Offspring death and subsequent psychiatric morbidity in bereaved parents: addressing mechanisms in a total population cohort.

BACKGROUND: It is unclear if psychiatric morbidity among parents bereaved of a child is related to major loss in general or if the cause of death matters. Whether such a link is consistent with a causal explanation also remains uncertain. METHOD: We identified 3,114,564 parents through linkage of Swedish nationwide registers. Risk of psychiatric hospitalization was assessed with log-linear Poisson regression and family-based analyses were used to explore familial confounding. RESULTS: A total of 3284 suicides and 14,095 any-cause deaths were identified in offspring between 12 and 25 years of age. Parents exposed to offspring suicide had considerably higher risk of subsequent psychiatric hospitalization than unexposed parents [relative risk (RR) 1.90, 95% confidence interval (CI) 1.72-2.09], higher than parents exposed to offspring non-suicide death relative to controls (RR 1.18, 95% CI 1.11-1.26). We found no risk increase among stepfathers differentially exposed to biologically unrelated stepchildren's death or suicide, and the relative risk was notably lower among full siblings differentially exposed to offspring death or suicide. CONCLUSIONS: Parental psychiatric hospitalization following offspring death was primarily found in offspring suicide. Familial (e.g. shared genetic) effects seemed important, judging from both lack of psychiatric hospitalization in bereaved stepfathers and attenuated risk when bereaved parents were contrasted to their non-bereaved siblings. We conclude that offspring suicide does not 'cause' psychiatric hospitalization in bereaved parents.

Parental schizophrenia and increased offspring suicide risk: exploring the causal hypothesis using cousin comparisons.

BACKGROUND: Little is known about suicide risk among offspring of parents hospitalized for schizophrenia and the mechanisms behind this association. METHOD: We applied a nested case-control design based on linkage of Swedish population-based registers. Among 12- to 30-year-old offspring, we identified 68 318 offspring with suicidal behavior (attempted and completed suicide) and their parents. Five healthy control-parent pairs were matched to each suicidal case-parent pair and conditional logistic regression used to obtain odds ratios (ORs). Further, to disentangle familial confounding from causal environmental mechanisms, we compared the population-based suicide risk with the risk found within full-cousins and half-cousins differentially exposed to parental schizophrenia. RESULTS: Offspring of parents with schizophrenia had significantly increased suicide risk after accounting for socio-economic status, parental suicidal behavior and offspring mental illness [OR 1.68, 95% confidence interval (CI) 1.53-1.85]. Suicide risks in offspring of schizophrenic mothers and fathers were similar in magnitude; so were risks across different developmental periods. Importantly, offspring suicide risk remained essentially unchanged across genetically different relationships; offspring of siblings discordant for schizophrenia had equivalent risk increases within full-cousins (OR 1.96, 95% CI 1.66-2.31) and half-cousins (OR 1.69, 95% CI 1.17-2.44). CONCLUSIONS: Parental schizophrenia was associated with increased risk of offspring suicidal behavior, independent of gender of the schizophrenic parent, and persisting into adulthood. The suicide risk in offspring remained at a similar level when comparing genetically different relationships, which suggests that at least part of the association is due to environmental mechanisms. These findings should inspire increased attention to suicidal ideation and prevention efforts in offspring of parents with schizophrenia.

Cognitive impairment in patients with stress-related exhaustion.

Patients who seek medical care for stress-related mental health problems frequently report cognitive impairments as the most pronounced symptom. The purpose of the present study was to compare cognitive function in patients with stress-related exhaustion with that in healthy controls, using a comprehensive battery of cognitive tests. We also explored whether neuropsychological findings were related to severity of illness measured using the Shirom-Melamed burnout questionnaire and hospital anxiety and depression scale. Thirty-three patients (15 males) and 37 healthy controls (11 males), mean age 46 years [standard deviation (SD) 3.9] and 47 years (SD 4.3), respectively, were included in the final analysis. Five cognitive domains were assessed: (1) speed, attention and working memory, (2) learning and episodic memory, (3) executive functions, (4) visuospatial functions and (5) language. The most pronounced difference between patients and controls was seen on executive function, when tested with a multidimensional test, including aspects of speed, control and working memory. The patients also performed poorer on Digit span, measuring attention span and working memory as well as on learning and episodic memory, when measured as delayed recall and the difference between immediate and delayed recall. Delayed recall was the only test that was significantly related to severity of burnout symptoms among the patients. This could reflect poor cognitive sustainability in the patients with the highest burnout scores, as this particular test was the last one performed during the test session. This study clearly shows that cognitive impairment should be considered when evaluating and treating patients who seek medical care for stress-related exhaustion.

