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Biomedical subjects

S Clark

Publications and source records attributed to S Clark.

At least 19 recordsLinked to original sources
PubMed2006

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗
PubMed2006

Carnitine transporter defect: diagnosis in asymptomatic adult women following analysis of acylcarnitines in their newborn infants.

Carnitine transporter defect (CTD) is an autosomal recessive disorder characterized by episodes of non-ketotic hypoglycaemia, hyperammonaemia and liver disease, or by the development of cardiomyopathy, both of which occur in infancy and childhood. Blood carnitine concentrations are extremely low. The diagnosis can be confirmed by finding abnormal fat oxidation and carnitine uptake in skin fibroblasts. The condition has not previously been thought to present later in life or to be benign. We report the identification of four women discovered to have CTD as a consequence of finding low carnitine concentrations in the cord blood or newborn samples from their infants. All four mothers had been asymptomatic and none had a cardiomyopathy.

Adult↗
PubMed2006

Nonstarter lactic acid bacteria biofilms and calcium lactate crystals in Cheddar cheese.

A sanitized cheese plant was swabbed for the presence of nonstarter lactic acid bacteria (NSLAB) biofilms. Swabs were analyzed to determine the sources and microorganisms responsible for contamination. In pilot plant experiments, cheese vats filled with standard cheese milk (lactose:protein = 1.47) and ultrafiltered cheese milk (lactose:protein = 1.23) were inoculated with Lactococcus lactis ssp. cremoris starter culture (8 log cfu/mL) with or without Lactobacillus curvatus or Pediococci acidilactici as adjunct cultures (2 log cfu/mL). Cheddar cheeses were aged at 7.2 or 10 degrees C for 168 d. The raw milk silo, ultrafiltration unit, cheddaring belt, and cheese tower had NSLAB biofilms ranging from 2 to 4 log cfu/100 cm2. The population of Lb. curvatus reached 8 log cfu/g, whereas P. acidilactici reached 7 log cfu/g of experimental Cheddar cheese in 14 d. Higher NSLAB counts were observed in the first 14 d of aging in cheese stored at 10 degrees C compared with that stored at 7.2 degrees C. However, microbial counts decreased more quickly in Cheddar cheeses aged at 10 degrees C compared with 7.2 degrees C after 28 d. In cheeses without specific adjunct cultures (Lb. curvatus or P. acidilactici), calcium lactate crystals were not observed within 168 d. However, crystals were observed after only 56 d in cheeses containing Lb. curvatus, which also had increased concentration of D(-)-lactic acid compared with control cheeses. Our research shows that low levels of contamination with certain NSLAB can result in calcium lactate crystals, regardless of lactose:protein ratio.

Animals↗
PubMed2006

Cheese pH, protein concentration, and formation of calcium lactate crystals.

The occurrence of calcium lactate crystals (CLC) in hard cheeses is a continual expense to the cheese industry, as consumers fail to purchase cheeses with this quality defect. This research investigates the effects of the protein concentration of cheese milk and the pH of cheese on the occurrence of CLC. Atomic absorption spectroscopy was used to determine total and soluble calcium concentrations in skim milk (SM1, 8.7% total solids), and skim milk supplemented with nonfat dry milk (CSM1, 13.5% total solids). Calcium, phosphorus, lactic acid, and citrate were determined in cheeses made with skim milk (SM2, 3.14% protein), skim milk supplemented with ultrafiltered milk (CSM2, 6.80% protein), and nonfat dry milk (CSM3, 6.80% protein). Supplementation with nonfat dry milk increased the initial total calcium in CSM1 (210 mg/100 g of milk) by 52% compared with the total calcium in SM1 (138 mg/100 g of milk). At pH 5.4, soluble calcium concentrations in CSM1 were 68% greater than soluble calcium in SM1. In cheeses made from CSM2 and CSM3, total calcium was 26% greater than in cheeses made from SM2. As the pH of cheeses made from SM2 decreased from 5.4 to 5.1, the concentration of soluble calcium increased by 61.6%. In cheeses made from CSM2 and CSM3, the concentrations of soluble calcium increased by 41.4 and 45.5%, respectively. Calcium lactate crystals were observed in cheeses made from SM2 at and below pH 5.1, whereas CLC were observed in cheeses from CSM2 and CSM3 at and below pH 5.3. The increased presence of soluble calcium can potentially cause CLC to occur in cheese manufactured with increased concentrations of milk solids, particularly at and below pH 5.1.

Animals↗
PubMed2005

Biochemical, clinical and molecular findings in LCHAD and general mitochondrial trifunctional protein deficiency.

