NF-κB-associated mechanisms underlying the response of embryonic cells to Doxorubicin.

The involvement of NF-κB in the regulation of teratogen-induced apoptosis has not been established yet. Therefore, we tried to assess the involvement of the p65 subunit of NF-κB in the embryonic response to the anti-cancer drug Doxorubicin (DOX). Thus, exposure of p65 knockout (p65(-/-)) or wild type (WT) mouse embryonic fibroblasts (MEFs) to DOX resulted in a decrease in cell survival, culture density and cell proliferation, which was found to be more prominent in p65(-/-) MEFs. Those phenomena were accompanied by a DOX-induced increase in the proportion of apoptotic cells, which was demonstrated only in p65(-/-) cells and a G2/M arrest, which was found to be more prominent in WT cells. Furthermore, DOX-treated WT and p65(-/-) MEFs differed in their expression of various apoptosis-associated molecules, when the former demonstrated a decrease in the percentage of p65-positive and a more prominent decrease in the percentage of p53-positive cells, while a decreased percentage of IκBα-positive and a more prominent decrease in the percentage of bcl-2-positive cells was detected among the latter. The fact that the response of the cells to the teratogen was clearly p65-dependent implicates this molecule to be involved in the response of the embryonic cells to DOX.

Bax-associated mechanisms underlying the response of embryonic cells to methotrexate.

Bax was shown previously to regulate apoptotic cell death in various experimental systems, however, its involvement in teratogen-induced apoptosis is not clear yet. Therefore, we explored the involvement of Bax in the response of mouse embryonic fibroblasts (MEFs) to the anti cancer drug methotrexate (MTX), using Bax wild type (WT) and knockout (Bax(-/-)) MEFs. Our results demonstrated a significant teratogen-induced dose- and time-dependant decrease in the survival and culture density of both cell lines, which were found to be somewhat more prominent in WT cells. Exposure to MTX resulted also in decreased cell proliferation of WT but not Bax(-/-) cells and accordingly, we observed an accumulation of cells in the S phase and an increased percentage of cells in the Sub-G(1) phase of the cell cycle and the appearance of condensed nuclei, which were found to be somewhat more prominent in WT MEFs. In parallel, WT MEFs demonstrated a MTX-induced increase in the percentage of Bax-positive cells and a significant decrease in the percentage of bcl-2-, p65- or IkappaBalpha-positive cells, which were not detected in Bax(-/-) MEFs. Altogether, the differential sensitivity of WT or Bax(-/-) MEFs to MTX suggests a possible involvement of this molecule in the response of embryonic cells to teratogens.

TNF-alpha acts to prevent occurrence of malformed fetuses in diabetic mice.

AIMS/HYPOTHESIS: Activation of apoptosis in embryos is thought to be a key event in the pathogenesis of diabetes-induced embryopathies such as early embryonic death and inborn structural anomalies. TNF-alpha can activate apoptotic and anti-apoptotic signalling cascades, indicating its ability to contribute to and counteract diabetes-induced maldevelopment. To investigate how TNF-alpha regulates the response of embryos to diabetes-induced embryopathic stress, we used streptozotocin-induced diabetic TNF-alpha knockout mice. MATERIALS: To evaluate the reproductive performance, mated diabetic female mice were examined on days 4 and 8 of pregnancy for the presence of blastocysts or embryos in uterine horns. To evaluate the teratogenic effect, the female mice were killed on day 18 of pregnancy and fetuses were examined for gross external anomalies. In addition, apoptotic nuclei were localised by the TUNEL assay and DNA-binding activity of the transcription factor NF-kappaB was evaluated by electrophoretic mobility shift assay in 10- and 11-day-old embryos respectively. RESULTS: Severely diabetic TNF-alpha(+/+) female mice had a much greater decrease in pregnancy rate but a lower incidence of malformed fetuses in litters than severely diabetic TNF-alpha(-/-) female mice. Also, the intensity of excessive apoptosis was higher, but the amount of active NF-kappaB complexes was lower in malformed TNF-alpha(-/-) embryos than in TNF-alpha(+/+) embryos. CONCLUSIONS/INTERPRETATION: TNF-alpha contributes to death of peri-implantation embryos and possibly protects postimplantation embryos exposed to diabetes-induced teratogenic stimuli via activation of NF-kappaB-mediated anti-apoptotic signalling. It seems that TNF-alpha prevents the birth of malformed offspring in severely diabetic mice.

