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Biomedical subjects

M Carey

Publications and source records attributed to M Carey.

At least 37 records · Page 2Linked to original sources
PubMed2001

Pubovaginal or vicryl mesh rectus fascia sling in intrinsic sphincter deficiency.

The aim of this study was to compare the pubovaginal sling with a new Vicryl mesh rectus fascia (VMRF) sling in the surgical treatment of low urethral pressure genuine stress incontinence. Fifty-one consecutive women who had a VMRF (n = 27) or a pubovaginal sling (n = 24) procedure between March 1995 and December 1997 were evaluated. The patient-determined subjective success rate of the VMRF sling (85%) was significantly higher than that of the pubovaginal sling (58%) in women with low urethral pressure stress incontinence (P=0.03). The objective success rates following the VMRF and the pubovaginal sling were 52% and 50%, respectively. The prevalence of postoperative symptomatic voiding dysfunction and de novo detrusor instability was 7% after the VMRF sling and 25% following the pubovaginal sling (P = 0.08). The VMRF sling had a higher patient-determined success rate and a lower complication rate than the pubovaginal sling, and should be considered in the surgical management of women with low urethral pressure stress incontinence.

Adult↗
PubMed2001

Graphical search for two-stage designs for phase II clinical trials.

In a typical two-stage design employed in a phase II cancer clinical trial for efficacy screening, a fixed number of patients are initially enrolled. The trial may be terminated for lack of clinical efficacy of treatment if the observed number of treatment successes after the first stage is too small. Otherwise, an additional fixed number of patients are enrolled to accumulate additional information on efficacy. Simon's optimal design and minimax design have often been applied to designing phase II clinical trials. Other designs have largely been ignored. In this paper, we introduce a graphical method to search for a good design that is a compromise between the optimal and the minimax designs.

Clinical Trials, Phase II as Topic↗
PubMed2001

Volatile release from an emulsion: headspace and in-mouth studies.

The headspace concentrations of three esters above solutions containing emulsified lipids were more resistant to dilution by a stream of gas than those above water alone. The effect was greatest for ethyl octanoate, and least for ethyl butyrate, with ethyl hexanoate showing intermediate behavior. This correlated with their solubility in the lipid fraction of the emulsion. Headspace analysis (comparing the emulsion with water) underestimated the release of the esters during consumption. The ratios observed between water and emulsion systems were different for the maximum breath concentration compared with headspace analysis. The emulsion appears to have acted as a reservoir for volatile release, counteracting the effects of sample dilution by saliva.

Administration, Inhalation↗
PubMed2001

Chimeric PSA enhancers exhibit augmented activity in prostate cancer gene therapy vectors.

The native PSA enhancer and promoter confer prostate-specific expression when inserted into adenovirus vectors capable of efficient in vivo gene delivery, although the transcriptional activity is low. By exploiting properties of the natural PSA control regions, we have improved the activity and specificity of the prostate-specific PSA enhancer for gene therapy and imaging applications. Previous studies have established that androgen receptor (AR) molecules bind cooperatively to AREs in the PSA enhancer core (-4326 to -3935) and act synergistically with AR bound to the proximal promoter to regulate transcriptional output. To exploit the synergistic nature of AR action we generated chimeric enhancer constructs by (1) insertion of four tandem copies of the proximal AREI element; (2) duplication of enhancer core; or (3) removal of intervening sequences (-3744 to -2855) between the enhancer and promoter. By comparing to the baseline construct, PSE, containing the PSA enhancer (-5322 to -2855) fused to the proximal promoter (-541 to +12), the three most efficacious chimeric constructs, PSE-BA (insertion of ARE4), PSE-BC (duplication of core) and PSE-BAC (insertion of core and ARE4), are 7.3-, 18.9-, and 9.4-fold higher, respectively. These chimeric PSA enhancer constructs are highly androgen inducible and retain a high degree of tissue discriminatory capability. Initial biochemical studies reveal that the augmented activity of the chimeric constructs in vivo correlates with their ability to recruit AR and critical co-activators in vitro. The enhanced activity, inducibility and specificity of the chimeric constructs are retained in an adenoviral vector (Ad-PSE-BC-luc). Systemic administration of Ad-PSE-BC-luc into SCID mice harboring the LAPC-9 human prostate cancer xenografts shows that this prostate specific vector retained tissue discriminatory capability compared with a comparable cytomegalovirus (CMV) promoter driven vector.

