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Biomedical subjects

G Young

Publications and source records attributed to G Young.

At least 37 records · Page 2Linked to original sources

Ovarian mitochondrial cytochrome b mRNA levels increase with sexual maturity in freshwater eels (Anguilla spp.).

Differential display of mRNA was used to identify an upregulated gene in ovaries of artificially maturing Japanese eels (Anguilla japonica). Accordingly, mitochondrial (mt) cytochrome b, whose transcript levels increased from early to late vitellogenesis, was isolated, cloned and sequenced. Temporal trends in artificially maturing eels were compared with those in naturally and artificially maturing New Zealand eels (longfinned eel, Anguilla dieffenbachii; shortfinned eel, Anguilla australis) by Northern blot and in situ hybridization analysis to rule out any experimental artifacts. An increase in ovarian mt cytochrome b signals was seen when comparing immature and midvitellogenic longfinned eels, but not immature and early vitellogenic shortfinned eels, from the wild. Long-term captivity yielded reduced target mRNA levels, but abundance increased after hormonal induction of vitellogenesis. These results imply that the increase in mt cytochrome b mRNA levels during artificial maturation reflects natural development, although its onset appears to be brought forward during artificial maturation in the Japanese eel. It is suggested that increased mt cytochrome b mRNA levels result from both mitochondrial replication and increased transcription, and that they reflect the build-up of machinery for enhanced ATP-synthesis at some stage of oogenesis and/or early zygote development.

Animals↗

Phenotype/genotype associations for yield and salt tolerance in a barley mapping population segregating for two dwarfing genes.

Barley traits related to salt tolerance are mapped in a population segregating for a dwarfing gene associated with salt tolerance. Twelve quantitative trait loci (QTLs) were detected for seven seedling traits in doubled haploids from the spring barley cross Derkado x B83-12/21/5 when given saline treatment in hydroponics. The location of QTLs for seedling growth stage (leaf appearance rate), stem weight prior to elongation, and tiller number are reported for the first time. In addition, four QTLs were found for the mature plant traits grain nitrogen and plot yield. In total, seven QTLs are co-located with the dwarfing genes sdw1, on chromosome 3H, and ari-e.GP, on chromosome 5H, including seedling leaf response (SGa) to gibberellic acid (GA(3)). QTLs controlling the growth of leaves (GS2) on chromosomes 2H and 3H and emergence of tillers (TN2) and grain yield were independent of the dwarfing genes. Field trials were grown in eastern Scotland and England to estimate yield and grain composition. A genetic map was used to compare the positions of QTLs for seedling traits with the location of QTLs for the mature plant traits. The results are discussed in relation to the study of barley physiology and the location of genes for dwarf habit and responses to GA.

Adaptation, Physiological↗

Radiotherapy for epithelial skin cancer.

PURPOSE: To retrospectively review patterns of failure, cosmesis, and outcomes according to treatment modality of patients with histologically confirmed epithelial skin cancer. METHODS AND MATERIALS: The records of 468 patients having 531 lesions were analyzed; 389 basal cell carcinomas and 142 squamous cell carcinomas were treated, 167 of which were recurrent tumors. Median follow-up was 5.8 years. Electron beam irradiation was used in 19%, superficial x-rays in 60%, a combination of electron beam and superficial x-rays in 20%, and megavoltage photons in <2%. RESULTS: The overall local tumor control rate was 89%; it was 93% for previously untreated lesions and 80% for recurrent lesions. Patients with basal cell carcinoma had a 92% overall control rate; patients with squamous cell carcinoma 80%. Multivariate analysis showed that local failure was related to the daily dose fractionation. The maximal diameter of the lesion and pathologic tumor type were also significant (p 0.01). Treatment type, patient age, and treatment duration were not significant. Overall, 92% of the treated population with cosmesis data had excellent or good results. The overall complication rate was 5.8%, consisting primarily of soft-tissue necrosis. CONCLUSIONS: Radiotherapy remains an excellent treatment modality for epithelial skin cancer. Local tumor control, cosmesis, and complications are related to the size of the primary lesion. Recurrent lesions fared worse, and therefore treatment at the earliest possible stage is strongly recommended.

