Does prophylactic decompression of distal nerves following nerve repair improve functional recovery? A systematic review.

BACKGROUND: Peripheral nerve injuries are burdensome on healthcare systems, individuals and society as a whole. The current standard of treatment for neurotmesis is primary neurorrhaphy or nerve grafting. However, several patients do not recover their full function. There has been a suggestion that primary distal neurolysis at common entrapment sites maximises surgical outcomes; however, no guidelines exist on this practice. This scoping review aims to ascertain the existing evidence on prophylactic distal decompression of peripheral nerves following repair. METHODS: A literature search was performed using Ovid Medline, PubMed, Embase and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews for studies published in the past 50 years. Studies were screened using a selection criteria and study quality was assessed using standardised tools. Furthermore, thematic content analysis was performed. RESULTS: Six studies were eligible for inclusion after screening; all studies were retrospective and at most level 3 evidence. No studies were designed specifically to assess the efficacy of distal neurolysis following proximal repair, thus no comparative data with control cohorts are available. All studies that recommended distal decompression of proximally repaired nerves based their conclusions on cases observed by the authors in practice or from theories on nerve regeneration. CONCLUSIONS: This systematic review suggests that the evidence on the role of immediate distal neurolysis in primary neurorrhaphy is inadequate. Recommendations are limited by the lack of large-scale and generalisable data. Further research is needed with definitive objective outcomes and patient-related outcome measures.

Psammomatous melanotic schwannoma - a rare neck lump.

This case report discusses a cervical psammomatous melanotic schwannoma - a rare form of peripheral nerve sheath tumour - which may be highly vascular and is often associated with the Carney complex. Significant intraneural bleeding, which was encountered intraoperatively, was controlled successfully with a gelatine-based thrombin haemostatic agent (Floseal®, Baxter International, Deerfield, IL, USA) without complication.

Quantifying regeneration in patients following peripheral nerve injury.

Healthy nerve function provides humans with the control of movement; sensation (such as pain, touch and temperature) and the quality of skin, hair and nails. Injury to this complex system creates a deficit in function, which is slow to recover, and rarely, if ever, returns to what patients consider to be normal. Despite promising results in pre-clinical animal experimentation effective translation is challenged by a current inability to quantify nerve regeneration in human subjects and relate this to measurable and responsible clinical outcomes. In animal models, muscle and nerve tissue samples can be harvested following experimental intervention. This allows direct quantification of muscle mass and quality and quantity of regeneration of axons; such an approach is not applicable in human medicine as it would ensure a significant functional deficit. Nevertheless a greater understanding of this process would allow the relationship that exists between neural and neuromuscular regeneration and functional outcome to be more clearly understood. This article presents a combined commentary of current practice from a specialist clinical unit and research team with regard to laboratory and clinical quantification of nerve regeneration. We highlight how electrophysiological diagnostic methods (which are used with significant recognised limitations in the assessment of clinical medicine) can potentially be used with more validity to interpret and assess the processes of neural regeneration in the clinical context, thus throwing light on the factors at play in translating lab advances into the clinic.

An assessment of fatigability following nerve transfer to reinnervate elbow flexor muscles.

AIMS: Improvements in the evaluation of outcomes following peripheral nerve injury are needed. Recent studies have identified muscle fatigue as an inevitable consequence of muscle reinnervation. This study aimed to quantify and characterize muscle fatigue within a standardized surgical model of muscle reinnervation. PATIENTS AND METHODS: This retrospective cohort study included 12 patients who underwent Oberlin nerve transfer in an attempt to restore flexion of the elbow following brachial plexus injury. There were ten men and two women with a mean age of 45.5 years (27 to 69). The mean follow-up was 58 months (28 to 100). Repeated and sustained isometric contractions of the elbow flexors were used to assess fatigability of reinnervated muscle. The strength of elbow flexion was measured using a static dynamometer (KgF) and surface electromyography (sEMG). Recordings were used to quantify and characterize fatigability of the reinnervated elbow flexor muscles compared with the uninjured contralateral side. RESULTS: The mean peak force of elbow flexion was 7.88 KgF (sd 3.80) compared with 20.65 KgF (sd 6.88) on the contralateral side (p < 0.001). Reinnervated elbow flexor muscles (biceps brachialis) showed sEMG evidence of fatigue earlier than normal controls with sustained (60-second) isometric contraction. Reinnervated elbow flexor muscles also showed a trend towards a faster twitch muscle fibre type. CONCLUSION: The assessment of motor outcomes must involve more than peak force alone. Reinnervated muscle shows a shift towards fast twitch fibres following reinnervation with an earlier onset of fatigue. Our findings suggest that fatigue is a clinically relevant characteristic of reinnervated muscle. Adoption of these metrics into clinical practice and the assessment of outcome could allow a more meaningful comparison to be made between differing forms of treatment and encourage advances in the management of motor recovery following nerve transfer. Cite this article: Bone Joint J 2019;101-B:867-871.

