Effect of acute hypoglycemia on visual information processing in adults with type 1 diabetes mellitus

Acute hypoglycemia in people with type 1 (insulin-dependent) diabetes mellitus causes general impairment in cognitive performance. The effects on more specific cognitive processes are less well defined. Acute hypoglycemia has been shown to impair visual information processing in nondiabetic human subjects and has now been examined in 16 adult subjects with type 1 diabetes. All subjects had normal visual acuity and no diabetic retinopathy, and their median (range) age was 24 (18-47) years with a median (range) duration of type 1 diabetes of 8 (2-18) years and a mean (SD) HbA1c of 8.5 (1.3)%. A hyperinsulinemic glucose clamp technique was used to maintain arterialized blood glucose at 5.0 mmol l(-1), and on separate test days, either euglycemia was continued or hypoglycemia (2.6 mmol l(-1)) was induced. During each condition subjects performed tests of visual processing and cognitive function. Hypoglycemia caused a significant disruption in general cognitive ability as assessed by digit symbol (p < 0.001) and trail-making B (p < 0.05) tasks. Conventional measures of visual acuity were unaffected by hypoglycemia, but visual information processing deteriorated significantly as indexed by inspection time (p < 0.005) and visual change detection (p < 0.01). Contrast sensitivity tended to deteriorate during hypoglycemia (p = 0.06). In conclusion, hypoglycemia impairs important aspects of early visual information processing and contrast sensitivity in adults with type 1 diabetes. Further research is needed to evaluate the functional relevance of such changes for everyday tasks that require the intake of visual information at speed and under conditions of low contrast.     

Binding and presentation of peptides derived from melanoma antigens MART-1 and glycoprotein-100 by HLA-A2 subtypes. Implications for peptide-based immunotherapy

Cellular immune responses to melanoma-associated Ags are the focus of ongoing studies aimed at developing immunotherapies for treatment of malignant melanoma. Melanoma predominantly affects Caucasians, a population in whom expression of HLA-A2 is prevalent. Among HLA-A2 subtypes, HLA-A*0201 is widely expressed, and HLA-A*0201-restricted, tumor-reactive CTL responses are well studied. We have observed in a group of melanoma patients an unexpectedly high frequency (approximately 20%) of non-HLA-A*0201 subtypes (*0202, *0204, and *0205), and little is known regarding antimelanoma response profiles in patients expressing such subtypes. We analyzed non-HLA-A*0201 peptide response profiles using HLA-A*0201-restricted epitopes from melanoma Ags MART-1/Melan A and glycoprotein 100. Most of these peptides bound to the majority of subtypes tested with 50% inhibitory concentrations less than 500 nM. Recognition of cells pulsed with different peptides (MART-1(27-35), G9(154), and G9(280) Flu M1(58-66)) and expressing different subtype molecules by HLA-A*0201-restricted CTL was limited to only a subset of non-HLA-A*0201 molecules, and the peptide/subtype complexes recognized varied among the effector populations tested. CTL responses elicited from PBL of patients and healthy donors expressing subtypes HLA-A*0202 and HLA-A*0205 suggested significant differences among HLA-A2 subtype function in the context of melanoma Ag presentation. These observations imply the necessity of subtyping patients considered for peptide-based protocols and highlight the need for further study of melanoma-directed cellular responses among patients expressing non-HLA-A*0201 subtypes.     

Comparison of methods for identifying transcription units and transcription map of the Werner syndrome gene region

OBJECTIVE: The audiologic presentation of vestibular schwannoma (VS) associated with neurofibromatosis type 2 (NF2) has not been well characterized. The goal of this study was to investigate the audiologic features of NF2-associated VS and to determine their relationship to the size of the tumor. STUDY DESIGN: A retrospective case review. SETTING: Quaternary governmental medical research institute evaluating patients fitting specific criteria for ongoing clinical studies. PATIENTS: Audiologic and magnetic resonance imaging data were available for 40 patients (25 males, 15 females), with an average age of 32 years, who had been recruited for ongoing clinical and genetic studies of NF2. MAIN OUTCOME MEASURES: The audiologic profile and magnetic resonance imaging characteristic of tumor were retrospectively reviewed. RESULTS: The average size of the tumor at presentation was 7.26 +/- 16.58 cm3 and measured 1.2, 1.6, and 1.1 cm in the anterior/posterior, lateral/medial, and superior/inferior dimensions, respectively. An increase in lateral/medial size of the tumor most significantly correlated with deterioration in mid- (1,000-2,000 Hz) and high- (4,000-8,000 Hz) frequency hearing levels, elevated speech reception threshold, and prolonged auditory brain stem response waves III and V latency. CONCLUSIONS: Patients with NF2 demonstrate a more predictable audiologic profile for a given size tumor than has been previously described with spontaneous or sporadic VS.     

