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Biomedical subjects

C J Strachan

Publications and source records attributed to C J Strachan.

At least 19 recordsLinked to original sources

Visualizing the conversion of carbamazepine in aqueous suspension with and without the presence of excipients: a single crystal study using SEM and Raman microscopy.

Visual observations of the hydration process of single carbamazepine (CBZ) crystals in water and in various excipient solutions [(1% w/v) - hydroxypropyl cellulose (HPC), poly(vinyl pyrrolidone) (PVP), sodium carboxymethylcellulose (CMC) at pH 7.5 and 3.0, and polyethylene glycol (PEG)] using scanning electron microscopy (SEM) are reported in this paper. Raman microscopy was used to confirm the chemical structures of the unconverted CBZ and the CBZ dihydrate (DH) needles. It was found that defect structures were a more important driving force than the nature of crystal faces for the initiation of the hydration, but face differences became obvious after 6 h immersion. The biggest crystal face grown from methanol, (100), was the slowest one to be covered with DH needles. A comparison of the molecular arrangements along the three crystal faces [(100), (010) and (001)] was carried out using crystal structure visualization software, and fewer polar groups exposed on the (100) face than on the (001) and (010) faces were found, explaining the comparatively weak interaction of the (100) face with water during hydration. Furthermore, investigation of the influence of excipients on the hydration of CBZ showed that both HPC and PVP strongly inhibited conversion, and no conversion of CBZ to DH was found after 18 h immersion in water. PEG and CMC (pH 7.5) were less potent inhibitors than HPC and PVP, and DH needles were observed on all the faces except the (100) face after 18 h immersion. No conversion was detected for the crystal immersed in CMC solution at pH 3.0. This is likely to be caused by the decreased polarity of CMC in water at pH 3.0 (pKa,cmc = 4.3), and thus a higher surface adsorption of CMC to the CBZ crystals in dispersion. The influence of excipients on the conversion of CBZ observed in this study agreed well with our previous quantitative studies using Raman spectroscopy. In this study, visual observation using electron microscopy has been demonstrated to be a unique and powerful tool to improve our understanding of polymorphic conversions of CBZ in aqueous suspension.

Carbamazepine↗

Analysis of lecithin-cholesterol mixtures using Raman spectroscopy.

FT-Raman spectroscopy has been used to investigate interactions between lecithin and cholesterol. Raman spectra of lecithin show multiple peaks which can be classified into three regions: hydrophobic chain, interfacial, and headgroup regions. Binary lipid mixtures (1:1, w/w, lecithin:cholesterol) were prepared by physical mixing, granulation, coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). Regardless of the preparation method, no changes in the spectra were observed in the hydrophobic region. A shift in the wavenumber of the choline methyl asymmetric stretching mode was observed when the samples were prepared by coprecipitation, hydration and heating (65 degrees C), and heating (120 degrees C). This may indicate a modification of phospholipids in the headgroup region in these samples. The difference in degrees of frequency shift (physical mixing approximately granulation<coprecipitation approximately hydration and heating (65 degrees C)<heating (120 degrees C)) suggests that different levels of hydrogen bonding may have occurred in mixtures prepared with these methods. Multivariate analysis utilizing partial least squares regression based on selected wavenumber ranges was applied for the quantitative analysis of the amount of lecithin in lipid mixtures. Calibration models from physical mixing and heating (120 degrees C) exhibited lower R2 and root mean square error of cross validation (RMSECV) values compared to the other models suggesting lower sample homogeneity for these preparation methods. Low values of the mean absolute residues and mean Mahalanobis distances imply that the calibration model generated from physical mixing samples may be appropriate for quantitative analysis of lecithin in lipid mixtures prepared by any of the other techniques.

Chemistry, Pharmaceutical↗

Characterizing the conversion kinetics of carbamazepine polymorphs to the dihydrate in aqueous suspension using Raman spectroscopy.

