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Biomedical subjects

G Decker

Publications and source records attributed to G Decker.

At least 37 records · Page 2Linked to original sources

Is there a role for radical esophagectomy.

The aim of primary surgery in the treatment of carcinoma of the esophagus and gastroesophageal junction (GEJ) is definite cure. To obtain this goal R0 resection, i.e. complete macroscopic and microscopic removal is of paramount importance. However, one of the most controversial questions remains the extent of lymph node dissection, in particular the value of cervical lymph node dissection (the so called third field). Three arguments are believed to favour more extended lymphadenectomy: optimal staging, prolonged tumour control, improved cure rate. (a) Optimal staging: available data indicate that unforeseen lymph node involvement in the neck is encountered in approximately 30% of the patients after 3-field lymphadenectomy. Even in tumours of the GEJ up to 20% of the patients in the T3N+ setting have unforeseen positive nodes in the neck. (b) Prolonged tumour control: radical esophagectomy and extensive lymphadenectomy is decreasing locoregional recurrence substantially, below 10%, in several published reports. More over extended lymphadenectomy seems to defer onset of locoregional recurrence and generalised metastasis for up to 3 years or more. (c) Improved cure rate: despite a lack of prospective randomised study many studies indicate a distinct survival benefit after radical esophagectomy and extensive lymphadenectomy. From the available data it becomes clear that radical surgery and extensive lymphadenectomy offers the best chances for prolonged survival or cure. This can be done without increasing hospital mortality and morbidity. Survival figures obtained by this technique are a gold standard to which survival obtained by other techniques (e.g. multimodality treatment forms, VATS resections) have to be compared.

Adenocarcinoma↗

Esophageal cancer.

Carcinoma of the esophagus and gastroesophageal junction continues to be an aggressive cancer with poor prognosis, despite improved surgical results and the potential benefit of combined multimodality regimens. Additional data seem to confirm the rising incidence of adenocarcinoma, although users of nonsteroidal anti-inflammatory drugs seem to have a decreased risk. Much attention is focused on detecting high-grade dysplasia and early carcinoma with promising results using red fluorescence after preceding 5-aminolevulinic acid (ALA) sensitization. Positron emission tomography made a major breakthrough and seems to be superior to computed tomography in detecting distant metastasis as well as lymph node metastasis. Endoscopic ablation of early carcinoma results in promising early results, but a major issue remains the EUS discrimination between Tis-T1a and T1b, as the latter is frequently associated with lymph node metastasis. In the field of molecular biology, research is unraveling the role of cadherins and catenins in the mechanism underlying cell adherence, cell movement, and progress toward tumor formation. Mutations of p53 are correlated with loss of apoptosis and form an early step in progress toward carcinoma as well as mutations of other tumor-suppressing genes (eg, p16 and Rb mutations). Detection of such mutations may become useful prognostic indicators, but illustrate the genetic polymorphism influencing the susceptibility to carcinoma. Several lines of evidence suggest that the stabilizing or overriding of p53 mutant cancer cells and restoration of the wild-type tumor suppressor gene p53 may improve results of DNA damaging treatment modalities. Further research in this field may lead to new forms of anticancer therapy.

Journal Article↗

Treatment of esophageal carcinoma.

Cancer of the esophagus and gastroesophageal junction remains a virulent malignancy with an overall poor prognosis. Especially in the Western hemisphere, the incidence of adenocarcinoma is sharply rising. Over the last two decades, surgery has become the mainstay of treatment. Decreased surgical mortality and standardization of oncologic principles focusing on the completeness of resection are believed to be responsible for the improved 5-year survival rates, which are reaching > or = 30%. Until now, there has been no proven benefit from combined neoadjuvant treatment modalities using chemotherapy or chemoradiotherapy except for the subset of patients showing a complete response at pathologic examination. Further research should focus on new chemotherapeutic agents and the development of molecular markers that allow better identification of candidates for multimodality regimens.

