Biomedical subjects

N Doll

Publications and source records attributed to N Doll.

18 recordsLinked to original sources

PubMed2006

Stentless mitral valve implantation in comparison to conventional mitral valve repair or replacement at five years.

OBJECTIVE: A chordally supported stentless mitral valve (SMV) may be a suitable prosthesis for patients with severe degenerative mitral valve disease. We analyzed the five-year results and compared them with results after conventional mitral valve repair or replacement. METHODS: 155 patients, operated on since August 1997, were evaluated. 53 patients (ages, 68 +/- 8 years, 37 female, valve repair not feasible) received a SMV (Quattro), 51 patients (69 +/- 9 years, 32 female) had mitral valve repair (MVR) and 51 patients (66 +/- 9 years, 32 female) had a conventional mitral valve replacement (MVP). There were no significant differences with respect to preoperative NYHA functional class, left ventricular ejection fraction, cardiac index and surgical risk, according to the EuroSCORE. Mean follow-up is 64 +/- 18 (21-89) months. RESULTS: Surgery was performed using a median sternotomy (32 [SMV]/20 [MVR]/34 [MVP]) or a lateral mini-thoracotomy 21/31/17 approach. The SMV was safely attached to the papillary muscles. In-hospital mortality was 1, 2 and 4 respectively; re-operation was required in 6, 2 and 3 patients. Five-year survival rate was 80.6 +/- 4.4 % (SMV), 80.2 +/- 5.6 % (CMV) and 82.6 +/- 5.6 % (MVP), p = n.s. After hospital discharge, there was no significant difference in mortality in comparison to an age-matched control population. Echocardiography revealed acceptable SMV hemodynamics with preservation of left ventricular function. CONCLUSION: Midterm results after SMV implantation are comparable to conventional approaches. Complete preservation of the annulo-ventricular continuity is advantageous and close to physiologic hemodynamics can be achieved. Long term follow-up is required.

Aged↗

PubMed2006

Autopsy findings in patients on postcardiotomy extracorporeal membrane oxygenation (ECMO).

OBJECTIVES: To assess the clinical sensitivity of causes of death, concomitant diseases and postoperative complications including thromboembolic events in ECMO patients. METHODS: Between January 2000 and December 2004 154/202 patients (76.2%) died after postcardiotomy ECMO circulatory support. Autopsy was performed in 78 (50.6%) consecutive patients. Clinical and post-mortem data were prospectively recorded and compared concerning causes of death and postoperative complications including venous and arterial thromboembolisms and significant comorbidities. RESULTS: Mean age was 62.1+/-11.3 years, ejection fraction was 43.4+/-17.3%. 39.7% were emergency operations including acute coronary syndrome in 25.6% and preoperative cardiogenic shock in 28.2%. Successful ECMO weaning rate was 43.6%. Mean postoperative survival was 11.3 days. Premortem unknown concomitant diseases were found in 63 patients (80.8%) with clinical relevance in 9 patients (11.5%). Clinically unrecognized postoperative complications were found in 59 patients (75.6%) including acute cerebral infarction (n=7), acute bowel ischemia (1), intestinal perforation (3), pneumonia (4), venous thrombus formation (25) and systemic thromboembolic events (24). Clinically based causes of death were cardiac in 62.8%, multi-organ failure in 10.3%, cerebral in 5.1%, respiratory in 10.3%, fatal pulmonary embolism in 2.6%, technical in 5.1%, and others in 3.8%. Unexpected causes of death were found by autopsy in 22 patients (28.2%) including myocardial infarction (n=5), acute heart failure (4), fatal pulmonary embolism (2), pneumonia (2), ARDS (1), lung bleeding (1), fatal cerebrovascular event (4) and multiorgan failure (3). CONCLUSIONS: In ECMO patients major discrepancies between clinical and post-mortem examination were found. The true incidence of thromboembolic events is highly underestimated by clinical evaluation.

Aged↗

PubMed2005

Diabetes in patients undergoing coronary artery bypass grafting. Impact on perioperative outcome.

