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Biomedical subjects

R Holland

Publications and source records attributed to R Holland.

At least 37 records · Page 2Linked to original sources
PubMed2003

The potential of dairy lactic acid bacteria to metabolise amino acids via non-transaminating reactions and endogenous transamination.

The metabolism of amino acids by 22 starter and 49 non-starter lactic acid bacteria (LAB) was studied in a system consisting of amino acids and non-growing cells without added amino acceptors such as alpha-ketoglutarate. There were significant inter- and intra-species differences in the metabolism of amino acids. Some amino acids such as alanine, arginine, aspartate, serine and branched-chain amino acids (leucine, isoleucine and valine) were utilised, whereas other amino acids such as glycine, ornithine and citrulline were produced. Alanine and aspartate were utilised by some LAB and accumulated during the incubation of other LAB. Arginine was degraded not only by Lactococcus lactis subsp. lactis (the lactococcal subspecies known to catabolise arginine), but also by pediococci, heterofermentative lactobacilli (Lactobacillus brevis and Lb. fermentum) and some unidentified homofermentative lactobacilli. Serine was utilised predominantly by homofermentative Lb. paracasei subsp. paracasei, Lb. rhamnosus and Lb. plantarum. Of the LAB studied, Lb. brevis and Lb. fermentum were the most metabolically active, utilising alanine, arginine, aspartate, glutamate and branched-chain amino acids. Leuconostocs were the least metabolically active, showing little potential to metabolise amino acids. The formation of ammonia and acetate from amino acid metabolism varied both between species and between strains within species. These findings suggest that the potential of LAB for amino acid metabolism via non-transaminating reactions and endogenous transamination will impact both on the physiology of LAB and on cheese ripening, especially when transamination is rate-limiting in the absence of an exogenous amino acceptor such as alpha-ketoglutarate.

Amino Acids↗
PubMed2003

Ester synthesis in an aqueous environment by Streptococcus thermophilus and other dairy lactic acid bacteria.

The ability of Streptococcus thermophilus ST1 and 19 other dairy lactic acid bacteria (LAB) to synthesize esters was investigated in an aqueous environment. These LAB were able to synthesize esters from alcohols and glycerides via a transferase reaction (alcoholysis) in which fatty acyl groups from glycerides were transferred to alcohols. S. thermophilus ST1 was active on tributyrin and on di- or monoglycerides of up to C10 with ethanol as the acyl acceptor. This strain was also active on a diglyceride of C6 and monoglyceride of C8 with 2-phenyl ethanol as the acyl acceptor. Alcoholysis occurred preferentially over hydrolysis. S. thermophilus ST1 had an apparent K(m) value of 250 mM for ethanol and an apparent K(m) value of 1.3 mM for tributyrin, measured against whole cells. Around 80% of both the transferase activity and the esterase activity were detected in the cell-free extract (CFE) of strain ST1. Both activities in the CFEs of five LAB tested were, to a similar degree, enhanced slightly by growth in the presence of ethanol and tributyrin. Using tributyrin and ethanol as substrates, the transferase activities ranged over 0.006-1.37 units/mg cell dry weight among the LAB tested and were both species- and strain-dependent.

Alcohols↗
PubMed2003

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

Breast Neoplasms↗
PubMed2003

Use of previous screening mammograms to identify features indicating cases that would have a possible gain in prognosis following earlier detection.

False-negative screening mammograms generally refer to breast cancers that were overlooked or misinterpreted at screening. An important question is whether earlier detection could have made a difference in the prognosis of the women concerned. We reviewed screening and diagnostic mammograms of 234 screen-detected and interval cancer cases (aged 44-84 years) diagnosed between 1991 and 1996 in the Nijmegen breast cancer screening programme. A lesion was visible on 117 (50%) of the screening mammograms prior to the diagnosis of breast cancer. Fifty-one out of the 117 cancers had poor prognostic characteristics at diagnosis (i.e. N+ and/or T2+) and could potentially have benefited from an earlier diagnosis ('possible gain'). The 'possible gain' cases were more often characterised by architectural distortion (29 vs. 10%; P=0.01) or a high-density mass (25 vs. 13%; P=0.06) on the mammogram prior to diagnosis than the 58 'no gain' cases. Our study shows that architectural distortion and non-spiculated high-density masses on the mammogram prior to diagnosis are associated with a possible gain in prognosis. Earlier detection of the carcinomas preceded by these signs may well have an impact on breast cancer mortality and thus warrant extra attention in radiological practice.