General mitochondrial trifunctional protein (TFP) deficiency leads to a wide clinical spectrum of disease ranging from severe neonatal/infantile cardiomyopathy and early death to mild chronic progressive sensorimotor poly-neuropathy with episodic rhabdomyolysis. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency resulting from the common Glu510Gln mutation usually gives rise to a moderately severe phenotype with multiorgan involvement with high morbidity and mortality. However, isolated LCHAD deficiency can also be consistent with long-term survival in patients identified and treated from an early age. We present biochemical, clinical and mutation data in 9 patients spanning the full spectrum of disease. Fibroblast acylcarnitine profiling shows good correlation with clinical phenotype using the ratio C18(OH)/(C14(OH)+C12(OH)). This ratio shows a gradation of values, from high in four patients with severe neonatal disease (2.5+/-0.8), to low in two neuromyopathic patients (0.35, 0.2). Fibroblast fatty acid oxidation flux assays also show correlation with the patient phenotype, when expressed either as percentage residual activity with palmitate or as a ratio of percentage activity of myristate/oleate (M/O ratio). Fibroblasts from four patients with severe neonatal disease gave an M/O ratio of 4.0+/-0.6 compared to 1.97 and 1.62 in two neuromyopathic patients. Specific enzyme assay of LCHAD and long-chain 3-ketothiolase activity in patient cells shows lack of correlation with phenotype. These results show that measurements in intact cells, which allow all determinative and modifying cellular factors to be present, better reflect patient phenotype. Mutation analysis reveals a number of alpha- and beta-subunit mutations. Peripheral sensorimotor polyneuropathy, often as the initial major presenting feature but usually later accompanied by episodic rhabdomyolysis, is a manifestation of mild TFP protein deficiency. The mild clinical presentation and relative difficulty in diagnosis suggest that this form of TFP is probably underdiagnosed.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed2005

Practical aspects to undertaking research in the primary care setting: experience from two studies.

AIMS: To discuss the practical aspects of conducting research in a primary care setting, from the perspectives of the practitioner and the research team. METHODS: Various issues are discussed, including the relevance of research questions being generated in this setting, the advantages to both parties and the processes involved in conducting a study in specialist practice. This paper describes two recent studies (a randomized clinical trial and a qualitative study) conducted within specialist practice, to illustrate some of the potential difficulties. CONCLUSIONS: The success of conducting a study in primary care is determined by a variety of factors, including an interested specialist practitioner, motivated staff in a well-organized practice and the close support of an academic-based research team.

Communication↗
PubMed2005

Enhanced lactose cheese milk does not guarantee calcium lactate crystals in finished cheddar cheese.

Three experimental batches of Cheddar cheese were manufactured in duplicate, with standardization of the initial cheese-milk lactose content to high (5.24%), normal (4.72%, control), and low lactose (3.81%). After 35 d of aging at 4.4 degrees C, the cheeses were subjected to temperature abuse (24 h at 21 degrees C, unopened) and contamination (24 h at 21 degrees C, packages opened and cheeses contaminated with crystal-containing cheese). After aging for 167 d, residual cheese lactose (0.08 to 0.43%) and L(+)-lactate concentrations (1.37 to 1.60%) were high and D(-)-lactate concentrations were low (<0.03%) for all cheeses. No significant differences in lactose concentrations were attributable to temperature abuse or contamination. No significant differences in L(+)- or D(-)-lactate concentrations were attributable to temperature abuse. However, concentrations of L(+)-lactate were significantly lower and D(-)-lactate were significantly higher in contaminated cheeses than in control cheeses, indicating inoculation (at d 35) with heterofermentative nonstarter lactic acid bacteria able to racemize L(+)-lactate to D(-)-lactate. The fact that none of the cheeses exhibited crystals after 167 d demonstrates that high cheese milk or residual lactose concentrations do not guarantee crystal formation. Contamination with nonstarter lactic acid bacteria can significantly contribute to D(-)-lactate accumulation in cheese.

Animals↗
PubMed2005

Gas-flushed packaging contributes to calcium lactate crystals in Cheddar cheese.

Gas-flushed packaging is commonly used for cheese shreds and cubes to prevent aggregation and loss of individual identity. Appearance of a white haze on cubed cheese is unappealing to consumers, who may refrain from buying, resulting in lost revenue to manufacturers. The objective of this study was to determine whether gas flushing of Cheddar cheese contributes to the occurrence of calcium lactate crystals (CLC). Cheddar cheese was manufactured using standard methods, with addition of starter culture, annatto, and chymosin. Two different cheese milk compositions were used: standard (lactose:protein = 1.47, protein:fat = 0.90, lactose = 4.8%) and ultrafiltered (UF; lactose:protein = 1.23, protein:fat = 0.84, lactose = 4.8%), with or without adjunct Lactobacillus curvatus. Curds were milled when whey reached 0.45% titratable acidity, and pressed for 16 h. After aging at 7.2 degrees C for 6 mo, cheeses were cubed (1 x 1 x 4 cm) and either vacuum-packaged or gas-flushed with carbon dioxide, nitrogen, or a 50:50 mixture of carbon dioxide and nitrogen, then aged for an additional 3 mo. Heavy crystals were observed on surfaces of all cubed cheeses that were gas-flushed, but not on cheeses that were vacuum-packaged. Cheeses without Lb. curvatus exhibited L(+)-CLC on surfaces, whereas cheeses with Lb. curvatus exhibited racemic mixtures of L(+)/D(-)-CLC throughout the cheese matrices. The results show that gas flushing (regardless of gas composition), milk composition, and presence of nonstarter lactic acid bacteria, can contribute to the development of CLC on cheese surfaces. These findings stress the importance of packaging to cheese quality.