Increased TNF-alpha expression in cultured mouse embryos exposed to teratogenic concentrations of glucose.

Diabetes-induced early embryonic death is accompanied by an increased expression of tumour necrosis factor alpha (TNF-alpha) in the embryonic microenvironment. The aim of the present study was to evaluate whether diabetes-induced embryopathic stress may also alter the expression of TNF-alpha produced by the embryo itself. As a model, whole postimplantation embryos were cultured for 24 h in a medium with high concentrations of glucose, one of the main diabetes-associated teratogenic metabolites. An anomaly such as an open neural tube was used as an end-point characterizing the glucose-induced teratogenic effect and the number of somites was counted to evaluate growth retardation induced by glucose. The expression of TNF-alpha (by immunohistochemistry), apoptosis (by TdT-mediated dUTP nick-end labelling; TUNEL) and the activity of caspases 3 and 8 (by a fluorometric assay) were evaluated in normal and malformed embryos. Ninety-seven per cent of the embryos exposed to 1300 mg glucose dl(-1) exhibited an open neural tube. The percentage of malformed embryos was smaller in media containing 800 and 500 mg glucose dl(-1) (68 and 37%, respectively) but it still exceeded significantly the value registered in embryos developing in a normoglycaemic medium (12%). In addition, a significant decrease in the number of somites was observed in embryos developing in media containing 1300 and 800 mg glucose dl(-1). Malformed embryos exhibited a greater number of nuclei that were positive in the TUNEL assay as well as a higher amount of active caspase 8 compared with normal embryos (with closed neural folds). TNF-alpha expression was detected in the neuroepithelial layer of the neural tube of the malformed embryos, whereas the expression of this cytokine was weak, if detectable, in normal embryos. Together, these findings indicate that TNF-alpha produced by the embryo may be involved in regulating the response of embryos to diabetes-generated embryopathic stress.

Cytokine expression in the uterus of mice with pregnancy loss: effect of maternal immunopotentiation with GM-CSF.

It is believed that failure of the maternal immune system to actively support embryonic development, through production of the appropriate cytokine network, might be responsible for embryonic death. Thus, the aim of this study was to evaluate the possible involvement of cytokines such as tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta2 (TGF-beta2), which are crucial for normal embryonic development, in the early stages of mechanisms that mediate induced pregnancy loss. The early stages of the resorption process induced by lipopolysaccharide (LPS) were characterized by blood accumulation in the vicinity of the embryo, preceding any visible embryonic damage. At that time, immunohistochemical analysis revealed an increased expression of TNF-alpha in the primary and secondary decidua, which was reduced as the resorption process was completed. In contrast, TGF-beta2 expression was decreased in the primary and secondary decidua, as well as in the glandular epithelium, at all the times assessed. Maternal immunopotentiation with granulocyte macrophage-colony stimulating factor (GM-CSF), which controls maternal immune activities supporting normal embryonic development, decreased the resorption rate in LPS-treated mice while normalizing the expression of TNF-alpha and TGF-beta2 in the uterus of these animals throughout the ongoing resorption process. These results indicate a possible role for maternal immunopotentiation with GM-CSF in the mechanisms mediating the early stages of pregnancy loss, possibly via modulation of TNF-alpha and TGF-beta2 activity.

Apoptosis in the uterus of mice with pregnancy loss.

