Reversing painful and non-painful diabetic neuropathy with the capsaicin 8% patch: Clinical evidence for pain relief and restoration of function via nerve fiber regeneration.

Introduction: Current oral treatments for pain in diabetic peripheral neuropathy (DPN) do not affect the progression of DPN i.e., "disease modification." We assessed whether Capsaicin 8% patch treatment can provide pain relief and also restore nerve density and function via nerve regeneration, in both painful (PDPN) and non-painful (NPDPN) diabetic peripheral neuropathy. Methods: 50 participants with PDPN were randomized to receive Capsaicin 8% patch Qutenza with Standard of Care (SOC) (PDPN Q+SOC group), or SOC alone (PDPN SOC group). Pain symptoms were assessed with a diary (Numerical Pain Rating Scale, NRPS) and questionnaires. Investigations included quantitative sensory testing (QST) and distal calf skin biopsies, at baseline and 3 months after baseline visit; subsequent options were 3-monthly visits over 1 year. 25 participants with NPDPN had tests at baseline, and 3 months after all received Capsaicin 8% patch treatment. Results: At 3 months after baseline, PDPN Q+SOC group had reduction in NPRS score (p = 0.0001), but not PDPN SOC group. Short-Form McGill Pain Questionnaire (SF-MPQ) showed significant reductions in scores for overall and other pain descriptors only in the PDPN Q+SOC group. Warm perception thresholds were significantly improved only in the PDPN Q+SOC group (p = 0.02), and correlated with reduction in SF-MPQ overall pain score (p = 0.04). NPDPN Q+SOC group did not report pain during the entire study. Density of intra-epidermal nerve fibers (IENF) with PGP9.5 was increased at 3 months in PDPN Q+SOC (p = 0.0002) and NPDPN Q+SOC (p = 0.002) groups, but not in the PDPN SOC group. Increased sub-epidermal nerve fibers (SENF) were observed with GAP43 (marker of regenerating nerve fibers) only in PDPN Q+SOC (p = 0.003) and NPDPN Q+SOC (p = 0.0005) groups. Pain relief in the PDPN Q+SOC group was correlated with the increased PGP9.5 IENF (p = 0.0008) and GAP43 (p = 0.004), whereas those with lack of pain relief showed no such increase; in some subjects pain relief and increased nerve fibers persisted over months. PGP9.5 IENF increase correlated with axon-reflex vasodilatation in a NPDPN Q+SOC subset (p = 0.006). Conclusions: Capsaicin 8% patch can provide pain relief via nerve regeneration and restoration of function in DPN (disease modification). It may thereby potentially prevent diabetic foot complications, including ulcers.

Capsaicin 8% Patch Treatment in Non-Freezing Cold Injury: Evidence for Pain Relief and Nerve Regeneration.

Introduction: Neuropathic pain associated with Non-freezing Cold Injury (NFCI) is a major burden to military service personnel. A key feature of NFCI is reduction of the intra-epidermal nerve fibre density in skin biopsies, in keeping with painful neuropathy. Current oral treatments are generally ineffective and have undesirable side effects. Capsaicin 8% patch (Qutenza) has been shown to be well-tolerated and effective for reducing neuropathic pain, for up to 3 months after a single 30-minute application. Methods: In this single-centre open label study, 16 military participants with NFCI (mean duration 49 months) received 30-minute Capsaicin 8% patch treatment to the feet and distal calf. Pain symptoms were assessed using a pain diary (with the 11-point Numerical Pain Rating Scale, NPRS) and questionnaires, the investigations included skin biopsies, performed before and three months after treatment. Results: Participants showed significant decrease in spontaneous pain (mean NPRS: -1.1, 95% CI: 0.37 to 1.90; p = 0.006), and cold-evoked pain (-1.2, 95% CI: 0.40 to 2.04; p = 0.006). The time-course of pain relief over 3 months was similar to other painful neuropathies. Patient Global Impression of Change showed improvement (p = 0.0001). Skin punch biopsies performed 3 months after the patch application showed significant increase of nerve fibres with structural marker PGP9.5 (intra-epidermal nerve fibres [IENFs], p < 0.0001; sub-epidermal nerve fibres [SENFs]; p =< 0.0001), and of regenerating nerve fibres with their selective marker GAP43 (p = 0.0001). The increase of IENFs correlated with reduction of spontaneous (p = 0.027) and cold-evoked pain (p = 0.019). Conclusions: Capsaicin 8% patch provides an exciting new prospect for treatment of NFCI, with regeneration and restoration of nerve fibres, for the first time, in addition to pain relief.