A quantitative assessment of the functional recovery of flexion of the elbow after nerve transfer in patients with a brachial plexus injury.

AIMS: Improvements in the evaluation of outcome after nerve transfers are required. The assessment of force using the Medical Research Council (MRC) grades (0 to 5) is not suitable for this purpose. A ceiling effect is encountered within MRC grade 4/5 rendering this tool insensitive. Our aim was to show how the strength of flexion of the elbow could be assessed in patients who have undergone a re-innervation procedure using a continuous measurement scale. METHODS: A total of 26 patients, 23 men and three women, with a mean age of 37.3 years (16 to 66), at the time of presentation, attended for review from a cohort of 52 patients who had undergone surgery to restore flexion of the elbow after a brachial plexus injury and were included in this retrospective study. The mean follow-up after nerve transfer was 56 months (28 to 101, standard deviation (sd) 20.79). The strength of flexion of the elbow was measured in a standard outpatient environment with a static dynamometer. RESULTS: In total, 21 patients (81%) gained MRC grade 4 strength of flexion of the elbow. The mean force of flexion was 7.2 kgf (3 to 15.5, sd 3.3). CONCLUSION: This study establishes that the dynamometer may be used for assessing the strength of flexion of the elbow in the outpatient department after nerve reconstructive surgery. Cite this article: Bone Joint J 2016;98-B:1517-20.

Pediatric fractures and dislocations of the hip and pelvis.

Recognition of an unstable pelvic fracture or a significant hip injury in children is important. Clinical assessment plays a valuable role as does the judicious use of imaging modalities in determining the most effective form of treatment, but the routine use of the standard AP pelvic radiograph is questioned. The concept of age and skeletal maturity has been re-evaluated, allowing the appropriate identification of cases that would benefit from an aggressive operative approach. A dual-tier approach to the treatment of pediatric pelvic trauma is suggested with an appreciation that there is no substantial evidence base for the surgical treatment of most injuries. Displaced femoral neck fractures and injuries to the hip joint that damage the articular or physeal cartilages require careful assessment and prompt and careful reduction and stabilization.

Control of retinoic acid receptor expression in mouse melanoma cells by cyclic AMP.

Retinoic acid receptor (RAR) alpha and gamma mRNAs were constitutively expressed in B16 melanoma cells with or without retinoic acid (RA) treatment. RAR beta mRNA, however, was significantly expressed only after exposure to RA. Induction of RAR beta by RA occurred within 1 h and was not inhibited by cycloheximide (i.e., did not require new protein synthesis). All three RAR mRNA levels were dramatically decreased with 8-bromo-cyclic AMP treatment and could not be rescued by addition of RA. Analysis of RAR gamma revealed that this decrease occurred within 1 h of exposure to 8-bromo-cyclic AMP and was not blocked by simultaneous treatment with cycloheximide. The stability of RAR gamma mRNA was not altered by cyclic AMP treatment. Nuclear extracts from 8-bromo-cyclic AMP-treated cells showed a large decrease in protein binding to a retinoic acid response element (RARE) oligonucleotide compared to control cells. This correlated with a marked reduction of RA-stimulated RARE-reporter gene activity in transfected cells which were treated with cyclic AMP. Pretreatment of B16 cells with cyclic AMP prior to RA addition dramatically reduced induction of PKC alpha, an early marker of RA-induced cell differentiation. Thus, cyclic AMP can antagonize the action of RA most likely via its ability to inhibit RAR expression.

N-(4-hydroxyphenyl)retinamide (4-HPR)-mediated biological actions involve retinoid receptor-independent pathways in human breast carcinoma.

