How point-of-care HbA1c testing changes the behaviour of people with diabetes and clinicians - a qualitative study.

AIM: To explore adults with diabetes and clinician views of point-of-care HbA1c testing. METHODS: Adults with diabetes and HbA1c ≥ 58 mmol/mol (7.5%) receiving HbA1c point-of-care testing in primary care were invited to individual interviews. Participants were interviewed twice, once prior to point-of-care testing and once after 6 months follow-up. Clinicians were interviewed once. A thematic framework based on an a priori framework was used to analyse the data. RESULTS: Fifteen participants (eight women, age range 30-70 years, two Asians, 13 white Europeans) were interviewed. They liked point-of-care testing and found the single appointment more convenient than usual care. Receiving the test result at the appointment helped some people understand how some lifestyle behaviours affected their control of diabetes and motivated them to change behaviours. Receiving an immediate test result reduced the anxiety some people experience when waiting for a result. People thought there was little value in using point-of-care testing for their annual review. Clinicians liked the point-of-care testing but expressed concerns about costs. CONCLUSIONS: This work suggests that several features of point-of-care testing may encourage behavioural change. It helped some people to link their HbA1c result to recent lifestyle behaviours, thereby motivating behavioural change and reinforcing healthy lifestyle choices.

Timings for HbA1c testing in people with diabetes are associated with incentive payments: an analysis of UK primary care data.

AIMS: Guidelines recommend testing HbA1c every 3-6 months in people with diabetes. In the United Kingdom (UK), primary care clinics are financially incentivized to monitor HbA1c at least annually and report proportions of patients meeting targets on 31 March. We explored the hypothesis that this reporting deadline may be associated with over-frequent or delayed HbA1c testing. METHODS: This analysis used HbA1c results from 100 000 people with diabetes during 2005-2014 in the Clinical Practice Research Datalink UK primary care database. Logistic regression was used to explore whether the four months prior to the deadline for quality reporting (December to March) or individual's previous HbA1c were aligned with retesting HbA1c within 60 days or > 1 year from the previous test, and identify other factors associated with the timing of HbA1c testing. RESULTS: Retesting HbA1c within 60 days or > 1 year was more common in December to March compared with other months of the year (odds ratio 1.06, 95% confidence interval 1.04-1.08 for retesting within 60 days). Those with higher HbA1c were more likely to have a repeat test within 60 days and less likely to have a repeat test > 1 year from the previous test. CONCLUSIONS: We have found that retesting HbA1c within 60 days and > 1 year from the previous test was more common in December to March compared with the other months of the year. This work suggests that both practice-centred administrative factors and patient-centred considerations may be influencing diabetes care in the UK.

Short- and medium-term effects of light to moderate alcohol intake on glycaemic control in diabetes mellitus: a systematic review and meta-analysis of randomized trials.

BACKGROUND: People with diabetes are told that drinking alcohol may increase their risk of hypoglycaemia. AIMS: To report the effects of alcohol consumption on glycaemic control in people with diabetes mellitus. METHODS: Medline, EMBASE and the Cochrane Library databases were searched in 2015 to identify randomized trials that compared alcohol consumption with no alcohol use, reporting glycaemic control in people with diabetes. Data on blood glucose, HbA1c and numbers of hypoglycaemic episodes were pooled using random effects meta-analysis. RESULTS: Pooled data from nine short-term studies showed no difference in blood glucose concentrations between those who drank alcohol in doses of 16-80 g (median 20 g, 2.5 units) compared with those who did not drink alcohol at 0.5, 2, 4 and 24 h after alcohol consumption. Pooled data from five medium-term studies showed that there was no difference in blood glucose or HbA1c concentrations at the end of the study between those who drank 11-18 g alcohol/day (median 13 g/day, 1.5 units/day) for 4-104 weeks and those who did not. We found no evidence of a difference in number of hypoglycaemic episodes or in withdrawal rates between randomized groups. CONCLUSIONS: Studies to date have not provided evidence that drinking light to moderate amounts of alcohol, with or without a meal, affects any measure of glycaemic control in people with Type 2 diabetes. These results suggest that current advice that people with diabetes do not need to refrain from drinking moderate quantities of alcohol does not need to be changed; risks to those with Type 1 diabetes remain uncertain.

