Cytocompatibility and hemocompatibility of a novel chitosan-alginate gel system

Two chitosan-alginate gel systems in the form of membranes were produced and evaluated. The first membrane was produced by a novel gel system formed after blending N-(methylsulfonic acid) chitosan with ammonium alginate (CAG1) and the second was an N-(methylsulfonic acid) chitosan-sodium alginate blend cross-linked with glutaraldehyde and calcium chloride (CAG2). The cytocompatibility and hemocompatibility of the gels were examined by assessing the cell viability of 3T3 Swiss mouse fibroblasts, whole blood hemolysis, and platelet activation. Cell viability was not significantly different by exposure to these gels compared to the controls. Both gel types had minimal effect on hemolysis of whole heparinized rabbit blood after 1-h exposure. Further platelet activation by the surfaces was also minimal. These results indicate that these novel gels merit further investigation for blood contact applications.     

The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal

Much research has focused on pathways leading to opiate addiction. Pathways opposing addiction are more difficult to study but may be critical in developing interventions to combat drug dependence and withdrawal. Galanin decreases firing of locus coeruleus neurons, an effect hypothesized to decrease signs of opiate withdrawal. The current study addresses whether galanin affects morphine withdrawal signs by using a galanin agonist, galnon, that crosses the blood-brain barrier, and mice genetically engineered to under- or overexpress galanin peptide. Galnon significantly decreased morphine withdrawal signs in C57BL/6 mice. Further, knockout mice lacking galanin showed exacerbated morphine withdrawal signs, suggesting that endogenous galanin normally counteracts opiate withdrawal. Transgenic mice overexpressing galanin in noradrenergic neurons also showed decreased morphine withdrawal signs, suggesting a possible neuroanatomical locus for these effects of galanin. Both c-fos immunoreactivity, a marker of neuronal activity, and phosphorylation of tyrosine hydroxylase at Ser-40, a marker of cAMP levels, are decreased in the locus coeruleus by galnon treatment after morphine withdrawal, suggesting a possible molecular mechanism for the behavioral effects of galanin. These studies suggest that galanin normally acts to counteract opiate withdrawal and that small molecule galanin agonists could be effective in diminishing the physical signs of withdrawal.     

Intestinal failure-associated liver disease in surgical infants requiring long-term parenteral nutrition

PurposeOur aim was to determine incidence, severity, and outcome, as well as predisposing factors and underlying diagnoses, of intestinal failure-associated liver disease (IFALD) in surgical infants requiring long-term parenteral nutrition (PN).MethodsWe retrospectively studied surgical infants receiving PN for at least 28 days for congenital or acquired intestinal anomalies over a 5-year period (January 2006 to December 2010). Intestinal failure-associated liver disease was defined as type 1 (early)—persistent elevation of alkaline phosphatase for 6 weeks or longer; type 2 (established)—additional elevated total bilirubin (≥50 μmol/L); and type 3 (late)—additional clinical signs of end-stage liver disease.ResultsEighty-seven infants required PN for at least 28 days. Intestinal failure-associated liver disease occurred in 29 infants (33%). Intestinal failure-associated liver disease was managed medically in all but 2 patients who underwent intestinal elongation. None were referred for intestinal or liver transplant. Intestinal failure-associated liver disease has been reversed in 17 (59%) of cases to date. Sixty-one children receiving long-term PN (70%) have achieved enteral autonomy, whereas 12 (14%) require home PN. Severity of IFALD was significantly associated with duration of PN and female sex.ConclusionIntestinal failure-associated liver disease remains a fairly common but rarely life-threatening complication of intestinal failure in surgical infants. Intestinal failure-associated liver disease can be reversed in more than half of these children, and enteral autonomy was achieved in more than two thirds, even with minimal use of intestinal elongation. This is the first study to demonstrate an association between the severity of IFALD in surgical infants and female sex.     

Impact of Routine Cavity Shave Margins on Breast Cancer Re-excision Rates

Purpose

Breast-conserving therapy (BCT) is an accepted method of treating early breast cancer. We hypothesized that routine excision of additional cavity shave margins (CSM) at time of initial partial mastectomy reduces the need for additional surgery.

Methods

A single-institution retrospective review was performed of women, 18 years or older, with a new diagnosis of breast cancer who underwent partial mastectomy between 1 January 2004 and 1 October 2009. Five hundred thirty-three charts were reviewed. Of those, 69 patients underwent CSM at time of initial operation. These 69 patients were matched with patients who had undergone partial mastectomy without CSM by tumor size, presence of extensive intraductal component, and primary histology.

