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Biomedical subjects

G Campbell

Publications and source records attributed to G Campbell.

At least 145 records · Page 8Linked to original sources

Heterogeneous size of the parathyroid glands in familial multiple endocrine neoplasia type 1.

OBJECTIVE: We wished to determine whether there was size heterogeneity of the parathyroid glands in patients with familial multiple endocrine neoplasia type 1 (FMEN1) and primary hyperparathyroidism. DESIGN: At the National Institutes of Health we performed a retrospective analysis of parathyroid gland volume either from initial or repeat parathyroid exploration. PATIENTS: We studied subjects with FMEN1 and primary hyperparathyroidism. MEASUREMENTS: The parathyroid gland volume was estimated from recorded orthogonal diameters. Volume could also be estimated conservatively in many glands for which one or more diameters were not recorded. Reproducibility of volume measurements was tested with a series of clay gland models. Indices of variability (among glands at an operation or among replicate measurements of a clay model) were the ratio of maximum volume/minimum volume and the average standard deviation of the log volume. RESULTS: The most complete data were from eight initial operations with three dimensions recorded for all four glands. Volume heterogeneity was indicated by the average ratio of 9.6 for the maximum/minimum gland volume within an operation. The size heterogeneity was even greater among other subgroups. For example, the average ratio of maximum/minimum gland volume within an operation was 17 among five initial operations with four glands removed, but lacking measurements of three dimensions for some glands. Little of this size heterogeneity could be attributed to measurement error since eight replicate measurements on a model gland yielded a maximum/minimum volume ratio of 1.45. CONCLUSIONS: There is a wide heterogeneity in size of the parathyroid glands in the patients with FMEN1 and primary hyperparathyroidism.

Humans↗

Aortic valve/root interactions in porcine hearts: implications for bioprosthetic valve sizing.

The implantation of aortic allografts as well as stentless, freehand porcine xenograft valves requires proper sizing of the graft for the recipient aortic root. To visualize the aortic valve in motion and measure the cyclic expansion of the aortic root, we developed an isolated porcine heart model and a computerized three-dimensional reconstruction technique. Dynamic and static expansions of the aortic root were obtained from beating and arrested porcine hearts, and additional static expansions at varying pressures were measured from reconstructed three-dimensional models of valves obtained with high-resolution magnetic resonance imaging. Measurements of aortic root expansion have shown that it is highly dependent upon the pressures imposed on the heart. Although the aortic root expanded by only 5% between systolic pressures of 60 and 100 mmHg, the total expansion was up to 40% between rest and cyclic pressurizing to 100 mmHg. This data suggest that unstented xenograft valves should be sized 30% to 40% larger than the collapsed size of the recipient aorta. Proper sizing of valves on stents should also be attempted to reduce the large amount of leaflet redundancy that current stenting techniques produce.

Animals↗

Host genetic background effect on the frequency of mouse mammary tumor virus-induced rearrangements of the int-1 and int-2 loci in mouse mammary tumors.

The frequency with which int-1 and int-2 are rearranged in mouse mammary tumors by mouse mammary tumor virus (MMTV)-induced insertional mutagenesis is a consequence of the host genetic background. In 75% of C3H mammary tumors, int-1 is rearranged by MMTV insertion, whereas only 30% of BALB/cfC3H tumors contain a virus-induced rearrangement of int-1. This difference is significant (P less than 0.005) and could not be accounted for by the potentially additive effect of the genetically transmitted Mtv-1-encoded virus in C3H mice. Similarly, MMTV-induced rearrangement of the int-2 gene in mammary tumors of the R111 mouse strain (59%) occurred at a significantly (P less than 0.025) higher frequency than in BALB/cfR111 (25%) mammary tumors. Moreover, in BALB/cfR111 mammary tumors, there is evidence that rearrangement of int-1 and int-2 does not occur independently (P less than 0.025). These results suggest that the long history of inbreeding for high tumor incidence of C3H and R111 mouse strains has selected for the fixation of host mutations which either complement the action of the particular int gene or affect the sensitivity of specific subpopulations of mammary epithelium to infection by particular strains of MMTV.

Animals↗

Vanadate inhibits both intercellular adhesion and spreading on fibronectin of BHK21 cells and transformed derivatives.

Both intercellular adhesion and spreading on fibronectin of BHK21 hamster cells are inhibited by vanadate at concentrations that cause specific regulatory effects rather than general metabolic inhibition. Inhibition of aggregation of these cells in suspension (half-maximal in 10(-5) M vanadate) is rapid and reversible. The extent of inhibition, and its decline with culture age parallel inhibition by agents that depolymerize microtubules. Vanadate also reversibly inhibits spreading of both BHK cells and transformed derivatives on fibronectin. If 10(-4) M vanadate is added to BHK cells that have spread in its absence, they remain spread, but transformed derivatives are sensitive to rounding by vanadate at 10(-6) M. The mechanisms by which vanadate inhibits both intercellular adhesion and spreading are unknown, and may be different for the two phenomena. Possible sensitive targets include cytoplasmic dynein for the former, and protein tyrosyl phosphatase for the latter.

