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Biomedical subjects

P McCann

Publications and source records attributed to P McCann.

At least 19 recordsLinked to original sources
PubMed2002

Guidelines for dosimetry and calibration in ultraviolet radiation therapy: a report of a British Photodermatology Group workshop.

This report examines the dosimetry of ultraviolet (UV) radiation applied to dermatological treatments, and considers the definition of the radiation quantities and their measurement. Guidelines are offered for preferred measurement techniques and standard methods of dosimetry. The recommendations have been graded according to the American Joint Committee on Cancer classification of strength of recommendation and quality of evidence (summarized in Appendix 5).

Humans↗
PubMed2002

The expression of p53, p21, Bax and induction of apoptosis in normal volunteers in response to different doses of ultraviolet radiation.

BACKGROUND: Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations. OBJECTIVES: This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR). METHODS: Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0.5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4.5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21waf1/Cip1 and Bax, by single and double labelling techniques. RESULTS: Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21waf1/Cip1 and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21waf1/Cip1 protein expression (9-48 h) and peak Bax protein expression (33 h). CONCLUSIONS: These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21waf1/Cip1, Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21waf1/Cip1 and Bax occurs in a dose-dependent manner.

Aged↗
PubMed2002

Comparison of the expression of p53, p21, Bax and the induction of apoptosis between patients with basal cell carcinoma and normal controls in response to ultraviolet irradiation.

AIM: Ultraviolet light (UV) is known to cause DNA damage in the epidermis. The damaged DNA is repaired or deleted by apoptosis to prevent the generation of cancer. It has been suggested that a deficient apoptotic mechanism may predispose individuals to skin cancer. Therefore, the response of normal controls and patients with basal cell carcinoma (BCC) to UV irradiation was investigated. METHODS: The buttock skin from normal volunteers and patients with BCC was irradiated using solar simulated radiation (SSR). SSR mimics the effect of natural sunlight. Skin biopsies were excised and examined for p53, p21, and Bax protein expression and for the induction of apoptosis. RESULTS: At 33 hours after UV irradiation, the induction of apoptosis was significantly higher (p = 0.04) in patients with BCC than in normal volunteers (Mann Whitney test). A trend towards higher p21 expression was found at 33 hours in patients with BCC (mean, 18.69 positive cells/field) than in normal volunteers (mean, 9.89), although this difference was not significant (p = 0.05 positive cells/field). CONCLUSION: These results may imply that patients with BCC have enhanced sensitivity to UV irradiation or that there is some defect in the cell arrest or repair pathways, which results in damaged cells been pushed into apoptosis rather than repair.

Apoptosis↗
PubMed1996

Phase I trial of a novel matrix metalloproteinase inhibitor batimastat (BB-94) in patients with advanced cancer.

Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. Batimastat inhibits at least 50% of MMP activity at concentrations less than or equal to 10 ng/ml in vitro. Batimastat retarded ascites accumulation and increased survival in mice with human ovarian tumor xenografts. Acute and long-term toxicological studies revealed no major toxicity in animals. Batimastat is poorly soluble and was administered intraperitoneally (i.p.) as a suspension. Previous studies in patients with malignant ascites have shown no major toxicities at doses as high as 1350 mg/m2.

Adult↗
PubMed1995

Systemic absorption of insulin and glucagon applied topically to the eyes of rats and a diabetic dog.

Nondiabetic rats were anesthetized with xylazine/ketamine to induce hyperglycemia and systemic insulin absorption from eyedrops formulated with dodecylmaltoside was quantitated by both a decrease in serum levels of D-glucose and an increase in immunoreactive insulin levels. When insulin eyedrop administration was delayed until 60 minutes after the administration of eyedrops containing 0.25% dodecylmaltoside, the enhanced systemic absorption of insulin was maintained, suggesting that dodecylmaltoside had an effect directly on the permeability of the nasal sinus epithelium. When glucagon was formulated in eyedrops or nosedrops containing dodecylmaltoside, systemic absorption of glucagon could be measured in the form of an increase in the serum D-glucose concentration following nasal application, but not after ocular application. Eyedrops containing insulin plus 0.125% dodecylmaltoside were administered to a diabetic dog; a dose of 20 units of regular insulin caused a modest decrease in serum D-glucose concentration and a concomitant increase in serum immunoreactive insulin content. These results provide evidence that peptide drugs such as insulin can be formulated in eyedrops with low concentrations of dodecylmaltoside, a mild nonionic surfactant.

Absorption↗
PubMed1995

Arterial supply to the human anterior cruciate ligament.

The arterial supply to the anterior cruciate ligament (ACL) was prepared for study by injecting a fresh cadaver knee with an epoxy lead-oxide solution and subsequently immersing it in 10% formalin for a 2-week period. The vasculature of the ACL was exposed through dissection for examination. A second specimen was prepared similarly and was evaluated by a CAT scan. ACL vascularization arises from the middle genicular artery and vessels of the infrapatella fat pad and adjacent synovium. The artery gives rise to periligamentous vessels which form a web-like network within the synovial membrane. These periligamentous vessels give rise to penetrating branches which transversely cross the ACL and anastomose with a network of longitudinally oriented endoligamentous vessels. Terminal branches of the inferior medial and lateral genicular arteries supply the distal portion of the ACL directly. The extremities of the ACL seem to be better vascularized than the middle part, and the proximal portion seems to have a greater vascular density than the distal portion. The arteries at the ligamentous-osseous junctions of the ACL do not significantly contribute to the ligament's vascularity. Ramifications concerning the ACL's blood supply as it relates to athletic training is also discussed.

