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Biomedical subjects

J Jameson

Publications and source records attributed to J Jameson.

At least 19 recordsLinked to original sources

Straight to test: introduction of a city-wide protocol driven investigation of suspected colorectal cancer.

OBJECTIVE: To decrease waiting times for colorectal cancer diagnosis. METHODS: Following extensive negotiations on three sites, we replaced the standard referral route of GP to outpatient clinic with city-wide implementation of a protocol driven sequence based on the patient's declared symptoms, the initial consultation being replaced by the first test taking place within 31 days. No choice in test allocation was granted; difficult cases were adjudicated by named consultants. We used a 'dry run' to make sure that our planned changes would not overload our local capacity, leading to a pilot run involving 1/3 clinicians, followed by a full cross-city implementation over two months. RESULTS: In 2001, before the pilot only 116/188 (62%) of our colorectal cancers who were referred either under the 2-week-wait arrangements or on a 'soon' basis were diagnosed within 31 days of referral. Our 'dry run' established that we did have the capacity to service our planned sequence of tests. In the pilot, all colorectal cancers were diagnosed within 31 days of referral, and 95% of all diagnoses (no abnormality or benign disease) were reached within 31 days of referral. After full implementation 19/19 (100%) of our cancers coming through our protocol system were diagnosed within 31 days and 95% of patients with benign disease. CONCLUSION: Follow-up audit of our system one and two years later shows that we now diagnose approximately 80% of our colorectal cancers who are referred under the 2 week wait or as 'soon' referrals within 31 days. We have successfully redesigned our service, at minimal expense, in a way, which should enable us to meet the government targets in the National Cancer Plan.

Clinical Protocols↗

Management of benign rectal strictures: a review of present therapeutic procedures.

PURPOSE: A significant benign stricture of the rectum is uncommon but can be a recalcitrant condition to treat. Case reports detailing a particular treatment option abound in the surgical literature. An overall précis of the different techniques available is presented, with a comparison of their relative strengths and weaknesses. METHODS: A literature search was undertaken from 1963 to the present day, using MEDLINE. Keywords were benign, strictures, and rectum. RESULTS: Balloon dilation is the most frequent intervention described in the literature. Repeated dilation with time often is required to achieve normal bowel function. Electrocautery resection or incision combined with dilation increases the success rate without increasing the complication rate. Transanal strictureplasty with mechanical staplers is reported as achieving the best success with the smallest complication rate; however, only a minority of strictures are suitable to be managed in this way, and therefore, the numbers treated are small. CONCLUSIONS: All of the techniques reviewed compared favorably with formal stricture resection in terms of success rate and complications.

Anastomosis, Surgical↗

Risk factors for intestinal ischaemia in cardiac surgical patients.

OBJECTIVE: Mesenteric ischaemia is an uncommon (<1%) but serious complication of cardiac surgery associated with a mortality >50%. Predictors of this complication are not well defined, and diagnosis can be difficult and prompt surgical intervention can be lifesaving. METHODS AND RESULTS: In a retrospective case-note analysis from May 1994 through to May 2000, we identified mesenteric ischaemia in 39 of 5349 consecutive patients (0.07%) undergoing cardiac surgery with cardiopulmonary bypass. By logistic multivariate analysis, we have identified six possible predictors of intestinal ischaemia: duration of cross-clamp, use of significant inotropic support, intra-aortic balloon counterpulsation for low cardiac output, need for blood transfusions, triple vessel disease and peripheral vascular disease. In all patients a combination of four predictors were present. Patients who survived this complication had surgical intervention earlier (6.4+/-3.8 h) than those who did not (16.9+/-10 h). CONCLUSIONS: The diagnosis and prompt treatment of mesenteric ischaemia post cardiac surgery requires a high degree of awareness. These predictors may be useful in alerting medical staff to the possibility of gastro-intestinal ischaemic complications after cardiac surgery particularly that early surgical intervention reduces mortality.

Cardiac Surgical Procedures↗

Partial agonist effect influences the CTL response to a heterologous dengue virus serotype.