Adult↗
PubMed2003

Interobserver variability between general and expert pathologists during the histopathological assessment of large-core needle and open biopsies of non-palpable breast lesions.

The purpose of this study was to assess whether general pathologists are able to make as accurate and reproducible a diagnosis on large-core needle biopsies as on open breast biopsy specimens. A total of 688 patients underwent a stereotactic large-core (14G) needle biopsy and subsequent surgical excision of 718 non-palpable breast lesions. Forty-two pathologists from 10 departments of pathology (generalists) made a diagnosis on both the needle and open biopsy specimens. Afterwards, three pathologists and two radiologists with extensive experience in breast pathology (experts) diagnosed all of the biopsy specimens. The general pathologists made a similar histological diagnosis as the experts in 632 (88%) of the needle biopsies and 649 (90%) of the open biopsy specimens. Accordingly, the interobserver agreement for the diagnosis of large-core needle biopsies between the general and experts pathologists was excellent (kappa 0.83) and not significantly different from the interobserver agreement for the diagnosis of open breast biopsies (kappa 0.86). However, many inconsistencies were observed in the category of borderline lesions: only 24% of the large-core needle biopsies and 43% of the open biopsies with an expert diagnosis of 'borderline' were diagnosed similarly by the general pathologists. Additionally, the risk of benign/malignant inconsistencies between general pathologists and experts was approximately 1 in 55 for both needle and open biopsies.

Adult↗
PubMed2002

Diagnostic strategies in non-palpable breast lesions.

The number of non-palpable breast lesions is growing. Needle-localised breast biopsy (NLBB) is the gold standard for evaluating these lesions. Cost-saving techniques and less invasive alternatives such as core-needle biopsy (LCNB) and fine-needle aspiration (FNA) have emerged. The aim of this study was to find out if the lesions of patients who were sent directly for surgery to undergo a NLBB differed from lesions of patients who were send for a non-operative procedure. Furthermore, if a benign result was obtained, we assessed the total and kind of subsequent diagnostic procedures that were undertaken. A retrospective study on 718 women with 749 non-palpable breast lesions was performed. In 58% of women with non-palpable breast lesion, a non-surgical procedure was chosen. Lesions sent directly for surgery were more frequently not visible on ultrasound (62%) and mainly consisted of microcalcifications only (56%). In 45%, this primary surgical approach could have been avoided. If the non-operative procedure showed a non-malignant result, 41% of these women received an additional surgical diagnostic procedure. These figures obtained from routine daily practice show the importance of protocols in order to standardise diagnostic procedures and prevent unnecessary surgery.

Adult↗
PubMed2002

An analysis of predictors of success in Part II MFPHM. Membership of the Faculty of Public Health Medicine.

BACKGROUND: The examination for Part II of the Membership of the Faculty of Public Health Medicine (MFPHM) has been held since 1974. Candidates and examiners have hypothesized a number of factors as likely to increase the chances of success in the exam. This study formally investigates factors which may predict a candidate's success at their first attempt. METHODS: Routinely available data on candidates sitting the exam from March 1996 to June 1999 were examined initially by univariate analysis. A logistic regression model was then constructed entering all variables identified as statistically significant as well as the following variables initially thought to be relevant (a priori hypotheses): age, sex, university versus NHS training location; splitting competencies evenly across two reports; and training within North Thames deanery. RESULTS: Four factors were identified as statistically significant within the logistic regression model. These were: possession of either MRCP (odds ratio (OR) of failure = 0.33, p = 0.003) or MRCGP (OR = 0.45, p = 0.016), success at UK Part I at first attempt (OR = 0.42, p = 0.014), and North Thames training (OR = 0.44, p = 0.048). CONCLUSION: Possession of MRCP or MRCGP, or passing UK Part I MFPHM are factors not normally open to change by candidates once they begin working towards Part II MFPHM. Training in North Thames was also identified as an independent predictor of success. It would seem advisable to investigate in further detail whether candidate selection (not adjusted for in the model) or aspects of the North Thames training programme are responsible for this observed phenomenon.