Retinoid response pathways involve retinoic acid receptors (RARs) and retinoid X receptors. N-(4-hydroxyphenyl) retinamide (4-HPR), a derivative of all-trans-retinoic acid (RA) is currently in clinical trials as a chemopreventive agent for breast cancer. The issue whether 4-HPR mediates its biological actions via classical retinoid receptor pathways remains to be investigated. In this study, we provide several lines of evidence that 4-HPR mediates its biological actions via a novel pathway(s) that does not involve the classical retinoid receptor pathways. For example, 4-HPR was more potent than RA as an antiproliferative agent and inhibited growth of otherwise RA-resistant human breast carcinoma cells. Exposure to 4-HPR resulted in the generation of DNA fragmentation with subsequent cell death in both RA-positive estrogen receptor (ER)-positive as well as RA-refractory ER-negative breast carcinoma cell lines. N-(4-Methoxyphenyl)retinamide (4-MPR), which is the major 4-HPR metabolite in circulation, was biologically inert in this system. 4-HPR and 4-MPR bound poorly to the RAR alpha, beta and gamma in vitro and only minimally activated the retinoic acid receptor element (RARE) and retinoid X receptor response elements (RXREs) in human breast carcinoma cells. Neither 4-HPR nor 4-MPR are metabolized to any of the known conventional retinoids. In addition, 4-HPR or 4-MPR transactivation of RAREs or RXREs transfected into MCF-7 and MDA-MB-231 cells was not noted at 48 h. Nevertheless 4-HPR-mediated cell death was observed at 48 h, further suggesting that neither 4-HPR nor 4-MPR are metabolized to retinoids which activate the RAREs or RXREs in breast carcinoma cells. Furthermore, unlike RA, which exhibited anti-AP1 activity, 4-HPR inhibition of growth did not involve anti-AP1 activity. These results suggest that 4-HPR acts by a unique pathway that is not mediated by retinoid receptors.

Correlation of retinoid binding affinity to retinoic acid receptor alpha with retinoid inhibition of growth of estrogen receptor-positive MCF-7 mammary carcinoma cells.

Both anchorage-dependent growth and anchorage-independent growth of the estrogen receptor-positive mammary carcinoma cell line MCF-7 are inhibited by all-trans-retinoic acid. This cell line has nuclear retinoic acid receptors (RARs) alpha and gamma. The natural retinoids all-trans-retinoic acid and 9-cis-retinoic acid and a series of 12 conformationally restricted retinoids, which showed a range of binding selectivities for these receptors and had either agonist or antagonist activity for gene transcriptional activation by the RARs, were evaluated for their abilities to inhibit anchorage-dependent (adherent) and anchorage-independent (clonal) growth of MCF-7 cells. Correlation analyses were performed to relate growth inhibition by these retinoids with their binding affinity to RAR alpha or RAR gamma. Inhibition of anchorage-dependent growth in culture after 7 days of retinoid treatment correlated with binding to RAR alpha (n = 14; P < or = 0.001) and not to RAR gamma (n = 14; P > 0.1). Both the RAR alpha-selective retinoid agonists and the two RAR antagonists that were evaluated inhibited adherent cell growth. The RAR gamma-selective agonists had very low growth inhibitory activity (< 10%) at concentrations as high as 12.5 microM. These results suggest that RAR alpha is the retinoid receptor involved in the inhibition of adherent cell growth by retinoids and that transcriptional activation by this receptor on a RAR response element does not appear to be required for this process to occur. For this series of retinoids, inhibition of anchorage-independent growth after 21 days of retinoid treatment only correlated (n = 12; P < or = 0.005) with binding affinity to RAR alpha for the retinoid agonists, although the RAR gamma-selective retinoids displayed weak activity. The RAR antagonists were very poor inhibitors of growth. These results suggest that activation of gene transcription by RAR alpha appears to be required for inhibition of anchorage-independent growth by retinoids in this estrogen receptor-positive mammary carcinoma cell line.

Identification of structurally altered estrogen receptors in human breast cancer by site-directed monoclonal antibodies.

We have developed and characterized site-directed monoclonal (MAb) and polyclonal antibodies to a specific domain in the N-terminal A/B region in order to assess estrogen receptor (ER) structural integrity in human breast tumor samples. The antibodies (Abs) reacted specifically with the native (undenatured) ER from various species. The synthetic peptides competed effectively for ER binding to the Abs, suggesting site-specificity. The Abs recognized the activated (4S) and transformed (5S) but not the unactivated, untransformed, molybdate-stabilized (8S) ER, suggesting that the epitope is inaccessible in the 8S form. Some of these Abs reacted with ER bound to its responsive elements, as determined by gel mobility shift assay. To evaluate the structural integrity of ER in breast cancer, we have utilized a) ligand binding analysis for the hormone binding domain; b) site-directed MAb to the DNA-binding domain; and c) site-directed MAb to the N-terminal transactivation domain. Analysis of ER from 29 human breast tumors revealed that 10 out of 29 tumors (35%) contained ER with intact hormone-, DNA-, and N-terminal domains. Thirteen out of 29 tumors (approximately 45%) contained ER with intact hormone binding and N-terminal domains but were defective only in the DNA-binding domain. Three out of 29 tumors (approximately 10%) contained ER defective only in the N-terminal domain. Another subgroup of tumors (3/29; approximately 10%) had ER with normal hormone binding domain but were defective in both the DNA-binding and the N-terminal activation domains.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin A metabolism in the human intestinal Caco-2 cell line.

