Biomedical subjects

M Suter

Publications and source records attributed to M Suter.

At least 37 records · Page 2Linked to original sources

PubMed2003

Laparoscopic Roux-en-Y gastric bypass: initial 2-year experience.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP)-essentially a restrictive bariatric procedure-is currently considered the gold standard for the surgical treatment of morbid obesity. Open surgery in obese patients is associated with a high risk of cardiopulmonary complications, wound infection, and late incisional hernia. Laparoscopic surgery has been shown to reduce perioperative morbidity and to improve postoperative recovery for various procedures. Herein we present our results with laparoscopic RYGBP after an initial 2-year experience. METHODS: A prospective database was created in our department beginning without the first laparoscopic bariatric procedure. To provide a complete follow-up of 6 months, the results of all patients operated on between June 1999 and August 2001 were reviewed. Early surgical results, weight loss, correction of comorbidities, and improvement of quality of life were evaluated. RESULTS: A total of 107 patients were included. There were 82 women and 25 men, with a mean age of 39.7 years (range, 19-58). RYGBP was a primary procedure in 80 cases (49 morbidly obese and 31 superobese patients) and a reoperation after failure or complication of another bariatric operation in 27 cases. Mean duration of surgery was 168 min for morbidly obese patients, 196 min for surperobese patients, and 205 min for reoperated patients (p <0.01). Conversion to open surgery was necessary in two cases. A total of 22 patients (20.5%) developed complication. Nine of them (8.4%) required reoperation for leak (five cases, or 4.6%), bowel occlusion (three cases, or 2.8%), or subphrenic abscess (one case, or 0.9%). mortality was 0.9%. Major morbidity decreased over time (first two-thirds, 12.5%, last third, 2.7%). major morbidity decreased over time (first two-thirds, 12.5%; last third, 2.7%). Excess weight loss of -50% was achieved in >80% of the patients, corresponding to a loss of 15 body mass index (BMI) units in morbidly obese patients and 20 BMI units in superobese patients. In the vast majority of patients, comorbidities improved or disappeared over time and quality of life improved. CONCLUSIONS: Laparoscopic Roux-en-Y gastric bypass is feasible, but it is a very complex operation. Indeed, it is associated with a long and steep learning curve, as reflected in the high number of major complications among our first 70 patients. The learning curve probably includes between 100 and 150 patients. With increasing experience, the morbidity rate becomes more acceptable and comparable to that of open RYGBP. The results in terms of weight loss and correction of comorbidities are similar to those obtained after open surgery, at least in the short term. However, only surgeons with extensive experience in advanced laparoscopic as well as bariatric surgery should attempt this procedure.

Adult↗

PubMed2003

Bone metabolism and risk of secondary hyperparathyroidism 12 months after gastric banding in obese pre-menopausal women.

OBJECTIVE: To evaluate, during the first postoperative year in obese pre-menopausal women, the effects of laparoscopic gastric banding on calcium and vitamin D metabolism, the potential modifications of bone mineral content and bone mineral density, and the risk of development of secondary hyperparathyroidism. SUBJECTS: Thirty-one obese pre-menopausal women aged between 25 and 52 y with a mean body mass index (BMI) of 43.6 kg/m(2), scheduled for gastric banding were included. Patients with renal, hepatic, metabolic and bone disease were excluded. METHODS: Body composition and bone mineral density (BMD) were measured at baseline, 6 and 12 months after gastric banding using dual-energy X-ray absorptiometry. Serum calcium, phosphate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bilirubin, urea, creatinine, uric acid, proteins, parathormone, vitamin D(3), IGF-1, IGF-BP3 and telopeptide, as well as urinary telopeptide, were measured at baseline and 1, 3, 6, 9 and 12 months after surgery. RESULTS: After 1 y vitamin D3 remained stable and PTH decreased by 12%, but the difference was not significant. Serum telopeptide C increased significantly by 100% (P<0.001). There was an initial drop of the IGF-BP3 during the first 6 months (P<0.05), but the reduction was no longer significant after 1 y. The BMD of cortical bone (femoral neck) decreased significantly and showed a trend of a positive correlation with the increase of telopeptides (P<0.06). The BMD of trabecular bone, at the lumbar spine, increased proportionally to the reduction of hip circumference and of body fat. CONCLUSION: There is no evidence of secondary hyperparathyroidism 1 y after gastric banding. Nevertheless biochemical bone markers show a negative remodelling balance, characterized by an increase of bone resorption. The serum telopeptide seems to be a reliable parameter, not affected by weight loss, to follow up bone turnover after gastroplasty.

