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Biomedical subjects

C Thompson

Publications and source records attributed to C Thompson.

At least 19 recordsLinked to original sources

Evaluating an optimal gastric closure method for transgastric surgery.

BACKGROUND: The transgastric approach is currently being studied as a potentially less invasive alternative to conventional laparoscopy for intra-abdominal surgery. A major obstacle to overcome is the closure of the transgastric incision in a rapid, reproducible, and safe manner. The effectiveness of various techniques for gastrotomy closure were compared by assessing leak pressures in an ex vivo porcine stomach model. METHODS: Whole stomachs from adult white pigs were suspended in a Plexiglas box to facilitate endoscopic technique. Standard gastrotomies were made by needle knife incision and dilation with a controlled radial expansion (CRE) balloon. The first arm used standard QuickClips; the second, a prototype device developed by LSI Solutions; the third, hand-sewn by a senior surgeon; the final, a control with open gastrotomy. Five stomachs were tested per study arm. After closure, each stomach was inflated by an automated pressure gauge. The pressures to achieve air leakage and liquid leakage were recorded. RESULTS: The unclosed controls demonstrated air leakage at a median pressure of 15 mmHg, representing baseline system resistance. The QuickClip closures leaked air at a median pressure of 33 mmHg. The prototype gastrotomy device yielded the highest median air leak pressure of 85 mmHg while dramatically diminishing time for incision and gastrotomy closure to approximately 5 min. The hand-sewn closures leaked air at a median pressure of 47 mmHg. Using Kruskal-Wallis statistical analysis, the comparisons were significant (p = 0.0019). Post hoc paired comparisons using MULTTEST procedure with both Bonferroni and bootstrap adjustments revealed that the difference between prototype and clips was significant; prototype versus hand-sewn was not. Liquid-leak pressures produced similar results. CONCLUSIONS: The prototype device decreases procedure time and yields leak-resistant gastrotomy closures that are superior to clips and rival hand-sewn interrupted stitches.

Animals↗

Laser Doppler flowmetry detection of endothelial dysfunction in end-stage renal disease patients: correlation with cardiovascular risk.

Prediction of cardiovascular (CV) complications represents the Achilles' heel of end-stage renal disease. Surrogate markers of endothelial dysfunction have been advocated as predictors of CV risk in this cohort of patients. We have recently adapted a noninvasive laser Doppler flowmetry (LDF) functional testing of endothelium-dependent microvascular reactivity and demonstrated that end-stage renal disease patients are characterized by profound alterations in thermal hyperemic responsiveness. We hypothesized that such functional assessment of the cutaneous microcirculation may offer a valid, noninvasive test of the severity of endothelial dysfunction and CV risk. To test this hypothesis, we performed a cross-sectional study, in which we compared LDF measurements to conventional risk factors, and performed a pilot longitudinal study. LDF studies were performed in 70 patients and 33 controls. Framingham and Cardiorisk scores were near equivalent for low-risk patients, but more divergent as risk increased. C reactive protein (CRP) levels and LDF parameters (amplitude of thermal hyperemia (TH), area under the curve of TH) showed significant abnormality in high-risk vs low-risk patients calculated using either Framingham or Cardiorisk scores. Patients who had abnormal LDF parameters showed increased CV mortality, however, had similar risk assessments (Framingham, Cardiorisk, CRP, and homocysteine) to those with unimpaired LDF tracings. In conclusion, LDF parameters of microvascular reactivity offer a sensitive characterization of endothelial dysfunction, which may improve CV risk assessment through incorporation into the Framingham or Cardiorisk algorithm.

Adult↗

Review of 212 individuals attending a city centre genitourinary medicine clinic following acute sexual assault.

