Minimally invasive photodynamic therapy (PDT) for ablation of experimental rat glioma.

OBJECTIVE: The feasibility of using ALA-mediated photodynamic therapy (PDT) tumor ablation as a minimally invasive treatment alternative for malignant brain tumors was evaluated in a rodent model. Treatment efficacy and side effects were evaluated with MRI, histopathology and survival rates. METHODS: BT (4)C orthotopic brain tumors were induced in BD-IX rats. At various time intervals following tumor induction the animals were given 5-aminolevulinic acid (ALA) and 4 hours later optical fibers were inserted directly into the tumor without mechanical debulking or cranial decompression. A 3-day course of steroid treatment was initiated immediately prior to PDT. RESULTS: All untreated animals inevitably died within one month after tumor implantation (28.5 +/- 2.5 days). Complete tumor eradication was achieved in only 1/17 rats, but a significant increase in survival was obtained in the group of animals receiving 125 mg/kg ALA and 26 Joules of light fluence. Histopathology revealed large areas of central tumor necrosis, although clusters of viable tumor cells were often found at the tumor periphery. Pronounced edema in the necrotic tumor center as well as in the surrounding brain, and along white matter tracts was evident in all the brains studied from PDT-treated animal. CONCLUSION: This study suggests that ALA-mediated PDT may become a promising alternative therapy for the minimally invasive treatment of brain tumors. A judicious choice of PDT regimens that minimizes inflammatory responses through the use multiple fractionated long-term treatment protocols would likely be required.

Phobic anxiety changes the function of brain-gut axis in irritable bowel syndrome.

OBJECTIVE: Disease severity in the irritable bowel syndrome (IBS) is highly influenced by psychiatric comorbidity. The mechanism of this influence is generally unknown, even if the brain-gut axis seems to be involved. Recent research has indicated that IBS patients have aberrant perception of visceral stimuli in the CNS. We compared IBS patients with and without comorbid phobic anxiety to see if the comorbid disorder influenced brain information processing of auditory stimuli, and looked for possible consequences with respect to visceral sensitivity thresholds and disease severity. METHODS: Eleven female patients with IBS with comorbid phobic anxiety disorder were compared with 22 age-matched female IBS patients without such comorbidity. The groups were compared with respect to event-related potentials (ERP), auditory-presented words with emotional contents, barostat-assessed visceral sensitivity thresholds, and symptom levels the last week before assessment. RESULTS: The comorbid group had a significantly enhanced first negative ERP wave (N1) to all stimuli, indicating increased use of brain attentional resources. It also had increased visceral threshold for the sensation of gas, and reduced gas-stool and gas-discomfort tolerances compared with the noncomorbid group. Enhanced N1 amplitude at the frontal electrode and reduced gas-stools tolerance significantly predicted subjective gas complaints, explaining 47% of the symptom variation. CONCLUSIONS: The study suggests an association between information processing in the frontal brain and visceral sensitivity characteristics in IBS patients, and indicates that subjective disease-related symptomatology is predicted by brain perceptual characteristics. The findings indicate that an interaction between IBS-related and anxiety-related hyperreactivity in the frontal brain may constitute a psychophysiological mechanism for the contribution of psychiatric comorbidity to severity and duration of the irritable bowel syndrome.

Perceptual hyperreactivity to auditory stimuli in patients with irritable bowel syndrome.

BACKGROUND: Patients with irritable bowel syndrome (IBS) have abnormal perception of visceral stimuli; however, no study has so far investigated the perception of non-visceral stimuli in IBS. In the present study we used event-related potentials (ERP) to study whether IBS patients differed from healthy controls in processing of auditory stimuli and, if so, how this was influenced by emotions. METHODS: We compared ERPs to auditory stimuli in 40 female diarrhoea-predominant IBS patients without current psychiatric illness with those in 20 healthy controls. Tones were used as standard and target stimuli, and words with emotional content as distractors. Characteristics of the first negative wave (N100) and mean amplitudes in 50-msec time intervals between 150 and 600 msec were assessed. RESULTS: At the frontal midline electrode IBS patients had significantly enhanced N100 amplitude to all stimuli, persisting after adjustment for age, current emotions, and personality traits. They additionally had enhanced waves 200-300 msec and 400-500 msec after stimulus. The latter differences disappeared after adjustment for emotions and personality traits. CONCLUSIONS: In the frontal brain region, IBS patients seem to have a hyperreactivity to auditory stimuli compared with controls. Later elements (P300, N400) of stimulus processing were influenced by emotions and personality traits. These may possibly contribute to changes in intestinal motility caused by stress. The study indicates that aberrant brain functioning may be an element of the irritable bowel syndrome. It may elucidate a mechanism for brain-gut interaction by which psychosocial stress may influence visceral pain perception in non-psychiatric subjects with an intestinal motility disorder and also the efficacy of psychiatric treatment on IBS symptoms.

Rectal tone and brain information processing in irritable bowel syndrome.

We studied differences in rectal tone between healthy controls, nonpsychiatric irritable bowel syndrome (IBS) patients, and IBS patients with comorbid phobic anxiety disorders to assess the impact of psychiatric comorbidity on rectal tone. The groups were additionally compared with respect to brain information processing of everyday words with emotional content to see if we could identify an association between perception of emotional material in the brain and rectal tone. We found that both nonpsychiatric IBS patients and IBS patients with phobic anxiety disorder had increased baseline rectal tone compared with healthy controls (F = 9.81, P < 0.001). The phobic anxiety patients tended to have increased tone compared with nonpsychiatric IBS patients, but the difference did not reach statistical significance. Similar differences were found in the attentional elements of brain information processing activity assessed by event-related potentials. Rectal tone significantly predicted brain reactivity to emotional words, suggesting that changes in intestinal motor function may influence brain perception.

Intestinal reactivity to words with emotional content and brain information processing in irritable bowel syndrome.

The intestinal reactivity to emotional experiences is poorly understood. We therefore compared healthy controls with nonpsychiatric irritable bowel syndrome (IBS) patients and IBS patients with comorbid phobic anxiety disorders with respect to rectal wall reactivity during exposure to everyday words with emotional content. We found that 70.3% of the subjects responded either with increased or decreased rectal tone during exposure to anger words, 75.0% when exposed to sadness words, and 76.6% when exposed to anxiety words. We also investigated event-related potentials in the brain to the same stimuli. We observed significant group differences in the frontal brain to sadness (P < 0.001) and anxiety (P = 0.013) distracter words, and threshold significant group difference to anger (P = 0.053) distracter words. Rectal wall reactivity during the word series significantly predicted frontal amplitude to the same word series, indicating a close interaction among mind, brain, and gut.

Aplasia cutis congenita associated with limb, eye, and brain anomalies in sibs: a variant of the Adams-Oliver syndrome?

Aplasia cutis congenita (ACC) may occur in isolation or with other congenital malformations. Peripheral limb anomalies and ACC are major elements of the Adams-Oliver syndrome, which is usually inherited as an autosomal dominant disorder. We report on a sister and brother with ACC and brain, eyes, and transverse limb anomalies. The phalanges of the hands and feet were either short or absent. The girl also had absence of right patella, was severely mentally retarded and blind with retinal nonattachment. The boy had a falciform fold in the left eye. He died at age one week and autopsy showed partial agenesis of corpus callosum. The findings in the sibs may represent a severe variant of the Adams-Oliver syndrome, or a previously unrecognized syndrome involving vascular disruption.