Association of obesity with failure of ultrasound-guided axillary brachial plexus block: a two-centre, prospective, observational, cohort study.

The objective of this study was to evaluate whether the failure rate of ultrasound-guided axillary brachial plexus block is similar in obese patients compared with non-obese patients when performed as the primary anaesthetic technique. We recruited 105 obese (body mass index ≥ 30 kg.m-2 ) and 144 non-obese patients to this prospective, observational, cohort study conducted at two Canadian centres. A perineural technique of axillary brachial plexus block was performed using 30 ml ropivacaine 0.5% under real-time ultrasound guidance. Sensory and motor block assessment was carried out every 5 min until 30 min after block completion in all four terminal nerve distributions (radial, median, ulnar and musculocutaneous nerve). A composite score consisting of three sensory points and three motor points was used for assessment in each nerve distribution. A failed block was defined as a score of less than 14 points out of a possible 16 points, or a sensory block score less than 7 out of 8 points 30 min after block completion. Thirty minutes after block completion, obese patients had a higher failure rate of 33.7% (34/101) compared with 17.8% (24/135) for non-obese patients, with a failure rate difference (95%CI) of 15.9% (6.4-27.1%) between the groups. The median (IQR [range]) time to achieve a successful block in obese patients was 25 (20-30 [5-30]) min, compared with non-obese patients at 20 (15-30 [5-30]) min (p = 0.003). Despite a higher sensory-motor failure rate as per the composite score, the axillary brachial plexus block provided adequate surgical anaesthesia as indicated by a low need for conversion to general anaesthetic in obese (8.6%) and non-obese patients (7.0%; p = 0.656). This study showed that despite ultrasound guidance, obese patients had a slower onset time and higher axillary brachial plexus block failure rate at 30 min compared with non-obese patients.

Expanding the genotypic spectrum of Perrault syndrome.

Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) in both sexes and primary ovarian insufficiency in 46, XX karyotype females. Biallelic variants in five genes are reported to be causative: HSD17B4, HARS2, LARS2, CLPP and C10orf2. Here we present eight families affected by Perrault syndrome. In five families we identified novel or previously reported variants in HSD17B4, LARS2, CLPP and C10orf2. The proband from each family was whole exome sequenced and variants confirmed by Sanger sequencing. A female was compound heterozygous for a known, p.(Gly16Ser) and novel, p.(Val82Phe) variant in D-bifunctional protein (HSD17B4). A family was homozygous for mitochondrial leucyl aminocyl tRNA synthetase (mtLeuRS) (LARS2) p.(Thr522Asn), previously associated with Perrault syndrome. A further family was compound heterozygous for mtLeuRS, p.(Thr522Asn) and a novel variant, p.(Met117Ile). Affected individuals with LARS2 variants had low frequency SNHL, a feature previously described in Perrault syndrome. A female with significant neurological disability was compound heterozygous for p.(Arg323Gln) and p.(Asn399Ser) variants in Twinkle (C10orf2). A male was homozygous for a novel variant in CLPP, p.(Cys144Arg). In three families there were no putative pathogenic variants in these genes confirming additional disease-causing genes remain unidentified. We have expanded the spectrum of disease-causing variants associated with Perrault syndrome.

Predictors of Disability and Quality of Life With an Upper-Extremity Peripheral Nerve Disorder.

OBJECTIVE: We sought to understand the wide range of problems that patients with upper-extremity peripheral nerve disorders experience and to identify predictors of disability and quality of life (QOL). METHOD: Data from standardized assessments of disability and QOL, physical examination results, and intake surveys from 627 patients were analyzed using descriptive and inferential statistics. We compared results between groups and built multivariate models measuring disability, work disability, and physical and mental QOL. RESULTS: The sample demonstrated substantial disability and even greater work disability, which both closely correlated with poorer QOL. Work status was integral in predicting disability. Common predictors across models included problems with sleep and intimate relationships, deficits in work and household performance, and higher pain. CONCLUSION: To decrease disability and improve QOL, occupational therapy practitioners should help patients with upper-extremity peripheral nerve disorders identify strategies to maintain meaningful work and household roles, intimate relationships, and sleep, while continuing to address pain.

