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R Sanders

Publications and source records attributed to R Sanders.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder.

Aromatic L-amino acid decarboxylase (AADC) is a relatively non specific enzyme involved in the biosynthesis of several classical neurotransmitters including dopamine and 5-hydroxytryptamine (5HT; serotonin). AADC does not catalyse the rate limiting step in either pathway, but is rate limiting in the synthesis of 2-phenylethylamine (2PE) which is a positive modulator of dopaminergic transmission and a candidate natural psychotogenic compound.1 We and others have proposed that polymorphism in AADC resulting in altered 2PE activity might contribute to the pathogenesis of psychosis. In order to test this hypothesis, we have used denaturing high performance liquid chromatography (DHPLC)3 to screen 3943 bases of the AADC gene and its promoter regions for variants that might affect protein structure or expression in 15 unrelated people with schizophrenia, and 15 unrelated people with bipolar disorder. Three polymorphisms were identified by DHPLC: a insertion/deletion polymorphism in the 5' UTR of the neuronal specific mRNA (g.-33-30delAGAG, bases 586-589 of GenBank M77828), a T>A variant in the non-neuronal exon 1 (g. -67T>A, GenBank M88070), and a G>A polymorphism within intron 8 (g. IVS8 +75G>A, GenBank M84598). Case-control analysis did not suggest that genetic polymorphism in the AADC gene is associated with liability for developing schizophrenia or bipolar disorder.

Aromatic-L-Amino-Acid Decarboxylases↗
PubMed2000

The high affinity neurotensin receptor gene (NTSR1): comparative sequencing and association studies in schizophrenia.

Neurotensin and its high affinity receptor (NTSR1) localise within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems and it is now clear that neurotensin can selectively modulate dopaminergic neurotransmission. This has led to the hypothesis that altered neurotensin function contributes to the pathogenesis of schizophrenia and other psychoses. This hypothesis has been supported circumstantially by a number of lines of evidence. (1) Central administration of neurotensin produces effects similar to those produced by the peripheral administration of atypical antipsychotics. (2) Observations of low levels of neurotensin in the CSF of schizophrenics. (3) Reduced numbers of neurotensin receptors in the brains of schizophrenics. Given the above link between neurotensin and dopamine, and the evidence implicating altered neurotensin function in psychosis, we have postulated that DNA sequence variation in neurotensin or its receptors might be associated with schizophrenia. In keeping with this hypothesis, an association has recently been reported between schizophrenia and the gene encoding the neurotensin high affinity receptor (NTSR1). However, caution is required because the associated marker, a tetranucleotide repeat, is located 3 kb away from the 3' end of the gene and there is no evidence that it is functional. Therefore, as a follow-up to our earlier work on neurotensin, we have now sought to test the hypothesis that DNA sequence variants that alter the structure or expression of the NTSR1 gene (VAPSEs) are associated with schizophrenia. However, while we found 14 novel sequence variants in 28 probands with psychosis, none resulted in an amino acid change, and neither direct nor indirect association studies suggested these are involved in susceptibility to schizophrenia.

Brain Chemistry↗
PubMed2000

An analysis of p16 tumour suppressor gene expression in acral lentiginous melanoma.

Acral lentiginous melanoma is a particularly aggressive melanocytic lesion but, due to its comparative rarity, biological investigations into the behaviour of this subtype of melanoma are lacking. The activity of the recently described p16 tumour suppressor gene, thought to be the 'familial melanoma gene', was studied in 24 patients with subungual melanoma and 44 patients with plantar melanoma. Lower levels of p16 oncoprotein were demonstrated than that found in other histogenetic types of melanoma. Stratification of patients of all disease stages revealed a poorer survival in patients with low p16 expression (log rank test, chi(2)= 3.9, P = 0. 05). These data suggest that p16 inactivation may play an important role in the development and progression of acral lentiginous melanomas. However, the level of p16 expression was not prognostic since survival analysis on stratification of stage I patients according to p16 level did not reach statistical significance for both survival and disease free interval.

Aged↗
PubMed2000

Aggressive basal cell carcinoma in young patients: fact or fiction?

