Search PubMed⌕ Search

Biomedical subjects

D Law

Publications and source records attributed to D Law.

At least 19 recordsLinked to original sources
PubMed2006

Influence of solid phase and formulation processing on stability of Abbott-232 tablet formulations.

Abbott-232 is a chemically stable, highly water soluble non-hygroscopic compound selected for development as a potent uroselective alpha(1A) agonist. An anhydrate, a monohydrate, and an amorphous phase were isolated. The anhydrate was chosen for formulation development based on solid-state characterization. Excipients for immediate release (IR) tablet formulations were selected according to compatibility studies. However, the prototype IR tablets designed for clinical trials were found to be chemically unstable. Thus, process-induced phase transformation was investigated as the likely cause of the observed instability. Since the drug loading in the formulations was low (1%), model granulations containing 30% drug were evaluated to test this hypothesis. Investigation using a variety of analytical techniques indicated that the observed degradation was, indeed, a result of a solution-mediated phase transformation from anhydrate to amorphous Abbott-232 during wet granulation. A new direct compression formulation was, therefore, developed to prevent the solution-mediated process induced phase transition. Since the drug loading was low, a polarized light microscope (PLM) method was used to evaluate the solid phase in the new formulation. PLM confirmed that the original anhydrate form remained unchanged in tablets manufactured by the dry process. Stability studies confirmed that both IR and extended release (ER) tablets of Abbott-232 were successfully developed for clinical trials using direct compression.

Adrenergic alpha-Agonists↗
PubMed2006

Oxygen alert cards and controlled oxygen: preventing emergency admissions at risk of hypercapnic acidosis receiving high inspired oxygen concentrations in ambulances and A&E departments.

BACKGROUND: Appropriate resuscitation of hypoxic patients is fundamental in emergency admissions. To achieve this, it is standard practice of ambulance staff to administer high concentrations of oxygen to patients who may be in respiratory distress. A proportion of patients with chronic respiratory disease will become hypercapnic on this. OBJECTIVES AND METHODS: A scheme was agreed between the authors' hospital and the local ambulance service, whereby patients with a history of previous hypercapnic acidosis with a Pao2 >10.0 kPa--indicating that oxygen may have worsened the hypercapnia--are issued with "O2 Alert" cards and a 24% Venturi mask. The patients are instructed to show these to ambulance and A&E staff who will then use the mask to avoid excessive oxygenation. The scheme was launched in 2001 and this paper present the results of an audit of the scheme in 2004. RESULTS: A total of 18 patients were issued with cards, and 14 were readmitted on 69 occasions. Sufficient documentation for auditing purposes was available for 52 of the 69 episodes. Of these audited admissions, 63% were managed in the ambulance, in line with card-holder protocol. This figure rose to 94% in the accident and emergency department. CONCLUSION: These data support the usability of such a scheme to prevent iatrogenic hypercapnia in emergency admissions.

Acidosis, Respiratory↗
PubMed2001

Physicochemical considerations in the preparation of amorphous ritonavir-poly(ethylene glycol) 8000 solid dispersions.

A systematic study of the properties of ritonavir and the influence of polyethylene glycol 8000 (PEG) on ritonavir revealed that amorphous ritonavir dispersions in PEG would have an improved dissolution profile and could exhibit long-term stability. Ritonavir, a human immunodeficiency virus (HIV) protease inhibitor, is highly lipophilic [distribution coefficient (log D)= 4.3, 25 degrees C, pH 6.8], poorly water soluble (400 microg/mL in 0.1 N HCl, 1 microg/mL at pH 6.8, 37 degrees C), and exhibits an exceedingly slow dissolution rate (0.03 mg/cm(2)-min in 0.1 N HCl at 37 degrees C). These properties indicated that a solid dispersion containing ritonavir might be useful for overcoming problems associated with slow dissolution. In addition, ritonavir is a good glass former [glass-transition temperature (T(g))/melting point (T(m)) > 0.7]. Amorphous ritonavir has an apparent solubility of 4 mg/mL in 0.1 N HCl at 37 degrees C and shows reasonable stability at 25 degrees C. Amorphous ritonavir, therefore, has properties desirable for preparing a solid dispersion containing this phase. Since PEG, a commonly used polymer, improved the aqueous solubility of crystalline ritonavir, it was expected to have a positive influence on the dissolution rate of ritonavir. Moreover, PEG was found to have negligible plasticizing effect on amorphous ritonavir, which was beneficial for the stability of the dispersion. Finally, solid dispersions of amorphous ritonavir in PEG were prepared, and these dispersions had improved in vitro dissolution rate and were physically stable for > 1.5 years at 25 degrees C when protected from moisture. The performance of this solid dispersion has been attributed to the physicochemical properties of amorphous ritonavir.

