Valve repair versus replacement for mitral insufficiency: when is a mechanical valve still indicated?

OBJECTIVES: Although many advantages of mitral valve reconstruction have been demonstrated, whether specific subgroups of patients exist in whom mechanical valve replacement offers advantages over mitral reconstruction remains undetermined. METHODS: This study examined the late results of mitral valve surgery in patients with mitral insufficiency who received either a St. Jude Medical valve (n = 514) or a mitral valve reconstruction with ring annuloplasty (n = 725) between 1980 and 1996. RESULTS: Overall operative mortality was 7.2% in the patients receiving a St. Jude Medical mitral valve and 5.4% in those undergoing mitral valve reconstruction (no significant difference); isolated mortality was 2.5% in the St. Jude Medical group and 2.2% in the valve reconstruction group (no significant difference). The follow-up interval was more than 5 years for 340 patients with a mean of 39.8 months (98.5% complete). Overall 8-year freedom from late cardiac death, reoperation, and all valve-related complications was 72.8% for the St. Jude Medical group and 64.8% for valve reconstruction group (no significant difference). For patients with isolated, nonrheumatic mitral valve disease, 8-year freedom from late cardiac death and reoperation was better in the mitral valve reconstruction group (88.3%) than in the St. Jude Medical valve group (86.0%; p = 0.05). Furthermore, Cox proportional hazards regression revealed that mitral valve reconstruction was independently associated with a lesser incidence of late cardiac death (p = 0.04), irrespective of preoperative New York Heart Association class. However, the St. Jude Medical valve offered better 8-year freedom from late cardiac death, reoperation, and all valve-related complications than did mitral valve reconstruction in patients with multiple valve disease (77.0% vs 45.3%; p < 0.01). CONCLUSIONS: Therefore, mitral valve reconstruction appears to be the procedure of choice for isolated, nonrheumatic disease, whereas insertion of a St. Jude Medical valve should be preferred for patients with multiple valve disease.     

Follow-up after inguinal hernia repair. Questionnaire compared with physical examination: a prospective study in 299 patients

OBJECTIVE: To assess the value of a written questionnaire in the follow-up of patients after inguinal hernia repair. DESIGN: Prospective study. SETTING: University and two district hospitals. The Netherlands. SUBJECTS: 314 patients with 362 inguinal hernias. MAIN OUTCOME MEASURES: Correlation between answers to questionnaire and clinical examination in the diagnosis of recurrent hernias. RESULTS: 13/24 recurrences (54%) after a mean follow-up of 33 months with a follow-up rate of 93% were not diagnosed by the questionnaire. CONCLUSION: Follow-up after hernia repair must be by physical examination.     

Osmoregulation of the Atlantic stingray (Dasyatis sabina) from the freshwater Lake Jesup of the St. Johns River, Florida

The goals of this study were to (1) measure plasma osmolytes and rectal gland weights of a freshwater (FW) Atlantic stingray (Dasyatis sabina) population in the St. Johns River, Florida, and (2) determine how these parameters change after acclimation to seawater (SW). We hypothesized that the FW D. sabina may show physiological divergence from marine D. sabina, because the FW individuals reproduce and complete their life cycle in the St. Johns River. The FW D. sabina hyperregulate their plasma osmolality (621.4 mOsm kg(-1)), with plasma Na+, Cl-, and urea concentrations of 211.9, 207.8, and 195.9 mmol L(-1), respectively. FW D. sabina were exposed to 100% SW for 8 d, and their hematocrit did not change significantly compared to control animals left in FW. However, plasma osmolality increased significantly (953 mOsm kg(-1)), with significant increases in plasma concentrations of Na+, Cl-, and urea to 319.13, 296.1, and 329.76 mmol L(-1), respectively. The plasma of the SW-adapted D. sabina was hypo-osmotic and hypoionic to 100% SW. Rectal gland weight to body weight (RGBW) ratios of FW D. sabina were about 80% lower than RGBW ratios reported for marine D. sabina; the RGBW ratio did not increase significantly after SW acclimation. This may indicate that branchial and renal mechanisms are also involved with ion excretion. We conclude that the FW D. sabina are physiologically euryhaline and have not evolved the osmoregulatory strategy of stenohaline FW Potamotrygonid stingrays.     