Genetic and environmental influences on adult attention deficit hyperactivity disorder symptoms: a large Swedish population-based study of twins.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) frequently persists into adulthood. Family and twin studies delineate a disorder with strong genetic influences among children and adolescents based on parent- and teacher-reported data but little is known about the genetic and environmental contribution to DSM-IV ADHD symptoms in adulthood. We therefore aimed to investigate the impact of genetic and environmental influences on the inattentive and hyperactive-impulsive symptoms of ADHD in adults. METHOD: Twin methods were applied to self-reported assessments of ADHD symptoms from a large population-based Swedish twin study that included data from 15 198 Swedish male and female twins aged 20 to 46 years. RESULTS: The broad heritability [i.e., A + D, where A is an additive genetic factor and D (dominance) a non-additive genetic factor] was 37% (A = 11%, D = 26%) for inattention and 38% (A = 18%, D = 20%) for hyperactivity-impulsivity. The results also indicate that 52% of the phenotypic correlation between inattention and hyperactivity-impulsivity (r = 0.43) was explained by genetic influences whereas the remaining part of the covariance was explained by non-shared environmental influences. These results were replicated across age strata. CONCLUSIONS: Our findings of moderate broad heritability estimates are consistent with previous literature on self-rated ADHD symptoms in older children, adolescents and adults and retrospective reports of self-rated childhood ADHD by adults but differ from studies of younger children with informant ratings. Future research needs to clarify whether our data indicate a true decrease in the heritability of ADHD in adults compared to children, or whether this relates to the use of self-ratings in contrast to informant data.

Early changes in rectal nitric oxide and mucosal inflammatory mediators in Crohn's colitis in response to infliximab treatment.

BACKGROUND: Treatment with tumor necrosis factor-alpha monoclonal antibody (infliximab) reduces clinical activity and intestinal inflammation in Crohn's disease. AIM: To study the time-course of the effects of infliximab with reference to mucosal cytokine and inducible nitric oxide synthase expression. METHODS: Thirty-two patients with Crohn's disease were treated with single dose infliximab (5 mg/kg). Disease activity was assessed days 1, 3, 7 and 28 using Harvey-Bradshaw index. Rectal nitric oxide levels were determined and rectal biopsies collected before treatment, 1 h after infusion and on days 3, 7 and 28. Immunohistochemical staining against inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1beta and interferon-gamma were performed. RESULTS: Clinical response was seen in 14 patients with down-regulation of global immunohistochemistry expression, reaching nadir day 3. Rectal nitric oxide was increased at baseline (3578 +/- 1199 parts per billion, ppb) compared with controls (89 +/- 13 ppb) (P < 0.001). In patients with clinical response, rectal nitric oxide decreased from 3926 +/- 1687 ppb to 1050 +/- 428 ppb day 28 (P < 0.05). CONCLUSIONS: Down-regulation of mucosal inflammatory mediators occurs after infliximab. Rectal nitric oxide levels parallel down-regulation of inducible nitric oxide synthase, tumor necrosis factor-alpha, interleukin-1beta and interferon-gamma and may serve as a quantitative biomarker of intestinal inflammation.

Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort from Stockholm County.

