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Biomedical subjects

M McLean

Publications and source records attributed to M McLean.

At least 91 records · Page 5Linked to original sources

The results of primary radiation therapy in the management of squamous cell carcinoma of the penis.

PURPOSE: The outcome of radical external beam radiation therapy for 26 consecutive patients with invasive carcinoma of the penis treated between 1970 and 1985 was assessed to test the efficacy, and side effects of such treatment. METHODS AND MATERIAL: A retrospective review of 26 patients with invasive carcinoma of the penis and 11 patients with carcinoma in-situ of the penis, treated at the Princess Margaret Hospital between 1970 and 1985, was performed. Radiation treatment was delivered using 60Co or 100-250 kv equipment to a dose ranging from 25 Gy in 10 fractions over 2 weeks to 60 Gy in 25 fractions over 5 weeks. The most often used XRT prescription was 50 Gy in 20 fractions over 4 weeks. RESULTS: The 5-year overall actuarial survival for patients with invasive cancers was 62% (+/- 10) and the cause-specific survival was 69% (+/- 9). The control of the primary lesion was 61.5%. Of five patients who progressed after initial radiotherapy, one patient was salvaged by penectomy. Of 11 patients who recurred after initial complete response, three did so in the penis alone and all were successfully salvaged by penectomy. Late complications were recorded in seven patients, two of whom underwent penectomy as a result. All patients with carcinoma in-situ achieved a complete response and, with follow-up ranging from 1 to 14 years, none recurred. CONCLUSION: We conclude that radiation therapy with surgery reserved for the management of local recurrence is an effective first line treatment for patients with carcinoma of the penis.

Actuarial Analysis↗

The impact of prostatic manipulation upon serum PSA in patients with adenocarcinoma of the prostate.

A prospective study was carried out to evaluate the possible impact of prostatic manipulation upon the serum prostate specific antigen (PSA) in a cohort of 98 patients prior to treatment of adenocarcinoma of the prostate. The PSA levels were assessed before and 1 hour after examination under anaesthetic (EUA). There were 87 complete pairs of observations. In 71 patients there was either no change (n = 2) or a rise (n = 69); in 16 there was a fall. The median change in the group as a whole was +2.0 ng/ml (range -10.8-36.2). The average percentage rise in PSA was 42.3% (median 17.4%) with the largest percentage changes seen in those with the lowest initial PSA levels, with those in the range < 4 ng/ml exhibiting a 66.7% rise and those with > 35 ng/ml a 3.2% rise (median values). An attempt is made to express these changes in a clinical sense by allocating patients (pre-EUA) to one of four ranges of values as follows, 0-4.0, 4.1-10.0, 10.1-35.0 and > 35 ng/ml and observing the frequency with which they climbed to a higher category after EUA. This occurred in 23%, 50%, and 15% of patients respectively. The changes in PSA were statistically significant but their clinical significance might depend upon the clinical setting. Thus no patient would have had their management changed as a result of such a rise in PSA, but this might assume greater importance during the months of follow-up after radiation therapy, where a rise in PSA after prostatic manipulation might result in undue patient anxiety and unnecessary investigations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Structure, expression, chromosomal location and product of the gene encoding Adh2 in Petunia.

In most higher plants the genes encoding alcohol dehydrogenase comprise a small gene family, usually with two members. The Adh1 gene of Petunia has been cloned and analyzed, but a second identifiable gene was not recovered from any of three genomic libraries. We have therefore employed the polymerase chain reaction to obtain the major portion of a second Adh gene. From sequence, mapping and northern data we conclude this gene encodes ADH2, the major anaerobically inducible Adh gene of Petunia. The availability of both Adh1 and Adh2 from Petunia has permitted us to compare their structures and patterns of expression to those of the well-studied Adh genes of maize, of which one is highly expressed developmentally, while both are induced in response to hypoxia. Despite their evolutionary distance, evidenced by deduced amino acid sequence as well as taxonomic classification, the pairs of genes are regulated in strikingly similar ways in maize and Petunia. Our findings suggest a significant biological basis for the regulatory strategy employed by these distant species for differential expression of multiple Adh genes.

Alcohol Dehydrogenase↗

Determination of relative fiber orientation in heart muscle: methodological problems.