Adult↗

PubMed2003

Rising role of obesity surgery caused by increase of morbid obesity, failure of conventional treatments and unrealistic expectations: trends from 1997 to 2001.

BACKGROUND: The authors analyzed the trends in anthropometric and behavioral characteristics among patients seeking weight loss and the trends in choice of treatments, between 1997 and 2001 in an outpatient obesity clinic. PATIENTS AND METHODS: 138 and 128 consecutive patients attending the out-patient obesity clinic at University Hospital of Lausanne were screened in 1997 and in 2001 respectively. Eating habits, body composition and treatment used were assessed. RESULTS: Median BMI was 35 kg/m2 in 1997 and 38 kg/m2 in 2001 (P <0.001) and waist circumference was 99 cm and 111 cm respectively (P <0.001). This increase in the average body weight involved especially patients <30 years old (P <0.01). Morbid obesity increased by 16% (P <0.01), and prevalence of abdominal obesity by 13% (P < 0.05). The median desired weight loss increased significantly from 25% to 29% (P <0.05). 64% of the patients in 1997 and 83% in 2001 (P <0.01) hoped for a weight loss of 20% of their baseline weight. Motivation to lose weight for esthetic reasons was found in 81% of the women and 55% of the men in 1997 (P <0.01), while in 2001 the percentage was 89 and 43 respectively (P <0.001). CONCLUSION: In spite of the increasing access to weight loss programs, we found that the patients are more severely obese, especially those <30 years old, and have more unrealistic expectations of weight loss. This may explain the doubling of the patients treated by surgery.

Adult↗

PubMed2002

Reduced acute phase response after laparoscopic total extraperitoneal bilateral hernia repair compared to open repair with the Stoppa procedure.

BACKGROUND: Although laparoscopic hernia repair has been shown to be associated with less postoperative pain and an earlier recovery, there is still controversy about its role in hernia surgery. In general, laparoscopy produces less trauma to tissues than open surgery. This has been reflected by the reduced acute phase inflammatory response observed after laparoscopic surgery compared to open surgery in various settings, such as cholecystectomy or hysterectomy. The aim of this study was to evaluate the acute phase response after bilateral hernia repair by comparing the open Stoppa procedure with the laparoscopic totally extraperitoneal prosthetic repair (TEPP). METHODS: Patients were randomly allocated to either technique after written informed consent was obtained. Measurements were made of complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-1b (IL-1b), IL-6, and tumor necrosis factor-a (TNF-a) preoperatively and 4, 24, and 48 h postoperatively. VAS pain scores, consumption of analgesics, and delay before resumption of normal activities were also recorded. All the procedures were performed under general anesthesia by or in the presence of the same surgeon. RESULTS: Thirty-nine patients were included: 19 underwent the Stoppa procedure and 20 had a laparoscopic repair. The two groups were well matched for age, sex, ASA score, and preoperative values. The operation took longer (p <0.001) in the group undergoing TEPP. Patients resumed their normal activities earlier (p <0.05) after laparoscopy. In the open group, there was a larger decrease of the lymphocyte count after 4 (p <0.01) and 24 h (p = 0.04); an increased elevation of ESR after 48 h (p = 0.02); a larger increase of IL-6 after 4 (p = 0.05), 24 (p = 0.003), and 48 h (p <0.001); and a larger increase in CRP after 24 (p = 0.05) and 48 h (p = 0.01). There was no morbidity. There was no difference in postoperative IL-1b, TNF-a, total white blood cell count, polymorphonuclear count, VAS for pain, or need for analgesics between the two groups, except on the operative day. CONCLUSIONS: The acute phase inflammatory response in clearly more active after the open Stoppa procedure than after TEPP, indicating that the former is associated with increased tissue trauma. This may play a role in the earlier recovery seen after the TEPP procedure.

