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C Porter

Publications and source records attributed to C Porter.

At least 19 recordsLinked to original sources
PubMed2006

Crystallization and preliminary X-ray diffraction analysis of the Bacillus subtilis replication termination protein in complex with the 37-base-pair TerI-binding site.

The replication terminator protein (RTP) of Bacillus subtilis binds to specific DNA sequences that halt the progression of the replisome in a polar manner. These terminator complexes flank a defined region of the chromosome into which they allow replication forks to enter but not exit. Forcing the fusion of replication forks in a specific zone is thought to allow the coordination of post-replicative processes. The functional terminator complex comprises two homodimers each of 29 kDa bound to overlapping binding sites. A preparation of RTP and a 37-base-pair TerI sequence (comprising two binding sites for RTP) has been purified and crystallized. A data set to 3.9 A resolution with 97.0% completeness and an R(sym) of 12% was collected from a single flash-cooled crystal using synchrotron radiation. The diffraction data are consistent with space group P622, with unit-cell parameters a = b = 118.8, c = 142.6 A.

Bacillus subtilis↗
PubMed2006

Increased acute GvHD and higher transplant-related mortality in non-caucasians undergoing standard sibling allogeneic stem cell transplantation.

We conducted a retrospective study to compare outcome in Caucasians and non-Caucasians undergoing standard sibling allogeneic SCT. End points of the study were to compare graft-versus-host disease (GvHD) occurrence and transplant-related mortality (TRM). There were 251 patients, 43 non-Caucasian and 208 Caucasian. A higher proportion of non-Caucasian patients developed acute GvHD (aGvHD) grade 2 or greater as compared to the Caucasian group (48 vs 26%, respectively) P = 0.02. With a median follow-up of 27 months, 26% (11/43) of non-Caucasians and 14% (29/208) of Caucasian patients had died from TRM, which accounted for 55% of all deaths in the non-Caucasian group compared to 33% in Caucasians, P = 0.02. Overall survival 12 months post transplant was 64 vs 69% in the non-Caucasian and Caucasian groups, respectively (P = 0.43). Although there were higher numbers of CMV-positive patients in the non-Caucasian group, there were no deaths from CMV reactivation in this subgroup. We conclude that there is increased TRM and aGvHD following standard sibling allograft in the non-Caucasian population and this could be due to either differences in tumour biology or extrinsic factors such as socio-economic factors, nutritional status, post transplant care or presenting with late stage disease.

Acute Disease↗
PubMed2005

Human bioavailability of propranolol from a matrix-in-cylinder system with a HPMC-Gelucire core.

The bioavailability of propranolol from a matrix-in-cylinder system for sustained drug delivery, consisting of a hot-melt extruded ethylcellulose pipe surrounding a drug-containing HPMC-Gelucire 44/14 core, was determined. An oral dose of 80 mg propranolol hydrochloride was administered to healthy volunteers (n = 10) in a randomized cross-over study design either as a commercial pellet formulation (Inderal retard mitis) or as a matrix-in-cylinder system. The influence of concomitant food intake on drug release from the matrix-in-cylinder system was also studied. During the first 10 h after administration, the matrix-in-cylinder system resulted in similar plasma levels as the reference formulation Inderal. The concomitant intake of a high-fat, high-calorie breakfast did not cause dose-dumping. Between 10 h and 24 h after administration of the matrix-in-cylinder system, a remarkable increase of the propranolol plasma levels was noticed (compared to Inderal). This effect was even more pronounced under fed conditions. The matrix-in-cylinder system had a relative bioavailability of 156% (fasted conditions) and 222% (fed conditions) compared to the marketed reference product. In order to elucidate the origin of this increased bioavailability, Caco-2 experiments and dog lymph studies were performed. However, none of these experiments was able to provide a conclusive answer.

Adolescent↗
PubMed2003

A prospective study of 1000 hernias: results of the Plymouth Hernia Service.

