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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 19 recordsLinked to original sources
PubMed2006

Hand-assisted laparoscopic colorectal surgery (HALS) at a community hospital: a prospective analysis of 104 consecutive cases.

BACKGROUND: We report 104 consecutive cases of hand-assisted laparoscopic (HAL) colectomy over 5 years performed by a single surgeon. METHODS: Data were gathered prospectively and include patient demographic data, diagnosis, operating time, conversion rate, length of hospital stay, and complications. Virtually all patients presenting for elective resection with benign disease and metastatic cancer were treated using HAL techniques. RESULTS: The mean age was 61 years; 48% of patients had diverticulitis; 21%, colorectal cancer; 18%, benign polyps. In addition, 55% of patients underwent sigmoid or left colectomy; 27%; right hemicolectomy; 9%, low anterior resection, and two double resections were performed. Mean operating room time was 135 minutes; in 12% of the patients conversion to open surgery became necessary, in most cases requiring only a small extension of the HAL incision. Mean and median discharge was postoperative day 4 and postoperative day 3, respectively. There was 1 death (1%) and 21% of patients had complications, 12% of them major. CONCLUSIONS: Hand-assisted laparotomy colectomy is a safe and effective procedure. The data in terms of length of hospital stay and operative time compare favorably with published data for conventional laparoscopic (CL) colectomy. Although further study is necessary, it appears that HALS confers all of the advantages of CL for colectomy, with no obvious drawbacks.

Colectomy↗
PubMed2006

Three-dimensional focusing of broadband microwave beams by a layered photonic structure.

Experiment and analysis confirm that a finite layered structure involving glass layers with broad strip metallizations can be characterized by broadband negative refractionlike behavior in three dimensions. The structure is further characterized as capable of 2:1 broadband focusing of near field radiation, with verified experimental focusing bandwidth of 1:5:1. This represents a significant improvement over the two-dimensional and narrow band focusing operation of current implementations of left-handed media. An electronic reconfigurable version is identified together with potential applications.

Journal Article↗
PubMed2006

A phase I and II study of 2-weekly irinotecan with capecitabine in advanced gastroesophageal adenocarcinoma.

We investigated 2-weekly intravenous irinotecan combined with oral capecitabine in patients with advanced gastroesophageal adenocarcinoma. In phase I, doses were escalated in chemotherapy naïve or pretreated patients to establish maximum tolerated doses (MTD). In phase II, patients were treated at MTD as first-line therapy with the primary end point of RECIST response. Dose levels in phase I were as follows: Level 1: irinotecan 150 mg m-2 on day 1; capecitabine 850 mg m-2 12-hourly on days 1-9. Level 2: as level 1 but capecitabine 1000 mg m-2. Level 3: as level 2 but irinotecan 180 mg m-2. Level 4: as level 3 but capecitabine 1250 mg m-2. In phase I, 21 patients were entered. Maximum tolerated dose was level 3. Dose-limiting toxicities were lethargy, diarrhoea, vomiting and mucositis. In phase II, 31 patients were entered at level 3. During the first six cycles, 13 of these patients underwent dose reduction and three patients stopped treatment for toxicity. A further six patients stopped for progressive disease. The commonest grade 3-4 toxicities were lethargy (20%), diarrhoea (17%), nausea (10%) and anorexia (10%). There were no treatment-related deaths. The response rate was 32% (95% CI 16-52%). Median overall survival was 10 months. This regimen is active in gastroesophageal adenocarcinoma. However, using the MTD defined in phase I, fewer than 50% patients tolerated six cycles without modification in phase II; therefore, modification of these doses is recommended for further study.

Adenocarcinoma↗
PubMed2006

Measurement of the K0 charge radius and a CP-violating asymmetry and a search for CP-violating E1 direct photon emission in the rare decay KL--> pi+ pi- e+ e-.

