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Biomedical subjects

D A Watson

Publications and source records attributed to D A Watson.

At least 55 records · Page 3Linked to original sources

Pneumococcal vaccination: work to date and future prospects.

In our opinion, the conclusion from all these studies is that pneumococcal polysaccharides in the form in which they have been administered are relatively poor immunogens when compared, for example, to certain proteins such as tetanus toxoid. Had pneumococcal vaccination been the success that might reasonably have been predicted, there would be no argument, this many years later, over its merits. Although polysaccharide vaccines appear to have been effective in mass vaccination programs and in epidemic situations where presumably healthy adults have been involved, it has been more difficult to document their efficacy in individuals who are most in need of them, namely those with aberrant or senescent immune systems. There seems to be no disagreement that antibody at some concentration (the precise level remains to be determined) will, in general, be associated with protection, although in any one individual, for a variety of reasons, infection with a vaccine serotype might still occur. Thus, the clear direction for the future should be not to argue further the merits of currently available vaccine preparations, but rather to work rapidly and efficiently to develop and test new and more effective polysaccharide antigens. Studies in the past 10 years have shown that the polyribosyl ribitolphosphate (PRP) of Haemophilus influenzae type b is a far more effective antigen when conjugated to diphtheria toxoid. For example, in a study in our laboratory, vaccination of healthy young adults with PRP-conjugated diphtheria toxoid yielded serum antibody levels 10- to 100-fold higher than after PRP alone. Responses may be even better if other proteins are used.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial↗

Quantitative relationship between anticapsular antibody measured by enzyme-linked immunosorbent assay or radioimmunoassay and protection of mice against challenge with Streptococcus pneumoniae serotype 4.

We have recently shown that a substantial proportion of antibody to pneumococcal polysaccharide as measured by enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay is removed by adsorption with pneumococcal cell wall polysaccharide (CWPS). The present study was undertaken to validate the hypothesis that only serotype-specific antibody that remains after adsorption with CWPS provides protection against pneumococcal infection. Serum samples were obtained from human subjects before and after they had been vaccinated with pneumococcal polysaccharide vaccine. Antibody to Streptococcus pneumoniae serotype 4 was measured by ELISA without adsorption or after adsorption of serum with CWPS. Groups of mice were injected with graded doses of serum and then challenged intraperitoneally with 10, 100, or 1,000 50% lethal doses (LD50) of S. pneumoniae serotype 4. Without adsorption, prevaccination sera from five healthy adults appeared to contain up to 33 micrograms of antibody to S. pneumoniae serotype 4 antigen per ml; adsorption with CWPS removed all detectable antibody, and pretreating mice with up to 0.1 ml of these sera (less than or equal to 3.3 micrograms of antibody) failed to protect them against challenge with 100 LD50. In contrast, postvaccination sera contained 2.9 to 30 micrograms of antibody per ml that was not removed by adsorption. Diluting sera to administer desired amounts of serotype-specific immunoglobulin G showed a significant relationship between protection and antibody remaining after adsorption (P less than 0.05 by linear regression analysis); 150 ng was uniformly protective against 1,000 LD50, and 50 ng was protective against 100 LD50. These studies have, for the first time, quantitated the amount of serotype-specific antibody that protects mice against challenge with S. pneumoniae type 4. In light of these observations, it is necessary to reassess current concepts regarding the presence of antipneumococcal antibody in the unvaccinated population, responses to pneumococcal vaccination, and protective levels of immunoglobulin G.

Adult↗

Interruption of capsule production in Streptococcus pneumonia serotype 3 by insertion of transposon Tn916.

Transposon Tn916 mutagenesis was used to produce mutant strains of Streptococcus pneumoniae serotype 3 that lacked only a polysaccharide capsule. Southern blotting, DNA-DNA hybridization, and immunochemical analyses demonstrated that the presence of a single copy of Tn916 was sufficient to produce unencapsulation. The 50% lethal dose for such mutants was greater than 5 x 10(7) CFU, as opposed to a 50% lethal dose of 1 CFU for wild-type strains. These experiments outline an effective method for targeting genes in S. pneumoniae by transposon interruption and provide molecular evidence to support the longstanding hypothesis that the capsule is the principal virulence factor in this pathogen.

Animals↗

Vasoactive pressure hormones during and after cardiopulmonary bypass.

