European guidelines for quality assurance in the surgical management of mammographically detected lesions.
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Breast Neoplasms↗
Biomedical subjects
P Roberts
Publications and source records attributed to P Roberts.
Trough-only monitoring of serum vancomycin concentrations in neonates.
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Adult↗
In vitro and in vivo antifungal activity of amphotericin B lipid complex: are phospholipases important?
Amphotericin B lipid complex for injection (ABLC) is a suspension of amphotericin B complexed with the lipids L-alpha-dimyristoylphosphatidylcholine (DMPC) and L-alpha-dimyristoylphosphatidylglycerol. ABLC is less toxic than amphotericin B deoxycholate (AmB-d), while it maintains the antifungal activity of AmB-d. Active amphotericin B can be released from ABLC by exogenously added (snake venom, bacteria, or Candida-derived) phospholipases or by phospholipases derived from activated mammalian vascular tissue (rat arteries). Such extracellular phospholipases are capable of hydrolyzing the major lipid in ABLC. Mutants of C. albicans that were resistant to ABLC but not AmB-d in vitro were deficient in extracellular phospholipase activity, as measured on egg yolk agar or as measured by their ability to hydrolyze DMPC in ABLC. ABLC was nevertheless effective in the treatment of experimental murine infections produced by these mutants. Isolates of Aspergillus species, apparently resistant to ABLC in vitro (but susceptible to AmB-d), were also susceptible to ABLC in vivo. We suggest that routine in vitro susceptibility tests with ABLC itself as the test material may not accurately predict the in vivo activity of ABLC and that the enhanced therapeutic index of ABLC relative to that of AmB-d in vivo may be due, in part, to the selective release of active amphotericin B from the complex at sites of fungal infection through the action of fungal or host cell-derived phospholipases.
Amphotericin B↗
Pulmonary tuberculosis in Harare, Zimbabwe: analysis by spoligotyping.
BACKGROUND: Over the last 10 years there has been a fourfold increase in cases of tuberculosis in Harare, Zimbabwe. The use of molecular epidemiology to understand tuberculosis transmission in this epidemic has been hampered by the availability of suitable culture facilities. A study was therefore undertaken to explore the potential of spoligotyping, a polymerase chain reaction based technique that does not require tuberculosis culture. METHODS: Adults attending a chest clinic with clinical or radiological pulmonary tuberculosis and one smear positive sputum were enrolled over one month. Demographic, socioeconomic, and clinical data were gathered using a standardised questionnaire. Molecular fingerprinting of genomic DNA recovered from sputum was performed by spoligotyping. RESULTS: Sixty one subjects (median age 28 years (range 18-73); 61% men) were recruited and 57 provided adequate sputum samples. Recent rural-urban migration or immigration was not common; 40% of subjects lived in crowded living conditions. DNA suitable for spoligotyping was recovered from 28 patients and 20 different genotypes of Mycobacterium tuberculosis were identified. Fifteen patients were infected with an M tuberculosis strain shared by one or more individuals. Patients infected with a shared spoligotype were not closely linked geographically within Harare, but were more likely to live in overcrowded conditions (69% versus 23%; odds ratio 6.85 (95% CI 1.2 to 47), p = 0.026). Analysis of the patients' original rural family homes revealed two geographically related spoligotype clusters. CONCLUSIONS: Spoligotyping may yield valuable molecular typing information in populations where tuberculosis culture is not available. This novel technique requires further development and evaluation in larger epidemiological studies.
Adolescent↗
Annual cycle in LH and testosterone release in response to GnRH challenge in male woodchucks (Marmota monax).
Testosterone and LH concentrations were determined in serum samples obtained before and 15 min after injections of GnRH (1 microgram kg-1) administered at 4-7 week intervals over 20 months to groups of male woodchucks (n = 6-7) born and maintained in Northern Hemisphere (boreal) versus Southern Hemisphere (austral) simulated natural photoperiods, beginning at 18-24 months of age. Nadir and peak unstimulated testosterone (0.1 +/- 0.01 and 7.0 +/- 0.1 ng ml-1, respectively) and LH (0.8 +/- 0.2 and 8.1 +/- 1.1 ng ml-1, respectively) concentrations did not differ in boreal versus austral males. In the five boreal and five austral males that were confirmed to be photoentrained, basal (pre-GnRH) concentrations of LH and testosterone were lowest in summer, increased simultaneously in late autumn or early winter, and declined in the spring. GnRH stimulated some LH release throughout the year except for a 1-4 month period in the summer. The initial annual increase in the LH response to GnRH occurred in early autumn, and in 17 of 20 cycles it occurred 1-2 months before the initial increase in basal LH was detected. In the three free-running males not entrained to the photoperiod, the endocrine patterns were similar but were advanced by several months. The results demonstrate that in woodchucks there is a late autumn increase in LH secretion associated with the onset of testicular recrudescence, and an early autumn increase in pituitary response to GnRH before a detectable increase in serum testosterone.
