A new therapy of post-trauma brain oedema based on haemodynamic principles for brain volume regulation

Objective

To evaluate a new therapy of posttraumatic brain oedema, with the main concept that opening of the blood-brain barrier upsets the normal brain volume regulation, inducing oedema formation. This means that transcapillary fluid fluxes will be controlled by hydrostatic capillary and colloid osmotic pressures, rather than by crystalloid osmotic pressure. If so, brain oedema therapy should include reduction of hydrostatic capillary pressure and preservation of normal colloid osmotic pressure.

Patients

11 severely head injured comatose patients with brain swelling, raised intracranial pressure (ICP), and impaired cerebrovascular response to hyperventilation.

Interventions

To reduce capillary hydrostatic pressure the patients were given hypotensive therapy (β₁-antagonist, metoprolol and α₂-agonist, clonidine) and a potential precapillary vasoconstrictor (dihydroergotamine). The latter may also decrease cerebral blood volume through venous capacitance constriction. Colloid osmotic pressure was maintained by albumin infusions. The concept implies the need of a negative fluid balance with preserved normovolaemia.

Results

ICP decreased significantly within a few hours of treatment with unaltered perfusion pressure in spite of lowered blood pressure. Of 11 patients 9 survived with good recovery/moderate disability, 2 died. This was compared to outcome in a historical control group with identical entry criteria, given conventional brain oedema therapy, where mortality/vegetativity/severe disability was 100%.

Conclusion

The results indicate that the therapy should focus on extracellular rather than intracellular oedema and that ischemia is not the main triggering mechanism behind oedema formation. We suggest that our therapy is superior to conventional therapy by preventing herniation during the healing period of the blood-brain barrier.     

Glomerular sieving of three neutral polysaccharides, polyethylene oxide and bikunin in rat. Effects of molecular size and conformation

AIM: Polysaccharides and many other non-protein polymers generally have a more open, flexible and asymmetrical structure compared with globular proteins. For a given molecular weight (MW), the Stokes-Einstein radius (a(e)) of the following polymers increases in the order: Ficoll < dextran 相似文献   

On the role of monocytes/macrophages in the pathogenesis of central nervous system lesions in hereditary cystatin C amyloid angiopathy.

The pathogenesis of the deposition of a variant cystatin C as amyloid in hereditary cystatin C amyloid angiopathy (HCCAA) is not known. To address this question the synthesis and secretion of cystatin C in cultured monocytes from 9 carriers of the mutated cystatin C gene (5 symptomatic and 4 asymptomatic) was examined. The quantity of cystatin C in cells and supernatants was determined by the ELISA method, Western blots were done and selected samples immunostained for cystatin C. Monocytes from individuals carrying the gene defect synthesized cystatin C that was apparently not truncated, a form found in the cerebral amyloid deposits in HCCAA, but showed a distinctly lower rate of cystatin C synthesis than monocytes from healthy controls. The main difference was that the quantity of cystatin C was significantly lower in the supernatants in monocyte cultures from carriers of the gene defect than from healthy controls, possibly due to a partial block in its secretion. This abnormal processing of the cystatin C could explain the low cerebrospinal fluid levels of cystatin C in HCCAA and might be a part of the pathogenetic pathway of amyloid deposition. Furthermore it could, through a lower extracellular concentration of this inhibitor of cysteine proteinases, contribute to destruction of the amyloidotic blood vessels, leading to the most serious clinical manifestation in HCCAA, intracerebral hemorrhage.     

High-definition colonoscopy increases adenoma detection rate

Background

The adenoma detection rate (ADR) is a quality indicator for colonoscopy. High-definition (HD) imaging has been reported to increase polyp detection rates.

Objective

The primary objective of this study was to compare polyp detection rate (PDR) and adenoma detection rate (ADR) before and after the implementation of HD colonoscopy.

Methods

A retrospective chart review was performed on patients aged 48–55 years old, who underwent first-time screening colonoscopy. The first group underwent standard-definition (SD) colonoscopy in the first 6 months of 2011. The second group underwent screening with HD colonoscopy during the first 6 months of 2012. We compared age, gender, PDR, ADR, and average sizes of adenomatous polyps between gastroenterologist and colorectal surgeon and among physicians themselves. Statistical analysis was performed with Fischer’s exact test and Pearson Chi-square.

