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J Harding

Publications and source records attributed to J Harding.

At least 19 recordsLinked to original sources

Isolated adrenal metastasis: the role of laparoscopic surgery.

BACKGROUND: Solitary adrenal metastases (AM) are rare and their management unclear. Surgery, especially laparoscopic adrenalectomy (LA), is debatable in the management of AM. This retrospective study analysed the feasibility and the results of LA for AM. METHODS: From 1997 to 2003, 16 patients underwent LA for isolated AM. Completeness of resection, postoperative morbidity and follow-up (FU) were recorded. RESULTS: There were 10 synchronous AM and 6 metachronous AM. Primary tumours included lung cancer (n = 9), melanoma (n = 3), mesothelioma (n = 1), rhabdomyosarcoma (n = 1), colonic adenocarcinoma (n = 1) and renal cell carcinoma (n = 1). Five patients required conversion to an open procedure. Minor complications occurred in three patients. Pathology confirmed the diagnosis of AM. Mean tumour size was 60 (range: 15-110) mm. Nine patients (56%) had complete resections, 3 had positive margins and 4 had incomplete macroscopic resections. Mean observed FU was 25 (range: 1-68) months. Median overall calculated survival was 23 months. Overall 5-year survival was 33% (Kaplan-Meyer). At the end of study, 8 patients were alive with a mean FU of 35 months (3 without evidence of disease). No patient presented with local relapse or port-site metastasis. We did not identify any predictive factors. All patients with incomplete macroscopic resection died within 24 months. CONCLUSIONS: LA can achieve an acceptable 5-year survival, comparable to open surgery but with better postoperative comfort. It should be considered for AM with the intention of complete resection. It offers the patient the possibility of tumour resection with the benefit of a laparoscopic approach.

Adrenal Gland Neoplasms↗

Endoscopic lateral approach thyroid lobectomy: safe evolution from endoscopic parathyroidectomy.

INTRODUCTION: Endoscopic thyroid surgery has been shown to be feasible. Most minimal access procedures have been performed via a midline approach. Based on our experience of more than 500 endoscopic parathyroidectomies via a lateral approach we have used the same method for thyroid lobectomy. METHODS: We present our experience of endoscopic thyroid lobectomy via a lateral approach (ETLA) and review of the results over a 1-year period (2004). Inclusion criteria for ETLA were (1) solitary nodule with atypical/suspicious fine-needle biopsy (FNB) or solitary toxic nodule; (2) lesions with a diameter of < 3 cm. Patients with a history of previous neck surgery or radiation exposure were excluded. All patients underwent postoperative vocal cord checks and plasma calcium evaluation. RESULTS: A total of 742 thyroid procedures were performed during 2004. Among them, 38 patients (5.1%) underwent ETLA. Indications for surgery were suspicious FNB results (36 patients) and a toxic nodule (2 patients). Mean nodule size was 19.2 mm. Mean +/- SD operating time was 102 +/- 27 minutes. All recurrent laryngeal nerves were identified (including one that was nonrecurrent). Of the 38 patients, the superior parathyroid gland was identified in 36 and the inferior parathyroid gland in 33. There were two conversions due to difficulty with the dissection. Two operations were converted because malignancy was diagnosed on frozen section examination. Two patients underwent a delayed completion thyroidectomy when definitive histology necessitated it. There were no permanent operative complications, and all patients were discharged on the first postoperative day. CONCLUSIONS: ETLA offers excellent intraoperative visualization of the vital structures and is a safe alternative to conventional thyroid lobectomy in selected cases.

Adult↗

Repeat doses of prenatal corticosteroids for women at risk of preterm birth for preventing neonatal respiratory disease.

