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C Townsend

Publications and source records attributed to C Townsend.

At least 19 recordsLinked to original sources
PubMed2003

Potential impact of [18F]3'-deoxy-3'-fluorothymidine versus [18F]fluoro-2-deoxy-D-glucose in positron emission tomography for colorectal cancer.

Fluorine-18 labelled fluoro-2-deoxy- d-glucose ((18)FDG) positron emission tomography (PET) imaging demonstrates the increased glucose consumption of malignant cells, but problems with specificity have led to the development of new PET tracers. [(18)F]3'-deoxy-3'-fluorothymidine ((18)FLT) is a new tracer which images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study we compared the cellular uptake of (18)FLT and (18)FDG in patients with colorectal cancer (CRC). Seventeen patients with 50 primary or metastatic CRC lesions were prospectively recruited. Lesions were initially identified using computed tomography. Patients underwent both (18)FDG and (18)FLT scanning. Semi-quantitative analysis of tracer uptake was carried out using standardised uptake values. All the primary tumours ( n=6) were visualised by both tracers, with (18)FDG showing on average twice the uptake of (18)FLT. Similar uptake of both tracers was seen in lung and peritoneal lesions, with (18)FLT imaging five of the six lung lesions and all of the peritoneal lesions. Of the 32 colorectal liver metastases, 11 (34%) were seen as avid for (18)FLT, compared with 31 (97%) for (18)FDG. No correlation was seen between the uptake of the two tracers ( R(2)=0.03). (18)FLT shows a high sensitivity in the detection of extrahepatic disease but poor sensitivity for the imaging of colorectal liver metastases, making it unlikely to have a role as a diagnostic tracer in CRC. We have demonstrated that (18)FDG and (18)FLT image two distinct processes. The prognostic implications of the uptake of (18)FLT need to be assessed in terms of response to chemoradiotherapy and survival.

Aged↗
PubMed2003

Positron emission and computed X-ray tomography: a coming together.

We describe the introduction of positron emission tomography/computed tomography (PET/CT) to the investigation of patients with cancer. The first such unit in the UK and its mode of operation is discussed and initial applications shown. Five hundred and thirty-five patients have been scanned with 2-[18F]fluoro-2-deoxy-D-glucose from mid-January 2002 to the end of August 2002. From this initial experience a clear view of the impact of this technology is emerging. It can now be stated that (1) PET/CT does speed up the throughput of patient studies by at least 25% and hence adds to the comfort of patients scanned; and (2) PET/CT leads to greater accuracy in the interpretation of data. In view of the routine availability of high quality PET and CT fused maps a significant development in radiotherapy planning is on the horizon. We discuss our experience at present and point to further developments in the near future.

Equipment Design↗
PubMed2002

Laparoscopic hysterectomy using a computer-enhanced surgical robot.

OBJECTIVE: The objective of this study was to describe the technique of laparoscopic hysterectomy using a computer-enhanced robotic surgical system. METHODS: Eleven patients underwent laparoscopic hysterectomy and bilateral salpingo-oophorectomy using a computer-enhanced surgical robot. Four trocars were used: one for the camera, two for the robotic arms controlled by the operating surgeon from the surgeon's console, and an additional port for use by the surgical assistant. RESULTS: Ages ranged from 27 to 77 years, and weight ranged from 54 to 100 kg. Operative time ranged from 4.5 to 10 hours. Estimated blood loss ranged from 50 to 1500 ml. The patients tolerated the procedure and recovered satisfactorily. CONCLUSION: This is the first case series reporting the use of a computer-enhanced surgical robot for performing hysterectomy in humans. It is feasible and well tolerated in this series of patients. As this technology develops, the applications for its use in gynecology and gynecologic oncology will increase.

Adult↗
PubMed2002

Fluorodeoxyglucose positron emission tomography in clinical oncology: the referrer's perspective.

From January 2000 to April 2002 a prospective audit based on a questionnaire was carried out concerning the attitudes and viewpoints of clinicians referring patients to fluorodeoxyglucose positron emission tomography (FDG PET) scanning. A standard and structured audit form was posted to each referring doctor with the formal clinical report issued by the nuclear medicine consultant. Three hundred and thirty evaluable forms were analysed, a return rate of approximately 22%, from a total of 1500 PET patients studied during this period. FDG PET scanning was deemed by the referring physician to have altered the staging of cancer patients in 39% of all cases. Twenty-five per cent of patients were upstaged with FDG PET and 14% of patients downstaged. Patient management was changed in 39% of cases whilst a change in treatment occurred in 10% of cases. The reported FDG PET study was judged as being helpful in over 75% of all cases. These data further support evidence of the increasing role of FDG studies in the investigation of patients with cancer.