PROBLEM: The mechanisms mediating pregnancy loss induced by various agents are far from being understood. Thus, we investigated the possible involvement of one such mechanism, the apoptotic process, in pregnancy loss induced by lipopolysaccharide (LPS) or cyclophosphamide (CP) as well as the associated changes in the apoptosis-regulating gene products p53 and bcl-2. METHOD OF STUDY: Pregnancy loss was induced by LPS or CP on days 9 or 12 of pregnancy, respectively. LPS- or CP-associated apoptosis was assessed by the TdT mediated dUTP-biotin nick end labeling (TUNEL) method as well as by DNA fragmentation analysis, while p53 or bcl-2 expression was evaluated by immunohistochemistry. RESULTS: Lipopolysaccharide treatment initiated a resorption process that was accompanied by the appearance of apoptotic cells in the uterus, which increased in number by 24 hr after treatment. Induction of pregnancy loss with CP resulted in the appearance of some apoptotic cells in the uterus, reaching a peak at 72 hr after treatment. DNA fragmentation analysis revealed a DNA ladder at 24 hr after LPS as well as 72 hr after CP treatment. Immunohistochemical analysis demonstrated a continuous p53 expression in the uterus of LPS- or CP-treated mice, which was somewhat elevated at the peak of the apoptotic process. On the other hand, bcl-2 expression in LPS-treated mice could be reciprocally correlated with the apoptotic process, appearing only at its initiation or completion, while in CP-treated mice it was continuously expressed except for some elevation at the completion of the apoptotic process. CONCLUSIONS: Our results suggest a possible role for the apoptotic process in mechanisms mediating pregnancy loss and indicate an involvement of p53 and bcl-2 in its regulation.

Diabetes teratogenicity in mice is accompanied with distorted expression of TGF-beta2 in the uterus.

Early embryonic deaths as well as malformed newborns are among complications of the diabetic pregnancy. Cytokines and growth factors operating in the embryonic vicinity are found to be among factors that determine the sensitivity of embryos to external and internal detrimental stimuli, including diabetes. Transforming Growth Factor-beta2 (TGF-beta2) has been shown to be essential for embryonic development and survival. In the present work, we evaluated the pattern of TGF-beta2 expression in the uterus of streptozotocin-induced diabetic mice, demonstrating a decreased reproductive performance and elevated percentage of litters with severely malformed fetuses. Since stimulation of the maternal immune system was found to increase the resistance of mouse embryos to the teratogenic effect of diabetes, the effect of immunopotentiation on the expression of the cytokine was also investigated. TGF-beta2 expression was studied at the mRNA level by using the in situ hybridization technique and at the protein level by using the immunohistochemical analysis. A clear decrease in TGF-beta2 mRNA expression in the uterus of diabetic mice was observed at examined time points: days 1, 5, and 9 of pregnancy. Also, an evident reduction in TGF-beta2, the protein expression in the uterus of diabetic mice, was demonstrated at these time points. Maternal immunopotentiation that improved the reproductive performance of diabetic mice and reduced the number of the litters with malformed fetuses was also accompanied by a clear increase in the level of TGF-beta2 mRNA expression in the pregnant uteri. The above results clearly demonstrate that the embryotoxic effect of diabetes is accompanied by an alteration of TGF-beta2 expression. Immunopotentiation that was shown to improve the reproductive performance of the diabetic mice was accompanied by a partial normalization of TGF-beta2 expression in embryonic vicinity.

Expression of tumor necrosis factor-alpha in the pregnant uterus of diabetic mice: effect of maternal immunopotentiation.