BACKGROUND: Infants born preterm are at high risk of neonatal lung disease and its sequelae. A single course of prenatal corticosteroids has not been shown to be of benefit in babies who are born more than seven days after treatment. It is not known whether there is benefit in repeating the dose of prenatal corticosteroids to women who remain at risk of preterm birth more than seven days after an initial course. OBJECTIVES: To assess the effectiveness and safety of a repeat dose(s) of prenatal corticosteroids, given to women who remain at risk of preterm birth seven or more days after an initial course of prenatal corticosteroids. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (January 2003), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2003), MEDLINE (1965 to January 2003), EMBASE (1988 to January 2003), Current Contents (1997 to January 2003). SELECTION CRITERIA: Randomised controlled trials of women who have already received a single course of corticosteroid seven or more days previously, and who are still considered to be at risk of preterm birth; outcomes compared for women randomised to receive a repeat dose(s) of prenatal corticosteroids, with women given no further prenatal corticosteroids. DATA COLLECTION AND ANALYSIS: We assessed trial quality and extracted the data independently. MAIN RESULTS: Five hundred and fifty one women were recruited into the three included trials between 24 and 30 weeks' gestation. Fewer infants in the repeat dose(s) of corticosteroids group had severe lung disease compared with infants in the placebo group (relative risk (RR) 0.64, 95% confidence interval (CI) 0.44 to 0.93, 1 trial, 500 infants). No statistically significant differences were seen for any of the other primary outcomes that included other measures of respiratory morbidity, small-for-gestational-age at birth, perinatal death, periventricular haemorrhage, periventricular leucomalacia and maternal infectious morbidity. Fewer infants in the repeat dose(s) of corticosteroids group received surfactant compared with infants in the placebo group (RR 0.64, 95% CI 0.44 to 0.93, 2 trials, 537 infants). REVIEWER'S CONCLUSIONS: Repeat dose(s) of prenatal corticosteroids may reduce the severity of neonatal lung disease. However, there is insufficient evidence on the benefits and risks to recommend repeat dose(s) of prenatal corticosteroids for women at risk of preterm birth for the prevention of neonatal respiratory disease. Further trials are required.

Adrenal Cortex Hormones↗

Evaluation of cognitive assessment and cognitive intervention for people with multiple sclerosis.

OBJECTIVES: Cognitive problems in multiple sclerosis are common but any possible benefits of treatment remain uncertain. The aim of the study was to evaluate the benefits of providing a psychology service, including cognitive assessment and intervention, to patients with multiple sclerosis. METHOD: The study was a single blind randomised controlled trial. A total of 240 patients with clinically definite, laboratory supported, or clinically probable multiple sclerosis were recruited from an multiple sclerosis management clinic and assessed on a brief screening battery. They were randomised into three groups. The control group received no further intervention. The assessment group received a detailed cognitive assessment, the result of which was fed back to staff involved in the patients' care. The treatment group received the same detailed cognitive assessment and a treatment programme designed to help reduce the impact of their cognitive problems. Patients were followed up 4 and 8 months later on the general health questionnaire (GHQ-28), extended activities of daily living scale, SF-36, everyday memory questionnaire, dysexecutive syndrome questionnaire, and memory aids questionnaire. RESULTS: The three groups were compared on the outcome measures at 4 and 8 months after recruitment. There were few significant differences between the groups and those that occurred favoured the control group. Overall, the results showed no effect of the interventions on mood, quality of life, subjective cognitive impairment or independence. CONCLUSIONS: The study failed to detect any significant effects of cognitive assessment or cognitive intervention in this cohort of people with multiple sclerosis.

Adult↗

Shared decision making in hypertension: the impact of patient preferences on treatment choice.

BACKGROUND: Recent guidelines for treatment of hypertension advocate a multifactorial approach based on absolute risk of a cardiovascular event. However, this does not take any account of individual patient values or preferences for health outcomes that result from having hypertension. OBJECTIVE: Our aim was to investigate the impact of patient preferences on treatment recommendations for hypertension using individual decision analysis. METHODS: We carried out an observational study based on interviews with 52 hypertensive patients. Patient preferences were measured using the standard gamble method. Associations between outcome of the individual decision analyses (recommendation to accept or decline antihypertensive medication) and treatment guidelines based on blood pressure and absolute cardiovascular risk were investigated. Adherence to medication during the 6 months following the interview was also assessed. RESULTS: Individual patient preferences have a substantial impact on the proportion of patients for whom drug treatment would be recommended. In 52 patients interviewed, decision analysis indicated that 29 [56%, 95% confidence interval (CI) 41--70] should be treated, compared with 27 (52%, 38--66) using a cardiovascular risk of > or =10% over 5 years and 19 (37%, 24--51) using a systolic blood pressure of > or =160 mmHG: There was marked disagreement between the decision analysis and these recommendations (kappas 0.18 or less). There was no relationship between outcome of the decision analysis and adherence to medication [chi-square (1 d.f.) = 0.5, P = 0.5]. CONCLUSIONS: Quantifying patients' preferences and using decision analysis as a shared decision-making aid appears to have an impact on whether patients would be recommended for antihypertensive medication. Further evaluation of this method as a shared decision-making tool is warranted.