BACKGROUND: Several placebo controlled studies have demonstrated the efficacy of infliximab in inflammatory bowel disease (IBD) but the potential toxicity of this new biological compound has been less studied. AIM: To assess the use of infliximab in IBD in a population based cohort, with special emphasis on the occurrence of severe adverse events and mortality. PATIENTS: All patients with IBD treated with infliximab between 1999 and 2001 in Stockholm County were evaluated. METHODS: Prospective registration of clinical data was carried out. Retrospective analyses were made of possible adverse events occurring in relation to infliximab treatment. Adverse events requiring pharmacological treatment or hospitalisation were defined as severe. Clinical response was assessed as remission, response, or failure. RESULTS: A cohort comprising 217 patients was assembled: 191 patients had Crohn's disease (CD), and infliximab was used off label for ulcerative colitis (UC) in 22 patients. Four patients were treated for indeterminate colitis (IC). Mean age was 37.6 (0.9) years (range 8-79). The mean number of infliximab infusions was 2.6 (0.1) (range 1-11). Forty two severe adverse events were registered in 41 patients (CD, n = 35). Eleven of the severe adverse events occurred postoperatively (CD, n = 6). Three patients with CD developed lymphoma (of which two were fatal), opportunistic infections occurred in two patients (one with UC, fatal), and two patients with severe attacks of IBD died due to sepsis (one with CD, one postoperatively with UC). One additional patient with UC died from pulmonary embolism after colectomy. Mean age in the group with fatal outcome was 62.7 years (range 25-79). The overall response rate was 75% and did not differ between the patient groups. CONCLUSIONS: Infliximab was efficacious as an anti-inflammatory treatment when assessed in a population based cohort of patients with IBD. However, there appear to be a significant risk of deleterious and fatal adverse events, particularly in elderly patients with severe attacks of IBD. Off label use of infliximab in UC and IC should be avoided until efficacy is proven in randomised controlled trials. The underlying risk of developing malignancies among patients with severe or chronically active CD in need of infliximab treatment is not known but the finding of a 1.5% annual incidence of lymphoma emphasises the need for vigilant surveillance with respect to this malignant complication.

Rise in morning saliva cortisol is associated with abdominal obesity in men: a preliminary report.

An abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with risk factors for cardiovascular disease and Type 2 diabetes mellitus. The objective of this study was to examine if morning saliva cortisols show similar associations. Twenty-eight men, all 53 yr of age, delivered during an ordinary working day saliva cortisol samples immediately upon awakening and 15 min thereafter as well as at different times during the day, including after a standardized lunch. Dexamethasone (0.5 mg) suppression of cortisol was also measured. The rise of morning cortisol values was positively associated with body mass index (r: 0.45, p=0.016), waist/hip ratio (r: 0.54, p=0.003), abdominal sagittal diameter (r: 0.54, p=0.003), glucose (r: 0.54, p=0.003), insulin (r: 0.57, p=0.002) and triglycerides (r: 0.46, p=0.014). The morning rise also correlated positively with the elevation of cortisol following lunch (r: 0.45, p=0.043) but not with other cortisol measurements or dexamethasone suppression. Elevation of cortisol immediately after awakening has previously been found to provide a simple indicator of HPA axis regulation, as suggested also by the results of this study, and an elevated rise has been reported after exposure to frequent or chronic perceived stress. The rise of cortisol immediately after awakening might be an indicator of an increased risk of developing serious, prevalent diseases via the metabolic syndrome.

Pyoderma gangrenosum associated with crohn disease: effect of TNF-alpha blockade with infliximab.

Eight patients with pyoderma gangrenosum associated with Crohn disease were treated with infliximab. All had active mucosal inflammation indicated by endoscopic examination. Within 1-4 months, infliximab treatment resulted in complete healing of the pyoderma gangrenosum in 3 cases (1 parastomal, 2 lower limb), partial healing in 3 (2 parastomal, 1 lower limb) and temporary improvement in 2. Adverse effects such as skin rash, pneumonia and diarrhoea were seen in three patients. Our results imply that infliximab has a therapeutic potential on skin manifestations associated with inflammatory bowel disease, even though successful treatment may require repeat courses of infliximab infusions.

Low-grade dysplasia in extensive, long-standing inflammatory bowel disease: a follow-up study.

PURPOSE: Extensive, long-standing inflammatory bowel disease is associated with an increased risk of developing colorectal carcinoma. Low-grade dysplasia has been used as a marker for malignant transformation and by some as an indication for prophylactic colectomy. The aim of the present study was to follow up all inflammatory bowel disease patients with extensive, long-standing colitis who had low-grade dysplasia in flat colonic mucosa. METHODS: All patients with low-grade dysplasia in flat mucosa found at screening or at surveillance colonoscopy with at least one follow-up colonoscopy or with colectomy were included. RESULTS: Sixty patients (40 males; mean age at diagnosis, 24 +/- 12 (range, 3-59) years) were found and followed up for a mean of 10 +/- 6 (range, 1-22) years. Mean time from onset of disease to discovery of low-grade dysplasia was 17 +/- 11 (range, 1-55) years. Low-grade dysplasia was present in more than 1 biopsy in 37 (62 percent) of 60 patients at the index colonoscopy. Low-grade dysplasia was again detected in 1.8 (1-6) subsequent colonoscopies in 44 (73 percent) of 60 patients. High-grade dysplasia was found in 2 of 11 patients with dysplasia-associated lesion or mass at follow-up. Thirteen patients were subjected to colectomy (7 for dysplasia, 6 for therapy failure). Dysplasia was confirmed in five of these patients. CONCLUSION: Although low-grade dysplasia occurred at several colonic levels and at repeated colonoscopies in 73 percent of the patients, no progression to high-grade dysplasia was found during 10 years of follow-up, except in 2 cases with dysplasia-associated lesion or mass. Colectomy in cases with single or repeated low-grade dysplasia in flat mucosa does not appear to be justified.

