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Biomedical subjects

P W Johnston

Publications and source records attributed to P W Johnston.

At least 19 recordsLinked to original sources

A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab.

Hepatosplenic gamma-delta T-cell lymphoma is a rare, usually fatal lymphoma and available literature on management is sparse. Allografting is probably the only curative option. We describe a further case with a dramatic, though transient response to Fludarabine and Alemtuzumab combination, following a failure of conventional chemotherapy. Given the dreadful prognosis with conventional chemotherapy, it is a regimen worth pursuing as a disease reduction strategy prior to allograft where appropriate.

Adolescent↗

Polymorphisms in the interleukin-10 and interferon gamma genes in Hodgkin lymphoma.

Genetic factors are known to be important in the development of Hodgkin lymphoma (HL). Interleukin-10 (IL-10) secretion by both malignant and reactive cells is thought to be important in the pathogenesis of HL especially Epstein-Barr virus (EBV) positive cases. Polymorphisms of the IL-10 gene have been reported to be associated with susceptibility to EBV infection. The cytotoxic response to EBV is determined by a Th1 biased immune response which is characterised by interferon gamma (IFNgamma) secretion. We therefore investigated polymorphisms in the IL-10 (-1082 G/A and -592 C/A) and IFNgamma (intron 1 CA repeat) genes as predisposing factors in the development 147 cases of HL. A difference of borderline statistical significance was demonstrated for the IFNgamma gene polymorphism but significance was lost when analysis was restricted to the common genotypes. No significant differences in the distributions of genotypes were found for the IL-10 gene polymorphisms. IL-10 and IFNgamma levels were also measured on 26 patients with HL. No statistically significant differences were detected when the results were analysed by genotype. We found little evidence IL-10 and IFNgamma genotypes predispose to the development of HL or influence the inflammatory host response.

Adolescent↗

Transfusion-associated graft-versus-host disease in a patient with Waldenstrom's macroglobulinaemia.

BACKGROUND AND OBJECTIVES: Routine irradiation of cellular blood products is not presently recommended for patients with non-Hodgkin's lymphoma (NHL). MATERIALS AND METHODS: We report the case of a 72-year-old-man with Waldenstrom's macroglobulinaemia who developed transfusion-associated graft-versus-host disease (TA-GvHD) 13 days following a non-irradiated red cell transfusion. RESULTS: The patient had not previously received purine analogues and none of the donors was homozygous for a human leucocyte antigen (HLA) haplotype that was shared by the recipient. Therefore, his only apparent risk factor was lymphoplasmacytoid NHL. CONCLUSIONS: This case further strengthens the argument that NHL per se is a risk factor for TA-GvHD and supports the proposal that the guidelines for prophylactic irradiation of cellular blood products be extended to include all cases of NHL.

Aged↗

Y stenting of a bifurcation stenosis using a new radiopaque stent.

A case of Y stenting using radiopaque stents for a bifurcation stenosis is described. Angiography and intravascular ultrasound demonstrate that in spite of optimal stent placement there is an area of the lesion that is not fully covered by the stents. This may predispose to subacute thrombosis and restenosis. This case illustrates a potential deficiency of this type of bifurcation stenting.

Contrast Media↗

Long-term survival of a patient with left ventricular free wall rupture without surgical repair.

This report describes the case of a patient who developed postinfarction left ventricular free wall rupture and cardiac tamponade. He was managed conservatively, made a successful recovery, and is alive and asymptomatic 10 months after the index episode. Only 17 cases in which the patients survived subacute rupture of the ventricular free wall over the long term without surgical repair have been reported in the literature.

Aged↗

Carcinoid constrictive pericarditis.

A 78 year old man presented with diarrhoea, anorexia, and progressive lower limb oedema. He was in atrial fibrillation and had a right pleural effusion and ascites. Ultrasound of the abdomen and 24 hour urinary hydroxyindoleacetic acid output indicated metastatic carcinoid syndrome. Cardiac catheterisation revealed pericardial constriction, and pericardial exploration showed a greatly thickened pericardium with no evidence of tumour invasion. The patient died within 24 hours of surgery. Necropsy findings were consistent with a diagnosis of constrictive pericarditis secondary to metastatic carcinoid syndrome.