Diabetes mellitus is an established risk factor related to significant morbidity and mortality after coronary artery bypass grafting. Data on 9682 patients undergoing coronary artery bypass grafting either with (n=8917) or without cardiopulmonary bypass (off-pump coronary artery bypass grafting; n=765) were subjected to an univariate analysis to identify potential associations between diabetes mellitus and 26 a priori selected perioperative outcome variables. Those having a significant association with diabetes were then subjected to a stepwise logistic regression model to identify the impact of diabetes as compared to additional 22 different a priori chosen patient related risk factors and treatment variables. Prevalence of outcome variables independently associated with diabetes has been determined in the subgroup of diabetics undergoing coronary artery bypass grafting with cardiopulmonary bypass or off-pump coronary artery bypass grafting surgery to evaluate the effect of avoiding cardiopulmonary bypass on perioperative patient outcome. Diabetes mellitus was defined as glucose intolerance either treated dietary, with oral hypoglycemics or with insulin. According to this definition of diabetes mellitus we found an overall prevalence of 37.1% (coronary artery bypass grafting with cardiopulmonary bypass: 37.5%; off-pump coronary artery bypass grafting: 32.5%). Eleven outcome variables having a significant association with diabetes were identified. Diabetes could be identified as an independent predictor of postoperative delirium, renal dysfunction and respiratory insufficiency. Prevalence of these three variables was lower in diabetics undergoing off-pump coronary artery bypass grafting as in those undergoing coronary artery bypass grafting with cardiopulmonary bypass surgery reaching statistical significance with regard to postoperative delirium and respiratory insufficiency. In conclusion, diabetes mellitus is a significant independent predictor for three postoperative outcome variables in coronary artery bypass surgery. Avoiding cardiopulmonary bypass in diabetics seems to have a beneficial effect.

Age Distribution↗

PubMed2005

Expression of connexins 40 and 43 in human left atrium in atrial fibrillation of different aetiologies.

OBJECTIVE: To test the hypothesis that atrial fibrillation (AF) is associated with changes in the expression of connexins 40 and 43 in the left atrium with more pronounced changes in mitral valve disease than in lone AF. METHODS: Protein concentrations of connexin 40 and connexin 43 were analysed in left atrial tissue of patients undergoing cardiac surgery. One group of patients had lone AF (n = 41), one group had AF and mitral valve repair (n = 36), and one group in sinus rhythm served as controls (n = 15). RESULTS: Western blot analysis of connexin 40 and connexin 43 expression showed an increase of both gap junctional proteins (connexin 43 > connexin 40) in patients with AF of all forms compared with patients in sinus rhythm (p = 0.01 and p = 0.011, respectively). Subgroup analysis showed increased concentrations of connexin 40 in lone AF and AF with mitral valve disease compared with sinus rhythm (p = 0.06 and p = 0.029, respectively), whereas the same analysis for connexin 43 reached significance only in the mitral valve disease group (p = 0.031). No differences in connexin 40 and connexin 43 expression were detectable between lone AF and AF with mitral valve disease. Within the groups connexin 40 and connexin 43 expression did not differ between patients with paroxysmal AF and patients with chronic AF. CONCLUSION: The present study shows for the first time that AF can induce changes in the left atrium with increased connexin expression. Furthermore, no systematic differences between patients with paroxysmal and chronic AF were detected.

Atrial Fibrillation↗

PubMed2004

Requirement for renal replacement therapy in patients undergoing cardiac surgery.

BACKGROUND: Despite refinements in perioperative patient management renal insufficiency requiring renal replacement therapy (RRT) is still a common complication after cardiac surgical procedures associated with impaired patient outcome and increased costs. METHODS: Prospective data on 16,184 patients undergoing different cardiac surgical procedures (CABG, n = 8917; beating heart CABG, n = 1842 [OPCAB, n = 765; MIDCAB, n = 1077]; aortic valve surgery, n = 1830; mitral valve surgery, n = 708; double valve surgery, n = 381; CABG and valve surgery, n = 2506) between April 1996 and August 2001 were subjected to univariate and multivariate logistic regression analysis. Postoperative RRT was defined as any postoperative renal insufficiency requiring first time hemofiltration or dialysis during the postoperative stay. Patients with preoperative dialysis dependent renal insufficiency were excluded from further analysis. RESULTS: The overall prevalence of postoperative RRT was 4.7% which varied according to different surgical procedures. 45 out of 49 selected pre- and intraoperative patient- and treatment-related variables had a significant association with postoperative RRT. 10 of these (renal disease, myocardial infarction, diabetes, cardiogenic shock, urgent operation, NYHA > or = 3, intraoperative hemofiltration, perfusion time > or = 2 hours, intraoperative low cardiac output, perioperative high transfusion requirement) were independent predictors. OPCAB surgery and younger patient age were identified as having a significantly lower predictive value for postoperative RRT. Patients with postoperative RRT were found to have a significantly longer ICU- and total postoperative hospital stay as well as a higher 30-day mortality. CONCLUSION: Identifying perioperative risk factors associated with postoperative RRT will help to reduce the incidence of this complication. Avoiding cardiopulmonary bypass seem to be beneficial with regard to the prevalence of postoperative RRT.