Acute-Phase Reaction↗

PubMed2002

Rapid clonal development in a relapsed CML 11 years post replete allogeneic bone marrow transplantation.

Long-term survival of chronic myeloid leukaemia (CML) patients transplanted in chronic phase with a replete marrow have been described previously. The same success has not been achieved with patients in more advanced stages of the disease. We describe a CML patient who received an allogeneic bone marrow transplantation in accelerated phase. Cytogenetic and molecular analysis confirmed donor chimaerism, and the absence of the BCR-ABL mRNA. Almost 12 years post-transplant relapse was noted. Cytogenetic analyses showed a complex evolving karyotype. These findings are correlated with the longitudinal molecular analysis utilising real-time and VNTR PCR.

Adolescent↗

PubMed2002

Laser fluorescence bronchoscopy for detection of fluorescent reporter genes in airway epithelia.

Current methods for detecting successful gene transfer to airway epithelia involve obtaining a sample of the target tissue. This may affect the longevity of expression of the transgene under evaluation. We describe a laser fluorescence bronchoscopic system that can detect the expression of the fluorescent protein, green fluorescence protein (GFP), in the airway of monkeys that have been transfected with adenovirus, without the need for obtaining tissue. This technique will have applications in pre-clinical and clinical studies of gene transfer to airway epithelia and other surface epithelia accessible by endoscopy.

Adenoviridae↗

PubMed2002

Morbid obesity and postoperative pulmonary atelectasis: an underestimated problem.

UNLABELLED: Perturbation of respiratory mechanics produced by general anesthesia and surgery is more pronounced in morbidly obese (MO) patients. Because general anesthesia induces pulmonary atelectasis in nonobese patients, we hypothesized that atelectasis formation would be particularly significant in MO patients. We investigated the importance and resorption of atelectasis after general anesthesia in MO and nonobese patients. Twenty MO patients were anesthetized for laparoscopic gastroplasty and 10 nonobese patients for laparoscopic cholecystectomy. We assessed pulmonary atelectasis by computed tomography at three different periods: before the induction of general anesthesia, immediately after tracheal extubation, and 24 h later. Already before the induction of anesthesia, MO patients had more atelectasis, expressed in the percentage of the total lung area, than nonobese patients (2.1% versus 1.0%, respectively; P < 0.01). After tracheal extubation, atelectasis had increased in both groups but remained significantly more so in the MO group (7.6% for MO patients versus 2.8% for the nonobese; P < 0.05). Twenty-four hours later, the amount of atelectasis remained unchanged in the MO patients, but we observed a complete resorption in nonobese patients (9.7% versus 1.9%, respectively; P < 0.01). General anesthesia in MO patients generated much more atelectasis than in nonobese patients. Moreover, atelectasis remained unchanged for at least 24 h in MO patients, whereas atelectasis disappeared in the nonobese. IMPLICATIONS: We compared the resolution over time of pulmonary atelectasis after a laparoscopic procedure by performing computed tomography scans in two different groups of patients: 1 group had 10 nonobese patients, and in the other group there were 20 morbidly obese patients.

Adult↗

PubMed2002

Postoperative pulmonary dysfunction after bilateral inguinal hernia repair: a prospective randomized study comparing the Stoppa procedure with laparoscopic total extraperitoneal repair (TEPP).