It has been suggested that basal cell carcinomas (BCC) arising in younger patients may be of a more aggressive phenotype than those that present in the older population. The purpose of this study was to investigate this hypothesis by comparing the histological types of BCC in a large cohort of young and old patients.A total of 271 histological specimens and clinical records were evaluated. A consecutive series of 120 patients under 50 years old were compared with a consecutive series of 151 patients over 50 years of age. Tumours were classified according to the accepted definition of aggressive (morphoeic, infiltrative and micronodular) and less aggressive (nodular and superficial) histological growth patterns. Aggressive growth types were found in 35% of patients over 50 and 33% of patients under 50. There was a higher rate of incomplete excision in younger patients but this did not reach significance (16% compared to 9%, P = 0.1). This study found that BCC arising in young patients are not histologically different to those found in the older population. Clinically observed aggressive behaviour of BCC in young patients may result from inadequate surgical excision due to cosmesis and diagnostic doubt.

Adolescent↗
PubMed2000

Flexor tendon blood vessels.

The aim of this study was to assess rabbit long flexor tendon vascularity in a qualitative and quantitative manner using immunohistochemistry. The endothelial cell surface marker CD31 was targeted with a specific monoclonal mouse-anti-human antibody with good species cross-reactivity. Subsequent signal amplification and chromogen labelling allowed vessel visualization. Computer image analysis was performed. Values for vessel number and total vessel area per section, as well as the sections' cross-sectional tendon areas, were obtained. There was a consistent deep tendon avascular zone between the A2 and A4 pulley in the rabbit forepaw. This was not the case in the hindpaw, with dorsally orientated longitudinal vessels coursing the length of the intrasynovial tendon. The area of least vascularity in the hindpaw was around the metacarpophalangeal joint. We therefore recommend the use of hindpaw tendons when using the rabbit as a flexor tendon experimental model. This is because its vascular pattern is similar to that of the human flexor digitorum profundus.

Animals↗
PubMed2000

Effects of aldose reductase inhibitors on antioxidant defense in rat and rabbit liver.

Aldose reductase has been implicated in the etiology of diabetic complications, atherosclerosis, and ischemia-reperfusion injury. Aldose reductase inhibitors are known to have species-dependent differences in biotransformation enzyme induction. Whether aldose reductase inhibitors, which have antioxidant potential, alter the oxidative stress pathway is unknown. This study has determined whether four daily ip treatments of either low (10 mg/kg) or high (50 mg/kg) doses of AL-1576 or AL-4114 alter the activities of the antioxidant defense enzymes catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and the concentrations of reduced and oxidized glutathione in livers of normal rats and rabbits. There was no change in the concentration of thiobarbituric acid reactive substances in either rat or rabbit livers, indicating that lipid peroxidation was not increased by any treatment. Hepatic catalase, superoxide dismutase, and glutathione peroxidase activities and concentrations of reduced and oxidized glutathione were not significantly altered in rat, though glutathione reductase activity was increased after high doses of both drugs. However, in rabbit liver, glutathione reductase activity decreased in a dose-dependent manner after AL-4114 treatment, while superoxide dismutase and glutathione peroxidase activities decreased only after the low dose of AL-4114. Although AL-4114 and AL-1576 did not directly generate increased lipid peroxidation within normal rat and rabbit livers, some of the enzymes responsible for oxidative defense were altered, particularly in rabbit livers.

Aldehyde Reductase↗
PubMed2000

Transgenic plants expressing geminivirus movement proteins: abnormal phenotypes and delayed infection by Tomato mottle virus in transgenic tomatoes expressing the Bean dwarf mosaic virus BV1 or BC1 proteins.