Cytomegalovirus pre-emptive therapy after hematopoietic stem cell transplantation in the era of real-time quantitative PCR: comparison with recipients of solid organ transplants.

BACKGROUND: Cytomegalovirus (CMV) continues to be an important complication of hematopoietic stem cell transplantation and solid organ transplantation. METHODS: In this study, 314 patients who underwent hematopoietic stem cell transplantation between January 2003 and October 2011 were tested serially for CMV DNA by real-time quantitative polymerase chain reaction (qPCR) for 90 days post transplantation. Patients with CMV viremia >3000 genomes/mL (equivalent to 2520 IU/mL) received pre-emptive therapy and were compared with previously published data from solid organ transplant (SOT) patients monitored and treated in exactly the same way. RESULTS: After stem cell transplant (SCT), 48% of patients developed at least 1 episode of viremia. The median duration of a viremic episode was 25 days and the peak viral load (VL) was 4784 genomes/mL whole blood (equivalent to 4019 IU/mL). The data demonstrated that recipients with positive CMV serostatus were at increased risk of developing viremia, with 0% of donor-negative/recipient-negative (D-R-), 3.7% of D+R-, 79.5% of D-R+, and 74.2% of D+R+ groups developing viremia over follow-up (adjusted hazard ratio for D+R- vs. D+R+ group 0.03; 95% confidence interval 0.004, 0.18; P = 0.0013). In contrast with SOT patients, where 58/74 (78%) D+R- patients had viremia, a low risk of CMV infection was seen after stem cell transplantation (1/27; 3.7%). CONCLUSION: As both groups of patients, the previously published SOT patients and the present hematopoietic SCT patients, were monitored using the same protocol and qPCR assay with pre-emptive therapy administered at the same VL cutoffs, the distinct differences seen cannot be explained by differences in testing or management and thus emphasize distinct aspects of the natural history of CMV infection post transplant in these 2 patient groups.

ENT trainees' experience of redeployment during the coronavirus disease 2019 pandemic: a qualitative study.

BACKGROUND: As a response to the acute strain placed on the National Health Service during the first wave of coronavirus disease 2019 in the UK, a number of junior doctors including ENT trainees were redeployed to other clinical specialties. This presented these trainees with novel challenges and opportunities. METHODS: A qualitative study was performed to explore these experiences, undertaking semi-structured interviews with ENT trainees between 17th and 30th July. Participants were recruited through purposeful sampling. Interview transcripts underwent thematic analysis using Dedoose software. RESULTS: Seven ENT trainees were interviewed, ranging from specialty trainee years four to eight ('ST4' to 'ST8') in grade. Six core themes were identified: organisation of redeployment, utilisation of skill set, emotional impact of redeployment, redeployed team dynamics, concerns about safety and impact on training. CONCLUSION: The ENT trainees' experiences of redeployment described highlight some important lessons and considerations for future redeployments.

Absence of damaging effects of stem cell donation in unrelated donors assessed by FISH and gene variance screening.

ASTRACT: Granulocyte-Colony-Stimulating factor (G-CSF) is currently the standard mobilising agent for peripheral blood stem cell (PBSC) donation. Concerns that it may trigger chromosome aberrations similar to those observed in leukaemia patients were refuted but long-term effects of G-CSF mobilisation on genome integrity remains unclear. In the setting of a multi-centre clinical trial we screened blood samples from 50 PBSC donors at cellular and gene level for aberrations common in haematological malignancies using fluorescence in situ hybridisation (FISH) and next generation sequencing (NGS) assays. Analysis of samples collected before, on the day of donation, 90 and 180 days after G-CSF admission confirmed the absence of short-term effects in PBSC donors on both quiescent and dividing cells. This data did not differ from the results of 50 individuals tested 3-5 years after bone marrow donation and 50 healthy persons. NGS using a panel targeting 54 genes recurrently affected in myeloid disorders (TruSight Myeloid panel, Illumina) showed that the gene profiles of samples from 48 PBSC donors remained stable throughout the study period. These data strongly indicate absence of detrimental effects on the genome integrity caused by PBSC donation.