Adult↗
PubMed2002

Repeated mammographic screening reduces breast cancer mortality along the continuum of age.

OBJECTIVE: The optimal age boundaries for breast cancer screening are still under debate. A case-referent design was used to describe the effect of mammographic screening on breast cancer mortality along the continuum of age, based on a 20 year follow up period. SETTING: The population based breast cancer screening programme in Nijmegen, The Netherlands, which has biennially invited women over 35 years since 1975. METHODS: Cases, defined as women who died from primary breast cancer between 1987 and 1997, were selected from the group of women who received at least one invitation to the screening programme. For 157 cases, 785 women from the same group were selected as referents. Information on the index screening (the screening examination preceding diagnosis of the case) was collected for both cases and referents. The risk of dying from breast cancer was calculated per 10 year moving age group for women who had attended the index screening versus those who had not. RESULTS: The youngest 10 year age group showing an effect in our study were women aged 45-54 at their index screening. Breast cancer mortality for women in this group who attended the index screening was 32% lower, although not significant, than for women who did not (odds ratio (OR) 0.68, 95% confidence interval (95% CI) 0.33 to 1.41). This reduction in risk was not explained solely by an effect in women over 50 because the OR in women aged 45-49 was 0.56 (95% CI 0.20 to 1.61). Reductions in mortality became smaller with increasing age. Nevertheless, for women over 60 at index screening, participation in screening over a maximum 4 year period before diagnosis of the case yielded protective effects at least up to an age around 80. CONCLUSIONS: Although our results are based on a relatively small number of cases, they suggest that even in a programme with a 2 year screening interval there may be a benefit of starting screening around age 45. Also older women who participate at least once every 4 years still have much to gain from screening.

Adult↗
PubMed2002

Molecular epidemiology of tuberculosis in London 1995-7 showing low rate of active transmission.

BACKGROUND: Tuberculosis notification rates for London have risen dramatically in recent years. Molecular typing of Mycobacterium tuberculosis has contributed to our understanding of the epidemiology of tuberculosis throughout the world. This study aimed to assess the degree of recent transmission of M tuberculosis in London and subpopulations of the community with high rates of recent transmission. METHODS: M tuberculosis isolates from all persons from Greater London diagnosed with culture positive tuberculosis between 1 July 1995 and 31 December 1997 were genetically fingerprinted using IS6110 restriction fragment length polymorphism (RFLP) typing. A structured proforma was used during record review of cases of culture confirmed tuberculosis. Cluster analysis was performed and risk factors for clustering were examined in a univariate analysis followed by a logistic regression analysis with membership of a cluster as the outcome variable. RESULTS: RFLP patterns were obtained for 2042 isolates with more than four copies of IS6110; 463 (22.7%) belonged to 169 molecular clusters, which ranged in size from two (65% of clusters) to 12 persons. The estimated rate of recent transmission was 14.4%. Young age (0-19 years) (odds ratio (OR) 2.65, 95% confidence interval (CI) 1.59 to 4.44), birth in the UK (OR 1.55, 95% CI 1.04 to 2.03), black Caribbean ethnic group (OR 2.19, 95% CI 1.15 to 4.16), alcohol dependence (OR 2.33, 95% CI 1.46 to 3.72), and streptomycin resistance (OR 1.82, 95% CI 1.15 to 2.88) were independently associated with an increased risk of clustering. CONCLUSIONS: Tuberculosis in London is largely caused by reactivation or importation of infection by recent immigrants. Newly acquired infection is also common among people with recognised risk factors. Preventative interventions and early diagnosis of immigrants from areas with a high incidence of tuberculosis, together with thorough contact tracing and monitoring of treatment outcome among all cases of tuberculosis (especially in groups at higher risk of recent infection), remains most important.