Age Factors↗

PubMed2003

[Transvenous-subcutaneous implantation of a cardioverter-defibrillator after bioprosthetic replacement of a tricuspid valve].

The implantation of transvenous devices in patients who underwent tricuspid valve replacement represents problems, especially if an epicardial position is not available. The implantation of a "pace-sense" lead via the coronary sinus is a safe and feasible procedure. For experienced surgeons in implantation of biventricular devices, the implantation of leads via the coronary sinus is a routine procedure. Bipolar leads are essential for the correct sensing and pacing of the implantable cardioverter-defibrillator (ICD). In patients who underwent tricuspid valve replacement who have the indication of an ICD implantation postoperatively, the combination of a shock electrode placed in the superior vena cava, a subcutaneous array positioned on the left posterior close to the spine and an active can, placed subpectorally in the left infraclavicular region, is an alternative solution.

Adult↗

PubMed2003

[Surgical treatment of therapy resistant atrial fibrillation].

Atrial fibrillation in patients with isolated, therapy resistant, chronic or paroxysmal atrial fibrillation (AF) or AF in combination with additional valvular and non-valvular cardiac pathology can be surgically treated by different techniques. Unipolar high frequency, cryotherapy and microwave energy is a curative approach for the treatment of the left atrium for AF. The postoperative mortality and morbidity rate is comparable to other cardiac surgery procedures. It is a technically less challenging procedure as compared to the MAZE procedure and can be applied using a minimally invasive approach. Alternative techniques such as new cryotechnologies, laser application and bipolar high frequency energy need to be evaluated for effectiveness and safety.

Atrial Fibrillation↗

PubMed2003

Impact of diabetes mellitus on cardiac surgery outcome.

BACKGROUND: Diabetes mellitus is an established independent risk factor related to significant morbidity and mortality after cardiac surgical procedures. METHODS: Data on 16,184 patients undergoing cardiac surgery with and without cardiopulmonary bypass between April 1996 and August 2001 were prospectively evaluated. Diabetes mellitus as a patient related risk factor was subjected to univariate analysis to identify potential associations to 28 intra- and postoperative outcome variables. Outcome variables having a significant association with diabetes mellitus (p < 0.05) were then subjected to a stepwise logistic regression model to identify the influence of diabetes mellitus as compared to additional 30 different patient related risk factors and treatment variables. Diabetes mellitus was defined as glucose intolerance treated either dietary, with oral hypoglycemics or with insulin. RESULTS: Overall prevalence of diabetes mellitus was 33.3 %. Compared to non-diabetic patients the group with diabetes mellitus was older (p < 0.0001) and had a significantly lower ejection fraction (p < 0.0001). 15 outcome variables having a significant association with diabetes mellitus were identified. Furthermore, diabetes mellitus could be identified as an independent predictor for 7 postoperative outcome variables (prolonged ICU-stay, sternal instability and/or infection, sternal revision and refixation respiratory insufficiency, postoperative delirium, perioperative stroke, renal dysfunction, postoperative reintubation). CONCLUSION: Diabetes mellitus is a significant independent predictor for several postoperative outcome variables after cardiac surgery associated with higher postoperative morbidity and prolonged hospital stay.

Aged↗

PubMed2003

Epicardial treatment of atrial fibrillation using cryoablation in an acute off-pump sheep model.

