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Biomedical subjects

S McKenzie

Publications and source records attributed to S McKenzie.

At least 37 records · Page 2Linked to original sources

Simple two-color array-based approach for mutation detection.

The ability to analyze multiple polymorphic/mutation sites rapidly and accurately is pivotal in all areas of genetic analysis. We have applied single nucleotide primer extension (SNE) for detection of multiple point mutations in a micro-array format using two-color, fluorescent dye-tagged dideoxynucleoside triphosphate terminators (ddNTPs). The oligonucleotide primer ending one nucleotide short of the mutation site being probed is bound to the slide and single-base extended in place with two different Cy5/Cy3 dye-tagged terminators using solution-phase, locus-specific, single-stranded complementary templates generated by PCR from genomic DNA. The composite fluorescence produced contains peaks of distinct wave lengths corresponding to each Cy dye-tagged terminator incorporated, resulting in a fluorescent 'fingerprint' for each DNA target. DNA polymerase-catalyzed incorporation of Cy dye-tagged dideoxynucleoside triphosphates was dependent on the particular dyes, the specific ddNTP, the DNA target concentration, sequence of the template, on-slide temperature cycling and washing conditions. Results from analysis of mutations in the human hemochromatosis and connexin 26 genes show that this approach has several advantages over existing methods and is simple, rapid, robust, cost effective and accurate with potential applications in many areas of genetic analysis.

Amino Acid Substitution↗

Diagnosis and investigation of bacterial pneumonias.

This overview has been supported by a review of the literature referring to the management of community-acquired pneumonia (in preparation). Difficulties diagnosing bacterial pneumonia include identifying the pathogens and the validation of radiographic signs suggesting bacterial or mycoplasmal infection. The World Health Organisation (WHO) has published guidelines for diagnosis which seem to be as relevant for developed as developing countries. The main diagnostic features are tachypnoea, fever greater than 38.5 degrees C and chest recession without wheeze. Radiographic features lag behind clinical findings and provide little additional help when antibiotic treatment is considered but are crucial in the proper management of complications.

Adolescent↗

Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women.

UNLABELLED: Creatine monohydrate (CrM) administration may enhance high intensity exercise performance and increase body mass, yet few studies have examined for potential adverse effects, and no studies have directly considered potential gender differences. PURPOSE: The purpose of this study was to examine the effect of acute creatine supplementation upon total and lean mass and to determine potential side effects in both men and women. METHODS: The effect of acute CrM (20 g x d(-1) x 5 d) administration upon systolic, diastolic, and mean BP, plasma creatinine, plasma CK activity, and body composition was examined in 15 men and 15 women in a randomized, double-blind experiment. Additionally, ischemic isometric handgrip strength was measured before and after CrM or placebo (PL). RESULTS: CrM did not affect blood pressure, plasma creatinine, estimated creatinine clearance, plasma CK activity, or handgrip strength (P > 0.05). In contrast, CrM significantly increased fat-free mass (FFM) and total body mass (P < 0.05) as compared with PL, with no changes in body fat. The observed mass changes were greater for men versus women. CONCLUSIONS: These findings suggest that acute CrM administration does not affect blood pressure, renal function, or plasma CK activity, but increases FFM. The effect of CrM upon FFM may be greater in men as compared with that in women.

Adult↗

Endurance exercise training attenuates leucine oxidation and BCOAD activation during exercise in humans.

