Symptom, alexithymia and self-image outcomes of Mentalisation-based treatment for borderline personality disorder: a naturalistic study.

BACKGROUND: Mentalisation-based treatment (MBT) in borderline personality disorder (BPD) has a growing evidence base, but there is a lack of effectiveness and moderator studies. The present study examined the effectiveness of MBT in a naturalistic setting and explored psychiatric and psychological moderators of outcome. METHOD: Borderline and general psychiatric symptoms, suicidality, self-harm, alexithymia and self-image were measured in a group of BPD patients (n = 75) receiving MBT; assessments were made at baseline, and subsequently after 6, 12 and 18 months (when treatment ended). Borderline symptoms were the primary outcome variable. RESULTS: Borderline symptoms improved significantly (d = 0.79, p < .001), as did general psychiatric symptoms, suicidality, self-harm, self-rated alexithymia and self-image. BPD severity or psychological moderators had no effect on outcome. Younger patients improved more on self-harm, although this could be explained by the fact that older patients had considerably lower baseline self-harm. CONCLUSIONS: MBT seems to be an effective treatment in a naturalistic setting for BPD patients. This study is one of the first studies of MBT showing that outcomes related to mentalisation, self-image and self-rated alexithymia improved. Initial symptom severity did not influence results indicating that MBT treatment is well adapted to patients with severe BPD symptoms. TRIAL REGISTRATION: The study was retrospectively registered 25 September 2017 in the ClinicalTrials.gov PRS registry, no. NCT03295838 .

The health effect of probiotics on high-fat diet-induced cognitive impairment, depression and anxiety: A cross-species systematic review.

Obesity is a complex disease with many co-morbidities, including impaired cognitive functions. Obese individuals often contain an aberrant microbiota. Via the microbiota-gut-brain axis, the altered microbiota composition can affect cognition or induce anxiety- or depressive-like behavior. Probiotics have been shown to alleviate both obesity- and neurobehavioral disorder-related symptoms. Here, we evaluated previously published results on the effectiveness of probiotic intervention in alleviating obesity- or high-fat diet (HFD)-related cognitive impairment, depression and anxiety. A systematic search was performed in PubMed, Embase, and Google Scholar until June 2021 to identify relevant articles. Seventeen studies were included: one human and sixteen animal studies. Overall, the findings support the beneficial health effect of probiotics on HFD-induced cognitive impairment and anxiety. However, the results suggest that multi-strain probiotic treatments should be used with caution, especially in the absence of HFD-induced impairment. Future studies should overcome the large variation in study design and high risk of bias found in the current evidence. Nevertheless, probiotic treatment, in particular using the Lactobacillus genus, seems promising.

Transdermal delivery of erythromycin lactobionate--implications for the therapy of gastroparesis.

BACKGROUND: The treatment of many diseases may be complicated by abnormalities in gastric emptying. Gastric motor dysfunction may lead to unpredictable food and medication delivery to the small intestine, their site of absorption. Prokinetic agents improve gastric motility, but orally administered drugs are unreliably absorbed, thereby limiting their effectiveness. A method of delivering prokinetic agents which bypasses the gastrointestinal tract could lead to more effective treatment. METHODS: Skin samples from rat, hairless mouse and man were placed in an in vitro diffusion chamber. The epidermal side of the skin was exposed to erythromycin lactobionate and passage of the drug across the skin sample monitored and quantitated by high-performance liquid chromatography with UV detection. RESULTS: Erythromycin passes across all skin types tested. Steady-state flux across hairless mouse skin was greater than for rat, full thickness human skin and human epidermis. In the first 3 h following introduction of erythromycin lactobionate, 1.85 mg/cm2 crossed human epidermis. Given that a dose of 50 mg may exert prokinetic effects in vivo in man, increasing the patch size to approximately equal to 28 cm2 should provide therapeutic levels of drug within 3 h. CONCLUSIONS: Erythromycin lactobionate, when administered transdermally, can be delivered at levels sufficient to treat gastroparesis. This technique warrants in vivo investigation.

Effects of psyllium therapy on stool characteristics, colon transit and anorectal function in chronic idiopathic constipation.