Hormonal and behavioural correlates of male dominance and reproductive status in captive colonies of the naked mole-rat, Heterocephalus glaber

Naked mole-rat colonies are societies with a high reproductive skew, breeding being restricted to one dominant female (the 'queen') and 1-3 males. Other colony members of both sexes are reproductively suppressed. Experimental removal of breeding males allowed us to investigate the relationship between urinary testosterone and cortisol, dominance rank, and male reproductive status. Dominance rank was strongly correlated with body weight, age, and urinary testosterone titres in males. No relationship between urinary cortisol levels and male reproductive status or dominance was found. Breeding males were among the highest-ranking, heaviest and oldest males in their respective colonies, and were succeeded by other high-ranking, large, old colony males. In contrast to females, no evidence of competition over breeding status was observed among males. Male-male agonism was low both before and after removal of breeders and mate guarding was not observed. The lower reproductive skew for males compared with female skew or queen control over male reproduction may explain why males compete less strongly than females over breeding status after removal of same-sexed breeders.     

Costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting

STUDY OBJECTIVE: To estimate the financial costs incurred by outpatient surgical centers in managing postoperative nausea and vomiting (PONV). DESIGN: Prospective, observational study. SETTING: 6 hospital-based outpatient surgery centers. PATIENTS: 211 adult patients undergoing outpatient surgery for laparoscopy, dilatation and curettage, knee arthroscopy, or hernia repair. MEASUREMENTS AND MAIN RESULTS: Of the 211 patients studied, 34 experienced PONV in the recovery room. For those patients experiencing PONV, personnel, supply, and drug costs for management of this condition averaged $14.94 per patient. In addition, PONV increased the centers' operating costs by delaying patient discharge by an average of 24 minutes. A minimum estimate of this cost, based on nurses' wage rates, was $7.12. This estimate is appropriate only for short-run considerations in outpatient surgery centers that operate at low capacity. An appropriate valuation for long-run considerations and for centers operating near capacity is based on the revenue that centers lose as a result of extended stays. Lost revenue was estimated to be $415 per patient experiencing PONV. CONCLUSIONS: PONV substantially increases the costs incurred by outpatient surgical centers.     

The incidence of artery puncture with central venous cannulation using a modified technique for detection and prevention of arterial cannulation

BACKGROUND: Cannulation of the central circulation is essential for management of patients who require major surgery, and for patients who are critically ill. Arterial puncture is the most frequent complication associated with central venous cannulation, and is potentially fatal. Detection of arterial puncture can be problematic, especially in patients with cyanotic congenital heart disease. METHODS: One thousand eleven consecutive cardiothoracic and vascular surgical patients who required central venous cannulation were studied using a new technique for detection of arterial puncture and prevention of arterial cannulation. This technique involves continuous pressure transduction of the steel introducer needle. Central venous cannulation was attempted in all patients. The sites of attempted catheterizations, number of arterial punctures and cannulations, and the number of successful catheterizations were noted. All patients were treated in accordance with standard anesthetic and surgical techniques in the institution. RESULTS: One thousand one hundred seventy-two central venous catheters were placed. The overall success rate was 99.6%. The incidence of arterial puncture was 9.3% for central venous cannulation attempts of the internal jugular, subclavian, and femoral veins. No arterial cannulation occurred, and none of the patients had significant complications. Congenital heart disease patients had a higher incidence of arterial puncture (14.1%) and a lower rate (96.8%) of successful cannulation. CONCLUSION: Pressure transduction of the steel needle is a useful technique for detecting arterial puncture and preventing arterial cannulation during attempts to achieve central venous cannulation.     