Estimating the effect of sulfonylurea on HbA1c in diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Sulfonylureas are widely prescribed glucose-lowering medications for diabetes, but the extent to which they improve glycaemia is poorly documented. This systematic review evaluates how sulfonylurea treatment affects glycaemic control. METHODS: Medline, EMBASE, the Cochrane Library and clinical trials registries were searched to identify double-blinded randomised controlled trials of fixed-dose sulfonylurea monotherapy or sulfonylurea added on to other glucose-lowering treatments. The primary outcome assessed was change in HbA1c, and secondary outcomes were adverse events, insulin dose and change in body weight. RESULTS: Thirty-one trials with a median duration of 16 weeks were included in the meta-analysis. Sulfonylurea monotherapy (nine trials) lowered HbA1c by 1.51% (17 mmol/mol) more than placebo (95% CI, 1.25, 1.78). Sulfonylureas added to oral diabetes treatment (four trials) lowered HbA1c by 1.62% (18 mmol/mol; 95% CI 1.0, 2.24) compared with the other treatment, and sulfonylurea added to insulin (17 trials) lowered HbA1c by 0.46% (6 mmol/mol; 95% CI 0.24, 0.69) and lowered insulin dose. Higher sulfonylurea doses did not reduce HbA1c more than lower doses. Sulfonylurea treatment resulted in more hypoglycaemic events (RR 2.41, 95% CI 1.41, 4.10) but did not significantly affect the number of other adverse events. Trial length, sulfonylurea type and duration of diabetes contributed to heterogeneity. CONCLUSIONS/INTERPRETATION: Sulfonylurea monotherapy lowered HbA1c level more than previously reported, and we found no evidence that increasing sulfonylurea doses resulted in lower HbA1c. HbA1c is a surrogate endpoint, and we were unable to examine long-term endpoints in these predominately short-term trials, but sulfonylureas appear to be associated with an increased risk of hypoglycaemic events.

Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials.

AIMS/HYPOTHESIS: Observational studies suggest that metformin may reduce cancer risk by approximately one-third. We examined cancer outcomes and all-cause mortality in published randomised controlled trials (RCTs). METHODS: RCTs comparing metformin with active glucose-lowering therapy or placebo/usual care, with minimum 500 participants and 1-year follow-up, were identified by systematic review. Data on cancer incidence and all-cause mortality were obtained from publications or by contacting investigators. For two trials, cancer incidence data were not available; cancer mortality was used as a surrogate. Summary RRs, 95% CIs and I (2)statistics for heterogeneity were calculated by fixed effects meta-analysis. RESULTS: Of 4,039 abstracts identified, 94 publications described 14 eligible studies. RRs for cancer were available from 11 RCTs with 398 cancers during 51,681 person-years. RRs for all-cause mortality were available from 13 RCTs with 552 deaths during 66,447 person-years. Summary RRs for cancer outcomes in people randomised to metformin compared with any comparator were 1.02 (95% CI 0.82, 1.26) across all trials, 0.98 (95% CI 0.77, 1.23) in a subgroup analysis of active-comparator trials and 1.36 (95% CI 0.74, 2.49) in a subgroup analysis of placebo/usual care comparator trials. The summary RR for all-cause mortality was 0.94 (95% CI 0.79, 1.12) across all trials. CONCLUSIONS/INTERPRETATION: Meta-analysis of currently available RCT data does not support the hypothesis that metformin lowers cancer risk by one-third. Eligible trials also showed no significant effect of metformin on all-cause mortality. However, limitations include heterogeneous comparator types, absent cancer data from two trials, and short follow-up, especially for mortality.

Evidence for a dose effect of renin-angiotensin system inhibition on progression of microalbuminuria in Type 2 diabetes: a meta-analysis.

