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Biomedical subjects

D Adams

Publications and source records attributed to D Adams.

At least 19 recordsLinked to original sources

Spectrum and prognosis of neurologic complications after hematopoietic transplantation.

OBJECTIVE: To describe the neurologic complications after hematopoietic progenitor cell transplantation (HPCT) in order to design rules for their management. METHODS: We reviewed 361 consecutive patients over 6 years, including 245 autologous and 116 allogeneic HPCT recipients for hematologic malignancies (87%) and solid cancers (13%). RESULTS: Fifty-seven patients developed 65 symptomatic neurologic complications (16%), with a higher incidence in allogeneic than in autologous HPCT recipients (p = 0.01) and in chronic myelogenous leukemia (42%) than in Hodgkin disease (2.5%) (p < 0.001). CNS infections (4.2%) were the main complications, marked by an early onset (within the first 4 months) after HPCT (87%), diagnostic difficulties, and a high mortality rate (47%). They mainly included cerebral toxoplasmosis, fungal infections, and viral encephalitis. Their incidence was markedly higher in allogeneic than in autologous HPCT recipients (p = 0.002). However, two CD34(+) selected autologous HPCT recipients developed cerebral toxoplasmosis. Other CNS complications included recurrent tumors (3.6%), metabolic encephalopathies (2.8%), and cerebrovascular events (1.7%). Seizures occurred in 5% of patients, most often associated with cerebral lesions. Peripheral nervous system manifestations occurred in 3.3%. Twenty-one patients (5.8%) died directly of neurologic complications. The 4-year probability of survival was markedly lower in the case of neurologic events than in the absence thereof (12% vs 58%, p < 0.0001). CONCLUSIONS: Severe neurologic complications after hematopoietic progenitor cell transplantations are common, vary according to the underlying disease and type of transplantation, and are associated with poor survival rates. Better prophylactic protocols and therapy for CNS infections are required in future studies.

Adolescent↗

An absence of cutaneous neurofibromas associated with a 3-bp inframe deletion in exon 17 of the NF1 gene (c.2970-2972 delAAT): evidence of a clinically significant NF1 genotype-phenotype correlation.

Neurofibromatosis type 1 (NF1) is characterized by cafe-au-lait spots, skinfold freckling, and cutaneous neurofibromas. No obvious relationships between small mutations (<20 bp) of the NF1 gene and a specific phenotype have previously been demonstrated, which suggests that interaction with either unlinked modifying genes and/or the normal NF1 allele may be involved in the development of the particular clinical features associated with NF1. We identified 21 unrelated probands with NF1 (14 familial and 7 sporadic cases) who were all found to have the same c.2970-2972 delAAT (p.990delM) mutation but no cutaneous neurofibromas or clinically obvious plexiform neurofibromas. Molecular analysis identified the same 3-bp inframe deletion (c.2970-2972 delAAT) in exon 17 of the NF1 gene in all affected subjects. The Delta AAT mutation is predicted to result in the loss of one of two adjacent methionines (codon 991 or 992) ( Delta Met991), in conjunction with silent ACA-->ACG change of codon 990. These two methionine residues are located in a highly conserved region of neurofibromin and are expected, therefore, to have a functional role in the protein. Our data represent results from the first study to correlate a specific small mutation of the NF1 gene to the expression of a particular clinical phenotype. The biological mechanism that relates this specific mutation to the suppression of cutaneous neurofibroma development is unknown.

Adolescent↗

Impact of safety needle devices on occupationally acquired needlestick injuries: a four-year prospective study.

A four-year prospective study was undertaken at the University Hospital Birmingham National Health Service Foundation Trust to evaluate the effect of the introduction of a range of safety hypodermic needle devices on the number of reported needlestick injuries (NSIs). Data on the number of reported NSIs for four clinical areas began in 2001. Following an enhanced sharps awareness strategy in 2002, the number of NSIs reduced from 16.9/100,000 devices used in 2001 to 13.9/100,000 devices (P=0.813). In 2003, when only standard training was provided, the number of NSIs increased to 20/100,000 devices. However, the subsequent introduction of three safety needle devices with concomitant training resulted in a significant reduction in the number of reported NSIs to 6/100,000 devices in 2004 (P=0.045). User satisfaction and acceptance of the safety needles was also very favourable. These results suggest that when safety needle devices are introduced into the clinical setting and appropriate training is given, a significant reduction in the number of occupationally acquired NSIs may ensue.

Equipment Safety↗

Infection risk associated with a closed luer access device.