BACKGROUND: A hernia service within a general hospital was prospectively evaluated to establish whether evidence-based protocols could deliver results comparable to those reported from specialist hernia clinics. METHODS: Protocols were devised according to established models. With the support of a nurse specialist, 1015 patients with inguinal hernia were treated. Quality-of-life analysis was undertaken using the Short Form 36. RESULTS: Patients ranged in age from 16-98 years (median, 56 years). Ambulatory day-case surgery was achieved in 820 patients (81%), with local anaesthesia in 891 (88%). Wound infection occurred in 10 patients (0.98%). Wound haematoma requiring surgical intervention occurred in three patients. Two patients formed wound seromas that settled spontaneously. One patient developed ischaemic orchitis resulting in testicular atrophy. At 5 days after operation, 91% of patients had returned to normal activity. At 1 year, 7 patients (0.7%) had pain sufficient to limit normal activity or employment. There were 8 recurrences (0.78%) at a median follow-up of 2.5 years. Quality-of-life was enhanced at 1 year postoperatively. CONCLUSION: A protocol-driven hernia service within a general hospital can provide patient outcomes comparable to specialist hernia clinics.

Adolescent↗
PubMed2001

Predictive modeling techniques in prostate cancer.

A number of new predictive modeling techniques have emerged in the past several years. These methods can be used independently or in combination with traditional modeling techniques to produce useful tools for the management of prostate cancer. Investigators should be aware of these techniques and avail themselves of their potentially useful properties. This review outlines selected predictive methods that can be used to develop models that may be useful to patients and clinicians for prostate cancer management.

Humans↗
PubMed2001

Artificial neural network model to predict biochemical failure after radical prostatectomy.

BACKGROUND: Biochemical failure, defined here as a rise in the serum prostate specific antigen (PSA) concentration to >0.3 ng/mL or the initiation of adjuvant therapy, is thought to be an adverse prognostic factor for men who undergo radical prostatectomy (RP) as definitive treatment for clinically localized cancer of the prostate (CAP). We have developed an artificial neural network (ANN) to predict biochemical failure that may benefit clinicians and patients choosing among the definitive treatment options for CAP. MATERIALS AND METHODS: Clinical and pathologic data from 196 patients who had undergone RP at one institution between 1988 and 1999 were utilized. Twenty-one records were deleted because of missing outcome, Gleason sum, PSA, or clinical stage data. The variables from the 175 remaining records were analyzed for input variable selection using principal component analysis, decision tree analysis, and stepped logistic regression. The selected variables were age, PSA, primary and secondary Gleason grade, and Gleason sum. The records were randomized and split into three bootstrap training and validation sets of 140 records (80%) and 35 records (20%), respectively. RESULTS: Forty-four percent of the patients suffered biochemical failure. The average duration of follow up was 2.5 years (range 0-11.5 years). Forty-two percent of the patients had pathologic evidence of non-organ-confined disease. The average area under the receiver operator characteristic (ROC) curve for the validation sets was 0.75 +/- 0.07. The ANN with the highest area under the ROC curve (0.80) was used for prediction and had a sensitivity of 0.74, a specificity of 0.78, a positive predictive value of 0.71, and a negative predictive value of 0.81. CONCLUSION: These results suggest that ANN models can predict PSA failure using readily available preoperative variables. Such predictive models may offer assistance to patients and physicians deciding on definitive therapy for CaP.

Adjuvants, Pharmaceutic↗
PubMed2001

Mucoepidermoid carcinoma of the thyroid gland: a case report and suggested surgical approach.

Mucoepidermoid carcinoma (MEC) of the thyroid gland is a rare neoplasm with 40 cases reported in the world literature to date. Controversy surrounds the treatment of this rare neoplasm. It has been described as a low-grade indolent tumor that rarely metastasizes and only recurs locally without morbidity. Suggested treatment has consisted of a lobectomy or subtotal thyroidectomy. We report a case of a 63-year-old woman with a 15-year history of a multinodular goiter with a dominant left lobe nodule. Fine-needle aspiration was inconclusive. The patient opted for a total thyroidectomy. Final pathology yielded a diagnosis of mucoepidermoid carcinoma. We propose that despite its low-grade appearance the morbidity and mortality associated with its ability to locally recur and metastasize justify the need for more aggressive surgical therapy.

Carcinoma, Mucoepidermoid↗
PubMed2000

A five year outbreak of methicillin-susceptible Staphylococcus aureus phage type 53,85 in a regional neonatal unit.