Adolescent↗
PubMed2001

Diverging breast cancer mortality rates in relation to screening? A comparison of Nijmegen to Arnhem and the Netherlands, 1969-1997.

Age-standardised breast cancer mortality rates have been stable for decades. However, rates have started to decline in several Western countries. In countries where population-based screening programmes for breast cancer were introduced in the late 1980s or early 1990s, the key question now is to what extent screening is responsible for the reported declines in mortality. This study compares breast cancer mortality rates in Nijmegen, where a screening programme for breast cancer was introduced in 1975, to a control city, Arnhem, and to the Netherlands as a whole over a 20-year period. Age-standardised breast cancer mortality rates as well as age-standardised mortality ratios were calculated for successive calendar years from 1969 to 1997. Further, a tailor-made period-cohort-group Poisson regression model was fitted. Figures displaying age-standardised mortality rates and ratios showed inconclusive patterns with regard to the expected impact of screening. Depending on when mortality rates were allowed to deviate between populations, the period-cohort-group analysis indicated a non-significant 6% to 16% reduction in breast cancer mortality after 2 decades in favour of the Nijmegen female population. Possible explanations are discussed as to why the mortality reductions reported by randomised trials might not be observed in a public health screening programme, such as the Nijmegen programme, evaluated by comparisons of geographical trends.

Aged↗
PubMed2001

[Diagnostics in clinically occult, radiologically suspect breast lesions more often surgery than needle diagnostics with image monitoring].

OBJECTIVE: To inventory the diagnostic methods used in patients with clinically occult, radiologically suspect breast lesions. DESIGN: Enquiry. METHOD: The departments of radiology of all Dutch hospitals were sent a list in January 2000 containing questions concerning the number of thread localizations in 1999 and the use of cytological or histological needle diagnostics with image monitoring prior to surgical intervention in clinically occult, radiologically suspect breast lesions. Of the 120 questionnaires mailed, 74 (62%) were completed and returned by clinics throughout the country. RESULTS: Fifty-one of the 74 hospitals (69%) had prior to operation carried out histological or cytological examinations and in these 51 hospitals this was done in 1743 of the 2857 lesions (61%): fine-needle aspiration cytology was performed in 1046 (/1743 = 60%; /4140 lesions in all 74 hospitals = 25%) and/or histological needle biopsy in 784 (45%; /4140 = 19%). CONCLUSION: In less than half of all non-palpable breast abnormalities non-surgical methods of diagnosis are used, histological needle biopsy less often than fine needle aspiration cytology.

Biopsy↗
PubMed2001

Breast carcinomas of limited extent: frequency, radiologic-pathologic characteristics, and surgical margin requirements.

