Long-term results of the Angelchik prosthesis for gastro-oesophageal reflux

INTRODUCTION: Between 1982 and 1989, 46 patients had insertion of an Angelchik prosthesis for gastro-oesophageal reflux. Eleven patients (24 per cent) subsequently had the prosthesis removed, all but one for intractable dysphagia. METHODS: Thirty-six of the original patients were followed by questionnaire, and 32 of these had a barium marshmallow swallow investigation. RESULTS: A high proportion of patients (20 of 26) with a prosthesis in situ had symptoms of dysphagia. On objective evaluation by marshmallow swallow, the transit time was significantly slower than that of an age-matched control group (P < 0.01), but showed no significant deterioration with time compared with previous postinsertion studies. CONCLUSION: The Angelchik prosthesis causes long-term dysphagia in a high proportion of patients, severe enough in one-quarter to necessitate its removal. Its continued use cannot, therefore, be recommended.     

Predictors of intracranial pathologic findings in patients who seek emergency care because of headache

BACKGROUND: Clinical criteria to select patients with headache in whom structural diagnostic studies (computed tomography) have a high yield disclosing intracranial pathologic findings, independent of abnormal findings on neurologic examination, have not been defined. OBJECTIVE: To determine which clinical characteristics predict the presence of intracranial pathologic findings, independently of neurologic examination, in patients with headache. DESIGN: Case-control, consecutive sample. SETTING: Major metropolitan trauma center emergency department. PATIENTS AND MATERIALS: Hospital records of 139 hospitalized and 329 randomly selected patients from 1720 nonhospitalized adult patients, consecutively evaluated for headache in the emergency department, were reviewed. Demographic data, clinical characteristics of the headache, results of neurologic and physical examinations, and diagnostic radiologic and laboratory results were correlated with final diagnosis and outcome at 6 months after emergency department visit. DATA ANALYSIS: Nonparametric statistical analysis. RESULTS: Intracranial pathologic findings were found in 18 (3.8%) of 468 patients. Acute onset and occipitonuchal location of headache, presence of associated symptoms, and patient age of 55 years or older were significantly associated with the finding of intracranial pathology, independently of the findings from neurologic examination. Abnormal findings on neurologic examination alone, whether focal or nonfocal, had a highly significant association and a positive predictive value for intracranial pathology of 39%. CONCLUSIONS: Abnormal results from neurologic examination are the best clinical parameters to predict structural intracranial pathology; however, in patients 55 years or older with headache of acute onset located in the occipitonuchal region that has associated symptoms, computed tomographic scan of the head is justified as part of their clinical evaluation independently of the findings of the neurologic examination.     

Evidence that levels of presenilins (PS1 and PS2) are coordinately regulated by competition for limiting cellular factors

Mutations in two related genes, PS1 and PS2, account for the majority of early onset cases of familial Alzheimer's disease. PS1 and PS2 are homologous polytopic membrane proteins that are processed endoproteolytically into two fragments in vivo. In the present report we examine the fate of endogenous PS1 and PS2 after overexpression of human PS1 or PS2 in mouse N2a neuroblastoma cell lines and human PS1 in transgenic mice. Remarkably, in N2a cell lines and in brains of transgenic mice expressing human PS1, accumulation of human PS1 derivatives is accompanied by a compensatory, and highly selective, decrease in the steady-state levels of murine PS1 and PS2 derivatives. Similarly, the levels of murine PS1 derivatives are diminished in cultured cells overexpressing human PS2. To define the minimal sequence requirements for "replacement" we expressed familial Alzheimer's disease-linked and experimental deletion variants of PS1. These studies revealed that compromised accumulation of murine PS1 and PS2 derivatives resulting from overexpression of human PS1 occurs in a manner independent of endoproteolytic cleavage. Our results are consistent with a model in which the abundance of PS1 and PS2 fragments is regulated coordinately by competition for limiting cellular factor(s).     

Reengineering a surgical service line: focusing on core process improvement

Integrating principles from a variety of theory has led to the development of a conceptual framework for reengineering in a clinical care delivery setting to improve the value of services provided to the customer. A conceptual framework involving the identification of three high level core processes to reengineer can provide clarity and focus for clinicians to begin directing reengineering efforts. Those core processes are: clinical management of the patient's medical needs, patient operational processes to support the clinical processes, and administrative decision-making processes to support the implementation of the clinical and operational processes. Improvement in any one of these areas has the potential to increase value, but the concurrent targeting of these core processes for reengineering has provided a synergy that has accelerated the achievement of the desired outcomes in the area of surgical services.     

Ultrasonographic diagnosis of ectopic pregnancy: importance of transabdominal imaging

Endovaginal sonography has greatly improved the diagnostic evaluation of suspected ectopic pregnancy. Some authors suggest imaging solely by endovaginal technique for diagnosis. We perform both a transabdominal scan for a global view of the pelvic and abdominal contents and an endovaginal sonographic examination for a higher resolution and focused view of the gynecologic structures. We report three patients with negative endovaginal examinations who had obvious ectopic pregnancies on our subsequent transabdominal examination. These cases remind us of the valuable information that can be obtained with the transabdominal approach and the complementary role it plays with endovaginal sonography.     