We identified a 5-year outbreak of a methicillin-susceptible Staphylococcus aureus (MSSA) strain, affecting 202 babies on a neonatal unit, by routine weekly phage typing all S. aureus isolates. Multiple staged control measures including strict emphasis on hand hygiene, environmental and staff surveillance sampling, and application of topical hexachlorophane powder failed to end the outbreak. S. aureus PT 53,85 (SA5385) was found on opened packs of Stomahesive, used as a neonatal skin protectant. Only following the implementation of aseptic handling of Stomahesive, and the use of topical mupirocin for staff nasal carriers of SA5385, and for babies colonized or infected with S. aureus, did the isolation rate of SA5385 decline. DNA fingerprinting indicated that > or =, 95% of SA5385 isolates were clonal. In vitro death rates of SA5385 on Stomahesive with human serum were significantly lower than on Stomahesive alone (P = 0.04), and on cotton sheet with serum (P = 0.04), highlighting the potential of this material as a survival niche. Phage typing remains a valuable, inexpensive and simple method for monitoring nosocomial MSSA infection.

Bacteriophage Typing↗
PubMed2000

Hormonal induced lactation in transgenic goats.

The aim of this study was to hormonally induce lactation in prepubertal, nulliparous, and male goats both transgenic and non-transgenic. Analysis of milk quality, recombinant protein expression levels, total amount of recombinant protein produced, and the affect on long-term reproductive capability was assessed. Fifty-one goats (Saanen, Alpine, and Toggenburg), male and non-pregnant females, 2-31 months of age, either non-transgenic or transgenic were evaluated with a total of 10 transgenes (constructs) represented. Animals were given estradiol (0.25 mg/kg, i.m.) and progesterone (0.75 mg/kg, i.m.) on days 1, 3, 5, 7, 9, 11 and 13, while prednisilone (0.4 mg/kg, i.m.) was administered on days 14-16 with mammary massage occurring daily from day 5 onward. Forty of 51 animals, (36 of 38 females and 4 of 13 males) produced milk with total volumes in the 30-day experiment, ranging from 20 microl to 530 mls per day, or approximately 500 microl to 6.8 liters total. Milk composition was analyzed for various parameters (total protein, fat content, total solids and somatic cell count) with no significant differences found between induced and natural milk. Expression levels of recombinant proteins from transgenic animals that were analyzed during the induced lactation, and subsequently during normal lactations, were found to have no significant differences. Total amount of recombinant protein produced was evaluated at different expression levels with no statistical significance seen. While over 90% of the females placed in the regimen became pregnant, there was a correlation between increased age at time of induction and an increase in number of breedings, or reproductive cycles needed to establish a pregnancy after induction. For males, 100% placed in the regimen settled females after hormonal induction of lactation. Semen quality was evaluated prior to, during, and after hormonal treatments. Semen volume and sperm number did not differ; however, for a small percentage of males, there was a decrease in sperm and post thaw motility after hormonal treatments. These levels returned to normal within 4-5 weeks. Subsequent natural lactations showed total milk volumes within breed standards. These findings indicate that hormonal induction of lactation in the caprine species is a viable alternative to pregnancy for initiating lactation and milk production, does not adversely impact reproductive performance long-term, and can benefit the early assessment of recombinant proteins produced in a transgenic founder program.

Animals↗
PubMed1999

Difluoromethylornithine chemoprevention of epidermal carcinogenesis in K14-HPV16 transgenic mice.

To be informative for chemoprevention, animal models must both closely emulate human disease and possess surrogate endpoint biomarkers that facilitate rapid drug screening. This study elucidated site-specific histopathological and biochemical surrogate endpoint biomarkers of spontaneous epidermal carcinogenesis in K14-HPV16 transgenic mice and demonstrated that the incidence and severity of these markers were decreased by the ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO). The cumulative incidence of visible epidermal cancers in 127 untreated transgenic mice was 42% by 52 weeks of age, most frequently affecting the chest as flat lesions in association with chronic ulcers, or in the ear as protuberant masses. Microscopic malignancies were detected in 39% of 32-week-old transgenic mice and were found to emerge from precursor lesions that were of two distinct types: dysplastic sessile ear papillomas and hyperproliferative follicular/interfollicular chest dysplasias. ODC activity and tissue polyamine contents were differentially elevated in ear and chest skin during carcinogenesis, such that there was a marked elevation of both parameters of polyamine metabolism as early as 4 weeks of age in the ear, whereas in the chest, polyamine metabolism was increased significantly only in the late stages of neoplastic progression and in epidermal cancers. Administration of 1.0% DFMO in the drinking water from 4 to 32 weeks of age prevented both visible and microscopic malignancies and significantly decreased the incidence of chest and ear precursor lesions. ODC activity and tissue putrescine content were markedly diminished by DFMO chemoprevention in ear skin, whereas there was a more modest decline of these parameters in chest skin. DFMO treatment of transgenic mice from 28 to 32 weeks of age was associated with an absence of ear cancer and a marked regression of dysplastic papillomas. In contrast, the results in chest skin were complex in that the severity of chest precursors diminished, but their incidence was unchanged, and microscopic cancers were still detectable within these lesions. Collectively, this study highlights the utility of multistage epidermal carcinogenesis in K14-HPV16 transgenic mice both for the study of the biology of, and as a screening tool for, novel drugs and chemopreventive regimens.