Results

The two groups were well matched for age, nuclear grade, associated lymphovascular invasion (LVI), receptor status, and multifocality. We found that 31.9% (44/138) required return to the operating room (OR) for re-excision of margins. Rate of return to the OR was 21.7% (15/69) in the CSM group and 42.0% (29/69) in the matched group (p = 0.011). Multivariate analysis found factors significantly associated with need for additional operation included lack of CSM (odds ratio 9.2, 95% CI 2.8–30.5, p = 0.0003), larger extent of intraductal component (odds ratio 7.0, 95% CI 1.8–27.0, p = 0.005), and lack of directed re-excision (odds ratio 6.4, 95% CI 1.7–25.1, p = 0.007).

Conclusions

CSM at time of initial partial mastectomy decreases rate of re-excision by as much as ninefold. CSM should be considered at time of initial operation to reduce the need for subsequent reoperation.     

Impact of radiotherapy for localized prostate cancer on bladder function as demonstrated on urodynamics study: A systematic review

IntroductionThis study aimed to describe the effects of bladder function following radiotherapy for localized prostate cancer by performing a systematic review on studies reporting on urodynamic findings after radiotherapy.MethodsThis systematic review was conducted in accordance with PRISMA guidelines. The review protocol was registered at PROSPERO (CRD42021229037). A systematic search was conducted using PubMed, Cochrane Library, Scopus, and OVID Embase. Studies were included if they involved men who underwent urodynamic studies following radiotherapy for localized prostate cancer. A total of 798 articles were screened and five articles included. A qualitative analysis was performed.ResultsBladder compliance appears to be impaired following radiotherapy, especially with longer followup. Impaired bladder compliance was reported in 18.8–62.5% of patients following radiotherapy. Bladder capacity was found to be statistically significantly lower following radiotherapy compared to pre-radiotherapy, and when compared with patients who did not undergo pelvic radiotherapy. Bladder outlet obstruction (BOO) persists post-radiotherapy in most patients at three and 18 months post-radiotherapy. De novo detrusor overactivity (DO) of 13.3% has been reported at 18 months post-radiotherapy. This review is limited by the absence of level I/II studies.ConclusionsRadiotherapy for localized prostate cancer results in decreased bladder compliance and capacity demonstrated on urodynamic studies. Resolution of BOO appears less likely in comparison to series on radical prostatectomy. De novo DO may develop following radiotherapy, especially with longer followup. With only low level of evidence studies available at present, further high-quality, prospective studies are important to elucidate the impact of radiotherapy on bladder and urethral function.     

Primary mucinous adenocarcinoma of the thymus: a case report and review of the literature

Primary thymic mucinous adenocarcinoma is extremely rare; to our knowledge, only 2 cases have been reported to date. We describe a third case of primary mucinous adenocarcinoma of the thymus in a 41-year-old man who presented with an anterior mediastinal mass with subsequent metastasis to the lung. The initial diagnosis was of metastatic mucinous adenocarcinoma, but extensive clinical workup of the patient failed to reveal a primary tumor elsewhere in the body. The specific identification of mucinous adenocarcinoma as a primary thymic neoplasm can be difficult or impossible. Morphologic and immunophenotypic similarities to mucinous adenocarcinomas of the gastrointestinal tract can pose diagnostic challenges for surgical pathologists, especially in small biopsy specimens.     

Kappa-opioid receptor modulation of the release of substance P in the dorsal horn

Substance P (SP), a member of the tachykinin peptide family, has been found in high concentrations in the superficial laminae of the dorsal horn and it is thought to play a major role in the transmission of nociceptive information. Dynorphin(1–8), an opioid peptide with high selectivity for the κ-opioid receptor subtype, is also found in the dorsal horn of the spinal cord. The aim of this study was to determine the effect of dynorphin(1–8) on the release of SP-like-immunoreactivity (SPLI) in the dorsal horn before and during the activation of peripheral nociceptors by a thermal stimulus. A push-pull canula was used to perfuse the dorsal horn of non-anesthetized decerebrate/spinal transected rats and the collected perfusates were assayed for SPLI by using radioimmunoassay. Dynorphin(1–8) applied to the spinal cord at a concentration of 1 μM elicited a 27 ± 8% decrease in the basal release of SPLI and prevented the increase in the release of SPLI evoked by the application of a noxious thermal stimulus to the ipsilateral hind paw and lower limb. The effect of dynorphin(1–8) was reversed by 2 μM of nor-binaltorphimine (nor-BNI), a selective kappa opioid receptor antagonist. Application of nor-BNI alone to the perfusate resulted in a 62 ± 23% increase in the basal release of SPLI. In conclusion, dynorphin(1–8) reduces the basal release of SPLI and prevents the increase in the release of SPLI elicited by the application of a noxious cutaneous thermal stimulus. This effect is mediated through the κ-opioid receptor, which appears to tonically regulate the release of SPLI in the dorsal horn.