Hindlimb unweighting (HU) causes upregulation of several muscle-specific genes responsible for the slow-to-fast transition in soleus skeletal muscle properties despite the profound muscle atrophy. The purpose of this study was to examine the expression of the fast and slow isoforms of the sarcoplasmic reticulum Ca(2+)-ATPase at the mRNA and protein level in the soleus muscle over a time course of HU and relate them to Ca(2+)-dependent ATPase activity and selected contractile properties. mRNA levels of the acetylcholine receptor (AChR) were measured to compare the signal of unweighting with denervation. Atrophy of the soleus muscles from tail-suspended rats was observed at all time points with muscle mass decreased by 52% at 28 days of HU (P < 0.05). Northern blot analysis showed the relative expression of the fast Ca2+ pump mRNA increased by 0, 250, 910, 1,340, and 4,050% over control levels at 1, 4, 7, 14, and 28 days of HU, respectively, whereas changes in slow mRNA were variable and modest in comparison. For the same time points, Western blot analysis showed relative expression of the fast Ca2+ pump protein increased by 30, 110, 320, 280, and 300% over control levels, whereas the slow-pump protein expression was unchanged except for a 75% decrease at 28 days of HU. Specific Ca(2+)-dependent ATPase activity was increased (P < 0.05) by 170% at 28 days of HU. Contractile properties measured in vitro at 14 and 28 days revealed time to peak tension and one-half relaxation time were shortened (P < 0.05) and a rightward shift in the tension-frequency curves in unloaded soleus muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous diaphyseal fractures of the radius and ulna, often referred to as both-bone forearm fractures, are frequently encountered by orthopaedic surgeons. Adults with this injury are typically treated with open reduction and internal fixation because of the propensity for malunion of the radius and ulna and the resulting loss of forearm rotation. Large case series support the use of plate and screw fixation for simple fractures. More complex fractures are managed according to strain theory, with the intention of controlling rather than eliminating motion at the fracture site. This can be achieved with flexible plate and screw constructs or intramedullary nails. In general, results of surgical fixation have been good, with only modest losses of forearm strength and rotation. Notable complications include nonunion, malunion, and refracture after device removal.

This study was undertaken as one approach to better understand how contractile activity regulates excitation-contraction coupling phenotype in skeletal muscle. The effects of denervation on the expression of the sarcoplasmic reticulum (SR) Ca(2+)-adenosinetriphosphatase (ATPase), a key protein of the contraction-relaxation cycle, was analyzed in fast-twitch (FT) and slow-twitch (ST) skeletal muscle. Muscle mass, mRNA, and protein expression of specific isoforms of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and contractile parameters related to muscle relaxation were measured in rat soleus and extensor digitorum longus (EDL) muscles at 1, 4, 7, 14, and 28 days after sciatic nerve transection. Wet muscle mass decreased to 35% of control by 28 days of denervation in both soleus and EDL muscles (P < 0.05). Northern and Western analyses showed decreases in mRNA and protein expression of the slow Ca2+ pump isoform (SERCA2a) in the denervated soleus muscle and in the fast Ca2+ pump isoform (SERCA1) in the denervated EDL muscle, particularly at later time points. There was no change in the expression of the alternate isoform in either muscle type. Prolongation of twitch contraction times, slowed rates of tension development, and leftward shifts in frequency-tension curves were consistent with the reduced Ca2+ pump density and suggested slowed Ca2+ handling in SR or denervated ST and FT muscles. The results are in marked contrast with those previously reported in non-weight-bearing muscle induced by biomechanical unloading.

Biomechanical unloading of the rat soleus by hindlimb unweighting is known to induce atrophy and a slow- to fast-twitch transition of skeletal muscle contractile properties, particularly in slow-twitch muscles such as the soleus. The purpose of this study was to determine whether the expression of the dihydropyridine (DHP) receptor gene is upregulated in unloaded slow-twitch soleus muscles. A rat DHP receptor cDNA was isolated by screening a random-primed cDNA lambda gt10 library from denervated rat skeletal muscle with oligonucleotide probes complementary to the coding region of the rabbit DHP receptor cDNA. Muscle mass and DHP receptor mRNA expression were assessed 1, 4, 7, 14, and 28 days after hindlimb unweighting in rats by tail suspension. Isometric twitch contraction times of soleus muscles were measured at 28 days of unweighting. Northern blot analysis showed that tissue distribution of DHP receptor mRNA was specific for skeletal muscle and expression was 200% greater in control fast-twitch extensor digitorum longus (EDL) than in control soleus muscles. A significant stimulation (80%) in receptor message of the soleus was induced as early as 24 h of unloading without changes in muscle mass. Unloading for 28 days induced marked atrophy (control = 133 +/- 3 vs. unweighted = 62.4 +/- 1.8 mg), and expression of the DHP receptor mRNA in the soleus was indistinguishable from levels normally expressed in EDL muscles. These changes in mRNA expression are in the same direction as the 37% reduction in time to peak tension and 28% decrease in half-relaxation time 28 days after unweighting. Our results suggest that muscle loading necessary for weight support modulates the expression of the DHP receptor gene in the soleus muscle.

Infections are a common complication of allogeneic bone marrow transplantation and the leading cause of transplantation-related mortality. It had been hypothesized that transplantation following nonmyeloablative preparative regimens would result in fewer infections by causing less mucosal injury, less graft-versus-host disease, and allowing earlier immune reconstitution. We have retrospectively reviewed the infectious complications of 65 consecutive patients with advanced hematologic malignancies who underwent bone marrow transplantation using a novel preparative regimen consisting of cyclophosphamide, thymic irradiation, and in vivo T-cell depletion. Cytomegalovirus (CMV) infection occurred in 52% of cases in which the donor or recipient had evidence of prior CMV exposure. Using a strategy of preemptive therapy and secondary prophylaxis with ganciclovir, no CMV disease occurred. Infections with gram-positive bacteria predominated over the first 100 days after bone marrow transplantation. Thereafter, the relative proportion of gram-negative infections increased without a significant increase in episodes of neutropenia. The rate of bacterial infections was not influenced by relapse of the underlying malignancy. Seven patients developed infections with Aspergillus species, which was the most common infectious cause of death in these patients. Infections with viruses other than CMV (n=10) and with protozoan organisms (n=2) also occurred. The use of HLA-mismatched donors, the occurrence of grade II-IV acute graft-versus-host disease, and treatment with corticosteroids did not influence the risk of CMV or bacterial or fungal infections in patients who underwent transplantation following this preparative regimen. Overall, the incidence and spectrum of infections in this series was similar to the reported incidence of infections following conventional myeloablative allogeneic stem cell transplantation. We conclude that a quantitative T-cell deficiency in these extensively T-cell depleted patients may be a risk factor for infection, even in the absence of graft-versus-host disease.