On the design and efficacy assessment of self-assembling peptide-based hydrogel-glycosaminoglycan mixtures for potential repair of early stage cartilage degeneration.

Peptide-based hydrogels are of interest for their potential use in regenerative medicine. Combining these hydrogels with materials that may enhance their physical and biological properties, such as glycosaminoglycans, has the potential to extend their range of biomedical applications, for example in the repair of early cartilage degeneration. The aim of this study was to combine three self-assembling peptides (P11 -4, P11 -8, and P11 -12) with chondroitin sulphate at two molar ratios of 1:16 and 1:64 in 130 and 230 mM Na+ salt concentrations. The study investigates the effects of mixing self-assembling peptide and glycosaminoglycan on the physical and mechanical properties at 37°C. Peptide alone, chondroitin sulphate alone, and peptide in combination with chondroitin sulphate were analysed using Fourier transform infrared spectroscopy to determine the ß-sheet percentage, transmission electron microscopy to determine the fibril morphology, and rheology to determine the elastic and viscous modulus of the materials. All of the variables (peptide, salt concentration, and chondroitin sulphate molar ratio) had an effect on the mechanical properties, ß-sheet formation, and fibril morphology of the hydrogels. P11 -4 and P11 -8-chondroitin sulphate mixtures, at both molar ratios, were shown to have a high ß-sheet percentage, dense entangled fibrillar networks, as well as high mechanical stiffness in both (130 and 230 mM) Na+ salt solutions when compared with the P11 -12/chondroitin sulphate mixtures. These peptide/chondroitin sulphate hydrogels show promise for biomedical applications in glycosaminoglycan depleted tissues.

Treatment of early caries lesions using biomimetic self-assembling peptides--a clinical safety trial.

OBJECTIVE: We previously reported that a rationally designed biomimetic self-assembling peptide, P11-4, nucleated hydroxyapatite de novo and was apparently capable of in situ enamel regeneration following infiltration into caries-like lesions. Our present aim was to determine the safety and potential clinical efficacy of a single application of P11-4 on early enamel lesions. MATERIALS AND METHODS: Fifteen healthy adults with Class V 'white spot' lesions received a single application of P11-4. Adverse events and lesion appearances were recorded over 180 days. RESULTS: Patients treated with P11-4 experienced a total of 11 adverse events during the study, of which two were possibly related to the protocol. Efficacy evaluation suggested that treatment with P11-4 significantly decreased lesion size (p = 0.02) after 30 days and shifted the apparent progression of the lesions from 'arrested/progressing' to 'remineralising' (p <0.001). A highly significant improvement in the global impression of change was recorded at day 30 compared with baseline (p <0.001). CONCLUSIONS: The results suggest that treatment of early caries lesions with P11-4 is safe, and that a single application is associated with significant enamel regeneration, presumably by promoting mineral deposition within the subsurface tissue.

Peptide synthesis and self-assembly.

Peptides and proteins are the most diverse building blocks in biomolecular self-assembly in terms of chemistry, nanostructure formation and functionality. Self-assembly is an intrinsic property of peptides. In this chapter, we attempt to address the following issues: How can we synthesize a self-assembling peptide? What are the fundamental physical and chemical principles that underpin peptide self-assembly? How can we learn to finely control peptide self-assembly? The merits of answering these questions are inspiring both for biology and medicine in terms of new opportunities for understanding, preventing and curing of diseases, and for nanotechnology in terms of new prescribed routes to achieving peptide-based nanostructures with a range of properties appropriate for specific applications.

Tetravalent silicon connectors MenSi(p-C6H4CO2H)(4-n) (n = 0, 1, 2) for the construction of metal-organic frameworks.

