Evidence of a role for GTP cyclohydrolase-1 in visceral pain.

BACKGROUND: The enzyme guanosine triphosphate-cyclohydrolase-1 (GCH-1) is a rate limiting step in the de novo synthesis of tetrahydrobiopterin (BH4) a co-factor in monoamine synthesis and nitric oxide production. GCH-1 is strongly implicated in chronic pain based on data generated using the selective GCH-1 inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP), and studies which have identified a pain protective GCH-1 haplotype associated with lower BH4 production and reduced pain. METHODS: To investigate the role for GCH-1 in visceral pain we examined the effects of DAHP on pain behaviors elicited by colorectal injection of mustard oil in rats, and the pain protective GCH-1 haplotype in healthy volunteers characterized by esophageal pain sensitivity before and after acid injury, and assessed using depression and anxiety questionnaires. KEY RESULTS: In rodents pretreatment with DAHP produced a substantial dose related inhibition of pain behaviors from 10 to 180 mg/kg i.p. (p < 0.01 to 0.001). In healthy volunteers, no association was seen between the pain protective GCH-1 haplotype and the development of hypersensitivity following injury. However, a substantial increase in baseline pain thresholds was seen between first and second visits (26.6 ± 6.2 mA) in subjects who sensitized to esophageal injury and possessed the pain protective GCH-1 haplotype compared with all other groups (p < 0.05). Furthermore the same subjects who sensitized to acid and possessed the haplotype, also had significantly lower depression scores (p < 0.05). CONCLUSIONS & INFERENCES: The data generated indicate that GCH-1 plays a role in visceral pain processing that requires more detailed investigation.

Results of a modified left atrial maze procedure as a combined procedure.

Starting in November 1999, we performed a left atrial radiofrequency ablation procedure concomitantly to a variety of cardiac surgical procedures. By January 2001, this ablation procedure had been performed on 100 patients (age 65.7 +/- 10.4 years, 53 % male, 47 % female, left atrium 51.0 +/- 7.5 mm) suffering either from chronic or paroxysmal atrial fibrillation. Primary cardiac pathology was mitral valve disease in most cases (43), aortic valve disease (28) or coronary heart disease (27). After bilateral pulmonary veins isolation, an additional ablation line was directed from the left pulmonary veins to the mitral valve annulus (Thermaline probe, Boston Scientific Corporation, USA). Finally, the left atrial appendage was resected. Surgical success was evaluated in the immediate postoperative course, 3 and 6 months postoperatively (ECG and echocardiography), and every year after that. Operative time was 229.7 +/- 56.5 min, ablation time 18.8 +/- 6.9 min. Follow-up is 95 % complete at the time of writing. Mean follow-up time was 7.3 months, ranging from 3 to 23 months. Success (sinus rhythm and atrial contraction) was proven in 72 out of 90 patients (80.0 %) (75.0 % mitral valve surgery, 84.0 % other cardiac surgery). The reported results support a broad spectrum of indications for this left atrial ablation procedure.

The Ross operation as a combined procedure and in complicated cases--is there an increased risk?

BACKGROUND: In this report we address the question whether the Ross operation can be recommended in combined and complicated cardiac procedures. METHODS: From February 1995 to July 2000, we performed 203 Ross operations, 129 with ideal clinical presentation (group 1: mean age 41 +/- 13 years, male 105). In 74 patients, the clinical presentation was complex (group 2: mean age 35 +/- 17 years, male 57), defined as previous aortic or cardiac operations in 32, active endocarditis in 8 or combined procedures in 40 patients. Follow-up is 95 % complete. RESULTS: Neither early mortality nor thromboembolic events were observed. Complications in group 1 vs. group 2 were prolonged ventilation in 1 vs. 1, pacemaker insertion in 1 vs. 2, minor myocardial infarction in none vs. 2 and postoperative bleeds in 2 vs. 3 patients. In group 1, one patient died of hemoptysis at 25 months, and in group 2 one sudden death occurred at 5 months. In the long term, two patients required reoperation for autograft failure in group 1, and one on group 2. Pulmonary stenosis required surgical treatment in one patient of group 2. Echocardiography revealed physiological gradients across the autograft with no significant regurgitation in either group. CONCLUSION: The Ross operation has excellent mid-term results and is a safe and attractive therapeutic approach, both in combined procedures and complex clinical presentations.