Adenine↗

Use of operating theatres: the effects of case-mix and training in general surgery.

Details of theatre occupancy times for a surgical unit in a district general hospital and associated cottage hospital were recorded over a 4-month period. The average time of the procedures individually and reclassified within the BUPA schedule showed that both the severity of the procedure and the grade of surgeon influenced future theatre needs. For almost every type of procedure, as expected, consultants were quicker than registrars, who in turn were faster than SHOs. The hidden cost of training surgeons in general surgical operative procedures can be estimated as a result. It is concluded that current measures of resource use which rely only on the bed use and ignore operating theatre needs and training requirements for non-consultant grades will be misleading, particularly in relation to the large element of minor or intermediate surgery which constitutes the bulk of most district health authorities' workload.

Diagnosis-Related Groups↗

Co-localization of calcitonin gene-related peptide- and substance P-like immunoreactivity in mucosal intra-epithelial nerves in the toad colon.

Mucosal intra-epithelial nerve terminals have been found in the colon of the toad, Bufo marinus. Co-localized in the fibres are calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and substance P (SP)-LI. The intraepithelial nerves are likely to be terminals of primary afferent sensory neurones. Fibres with vasoactive intestinal peptide (VIP)-LI or neuropeptide Y (NPY)-LI also supply the mucosa but do not penetrate the epithelium.

Afferent Pathways↗

Loss of heterozygosity on chromosomes 17 and 18 in breast carcinoma: two additional regions identified.

The loss of heterozygosity (LOH) at specific regions of the human genome in tumor DNA is recognized as evidence for a tumor-suppressor gene located within the corresponding region of the homologous chromosome. Restriction fragment length polymorphism analysis of a panel of primary human breast tumor DNAs has led to the identification of two additional regions on chromosomes 17q and 18q that frequently are affected by LOH. Deletions of each of these regions have a significant correlation with clinical parameters that are associated with aggressive breast carcinomas. Previous restriction fragment length polymorphism analysis of this panel of tumors has uncovered several other frequently occurring mutations. LOH on chromosome 18q frequently occurs in tumors with concomitant LOH of loci on chromosomes 17p and 11p. Similarly, tumors having LOH on 17q also have LOH on chromosomes 1p and 3p. This suggests that certain combinations of mutations may collaborate in the development and malignant progression of breast carcinomas.

Blotting, Southern↗

A computerized system for video analysis of the aortic valve.

A novel technique was developed to study the dynamic behavior of the porcine aortic valve in an isolated heart preparation. Under the control of a personal computer, a video frame grabber board continuously acquired and digitized images of the aortic valve, and an analog-to-digital (A/D) converter read four channels of physiological data (flow rate, aortic and ventricular pressure, and aortic root diameter). The valve was illuminated with a strobe light synchronized to fire at the field acquisition rate of the CCD video camera. Using the overlay bits in the video board, the measured parameters were super-imposed over the live video as graphical tracing, and the resultant composite images were recorded on-line to video tape. The overlaying of the valve images with the graphical tracings of acquired data enabled the data tracings to be precisely synchronized with the video images of the aortic valve. This technique enabled us to observe the relationship between aortic root expansion and valve function.

Animals↗

Comparative safety and efficacy of short ragweed extracts differing in potency and composition in the treatment of fall hay fever. Use of allergenically bioequivalent doses by parallel line bioassay to evaluate comparative safety and efficacy.

One high potency (HP) and two low potency (LP) commercial whole short ragweed (WSR) extracts were assayed for relative potency (RP) by antigen E (AgE-Amb a 1), RAST inhibition, and parallel line bioassay (PLBA). The RP of the HP extract (300 micrograms AgE) was equal to the reference WSR, but the LP extracts were only approximately 0.01 of the RP of the reference. Each extract was administered to fall hay fever patients with skin sensitivity to WSR (less than or equal to 10(-3) micrograms/ml AgE for sum of erythema = 50 mm) to the maximum tolerated dose, or 0.5 cc of the concentrate, by either a 9- or 40-dose regimen. HP-treated patients had significantly lower symptom scores than untreated controls. No significant difference was noted in the total symptom scores between HP and LP extract-treated patients. Despite approximately 100-fold differences in the RP of HP versus LP extracts, both produced similar frequencies of severe systemic and severe late phase local reactions. Furthermore, when RP of HP and LP extracts were estimated by PLBA, both reached similar peak dosages, similar dosage for IgG WSR antibody response, and comparable IgG WSR antibody levels, indicating that the WSR dose estimates based on RP were bioequivalent. The 9-dose HP regimen produced fewer late phase local and systemic reactions per patient than the 40-dose HP regimen. Most patients experiencing severe systemic reactions were among those most skin sensitive to WSR. The number of systemic reactions per injection was significantly higher at higher WSR doses. One LP extract produced a high incidence of systemic reactions in the initial three injections. With respect to HP, its RP varied approximately 10-fold depending on the skin sensitivity of the patient to heat-stable ragweed allergens, demonstrating that it was compositionally different. However, when the dose of this extract was estimated by RP based on the skin sensitivity of each patient, the peak dose of the extract as well as the doses associated with late phase and systemic reactions were found to be similar to the HP doses. This indicated that immunizing dose estimates of compositionally different WSR extracts based on RP by PLBA were also bioequivalent.

