Ghrelin alterations during experimental and human sepsis.

BACKGROUND: Ghrelin is a hormone mainly produced by cells of the gastric mucosa, which has been shown to possess anti-inflammatory and immunomodulatory properties. The objective of the study was to investigate ghrelin levels during sepsis, as well as in an experimental sepsis model. METHODS: All consecutive admissions to the ICU of a tertiary hospital in Athens, Greece were screened for eligibility during the study. Thirty four non-septic patients upon ICU admission who subsequently developed sepsis were enrolled. Clinical data and scores were recorded, and blood samples were obtained at baseline (upon ICU admission), and at sepsis development. Total and active ghrelin, leptin, and cytokines were measured. Moreover, lipopolysaccharide (LPS) was administered to mice in order to induce endotoxemia and at specified time points, blood and tissue samples were collected. RESULTS: In patients, serum total and active ghrelin concentrations were significantly elevated in sepsis compared to baseline (553.8 ±â€¯213.4 vs 193.5 ±â€¯123.2, p < 0.001; 254.3 ±â€¯70.6 vs 56.49 ±â€¯16.3, p < 0.001). Active ghrelin levels at the sepsis stage were inversely correlated with SOFA score and length of stay in the ICU (p = 0.023 and p = 0.027 respectively). In the mouse endotoxemia model ghrelin levels were elevated following LPS treatment, and the same trend was observed for leptin, TNFα and IL-6. Ghrelin administration managed to reduce IL-6 levels in mouse serum and in BALF. Pulmonary expression of ghrelin and its receptor GHSR1a was found decreased in LPS-treated mice. CONCLUSIONS: In a well-defined cohort of ICU patients, we have demonstrated that active and total ghrelin increase in sepsis. The same is true for the experimental sepsis model used in the study. The inverse correlation of active ghrelin levels with SOFA score and length of ICU stay among septic patients is indicative of a potential protective role of active ghrelin during the septic process.

Left ostial stenosis surgical angioplasty.

BACKGROUND: Left main coronary stenosis, including ostial lesions, is conventionally treated by coronary bypass surgery. This approach, however, restores a less physiological retrograde perfusion to part of the myocardium and may contribute to a competition of flows in non-occluded coronaries. Direct surgical reconstruction of the LMCA has been described and theoretically avoids these potential drawbacks. METHODS: From May 1995 until December 2005, 25 patients with ostial left main stenosis underwent surgical angioplasty in our unit. Patients were all followed up clinically and with transesophageal echocardiography. RESULTS: Mean age of the patients was 59.7 years (range, 33 - 73 years). The male to female ratio was 14 : 11. The left main coronary stem was approached anteriorly in all patients. The onlay patch consisted of saphenous vein and was extended across the aortotomy suture line. There were no early deaths or perioperative myocardial infarctions. All patients underwent follow-up clinical examination and transesophageal (TOE) echocardiography as well as other investigations when required. TOE demonstrated a wide open left main coronary artery normal flow pattern, and no aneurysmal dilatation or calcification of the onlay patch in 24 patients. After a mean follow-up of 8 years, the all-cause survival was 88 %, while event-free survival was 80 % with 21 pts remaining in CCS I. CONCLUSION: Surgical reconstruction of the LMCA is a safe and effective treatment for left main stenosis. Re-institution of normal blood flow through the left main coronary artery possibly confers advantages over bypass surgery.

Extended ganciclovir prophylaxis in lung transplantation.

BACKGROUND: Positive cytomegaloviral status of the donor or of the recipient adversely affects survival and enhances the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. The role of ganciclovir prophylaxis in cytomegalovirus infection in respect to obliterative bronchiolitis or to BOS development is not known. METHODS: From the Papworth transplant database, we identified 146 patients who received organs from cytomegalovirus-positive donors. We classified patients into 3 groups as follows: Group 1 consisted of 42 patients who underwent transplantation between 1990 and 1992 when no prophylaxis was given; Group 2 consisted of 49 patients who underwent transplantation between 1992 and 1995 when 4 weeks of IV ganciclovir was given as prophylaxis; and Group 3 consisted of 55 patients who underwent transplantation between 1995 and 1998 when cytomegalovirus prophylaxis consisted of IV (1 week) followed by oral ganciclovir for a total of 3 months. Donor management, recipient management during and after surgery, and pharmacotherapy were uniform during the study period. We used survival and regression methods to compare these groups, adjusting for the transplantation type (single lung, double lung, or heart-lung) and for HLA typing. RESULTS: We found a significant difference among all 3 groups in numbers of cytomegaloviral disease episodes in the 1st year after transplantation. The number of rejection episodes in the 3 groups during the 1st post-transplant year gradually decreased from Group 1 to Group 3. We identified no statistically significant benefit in the time to BOS occurrence or in actuarial survival. CONCLUSION: Extended prophylaxis with IV and oral ganciclovir practically abolishes cytomegaloviral disease and is related to a decreased incidence of rejection episodes. However, ganciclovir prophylaxis is not related to a decreased incidence or progression of BOS or survival.

