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Biomedical subjects

J Black

Publications and source records attributed to J Black.

At least 19 recordsLinked to original sources
PubMed2006

Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials.

Gastrin has been shown to be a growth stimulant in pancreatic cancer cells. Gastrazole is a potent and selective gastrin receptor antagonist. Two randomised blinded trials were conducted to assess the effect of gastrazole in advanced pancreatic cancer. Patients with biopsy-proven, inoperable pancreatic carcinoma were recruited. Trial A compared protracted venous infusion (PVI) gastrazole with PVI placebo, whereas trial B compared PVI gastrazole with PVI fluorouracil (5-FU). Eighteen patients were randomised in trial A. Gastrazole produced significantly better survival compared to placebo (median 7.9 months vs 4.5 months; 1-year survival: 33 vs 11%, respectively; log rank P=0.02). No difference in toxicity was seen between gastrazole and placebo, except central venous catheter and pump complications. Ninety-eight patients were randomised in trial B. No significant survival difference was detected between gastrazole and 5-FU (median: 3.6 vs 4.2 months; 1-year survival: 13.2 vs 26.2%, respectively; log rank P=0.42). Toxicity of gastrazole was mild with significantly less diarrhoea (P=0.03), stomatitis (P<0.001) and hand- foot syndrome (P<0.001) compared to 5-FU. Quality of life (QoL) assessment showed similar QoL between gastrazole and 5-FU at baseline and no significant differences occurred with treatment either between arms or within arms. Compared to placebo, patients with advanced pancreatic cancer treated with gastrazole appeared to live longer, albeit in a very small trial and will require confirmation with large-scale randomised data. However, it did not produce survival advantage over PVI 5-FU. Lack of toxicity for gastrazole may allow its combination with cytotoxic drugs.

Adult↗
PubMed2006

Development, application and validation of a Taqman real-time RT-PCR assay for the detection of infectious salmon anaemia virus (ISAV) in Atlantic salmon (Salmo salar).

Infectious salmon anaemia (ISA) is a disease of cultured Atlantic salmon (Salmo salar) which was successfully eradicated from Scotland following its emergence in 1998. The rapid deployment of sensitive diagnostic methods for the detection of ISA virus (ISAV) was fundamental to the swift eradication of ISA disease in Scotland and continues to be of crucial importance to surveillance of the aquaculture industry. This study reports the development, validation, application and interpretation of two independent, highly sensitive and specific semi-quantitative Taqman real-time RT-PCR (qRT-PCR) methods for the detection of ISAV. Such technology offers considerable advantages over conventional RT-PCR methods in current routine use for ISAV surveillance. These include an increased sensitivity, enhanced specificity, semi-quantification using endogenous controls, a lack of subjectivity in results interpretation, speed of processing and improved contamination control.

Animals↗
PubMed2005

Clinician-led surgical site infection surveillance of orthopaedic procedures: a UK multi-centre pilot study.

The UK Department of Health established the Healthcare-associated Infection (HAI) Surveillance Steering Group in 2000 to develop a strategy for implementing a national programme for HAI surveillance in National Health Service trusts. A subgroup of this committee examined the surveillance of surgical site infections following orthopaedic surgery. This group oversaw a pilot scheme that was set up in 12 hospitals around the UK to explore the feasibility of implementing a system of surveillance that engaged clinical staff in its operation, provided a process for continuous data collection and could be maintained as part of routine hospital operation over time. A minimum data set was established by the subgroup, and Centers for Disease Control and Prevention (CDC) definitions of infection were used. By March 2003, the surveillance had been undertaken continuously in 11 sites for one to two years, depending on the date of implementation. Only one hospital had ceased data collection. The information was collected mainly by clinical staff, with support and co-ordination usually provided by infection control teams. Data on more than 5400 procedures were available for analysis for four core procedures: arthroplasty of the hip and knee; hemi-arthroplasty of the hip; and internal fixation of trochanteric fractures of the femur. The data set permitted the calculation of risk-adjusted rates, allowing comparisons between hospitals and within a hospital over time. The methodology enhanced clinical ownership of the surveillance process, re-inforced infection control as the responsibility of all staff, and provided timely feedback and local data analysis. The use of CDC definitions permitted international comparisons of the data.