Superiority of reduced-intensity allogeneic transplantation over conventional treatment for relapse of Hodgkin's lymphoma following autologous stem cell transplantation.

This study compares outcome of reduced-intensity conditioned transplant (RIT) with outcome of conventional non-transplant therapy in patients with Hodgkin's lymphoma relapsing following autograft. There were 72 patients in two groups who had relapsed, and received salvage therapy with chemotherapy+/-radiotherapy. One group (n=38) then underwent alemtuzumab-containing RIT. The second group-historical controls (n=34), relapsing before the advent of RIT-had no further high-dose therapy. This group was required to respond to salvage therapy and live for over 12 months post-relapse, demonstrating potential eligibility for RIT, had this been available. Overall survival (OS) from diagnosis was superior following RIT (48% at 10 years versus 15%; P=0.0014), as was survival from autograft (65% at 5 years versus 15%; P< or =0.0001). For the RIT group, OS at 5 years from allograft was 51%, and in chemoresponsive patients was 58%, with current progression-free survival of 42%. Responses were seen in 8 of 15 patients receiving donor lymphocyte infusions (DLI) for relapse/progression, with durable remission in five patients at median follow-up from DLI of 45 months (28-55). These data demonstrate the potential efficacy of RIT in heavily pre-treated patients whose outlook with conventional therapy is dismal, and provide evidence of a clinically relevant graft-versus-lymphoma effect.

Costimulation blockade of CD40 and CD28 pathways in limb transplantation.

Costimulation blockade remains a promising experimental regimen for the induction of transplantation tolerance. The simultaneous blockade of both the CD40 and CD28 pathways has been synergistic in prolonging organ allograft survival but has not previously been investigated in a model of limb allotransplantation. This study determined the efficacy of this combination in the murine limb allograft model. C57B1/6 (H-2K(b)) female mice were recipients of heterotopic vascularized limb allografts from Balb/c (H-2K(d)) male donors. Experimental groups received treatment with a short course of MR1 (hamster anti-mouse anti-CD40 ligand antibody) alone or in combination with CTLA4-Ig, a fusion protein that blocks the B7/CD28 pathway. Untreated recipients rejected limb allografts at a mean of 9.6 +/- 1.1 (standard error of the mean) days postoperatively. Recipients of a prolonged course of MR1 rejected limb allografts at 75 +/- 25 days. When both MR1 and CTLA4-Ig were used, limb allograft survival of >120 days was observed despite a much shorter course of therapy. Rejection in both treatment groups was consistent with a chronic antibody-mediated process. Donor antigen rechallenge in these recipients by in vitro assay and skin allograft demonstrated a hyperacute response consistent with presensitization. Long-term limb allograft survival is produced by the synergistic effect of blocking both the CD40 and CD28 costimulatory pathways. However, permanent acceptance was not achieved, and allografts eventually succumbed to what appeared to be antibody-mediated rejection. The additional use of newer agents that block more recently described costimulatory pathways may be essential for the induction of tolerance by costimulation blockade.

Recipient/donor HLA and CMV matching in recipients of T-cell-depleted unrelated donor haematopoietic cell transplants.

