Search PubMed⌕ Search

Biomedical subjects

D Kirk

Publications and source records attributed to D Kirk.

At least 19 recordsLinked to original sources
PubMed2005

Simultaneous functional magnetic resonance imaging in the rat spinal cord and brain.

Functional magnetic resonance imaging (fMRI) method was developed to investigate the pattern and temporal relationship in neuronal pathways of brain and spinal cord. Signal intensity changes correlating with stimulation patterns were observed simultaneously in the rat spinal cord and brain using fMRI at 9.4 T. Electrical stimulation of the forepaw was used to elicit activity. A quadrature volume RF coil covering both brain and the cervical spinal cord was used. Sets of fast spin echo (FSE) images were acquire simultaneously for both brain and spinal cord fMRI. Experiments were repeated in single animal and across animals. Activities within the dorsal horn of the spinal cord and within the somatosensory cortex were observed consistently within each animal as well as across animals.

Animals↗
PubMed2005

Coat proteins of Rice tungro bacilliform virus and Mungbean yellow mosaic virus contain multiple nuclear-localization signals and interact with importin alpha.

Transport of the viral genome into the nucleus is an obligatory step in the replication cycle of plant pararetro- and geminiviruses. In both these virus types, the multifunctional coat protein (CP) is thought to be involved in this process. Here, a green fluorescent protein tagging approach was used to demonstrate nuclear import of the CPs of Rice tungro bacilliform virus (RTBV) and Mungbean yellow mosaic virus--Vigna (MYMV) in Nicotiana plumbaginifolia protoplasts. In both cases, at least two nuclear localization signals (NLSs) were identified and characterized. The NLSs of RTBV CP are located within both N- and C-terminal regions (residues 479KRPK/497KRK and 744KRK/758RRK), and those of MYMV CP within the N-terminal part (residues 3KR and 41KRRR). The MYMV and RTBV CP NLSs resemble classic mono- and bipartite NLSs, respectively. However, the N-terminal MYMV CP NLS and both RTBV CP NLSs show peculiarities in the number and position of basic residues. In vitro pull-down assays revealed interaction of RTBV and MYMV CPs with the nuclear import factor importin alpha, suggesting that both CPs are imported into the nucleus via an importin alpha-dependent pathway. The possibility that this pathway could serve for docking of virions to the nucleus is discussed.

Capsid Proteins↗
PubMed2005

Recurrent severe hyperandrogenism during pregnancy: a case report.

This report describes the case of a 28 year old woman with virilisation occurring in two successive pregnancies. Recurrent maternal virilisation is rare (seven previous reports) and this case is unique in its severity. Differential diagnoses include ovarian disease and fetal aromatase deficiency. New techniques to exclude a fetal cause were used in this case. This patient presented during the third trimester of her first pregnancy with rapid onset of hirsuitism, increased musculature, and deepening voice. A blood hormone profile revealed significant hyperandrogenism (testosterone, 72.4 nmol/litre; normal range, 0.5-3.0). She delivered a normal boy and maternal androgen concentrations returned rapidly to normal (testosterone, 0.8 nmol/litre). She presented two years later, during her second pregnancy, with similar symptoms and biochemistry (testosterone, 47.5 nmol/litre). Again, she delivered a healthy normal boy and androgens returned immediately to normal (serum testosterone, 2.0 nmol/litre). Ultrasonography revealed no evidence of ovarian (or adrenal) masses in either pregnancy. Umbilical cord venous blood sampling and placental assays revealed no evidence of fetal aromatase deficiency. Recurrent hyperandrogenism during pregnancy is rare. Ovarian luteoma rarely recurs and hyperreactio luteinalis does not lead to such pronounced androgen concentrations. Therefore, this patient has a unique ovarian condition that could be harmful to offspring and mother.

Adult↗
PubMed2004

Chronic testicular pain: an overview.

Chronic testicular pain (orchialgia, orchidynia or chronic scrotal pain) is common and well recognized but its pathophysiology is poorly understood. Currently treatment is largely empirical. This article aims to present an overview of its prevalence, possible aetiology and the available treatment options. The contribution of psychological factors is unclear, although some of these patients undoubtedly are depressed. Post vasectomy chronic testicular pain may be due to functional obstruction of the vas, or to spermatic granuloma. The surgical technique used may be relevant and the application of intraoperative local anaesthetic may have a role in reducing the risk. The importance of the sympathetic nervous system and the role of a possible alteration of the adrenergic receptors of the vas deferens in patients with chronic testicular pain are discussed. For patients failing to respond to conservative treatment, microsurgical denervation of the spermatic cord, epididymectomy and vasovasostomy have all shown a degree of relief. Unfortunately a small number of patients fail to respond to both conservative and more invasive treatment methods and for them the only available therapeutic option is inguinal orchiectomy.

Adrenergic alpha-Antagonists↗
PubMed2004

Timing and choice of androgen ablation.