The organization and animal-vegetal asymmetry of cytokeratin filaments in stage VI Xenopus oocytes is dependent upon F-actin and microtubules

Confocal immunofluorescence microscopy with anti-cytokeratin antibodies revealed a continuous and polarized network of cytokeratin (CK) filaments in the cortex of stage VI Xenopus oocytes. In the animal cortex, CK filaments formed a dense meshwork that both was thicker and exhibited a finer mesh than the network of CK filaments previously observed in the vegetal cortex (Klymkowsky et al., 1987). CK filaments first appeared in association with germinal vesicle (GV) and mitochondrial mass (MM) of oocytes in early mid stage I, indicating that CK filaments are the last of the three cytoskeletal networks to be assembled. By late stage I, CK filaments formed complex networks surrounding the GV, surrounding and penetrating the MM, and linking these networks to a meshwork of CK filaments in the oocyte cortex. During stage III-early IV, CK filaments formed a highly interconnected, apparently unpolarized, radial array linking the perinuclear and cortical CK filament networks. Polarization of the CK filament network was observed during mid stage IV-stage V, as first the animal, then the vegetal CK filament networks adopted the organization characteristic of stage VI oocytes. Treatment of stage VI oocytes with cytochalasin B disrupted the organization of both cortical and cytoplasmic CK filaments, releasing CK filaments from the oocyte cortex and inducing formation of numerous cytoplasmic CK filament aggregates. CB also disrupted the organization of cytoplasmic microtubules (MTs) in stage VI oocytes. Disassembly of oocyte MTs with nocodazole resulted in loss of the characteristic A-V polarity of the cortical CK filament network. In contrast, disruption of cytoplasmic CK filaments by microinjection of anti-CK antibodies had no apparent effect on cytoplasmic or MT organization. We propose a model in which the organization and polarization of the cortical network of CK filaments in stage VI Xenopus oocytes are dependent upon a hierarchy of interactions with actin filaments and microtubules.     

Birth weight, adult weight, and girth as predictors of the metabolic syndrome in postmenopausal women: the Rancho Bernardo Study

OBJECTIVE: Recent studies have demonstrated an association between low birth weight and chronic and metabolic disorders in adulthood such as type 2 diabetes, hypertension, and dyslipidemia. These disorders tend to cluster in a condition known as the metabolic syndrome (syndrome X). Only two studies have reported an association of birth weight to the metabolic syndrome. The present study is distinguished as the only study to focus on postmenopausal women. RESEARCH DESIGN AND METHODS: Subjects were 303 community-dwelling, postmenopausal Caucasian women aged 50-84 years. Metabolic and anthropometric variables were measured at a clinic visit; birth weight was assessed by self-report on a mailed questionnaire. RESULTS: The metabolic syndrome, defined as the simultaneous presence of hypertension, dyslipidemia, and abnormal glucose tolerance, was present in 7.9% of these women. Compared with women in the highest birth weight tertile (8.1-13.0 lb, mean 9.4 lb), those in the lowest birth weight tertile (2.5-6.8 lb, mean 5.5 lb) exhibited an increased prevalence (12.0 vs. 4.3%, P < 0.05) and 2.41 times the risk (95% CI 1.06-5.51) of developing the metabolic syndrome. Women with a heavy birth weight had an increased risk of adult obesity. Nevertheless, women in the lowest birth weight tertile who became adults in the highest tertile of BMI (>25.2 kg/m2) or waist circumference (>80.7 cm) had the highest prevalence of the metabolic syndrome (approximately 30%). CONCLUSIONS: Low birth weight coupled with adult obesity is a strong determinant of the metabolic syndrome in postmenopausal women.     

Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons

Recent studies show that the cytokine interleukin-6 (IL-6) is expressed at elevated levels in the CNS in several disease states and contributes to the neuropathological process. The mechanisms through which IL-6 exerts its CNS effects are primarily unknown. We have investigated the pathophysiological effects of IL-6 on developing CNS neurons using a culture model system and a chronic treatment paradigm. Here, we show, using current- and voltage-clamp recordings, that chronic IL-6 treatment of developing cerebellar granule neurons increases the membrane and current response to NMDA and that these effects are the primary mechanism through which IL-6 produces an enhanced calcium signal to NMDA. We also show that calcium influx through voltage-sensitive calcium channels contributes to the enhanced calcium signal to NMDA in the IL-6-treated neurons in a developmentally regulated manner and that the membrane depolarization to NMDA is more sensitive to the NMDA receptor antagonist ifenprodil in the IL-6-treated neurons compared with control neurons at a late developmental stage, consistent with a larger proportion of NMDA receptors containing the NMDAR2B subunit in the IL-6-treated neurons. Additional studies show that IL-6 treatment reduces the number of granule neurons in culture and enhances neurotoxicity involving NMDA receptors. These results support a pathological role for IL-6 in the CNS and indicate that NMDA receptor-mediated functions are likely to play a critical role in neuropathological changes observed in CNS diseases associated with elevated CNS levels of IL-6.