We studied the effects of a 38-day endurance exercise training program on leucine turnover and substrate metabolism during a 90-min exercise bout at 60% peak O(2) consumption (VO(2 peak)) in 6 males and 6 females. Subjects were studied at both the same absolute (ABS) and relative (REL) exercise intensities posttraining. Training resulted in a significant increase in whole body VO(2 peak) and skeletal muscle citrate synthase (CS; P < 0.001), complex I-III (P < 0.05), and total branched-chain 2-oxoacid dehydrogenase (BCOAD; P < 0.001) activities. Leucine oxidation increased during exercise for the pretraining trial (PRE, P < 0.001); however, there was no increase for either the ABS or REL posttraining trial. Leucine oxidation was significantly lower for females at all time points during rest and exercise (P < 0.01). The percentage of BCOAD in the activated state was significantly increased after exercise for both the PRE and REL exercise trials, with the increase in PRE being greater (P < 0.001) compared with REL (P < 0.05). Females oxidized proportionately more lipid and less carbohydrate during exercise compared with males. In conclusion, we found that 38 days of endurance exercise training significantly attenuated both leucine oxidation and BCOAD activation during 90 min of endurance exercise at 60% VO(2 peak) for both ABS and REL exercise intensities. Furthermore, females oxidize proportionately more lipid and less carbohydrate compared with males during endurance exercise.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Cryptococcal arthritis in an immunocompetent host.

Cryptococcus neoformans is an opportunistic pathogen that occasionally causes indolent disease in the immunocompetent. Cryptococcal arthritis is especially rare, and diagnosis is typically delayed. Fungal arthritis should be considered in cases of chronic, indolent joint inflammation. To our knowledge, this report documents the first use of fluconazole for treatment of cryptococcal infection confined to a joint.

Antifungal Agents↗

Ozonation and alkaline-peroxide pretreatment of wheat straw for Cryptococcus curvatus fermentation.

Crop residues in an Advanced Life Support System (ALS) contain many valuable components that could be recovered and used. Wheat is 60% inedible, with approximately 90% of the total sugars in the residue cellulose and hemicellulose. To release these sugars requires pretreatment followed by enzymatic hydrolysis. Cryptococcus curvatus, an oleaginous yeast, uses the sugars in cellulose and hemicellulose for growth and production of storage triglycerides. In this investigation, alkaline-peroxide and ozonation pretreatment methods were compared for their efficiency to release glucose and xylose to be used in the cultivation of C. curvatus. Leaching the biomass with water at 65 degrees C for 4 h prior to pretreatment facilitated saccharification. Alkaline-peroxide and ozone pretreatment were almost 100% and 80% saccharification efficient, respectively. The sugars derived from the hydrolysis of alkaline-peroxide-treated wheat straw supported the growth of C. curvatus and the production of edible single-cell oil.

Biomass↗

An examination of the role of clinical psychology in meeting the needs of young disabled clients and their families/carers.

This paper examines the views of clients with a physical disability, general practitioners and staff working in health and social work physical disability services about the needs of young disabled people. The most common area of disability seen by GPs was respiratory, followed by cardiac problems and stroke. With the exception of cardiac patients a third to over half of GPs felt that the needs of the identified groups were not being adequately met, in particular the needs of individuals with progressive neuromuscular problems. Over a quarter of clients felt that their needs were not being adequately met. Ninety-five percent of GPs and 100% of staff identified psychological needs of clients. For clients themselves, physical needs are ranked highest, with over 33 percent identifying psychological problems, 50 percent neuropsychological problems and 25 percent psychosexual difficulties as priority needs. In relation to carers, over 90 percent of GPs, 100% of staff and 50 percent of clients highlighted psychological needs. The majority of participants felt that clinical psychology had an important role to play in physical disability services. There was broad agreement on the areas of need which psychology would be seen to address. These were psychological needs, behavioural problems, neuropsychological problems and relationship/psychosexual difficulties. A high percentage of both staff and GPs also saw a role for clinical psychology in meeting the psychological, relationship and psychosexual needs of carers.

Attitude of Health Personnel↗

The awesome Asthma School Days Program: educating children, inspiring a community.

Program planners developed an educational program to improve the health of children with asthma in grades three to five in Milwaukee (Wis.) Public Schools. During 1997-1998, 1,400 students from 74 elementary schools participated in the Awesome Asthma School Days education program. In a cross-sectional survey, about 40% of children reported play interrupted and sleep disturbed by asthma, more than 50% of children reported exposure to smoke in their home, most children lacked asthma self-care tools, and most children with persistent symptoms did not use an anti-inflammatory inhaler. The educational program improved students' expectations about normal play and sleep and improved their understanding of asthma. Leaders in Milwaukee used the survey results to develop a community action plan. The educational program, surveys, community partnerships, and strategic plans can be replicated in other schools.