Knowledge of the muscle pattern in the heart is important to understanding cardiac contraction and propagation of the electrical stimulus. Most work on this pattern has been carried out by blunt gross dissection, whereby fiber bundles are easily visible on the peeled heart wall. However, it has never been shown, to our knowledge, that the orientation of macroscopic fiber bundles seen in a peeled heart corresponds to that of the constituent myofibers (muscle cells). For this purpose, one needs to carry out a three-dimensional microscopic reconstruction within a documented macroscopic reference frame. To draw valid conclusions in such a coordinated macroscopic and microscopic study, one must estimate the (slice) angle between the long axis of a muscle cell and the plane of section. Otherwise any alleged differences between the macroscopic and microscopic orientations may be just an artifact of sectioning. In this study we have shown that, provided the images of the myofibers meet simple criteria, one can be reasonably confident that the potential error incurred by sectioning is small. On this basis, we demonstrated that while there is a general correspondence between the macroscopic fiber and the microscopic myofiber orientations, there are significant differences in detail.

Animals↗

Myofiber orientation in the weanling mouse heart.

This study provides a quantitative description at the cellular level of myofiber orientation throughout the ventricles of the mouse heart. We employed computer-based methods of three-dimensional reconstruction from 3 microns plastic-embedded serial sections. Registration marks were introduced by drilling minute holes into each plastic block. Subfields of selected sections were photographed at 20 x magnification, using a computer-controlled microscope. The 35-mm film frames were projected onto a digitizer tablet and the epi- and endocardial boundaries were digitized manually. The "heads" and "tails" of linear segments of a representative myofiber sample present in each projected image were digitized in point mode. The many x-, y-, z-coordinate tables generated by digitization were reassembled automatically, giving a numerical description of the myofiber pattern. This pattern was studied interactively on a high-performance graphics workstation. We find that the heart wall is, to a first approximation, a "sandwich," in which the myofibers in the middle layer run mainly circumferentially, whereas those in the inner and outer layers run parallel or oblique to the apical-basal axis, a variant of the classical model of the myofiber pattern. We observed a "sleeve" in the interventricular septum, formed by longitudinal and oblique myofibers, a feature which apparently has not been described previously. Myofibers not running parallel to the transverse or longitudinal planes were not resolved in this study. We conclude that three-dimensional reconstruction of the cardiac myofiber pattern at the light-microscopic level, while laborious, is technically feasible and scientifically worthwhile.

Animals↗

Structure, expression, chromosomal location and product of the gene encoding ADH1 in Petunia.

A genomic clone for an alcohol dehydrogenase (Adh) gene has been isolated from Petunia hybrida cv. V30 by screening a Petunia genomic library with a maize Adh1 probe. A combination of RFLP and allozyme segregation data failed to demonstrate which of two Adh loci, both of which map to chromosome 4, was the source of the cloned gene. The product of the cloned genes has been identified unequivocally by a transient expression assay in Petunia protoplasts. We have designated this gene Petunia Adh1. The expression of this gene is tightly regulated in the developing anther, where its gene product is the predominant ADH isozyme. It is anaerobically inducible in roots, stems and leaves of seedlings. The induction of enzyme activity is correlated with induction of Adh1 mRNA.

Alcohol Dehydrogenase↗

Perifused ovine placental tissue secretes beta-endorphin immunoreactivity.

In vitro release of one of the pro-opiomelanocortin (POMC)-derived peptides, the endogenous opioid beta-endorphin (beta EP) has been examined in the sheep placenta by means of a perifusion system. Two zones of the cotyledon, the chorionic villus (highly vascularized fetal and maternal tissues in close apposition) and the maternal basal plate (or capsule), were examined in placenta at two stages of gestation--120 days (119.0 +/- 4.7, N = 4) and 140 days (143 +/- 1.8, N = 5) just before term. The chorionic villous tissue released more beta EP-like immunoreactivity (beta EP-IR) than did the basal plate tissue at both gestational ages. At 120 days' gestation the basal concentration of beta EP-IR released from the chorionic villus was 52 +/- 0.5 fmol mL-1 (n = 4), almost double the maternal basal plate tissue at 28.4 +/- 0.4 fmol mL-1 (n = 8). beta EP-IR secretory capacity increased significantly (P less than 0.05) with advancing gestational age. By Day 140, release had increased 3-4-fold to 181.8 +/- 0.8 fmol mL-1 (n = 16) in the chorionic villous tissue, and to a lesser extent in the basal plate tissue to 50.7 +/- 0.6 fmol mL-1 (n = 14). No stimulation of beta EP-IR secretion was observed in any tissue as a result of 30 min exposure to corticotrophin-releasing hormone (100 nmol L-1), a vital physiological secretagogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Three-dimensional reconstruction from serial sections. V. Calibration of dimensional changes incurred during tissue preparation and data processing.