Adenoviridae↗
PubMed2001

Sacral nerve root stimulation for lower urinary tract dysfunction: overcoming the problem of lead migration.

OBJECTIVE: To evaluate lead migration for two different test electrodes and the response to trial stimulation of the S3 nerve root during the selection of patients for a sacral neuromodulation implant to manage lower urinary tract dysfunction. PATIENTS AND METHODS: Twelve women (mean age 49 years, range 23-79; seven with detrusor instability and five with sensory urgency) undergoing peripheral nerve evaluation for refractory lower urinary tract symptoms were recruited. Urodynamics and a urinary diary were completed before and during test stimulation. Two electrodes (the original 041830-002 and new 3057 models, Medtronics Inc, USA) were inserted under local anaesthesia into the S3 nerve roots bilaterally. The location was determined by the functional response to stimulation. Stimulation was applied for one week using the new lead; a positive response was defined as a subjective improvement (> 50%) in urinary symptoms. Lateral sacral X-rays were taken after placement and before removing the lead. The distance from the lead tip to the ventral aspect of the S3 sacral foramen was measured by two assessors. RESULTS: Ten of the women had a positive response; the mean (range) migration of the new lead (on X-ray) was 4 (2-11) mm, and of the old lead was 12 (10-45) mm (P = 0.02). CONCLUSION: The response rate to trial stimulation was greater than in previous studies, possibly reflecting reduced migration of the new lead. The new electrode may reduce the number of test failures caused by lead migration rather than no response.

Adult↗
PubMed2001

The effect of vagus nerve stimulation on epileptiform activity recorded from hippocampal depth electrodes.

PURPOSE: To assess the effect of vagus nerve stimulation (VNS) on interictal epileptiform activity in the human hippocampus. Clinical studies have established the efficacy of vagus nerve stimulation in patients with epilepsy (VNS Study Group, 1995), although the electrophysiologic effects of VNS on the human hippocampus and mesial temporal lobe structures remain unknown. METHODS: We report a case study in which a patient with an implanted VNS underwent intracranial electrode recording before temporal lobectomy for intractable complex partial seizures. Epileptiform spikes and sharp waves were recorded from a depth electrode placed in the patient's left hippocampus. Spike frequencies and sharp-wave frequencies before and during VNS were compared using both a 5- and a 30-Hz stimulus. Different stimulation rates were tested on different days, and all analyses were performed using a Student's t test. RESULTS: We found no significant differences in spike frequency between baseline periods and stimulation at 5 and 30 Hz. In contrast, stimulation at 30 Hz produced a significant decrease in the occurrence of epileptiform sharp waves compared with the baseline, whereas stimulation at 5 Hz was associated with a significant increase in the occurrence of epileptiform sharp waves. CONCLUSIONS: VNS produces a measurable electrophysiologic effect on epileptiform activity in the human hippocampus. Although a clinical response to VNS did not occur in our patient before surgery, 30-Hz VNS suppressed interictal epileptiform sharp waves that were similar in appearance to those seen during the patient's actual seizures. In contrast, 5-Hz stimulation appeared to increase the appearance of interictal sharp waves.

Adolescent↗
PubMed2001

Supraventricular tachycardia complicating the use of prostaglandin vaginal gel for induction of labour.

We present a case of a 31-year-old female patient who developed a supraventricular tachycardia and haemodynamic instability secondary to the use of vaginal prostaglandin E(2)gel for induction of labour. This complication occurred despite the patient's young age, absence of pre-existing ischaemia or coronary artery spasm, and the use of vaginal, rather than intravenous or intramyometrial prostaglandin. Physicians should be aware that serious cardiovascular complications can occur with vaginal prostaglandin E(2)therapy even in the absence of pre-existing risk factors.

Journal Article↗
PubMed2001

Postictal EEG suppression and hippocampal atrophy in temporal lobe epilepsy.