Using the complete KTeV data set of 5,241 candidate K(L)--> pi(+) pi(-) e(+) e(-) decays (including an estimated background of 204 +/- 14 events), we have measured the coupling g(CR)= 0.163 +/- 0.0149(stat) +/- 0.023(syst) of the CP conserving charge radius process and from it determined a K(0) charge radius of = [-0.077 +/- 0.007(stat) +/- 0.011(syst)]fm(2). We have determined a first experimental upper limit of 0.04 (90% C.L.) /g(e1)/ / /g(M1)/ of the couplings for the E1 and M1 direct photon emission processes. We also report the measurement of /g(M1)/ including a vector form factor /g(M1)/(1 + (a(1)/a(2))/((M(2)(p)-(M(2)(k))= 2M(K)E(gamma*)), where vector /g(M1)/= 1.11+/- 0.12(stat) +/- 0.08(syst) and a(1)/a(2) = [-0.744 +/- 0.027(stat) +/- 0.032(syst)] GeV(2)/c(2). Finally, a CP-violating asymmetry of [13.6 +/- 1.4(stat) +/- 1.5(syst)]% in the CP and T odd angle phi between the decay planes of the e(+) e(-) and pi(+) pi(-) pairs in the K(L) center of mass is reported.

Journal Article↗
PubMed2006

The renal sequelae of a novel triphasic approach to blood loss reduction during hepatic resection.

AIMS: To report our novel triphasic approach to minimising blood loss during hepatic resection and the renal sequelae. METHODS: Fifty consecutive patients (median age 63.3 years, range 37-86) underwent hepatic resection. Triphasic approach consisted of: pre-operative bowel preparation with no supplementary fluids; intraoperative intravenous fluid restriction with low central venous pressure (<5 cmH2O) and continuous selective occlusion of the left or right portal structures and corresponding hepatic vein/s. The following variables were analysed: blood loss; transfusion requirements; perioperative renal function; perioperative morbidity and mortality. RESULTS: Median estimated blood loss was 330 mL (range 50-1200). No patient was transfused intraoperatively, with two patients transfused post-operatively. Median intraoperative urine output prior to hepatic re-perfusion was 28.4 mL/h (range 13.3-40.0) with no patient developing renal impairment. Morbidity occurred in 22% of patients with no documented hepatic failure. There was zero 30-day mortality. CONCLUSIONS: Pre-operative dehydration and intraoperative fluid restriction combined with continuous selective vascular occlusion minimizes blood loss during hepatic resection with no consequent detriment to renal function.

Adult↗
PubMed2006

The development of a city-wide epilepsy register.

The provision of care for patients with epilepsy in the UK is fragmented and inadequate. Lack of support in the community, poor communication across the primary-secondary care interface and inaccessibility of specialist services are contributory factors. The inclusion of epilepsy as a quality marker in the new general practitioner (GP) contract provides an opportunity to improve co-ordination of services. Prior to the acceptance of the New GP Contract in April 2004, the first part of this audit aimed to (a) assess the documentation of the process of care of patients with epilepsy in the city of Chester; and (b) provide GPs with a clinical resource to facilitate review of patients and targeting of referrals to secondary care. The case notes of 610 patients were scrutinised to identify the proportion (a) receiving regular review, (b) in whom diagnosis was uncertain, (c) in documented remission, (d) who were women of child-bearing age, (e) who were non-compliant with treatment. A computerised template, including specific suggestions, was produced for every patient but responsibility for review remained with each GP. Re-audit in 2 years was planned. Two hundred and fifty (41%) had been seen by a GP in the previous year. One hundred and sixteen (19%) had regular review arrangements. One hundred and thirty-eight (22.6%) had shared care of whom 79 had seen their GP in previous year. Three hundred and one (49%) had not seen any doctor concerning their epilepsy in the previous year. Forty-three percent of adults who should be receiving shared care were not doing so. In 67 (11%) cases, there was diagnostic uncertainty. Only 178 (29.2%) patients were in documented remission. One hundred and nine (17.8%) patients were women of child-bearing age of whom 37 were receiving sodium valproate. In 84 (14%), there was evidence of non-compliance. Haphazard follow-up arrangements preclude review of diagnostic accuracy, estimation of remission rate, assessment of adherence to prescribed treatment and awareness of level of patients' knowledge especially women of child-bearing age on teratogenic drugs. One cannot identify those patients who can be managed solely in the community and those who merit reassessment in hospital clinics. Assuming these findings are representative, primary and specialist secondary care face an enormous task in reorganising services to ensure that all patients receive appropriate care. This project describes a method of improving local co-ordination of patient care.