Correction to: Economic evaluation of AbobotulinumtoxinA vs OnabotulinumtoxinA in real-life clinical management of cervical dystonia.

[This corrects the article DOI: 10.1186/s40734-020-0083-0.].

Surgical and Radiotherapeutic Management of Malignant Extradural Spinal Cord Compression.

Malignant spinal cord compression is one of the most dreaded complications of advanced malignancy, with patients presenting with progressive paralysis, paresthesia and/or autonomic dysfunction. The choice of management should be guided by the expected prognosis and outcome, not just from a neurological function point-of-view but also from the metastatic cancer itself. The main indications for surgery are: impending cord compression, spinal instability from tumour progression, bony retropulsion, for tissue diagnosis and for pain resistant to conventional therapies. Here, surgical principles, traditional and novel techniques and complications will be reviewed. For radiotherapy, multiple randomised studies have shown that for most patients a single fraction of external radiation has the same functional outcomes compared with multi-fractionation protocols. The experience of a specialised centralised interdisciplinary team will also be discussed.

Economic evaluation of AbobotulinumtoxinA vs OnabotulinumtoxinA in real-life clinical management of cervical dystonia.

BACKGROUND: Botulinum neurotoxins type A (BoNT-As) are commonly used treatments for cervical dystonia (CD). Clinical trials have demonstrated the benefits of them in these patients, but data from real-life clinical practice as well as comparative data on the cost and outcome of different BoNT-A formulations are limited. The aim of this study was to compare abobotulinumtoxinA (aboBoNT-A) and onabotulinumtoxinA (onaBoNT-A) on their clinical outcomes and drug costs in real-life clinical practice. METHODS: This analysis included 356 adult patients with idiopathic CD treated with aboBoNT-A (n = 253) or onaBoNT-A (n = 103) from 38 centres across Europe and Australia (NCT00833196). The clinical outcome measures were treatment responses, changes in TWSTRS scores and changes in health utility scores from baseline to study visit 2 and 3. Health utility score was mapped from the TWSTRS total scale, using a previous publication. Costs included drug cost for France. RESULTS: The aboBoNT-A treated group had 2.06 (95% CI: 1.15 to 3.69) times higher odds of achieving treatment response than the onaBoNT-A treated group. The adjusted mean change in TWSTRS total score from baseline to visit 3 were - 6.42 (95% CI: - 7.52 to - 5.33) for aboBoNT-A and - 3.94 (95% CI: - 5.68 to - 2.2) for onaBoNT-A, with a difference of - 2.48 (95% CI: - 4.57 to - 0.39). The corresponding difference in the adjusted mean change for health utility score was 0.008 (95% CI: 0.001 to 0.014). Mean treatment costs for aboBoNT-A and onaBoNT-A were 314.1 (95% CI: 299.1 to 329.0) and 346.6 (95% CI: 322.9 to 370.4) Euros, respectively. CONCLUSIONS: This comparative analysis indicated that treatment with aboBoNT-A may be less costly and lead to improved clinical outcomes when compared with onaBoNT-A, from a French healthcare system perspective. Additional comparative clinical data from larger patient cohorts, as well as more information about cost consequences of an improvement in clinical outcome would be of value to further confirm the findings.

Novel phase I trial design to evaluate the addition of cediranib or selumetinib to preoperative chemoradiotherapy for locally advanced rectal cancer: the DREAMtherapy trial.

