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Biomedical subjects

Michael Murphy

Publications and source records attributed to Michael Murphy.

At least 37 records · Page 2Linked to original sources
PubMed2005

Ovulation induction, assisted conception and childhood cancer.

Rapid advances have been made in the treatment of infertility over the last 30 years following the introduction of in vitro fertilisation and intracytoplasmic sperm injection. Whilst effects of assisted reproductive technology (ART) on birth outcomes are well documented little is known about effects on child health after the neonatal period. Childhood cancer is one area warranting further examination. The hypothesis that cancer in children may be initiated during early fetal development means that events leading up to and around conception may be important. Whilst the few large-scale epidemiological studies that have looked at childhood cancer incidence following ART have failed to find any significant increased risk, some case-control studies have reported an increased risk of specific cancers. However, it is important not to over interpret these findings as the reason for the infertility may be the predisposing factor, rather than the procedure itself. Recent recommendations by the UK's National Health Service to offer intra-uterine insemination and one free treatment cycle for infertile couples will result in increasing numbers of children born following ART. More detailed investigations that include larger numbers plus sufficient follow-up periods and information on the underlying causes of the infertility are needed since long term outcomes for these children, in particular the risk of developing cancer, remain largely unknown.

Adult↗
PubMed2004

Cytokine-modified Mycobacterium smegmatis as a novel anticancer immunotherapy.

Intravesical administration of live M. bovis BCG organisms for carcinoma in situ of the urinary bladder is the most successful immunotherapy for solid malignancy. Nevertheless BCG-therapy is associated with significant toxicity and is ineffective in 30-40% of cases. Recently it has been proposed that cytokine-modified mycobacteria may give greater efficacy. As any immunotherapy involving administration of live BCG organisms (wild-type or recombinant) is likely to have associated toxicity (notably in the immunocompromised), we examined the anti-tumour potential of the closely related nonpathogenic organism, Mycobacterium smegmatis, and a TNFalpha gene-modified recombinant M. smegmatis. When wild-type M. smegmatis were delivered to immunocompetent C57Bl/6 mice bearing the transplantable MB49 bladder tumour, efficacy comparable to live BCG was observed with 10-20% long-term survival. However, this effect was lost in both Nude and Beige mice, lacking functional T and NK cells, respectively. Recombinant M. smegmatis secreting TNFalpha, however, gave a 70% durable tumour-free survival. Lymphocytes from draining lymph-nodes and spleens of these mice exhibited pronounced IFNgamma production to mycobacterial-antigen and tumour-lysate, indicating a bias towards cell-mediated immunity. This was further supported by histopathological examination of the tumour site, which revealed significantly increased numbers of CD3+ lymphocytes in animals receiving the recombinant vaccine, but not in those receiving wild-type bacteria. Importantly, tumour rejection following M. smegmatis/TNFalpha was independent of T lymphocytes, as athymic Nude mice efficiently eradicated MB49 tumours. In contrast, the therapeutic efficacy of M. smegmatis/TNFalpha was reduced in animals deficient in NK cytolytic function, suggesting a role for NK-cells in initial tumour destruction. Furthermore the absence of NK-function in Beige mice did not prevent the establishment of tumour-protective memory. No toxicity was observed with wild-type or recombinant M. smegmatis in immunocompetent, T-deficient or NK-deficient models. We demonstrate for the first time that recombinant mycobacteria expressing mammalian cytokines have markedly increased anti-tumour properties. The lack of toxicity suggests that M. smegmatis is a "safe" vehicle for use in immunocompromised patients.

Animals↗
PubMed2004

Subfrontal schwannoma: a case report and literature review.

Subfrontal schwannomas are rare and usually misdiagnosed preoperatively. We present the third reported case of a schwannoma arising from the olfactory nerve. The neuroradiological and pathological features of the case, as well as the origin of the tumour are discussed.