BACKGROUND: The purpose of this study was to test the feasibility and effectiveness of cryoablation therapy (SurgiFrost trade mark CryoCath, Endocare Inc., Irvine, California, USA) for linear epicardial treatment of atrial fibrillation in an acute off-pump sheep model. METHODS: After thoracotomy, we performed epicardial cryoablation (2 min intervals at -160 degrees C) with pacing electrodes positioned at the left atrial appendage (LAA), the pulmonary veins (PVs), the right atrial appendage (RAA), and the vena cava cranialis (VCC) in 8 sheep. Circular epicardial ablations were performed with online temperature measurement in the ascending aorta and in the esophagus. The sheep were sacrificed two hours after ablation procedure, and heart, lungs, and esophagus were retrieved for histological examination. Out of all 8 sheep, histo-pathological analysis was performed on the RAA and VCC in 6 sheep and on the CAA and PV in all 8 sheep. RESULTS: Thin-walled structures such as PVs and VCC showed electrical isolation. No significant changes in temperature in the descending aorta and the esophagus were observed. There was evidence of extensive transmural alteration including vascular lesions, myocardial degeneration and necrosis as well as epi- and endocardial necrosis in the left atria in three of 8 cases, in the right atria in 5 of 6 cases, in the VCC in 6 of 6 cases, and in the PV in 5 of 8 cases. Mild lesions of the muscular layer of the esophagus were found in 7 of 8 cases. CONCLUSIONS: Epicardial cryoablation is not effective on thicker tissues like LAA and RAA due to the rewarming of the current blood flow. However, thin tissues like VCC and PV can be isolated. Further chronic studies are necessary to evaluate the potential for regeneration of adjacent structures.

Animals↗

PubMed2002

Mediastinitis and cardiac surgery--an updated risk factor analysis in 10,373 consecutive adult patients.

BACKGROUND: Deep sternal wound infection (DSWI) remains a serious complication after cardiac surgery. New evolving techniques including the utilization of internal mammary arteries (IMA), beating heart procedures, and minimal invasive surgery (MIC) require an updated risk factor analysis to identify high risk patients in order to improve perioperative treatment. METHODS: 10,373 consecutive patients receiving cardiac surgery between May 1996 and August 1999 were evaluated: 9,303 underwent full sternotomy whereas a minimally invasive (MIC) approach using partial sternotomy or lateral thoracotomy was used in 1,070 patients. DSWI was defined as the evidence of mediastinitis seen at reoperation along with one or more of the following: positive culture of mediastinal fluid, positive blood culture or temperature higher than 38 degrees C and/or leukocytosis. RESULTS: The overall incidence of DSWI in the "full sternotomy" group was 1.44 % (134 of 9,303). Univariate risk factor analysis showed a significant influence of IMA use, ICU / IC treatment > 5 days, postoperative ventilator time > or = 72 h, need for reexploration, diabetes, surgery time > or = 180 min, assist device implantation (including use of IABP), peripheral vascular disease and increased body mass index. Multivariate analysis identified double IMA, ICU treatment > 5 days, single IMA, diabetes, reexploration and increased body mass as significant risk factors. No mediastinitis was observed in the MIC group. CONCLUSION: As DSWI is related to sternotomy, a MIC approach should be considered for patients at high risk for DSWI. IMA takedown as a pedicled graft should be especially avoided in patients with diabetes since the risk for postoperative mediastinitis is unacceptably high in this patient group.

Aged↗

PubMed2001

Regression of left ventricular hypertrophy after surgical therapy for aortic stenosis is associated with changes in extracellular matrix gene expression.

BACKGROUND: Regression of left ventricular hypertrophy (LVH) after surgical correction for aortic stenosis is not fully understood on the molecular level. The aim of this study was to examine whether there is an association between LVH regression and extracellular matrix (ECM) gene expression. METHODS AND RESULTS: A standard model of controlled LVH induction by supracoronary banding (A=baseline) was applied in 44 growing sheep (age, 6 to 8 months). Surgical correction to release the pressure gradient was performed 8.3+/-1 months later (B). The animals were killed after another 10.1+/-2 months (C). At all time points, hemodynamic evaluations and quantitative analysis of mRNA and protein expression for matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) was performed. Left ventricular mass index was 82+/-21 (A) versus 150+/-33 (B), P<0.01, and 78+/-18 g/m(2) (C), P<0.01. Left ventricular function and cardiac index remained stable. Myocardial fiber diameter index was 9.1+/-1.2 (A) versus 12.3+/-1.4 (B), P<0.01, and 8.4+/-1.3 micrometer/m(2) (C), P<0.01. In parallel to the development of LVH at B, gene expression was increased significantly for MMP-1, MMP-2, MMP-3, and MMP-9 and for TIMP-1 and TIMP-2 and decreased significantly for TIMP-3. After surgical correction (C), there was a complete regression of gene expression to baseline measures. CONCLUSIONS: Controlled induction of compensated LVH leads to significant increase in ECM gene expression. The regression of LVH after surgical therapy is associated with complete regression of ECM gene expression. However, no cause-and-effect relation could be demonstrated.