BACKGROUND: Psyllium is widely used in the symptomatic therapy of constipation. Its effects on colonic function and their correlation with symptomatic response have not been defined. METHODS: After a 4-week baseline, placebo, run-in phase, 22 subjects with idiopathic constipation confirmed by prospectively administered stool diaries were randomly assigned to receive either psyllium (5 g b.d., 11 patients) or placebo (11 patients) for 8 weeks, followed by another 4-week wash-out, placebo phase. A colon transit study and anorectal manometry were performed at the beginning and at the end of each study phase. Subjects recorded, in diaries, their daily stool frequency, difficulty with defecation and weekly stool weight. RESULTS: Stool frequency increased significantly after 8 weeks of psyllium treatment (3.8 +/- 0.4 vs. 2.9 +/- 0.1 stools/week, P < 0.05) as did stool weight (665.3 +/- 95.8 g vs. 405.2 +/- 75.9 g, P < 0.05). Subjects also reported an improvement in stool consistency (stool consistency score: 3.2 +/- 0.2 vs. 3.8 +/- 0.2, P < 0.05) and pain on defecation (pain score: 2.0 +/- 0.4 vs. 2.6 +/- 0.5, P < 0.05) on psyllium. Colon transit and anorectal manometry parameters were unchanged on psyllium. Subjects treated with placebo did not show any change in either subjective or objective measures of constipation. CONCLUSIONS: Psyllium increases stool frequency and weight and improves stool consistency in idiopathic constipation. These effects are not associated with significant changes in either colonic or rectal motor function. We suggest that the beneficial effects of psyllium in constipation are primarily related to a facilitation of the defecatory process.

Comparative effects of intraduodenal psyllium and senna on canine small bowel motility.

BACKGROUND/AIM: To define the possible contribution of altered small intestinal motor activity to side-effects of bulking fibres, we sought to compare the relative effects of intraduodenal and intracolonic administration of the bulking fibre psyllium and the anthraquinone laxative senna on canine small intestinal motor activity. METHODS: Motor activity was recorded by serosal strain gauges implanted along the small intestine in 6 dogs. In random order, the motor responses to the instillation of psyllium (in doses of 5 or 10 g), senna (10 mg/kg) or appropriate vehicle (200 ml water infusion or saline 5 ml bolus) into either the proximal duodenum or proximal colon were assessed. RESULTS: The intra-duodenal administration of psyllium in either dose consistently induced a prolonged burst of 'clustered' contractions; in contrast, clusters were infrequent and of short duration following instillation of either vehicle or senna (P < 0.05). Intraduodenal instillation of psyllium inhibited migrating motor complex (MMC) migration and consistently delayed the onset of the next MMC cycle; a similar inhibition occurred with vehicle, however. Neither senna nor its vehicle inhibited MMC migration. None of these agents had any effect on small intestinal motor activity when instilled directly into the colon. CONCLUSIONS: Psyllium administered directly into the duodenum inhibits MMC activity and consistently induces 'clustered' contractions. Whilst the MMC-inhibitory effect appears to be a non-specific volume-related phenomenon, the induction of clusters is independent of volume or laxation. These motor effects of psyllium may contribute to the gastrointestinal symptomatology related to such agents and could be avoided by the preferential release of psyllium in the colon.

An adaptive control algorithm for optimization of intensity modulated radiotherapy considering uncertainties in beam profiles, patient set-up and internal organ motion.

A new general beam optimization algorithm for inverse treatment planning is presented. It utilizes a new formulation of the probability to achieve complication-free tumour control. The new formulation explicitly describes the dependence of the treatment outcome on the incident fluence distribution, the patient geometry, the radiobiological properties of the patient and the fractionation schedule. In order to account for both measured and non-measured positioning uncertainties, the algorithm is based on a combination of dynamic and stochastic optimization techniques. Because of the difficulty in measuring all aspects of the intra- and interfractional variations in the patient geometry, such as internal organ displacements and deformations, these uncertainties are primarily accounted for in the treatment planning process by intensity modulation using stochastic optimization. The information about the deviations from the nominal fluence profiles and the nominal position of the patient relative to the beam that is obtained by portal imaging during treatment delivery, is used in a feedback loop to automatically adjust the profiles and the location of the patient for all subsequent treatments. Based on the treatment delivered in previous fractions, the algorithm furnishes optimal corrections for the remaining dose delivery both with regard to the fluence profile and its position relative to the patient. By dynamically refining the beam configuration from fraction to fraction, the algorithm generates an optimal sequence of treatments that very effectively reduces the influence of systematic and random set-up uncertainties to minimize and almost eliminate their overall effect on the treatment. Computer simulations have shown that the present algorithm leads to a significant increase in the probability of uncomplicated tumour control compared with the simple classical approach of adding fixed set-up margins to the internal target volume.