BACKGROUND: The DREAMtherapy (Dual REctal Angiogenesis MEK inhibition radiotherapy) trial is a novel intertwined design whereby two tyrosine kinase inhibitors (cediranib and selumetinib) were independently evaluated with rectal chemoradiotherapy (CRT) in an efficient manner to limit the extended follow-up period often required for radiotherapy studies. PATIENTS AND METHODS: Cediranib or selumetinib was commenced 10 days before and then continued with RT (45 Gy/25#/5 wks) and capecitabine (825 mg/m2 twice a day (BID)). When three patients in the cediranib 15-mg once daily (OD) cohort were in the surveillance period, recruitment to the selumetinib cohort commenced. This alternating schedule was followed throughout. Three cediranib (15, 20 and 30 mg OD) and two selumetinib cohorts (50 and 75 mg BID) were planned. Circulating and imaging biomarkers of inflammation/angiogenesis were evaluated. RESULTS: In case of cediranib, dose-limiting diarrhoea, fatigue and skin reactions were seen in the 30-mg OD cohort, and therefore, 20 mg OD was defined as the maximum tolerated dose. Forty-one percent patients achieved a clinical or pathological complete response (7/17), and 53% (9/17) had an excellent clinical or pathological response (ECPR). Significantly lower level of pre-treatment plasma tumour necrosis factor alpha (TNFα) was found in patients who had an ECPR. In case of selumetinib, the 50-mg BID cohort was poorly tolerated (fatigue and diarrhoea); a reduced dose cohort of 75-mg OD was opened which was also poorly tolerated, and further recruitment was abandoned. Of the 12 patients treated, two attained an ECPR (17%). CONCLUSIONS: This novel intertwined trial design is an effective way to independently investigate multiple agents with radiotherapy. The combination of cediranib with CRT was well tolerated with encouraging efficacy. TNFα emerged as a potential predictive biomarker of response and warrants further evaluation.

Open darn repair vs open mesh repair of inguinal hernia: a systematic review and meta-analysis of randomised and non-randomised studies.

OBJECTIVES: To compare the outcomes of open darn repair vs open mesh repair in patients undergoing inguinal hernia repair. METHODS: We performed a systematic review and conducted a search of electronic information sources to identify all observational studies and randomised controlled trials (RCTs) investigating outcomes of open darn repair vs open mesh repair for inguinal hernias. Hernia recurrence was considered as the primary outcome measure. The secondary outcome measures included surgical site infection (SSI), haematoma, seroma, neuralgia, urinary retention, length of hospital stay, time to return to normal activities or work, testicular atrophy, operative time and chronic pain. Random or fixed effects modelling was applied to calculate pooled outcome data. RESULTS: Six RCTs, enrolling 1480 patients with 1485 hernias, and 4 observational studies, enrolling 1564 patients with 1641 hernias, were included. Meta-analysis of RCTs showed no significant difference in terms of recurrence (RD 0.00, 95% CI - 0.01 to 0.01, P = 0.86), SSI (OR 0.83, 95% CI 0.46-1.49, P = 0.52), haematoma (OR 1.21, 95% CI 0.62-2.38, P = 0.57), seroma (OR 0.83, 95% CI 0.42-1.65, P = 0.60), neuralgia (OR 1.05, 95% CI 0.29-3.73, P = 0.94), urinary retention (OR 1.44, 95% CI 0.64-3.21, P = 0.38), length of hospital stay (MD 0.09, 95% CI - 0.28 to 0.46, P = 0.63), time to return to normal activities or work (MD 0.88, 95% CI - 0.90 to 2.66, P = 0.33), testicular atrophy (RD 0.00, 95% CI - 0.02 to 0.02, P = 1.00), and operative time (MD 2.69, 95% CI - 1.75 to 7.14, P = 0.62) between the darn repair and mesh repair groups. Meta-analysis of observational studies also showed no significant difference in terms of recurrence (RD 0.00, 95% CI - 0.02 to 0.02, P = 0.99), SSI (OR 0.47, 95% CI 0.14-1.62, P = 0.23), haematoma (OR 1.07, 95% CI 0.45-2.55, P = 0.89), seroma (OR 0.12, 95% CI 0.01-2.27, P = 0.16), neuralgia (OR 0.25, 95% CI 0.05-1.21, P = 0.08), urinary retention (OR 1.53, 95% CI 0.20-11.96, P = 0.69), time to return to normal activities or work (MD 2.13, 95% CI - 2.18 to 6.44, P = 0.33), testicular atrophy (RD - 0.01, 95% CI - 0.02 to 0.01, P = 0.49), and operative time (MD - 4.76, 95% CI - 13.23 to 3.71, P = 0.27) between the two groups. The evidence was inconclusive for chronic pain. The quality of available evidence was moderate. CONCLUSIONS: Our results suggest that open darn repair is comparable with open mesh repair for inguinal hernias. Considering that consequences of mesh complications in inguinal hernia repair, albeit rare, can be significant, open darn repair provides an equally credible alternative to open mesh repair for inguinal hernias. Further studies are required to investigate patient-reported outcomes and to elicit a superior non-mesh technique.