Epilepsy↗
PubMed2006

An association between type 1 diabetes and idiopathic generalized epilepsy.

OBJECTIVE: Idiopathic generalized epilepsies (IGEs) account for approximately 30% of all patients with epilepsy. Both the IGEs and type 1 diabetes mellitus (T1D) represent serious worldwide problems, because of related medical and social management costs. Clinical experience suggested the two conditions were seen in individuals more frequently than might be expected by chance. METHODS: We compared the population prevalence of T1D in 15- to 30-year-olds to a cohort of 518 15- to 30-year-olds with IGE. RESULTS: We found a highly significant excess of T1D in our IGE cohort, with an odds ratio of 4.4 (95% confidence interval, 2.1-9.2). INTERPRETATION: Our results suggest that the prevalence of T1D is increased by a factor of four in young adults with IGE. To our knowledge, this is the first published association between the two conditions and expands the diseases known to be associated with T1D.

Adolescent↗
PubMed2006

Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer.

BACKGROUND AND OBJECTIVES: Interstitial photodynamic therapy (PDT) is an emerging modality for the treatment of solid organ disease. Our group at the University of Pennsylvania has performed extensive studies that demonstrate the feasibility of interstitial PDT for prostate cancer. Our preclinical and clinical experience is herein detailed. STUDY DESIGN/MATERIALS AND METHODS: We have treated 16 canines in preclinical studies, and 16 human subjects in a Phase I study, using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light fluence, drug level and oxygen distribution for these patients were performed. RESULTS: We demonstrate the safe and comprehensive treatment of the prostate using PDT. However, there is significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate. CONCLUSIONS: PDT is an attractive option for the treatment of prostate adenocarcinoma. However, the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility. Our future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time, in order to deliver a consistent overall PDT dose distribution.

Adenocarcinoma↗
PubMed2006

Adipsic diabetes insipidus following pituitary surgery for a macroprolactinoma.

Adipsic diabetes insipidus (ADI) is a rare condition in which thirst, an essential clinical feature for the prevention of hypernatraemic dehydration, is absent. We report the first case of adipsic diabetes insipidus to occur following surgery for a pituitary macroprolactinoma, with loss of both osmoregulated and baroregulated vasopressin release. Following extensive surgery for a vision threatening macroprolactinoma a 14-year-old boy developed profound hypernatraemia with absent thirst sensation. Detailed investigation, with hypertonic saline infusion and trimetaphan infusion, revealed absence of both osmoregulatory and baroregulatory release of vasopressin. We discuss the investigation and management of such patients and the physiology of hypothalamic-neurohypophyseal dysfunction in such patients.

Adolescent↗
PubMed2006

Individualized exercise program for the treatment of severe fatigue in patients after allogeneic hematopoietic stem-cell transplant: a pilot study.

Chronic cancer-related fatigue in otherwise asymptomatic post-allogeneic hematopoietic stem cell transplant (HSCT) patients is common and debilitating. This pilot study investigated whether patients with no clinical or psychological abnormalities but severe fatigue would respond to an individually adapted aerobic exercise program. Participants were 12 patients (eight male, and four female patients), median age 47 years and 41 months post-HSCT with a variety of hematopoietic cancer diagnoses. All underwent a 12-week individualized mild aerobic exercise program, preceded by a 4-week introduction and baseline testing phase. Psychological measures included fatigue, mood and depression. Exercise-related physiological outcomes included power output at ventilatory threshold 2 (VT2) and associated changes in stroke volume, heart rate, blood lactate concentration and ratings of perceived exertion. Patients were assessed for fatigue before, immediately after and at 3, 6, 9 and 12 months post-program. Significant improvements were found on both measures of fatigue (both P<0.001), with a very large effect size of 1.82 on the The Functional Assessment of Cancer Therapy - Fatigue Module, which were maintained over the follow-up period. Exercise testing revealed a mean increase (P<0.001) of 28% in power output at VT2 with an increase (P<0.001) in stroke volume and a decrease (P<0.001) in heart rate, blood lactate and perceived exertion at pre-intervention VT2 power output.