Postictal EEG suppression and slowing recorded with scalp electrodes in patients with partial epilepsy is often maximal over the cortical area of ictal onset. The aim of this study was to determine whether a quantitative relationship exists between immediate postictal EEG suppression and hippocampal atrophy. Immediate postictal EEG was analyzed in 31 scalp-recorded seizures obtained from 8 patients who underwent temporal lobectomy with seizure-free outcomes (2 left, 6 right). Quantitative EEG analysis was performed using a temporal power asymmetry index for each frequency band. The hippocampal asymmetry (left-to-right ratio) based on T1- and T2-weighted MR images was determined by hippocampal volumetric analysis. The relationship between the average temporal power asymmetry index and either T1 or T2 hippocampal asymmetry ratio was assessed for each frequency band using Pearson's correlation coefficient. Only correlations of the temporal power asymmetry index with T1 hippocampal asymmetry were significant for the total bands (r = 0.768, P < 0.026) and 8-bands (r = 0.728, P < 0.041). The findings suggest that a quantitative relationship exists between postictal EEG suppression in the 6-frequency band and hippocampal atrophy in temporal lobe epilepsy.

Adult↗
PubMed2001

Brucella abortus genes identified following constitutive growth and macrophage infection.

The chronicity of Brucella abortus infection in humans and animals depends on the organism's ability to escape host defenses by gaining entry and surviving inside the macrophage. Although no human vaccine exists for Brucella, vaccine development in other bacteria has been based on deletions of selective nutritional as well as regulatory systems. Our goal is to develop a vaccine for Brucella. To further this aim, we have used a green fluorescent protein (GFP) reporter system to identify constitutively and intracellularly induced B. abortus genes. Constitutively producing gfp clones exhibited sequence homology with genes associated with protein synthesis and metabolism (initiation factor-1 and tRNA ribotransferase) and detoxification (organic hydroperoxidase resistance). Of greater interest, clones negative for constitutively produced gfp in agar were examined by fluorescence microscopy to detect promoter activity induced within macrophages 4 and 24 h following infection. Bacterial genes activated in macrophages 4 h postinfection appear to be involved in adapting to intracellular environmental conditions. Included in this group were genes for detoxification (lactoglyglutathione lyase gene), repair (formamidopyrimidine-DNA glycosylase gene), osmotic protection (K(+) transport gene), and site-specific recombination (xerD gene). A gene involved in metabolism and biosynthesis (deoxyxylulose 5' phosphate synthase gene) was also identified. Genes activated 24 h following infection were biosynthesis- and metabolism-associated genes (iron binding protein and rhizopine catabolism). Identification of B. abortus genes that are activated following macrophage invasion provides insight into Brucella pathogenesis and thus is valuable in vaccine design utilizing selective targeted deletions of newly identified Brucella genes.

Brucella abortus↗
PubMed2001

Phase I trial of intratumoral liposome E1A gene therapy in patients with recurrent breast and head and neck cancer.

PURPOSE: We conducted a Phase 1 study to determine the maximal tolerated dose and maximum biologically active dose of the E1A gene delivered by intratumoral injection as a lipid complex with 3 beta[N-(n',n'-dimethylaminoethane)-carbamoyl] cholesterol/dioleoylphosphatidyl-ethanolamine (tgDCC-E1A). The E1A adenovirus gene functions as a tumor inhibitor gene by repressing oncogene transcription; modulating gene expression, resulting in cellular differentiation; and inducing apoptosis of cancer cells. E1A also sensitizes cancer cells to chemotherapeutic drugs such as etoposide, cisplatin, and taxol. EXPERIMENTAL DESIGN: Nine patients with recurrent and unresectable breast cancer and nine patients with head and neck cancer were enrolled. One tumor nodule in each patient was injected with tgDCC-E1A. Safety, tumor response, E1A gene transfer, and down-regulation of HER-2/neu were evaluated. RESULTS: No dose-limiting toxicity was observed in the four dose groups (15, 30, 60, and 120 microg DNA/cm of tumor). All patients tolerated the injections, although several experienced pain and bleeding at the injection site. A maximally tolerated dose was not reached in this study. E1A gene transfer was demonstrated in 14 of 15 tumor samples tested, and down-regulation of HER-2/neu was demonstrated in two of the five patients who overexpressed HER-2/neu at baseline. HER-2/neu could not be assessed in other posttreatment tumor samples because of extensive necrosis. In one breast cancer patient, no pathological evidence of tumor was found on biopsy of the treated tumor site at week 12. In 16 patients evaluable for tumor response, 2 had minor responses, 8 had stable disease, and 6 had progressive disease. CONCLUSIONS: Gene therapy with an E1A gene:lipid complex appears to be safe and warrants further testing.