The potential for microbial contamination associated with a recently developed needleless closed luer access device (CLAD) (Q-Syte; Becton Dickinson, Sandy, UT, USA) was evaluated in vitro. Compression seals of 50 multiply activated Q-Syte devices were inoculated with Staphylococcus epidermidis NCTC 9865 in 25% (v/v) human blood and then disinfected with 70% (v/v) isopropyl alcohol followed by flushing with 0.9% (w/v) sterile saline. Forty-eight of 50 (96%) saline flushes passed through devices that had been activated up to a maximum of 70 times remained sterile. A further 25 Q-Syte CLADs that had undergone multiple activations were challenged with prefilled 0.9% (w/v) sterile saline syringes, the external luer tips of which had been inoculated with S. epidermidis NCTC 9865 prior to accessing the devices. None of the devices that had been accessed up to 70 times allowed passage of micro-organisms, despite challenge micro-organisms being detected on both the syringe tip after activation and the compression seals before decontamination. These findings suggest that the Q-Syte CLAD may be activated up to 70 times with no increased risk of microbial contamination within the fluid pathway. The device may also offer protection from the external surface of syringe tips contaminated with micro-organisms.

2-Propanol↗

Combined multichannel intraluminal impedance-pH monitoring to select patients with persistent gastro-oesophageal reflux for laparoscopic Nissen fundoplication.

BACKGROUND: Combined multichannel intraluminal impedance-pH (MII-pH) monitoring detects gastro-oesophageal reflux and identifies acid and non-acid reflux events. It can be used in patients with persistent symptoms on proton-pump inhibitor (PPI) therapy. The aim of this study was to assess laparoscopic Nissen fundoplication as a treatment for patients with persistent symptoms associated with reflux despite acid suppression documented by MII-pH monitoring. METHOD: A prospectively maintained database identified patients with persistent symptoms of gastro-oesophageal reflux disease despite PPI therapy who had undergone MII-pH monitoring and this was cross-referenced with patients who had undergone fundoplication at this institution. Follow-up after fundoplication was by periodic telephone interview and review of clinical records. RESULTS: Of 200 evaluated patients, 19 (14 female; mean age 40 (range 0.7-78) years) underwent laparoscopic Nissen fundoplication. Before surgery, 18 of 19 patients had a positive symptom index (at least half of symptoms associated with reflux) and one, a negative symptom index. After a mean follow-up of 14 (range 7-25) months, 16 of 17 (94 per cent) patients with a positive symptom index were asymptomatic or markedly improved (one patient was lost to follow-up). Persistent symptoms occurred in the patient with a negative symptom index, and one patient had recurrent symptoms after 9 months. CONCLUSION: Patients with a positive symptom index resistant to PPIs with non-acid or acid reflux demonstrated by MII-pH monitoring can be treated successfully by laparoscopic Nissen fundoplication.

Adolescent↗

Transfusion-transmitted hepatitis E in a 'nonhyperendemic' country.

Indigenous hepatitis E is increasingly recognized in developed countries, where it may be a zoonosis. We describe the first case of transfusion-transmitted hepatitis E in the UK from a blood donor who had no history of recent travel abroad. Follow-up of the donor and recipients of the blood products was carried out using serological and molecular techniques. Acute hepatitis E was transmitted to one of two recipients. The infected patient would have received a larger volume of the donor's plasma. HEV subgenomic sequences carried by the donor and recipient were identical. This is the first case of post-transfusion hepatitis E in the UK. Secondary transmission of hepatitis E indigenous to a nonhyperendemic country may occur by blood transfusion. It is important that blood donors inform the transfusion service of all post-donation illnesses so that appropriate interventions can take place.

Adult↗

Evaluation of a 2% chlorhexidine gluconate in 70% isopropyl alcohol skin disinfectant.

The efficacy of a new skin disinfectant, 2% (w/v) chlorhexidine gluconate (CHG) in 70% (v/v) isopropyl alcohol (IPA) (ChloraPrep), was compared with five commonly used skin disinfectants against Staphylococcus epidermidis RP62A in the presence or absence of protein, utilizing quantitative time-kill suspension and carrier tests. All six disinfectants [70% (v/v) IPA, 0.5% (w/v) aqueous CHG, 2% (w/v) aqueous CHG, 0.5% (w/v) CHG in 70% (v/v) IPA and 10% (w/v) aqueous povidone iodine (PI)] achieved a log(10) reduction factor of 5, in colony-forming units/mL, in a suspension test (exposure time 30s) in the presence and absence of 10% human serum. Subsequent challenges of S. epidermidis RP62A in a biofilm (with and without human serum) demonstrated reduced bactericidal activity. Overall, the most effective skin disinfectants tested against S. epidermidis RP62A were 2% (w/v) CHG in 70% IPA and 10% (w/v) PI. These results suggest that enhanced skin antisepsis may be achieved with 2% (w/v) CHG in 70% (v/v) IPA compared with the three commonly used CHG preparations [0.5% (w/v) aqueous CHG, 2% (w/v) aqueous CHG and 0.5% (w/v) CHG in 70% (v/v) IPA].