Technical evolution of the Ross operation: midterm results in 186 patients.

BACKGROUND: The Ross operation approaches the ideal aortic valve replacement. Between February 1995 and February 2000 we performed 186 procedures. This article reviews modifications introduced reflecting our experience. METHODS: In all patients the Ross operation was performed as root replacement. Echocardiographic follow-up was complete in 94% of patients. RESULTS: No operative death or early mortality occurred, nor did thromboembolic or hemorrhagic events. One patient died at 25 months from hemoptysis with pulmonary valve vegetations. Three patients required reoperation for autograft insufficiency. In 1 patient a tethered cusp was repairable and in 2 patients progressive autograft dilatation required autograft replacement. After routinely incorporating support into the aortic annulus and replacing all dilated ascending aorta, autograft dilatation did not recur. For the pulmonary homograft, one outflow patch was placed to relieve a symptomatic gradient. Nine patients with elevated gradients were under observation. Echocardiography revealed autograft median peak systolic gradients of 4.6+/-2.8 mm Hg, pulmonary homograft gradients of 14.8+/-9.6 mm Hg, and nil or insignificant regurgitation. CONCLUSIONS: The aortic annulus must be supported and the dilated ascending aorta replaced. Root replacement with a short autograft allows consistent results. Pulmonary homograft dysfunction is rare but unpredictable.

The ross operation in 225 patients: a five-year experience in aortic root replacement.

BACKGROUND AND AIM OF THE STUDY: The Ross operation, introduced more than 30 years ago, has recently undergone several modifications to improve both technical feasibility and results. At the authors' institution, the Ross operation, performed as root replacement in all cases, was commenced in February 1995. METHODS: A total of 225 patients (177 males, 48 females; mean age 39+/-15 years; range: 2 to 67 years) were operated on up to December 2000. Aortic regurgitation was present in 80 patients, stenosis in 69, and combined disease in 73; prostheses were replaced in three patients. Combined procedures were performed in 51 patients. Nine patients had active endocarditis. Follow up was 98% complete and totaled 471 patient-years. RESULTS: There was no early mortality, and no thromboembolic or hemorrhagic events. Complications included prolonged ventilation in two patients, perioperative myocardial infarction in three, pacemaker implants in three and perioperative bleeding in six. One patient died at 25 months from hemoptysis, and one at five months of unknown cause. In the long term, four patients required reoperation due to autograft regurgitation (one autograft repair, three autograft replacements). Routine aortic annulus support, a lowered threshold in replacing all dilated ascending aorta and keeping the autograft short to the level of the sinotubular junction seems to have prevented further autograft failure. Pulmonary homograft stenosis led to reoperation in one patient. Six patients with elevated gradients are currently under observation. Echocardiography revealed autograft median peak gradients of 5.1+/-2.8 mmHg, pulmonary homograft gradients of 14.2+/-11.5 mmHg, and no significant regurgitation, except in one additional patient with recently diagnosed aortic insufficiency (grade >2). CONCLUSION: Mid-term excellent hemodynamic results, low morbidity and reoperation requirement support the evolved root replacement technique and justify its further utilization.

Animal husbandry in Moretele 1 of North-West Province: implications for veterinary training and research.