Adolescent↗

Thalidomide and immunomodulatory derivatives augment natural killer cell cytotoxicity in multiple myeloma.

The antiangiogenic activity of thalidomide (Thal), coupled with an increase in bone marrow angiogenesis in multiple myeloma (MM), provided the rationale for the use of Thal in MM. Previously, the direct anti-MM activity of Thal and its analogues (immunomodulatory drugs, IMiDs) on MM cells was demonstrated, suggesting multiple mechanisms of action. In this study, the potential immunomodulatory effects of Thal/IMiDs in MM were examined. It was demonstrated that Thal/IMiDs do not induce T-cell proliferation alone but act as costimulators to trigger proliferation of anti-CD3-stimulated T cells from patients with MM, accompanied by an increase in interferon-gamma and IL-2 secretion. However, an increase in autologous T-cell killing of patient MM cells could not be demonstrated. A role for natural killer (NK)- and LAK-cell-mediated killing is suggested because IL-2-primed peripheral blood mononuclear cells (PBMCs) treated with Thal/IMiDs demonstrated significantly increased lysis of MM cell lines. Cold target inhibition assays suggested NK- rather than LAK-cell-mediated killing. Furthermore, this killing was not major histocompatibility complex-class restricted, and the depletion of CD56(+) cells blocked the drug-induced MM cell lysis. It was significant that increased killing of patient MM cells by autologous PBMCs treated with Thal/IMiDs was also observed. Although the in vivo relevance of NK-cell-mediated MM cell killing is unknown, phenotypic analysis performed in MM patients receiving Thal therapy demonstrated an increase in CD3(-)CD56(+) cells in patients responding to therapy. Thus in vitro and in vivo data support the hypothesis that Thal may mediate its anti-MM effect, at least in part, by modulating NK cell number and function.

Adjuvants, Immunologic↗

Changes in steroid hormone profiles and ovarian histology during salmon pituitary-induced vitellogenesis and ovulation in female New Zealand longfinned eels, Anguilla dieffenbachii gray.

To assess whether induced vitellogenesis in longfinned eels mimics that in naturally maturing conspecifics, female eels were artificially matured and steroid hormone status and oocyte cytology during oogenesis were evaluated. Successful induction of vitellogenesis was evident from the presence of yolk granules in the ooplasm of salmon pituitary homogenate (SPH)-injected, but not saline-, 17-hydroxyprogesterone-, and/or gonadotropin-releasing hormone-treated fish. In SPH-treated females, the migratory nucleus stage was reached after 33-53 days, followed by ovulation around 30 hours after induction of final maturation and ovulation. Only a portion of the germ cells matured, although resumption of vitellogenesis was seen in the majority of oocytes. In contrast, in ovaries of saline-injected controls, the most advanced oocytes were early vitellogenic. Atretic follicles were observed in ovaries of all eels, but abundance was greater in controls than in SPH-treated fish. SPH injections elevated plasma levels of estradiol-17beta and androgens, but not pregnenes, from within three days of treatment. Our results indicate that sex steroid levels in midvitellogenic hormone-treated females are similar to those in wild midvitellogenic females. In contrast, differences in yolk morphology of midvitellogenic follicles were seen between SPH-treated and wild females, especially in the second crop of midvitellogenic-sized oocytes measuring 300-400 microm in diameter. We discuss whether the observed differences affect egg quality, and perhaps explain the short life span of captive-bred eel larvae. J. Exp. Zool. 289:119-129, 2001.

17-alpha-Hydroxyprogesterone↗

11-Ketotestosterone induces silvering-related changes in immature female short-finned eels, Anguilla australis.