Improving haematopoietic cell transplantation outcomes by selection of an HLA-matched unrelated donor is best practice; however, donor selection by secondary characteristics is controversial. We studied 1271 recipients with haematological malignancies who underwent T-cell-depleted allografts and had complete data on HLA-matching status for six loci (HLA-A, -B, -C, -DRB1, -DQB1, -DPB1) and clinical outcome data. Five-year overall survival was 40.6%. HLA mismatching (at HLA-A, -B, -C, -DRB1, -DQB1) relative risk (RR) 1.22, 95% confidence interval (CI) 1.2-1.5, P=0.033 for 1 mismatch and RR 1.46, 95% CI 1.1-1.9, P=0.009 for >1 mismatch) and CMV mismatching (RR 1.37, 95% CI 1.2-1.6, P<0.001) were significantly associated with inferior survival. Donors aged <30 years showed a trend towards better survival. The multivariate model for mortality, combining CMV and HLA-match status, found an RR of 1.36 (95% CI 1.1-1.7, P=0.003) for HLA matched/CMV mismatched, an RR of 1.22 (95% CI 0.99-1.5, P=0.062) for HLA mismatched/CMV matched and an RR of 1.81 (95% CI 1.4-2.3, P=<0.001) for HLA/ CMV mismatched, compared with the HLA/CMV-matched recipients. These data suggest that HLA and CMV matching status should be considered when selecting unrelated donors and that CMV matching may abrogate the effect of an HLA mismatch.

Polyphenolics enhance red blood cell resistance to oxidative stress: in vitro and in vivo.

In this study we investigated the potential antioxidant properties of blueberry polyphenolics in vitro and vivo, using red blood cell (RBC) resistance to reactive oxygen species (ROS) as the model. In vitro incubation with anthocyanins or hydroxycinnamic acids (HCA) (0.5 and 0.05 mg/ml) was found to enhance significantly RBC resistance to H2O2 (100 microM) induced ROS production. This protection was also observed in vivo following oral supplementation to rats at 100 mg/ml. However, only anthocyanins were found to afford protection at a significant level, this at 6 and 24 h post supplementation. This protection was not consistent with the measured plasma levels of anthocyanins. Indeed, plasma polyphenolic concentrations were highest after 1 h, declining considerably after 6 h and not detected after 24 h. The difference in absorption between anthocyanins and HCA is likely to have contributed to the observed difference in their abilities to afford protection to RBC. This protection represents a positive role following dietary consumption of polyphenolics from blueberries, against ROS formation within RBC in vivo.

The effect of low-dose aciclovir on reactivation of varicella zoster virus after allogeneic haemopoietic stem cell transplantation.

Patients undergoing haemopoietic stem cell transplants (HSCT) are at high risk of varicella zoster virus (VZV) reactivation, with a significant incidence of dissemination. This study reports a retrospective analysis of 247 allogeneic HSCT recipients receiving anti-viral prophylaxis with low-dose oral aciclovir 400 mg/day, administered until immunosuppression was discontinued and the CD4(+) cell count exceeded 200/mm(3). Viral reactivation was successfully suppressed by aciclovir prophylaxis, with only one case of breakthrough infection. The cumulative incidence of zoster infection at 1 year post transplant was 2% and at 5 years 34%. In all, 64 patients discontinued prophylaxis. Zoster developed in 26 of these, giving a cumulative incidence of infection at 1 year after stopping aciclovir of 39% and at 3 years 44%. Infection occurred in a localised dermatomal distribution in 93% of cases. This supports previous findings that aciclovir prophylaxis prevents early VZV reactivation, although the long-term incidence is not affected as infection occurs once prophylaxis is discontinued. Such infection, however, is mild and localised. This study does not support the idea that use of such low-dose aciclovir regimens reduces the zoster incidence by permitting subclinical reactivation during prophylaxis, and therefore the re-establishment of protective anti-viral immunity.

Induction of a syngeneic graft-versus-leukemia effect following bone marrow transplantation for chronic myeloid leukemia.