PROBLEM: Tumor necrosis factor (TNF)-alpha mRNA and protein are expressed in the pregnant uterus of streptozotocin-induced diabetic mice at various stages of pregnancy. We intend to characterize their pattern and to evaluate whether the potentiation of the maternal immune system alters the pattern of the expression of the cytokine. METHOD OF STUDY: Diabetes was induced in ICR mice by streptozotocin injection. To modulate maternal immune responses, ICR mice were injected intrauterine with rat splenocytes 3 weeks before mating. The expression of TNF-alpha mRNA and protein was evaluated by in situ hybridization and immunohistochemistry techniques. RESULTS: The population of diabetic mice used in this study demonstrated a reduction in pregnancy rate and an increased number of litters with severely malformed fetuses. It has been observed that these disturbances are associated with a clear increase in TNF-alpha mRNA and protein expression in the uterus of these mice. Maternal immunopotentiation, while improving reproductive performance of these diabetic mice, was found to be accompanied by a reduced expression of TNF-alpha, both at the mRNA and protein level. CONCLUSIONS: The results of the present study suggest a possible involvement of TNF-alpha in mechanisms underlying diabetes-associated dismorphogenesis. Normalization of TNF-alpha expression by maternal immunopotentiation might represent a mechanism mediating its protective effect against diabetes-induced embryotoxic insult.

TGFbeta2 in embryos with inborn anomalies: effect of maternal immunopotentiation.

PROBLEM: TGFbetas are among the main immunoregulatory molecules contributing to successful embryonic development. Besides, our and other studies revealed that maternal immunopotentiation has a potential to increase the resistance of the embryo to the teratogenic insult. This work was designed to evaluate: (1) whether the formation of teratogen-induced anomalies is accompanied by an altered pattern of TGFbeta2 expression in embryonic cells and (2) whether maternal immunopotentiation modifies the pattern of TGFbeta2 expression in embryos responding to the teratogenic insult. METHOD OF STUDY: Experiments were performed in embryos of ICR mice exposed to 15 and 40 mg/kg of a reference teratogen, cyclophosphamide (CP) on day 12 of gestation. A group of mice was immunopotentiated with xenogeneic rat splenocytes 21 hr before the beginning of mating. Embryos were examined for the occurrence of gross structural anomalies 24 and 72 hr after CP treatment. Then, immunohistohemistry and in situ hybrydization assays were used to evaluate the expression of TGFbeta2 protein and mRNA in the brain, face, limbs and liver of these embryos. RESULTS: No external anomalies were observed in embryos examined 24 hr after CP treatment. Embryos examined 72 hr after CP treatment at 40 mg/kg exhibited agnathia, micrognathia, kinky tail, phocomelia, but no signs of dismorphogenesis were observed in the liver at the organ level. A significant increase in the expression of TGFbeta2 mRNA was observed in cells, residing in the brain, face and limbs but not in the liver of CP-exposed embryos tested 24 hr after CP injection in both doses. The level of TGFbeta2 protein in these embryos did not differ from that of controls. In embryos tested 72 hr after CP injection in the high dose both TGFbeta2 protein and mRNA expression were found to be elevated. Maternal immunopotentiation while enhancing the embryo's resistance to CP practically abolished an elevated expression of the TGFbeta2 mRNA detected in tested organ structures of embryos of non-immunopotentiated CP treated mice 24 hr after CP injection in both the low and the high doses. Also, a significant decrease in the level of TGFbeta2 mRNA expression was observed in embryos of immunopotentiated mice examined 72 hr after CP treatment. CONCLUSIONS: The results of this work show a possible involvement of TGFbeta2 in the formation of teratogen-induced structural anomalies and suggest that the stimulation of the maternal immune system may realize its protective effect by normalizing the level of TGFbeta2 expression in teratogen-targeted embryonic structures.

Restoration of elbow flexion after brachial plexus injury: the role of nerve and muscle transfers.

Brachial plexus trauma results in a variable loss of upper extremity function. The restoration of this function requires elbow flexion of adequate strength and range of motion. A proper evaluation of brachial plexus lesions is a prerequisite to any reconstructive procedure, and appropriate guidelines are presented. One option for restoring elbow flexion is a nerve transfer. The best results with this procedure are obtained in young patients treated within 6 months of injury. Another option is a free or pedicled muscle transfer, which should be considered in older patients or patients treated more than 6 months after an injury. Muscle transfers may also be used to augment the results of nerve transfer procedures. Choices and clinical results of donor nerves and muscle for transfer are discussed, and an algorithm for treatment is presented.