Calorimetry, Differential Scanning↗
PubMed2000

Initial functional independence measure score and interval post stroke help assess outcome, length of hospitalization, and quality of care.

OBJECTIVE: This study tests the hypothesis that the rehabilitation hospital admission functional Independence Measure (FIM) score and interval post stroke can be used to define clinically relevant functional recovery goals, estimate length of stay, and compare quality of care. BACKGROUND: The effects of time from stroke to rehabilitation unit admission on admission and discharge FIM scores, length of rehabilitation stay, and change in FIM score/day have not yet been reported. METHODS: Analysis was based on prospectively collected data from patients admitted to an inpatient stroke rehabilitation unit with FIM scores < or = 90 and an initial, unilateral, hemispheric, thrombotic, or embolic stroke who were fully independent without the use of an assistive device before their stroke. Patients with severe (admission FIM < 54) and moderate (admission FIM 54-90) stroke deficits were divided into cohorts based on interval from stroke to rehabilitation hospital admission: 0-2, 2-4, and 4-6 weeks. RESULTS: Over a 17-month interval, 87 patients met selection criteria. Significant improvements were seen in total FIM scores for all. For those with moderate stroke, all three time cohorts reached a FIM score of 102 +/- 2 SEM after 35 +/- 2 days on the rehabilitation unit. Patients admitted within 2 weeks of a severe stroke reached a plateau FIM score of 72 +/- 6 after 43 +/- 3 days on the rehabilitation unit compared with the 2-4 week group (FIM = 57 +/- 5 after 53 +/- 4 days) and the 4-6 week group (FIM = 54 +/- 10 after 40 +/- 6 days). Complications increased with severity of stroke and delay in rehabilitation hospital transfer. CONCLUSIONS: Admission FIM score and interval from stroke to rehabilitation hospital admission can be used to set FIM outcome goals, predict length of rehabilitation hospitalization needed to meet those goals, and compare quality of care across institutions with different referral patterns. Our results provide a benchmark against which to compare less intense or shorter duration inpatient treatment options.

Activities of Daily Living↗
PubMed1999

Phospholipid analogue distribution in Capnocytophaga.

Polar lipids of nineteen previously characterised culture collection strains of Capnocytophaga were analysed using fast atom bombardment mass spectrometry (FAB MS) in negative mode. All strains examined had a major peak at m/z 241, consistent with the expected presence of the pentadecanoate anion. The most intense higher mass anions, consistent with expected presence of phospholipid molecular species, were as follows: m/z 574, 588, 618 and 662 which are consistent with presence of PE(24:2), PE(25:2), PE(27:1) and PE(30:0) respectively. Other anions putatively identified as phospholipid anions were: m/z 572, 578, 592, 602, 604, 616 and 720 consistent with presence of PE(24:3), PE(24:0), PE(25:0), PE(26:2), PE(26:1), PE(27:2) and OH-PE(33:0). Capnocytophaga isolates share a distinctive phospholipid fingerprint which appears to lack the somewhat higher mass phospholipid analogues observed in related oral bacteria. Within the genus, the profiles obtained showed only quantitative differences which did not correlate with previous studies.

Capnocytophaga↗
PubMed1999

Nucleation and crystallization kinetics of hydrated amorphous lactose above the glass transition temperature.