Hormone therapy remains central to the management of advanced prostate cancer. Evidence has accrued to suggest benefits from earlier treatment. Trials which demonstrate significant improvements in disease-specific survival may be underpowered to show overall survival benefits, due to the effect of mortality from unrelated causes. Toxicity, particularly the risk of osteoporosis, causes increasing concern, particularly where many years of use may be contemplated as in early relapse after curative treatment. Strategies to reduce toxicity include use different drugs, notably antiandrogens and with renewed interest in oestrogens in low dose or administered parenterally, and deferred and intermittent treatment. Further improvements in drug development, reducing toxicity, and identification of the cause of hormone refractory disease and its prevention would revolutionise the use of hormone therapy. Currently, deferred treatment, used selectively and with careful follow-up, remains an option for selected patients.

Androgen Antagonists↗
PubMed2004

Combining a targeted radiotherapy and gene therapy approach for adenocarcinoma of prostate.

A targeted radiotherapy/gene therapy approach for prostate cancer, using the radiopharmaceutical [(131)I]meta-iodobenzylguanidine ([(131)I]MIBG), would restrict the effects of radiotherapy to malignant cells, thereby increasing efficacy and decreasing morbidity of radiotherapy. Prostate cancer cells were transfected with a transgene encoding the noradrenaline transporter (NAT) under the control of tumour-specific telomerase promoters, enabling them to actively take up [(131)I]MIBG. This led to tumour-specific cell kill. This strategy has the advantage of generating a radiological bystander effect, leading to the destruction of neighbouring tumour cells that have escaped transfection. This targeted approach could be a promising tumour-specific treatment option for prostate cancer.

3-Iodobenzylguanidine↗
PubMed2003

Improved prognosis of patients with intermediate- and poor-risk nonseminomatous germ cell tumours by optimizing combined treatment.

OBJECTIVE: To assess whether the optimal use of combined treatment with chemotherapy and appropriately timed surgical intervention by a specialized team might improve the outcome for patients with poor- and intermediate-prognosis (International Germ Cell Consensus Classification, IGCCC) nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: Between 1984 and 1998, 47 patients with intermediate (16) and poor prognosis (31) NSGCT were treated; 43 had a testicular and four a retroperitoneal primary. RESULTS: Of the 47 patients only seven (15%) had a complete radiological response after primary chemotherapy; 36 (77%) required surgery after chemotherapy (29 para-aortic lymphadenectomy, 13 resection of pulmonary metastases, two each excision of supraclavicular and retrocrural lymph nodes and one resection of brain metastases; 13 required surgery at more than one site). There was no surgical mortality, with postoperative wound pain the commonest morbidity. On pathology, the resected masses were mature teratoma in 13, necrosis in 12 and malignant disease in 11 patients, the resection being complete in 30. There were microscopically positive margins in the other six patients, all but one having viable residual cancer. Of the 47 patients, 18 needed treatment for relapse, with four having surgery for growing mature teratoma, six chemotherapy plus surgery and eight salvage chemotherapy alone. Of 31 patients, 22 (71%) with a poor and 13 of 16 with an intermediate prognosis were alive at a median (range) follow-up of 94 (41-171) months; of all 47, 34 (72%) remain in complete remission. Ten patients died from disease progression. The presence of residual malignant disease at the resection margin was significantly associated with poorer survival (hazard ratio 7.21, P = 0.0016). Prognostic factors, e.g. number of involved sites, IGCCC group and viable tumour in resected masses, were not significant. The 5-year overall and relapse-free survival (95% confidence interval) was 81 (69-93)% and 57 (43-71)%, respectively. CONCLUSION: The optimal delivery and timing of chemotherapy and surgical resection by a specialist team of oncologists, urological and cardiothoracic surgeons is critical in treating poor-risk NSGCT and might be responsible for improving the outcome of these patients. The detection of residual malignant disease after chemotherapy by positron emission tomography should be investigated to identify those who might benefit from further systemic treatment before complete surgical resection.

Adult↗
PubMed2003

Bilateral testicular cancer: a preventable problem? Experience from a large cancer centre.

OBJECTIVE: To report a retrospective review of patients with a testicular germ cell tumour treated in a large cancer centre who developed a second tumour, as 1.8-5% of such patients will subsequently develop a new primary tumour in the contralateral testis. PATIENTS AND METHODS: From a database of 570 men treated for testicular cancer in the West of Scotland between 1989 and 1998, all those who developed bilateral testicular tumours were identified. RESULTS: Nineteen men (3.3%) developed a second primary testicular malignancy; the mean age at diagnosis of the first tumour was 29.5 years, with the mean (range) interval to diagnosis of the second tumour of 76 (11-181) months (except for one man with synchronous tumours). The first tumour was teratoma in 11 and seminoma in seven; one patient had synchronous bilateral teratoma. The second primary was teratoma in 10 and seminoma in eight. Known risk factors for carcinoma in situ were present in nine patients, i.e. a small atrophic contralateral testis in five, a family history of testicular cancer in two, a history of infertility in two and unilateral undescended testis in one. Two patients had had contralateral testicular biopsies at the first diagnosis; both were negative for intratubular germ cell neoplasia (IGCN). Eight patients had chemotherapy to treat the first tumour and 14 for the second. All underwent bilateral orchidectomy. Overall, 18 of 19 men are alive and disease-free, with a median follow-up of 51 months. Pathology for 12 of the second testicular tumours was available for review; there was no IGCN in any of the slides from three patients, it was only present focally around the tumour in seven, and was diffuse in two patients. CONCLUSIONS: Chemotherapy for the first testicular tumour does not eliminate the risk of developing a contralateral tumour. Despite careful follow-up, in most patients the second primary tumour was not diagnosed early enough to avoid chemotherapy. The focal nature of IGCN in the second testis in most patients questions the value of biopsy of the contralateral testis. Improved methods of detecting patients at risk of second testicular tumours are needed.