A retrospective case note review of 212 individuals (190 women) attending a city-centre Genitourinary Medicine clinic between 1/4/2002 and 31/3/2004 following an acute sexual assault. Direct referral by the Forensic Medical Examiner to the dedicated weekly clinic for victims of sexual assault facilitated the attendance of 55/113 attending the dedicated clinic. The 99 individuals who did not disclose a recent assault as the reason for attendance were seen at routine clinics. One third of individuals attending the dedicated clinic were less than 16 years old, reflecting the facilitated referral pathway. Those attending the dedicated clinic were more likely to be offered the extended service outlined in the departmental protocol. Twenty four sexually transmitted infections were detected in 23 (11%) individuals but 23/24 could have been acquired during other recent consensual sexual activity. Overall, the assailant was known to the victim in 53% cases, there was an allegation of violence associated with the assault in 20%, suspicion of a drug facilitated ('spiked drink') assault in 24% and admission of alcohol intoxication in 11% cases. The 22/212 (10%) who were male were more likely to present to a routine clinic.

Adolescent↗

Barriers to implementing a policy not to attempt resuscitation in acute medical admissions: prospective, cross sectional study of a successive cohort.

OBJECTIVE: To establish whether acutely unwell patients admitted to hospital wish to participate in discussions about resuscitation. DESIGN: Prospective, cross sectional study of a successive cohort of patients. SETTING: Admission through the emergency department. PARTICIPANTS: 374 adult patients. MAIN OUTCOME MEASURE: Whether acutely unwell patients wished to participate in discussions about resuscitation. RESULTS: Of the total sample, 74 patients consented to take part in the study and provide full data. Of the remaining patients, 189 could not be approached for practical reasons and 111 did not wish to participate. Of the 74 patients who read the leaflet, 65 (88%) reported having little or no prior knowledge, 70 (96%) understood it, 56 (77.8%) preferred for resuscitation decisions to be discussed with them, and 55 (77.5%) did not mind discussing resuscitation within 24 hours of admission and overall showed a decline in their anxiety score. CONCLUSION: Many patients admitted through the emergency department for medical reasons cannot participate in their decision not to attempt resuscitation within 24 hours of admission. Patients who were willing to participate rated the information leaflet that was provided positively.

Adult↗

A systematic review of the efficacy and safety of second generation antipsychotics in the treatment of mania.

Second generation antipsychotic agents are increasingly used in the management of acute mania. A systematic review of the efficacy and safety of these agents, as both monotherapy and in combination with mood stabilisers, was performed to establish the evidence for their use. Randomised controlled trials (RCTs) were critically appraised in more detail than studies that presented lower levels of evidence such as case reports, case series and open label follow up studies. We found 11 RCTs reporting on patients treated with second generation antipsychotics for acute bipolar mania, of which three included randomisation between the second generation antipsychotic and placebo, and eight between a mood stabiliser combined with either the second generation antipsychotic or placebo. Data from non-randomised trials is also presented.

Antipsychotic Agents↗

Blood gene expression profiling in liver transplant recipients with hepatitis C virus and posttransplantation diabetes mellitus.

BACKGROUND: Hepatitis C virus (HCV) is a risk factor for developing posttransplantation diabetes mellitus (PTDM) after liver transplantation; little is known about the biological mechanisms involved with this risk. This study investigated gene expression differences to provide insight into potential mechanisms. PATIENTS AND METHODS: Gene expression profiles of blood samples obtained from 6 HCV+ liver transplant recipients were determined using Affymetrix U133 Plus 2.0 microarrays. Differential gene expression was assessed between HCV+ recipients with PTDM (n = 3) and without PTDM (n = 3) using the GeneSpring 7.3 software package. The Welch t test was used to identify significant differences (P < .05) between groups. Gene expression profiles for 6 HCV- liver transplant recipients (with PTDM = 3, without PTDM = 3) were used as a blind test set to evaluate a subset of genes to predict PTDM. RESULTS: Expression levels of 347 genes were significantly different between recipients with PTDM and those without PTDM. Seventy-four genes were up-regulated and 270 were down-regulated in PTDM. Genes were categorized into functional classes: apoptosis (n = 69 genes); immune function (n = 110); diabetes (n = 17); hepatitis C (n = 12); liver transplant (n = 69). The expression profile of a subset of genes was evaluated for predicting PTDM in 6 HCV- transplant recipients. We accurately predicted the presence or absence of PTDM in 5/6 recipients. CONCLUSIONS: PTDM in HCV+ liver transplant recipients was associated with down-regulated expression of a large number of genes. A subset of these genes was useful to predict PTDM in HCV- recipients. Most genes were associated with apoptosis and immune function. HCV may act as a primer by affecting a group of genes involved in developing diabetes.