AIMS: Renin-angiotensin inhibitors in Type 2 diabetes and microalbuminuria reduce renal and cardiovascular risk, but evidence supporting use of maximal tolerated dose is unclear. We aimed to determine the extent of renin-angiotensin inhibitor dose-dependent effects from randomized trials carried out in a clinical setting. METHODS: In a meta-analysis of randomized clinical trials, alternate doses of angiotensin receptor blockers or angiotensin converting enzyme inhibitors in patients with Type 2 diabetes and microalbuminuria were compared. MEDLINE, EMBASE and the Cochrane Register of Controlled Trials were searched from January 2006 to August 2010. Trials prior to January 2006 were identified from a prior systematic review. Identified outcomes were albumin excretion rate, progression and regression of albuminuria and adverse events. RESULTS: Four trials including 1051 patients compared doses of angiotensin receptor blockers. No trials compared doses of angiotensin converting enzyme inhibitor. The percentage decline in albumin excretion rate from baseline was greater with higher doses (18% higher, 95% CI 8-28%), the regression to normoalbuminuria was greater (OR 1.66, 95% CI 1.22-2.27), with less progression to macroalbuminuria (OR 0.62, CI 0.38-1.02). Adverse events were fewer with lower-dose angiotensin receptor blockers (OR 1.32, 95% CI 0.90-1.92). CONCLUSIONS: Higher-dose compared with lower-dose angiotensin receptor blockers in Type 2 diabetes with microalbuminuria are associated with significantly reduced albumin excretion rate and increased regression to normoalbuminuria. Adverse events are more frequent, but not significantly so. There is potential for trials to determine clinical cardiovascular and renal outcomes at differing doses. Our findings support current recommendations to titrate renin-angiotensin inhibitors to maximum dose whilst considering risk of adverse side effects with higher doses.

How can point-of-care HbA1c testing be integrated into UK primary care consultations? - A feasibility study.

AIMS: Point-of-care (POC) HbA1c testing gives a rapid result, allowing testing and treatment decisions to take place in a single appointment. Trials of POC testing have not been shown to improve HbA1c, possibly because of how testing was implemented. This study aimed to identify key components of POC HbA1c testing and determine strategies to optimise implementation in UK primary care. METHODS: This cohort feasibility study recruited thirty patients with type 2 diabetes and HbA1c>7.5% (58mmol/mol) into three primary care clinics. Patients' clinical care included two POC HbA1c tests over six months. Data were collected on appointment duration, clinical decisions, technical performance and patient behaviour. RESULTS: Fifty-three POC HbA1c consultations took place during the study; clinical decisions were made in 30 consultations. Five POC consultations with a family doctor lasted on average 11min and 48 consultations with nurses took on average 24min. Five POC study visits did not take place in one clinic. POC results were uploaded to hospital records from two clinics. In total, sixty-three POC tests were performed, and there were 11 cartridge failures. No changes in HbA1c or patient behaviour were observed. CONCLUSIONS: HbA1c measurement with POC devices can be effectively implemented in primary care. This work has identified when these technologies might work best, as well as potential challenges. The findings can be used to inform the design of a pragmatic trial to implement POC HbA1c testing.

Abciximab in primary coronary angioplasty for acute myocardial infarction improves short- and medium-term outcomes.

OBJECTIVES: The purpose of this study was to compare the outcome of primary percutaneous transluminal coronary angioplasty for acute myocardial infarction (MI) when performed with or without the platelet glycoprotein IIb/IIIa antibody, abciximab. BACKGROUND: Abciximab improves the outcome of angioplasty but the effect of abciximab in primary angioplasty has not been investigated. METHODS: Data were collected from a computerized database. Follow-up was by telephone or review of outpatient or hospital readmission records. RESULTS: A total of 182 consecutive patients were included; 103 received abciximab and 79 did not. The procedural success rate was 95% in the two groups. At 30-day follow-up, the composite event rate of unstable angina, reinfarction, target vessel revascularization and death from all causes was 13.5% in the group of patients who did not receive abciximab, 4% (p < 0.05) in the abciximab group and 2.4% (p < 0.05) in the subgroup of patients (n = 87) who completed the 12-h abciximab infusion. At the end of follow-up (mean 7+/-4 months), the composite event rate was 32.4%, 17% (p < 0.05) and 13.1% (p < 0.01) in these three categories respectively. Abciximab bolus followed by a 12-h infusion was an independent predictor of event-free survival, in a Cox proportional hazards model (relative risk 0.49; 95% confidence interval 0.24 to 0.99; p < 0.05). CONCLUSIONS: Abciximab given at the time of primary angioplasty may improve the short- and medium-term outcome of patients with acute MI, especially when a 12-h infusion is completed.

Intracardiac echocardiography in humans using a small-sized (6F), low frequency (12.5 MHz) ultrasound catheter. Methods, imaging planes and clinical experience.

