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Biomedical subjects

J Howlett

Publications and source records attributed to J Howlett.

At least 19 recordsLinked to original sources

Treating the right patient at the right time: access to heart failure care.

Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).

Follow-Up Studies↗

Sirolimus, a new potent immunosuppressant agent for refractory cardiac transplantation rejection: two case reports.

Rejection remains a major cause of both early and late morbidity and mortality following heart transplantation despite major advances in immunosuppressive therapy. A major hurdle in the successful management of patients who have undergone heart transplantation is preventing and treating graft rejection. Cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus (FK506) and OKT3 are well documented, effective immunosuppressive medications that prevent and treat acute or chronic rejection following heart transplantation. One of the macrolide antibiotics, sirolimus, is known to have immunosuppressant activity. In two patients with chronic rejection of cardiac grafts refractory to usual antirejection medications, sirolimus was successfully used to suppress graft rejection. Both patients continued to be rejection free after 10 months of sirolimus treatment despite significant decreases in doses of other immunosuppressants.

Administration, Oral↗

Age-related plasma chemistry changes in houbara and kori bustards in the United Arab Emirates.

Plasma chemistry parameters were measured in adult (> 1.5 yr) and juvenile (4-8 and 9-16 wk) captive houbara bustards (Chlamydotis undulata macqueenii) and from adult (> 1.5 yr) and juvenile (4-8, 9-16, 17-24, 25-32, 33-40 and 41-52 wk) captive kori bustards (Ardeotis kori) to study age-related changes. A comparison of the values obtained was made between adult and juvenile bustards of both species and from the literature with other bustard species. Significant differences between adult and juvenile bustards of both species were found for glucose, total protein, alkaline phosphatase (ALKP), aspartate amino transferase (AST), lactate dehydrogenase, and calcium. Some parameters, such as calcium, showed comparable age-related changes in both species. In contrast, other parameters showed clear differences in the type (ALT, AST) or magnitude (ALKP) of age-related change between the species, demonstrating the importance of determining normal values for individual species. The results obtained from this study provide blood chemistry values for these species and demonstrate age-related differences between adult and juvenile birds.

Aging↗

Age-related plasma chemistry findings in the buff-crested bustard (Eupodotis ruficrista gindiana).

Blood samples were obtained from adult (> 1.5 years) and juvenile (2-8 weeks, 9-16 weeks and 17-24 weeks) captive buff-crested bustards (Eupodotis ruficrista gindiana) to study age-related changes. A total of twelve different tests were conducted using a Hitachi 90011 wet chemistry analyzer. A comparison of the values obtained was made between adult and juvenile buff-crested bustards and from the literature with other bustard species. Significant differences between adult and juvenile buff-crested bustards were found for glucose, uric acid, total protein, alkaline phosphatase, asparatate amino transferase and calcium. The results obtained from this study provide blood chemistry values for this species and demonstrate age-related differences between adult and juvenile birds.

Aging↗

Polymacron enzyme immunoassay system for detection of naturally contaminating Salmonella in foods, feeds, and environmental samples.

A simple dot blot enzyme immunoassay was developed to screen enrichment broth cultures for the presence of Salmonella. This unique system utilizes macroporous polyester cloth (Polymacron) with an inexpensive hemoglobin coating to provide a high-affinity adsorbent for lipopolysaccharide (LPS) antigens in test samples. Bound LPS antigens are then detected using a monoclonal antibody conjugate recognizing a core oligosaccharide epitope common to all salmonellae frequently found in foods and related samples. The entire test (not including enrichment culture) could be completed in less than 1 h. The performance of this assay was evaluated in the analysis of enrichment broth cultures from a variety of egg and dairy products, chicken carcasses, animal feeds, and food-processing plant environmental samples for the presence of Salmonella.

Animal Feed↗

Surveillance imaging of the operated artery does not alter clinical outcome following carotid endarterectomy.