Stochastic optimization of intensity modulated radiotherapy to account for uncertainties in patient sensitivity.

The aim of the present work is to better account for the known uncertainties in radiobiological response parameters when optimizing radiation therapy. The radiation sensitivity of a specific patient is usually unknown beyond the expectation value and possibly the standard deviation that may be derived from studies on groups of patients. Instead of trying to find the treatment with the highest possible probability of a desirable outcome for a patient of average sensitivity, it is more desirable to maximize the expectation value of the probability for the desirable outcome over the possible range of variation of the radiation sensitivity of the patient. Such a stochastic optimization will also have to consider the distribution function of the radiation sensitivity and the larger steepness of the response for the individual patient. The results of stochastic optimization are also compared with simpler methods such as using biological response 'margins' to account for the range of sensitivity variation. By using stochastic optimization, the absolute gain will typically be of the order of a few per cent and the relative improvement compared with non-stochastic optimization is generally less than about 10 per cent. The extent of this gain varies with the level of interpatient variability as well as with the difficulty and complexity of the case studied. Although the dose changes are rather small (<5 Gy) there is a strong desire to make treatment plans more robust, and tolerant of the likely range of variation of the radiation sensitivity of each individual patient. When more accurate predictive assays of the radiation sensitivity for each patient become available, the need to consider the range of variations can be reduced considerably.

Efficiency of Dispatch and Infiltrator cardiac infusion catheters in arterial localization of nanoparticles in a porcine coronary model of restenosis.

Localized intramural delivery of sustained release biodegradable nanoparticles containing an antiproliferative agent could provide prolonged drug effect at the site of vascular injury that could inhibit the proliferation of smooth muscle cells and hence restenosis. The efficiency of arterial localization of nanoparticles is crucial in maximizing the drug effect in the target tissue. Therefore, the objective of the present study was to determine the comparative efficiency of the Dispatch and the Infiltrator cardiac infusion catheters to localize nanoparticles in the arterial wall. Following a standard balloon angioplasty procedure on the left anterior descending artery (LAD) in a porcine coronary model of restenosis, a suspension of nanoparticles containing a fluorescent marker was infused at the site of injury using either the Dispatch or the Infiltrator catheter. One hour following the infusion, animals were sacrificed and the nanoparticle levels in the LAD and other tissue were analyzed. The Dispatch catheter resulted in 3.3 folds greater efficiency of nanoparticle localization in the LAD than the Infiltrator catheter (309 +/- 124 vs. 93 +/- 43 microg/g of tissue, n = 6 for Dispatch and n = 5 for Infiltrator, p = 0.082, t-test). It is estimated that about 2% of the arterial volume can be displaced with the nanoparticle infusion. Fluorescence microscopy of the cross-sections of the LAD revealed greater fluorescence activity in the intimal layer with both the catheters, however the arteries infused using the Dispatch catheter demonstrated relatively higher degree of fluorescence activity in the medial and adventitial layers. The transmission electron microscopy of the arterial sections demonstrated infiltration of nanoparticles in the arterial wall and the histological analysis of the sections demonstrated no apparent damage to the endothelium due to the infusion of nanoparticles.

Development and evaluation in an ex vivo rat model of a technique for the endoscopic assessment of mucosal defense in man.