Animals↗
Intensive cardiovascular risk factor intervention in a rural practice: a glimmer of hope?
BACKGROUND: Large trials of primary care-based health promotion to modify coronary heart disease risks have shown only modest benefits. Could more intensive intervention, with doctors sharing with practice nurses in health promotion, produce better health outcomes in the context of the small family practice? How cost-effective might these interventions be? AIM: To assess the cost-effectiveness of an intensive programme of coronary heart disease (CHD) risk factor modification in a rural general practice in which doctors had a major input. METHOD: A longitudinal study of changes in risk factors in a group of adult patients identified as having one or more major CHD risk factor and monitored for one to seven years. Patients were recruited from and followed up in health promotion clinics, routine practice nurse appointments, or routine doctors' surgeries. All received the practice's routine interventions to modify risk, and changes in risk factors were recorded. Time spent by members of the primary health care team on CHD health promotion was recorded over a two-year period. RESULTS: From a practice list of 2040, 760 patients with one or more CHD risk factors were identified and followed up over a mean of 3.61 years (range six months to seven years). Significant improvements in each of the risk factors occurred, except in body mass index (BMI). Mean Dundee risk scores fell from 7.4 to 5.7 (by 23.3%). The annual cost to the practice (including doctor/nurse/secretarial time plus sundry practice expenses and laboratory costs, but excluding drug costs) was 6000 pounds. Cost per coronary death prevented was calculated as approximately 10,000 pounds. CONCLUSION: The results show an effect on risk factors broadly similar but slightly greater in magnitude than that achieved in the OXCHECK and British Family Heart Studies of nurse-delivered risk factor intervention in primary care. The results suggest that more intensive effort in lifestyle modification and health promotion, with more active involvement of doctors, could produce significant additional benefit. The cost-effectiveness of this approach compares favourably with many other accepted measures in coronary heart disease prevention.
Aged↗
Enhancement of the in vivo circulation lifetime of L-alpha-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization.
Incorporation of N-(omega-carboxy)acylamido-phosphatidylethanolamines (-PEs) into large unilamellar vesicles (LUVs) of L-alpha-distearoylphosphatidylcholine (DSPC) was found to dramatically increase the in vivo liposomal circulation lifetime in rats, reaching a maximal effect at 10 mol.% of the total phospholipid. Neither pure DSPC liposomes nor those with the longest circulating derivative, N-glutaryl-dipalmitoylphosphatidylethanolamine (-DPPE), were found to significantly bind complement from serum. Therefore, the relatively short circulation time of pure DSPC liposomes did not appear to be related to greater complement opsonization leading to uptake by the reticuloendothelial system. However, N-(omega-carboxy)acylamido-PEs were particularly efficient inhibitors of a limited aggregation detected for pure DSPC liposomes. The aggregation tendency of DSPC liposomes incorporating various structural analogs of N-glutaryl-DPPE correlated inversely with the circulation lifetimes. Therefore, it is concluded that such PE derivatives enhance the circulation time by preventing liposomal aggregation and avoiding a poorly understood mechanism of clearance that is dependent on size but is independent of complement opsonization. At high concentrations of N-glutaryl-DPPE (above 10 mol.%), the liposomes exhibited strong complement opsonization and were cleared from circulation rapidly, as were other highly negatively charged liposomes. These data demonstrate that both the lack of opsonization and the lack of a tendency to aggregate are required for long circulation. Liposomal disaggregation via N-(omega-carboxy)acylamido-PEs yields a new class of large unilamellar DSPC liposomes with circulation lifetimes that are comparable to those of sterically stabilized liposomes.
Amino Acids↗
Achieving interprofessional working in mental health.
Interprofessional collaboration in health care has been high on the political agenda in recent years. However, despite several government reports, progress has been relatively slow. Several structural and organisational challenges need to be addressed, alongside the development of valid research in this field, to accelerate the pace of change. This article describes how interprofessional education, in conjunction with service initiatives, offers a way forward for the development of collaborative practice based on users' and carers' needs.
Health Personnel↗
Inv(10)(p11.2q21.2), a variant chromosome.