Journal Article↗
PubMed1993

Selective sparing of later-born ganglion cells after neonatal transection of the infraorbital nerve.

A combination of [3H]thymidine labelling and retrograde tracing with either horseradish peroxidase (HRP) or true blue (TB) was used to determine whether V primary afferent neurons born on different embryonic (E) days were differentially susceptible to neonatal transection of the infraorbital nerve (ION). In one experiment, rat fetuses were exposed to [3H]thymidine on E-8.5, 9.5, 10.5, 11.5, 12.5, 13.5, 14.5, or 15.5, the left infraorbital nerve (ION) was transected on the day of birth, and both the regenerate and intact IONs were labelled with HRP when the animals reached adulthood. The percentage of HRP labelled cells that were also heavily labelled by [3H]thymidine was calculated for both the intact ganglion and that ipsilateral to the damaged nerve for each animal. A consistently higher percentage of double labelled cells on the lesioned rather than on the intact side for a given E-day was taken as an indication that cells born on the day in question had an increased probability of survival relative to the entire population of V ganglion cells that contributed axons to the ION. Cells born late in gestation on E-12.5 through 14.5 were significantly more likely than early born (E-9.5 through 11.5) cells to survive neonatal axotomy. In a second experiment, fetuses were exposed to [3H]thymidine on either E-9.5, E-10.5, or E-14.5, the vibrissa pads on both sides of the face were injected with TB within 6 hours of birth, and the ION was transected 6-8 hours later.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Intramuscular wire electromyography of the subscapularis.

The action of the subscapularis muscle is an important component in maintaining shoulder stability. Because of its relative inaccessibility, there have been few electromyographic (EMG) studies of its normal patterns of activity. The subscapularis is innervated by two or more distinct nerves, and therefore the upper and lower parts of the muscle may have different functional roles depending on the position of the humerus. The purpose of this study was to develop safe, reproducible insertion paths to the upper and lower parts of the subscapularis. Six subjects with no previous history of shoulder injury were evaluated. The paths of insertion were designed based on previous anatomical studies as well as dissections. Two pairs of intramuscular wire electrodes were inserted: one directed toward the upper subscapularis and one toward the lower subscapularis. Electrode locations were confirmed using posteroanterior and lateral radiographs and through electrical stimulation. EMG data were recorded during isometric internal rotation exercises with the humerus in 0 or 90 degrees abduction. Significant differences were observed in the EMG activity recorded from the two pairs of electrodes. The EMG activity of the upper subscapularis either remained the same or decreased in going from 0 to 90 degrees abduction, while that of the lower subscapularis increased. The observed differential response confirmed that the electrodes were in different parts of the subscapularis. These preliminary results suggest that in future EMG studies, the subscapularis should be considered as at least two independent muscle units.

Electric Stimulation↗
PubMed1991

Birthdates of trigeminal ganglion cells contributing axons to the infraorbital nerve and specific vibrissal follicles in the rat.

Prenatal labelling with [3H]-thymidine was combined with retrograde tracing techniques in adult rats to determine the birthdates of the trigeminal (V) ganglion cells that contributed axons to the infraorbital nerve (ION) and the generation of the subsets of ION cells that innervated specific vibrissae follicles (C-1 and C-5). The V ganglion cells contributing axons to the ION are born between embryonic (E-, E-0 = the day of conception) days 9.5 and 14.5. The percentages (normalized so that they total 100%) of the total V ganglion population born on E-9.5 through E-14.5 were 5.8, 25.7, 19.8, 23.4, 21.0, and 4.4%, respectively. The distribution of birthdates for the V ganglion cells that were retrogradely labelled from the ION closely matched that for the ganglion as a whole. All of these neurons were also born on E-9.5 through E-14.5, and the percentages born on each day were 6.3, 23.6, 18.1, 24.0, 23.6, and 4.4%. Finally, a similar distribution of birthdates was obtained for the V ganglion cells that were retrogradely labelled after injection of retrograde tracers into either the C-1 or C-5 vibrissae follicles. We were unable to detect any distinctive spatial distributions for either all V ganglion or ION cells born on a specific embryonic day. Furthermore, neurons with a given birthdate and that innervated a given follicle were distributed throughout the entire region containing all of the ganglion cells supplying the follicle in question. Therefore, it appears that the V ganglion cells contributing axons to the ION are born over the entire period of ganglion neurogenesis and further that the organization of the ION's innervation of the periphery is not a function of cell birthdate.

Animals↗
PubMed1991

Effect of anaesthesia on intraocular blood flow.

Pulsatile ocular blood flow, intraocular pressure, systemic blood pressure, and heart rate was measured in two groups of 15 patients. One received lignocaine 1.5 mg/kg intravenously prior to induction. There was a significant increase in intraocular pressure after suxamethonium, which was not associated with any rise in ocular blood flow. Both the IOP and ocular blood flow increased significantly after tracheal intubation. A rise in ocular blood flow reflects the stress response associated with intubation. Lignocaine failed to attenuate either response.

Anesthesia, General↗
PubMed1986

Pain responsivity in women with premenstrual syndrome across the menstrual cycle.

11 women with a clinical diagnosis of Premenstrual Syndrome (PMS) and 10 control women with no such diagnosis were compared on pain threshold and pain-tolerance measures in the intermenstrual and premenstrual phases of their menstrual cycles. No significant differences were found between the groups for behavioral measures of pain sensitivity. Ratings of pain intensity, however, were higher in both phases for the PMS group.

Adult↗