Three-dimensional (3-D) reconstructions from serial tissue sections produce a table of x, y, z coordinates (i.e., a numerical description of the object) that will support 3-D computer graphics displays and morphometric analyses. While measures such as volume or surface area can be generated interactively, almost instantaneously, they are usually of unknown accuracy due to artifacts that may be introduced at two different stages: (1) tissue shrinkage during dehydration and polymerization of a plastic and compression or expansion during sectioning and mounting and (2) geometric and intensity distortions during image capture and data processing. This paper describes simple methods for (1) introducing fiducials (reference marks) that allow measurement of the net distortion incurred during tissue preparation and (2) estimating the amount of geometric distortion arising during image capture and data processing. Application of these methods showed that the net areal change introduced in dog and sheep hearts during tissue processing amounted to +/- 5%. Apparently, the substantial shrinkage that occurs during tissue processing is largely compensated for by the expansion during tissue sectioning and mounting. The methods described may have application to other semisolid tissues.

Animals↗

Measuring malnutrition in famines: are weight-for-height and arm circumference interchangeable?

Data from two surveys in Sudan have been used to examine whether weight-for-height (WFH) and mid-upper arm circumference (MUAC) can be used interchangeably at a population level to define the proportion of children aged one to four years that are malnourished, whether they identify the same individual children as malnourished, and whether the relationship between WFH and MUAC varies with age. A MUAC cut-off of 13.0 cm consistently defined approximately the same proportion of children malnourished as 80% WFH in all seven groups of children examined, even though the proportion of children with less than 80% WFH varied between 8.6% and 30.7%. However, sensitivity/specificity analysis showed that many of the children identified as malnourished by the two indices were not the same individuals. Both the MUAC cut-off defining the same proportion malnourished as 80% WFH, and the sensitivity/specificity values, varied substantially with age. Studies of other populations have revealed both different MUAC cut-offs defining the same proportion of children malnourished as 80% WFH, and different sensitivities and specificities of MUAC relative to WFH. We do not recommend the direct comparison of data from surveys using WFH and those using MUAC.

Age Factors↗

Urinary corticotropin-releasing hormone immunoreactivity is elevated during human pregnancy.

Plasma corticotropin-releasing hormone immunoreactivity (CRH IR) rises with gestational age in women. In order to investigate the physiological changes of the hormone in pregnant women's urine, CRH IR was measured by radioimmunoassay in urine collected over a 24-hour period, a blood sample and a subsequent single collection of urine after the 24-hour collection (spot urine). Plasma CRH IR in pregnant subjects, 8682.8 +/- 2063.0 pg CRH IR/ml plasma (mean +/- SEM, n = 25), was significantly higher than that in the non-pregnant controls (7.2 +/- 1.6 pg/ml, n = 5; separate t = 4.21, p = 0.0003, d.f. = 24). Similarly, pregnant women had higher spot urine CRH IR - 54.6 +/- 15.5 pg/mumol creatinine (Cr) versus 5.0 +/- 0.5 pg/mumol Cr (separate t = 3.20, p = 0.0038, d.f. = 24.0) - and 24-hour urine CRH IR - 13.7 +/- 1.2 pg/mumol Cr compared with 7.7 +/- 0.8 pg/mumol Cr (separate t = 4.28, p = 0.003, d.f. = 24.4) than the non-pregnant cohort. The difference between urinary excretion of CRH IR as estimated by 24-hour urine (13.7 +/- 1.2 pg/mumol Cr) and spot urine (54.6 +/- 15.5 pg/mumol Cr) indicated that CRH IR in 24-hour urine may be degraded during storage. The weak associations between plasma and 24-hour urine CRH IR of pregnant women (correlation coefficient r = 0.34, p greater than 0.1), and total 24-hour urine and spot urine CRH IR (r = 0.25, p less than 0.1) further indicate CRH degradation. Plasma and spot urinary CRH IR, however, were strongly correlated (r = 0.80, p = 0.001). The total CRH IR excreted as estimated from the spot urine value (0.5 +/- 0.1 micrograms/day) compared with the total filtered load of CRH IR in the pregnant group (1306.9 +/- 324.6 micrograms/day) showed that 99.97% of the filtered CRH IR was reabsorbed or metabolized by the kidneys. Acidic gel chromatography of spot and 24-hour urine samples showed a CRH IR peak at CRH41 standard elution position (Kd = 0.5), indicating that the molecular form in urine is similar to the 41-residue standard. Pregnancy-induced hypertension correlated positively with plasma CRH IR (r = 0.62, p less than 0.001) and spot urine CRH IR (r = 0.46, p less than 0.01), and negatively with parity (r = -0.60, p less than 0.001). Plasma CRH IR and parity also negatively correlated (r = -0.41, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Corticotropin-Releasing Hormone↗