We present 33 families in which a pericentric inversion of chromosome 10 is segregating. In addition, we summarise the data on 32 families in which an apparently identical inv(10) has been reported in the literature. Ascertainment was through prenatal diagnosis or with a normal phenotype in 21/33 families. In the other 12 families, probands were ascertained through a wide variety of referral reasons but in all but one case (a stillbirth), studies of the family showed that the reason for referral was unrelated to the chromosome abnormality. There has been, to our knowledge, no recorded instance of a recombinant chromosome 10 arising from this inversion and no excess of infertility or spontaneous abortion among carriers of either sex. We propose that inv(10)(p11.2q21.2) can be regarded as a variant analogous to the pericentric inversion of chromosome 2(p11q13). We conclude that prenatal chromosome analysis is not justified for inv(10) carriers. In addition, family investigation of carrier status is not warranted in view of the unnecessary concern this may cause parents and other family members.
Abortion, Spontaneous↗
Efficient removal of viruses by a novel polyvinylidene fluoride membrane filter.
Virus removal by a novel filter (Ultipor VF DV50), comprising three layers of PVDF membrane, has been evaluated by infectivity studies using a range of viruses and conditions. The filter was able to remove at least 6 log of various viruses, i.e. Sindbis and Semliki Forest (40-70 nm), herpes simplex (120-200 nm) and vaccinia (200 x 350 nm), from cell-culture medium or phosphate buffered saline pH 6.8 containing 0.5% albumin. However, the removal of polio virus (25-30 nm) under these conditions was only limited, i.e. about 1 log. This filter is thus effective for removing viruses of about 50 nm or larger. Proteins as large as immunoglobulins (MW 160,000), were able to pass through the filter with recoveries of at least 85%. Due to its ability to remove viruses of medium to large size, this filter shows potential for increasing the safety of biological products where viruses such as hepatitis B, C, herpes and retroviruses are of concern.
Evaluation Studies as Topic↗
Gain of chromosome arm 17q predicts unfavourable outcome in neuroblastoma patients. U.K. Children's Cancer Study Group and the U.K. Cancer Cytogenetics Group.
Gain of chromosome arm 17q has recently been reported in neuroblastoma tumours. We analysed 17q status in relation to other known prognostic features and clinical outcome in a series of 45 tumours. Chromosome 17 status was detected by cytogenetic analysis, fluorescence in situ hybridisation (FISH) anc comparative genomic hybridisation (CGH) and correlated with other clinical and genetic factors. Survival analysis was calculated by the Kaplan-Meier estimation. Twenty-eight out of 45 tumours showed 17q gain, and this was associated with established indicators of poor prognosis; stage 4 disease (P < 0.001), age above 1 year at diagnosis (P < 0.001), 1p deletion (P < 0.01), MYCN amplification (P = 0.03) and diploidy/tetraploidy (P = 0.04). 17q gain was associated with poor outcome: 3-year survival was 13.5% compared with 100% for tumours without 17q gain (P = 0.0001); and progression-free survival (PFS) was 8.1% after 3 years compared with 83% for 17q normal tumours (P = 0.0001). PFS in 28 MYCN non-amplified patients indicated that 17q status has discriminatory power within this group: PFS 0% for 17q gain (n = 14) versus 100% for normal 17q (n = 14) (P = 0.0001). This study indicates that 17q changes have prognostic significance in neuroblastoma and should be a target for molecular cytogenetic detection at diagnosis.
Adolescent↗
Hepatitis A transmission by factor IX concentrates: control by severe dry heat treatment at 80 degrees C.
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Factor IX↗
The host environment determines strain-specific differences in the timing of skeletal muscle regeneration: cross-transplantation studies between SJL/J and BALB/c mice.
The difference in the timing of the regeneration process of skeletal muscle between SJL/J and BALB/c mice was investigated using grafts of whole skeletal muscle (both autografts and allografts). Histological, autoradiographic and immunohistochemical techniques were used in the investigation. Infiltration of leucocytes into autografts, numbers of desmin-positive myogenic cells and myotube formation were all more advanced in the SJL/J compared with BALB/c mice. Furthermore, autoradiographic evidence showed that myoblasts in the SJL/J autografts were synthesising DNA 12 h earlier than myoblasts in BALB/c autografts. In allografts, where SJL/J host mice received BALB/c grafts, and vice versa, leucocyte infiltration and myotube formation occurred earlier in the BALB/c muscles grafted into SJL/J hosts, than in the reverse situation with BALB/c hosts. The results show that, at least for whole muscle grafts, it is the host environment which determines the speed and outcome of the regenerative process.
Animals↗
Antecedent antimicrobial use increases the risk of uncomplicated cystitis in young women.