Adult↗
PubMed2004

The genetic basis for smoking behavior: a systematic review and meta-analysis.

Considerable evidence indicates that smoking behavior is under a degree of genetic influence. We conducted a systematic review of candidate gene studies of smoking behavior and, where sufficient studies existed, combined reported data using meta-analytic techniques. A total of 41 studies were identified by the search strategy, of which 28 contributed to the meta-analysis. The meta-analysis included data on the DRD2, DAT, 5HTT, and CYP2A6 genes and smoking behavior. Categorical data were extracted on smoking status (never-smoker, ex-smoker, current smoker). Continuous data were extracted on number of cigarettes smoked per day. Evidence indicated effects of the DRD2 Taq1A polymorphism and smoking initiation, the 5HTT LPR and CYP2A6 reduced-activity polymorphisms and smoking cessation, and the DRD2 Taq1A and CYP2A6 reduced-activity polymorphisms and cigarette consumption. The evidence for an effect of specific genes was modest, however, and evidence indicated substantial between-study heterogeneity in most cases, with the exception of the effects of the 5HTT and CYP2A6 genes on smoking cessation. When a random-effects model was applied to analyses in which evidence indicated significant heterogeneity, the effects were in all cases no longer statistically significant. The evidence for a contribution of specific genes to smoking behavior remains modest. Implications for the design of future studies are discussed, such as the need for the development of more specific phenotypes to increase the genetic signal in candidate gene studies.

Genetic Predisposition to Disease↗
PubMed2004

Unanticipated difficult intubation.

PURPOSE OF REVIEW: While there are many predictors of difficult laryngoscopic intubation, they all have a low positive predictive value. Therefore, unanticipated difficult laryngoscopic intubation will likely occur in our day-to-day practice. This review discusses recent developments in alternative airway devices and techniques in addressing these difficulties. RECENT FINDINGS: There is emerging evidence to suggest that new supraglottic devices are useful rescue appliances, particularly for unanticipated difficulties in laryngoscopic intubation. Other new intubating devices, including the Glidescope, may also play an important role in the management of patients with unanticipated difficult or failed laryngoscopic intubation. SUMMARY: The evidence to date does not always arm us with the ability to predict a difficult laryngoscopic intubation. Therefore, it is imperative that we equip ourselves with devices and techniques that will help us to maintain effective oxygenation and ventilation in a safe manner in the face of such failure.

Journal Article↗
PubMed2004

Plasma ropivacaine levels following scalp block for awake craniotomy.

The plasma levels of ropivacaine HCl with 5 mcg/mL epinephrine were measured in 10 patients following scalp blockade for awake craniotomy. A mean dose of 260 mg (3.6 mg/kg) resulted in peak plasma concentrations of 1.5 +/- 0.6 mcg/mL, with a median time to peak plasma concentration of 15 minutes. The pattern of rise of plasma level was similar in all patients and rapid compared with other regional blocks (epidural, intercostal, and axillary brachial plexus block). Despite this rapid rise of plasma level, no signs of cardiovascular or central nervous system toxicity were observed. In this group of patients undergoing awake craniotomy for excision of lesions in the eloquent areas of the cerebral cortex, ropivacaine HCl with epinephrine appeared to be a safe and effective local anesthetic agent in the dosages used.

Adolescent↗
PubMed2004

CD34-reactive trichodiscoma.

BACKGROUND: Trichodiscomas are rare hamartomas of the dermal portion of the hair disc, a specialized component of the perifollicular mesenchyme. They are usually found as asymptomatic multiple skin-colored papules on the face and extremities and may have an autosomal dominant inheritance pattern. However, a solitary variant has been described. CASE REPORT: A 78-year-old woman presented with a single, non-pigmented, firm papule on the left tip of the nose, measuring 3.5 mm in diameter. RESULTS: The histological examination revealed the previously described features of a trichodiscoma. The immunohistochemical analysis showed strong immunoreactivity for CD34 in the spindle cell component. Spindle cells were negative for S-100, HMB-45, Melan-A, EMA, neurofilament, desmin, and Factor XIIIa by immunohistochemistry. CONCLUSIONS: We report strong reactivity for CD34 in the spindle cell component of a trichodiscoma. We suggest that this lesion be considered in the differential diagnosis of any CD34+ dermal spindle cell proliferation, in which an adjacent epithelial component cannot be entirely excluded.