Adenocarcinoma↗

Laparoscopic splenectomy for benign and malignant hematologic diseases: 35 consecutive cases.

The feasibility and safety of laparoscopic splenectomy (LS) has been shown for a variety of diseases with small or moderately enlarged spleens. Immune thrombocytopenic purpura thus has become the typical indication for LS, although few data are available to demonstrate any superiority of the laparoscopic approach over conventional surgery for this indication. We retrospectively analyzed 35 cases of LS for benign (22 patients) or malignant (13 patients) hematologic disorders. LS was attempted irrespective of the volume of the spleen. The overall operative mortality rate was 2.9%, and complications occurred in 23% of all patients. The conversion rate was 9%, and accessory spleens were found in 17% of patients. Although the patients with malignant disease were significantly older, were higher operative risks (ASA score), had much larger spleens, and required longer operative times, more conversions to laparotomy, and more blood transfusions than patients with benign disease, their mortality and complication rates and the duration of their hospital stays were not significantly different from those with benign disease. They also compare favorably with the results of conventional surgery for the same indications. Patient selection, operative technique, and outcome of laparoscopic and conventional splenectomy are discussed with regard to the literature. Although the experience with LS for these indications is still limited, the reported results indicate that LS may be as beneficial for patients with malignant as for those with benign hematologic conditions.

Adult↗

Retention of cartilage oligomeric matrix protein (COMP) and cell death in redifferentiated pseudoachondroplasia chondrocytes.

Cartilage oligomeric matrix protein (COMP) is a large extracellular glycoprotein that is found in the territorial matrix surrounding chondrocytes. Two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1) are caused by mutations in the calcium binding domains of COMP. In this study, we identified two PSACH mutations and assessed the effect of these mutations on redifferentiated chondrocyte structure and function. We confirmed, in vitro, that COMP is retained in enormous cisternae of the rough endoplasmic reticulum (rER) and relatively absent in the PSACH matrix. The rER accumulation may compromise chondrocyte function, leading to chondrocyte death. Moreover, while COMP appears to be deficient in the PSACH matrix, the matrix appeared to be normal but the over-all quantity was reduced. These results suggest that the abnormality in linear growth in PSACH may result from decreased chondrocyte numbers which would also affect the amount of matrix produced.

Achondroplasia↗

Integrating proactive nutritional assessment in clinical practices to prevent complications and cost.

Timely and appropriate nutritional interventions for patients with cancer and/or human immunodeficiency virus (HIV) infection require adoption of routine nutritional screening and comprehensive evaluations into clinical practice. Traditionally, the clinical skills necessary for comprehensive nutritional evaluation have not been a part of medical education. Likewise, the importance of nutritional screening and assessment has not been fully appreciated. In the context of current health care, these skills are increasingly important in maintaining or improving patient care and improving clinical and economic outcomes. It is imperative that nutritional screening be routinely implemented in all clinical settings (eg, office practices, clinics, preadmission units, homecare) to offset the impact of decreased rates of hospital admission. Hospitals have traditionally been the setting for dietetic screening and intervention and nutritional support services. Therapy for patients with cancer or HIV infection is increasingly being managed primarily or entirely in an outpatient setting. When nutritional risk or deficit is identified on screening, it is important to carry out sequential reassessment after intervention. This article reviews the principles of nutritional screening and comprehensive assessment. It includes a detailed overview of an instrument that can be used for either nutritional screening or assessment in patients with either malignancy or HIV infection.

HIV Infections↗

The oncology nursing image: lifting the mist.