Administration, Oral↗
PubMed1999

Exercise and nutrition: what adolescents think is important.

The purpose of this qualitative study was to examine adolescents' experiences with health promotion, particularly physical activity and eating patterns. Adolescents' reported experiences were triangulated with measures of physical activity and food frequency to assess congruence with goals of Healthy People 2000 (published by the U.S. Department of Health and Human Welfare in 1995). Fifteen ethnically and racially diverse adolescents, ages 10 to 18, were interviewed in an adolescent primary care clinic or in their homes. Interviews were transcribed and coded line-by-line for themes apparent in the data. Major themes were compared and contrasted with previous research as a guide for developmentally appropriate health promotion interventions.

Adolescent↗
PubMed1999

Induction of complement attack on human cells by Gal(alpha1,3)Gal xenoantigen expression as a gene therapy approach to cancer.

Galactose(alpha1,3)galactose on the surface of cells of non-primate organs is the major xenoantigen responsible for hyperacute rejection in xenotransplantation. The antigen is synthesised by (alpha1, 3)galactosyl transferase. Humans lack this enzyme and their serum contains high levels of pre-existing natural antibody which recognises the structure and activates complement. We have evaluated in vitro the potential for delivery of this enzyme to sensitise human cells to complement attack as a gene therapy approach to cancer. Retrovirus-mediated delivery of (alpha1,3)galactosyl transferase resulted in high level expression which led to serum-mediated lysis of five human cell targets, including endothelial and primary melanoma cells. Lysis was specific for those cells expressing the antigen in a mixed cell population. The mechanism of cell lysis mimicked that involved in hyperacute rejection: activation of the classical complement pathway by natural antibody specific for galactose(alpha1,3)galactose. The degree of lysis was determined by both the level of specific antibody and the expression of glycophosphatidylinositol-linked complement regulatory proteins. We conclude that expression of (alpha1,3)galactosyl transferase is a promising new therapeutic approach for cancer gene therapy, avoiding toxicity problems associated with application of prodrugs and with the potential to elicit further immunological responses.

Antigens, Heterophile↗
PubMed1999

Increased platelet activation in renal transplant patients.

BACKGROUND: Patients with functioning renal transplants are at risk of graft thrombosis in the postoperative period, and of fistula thrombosis and other thrombotic events thereafter. Investigation and therapeutic manipulation of haemostasis in these patients offers a means to counter this thrombotic tendency. METHODS: Platelet aggregation in whole blood, plasma von Willebrand factor and plasma fibrinogen levels were measured in 32 stable renal transplant patients (creatinine <200 micromol/litre, age of graft >4 months) and in 32 age, sex and smoking-habit matched normal controls. RESULTS: In both patient and control groups, seven patients were smokers and the remaining 25 were non-smokers. There was no significant difference in age between patients and controls [patients, median: 39 (20-64) years; controls: 38 (24-60) years]. Spontaneous platelet aggregation was significantly higher in the patients at all time points studied [30s-6 min; at 4 min: patients median (interquartile range) 19.4 (11.3-27.3)%; controls, 8.0 (5.1-15.0)%, P < 0.0005]. ADP-induced aggregation was also increased at a concentration range of 0.1-3 microM (at 1 microM, 1 min, patients median (interquartile range) was 52.4 (30.5-70.0)%; controls was 16.5 (1.4-31.4)%, P < 0.0001). Transplant patients had significantly higher von Willebrand factor and fibrinogen levels compared with the controls (von Willebrand factor, patients median (range): 158 (13-269)%; controls: 85 (43-223)%, P < 0.00001; fibrinogen, patients: 3.29 (2.12-7.39) g/litre; controls: 2.81 (1.84-4.65) g/litre, P < 0.0002). CONCLUSION: Patients with stable renal transplants have in vitro evidence of enhanced platelet activation, and increased plasma von Willebrand factor and fibrinogen levels.