Mersilene suture as a vehicle for delivery of growth factors in tendon repair.

Extensive clinical and laboratory studies have demonstrated that growth factors accelerate and modulate the wound-healing process. The purpose of this experiment was to apply the principles of growth factor-enhanced wound healing to an in vitro rat tendon model. A method was developed for covalently binding a biologically active peptide to nonabsorbable braided polyester suture (Mersilene). Sutures were treated with various growth factors, which included epidermal growth factor, platelet-derived growth factor, and keratinocyte growth factor, and bovine serum albumin was the control. Spectrophotometric assessment was used to verify the peptide's activity. The suture was subsequently placed through individual harvested rat flexor tendons, which were arranged in standard tissue culture conditions. Markedly increased cellular proliferation along the suture was appreciated on the tendons treated with epidermal growth factor-bound suture. Platelet-derived growth factor was shown to have a lesser effect, whereas keratinocyte growth factor had no visible effect on cellular proliferation. This preliminary study describes a new technique of binding growth factors to suture. It also demonstrates that the presence of growth factors may help facilitate flexor tendon healing and allow early postoperative rehabilitation to decrease adhesion formation.

TNF-alpha messenger RNA and protein expression in the uteroplacental unit of mice with pregnancy loss.

An elevated expression of TNF-alpha in embryonic microenvironment was found to be associated with postimplantation loss. In this work, we examined the pattern of TNF-alpha expression at both the mRNA and the protein level as well as the distribution of TNF-alpha receptor mRNA in the uteroplacental unit of mice with induced (cyclophosphamide-treated) or spontaneous (CBA/J x DBA/2J mouse combination) pregnancy loss. RNase protection analysis demonstrated an increase in TNF-alpha mRNA expression in the placentae of mice with pregnancy loss compared with that in control mice. TNF-alpha messages were localized to the uterine epithelium and stroma as well as the giant and spongiotrophoblast cells of the placenta. The intensity of the hybridization signal in placentae of mice with pregnancy loss was substantially higher than that in control mice. The up-regulation of TNF-alpha mRNA was accompanied by an increase in the expression of TNF-alpha receptor I mRNA in the same cell populations. The elevation of TNF-alpha production was also demonstrated at the protein level. Western blot analysis showed an increased level of the 18- and 26-kDa TNF-alpha protein species in the uteroplacental unit of mice with pregnancy loss. Immunostaining revealed TNF-alpha-positive leukocytes located in the uterus and placenta. Finally, we found that immunization of mice with cyclophosphamide-induced pregnancy loss while decreasing the resorption rate in these females resulted in a decline in TNF-alpha expression at the fetomaternal interface. These data clearly suggest an involvement of TNF-alpha in pathways leading to both spontaneous and induced placental death.

Does display configuration affect information sampling performance?

This investigation sought to determine the influence of a visual display's spatial configuration on participant's ability to sample linguistic information. Line drawings circumscribed 36 areas shaped like squares, rectangles, 'T', 'L' and '+', among others. Each such 'shape' was presented for 1000 ms, followed by a 12-letter matrix presented for 50 ms. Participants then reported the letters that would have been inside the boundary contour if it were superimposed on the letter matrix. The results indicated that single, spatially contiguous areas could be monitored better than separate areas; the recall of simple configurations seemed better than that of more complex ones, while outlying positions tended to be ignored. The data were thus viewed as compatible with recent theories of perceptual organization in displays, such as the notion of 'common region' and the proximity compatibility principle. Informational complexity (IC) proved somewhat better than figural compactness (FC) in accounting for the data in terms of information theory. The findings may help to specify the optimal spatial configurations for visually displayed linguistic information in a variety of contexts, including head-up displays (HUDs).

TNF-alpha expression in embryos exposed to a teratogen.