Activation of dengue serotype-cross-reactive memory CTL during secondary dengue virus (DV) infection is thought to be important in the pathogenesis of dengue hemorrhagic fever. To model this effect, we studied the CTL responses to DV types 2 (D2V) and 3 (D3V) in PBMC from an individual previously infected with D3V. DV-specific CD8+ CTL from this donor recognized two HLA-B62-restricted epitopes on the NS3 protein, aa 71-79 (SVKKDLISY) and 235-243 (AMKGLPIRY). Both D3V-specific and D2V/D3V-cross-reactive CTL clones were detected for each epitope; all D2V-reactive CTL clones could lyse D2V-infected autologous cells. CTL responses to both epitopes were detected in bulk cultures stimulated with D3V, but PBMC stimulated with D2V recognized only the 235-243 epitope. IFN-gamma enzyme-linked immunospot assay showed that the D2V (71-79) peptide (DVKKDLISY) did not efficiently activate T cells. Analysis of a CTL clone suggests that the D2V (71-79) peptide acts as a partial agonist, able to sensitize target cells for lysis and inducing only minimal proliferation at high concentrations. These results suggest that variant peptide sequences present in the heterologous DV serotype can influence the CTL response in vivo during secondary DV infection.

Adult↗

Augmentation of human influenza A virus-specific cytotoxic T lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS).

There is a need to improve the ability of subunit vaccines to induce CD8(+) CTL responses in humans, especially for vaccines used to prevent illness by organisms that undergo antigenic variation at their major neutralizing antibody sites, e.g., influenza A viruses and human immunodeficiency virus. Murine models have demonstrated the protective role of cross-reactive CTL against influenza A virus antigenic drift. We tested the ability of an adjuvanted carrier (Iscomatrix) to help human antigen-presenting cells present formalin-killed influenza vaccine to human CD8(+) CTL clones in vitro and in vaccinated humans. The results of a randomized, double-blind, controlled clinical study demonstrate that a single dose of a vaccine formulated into Iscom particles increased influenza A virus-specific CTL memory in 50-60% of recipients, compared to 5% of the recipients of the standard influenza vaccine.

Adolescent↗

High-yield reassortant influenza vaccine production virus has a mutation at an HLA-A 2.1-restricted CD8+ CTL epitope on the NS1 protein.

Current influenza virus vaccines are prepared using high-yield reassortant virus strains obtained from a mixed infection of the new virus strain and a prototype high-yielding virus strain. The high-titered reassortant virus strain used as vaccine seed virus possesses the recent virus HA and NA and contains the internal genes from the high-growing prototype parent. We established a human CD8(+) cytotoxic T cell (CTL) line, 10-2C2, which recognizes an HLA-A2.1-restricted influenza A virus H1, H2, H3 cross-reactive T cell epitope on amino acids 122-130 of the NS1 protein, and unexpectedly we observed that there was decreased lysis of target cells infected with the A/Texas/36/91 (H1N1) vaccine virus strain compared to the lysis of target cells infected with the prototype A/PR/8/34 (H1N1) virus. RT-PCR results showed that the A/Texas vaccine virus strain contained a quasispecies. Approximately 50% of viral RNA of the NS1 gene had a nucleotide substitution that resulted in the N --> K amino acid change at the sixth position of the nonamer peptide. Current influenza vaccines are inactivated and do not contain the NS1 protein; however, future influenza vaccines may include live attenuated vaccines and with this mutation a live virus would fail to induce a CD8(+) CTL response to this epitope in individuals with HLA-A2.1, a very common allele, and potentially have reduced efficacy.

Base Sequence↗

Human CD8+ and CD4+ T lymphocyte memory to influenza A viruses of swine and avian species.

Recently, an avian influenza A virus (A/Hong Kong/156/97, H5N1) was isolated from a young child who had a fatal influenza illness. All eight RNA segments were of avian origin. The H5 hemagglutinin is not recognized by neutralizing Abs present in humans as a result of infection with the human H1, H2, or H3 subtypes of influenza A viruses. Subsequently, five other deaths and several more human infections in Hong Kong were associated with this avian-derived virus. We investigated whether influenza A-specific human CD8+ and CD4+ T lymphocytes would recognize epitopes on influenza A virus strains derived from swine or avian species, including the 1997 H5N1 Hong Kong virus strains. Our results demonstrate that adults living in an urban area of the U.S. possess influenza A cross-serotype reactive CD8+ and CD4+ CTL that recognize multiple epitopes on influenza A viruses of other species. Bulk culture cytotoxicity was demonstrated against avian and human influenza A viruses. Enzyme-linked immunospot assays detected precursor CTL specific for both human CTL epitopes and the corresponding A/HK/97 viral sequences. We hypothesize that these cross-reactive CTL might provide partial protection to humans against novel influenza A virus strains introduced into humans from other species.