Although clinical data support the concept of a graft-versus-leukemia (GVL) effect following allogeneic bone marrow transplantation (BMT), there are few data to support a similar GVL activity following syngeneic BMT in man. To identify cells with a potential antileukemic activity post-BMT, we monitored the immunological reconstitution in a patient with chronic phase chronic myeloid leukemia (CML) who received a syngeneic BMT from his identical twin brother. Peripheral blood mononuclear cells (PBMC) from the donor prior to the transplant and from the recipient posttransplant were cultured with recombinant interleukin-2 to generate lymphokine activated killer (LAK) cells. LAK cells from both sources lysed the cell line target cells K562 and LCL and also recipient and allogeneic CML target cells in a 51Cr release cytotoxicity assay. Donor-derived LAK cells did not kill normal donor marrow. LAK cells had similar effects on granulocyte-macrophage progenitor cells (CFU-GM): LAK cells from both donor pre-BMT and recipient post-BMT inhibited the proliferation of CFU-GM from the patient's CML cells, but again donor LAK cells did not inhibit the colony growth of normal donor marrow. These results suggest that a syngeneic GVL effect is inducible following BMT in man and that this activity may be truly antileukemic and spare normal marrow progenitors.

Transcription-mediated amplification and hybridisation protection assay to determine BCR-ABL transcript levels in patients with chronic myeloid leukaemia.

Detection of BCR-ABL transcripts in chronic myeloid leukaemia (CML) is used to confirm the diagnosis and to monitor residual disease. Quantitative techniques are required to predict response to therapy or early relapse. We have evaluated an assay in which transcription-mediated amplification (TMA) of BCR-ABL and ABL transcripts is achieved using reverse transcriptase and RNA polymerase. The products are quantified in the hybridisation protection assay (HPA) using acridinium ester-labelled DNA probes and chemiluminescence. The method is a single tube procedure which uses small amounts of RNA (<500 ng/triplicate analysis), is technically simple (requiring just two waterbaths and a luminometer), rapid (total assay time <4 h) and sensitive (capable of detecting one BCR-ABL-positive K562 cell in the presence of 10(4)-10(5) BCR-ABL-negative cells). BCR-ABL signals from patient RNA samples were quantified relative to known amounts of K562 RNA and normalised to levels of ABL. BCR-ABL/ABL ratios ranged from 0.15 to 1.59 (median 0.65) in RNA from diagnostic blood or bone marrow of 18 CML patients and were < or =0.0001 in 20 normal controls. Sequential samples analysed from six CML patients post-allogeneic bone marrow transplantation who relapsed and received donor lymphocyte infusions showed BCR-ABL/ABL ratios which reflected patient status or treatment. A BCR-ABL/ABL ratio of 0.01 served as a useful arbitrary indicator value, with results above and below this value generally correlating with relapse or remission, respectively.

Prevention of graft-versus-host disease by ex vivo T cell depletion: reduction in graft failure with augmented total body irradiation.

Graft-versus-host disease prevention was attempted in 35 consecutive patients with hematological malignancy who received bone marrow from an HLA match sibling donor who was depleted of T cells ex vivo. Five of the first 8 patients who received cyclophosphamide 60 mg/kg on 2 consecutive days followed by fractionated total body irradiation (TBI) (6 x 2 Gy) had graft failure. The subsequent 27 patients had received an extra fraction of TBI (7 x 2 Gy), and only one failed to have stable engraftment. There were no differences in nucleated cell dose, granulocyte-macrophage colony-forming units, or T cell numbers given to the two groups. Neutrophil but not platelet regeneration of those patients who successfully grafted was slower than in a group of historical controls receiving unmanipulated marrow. Significant graft-versus-host disease was prevented with no increase in relapse rate. We suggest that engraftment can be reliably achieved by augmenting the TBI conditioning in recipients of T cell-depleted matched allogeneic bone marrow.

Bone marrow transplantation for chronic myeloid leukemia: the use of histocompatible unrelated volunteer donors.

