A randomized trial of low-protein diet in type 1 and in type 2 diabetes mellitus patients with incipient and overt nephropathy.

OBJECTIVE: The efficacy of a low-protein diet in the secondary prevention of diabetic nephropathy is not established in patients with type 1 or type 2 diabetes mellitus. To determine whether a low-protein diet slows the decrease in glomerular filtration rate (GFR) and decreases the albumin excretion rate (AER) in diabetic patients with incipient and overt nephropathy, we performed a 2-year prospective, randomized controlled trial comparing the effects of a low-protein diet (0.8 g/kg/day) with a usual-protein diet. SETTING AND PATIENTS: The study was conducted in a University hospital and included 63 type 1 and type 2 diabetic patients with either incipient or overt nephropathy and mild renal failure (prestudy GFR, 80 +/- 20 mL/min). The primary outcome measures were decreased in GFR and 24-hour AER. RESULTS: In the low-protein-diet group, patients were younger (52 +/- 12 versus 63 +/- 9 years old) and more often were type 2 diabetic. During the follow-up period, according to dietary records the low-protein-diet group consumed 16% +/- 3% of total caloric intakes as compared with 19% +/- 4% in the usual-protein-diet group (P < .02), but 24-hour urinary urea excretions did not differ between the two groups. The 2-year GFR decrease was 7 +/- 11 mL/min in the low-protein-diet group and 5 +/- 15 mL/min in the usual-protein-diet group (P = not significant). AER did not increase significantly in the two diet groups during the follow-up period. Blood pressure and glycemic control were similar in the two groups all along the study. The decrease in GFR and AER were also similar in 6 compliant patients according to dietary records and to 24-hour urinary urea excretions from the low-protein-diet group and in 12 patients from the usual-protein-diet group. CONCLUSIONS: A 2-year low-protein diet did not alter the course of GFR or of AER in diabetic patients with incipient or overt nephropathy receiving renin-angiotensin blockers with strict blood pressure control.     

Prevention of nosocomial pressure ulcers: a process improvement project.

Nosocomial pressure ulcers (PU) occur in approximately 12% of all hospitalized patients. The risk can be determined by a variety of intrinsic and extrinsic factors. As a first line of defense against nosocomial PU, we use the Braden Scale to determine the potential risk of PU development during hospitalization. Once risk was identified, our standard was to implement an individualized plan of care. However, consistent implementation of PU preventative measures was lacking. As a result, a process improvement project was developed and implemented. The purpose of this process improvement project was to increase communication about and awareness of the need to vigorously intervene and document whenever there is risk of, or development of, a nosocomial PU. By initiating consistent use of a PU Tracking Form, developing unit-based wound champions that serve as experts in ulcer prevention, and creating an individual case analysis process, PU prevention and tracking was institutionalized. Results indicate that our nosocomial PU rate has declined from 7% to 4%.     

Synergistic actions of the vitamin D analogue MC 1288 and 15-deoxyspergualin in xenotransplantation

Abstract: The vitamin D analogue MC 1288 (20-epi-1α,25-dihydroxycholecalciferol) effectively postpones rejection of cardiac, intestinal, skin, and aortic allografts. MC 1288 binds to the vitamin D receptor and is thus assumed to exert its immunosuppressive effects via the same mechanisms as 1α,25-dihydroxycholecalciferol, the active form of vitamin D. 1α,25-Dihydroxycholecalciferol has been demonstrated to inhibit the production of various cytokines (interleukin-2, interferon-γ, granulocyte macrophage colony-stimulating factor, and interleukin-12) and to prevent B lymphocyte secretion of immunoglobulins. In the present study MC 1288 was evaluated for its ability to prevent rejection of mouse-to-rat cardiac xenografts, alone and in combination with 15-deoxyspergualin (DSG). Combined treatment with MC 1288 (given days -1 to 9) and DSG (given day -1 and onward) postponed rejection from day 3.0 (untreated recipients) until day 19.5. In rats treated with MC 1288 or DSG as monotherapy, rejection occurred after 3.0 and 7.5 days, respectively. Functioning grafts, obtained on day 9 from recipients treated with MC 1288 and DSG in combination, displayed an almost normal morphology without any obvious deposition of immunoglobulins in the vessels of the grafts and with just a few infiltrating cells. Thus, we have demonstrated synergistic actions of MC 1288 and DSG in delaying rejection of xenografts. Analysis of cellular infiltration, immunoglobulin deposition and graft survival times in the various treatment groups indicate a combined inhibitory effect of these two drugs on the level of macrophage effector function, direct or indirect via T lymphocytes, as well as on antibody production.     

A 2‐year report on maxillary and mandibular fixed partial dentures supported by Astra Tech dental implants. A comparison of 2 implants with different surface textures.