Body Mass Index↗

Progress and prospects: cell based regenerative therapy for cardiovascular disease.

Experimental and clinical studies are progressing simultaneously to investigate the mechanisms and efficacy of progenitor cell treatment after an acute myocardial infarction and in chronic congestive heart failure. Multipotent progenitor cells appear to be capable of improving cardiac perfusion and/or function; however, the mechanisms still are unclear, and the issue of whether or not trans-differentiation occurs remains unsettled. Both experimentally and clinically, cells originating from different tissues have been shown capable of restoring cardiac function, but more recently multiple groups have identified resident cardiac progenitor cells that seem to participate in regenerating the heart after injury. Clinically, cells originating from blood or bone marrow have been proven to be safe whereas injection of skeletal myoblasts has been associated with the occurrence of ventricular arrhythmias. Myoblasts can transform into rapidly beating myotubes; however, thus far convincing evidence for electro-mechanical coupling between myoblasts and cardiomyocytes is lacking. Moving forward, mechanistic studies will benefit from the use of genetic markers and Cre/lox reporter systems that are less prone to misinterpretation than fluorescent antibodies, and a more convincing answer regarding therapeutic efficacy will come from adequately powered randomized placebo controlled trials.

Animals↗

Identification of nuclear spliceosomal antigens targeted by NOD mouse antibodies following sodium iodide intake.

The non-obese diabetic (NOD) mouse spontaneously develops a range of autoreactive responses including an autoantibody response to nuclear antigens. As elevated dietary iodine has been shown to increase thyroid autoimmune pathology in NOD mice, the effect of sodium iodide (NaI) on the development of anti-nuclear antibodies (ANA) was assessed. Interestingly, the NaI symporter is expressed in both thyroid and salivary glands. Elevated dietary iodine was found to increase the percentage of male NOD mice developing autoantibodies. Specifically, the nuclear autoantibodies that develop in NOD mice were shown to target specific spliceosomal components. The target specificity of the autoantibodies was determined using recombinant spliceosomal proteins and shown to include U1A, U170K, U2B'', U2A', as well as the Sm proteins D1, D2, and B. The autoantibody isotypes most consistently represented were IgG2a and IgG2b.

Amino Acid Sequence↗

Cost-effectiveness of referral for generic care or problem-solving treatment from community mental health nurses, compared with usual general practitioner care for common mental disorders: Randomised controlled trial.

BACKGROUND: UK general practitioners (GPs) refer patients with common mental disorders to community mental health nurses. AIMS: To determine the effectiveness and cost-effectiveness of this practice. METHOD: Randomised trial with three arms: usual GP care, generic mental health nurse care, and care from nurses trained in problem-solving treatment; 98 GPs in 62 practices referred 247 adult patients with new episodes of anxiety, depression and life difficulties, to 37 nurses. RESULTS: There were 212 (86%) and 190 (77%) patients followed up at 8 and 26 weeks respectively. No significant differences between groups were found in effectiveness at either point. Mean differences in Clinical Interview Schedule - Revised scores at 26 weeks compared with GP care were -1.4 (95% CI -5.5 to 2.8) for generic nurse care, and 1.1 (-2.9 to 5.1) for nurse problem-solving. Satisfaction was significantly higher in both nurse-treated groups. Mean extra costs per patient were 283 pound (95% CI154-411) for generic nurse care, and 315 pound (183-481) for nurse problem-solving treatment. CONCLUSIONS: GPs should not refer unselected patients with common mental disorders to specialist nurses. Problem-solving should be reserved for patients who have not responded to initial GP care.

Adolescent↗

How many sexually transmitted infections (STIs) will we miss?--an algorithm to assess risk factors for STI.