Animals↗

Human cytotoxic T-lymphocyte repertoire to influenza A viruses.

The murine CD8(+) cytotoxic-T-lymphocyte (CTL) repertoire appears to be quite limited in response to influenza A viruses. The CTL responses to influenza A virus in humans were examined to determine if the CTL repertoire is also very limited. Bulk cultures revealed that a number of virus proteins were recognized in CTL assays. CTL lines were isolated from three donors for detailed study and found to be specific for epitopes on numerous influenza A viral proteins. Eight distinct CD8(+) CTL lines were isolated from donor 1. The proteins recognized by these cell lines included the nucleoprotein (NP), matrix protein (M1), nonstructural protein 1 (NS1), polymerases (PB1 and PB2), and hemagglutinin (HA). Two CD4(+) cell lines, one specific for neuraminidase (NA) and the other specific for M1, were also characterized. These CTL results were confirmed by precursor frequency analysis of peptide-specific gamma interferon-producing cells detected by ELISPOT. The epitopes recognized by 6 of these 10 cell lines have not been previously described; 8 of the 10 cell lines were cross-reactive to subtype H1N1, H2N2, and H3N2 viruses, 1 cell line was cross-reactive to subtypes H1N1 and H2N2, and 1 cell line was subtype H1N1 specific. A broad CTL repertoire was detected in the two other donors, and cell lines specific for the NP, NA, HA, M1, NS1, and M2 viral proteins were isolated. These findings indicate that the human memory CTL response to influenza A virus is broadly directed to epitopes on a wide variety of proteins, unlike the limited response observed following infection of mice.

Adult↗

Assessment of human CD4+ and CD8+ T lymphocyte responses in experimental viral vaccine studies.

The traditional in vitro correlate of immunological protection is the induction by a vaccine of neutralizing antibodies against the virus. It was formerly assumed that protection induced by a vaccine was solely due to neutralizing antibodies. Neutralizing antibodies are potent in the prevention of certain diseases, but virus-specific CD4+ T helper cells aid in the proliferation of specific antigen-triggered B cells to make antibodies. CD8+ T cells are responsible for eliminating virus-infected cells during viral illness, and may act as a second line of defence by becoming activated and eliminating any cells that become infected despite the presence of neutralizing antibodies, for example because of a large challenge dose or antigenic variation at the antibody combining sites. We will briefly review our approaches for measuring human virus-specific CD4+ and CD8+ T cell responses to experimental vaccines. It is critically important to have sensitive, quality controlled assays, including positive controls. There are many potential variables in human T cell assays and pitfalls, which usually result in negative CTL results. Uninterpretable data are to be expected unless adequate preliminary testing has been done to establish sensitive, specific and controlled human antigen specific CD4+ and CD8+ T cell assays.

B-Lymphocytes↗

The impact of a pharmacotherapy consultation on the cost and outcome of medical therapy.

BACKGROUND: One important task for physicians is to optimize their patients' medication regimen. Involvement of clinical pharmacists who have specific training in drug regimen design has been associated with improved patient outcomes for specific medical conditions, eg, hypertension and anticoagulation. This prospective, randomized trial investigated whether a single consultation by a clinical pharmacist with high-risk patients and their primary physicians would result in improved prescribing outcomes. METHODS: Patients at risk for medication-related problems were identified and randomized to receive a pharmacotherapy consultation (consult group) or usual medical care (control group). Outcomes, including the number of drugs, number of doses per day, cost of medications, and patient reports of adverse effects, were recorded at baseline and at 6 months following the intervention. RESULTS: Fifty-six subjects were evaluable: 29 in the control group, and 27 in the consult group. Six months after the consultation, the number of drugs, the number of doses, and the 6-month drug costs all decreased in the consult group and increased in the control group; the net difference was 1.1 drugs (P = .004), 2.15 doses per day (P = .007), $586 per year (P = .008). The side effects score improved by 1.8 points more in the consult group compared with the control group (P = NS). Similarly, the prescribing convenience score in the consult group improved by 1.4 points more than that of the control group (P = NS). CONCLUSIONS: This study demonstrates several important benefits of integration of a clinical pharmacist into a primary care setting, including improvement in cost and simplification of the medication regimen with no reduction in quality of care.