BACKGROUND: Clinical trials established the value of breast-conserving treatment (BCT) including the macroscopic removal of the tumor followed by local radiation therapy (RT) for Stage I and II invasive carcinomas. The occurrence of local tumor recurrence is related to the extent and multifocality of the tumor. Various studies aim to identify those tumors that could be proper candidates for conventional BCT. Furthermore, recent studies have focused on the identification of tumors that may be treated by breast-conserving surgery alone without RT. Small, localized tumors theoretically should be the potential candidates for this type of treatment. The mammographic and pathologic criteria for the identification of tumors with limited extent are not yet established; furthermore, the optimal extent of the surgical excision and the method for margin examination are controversial. METHODS: Surgical breast-conserving procedures were simulated in a review of 135 mastectomy specimens of patients treated for an invasive carcinoma (> or = 4 cm in size, all pathologic types except invasive lobular carcinoma) who were theoretically eligible for conservative treatment. Tumor spread including possible multifocality and multicentricity was studied by the technique of correlated specimen radiography and pathology. Breast carcinoma of limited extent (BCLE), the proper tumor profile for BCT, was defined as having no invasive carcinoma, ductal carcinoma in situ, and lymphatic emboli foci beyond 1 cm from the edge of the dominant mass. RESULTS: Fifty-three percent of the patients in this series had a BCLE. No statistically significant relation was found between BCLE and patient age, pathologic size, type and grade of the tumor, lymph node status, mode of detection, and mammographic aspect of the index tumor. Based on mammography, the absence of calcification or tumor density beyond the edge of index tumor appears to be the best predictor for BCLE (P < 0.0001). A 1-cm microscopically tumor free margin as the outer rim of a macroscopic surgical margin of 2 cm gives the best positive predictive value based on pathology (P < 0.0001). By applying the above conditions, 72 of the 135 cancers were identified as being potential BCLE cases in this series. However, whereas 64 of these 72 tumors (89%) were correctly identified as being true BCLE, 8 (11%) were erroneously identified as such (non-BCLE cases), having "residual" tumor foci beyond 2 cm from the edge of the dominant tumor. CONCLUSIONS: We conclude, that approximately 50% of invasive ductal carcinomas may have limited extent. The accuracy of identifying this group of cancers, the proper candidates for BCT, by applying state-of-the-art mammography and pathology may be as high as 90%. A subset of these tumors might represent the potential candidates for treatment with surgery alone without RT. As a result, the routine application of BCT complemented by RT would have led to the overtreatment of 89% of the patients with a BCLE in this series; conversely, 11% of the tumors may have recurred without the use of RT. Considering that these conclusions are based on a theoretic morphologic model, further clinical studies with facilities for high quality team approach in diagnosis and therapy are needed to evaluate the impact of BCLE on BCT strategies. The results of this study should not justify the withholding of RT outside the context of clinical trials.

Breast Neoplasms↗
PubMed2001

Characterization of consecutive Streptococcus pyogenes isolates from patients with pharyngitis and bacteriological treatment failure: special reference to prtF1 and sic / drs.

To analyze bacteriological treatment failure in streptococcal pharyngitis, 40 consecutive Streptococcus pyogenes isolates from 18 patients were characterized. For 17 patients, isolates were indistinguishable with respect to emm type, random amplified polymorphic DNA pattern, and presence of prtF1 encoding the fibronectin-binding protein F1. prtF1 was detected only in the 11 isolates (4 patients) with emm12 and in the single isolate with emm6. Further analysis by vir(mga) regulon typing, sequencing of sic encoding the streptococcal inhibitor of complement from 19 isolates with emm1 (9 patients), and sequencing of drs (distantly related sic) from 11 isolates with emm12 revealed distinct sic alleles with insertions and/or deletions in sic that corresponded to differences in restriction patterns of the vir(mga) regulon only for paired isolates of 2 patients. Among isolates with emm12, 2 novel drs alleles were found. Analysis of these data suggests that neither the presence of prtF1 nor the diversification of sic / drs is required for the persistence of S. pyogenes in pharyngitis.

Adhesins, Bacterial↗
PubMed2001

Self-other representations and relational and overt aggression in adolescent girls and boys.

Aggressive behavior in girls has received far less attention than similar problems in boys. This study examined self-representation, and others' representation of self, as predictors of relational aggression, overt aggression, and assaultive behavior in 32 girls and 52 boys, 10 to 17 years of age, referred for assessment due to significant aggressive and delinquent behavior problems. As predicted, negativity of self-representation predicted relational aggression in girls but not boys. Negativity of self-representation also predicted overt aggression and assaultive behavior in both girls and boys. Parental representations of self were not predictive in this sample; however, negativity of peer representations of self, was associated with increased relational aggression in girls and decreased relational aggression in boys. Negativity of peer representations of self also predicted overt aggression and assaultive behavior in both girls and boys. Results suggest that the evaluation of self-other representations may be valuable in the assessment of risk for gender specific patterns of aggression.