A self-administered algorithm for the assessment of symptoms of, and risk factors for, sexually transmitted infection (STI) was developed. The algorithm was applied retrospectively to all cases of STI other than chlamydia diagnosed over a one-year period, to estimate the risk of missing STI diagnoses by its introduction. Three hundred and eighty-nine cases were identified, of whom 81 (21%) were asymptomatic. Seven asymptomatic cases had no identifiable risk factors for infection and might potentially have been offered a postal testing kit for chlamydia rather than a full STI screen. We estimate that 1.8% of STIs diagnosed in the unit might be missed by the introduction of the algorithm.

Algorithms↗

Selective cerebral hypothermia for post-hypoxic neuroprotection in neonates using a solid ice cap.

OBJECTIVE: The main objective of this study was to study the safety and efficacy of a simple, cost-effective method of selective head cooling with mild systemic hypothermia in newborn infants with hypoxic ischaemic encephalopathy. DESIGN: Ethical approval was obtained for a randomized controlled study in which 20 asphyxiated neonates with clinical signs of hypoxic ischaemic encephalopathy would be randomised into cooled and non-cooled groups. However, after cooling the first 4 babies, it was clear that repeated revisions to the cooling technique had to be made which was inappropriate in the context of a randomised controlled trial. The study was therefore stopped and the data for the 4 cooled infants are presented here in the form of a technical report. Hypothermia was achieved by applying an insulated ice cap to the heads of the infants and replacing it at 2-3-hourly intervals, aiming to achieve a target rectal temperature of 35-35.5 degrees C and a target scalp temperature of 10-28 degrees C. SETTING: This study was carried out between July 2000 and September 2001 in the neonatal units of Groote Schuur Hospital and Mowbray Maternity Hospital, Cape Town. SUBJECTS: Term infants with signs of encephalopathy were recruited within the first 8 hours of life if they had required resuscitation at birth and had significant acidosis within the first hour of life. RESULTS: Target rectal temperature was achieved in all infants, but large variations in incubator and scalp temperatures occurred in 3 of the 4 infants. Reducing the target core temperature in a stepwise manner did not prevent excessive temperature variation and resulted in a longer time to reach target temperature. There was least variation in scalp temperature when the ice pack was covered in two layers of mutton cloth before application, but the resulting scalp temperatures were above the target temperature. The maximum scalp temperature variation was reduced from 22 degrees C to 12 degrees C using this method. Nasopharyngeal temperatures varied excessively within less than a minute, suggesting that air cooling via mouth breathing was occurring. The surface site that correlated best with deep rectal temperature was the back, with the infant supine. During cooling, the respiratory rate and heart rate dropped while the mean arterial blood pressure was elevated. There were no irreversible adverse events due to cooling, but infants did become agitated and exhibited shivering which required sedation and analgesia. CONCLUSIONS: Nasopharyngeal temperature monitoring was not reliable as an acute clinical indicator of brain temperature in these spontaneously breathing infants, and the back temperature in supine infants correlated better with deep rectal temperature than did exposed skin temperature. This method of cooling achieved systemic cooling but there were large variations in regional temperatures in 3 of the 4 infants. The variations in temperature were probably due to the excessive cooling effect of the ice cap, coupled with the use of external heating to maintain systemic temperature at 35-35.5 degrees C. Variation in temperature was reduced when additional insulation was provided. However, the additional insulation resulted in the loss of the selective cerebral cooling effect. This cooling technique was therefore not an appropriate method of selective head cooling, but did successfully induce systemic hypothermia. This method of insulating an ice cap could therefore be used to induce whole-body cooling but the use of lower core temperatures of 33-34 degrees C is recommended as this will probably result in fewer regional temperature fluctuations. Ideally a more uniform method of cooling should be used.

Body Temperature↗

Consensus guidelines on screening for hypopituitarism following traumatic brain injury.