In an aqueous environment, polymorphic forms I-III of carbamazepine all convert to the dihydrate. This study investigated the conversion of each polymorphic form individually and of a mixture of forms III and I to the dihydrate. Two batches of form I with different crystal morphology were used. Samples were dispersed independently in water at 23+/-1 degrees C and recovered at various timepoints varying from 10 to 210 min. Scanning electron microscopy, X-ray powder diffraction and Raman spectroscopy were used to characterize the initial polymorphic forms and the recovered samples after 210 min. Raman spectroscopy combined with partial least squares analysis was used to generate quantitative models of binary and ternary mixtures of the different polymorphic forms with the dihydrate. On the basis of these models the conversion kinetics of the polymorphic forms I-III were characterized. First-order kinetics with an unconverted portion were used to model the data (R2> or =0.95). The unconverted portions ranged from 16 to 51% after dispersion for 210 min. The conversion kinetics were similar between polymorphic forms with comparable crystal morphology, but differed significantly between batches of the same polymorph (form I) with different crystal morphology. Furthermore, the conversion of forms III and I in the aqueous suspension was not influenced by the presence of the other polymorph when dispersed together.

Anticonvulsants↗

The prevention of orthopaedic implant and vascular graft infections.

The infection rate for any surgical prosthesis insertion should be less than 1% in the first postoperative year. If infection occurs the patients will lose their new found mobility, lose their independence, be hospitalized with sepsis, both local and systemic, and perhaps die. Preoperative and intraoperative measures to prevent infection are well established in orthopaedic surgery but less scientifically applied in peripheral vascular surgery. In both specialties the problem of late infection has promoted research on the protection of the peri-prosthetic environment against both bacteria and biofilm. In orthopaedics, the incorporation of various antibiotics into bone cement is well accepted in revision surgery, but still debated for the primary operation. On-going research on bioresorbable ceramics and the incorporation of antibiotics more effective against coagulase-negative staphylococci should eventually counter late infections. As HIV-positive patients increasingly present with sepsis around implanted prostheses this need will increase. In vascular surgery as the risk factors for biomaterial infection are better understood, new generations of protein-sealed grafts are permitting ionically compatible antibiotic coatings. Large well-designed clinical trials have begun and are needed to confirm the forecast of improved long-term clinical outcomes.

Anti-Bacterial Agents↗

Antibiotic prophylaxis in peripheral vascular and orthopaedic prosthetic surgery.

Peripheral vascular by-pass and orthopaedic joint replacement surgery have much in common. The consequences of infection are serious and occasionally fatal. The incidence of infection varies from 0.5% to 3% depending on the anatomical site; the infecting organisms and distribution of organisms are similar. In orthopaedics a clean theatre environment, high local concentrations of antibiotic in the cement and systemic antibiotic prophylaxis are well established methods of reducing infection rates and are supported by clinical trials. In contrast, scientific evidence supporting these three tenets is lacking for peripheral vascular surgery. There are wide variations in the choice of prophylaxis cover for peripheral vascular surgery and the first clinical cases of antibiotic containing graft material have only recently been described. The choice of an ideal antibiotic for the prophylaxis of infections associated with vascular surgery is debatable; wound and graft infections in those receiving antibiotic prophylaxis range from 0.9% to 5.8% and 0.0 to 0.9%, respectively. For both forms of surgery whether single dose, short course or longer periods of prophylaxis is preferred, it is agreed that the antibiotic must achieve adequate concentrations at the time of potential bacterial contamination. One of the limiting factors of single dose prophylaxis is the ability of the antibiotic to penetrate bone, soft tissue or haematoma. However, single dose prophylactic antibiotic cover in prosthetic surgery will attract increasing support whenever the criteria of spectrum and 'risk period' cover is fulfilled. This may help to contain the increase in multi-resistant bacteria, particularly staphylococci within the hospital ecosystem. Prolonged systemic administration can now be replaced by high local antibacterial activity at the site of prosthesis insertion via a bonded sealant or an impregnated cement. This permits high activity which can last for several weeks until all the lines are removed and tissue incorporation has become established.