In 50 partially edentulous patients, 133 (48 maxillary; 85 mandibular) Astra Tech dental implants of 2 different surface textures (machined; TiO‐blasted) were alternately installed, supporting 52 fixed partial dentures (FPDs). Before abutment connection 2 machined implants (1 mandibular; 1 maxillary) were found to be non-osseointegrated and were replaced. Another implant could not be restored due to a technical complication. Two FPDs were remade because of technical complications, both because of abutment fractures. Thus, after 2 years in function, the cumulative survival rates were 97.7% and 95.7% for implants and prostheses, respectively. There was no statistically significant difference in survival rate between the 2 types of implants, 100%(TiO‐blasted) vs 95.3%(machined), P =0.24. After 2 years in function, when both jaw and type of implants were combined, the mean (SD) marginal bone loss was 0.24 (0.69) mm. No statistically significant difference in bone loss was found between the 2 tvues of implant after 2 years of loading, 0.04 (0.82) mm, P >0.30.     

Overexpression of connexin43 alters the mutant phenotype of midgestational wnt-1 null mice resulting in recovery of the midbrain and cerebellum

The midbrain-hindbrain (MHB) junction plays a key role in the patterning of the embryonic neural tube and the formation of brain structures such as the cerebellum. The mitogen wnt-1 is critical for cerebellar development, as evidenced by the lack of MHB region and cerebellar formation in the wnt-1 null embryo. We have generated wnt-1 null embryos overexpressing the gap junction gene connexin43 by crossing wnt-1 null heterozygotes into the CMV43 mouse line. We have confirmed that these mice show an increase in gap junctional communication by dye coupling analysis. Two-thirds of wnt-1 null CMV43(+) mouse embryos at E18.5 have a cerebellum. In addition, changes in the wnt-1 null phenotype in mouse embryos overexpressing connexin43 are observed as early as E9.5. At this stage, one-quarter of wnt-1 null CMV43(+) embryos display extra or expanded tissue present at the MHB boundary (a wnt-1 null enlarged phenotype). In situ hybridization studies conducted on these embryos have indicated no changes in the expression of embryonic brain positional markers in this region. We conclude from these studies that overexpression of the connexin43 gap junction restores cerebellar formation by compensating for the loss of wnt-1.     

Effect of stimulation and hyperpolarization on non-electrolyte and sodium permeability in perfused axons of squid

1. The permeability for micro-injected [(3)H]ethylene glycol was measured in resting state and during stimulation at 100/sec in squid giant axons. No detectable changes during electrical activity were observed.2. The influxes of urethane, tritiated water, ethylene glycol, urea and sodium were measured in internally perfused squid axons. Ethylene glycol and urea influxes were determined simultaneously with sodium influxes. The electrical stimulation of the fibre produced an increase in the influx of sodium but did not alter the influxes of the non-electrolytes listed above.3. Experiments were done with the combined voltage clamp-perfusion technique. The influxes of ethylene glycol and sodium were simultaneously measured in resting state and during maximum sodium current under stimulation at 10/sec. The influx of sodium increased in these conditions but the influx of ethylene glycol remained constant. In some experiments, the fibre was hyperpolarized to 10 or 20 mV, above the resting potential and the influxes of ethylene glycol and sodium were measured. The sodium influx decreased to 60% at 20 mV above the resting potential whereas the influx of ethylene glycol remained constant.4. These results indicate that in the giant axons of the squid Dosidicus gigas, sodium and non-electrolytes fluxes are not coupled.     

A B7-1-transfected human melanoma line stimulates proliferation and cytotoxicity of autologous and allogeneic lymphocytes

B7 co-stimulation is necessary to activate resting T cells upon antigen recognition by the T cell receptor. To see whether expression of B7 may render human melanoma cells able to stimulate T cells, a cloned melanoma line (Me1B6), which did not express B7-1, was transfected with the human B7-1 gene. In proliferation assays, B7-1 transfected cells (Me1B6/B7) showed greater stimulatory activity of allogeneic and autologous peripheral blood lymphocytes (PBL) compared to parental, non-transfected tumor cells. This effect was also seen when allogeneic CD8⁺ and CD4⁺ subpopulations were used as effectors. In these studies, activation of lymphocytes was B7-1-dependent and HLA classes I and II mediated. The higher proliferation correlated with an increased lytic activity by PBL stimulated with B7-1⁺ tumor cells against the untransfected Me1B6. Furthermore, PBL from a metastatic melanoma patient stimulated by Me1B6/B7 developed an higher lytic activity not only against Me1B6 but also against their autologous, B7-1^? tumor. Finally, after Me1B6/B7 stimulation, PBL released interleukin (IL)-2 and interferon-γ, but not IL-4, suggesting a Th1-mediated response. These data support the use of B7-1 transfected melanoma cells in the therapeutic vaccination of melanoma patients.