Antihypertensive Agents↗

Tolerability and safety of alosetron during long-term administration in female and male irritable bowel syndrome patients.

OBJECTIVES: Alosetron (Lotronex) is a new therapeutic agent for irritable bowel syndrome (IBS) in women with diarrhea-predominant IBS. This multicenter randomized, double-blind, placebo-controlled study assessed the safety and tolerability of alosetron during long-term (< or = 12 months) treatment. METHODS: A total of 859 subjects (637 female and 222 male) with IBS were enrolled from 130 sites in the United States and were randomized 3:1 to receive 1 mg alosetron or placebo b.i.d. for 48 wk; of the subjects, 649 (76%) were randomized to the alosetron group and 212 (24%) to the placebo group. Of the original group, 850 subjects received at least one dose of alosetron (n = 640) or placebo (n = 210). RESULTS: In all, 59% of the subjects completed the study. Safety data were similar in treatment groups and within age, sex, racial origin, and hormone use. Adverse events were reported by 83% (530/640) and 76% (159/210) of subjects in the alosetron and placebo groups, respectively, (p < 0.05) and were similar with the exception of constipation; 32% of subjects receiving alosetron reported constipation, compared to 5% in the placebo group (p < 0.001). Most reports (72%) of constipation were of mild or moderate severity, and 66% of subjects with constipation had single episode of 8 days median duration. Constipation occurred a median of 13 days after initiating treatment and resolved spontaneously, with laxative, or after a brief interruption of therapy. Of the subjects, 4% (11/210) in the alosetron and 5% (28/ 640) in the placebo group experienced serious adverse events. Two deaths occurred in subjects with pre-existing cardiovascular risk factors; neither death was attributed to the study drug. CONCLUSIONS: Alosetron 1 mg b.i.d. for 12 months was well tolerated. Constipation is the most frequent adverse event, with a higher incidence of transient constipation in alosetron-treated patients, typically occurring in the first month of treatment.

Carbolines↗

Event-related potential evidence for age-related differences in attentional allocation during a source monitoring task.

Event-related potentials (ERPs) were recorded while older and younger adults were engaged in a source monitoring task. After studying a list of words, participants were presented with a recognition test during which some of the new words were repeated, rendering them as familiar as the study words. Instructions at test indicated whether the goal was to select the previously studied words or the repeated test items. Behaviorally, the younger adults were less likely to make source monitoring errors. ERPs, averaged only for correct trials, indicated that younger adults produced late positivities of greatest amplitude in response to whichever word type was designated as target irrespective of its familiarity. The ERPs of the older adults were generally less differentiated and their late positivities greater for recently repeated words irrespective of target designation. These results suggest that source monitoring in young adults is facilitated by their ability to allocate and withdraw attention from stimuli on the basis of task relevance rather than familiarity alone, and that this attentional flexibility declines with age.

Adult↗

Antibody targeting of doxorubicin-loaded liposomes suppresses the growth and metastatic spread of established human lung tumor xenografts in severe combined immunodeficient mice.

Beta1 integrins, expressed on the cell surface of human non-small cell lung carcinomas, are used here as a target for the selective delivery of anti-cancer drug-loaded liposomes. Fab' fragments of a monoclonal antibody specific for human beta1 integrins were conjugated to sterically stabilized liposomes. Confocal microscopy of beta1 integrin-positive lung tumor cells incubated with fluorescently labeled anti-beta1 Fab immunoliposomes revealed a tumor-specific binding and efficient internalization of the liposomes into the tumor cells. The ability of these liposomes to deliver cytotoxic drugs to the tumor and kill these cells was demonstrated in vitro by incubating tumor cells with doxorubicin-loaded anti-beta1 Fab' immunoliposomes. The drug-loaded immunoliposomes were >30-fold more cytotoxic to the tumor cells than drug-loaded liposomes without antibody, nonspecific Fab' control immunoliposomes with drug or immunoliposomes without drug. The therapeutic efficacy of doxorubicin-loaded immunoliposomes was also evaluated in a metastatic human lung tumor xenograft/severe combined immunodeficient (SCID) mouse model. SCID mice that received i.v. injections of human lung tumor cells developed primary tumor nodules in the lung that subsequently metastasized to the liver and adrenal gland. Treatment of SCID mice bearing established lung tumor xenografts with doxorubicin-loaded anti-beta1 Fab immunoliposomes resulted in a significant suppression of tumor growth (monitored periodically by quantifying serum levels of a tumor marker), whereas tumors grew progressively in mice treated with control formulations. In addition to suppressing the growth of the primary lung tumor nodules, the immunoliposomes prevented the metastatic spread of the tumor to the liver and adrenal glands and increased the median survival time of the tumor-bearing mice. We conclude that Fab' immunoliposomes directed to tumor-associated integrins represent a potentially viable approach clinically for the selective delivery of drugs to solid tumors and may be useful in preventing the metastatic spread of lung cancer.