The developmental transition from a residential, immature 'yellow' eel to a migratory, maturing adult 'silver' eel is accompanied by many morphological changes that appear to be under endocrine control. High circulating levels of the teleost, and usually male-specific, androgen 11-ketotestosterone (11-KT) are found in migrating female short-finned eels, Anguilla australis. We examined the role of this steroid in silvering by implanting immature, female short-finned eels either with blank vehicles or with vehicles containing 11-KT. Six weeks after they had received the implants, eels treated with 11-KT had developed 'chisel-shaped' snouts and black pectoral fins with tapered ends, and the size of their eyes had increased significantly. 11-KT treated eels had a thicker dermis than control eels and an epidermis with fewer or no mucous cells. Ventricular mass at the end of the experiment was two-fold larger than in control eels. 11-KT treated eels also had larger livers and gonads. Ovaries contained predominantly cortical alveolus stage III oocytes, as opposed to the smaller gonads of control eels containing previtellogenic stage II oocytes. All of these changes correspond to changes during the developmental transition from yellow to silver eels in the wild. This demonstrates that silvering in eels is under endocrine control and that the presumed male-specific steroid 11-KT is capable of inducing silvering-related changes in a female teleost. We discuss how species-specific responses to 11-KT may differ depending on tissue-specific androgen receptor abundance and how a dual demand on liver function can explain the apparently positive effects of 11-KT on liver growth.

Animals↗

Process capability measurement of frequent replacement toric soft contact lenses.

PURPOSE: Frequent replacement soft contact lenses, and particularly toric soft lenses, require good reproducibility in order to avoid clinical problems arising from manufacturing variations in their parameters. This study assessed the actual and potential process capability of six frequent replacement toric soft lenses in relation to sphere power, cylinder power, cylinder axis, total diameter, back optic zone radius and centre thickness. METHOD: In total, 1260 lenses consisting of three sphere powers (plano, -3.00 and -6.00 D) were measured for six lens types. Three cylinder powers and six cylinder axes were assessed for each sphere power, except for one lens type where only two cylinder powers were available. RESULTS: Significant differences in reproducibility were found between the lens types tested. Process capability and optical quality decreased with increasing sphere power for all lenses. Cylinder power process capability tended to be better than that for sphere power. In general, lenses showed adequate reproducibility with those dimensions likely to affect lens fit, namely total diameter, back optic zone radius and centre thickness. CONCLUSIONS: Process capability was shown to be a useful measure of contact lens reproducibility for comparing toric soft lenses and assessing their potential for use on a frequent replacement basis. The results suggest some need for improvement in manufacturing accuracy and precision.

Journal Article↗

Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia.

The Australian Leukaemia Study Group (ALSG) investigated whether G-CSF would accelerate haemopoietic recovery after induction treatment for acute myeloid leukaemia (AML) intensified with high-dose cytarabine, and therefore improve response rates and survival. Patients were randomised to receive lenograstim (glycosylated recombinant human G-CSF) 5 microg per kg body weight subcutaneously daily from day 8 after starting chemotherapy, or no cytokine, following chemotherapy with cytarabine 3 g/m2 every 12 h on days 1, 3, 5, and 7, together with idarubicin 9 or 12 mg/m2 on days 1, 2, and 3, plus etoposide 75 mg/m2 on days 1 to 7 inclusive. Patients had untreated AML, and were aged 16 to 60 years. Overall, 54 evaluable patients were randomised to receive lenograstim and 58 to no cytokine. Patients in the lenograstim arm had a significantly shorter duration of neutropenia <0.5 x 10(9)/l compared to patients in the no cytokine arm (median 18 vs 22 days; P = 0.0005), and also shorter duration of total leucopenia <1.0 x 10(9)/l (17 vs 19 days; P = 0.0002), as well as a reduction in duration of treatment with therapeutic intravenous antibiotics (20 vs 24 days; P= 0.015) and a trend to reduced number of days with fever >38.0 degrees C (9 vs 12 days; P = 0.18). There were no differences between the two groups in platelet recovery, red cell or platelet transfusions, or non-haematological toxicities. For patients achieving CR after their first induction course, a reduction in the time to the start of the next course of therapy was observed in the lenograstim arm, from a median of 40.5 days to a median of 36 days (P = 0.082). The overall complete response rates to chemotherapy were similar, 81% in the lenograstim arm vs 75% for the no cytokine arm (P = 0.5), and there was no significant difference in the survival durations. We conclude that the granulopoietic stimulating effect of G-CSF is observed after induction therapy for AML intensified by high-dose cytarabine, resulting in an improvement in a number of clinically important parameters with no major adverse effects.

Acute Disease↗

Current therapy for rare factor deficiencies.