Dual-probe 24-hour ambulatory pH monitoring for diagnosis of laryngopharyngeal reflux.

BACKGROUND: Patients with gastroesophageal reflux disease may suffer from a variety of symptoms from the upper aerodigestive tract. The objective of this study was to determine the impact of dual-probe 24-hr pH monitoring in the diagnosis of reflux-related otolaryngological disorders. METHODS: Twenty-two patients with symptoms such as chronic cough, globus pharyngeus, heartburn, dysphonia and burning sensation of the tongue underwent a complete ear, nose and throat examination, 24-hr dual-probe pH monitoring, and oesophago-gastro-duodenoscopy. RESULTS: pH monitoring revealed gastroesophageal (distal) reflux in all patients and pharyngeal (proximal) reflux in 21 patients. Treatment consisted of a proton pump inhibitor (esomeprazole). Within 4 weeks 68 per cent of patients had no laryngopharyngeal symptoms; within 8 weeks 95 per cent of patients were symptom-free. CONCLUSIONS: Patients with atypical reflux symptoms such as hoarseness, globus sensation or throat-clearing responded well to anti-reflux treatment.

Heart-lung transplantation for Eisenmenger syndrome: early and long-term results.

BACKGROUND: Heart-lung transplantation (HLT) for Eisenmenger syndrome (ES) provides superior early and intermediate survival when compared with other forms of transplantation. The early risk factors and long-term outcome of HLT for ES are less well defined. METHODS: We analyzed 263 patients who had undergone HLT at our institution during more than 15 years. Fifty-one consecutive patients with ES who underwent HLT, 33 (65%) of which had simple anatomy, were compared with 212 cases having HLT for other indications (non-ES). RESULTS: Female sex and previous thoracotomy were more prevalent in the ES group. Patients with ES had greater postoperative blood loss and returned more frequently to the operating room for control of bleeding. There were 8 (16%) early deaths in the ES group compared with 27 (13%) in non-ES (p = 0.65). One-, 5-, and 10-year survival rates for ES were 72.6%, 51.3%, and 27.6%, respectively, compared with non-ES of 74.1%, 48.1%, and 26.0%, respectively, and there was no difference in survival overall (p = 0.54). Among ES patients, previous thoracotomy was a risk factor for hospital death. A subgroup analysis based on simple versus complex type of ES did not show statistically significant differences in terms of postoperative course or early or late survival. CONCLUSIONS: Heart-lung transplantation is a successful procedure for ES. Despite a greater frequency of risk factors and a more difficult operative course, early and late outcome with HLT is comparable to non-ES recipients.

A simple and flexible blood cardioplegia delivery system.

We describe a simple technique for the delivery of high haematocrit blood cardioplegia. The system allows for a user defined, variable concentration of warm, tepid or cold solution to be delivered. The concentration can be varied based upon the pressure regulated flow of blood, and is manipulated by a four variable equation calculated by a spreadsheet formula stored in a hand-held computer. The system provides a very accurate and rapid method of titration and administration of the cardioplegic solution.

Thoracic organ transplantation at Papworth Hospital.

More than 1,200 patients have now undergone thoracic transplantation at Papworth Hospital and about 90 transplants are performed annually. Papworth remains one of the largest transplant units in the UK. Unique activities include a very large heart-lung transplant program: 247 patients have now undergone heart-lung transplants and 73 domino heart transplants have been performed. The 5-year survival rates are 71% for heart transplants, 48% for heart-lung and 41% for lung transplants, respectively. Chronic obliterative bronchiolitis remains an important limitation for heart-lung and lung transplant survival.