Central and peripheral glucocorticoid receptor function in abdominal obesity.

Abdominal obesity seems to be associated with a moderately deranged feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis where central glucocorticoid receptors (GR) are involved. Therefore, functions of central and peripheral GR were compared in this study. Furthermore, since trinucleotide repeats in early exons of steroid hormone receptor genes influence transcription, and therefore may influence receptor density, this was also studied. Ten middle-aged men, 5 with abdominal obesity and 5 controls, were studied. The suppression of dexamethasone (dex) on serum cortisol was used in dose-response tests to assess the function of central GR. Abdominal adipose tissue biopsies were incubated and exposed to cortisol in different concentrations, and the function of the peripheral GR assayed as induction of lipoprotein lipase (LPL) activity. Aberrant expansion of exonic trinucleotide repeats in the first coding exon of the GR gene was studied by sequencing of genomic DNA. Results showed that men with abdominal obesity showed less inhibition of serum cortisol by dex, particularly at lower concentrations, while in the controls cortisol secretion was inhibited in an apparent dose-response manner. LPL activity in adipose tissue was lower in abdominal obese men than in controls. However, the sensitivity to cortisol was not different between the groups. There was no evidence for expansion of trinucleotide repeats. These results suggest that the central GR and the peripheral GR in adipose tissue exhibit functional differences in abdominal obesity.

Colorectal carcinoma in ulcerative colitis is decreasing in Scandinavian countries.

A total of 31 cases with Ulcerative Colitis (UC) and colorectal carcinoma were retrieved from the files of the Karolinska Hospital, Stockholm between 1951 and 1998. Sections from 16 colectomy specimens (operable cases) and 15 biopsies obtained at laparotomy (inoperable cases), were available for the study. Of the 31 patients reported here, 22 (71%) were 49 years of age or younger at the time of surgery for carcinoma. In comparison only 47 (5.5 %) of the 855 colorectal carcinomas without UC reported in the Stockholm area in 1990 were 49years of age oryounger. When this hospital was a referral Center (1951 through 1969) 18 cases of carcinoma in UC were operated between 1951 and 1960 (1.8 patients/year), but only 4 between 1961 and 1969 (0.44 patients/year). During the surveillance period of 29 years (1970 to March 1998) only 9 patients (0.31 cases/year) were found to have carcinoma complicating UC. Notably, 8 of the 9 patients were operated on between 1970 and December 1989 (0.42 patients/year), but only one case between January 1990 and March 1998 (0.11 patients/year). The data presented indicate that the frequency of carcinoma cases in pancolitics has decreased at this hospital, not only during the referral period, from 1.8 patients/year during the 50's to 0.40 patients/year during the 60's, but also during the surveillance period (from 0.44 patients/year/during the 70's and 80's to 0.11 patients/year between 1990 and March 1998). This, despite the incidence of UC in the Stockholm County remained stable for the past 40 years (4.2 to 5 patients/10(5) inhabitants) and that the population in the Stockholm County has steady increased since 1950. A review of the present literature indicated that the ris for colorectal carcinoma in pancolitics is presently decreasing, not only in Sweden but also in other Scandinavian countries.

Rectal nitric oxide assessment in children with Crohn disease and ulcerative colitis. Indicator of ileocaecal and colorectal affection.