We evaluated, in an ex vivo rat model, two electrodes suitable for use in man for the endoscopic assessment of luminal and juxtamucosal pH in the upper gastrointestinal tract. Luminal and mucosal pH measurements were performed under stereomicroscopic control in the exposed stomach of the anesthetized rat, using 0.5-mm and 1-mm immersion depth electrodes in the presence of various luminal pH values and after pre-exposure to the mucolytic agent N-acetylcysteine. Both electrodes consistently recorded lumen-to-mucosa pH gradients in the gastric corpus and antrum, the neutralizing zone being located over the surface of the mucosa. These gradients were dissipated on mucosal exposure to a highly acid luminal fluid and after pre-treatment with N-acetylcysteine. These studies indicate that these microelectrodes do, indeed, reliably record lumen-to-mucosa pH gradients and suggest that this method may prove a useful tool for the investigation of mucosal protection in man. Discrepancies between the size of the electrode and the depth of the mucus gel layer, which predispose to simultaneous sampling of luminal and mucosal pH, together with a slow response time, may, however, limit the sensitivity of the technique.

An examination of the reliability of reported stool frequency in the diagnosis of idiopathic constipation.

OBJECTIVES: To investigate the reliability of reported stool frequency in the diagnosis of constipation. METHODS: Our criterion for the diagnosis of idiopathic constipation was < or = 3 stools per week for > or = 6 months. Subjects who believed that they met this criterion were invited to participate. Daily stool frequency was recorded over a 4-wk period, and all stools were weighed during the final week. A colon transit study and anorectal manometry were performed at the beginning and at the end of the study. RESULTS: On review of stool diaries from 45 subjects who described chronic constipation and who completed the 4-wk study, only 22 (49%) actually satisfied our criterion for idiopathic constipation. The remaining 23 (51%) subjects, although describing constipation, had, on average, 6 stools/wk. A history of psychiatric illness was 5 times more frequent among those whose bowel symptoms correlated poorly with objective measures. Measures of difficult defecation were similar in the two groups. Mean colon transit time was significantly longer and correlated closely with stool weight only in subjects who truly were constipated (p < 0.05). Anorectal manometry was not helpful in discriminating between those who satisfied our criterion for constipation and those who did not. CONCLUSIONS: Defining constipation on the basis of a patient's reported stool frequency may prove misleading; the diagnosis of idiopathic constipation should be supported by the use of stool diaries and a colon transit study.

Can symptoms predict esophageal motor function or acid exposure in gastroesophageal reflux disease? A comparison of esophageal manometric and twenty-four-hour pH parameters in typical and extraesophageal gastroesophageal reflux disease.

It has been suggested that patterns of esophageal motor function and acid exposure may differ between those patients with gastroesophageal reflux disease (GERD) with classic symptoms and those with extraesophageal manifestations. Our objective was to compare various parameters of esophageal motility and acid exposure between groups of patients who had presented with extraesophageal manifestations of GERD alone, a combination of classic and extraesophageal manifestations, or classic GERD symptoms alone. A retrospective review of consecutive patients undergoing esophageal manometry and 24-hour dual-channel esophageal pH testing was performed. Information on patient demographics, symptoms, and results of various manometric and pH testing parameters was examined. We evaluated 84 patients: 32 with extraesophageal symptoms alone, 24 with both classic and extraesophageal symptoms, and 28 with classic symptoms alone. Apart from a trend toward less supine acid exposure in those with extraesophageal symptoms alone, no significant differences were evident among the three patient groups in any of the other parameters of proximal or distal esophageal acid reflux. With respect to motility parameters, lower esophageal sphincter pressure was lower in those with combined symptoms; otherwise, manometric findings were similar in the three patient groups. Our data do not support the hypothesis that the nature of the clinical presentation of GERD, whether in the form of classic or extraesophageal manifestations, is related to differing patterns of esophageal motor function or esophageal acid exposure.

Disruption of canine jejunal interdigestive myoelectrical activity by artificial ileocolonic sphincter. Studies of intestinal motor response to surgically fashioned sphincter substitute.

