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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 37 records · Page 2Linked to original sources

The crossing of the spinothalamic tract.

The question whether the spinothalamic and spinoreticular fibres cross the cord transversely or diagonally was investigated in cases of anterolateral cordotomy and in a case of thrombosis of the anterior spinal artery. The pattern of sensory loss following transection of the anterolateral quadrant of the cord consists of a narrow area of decreased nociception and thermanalgesia at the level of the incision; it extends for 1-2 segments cranial and cordal to the incision. This area is immediately cranial to the area of total loss of these modalities. This pattern of sensory loss is explained as follows. The cordotomy incision transects two groups of fibres: those that are already within the anterior and anterolateral funiculi and those that are crossing the cord. The area of total thermanaesthesia and analgesia is due to transection of fibres that are already within this region. The area of partial sensory loss is due to transection of the fibres that are crossing the cord at that level. Owing to the craniocaudal extent of the branches of the dorsal roots, there is an overlap of their collaterals that results in every spinothalamic neurone receiving an input from several dorsal roots. The narrow cordotomy incision thus divides the few fibres crossing at that level, causing diminished noxious and thermal sensibility over a few segments above and below the incision. These facts can be accounted for only on the assumption that these spinothalamic fibres are crossing the cord transversely. This evidence of transverse crossing was found in the cervical, thoracic and lumbar segments. There were three of 63 cordotomies for which this explanation of the partial sensory loss could not be maintained. Although no explanation has been suggested, this is unlikely to be due to the fibres crossing the cord diagonally.

Afferent Pathways↗

Lashing out.

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Attitude of Health Personnel↗

The effect of isolated soy protein on plasma biomarkers in elderly men with elevated serum prostate specific antigen.

PURPOSE: We performed a randomized double-blind crossover pilot study in elderly men with elevated prostate specific antigen (PSA) on the effects of the daily consumption of 2 soy beverages, each containing 20 gm. of isolated soy protein, on the isoflavone concentration in blood and urine, and on the 3 serum biomarkers cholesterol, PSA and the soluble p105 component of the p185erbB-2 proto-oncogene. MATERIALS AND METHODS: A total of 34 men supplemented their diet by consuming 1 of 2 soy protein beverages assigned randomly twice daily for a 6-week period. In a second 6-week period they consumed the other soy protein beverage. The beverage ISP+ provided 42 mg. of genistein and 27 mg. of daidzein daily, whereas the other beverage, ISP-, provided only 2.1 and 1.3 mg. of these isoflavones daily, respectively. Blood and 24-hour urine samples were obtained before the study, at 2-week intervals during the study and 2 weeks after study completion. RESULTS: ISP+ and to a lesser extent ISP- substantially increased the serum concentration and urinary output of the isoflavones and their metabolites. Serum cholesterol was significantly decreased by ISP+ irrespective of the order in which the 2 soy beverages were administered and in apparent correlation with the total isoflavone concentration. There was no significant effect of the soy beverages on serum PSA and p105erbB-2 values. CONCLUSIONS: This study reveals that short-term exposure of elderly men with elevated serum PSA values to soy protein containing isoflavones decreases serum cholesterol but not the serum biomarkers PSA and p105erbB-2.

Aged↗

Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day.

BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.

Adult↗

Improving general practitioners' assessment and management of suicide risk.

Standards for assessing and managing suicide risk were developed and incorporated into a guidance manual for general practitioners. The effects of the manual on opinions and practice were evaluated using a quasi-experimental controlled before/after design, comparing participating general practitioners with others who did not use the manual. Thirty four general practitioners participated over a six-month period. The intervention group showed changes in perceptions, with increased satisfaction with their own methods and in their recognition and assessment of suicide risk. Their practice changed, with increased recording of relevant factors in notes. The comparison group did not change in these ways. It is concluded that general practitioners' practice and opinions in assessing and managing suicide risk were significantly improved using a minimal intervention. Given the importance of the topic and the small size of this study, further research is needed, examining changes in professional practice, knowledge and attitudes.

Affective Symptoms↗

The effects of restricted energy and fluid intake on simulated amateur boxing performance.

This study examined the effects of serial reductions in energy and fluid intake on two simulated boxing performances separated by 2 days recovery. Eight amateur boxers (age: 23.6 +/- 3.2 years; height 175 +/- 5 cm; body mass [BM] 73.3 +/- 8.3 kg [Mean +/- SD]) performed two simulated boxing bouts (BB) under normal (N-trial) and restricted (R-trial) diets in a counterbalanced design over 5 days. The trials were separated by a 9-day period of normal dietary behavior (X-trial). BM was recorded on days 1, 3, and 5 of each trial. Simulated bouts of three, 3-min rounds with 1-min recovery were completed on days 3 (BB1) and 5 (BB2) of each 5-day trial. Punching force (N) was recorded from 8 sets of 7 punches by a purpose-built boxing ergometer. Heart rate (fC) was monitored continuously (PE3000 Polar Sports Tester, Kempele, Finland), and blood lactate (BLa) and glucose (BG) were determined 4-min post-performance (2300 StaPlus, YSI, Ohio). Energy and fluid intakes were significantly lower in the R-trial (p < .05). Body mass was maintained during the N-trial but fell 3% (p < .05) during the R-trial. There were no significant differences in end-of-bout fC or post-bout BG, but BLa was higher in the N- than the R-trial (p < .05). R-trial punching forces were 3.2% and 4.6% lower, respectively, compared to the corresponding N-trial bouts, but the differences did not reach statistical significance. These results suggest that energy and fluid restrictions in weight-governed sports do not always lead to a significant decrease in performance, but because of the small sample size and big variations in individual performances, these findings should be interpreted with care.