Adult↗
PubMed2004

Genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV).

The nucleotide sequences of a specific region of the nucleoprotein gene were compared in order to investigate the genetic population structure of marine viral haemorrhagic septicaemia virus (VHSV). Analysis of the sequence from 128 isolates of diverse geographic and host origin renders this the most comprehensive molecular epidemiological study of marine VHSV conducted to date. Phylogenetic analysis of nucleoprotein gene sequences confirmed the existence of the 4 major genotypes previously identified based on N- and subsequent G-gene based analyses. The range of Genotype I included subgroups of isolates associated with rainbow trout aquaculture (Genotype Ia) and those from the Baltic marine environment (Genotype Ib) to emphasise the relatively close genetic relationship between these isolates. The existence of an additional genotype circulating within the Baltic Sea (Genotype II) was also confirmed. Genotype III included marine isolates from around the British Isles in addition to those associated with turbot mariculture, highlighting a continued risk to the development of this industry. Genotype IV consisted of isolates from the marine environment in North America. Taken together, these findings suggest a marine origin of VHSV in rainbow trout aquaculture. The implications of these findings with respect to the future control of VHSV are discussed. The capacity for molecular phylogenetic analysis to resolve complex epidemiological problems is also demonstrated and its likely future importance to disease management issues highlighted.

Animals↗
PubMed2004

Assessment of airway function in young children with asthma: comparison of spirometry, interrupter technique, and tidal flow by inductance plethsmography.

The assessment of airway function in young children requires adaptation of techniques designed for adults and/or application of techniques that do not require complex respiratory maneuvers. We sought to assess two methods of measuring airway function: time to peak expiratory flows as a ratio of expiratory time (T(PTEF)/T(E)), derived from respiratory inductance plethysmography, and total respiratory resistance by the interrupter technique (Rint), both obtained during quiet tidal breathing. Both techniques were referenced to FEV1 and flow at 50% expired volume (FEF50) from conventional spirometry in 30 children aged 4-8 years (median age, 6.9; range, 4.5-8.5 years) with a physician diagnosis of asthma and who were able to perform FEV1 with a repeatability of at least 8%. T(PTEF)/T(E) and Rint were performed in random order followed by spirometry, in order to reduce the possible effects of pulmonary stretch on tidal breathing measures. Coefficients of variation (CV) and mean absolute change/baseline standard deviation were derived for each measurement. Baseline FEV1 did not correlate significantly with T(PTEF)/T(E) (r = 0.025), but did correlate with Rint (r = 0.737, P < 0.001); respective relationships for change after bronchodilator were r = 0.09 (ns) and r = 0.64 (P < 0.001). FEF50 also correlated significantly with Rint (R = 0.769, P < 0.001) but not with T(PTEF)/T(E). FEV1 and FEF50 both increased postbronchodilator, with respective mean changes of 11.4% and 28% (P < 0.001), while Rint decreased by 24.3% (P < 0.001). No significant changes were noted for T(PTEF)/T(E). T(PTEF)/T(E) derived from inductance plethysmography does not detect mild airway obstruction or modest changes in airway caliber following bronchodilator in young children with asthma. The interrupter technique may have a role in assessing baseline airway function and response to therapy in children unable to perform reliable spirometry, and/or when the investigator wishes to avoid the possible influence of forced maneuvers on airway tone.

Age Factors↗
PubMed2004

Educational intervention in the management of acute procedure-related wound pain: a pilot study.

OBJECTIVE: This report describes the pilot testing of an educational intervention to manage acute pain associated with wound care in an outpatient clinic. The intervention included essential elements of pain education identified in the acute pain literature: provision of information; pain measurement; establishing expectations; treatment planning; teaching environment. METHOD: The intervention was tested on five patients attending a wound clinic for scheduled treatment. Patients were aged 65 years or older and had a history of experiencing pain during treatment procedures such as dressing changes and debridement. Before the intervention, the study nurse gave the patients information about the procedure, discussed strategies they could use to make it as comfortable as possible, and explained how they could use a rating scale to denote any physical and emotional distress. RESULTS: All patients used the intervention strategies. Three out of five reported reduced pain and/or distress following the intervention. CONCLUSION: The pilot study supported the use of education as a pain control strategy in wound care and illuminated key methodological issues for further research on this topic.