Adult↗
PubMed2001

Shunting is a translation strategy used by plant pararetroviruses (Caulimoviridae).

In eukaryotes standard initiation of translation involved 40S ribosome scanning to bridge the distance from the cap to the initiation codon. Recently deviations from that rule had been described, including "internal initiation", "poly-A dependent translation", and "ribosome shunting". In ribosome shunting, ribosomes start scanning at the cap but large portions of the leader are skipped. Thereby the secondary structure of the shunted region is preserved. Scanning in plant caulimoviruses involve a small open reading frame properly spaced in front of a strong stem structure, and, in order to function, the small open reading frome has to be translated and the peptide released. This arrangement can be mimicked by artificial small open reading frames and stem structures. Shunting with viral and synthetic leaders occurs not only in plant-, but also in mammalian and yeast systems. Thus it responds to an intrinsic property of the eukaryotic translational machinery and probably acts in many cases where coding regions are preceded by complex leaders.

Caulimovirus↗
PubMed2001

A non-circadian role for cAMP signaling and CREB activity in Drosophila rest homeostasis.

In the fruit fly, Drosophila melanogaster, rest shares features with mammalian sleep, including prolonged immobility, decreased sensory responsiveness and a homeostatic rebound after deprivation. To understand the molecular regulation of sleep-like rest, we investigated the involvement of a candidate gene, cAMP response-element binding protein (CREB). The duration of rest was inversely related to cAMP signaling and CREB activity. Acutely blocking CREB activity in transgenic flies did not affect the clock, but increased rest rebound. CREB mutants also had a prolonged and increased homeostatic rebound. In wild types, in vivo CREB activity increased after rest deprivation and remained elevated for a 72-hour recovery period. These data indicate that cAMP signaling has a non-circadian role in waking and rest homeostasis in Drosophila.

Animals↗
PubMed2000

Improving the outcome of salvage treatment for non-seminomatous germ cell tumours (NSGCT).

Between 1991-96, 41 patients were treated in this unit for relapsed non-seminomatous germ cell tumours (NSGCT). Twenty-eight patients had raised markers at relapse: 17 required salvage chemotherapy and post-chemotherapy surgery, 11 only chemotherapy. In addition 9 patients received high dose chemotherapy. Overall 16/28 patients (57%) requiring chemotherapy remain alive, 14 (50%) disease free. Of the 17 patients treated with chemotherapy and surgery: 12 remain alive, 10 (59%) with no evaluable disease. Only 4/11 (36%) patients treated with chemotherapy alone remain alive, all in complete remission (CR). For relapse with raised markers, univariate analysis suggests that less than CR to induction therapy, resulting in the presence of residual disease is the most important predictor of poor outcome (P<0.001). All of the 13 patients relapsing with normal markers remain alive, having been primarily treated surgically. Overall these results indicate an improving outlook for relapsed NSGCT.

Adult↗
PubMed1999

Endoscopy-based triage significantly reduces hospitalization rates and costs of treating upper GI bleeding: a randomized controlled trial.

BACKGROUND: Many patients with upper gastrointestinal (GI) bleeding have a benign outcome and could receive less intensive and costly care if accurately identified. We sought to determine whether early endoscopy performed shortly after admission in the emergency department could significantly reduce the health care use and costs of caring for patients with nonvariceal upper GI bleeding without adversely affecting the clinical outcome. METHODS: All eligible patients with upper GI bleeding and stable vital signs were randomized after admission to undergo endoscopy in 1 to 2 days (control) or early endoscopy in the emergency department. Patients with low-risk findings on early endoscopy were discharged directly from the emergency department. Clinical outcomes and costs were prospectively assessed for 30 days. RESULTS: We randomized 110 consecutive stable patients with nonvariceal upper GI bleeding during the 12-month study period. The baseline demographic features, endoscopic findings, and the clinical outcomes were no different between the two groups. However the findings of the early endoscopy allowed us to immediately discharge 26 of 56 (46%) patients randomized to that group. No patient discharged from the emergency department suffered an adverse outcome. The hospital stay (median of 1 day [interquartile range of 0 to 3 days] vs. 2 days [interquartile range of 2 to 3 days], p = 0.0001) and the cost of care ($2068 [interquartile range of $928 to $3960] versus $3662 [interquartile range of $2473 to $7280], p = 0.00006) were significantly less for the early endoscopy group. CONCLUSIONS: Early endoscopy performed shortly after admission in the emergency department safely triaged 46% of patients with nonvariceal upper GI bleeding to outpatient care, which significantly reduced hospital stay and costs.

Adult↗