Adult↗
PubMed2006

Prevalence of conception and pregnancy outcomes after hematopoietic cell transplantation: report from the Bone Marrow Transplant Survivor Study.

We conducted a retrospective study to describe the magnitude of compromise in reproductive function and investigate pregnancy outcomes in 619 women and partners of men treated with autologous (n=241) or allogeneic (n=378) hematopoietic cell transplantation (HCT) between 21 and 45 years of age, and surviving 2 or more years. Median age at HCT was 33.3 years and median time since HCT 7.7 years. Mailed questionnaires captured pregnancies and their outcomes (live birth, stillbirth, miscarriage). Thirty-four patients reported 54 pregnancies after HCT (26 males, 40 pregnancies; eight females, 14 pregnancies), of which 46 resulted in live births. Factors associated with reporting no conception included older age at HCT (> or =30 years: odds ratio (OR)=4.8), female sex (OR=3.0), and total body irradiation (OR=3.3). Prevalence of conception and pregnancy outcomes in HCT survivors were compared to those of 301 nearest-age siblings. Although the risk for not reporting a conception was significantly increased among HCT survivors (OR=36), survivors were not significantly more likely than siblings to report miscarriage or stillbirth (OR=0.7). Although prevalence of conception is diminished after HCT, if pregnancy does occur, outcome is likely to be favorable. Patients should be counseled prior to transplant regarding strategies to preserve fertility.

Adult↗
PubMed2006

A multicenter, randomized, double-blind, placebo-controlled, dose-finding trial of a long-acting formulation of octreotide in promoting weight loss in obese adults with insulin hypersecretion.

OBJECTIVE: To compare changes in weight in obese patients who received long-acting octreotide (octreotide LAR) at one of three dose levels (20, 40, or 60 mg) or placebo over 6 months and to identify the lowest dose of octreotide LAR that safely achieved optimal weight loss. DESIGN: Randomized, double-blind, placebo-controlled trial of octreotide LAR at three dose levels. PATIENTS: A total of 172 adults (28 men and 144 women) with at least moderate obesity (body mass index (BMI) range 30-65 kg/m2) and evidence of insulin hypersecretion were enrolled. Patients were predominantly either Caucasian (50.0%) or African American (45.3%). The mean age (38 +/- 11 year), weight (110.7 +/- 23 kg), and BMI (39.8 +/- 6.5 kg/m2) were similar across the four treatment groups. MEASUREMENTS: Efficacy measures included weight, BMI, fasting serum glucose; triglycerides; percentage of total body fat and abdominal fat as measured by dual-energy X-ray absorptiometry; skin fold thickness; waist-to-hip circumference; leptin; percentage of carbohydrates, fat, and protein ingested; nutritional evaluation (including dietary analysis--3-day food record); quality of life (QoL; using the Impact of Weight on Quality of Life-Lite); Beck Depression Inventory; and Carbohydrate Craving Questionnaire. Safety measures included medical history, vital signs, physical examinations, hematology, blood chemistries, thyroid function tests, hemoglobin A1c, gallbladder ultrasound, electrocardiograms, and adverse events. RESULTS: After 6 months of treatment, patients receiving 40 or 60 mg of octreotide LAR experienced statistically significant weight loss compared to baseline, with mean differences from placebo in percent weight change of -1.98 and -1.87%, respectively. This finding was accompanied by statistically significant mean decreases in BMI compared to baseline, that is, a mean decrease of 0.73 and 0.79 kg/m2 for the 40 and 60 mg treatment arms, respectively. The observed weight loss was progressive during the 6-month treatment in the two higher dose groups. The lowest dose to reach statistical significance in weight loss after 6 months' treatment was 40 mg. Post hoc analysis revealed a 3.5-3.8% weight loss at month 6 in the two higher dose groups among Caucasian patients having insulin secretion greater than the median of the cohort, defined as CIR(gp) (corrected insulin response at the glucose peak) > or = 1.43. There were no statistically significant changes in QoL scores, body fat, leptin concentration, Beck Depression Inventory, or macronutrient intake. Mean changes of blood glucose AUC(0-180 min) during an oral glucose tolerance test in patients taking octreotide LAR were 39-40 mg/dl h higher than those on placebo. A total of 7-21% of the patients taking octreotide LAR reached a 5% or greater decrease in body weight from Baseline, compared to 11% for the placebo group. This was not statistically significant. The most common adverse events included diarrhea, headache, cholelithiasis, nausea, and abdominal pain. CONCLUSION: Octreotide LAR given at 40 or 60 mg resulted in statistically significant weight loss. A post hoc analysis stratifying patients by race and CIR(gp) indicated that Caucasian patients with the greater degree of insulin hypersecretion appeared to derive the most benefit from treatment. The observed safety profile was consistent with the known effects of octreotide from previous studies.

