Short-term outcome of percutaneous tibial nerve stimulation for low anterior resection syndrome: results of a pilot study.

AIM: Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive procedure which has been demonstrated to be effective in faecal/urinary incontinence but has never been tested in low anterior resection syndrome (LARS). The severity of LARS may be evaluated by the LARS score, but rectal cancer treatments may also affect urinary and sexual function, which are not explored by the LARS score. The Three Axial Perineal Evaluation (TAPE) score is a new validated index addressing the overall pelvic floor functions. This study aims to assess the efficacy of PTNS in LARS patients and to evaluate the results by the LARS and TAPE scores. METHODS: Twenty-one patients operated on for rectal cancer between 2009 and 2014 complaining of LARS underwent PTNS (12 sessions of 30 min each). Six patients reported urinary incontinence and all except two (men) were sexually inactive. The LARS score and the TAPE score questionnaires were administered at baseline and after 6 months of follow-up. RESULTS: At 6 months' follow-up, nine patients reported a significant improvement of faecal incontinence and 3/6 an improvement of urinary incontinence after PTNS. Median LARS score significantly decreased from 32 to 27 (P = 0.009), while the median TAPE score improved significantly from 55 to 58 (P = 0.004). CONCLUSIONS: PTNS may be a further option in the treatment of selected patients with LARS and in addition may improve associated urinary incontinence. The severity of LARS can be detected by the LARS score; however, the adoption of the TAPE score is preferred in the case of concomitant urinary and/or sexual problems not explored by the LARS score.

Long-term treatment of phenylketonuria with a new medical food containing large neutral amino acids.

BACKGROUND/OBJECTIVES: Phenylketonuria (PKU) is an autosomal recessive disease caused by deficient activity of phenylalanine hydroxylase. A low phenylalanine (Phe) diet is used to treat PKU. The diet is very restrictive, and dietary adherence tends to decrease as patients get older. Methods to improve dietary adherence and blood Phe control are continuously under investigation. SUBJECTS/METHODS: A new formula Phe-neutral amino acid (PheLNAA) has been tested in this study with the purpose of improving the compliance and lowering blood phenylalanine. The formula has been tested for nitrogen balance, and it is nutritionally complete. It is fortified with more nutritional additives that can be deficient in the PKU diet, such as B12, Biotin, DHA, Lutein and increased levels of large neutral amino acids to help lower blood Phe. The new formula has been tested on 12 patients with a loading test of 4 weeks. RESULTS: Fifty-eight percent of patients had a significant decline in blood Phe concentration from baseline throughout the study. The PheLNAA was well tolerated with excellent compliance and without illnesses during the study. CONCLUSIONS: In conclusion, the new formula is suitable for life-long treatment of PKU, and it offers the PKU clinic a new choice for treatment.

Second-line chemotherapy with a hybrid-alternating regimen of bolus 5FU modulated by methotrexate and infusional 5FU modulated by folinic acid in patients with metastatic colorectal cancer pretreated with 5FU. A phase 2 study.

BACKGROUND AND AIM: In vitro, methotrexate (MTX) is the best modulator for bolus 5-fluorouracil (5FU), whereas folinic acid (FA) is the best for continuous infusion. We evaluated the effect of 5FU modulated by both MTX (bolus administration) and FA (continuous infusion) as second-line treatment of patients with metastatic colorectal cancer. PATIENTS AND METHODS: Entry criteria were: at least one 5FU-based chemotherapy regimen as first-line treatment for metastatic disease, or progression within twelve months after 5FU-containing adjuvant therapy. Treatment schedule: MTX 200 mg/m2 i.v. days 1 and 15; 5FU 600 mg/m2 i.v. bolus, days 2 and 16; 5FU 200 mg/m2 i.v. continuous infusion for 21 days, starting on day 29; FA 20 mg/m2 i.v. bolus weekly during the three weeks of 5FU infusion. Cycles were repeated every 56 days. The primary end-point was tumour control rate, including partial responses and stabilizations. RESULTS: 34/35 patients enrolled were evaluable for response. Five (14.7%) had a partial response, 13 (38.2%) disease stabilization, and 16 (47.1%) progressed; tumour control rate was 52.9%. Median TTP was 5.8 months (95% CI 4.03-7.83); 29 patients had died. Median OAS was 15.9 months (95% CI 8.8-21.9). Toxicity was mild. CONCLUSIONS: The regimen constituted by 5FU modulated by MTX (bolus administration) and FA (continuous infusion) is active as second-line treatment of metastatic colorectal cancer.

Priming effects of substance P on calcium changes evoked by interleukin-8 in human neutrophils.

The neurokinin (NK) substance P (SP), which is a mediator of neurogenic inflammation, has been reported to prime human polymorphonuclear neutrophils (PMNs). The priming effects of SP on PMNs activated by recombinant interleukin-8 (rIL-8) were investigated. SP enhanced, in a dose- and time-dependent way, the rise in cytosolic free-calcium concentration, [Ca(2+)]i, evoked by the chemokine. The priming effects of SP were abolished by exposing PMNs to a calcium-free medium supplemented with EGTA. The C-terminal peptides SP(4-11) and SP(6-11) but not the N-terminal peptide SP(1-7) shared the priming effects of SP. The selective NK-1 receptor agonist [Sar-9, MetO2-11]SP mimicked the effects of SP, which were not reproduced by the selective NK-2 receptor agonist [betaAla-8]-NKA(4-10) or the selective NK-3 agonist senktide. Two selective NK-1 antagonists, CP96,345 and L703,606, dose dependently inhibited SP priming effects. These results demonstrated that SP primes PMNs exposed to rIL-8 and suggested that SP priming effects are receptor mediated.

Somatostatin in the hippocampus mediates dexamethasone-induced suppression of corticosterone secretion in the rat.

We evaluated the effect of different manipulations of central somatostatin (SS) neurons on dexamethasone (Dex) induced suppression of the hypophyseal-pituitary axis. The Dex suppression test was performed in male rats by evaluating the reduction of plasma levels of corticosterone occurring 4 h after administration of Dex. Administration of cysteamine, a depletor of SS stores, or passive immunization by intracerebroventricular administration of a saturating dose of anti-SS gamma-globulins completely suppressed the ability of Dex to reduce plasma corticosterone levels. Additionally, anti-SS gamma-globulins, infused under stereotaxic control into two discrete areas of the hippocampus (CA3 and DG), completely blocked Dex-induced inhibition of corticosterone secretion. These data indicate that hippocampal SS neurons play a role in the negative feedback regulation of glucocorticoid secretion.