Adolescent↗
PubMed2001

International investigation of breast MRI: results of a multicentre study (11 sites) concerning diagnostic parameters for contrast-enhanced MRI based on 519 histopathologically correlated lesions.

A multicentre study was undertaken to provide fundamentals for improved standardization and optimized interpretation guidelines of dynamic contrast-enhanced MRI. Only patients scheduled for biopsy of a clinical or imaging abnormality were included. They underwent standardized dynamic MRI on Siemens 1.0 (163 valid lesions > or = 5 mm) or 1.5 T (395 valid lesions > or = 5 mm) using 3D fast low-angle shot (FLASH; 87 s) before and five times after standardized bolus of 0.2 mmol Gd-DTPA/kg. One-Tesla and 1.5 T data were analysed separately using a discriminant analysis. Only histologically correlated lesions entered the statistical evaluation. Histopathology and imaging were correlated in retrospect and in open. The best results were achieved by combining up to five wash-in or wash-out parameters. Different weighting of false-negative vs false-positive calls allowed formulation of a statistically based interpretation scheme yielding optimized rules for the highest possible sensitivity (specificity 30%), for moderate (50%) or high (64-71%) specificity. The sensitivities obtained at the above specificity levels were better at 1.0 T (98, 97, or 96%) than at 1.5 T (96, 93, 86%). Using a widely available standardized MR technique definition of statistically founded interpretation rules is possible. Choice of an optimum interpretation rule may vary with the clinical question. Prospective testing remains necessary. Differences of 1.0 and 1.5 T are not statistically significant but may be due to pulse sequences.

Adult↗
PubMed2001

MRI screening for breast cancer in women with familial or genetic predisposition: design of the Dutch National Study (MRISC).

Mammography screening of women aged 50-70 years for breast cancer has proven to be effective in reducing breast cancer mortality. There is no consensus about the value of breast cancer screening in women aged 40-49 years. Five to ten per cent of all breast cancers are hereditary. One of the options to reduce the risk of breast cancer mortality for women with a familial or genetic predisposition is intensive surveillance. However, the effectiveness of mammography screening for breast cancer in these women, who are mainly younger than 50 years, is unproven. MRI might increase the effectiveness of screening in women with a familial or genetic predisposition. This paper describes the design of the Dutch national study for Magnetic Resonance Imaging (MRI) screening in women with a familial or genetic predisposition. The aims of this study are to investigate: the value of regular surveillance in women with a familial or genetic predisposition for breast cancer, the efficacy of MRI as compared to mammography, cost-effectiveness of regular screening and quality of life during surveillance. Included are women with a lifetime risk of familial breast cancer of 15% or more or BRCA1/2 mutation carriers, who visit one of the Dutch family cancer clinics. The aim is to include 2,500 women. The study started on 1 November 1999. On 1 January 2002, more than 1,700 women, including 210 proven carriers of a BRCA1 or BRCA2 mutation, were included in the study.

Adult↗
PubMed2001

Response of the pulp of dogs to capping with mineral trioxide aggregate or a calcium hydroxide cement.

This study was conducted to observe the response of dogs' dental pulp to mineral trioxide aggregate (MTA) and a calcium hydroxide cement when used as pulp capping materials. After the pulps of 30 teeth were exposed, they were capped with either MTA or a calcium hydroxide cement. Histological analysis was performed 2 months after treatment. Results showed a healing process with complete tubular dentin bridge formation and no inflammation in any of the pulps capped with MTA. On the other hand, only five specimens from the calcium hydroxide cement group formed a complete dentin bridge. In this experimental group, pulp inflammation was observed in all but three cases. In conclusion, MTA exhibited better results than the calcium hydroxide cement for the capping of the pulp in dogs.

Aluminum Compounds↗