A series of silicon-centered connecting units, Me(n)Si(p-C6H4CO2H)(4-n) (n = 0, 1, 2), have been prepared and their coordination polymers with Zn(II) metal atoms studied. The tetra-acid L1 (n = 0) acts as a tetrahedral node and reacts with Zn(II) centers to give 1, a novel interpenetrating 3D network containing distorted tetrahedral bimetallic secondary building units (SBUs). The triacid L2 (n = 1) acts as a trigonal pyramidal node and forms an intercalated 2D layered network, 2, with Zn(II) ions, containing distorted octahedral tetranuclear SBUs. Last, the bent diacid L3 (n = 2) reacts with Zn(II) centers to give 3, a corrugated 2D layered structure containing 1D zinc hydroxo chains. Together these three new coordination polymers demonstrate the potential versatility of tetravalent silicon containing connecting ligands for metal-organic framework construction.

Use of routine computed tomography brain scanning of psychiatry patients.

The aim of this study was to evaluate the usefulness of CT of the brain in patients presenting with a psychiatric condition without focal neurological signs. The reports of 397 consecutive CT brain scans of patients presenting to two acute tertiary hospital psychiatric services over a 2-year period were assessed retrospectively. Of the 397 patients, 241 had psychosis, 87 had depression, 44 had bipolar affective disorder, seven had alcohol dependence, five had dementia, and the remaining 13 had a variety of diagnoses including personality disorder and transient ischaemic attack. Findings on 377 (95%) of the CT scans showed no abnormality. Specific abnormalities were described in 20 (5%) of the CT scans. Three scans showed non-specific minor abnormalities, which, when followed up by MRI, showed no relevant abnormality. All the abnormalities shown on CT were considered to be clinically unrelated to the patient's psychiatric condition. In conclusion, the pretest probability of finding a space-occupying lesion or other pertinent abnormality in patients presenting with psychiatric illnesses in this retrospective study appears not to be greater than that of the general population. The outcome of this study could be implemented to develop a clinical pathway for limiting assessment by CT for possible organic pathology in acute psychiatric illness.

Gadolinium-enhanced computed tomographic aortography.

Radiographic contrast agents using gadolinium have a better safety profile and photoelectric effect than iodinated contrast, allowing use where iodinated contrast is contraindicated. A case of gadolinium-enhanced computed tomographic aortography (CTA) for suspected thoracic dissection is reported. Aortic enhancement was sufficient for confident exclusion of an intimal flap. The findings were later confirmed by MRI. Vascular enhancement diminished below the diaphragm and tissue enhancement was minimal. Gadolinium diethylenetriamine penta-acetic acid (Gd-DTPA) may be used for CTA of the thoracic aorta, where the use of iodinated contrast is contraindicated. Multi-slice CT may expand the role of gadolinium enhancement in the future.

Oxygen capture by lithiated organozinc reagents containing aromatic 2-pyridylamide ligands.

The sequential reaction of ZnMe2 with a 2-pyridylamine (HN(2-C5H4N)R, R = Ph: 1; 3,5-Xy (=3,5-xylyl): 2; 2,6-Xy: 3; Bz (=benzyl): 4; Me: 5), tBuLi and thereafter with oxygen affords various lithium zincate species, the solid-state structures of which reveal a diversity of oxo-capture modes. Amine 1 reacts to give both dimeric THF [Li(Me)OZn[N(2-C5H4N)Ph]2] (6), wherein oxygen has inserted into the Zn-C bond of a [MeZn[N(2-C5H4N)-Ph]2] ion, and the trigonal Li2Zn complex, bis(OtBu)-capped (THF x Li)2-[[(mu3-O)tBu]2Zn[N(2-C5H4N)Ph]2] (7). The structural analogue of 6 (8) results from the employment of 2, while the use of more sterically congested 3 yields a pseudo-cubane dimer [(THF x [Li(tBu)OZn(OtBu)Me]]2] (9) notable for the retention of labile Zn-C(Me). Amines 4 and 5 afford the oxo-encapsulation products [mu4-O)Zn4[(2-C5H4N)-NBz]6] (10b), and [tBu(mu3-O)-Li3(mu6-O)Zn3[(2-C5H4N)NMe]6] (11), respectively, with concomitant oxo-insertion into a Li-C interaction resulting in capping of the fac-isomeric (mu6-O)M3M'3 distorted octahedral core of the latter complex by a tert-butoxide group.