We studied the effects of an ileocolonic sphincter substitute on canine small intestine motor activity. Recordings of fasting and postprandial myoelectrical activity were performed in three groups of animals in whom the following procedures had been performed: (1) electrode placement alone, intestinal continuity undisturbed (controls); (2) ileocolonic sphincter substitute fashioned in mid-jejunum; and (3) transection and reanastomosis at a similar location in mid-jejunum. Transection alone resulted in a decrease in slow-wave frequency, a shortening of the period of the interdigestive myoelectrical complex (IDMEC) and a prolongation of phase III of the IDMEC in the jejunum distal to the site of transection. The IDMEC period was also shorter at proximal electrode sites, but the incidence of IDMEC phase III complexes was similar on either side of the transection. However, in those animals in whom a sphincter substitute had been fashioned at the site of the transection, the incidence of IDMEC phase III complexes was significantly suppressed in the proximal intestine; IDMEC phase III frequency per hour (mean +/- SD transection vs sphincter substitute) was 0.59 +/- 0.20 vs 0.23 +/- 0.24, P less than 0.002; 0.61 +/- 0.24 vs 0.28 +/- 0.30, P less than 0.006; 0.61 +/- 0.24 vs 0.29 +/- 0.30, P = 0.008, at electrodes 10, 35, and 85 cm proximal to the sphincter substitute, respectively. In addition, the sphincter-substitute animals alone demonstrated, during fasting, recurrent propagated bursts of spike clusters and occasional prolonged spike bursts in electrodes proximal to the sphincter substitute.(ABSTRACT TRUNCATED AT 250 WORDS)

Generalization of the normalized dose-response gradient to non-uniform dose delivery.

A generalization of the standard dose-response gradient to arbitrarily heterogeneous dose distributions has been developed. The generalized dose-response gradient is the scalar product of the vector representing the dose distribution and the gradient of the dose-response relation with respect to that dose vector. It is shown that, for a tumor, the individual gamma-values for each portion of the tumor divided by the corresponding local tumor control probability should be added to get the total value for the heterogeneously irradiated tumor. This corresponds to summing up the contributions of all tumor volumes so that the total value of the gradient is related to the logarithm of the total tumor clonogen number. General expressions are also derived for the change in the dose-response relation as a function of a change in the delivered dose distribution.

Constipation in Parkinson's disease: objective assessment and response to psyllium.

We evaluated the reliability of patient history and the effect of psyllium on symptoms and colorectal function in 12 patients with Parkinson's disease (PD) and constipation. In all but two, constipation anteceded the development of parkinsonian symptoms. A comparison with prospectively obtained stool diaries confirmed the patients' reported constipation in 7 of the 12 patients. Those patients with confirmed constipation had lower stool weights and reported more straining at stool. Measures of colonic and anorectal function were similar in those who were truly constipated and those who were not. Among those PD subjects with confirmed constipation, psyllium increased stool frequency and weight but did not alter colonic transit or anorectal function. We conclude that prospectively obtained stool diaries should be employed to confirm constipation in PD and that psyllium produces both subjective and objective improvements in constipation related to PD.

Evaluation of effects of ethyl alcohol and bismuth subsalicylate on gastric mucosal barrier in man.

The mucus-bicarbonate barrier provides the first line of defense against potentially harmful gastric luminal contents. Its integrity can be assessed in man by demonstrating the presence of a pH gradient across the mucus gel layer, from the acidified lumen to near-neutral pH at the mucosa. Our aim was, firstly, to assess the effects of ethyl alcohol and bismuth subsalicylate on the integrity of this lumen-to-mucosal pH gradient and, secondly, to evaluate whether pretreatment with bismuth subsalicylate would protect against any deleterious effects of ethyl alcohol. Ten healthy adults underwent two upper endoscopic procedures with microelectrode measurement of juxtamucosal pH gradients. At the first endoscopy, the effects of 30 ml of bismuth subsalicylate on the gradient was evaluated. At the second endoscopy, gradients were measured before and after luminal installation of 60 ml of ethyl alcohol (40% v/v) and following pretreatment with either 30 ml of bismuth subsalicylate or placebo. pH measurements were technically easy to perform and provided consistently reproducible results. A distinct juxtamucosal pH gradient (pH 4.0 +/- 0.2 units) was identified in all subjects in the basal state. Neither bismuth subsalicylate nor ethyl alcohol had a significant effect on these gradients. We conclude that a distinct pH gradient between gastric luminal fluid and the mucus gel layer can be readily demonstrated in man. Neither bismuth subsalicylate nor ethyl alcohol have a significant effect on this gradient.

The effect of mesenteric venous hypertension on gut motility and absorption.