2-Propanol↗

A new Mother-to-Infant Bonding Scale: links with early maternal mood.

Some mothers find it hard to relate to their new baby, and such failure may have long-term effects on the infant. This has been a neglected area of research. A new simple 8 item self-rating mother-to-infant bonding questionnaire has been designed to assess the feelings of a mother towards her new baby. A principal components and reliability analysis demonstrated an alpha score of 0.71. One hundred and sixty two women filled in the Kennerley Blues Scale, the Edinburgh Postnatal Depression Scale (EPDS) the Highs Scale and the new Mother to Infant Bonding Scale on day 3 postpartum. Twelve weeks later they were sent the EPDS and the Bonding scales again. One hundred and forty four returned all questionnaires. There was a strong correlation between the Bonding scores at 3 days and at 12 weeks (r(s)=0.54 p<0.001). Multiple regression analysis showed that those with raised Blues scores had worse, and those with raised Highs scores had better bonding at 3 days. Those with raised EPDS scores at 3 days (13 and over) had worse bonding scores in the "first few weeks" (median 4 versus 1, p = 0.028), as recalled at 12 weeks. This simple questionnaire is acceptable for use with mothers and gives significant correlations with their early mood.

Adult↗

Tear film lipid layer thickness and ocular comfort after meibomian therapy via latent heat with a novel device in normal subjects.

AIM: This study measures changes in tear film lipid layer thickness (LLT) and ocular comfort in normal subjects after 10 min use of a novel device, which delivers meibomian therapy with latent heat. The device is designed to promote the release of meibomian sebum into the tear film by delivering latent heat to the eyelids, thus thickening the lipid layer. Normal lid movements are maintained, facilitating resurfacing of the tear film. METHOD: A prospective, controlled, observer masked, single intervention trial in which 24 normal subjects were randomised into three groups. Group I underwent 10 min treatment with the activated device, Group II used the inactivated device for the same duration of time, and Group III had no intervention. The LLT of each subject was measured with a Keeler Tearscope prior and subsequent to the 10-min period. Subjective alteration in ocular comfort was also assessed. RESULTS: Seven of eight subjects (87.5%) in Group I exhibited an increase in LLT. The mean LLT in this group showed a statistically significant increase (left eyes 1.0 levels, P<0.001, right eyes 0.9 levels, P<0.003) compared to Groups II and III. Six of eight subjects (75%) using the activated device experienced subjective improvement in ocular comfort. CONCLUSION: Meibomian therapy with this device increases LLT in normal individuals. This implies a more stable tear film, reflected in subjective improvement in ocular comfort.

Adult↗

Fetal plasma testosterone correlates positively with cortisol.

BACKGROUND: Fetal exposure to testosterone has been implicated in programming childhood behaviour, but little is known about the determinants of fetal testosterone concentrations. AIMS: To investigate the relation between fetal testosterone and maternal and fetal cortisol. METHODS: Clinically indicated blood samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15-38), together with paired maternal samples, were analysed for testosterone and cortisol concentrations. RESULTS: Male fetuses had significantly higher concentrations of testosterone than females. Female but not male fetal concentrations rose significantly with gestational age. Fetal testosterone correlated positively with both fetal cortisol and maternal testosterone concentrations. Multiple regression showed that maternal testosterone and fetal cortisol were independently correlated with fetal plasma testosterone in both sexes. CONCLUSION: Unlike the norm in the adult, where testosterone production is often inhibited by cortisol, in the fetus there is a positive link between the two.

Adult↗

Four common glomulin mutations cause two thirds of glomuvenous malformations ("familial glomangiomas"): evidence for a founder effect.

BACKGROUND: Glomuvenous malformation (GVM) ("familial glomangioma") is a localised cutaneous vascular lesion histologically characterised by abnormal smooth muscle-like "glomus cells" in the walls of distended endothelium lined channels. Inheritable GVM has been linked to chromosome 1p21-22 and is caused by truncating mutations in glomulin. A double hit mutation was identified in one lesion. This finding suggests that GVM results from complete localised loss of function and explains the paradominant mode of inheritance. OBJECTIVE: To report on the identification of a mutation in glomulin in 23 additional families with GVM. RESULTS: Three mutations are new; the others have been described previously. Among the 17 different inherited mutations in glomulin known up to now in 43 families, the 157delAAGAA mutation is the most common and was present in 21 families (48.8%). Mutation 108C-->A was found in five families (11.8%), and the mutations 554delA+556delCCT and 1179delCAA were present together in two families (4.7% each). Polymorphic markers suggested a founder effect for all four mutations. CONCLUSIONS: Screening for these mutations should lead to a genetic diagnosis in about 70% of patients with inherited GVM. So far, a mutation in glomulin has been found in all GVM families tested, thus demonstrating locus homogeneity.