PRIMARY OBJECTIVE: The goal of this consensus statement is to increase awareness among endocrinologists and physicians treating patients with traumatic brain injury (TBI) of the incidence and risks of hypopituitarism among patients with TBI. RATIONALE: TBI poses significant risk to the pituitary gland, leading to elevated risks of diabetes, hypopituitarism and other endocrinopathies. Signs and symptoms associated with hypopituitarism often mimic the sequellae of TBI, although the severity of symptoms is not necessarily related to the severity of the injury. Patients with TBI-induced hypopituitarism may benefit both physically and psychologically from appropriate hormone replacement therapy (HRT). Participants at this unique consensus meeting attempted to define and spearhead an approach to increase awareness of the risks of TBI-induced endocrinopathies, in particular growth hormone deficiency (GHD), and to outline necessary and practical objectives for managing this condition. RECOMMENDATIONS: Systematic screening of pituitary function is recommended for all patients with moderate-to-severe TBI at risk of developing pituitary deficits. Patients with hypopituitarism benefit from appropriate hormonal replacement and prospects for rehabilitation of patients with TBI-induced hypopituitarism may be enhanced by appropriate HRT. Further exploration of this possibility requires: (1) active collaboration between divisions of endocrinology and rehabilitation at the local level to perform a screening of pituitary function in patients after TBI, (2) creation of a consultancy service by endocrine societies for use by rehabilitation centres, (3) development of continuing medical education (CME) programmes that can be offered as crossover training to the physicians who manage the care of patients with TBIs, (4) targeting of patient organizations with educational information for dissemination to patients and their families, (5) continued efforts to more clearly define the population at greatest risk of TBI-induced hypopituitarism and (6) monitor results of efficacy studies as they become available to evaluate whether and how much replacement therapy can improve the symptoms of individuals with TBI-induced hypopituitarism.

Brain Injuries↗

An exceptionally bright flare from SGR 1806-20 and the origins of short-duration gamma-ray bursts.

Soft-gamma-ray repeaters (SGRs) are galactic X-ray stars that emit numerous short-duration (about 0.1 s) bursts of hard X-rays during sporadic active periods. They are thought to be magnetars: strongly magnetized neutron stars with emissions powered by the dissipation of magnetic energy. Here we report the detection of a long (380 s) giant flare from SGR 1806-20, which was much more luminous than any previous transient event observed in our Galaxy. (In the first 0.2 s, the flare released as much energy as the Sun radiates in a quarter of a million years.) Its power can be explained by a catastrophic instability involving global crust failure and magnetic reconnection on a magnetar, with possible large-scale untwisting of magnetic field lines outside the star. From a great distance this event would appear to be a short-duration, hard-spectrum cosmic gamma-ray burst. At least a significant fraction of the mysterious short-duration gamma-ray bursts may therefore come from extragalactic magnetars.

Journal Article↗

Audit of the management of victims of sexual assault in a city centre genitourinary medicine clinic.

A total of 113 individuals (101 women, 12 men) who had experienced sexual assault (SA) attended the genitourinary medicine clinic. Of the 60 patients who were seen at a dedicated clinic for victims of SA, the median age was lower, a greater number had reported to the police and the interval between assault and attendance was shorter, compared with the 53 who attended the routine walk-in service. However, the majority of the men attended routine clinics. Drug-facilitated rape was reported in 20%, excess alcohol in 10% and the use of violence in 20% cases. Overall, the prevalence of sexually transmitted infections was the same as the total clinic population.

Adolescent↗

A randomised controlled trial to compare the cost-effectiveness of tricyclic antidepressants, selective serotonin reuptake inhibitors and lofepramine.