BACKGROUND: Nitric oxide (NO) production is increased in inflammatory bowel disease (IBD). Measurements of luminal NO in Crohn disease and ulcerative colitis have revealed that levels are increased during active disease. We aim to evaluate whether rectal measurements of NO can reveal active disease of the colon as well as ileum. METHODS: Sixteen children with active Crohn disease in the ileocaecal or colorectal regions of the gut and 6 children with active ulcerative colitis were compared to a group of 14 healthy children. Gaseous samples for analysis of luminal NO were collected using a Foley catheter inserted into rectum. The balloon of the catheter was filled with NO-free air and incubated for 10 min. After aspiration, samples were analysed using chemiluminescence. Values are expressed as median and range. RESULTS: In healthy children, rectal NO values were 60 (0-275) ppb. In children with Crohn disease of the colorectal region, NO concentrations were 5,675 (300-49,350) ppb (P < 0.001), while those with Crohn disease of the ileocaecal region had NO levels of 2,625 (300-15,000) ppb (P < 0.01). In children with ulcerative colitis, NO values of 5,500 (950-34,000) ppb were found (P < 0.001). CONCLUSION: Rectal NO levels are greatly increased in children with IBD. Highest values were found in patients with colorectal engagement, but rectal NO was increased also in ileocaecal disease. Rectal sampling of luminal NO is a simple and minimally invasive method and should be considered a diagnostic tool for intestinal inflammatory activity in children regardless of primary disease location.

Treatment of abdominally obese men with a serotonin reuptake inhibitor: a pilot study.

OBJECTIVE: To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity. DESIGN: Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods. SUBJECTS: Sixteen healthy men, 45-60 years, moderately obese and with an abdominal fat distribution. MEASUREMENTS: Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h. RESULTS: Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change. CONCLUSION: The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.

Increased rectal nitric oxide in coeliac disease after local challenge with gluten.

BACKGROUND: Coeliac disease is an inflammatory disorder characterized by reversible atrophy of small intestinal villi following the ingestion of gluten. Earlier studies indicate that the inflammatory response to gluten may occur also very distally in the gastrointestinal tract. The aim of this study was to evaluate whether rectal challenge with gluten would trigger an increased local production of the gas nitric oxide (NO), a novel marker of intestinal inflammation. METHODS: Rectal challenge with partially digested gluten was performed in 20 patients with treated coeliac disease and in 13 healthy controls. Luminal levels of NO were measured in the rectum at 0, 8 and 24 h using a chemiluminescence technique. RESULTS: In patients with coeliac disease mean rectal NO increased from 235+/-90 parts per billion (ppb) at 0 h to 4965+/-1653 ppb at 24 h (P < 0.005). In the control group there was no significant increase. One control subject responded with high NO levels at 24 h and the same individual tested positive for anti-endomysium IgA antibodies. Subsequent duodenal biopsing showed substantial villusatrophy. CONCLUSIONS: Rectal challenge with gluten results in increased luminal levels of NO in a group of patients with treated coeliac disease. Further studies are needed to evaluate the role of NO in coeliac disease and the potential usefulness of rectal NO measurements in aiding diagnosis of this intestinal disorder.

The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men.

OBJECTIVE: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. RESEARCH METHODS AND PROCEDURES: Fifty non-diabetic, middle-aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables. RESULTS: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin-releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites. DISCUSSION: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.

Beneficial effects of ropivacaine in rat experimental colitis.

Ropivacaine, a new, long-acting local anesthetic agent, has been shown to have beneficial effects in the treatment of ulcerative colitis. Treatment with this drug results in prompt symptomatic relief. The aim of this study was to examine the effects of ropivacaine on mucosal healing and to investigate whether ropivacaine can restore the decreased colonic contractility seen in the diseased state. Colitis was induced in rats by a single intrarectal administration of trinitrobenzene sulfonic acid. Mucosal healing was assessed after 1 week of therapy. The effects on colonic contractility were examined either after 1 week of treatment or by application of the drugs to untreated, inflamed rat colon segments placed in organ baths. After the induction of colitis, daily intracolonic treatment with ropivacaine for 1 week reduced morphological damage and myeloperoxidase activity. One week of treatment also restored the contractile response to acetylcholine. By adding ropivacaine directly to untreated inflamed colonic segments in organ baths, the contractile response to acetylcholine was increased compared with controls. For comparison, the effects of budesonide and 5-aminosalicylic acid were also examined. Ropivacaine improved mucosal healing and restored colonic motor activity in experimental colitis, similar to budesonide but superior to 5-aminosalicylic acid.