Adrenal Gland Neoplasms↗

Studies of the immortalizing activity of HTLV type 1 Tax, using an infectious molecular clone and transgenic mice.

Expression of Tax in the mature lymphoid compartment of transgenic mice resulted in a lymphoproliferative malignancy of natural killer cells and cytotoxic T lymphocytes. Transgenic mouse tumors exhibited mutations in the p53 tumor suppressor gene, and functional inactivation of wild-type p53 protein. Tax transgenic mice heterozygous for the p53 gene exhibited more rapid tumor dissemination and accelerated mortality. Studies of Tax trans-activation in an infectious clone of HTLV-1 demonstrated a critical role for nuclear factor B activation in lymphocyte immortalization. A mutant disrupting Tax activation of the cAMP response element binding (CREB) protein resulted in preferential immortalization of CD8(+) lymphocytes, rather than preferential immortalization of CD4(+) lymphocytes seen with the wild-type infectious clone. A mutation disrupting Tax interaction with CREB-binding protein, CBP, did not affect lymphocyte immortalization by the infectious molecular clone. These models provide new insights into the molecular details of HTLV-1 leukemogenesis.

Animals↗

Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome.

Postweaning multisystemic wasting syndrome (PMWS) is an emerging disease in swine. Recently, the disease has been reproduced with inocula containing a newly described porcine circovirus (PCV), designated PCV 2, and porcine parvovirus (PPV). In order to determine if these viruses interact in naturally acquired PMWS, affected tissues from field cases were examined by immunohistochemistry (IHC) and polymerase chain reaction (PCR) for PCV 2 and PPV, as well as by PCR for the other recognized porcine circovirus, PCV 1. Porcine circovirus 2 was detected by PCR or IHC in affected fixed or frozen tissues from 69 of 69 cases of PMWS collected over 3 years from 25 farms. Porcine parvovirus was detected in 12 of the same cases, and PCV 1 was detected in 9 of 69; however, an apparent decrease was found in the sensitivity of the PCRs used to detect the latter 2 viruses when fixed tissue from the same cases were compared with the use of frozen tissues. Porcine circovirus 2 was not detected by PCR in affected tissues from 16 age-matched pigs that had Streptococcus suis-associated disease. Electron microscopic examination of plasma pooled from 15 pigs with PMWS revealed the presence of PCV and PPV, whereas these viruses were not observed in pooled plasma from 5 age-matched clinically normal pigs. These results confirm and extend previous findings documenting a consistent association of PCV 2 with PMWS. As well, infection by PPV or PCV 1 or both may be an important cofactor in the pathogenesis of some, but apparently not all, cases of PMWS.

Animals↗

An observational study of the Stroke Association family support organizer service.

OBJECTIVE: The aim was to investigate the role of Stroke Association family support organizers, in order to decide what outcome measures would be appropriate for evaluating their service. DESIGN: Family support organizers (FSOs) were observed on home and hospital visits by an independent observer. Every two minutes recordings were made of the location, individuals present and activity taking place. SETTING: FSOs working in the North-West and Midland regions of Britain. RESULTS: The majority (71%) of visits took place in the patient's home, with both patients and carers (39%). The most frequently occurring activities were enquiry (17%), task-related conversation (14%) and support-related conversations (14%). Comparison of FSOs showed variation in the time dedicated to each activity. CONCLUSIONS: FSOs spend more time engaged in practical rather than emotional activities. The role of the FSO is multifaceted. Evaluation of the FSO service needs to measure the patient's mood and functional abilities, the carer's mood and strain, and patients' and carers' knowledge and satisfaction with information and services.