The differences in the pattern of the vasoactive hormone release in response to the stress of surgery and cardiopulmonary bypass (CPB) (pulsatile n = 15 and non pulsatile n = 23) were studied in the adult patients with mitral valve disease (MVD), aortic valve disease (AVD), and the coronary artery disease (CAD). A differential stimulation of the osmoreceptors, baroceptors, renin-angiotensin and the sympathetico-adrenal systems in these patients, resulted in the variations in the pattern of hormone release. Patients with MVD showed a greater stimulation of osmoreceptors, baroceptors and release of Arginine vasopressin (AVP). Renin-angiotensin system was more easily triggered in patients with AVD or CAD; and sympathetico-adrenal system in patients with CAD. The renin-angiotensin-aldosterone axis was better preserved in patients with CAD (r = 0.49, p less than 0.001) than in the patients with MVD (r = 0.38, p less than 0.02). Plasma renin release showed a significant correlation with noradrenaline release in the patients with MVD (r = 0.47, p less than 0.01); but this relationship was lost in the patients with the CAD, due to an excessive noradrenaline release. Pulsatile bypass reduced but did not abolish this response. Under unfavourable conditions, the stress response may persist in the early post-operative period.

Aortic Valve↗

Aortic valve disease and the ST segment/heart rate relationship: a longitudinal study before and after aortic valve replacement.

The ST segment/heart rate relationship or maximal ST/HR slope has been validated as an index of myocardial ischemia in selected populations of patients with angina pectoris. The present study involved patients selected as having aortic valve disease unaccompanied by angiographic coronary artery narrowing. In each of seven patients, so far examined, a slope value and ST segment depression of greater than 1 mm were obtained which, according to previous experience, indicated myocardial ischemia equivalent to coronary heart disease. After aortic valve replacement, there was a significant reduction in heart size as assessed using the cardiothoracic ratio, and the amplitude of QRS complex on the electrocardiogram. The slope was abolished (two patients) or markedly reduced (five patients), and the decrease in the seven patients was statistically significant. ST segment depression could be obtained in one patient. This study has shown the occurrence of maximal ST/HR slope in patients without large coronary artery disease who have aortic valve disease and cardiac enlargement.

Aortic Valve↗

Vaccination of 18-month-old children with conjugated polyribosyl ribitol phosphate stimulates production of functional antibody to Haemophilus influenzae type b.

Eighteen-month-old children were immunized with polyribosyl ribitol phosphate (PRP) of Haemophilus influenzae type b or with PRP that had been conjugated to diphtheria toxoid. Conjugated vaccine stimulated significant mean increases in antibody titer as measured by radioimmunoassay and bactericidal effect, as well as a modest increase in opsonizing activity. In contrast unconjugated vaccine caused lesser albeit significant rises in antibody titer, but a negligible antibacterial effect. These results suggest that vaccinating infants with conjugated PRP is more likely to stimulate production of antibodies that are protective against systemic infection caused by H. influenzae type b than vaccinating with unconjugated PRP.

Antibodies, Bacterial↗

The role of serum tumour markers to aid the selection of lung cancer patients for surgery and the assessment of prognosis.

We have measured the following ten serum proteins in a sample of 290 patients presenting with possible lung cancer: carcinoembryonic antigen (CEA), alpha 1-acid glycoprotein (AGP), C-reactive protein (CRP), ferritin (FER), prealbumin (PAB), third component of complement (C3), immunoglobin E (IgE), alpha 2-pregnancy-associated glycoprotein (PAG), beta 2-microglobulin (beta 2-m) and retinol binding protein (RBP). It is found that, with the exception of PAG, C3 and IgE, there are significant differences between protein concentrations in the subsequently diagnosed cancer and non-cancer patients. However, protein concentrations in the cancer patients who were suitable for surgery do not differ significantly from the concentrations in inoperable patients. The prognostic significance of the proteins in the inoperable and operable cancer patients is also envisaged. In the operable group C3 appears to be useful, whilst AGP and RBP are prognostic indicators in the inoperable group.

Blood Proteins↗

Mechanism of late failure of the Alvarez disc valve prosthesis.

An Alvarez disc valve prosthesis had been implanted in the mitral and tricuspid positions in 15 patients between 1964 and 1967 in this hospital. Of these 15 patients, only three survived longer than 10 years, all three dying unexpectedly between 16 and 18 years postoperatively. Two deaths were a direct result of disruption of the Alvarez prosthesis. The third patient was not examined at necropsy, but in retrospect the history was highly suggestive of valve malfunction. Cross sectional and pulsed Doppler echocardiography made valuable contributions to the diagnosis in both cases of valve disruption and, when available, should be part of the primary investigation of suspected prosthetic heart valve failure. The Alvarez valve prosthesis is liable to erosive wear which may cause late detachment of the disc from the valve ring with abrupt and catastrophic haemodynamic consequences.