We treated 17 patients with chronic myeloid leukemia (CML) by bone marrow transplantation using marrow from human leukocyte antigen (HLA)-matched unrelated donors. Patients were conditioned with a combination of in vivo monoclonal antibodies, chemotherapy with daunorubicin (n = 7) or busulfan (n = 10) and cyclophosphamide, and both total body and total lymphoid irradiation. Donor marrow was depleted of T cells by incubation with monoclonal antibodies of the Campath series. Fourteen (88%) of 16 evaluable patients had sustained engraftment. Four (27%) of the 15 evaluable patients developed acute graft-versus-host disease (GVHD) of grade II or greater, and 4 of 12 evaluable patients developed chronic GVHD. Three patients developed hematological and two developed cytogenetic evidence of relapse. Eight patients (47%) survive at a median follow-up of 32 months (range 10-51 months), giving an actuarial survival of 44%. Five patients remain alive without evidence of hematological or cytogenetic relapse, giving an actuarial disease-free survival of 27%. Pneumonitis caused or contributed to death in six of the nine patients who died. We conclude that T-cell depletion can prevent the severest forms of GVHD but also increases the risk of relapse after transplant with unrelated donors, as it does with HLA-identical siblings. Nevertheless the use of matched unrelated donors should be considered for CML patients who lack HLA-identical siblings.

Long-term behavioral impairment following acute embryonic ethanol exposure in zebrafish.

BACKGROUND: Developmental exposure to ethanol has long been known to cause persisting neurobehavioral impairment. However, the neural and behavioral mechanisms underlying these deficits and the importance of exposure timing are not well-characterized. Given the importance of timing and sequence in neurodevelopment it would be expected that alcohol intoxication at different developmental periods would result in distinct neurobehavioral consequences. METHODS: Zebrafish embryos were exposed to ethanol (0%, 1%, 3%) at either 8-10 or 24-27 h post-fertilization (hpf) then reared to adolescence and evaluated on several behavioral endpoints. Habituation to a repeated environmental stimulus and overall sensorimotor function were assessed using a tap startle test; measurements of anxiety and exploration behavior were made following introduction to a novel tank; and spatial discrimination learning was assessed using aversive control in a three-chambered apparatus. Overt signs of dysmorphogenesis were also scored (i.e. craniofacial malformations, including eye diameter and midbrain-hindbrain boundary morphology). RESULTS: Ethanol treated fish were more active both at baseline and following a tap stimulus compared to the control fish and were hyperactive when placed in a novel tank. These effects were more prominent following exposure at 24-27 hpf than with the earlier exposure window, for both dose groups. Increases in physical malformation were only present in the 3% ethanol group; all malformed fish were excluded from behavioral testing. DISCUSSION: These results suggest specific domains of behavior are affected following ethanol exposure, with some but not all of the tests revealing significant impairment. The behavioral phenotypes following distinct exposure windows described here can be used to help link cellular and molecular mechanisms of developmental ethanol exposure to functional neurobehavioral effects.

Generation of memory T cells for adoptive transfer using clinical-grade anti-CD62L magnetic beads.

Pre-clinical studies of allogeneic stem cell transplantation suggest that depletion of naive T cells from donor lymphocytes will reduce the risk of GvHD but preserve immunity to infectious pathogens. In this study, we have established a clinical-grade protocol under good manufacturing practice conditions for purging CD62L(+) naive T cells from steady-state leukapheresis products using the CliniMACS system. The efficacy of immunomagnetic CD62L depletion was assessed by analysis of cell composition and functional immune responses. A median 2.9 log CD62L depletion was achieved with no evidence of CD62L shedding during the procedure and a mean T-cell yield of 47%. CD62L(-) cells comprised an equal mix of CD4(+) and CD8(+) T cells, with elimination of B cells but maintenance of regulatory T cells and natural killer cell populations. CD62L-depleted T cells were predominantly CD45RA(-) and CD45RA(+) effector memory (>90%) and contained the bulk of pentamer-staining antivirus-specific T cells. Functional assessment of CD62L(-) cells revealed the maintenance of antiviral T-cell reactivity and a reduction in the alloreactive immune response compared with unmanipulated cells. Clinical-grade depletion of naive T cells using immunomagnetic CD62L beads from steady-state leukapheresis products is highly efficient and generates cells suitable for adoptive transfer in the context of clinical trials.