The human intestinal Caco-2 cell line, described as enterocyte-like in a number of studies, was examined for its ability to carry out the metabolism of vitamin A normally required in the absorptive process. Caco-2 cells contained cellular retinol-binding protein II, a protein which is abundant in human villus-associated enterocytes and may play an important role in the absorption of vitamin A. Microsomal preparations from Caco-2 cells contained retinal reductase, acyl-CoA-retinol acyltransferase (ARAT), and lecithin-retinol acyltransferase (LRAT) activities, which have previously been proposed to be involved in the metabolism of dietary vitamin A in the enterocyte. When intact Caco-2 cells were provided with beta-carotene, retinyl acetate, or retinol, synthesis of retinyl palmitoleate, oleate, palmitate, and small amounts of stearate resulted. However, exogenous retinyl palmitate or stearate was not used by Caco-2 cells as a source of retinol for ester synthesis. While there was a disproportionate synthesis of monoenoic fatty acid esters of retinol in Caco-2 cells compared to the retinyl esters typically found in human chylomicrons or the esters normally synthesized in rat intestine, the pattern was consistent with the substantial amount of unsaturated fatty acids, particularly 18:1 and 16:1, found in the sn-1 position of Caco-2 microsomal phosphatidylcholine, the fatty acyl donor for LRAT. Both ARAT and LRAT have been proposed to be responsible for retinyl ester synthesis in the enterocyte.(ABSTRACT TRUNCATED AT 250 WORDS)

Analise da aptidao do chagasico para o trabalho. / Analysis of the ability to work of patients with Chagas' disease

Os autores advertem inicialmente quanto a presenca de trabalhadores chagasicos nas empresas, caracterizando-os como doentes em sua maioria, com alteracoes minimas no coracao, nao detectadas em exames clinicos nao complementados por propedeuticas mais sofisticadas, mas que podem, no entanto, levar uma vida praticamente normal. Apresentam um estudo de 19 trabalhadores chagasicos, de uma industria siderurgica, por tempo de servico prestado antes e apos o diagnostico, licencas e acidentes do trabalho, circunstancias dos diagnosticos, condicoes na admissao, e tipos de lesao encontrados. Concluem que nao ha razao para temer-se o trabalhador chagasico em servico, desde que sob controle, pois a sua maioria podera levar uma vida praticamente normal. O afastamento do trabalho fica restrito aquela minoria que apresenta cardiopatia grave

Analise do absentismo em usina siderurgica. / Analysis of the absenteeism in steel metallurgy plants

Os autores abordam o absentismo em seus varios aspectos, apresentando dados estatisticos de uma empresa siderurgica no ano de 1980, que sao comparados com anos anteriores. Os periodos de afastamento, os dados percentuais com que cada doenca interfere nas ausencias, alem de outras formas de absentismo sao mostrados. Os afastamentos pelo INPS, destacando uma maior incidencia em empregados jovens e de menor tempo de servico sao estudados - esse dados coincidem com os de acidentes do trabalho, de maior prevalencia nos empregados com ate tres anos de casa. Destacam a complexidade da luta contra o absentismo ressaltando o aumento gradativo das faltas por acidentes que nao do trabalho, e a diminuicao constante dos classificados como transtornos mentais. Analisam e comentam, ao final, os dados coletados, resaltando a sua importancia no processo de tomada de decisoes que tem por finalidade a diminuicao de falhas ao trabalho

Contribuicao ao estudo das alteracoes auditivas e de ordem neuro-vegetativas atribuiveis ao ruido. / Auditive and autonomic changes induced by noise

Apos considerarem a nocividade do ruido sobre o aparelho auditivo e a saude psicossomatica, os autores fazem um estudo de dois grupos de individuos: os que trabalham em areas de ruido acima de 85 dB e, abaixo de 70 dB, respectivamente. A investigacao e dirigida para alteracoes do aparelho auditivo por trauma sonoro e disturbios de ordem neuro-vegetativa, considerando-se idade e tempo de exposicao ao agente agressivo. Os resultados indicam que as queixas de ordem neuro-vegetativa aparecem predominantemente, na faixa de 2 a 5 anos de funcao, no grupo de individuos que trabalham em area de ruido, e que, no grupo controle, tais queixas surgiram em individuos mais idosos. Ressaltam, comparativamente aos acidentes do trabalho com perda, que ha equivalencia de queixas e acidentes na faixa de 2 a 5 anos de servico. Foram encontrados 16 casos de surdez por trauma sonoro no grupo estudado e 5 no grupo controle, podendo estes ultimos ser relacionados a funcoes anteriores em ambientes ruidosos. Concluem que, alem de influencia negativa do ruido sobre a audicao, fato inconteste, e ele fator desencadeante de diversos sintomas de ordem neuro-vegetativa, chamando a atencao para uma possivel faixa de alarme, apos a qual os sintomas diminuem