The infraumbilical incision required for open repair of bilateral inguinal hernia with a giant prosthesis is associated with postoperative pain and respiratory impairment. The aim of this study was to evaluate the postoperative respiratory dysfunction after bilateral hernia surgery. Thirty-nine patients were randomized into two groups: open repair according to the Stoppa technique and laparoscopic extraperitoneal repair (TEPP). Respiratory function tests were performed before and 24 hours after surgery. The two groups were well matched for age, American Society of Anesthesiologists (ASA) risk score, type of hernia, and preoperative lung function. The postoperative forced vital capacity (FVC), peak expiratory flow (PEF), and forced expiratory volume in 1 second (FEV 1.0) were significantly altered in both groups. The PEF dropped 15% in both groups. The FVC dropped 22% after Stoppa versus 25% after laparoscopy (P = 0.7). The FEV 1.0 dropped 21% after Stoppa versus 9% after laparoscopy (P = 0.12). We conclude that laparoscopic preperitoneal and open bilateral hernia repair are followed by similar ventilatory dysfunction, although a trend toward better postoperative FEV 1.0 was noted after laparoscopy. This might play a role in selected patients with severe pulmonary limitations. Overall, the limited drop in pulmonary function following bilateral hernia repair under general anesthesia may serve to explain the low pulmonary morbidity that follows these procedures.

Adult↗

PubMed2002

Band infection with splenoportal venous thrombosis: an unusual but severe complication of gastric banding.

BACKGROUND: Band infection after gastric banding is a relatively rare complication. In most cases, it is manifested by abdominal pain associated with fever, and/or an abscess surrounding the access port. The treatment of choice consists of band removal and antibiotic therapy, and is usually effective. METHODS: Among the 322 patients having undergone gastric banding in our department, we report a 31-year-old woman who developed an infection of the band complicated by splenic and portal vein thrombosis 21 months after gastric banding. RESULTS: BMI was 40.9 kg/m2 when she underwent gastric banding. Postoperative course was uneventful, and excess weight loss reached 105% after 18 months. An abdominoplasty combined with bilateral mammoplasty and thigh dermolipectomy were performed. About 3 weeks later, she developed an otitis with fever and left upper abdominal pain. Despite antibiotics, pain and fever persisted. The operative wounds showed no sign of infection, and there was no sign of peritonitis. Computerized tomography showed a left subdiaphragmatic abscess surrounding the catheter and thrombosis of the splenic and portal veins. Treatment consisted of band removal, antibiotics and heparin. Recovery was uneventful with complete resolution of the thrombosis. CONCLUSIONS: Late band infection after gastric banding is rare, and is usually secondary to band erosion. Our case demonstrates that severe band infection can be caused by any infection causing bacteremia. Prompt band removal along with antibiotic therapy is the treatment of choice. Rapid treatment of any infection is mandatory in patients with a gastric band. Antibiotic prophylaxis during surgical and dental procedures could be useful in these patients.

Adult↗

PubMed2001

Monovalent fusion proteins of IgE mimotopes are safe for therapy of type I allergy.

By screening phage display random peptide libraries with purified immunoglobulin E (IgE) from birch pollen-allergic patients, we previously defined peptides mimicking natural IgE epitopes (mimotopes) of the major birch pollen allergen Bet v 1. The present study aimed to define a monovalent carrier for the IgE mimotopes to induce protective antibodies directed to the IgE epitopes, suitable for mimotope-specific therapy. We expressed the selected mimotopes as fusion proteins together with streptococcal albumin binding protein (ABP). The fusion proteins were recognized specifically by anti-Bet v 1 human IgE, which demonstrated that the mimotopes fused to ABP resemble the natural IgE epitope. Bet v 1-specific IgG was induced by immunization of BALB/c mice with fusion proteins. These IgG antibodies could inhibit IgE binding to Bet v 1. Skin testing of Bet v 1 allergic mice showed that the ABP mimotope constructs did not elicit type I skin reactions, although they possess IgE binding structures. Our data suggest that IgE mimotopes are safe for epitope-specific immunotherapy of sensitized individuals, when presented in a monovalent form. Therefore, ABP-fused mimotopes are promising candidates for a new type of immunotherapy based on the precise induction of blocking antibodies.