The fate of Schwann cells in peripheral nerve allografts.

The phenotype of Schwann cells, whether of host or donor origin, in nerve allografts has been a source of debate. The origin of Schwann cells in peripheral nerve allografts under conditions of no, temporary or continuous immunosuppression was assessed by immunohistochemistry. We hypothesized that host-derived Schwann cells would replace rejected foreign donor Schwann cells after withdrawal of immunosuppression. A murine model of nerve transplantation to normal (wild-type) hosts from donor Shiverer mice, a mutant whose Schwann cells are deficient in myelin basic protein, was used and antibody reactivity against myelin basic protein was employed to ascertain the identity of Schwann cells in the nerve allograft. Without immunosuppression, donor Shiverer Schwann cells were rejected and the nerve graft morphology was restored by host-derived Schwann cells. With continuous immunosuppression, donor Shiverer Schwann cells persisted in the graft segment, associated with a chronic rejection phenomenon. The latter allowed migration of host-derived Schwann cells, over time, into the graft segment in approximately half the cases. After withdrawal of finite (6 weeks) immunosuppression, a rejection response eliminated donor Schwann cells. Replacement by host Schwann cells ensured as was hypothesized.

Motor and sensory specificity of host nerve axons influence nerve allograft rejection.

Previous studies have shown both survival and loss of regenerated host axons within nerve allograft segments after withdrawal of Cyclosporin A (CsA) immunosuppression. We hypothesized that the nature of end-organ reinnervation may influence the response of the axon, with survival of axons for appropriate innervation vs degeneration for inappropriate innervation. The rat femoral nerve model was chosen, as it has approximately equal sensory (S) and motor (M) divisions. Four ACI rat peroneal nerve allografts were sutured in straight (right leg: MM and SS) or switched (left leg; MS and SM) orientation in each femoral nerve transection gap in each Lewis rat recipient. Rats received CsA for 8 weeks to allow end-organ reinnervation, after which immunosuppression was discontinued. Rats were killed at various times thereafter, and underwent histologic and morphometric analysis of the graft segment axons. The regenerated axon population in the allograft reflected the nerve of origin: significantly more but smaller fibers when the proximal nerve was sensory and fewer but larger fibers when the proximal nerve was motor. After CsA withdrawal, there was a marked decrease of host axons as part of an ensuing rejection episode. The overall proportional decrease of axons was similar across all nerve orientation groups and, therefore, did not appear to be influenced by the nerve of origin or by the end-organ. However, the sensory proximal groups (SS and SM) contained more mature, noninjured fibers, while the motor proximal groups (MM and MS) contained significantly more degeneration and newly regenerating axons. We conclude that the motor or sensory nerve origin of the host axon, rather than the end-organ, influences axon survival after immunosuppression cessation. It is hypothesized that sensory axons may be more resilient while motor axons are selectively vulnerable to this second injury.

Tibial nerve branching in the tarsal tunnel.

To provide an anatomical basis for diagnosis and treatment of the tarsal tunnel syndrome, the relationship of the tibial nerve to the tarsal tunnel was investigated in 31 feet of 20 cadavers. The bifurcation into medial and lateral plantar nerves occurred within 1 cm of the malleolar-calcaneal axis in 90% of the feet. Seven of 11 bilateral specimens were bilaterally symmetrical in the bifurcation location; three varied within 1 cm between sides; and in the fourth cadaver, one side bifurcated at 3 cm and the other at 5 cm proximal to the axis. The calcaneal nerve showed great variability; in seven cadavers, it arose within, in eight cadavers proximal to, and in five cadavers there were multiple branches arising both proximal to and within the tarsal tunnel.