Adult↗

Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma.

PURPOSE: A randomized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas. METHODS AND MATERIALS: Inclusion criteria included the following: biopsy-proven supratentorial malignant astrocytoma of brain < or =6 cm in size, not crossing midline or involving corpus callosum, age 18-70, Karnofsky Performance Status (KPS) > or =70. Patients were randomized to external radiation therapy only delivering 50 Gray (Gy) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy. Patients were stratified to age < or =50 or >50, and KPS > or =90 or < or =80. RESULTS: There were 140 patients randomized between 1986 and 1996, 71 to the implant arm and 69 to external irradiation only. Pathologically 125 patients had necrosis noted in their tumor specimen. Factors associated with improved survival in univariate analysis were age < or =50, KPS > or =90, chemotherapy at recurrence, and reoperation at the original tumor site. The Cox proportional hazards model revealed the following significant factors: treatment at recurrence (chemotherapy or reoperation) with a relative risk (RR) of 0.6 (p = 0.004) and KPS > or =90 with a RR 0.6 (p = 0.007). Randomization to the implant arm was associated with a RR of 0.7 (p = 0.07). Median survival for patients randomized to brachytherapy or not were 13.8 vs. 13.2 months, respectively, p = 0.49. CONCLUSIONS: We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma.

Adult↗

Experimental evaluation of possible new short-term drug regimens for treatment of multibacillary leprosy.

Groups of nude mice, with both hind footpads infected with 10(8) Mycobacterium leprae organisms, were treated with 4-week courses of different drug combinations. The effect treatment on each group was evaluated by subinoculating footpad homogenates from the treated mice into groups of normal and nude mice for subsequent regrowth, assessed 1 year later. A combination of rifampin (RMP) with clarithromycin (CLARI), minocycline (MINO), and ofloxacin (OFLO) resulted in the complete killing of M. leprae after 3 weeks of treatment. A combination of sparfloxacin (SPAR) and RMP also resulted in a similar bactericidal effect after 3 weeks of treatment. Other drug combinations showed variable effects. Very little or no effect was observed with any regimen if the treatment was given for less than 2 weeks. World Health Organization (WHO) multidrug therapy (MDT) given for 8 weeks was as effective as the two combinations described above. The results suggest that multidrug combinations consisting of RMP-OFLO (or SPAR)-CLARI (and/or MINO) are as effective as the WHO MDT for the treatment of experimental leprosy. Moreover, they imply that these combinations, which were found to be active in a 4-week experimental treatment protocol, could be administered as treatment to patients for a period of time shorter than the present 2-year regimen without a loss of effectiveness.

Animals↗

Optimising a varicose vein service to reduce recurrence.

A prospective observational study of 63 legs in 49 patients was undertaken to evaluate the adequacy of primary varicose vein surgery performed by surgical trainees. Appropriate surgery was carried out by a surgical senior house officer (SHO) under direct consultant supervision. All patients underwent pre- and postoperative duplex scanning. The preoperative duplex scan demonstrated incompetence of the saphenofemoral junction (SFJ) or long saphenous vein (LSV) in 59 limbs, a mid-thigh perforator (MTP) in 11 limbs, and saphenopopliteal junction (SPJ) in 5 limbs. Surgery successfully abolished all sites of pre-existing reflux. The postoperative duplex scan revealed that 17 new sites of reflux, not identified preoperatively, had developed in 12 limbs. With a consultant-led service and accurate preoperative identification of sites of reflux, the surgical trainee can adequately perform varicose vein surgery. This would seem a reasonable approach to training and eliminating recurrence owing to inadequate surgery. The development of new sites of reflux within 6 months of varicose vein surgery may be owing to altered venous haemodynamics consequent upon this surgery.

Adult↗