Adolescent↗
PubMed2001

Effect of 5-HT on binding of [(11)C] WAY 100635 to 5-HT(IA) receptors in rat brain, assessed using in vivo microdialysis nd PET after fenfluramine.

By using a combination of positron emission tomography (PET) and postmortem tissue dissection, the effect of increased endogenous serotonin on specific binding of [(11)C]WAY 100635 to the 5-HT(1A) receptor was investigated in rat brain in vivo. The binding studies were complemented by in vivo microdialysis to monitor 5-HT levels in similarly treated isoflurane-anaesthetised rats, with the dialysis probe locations corresponding to two of the tissues sampled for specific binding of the radioligand. Fenfluramine treatment (10 mg/kg i.p.) resulted in a approximately 5-fold increase in extracellular 5-HT in medial prefrontal cortex and a approximately 15-fold increase in lateral hippocampus, maximal at approximately 40 min after injection. PET scan duration was either 60 or 90 min, beginning 30 min after fenfluramine injection. The specific binding of [(11)C]WAY 100635 was reduced by 10-20% in hippocampus, which showed highest binding in control animals. Specific binding, however, was unaffected in both prefrontal cortex and midbrain raphe, each additional high binding regions. The minimal effects are consistent with a low baseline occupancy of the 5-HT(1A) receptor by 5-HT in vivo, so that only a large change in endogenous agonist concentration will affect radioligand binding. This implies that utilisation of [(11)C]WAY 100635 in human PET to quantify 5-HT(1A) receptor expression can be extended to pathology where synaptic 5-HT levels are altered as a consequence of the disease state.

Animals↗
PubMed2001

Cancer prevention in rural youth: teaching goals for health: the pilot.

BACKGROUND: The Goals for Health project is designed to change the cancer-related behaviors of tobacco use and dietary fat and fiber consumption. The intervention teaches health and life skills to rural, minority sixth and seventh graders in rural Virginia and New York. This article presents the results of the pilot. METHODS: Participants were 129 sixth graders at one rural middle school who were surveyed prior to and following delivery of the pilot sixth-grade intervention. RESULTS: Results include significant changes from pre- to post-intervention in several diet and smoking attitude and self-efficacy variables, dietary fat and fiber knowledge, high-fat snack consumption, and dietary fat scores. Multivariate analyses reveal important contributions of personal control over food choices and family and friend influence on change in dietary fat score from pre- to post-intervention. CONCLUSIONS: These pilot program results suggest avenues for dietary and cancer prevention interventions in high-risk, rural adolescents.

Child↗
PubMed2001

In vitro activity of a novel antimycobacterial compound, N-octanesulfonylacetamide, and its effects on lipid and mycolic acid synthesis.

beta-Sulfonyl carboxamides have been proposed to serve as transition-state analogues of the beta-ketoacyl synthase reaction involved in fatty acid elongation. We tested the efficacy of N-octanesulfonylacetamide (OSA) as an inhibitor of fatty acid and mycolic acid biosynthesis in mycobacteria. Using the BACTEC radiometric growth system, we observed that OSA inhibits the growth of several species of slow-growing mycobacteria, including Mycobacterium tuberculosis (H37Rv and clinical isolates), the Mycobacterium avium complex (MAC), Mycobacterium bovis BCG, Mycobacterium kansasii, and others. Nearly all species and strains tested, including isoniazid and multidrug resistant isolates of M. tuberculosis, were susceptible to OSA, with MICs ranging from 6.25 to 12.5 microg/ml. Only three clinical isolates of M. tuberculosis (CSU93, OT2724, and 401296), MAC, and Mycobacterium paratuberculosis required an OSA MIC higher than 25.0 microg/ml. Rapid-growing mycobacterial species, such as Mycobacterium smegmatis, Mycobacterium fortuitum, and others, were not susceptible at concentrations of up to 100 microg/ml. A 2-dimensional thin-layer chromatography system showed that OSA treatment resulted in a significant decrease in all species of mycolic acids present in BCG. In contrast, mycolic acids in M. smegmatis were relatively unaffected following exposure to OSA. Other lipids, including polar and nonpolar extractable classes, were unchanged following exposure to OSA in both BCG and M. smegmatis. Transmission electron microscopy of OSA-treated BCG cells revealed a disruption in cell wall synthesis and incomplete septum formation. Our results indicate that OSA inhibits the growth of several species of mycobacteria, including both isoniazid-resistant and multidrug resistant strains of M. tuberculosis. This inhibition may be the result of OSA-mediated effects on mycolic acid synthesis in slow-growing mycobacteria or inhibition via an undescribed mechanism. Our results indicate that OSA may serve as a promising lead compound for future antituberculous drug development.