Adult↗

Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression mediated by dominant negative Fra-2.

Fos-related antigen 2 (Fra-2) is a member of the Fos family of immediate-early genes, most of which are rapidly induced by second messengers. All members of this family act by binding to AP-1 sites as heterodimeric complexes with other proteins. However, each appears to have a distinct role. The role and biology of Fra-2 are less well understood than those of its relatives c-Fos, Fra-1, and FosB; moreover, Fra-2 target genes remain largely unknown, as does the basis of its selective effects on transcriptional activity. To pursue these issues, we created a transgenic rat line (NATDNF2) in which a dominant negative fra-2 (DNF2) gene is strongly expressed in the pineal gland; tissue selectivity was achieved by putting the DNF2 gene under the control of the rat arylalkylamine N-acetyltransferase (AANAT) regulatory region, which targets gene expression to a very restricted set of tissues (pineal gland >> retina). Expression of AANAT is normally turned on after the onset of darkness in the rat; as a result, pineal DNF2 expression occurs only at night. This was associated with marked suppression of the nocturnal increase in fra-2 mRNA and protein levels, indicating that DNF2 expression inhibits downstream effects of Fra-2, including the maintenance of high levels of fra-2 gene expression. Analysis of 1,190 genes in the NATDNF2 pineal gland, including the AANAT gene, identified two whose expression is strongly linked to fra-2 expression: the genes encoding type II iodothyronine deiodinase and nectadrin (CD24).

3T3 Cells↗

Development and validation of a monoclonal based immunoassay for the measurement of fungal alpha-amylase: focus on peak exposures.

The inhalation of flour dust has been implicated in the induction of sensitisation and elicitation of respiratory symptoms, such as asthma in bakers. In addition to the cereal allergens present in wheat flour, enzymes in flour improvers, in particular fungal alpha-amylase, are now known to be a significant cause of respiratory allergy in the baking industry.A monoclonal antibody based enzyme-linked immunoassay (ELISA) was developed using two monoclonal antibodies that recognised two distinct epitopes of the fungal alpha-amylase enzyme. The ELISA had an inter-assay variation of 12.0% at 1360 pg/ml and 12.8% at 564 pg/ml and intra-assay variation of 4.9% at 1340 pg/ml and 6.1% at 504 pg/ml. The assay had a sensitivity of 200 pg/ml. Competitive inhibition assays confirmed that the monoclonal antibodies had no cross reactivity with other enzymes used in the baking industry and could distinguish added fungal alpha-amylase from cereal amylase. We assessed the levels of exposure to dust, total protein and fungal alpha-amylase in four UK bakeries ranging in size and technical capabilities. Within the bakeries we surveyed, workers were exposed to variable levels of inhalable dust (0.8-39.8 mg/m3), total protein (0-5.7 mg/m3) and fungal alpha-amylase (0-29.8 ng/m3). Consecutive 15 min personal samples taken over a 1 h period demonstrated that the ELISA could measure fungal alpha-amylase exposure in such a 15 min period. Short term peak exposures to fungal alpha-amylase could be identified which may contribute to the sensitisation in individuals who appear to have low exposure levels if measured over a full shift period.

Antibodies, Monoclonal↗

Bupropion overdose: a potential problem with the new 'miracle' anti-smoking drug.

Bupropion (Zyban) has recently been launched in the UK as an aid to smoking cessation. As a result of the considerable publicity, there has been unprecedented demand for this new drug in primary care. Within a few weeks of its launch, four patients presented to our A&E department having taken bupropion as an intentional overdose. Three recovered with simple supportive measures; one one was critically ill and required admission to the intensive care unit. There are several case reports on bupropion overdose in the US but none so far in the UK.

Adolescent↗

Fatal phrases.

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Communication↗

[Platinum compounds in cancer therapy--past, present, and future].

Platinum cytotoxics play an important role globally in the management of solid tumours. Cisplatin sets the standard for efficacy in both regions with careful administration to reduce nephrotoxicity. Carboplatin is associated with neurotoxicity, but has become the leading product in the US due largely to the easier to manage toxicity profile. Both agents have been widely used in both registered and non registered indications and are frequently combined with other cytotoxics. In Japan, cisplatin has been used successfully at low doses in combination with 5-FU based regimens and appears to achieve a synergistic effect, but controlled data are not yet available. More recently oxaliplatin (Europe) and nedaplatin (in Japan) have been introduced, but their clinical roles in therapy have yet to be established. One of the limiting features of the first generation of platinum compounds is that a significant proportion of tumours develop cross resistance to platins due to either changes in uptake or excretion, intracellular detoxification or accelerated DNA repair. The forum discussed the possibility for the development of better new platinum compounds, A new platin agent which had lower toxicity and higher efficacy across a wide range of cancers without the development of resistance would be a significant step forward. If the tolerability profile was suitable, an oral formulation may improve the quality of life for patients but this must not be at the expense of efficacy. Even after the introduction of new target based drugs, platinum cytotoxics are likely to be used to reduce the tumour mass and in some cases can be expected to potentiate the effects of the new agents. In preclinical studies, ZD0473 has been shown to by-pass some major mechanisms of resistance and has the potential to achieve these objectives and is now being evaluated in clinical studies in both Japan and the West.

Antineoplastic Combined Chemotherapy Protocols↗