Haemophilia A and B and von Willebrand disease account for 80-85% of all inherited bleeding disorders. The other 15% are represented by deficiencies of fibrinogen, prothrombin, or factors V, VII, X, XI, or XIII. In addition, acquired factor deficiencies are seen in a variety of conditions ranging from malignancies to autoimmune disorders. The spectrum of symptoms in these conditions varies from severe and life-threatening haemorrhage to a mild bleeding diathesis. The diagnosis depends on demonstration of decreased activity of one of the clotting factors. Due to the rarity of each of the individual factor deficiencies, purified factor concentrates are not as readily available as they are for haemophilia A and B. Treatment of rare clotting factor deficiencies consists of the most purified blood product available that contains the missing factor. Depending on which factor is deficient, either purified concentrates, prothrombin complex concentrates, cryoprecipitate, or fresh frozen plasma can be used. In addition, recombinant factor VIIa is available for treating factor VII deficient patients.

Blood Coagulation Factors↗

How does the degree of carotid stenosis affect the accuracy and interobserver variability of magnetic resonance angiography?

OBJECTIVES: The accuracy of magnetic resonance angiography (MRA) was determined in patients with recently symptomatic tight (80%-99%) carotid stenosis (on Doppler ultrasound), and the effect of stenosis severity on the accuracy and interobserver variability of MRA was studied. METHODS: Forty four consecutive patients undergoing intra-arterial angiography (IAA) before carotid endarterectomy were prospectively studied, in two centres with identical MR scanners and sequences. All patients had undergone Doppler ultrasound, showing a 70% or worse carotid stenosis on the symptomatic side. MRA and IAA were done during the same admission. The MRA films were each independently and blindly read for percentage stenosis (signal gap if present) by four observers. The IA angiograms were read separately by one observer, blind to symptoms, and Doppler and MRA results. RESULTS: Signal gaps on MRA were seen in stenoses ranging from 67% to 99% on intra-arterial angiography. Magnetic resonance angiograms consistently overestimated the percentage stenosis according to intra-arterial angiography. Clinically significant misclassification of stenosis occurred according to MRA in 7% of patients, and was more frequent as carotid stenosis increased. CONCLUSION: Significant diagnostic errors occur with MRA in patients with tight carotid stenosis. Any morbidity occurring as a result of misclassification by MRA is likely to be offset by the avoidance of complications; however, this could only be determined with certainty in a randomised controlled trial.

Analysis of Variance↗

The sexual history provisions in the Youth Justice and Criminal Evidence Act 1999--a violation of the right to a fair trial?

In response to the Home Office recommendations contained in Speaking Up for Justice (1998) the Youth Justice and Criminal Evidence Act (YJCEA) 1999 introduced a new regime for the conduct of sexual offence trials. Section 41 of the Act, which came into force on 4 December 2000, brings about dramatic changes to the rules on the admissibility of evidence of complainants' sexual behaviour, severely restricting the discretion of trial judges to introduce such evidence or to allow questioning concerning it. This represents a radical new departure that will fundamentally affect an accused's position at trial. Responses to section 41 have predictably been divided given the extremely sensitive nature of this area of the law of evidence and the complex set of social and political issues which are at stake. Many have greeted it as a long overdue reform of a system premised upon outmoded and sexist beliefs concerning women's sexual behaviour which has routinely functioned to admit prejudicial and irrelevant evidence. Others, predominantly within the legal profession, have expressed serious concerns over whether the new law is workable and the extent to which, by potentially excluding critically relevant evidence, it may infringe upon a defendant's right to a fair trial. The quality of the legislation is soon to be tested. On 26 and 27 March 2001 the House of Lords heard an interlocutory appeal in the case of R v. A and were asked to decide if the new provisions, by excluding previous sexual history evidence between the complainant and the defendant, contravened Article 6 of the European Convention of Human Rights. Their Lordships are, at the time of writing, yet to give judgment and the fate of the defendant in question, and several others whose trials have been postponed pending their decision, hangs in the balance. This article seeks to show that the new Act, despite being well-intentioned, does not adopt a coherent or sustainable approach to the relevance of previous sexual history evidence and the restrictive nature of its provisions are such that genuinely relevant material will be rendered inadmissible. This creates the risk of disembodying the case before the jury and raises the significant possibility that miscarriages of justice will occur. As a consequence, unless the legislation can be read down in such a way as to reintroduce a measure of judicial discretion to admit such evidence, a declaration of incompatibility may be called for.