The effects of portal hypertension on gut function may be mediated by venous congestion and altered circulating levels of enteric hormones and neuropeptides. We designed this study to determine the effects of chronic intestinal venous hypertension (VHT), in isolation, on gut motility and absorption. In 10 dogs, a 20- to 25-cm loop of jejunum was isolated from the fecal stream, but myoneural continuity was maintained with the proximal bowel by a seromuscular bridge. In 5 dogs, VHT was created in the loop by a fixed stenosis of its venous drainage; a sham procedure was performed in a further 5 animals. Serosal monopolar electrodes were placed in all animals. Absorptive function and myoelectrical activity were studied over a 4-week period. Venous hypertension was achieved and sustained in the VHT animals; loop vein pressures for VHT vs control in cm H2O (means +/- SEM) are: initial--29.8 +/- 1.8 vs 7.5 +/- 0.4 (P less than 0.01), and at 4 weeks--17.6 +/- 6.88 vs 7.3 +/- 0.2 (P less than 0.01). Absorption of Na+, Cl-, glucose, and water was impaired in VHT loops. Normal patterns of fasting and postprandial myoelectrical activity were preserved in the VHT animals. We conclude that chronic VHT, in the absence of portosystemic shunting, results in impaired absorption of water, glucose, and electrolytes without any change in intestinal motility.

Long-term effects of jejunoileal autotransplantation on myoelectrical activity in canine small intestine.

We studied the longitudinal effects of autotransplantation on the motor function of the jejunoileum. By performing the autotransplantation procedure in a manner similar to that employed for allotransplantation, we sought to examine the long-term effects of both extrinsic denervation and the operative procedure itself on small intestinal motor function. Although initially disrupted, interdigestive myoelectrical activity demonstrated progressive organization: 88% of migrating myoelectrical complexes in animals studied between 12 and 20 months following autotransplantation demonstrated each phase of the complex in normal sequence. Longitudinal studies of several parameters of myoelectrical activity provided further evidence of progressive organization and entrainment of motor functions within the denervated intestine. Several abnormal myoelectrical patterns were observed within the autotransplanted segment, however, and coordination of either slow wave or phase III activity with the proximal innervated intestine did not recover with time. The major component of the myoelectrical response to feeding was permanently impaired with a delayed onset and shortened duration of the fed response. We conclude that the extrinsically denervated intestine recovers the ability to generate and organize all phases of the MMC but demonstrates permanent impairment of the major motor response to food. However, anoxic and cooling damage to enteric nerves and muscle, incurred during the autotransplantation procedure, may explain the persistence of abnormal motor patterns and impaired myoelectrical conduction and could play an important role, additional to that of extrinsic denervation, in the long-term motor function of the allotransplanted intestine.

Effectiveness of transcranial and transthoracic ultrasound and microbubbles in dissolving intravascular thrombi.

OBJECTIVE: To examine the effectiveness of 1 -MHz and 40-kHz ultrasound with and without microbubbles in fragmenting thrombi in attenuated conditions. METHODS: First, an vitro transcranial model was used to examine the ability of these frequencies to fragment thrombi in the presence or absence of perfluorocarbon-exposed sonicated dextrose albumin microbubbles. Second, an in vivo transthoracic model was used to test the effectiveness of these same frequencies with intravenous perfluorocarbon-exposed sonicated dextrose albumin in fragmenting left circumflex coronary thrombotic occlusions. RESULTS: In the in vitro model, both transcranial 1-MHz and 40-kHz ultrasonic frequencies were effective at fragmenting thrombi only in the presence of microbubbles. In the in vivo model, 1-MHz ultrasound with intravenous perfluorocarbon-exposed sonicated dextrose albumin angiographically recanalized only 4 of 14 occlusions but was consistently effective at improving myocardial blood flow to the risk area even in the absence of angiographic recanalization. Both 40-kHz and 1-MHz ultrasound with perfluorocarbon-exposed sonicated dextrose albumin improved regional wall-thickening and electrocardiographic abnormalities (P < .05 compared with control or ultrasound alone). CONCLUSIONS: Transcranial and transthoracic ultrasound in the presence of intravenous microbubbles can improve flow to ischemic regions and should be considered as a supplement to current pharmacologic therapy.