Fate of infected and eroded hemodialysis grafts and autogenous fistulas

Between 1970 and 1991, we placed 1,090 grafts (bovine and polytetrafluoroethylene) in 1,041 patients and created 1,034 autogenous fistulas in 856 patients for hemodialysis. Subsequent revisions for complications resulted in a total of 3,944 operations performed in patients with grafts and 1,633 operations in patients with autogenous fistulas. A total of 255 infections developed in 158 of the patients with grafts, whereas 8 infections developed in 7 patients with autogenous fistulas. The puncture infection rate was 5%/yr (12%/yr for a second puncture infection). The clean wound infection rate was 3% for grafts and 0.4% for autogenous fistulas. We made an attempt to salvage the graft, usually with a segmental bypass, in 75% of patients with a graft infection. Grafts were salvaged in 80% of patients in whom salvage was attempted (60% of all patients with an infection). The results in the few patients with infected autogenous fistulas were relatively poor.     

Membrane potential regulates inositol 1,4,5-trisphosphate-controlled cytoplasmic Ca2+ oscillations in pituitary gonadotrophs

The influence of membrane potential (Vm) on cytoplasmic calcium ([Ca2+]i) oscillations during the sustained extracellular Ca(2+)-dependent phase of the Ca2+ signaling response to gonadotropin-releasing hormone (GnRH) was analyzed in cultured pituitary gonadotrophs. In agonist- and inositol (1,4,5)-trisphosphate (Ins(1,4,5)P3)-stimulated cells, sustained [Ca2+]i oscillations were extinguished by hyperpolarization after 3-15 min despite the availability of Ca2+ in the extracellular medium. Single depolarizing pulses transiently restored the amplitude of the sustained spiking in a dihydropyridine- and extracellular Ca(2+)-sensitive manner. The responses to depolarization showed a marked dependence on Vm that was correlated with the steady-state inward Ca2+ current. In addition, repetitive application of brief depolarizing pulses modulated the frequency of agonist- and Ins(1,4,5)P3-controlled spiking; depolarization pulses at frequencies lower than the intrinsic rate of episodic Ca2+ release triggered large transients between the autonomous spikes, whereas higher frequencies of depolarizing pulses overcame the original Ca2+ spiking frequency. These extrinsically driven and extracellular Ca(2+)-dependent oscillations were sensitive to the Ca(2+)-ATPase blocker, thapsigargin, but not to ryanodine. On the other hand, spontaneous firing and application of depolarizing pulses to nonstimulated cells failed to induce thapsigargin-sensitive oscillations. These findings demonstrate that the pattern of Ca2+ signaling in gonadotrophs does not depend exclusively on the Ins(1,4,5)P3 concentration, but also on the excitable status of the cell. Such modulation of the Ins(1,4,5)P3-controlled Ca2+ signaling system by changes in Vm could provide a mechanism for the integration of multiple inputs that utilize diverse signal transduction pathways.     

Oligonucleotide-poly-L-ornithine conjugates: binding to complementary DNA and RNA

A lysate of human herpesvirus type 6 (HHV6) infected HSB2 cells was used as antigen for an enzyme-linked immunosorbent assay (ELISA) for the detection of IgG and IgM antibody to HHV6. 78 clinical samples were tested for the presence of HHV6-specific IgM. Nine specimens, all from children under 4.5 years of age, were found to be reactive indicating probable acute infection with HHV6. Sera from 12 healthy adult blood donors and from 88 of 90 adults over the age of 35 with unspecified health conditions tested negative for HHV6 IgM, indicating a minimum specificity estimate of nearly 98% in these patients. Cross-reactivity of antibody to other herpes viruses with the HHV6 ELISA antigen was not detected. Six hundred and ninety-six serum samples from individuals of different age groups were examined for IgG antibody status. In 94% of these samples, IgG antibody was detected. Our data suggests that most Canadians possess antibody to HHV6 by 1 yr of age and that on average, antibody levels remain high through early adulthood but begin to decline with advancing age. The ELISA described is a reliable test for the measurement of IgG and IgM antibodies for both clinical diagnosis and epidemiological studies.     

A dominant-negative mutant of Max that inhibits sequence-specific DNA binding by Myc proteins

Myc proteins are basic helix-loop-helix/leucine-zipper proteins that bind to specific DNA sequences. In vivo, Myc proteins have been found associated with Max, another basic helix-loop-helix/leucine-zipper protein. However, it is not known to what extent the dimerization of Myc with Max is required for the manifestation of the Myc-induced phenotype. To investigate this, we constructed a dominant-negative mutant of Max, named dMax, that inhibits sequence-specific DNA binding of Myc proteins. Using a rat neuroblastoma model system, we show that dMax reverts N-Myc-induced changes in cellular gene expression. A control mutant of dMax that contains a proline residue in the leucine-zipper region was unable to bind to N-Myc and did not revert the N-Myc-induced changes in cellular gene expression. These data support the hypothesis that N-Myc affects neuroblastoma gene expression through the formation of a DNA-binding heterodimeric complex with Max in vivo.     