The crystallization kinetics of amorphous lactose in the presence and absence of seed crystals were investigated at 57.5% relative humidity. Isothermal crystallization studies were conducted gravimetrically in an automated vacuum moisture balance at several temperatures between 18 and 32 degrees C. The crystallization rate constants were then determined from Johnson-Mehl-Avrami (JMA) treatment and isothermal activation energies were obtained from Arrhenius plots. Based on microscopic observations, a reaction order of 3 was used for JMA analysis. The nonisothermal activation energies were determined by differential scanning calorimetry using Kissinger's analysis. Isothermal activation energies for amorphous lactose with and without seed crystals were 89.5 (+/-5.6) kJ/mol and 186.5 (+/-17.6) kJ/mol, respectively. Nonisothermal activation energies with and without seed crystals were 71 (+/-7.5) kJ/mol and 80.9 (+/-8.9) kJ/mol, respectively. The similarity of the isothermal and nonisothermal activation energies for the sample with seeds suggested that crystallization was occurring by growth from a fixed number of preexisting nuclei. Markedly different isothermal and nonisothermal activation energies in the absence of seeds suggested a site-saturated nucleation mechanism, and therefore allowed calculation of an activation energy for nucleation of 317 kJ/mol.

Calorimetry, Differential Scanning↗
PubMed1998

Variation in morphotype, karyotype and DNA type of fluconazole resistant Candida albicans from an AIDS patient.

Azole-resistant oropharyngeal and oesophageal candidiasis is a recent phenomenon observed in patients with AIDS usually previously treated with fluconazole. Some variation has been observed in antifungal susceptibility testing among separate colonies of Candida albicans from the same patient. This raises the question of whether there are multiple clones present or simply phenotypic variation in expression of azole resistance. To address this question we took 18 isolates grown from multiple swabs taken before and after experimental azole therapy from a single HIV-positive individual with fluconazole-resistant oral candidiasis and compared morphotype, karyotype, PCR-based DNA typing and azole susceptibility. Ten of the isolates were from a single 2-day period. Amongst these 10 there were seven morphotypes, five karyotypes and four polymerase chain reaction (PCR) types. Three further morphotypes, one karyotype and two PCR types were found amongst the eight isolates obtained during the subsequent 4 months. Limited variation in susceptibility to two azoles--fluconazole and D0870--was also seen. This work emphasizes both the large genotype and phenotypic variability of C. albicans isolates in the mouth of AIDS patients with fluconazole resistance, and the difficulties in interpretation of present typing methods.

AIDS-Related Opportunistic Infections↗
PubMed1998

Enteroaggregative Escherichia coli.

Enteroaggregative Escherichia coli (EAggEC) are a group of E. coli characterized by the ability to adhere to cultured cell monolayers with an aggregative or 'stacked brick' adhesion phenotype. These strains of E. coli are distinct from other pathogenic groups of E. coli. Epidemiological evidence suggests that strains of EAggEC are a significant cause of protracted diarrhoea in children, and may cause diarrhoea in adults. The group is heterogeneous, comprising a diverse range of serotypes that possess a variety of putative virulence factors. These include an enterotoxin similar to the heat-stable enterotoxin of enterotoxigenic E. coli, putative haemolysins and toxins, and various types of fimbriae and outer membrane proteins that may be involved in the adhesion process. The role of these factors in the production of disease is unclear. Diagnosis of EAggEC infection is problematic; serotyping alone cannot identify strains of E. coli expressing an EAggEC phenotype. Currently, EAggEC are identified by either cell adhesion tests or DNA-based tests involving gene probes or polymerase chain reaction (PCR) for detecting the genes encoding cell adhesion. The nature and significance of strains of E. coli expressing an EAggEC phenotype are poorly understood. This article reviews the current literature and speculates on the direction of future studies to define this emerging group of bacteria.

Adult↗
PubMed1997

Cutaneous epithelioid angiosarcoma: a potential diagnostic trap for cytopathologists.