OBJECTIVES: This study was designed to determine the clinical utility and feasibility of using 12.5-MHz ultrasound catheters for intracardiac echocardiography. BACKGROUND: Intracardiac echocardiography is a potentially useful technique of cardiac imaging and monitoring in certain settings. The feasibility of intracardiac echocardiography using 20-MHz ultrasound catheters in patients has been demonstrated. High resolution images of normal cardiac structures as well as cardiac abnormalities have been obtained. However, imaging has been limited by the shallow depth of field inherent in high frequency ultrasound imaging. METHODS: Intracardiac echocardiography with 12.5-MHz catheters was performed in eight mongrel dogs and 92 patients. Catheters were introduced percutaneously in 80 patients studied in the catheterization laboratory and directly into the heart in 12 patients in the operating room. Right heart imaging was performed in 68 patients and arterial and left heart imaging in 35 patients. RESULTS: When these catheters were introduced into the venous system, the right atrium, tricuspid valve, right ventricle, pulmonary valve and pulmonary artery were visualized. Pericardial effusion, intracardiac masses and atrial septal defects were correctly identified. The left ventricle, left atrium, mitral valve, aortic valve, aorta and coronary arteries could be imaged from the arterial circulation. Diseases identified included valvular aortic stenosis, subvalvular aortic stenosis and Kawasaki disease. Average imaging time was 10 min. No complications occurred as a result of intracardiac echocardiography. CONCLUSIONS: Intracardiac echocardiography with 12.5-MHz ultrasound catheters is safe and feasible; it also provides anatomic and physiologic information. This feasibility study provides a foundation for wider clinical use of intracardic echocardiography.

Separation of self-renewing hematopoietic progenitors on the basis of CD45 (T-200) antigen expression.

Using monoclonal antibodies recognizing the shared determinants of the CD45 (T-200) antigen we have been able to distinguish spleen colony-forming units (CFU-s) whose progeny are self-renewing from other colony formers on the basis of their quantitative expression of this antigen(s). We have also been able to identify a population of cells that is capable of producing 12-day colonies but has only a limited capacity to produce 8-day colonies. CFU-s8 are found primarily in the dim T-200 population, whereas CFU-s12 were found in both the bright and dim population, but the cells within the colonies produced by these two populations differ in their capacity for self-renewal as CFU-s. Only the colonies dissected after 12 days from the spleens of mice receiving T-200-bright bone marrow cells contained significant numbers of cells that were capable of forming colonies after retransplantation. We calculate the frequency of these cells in total bone marrow to be approximately 1 in 5000.

Synergy between intracoronary stenting and abciximab in improving angiographic and clinical outcomes of primary angioplasty in acute myocardial infarction.

This study examined 650 consecutive patients who presented with an acute myocardial infarction and were treated with primary angioplasty within 12 hours of symptom onset between August 1995 and December 1998. Patients were placed into 4 treatment groups depending on the adjunctive therapy they received: group 1, percutaneous transluminal coronary angioplasty (PTCA) ("balloon PTCA alone"; n = 220); group 2, PTCA plus intracoronary stent placement ("stent"; n = 128); group 3, PTCA plus abciximab therapy ("abciximab"; n = 104); and group 4, PTCA plus intracoronary stent placement plus abciximab therapy ("stent/abciximab"; n = 198). The patients' clinical characteristics, severity of disease, and total ischemia time on presentation were similar. At baseline, abciximab and stent/abciximab groups had a higher incidence of thrombus on coronary angiography. Postprocedural quantitative coronary analysis showed a significantly larger minimum luminal diameter in the stent and stent/abciximab groups than PTCA alone. Overall, stents were most efficacious in reducing target vessel revascularization rate, whereas abciximab was associated with a higher postprocedural Thrombolysis In Myocardial Infarction-3 trial flow and less "no reflow." The best angiographic result was achieved in the stent/abciximab group. Similarly, the primary combined end point of death, myocardial infarction, and target vessel revascularization at 30 days was the lowest (6.1%) in the stent/abciximab group. The combination of abciximab and stenting in primary angioplasty for acute myocardial infarction is thus synergistic and is associated with improved angiographic and clinical results at 30-day follow-up.

Short- and medium-term outcome differences in women and men after primary percutaneous transluminal mechanical revascularization for acute myocardial infarction.