Aged↗

Noncritical disease of the left main coronary artery: limitations of angiography and the role of intravascular ultrasound.

OBJECTIVE: To review the diagnosis and management of noncritical left main stem disease. DATA SOURCES: MEDLINE was searched using the key phrases 'intravascular ultrasound' and 'left main coronary artery'. DATA EXTRACTION: Articles addressing the angiographic or ultrasound assessment of left main stem disease were systematically reviewed. Reference is also made to articles dealing with outcomes for patients with left main stem disease. DATA SYNTHESIS: The assessment of left main stem disease by coronary angiography is often suboptimal. Intravascular ultrasound has demonstrated significant left main stem disease in angiographically normal arteries. It has also demonstrated that mild to moderate left main stem disease frequently accompanies disease in the other coronary arteries. The natural history of mild to moderate left main stem disease has not been well characterized; thus, the optimum management of this condition is not known. CONCLUSIONS: To establish the natural history of noncritical left main stem stenosis, it is proposed that centres performing frequent intravascular ultrasound examinations systematically and quantitatively interrogate the left main stem during all left coronary examinations. Angiographic and ultrasonic measures of left main stem disease can then be correlated with clinical outcome during long term follow-up. This will clearly require the collaboration of several centres to generate a sufficiently large database to address these clinical questions.

Coronary Angiography↗

A survey of factors affecting the recruitment and retention of Medical Laboratory Scientific Officers in Pathology.

OBJECTIVE: To survey the perceptions and attitudes of Medical Laboratory Scientific Officer (MLSO) staff in Pathology to explain difficulties in recruitment and retention and inform attempts to solve the difficulties. DESIGN: Questionnaire to a defined group of MLSOs. SETTING: The Laboratory Medicine Directorate, Aberdeen Royal Infirmary. SUBJECTS: MLSO1 and MLSO2 staff currently or recently working in Pathology (histopathology) in Aberdeen. RESULTS: The survey return rate was 100%. Opportunities for career development in Pathology are poor, this being the worst feature of working in Pathology. Remuneration is poor and is a disincentive to remaining in the speciality. MLSOs feel undervalued in relation to other health care workers. Many have concerns about laboratory organisation, but find a sociable and supportive environment that provides job satisfaction. Staff seek work in other laboratories because of opportunities for promotion, learning new skills and increased pay, although pay in specialities other that Pathology is greater only because of shift working in these disciplines. There is a need to increase public awareness of MLSOs' central role in providing and maintaining excellence in Pathology services. CONCLUSION: MLSO staff have concerns about their career structure and salary scales. The responsibility of MSLOs in Pathology for quality assurance and managing MLAs is not recognised. These factors form a disincentive to working in Pathology laboratories and threaten our ability to staff the service and to maintain the turnover and quality of Pathology services. These issues require to be addressed nationally and rapidly to prevent the continuing decline in MLSO numbers. Matters of local organisation might be addressed by trusts and departments, but recognition of the need to resource changes would require reflection in budgets.

Career Mobility↗

The transthoracic impedance cardiogram is a potential haemodynamic sensor for an automated external defibrillator.