Allergens↗

PubMed2001

Plant adenosine 5'-phosphosulfate reductase is a novel iron-sulfur protein.

Adenosine 5'-phosphosulfate reductase (APR) catalyzes the two-electron reduction of adenosine 5'-phosphosulfate to sulfite and AMP, which represents the key step of sulfate assimilation in higher plants. Recombinant APRs from both Lemna minor and Arabidopsis thaliana were overexpressed in Escherichia coli and isolated as yellow-brown proteins. UV-visible spectra of these recombinant proteins indicated the presence of iron-sulfur centers, whereas flavin was absent. This result was confirmed by quantitative analysis of iron and acid-labile sulfide, suggesting a [4Fe-4S] cluster as the cofactor. EPR spectroscopy of freshly purified enzyme showed, however, only a minor signal at g = 2.01. Therefore, Mössbauer spectra of (57)Fe-enriched APR were obtained at 4.2 K in magnetic fields of up to 7 tesla, which were assigned to a diamagnetic [4Fe-4S](2+) cluster. This cluster was unusual because only three of the iron sites exhibited the same Mössbauer parameters. The fourth iron site gave, because of the bistability of the fit, a significantly smaller isomer shift or larger quadrupole splitting than the other three sites. Thus, plant assimilatory APR represents a novel type of adenosine 5'-phosphosulfate reductase with a [4Fe-4S] center as the sole cofactor, which is clearly different from the dissimilatory adenosine 5'-phosphosulfate reductases found in sulfate reducing bacteria.

Amino Acid Sequence↗

PubMed2001

A 10-year experience with the use of laparoscopic cholecystectomy for acute cholecystitis: is it safe?

BACKGROUND: In the era of open surgery, emergency open cholecystectomy has been shown for many reasons to be preferred to delayed surgery for acute cholecystitis. Despite the fact that elective laparoscopic cholecystectomy (LC) has become the gold standard for the treatment of symptomatic gallstone disease, the same procedure remains controversial for the management of acute cholecystitis because it is considered to be associated with more complications and an increased risk of common bile duct injuries than interval LC after resolution of the acute episode. The purpose of this report is to describe our experience with LC for acute cholecystitis during a 10-year period. METHODS: Patients undergoing laparoscopic surgery have been entered prospectively into a database since 1995. Those who underwent surgery before 1995 were added retrospectively to the same database. Patients were included in this study if they underwent emergency laparoscopic cholecystectomy for suspected acute cholecystitis. The diagnosis was based on clinical, laboratory, and echographic examinations. Analysis was performed to identify risk factors associated with conversion or morbidity. RESULTS: Of the 1,212 patients subjected to LC between 1990 and 1999, 268 (151 women and 117 men), with a mean age of 53 years, underwent surgery on an emergency basis for suspected acute cholecystitis. Their mean age (p = 0.002) and the proportion of men (p < 0.001) were higher than in the elective group. Delay before admission and surgery varied widely, but 72% of the patients underwent surgery within 48 h of admission. An intraoperative cholangiography, attempted in 218 patients, was successful in 207 (95%). Histologic examination confirmed acute cholecystitis in 82% of the patients. Conversion was necessary in 15.6% of the cases. It occurred more frequently in patients who underwent surgery later than 48 (p = 0.03) or 96 h (p = 0.006) after admission. No other predictor of conversion was found. Overall morbidity was 15.3%, and major morbidity was 4.4%. The only risk factor for morbidity was a bilirubin level greater than 20 mmol/l (p = 0.02). Three partial lesions of the common bile duct occurred. All were recognised and repaired immediately with no adverse effect. There was no difference in the overall rate of biliary complications between the patients operated for acute cholecystitis and those who underwent elective surgery. No reoperation was necessary, and there was no mortality. CONCLUSIONS: Although LC is safe and effective for acute cholecystitis, its associated morbidity and conversion rate are higher than for elective LC. The conversion rate decreases with experience. When surgery is performed within 2 or maximally 4 days of admission, in experienced hands, LC represents the treatment of choice for acute cholecystitis. Intraoperative cholangiography should be performed in every case because it helps to clarify the anatomy and allows for early diagnosis and repair of bile duct injuries.