Journal Article↗
PubMed1999

Factors contributing to dehydration in nursing homes: inadequate staffing and lack of professional supervision.

OBJECTIVE: To investigate the factors that influenced fluid intake among nursing home residents who were not eating well. DESIGN: A prospective, descriptive, anthropological study. SETTING: Two proprietary nursing homes with 105 and 138 beds, respectively. PARTICIPANTS: Forty nursing home residents. MEASUREMENTS: Participant observation, event analysis, bedside dysphagia screening, mental and functional status evaluation, assessment of level of family/advocate involvement, and chart review were used to collect data. Data were gathered on the amount of liquid served and consumed over a 3- day period. Daily fluid intake was compared with three established standards: Standard 1 (30 mL/kg body weight), Standard 2 (1 mL/kcal/energy consumed), and Standard 3 (100 mL/kg for the first 10 kg, 50 mL/kg for the next 10 kg, 15 mL/kg for the remaining kg). RESULTS: The residents' mean fluid intake was inadequate; 39 of the 40 residents consumed less than 1500 mL/day. Using three established standards, we found that the fluid intake was inadequate for nearly all of the residents. The amount of fluid consumed with and between meals was low. Some residents took no fluids for extended periods of time, which resulted in their fluid intake being erratic and inadequate even when it was resumed. Clinical (undiagnosed dysphagia, cognitive and functional impairment, lack of pain management), sociocultural (lack of social support, inability to speak English, and lack of attention to individual beverage preferences), and institutional factors (an inadequate number of knowledgeable staff and lack of supervision of certified nursing assistants by professional staff) contributed to low fluid intake. During the data collection, 25 of the 40 residents had illnesses/conditions that may have been related to dehydration. CONCLUSIONS: When staffing is inadequate and supervision is poor, residents with moderate to severe dysphagia, severe cognitive and functional impairment, aphasia or inability to speak English, and a lack of family or friends to assist them at mealtime are at great risk for dehydration. Adequate fluid intake can be achieved by simple interventions such as offering residents preferred liquids systematically and by having an adequate number of supervised staff help them to drink while properly positioned.

Activities of Daily Living↗
PubMed1999

Malignant eccrine spiradenoma: a previously unreported presentation and review of the literature.

Malignant eccrine spiradenomas (MESs) are rare tumors arising from previously benign eccrine spiradenomas. A review of the literature reveals only 25 published reports of malignancy arising from eccrine spiradenoma and no prior reports of an MES of the scalp. The tumors have a metastasis rate of >50 per cent in reported cases with high resultant mortality rates. We present the first case report of a single MES of the scalp. Multiple resections were required for local control. Both magnetic resonance imaging and lymphoscintigraphy were used to assess regional spread. A review of the literature follows to include histopathology, diagnosis, and both surgical and adjuvant therapeutic options.

Adenoma, Sweat Gland↗
PubMed1999

A three-year study of viable airborne fungi in the North Carolina Zoological Park R.J.R. Nabisco Rocky Coast Alcid Exhibit.

Aspergillosis is a common cause of mortality in captive birds, particularly in recently imported birds or captive chicks and their parents. Use of the Andersen N-6 single-stage viable air sampler in the North Carolina Zoological Park (NCZP) R.J.R. Nabisco Rocky Coast Alcid Exhibit before and after the introduction of birds allowed a unique study of the mycological content of the air in a developing self-contained ecosystem. The Alcid Exhibit had a median count of 17 colony-forming-units (CFU)/m3 of air in comparison to 200-500 CFU/m3 and 1,000-3,500 CFU/m3 reported in human dwellings and the NCZP R.J. Reynolds Forest Aviary, respectively. Cladosporium and Penicillium represented 21.3% and Aspergillus 1.08% of the fungi collected. During the study, no respiratory mycoses were reported in any of the alcids. Continuous high-efficiency particulate air filtration, maintenance of low exhibit air temperatures, and an environment with little residual organic material capable of supporting fungal growth were important factors contributing to low colony counts. All colony counts >100 CFU/m3 in the exhibit were related to the apparent introduction of fungi from outside the facility. A reduction in the number of fungi transported from an external source into enclosed cool-temperature aviaries may be sufficient to avoid outbreaks of aspergillosis.

Air Microbiology↗