Aged↗
PubMed2003

Intussusception and the great smog of London, December 1952.

AIM: To discuss the possible significance of the increased incidence of intussusception in children in relation to the "Great Smog" of London in December 1952. METHODS: Cases of intussusception were recorded in two hospitals in East London for the years 1951, 1952, 1953, and 1954. For 1952 the actual dates of admission were recorded. RESULTS: During the year 1952 the total number of cases of intussusception greatly exceeded that in the previous and succeeding years. Immediately during and after the fog there was a clustering of cases, which only occurred during this period. CONCLUSIONS: The increased incidence of cases during 1952 is thought to reflect the annual variation in incidence resulting from changes in the prevalence of viruses capable of causing intussusception. The clustering of cases in relation to the fog may reflect a facilitated entry of virus through the wall of the terminal ileum due to the effect of swallowed irritants such as sulphurous acid and smoke particles.

Child↗
PubMed2002

Establishment of an oriP/EBNA1-based episomal vector transcribing human genomic beta-globin in cultured murine fibroblasts.

A novel oriP/EBNA1-based episomal vector has been constructed that persists episomally in cultured murine fibroblasts. The vector, pBH148, is equipped with the entire 185-kb human beta-globin gene locus. After amplification in bacteria, column-purified episomal pBH148 was transfected into both cultured EBNA1-expressing human D98/Raji positive control fusion cells (DRpBH148) and cultured EBNA1-negative murine fibroblast cells (A9pBH148). Cell cultures were maintained concurrently with and without hygromycin selection for a period of 3 months. We show long-term stable episome maintenance of the full-size 200-kb circular double-stranded pBH148 in both the DRpBH148 cultures and the A9pBH148 cultures, regardless of selective pressure by agarose gel electrophoresis and Southern blot. EBNA1 transgene was detected by PCR in all transfected cultures. In addition, we were able to detect correctly spliced human beta-globin mRNA by RT-PCR in all transfected late-passage DRpBH148 and A9pBH148 cell cultures. These findings illustrate that this oriP/EBNA1-based episomal vector is stable in a previously nonpermissive murine cell line and is a potential vector for human gene therapy.

Animals↗
PubMed2001

In vivo analysis of porcine endogenous retrovirus expression in transgenic pigs.

Xenotransplantation offers a potential solution to the shortage of donor organs for allotransplantation. In vitro studies that demonstrate the transmission of porcine endogenous retroviruses (PERV) from porcine cells to human cells and cell lines have raised concerns regarding the potential transmission of PERV to both xenograft recipients and their contacts (1-4). While no evidence of infection has been detected in any patients who have been treated with a variety of different porcine tissues (5-8), two studies have shown that severe combined immunodeficient (SCID) mice can be infected by PERV after the transplantation of porcine islets (9-10). To further address the concerns of PERV, expression of this virus in tissues and serum from transgenic pigs that express human decay accelerating factor was investigated. Although viral mRNA expression was detected in a variety of tissues, no evidence of viral release was observed in any of the porcine tissues analyzed by transmission electron microscopy. Analysis of porcine serum using the product-based reverse transcriptase assay suggested that virions may be present in porcine serum from large white pigs. However, using methods based on those previously described by Wilson et al. (4), infectious virus was not detected when activated peripheral blood mononuclear cells from these pigs were cocultivated with human cells known to be permissive for PERV.

Animals↗
PubMed2001

Polyethylene glycol induces apoptosis in HT-29 cells: potential mechanism for chemoprevention of colon cancer.