PURPOSE/OBJECTIVES: To examine oncology nurses' perceptions of their professional image and describe implications and strategies for practice. DATA SOURCES: Individuals in 28 Oncology Nursing Society (ONS) image focus groups and 13 validation focus groups in local ONS chapters throughout the United States. DATA SYNTHESIS: Although they used both negative and positive descriptors, participants believed the primary perceptions of physicians, administrators, and other nurses regarding oncology nurses were negative, whereas the perceptions of patients and families generally were more positive. Participants believed a lack of understanding exists about oncology nurses, their duties, and the impact of their specialized skills and knowledge on patient-care outcomes. They also believed that the current image of oncology nursing was not one they desired. CONCLUSIONS: Oncology nurses were concerned about their image and believed their external publics (e.g., physicians, administrators, nononcology nurses, patients, families) did not have a clear picture of who they are and what they do. They felt this lack of understanding led to diminished relationships with colleagues and patients/families and a lack of recognition of the oncology nurse as a valued member of the healthcare team. Participants felt this image could be changed and identified strategies to achieve their desired image through activities related to research, education, professionalism, communication, and influence. IMPLICATIONS FOR NURSING PRACTICE: Understanding the possible barriers to collaborative relationships, cost-effective care, disparate feelings of colleagues and external publics, and negative stereotypes will foster strategies to enhance relationships and improve care.

Adult↗

A cell-free protein translocation system prepared entirely from a gram-positive organism.

A cell-free protein translocation system derived exclusively from a Gram-positive bacterium is described here for the first time. Highly efficient in vitro synthesis of plasmid encoded preprolipase of Staphylococcus hyicus is accomplished by coupled transcription/translation using either a cytosolic extract of S. carnosus alone or in combination with T7-RNA-polymerase. Addition of inside-out cytoplasmic membrane vesicles of S. carnosus leads to the partial conversion (processing) of preprolipase to prolipase. In addition, as shown in a protease protection assay, a significant part of preprolipase plus prolipase is translocated in vitro into the lumen of the vesicles. Translocation of preprolipase into the membrane vesicles requires the proton-motive force and the S. carnosus SecA protein.

Adenosine Triphosphatases↗

Anomalous blood supply to the serratus anterior muscle flap.

The serratus anterior free muscle flap is useful in lower limb reconstruction, as it combines a moderate quantity of muscle with a long vascular pedicle. There are known vascular anatomical variations, for example the blood supply may come from the thoracodorsal pedicle, directly from the subscapular pedicle or from the axillary artery and vein. We present a case with a totally independent arterial supply to the flap from the first intercostal artery, while venous return from the flap went back as usual to the subscapular pedicle.

Foot↗

Egg cortical granule N-acetylglucosaminidase is required for the mouse zona block to polyspermy.

The mammalian egg must be fertilized by only one sperm to prevent polyploidy. In most mammals studied to date, the primary block to polyspermy occurs at the zona pellucida, the mammalian egg coat, after exocytosis of the contents of the cortical granules into the perivitelline space. The exudate acts on the zona, causing it to lose its ability to bind sperm and to be penetrated by sperm previously bound to the zona. However, the cortical granule components responsible for the zona block have not been identified. Studies described herein demonstrate that N-acetylglucosaminidase is localized in cortical granules and is responsible for the loss in sperm-binding activity leading to the zona block to polyspermy. Before fertilization, sperm initially bind to the zona by an interaction between sperm surface GalTase and terminal N-acetylglucosamine residues on specific oligosaccharides of the zona glycoprotein ZP3 (Miller, D. J., M. B. Macek, and B. D. Shur. 1992. Nature (Lond.). 357:589-593). These GalTase-binding sites are lost from ZP3 after fertilization, an effect that can be duplicated by N-acetylglucosaminidase treatment. Therefore, N-acetylglucosaminidase, or a related glycosidase, may be present in cortical granules and be responsible for ZP3's loss of sperm-binding activity at fertilization. Of eight glycosidases assayed in exudates of ionophore-activated eggs, N-acetylglucosaminidase was 10-fold higher than any other activity. The enzyme was localized to cortical granules using immunoelectron microscopy. Approximately 70 or 90% of the enzyme was released from cortical granules after ionophore activation or in vivo fertilization, respectively. The isoform of N-acetylglucosaminidase found in cortical granules was identified as beta-hexosaminidase B, the beta, beta homodimer. Inhibition of N-acetylglucosaminidase released from activated eggs, with either competitive inhibitors or with specific antibodies, resulted in polyspermic binding to the zona pellucida. Another glycosidase inhibitor or nonimmune antibodies had no effect on sperm binding to activated eggs. Therefore, egg cortical granule N-acetylglucosaminidase is released at fertilization, where it inactivates the sperm GalTase-binding site, accounting for the block in sperm binding to the zona pellucida.