Adenovirus E1A Proteins↗
PubMed2001

Irish orthopaedic patients' attitudes to blood transfusion.

This study was designed in response to perceived increased public anxiety about the risks of allogenic blood transfusion. A questionnaire was completed by 203 patients attending an elective orthopaedic hospital. The questionnaire examined patients' factual knowledge about various aspects of transfusion, their attitudes to blood transfusion and confidence in the safety of blood products. Despite recent publicity, only 124 patients (61%) regarded blood transfusion as a risk for hepatitis transmission while 172 patients (85%) knew of the risk of blood transmission of HIV. 22 patients (11%) reported that they would have no concerns about receiving a blood transfusion, while at the other extreme, 9 (5%) would not be willing to receive blood under any circumstances. 162 patients (80%) felt that allogenic blood transfusion was either entirely safe or that there was an acceptable small risk associated with it. A majority of responders (109 patients, 54%) reported they would favour autologous transfusion if available. Current practices and alternatives to traditional allogenic blood transfusion are discussed in the context of elective orthopaedic surgery.

Adult↗
PubMed2001

Markers of low level arsenic exposure for evaluating human cancer risks in a US population.

Epidemiologic studies conducted in the US have not previously detected an association between regional drinking water arsenic concentrations and corresponding cancer occurrence or mortality rates. To improve our estimation of cancer risk and arsenic exposure in the USA, we have investigated the reliability of several exposure markers. In the current study, we specifically evaluated the long-term reproducibility of tap water and toenail concentrations of arsenic, and the relation between water, toenail, and urinary measurement. Subjects included 99 controls in our case-control study on whom we requested a household tap water sample and toenail clipping three to five years apart. Additionally, participants were asked to provide a first morning void sample at the second interview. Tap water arsenic concentrations ranged from undetectable (<0.01 microg/L) to 66.6 microg/L. We found a significant correlation between both replicate water and toenail samples (intraclass correlation coefficient = 0.85, 95% confidence interval = 0.79-0.89 for water, and intraclass correlation coefficient = 0.60, 95% confidence interval = 0.48-0.70 for toenails). The inter-method correlations for water, urinary and toenail arsenic were all statistically significant (r = 0.35, p = 0.0024 for urine vs water; r = 0.33, p = 0.0016 for toenail vs water and r = 0.36, p = 0.0012 for urine vs toenails). Thus, we found both toenail and water measurements of arsenic reproducible over a three- to five-year period. Our data suggest that biologic markers may provide reliable estimates of internal dose of low level arsenic exposure that can be used to assess cancer risk.

Aged↗
PubMed2000

The rational clinical examination. Does this patient have strep throat?

CONTEXT: Sore throat is a common complaint, and identifying patients with group A beta-hemolytic streptococcal pharyngitis (strep throat) is an important task for clinicians. Previous reviews have not systematically reviewed and synthesized the evidence. OBJECTIVE: To review the precision and accuracy of the clinical examination in diagnosing strep throat. DATA SOURCE: MEDLINE search for articles about diagnosis of strep throat using history-taking and physical examination. STUDY SELECTION: Large blinded, prospective studies (having > or =300 patients with sore throat) reporting history and physical examination data and using throat culture as the reference standard were included. Of 917 articles identified by the search, 9 met all inclusion criteria. DATA EXTRACTION: Pairs of authors independently reviewed each article and used consensus to resolve discrepancies. DATA SYNTHESIS: The most useful findings for evaluating the likelihood of strep throat are presence of tonsillar exudate, pharyngeal exudate, or exposure to strep throat infection in the previous 2 weeks (positive likelihood ratios, 3.4, 2.1, and 1.9, respectively) and the absence of tender anterior cervical nodes, tonsillar enlargement, or exudate (negative likelihood ratios, 0.60, 0.63, and 0.74, respectively). No individual element of history-taking or physical examination is accurate enough by itself to rule in or rule out strep throat. Three validated clinical prediction rules are described for adult and pediatric populations. CONCLUSIONS: While no single element of history-taking or physical examination is sufficiently accurate to exclude or diagnose strep throat, a well-validated clinical prediction rule can be useful and can help physicians make more informed use of rapid antigen tests and throat cultures.