Acetamides↗
PubMed1999

Interaction between the pore and a fast gate of the cardiac sodium channel.

Permeant ions affect a fast gating process observed in human cardiac sodium channels (Townsend, C., H.A. Hartmann, and R. Horn. 1997. J. Gen. Physiol. 110:11-21). Removal of extracellular permeant ions causes a reduction of open probability at positive membrane potentials. These results suggest an intimate relationship between the ion-conducting pore and the gates of the channel. We tested this hypothesis by three sets of manipulations designed to affect the binding of cations within the pore: application of intracellular pore blockers, mutagenesis of residues known to contribute to permeation, and chemical modification of a native cysteine residue (C373) near the extracellular mouth of the pore. The coupling between extracellular permeant ions and this fast gating process is abolished both by pore blockers and by a mutation that severely affects selectivity. A more superficial pore mutation or chemical modification of C373 reduces single channel conductance while preserving both selectivity of the pore and the modulatory effects of extracellular cations. Our results demonstrate a modulatory gating role for a region deep within the pore and suggest that the structure of the permeation pathway is largely preserved when a channel is closed.

Algorithms↗
PubMed1997

Anomalous effect of permeant ion concentration on peak open probability of cardiac Na+ channels.

Human heart Na+ channels were expressed transiently in both mammalian cells and Xenopus oocytes, and Na+ currents measured using 150 mM intracellular Na+. Decreasing extracellular permeant ion concentration decreases outward Na+ current at positive voltages while increasing the driving force for the current. This anomalous effect of permeant ion concentration, especially obvious in a mutant (F1485Q) in which fast inactivation is partially abolished, is due to an alteration of open probability. The effect is only observed when a highly permeant cation (Na+, Li+, or hydrazinium) is substituted for a relatively impermeant cation (K+, Rb+, Cs+, N-methylglucamine, Tris, choline, or tetramethylammonium). With high concentrations of extracellular permeant cations, the peak open probability of Na+ channels increases with depolarization and then saturates at positive voltages. By contrast, with low concentrations of permeant ions, the open probability reaches a maximum at approximately 0 mV and then decreases with further depolarization. There is little effect of permeant ion concentration on activation kinetics at depolarized voltages. Furthermore, the lowered open probability caused by a brief depolarization to +60 mV recovers within 5 ms upon repolarization to -140 mV, indicative of a gating process with rapid kinetics. Tail currents at reduced temperatures reveal the rapid onset of this gating process during a large depolarization. A large depolarization may drive a permeant cation out of a site within the extracellular mouth of the pore, reducing the efficiency with which the channel opens.

Animals↗
PubMed1997

Effect of alkali metal cations on slow inactivation of cardiac Na+ channels.

Human heart Na+ channels were expressed transiently in both mammalian cells and Xenopus oocytes, and Na+ currents measured using 150 mM intracellular Na+. The kinetics of decaying outward Na+ current in response to 1-s depolarizations in the F1485Q mutant depends on the predominant cation in the extracellular solution, suggesting an effect on slow inactivation. The decay rate is lower for the alkali metal cations Li+, Na+, K+, Rb+, and Cs+ than for the organic cations Tris, tetramethylammonium, N-methylglucamine, and choline. In whole cell recordings, raising [Na+]zero from 10 to 150 mM increases the rate of recovery from slow inactivation at -140 mV, decreases the rate of slow inactivation at relatively depolarized voltages, and shifts steady-state slow inactivation in a depolarized direction. Single channel recordings of F1485Q show a decrease in the number of blank (i.e., null) records when [Na+]0 is increased. Significant clustering of blank records when depolarizing at a frequency of 0.5 Hz suggests that periods of inactivity represent the sojourn of a channel in a slow-inactivated state. Examination of the single channel kinetics at +60 mV during 90-ms depolarizations shows that neither open time, closed time, nor first latency is significantly affected by [Na+]0. However raising [Na+]0 decreases the duration of the last closed interval terminated by the end of the depolarization, leading to an increased number of openings at the depolarized voltage. Analysis of single channel data indicates that at a depolarized voltage a single rate constant for entry into a slow-inactivated state is reduced in high [Na+]0, suggesting that the binding of an alkali metal cation, perhaps in the ion-conducting pore, inhibits the closing of the slow inactivation gate.

Alkalies↗
PubMed1997

Urban medicine.

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Adult↗
PubMed1995

Characterization of a chloride channel reconstituted from cardiac sarcoplasmic reticulum.