A real-world study of cardiac events in > 3700 patients with HER2-positive early breast cancer treated with trastuzumab: final analysis of the OHERA study.

PURPOSE: Cardiac dysfunction risk associated with intravenous trastuzumab (H IV) treatment may differ in real-world practice versus randomized trials. We investigated cardiac events in patients with HER2-positive early breast cancer (EBC) treated with H IV as adjuvant therapy in routine practice. METHODS: The observational study of cardiac events in patients with HER2-positive EBC treated with Herceptin (OHERA; NCT01152606) enrolled patients with stage I-IIIb disease eligible for H IV in the adjuvant setting per the European Summary of Product Characteristics (SmPC). Primary outcomes were symptomatic congestive heart failure incidence (CHF; New York Heart Association class II-IV) and cardiac death. Patient visits/assessments were per local practice. RESULTS: 3733 Patients received ≥ 1 H IV dose per local practice; 88.9% received H IV for > 300 days (median follow-up: ~ 5 years). Prior to disease recurrence (if any), symptomatic CHF occurred in 106 patients (2.8%); 6 (0.2%) cardiac deaths occurred (5 in patients with cardiac disease history). Median time to symptomatic CHF onset was 5.7 months (95% CI 5.3-6.5); 77/106 (72.6%) patients with symptomatic CHF achieved resolution. CHF incidence was higher in patients ≥ 65 years, and those with pre-existing cardiac conditions, hypertension, or left ventricular ejection fraction ≤ 55% at baseline. CONCLUSIONS: OHERA is the largest prospective observational study to investigate the cardiac safety of H IV as adjuvant EBC therapy in a real-world setting. Symptomatic CHF and cardiac event incidences were consistent with randomized trials in this setting and baseline risk factors identified in the H IV European SmPC.

A phase II trial of low-dose estradiol in postmenopausal women with advanced breast cancer and acquired resistance to aromatase inhibition.

BACKGROUND: High-dose oestrogen (HDE) is effective but toxic in postmenopausal women with advanced breast cancer (ABC). Prolonged oestrogen deprivation sensitises BC cell lines to estrogen and we hypothesised that third-generation aromatase inhibitors (AIs) would sensitise BCs to low-dose estradiol (LDE). METHODS: A single-arm phase II study of LDE (2 mg estradiol valerate daily) in postmenopausal women with estrogen receptor-positive (ER+) ABC. The primary end-point was clinical benefit (CB) rate. If LDE was ineffective, HDE was offered. If LDE was effective, retreatment with the pre-LDE AI was offered on progression. RESULTS: Twenty-one patients were recruited before the trial was closed early due to slow accrual; 19 were assessable for efficacy and toxicity. CB was seen in 5 in 19 patients (26%; 95% confidence interval 9.1-51.2%), all with prolonged SD (median duration 16.8 months; range 11.0-29.6). Treatment was discontinued for toxicity in 4 in 19 patients (21%) and 8 in 11 women without hysterectomy experienced vaginal bleeding (VB). After primary LDE failure, three patients received HDE and one achieved a partial response (PR). Following CB on LDE, four patients restarted pre-LDE AI and three achieved CB including one PR. Those with CB to LDE had a significantly longer duration of first-line endocrine therapy for ABC than those without (54.9 versus 16.8 months; p < 0.01) CONCLUSION: LDE is an effective endocrine option in women with evidence of prolonged sensitivity to AI therapy. LDE is reasonably well tolerated although VB is an issue. Re-challenge with the pre-LDE AI following progression confirms re-sensitisation as a true phenomenon.

Histopathological study of placentae in low birth weight babies in India.