Increased nitric oxide in infective gastroenteritis.

Nitric oxide (NO) production is increased in several inflammatory disorders, although the role of this gas is not clear. The purpose of this study was to determine whether luminal NO in the intestine is increased in infective gastroenteritis. Rectal gas was sampled in 17 patients with gastroenteritis and 10 healthy volunteers, with balloon catheters made of 100% silicone and analyzed for NO by chemiluminescence. Plasma nitrate and nitrite levels were determined by capillary electrophoresis. Rectal NO was (mean+/-SEM) 9441+/-3126 parts per billion (ppb) in the patients and 74+/-13 ppb in controls (P<.0001). There was no individual overlap. Plasma nitrite but not nitrate was significantly increased in patients compared with controls. These data indicate that luminal NO is greatly increased in gastroenteritis. The high levels of NO are easily measurable by rectal sampling, and measurement of luminal NO seems to be useful for evaluating local NO production in the gut in health and disease.

Pelvic reservoir with S-pouch: can surgeons evaluate the results of their own operations?

PURPOSE: This study was designed to evaluate whether operating surgeons could follow up the functional outcome of their own operations, without bias, by using standardized methods at follow-up. METHODS: Fifty-five patients who received a pelvic reservoir with an S-pouch were evaluated regarding functional outcome after at least one year postoperative follow-up. The functional surgical outcome was evaluated by an internist especially trained in gastroenterology and the operating surgeon by using a standardized scale comprising eight functional variables. RESULTS: None of the variables analyzed reached statistically significant difference between the two observers, and a high degree of agreement could be shown by using kappa and weighted kappa analysis. CONCLUSIONS: Our results indicate that it is possible for an operating surgeon to assess the postoperative surgical outcome using standardized methods at follow-up.

Vasoactive intestinal peptide suppresses migrating myoelectric complex of rat small intestine independent of nitric oxide.

The involvement of nitric oxide (NO) in the biological response to vasoactive intestinal peptide (VIP) on the migrating myoelectric complex (MMC) of small bowel and systemic arterial blood pressure was investigated in the rat. Animals were supplied with bipolar electrodes for electromyography of the small intestine and blood pressure was assessed by a pressure transducer connected to a carotid artery. In the first session, Nomega-nitro-L-arginine (L-NNA) was administered intravenously at 1, 2, 4 and 20 mg kg(-1). Effects of L-NNA at 1 and 20 mg kg(-1) were also studied after L-arginine 300 mg kg(-1). In the second session, intravenous infusion of VIP 500 pmol kg(-1) min(-1) was administered before and after L-NNA at 1 and 20 mg kg(-1). L-NNA at increasing doses stimulated myoelectric spiking of the small bowel until at 4 mg kg(-1) the MMC was disrupted and irregular spiking induced. Neither at 1 nor 20 mg kg(-1) did L-NNA affect the inhibitory motility response or decrease of blood pressure induced by VIP at a dose of 500 pmol kg(-1) min(-1). Our results show that effects of VIP on motility of the small intestine and systemic arterial blood pressure are direct and not dependent on NO as a common final link.

Urinary albumin excretion and heart rate variability in obese women.

OBJECTIVE: The aim of this work was to examine the relationship between cardiac autonomic function and urinary albumin excretion in obesity. SUBJECTS: These were 27 obese non-diabetic postmenopausal women and 18 non-obese healthy postmenopausal women. MEASUREMENTS: Urinary albumin excretion as well as plasma nitrate, both indices of capillary function, were measured. Power spectral analysis of heart rate variability was performed, as a measurement of vagal function. An oral glucose tolerance test (OGTT) was performed and blood lipids were analysed. RESULTS: The obese women were characterized by higher fasting insulin, sum of glucose, triglycerides and lower high density lipoprotein cholesterol (HDL), the latter of borderline significance, than controls. Urinary albumin excretion (UAE), plasma nitrate and heart rate variability were not different between obese and control women. However, in obese women log UAE correlated positively with systolic and diastolic blood pressure, and inversely with heart rate variability, the latter independent of body mass index (BMI) and the waist/hip circumference ratio. CONCLUSION: It was concluded that this inverse association between UAE and parasympathetic activity in obese women may be an early sign of derangements of endothelial function and autonomic nervous system control, which may contribute to the increased risk of cardiovascular mortality in abdominal obesity.