Animals↗

PubMed2001

Acute aortic dissection during pregnancy.

We review the cases of two women with acute aortic dissection during their last trimester of pregnancy who underwent aortic root replacement. One patient with type A dissection had to undergo surgical intervention immediately, and required extracorporal membrane oxygenation for four days. The other patient with a pre-diagnosed Marfan's disease had suffered a type B dissection and had to undergo emergency operation after developing a type A dissection nine days later.

Adult↗

PubMed2000

Humoral immune response during coronary artery bypass grafting: A comparison of limited approach, "off-pump" technique, and conventional cardiopulmonary bypass.

BACKGROUND: The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques. METHODS AND RESULTS: Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-alpha receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (P:<0.05). TNF-alpha receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach. CONCLUSIONS: There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma. The release of immune mediators is enhanced by the use of CPB during various perioperative and postoperative phases. The type of operative approach did not influence this immune response.

Aged↗

PubMed2000

Minimally invasive saphenous vein harvesting techniques: morphology and postoperative outcome.

BACKGROUND: Conventional saphenous vein harvest is associated with numerous complications, which may be reduced by minimally invasive vein-harvesting techniques. The integrity of the venous endothelium must be guaranteed before using new saphenous vein harvesting techniques. This short-term study compared the clinical outcome of two minimally invasive techniques with the conventional technique, and compared morphology as documented by light and electron microscopy. METHODS: Ninety-two patients were prospectively randomized into three groups. Two different minimally invasive techniques of greater saphenous vein harvesting were used in sixty-two patients. One used a video-assisted dissector (group A, n = 31), and one used a light-coupled retractor (group B, n = 31). Thirty patients were treated by the conventional technique (group C). RESULTS: Incision lengths were 7.6+/-2.1 cm in group A and 9.3+/-3.2 cm in group B, as compared with 38.9+/-8.7 cm in the conventional group. Harvesting time was prolonged by a mean of 26% when using a minimally invasive technique. Conversion rate to the open technique was 3 of 31 (9.3%) in group A and 2 of 31 (6.2%) in group B. No wound complications were noted in group A, but one wound inflammation was seen in group B; only a mild hematoma was seen in both groups. Edge necrosis, wound separation and inflammation were noted in the conventional group. Light and electron microscopy revealed no significant denudation of the endothelial layer in groups A and B as compared with group C. CONCLUSIONS: These data show an excellent postoperative result when using the minimally invasive technique as compared with the conventional group. The safety of the technique is demonstrated by the preservation of endothelial integrity.

Feasibility Studies↗

PubMed2000

Pain is significantly reduced by cryoablation therapy in patients with lateral minithoracotomy.

BACKGROUND: In minimally invasive cardiac surgery use of a lateral minithoracotomy is associated with early postoperative rehabilitation but also relatively high pain levels during the first 3 postoperative days. Cryoablation therapy was evaluated prospectively. METHODS: From April 1999 until September 1999, 57 patients underwent lateral minithoracotomy for mitral valve operation (n = 18) or minimally invasive direct coronary artery bypass grafting (n = 39). Intraoperatively, patients were randomly assigned to cryoablation or intercostal application of local anesthetic agents. A standardized questionnaire was used for prospective pain assessment on postoperative days 1 to 7. RESULTS: From postoperative day 1 to 7 pain levels declined in all groups. Overall pain levels were significantly lower in the cryo group than in the control group (p < 0.0001, GLM). According to diagnoses, pain levels were significantly lower after MIDCABG and cryo versus control; after mitral valve operation they were lower in the cryo group and almost reached significance. CONCLUSIONS: Cryoablation is easy to perform and leads to a significant reduction in pain and lower request for additional pain medication after lateral minithoracotomy in minimally invasive cardiac operation.