Adult↗

Acetylsalicylic acid and dipyridamole improve the early patency of aorta-coronary bypass grafts. A double-blind, placebo-controlled, randomized trial.

A total of 125 patients undergoing aorta-coronary bypass grafting for disabling angina were randomized to receive either 330 mg of acetylsalicylic acid (aspirin) plus 75 mg of dipyridamole three times daily or a placebo for 6 months postoperatively. In addition, all patients were given warfarin for 3 months. Repeat angiography was performed at 6 months in 103 patients. In the treatment group 95 grafts were implanted in 48 patients, of which 87 were patent (91.6% patency rate). This figure compares with 88 grafts patent out of 118 implanted in 55 patients in the placebo group (74.6% patency rate) (p less than 0.01). We conclude that antiplatelet therapy improves the early patency of saphenous vein aorta-coronary bypass grafts.

Adult↗

Immune complexes in urine and serum of patients with bladder cancer.

The urine and/or serum of 43 patients with bladder cancer was tested for the presence of immune complexes. Immune complexes were present more frequently in the urine (38 per cent) than in the serum (23 per cent). Urinary immune complexes were elevated in 10 per cent of the patients with no tumor (group 1), 25 per cent with superficial neoplasms (group 2) and 89 per cent with infiltrating or metastatic disease (group 3), which compared favorably to elevated serum immune complexes in 20, 25 and 33 per cent of the patients, respectively. The incidence of urinary immune complexes was statistically significant when compared in patients with and without active tumors (p less than 0.03), and when group 3 patients were compared to those in group 1 or 2 (p less than 0.01 and p less than 0.03, respectively). Unlike serum immune complexes urinary immune complexes appeared to correlate with the presence and stage of bladder cancer.

Adult↗

Assessment of aortocoronary bypass grafting using exercise ST segment/heart rate relation.

The maximal rate of progression of ST segment depression relative to increases in heart rate (maximal ST/HR slope) has recently been shown to be an accurate index of the presence and the severity of coronary heart disease in patients with angina. The value of this new exercise test was assessed in patients undergoing aortocoronary bypass. The maximal ST/HR slope and the results of coronary angiography were obtained in each of 46 patients before aortocoronary bypass surgery and in 26 of the 46 patients six months after the operation. At each stage of the investigation the maximal ST/HR slope detected without false results the absence and the number of significantly diseased vessels as shown by angiocardiography. As in previous findings the ranges of the maximal ST/HR slope showed no overlap between the four groups of patients: those with no significant disease and those with single, double, or triple vessel disease. In each of the 46 patients in whom the maximal ST/HR slope was determined before operation and three months afterwards the slope was lower after operation than before, indicating improvement. Follow up examinations showed that the maximal ST/HR slopes accurately detected the number of patent grafts used to bypass significantly diseased coronary arteries. Furthermore, the development of a significant narrowing or occlusion in any vein graft caused an increase in the maximal ST/HR slope which was equivalent to the value of single vessel disease. It is suggested that the maximal ST/HR slope may be used reliably in individual patients to indicate restoration of adequate blood supply to the myocardium after successfully aortorcoronary bypass surgery and the to detect in the period of six months after the operation the degree of severity of coronary heart disease whether it is caused by occlusion of the graft of significant disease of the coronary arteries.

Adult↗

Comparison between irrigation and conventional treatment for empyema and pneumonectomy space infection.

A new method of treating pleural empyema or pneumonectomy space infection by irrigation was evaluated in 11 patients. The infected cavities were filled with an antibiotic or antiseptic solution for three hours, and allowed to drain for one hour. This cycle was repeated every four hours for seven to 10 days. When cultures of the infected cavity became sterile the irrigation tube was removed and the wound sealed. Using this method, infection was eradicated after an average of 11 days in five of six patients with pleural empyema and in all five patients treated for an infected pneumonectomy space, including one with a bronchopleural fistula. The results of treating 58 similar cases of intrapleural sepsis over a 10-year period by the standard methods of aspiration, open drainage, decortication, or thoracoplasty were compared with the results of irrigation. In general, cyclical irrigation resulted in a shorter hospital stay and a shorter period of wound drainage than other methods.

Adolescent↗