Little is known regarding the keeping of animals in the Moretele 1 area of North-West Province, South Africa. Therefore, the status and dynamics of animal husbandry, as well as a general assessment of the needs of animal owners in this area were researched. Results of the investigation will be used to make recommendations for improved veterinary extension servicing in the area. Semi-structured interviews, based on discussions with relevant stakeholders in the community and a resultant problem conceptualisation, were undertaken at 266 randomly selected households in 51 villages and centres in the area, after which the data was checked and verified before being captured and analysed. The findings reveal that within the field of veterinary extension delivery: 1) there is a demand for visual and written extension material, 2) the extension services must function where clients reside, 3) limitations in terms of infrastructure are present and should be addressed through partnerships and coordination amongst all the role-players in the Moretele 1 area, and 4) cattle and poultry are the most important of the animal species and should be the focus points of extension, but the need to curb zoonotic disease should not be disregarded. In this regard veterinary clinics, private veterinarians and other role-players should be used in partnership with extension workers. Lastly, the veterinary clinic is regarded as helpful in many respects by the community consulted and the service should be upgraded and made available to a wider client base, especially where private and state veterinarians are unavailable or too expensive in such resource-limited communities.

The Ross operation: do native aortic, native pulmonary, and homograft pulmonary valve size and form differences influence results?

BACKGROUND: The pulmonary autograft approaches the ideal aortic valve substitute but numerous technical modifications are debated. The valves involved often differ in diameter and shape of the recipient annulus. We previously reported simplified surgical rules and early results of 52 patients and here we extend the report to 76 patients and analyze the mid-term results with respect to valve mismatch. METHODS: We studied the influence of geometric discrepancies. Valve regurgitation and gradient are compared for size discrepancies up to or more than 3 mm between recipient annulus and pulmonary autograft. The normal tricuspid recipient aortic annulus is compared with the flat circular redo-prosthetic or bicuspid annulus. Patients with plication of the aortic annulus and remodeling of the distal aorta are reviewed, and lastly donor homograft to pulmonary autograft discrepancies up to and more than 3 mm are compared. RESULTS: The results were comparable in all groups and no significant differences were observed. CONCLUSION: The pulmonary autograft operation may be simplified, with good results at the least in the first year despite operative tailoring due to valve discrepancies.

The influence of geometric mismatch between the native aortic, native pulmonary and homograft pulmonary valve on the results of the pulmonary autograft operation.

BACKGROUND: The pulmonary autograft operation has achieved broad acceptance and may be the ideal aortic valve substitute. Both the pulmonary autograft and the aortic homograft are more complicated procedures than prosthetic valve replacement. The trend to insert the pulmonary autograft as a root replacement rather than in the subcoronary position has achieved greater uniformity in the results, but there is still confusing diversity in opinions on technical details and anatomical dimensions. The importance of both size and shape mismatches between the three valves involved has received little attention. The valves often differ in diameter and in the shape of the recipient aortic annulus. This uncertainty and the diversity of opinions on essential technical details was disconcerting when we proceeded from aortic homograft-to-pulmonary autograft operations, this was compounded by only a single homograft being available for every operation as we have no homograft bank. METHODS: We compared the hemodynamic results regarding various geometric mismatches. All operative details were the same and patients were studied at regular intervals. Comparisons were made in patients with mismatch between recipient aortic annulus and pulmonary autograft. Patients with a normal tricuspid aortic annulus were compared to those with either a circular redo prosthetic valve annulus or a bicuspid recipient annulus. Thirdly we compared the patients with plication of the aortic annulus to those with remodeling of the distal aorta. Lastly we compared mismatch between donor homograft and pulmonary autograft. RESULTS: No influence of geometric mismatch between the three valves could be found on the results of the pulmonary autograft operation. CONCLUSIONS: Good results are obtainable without a painful learning curve if one keeps to certain surgical principles. It need not be a complicated operation and geometric mismatches between the three valves involved may be compensated for adequately.

Endaortitis of coarctation of the aorta after invasive diagnostics.

We report the case of a young woman in whom endaortitis developed at the site of a coarctation of the aorta after the invasive investigation of right fossa iliac pain. The organism responsible suggests a causal relationship to the investigations without antibiotic prophylaxis, and we emphasize the need for antibiotic prophylaxis in these cases. Invasive investigation of isolated coarctation in a young adult or adolescent is probably superfluous.