Sustained pyridoxine response in primary hyperoxaluria type 1 recipients of kidney alone transplant.

Combined liver kidney transplant is the preferred transplant option for most patients with primary hyperoxaluria type 1 (PH1) given that it removes the hepatic source of oxalate production and improves renal allograft survival. However, PH1 patients homozygous for the G170R mutation can develop normal urine oxalate levels with pyridoxine therapy and may be candidates for kidney alone transplant (KTx). We examined the efficacy of pyridoxine therapy following KTx in five patients homozygous for G170R transplanted between September 1999 and July 2013. All patients were maintained on pyridoxine posttransplant. Median age at transplant was 39 years (range 33-67 years). Median follow-up posttransplant was 8.5 years (range 0.2-13.9 years). At the end of follow-up, four grafts were functioning. One graft failed 13.9 years posttransplant due to recurrent oxalate nephropathy following an acute medical illness. After tissue oxalate stores had cleared, posttransplant urine oxalate levels were <0.5 mmol/24 h the majority of times checked. Calcium oxalate crystals were noted in only 3/13 allograft biopsies. This series suggests that a subgroup of PH1 patients demonstrate sustained response to pyridoxine therapy following KTx. Therefore, pyridoxine combined with KTx should be considered for PH1 patients with a homozygous G170R mutation.

Effects of glucagon-like peptide-1 and sympathetic stimulation on gastric accommodation in humans.

In humans, glucagon-like peptide-1 (GLP-1) delays gastric emptying by inhibiting vagal activity and also increases gastric volumes, by unclear mechanisms. Because GLP-1 inhibits intestinal motility by stimulating the sympathetic nervous system in rats, we assessed the effects of a GLP-1 agonist and yohimbine, an alpha(2)-adrenergic antagonist, on gastric volumes in humans. In this double-blind study, 32 healthy volunteers were randomized to placebo, a GLP-1 agonist, yohimbine or GLP-1 and yohimbine. Gastric volumes (fasting predrug and postdrug, and postprandial postdrug) were measured by (99m)Tc single photon emission computed tomography imaging. Plasma catecholamines and haemodynamic parameters were assessed. Compared with placebo, GLP-1 increased (P = 0.03) but yohimbine did not affect fasting gastric volume. However, GLP-1 plus yohimbine increased (P < 0.001) postprandial gastric accommodation vs placebo and vs GLP-1 alone [postprandial volume change = 542 +/- 29 mL (mean +/- SEM, placebo), 605 +/- 31 mL (GLP-1), 652 +/- 54 mL (yohimbine) and 810 +/- 37 mL (GLP-1 and yohimbine)]. Plasma noradrenaline and dihydroxyphenylglycol concentrations were higher for yohimbine vs placebo and for GLP-1 and yohimbine vs GLP-1. Yohimbine stimulates central sympathetic activity and in combination with GLP-1, augments postprandial accommodation in humans.

A new questionnaire for constipation and faecal incontinence.

BACKGROUND: The prevalence, severity and risk factors of faecal incontinence in women in the community are incompletely characterized. AIM: To develop and validate a self-report questionnaire (faecal incontinence and constipation assessment) to address these issues. METHOD: Eighty-three women completed the instrument; 20 randomly selected patients answered the faecal incontinence and constipation assessment again 6 weeks later. A gastroenterologist also completed the faecal incontinence and constipation assessment in all 83 subjects after a detailed clinical assessment. Concurrent validity was evaluated by comparing the patient's self-report to a doctor interview for every question. Reproducibility was evaluated by a test-retest approach for every question. The severity of faecal incontinence was rated by incorporating the frequency and type of faecal incontinence, rectal urgency and use of sanitary devices. RESULTS: The questionnaire was well-understood. Reproducibility [median kappa statistic, 0.80 (interquartile range: 0.66-0.90)]; and concurrent validity [0.59 (0.47-0.67)] were acceptable. For the index question on faecal incontinence, the kappa for reproducibility and concurrent validity was 0.90 and 0.95, respectively. The faecal incontinence severity score was also valid (kappa = 0.5). CONCLUSION: The faecal incontinence and constipation assessment has excellent reproducibility and reasonable validity for assessing the presence, risk factors and severity of faecal incontinence and associated bowel disorders in women when compared against clinical assessment.

Effects of vaginal hysterectomy on anorectal sensorimotor functions--a prospective study.

BACKGROUND: While bowel and bladder dysfunction are recognized consequences of a radical hysterectomy, the effects of a simple hysterectomy on anorectal sensorimotor functions, particularly rectal sensation, vary among studies and the effects on rectal compliance remain unknown. Our aims were to prospectively evaluate anorectal sensorimotor functions before and after a hysterectomy. METHODS: Anal pressures, rectal compliance, capacity, sensation, and bowel symptoms were assessed before, at 2 months, and at 1 year after a simple vaginal hysterectomy for benign indications in 19 patients. Rectal staircase (0-44 mmHg, 4-mmHg steps), ramp (0-200 mL at 50, 200 and 600 mL min(-1)) and phasic distentions (8, 16, and 24 mmHg above operating pressure) were performed. KEY RESULTS: Anal resting (63 ± 4 before, 56 ± 4 mmHg after) and squeeze pressures (124 ± 12 before, 124 ± 12 mmHg after), rectal compliance and capacity (285 ± 12 before, 290 ± 11 mL 1 year after), and perception of phasic distentions were not different before vs after a hysterectomy. Sensory thresholds for first sensation and the desire to defecate were also not different, but pressure and volume thresholds for urgency were somewhat greater (Hazard ratio = 0.7, 95% CI [0.5, 1.0]) 1 year after (vs before) a hysterectomy. Rectal pressures were higher (P < 0.0001) during fast compared with slow ramp distention; this rate effect was greater at 1 year after a hysterectomy, particularly at 100 mL (P = 0.04). CONCLUSIONS & INFERENCES: A simple vaginal hysterectomy has relatively modest effects (i.e., somewhat reduced rectal urgency and increased stiffness during rapid distention) on rectal sensorimotor functions.

The effects of clonidine on symptoms and anorectal sensorimotor function in women with faecal incontinence.

BACKGROUND: Women with faecal incontinence and rectal urgency have increased rectal stiffness and sensation. AIM: To evaluate the effects of clonidine, an alpha(2) -adrenergic agonist, in faecal incontinence. METHODS: In this open-label uncontrolled study, bowel symptoms and anorectal functions (anal pressures, rectal compliance, and sensation) were assessed before and during treatment with transdermal clonidine (0.2 mg daily, 4 weeks) in 12 women with urge-predominant faecal incontinence. RESULTS: Clonidine reduced the frequency (17.8 +/- 3.1 before vs. 8.8 +/- 3.9 after, P = 0.03) and number of days with faecal incontinence (11.8 +/- 1.6 before vs. 6.1 +/- 1.8 after, P = 0.02), faecal incontinence symptom severity score (max = 13, 8.3 +/- 0.7 vs. 5.6 +/- 0.9, P < 0.01), and allowed patients to defer defecation for a longer duration (P = 0.03). Although overall effects on anorectal functions were not significant, the treatment-associated reduction in faecal incontinence episodes was associated with increased rectal compliance (r = -0.58, P < 0.05) and reduced rectal sensation. (r = -0.73, P = 0.007 vs. desire to defecate pressure threshold). CONCLUSIONS: Clonidine improves symptoms in women with faecal incontinence; this improvement is associated with increased rectal compliance and reduced rectal sensitivity. A controlled study is necessary to confirm these observations.