Female↗

Effects of escape to alone versus escape to enriched environments on adaptive and aberrant behavior.

Escape-maintained aberrant behavior may be influenced by two outcomes: (a) a break from the activity and (b) subsequent access to preferred activities. To assess this hypothesis, a treatment was developed that analyzed response allocation across two break options: break alone and break with access to preferred social activities. The break with preferred activities decreased aberrant behavior and increased appropriate behavior.

Adaptation, Psychological↗

The effects of presession exposure to attention on the results of assessments of attention as a reinforcer.

The effects of presession exposure to attention on responding during subsequent assessments of attention as a reinforcer were evaluated across three behavioral assessments. In Experiment 1, a contingent attention assessment condition was preceded by either a noncontingent attention condition (free play) or a contingent escape condition. In Experiment 2, a diverted attention with extinction condition was preceded by either an alone or a free-play condition. In Experiment 3, a two-choice preference assessment was preceded by either 10 min of free play or 10 min of playing alone. In each experiment, the participant responded differentially within the test condition according to the presence or absence of dense schedules of attention immediately prior to that condition. The results of this study show that events occurring immediately prior to an assessment condition can influence behavior within the assessment.

Attention↗

Reply

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Journal Article↗

Perinatal predictors of growth at six months in small for gestational age babies.

Poor growth in childhood is associated with a number of later complications and early recognition may enable early intervention to improve outcomes. Approximately 20% of small for gestational age (SGA) babies remain small at two years. Most catch up growth occurs in the first 6 months and smallness at 6 months predicts later small size in the majority of cases. There are no previous reports of perinatal predictors of size at 6 months in SGA babies. The aim of this study was to identify the perinatal factors associated with small size at 6 months in infants who were SGA at birth (birthweight < 10th%). SGA infants had assessments of length, weight, and head circumference performed at three monthly intervals by the same researcher. Detailed perinatal data was collected in all cases. Abnormal size was defined as a length, weight or head circumference measurement < 10th% for 6 months corrected age. Infants were considered to show failure of catch-up growth if measurements at 6 months were further below the population mean than birth measurements. Two hundred and forty eight babies were recruited of whom 203 (82%) completed followup at 6 months. Forty (20%) babies were short, and in logistic regression shortness at 6 months was predicted by shortness at birth and male sex. Thirty one (16%) had weight < 10th% and low weight was predicted in logistic regression by early gestation at diagnosis of SGA (median 30.8 weeks in those who were under weight and 33.9 weeks in those of normal weight p < 0.0001). Thirty seven (18%) had a low head circumference which was predicted by small head size at birth. Three quarters of the babies who were short, underweight, or had low head circumference at 6 months also showed failure of catch-up growth. Shortness and small head circumference at 6 months were predicted by shortness and small head circumference at birth, especially in boys. Underweight was predicted by early detection of SGA antenatally. Most SGA babies who remained small at 6 months failed to show catch up growth after birth.

Adult↗

Administration of low-dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double-blind controlled trial.

OBJECTIVE: To determine whether antenatal treatment (for > or = 14 days) with 100 mg aspirin daily, given to mothers with small for gestational age fetuses and abnormal umbilical Doppler, will increase birthweight. DESIGN: Randomised, double-blind placebo controlled trial. SETTING: A tertiary referral centre. PARTICIPANTS: Ninety-nine women, of whom 65 were treated for > or = 14 days (32 with aspirin and 33 with placebo) and comprised the study group. The entry criteria were: singleton pregnancy with ultrasound evidence of a small for gestational age fetus (abdominal circumference < 10%); previous anatomy scan < 20 weeks and no evidence of fetal abnormality; gestation between 24 and 36 weeks; umbilical artery Doppler resistance index > 95% for gestation; no previous aspirin treatment in pregnancy; and no contra-indication to aspirin treatment. RESULTS: The mean duration of treatment was 30 days for aspirin treated, and 29 for placebo. No difference was found in birthweight or other measures of fetal growth or newborn morbidity between those treated with aspirin or placebo. Compliance, assessed by thromboxane B2 analysis, showed almost complete suppression of thromboxane B2 in aspirin treated women. CONCLUSION: Low-dose aspirin did not increase birthweight in pregnancies where the fetus has abnormal umbilical Doppler and is thought to be small for gestational age.

Adult↗