Animals↗

Chondrodysplasia in transgenic mice harboring a 15-amino acid deletion in the triple helical domain of pro alpha 1(II) collagen chain.

We have generated transgenic mice by microinjection of a 39-kb mouse pro alpha 1(II) collagen gene construct containing a deletion of exon 7 and intron 7. This mutation was expected to disturb the assembly and processing of the homotrimeric type II collagen molecule in cartilage. Expression of transgene mRNA at levels equivalent or higher than the endogenous mRNA in the offspring of two founder animals resulted in a severe chondrodysplastic phenotype with short limbs, hypoplastic thorax, abnormal craniofacial development, and other skeletal deformities. The affected pups died at birth due to respiratory distress. Light microscopy of epiphyseal growth plates of transgenic pups demonstrated a marked reduction in cartilaginous extracellular matrix and disruption of the normal organization of the growth plate. The zone of proliferating chondrocytes was greatly reduced whereas the zone of hypertrophic chondrocytes was markedly increased extending deep into the diaphysis suggestive of a defect in endochondral ossification. Electron microscopic examination revealed chondrocytes with extended RER, a very severe reduction in the amount of cartilage collagen fibrils, and abnormalities in their structure. We postulate that the deletion in the alpha 1(II) collagen acts as a dominant negative mutation disrupting the assembly and secretion of type II collagen molecules. The consequences of the mutation include interference with normal endochondral ossification. These mice constitute a valuable model to study the mechanisms underlying human chondrodysplasias and normal bone formation.

Animals↗

Bringing the medical library to the office desktop.

This demonstration illustrates LRC Remote Computer Services- a dual operating system, multi-protocol system for delivering medical library services to the medical professional's desktop. A working model draws resources from CD-ROM and magnetic media file services, Novell and AppleTalk network protocol suites and gating, LAN and asynchronous (dial-in) access strategies, commercial applications for MS-DOS and Macintosh workstations and custom user interfaces. The demonstration includes a discussion of issues relevant to the delivery of said services, particularly with respect to maintenance, security, training/support, staffing, software licensing and costs.

CD-ROM↗

Localization of the sea urchin Spec3 protein to cilia and Golgi complexes of embryonic ectoderm cells.

Expression of the Spec3 gene of Strongylocentrotus purpuratus is associated with ectodermal ciliogenesis. An antiserum was raised against the amino terminus of the deduced Spec3 amino acid sequence and used for immunofluorescent staining. Cilia and an apical structure at the base of the stained cilium of each ectodermal cell stained intensely in gastrula and later stage embryos. Microtubule-depolymerizing agents dispersed the concentrated spot of apical staining, suggesting a localization of Spec3 antigen to the Golgi complex. Immunogold electron microscopy confirmed the localization of Spec3 antigen on cilia and in the Golgi complex. Spec3 antigen showed a diffuse punctate staining pattern in the ectodermal cytoplasm of hatching blastula when Spec3 transcripts are most prevalent, suggesting that after synthesis, Spec3 is sequestered in the Golgi complex before appearing on cilia. Whereas the predicted Mr of the Spec3 protein is 21,600, immunoblotting with S. purpuratus proteins indicated that a Spec3 antigen was concentrated in cilia and migrated as an SDS-resistant aggregate of Mr approximately 350,000. Spec3 is also concentrated in cilia of Lytechinus pictus but the protein migrated with an Mr approximately 23,000 in this species. The S. purpuratus Spec3 antigen remains associated with the ciliary axoneme after extraction of membrane proteins.