BACKGROUND: The antenatal health-care given to pregnant women has great influence on the rates of perinatal death and morbidity. Amongst the different causes of perinatal mortality, low birth weight (LBW) is the single most significant factor therefore placenta from all the LBW babies (LBWB) should be examined routinely to find out the likely cause. AIMS: The aims of this study were to assess the pathological changes in the placenta in association with LBWB. MATERIALS AND METHODS: This is a Case control study performed at Medical College Allahabad,(MLN) India. In this study, 90 placentae were included. 30 placentae from full-term vaginally delivered babies, weighing more than 2500 g were included as the control group. 60 placentae belonged to babies whose birth weight was less than 2500 g (LBW). Weight of the baby was taken within the 1(st) h of birth and Apgar score was noted. Gross and microscopic examination of placentae was done. Statistical correlation of was carried out between them by using SPSS 18 version. Chi-square test with or without yate's correction was used as and when required. P < 0.05 was taken as critical level of significance. RESULTS: Placenta was circum-marginal in both groups. Attachment of cord was mainly central in the control group 90% (27/30), whereas eccentric attachment was prominent in patient group 66.67% (40/60). The difference was statistically significant (P < 0.001). Calcification and sub-chorionic fibrin deposition was seen in significantly higher numbers of placentae from patients than controls (P < 0.01) infarction and meconium staining were seen in placentae from patients only. Histologically placental ischemia, infarction and calcification were seen in significantly higher number of patients (P < 0.001, P < 0.001 and < 0.01 respectively). Fibrinoid necrosis, stromal fibrosis, placental dysmaturity and obstructive vasculopathy were seen in placentae from patients only. CONCLUSION: Placental pathology among LBW infants was high in comparison to control group. The findings suggest that chronic ischemia and associated secondary changes probably lead to improper perfusion and LBWB.

Reducing febrile neutropenia rates in early breast cancer. Experience of two UK cancer centres.

PURPOSE: Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is used in many institutions across the UK due to unacceptable febrile neutropenia (FN) rates with FEC-D (fluorouracil, epirubicin, cyclophosphamide-docetaxel). The resultant reduction in FN rate is thought to maintain dose intensity and improve patient experience. This retrospective study was performed to assess whether the addition of G-CSF primary prophylaxis into daily clinical practice has achieved these aims. METHODS: Collaborative audit performed in two UK cancer centres before and after the integration of G-CSF primary prophylaxis with FEC-D. The primary objective was FN rate. RESULTS: Data from 342 patients were analysed, 151 before routine use of primary G-CSF and 191 after. The FN rates were 30 and 11%, respectively. Despite the 99% adherence to primary G-CSF policy, there were more dose reductions (8 increased to 13%) and dose delays (11 increased to 23%) following the use of G-CSF primary prophylaxis. This appeared to be due to non-FN toxicities. Inpatient days decreased substantially from 93 to 16 and antibiotic courses from 28 to 13 (per hundred patients). CONCLUSIONS: Near universal adherence to the G-CSF policy in FEC-D treatment has led to a reduction in FN rate and inpatient days but has not translated into improved dose intensity. This collaborative audit allows sufficient data to give insight into current practice and generate hypotheses for further investigation.

Anesthetic management in parturients with chronic kidney disease undergoing elective Caesarean delivery: Our experience of nine cases.

In this retrospective study, we describe the anesthetic management and its implications in parturients with chronic kidney disease (CKD; n = 9), who underwent elective caesarean delivery. Nine parturients with CKD of various etiologies, who underwent elective Caesarean delivery, were included in this study. Spinal anest-hesia was administered in all parturients with normal coagulation profile through a 25-gauze spinal needle (Quincke) with 0.5% (H) bupivacaine in L2-3 space and T6 level was achieved. Hemodynamics and side effects such as nausea, vomiting, headache, and backache were record. The mean age was 28.22 ± 4.43 years. The mean levels of serum creatinine and serum potassium were 2.78 ± 1.29 mg/dl and 4.11 ± 0.46 meq/l, respectively. Mean baseline values of systolic blood pressure, diastolic blood pressure, and pulse rate were higher which decreased after spinal anesthesia. However, the incidence of hypotension, which required mephentermine treatment, was 11.1%. One patient had symptoms of nausea and vomiting/dizziness at the time of hypotension, which disappeared after treatment with 5 mg of intravenous mephentermine. Baseline value of PR remained high throughout the operation. Parturients with CKD with normal coagulation profile remained hemodynamically stable under spinal anesthesia with minimal side effects. However, a large number of studies are required to determine the safety of spinal anesthesia in this setting.