Percutaneous ultrasound-guided thrombin injection for coagulation of post-traumatic pseudoaneurysms.

Most peripheral pseudoaneurysms are iatrogenic or, less commonly, post-traumatic. Pseudoaneurysms are associated with characteristic findings of a pulsatile palpable mass and an audible to and fro murmur. The diagnosis can be easily confirmed using colour duplex ultrasound. A successful treatment for the coagulation of pseudoaneurysms as an alternative to ultrasound-guided manual compression is described. The method involves ultrasound-guided direct percutaneous injection of a small quantity of thrombin through a fine needle. This technique is simple and effective, resulting in rapid occlusion of the pseudoaneurysm. Two cases are reported.

Treatment of post-stent gastroesophageal reflux by anti-reflux Z-stent.

Severe symptoms of heartburn and retrosternal pain consistent with gastro-esophageal reflux (GER) developed in a patient following placement of a conventional self-expanding 16-24-mm-diameter x 12-cm-long esophageal stent across the gastroesophageal junction to treat an obstructing esophageal carcinoma. A second 18-mm-diameter x 10-cm-long esophageal stent with anti-reflux valve was deployed coaxially and reduced symptomatic GER immediately. Improvement was sustained at 4-month follow-up. An anti-reflux stent can be successfully used to treat significant symptomatic GER after conventional stenting.

Historical declines in tuberculosis in England and Wales: improving social conditions or natural selection?

OBJECTIVES: A reinvestigation of the relationship between the decline of tuberculosis and improvement in social conditions in England and Wales during Victorian times. DESIGN: A retrospective study using data published in the annual reports of the Registrar General from 1853 to 1910. MEASURES ASSESSED: The diseases studied, in addition to tuberculosis were dysentery and cholera, including their total and infant mortality. Social conditions were evaluated from earnings and population density per house. RESULTS: Tuberculosis mortality declined at an annual average rate of 1.71% (95% confidence interval [Cl] 0.77-2.63), whereas total mortality, infant mortality and mortality from cholera and dysentery and house population density showed no statistically significant decline over the same period. Real earnings increased by 1.05% (95% CI 0.29-1.81). CONCLUSION: Improving social conditions do not provide the total explanation for the decline in tuberculosis during Victorian times. Other factors, principally natural selection, probably played a role. Part of the current increase in tuberculosis may be caused by effective drug therapy eliminating natural selection.

Percutaneous retrieval of a right atrioventricular embolus.

Percutaneous retrieval of a 12-cm-long serpiginous clot lodged in the right atrium and ventricle is reported. Following bilateral common femoral vein puncture, a Bird's Nest cava filter was first positioned ready to deploy immediately below the renal veins via the right femoral vein. From the left femoral vein, a Cook intravascular retrieval basket was advanced to the right atrium. Under transthoracic echocardiographic visualization, the basket was used to engage, trap, and gently withdraw the clot in a single long strand below the prepositioned inferior vena cava filter. The filter was immediately deployed, leaving the clot trapped inferior to the renal veins, in the cava and left iliac vein. The patient remained well and asymptomatic at discharge.

Interventional sialography: a single-center experience.

PURPOSE: To evaluate interventional sialography for the treatment of chronic recurrent sialadenitis due to calculus and/or stricture. METHODS: We performed a retrospective review and follow-up of 12 patients treated over a 3-year period. The techniques for calculus extraction by papillotomy and basket extraction, and stricture dilatation by a combination of predilation with lacrimal dilators and then angioplasty balloons are described and the literature is reviewed. RESULTS: Follow-up of 1-40 months (mean 14.6 months) showed that 7 of 12 patients remained symptom free and 2 others became asymptomatic after an interval. There were no major complications from the procedure. CONCLUSION: Interventional sialography is a safe and acceptable alternative to surgery and can be considered as first-line therapy for symptomatic salivary duct calculus and stricture.

