognosis than melanomas arising at other cutaneous sites. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 25 patients with scalp melanoma using the technique of flow cytometry. Survival analysis revealed that stratification of patients according to oncogene activity provided a prognostic marker with shorter overall survival (log rank test, chi 2 = 3.9, P = 0.05) in tumours with high nuclear c-myc oncoprotein positivity. These results support our previous studies of the prognostic value of c-myc expression in melanoma and suggest that estimation of c-myc oncoprotein may be of clinical significance in identifying high risk patients.

Adult↗

Comparison of cloth gloves used in orthopaedic surgery: a clinical and experimental evaluation.

OBJECTIVES: (a) To compare the effectiveness of five cloth gloves for cut resistance and their ability to prevent inner latex glove perforation. (b) To evaluate the safety, efficacy, and comfort of the outer gloves when reused. SETTING: Tertiary care level I trauma hospital and biomechanics laboratory. METHODS: Laboratory evaluation consisting of assessing cut resistance and fabric deterioration and clinical assessment of all cloth gloves worn as a liner between two latex gloves. RESULTS: Laboratory testing demonstrated significant differences in cut resistance, with gloves divided into three groups: most resistant (Centurion, which required over 3,000 slices or 1,300 chops to failure), resistant (MedArmor, failing at eighty-five slices or 121 chops; Paraderm, failing at thirty-eight slices or ninety-four chops; and Repel, failing at forty-six slices or seventy-five chops), and least resistant (Protek, failing at two slices and less than two chops). Clinically, 3 percent of all the inner latex gloves demonstrated a perforation, with no violation of the skin in any of the five types of cloth gloves used. Only the Protek and MedArmor cloth gloves were positively ranked for comfort. CONCLUSION: All gloves provided equal protection with respect to inner latex glove perforation during all of the orthopaedic procedures, with comfort being the most important variable. Gloves should be selected based on comfort, because it appears that all gloves provide equal protection during surgery regardless of the material woven into the fabric.

Equipment Failure Analysis↗

An analysis of p16 protein expression in sporadic malignant melanoma.

Inactivation of p16 tumour suppressor gene has been reported frequently in melanoma cell lines, and mutations have been detected in familial melanoma kindreds. The aim of this study was to assess the role of p16 inactivation in melanocytic progression by measuring the level of p16 protein in a range of sporadic, benign and malignant melanocytic lesions. Using dual parameter flow cytometry, p16 protein expression was measured in 30 benign melanocytic naevi, 38 primary and 51 metastatic melanomas. A high level of p16 expression was demonstrated in benign melanocytic naevi (96% median nuclear positivity), with a significant reduction in primary melanomas (69%, P < 0.001). The median nuclear positivity of primary melanomas was significantly higher (P < 0.03) than the level of expression in metastatic lesions (median positivity 37%). A progressive loss of p16 expression was demonstrated from benign melanocytic naevi through to primary and metastatic lesions. These data suggest that loss of p16 protein expression is not only associated with the early transformation of benign lesions, but also with the later stages of malignant progression.

Adolescent↗

Intracellular and extracellular blood magnesium fractions in hemodialysis patients; is the ionized fraction a measure of magnesium excess?

To establish the best measure for determining magnesium overload, we measured ionized and total magnesium in serum and mononuclear blood cells and total magnesium in erythrocytes in blood of 23 hemodialysis patients, known for their disturbed magnesium homeostasis. When comparing the mean magnesium values obtained in the patient population with those of a control population, all of these magnesium markers, including the biologically active fractions, were significantly (P < 0.05) increased. Because serum total magnesium was not increased in all dialysis patients studied, the population was divided into two groups, according to total serum magnesium > 1.0 mmol/L or less than that. Results in these two populations showed that ionized serum magnesium and ionized magnesium in mononuclear blood cells might give a better indication about the magnesium status of the tested patients than the currently used total serum magnesium data. However, neither of the two markers, especially ionized serum magnesium, was able to discriminate fully between normal magnesium homeostasis and magnesium excess. We therefore conclude that the two ionized magnesium markers offer minimal advantage for this discrimination, and that the total magnesium concentration in serum remains the measurement of choice.

Adult↗