Changes in adipose tissue distribution during pregnancy in overweight and obese compared with normal weight women.

OBJECTIVE: Differences in body fat distribution contribute to the metabolic abnormalities associated with overweight and obesity; however, such differences have not been adequately explored during pregnancy. Our aim was to compare longitudinal trends in maternal abdominal adipose tissue deposition during pregnancy in overweight/obese compared with normal weight women. STUDY DESIGN: Pregnant women, classified as normal weight (body mass index (BMI) <25 kg m(-2); N=61) or overweight/obese (BMI 25 kg m(-2); N=57), were enrolled in a prospective cohort study starting in the first trimester. Maternal subcutaneous (smin) and preperitoneal (pmax) fat were measured by ultrasound at five time points starting between 6 and 10 weeks gestation. The abdominal fat index (AFI), an established marker of visceral adipose tissue, was calculated as the ratio of pmax to smin. The trajectories of smin, pmax, cumulative fat index (smin plus pmax) and the AFI across pregnancy were analyzed using mixed linear models. RESULTS: The rate of maternal weight gain during pregnancy was significantly lower for overweight/obese women compared with their non-overweight counterparts (P<0.05). Accordingly, the rate of change of pmax and smin differed significantly in normal weight compared with overweight/obese women (P=0.0003 and 0.01, respectively). The cumulative fat index did not change across gestation in normal weight women, whereas it decreased for overweight/obese women (P=0.0005). The log AFI increased across pregnancy in both strata, but significantly more rapidly for normal weight compared with overweight/obese women (P=0.06). CONCLUSIONS: Adipose tissue is preferentially deposited in the more metabolically active visceral compartment as pregnancy progresses. However, this process differs in normal weight compared with overweight/obese women and may contribute to metabolic differences between these groups. Our study is a step toward a more refined description of obesity and its consequences during pregnancy.

Intra-operative neurophysiological prediction of upper trunk recovery in obstetric brachial plexus palsy with neuroma in continuity.

We investigated the predictive value of intra-operative neurophysiological investigations in obstetric brachial plexus injuries. Between January 2005 and June 2011 a total of 32 infants of 206 referred to our unit underwent exploration of the plexus, including neurolysis. The findings from intra-operative electromyography, sensory evoked potentials across the lesion and gross muscular response to stimulation were evaluated. A total of 22 infants underwent neurolysis alone and ten had microsurgical reconstruction. Of the former, one was lost to follow-up, one had glenoplasty and three had subsequent nerve reconstructions. Of the remaining 17 infants with neurolysis, 13 (76%) achieved a modified Mallet score > 13 at a mean age of 3.5 years (0.75 to 6.25). Subluxation or dislocation of the shoulder is a major confounding factor. The positive predictive value and sensitivity of the intra-operative EMG for C5 were 100% and 85.7%, respectively, in infants without concurrent shoulder pathology. The positive and negative predictive values, sensitivity and specificity of the three investigations combined were 77%, 100%, 100% and 57%, respectively. In all, 20 infants underwent neurolysis alone for C6 and three had reconstruction. All of the former and one of the latter achieved biceps function of Raimondi grade 5. The positive and negative predictive values, sensitivity and specificity of electromyography for C6 were 65%, 71%, 87% and 42%, respectively. Our method is effective in evaluating the prognosis of C5 lesion. Neurolysis is preferred for C6 lesions.

Comparative study of intra-operative cytology, frozen sections, and histology of tumor and tumor-like lesions of nose and paranasal sinuses.