Ambulatory Care↗

Short term benefits of post-operative oral dietary supplements in surgical patients.

The present study was undertaken to investigate the short term clinical efficacy of oral dietary supplements administered post-operatively to patients undergoing predetermined moderate to severe gastrointestinal surgery. Trial end points for comparison included effects of oral dietary supplements on nutritional intake, nutritional status and incidence of serious complications. 54 patients who were scheduled to undergo predetermined moderate to major gastrointestinal surgical procedures entered the study. They were randomly assigned to receive a normal ward diet post-operatively or the same diet supplemented ad libitum by an oral nutritional sip feed. The study period was defined as commencing from the day patients were adjudged to be capable of ingesting 'free fluids' to the day of hospital discharge. 40 patients (20 in each group) completed the study. The mean daily energy intake (KCal/day) assessed from 7 day food diaries was significantly higher in the treatment group (1833 +/- SEM 99) than in the control group (1108 +/- 56, p < 0.0001). This increase occurred not only as a consequence of energy intake from the oral dietary supplements (470 +/- 30) but also because more energy was consumed from the ward diet by the treatment than the control patients (1353 +/- 92 vs 1108 +/- 56, p < 0.02). The mean daily protein intake g/day in the treatment group (66.0 +/- 3.4) was also greater than in the control group (52.9 +/- 29 p < 0.0001). This difference was due solely to the intake in protein from the oral dietary supplements (15.7 +/- 1.0), protein intake from the ward diet being similar in the treatment (50.1 +/- 3.2) and control (52.9 +/- 29) groups. Patients in the treatment group maintained their pre-operative weight where as control patients had lostsignificant amount of their pre-operative weight by study day 3 (4.5 +/- 12 kg and by discharge (4.7 +/- 1.2 kg, p < 0.02). Pre-operative muscle function as evidenced by grip strength dynamometry decreased to a greater extent in the control than treatment group patients by study day 3 (14.6 +/- 2.2 KPa vs 2.8 +/- 2.4 < 0.03) and by discharge (10.4 +/- 3.1 KPa vs 0.10 +/- 1.9 p < 0.03). The incidence of serious infections (pneumonia, wound infection) was significantly higher in the control group (10) than in the treatment group (3, p < 0.02). It is concluded that the prescription of oral dietary supplements on an ad libitum basis to post-operative patients undergoing moderate to major gastrointestinal surgery results in clinically significant short term benefits.

Journal Article↗

Functional assessment of nursing home patients. Reliability and relevance.

Functional assessment of patients for resource allocation or staffing requires a higher level of interrater reliability than functional assessment in normal clinical settings. Although many functional assessment instruments are available, interrater reliability of these items has frequently not been reported. An assessment instrument based on the Long Term Care Minimum Data Set format was used for 290 patients in six wards in two Veterans Administration nursing homes. Each patient was assessed independently by two nurse caregivers to obtain reliability information. Different reliability measures yielded differing evaluations of the reliability of the instrument. Absolute agreement rates combined with Kendall's tau-b were most useful in deciding on the reliability of items in the instrument.

Activities of Daily Living↗

Study of HLA alloantigens of the Navajo Indians of North America. II. HLA-A, B, C, DR and other genetic markers.

This report presents the antigen frequencies for HLA-A, B, C, DR, immunoglobulin, and red blood cell systems for the Navajo Indians of North America. HLA-A-B,B-C, and B-DR haplotype frequencies and significant delta values are given. These data are compared with similar data for other American Indians and major non-Indian ethnic groups. Very restricted HLA polymorphism is unique for the Navajo as well as American Indians in general and this feature has important implications with regard to disease association and transplantation.

Chromosome Mapping↗

Positive pressure respiratory assist for wheelchair-mobile persons.

A compact, lightweight, battery-powered respiratory has been developed that fits under a wheelchair lapboard. The device eliminates the need for a mouthpiece, tracheal tube or similar interface. Its operation is based on pressurizing the viscera to compress the lungs and force exhalation. The system has been used continuously for over 9 months for as long as 9 hours/day.

Humans↗