Tandem balloon dilatation for childhood achalasia.

BACKGROUND: There are no previous reports of tandem balloon dilatation in childhood achalasia. OBJECTIVE: To report the treatment of four cases of paediatric achalasia using tandem balloon dilatation of the lower oesophageal sphincter. A review of the literature since 1986 was undertaken to compare outcomes of balloon dilatation and surgery. MATERIALS AND METHODS: A retrospective review of the patients diagnosed with this condition and treated at our institution over the past 6 years: all four patients were treated by balloon dilatation of the lower oesophageal sphincter using two or three balloons in tandem. The definition of technical success was demonstration of a waist at 1-1.5 atmospheres of inflation pressure followed by abolition of the waist at higher pressures. Where this was unable to be achieved using a single balloon, two or three balloons in tandem were used. RESULTS: No patient required oesophagomyotomy, and symptomatic control has been good to excellent in three of four patients. No significant side effects were encountered. CONCLUSIONS: Balloon dilatation and surgery have similar success rates in paediatric achalasia. Because of the low morbidity associated with balloon dilatation, the procedure should be considered as first line treatment of this condition. If the lower oesophageal sphincter is stretched insufficiently using a single balloon, tandem balloon dilatation should be utilised.

Small gauge gelfoam plug liver biopsy in high risk patients: safety and diagnostic value.

The performance of a percutaneous core biopsy of the liver may be contraindicated in patients at higher risk of haemorrhage. In this clinical setting, gelfoam plug embolization of the needle track has been proposed to minimize haemorrhagic complications of biopsy. In the present study, gelfoam plug liver biopsy was performed in 51 consecutive patients at increased risk of haemorrhage. An 18 gauge spring-loaded disposable cutting needle was used through a 4 French sheath. The biopsy track was embolized by three to four gelfoam pledgets. In every patients, the cores of hepatic tissue were adequate for histopathological diagnosis. There were no fatalities and no serious complications. Gelfoam plug liver biopsy using this needle and sheath in combination appears to be a safe procedure and produces diagnostic cores for histological analysis. This method represents an alternative to transjugular liver biopsy and is technically more straight-forward to perform.

Three year follow-up of a case of giant cell arteritis presenting with a chronic cough and upper limb ischaemic symptoms.

A case of giant cell arteritis presenting in an atypical fashion with respiratory and upper limb ischaemic symptoms is described. The subclavian and axillary arterial involvement is demonstrated in this case, and followed up with repeated angiographic examinations over the next 3 yr. Despite resolution of all symptoms and return of pulses and a recordable blood pressure in the ischaemic upper limb, there was no angiographic evidence of resolution of the axillary artery stenoses.

Percutaneous cystogastrostomy with a new catheter for drainage of pancreatic pseudocysts and fluid collections.

We describe a new catheter for the initial percutaneous drainage of large symptomatic pancreatic fluid collections and abscesses using a transgastric approach to allow fluid drainage into the gastric lumen. A double-mushroom stent is placed secondarily for long-term internal drainage to the stomach, avoiding the need for an extended period of external catheter drainage. This technique, termed percutaneous cystogastrostomy (PCG), has been used in 19 consecutive patients with one recurrent symptomatic pseudocyst in the follow-up period fo 9-43 months. There was one death within 30 days of PCG and 1 patient proceeded to surgical necrosectomy. After evidence of resolution of the pseudocysts, the internal stent was retrieved in 17 patients by endoscopic snare.

Sporting 'groin strains': not always muscular!

A gluteal artery pseudoaneurysm presenting as a 'groin strain' following minor trauma is reported. Diagnosis was made by CT scan and arteriography. Treatment was with superselective catheterization and microcoil embolization.