Acute Disease↗

PubMed2001

Wet and dry deposition of 129I in Seville (Spain) measured by accelerator mass spectrometry.

Iodine-129 (T1/2 = 1.57 x 10(7) yr) concentrations have been determined by accelerator mass spectrometry in rainwater samples taken at Seville (southwestern Spain) in 1996 and 1997. This technique allows a reduction in the detection limits for this radionuclide in comparison to radiometric counting and other mass spectrometric methods such as ICP-MS. Typical 129I concentrations range from 4.7 x 10(7) 129I atoms/l (19.2%) to 4.97 x 10(9) 129I atoms/l (5.9%), while 129I depositions are normally in the order of 10(8)-10(10) atoms/m2d. These values agree well with other results obtained for recent rainwater samples collected in Europe. Apart from these, the relationship between 129I deposition and some atmospheric factors has been analyzed, showing the importance of the precipitation rate and the concentration of suspended matter in it.

Europe↗

PubMed2001

Protective T-cell-based immunity induced in neonatal mice by a single replicative cycle of herpes simplex virus.

Newborns are very susceptible to infections because their immune systems are not fully developed and react to antigen exposure preferentially with unresponsiveness. UV-inactivated herpes simplex virus type 1 (HSV-1) represents such an antigen and does not induce an immune response in neonates. In contrast, protective T cells were primed in newborn mice by a single replicative cycle of DISC HSV-1 given once within 24 h of birth. Each of the HSV-1-primed CD4(+) or CD8(+) T cells induced in wild-type or interferon-deficient mice conferred resistance to naive animals exposed to a lethal virus challenge. Inactivated HSV-1, injected at variable doses up to 10(4) times that of DISC HSV-1, was ineffective in inducing any detectable immune responses in neonates. Thus, the capacity of HSV-1 to replicate once, but not the number of virus particles per se, was decisive in inducing protective T-cell-associated immunity in newborn mice.

Animals↗

PubMed2001

Interleukin-12- and gamma interferon-dependent innate immunity are essential and sufficient for long-term survival of passively immunized mice infected with herpes simplex virus type 1.

Interferon (IFN) type I (alpha/beta IFN [IFN-alpha/beta]) is very important in directly controlling herpes simplex virus type I (HSV-1) replication as well as in guiding and upregulating specific immunity against this virus. By contrast, the roles of IFN type II (IFN-gamma) and antibodies in the defense against HSV-1 are not clear. Mice without a functional IFN system and no mature B and T cells (AGR mice) did not survive HSV-1 infection in the presence or absence of neutralizing antibodies to the virus. Mice without a functional IFN type I system and with no mature B and T cells (AR129 mice) were unable to control infection with as little as 10 PFU of HSV-1 strain F. By contrast, in the presence of passively administered neutralizing murine antibodies to HSV-1, some AR129 mice survived infection with up to 10(4) PFU of HSV-1. This acute immune response was dependent on the presence of interleukin-12 (IL-12) p75. Interestingly, some virus-infected mice stayed healthy for several months, at which time antibody to HSV-1 was no longer detectable. Treatment of these virus-exposed mice with dexamethasone led to death in approximately 40% of the mice. HSV-1 was found in brains of mice that did not survive dexamethasone treatment, whereas HSV-1 was absent in those that survived the treatment. We conclude that in the presence of passively administered HSV-1-specific antibodies, the IL-12-induced IFN-gamma-dependent innate immune response is able to control low doses of virus infection. Surprisingly, in a significant proportion of these mice, HSV-1 appears to persist in the absence of antibodies and specific immunity.