Adult↗
PubMed2000

Down-Regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor gamma in human prostate cancer.

The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily. Recent studies found that ligand-activated PPARgamma regulated differentiation and clonal growth of several types of cancer cells, including prostate cancer, suggesting that PPARgamma could be a tumor suppressor. Troglitazone was a widely used antidiabetic drug that activates PPARgamma. Recently, we reported that this agent had antiprostate cancer effects in vitro and in vivo. In this study, we administered troglitazone for over 1.5 years to an individual with occult recurrent prostate cancer. Using the prostate-specific antigen (PSA) levels as a surrogate marker of the disease, the oral administration of troglitazone (600-800 mg/day) reduced the increase velocity of PSA levels, suggesting clinical efficacy of troglitazone in prostate cancer. PSA promoter/ enhancer reporter assays showed that the PPARgamma ligands troglitazone (10(-5) M), pioglitazone (10(-5) M), or 15-deoxy-delta12,14-prostaglandin J2 (10(-5) M) down-regulated androgen-stimulated reporter gene activity in LNCaP cells, a prostate cancer cell line. The PSA promoter contains androgen receptor response elements (AREs). Reporter gene studies showed that troglitazone inhibited androgen activation of the AREs in the PSA regulatory region. Consistent with inhibition of gene expression, 2 days of incubation of LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression, suggesting that troglitazone inhibited ARE activation by a mechanism other than down-regulation of expression of the AR. Taken together, ligands of PPARgamma may be a useful therapeutic approach for the treatment of prostate cancer and may be acting, in part, by inhibiting transactivation of androgen-responsive genes.

Adenocarcinoma↗
PubMed2000

Variations in prudent laypersons' perceptions of the need for emergent medical care.

The objective of this study was to determine whether differences exist among distinct demographic groups' tendencies to view various medical symptoms as emergent in nature. A questionnaire containing six demographic questions and listing 29 common medical complaints was distributed to 306 respondents who agreed to participate; they were asked to indicate when (if at all) they would be likely to seek medical care for each problem. Overall, across the series of complaints, African American respondents desired statistically significantly more acute care than Caucasians. Those with a high school education or lower also wanted to be seen statistically significantly sooner for more symptoms than those with some college education or higher. We conclude that opinions as to the urgency of medical symptoms vary widely among demographic groups.

Adult↗
PubMed2000

High dose alfentanil as sole anaesthetic induction agent for caesarean section in a patient with severe ischaemic heart disease.

A 43-year-old woman presented at 34 weeks' gestation with pre-eclampsia and intra-uterine growth restriction. She had a past medical history of myocardial infarction and had angina on moderate effort. She also had non-insulin dependent diabetes mellitus, chronic obstructive airways disease and hypercholesterolaemia. The onset of unstable angina, cardiac failure and a deteriorating fetal condition necessitated urgent delivery by caesarean section. General anaesthesia was chosen. High dose alfentanil was used as sole induction agent resulting in minimal haemodynamic change and a successful maternal and fetal outcome.

Journal Article↗
PubMed2000

A tale of two syndromes: ovarian hyperstimulation and abdominal compartment.

Abdominal compartment syndrome complicated severe ovarian hyperstimulation in a 35 year old woman with multiple bowel resections due to Crohn's disease. Pain from ovarian enlargement necessitated hospital admission. Despite intravenous fluid administration and heparin prophylaxis, ilio-femoral deep vein thrombosis developed. Treatment by intravenous heparin was complicated by repeated intra-ovarian bleeding, anaemia and acute renal failure requiring haemodialysis. Intra-abdominal pressures were elevated. After placement of an inferior vena caval filter and discontinuation of heparin, there was slow spontaneous recovery without surgery.

Abdomen↗