A noniterative solution approach for parallel pseudospectral domain decomposition

A simple superposition technique is proposed for the solution of spectral collocation equations in multi-nonoverlapping subdomains. It is based on a property of linear differential equations that allows the interface conditions to be fully decoupled; thus yielding a strategy with a very high level of concurrency suitable for parallel computations. Numerical experiments indicate, for a fixed total number of collocation points, a significant degradation of spectral accuracy as the number of subdomains increases. While the technique generally yields reasonably good solution, a compromise between accuracy and geometric flexibility must be realized.     

Utility of the American Diabetes Association risk test in a community screening program

In many patients with superficial siderosis of the central nervous system (CNS) no source of bleeding can be established, despite extensive examinations. The authors report a patient with superficial siderosis and a spinal arteriovenous malformation (AVM) that was not visible on magnetic resonance (MR) imaging or myelography but was identified on angiographic studies. This 71-year-old man presented with a 2-year history of progressive gait difficulties and hearing loss. Examination showed ataxia, hearing loss, and quadriparesis. On MR imaging superficial siderosis of the brain and spinal cord as seen; however, MR imaging of the CNS, as well as cerebral angiography and myelography studies, did not reveal the source of hemorrhage. Spinal angiography revealed a small slow-flow pial AVM at the C-5 level originating from the anterior spinal artery. A C-5 corpectomy was performed and the AVM was obliterated. The patient did well and reported no further progression of his symptoms during 3 months of follow up. Spinal angiography is indicated to complete the evaluation of patients with superficial siderosis, even if results of spinal MR imaging and myelography studies are normal. Obliteration of spinal AVMs may successfully prevent the progression of superficial siderosis.     

Genetic analysis of the mechanisms controlling target selection: complementary and combinatorial functions of netrins, semaphorins, and IgCAMs

Bacterial symbionts may be used as vehicles for expressing foreign genes in arthropods. Expression of selected genes can render an arthropod incapable of transmitting a second microorganism that is pathogenic for humans and is an alternative approach to the control of arthropod-borne diseases. We discuss the rationale for this alternative approach, its potential applications and limitations, and the regulatory concerns that may arise from its use in interrupting disease transmission in humans and animals.     

Brain systems mediating aversive conditioning: an event-related fMRI study

We have used event-related functional magnetic resonance imaging (fMRI) to characterize neural responses associated with emotional learning. Employing a classical conditioning paradigm in which faces were conditioned by pairing with an aversive tone (US), we compared responses evoked by conditioned (CS+) and nonconditioned (CS-) stimuli. Pairing 50% of the CS+ with the US enabled us to constrain our analysis to responses evoked by a CS+ not followed by a US. Differential evoked responses, related to conditioning, were found in the anterior cingulate and the anterior insula, regions with known involvement in emotional processing. Differential responses of the amygdalae were best characterized by a time by stimulus interaction indicating a rapid adaptation of CS+-specific responses in this region.     

Skeletal cell stresses and bone adaptation

BACKGROUND: We have previously shown that growth hormone (GH) consistently stimulates proliferation of human osteoblasts in vitro. In rat osteoblasts, GH augments the effects of insulin-like growth factor (IGF) I on cell proliferation and differentiation. We therefore investigated the effects of IGF-I and -II alone and in combination with GH on human osteoblasts in vitro. METHODS: Human osteoblast-like cells (HOB) were established from trabecular explants (n = 18) and human marrow stromal cells (HMS) from marrow aspiration (n = 21). The cell cultures were stimulated with IGF-I or IGF-II (1, 10 or 100 ng mL-1) alone, in combination with hGH (100 ng mL-1) or after prestimulation with hGH. RESULTS: IGF-I alone, in combination with hGH and after pretreatment with hGH, increased proliferation of HOB and HMS by 49-190% (P < 0.05-0.01). IGF-II alone, in combination with hGH and after pretreatment with hGH increased proliferation of HOB by 57-158% (P < 0.01). In HMS only IGF-II in combination with hGH and after prestimulation with hGH increased proliferation. IGF-I alone and in combination with hGH decreased alkaline phosphatase (AP) in both cell types. IGF-II did not affect AP in HOB, but increased AP in HMS, this effect was abolished by hGH. In HOB, collagen production (PICP) was increased by IGF-II but unaffected by IGF-I. In HMS, PICP was decreased by IGF-I and -II but increased by hGH. Co-stimulation further increased PICP. CONCLUSION: IGF-I and -II exerted proliferative effects on both HOB and HMS. Co-stimulation with GH exhibited synergism in enhancing the proliferative response. In HMS prestimulation improved the proliferative response significantly. The effects of the IGFs on differentiation are more complex and dependent on cell maturation and of the IGF used.     

A mechanical comparison of subtrochanteric femur fracture fixation

The aim of this study was to compare in vitro diagnostic performance of three electrical methods for occlusal caries diagnosis with that of visual inspection and bite-wing radiography. One hundred and seven extracted molar and premolar teeth were subjected to the diagnostic methods by 2 operators and subsequently sectioned for histological validation. Electrical measurements were made at site level and at surface level using two different instruments. The diagnostic parameters calculated from the results were: sensitivity, specificity, diagnostic accuracy at a theoretical caries prevalence of 10% and area under the ROC curve. The electrical methods and bite-wing radiography showed higher sensitivity and lower specificity than visual inspection. Diagnostic accuracy was significantly lower for bite-wing radiography and one electrical method than for visual inspection. Overall diagnostic performance of two electrical methods was superior.