OBJECTIVE: To determine the relative cost-effectiveness of three classes of antidepressants: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and the modified TCA lofepramine, as first choice treatments for depression in primary care. DESIGN: Open, pragmatic, controlled trial with three randomised arms and one preference arm. Patients were followed up for 12 months. SETTING: UK primary care: 73 practices in urban and rural areas in England. PARTICIPANTS: Patients with a new episode of depressive illness according to GP diagnosis. INTERVENTIONS: Patients were randomised to receive a TCA (amitriptyline, dothiepin or imipramine), an SSRI (fluoxetine, sertraline or paroxetine) or lofepramine. Patients or GPs were able to choose an alternative treatment if preferred. MAIN OUTCOME MEASURES: At baseline the Clinical Interview Schedule, Revised (CIS-R PROQSY computerised version) was administered to establish symptom profiles. Outcome measures over the 12-month follow-up included the Hospital Anxiety and Depression Scale self-rating of depression (HAD-D), CIS-R, EuroQol (EQ-5D) for quality of life, Short Form (SF-36) for generic health status, and patient and practice records of use of health and social services. The primary effectiveness outcome was the number of depression-free weeks (HAD-D less than 8, with interpolation of intervening values) and the primary cost outcome total direct NHS costs. Quality-adjusted life-years (QALYs) were used as the outcome measure in a secondary analysis. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were computed. Estimates were bootstrapped with 5000 replications. RESULTS: In total, 327 patients were randomised. Follow-up rates were 68% at 3 months and 52% at 1 year. Linear regression analysis revealed no significant differences between groups in number of depression-free weeks when adjusted for baseline HAD-D. A higher proportion of patients randomised to TCAs entered the preference arm than those allocated to the other choices. Switching to another class of antidepressant in the first few weeks of treatment occurred significantly more often in the lofepramine arm and less in the preference arm. There were no significant differences between arms in mean cost per depression-free week. For values placed on an additional QALY of over 5000 pounds, treatment with SSRIs was likely to be the most cost-effective strategy. TCAs were the least likely to be cost-effective as first choice of antidepressant for most values of a depression-free week or QALY respectively, but these differences were relatively modest. CONCLUSIONS: When comparing the different treatment options, no significant differences were found in outcomes or costs within the sample, but when outcomes and costs were analysed together, the resulting cost-effectiveness acceptability curves suggested that SSRIs were likely to be the most cost-effective option, although the probability of this did not rise above 0.6. Choosing lofepramine is likely to lead to a greater proportion of patients switching treatment in the first few weeks. Further research is still needed on the management of depressive illness in primary care. This should address areas such as the optimum severity threshold at which medication should be used; the feasibility and effectiveness of adopting structured depression management programmes in the UK context; the importance of factors such as physical co-morbidity and recent life events in GPs' prescribing decisions; alternative ways of collecting data; and the factors that give rise to many patients being reluctant to accept medication and discontinue treatment early.

Adolescent↗

A trial of problem-solving by community mental health nurses for anxiety, depression and life difficulties among general practice patients. The CPN-GP study.

OBJECTIVES: To compare the effectiveness of community mental health nurse (CMHN) problem-solving and generic CMHN care, against usual general practitioner (GP) care in reducing symptoms, alleviating problems, and improving social functioning and quality of life for people living in the community with common mental disorders; and to undertake a cost comparison of each CMHN treatment compared with usual GP care. DESIGN: A pragmatic, randomised controlled trial with three arms: CMHN problem-solving, generic CMHN care and usual GP care. SETTING: General practices in two southern English counties were included in the study. CMHNs were employed by local NHS trusts providing community mental health services. PARTICIPANTS: Participants were GP patients aged 18--65 years with a new episode of anxiety, depression or reaction to life difficulties and had to score at least 3 points on the General Health Questionnaire-12 screening tool. Symptoms had to be present for a minimum of 4 weeks but no longer than 6 months. INTERVENTIONS: Patients were randomised to one of three groups: (1) CMHN problem-solving treatment, (2) generic CMHN treatment, or (3) usual GP care. All three groups of patients remained free to consult their GPs throughout the course of the study, and could be prescribed psychotropic drug treatments. MAIN OUTCOME MEASURES: Patients were assessed at baseline, and 8 weeks and 26 weeks after randomisation. The primary outcome measure was psychological symptoms measured on the Clinical Interview Schedule -- Revised. Other measures included social functioning, health-related quality of life, problem severity and satisfaction. The economic outcomes were evaluated with a cost--utility analysis. RESULTS: Twenty-four CMHNs were trained to provide problem-solving under supervision, and another 29 were referred patients for generic support. In total, 247 patients were randomised to the three arms of the study, referred by 98 GPs in 62 practices. All three groups of patients were greatly improved by the 8-week follow-up. No significant differences were found between the groups at 8 weeks or 26 weeks in symptoms, social functioning or quality of life. Greater satisfaction with treatment was found in the CMHN groups. CMHN care represented a significant additional health service cost and there were no savings in sickness absence. CONCLUSIONS: The study found that specialist mental health nurse support is no better than support from GPs for patients with anxiety, depression and reactions to life difficulties. The results suggest that healthcare providers could consider adopting policies of restricting referrals of unselected patients with common mental disorders to specialist CMHNs, although there may be other roles in primary care that CMHNs could play effectively. Further research should address the predictors of chronicity in common mental disorders and target extra treatment. More research is also needed into the effectiveness and cost-effectiveness of problem-solving treatment for other disorders, of facilitated self-help treatments for common mental disorders and of CMHN care for people with severe and enduring mental illnesses, as well as the prevention of mental disorders.