PROBLEM: The role of tumor necrosis factor (TNF)-alpha produced by embryonic cells in normal and abnormal development is poorly understood. To assess to what extent TNF-alpha may be involved in the process of induced dysmorphogenesis, the expression of TNF-alpha and TNF-alpha receptor (TNFRI) mRNA as well as TNF-alpha protein was evaluated in embryos responding to a cyclophosphamide (CP)-induced teratogenic insult. The effect of maternal immunostimulation increasing the embryo's tolerance to CP on TNF-alpha expression was also investigated. METHOD OF STUDY: ICR female mice were treated intraperitoneally with 40 mg/kg CP on day 12 of pregnancy. The immunostimulator, xenogeneic rat splenocytes, was injected intrauterine 21 days before mating. Embryos were collected on days 13, 14, or 15 of pregnancy. TNF-alpha mRNA, TNFRI mRNA, and TNF-alpha protein expression were evaluated by in situ hybridization and immunostaining techniques in control, teratogen-treated, and immuno-stimulated teratogen-treated embryos. RESULTS: CP-treated embryos showed severe external brain and craniofacial anomalies already visible on day 14 of pregnancy. TNF-alpha mRNA transcripts were detected in cells of the brain and the head of 13-day embryos, which preceded the occurrence of CP-induced external craniofacial anomalies. On day 15 of pregnancy, when severe craniofacial anomalies increased, a significant increase in the intensity of TNF-alpha, TNFR1 mRNA transcripts, and TNF-alpha protein expression were observed in cells of the malformed regions of the head and the brain. In other nonmalformed organs of CP-treated embryos such as the liver (not macroscopically different from controls), neither TNF-alpha nor TNFR1 transcripts were detected. Immunostimulation substantially diminished the severity of CP-induced brain and craniofacial anomalies, decreased the resorption rate, and was associated with decreased intensity of TNF-alpha mRNA transcripts detected on day 15 of pregnancy in the head and the brain of CP-treated embryos. CONCLUSIONS: TNF-alpha expressed in the embryo may be one of the molecules promoting the formation of CP-induced brain and craniofacial anomalies. The decrease of TNF-alpha expression in embryos of immunostimulated females may be one of the mechanisms responsible for the increased tolerance to the teratogenic insult.

Immunostimulation increases the resistance of mouse embryos to the teratogenic effect of diabetes mellitus.

The present work was aimed to assess the possible effect of stimulation of the maternal immune system on the teratogenic potential of diabetes mellitus. ICR female mice were immunized with splenocytes of male rats 3 weeks before the beginning of mating and were injected with 240 mg/kg streptozocin (STZ) 10 days after immunization. Females with blood glucose levels over 27.8 mmol/l and HbA1c levels over 6 standard deviations (SD) above the mean of intact animals were used for teratological studies. The rate of malformed fetuses, resorptions and fetal weights were evaluated for animals killed on day 19 of pregnancy using routine teratological methods. Also, phenotyping of spleen cells of these females was performed by fluorescein activated cell sorter analysis. Two main effects possibly due to immunostimulation of ICR females were observed: 1) immunostimulated females had significantly fewer litters with malformed fetuses than non-immunized females: only 4 litters out of 22 (18%) compared to 10 out of 16 (63%). Correspondingly, the incidence of malformed fetuses was also decreased: 2.1 compared to 8.9%; 2) a significant increase in the pregnancy rate in immunized diabetic ICR mice: 69% as compared to 44% in non-immunized diabetic females. Also, immunostimulation resulted in a visible increase in spleen cellularity and a certain increase in the number of cells with mature T-cell and macrophage surface markers. These results strongly suggest that immunostimulation increases the tolerance of ICR females to the teratogenic effect of STZ-induced diabetes.

In vivo evidence for the existence of a threshold for hyperglycemia-induced major fetal malformations: relevance to the etiology of diabetic teratogenesis.