Three-dimensional reconstruction of the myofiber pattern in the fetal and neonatal mouse heart.

A methodology for three-dimensional reconstruction from serial sections and interactive computer graphics is described briefly. This methodology was applied to study the morphogenesis of the cardiac myofiber pattern in the fetal and neonatal mouse heart (ventricles). Few organized in-plane myofibers were found in the myocardial wall before 12 days postconception, but many fibers were observed in the very numerous trabeculae at all times up to birth. However, beginning at about 12 days, the number of fibers in the myocardial wall increases rapidly: these are seen predominantly in the transverse plane. The neonatal mouse heart, especially the left ventricle, resembles a small adult muscular artery. But the global myofiber pattern in the mouse heart at these stages appears to be more complex than might be inferred from earlier studies of the local myofiber pattern at a few sites in the ventricles of a few species of adult mammals. In particular, the pattern in and adjacent to the interventricular septum appears quite complex.

Animals↗

The relationship of age, level of formal education, and duration of employment toward attitudes concerning the use of computers in the workplace.

The introduction of computer technology in the Canadian health care environment necessitates an adaptation by hospital employees in order to perform their jobs. One thousand twenty-two hospital staff were surveyed immediately following their initial orientation to computers. The survey identified attitudes toward change, and the use of computers in the workplace. Demographic data and job classifications of all respondents were tabulated. Hypotheses were tested regarding the relationships between age, formal education, and duration of employment, and attitudes toward computers and change. Results indicated a generally positive response toward the use of computers in the workplace and to change in general. However, statistically significant results were obtained indicating that age, level of education, and length of employment affect the degree of positive response to both computers and change. The results suggest that demographic variables such as age, level of education, and employment duration must be taken into consideration when planning for the implementation of computer systems in the health care setting.

Adult↗

Primary management of limited laryngeal cancer by radiotherapy and surgical salvage: results of 164 cases treated in a district hospital.

A total of 164 patients with limited laryngeal cancer (all sites, stages T1T2T3, N0N1) were treated between 1966 and 1979 at the Derbyshire Royal Infirmary by a policy of radical radiation therapy and surgical salvage. Of 122 cases of glottic cancer, 32 recurred of which 12 were successfully salvaged by laryngectomy. The corrected actuarial survival at 6 years was T1 95.1%, T2 83.0% and T3 31.3%. Of 38 cases of supraglottic cancer, 18 recurred but none was salvaged. The corresponding survival rates were T1 84.6% and T2 36.4%. A number of factors were analysed by a multivariate stepwise regression method to assess their impact upon radiation failure. These were: tumour status, nodal disease, the presence of symptoms other than hoarseness, histological grade, age, length of history and dose (TDF). Significant determinants in glottic cancer were tumour stage (P less than 0.0005), nodal disease (P less than 0.05) and presence of symptoms (P less than 0.05). In supraglottic cancer dose (P less than 0.001) and severity of symptoms (P less than 0.005) were predictive. It is concluded that this policy was effective in the management of T1 and T2 glottic cases and that T1 supraglottic cases responded well if an adequate radiation dose was delivered. The more advanced stages in both sites, however, did not fare as well, especially if initially node positive and in the presence of severe pretreatment symptoms. Surgical salvage had little impact on overall survival in this group.

Adult↗