Aged↗
PubMed2004

Hypoxia regulation of the cell cycle in malignant melanoma: putative role for the cyclin-dependent kinase inhibitor p27.

BACKGROUND: Intratumor hypoxia has been shown to promote more aggressive and metastatic cancer phenotypes that are associated with treatment resistance and poor prognosis. Cellular proliferation and its control are known to be important components of tumor progression. Hypoxia induces cell-cycle arrest in cultured cell lines, possibly via up-regulation of the cyclin-dependent kinase inhibitor p27. The effect of hypoxia on cell-cycle regulation in excised human tumors has not been investigated. METHODS: We performed immunohistochemistry for p27 and Ki-67 on 10 formalin-fixed paraffin-embedded metastatic melanomas, selected on the basis of histological evidence of zonal/geographic necrosis, adjacent to areas with viable perivascular tumor cells. RESULTS: In the majority of cases, there was a significant increase in p27 staining in cells adjacent to necrotic areas compared to perivascular zones. An inverse staining pattern between Ki-67 and p27 was identified in these tumors. Tumors with no zonal increase in p27 staining demonstrated a diffuse pattern of staining for Ki-67 within tumor nests. CONCLUSIONS: While increased cellular proliferation is a characteristic of cancer, subsets of human melanomas may retain the ability to regulate their rate of proliferation in response to changes in the tumor microenvironment. The hypoxia-mediated cell-cycle arrest (decreased Ki-67) in these tumors may be mediated by p27 up-regulation.

Cell Cycle↗
PubMed2004

Skp2 and p27kip1 expression in melanocytic nevi and melanoma: an inverse relationship.

BACKGROUND: S-phase kinase associated protein-2 (Skp2) ubiquitin ligase p45(SKP2) is important in the degradation of p27kip1 (a cyclin dependent kinase inhibitor) and progression through the G1-S cell-cycle checkpoint. Low levels of p27 and high levels of Skp2 are related to poor prognosis in some cancers. METHODS: Clinicopathologic features and immunohistochemical expression of Skp2 and p27kip1 were investigated in 198 melanocytic proliferations: 21 melanocytic nevi, 23 melanoma in situ, 119 primary melanoma, and 35 metastatic melanoma samples. Comparative and survival analyses were performed. RESULTS: Progressive and significant increases and decreases in the nuclear expression of Skp2 and p27kip1, respectively, was identified moving from melanocytic nevi (0.05 +/- 0.2/85 +/- 15) to melanoma in situ (3 +/- 2/45 +/- 20) to primary cutaneous melanoma (12 +/- 9/30 +/- 25) to metastatic melanoma (25 +/- 15/15 +/- 20) (p < or = 0.006). Expression of these proteins also significantly correlated with increasing American Joint Committee on Cancer (AJCC) T (tumor) classification and AJCC stage (p < or = 0.01). Moreover, the level of these two proteins exhibited a significant inverse relationship (r = -0.4, p = 0.0001). Skp2 cytoplasmic labeling index of >20% predicted worse 10-year overall survival (38% vs. 86%, p = 0.04) in primary melanoma. Neither p27 nor Skp2 nuclear expression impacted significantly on prognosis. CONCLUSIONS: Gain of Skp2 and loss of p27kip1 protein expression are implicated in melanoma progression where the level of p27kip1 may be regulated by targeted proteolysis via Skp2. Cytoplasmic expression of Skp2 defines a subset of aggressive melanomas and could represent another pathway of deregulation of the cell cycle.