Transgenic tomato plants expressing wild-type or mutated BV1 or BC1 movement proteins from Bean dwarf mosaic virus (BDMV) were generated and examined for phenotypic effects and resistance to Tomato mottle virus (ToMoV). Fewer transgenic plants were recovered with the wild-type or mutated BC1 genes, compared with the wild-type or mutated BV1 genes. Transgenic tomato plants expressing the wild-type or mutated BV1 proteins appeared normal. Interestingly, although BDMV induces only a symptomless infection in tomato (i.e., BDMV is not well adapted to tomato), transgenic tomato plants expressing the BDMV BC1 protein showed a viral disease-like phenotype (i.e., stunted growth, and leaf mottling, curling, and distortion). This suggests that the symptomless phenotype of BDMV in tomato is not due to a host-specific defect in the BC1 protein. One transgenic line expressing the BC1 gene did not show the viral disease-like phenotype. This was associated with a deletion in the 3' region of the gene, which resulted in expression of a truncated BC1 protein. Several R0 plants, expressing either wild-type or mutated BV1 or BC1 proteins, showed a significant delay in ToMoV infection, compared with non-transformed plants. R1 progeny plants also showed a significant delay in ToMoV infection, but this delay was less than that in the R0 parents. These results also demonstrate that expression of viral movement proteins, in transgenic plants, can have deleterious effects on various aspects of plant development.

Blotting, Northern↗
PubMed2000

The temperatures reached and the damage caused to hair follicles by the normal-mode ruby laser when used for depilation.

Although it is proposed that heat is the cause of follicular damage leading to depilation, this has never been proved. This study aims to determine the mode by which depilation is effected and, if heat is the mechanism, what temperatures are reached within treated follicles and if sufficient damage is produced therein. Two excised specimens of hair-bearing skin from 5 patients undergoing facelifts were dissected to reveal the hair bulbs/shafts on the deep surface. They were placed on a jig, and one pulse from a normal-mode ruby laser (NMRL) of 15 J per square centimeter was fired on the epidermal surface. A thermal imaging camera recorded dermal temperature changes on the deep surface in real time. Specimens were then examined histologically for the site and extent of cellular damage by immunohistochemical staining for a protein marker of cell damage (p53). The NMRL targeted hair follicles specifically. The most common follicular temperature increase ranged from 5 to 10 degrees C. In specimens from 1 patient the increase was more than 30 degrees C (p < 0.001). Heat dissipation into interfollicular tissue in all specimens occurred 2 seconds after exposure. Evidence of laser-induced damage to follicle-lining cells was found only in those follicles with damaged hair shafts. The changes were found to a greater depth (to the bulb) and greater extent (beyond the bulge) in those follicles reaching higher temperatures. These findings suggest that the NMRL should produce permanent depilation. The variability between follicles and between patients explains, perhaps, the uneven outcome regarding depilation using the NMRL. Success appears to depend on peak follicular temperatures achieved during laser exposure, which may result from the follicular characteristics of the individual patient.

Body Temperature↗
PubMed2000

A review of the ruby laser with reference to hair depilation.

There is a clinical need in the fields of reconstructive and cosmetic plastic surgery for a safe, simple, and effective method of hair depilation. Depilatory clinics have been established throughout the country, commonly using the ruby laser, to treat a cohort of the population, estimated to be between 6% and 10%, recognized as being hirsute. Clinical trials performed to date have not established a protocol that suits the previously mentioned criteria and have been, usually, small in number and short in follow-up. With the increased use that this form of laser treatment will inevitably undergo, it is the belief of the authors that the only way of ascertaining whether the treatment is safe, simple, and effective is first to establish how the ruby laser works. This review relates the knowledge that is currently available regarding the function of the ruby laser to a number of the clinical studies that have been undertaken, including three that have used other types of laser. Using this information, future areas in which research is required can be defined, ultimately to improve the clinical efficacy of ruby laser-assisted hair removal while lessening the current side effects (namely, superficial burning, and hypo- and hyperpigmentation).

Hair Follicle↗
PubMed2000

Treatment of complex tibial periarticular fractures using percutaneous techniques.

Open reduction and internal fixation typically is reserved for the treatment of patients with articular or periarticular tibia fractures, or other tibial injuries that are treated inadequately with intramedullary nailing. This approach can result in extensive dissection and tissue devitalization. By modifying the method of fixation, the plating of tibial fractures has been expanded using a percutaneous technique. Using this approach, the fracture is reduced indirectly and plates are placed through subcutaneous or submuscular tunnels through limited incisions. Between 1992 and 1998, 17 patients with tibial shaft fractures and associated severe soft tissue injury, were treated using a percutaneous plating technique. Followup was available in 14 patients. Six patients required bone grafting procedures for delayed union or nonunion, although four of these patients had significant bone loss related to their injury. There were no malunions. Three patients had superficial infections related to external fixator pin sites and one patient had osteomyelitis develop. Percutaneous plating of the tibia offers an alternative method for stabilizing complex fractures with severely compromised soft tissues, especially those injuries with periarticular extension. This technique is thought to cause no increase in the risk of infection or soft tissue damage and permits rapid mobilization of the limb and patient. When using this treatment for patients with significant bone loss, bone grafting should be considered.