BACKGROUND: The nasal cavity and paranasal sinuses - including the maxillary, ethmoid, sphenoid, and frontal sinuses are collectively referred to as the sinonasal tract. Fine needle aspiration (FNA) of paranasal sinus lesions for early diagnosis of neoplastic lesions is difficult due to closed architecture, and only one study has been documented in the literature. AIMS: To find the efficacy of intra-operative cytology and frozen section for frequently encountered tumor and tumor-like lesions of the nose and paranasal sinuses. MATERIALS AND METHODS: Thirty cases were included in this study. The material for cytologic examination and frozen sections were taken per-operatively. Cytological smears were prepared by imprint/squash methods from the representative tissue pieces and stained with Leishman-Giemsa and Papanicolaou. Frozen section and paraffin-embedded section were stained with hematoxylin and eosin stain. A rapid opinion regarding the benign or malignant nature of the lesion and the type of tumor was given. RESULTS: The sensitivity, specificity, and positive predictive value of imprint cytology, squash cytology, and frozen section were 100%, 100%, and 100%; 100%, 96.15%, and 80.0%; and 100%, 96.15%, and 80.0%, respectively. Overall diagnostic accuracy of imprint smears, squash smears, and frozen section was100%, 96.7%, and 96.7%, respectively. Imprint smears had better specificity as cells morphology could be more accurately appreciated. CONCLUSIONS: Intra-operative cytology and frozen section examinations of lesions of nose and paranasal sinuses are useful, quick, and reliable diagnostic technique for rapid diagnosis in the operation theatre and can be used as an adjunct to histopathology for better management of patients.

The effect of Zhangfei on the unfolded protein response and growth of cells derived from canine and human osteosarcomas.

The objective of this study was to determine whether the protein Zhangfei could suppress the unfolded protein response (UPR) and growth of osteosarcoma cells. Dog (D-17) and a human (Saos-2) osteosarcoma cells were infected with adenovirus vectors expressing either Zhangfei or the control protein beta- galactosidase. We monitored cell growth as well as levels of UPR gene transcripts and proteins. We found that Zhangfei suppressed the growth of both D-17 and Saos-2 cells. Zhangfei-expressing D-17 cells displayed large vacuoles containing culture medium and expressed phosphatidylserine on their external surface suggesting that Zhangfei induced macropinocytosis and apoptosis in these cells. While Zhangfei inhibited the growth of both D-17 and Saos-2 cells, it inhibited thapsigargin-induced UPR, as detected by a decrease in transcripts for UPR genes, and HERP and GRP78 proteins, only in D-17 cells, suggesting that the ability of Zhangfei to suppress the UPR and tumour cells growth may not be linked.

A longitudinal study of sensory biomarkers of progression in patients with diabetic peripheral neuropathy using skin biopsies.

We aimed to identify biomarkers in skin punch biopsies that could be used to monitor progression of diabetic peripheral neuropathy (DPN), and, in future studies, to assess the efficacy of agents that may reduce progression. Patients with DPN were studied with clinical assessments, skin biopsies, quantitative sensory testing (QST), histamine-induced skin flare, nerve conduction studies and contact heat-evoked potentials (CHEPS). Skin biopsies were performed on two visits with a 6 month interval (n=29 patients) to quantify intraepidermal (IENF) and subepidermal (SENF) nerve fibres immunoreactive for: protein gene product 9.5 (PGP9.5), a pan-neuronal marker; transient receptor potential cation channel vanilloid 1 (TRPV1), the heat and capsaicin receptor; and growth associated protein-43 (GAP-43), a marker of regenerating fibres. The IENF were counted along the length of four non-consecutive sections, and results were expressed as fibres per millimetre length of section. SENF were measured by image analysis, and the area of highlighted immunoreactivity was obtained as a percentage (% area) of the field scanned. QST, skin flare and CHEPS were also performed at the two visits. We found that IENF and SENF were significantly reduced for both PGP9.5 and TRPV1 between the first and second skin biopsy over 6months. The annual rate ± standard error of the mean of IENF loss was 3.76 ± 1.46 fibres/mm for PGP9.5, and 3.13 ± 0.58 fibres/mm for TRPV1. The other tests did not show significant changes. Strongly positive GAP-43 nerve fibres were found in deep dermis in the patients with diabetes, even in those with an absence of IENF. We conclude that PGP9.5 and TRPV1 IENF and SENF in skin biopsies are useful markers of progression in DPN, whereas GAP-43 SENF could potentially help detect nerve regeneration in severe neuropathy.

Accumulation, detoxification, and genotoxicity of heavy metals in Indian mustard (Brassica juncea L.).