To examine whether antecedent antimicrobial use influenced subsequent relative risk of urinary tract infection (UTI) in premenopausal women, data were analyzed from two cohorts of women observed prospectively for 6 months to determine risk factors for UTI. Using a Cox proportional hazards model to adjust for covariates, we found that 326 women in a University cohort and 425 women in a health-maintenance organization cohort were at increased risks for UTI (2.57 [95% confidence interval (CI), 1.24-5.32] and 5.83 [95% CI, 3.17-10.70], respectively) if antimicrobials had been taken during the previous 15-28 days but not during the previous 3, 7, or 14 days. The increased risks were noted both for women whose antimicrobial use was for treatment of a previous UTI and for women who received antimicrobials for other illnesses. These results suggest that recent antimicrobial use increases a woman's risk of UTI, perhaps by altering the indigenous urogenital flora and predisposing to vaginal colonization with uropathogens.
Adolescent↗
Long-term entrainment of circannual reproductive and metabolic cycles by Northern and Southern Hemisphere photoperiods in woodchucks (Marmota monax).
Woodchucks were exposed to simulated Northern Hemisphere (boreal) or Southern Hemisphere (austral) natural photoperiods in groups of 17 males and 17-18 females at 20-23 degrees C for 69 mo and examined monthly. Photoentrainment of endogenous cycles was evaluated based on dates of peak body weight, peak testis volume, increased serum testosterone in males, and increased serum progesterone in females. Boreal photoperiods entrained and synchronized annual cycles in 15 of 17 males and in all 17 females; 2 males never entrained and free-ran at 9- to 11-mo intervals. Austral photoperiods phase-advanced cycles by approximately 6 mo after 2.5 yr in 34 of 35 animals. Four entrained males became refractory after 4 yr, free-running at 6- to 10-mo intervals. Photoentrained boreal animals became phase-advanced by 1 mo during the first 2 yr, and then had 12-mo cycles for 4 yr. In Year 5, on average, boreal cycles included initial testosterone elevations in mid-January (vs. mid-July in australs), parturition in early March (vs. early September in australs), and peak body weight in mid-July (vs. late January in australs). The results confirm that endogenous circannual cycles of woodchucks can be entrained and synchronized for 6 yr by daily changes in photoperiod similar to those of midnorthern latitudes, and can be re-entrained and phase-advanced 6 mo by photoperiods of midsouthern latitudes.
Animals↗
Hip and ankle range of motion in elite classical ballet dancers and controls.
OBJECTIVE: To report range of motion at the hip and ankle in male and female ballet dancers compared with controls. DESIGN: Cross-sectional cohort study with convenience control sample. SETTING: National classical ballet school in Australia. PARTICIPANTS: Thirty-three female and 30 male full-time ballet students of mean (SD) age 16.9 (0.8) and 18.0 (1.4) years, respectively. Controls were 31 female and 16 male nondancing, normally active university students of average ages 18.8 +/- 0.6 and 18.8 +/- 0.9 years, respectively. MAIN OUTCOME MEASURES: Degrees of range of motion of left and right sides for the following four movements: standing plié in parallel-passive ankle dorsiflexion (DF), standing turnout in the balletic first position-lower limb external rotation (LLER), supine hip external rotation (ER), supine hip internal rotation (IR). Two additional ranges of motion were calculated. External rotation below the hip joint (BHER) was derived by subtracting hip ER from LLER, and total supine hip rotation (Hip IR + ER) was derived by summing hip ER and hip IR. MAIN RESULTS: On both left and right sides, dancers had greater LLER (p < 0.0001) and hip ER (p < 0.0001) but lesser hip IR than the controls (p < 0.0001). Female but not male dancers had greater total supine hip rotation (hip ER+IR) than controls (p < 0.05). There was no difference in either BHER or ankle DF between dancers and controls. Within dancers, females had greater range in both left and right hip IR, LLER, and hip IR + ER. There was no difference in hip ER. Regression analysis revealed that LLER related to hip ER in both males and females. CONCLUSIONS: Elite classical dance students had greater hip external rotation (both ER and LLER) and less hip internal rotation than controls but similar BHER and ankle DF. Since ER below the hip joint and ankle DF do not differ between dancers and controls, despite repeated training of these movements in ballet, there may be anatomical (bony/ligamentous) limitations to these movements.
Ankle Joint↗
Saccharomyces cerevisiae Nip7p is required for efficient 60S ribosome subunit biogenesis.