Adolescent↗
PubMed2000

Percutaneous fixation of proximal humeral fractures.

The purpose of the current study is to evaluate the technique of closed reduction and percutaneous pinning of proximal humeral fractures and to determine whether this technique provides enough stability to permit early active range of motion and subsequent fracture healing. Fractures were classified according to Neer et al and were included if the surgical or anatomic neck were angulated greater than 45 degrees, separation between fragments was greater than 1 cm, or the greater tuberosity was displaced more than 0.5 cm. There were 21 Type II, 16 Type III, and four Type IV fractures. Fractures were pinned using distally threaded Dynamic Hip Screw guide pins, 2-mm Kirschner wires, or 2.5-mm distally threaded Schantz pins. Patients were evaluated for union rates and motion. Assessment was made using the Modified American Shoulder and Elbow Surgeons Form. Thirty-six patients with 37 fractures were available for review with followup averaging 40 months (range, 12-68 months). All patients with Neer Type IV fractures did not respond to fixation and three had avascular necrosis develop, irrespective of the type of pin used. In the remaining 33 patients with Neer Type II and Type III fractures, a union rate of 94% was observed at an average of 2.6 months. All patients had good functional results. In the current series, there were no failures using Schantz pins. There was a 20% failure rate with Dynamic Hip Screw pins (2% if the patients with Type IV fractures were excluded) and a 100% failure rate with Kirschner wires. Stable fixation with early motion and subsequently good results can be obtained using percutaneous fixation in patients with Type II and Type III fractures; however, terminally threaded pins must be used and smooth Kirschner wires must be avoided. Percutaneous fixation cannot be recommended in patients with Type IV fractures.

Adult↗
PubMed2000

Treatment of femoral shaft fracture using unreamed interlocked nails.

OBJECTIVE: To evaluate healing rates of femoral shaft fractures treated with interlocked nails inserted without reaming. STUDY DESIGN: Review of prospectively collected data. SETTING: Level I trauma center. METHODS: From the trauma registry, 159 patients with 164 femoral shaft fractures were identified who had been treated from March 1993 through December 1995 with femoral nails inserted without reaming in either an antergrade or retrograde manner. Fractures were classified according to the AO/OTA method. Patients were followed for a minimum of one year with clinical and radiographic examinations. RESULTS: One hundred twenty-one patients with 125 fractures were available for review. Average follow-up was 18.3 months (range 12 to 59 months). One hundred sixteen of the 125 fractures (93 percent) healed after the index procedure. Type A fractures healed at an average of 3.8 months (range 2 to 8 months), Type B fractures at 4.8 months (range 2 to 16 months), and Type C fractures at 6.2 months (range 3 to 12 months). There were no increases in complication rates or differences in ranges of knee and hip motion as compared with other published series. Overall, there was no difference in the length of time to union between antegrade or retrograde nailings, and the healing rates for the two methods showed only a small statistical difference. CONCLUSIONS: The use of femoral nails inserted in an unreamed manner in this series produced healing rates comparable with historic standards using reamed insertion. Smaller diameter nails inserted without reaming did not compromise fracture management and produced no increase in complication rates. The causes for delayed union or nonunion appear to be multifactorial, and secondary procedures should be considered if fractures have demonstrated little or no healing by three months.

Adolescent↗
PubMed2000

Magnesium levels in critically ill patients. What should we measure?