AIMS: The American Heart Association has endorsed the concept of Public Access Defibrillation. However, there have been reports of inappropriate direct current shocks from automatic external defibrillators. The specificity of automatic external defibrillators for shockable rhythms may be improved by the incorporation of a haemodynamic sensor. METHODS AND RESULTS: This study examined the use of four parameters extracted from the impedance cardiogram i.e. Peak dz/dt (the peak of the impedance cardiogram measured from the line dz/dt=0 ohms(-1)), Peak-trough (the peak-to-trough measurement of the impedance cardiogram ohms(-1)), Area 1 (the area under the C wave of the impedance cardiogram above the line dz/dt=0 mohm) and Area 2 (the area under the impedance cardiogram 50 ms on either side of the Peak and above the line dz/dt=0 mohm) as predictors of cardiac output. At 116 cardiac arrest calls the ECG and impedance cardiogram were recorded through two ECG/defibrillator pads placed in an antero-apical position. Nine recordings were rejected for artefact. The rhythm recorded in the remaining 107 calls was asystole (19), ventricular fibrillation (14), agonal rhythm (20), electromechanical dissociation (22), ventricular tachycardia (27) and sinus rhythm (5). These rhythms were divided into those associated with haemodynamic collapse i.e. no pulse -- asystole, ventricular fibrillation, agonal rhythm, electromechanical dissociation and shockable ventricular tachycardia (associated with loss of consciousness, pulselessness or a systolic blood pressure of <80 mmHg) (Group 1) and those associated with a satisfactory cardiac output i.e. non-shockable ventricular tachycardia (conscious with a pulse) and sinus rhythm (Group 2). On univariate analysis each of the four impedance cardiogram parameters were significantly greater in Group 2 than Group 1 (P<0.001). On multivariate analysis the parameters which best differentiated the two groups were Area 1 and Peak-trough. CONCLUSION: Thus the impedance cardiogram is a potential haemodynamic sensor for an automatic external defibrillator.

Adult↗

Nitric oxide: a cytokine-induced regulator of bone resorption.

Nitric oxide (NO) has been reported to inhibit osteoclastic bone resorption, yet potent stimulators of bone resorption, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), are known to stimulate NO production. This paradox prompted us to reinvestigate the relationship between NO production and bone resorption in mouse calvarial organ cultures. Control cultures and those stimulated with calciotropic hormones and individual cytokines produced little NO, and under these conditions the NO synthase inhibitor, L-NG-monomethyl arginine (LMMA), had no significant effect on bone resorption. Cytokine combinations were much more potent stimulators of NO production than individual cytokines. Dramatic stimulation of NO production and inhibition of bone resorption resulted when gamma-interferon (IFN) was combined with IL-1 or TNF and these effects were reversed by LMMA. IFN had no effect on bone resorption and little effect on NO production when used alone or in combination with calciotropic hormones, however, suggesting that IFN selectively inhibits cytokine-induced bone resorption by generating large amounts of NO. IL-1 and TNF acted together to stimulate NO production but to a lesser degree than when combined with IFN. LMMA inhibited bone resorption induced by IL-1 and TNF, suggesting that lower concentrations of NO stimulate bone resorption. Experiments with the pharmacological NO donor S-nitroso-acetyl-penicillamine (SNAP) supported this view in showing generalized suppression of bone resorption at high SNAP concentrations, but potentiation of IL-1 induced bone resorption at lower SNAP concentrations. We conclude that cytokines are potent inducers of NO in bone and that cytokine-induced NO production has biphasic effects on bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sudden cardiac death and substance abuse.

There has been a steady increase in the number of deaths occurring from volatile substance abuse per year. The majority of deaths are in males, the peak age group being 15-19 years. Fuel gases i.e. cigarette lighter refills (butane), propane and gasoline and other solvents such as typewriter correction fluid, dry-cleaning fluids (trichloroethane) and fire extinguishers (bromochlorodifluoromethane) are responsible for approximately 60% of these deaths. Volatile substances sensitise the heart to circulating catecholamines, such that sudden alarm or exercise may precipitate sudden death. The main mechanism of cardiac arrest is a cardiac arrhythmia, but anoxia, respiratory depression and vagal stimulation along with aspiration of vomit or trauma may be contributing factors to the sudden death. In addition, particularly butane gas inhalation may be associated with severe laryngeal oedema and laryngospasm. Resuscitation from sudden death associated with volatile substance abuse is rare, since the majority of deaths are unwitnessed. It is suggested that cardiac arrhythmias should be treated conventionally. Sympathomimetic drugs should be avoided. Early during the resuscitation process, beta-adrenergic blocking agents should be administered to protect the catecholamine-sensitised heart. Early intubation in the management of the cardiac arrest should be avoided, if the inhalational agent is known to be associated with laryngospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