Increased level of hemoglobin A1c, but not impaired insulin sensitivity, found in hypertensive and normotensive smokers

The objective of this study was to compare the gastric acidity patterns of patients with duodenal ulcers and normal children. Eight patients with duodenal ulcer had their intragastric pH monitored for two consecutive 24 h periods using intragastric glass electrodes. The first 24 h period elucidated pH patterns in the absence of treatment and the second period evaluated the acid suppressive effect of 15 mg/kg of cimetidine when given in three divided doses. Results showed that the ulcer patients were hyperacidic, particularly at midnight. This finding was in marked contrast to the results obtained in the study of normal controls. The mean pH of normal children was above 3 around midnight. This phenomenon is known as intragastric pH inversion. The mean pH 3 time (the cumulative duration of the time for which gastric pH is maintained at > or = pH 3) was significantly shorter in patients with ulcers. However, pH 3 time of these patients significantly increased throughout the 24 h recording period during the daytime and at night after the introduction of cimetidine. This resulted in an induction of apparent nocturnal intragastric pH inversion for the ulcer patients. This study demonstrates the usefulness of 24 h continuous intragastric pH monitoring in children. The data showed that there was a pattern of gastric hyperacidity in pediatric ulcer patients which is clearly distinct from that of normal children, particularly in the patterns occurring at midnight. Cimetidine at 15 mg/kg per day in three divided doses was effective in suppressing secretion even at night.     

A nitrilase-like protein interacts with GCC box DNA-binding proteins involved in ethylene and defense responses

Ethylene-responsive element-binding proteins (EREBPs) of tobacco (Nicotiana tabacum L.) bind to the GCC box of many pathogenesis-related (PR) gene promoters, including osmotin (PR-5). The two GCC boxes on the osmotin promoter are known to be required, but not sufficient, for maximal ethylene responsiveness. EREBPs participate in the signal transduction pathway leading from exogenous ethylene application and pathogen infection to PR gene induction. In this study EREBP3 was used as bait in a yeast two-hybrid interaction trap with a tobacco cDNA library as prey to isolate signal transduction pathway intermediates that interact with EREBPs. One of the strongest interactors was found to encode a nitrilase-like protein (NLP). Nitrilase is an enzyme involved in auxin biosynthesis. NLP interacted with other EREBP family members, namely tobacco EREBP2 and tomato (Lycopersicon esculentum L.) Pti4/5/6. The EREBP2-EREBP3 interaction with NLP required part of the DNA-binding domain. The specificity of interaction was further confirmed by protein-binding studies in solution. We propose that the EREBP-NLP interaction serves to regulate PR gene expression by sequestration of EREBPs in the cytoplasm.     

Spatially controlled cell engineering on biodegradable polymer surfaces

Controlling receptor-mediated interactions between cells and template surfaces is a central principle in many tissue engineering procedures (1-3). Biomaterial surfaces engineered to present cell adhesion ligands undergo integrin-mediated molecular interactions with cells (1, 4, 5), stimulating cell spreading, and differentiation (6-8). This provides a mechanism for mimicking natural cell-to-matrix interactions. Further sophistication in the control of cell interactions can be achieved by fabricating surfaces on which the spatial distribution of ligands is restricted to micron-scale pattern features (9-14). Patterning technology promises to facilitate spatially controlled tissue engineering with applications in the regeneration of highly organized tissues. These new applications require the formation of ligand patterns on biocompatible and biodegradable templates, which control tissue regeneration processes, before removal by metabolism. We have developed a method of generating micron-scale patterns of any biotinylated ligand on the surface of a biodegradable block copolymer, polylactide-poly(ethylene glycol). The technique achieves control of biomolecule deposition with nanometer precision. Spatial control over cell development has been observed when using these templates to culture bovine aortic endothelial cells and PC12 nerve cells. Furthermore, neurite extension on the biodegradable polymer surface is directed by pattern features composed of peptides containing the IKVAV sequence (15, 16), suggesting that directional control over nerve regeneration on biodegradable biomaterials can be achieved.     

Infection with human immunodeficiency virus type 1 upregulates DNA methyltransferase, resulting in de novo methylation of the gamma interferon (IFN-gamma) promoter and subsequent downregulation of IFN-gamma production

The immune response to pathogens is regulated by a delicate balance of cytokines. The dysregulation of cytokine gene expression, including interleukin-12, tumor necrosis factor alpha, and gamma interferon (IFN-gamma), following human retrovirus infection is well documented. One process by which such gene expression may be modulated is altered DNA methylation. In subsets of T-helper cells, the expression of IFN-gamma, a cytokine important to the immune response to viral infection, is regulated in part by DNA methylation such that mRNA expression inversely correlates with the methylation status of the promoter. Of the many possible genes whose methylation status could be affected by viral infection, we examined the IFN-gamma gene as a candidate. We show here that acute infection of cells with human immunodeficiency virus type 1 (HIV-1) results in (i) increased DNA methyltransferase expression and activity, (ii) an overall increase in methylation of DNA in infected cells, and (iii) the de novo methylation of a CpG dinucleotide in the IFN-gamma gene promoter, resulting in the subsequent downregulation of expression of this cytokine. The introduction of an antisense methyltransferase construct into lymphoid cells resulted in markedly decreased methyltransferase expression, hypomethylation throughout the IFN-gamma gene, and increased IFN-gamma production, demonstrating a direct link between methyltransferase and IFN-gamma gene expression. The ability of increased DNA methyltransferase activity to downregulate the expression of genes like the IFN-gamma gene may be one of the mechanisms for dysfunction of T cells in HIV-1-infected individuals.