Treatment of intracerebral arteriovenous malformations with isobutyl 2- cyanoacrylate: initial clinical experience

From November 1976 to September 1979, 46 patients with intracranial arteriovenous malformations or fistulas participated in a clinical study using isobutyl 2-cyanoacrylate (IBCA), with tantalum, for palliative or preoperative occlusion of the blood supply to the abnormalities. Although failure to obtain satisfactory position of a functioning microcatheter precluded deposition of IBCA 10 times, a total of 51 of a possible 62 feeding vessels were occluded with the tantalum-impregnated glue. The technique, results, and complications are discussed in light of the clinical follow-up, which varied from 12 to 48 months.     

Surface response modeling to examine the combination of amphotericin B deoxycholate and 5-fluorocytosine for treatment of invasive candidiasis

The strategy of combining antifungal drugs in a treatment regimen may improve the outcome of invasive candidiasis. Using a well-validated pharmacodynamic murine model of invasive candidiasis, we defined the effect of the combination of amphotericin B deoxycholate (AmB) and 5-fluorocytosine (5FC) by use of the Greco model of drug interaction. The combination was additive, meaning that the experimental effect did not deviate in a statistically significant manner from the null reference model (or additive surface) of the combined effect. From a clinical perspective, the addition of 5FC to a regimen of AmB may enable the near-maximum effect to be reached in circumstances in which the administration of a given dose of AmB alone produces a submaximum effect but an increase in the dose is not possible, because of dose-related toxicity. Our methods provide a way in which some of the complex issues surrounding antifungal combination treatment can be addressed.     

Pharmacological characterization of LPS and opioid interactions at the toll-like receptor 4

Background and Purpose

Previous work in our laboratory showed opioid agents inhibit cytokine expression in astrocytes. Recently, Watkins and colleagues hypothesized that opioid agonists activate toll-like receptor 4 (TLR4) signalling, which leads to neuroinflammation. To test this hypothesis, we characterized LPS and opioid effects on TLR4 signalling in reporter cells.

Experimental Approach

NF-κB reporter cells expressing high levels of TLR4 were used to compare LPS and opioid effects on NF-κB activation, a pathway activated by TLR4 stimulation.

Key Results

LPS increased TLR4 signalling in a concentration-dependent manner and was antagonized by LPS antagonist (LPS-RS, from Rhodobacter sphaeroides). A concentration ratio analysis showed that LPS-RS was a competitive antagonist. The opioid agonists, morphine and fentanyl, produced minor activation of TLR4 signalling when given alone. When tested following LPS stimulation, opioid agonists inhibited NF-κB activation but this inhibition was not blocked by the general opioid antagonist, naloxone, nor by the selective μ opioid receptor antagonist, β-FNA. Indeed, both naloxone and β-FNA also inhibited NF-κB activation in reporter cells. Further examination of fentanyl and β-FNA effects revealed that both opioid agents inhibited LPS signalling in a non-competitive fashion.

Conclusions and Implications

These results show that LPS-RS is a competitive antagonist at the TLR4 complex, and that both opioid agonists and antagonists inhibit LPS signalling in a non-competitive fashion through a non-GPCR, opioid site(s) in the TLR4 signalling pathway. If confirmed, existing opioid agents or other drug molecules more selective at this novel site may provide a new therapeutic approach to the treatment of neuroinflammation.     

Secrets,shame and guilt: HIV disclosure in rural Chinese families from the perspective of caregivers

This in-depth ethnographic study examines the processes, barriers and impacts experienced by Mainland Chinese caregivers residing in rural Yunnan for disclosing HIV status to their adolescents born with the infection and other community members. In particular, highlighted are their associated personal, social, relational and cultural vulnerabilities. A purposeful sample of 13 pairs of HIV-born adolescents between the ages of 11–19 years and their primary caregivers were recruited in December 2014. The Conceptual Model Sexual Health Disclosure (CMSHD) was modified with Chinese culturally specific adaptation to guide the exploration of the complex aspects of the adolescents and caregiver’s relationships. All interviews were audiotaped, transcribed verbatim and then translated into English.

Complex sociocultural interactions emerging in these dyadic interviews included guilt, shame, unintended disclosure, the need for secrecy, perceived stigma, ‘loss of face’, protection of parents, inability to support their families and deep concerns over lineage and future marriage prospects amongst the parents, which had significant psychosocial and even physical impacts for these adolescents born with HIV and their families. Frontline health-care workers and HIV peer support programs are recommended to counteract China’s current top-down biomedical disease-related approach to health services. It is crucial to provide instrumental avenues of confidential psychosocial support including disclosure approaches for caregivers of HIV positive adolescents within a uniquely Chinese cultural context.     

Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract

Esophageal atresia(EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia(72%) and gastroesophageal reflux(GER)(67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.     

Effects of Erxian decoction, a Chinese medicinal formulation, on serum lipid profile in a rat model of menopause

Background

Infantile colic is a common painful clinical condition associated with signs of distended intestines and an increase in colon peristalsis. However, clinical documentation of observed gastrointestinal functions in the condition is still lacking. Even though the ailment is common, no clear treatment guidelines exist. While acupuncture with minimal stimulation has been shown to be effective in reducing crying behaviour of infants suffering from colic, the documented effect of acupuncture on gastrointestinal function in children with infantile colic is scarce. This case series study aims to document the symptoms of routinely rated gastrointestinal function and the changes in these symptoms after minimal acupuncture in a larger group of children with infantile colic.

Methods

This study included 913 infants with normal weights, and lengths at birth. The infants' mean age was 5.4 weeks when the observations started, and had colic symptoms since two weeks after birth. Light needling stimulation of the acupuncture point LI4 was performed for 10-20 seconds bilaterally on a daily basis for a mean of 6.2 consecutive days. A questionnaire with verbal rating scales for the parents' evaluation was used before and after the treatment period.

Results

Before treatment the infants were assessed by the parents in terms of 'often have inflated stomachs' (99%) and 'seldom drool' (76%), 'regurgitate' (53%) and 'belch' (62%). Moreover, the reported frequency of defecation was 5-8 times per day (64%), with a yellowish-green colour (61%) and with a water-thin consistency (74%). After treatment, the variables of inflated stomachs, drooling and regurgitating were systematically changed, and rated by the parents as occurring 'sometimes' while belching was rated as occurring 'often' and the frequency of defecation was reduced to 1-4 times/day with a mustard yellow colour and a gruel-like consistency. The parents also rated their impression of the infants' general colic symptoms including crying behaviour as much ameliorated in 76% of the cases.

Conclusion

The results of the present study show that minimal acupuncture at LI4 in infantile colic is an effective and easy treatment procedure that, furthermore, is reported to be without serious side effects.