Anesthetics, Local↗

PubMed1999

Women and cardiac rehabilitation: referral and compliance patterns.

Heart disease is the primary killer among American women. Differences in referral for cardiac rehabilitation, as well as compliance rates, have been reported between male and female cardiac patients. This study explored the use of Phase I and Phase II cardiac rehabilitation programs by male and female patients. In particular, the study aimed to investigate the relationship between eligibility and subsequent referral to Phase II cardiac rehabilitation in both men and women, as well as their compliance rates in completing Phase II. In addition, for those patients who never started a Phase II program, their reasons for nonparticipation were explored. Structured patient interviews and chart audits were used to explore cardiac rehabilitation eligibility criteria, referral and completion rates. The sample consisted of 87 patients (46 women and 41 men) who were admitted with a medical diagnosis of angina, myocardial infarction, coronary artery bypass grafting, or valve replacement surgery. Men had higher eligibility rates for Phase I, whereas women had higher eligibility rates for Phase II; more men received a referral for Phase II from their physician than women did. Men had a higher completion rate with Phase II compared with women. For those patients who chose not to start a Phase II program, the most common reasons cited included transportation problems, insurance issues, and having exercise equipment at home. Although women are being referred for cardiac rehabilitation, fewer complete the programs. Continued education is essential to teach women the importance of cardiac rehabilitation to overall recovery and adaptation to an acute cardiac event. In addition, cardiac rehabilitation programs must be structured to meet the unique needs of women and thereby remove obstacles that have prevented higher participation rates by women in the past.

Adult↗

PubMed1998

Women and coronary disease: relationship between descriptors of signs and symptoms and diagnostic and treatment course.

BACKGROUND: Heart disease is the No. 1 killer among women in the United States. Differences in the clinical features of coronary heart disease among men and women have been reported, along with various approaches to the diagnostic workup and therapeutic interventions. PURPOSE: To explore the relationship between descriptors of signs and symptoms of coronary heart disease and follow-up care and to investigate any differences between male and female patients. METHODS: Structured interviews with patients and chart audits were used to assess initial signs and symptoms, associated cardiac-related signs and symptoms, and the diagnostic tests and interventions used for treatment. The sample consisted of 98 patients (51 women and 47 men) who were admitted with a medical diagnosis of myocardial infarction. RESULTS: Chest pain was the most common sign or symptom reported by both men and women. The 4 most common associated signs and symptoms were identical in men and women: fatigue, rest pain, shortness of breath, and weakness. However, significantly more women than men reported loss of appetite, paroxysmal nocturnal dyspnea, and back pain. Women were also less likely than men to have angiography and to receive i.v. nitroglycerin, heparin, and thrombolytic agents as part of acute management of myocardial infarction. CONCLUSION: Chest pain remains the initial symptom of acute myocardial infarction in both men and women. However, women may experience some different associated signs and symptoms than do men. Despite these similarities, men still are more likely than women to have angiography and to receive a number of therapies.

Adult↗

PubMed1989

High dose nicotinamide fails to prevent diabetes in BB rats.

Nicotinamide which is an inhibitor of poly (ADPR) synthetase and precursor of NAD has been observed to prevent diabetes in some experimental models possibly by protecting beta cells. To determine whether nicotinamide could cure or prevent type 1 diabetes, we administered large doses (0.5 g/Kg/d) to BB rats. When used in the 45 days following diagnosis nicotinamide failed to bring remission. As a preventive treatment, nicotinamide administered between the 40th and 90th day of age, alone or in association with desferrioxamine did not significantly lower the incidence of diabetes (23% and 30.8% respectively vs. 56.6%). When used earlier, immediately after weaning, nicotinamide did not affect the incidence of diabetes in this model (62.5%). The degree of protection was not comparable with that obtained with cyclosporin A (15% of diabetic animals). Histology study of the pancreas from the animals killed either immediately or 1 year after treatment revealed no endocrine tumor. These findings suggest that in BB rats nicotinamide has little or no effect on the course of autoimmune diabetes mellitus thus dampening the high hopes for this drug in the treatment of human diabetes.

Age Factors↗