We have characterized a voltage-sensitive chloride channel from cardiac sarcoplasmic reticulum (SR) following reconstitution of porcine heart SR into planar lipid bilayers. In 250 mM KCl, the channel had a main conductance level of 130 pS and exhibited two substrates of 61 and 154 pS. The channel was very selective for Cl- over K+ or Na+ (PK+/PCl- = 0.012 and PNa+/PCl- approximately 0.040). It was permeable to several anions and displayed the following sequence of anion permeability: SCN- > I- > NO3- approximately Br- > Cl- > F- > HCOO-. Single-channel conductance saturated with increasing Cl- concentrations (Km = 900 mM and gamma max = 488 pS). Channel activity was voltage dependent, with an open probability ranging from approximately 1.0 around 0 mV to approximately 0.5 at +80 mV. From -20 to +80 mV, channel gating was time-independent. However, at voltages below -40 mV the channel entered a long-lasting closed state. Mean open times varied with voltage, from approximately 340 msec at -20 mV to approximately 6 msec at +80 mV, whereas closed times were unaffected. The channel was not Ca(2+)-dependent. Channel activity was blocked by disulfonic stilbenes, arylaminobenzoates, zinc, and cadmium. Single-channel conductance was sensitive to trans pH, ranging from approximately 190 pS at pH 5.5 to approximately 60 pS at pH 9.0. These characteristics are different from those previously described for Cl- channels from skeletal or cardiac muscle SR.

Animals↗
PubMed1993

Regulation of cardiac L-type Ca channels in planar lipid bilayers by G proteins and protein phosphorylation.

We have studied the effects of activated G proteins (Gs alpha and Gi1 alpha), adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA), and okadaic acid on L-type Ca channels incorporated from porcine ventricular sarcolemma into planar lipid bilayers. Channel activity evoked by membrane depolarizations diminished to extremely low levels within 2 min of incorporation (channel "rundown"). When Gs alpha [activated with guanosine 5'-O-(3-thiotriphosphate)] was present in the intracellular chamber, the initial level of channel activity was increased and rundown was delayed, so that channel activity was sustained for longer times after incorporation. The effect was specific for activated Gs alpha; activated Gi1 alpha, heat-denatured, activated Gs alpha, and unactivated Gs alpha did not augment channel activity. Activated Gi1 alpha inhibited the stimulation of Ca channel activity by Gs alpha. Treatment of the sarcolemmal membranes with PKA and Mg-ATP also increased the initial channel open probability and delayed their rundown. Addition of intracellular Gs alpha to PKA-treated channels increased the initial level of activity above that seen with PKA or Gs alpha alone, suggesting different nonocclusive pathways for the channel stimulation. This was also supported by the observation that activated Gi1 alpha had no effect on PKA-treated channels. Okadaic acid (100 nM) increased the level of Ca channel activity, suggesting that dephosphorylation by endogenous phosphatases participated in the downregulation of the channels in cell-free membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Gonadotrophin surge-attenuating factor attenuates in-vitro LH secretion induced by gonadotrophin-releasing hormone from cultured ovine pituitary cells only during the breeding season.

Primary cultures of ovine pituitaries from adult ewes were used to investigate aspects of gonadotrophin surge-attenuating factor (GnSAF) bioactivity in human follicular fluid (hFF) from superovulated women. During the autumn and first half of the winter, LH secretion induced by gonadotrophin-releasing hormone (GnRH) was markedly reduced (43.5 +/- 5.2% of control GnRH-induced LH secretion) by incubation for 48 h with steroid-free hFF. For the rest of the year, treatment with the same batch of steroid-free hFF resulted in non-significant reduction or stimulation of GnRH-induced LH secretion (71.3 +/- 13.2 to 117.8 +/- 11.2% of control GnRH-induced LH secretion). Incubation of pituitary cells for 48 h with oestradiol (1 pmol/l to 1 mumol/l), progesterone (1 pmol/l to 1 mumol/l) or oestradiol and progesterone combined (1 pmol/l to 1 mumol/l) in a two-way titration for 48 h had no significant effect on GnRH-induced LH secretion (83.4 +/- 7.6 to 110.6 +/- 5.0% of control secretion). Separating hFF into fractions of different molecular mass by ultrafiltration demonstrated that GnSAF bioactivity was present in a form 10-30 kDa in size. Incubation for 48 h with these fractions had no significant effect on basal FSH secretion but significantly attenuated GnRH-induced LH secretion during the autumn. The same fractions had little effect on GnRH-induced LH secretion from pituitary cells collected during the summer. We conclude that ovine pituitaries display at least partial reduction in sensitivity to GnSAF outside the breeding season.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

We can't abandon the elderly client.

An interdisciplinary team approach, supported by the ethics committee, is essential to managing effectively the difficult-to-service client living in an urban setting. At New York's Calvary Hospital's Certified Home Health Agency, this process has distributed decisionmaking and planning of care throughout all levels of personnel, improved staff morale, and brought desperately needed home care services to patients society has abandoned.

Aged↗