Results

A total of 1268 patients were involved in the study (634 in each group). PDR (35.6 vs. 48.2 %, p < 0.001) and ADR (22.2 vs. 30.4 %, p = 0.02) were higher in the HD group. The average size of an adenomatous polyp was the same in the two groups (0.58 vs. 0.57, p = 0.69). However, this difference was not seen among colorectal surgeons PDR (35.7 vs. 37 %, p = 0.789), ADR (22.9 vs. 24.5 % p = 0.513), but clearly seen among gastroenterologist, PDR (35.6 vs. 53.1 % p < 0.001) and ADR (21.9 vs. 32.9 % p < 0.001). When polyps were categorized into size groups, there was no difference in ADR between the two timeframes (<5 mm in size (41.5 vs. 35.4 %), 5–10 mm (49.3 vs. 60.1 %) and >10 mm (9.2 vs. 4.5 %), p = 0.07). Polyps were most commonly seen in the sigmoid colon (26.1 vs. 24.7 %). There was no difference in the rate of synchronous polyp detection between modalities (25.6 vs. 29 %, p = 0.51). Withdrawal time was the same in both procedure (9.2 vs. 8.5 min, p = 0.10).

Conclusion

Screening colonoscopy with high-definition technology significantly improved both PDR and ADR. In addition, high-definition colonoscopy may be particularly useful and advantageous among less experienced endoscopists in various community settings. However, there needs to be application to specific patient populations in future studies to assess for any statistical differences between standard- and high-definition modalities to determine clinical utility.

     

Pregnancy-associated breast cancer

Currently, it is estimated that approximately one in every 3,000 births are from women who have or are being treated for breast cancer. Although rare, the incidence of pregnancy-associated breast cancer (PABC) is increasing as women are delaying childbirth. Diagnostic and treatment recommendations have been mainly based on evidence from retrospective single institutional and collective series and expert consensus, as randomized trials on this entity are understandably lacking. PABC is often associated with a poor outcome, but this is mainly due to delay in diagnosis and initiation of treatment. For the most part, women with PABC should be managed like non-pregnant breast cancer patients and should expect a similar outcome, without causing harm to the unborn child. Increased awareness and knowledge of how to assess symptomatic breast problems in pregnancy and a specialized multidisciplinary team approach for established PABC is likely to improve outcomes. This review analyses the evidence on the diagnosis, treatment and prognosis of patients with PABC.     

Similarity of permeabilities for Ficoll,pullulan, charge‐modified albumin and native albumin across the rat peritoneal membrane

Aim: Compared to neutral globular proteins, neutral polysaccharides, such as dextran, pullulan and Ficoll, appear hyperpermeable across the glomerular filtration barrier. This has been attributed to an increased flexibility and/or asymmetry of polysaccharides. The present study investigates whether polysaccharides are hyperpermeable also across the continuous capillaries in the rat peritoneum. Methods: In anaesthetized Wistar rats, FITC–Ficoll or FITC–pullulan together with ¹²⁵I‐human serum albumin (RISA) or neutralized ¹²⁵I‐bovine serum albumin (nBSA) were given intravenously, after which peritoneal dialysis (PD) using conventional PD fluid (Gambrosol 1.5%) was performed for 120 min. Concentrations of FITC‐polysaccharides and radioactive albumin species in plasma and dialysis fluid were analysed with high‐performance size exclusion chromatography and a gamma counter respectively. Transperitoneal clearance values were calculated for polysaccharides in the molecular radius range 36–150 Å, and for RISA and nBSA. Results: Ficoll and pullulan showed more or less identical permeabilities, compared to RISA and nBSA, across the peritoneal membrane. Although RISA‐clearance, 5.50 ± 0.28 (μL min^?1; ±SEM), tended to be lower than the clearances of Ficoll_36Å (6.55 ± 0.25), pullulan_36Å (6.08 ± 0.22) and nBSA (6.56 ± 0.23), the difference was not statistically significant. This is in contrast to the hyperpermeability exhibited by polysaccharides across the glomerular filtration barrier and also contrasts with the charge selectivity of the latter. Conclusion: The phenomenon of molecular flexibility is more important for a macromolecule’s permeability through the glomerular filter than across the continuous peritoneal capillary endothelium. Furthermore, it seems that charge plays a subordinate role in the steady‐state transport across the combined peritoneal capillary–interstitial barrier.     

Invasive Procedures Associated With the Development of Infective Endocarditis

Background

Various invasive medical procedures might induce bacteremia and, hence, act as triggers for infective endocarditis. However, empirical data in humans on the potential dangers of invasive medical procedures in this regard are very sparse. Due to lack of sufficient data, it is currently debated whether the risk for endocarditis with medical procedures is substantial or rather negligible.