Plants of Indian mustard (Brassica juncea L.) were exposed to different concentrations (15, 30, 60, 120 microM) of (Cd, Cr, Cu, Pb) for 28 and 56 d for accumulation and detoxification studies. Metal accumulation in roots and shoots were analyzed and it was observed that roots accumulated a significant amount of Cd (1980 microg g(-1) dry weight), Cr (1540 microg g(-1) dry weight), Cu (1995 microg g(-1) dry weight), and Pb (2040 microg g(-1) dry weight) after 56 d of exposure, though in shoot this was 1110, 618, 795, and 409 microg g(-1) dry weight of Cd, Cr, Cu, and Pb, respectively. In order to assess detoxification mechanisms, non-protein thiols (NP-SH), glutathione (GSH) and phytochelatins (PCs) were analyzed in plants. An increase in the quantity of NP-SH (9.55), GSH (8.30), and PCs (1.25) micromol g(-1) FW were found at 15 microM of Cd, however, a gradual decline in quantity was observed from 15 microM of Cd onwards, after 56 d of exposure. For genotoxicity in plants, cytogenetic end-points such as mitotic index (MI), micronucleus formation (MN), mitotic aberrations (MA) and chromosome aberrations (CA) were examined in root meristem cells of B. juncea. Exposure of Cd revealed a significant (P < 0.05) inhibition of MI, induction of MA, CA, and MN in the root tips for 24 h. However, cells examined at 24 h post-exposure showed concentration-wise recovery in all the endpoints. The data revealed that Indian mustard could be used as a potential accumulator of Cd, Cr, Cu, and Pb due to a good tolerance mechanisms provided by combined/concerted action of NP-SH, GSH, and PCs. Also, exposure of Cd can cause genotoxic effects in B. juncea L. through chromosomal mutations, MA, and MN formation.

Return of spinal reflex after spinal cord surgery for brachial plexus avulsion injury.

Motor but not sensory function has been described after spinal cord surgery in patients with brachial plexus avulsion injury. In the featured case, motor-related nerve roots as well as sensory spinal nerves distal to the dorsal root ganglion were reconnected to neurons in the ventral and dorsal horns of the spinal cord by implanting nerve grafts. Peripheral and sensory functions were assessed 10 years after an accident and subsequent spinal cord surgery. The biceps stretch reflex could be elicited, and electrophysiological testing demonstrated a Hoffman reflex, or Hreflex, in the biceps muscle when the musculocutaneous nerve was stimulated. Functional MR imaging demonstrated sensory motor cortex activities on active as well as passive elbow flexion. Quantitative sensory testing and contact heat evoked potential stimulation did not detect any cutaneous sensory function, however. To the best of the authors' knowledge, this case represents the first time that spinal cord surgery could restore not only motor function but also proprioception completing a spinal reflex arch.

Safety of high doses of urokinase and reteplase for acute ischemic stroke.

BACKGROUND AND PURPOSE: ET is considered in selected patients with AIS with persistent arterial occlusion after receiving IVT. Limited data exist on the safety of IA high doses of UK and RT for ET. We investigated any correlation between IA doses of UK or RT and safety outcomes in patients who underwent ET. MATERIALS AND METHODS: We identified all patients from our stroke registry who received UK or RT for ET from 1998 to 2008. Demographics, baseline National Institutes of Health Stroke Scale scores, recanalization rates, rates of attempted MT, mortality, SICH, and discharge modified Rankin Scale scores were collected. RESULTS: Of 197 patients; 72 received UK and 125 received RT. More than 90% of patients in both groups had received prior IVT. The median IA dose of UK was 200,000 U (range, 25,000-1,500,000 U) and of RT was 2 mg (range, 1-8 mg). Concurrent MT was attempted in 59.7% of UK-treated patients and 72.0% of RT-treated patients, with SICH rates of 4.2% and 8.0%, respectively. Logistic regression adjusting for prior IVT and MT revealed no correlation between SICH and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .94) or RT (OR, 0.803; 95% CI, 0.48-1.33; P = .39). There was no correlation between mortality and doses of UK (OR, 1.00; 95% CI, 0.99-1.00; P = .51) or RT (OR, 1.048; 95% CI, 0.77-1.42; P = .75). CONCLUSIONS: High IA doses of UK and RT may be safe when given with or without MT in patients with AIS despite receiving a full dose of intravenous recombinant tissue plasminogen activator. These results need prospective validation.