Murine IgG1 complexes trigger immune effector functions predominantly via Fc gamma RIII (CD16)

Previously, we have demonstrated that phagocytosis of IgG1-coated particles by macrophages in vitro is impaired by deletion of Fc gamma RIII in mice, suggesting that IgG1 may interact preferentially with Fc gamma RIII. In the present study, the biologic relevance of this observation was addressed by triggering various effector functions of the immune system in Fc gamma RIII(-/-) mice, using panels of mAbs of different IgG subclasses. Both binding and phagocytosis of IgG1-coated sheep or human erythrocytes by Fc gamma RIII(-/-) macrophages in vitro were strongly impaired, indicating that the impaired ingestion of complexed IgG1 by Fc gamma RIII(-/-) macrophages is due to a defect in binding. An in vivo consequence of the defective phagocytosis was observed by resistance of Fc gamma RIII-deficient mice to experimental autoimmune hemolytic anemia, as shown by a lack of IgG1-mediated erythrophagocytosis in vivo by liver macrophages. Furthermore, trapping of soluble IgG1-containing immune complexes by follicular dendritic cells in mesenteric lymph nodes from Fc gamma RIII(-/-) mice was abolished. Whole blood from Fc gamma RIII(-/-) mice was unable to induce lysis of tumor cells in the presence of IgG1 antitumor Abs. Finally, IgG1 mAbs proved unable to mount a passive cutaneous anaphylaxis in Fc gamma RIII(-/-) mice. Together, these results demonstrate that IgG1 complexes, either in particulate or in soluble form, trigger in vitro and in vivo immune effector functions in mice predominantly via Fc gamma RIII.     

The role of nitric oxide and NMDA receptors in the development of motor neuron dendrites

Nitric oxide (NO) has been implicated in the establishment of precise synaptic connectivity throughout the neuroaxis in several species. To determine the contribution of NO to NMDA receptor-dependent dendritic growth in motor neurons, we administered the NMDA antagonist MK-801 to wild-type mice and neuronal nitric oxide synthase (nNOS) knock-out mice between postnatal days 7 and 14. Compared to saline-treated wild-type animals the number of dendritic bifurcations was significantly reduced in nNOS knock-out animals and MK-801-treated wild-type animals. There was no significant difference in dendritic bifurcation between MK-801-treated wild-type, MK-801-treated nNOS knock-out, and saline-treated nNOS knock-out animals, suggesting that nNOS knock-out and NMDA receptor block had similar effects. The path of the longest dendrite and the number of primary dendrites was the same in all treatment groups, indicating an effect specific to bifurcation. Sholl analysis revealed that differences in bifurcation numbers occurred between 160 and 320 micrometers from the cell body, the distance at which second, third, and fourth order dendrites are most prevalent. Dendrite order analyses confirmed a significant reduction in numbers, but not lengths, of third and fourth order dendrites in nNOS knock-out and drug-treatment groups. Finally, immunohistochemical examination of the developing spinal cord indicated that NMDA receptors and nNOS are colocalized within interneurons surrounding the motor neuron pool. These results support the view that at least part of NMDA receptor-dependent arborization of motor neuron dendrites is mediated by the local production of NO within the developing spinal cord.     

Long-term follow-up of an EORTC randomized prospective trial comparing intravesical bacille Calmette-Guérin-RIVM and mitomycin C in superficial bladder cancer. EORTC GU Group and the Dutch South East Cooperative Urological Group. European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Collaborative Group

Posterior laryngeal clefts (PLCs) are described in the literature as rare laryngeal abnormalities. The authors believe type I clefts are much more common than previously reported. In two busy pediatric tertiary care centers, such clefts are the second most common congenital laryngeal finding at rigid endoscopy, second only to laryngomalacia. PLCs frequently present with symptomatology that can be attributed to other common disease processes and are often undiagnosed unless the surgeon maintains a high index of suspicion and specifically examines the posterior glottis by palpation during microlaryngoscopy. This report presents a series of 41 patients with type I PLCs, reviews their subtle and often confusing presenting signs and symptoms, and describes a simple yet reliable method of diagnosis.