Canada↗

Development of a fecal occult blood test using a monoclonal antibody to haptoglobin.

Monoclonal antibodies (mAbs) were produced to human haptoglobin by immunising with fecal extracts from patients with colon cancer. An enzyme-linked immunosorbent assay was developed with one of the mAbs (FE14.1), and its ability to diagnose colorectal carcinoma evaluated. Patients with colorectal cancer were positive (43/46 = 93.5%) compared to normal individuals (4/211 = 1.9%). The assay has a specificity 93.5% and sensitivity 98.1% and has several advantages over current fecal occult blood tests. The test is potentially useful for bowel cancer diagnosis and to quantitate the level of haptoglobin in other body fluids such as urine and in effusions.

Adult↗

Subtotal pedal amputations. Biomechanical and intraoperative considerations.

Proper treatment for the compromised diabetic foot often requires surgical correction and subtotal pedal amputation. This article discusses various levels of amputation of the human foot, including digital, ray, transmetatarsal, midfoot, and Syme amputations. Surgical techniques and biomechanical considerations are presented in order to assist the surgeon in planning for the most functional outcome of the patient. A review of the literature and the experiences of the authors are presented.

Amputation, Surgical↗

Poorly fitting soft lenses affect ocular integrity.

PURPOSE: The purpose of this study was to determine whether borderline fitting soft lenses have a greater effect on ocular physiology than well fitting lenses. METHOD: The study was a retrospective analysis of data from seven soft lens clinical studies. The results of 63 eyes wearing borderline fitting lenses (31 tight and 32 loose fittings) were evaluated and compared with control eyes wearing optimally fitting lenses. Tight and loose lens fittings were defined as those showing tightness on push-up of > or =65% and < or =35%, respectively. An optimally fitting lens was defined as one showing tightness on push-up in the range 45-50% and decentration less than 0.7 mm. Slit lamp findings at the 1-month follow-up visit were compared. RESULTS: There was a significantly greater level of corneal staining among the tight lens wearing group than the controls (P=0.001); 68% of eyes wearing tight lenses showed staining as compared with 42% of eyes wearing well fitting lenses. There was also a greater level of conjunctival staining among tight lens wearing eyes but no significant difference in bulbar or limbal hyperemia. The loose lens wearing eyes showed a higher level of corneal staining: 69% vs 39% (P=0.04). In addition, the loose lens wearing eyes showed a higher level of bulbar (P=0.03) and limbal hyperemia (P=0.006). From supplementary analysis of 408 lens fittings, the incidence of corneal staining was found to increase with increasing tightness or looseness of fit. CONCLUSION: The results show that corneal staining and other physiological effects of soft lens wear vary with the quality of lens fit suggesting that practitioners should be less tolerant of sub-optimal fitting soft lenses.

Conjunctiva↗

Haemodialysis in a rural area: a demanding form of treatment.

OBJECTIVE: To determine distances travelled and time spent waiting for transport among hospital haemodialysis patients living in a rural area. DESIGN: Cross sectional survey comparing the subregional dialysis unit in south west Scotland with 12 of the other 13 Scottish Adult Renal Units. SUBJECTS: Forty three Dumfries and Galloway patients and 935 other Scottish patients receiving hospital haemodialysis in November 1999. RESULTS: At the time of the survey 8/43 (19%) Dumfries patients travelled in excess of 100 miles per dialysis day (15,000 miles per year) solely for the purpose of dialysis, compared to 20/935 (2%) elsewhere in Scotland (p < 0.001). Twenty seven (63%) Dumfries and 594 (64%) patients in other Scottish Units relied on hospital car, Patient Transport Service bus or ambulance for the journey home after treatment. Dumfries patients who travelled by Patient Transport Service or hospital ambulance had to wait twice as long before they left the renal unit as patients using a dedicated hospital car or private car. CONCLUSION: Haemodialysis in a rural area has every reason to be considered a demanding form of treatment. Greater promotion of home based treatment would improve the quality of life for many of these patients, while dedicated hospital cars would reduce 'car to needle time' for those who remain on hospital haemodialysis.

Appointments and Schedules↗