Women presenting with acute myocardial infarction (AMI) have a higher mortality with conventional medical and thrombolytic therapy when compared with men. The outcome after primary percutaneous transluminal mechanical revascularization has not yet been fully investigated. This study was performed to compare the characteristics and the short- and medium-term outcomes of women and men with AMI treated with primary percutaneous revascularization. A total of 182 consecutive patients (62 women and 120 men) were included. Baseline clinical characteristics were similar except that women were older than men, presented more often in cardiogenic shock, and had smaller reference vessel diameters. Stents and abciximab were used equally, but abciximab was stopped more often in women before completion of the 12-hour infusion because of higher bleeding rates. Acute procedural success rates were similar (92% and 97%) but mortality was much higher in women, both at 30-day follow-up (100% vs 0.9%; p <0.05) and during a mean follow-up of 6.9 +/- 4.1 months (15% vs 4.4%; p <0.05). Women also experienced more unfavorable cardiovascular events (recurrent unstable angina or AMI, target vessel revascularization) than men. However, after control for baseline clinical differences in a multivariate analysis, gender was not an independent predictor of survival, whereas age, cardiogenic shock, and completion of a 12-hour abciximab infusion were.

Intracardiac ultrasound imaging during transseptal catheterization.

STUDY OBJECTIVE: The purpose of this study was to assess the feasibility of using small 12.5- or 20-MHz intracardiac ultrasound catheters to image the fossa ovalis and guide transseptal catheterization. DESIGN: The study was performed in three phases. First, in vitro imaging of human autopsy hearts was performed to define the intracardiac ultrasound appearance of the fossa ovalis and transseptal apparatus. Subsequently, the optimum approach for imaging the fossa ovalis in vivo was established in 30 patients. Finally, intracardiac ultrasound imaging was performed during transseptal catheterization of 10 patients undergoing percutaneous mitral commissurotomy. INTERVENTIONS: Intracardiac ultrasound imaging was performed with a 12.5- or 20-MHz single-element mechanical device in which a central imaging core is rotated within a 6F polyethylene sheath. MEASUREMENTS AND RESULTS: In both in vitro and in vivo studies, the fossa ovalis was easily identifiable as a thin membranous region surrounded by the thicker muscular portion of the interatrial septum. Initial in vivo studies established venous access by the femoral route to be superior to the internal jugular approach for catheter introduction. Studies performed during transseptal catheterization established the utility of using the fluoroscopic image of the catheter adjacent to the fossa ovalis to generate a guiding shot for positioning the transseptal apparatus. In addition, distention of the fossa prior to needle perforation could be demonstrated. However, since it was often difficult to track the tip of the needle, actual puncture of the fossa was rarely demonstrated. CONCLUSIONS: Intravascular ultrasound imaging can precisely locate the fossa ovalis in virtually all subjects. It therefore may assist transseptal catheterization.

Coronary stent placement as a bridge to coronary artery bypass surgery in an unstable, anemic Jehovah's Witness patient: a case report and review of bloodless surgery techniques.

Bloodless cardiac surgery would be optimal for all patients undergoing major or complex heart surgery; however, for Jehovah's Witnesses it involves a religious law and is fundamentally mandated. In this context, we review a case of unstable angina with associated anemia requiring catheterization and definitive intervention in a Jehovah's Witness patient. Coronary stenting to stabilize the acute coronary syndrome is described with definitive total revascularization performed by coronary artery bypass graft surgery after utilizing erythropoietin and aggressive blood conservation techniques.

Conditional requirement for accessory cells in the response of T cells to Con A.

The response to Concanavalin A (Con A) of unseparated lymph node cells and of T cells isolated from them has been studied over a mitogen dose range of 0.2 microgram to 16 micrograms/ml. Accessory cell depleted T cells respond only to high doses of Con A and then only weakly. The magnitude (proliferative activity) of the response as well as the sensitivity to the mitogen can be modified by accessory cells (AC), lymphokines and by chemical modification of cell surface glycoproteins. Accessory cell function can be inhibited by antibodies directed against cell surface molecules on accessory cells (Ia) or on T cells (L3T4). Changes in the mitogen sensitivity of the response are not necessarily associated with changes in the magnitude of the response. The mitogen sensitivity can be decreased with anti-Ia antibody and can be increased by treatment with IL-l and/or interferon gamma (IFN-). We postulate that the increase in sensitivity to Con A is a function of the density of cell surface molecules with which T and AC cells interact. The magnitude of the response is primarily determined by the frequency of AC in culture; it decreases as the number of AC is reduced and increases as AC are added to the cultures. Mitogen sensitivity is a new tool for the analysis of nonspecific T cell activation. Our data bring the accessory cell requirement for mitogen activation of T cells into a new perspective: AC--or factors produced by them--are essential when low (1-2 micrograms/ml Con A) doses are used and are less or not at all necessary when high doses (6-10 micrograms/ml) of mitogen are applied.