The present study was carried out to evaluate whether hyperglycemia-induced major fetal anomalies are thresholded phenomena. Streptozotocin (STZ)-treated female ICR mice were examined on day 19 of pregnancy by methods routinely used in Segment II teratological studies. Simultaneously, the glucose and hemoglobin A1c (HbA1c) levels in maternal-blood were measured and mice with glucose levels > 9.5 mmol/l (mean + 3 SD) were considered to be diabetic. The occurrence of litters with fetuses having gross structural anomalies was clearly associated with glucose levels > 27.8 mmol/l. A wide range of HbA1c levels (between 6 and 18 SD above the mean) were observed, within which only single malformed fetuses were found in the litters of diabetic females. A decreased pregnancy rate in diabetic ICR mice was associated with glucose levels > 16.7 mmol/l and with HBA1c levels > 6 SD above the mean. The results of this study suggest that there is a threshold glucose level associated with a clear increase of the number of litters with severely malformed fetuses in diabetic ICR mice. Results of this study also suggest the existence of HbA1c-associated factors determining, along with glucose, the teratogenic response of ICR mice to diabetes. The interpretation of results obtained in terms of the multifactorial/threshold model leads to the hypothesis that the teratogenic potential of diabetes may consist of two components; one associated with 'direct' teratogens perturbing developmental processes in embryos at a 'critical moment' in organogenesis, and a second component, associated with a direct or indirect influence of the diabetic environment on developmental processes in the preimplantation embryos.

Idiopathic midline granuloma--current classification and management controversies.

Midline granuloma is a mutilating process produced by a number of diseases that progressively destroy the nose, paranasal sinuses, and palate. Infectious, neoplastic, and idiopathic forms of this disease have been described. The specific diagnoses must be ascertained, as the treatment is different depending on the etiology of the disease. Radiation therapy is the treatment of choice for idiopathic midline destructive disease, while cytoxan is appropriate for Wegener's granulomatosis, polymorphic reticulosis, and primary nasal lymphomas. When the diagnosis is uncertain, the least-toxic therapy should be used. If the treatment is failing, an alternate therapy should be tried. This article reviews the history of idiopathic midline granuloma, describes the current classification of the disease, and discusses controversial issues demonstrated by two patient presentations.

The effect of a muscle wrap on nerve healing in a rat model.

Sixty Sprague-Dawley rats were studied to determine if peripheral nerve healing could be enhanced by translocation of an injured segment of sciatic nerve from an interfascial to an intramuscular environment. Group 1 (n = 12) were unoperated controls; Group 2 (n = 12) were sham-operated; Group 3 (n = 12) sustained an acute, double-crush injury to the sciatic nerve; and Group 4 (n = 12) sustained the same acute, double-crush injury as in Group 3, but the injured segment of nerve was transposed intramuscularly. All animals had sciatic function indices (SFI) computed at weekly intervals. At 2 weeks, Group 4 appeared to have improved gait function (SFI), compared to Group 3 (-39.7 vs. -56.4, p < 0.08). The experiment was repeated for Groups 3 and 4 using two groups of six additional rats each. The data were collected three times for each rat in the second experiment. No statistically significant differences in return of gait function or in nerve conduction evaluation could be demonstrated between the two study groups. From the results of this study, it appears that an intramuscular location does not enhance nerve recovery, compared to an interfascial location.

Soft tissue coverage for the upper extremity.

Soft tissue coverage of the upper extremity continues to be a challenging and evolving field. The expeditious and reliable methods of soft tissue coverage currently in use are discussed with reference to their shortcomings and advantages. For soft tissue coverage of fingertip injuries, open treatment or local flaps from the hand remain the mainstay of treatment. For dorsal and volar hand defects, distal axial flaps, such as the groin flap or microvascular tissue transfer, are utilized most commonly. For large defects proximal to the wrist, trunk axial pattern flaps, microvascular transfer, or the radial forearm flap have the greatest utility. Finally, technical points necessary for the success of some of the flaps are discussed.