The Saccharomyces cerevisiae temperature-sensitive (ts) allele nip7-1 exhibits phenotypes associated with defects in the translation apparatus, including hypersensitivity to paromomycin and accumulation of halfmer polysomes. The cloned NIP7+ gene complemented the nip7-1 ts growth defect, the paromomycin hypersensitivity, and the halfmer defect. NIP7 encodes a 181-amino-acid protein (21 kDa) with homology to predicted products of open reading frames from humans, Caenorhabditis elegans, and Arabidopsis thaliana, indicating that Nip7p function is evolutionarily conserved. Gene disruption analysis demonstrated that NIP7 is essential for growth. A fraction of Nip7p cosedimented through sucrose gradients with free 60S ribosomal subunits but not with 80S monosomes or polysomal ribosomes, indicating that it is not a ribosomal protein. Nip7p was found evenly distributed throughout the cytoplasm and nucleus by indirect immunofluorescence; however, in vivo localization of a Nip7p-green fluorescent protein fusion protein revealed that a significant amount of Nip7p is present inside the nucleus, most probably in the nucleolus. Depletion of Nip7-1p resulted in a decrease in protein synthesis rates, accumulation of halfmers, reduced levels of 60S subunits, and, ultimately, cessation of growth. Nip7-1p-depleted cells showed defective pre-rRNA processing, including accumulation of the 35S rRNA precursor, presence of a 23S aberrant precursor, decreased 20S pre-rRNA levels, and accumulation of 27S pre-rRNA. Delayed processing of 27S pre-rRNA appeared to be the cause of reduced synthesis of 25S rRNA relative to 18S rRNA, which may be responsible for the deficit of 60S subunits in these cells.
Alleles↗
Estrus, fertility, early embryo development, and autologous embryo transfer in laboratory woodchucks (Marmota monax).
Reproductive parameters were studied in female laboratory woodchucks over a 6-year period. The pregnancy rate in adult females after ad libitum exposure to a male (n = 643) was 72%; that after limited (4 to 8 h) exposure with video observations (n = 31) was only 37%. However, limited exposure resulted in a 75% ovulation rate, suggesting a problem with fertilization and not ovulation. The ovulation rate was 0% in the absence of mating (n = 10), suggesting that spontaneous ovulation is not the usual situation in this species. With ad libitum mating, fertility was greater (P < 0.05) for 2- to 4-year-old females (73%) than for 1-year-old (56%) or > or = 5-year-old (58%) females. Mean (+/-SEM) litter size at birth was greater (P < 0.05) for 2- to 5-year-old animals (4.0 +/- 0.1) than for 1-year-old animals (2.9 +/- 0.2). However, in 1-year-old females the neonatal mortality was low, and the litter size at weaning (2.4 +/- 0.3 pups) did not differ from that of older females (2.7 +/- 0.1 pups). The measurement of vulval diameter every 3 to 4 days in 31 adult females suggested that enlargement to > or = 7 mm was indicative of proestrus or estrus and was a good indicator of willingness to accept mounting by males. Vulval swelling > or = 7 mm (n = 31) lasted 5 to 47 days. Fertile mating occurred from 3 to 30 days after vulval diameter reached > or = 7 mm, near the time of peak enlargement (10.1 +/- 0.2 mm), and was followed in several days by a decrease in vulval size. Fifty-three females were allowed only limited (6 to 10 h) video-observed exposure to males, with (n = 26) or without (n = 27) another 12 to 24 h of unobserved exposure, and were examined surgically for ovulation and pregnancy at known times after mating. There were no consistent differences among nonovulating, ovulating nonfertile, and fertile females in the longest duration of mating (7.2 +/- 0.4 min) or in the number of matings lasting > or = 1 min (5.7 +/- 0.8). Compared with nonfertile females, fertile females experienced more matings > or = 3 min in duration (3.3 +/- 0.4 versus 1.8 +/- 0.2) and > or = 5 min in duration (2.9 +/- 0.4 versus 1.1 +/- 0.1). At postmating days 1, 2, 3, 4, 5, 6, and 7 the embryos were observed to be 1-, 4-, 4- to 32-cell morulae, 16- to 60-cell morulae, free-floating blastocysts, anti-measometrial peri-implantation blastocysts, and attached blastocysts respectively. Autologous transfer of day-5 uterine embryos of normal appearance into the noncontiguous contralateral uterine horn was performed in five females that had been subjected to a hemi-ovariectomy. Transfers resulted in pregnancy and litters in four of the five females. The results suggest that this large, circannual sciurid rodent can be successfully and predictably bred as a laboratory animal model, has vulval changes indicative of proestrus, is principally an induced ovulator, has an early embryo development rate similar to that of rats and mice, and may be amenable to reproductive technologies developed for more common laboratory rodents.
Animals↗