Animals↗
PubMed2004

Fracture of the radial donor site after composite free flap harvest: a ten-year review.

The options for donor sites as a source of tissue for free vascularised osteocutaneous flaps are numerous, however, the radial forearm still has an important role. This series reports the largest published record of radial donor site fracture following the harvesting of osteocutaneous radial forearm free flaps used for reconstruction after ablative surgery for malignant disease. The relevant literature is reviewed. A retrospective review of cases treated using these flaps from 1991-2000 (inclusive) is carried out. Factors involved in the aetiology of fractures are discussed. Thirteen fractures are identified from seventy one osteocutaneous flaps (18%). A statistically significant majority of fractures occur in females. Limiting the percentage of radius diameter harvested is important and beveling of the osteotomy cuts may be advantageous in minimising weakening. Prophylactic plating of the donor site, particularly in the female patient, should be actively considered. The earlier the fracture occurs in the post-operative period, the more likely the need for operative intervention.

Aged↗
PubMed2004

Intranasal bacille Calmette-Guerin (BCG) vaccine dosage needs balancing between protection and lung pathology.

Intranasal vaccination may offer practical benefits and better protection against respiratory infections, including tuberculosis. In this paper, we investigated the persistence of the Mycobacterium bovis-strain bacille Calmette-Guerin (BCG) Pasteur, lung granuloma formation and protection against pathogenic tuberculous challenge in mice. A pronounced BCG dose-dependent granulomatous infiltration of the lungs was observed following intranasal, but not after subcutaneous, vaccination. Corresponding doses of BCG, over a 100-fold range, imparted similar protection against H37Rv challenge when comparing the intranasal and subcutaneous vaccination routes. Interestingly, a BCG dose-dependent reduction of the H37Rv challenge infection was observed in the lungs, but not in the spleens, following both intranasal and subcutaneous vaccination. In the light of the observed concurrence between the extent of granuloma formation and the level of protection of the lungs, we conclude that intranasal vaccination leading to best protective efficacy needs to be balanced with an acceptable safety margin avoiding undue pathology in the lungs.

Administration, Intranasal↗
PubMed2003

Mutation and biochemical analysis in carnitine palmitoyltransferase type II (CPT II) deficiency.

Carnitine palmitoyltransferase type II (CPT II) deficiency has three basic phenotypes, late-onset muscular (mild), infantile/juvenile hepatic (intermediate) and severe neonatal. We have measured fatty acid oxidation and CPT II activity and performed mutation studies in 24 symptomatic patients representing the full clinical spectrum of disease. Severe and intermediate phenotypes show a clear correlation with biochemical indices and genetic analysis revealed causative mutations in most patients. Studies of mild phenotypes suggest a more complex interaction, with higher residual fatty acid oxidation, a wider range of CPT II activity (10-60%) but little evidence of genotype-phenotype correlation. Residual CPT II mutant protein from myopathic patients shows thermal instability at 41 degrees C. The common 'polymorphisms' V3681 and M647V are strikingly overrepresented in the myopathic patients, the implication being that they may significantly influence the manifestation of clinical disease and could therefore potentially be considered as a susceptibility variants. Among myopathic individuals, males comprised 88% of patients, suggesting increased susceptibility to clinical disease. A small number of symptomatic patients appear to have significant residual CPT II activity (42-60%) The synergistic interaction of partial deficiencies of CPT II, muscle adenosine monophosphate deaminase and possibly other enzymes of muscle energy metabolism in the aetiology of episodic myopathy deserves wider consideration.

AMP Deaminase↗
PubMed2003

Evaluation of the Dade Behring Syva EMIT 2000 tacrolimus assay on the Bayer Advia 1650.