Adult↗
PubMed2004

A computer-generated stereotactic "Virtual Subdural Grid" to guide resective epilepsy surgery.

BACKGROUND AND PURPOSE: In selected patients undergoing epilepsy surgery, subdural electrode grids play an important role in localizing the epileptogenic zone and identifying eloquent cortex. Determining the relationship of the electrodes to underlying brain architecture traditionally has been difficult. This report describes and validates the use of an original computer-aided method that displays a representation of the electrode positions, based on postimplantation CT or MR findings, coregistered with a 3D-rendered image of the brain, on an image-guided surgery system. METHODS: Seventeen patients underwent the procedure with visual verification of the actual and virtual grids undertaken during the second (postimplantation) surgery. The accuracy of the Virtual Grid electrode positions was further studied in a subgroup of five patients during surgery by plotting the distance from the actual electrode positions by using an infrared stereotactic probe. RESULTS: The accuracy of the Virtual Grid electrode positions by visual inspection was satisfactory in all 17 cases. In the five cases in which quantitative measurements were performed, the mean error for the CT derived electrode positions was 3.4 mm (range 0.5-5.4) compared with the mean error for the MR-derived electrode positions of 2.5 mm (range 0.5-5.2). CONCLUSION: The Virtual Grid electrode positions were highly accurate in localizing the actual position of the subdural electrodes with both CT- and MR-derived images. The MR-derived electrodes demonstrated a trend toward better accuracy, but the CT images were quicker and easier to process. This technology has the potential to minimize both human and technical errors, allowing for a more precise tailoring of the cortical resection in epilepsy surgery.

Brain Mapping↗
PubMed2004

Extracerebral cavernous hemangioma of the cavernous sinus: diagnosis with MR imaging and labeled red cell blood pool scintigraphy.

We present the case of a 64-year-old man with a presumed diagnosis of extracerebral cavernous hemangioma involving the cavernous sinus. The diagnosis was made on the basis of labeled red cell blood pool scintigraphy findings in conjunction with those of MR imaging. This lesion was not altered in appearance at 6-year follow-up MR imaging. We also present the labeled red cell blood pool scintigraphy findings obtained in three other patients with similar-appearing cavernous sinus lesions at MR imaging who underwent subsequent biopsy; histologic findings confirmed chondrosarcoma, chordoma, and meningioma, respectively.

Adult↗
PubMed2004

Improving the ascertainment of families at high risk of colorectal cancer: a prospective GP register study.

BACKGROUND: Screening for colorectal cancer is effective in family members with a high risk of this condition, owing to single gene mutations. However, it is not known which is the most effective method of ascertaining these families at high risk. AIMS: To investigate whether a case-finding approach using computerised general practitioner (GP) registers would improve the ascertainment of families at high risk of colorectal cancer due to family history. DESIGN OF STUDY: Prospective GP register study. SETTING: General practices in Oxfordshire. METHOD: Identification of patients with colorectal cancer using GP registers, followed by a family history questionnaire survey to identify those at high risk. RESULTS: Using GP registers, 758 patients with a diagnosis of colorectal cancer were identified; a prevalence of 172 cases per 100 000 (95% confidence interval = 159 to 184). Of these, 305 patients, diagnosed under the age of 65 years, were sent a family history questionnaire. Two hundred and one (66%) patients responded to the survey; 10 (5%) patients were assessed as having high-risk families and 47 (23%) patients were assessed as having families at moderate risk. Eight of the high-risk patients had 34 first degree relatives who would benefit from routine disease surveillance, and 37 moderate-risk patients had 153 first degree relatives. Only two high-risk and six moderate-risk patients identified were previously known to the local Clinical Genetics Department. CONCLUSION: A case-finding approach using GP records and a family history questionnaire is an effective way of identifying families at high risk of developing colorectal cancer, who can then be offered disease surveillance.

Adult↗