We studied the relation between ionized magnesium, total magnesium, and albumin levels in serum of 115 critically ill patients and the role of extracellular and intracellular magnesium in outcome prediction. Levels of serum total and ionized magnesium, serum albumin, and magnesium in mononuclear blood cells and erythrocytes were measured and the APACHE II score and 1-month mortality recorded. Of all patients, 51.3% had a serum total magnesium concentration below the reference range. In 71% of these hypomagnesemic patients, a normal serum ionized magnesium concentration was measured. None of the patients had an intracellular magnesium concentration below the reference limit. Except for serum total and ionized magnesium, none of the magnesium parameters correlated significantly with each other. A significantly negative correlation was found between serum albumin and the fraction ionized magnesium. There was no association between low extracellular or intracellular magnesium and clinical outcome. The observation of hypomagnesemia in critically ill patients depends on which magnesium fraction is measured. The lack of correlation with clinical outcome suggests hypomagnesemia to be merely an epiphenomenon. Reliable concentrations of serum ionized magnesium can be obtained only by direct measurement and not by calculation from serum total magnesium and albumin.

Cations, Divalent↗
PubMed2000

Three-dimensional analysis of the child cleft face.

OBJECTIVE: This study examined the facial surfaces of cleft children and unaffected children aged 8-11 years with the aim of identifying and assessing differences in their facial surface morphology. The investigation was carried out using an Optical Surface Scanner, an instrument that utilizes laser light to construct and archive a three-dimensional image of the face suitable for linear measurement and direct surface comparisons. DESIGN, SETTING, AND PATIENTS: Thirty-nine cleft lip and palate (CLP) patients and 25 unaffected subjects were voluntarily recruited from two southeast England hospitals. A range of linear facial measurements was compared. Three-dimensional differences between the cleft subgroups and the control group were visualized by superimposition of averaged cleft scans over the averaged control group images. RESULTS: Statistically significant dimensional differences (p < or = .05) in interocular width, nose base widths, mouth widths, and nose base/mouth width ratios were found between the cleft group and the control group. Qualitative differences over the whole of the face were readily demonstrated between the groups by superimposition. Face width and submandibular area depth differed consistently between the groups, the cleft face appearing narrower with a deeper submandibular area. CONCLUSION: Significant differences exist between the facial surface morphology of CLP patients and control subjects.

Analysis of Variance↗
PubMed2000

An investigation of the dentition of parents of children with cleft lip and palate.

OBJECTIVE: The aim of this investigation was to identify whether any dental features in parents of children with cleft lip and palate can be useful as predictors of clefting. METHODS: The dentition of 28 pairs of parents of children with complete unilateral (17) and bilateral (11) cleft lip and palate and 21 pairs of parents of noncleft children were evaluated. Clinical and radiographic examinations were carried out to identify abnormalities of tooth number and morphology. Study cast assessment was undertaken to evaluate incisor relationship, overjet, overbite, intercanine widths, and mesiodistal widths of individual teeth, and these data were subjected to statistical analysis. RESULTS: The prevalence of abnormalities of tooth number in parents of cleft children was similar to those reported elsewhere for general populations. In parents of children with unilateral clefts, there was no tooth-size asymmetry between teeth on the side corresponding to the child's cleft and noncleft sides, respectively. No differences were found in tooth widths and intercanine widths between parents of children with unilateral clefts and parents of children with bilateral clefts. The incisor relationship, overjet, overbite, and intercanine widths were found not to differ statistically between the parents of cleft children and parents of noncleft children. CONCLUSIONS: No predictors of clefting could be identified in the dentition of parents of children with cleft lip and palate.

Adult↗
PubMed2000

The influence of learning styles on collaborative performances of allied health students in a clinical exercise.

With the increasing emphasis on interdisciplinary practice, there is a need to recognize factors that promote effective interdisciplinary teams. The influence of individual learning-style preference on collaborative performance was examined in 78 occupational and physical therapy students in a neuroscience course. They were randomly assigned in pairs to one of three subsets based upon their Kolb Learning Style Inventory scores (active experimenters vs reflective observers). The students viewed a videotape of a quadriplegic patient's physical examination and completed a collaborative exercise that required performance skills on all levels of Bloom's taxonomy of learning. Analysis of variance revealed no significant difference among learning-style subset pairs in performance (F2, 36 = 0.43, p > 0.05), but the exercise's overall grade correlated with the average of the pair's highest individual scores on two prior written exams (r = 0.631, p < 0.05), suggesting that background knowledge may predict performance better than learning styles do. It is suggested that differences in information-processing styles as measured by the Kolb inventory do not affect interdisciplinary team performance.

Adult↗