We report on the cytologic features of a rare case of cutaneous epithelioid angiosarcoma of the scalp occurring in a 65-yr-old Chinese male. The prominent epithelioid features may cytologically mimic poorly-differentiated carcinoma, malignant melanoma, and even epithelioid sarcoma. Recognition of subtle cytologic features of vasoproliferation, immunohistochemical demonstration of endothelial markers, and ultrastructural examination are necessary before a final conclusion may be drawn.

Aged↗
PubMed1997

Anti-cell surface endothelial antibodies in sera from cardiac and kidney transplant recipients: association with chronic rejection.

The aetiologies of accelerated or transplant-associated coronary artery disease (TxCAD) following cardiac transplantation and chronic rejection following renal transplantation remain ill-defined. Previous studies have used Western blotting to demonstrate an association between the formation of anti-endothelial (anti-EC) antibodies and TxCAD after heart transplantation. However, Western blotting favours detection of cytosolic proteins. The objectives of this study were to determine whether flow cytometry, a method which detects antigens on the cell surface, could be used to detect anti-EC antibodies and also whether the observations would extend to renal transplant patients with chronic rejection. Flow cytometry was used to look for antibodies reactive with the surface antigens of macrovascular and microvascular endothelial cell lines in sera from 44 cardiac and 35 renal transplant recipients before and after transplantation. In addition, sera from normals (n = 20), patients with nontransplant CAD (n = 50) and patients with unrelated diseases (n = 40) were investigated. Of 23 cardiac recipients who had developed TxCAD at one or two years post-transplant, 61% had IgM and 13% had IgG anti-EC antibodies post-transplantation. In contrast, in 21 cardiac recipients who had not developed TxCAD 14% had IgM and 14% IgG anti-EC antibodies. There was little evidence for the presence of anti-EC antibodies in cardiac recipients before transplantation. Of 26 renal transplant recipients whose transplants failed due to chronic rejection, 42% had IgG and 19% IgM anti-EC antibodies post-transplantation. Of nine renal recipients whose grafts were either functioning normally or who had acutely rejected, none had IgG or IgM anti-EC antibodies either pre- or post-transplantation. The anti-EC antibodies were not found in normals and were rare (less than 4%) in the other disease groups; they do not appear to be autoantibodies. In conclusion, these results suggest the FACS assay could be an informative and rapid test to provide more information on chronic rejection following cardiac and renal transplantation.

Adolescent↗
PubMed1997

Amphotericin B resistance testing of Candida spp.: a comparison of methods.

Several methods of susceptibility testing were compared for their ability to detect amphotericin B resistance among yeast isolates, including isolates known to be amphotericin-B-resistant in an animal model. A microtitre MIC method using antibiotic medium no. 3 and Etest strips were able to discriminate susceptible and resistant isolates. A disc susceptibility test was also able to identify resistant isolates and this method may be suitable for routine use as a screening test. A survey of resistance in 644 clinical isolates showed that the incidence of elevated MICs (> or = 0.25 mg/L) was only 1.2%.

Amphotericin B↗
PubMed1996

Rapid genotyping of Escherichia coli O157 isolates by random amplification of polymorphic DNA.

Although several typing methods have been described for Shiga-like toxin-producing Escherichia coli O157, the methods are somewhat cumbersome. Using 22 isolates of Escherichia coli O157 and five other Escherichia coli isolates, two primers (M13 core sequence and 970-11) were found to give excellent differentiation between isolates using random amplified polymorphic DNA (RAPD). Using only the presence or absence of variable bands, a matrix of 20 variable characters was identified. From these characters, similarity coefficients were calculated and a phenogram constructed. All of the Escherichia coli O157 isolates were easily distinguished from the non-O157 Escherichia coli isolates. Using a 95% similarity cutoff, we found 13 RAPD types among the 22 Escherichia coli O157 isolates. Isolates thought to be identical by toxin and phage typing as well as by epidemiological association were distinguished, and others thought to be distinct by lack of epidemiological association were identical. RAPD using M13 and 970-11 primers is a potentially useful typing tool for Escherichia coli isolates of serotype O157 and possibly other Escherichia coli isolates.

Bacteriophage Typing↗