Clinical outcome was studied in 243 patients undergoing 260 carotid endarterectomies; 166 of these patients underwent serial postoperative surveillance imaging. Including perioperative events, cumulative freedom from ipsilateral stroke was 86 and 82 per cent at 5 and 10 years respectively; the mean incidence of ipsilateral stroke was 1.8 per cent per annum. Twenty patients (8 per cent) suffered cerebral ischaemic events in the hemisphere of the operated side during follow-up: eight transient ischaemic attacks (TIA) and 12 strokes (only two preceded by TIA). Two symptomatic patients were found to have occluded the operated artery but the remainder had no evidence of significant recurrent disease. Cumulative freedom from occlusion or severe (greater than 70 per cent) recurrent stenosis was 87 and 78 per cent at 5 and 10 years respectively; the mean incidence of recurrence of significant disease was 2.2 per cent per annum. No revisional surgery was performed on the operated arteries. In its current format, neither clinical nor surveillance imaging could have prevented any of the strokes observed during follow-up.

Angiography, Digital Subtraction↗

Growth rate of infrarenal aortic aneurysms.

OBJECTIVE: To delineate the natural history of infrarenal aortic aneurysms with respect to growth rate. METHODS: A referral based series of 233 patients with abdominal aortic aneurysm was serially assessed by abdominal ultrasound. RESULTS: The mean age was 71 years and the median follow up 26 months (range 6-146). The mean growth rate of the series was 3.2mm/year. Division of the initial size into those less than 41 mm (128 patients), between 41-60 mm (92 patients) and those above 60 mm (13 patients) in AP diameter showed mean growth rates per year were 2.6 mm/year, 4.1 mm/year and 6.5 mm/year. Examination of the relationship between aneurysm size and subsequent growth rate over the whole study period revealed a rank correlation of 0.19 (p = 0.002). Aneurysms were also observed to expand at an erratic rate both in terms of time and size. CONCLUSIONS: When the initial decision is to observe the patient, serial ultrasound examinations facilitate later judgements on the balance of risks in relation to surgical treatment.

Adult↗

Fate of the non-operated carotid artery after contralateral endarterectomy.

The long-term fate of the non-operated internal carotid artery (ICA) in 219 patients undergoing contralateral carotid endarterectomy was studied; 151 patients underwent serial postoperative imaging of the vessel. Cumulative freedom from stroke in the non-operated hemisphere was 99, 96 and 86 per cent at 1, 5 and 10 years respectively, giving a mean incidence of stroke of 1 per cent per annum. Only one stroke was preceded by a transient ischaemic attack and no stroke was associated with severe (70 per cent or greater) stenosis of the ICA. Ten patients (7 per cent) with initially mild or moderate disease of the non-operated ICA progressed to severe stenosis during follow-up, but only three became symptomatic and, in each case, the onset of symptoms preceded recognition of disease progression. The long-term risk of stroke in the non-operated ICA territory is very small. Of practical importance is that none of the observed strokes could have been prevented by postoperative surveillance of this type.

Carotid Artery Diseases↗

Hematology of fledgling Manx shearwaters (Puffinus puffinus) with and without 'puffinosis'.

Hematological parameters were measured in 14 fledgling Manx shearwaters (Puffinus puffinus), with the disease puffinosis and in 10 birds that did not have the disease, on the Island of Skomer between 2 and 11 September 1991. The mean plasma fibrinogen concentration was significantly higher in the diseased birds and some of these had abnormally elevated monocyte counts. No other significant differences were observed.

Animals↗

An audit of trends and current practice of carotid endarterectomy in Edinburgh (1975-1990).

Changes in the patient population and trends in management were studied for 260 consecutive carotid endarterectomies performed during the periods 1975-1982 and 1983-1990. A 43% increase was observed in the number of operations (from 107 to 153), an 81% increase taking into account patients randomized to medical treatment in the European Carotid Surgery Trial. There were significant reductions in patients continuing to smoke (79 to 60%, P = 0.001), in those with systolic hypertension (21 to 11%, P = 0.018) and diastolic hypertension (26 to 12%, P = 0.002), and in those with asymptomatic carotid lesions (8 to 2%, P = 0.031). There were significant increases in the proportion of patients with strokes presenting with a residual neurological deficit (40 to 66%, P = 0.024), and in those with ocular symptoms (30 to 50%, P = 0.001) and with stenoses greater than 50% (58 to 71%, P = 0.018). This study suggests a trend for a higher risk population with more severe carotid disease. In the light of results of clinical trials, further evolution of patient selection is likely to occur and should be taken into account when evaluating the risk of carotid endarterectomy.