IL 1 requirement for B cell activation revealed by use of adult serum.

Fetal calf serum is an essential component of the culture medium developed by Mishell and Dutton for the immunization of murine spleen cells in vitro. Serum from adult donors (mouse, human, rabbit) does not support antibody synthesis in this system. This "deficiency" of adult serum can be overcome with IL 1. Adult serum in the presence of IL 1 is as effective in stimulating a B cell response against xenogeneic red cells as fetal calf serum. We attribute the capacity of fetal calf serum to support an immune response in the absence of exogenous IL 1 to serum factors that cause macrophages to release IL 1 endogenously. Our findings strengthen the notion that IL 1 plays an essential role in the process of B cell activation and suggests that the use of fetal calf serum should be avoided in studies concerned with the function of interleukin 1.

Enhancement of cytotoxic activity of natural killer cells by interleukin 2, and antagonism between interleukin 2 and adenosine cyclic monophosphate.

Two cytokines, interferon (IFN) and interleukin 2 (IL-2), activate murine natural killer (NK) cells in vitro. Together both factors synergize considerably. Antibody against IFN eliminates the response of NK cells to IFN as well as to IL-2, whereas antibody against IL-2 blocks the effect of IL-2 but not of IFN. These findings as well as previous observations imply that both factors act on the same cell but have different roles. We suggest that IFN induces NK cell activation and IL-2 enhances this effect. Further studies revealed that besides inducing cytotoxicity in NK cells IFN induces the production of prostaglandin E (PGE) which inhibits NK cell activation. We propose therefore that IFN has a dual effect on NK cells: it induces NK cells to become cytotoxic and initiates a negative feedback by increasing the production of PGE. IL-2, which synergizes with IFN in the activation of NK cells, ceases to do so when the negative feedback (PGE-mediated) is blocked with indomethacin. We infer that IL-2 enhances NK cell activity by interfering with the negative feedback rather than by aiding NK cell activation.

An essential role for interleukin 1 and a dual function for interleukin 2 in the immune response of murine B lymphocytes to sheep erythrocytes.

The macrophage-derived lymphokine interleukin 1 (IL-1) and the T cell-derived lymphokine interleukin 2 (IL-2) help B lymphocytes to generate antibodies against sheep erythrocytes in vitro. It has been difficult to determine whether these factors act on antigen-reactive B cells directly or via accessory cells, since it is not technically feasible to prepare completely homogenous cell populations. Therefore we examined the question of lymphokine action on B cells using an indirect approach. First we determined effects of the two factors in the phenotypic differentiation assay, a short-term culture of cloned B cells certainly free of accessory cells. Next, we investigated whether the effects seen in this assay could be related to results obtained in the long-term (four-day) assay of antibody production. Interleukin 1 induced cloned 70Z/3 B lymphocytes to express new cell surface markers in the phenotypic B cell differentiation assay. IL-2 rendered these B cells refractory to differentiation caused by IL-1. In the antibody production assay, IL-1 controlled, as was shown previously, an early phase of the response in which B cells become responsive to T cell-derived helper factors. In order to demonstrate the requirement for IL-1, it was necessary to rigorously prevent endogenous IL-1 production. Synergy between IL-1 and IL-2 was observed when IL-2 was given as late as day 2 of a four-day culture period. This synergy was seen over a broad dose range of IL-2 (10-1,000 U/ml). However, IL-2, when added in high concentrations (200-1,000 U/ml) during the early (IL-1-dependent) phase of the B cell response inhibited antibody production.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression and enhancement of the T cell-dependent production of antibody to SRBC in vitro by bacterial lipopolysaccharide.

LPS induced the production of antibody to sheep red blood cells (SRBC) in cultures of spleen cells from normal and T cell-depleted mice, and addition of SRBC to the cultures enchanced this T cell-independent response very little. By contrast, the T cell-dependent production of antibody to SRBC in vitro was suppressed when lipopolysaccharide (LPS) was added at the time when the spleen cells were cultured. Later addition of LPS to spleen cell cultures caused enhancement of antibody production, but only when LPS had not been added before. Addition of T cells that had been primed with SRBC in vivo did not reverse the LPS-induced suppression of antibody production. The data are interpreted to mean that either B cells are rendered incapable of receiving T cell signals in the presence of LPS or that LPS interferes with the appropriate association of cellular components which cooperate in the immune response to SRBC.