Adolescent↗

AFM studies of the crystallization and habit modification of an excipient material, adipic acid.

Atomic force microscopy (AFM) has been used to investigate the (1 0 0) face of crystalline adipic acid, both in air and liquid environments. In air, surface reorganization occurred during scanning of the AFM probe, which has been investigated using single point force-distance analysis under a controlled relative humidity (RH) environment. We suggest such reorganization can be attributed to the influence of a network of water molecules bound to the hydrophilic (1 0 0) surface permitting local AFM tip-enhanced dissolution and reorganization of the solute. In situ imaging was also carried out on the crystals, revealing etch-pit formation during dissolution, and rapid growth at higher levels of supersaturation (sigma), both of which are direct consequences of the hydrophilic nature of the (1 0 0) face. Also presented here are nanoscale observations of the effect of octanoic acid, a structurally-related habit modifier, on crystalline adipic acid. Using AFM, we have been able to show that the presence of octanoic acid at low concentration has little observable affect on the development of the (1 0 0) face; however, as this concentration is increased, there are clear changes in step morphology and growth mode on the (1 0 0) face of the crystal. At a concentration of 1.26 mmol dm(-3) (a concentration corresponding to a molar ratio of approximately 1:175 octanoic acid:adipic acid), growth on the (1 0 0) face is inhibited, with in situ AFM imaging indicating this is a direct consequence of octanoic acid binding to the surface, and pinning the monomolecular growth steps.

Adipates↗

Hydroxy-methylglutaryl-coenzyme A reductase inhibition improves endothelial dysfunction in type-1 diabetes.

OBJECTIVE: We hypothesize that treatment with Pravastatin, a HMG CoA reductase inhibitor would improve flow-mediated dilation (FMD), a nitric oxide dependent phenomenon and the earliest detectable marker of endothelial dysfunction, in asymptomatic patients with type-1 diabetes. MATERIALS AND METHODS: FMD of the brachial artery in response to reactive hyperaemia was measured using high-resolution ultrasonography. Young male patients with type-1 diabetes (n=9) were compared with age matched non-diabetic controls (n=8). RESULTS: The FMD response in the control group was a median increase in diameter of 7.9 (range 3.8-12.6)%. In the diabetic group the FMD response was impaired when compared with controls with a median increase only of 4.4 (range 3.7-5.8)% (p<0.01). Following Pravastatin, 40 mg per day for one month in the diabetic group, there was a significant diameter change in response to reactive hyperaemia with a median of 8.4 (range 6.9-12.6)% (p<0.01). CONCLUSIONS: These data confirm the presence of endothelial dysfunction in young patients with type-1 diabetes. We have shown that 1-month of Pravastatin treatment normalizes FMD. This suggests that HMG CoA reductase inhibitors may have a role in the management of diabetes mellitus, even in the presence of normal serum cholesterol levels.

Adolescent↗