Adult↗

Application of monoclonal antibody panels in the virological and epidemiological review of poliomyelitis in Poland, 1981-1990.

Monoclonal antibody panels developed to differentiate vaccine-derived and wild-type strains of polio-viruses were applied to isolates from cases of paralytic poliomyelitis, non-paralytic poliomyelitis, and healthy excreters of poliovirus from Poland. All isolates from poliomyelitis cases were shown to be vaccine-derived, as were most other strains. However, two strains associated with meningitis had wild-type antigenic phenotypes and, as shown by partial genomic sequencing, wild-type genotypes. Correlation of laboratory and epidemiological data suggested that residual cases of paralytic poliomyelitis in Poland between 1981 and 1990 were vaccine-related. Study of the non-paralytic cases, however, helped identify the circulation of endemic wild-type viruses in a well-vaccinated community.

Adult↗

Lipoxygenase metabolites of arachidonic and linoleic acids modulate the adhesion of tumor cells to endothelium via regulation of protein kinase C.

12(S)-hydroxyeicosatetraenoic acid (12[S]-HETE) and 13(S)-hydroxyoctadecadienoic acid (13[S]-HODE), lipoxygenase metabolites of arachidonic acid and linoleic acid, respectively, previously have been suggested to regulate tumor cell adhesion to endothelium during metastasis. Adhesion of rat Walker carcinosarcoma (W256) cells to a rat endothelial cell monolayer was enhanced after treatment with 12(S)-HETE and this 12(S)-HETE enhanced adhesion was blocked by 13(S)-HODE. Protein kinase inhibitors, staurosporine, calphostin C, and 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, inhibited the 12(S)-HETE enhanced W256 cell adhesion. Depleting W256 cells of protein kinase C (PKC) with phorbol 12-myristate-13-acetate abolished their ability to respond to 12(S)-HETE. Treatment of W256 cells with 12(S)-HETE induced a 100% increase in membrane-associated PKC activity whereas 13(S)-HODE inhibited the effect of 12(S)-HETE on PKC translocation. High-performance liquid chromatographic analysis revealed that in W256 cells 12-HETE and 13-HODE were two of the major lipoxygenase metabilites of arachidonic acid and linoleic acid, respectively. Therefore, these two metabolites may provide an alternative signaling pathway for the regulation of PKC. Further, these findings suggest that the regulation of tumor cell adhesion to endothelium by 12(S)-HETE and 13(S)-HODE may be a PKC-dependent process.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Antigenic structure of chimeras of type 1 and type 3 polioviruses involving antigenic sites 2, 3 and 4.

Chimeric polioviruses have been made in which regions of the type 1 Sabin strain corresponding to antigenic sites 2, 3 and 4 have been replaced by the corresponding regions of the type 3 Sabin strain. Manipulation of one site or a component of it generally did not affect the reactions of the others, suggesting that they form independent structural features. The extent to which the inserted site expressed the antigenic properties of type 3 could be assessed by reaction with polyclonal or monoclonal antibodies, or by immunogenicity. Site 2 could be expressed on infectious virus and site 3 on heated non-infectious virus (C antigen), but not on the native virion. The results are consistent with the view that sites consisting of a continuous sequence of amino acids may be presented on chimeras, whereas more complex sites, such as site 4 or site 3 of the native virion, are transferred less readily from type 3 to type 1.

Amino Acid Sequence↗

Antigenic structure of chimeras of type 1 and type 3 poliovirus involving antigenic site 1.

Chimeric polioviruses have been prepared in which part of the antigenic site 1-encoding sequence of the Sabin strain of type 1 poliovirus has been replaced by sequences based on those found in the homologous region of the Sabin type 3 strain. The chimeras were analysed for their reaction with polyclonal and monoclonal antibodies raised against type 1 and type 3 viruses, and with polyclonal antipeptide sera, as well as for their immunogenicity in animals. The effectiveness with which the type 3 site was presented antigenically varied in ways which were partially predictable, based on the behaviour of type 3 mutants with monoclonal antibodies. However, other factors were implicated which may include conformational effects and other components of the site in addition to those altered in the chimeras. The ability of the chimeras to induce antibodies reacting with type 3 polioviruses paralleled their antigenic reactivity, and evidence is presented for the induction of strain-specific antibodies.

Animals↗