Animals↗

PubMed2001

Laparoscopic band repositioning for pouch dilatation/slippage after gastric banding: disappointing results.

BACKGROUND: Pouch dilatation with or without slippage of the band is a serious complication of gastric banding, often attributed to initial malpositioning of the band. Food intake is increased, and weight regain occurs. Progressive rotation of the band follows, leading to functional stenosis and dysphagia. Reoperation is necessary in most cases, and may consist of band removal, band change, band repositioning, or conversion to another bariatric procedure. MATERIAL AND METHODS: The study consisted of chart review of all patients who underwent laparoscopic repositioning of the band for pouch dilatation/slippage, and long-term follow-up through regular office visits and phone calls. RESULTS: Among 272 patients who had laparoscopic gastric banding, 20 (7.3%) developed pouch dilatation and/or slippage, of whom 19 underwent reoperation. Laparoscopic band repositioning was performed in 9 patients. One of them developed an intraabdominal collection postoperatively and required percutaneous CT-guided drainage. Recovery was uneventful in the other 8. Follow-up since reoperation varies from 13 to 42 months (mean 20 months). The result was good in 2 patients who lost further weight, satisfactory in 1 whose weight remained stable, and unsatisfactory in 6 patients. Weight loss was insufficient in 2, dilatation recurred in 2, and band infection or erosion developed each in 1 patient. 5 patients required further surgery: band removal in 3 and conversion to gastric bypass in 2. CONCLUSIONS: Laparoscopic band repositioning is feasible and safe if pouch dilatation and/or slippage develops after gastric banding. The mid-term results are disappointing in two-thirds of the patients. In some patients, pouch dilatation could result from poor adjustment to diet restriction rather than merely from original malplacement. Conversion to gastric bypass may be a better option in these cases.

Adult↗

PubMed2001

[Validation of laparoscopic surgical techniques].

The use of laparoscopic surgery has increased rapidly. However, a technically feasible procedure is not automatically recommendable. Thus, if cholecystectomy and fundoplication are currently fully validated techniques, this does not hold true for gastroplasty and kidney harvesting for transplantation: these operations are feasible indeed but their efficacy remains to be proved. Laparoscopic oncology has been shown to be feasible too, but its efficacy has not been documented yet.

Evidence-Based Medicine↗

PubMed2000

Age-related macular degeneration. The lipofusion component N-retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells.

10-20% of individuals over the age of 65 suffer from age-related macular degeneration (AMD), the leading cause of severe visual impairment in humans living in developed countries. The pathogenesis of this complex disease is poorly understood, and no efficient therapy or prevention exists to date. A precondition for AMD appears to be the accumulation of the age pigment lipofuscin in lysosomes of retinal pigment epithelial (RPE) cells. In AMD, these cells seem to die by apoptosis with subsequent death of photoreceptor cells, and light may accelerate the disease process. Intracellular factors leading to cell death are not known. Here we show that the lipophilic cation N-retinyl-N-retinylidene ethanolamine (A2E), a lipofuscin component, induces apoptosis in RPE and other cells at concentrations found in human retina. Apoptosis is accompanied by the appearance of the proapoptotic proteins cytochrome c and apoptosis-inducing factor in the cytoplasm and the nucleus. Biochemical examinations show that A2E specifically targets cytochrome oxidase (COX). With both isolated mitochondria and purified COX, A2E inhibits oxygen consumption synergistically with light. Inhibition is reversed by the addition of cytochrome c or cardiolipin, a negatively charged phospholipid that facilitates the binding of cytochrome c to membranes. Succinate dehydrogenase activity is not altered by A2E. We suggest that A2E can act as a proapoptotic molecule via a mitochondria-related mechanism, possibly through site-specific targeting of this cation to COX. Loss of RPE cell viability through inhibition of mitochondrial function might constitute a pivotal step toward the progressive degeneration of the central retina.

Aging↗