Adaptor Proteins, Signal Transducing↗

Evaluating the costs of mosquito resistance to malaria parasites.

Costly resistance mechanisms have been cited as an explanation for the widespread occurrence of parasitic infections, yet few studies have examined these costs in detail. A malaria-mosquito model has been used to test this concept by making a comparison of the fitness of highly susceptible lines of mosquitoes with lines that are resistant to infection. Malaria infection is known to cause a decrease in fecundity and fertility of mosquitoes; resistant mosquitoes were thus predicted to be fitter than susceptible ones. Anopheles gambiae were selected for refractoriness/resistance or for increased susceptibility to infection by Plasmodium yoelii nigeriensis. Additional lines that acted as controls for inbreeding depression were raised in parallel but not exposed to selection pressure. Selections were made in triplicate so that founder effects could be detected. Resistance mechanisms that were selected included melanotic encapsulation of parasites within 24 h postinfection and the complete disappearance of parasites from the gut. Costs of immune surveillance were assessed after an uninfected feed, and costs of immune deployment were assessed after exposure to infection and to infection and additional stresses. Mosquito survivorship was unaffected by either resistance to infection or by an increased burden of infection when compared with low levels of infection. In most cases reproductive fitness was equally affected by refractoriness or by infection. Resistant mosquitoes did not gain a fitness advantage by eliminating the parasites. Costs were consistently associated with larval production and egg hatch rate but rarely attributed to changes in blood feeding and never to changes in mosquito size. No advantages appeared to be gained by the offspring of resistant mosquitoes. Furthermore, we were unable to select for refractoriness in groups of mosquitoes in which 100% or 50% of the population were exposed to infection every generation for 22 generations. Under these selection pressures, no population had become completely refractory and only one became more resistant. Variations in fitness relative to control lines in different groups were attributed to founder effects. Our conclusion from these findings is that refractoriness to malaria is as costly as tolerance of infection.

Animals↗

Type 2 diabetes mellitus--genes or intrauterine environment? An embryo transfer paradigm in rats.

AIMS/HYPOTHESIS: The familial predisposition to Type 2 diabetes mellitus is mediated by both genetic and intrauterine environmental factors. In the normal course of events, maternal genes always develop in the same uterus, thus restricting studies aimed at investigating the relative contribution of these factors. We have developed an embryo transfer paradigm in rats to overcome this difficulty. METHODS: Euglycaemic female Wistar rats were superovulated and mated with male Wistar rats. The following day, fertilised eggs were transferred into pseudo-pregnant female Wistar rats or hyperglycaemic Goto Kakizaki (GK) rats. Pregnancies were allowed to go to term. Offspring were weighed at 6 weeks, 3 months and 6 months of age and an intravenous glucose tolerance test was carried out at 6 months of age. RESULTS: Offspring from Wistar into Wistar embryo transfers (n=20) were not significantly hyperglycaemic compared to the non-manipulated Wistar stock colony (n=26). However, offspring from Wistar gametes reared in hyperglycaemic GK mothers (n=51) were significantly lighter at 6 weeks of age (156+/-4.1 g vs 180+/-6.1 g [mean +/- SEM], p<0.01) and significantly more hyperglycaemic at 6 months of age (fasting glucose 6.6+/-0.18 mmol/l vs 4.8+/-0.21 mmol/l, mean blood glucose during glucose tolerance test 14.3+/-0.31 mmol/l vs 11.1+/-0.28 mmol/l, p<0.01) than Wistar gametes transferred back into euglycaemic Wistar mothers. When GK rats were superovulated and mated together, transfer of 1-day-old embryos into pseudo-pregnant Wistar dams did not alleviate hyperglycaemia in adult offspring. CONCLUSIONS/INTERPRETATION: In GK rats, a euglycaemic intrauterine environment cannot overcome the strong genetic predisposition to diabetes. However, in Wistar rats with a low genetic risk of diabetes, exposure to hyperglycaemia in utero significantly increases the risk of diabetes in adult life.

Animals↗

[MRI of the brachial plexus].

Magnetic resonance imaging is the method of choice for the evaluation of brachial plexopathy. Knowledge of the anatomy and normal imaging appearance is required. High-resolution imaging technique is necessary with the use of adequate coils. Evaluation of the brachial plexus requires T1 weighted sequences in three plans, T2 weighted sequences with fat suppression and if necessary the study is completed with gadolinium injection sequences with fat suppression. A CISS sequence is used if a nerve root avulsion is suspected. The spatial resolution must be optimized with the use of adapted parameters. We illustrate a variety of pathologies that can involve the brachial plexus. The pathology includes trauma, primary (neurogenic tumors, lymphomatosis) or secondary tumors, radiation plexopathy or inflammatory polyneuropathy.

Brachial Plexus↗