Recent experimental evidence suggests that polyethylene glycol (PEG) is a highly effective chemopreventive agent against colon cancer; however, the mechanism(s) remain largely unexplored. To further elucidate this issue, we evaluated the effect of PEG on two human colon cancer cell lines. PEG treatment resulted in a dose- and time-dependent reduction in cell number without alteration in markers of cell proliferation. However, there was a dramatic and specific, concentration-dependent induction of apoptosis, with 50 mM PEG rendering approximately half the cells apoptotic. This corresponded with a 17-fold induction in the expression of the pro-apoptotic protein, prostate apoptosis response-4. Our data suggest that induction of apoptosis may be responsible, at least in part, for the ability of PEG to prevent experimental colon cancer.

Apoptosis↗
PubMed2001

Coxsackie virus A24 infection presenting as acute flaccid paralysis.

Enteroviruses can cause outbreaks of acute flaccid paralysis (AFP), mimicking wild poliovirus infections. Coxsackie virus A24 has never been implicated and yet it is a virus with high outbreak potential. We describe the association of coxsackie virus A24 with AFP in East Timor.

Acute Disease↗
PubMed2001

Primary fibroblast cell cultures from transbronchial biopsies of lung transplant recipients.

BACKGROUND: Survival after lung transplantation is limited by the development of bronchiolitis obliterans (BO) that is a fibroproliferative process and regarded as the histological marker of chronic rejection. To study further the pathogenesis of BO we attempted to establish primary fibroblast cell cultures from transbronchial lung biopsies (TBBs)of lung transplant recipients. METHODS: One to two TBB samples from each patient were collected in sterile phosphate-buffered saline. Biopsies were cut into small pieces and placed onto 25-cm2 culture flasks for cell culture and kept under standard cell culture conditions (21% O2, 5% CO2, 37 degrees C). Culture medium consisted of RPMI 1640, 10% fetal calf serum, L-glutamine, HEPES, and antibiotics. After reaching confluence, fibroblasts were passaged into 75-cm2 flasks. RESULTS: The success rate of establishing fibroblast cultures from transbronchial lung biopsies was 54% (27/50). Cell growth was independent of patient age, transplant type, underlying lung disease, indication for transbronchial lung biopsies, grade, or type of re jection and infection. CONCLUSIONS: We have established a novel method of culturing fibroblasts from lung transplant recipients. We consider this method as an unique human in vitro model to study the pathogenetic mechanisms leading to BO.

Adult↗
PubMed2001

Prevalence and clinical characteristics of celiac disease in Downs syndrome in a US study.

Celiac disease is an autoimmune gastrointestinal disorder characterized by mucosal atrophy of the jejunum on exposure to gluten, a protein found in grains. The purpose of our study was to determine the prevalence of celiac disease in children with Downs syndrome in a U.S.-based Caucasian population. The 97 Downs syndrome children were screened for celiac disease using serum IgA-anti-endomysial antibody testing, which is highly specific and sensitive for the disorder. Children with titers greater than 1:5 (using the IgA endomysial antibody [EMA] test; EMA+) were considered affected. Ten children (10.3%) were EMA+. We examined their HLA DQA1 DQB1 genotype, karyotype, clinical characteristics, and the prevalence of celiac disease in their first-degree relatives. The nine available karyotypes were trisomy 21. Downs syndrome-specific mean height percentile was 64%+/-26% (range <5-99%) and weight percentile was 43%+/-28% (range 5-95%). Presence of diarrhea, constipation, vomiting, and abdominal pain was similar for children with and without celiac disease. Only bloating symptoms were significantly more frequent in those with celiac disease (EMA+). Seven of eight (88%) genotyped EMA+ children had the celiac disease-associated high-risk HLA DQA1*0501 DQB1*0201 genotype as compared with 13/ 80 (16%) of EMA- children. Five of 48 (10%) first-degree relatives of the celiac disease (EMA+) children were EMA+. In conclusion, celiac disease, as diagnosed by positive endomysial antibody tests, has an increased prevalence in children with Downs syndrome in the U.S. as compared with the general population (1/250). Clinical and growth characteristics do not distinguish between children with and without celiac disease. Based on these observations, it is recommended that children with Downs syndrome be screened for celiac disease.

Adolescent↗