Anti-Bacterial Agents↗

The clinical use of an antibiotic-bonded graft.

Attempts to produce an antibiotic-bonded prosthesis have failed owing to poor binding, drug toxicity or inadequate antimicrobial activity of the antibiotic particularly against Staphylococcus epidermidis. Rifampicin, with an ideal spectrum, but untested against slime-forming S. epidermidis has recently been shown to bind with carboxyl groups on gelatin-sealed Dacron. We therefore investigated rifampicin activity against 30 slime-forming adherent S. epidermidis colonies, isolated from 40 consecutive aortic graft recipients, and compared it with their methicillin, gentamicin, cefuroxime, tetracycline and vancomycin resistance patterns. The S. epidermidis colonies were highly sensitive to very low levels of rifampicin. Rifampicin was then bonded to gelatin-sealed Dacron aortic prostheses which were inserted in four patients at high risk of developing subsequent infection.

Aged↗

Multiple microemboli after disintegration of clot during thrombolysis for acute myocardial infarction.

Seven of 475 consecutive patients treated with thrombolysis for acute myocardial infarction had severe embolic complications that were believed to be caused by disintegration of pre-existing clot. Three patients had symptoms that persisted for many weeks, and five died. Any potential site of pre-existing blood clot within the vascular system, notably an enlarged left atrium, ventricular aneurysm, or aortic aneurysms, should be regarded as a contraindication to treatment with thrombolytic agents.

Aged↗

The acquisition of antibiotic resistant coagulase-negative staphylococci by aortic graft recipients.

The staphylococcal flora of the groin and perianal area was studied in 12 patients undergoing aortic grafts and 3 patients having repair of ventral abdominal hernias. A total of 892 isolates of coagulase-negative staphylococci (CNS) were identified and their antibiotic resistance determined. The species most frequently isolated were S. epidermidis and S. haemolyticus with the latter showing the highest incidence of antibiotic resistance. Five of 15 patients had CNS resistant to methicillin and gentamicin on admission. The effect of pre-operative bathing with chlorhexidine was studied in 6 patients and appeared to reduce the acquisition of multi-resistant CNS in the week after operation.

Anti-Bacterial Agents↗

Current thoughts on Staphylococcus epidermidis in vascular surgery.

Staphylococcus epidermidis (CNS) is a major cause of infection in peripheral vascular surgery. It occurs as commonly in vascular prostheses as in orthopaedic, cardiac and neurosurgical implants. Greater awareness of the possible presence of CNS in initially indolent infections, particularly in the groin, is necessary. More rapid isolation and identification techniques to separate the contaminant from the pathogenic CNS are needed. It seems that better preoperative antiseptic care of vascular patients may reduce the tendency for even 24 h cephalosporin prophylaxis to encourage the emergence of resistant CNS strains.

Anti-Bacterial Agents↗

Cefotetan compared with gentamicin and tinidazole in acute abdominal surgery.

In a prospective randomised trial 190 consecutive admissions undergoing emergency abdominal surgery were allocated to receive a 24-h peri-operative prophylactic regime of either cefotetan or gentamicin and tinidazole. Wound sepsis developed in 14 patients in each group and one patient in each group developed intra-abdominal abscess. Nine patients in the cefotetan group and 10 patients in the gentamicin and tinidazole group died within 1 month of surgery. The death of one patient in each group was directly related to sepsis. Sixty-five per cent of aerobes isolated at operation were sensitive to cefotetan and 62% sensitive to gentamicin. The in vitro anaerobic cover of tinidazole was complete, whereas 13% of anaerobes isolated at operation were resistant to cefotetan. Anaerobes, predominantly Bacteroides fragilis, were isolated from six of the 14 infected wounds following cefotetan prophylaxis and two of the 14 infected wounds in the gentamicin and tinidazole group. It is therefore recommended that cefotetan should be combined with a nitroimidazole in patients undergoing emergency colo-rectal procedures.

Abdomen, Acute↗