Amino Acid Sequence↗

NMDA receptor antagonists block norepinephrine-induced long-lasting potentiation and long-term potentiation in rat dentate gyrus.

In the in vitro rat dentate gyrus, norepinephrine-induced long-lasting potentiation (NELLP) and long-term potentiation (LTP) of responses to perforant path stimulation were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists, D(-)-2-amino-5-phosphonovaleric acid (D(-)APV) and 3-[(+/-)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP). CPP and D(-)APV, but not L(+)APV, also depressed the orthodromic population spike but not the antidromic spike, which suggests that these receptors may function in low-frequency evoked activity of granule cells. We conclude that NELLP, like LTP in the dentate gyrus, requires NMDA receptor activation.

2-Amino-5-phosphonovalerate↗

Long-term potentiation: studies in the hippocampal slice.

Long-term potentiation (LTP) is an example of activity-dependent plasticity that was discovered in the hippocampal formation. There is growing evidence that LTP not only is a useful model for mnemonic processes, but also may represent the cellular substrate for at least some kinds of learning and memory. The hippocampal slice preparation has proven exceptionally useful in pharmacological studies of possible mechanisms of LTP. A slice remains viable and stable for several hours, and known concentrations of drugs in the bathing medium can be added and then washed out. Drugs can also be applied under visual guidance from micropipettes to discrete neuronal regions, an accomplishment that is aided by the lamellar organization of the hippocampus. Electrical stimulation of the perforant path (PP) in the molecular layer of the dentate gyrus produces a monosynaptic excitatory postsynaptic potential (EPSP) and action potential, which can be recorded extracellularly as a population EPSP and population spike, respectively. Presentation of a high-frequency train (HFT; 100 Hz X 1 s) to the PP results in a long-lasting (greater than 30 min) potentiation of the maximal EPSP slope and of the population spike amplitude. Similarly, exposure of the slice to norepinephrine (e.g. 20 microM for 30 min) results in a long-lasting potentiation (LLP) of both EPSP and population spike (Stanton and Sarvey (1987) Brain Res. Bull., 18: 115). No such LLP was seen in field CA1 following NE application (Stanton and Sarvey (1985) Brain Res., 361: 276). beta-Adrenergic antagonists, such as propranolol, inhibit both LTP and NE-induced LLP in dentate (Stanton and Sarvey, J. Neurosci., 5: 2169 (1985); Stanton and Sarvey (1985) Brain Res., 361: 276). Cyclic AMP levels are increased by either an HFT or NE (Stanton and Sarvey (1985) Brain Res., 358: 343). Thus, NE, acting through a beta-receptor, appears to be both necessary and sufficient to produce long-lasting enhancement of synaptic responses. Finally, inhibitors of protein synthesis, such as emetine, also block both LTP and NE-induced LLP (Stanton and Sarvey, J. Neurosci., (1984) 4: 3080; Stanton and Sarvey (1985) Brain Res., 361: 276). The N-methyl-D-aspartate (NMDA) excitatory amino acid receptor subtype appears to play a role in a number of forms of neuronal plasticity. Bath-application of a 1 microM concentration of the NMDA antagonists D-2-amino-5-phosphonavaleric acid (AVP) or 3-((+/-)2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) blocked both LTP and NE-induced LLP in the dentate gyrus.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

The Hartmann procedure. Extended indications in severe intra-abdominal infection.

During a three-year period, 30 patients had emergency Hartmann procedures for diverticular disease (N = 12), carcinoma (N = 6), trauma (N = 3), and miscellaneous causes (N = 9). Two patients died postoperatively (6.7 percent) and wound infection developed in 60 percent of the patients. Planned relaparotomies for severe intra-abdominal infection were performed in ten patients (an average of 2.5 procedures per patient) with no mortality. In five cases a mucous fistula was converted into a Hartmann pouch; a preference for the Hartmann pouch in patients undergoing repeated explorations is discussed. Colorectal continuity was subsequently restored in 23 patients (76.6 percent).

Abdomen, Acute↗