Adult↗
PubMed2006

The adenoma carcinoma sequence: an indoctrinated model for tumorigenesis, but is it always a clinical reality?

OBJECTIVE: Evidence exists to support alternative pathways to the adenoma carcinoma sequence. Some mutations in key onco-suppressor genes relate to the anatomical site of the tumour. This link is typified by microsatellite instability and proximal neoplasia. However, rectal tumours are rarely considered separately. We hypothesized that tumour behaviour in the rectum may differ in terms of pathogenesis and malignant propensity. Therefore, we aimed to look for an association between the histopathological features of adenomas and their anatomical location as compared with the distribution of cancers. METHODS: A single centre prospective study was undertaken over a four-year period. Patients referred to a colorectal assessment clinic with bowel symptoms underwent a minimum investigation of flexible sigmiodoscopy. Neoplastic lesions were either biopsied or removed after noting distance from the anal margin. Adenomas, differentiated by size, villous architecture and degree of dysplasia were compared to both early and advanced carcinomas. RESULTS: Of 4089 patients, polyps were identified in 8.0% and cancer in 4.2%. There was a clear difference between the distribution of cancer and adenomas > 1 cm, P < 0.001. All degrees of dysplasia in large adenomas were more prevalent in the sigmoid colon as compared to cancer, P < 0.001. Seventy-five percent of high risk diminutive adenomas were rectal in origin. CONCLUSION: Our data provides indirect evidence to support the concept that a significant proportion of rectal cancers may arise via an alternative pathway to the Vogelstein model. Polyp behaviour along with malignant propensity may actually be site dependent, with rectal polyps harbouring a more aggressive phenotype.

Adenoma↗
PubMed2006

Hypopharyngeal perforation following minor trauma: a case report and literature review.

Hypopharyngeal perforation is mainly reported in association with high velocity road traffic accidents, or with low velocity direct blows to the neck. We report a case of hypopharyngeal perforation following a low velocity motorcycle accident where neither of these mechanisms of injury was apparent. A 52 year old man was referred from the emergency department (ED) with a sore throat and dysphagia, following a low speed side impact accident. A gastrograffin swallow demonstrated a posterior pharyngeal wall tear. After 11 days of conservative hospital treatment, he recovered and was discharged. The presumed mechanism of injury in this case was cervical spine hyperextension without cervical compression.

Accidents, Traffic↗
PubMed2006

Symptomatic presentation of early colorectal cancer.