BACKGROUND: The Dade Behring Syva(R) EMIT (enzyme multiplied immunoassay technique) method for the measurement of tacrolimus in whole blood was evaluated against the Abbott IMx(R) microparticle enzyme immunoassay (MEIA) method. EMIT measures tacrolimus colorimetrically, whereas MEIA measures the analyte using fluorimetry. Both methods incorporate a protein precipitation step prior to measurement. METHOD: Whole blood specimens were treated by two types of precipitation technique followed by analysis for tacrolimus by either MEIA or EMIT on the Bayer Advia 1650. Linearity and precision were assessed and correlation analysis performed to evaluate the EMIT assay on the Bayer Advia 1650. RESULTS: The EMIT tacrolimus assay was linear over the concentration range 0.0-22.0 micro g/L; the limit of detection was 1.2 micro g/L. Correlation between the Syva EMIT and IMx tacrolimus assays was excellent (r = 0.959) and no significant bias existed between the two methods (mean difference, delta = 0.221 micro g/L). Calibration data for the EMIT assay was stable for a period of 24-48 h on the Advia between runs. CONCLUSION: The Syva EMIT assay for the measurement of tacrolimus in whole blood is suited for daily routine use on the Bayer Advia 1650.

Blood Chemical Analysis↗
PubMed2003

Nonstarter lactic acid bacteria and aging temperature affect calcium lactate crystallization in cheddar cheese.

The occurrence of unappetizing calcium lactate crystals in Cheddar cheese is a challenge and expense to manufacturers, and this research was designed to understand their origin. It was hypothesized that nonstarter lactic acid bacteria (NSLAB) affect calcium lactate crystallization (CLC) by producing D(-)-lactate. This study was designed to understand the effect of NSLAB growth and aging temperature on CLC. Cheeses were made from milk inoculated with Lactococcus lactis starter culture, with or without Lactobacillus curvatus or L. helveticus WSU19 adjunct cultures. Cheeses were aged at 4 or 13 degrees C for 28 d, then half of the cheeses from 4 and 13 degrees C were transferred to 13 and 4 degrees C, respectively, for the remainder of aging. The form of lactate in cheeses without adjunct culture or with L. helveticus WSU19 was predominantly L(+)-lactate (> 95%, wt/wt), and crystals were not observed within 70 d. While initial lactate in cheeses containingL. curvatus was only L(+)-lactate, the concentration of D(-)-lactate increased during aging. After 28 d, a racemic mixture of D/L-lactate was measured in cheeses containing L. curvatus; at the same time, CLC was observed. The earliest and most extensive CLC occurred on cheeses aged at 13 degrees C for 28 d then transferred to 4 degrees C. These results showed that production of D(-)-lactate by NSLAB, and aging temperature affect CLC in maturing Cheddar cheese.

Calcium Compounds↗
PubMed2002

Misoprostol use in obstetrics and gynecology in Brazil, Jamaica, and the United States.

OBJECTIVES: To investigate current clinical use of misoprostol for the treatment of a range of reproductive health indications by providers in Brazil, Jamaica, and the United States. METHODS: Using a 'snowball' sampling technique, we surveyed 228 gynecologists and obstetricians in Brazil (n=123), Jamaica (n=52), and the United States (n=53). RESULTS: Providers use misoprostol for labor induction (46%), postpartum hemorrhage (8%), intra-uterine fetal death (61%), cervical priming (21%), missed abortion (57%), and incomplete abortion (16%) as well as first and second trimester abortion induction (27% and 13%, respectively). CONCLUSIONS: There is considerable variation in the regimens used; moreover, the regimens commonly used in clinical practice often differ from those recommended in the medical literature. While misoprostol is an appealing alternative for many reproductive health indications in developing countries, the varied regimens and lack of registration raise critical medical and policy questions.

Brazil↗
PubMed2002

Prevalence of moderate penicillin resistant invasive Neisseria meningitidis infection in Scotland, 1994-9.

We examined the serological characteristics of 774 invasive meningococcal isolates collected through an active laboratory-based surveillance system in Scotland from 1994 to 1999. Of these, 72-73% of isolates were tested for susceptibility to several antimicrobial agents. Meningococci with high-level resistance to sulphadiazine had a prevalence of 10% and incidence of 0.22 per 100,000 population. High-level resistance to penicillin and other antibiotics was not detected. The prevalence of moderate penicillin resistant meningococci was 8.3%. There was no increase in moderate penicillin resistant meningococcal isolates during the study period, but there were temporal and geographic variations. The estimated incidence of moderate penicillin resistant meningococci was 0.15 per 100,000 population. High and low incidence of moderate penicillin resistant meningococci appeared to correlate with the number of doses of penicillin prescribed in some geographic locations. The majority of moderate penicillin resistant isolates belonged to serogroups B (52.2%) and C (39.2%). However, the prevalence of moderate penicillin resistance in serogroup W135 was substantially higher (51.7%) than serogroups B (7.8%) and C (7.6%). Serogroup W135 accounted for a higher proportion of moderate penicillin resistance (8.7%) than disease (1%). There was no predominant penicillin resistant serotype/subtype within any serogroup. Constant surveillance is necessary to monitor the emergence and spread of resistance and to guide appropriate public health interventions in preventing drug resistant meningococci.

Humans↗