INTRODUCTION: It is believed that increased detection of earlier stage colorectal cancer can only be achieved by screening asymptomatic individuals. We describe a referral pathway for a symptomatic population which achieves a 30% Dukes' A detection rate. PATIENTS AND METHODS: From October 1999, 4253 patients with distal colonic symptoms, referred by general practitioners, completed a patient consultation questionnaire (PCQ) linked to a computerised record. A weighted numerical score (WNS) was derived for each patient. Patients underwent flexible sigmoidoscopy, a diagnostic outcome was recorded and later Dukes' stage appended. Early and advanced colorectal cancers were separated and PCQ derived symptom profiles compared. Chi-square, Fisher exact, Student's t-test and logistic regression were used for statistical analysis. RESULTS: A total of 183 patients had cancer, 55 (30%) were Dukes' A early colorectal cancers, 112 were advanced colorectal cancers (Dukes' B-D) and 16 could not be staged. Early colorectal cancers had significant symptoms and comparable profile to advanced colorectal cancers. The tendency in advanced colorectal cancers was towards greater symptom prevalence for only a few primary and systemic symptoms, as reflected by a higher WNS of 75 (P = 0.001). CONCLUSIONS: Early colorectal cancers do have significant symptoms which can easily be captured by a PCQ and objective scoring tool in the secondary care setting. Detection of these cancers has the potential to improve survival.

Aged↗
PubMed2006

Cystic fibrosis-related diabetes in adults.

We aimed to examine the differences between patients with cystic fibrosis-related diabetes (CFRD), and those with normal glucose handling in adults with cystic fibrosis (CF) in Ireland. We conducted a retrospective analysis of patients who attend the national referral centre for adult CF. Patients were diagnosed as having CFRD by the American Cystic Fibrosis Foundation criteria for diagnosis of CFRD. Of 259 patients, 150 were classifiable and 81 (54%) were classified as having CFRD. The groups with and without CFRD were not significantly different with regard to age (median 28.4 vs 26.0 years), sex (males 56% vs 55%) or BMI (median 20.9 vs 21.3 kg/m2). The group with CFRD had poorer lung function (mean % predicted FEV1 49.9 vs 66.4, P < 0.001), poorer bone mineral density (T-scores at the lumbar spine -1.95 vs -1.44, P < 0.05 and femur -1.19 vs -0.57, P < 0.01) and a greater proportion of PSEUDOMONAS AERUGINOSA positive sputum cultures (82.5% vs 64.2%, P < 0.05). No patients with CFRD carried the R1 17H mutation whilst 19% of the group without CFRD were heterozygous for this defect (P < 0.001). In conclusion, CFRD was highly prevalent in adults. The presence of CFRD was associated with poorer lung function, poorer bone mineral density and an increased prevalence of PSEUDOMONAS AERUGINOSA in sputum. The R1 17H mutation may be protective for CFRD.

Adult↗
PubMed2005

A prospective evaluation of treatment with Selective Internal Radiation Therapy (SIR-spheres) in patients with unresectable liver metastases from colorectal cancer previously treated with 5-FU based chemotherapy.

BACKGROUND: To prospectively evaluate the efficacy and safety of Selective Internal Radiation (SIR) spheres in patients with inoperable liver metastases from colorectal cancer who have failed 5FU based chemotherapy. METHODS: Patients were prospectively enrolled at three Australian centres. All patients had previously received 5-FU based chemotherapy for metastatic colorectal cancer. Patients were ECOG 0-2 and had liver dominant or liver only disease. Concurrent 5-FU was given at investigator discretion. RESULTS: Thirty patients were treated between January 2002 and March 2004. As of July 2004 the median follow-up is 18.3 months. Median patient age was 61.7 years (range 36-77). Twenty-nine patients are evaluable for toxicity and response. There were 10 partial responses (33%), with the median duration of response being 8.3 months (range 2-18) and median time to progression of 5.3 mths. Response rates were lower (21%) and progression free survival shorter (3.9 mths) in patients that had received all standard chemotherapy options (n = 14). No responses were seen in patients with a poor performance status (n = 3) or extrahepatic disease (n = 6). Overall treatment related toxicity was acceptable, however significant late toxicity included 4 cases of gastric ulceration. CONCLUSION: In patients with metastatic colorectal cancer that have previously received treatment with 5-FU based chemotherapy, treatment with SIR-spheres has demonstrated encouraging activity. Further studies are required to better define the subsets of patients most likely to respond.

Adult↗