Adult↗

Hypothalamic-pituitary-adrenal function in patients with the premenstrual syndrome.

Patients with primary affective disorders, such as melancholic depression and anorexia nervosa, frequently have a hyperactive hypothalamic-pituitary-adrenal (HPA) axis, characterized by hypersecretion of CRH and a blunted ACTH response to exogenous CRH. Premenstrual syndrome (PMS) is a luteal phase dysphoric disorder characterized by primarily affective and behavioral disturbances. HPA axis function was compared in PMS patients and control women, respectively, diagnosed by DSM3-R criteria or found to have no current psychiatric disorders, determined by the Schedule for Affective Disorders and Schizophrenia-Lifetime Interview. Urinary free cortisol excretion was the same in PMS and normal women, and no differences in urinary free cortisol excretion between the follicular and luteal phases occurred in either group. Two HPA axis abnormalities, however, were noted when PMS patients were compared to normal women. First, basal evening cortisol concentrations in plasma were significantly decreased, while the time-integrated response of plasma cortisol to ovine (o) CRH was significantly increased. Second, the negative correlation between time-integrated plasma ACTH and cortisol responses to oCRH and basal luteal progesterone concentrations present in normal control women was not seen in the PMS patients. These changes in basal and oCRH-stimulated plasma cortisol levels in association with normal urinary free cortisol excretion suggest that women with PMS might have transient or episodic disturbances of their HPA axis, which appear adequately corrected by this system's servomechanisms. This probably explains the maintenance of regular menstrual cycles in PMS patients, which contrasts with the irregular menses observed in patients with depression, anorexia nervosa, or women who participate in chronic strenuous exercise.

Adrenocorticotropic Hormone↗

Development of the mammalian retinogeniculate pathway: target finding, transient synapses and binocular segregation.

This review is concerned with the development of the mammalian retinogeniculate projection from the perspective of our studies on the hamster and to a lesser extent on the cat. In these, and other mammalian species, axons from the two eyes initially spread throughout the dorsal lateral geniculate nucleus (dLGN) and thus completely overlap. Later they segregate, the axons from each eye coming to occupy discrete, non-overlapping territories within the dLGN. The process of segregation to establish the adult pattern coincides with the death of retinal ganglion cells projecting to inappropriate areas of the dLGN and with the loss, by degeneration or retraction, of the axons and/or axonal branches initially located within inappropriate territory of the dLGN. These events occur in the early postnatal period in hamsters, before the eyes have opened, and in cats and monkeys they occur entirely during embryonic life: thus, they do not depend on the onset of normal visual function. If one eye is removed before segregation has begun, the terminal fields of the crossed and uncrossed axons from the remaining eye do not segregate, suggesting that segregation in normal development may depend on some form of interaction between retinal ganglion cells from the two eyes. Attractive and/or repulsive influences exerted by the dLGN on retinogeniculate axons may also be involved in the formation of eye-specific territories. Experimental ultrastructural studies in hamster and cat show that the overlap phase is associated with the formation, by inappropriately located axons, of transient synapses similar to those made by retinogeniculate axons in appropriate parts of the dLGN. In the cat, the transient synapses are made by the axon trunk and by side branches of retinogeniculate axons with terminal arbors in appropriate parts of the nucleus; the transient synapses disappear as the side branches are shed or retracted during the segregation period. Because of good evidence that electrical activity of the retinogeniculate axons may be involved in binocular segregation of inputs, we suggest that the formation and elimination of transient synapses play a significant role in the development of the orderly retinogeniculate projections.

Aging↗

Mutations in human breast cancer: an overview.

Studies of mammary tumorigenesis in mice infected with the mouse mammary tumor virus and in certain strains of transgenic mice with an activated oncogene have provided strong evidence that multiple mutations contribute to the initiation and progression of malignancies in the breast. The increasing availability of recombinant DNA probes that detect various proto-oncogenes, growth factor genes, and growth factor receptor genes, as well as restriction fragment length polymorphisms in the human population, have made possible a molecular approach for the identification of frequently occurring mutations in primary human breast tumor DNA. The aim of studies using this molecular approach has been to investigate whether specific mutations are highly associated with various clinical parameters, including disease prognosis. Eight mutations have been identified, including amplification of c-myc, c-erbB2, and int-2, as well as loss of heterozygosity on five chromosomes (1q, 3p, 11p, 13q, and 17p). Loss of heterozygosity is thought to unmask recessive mutations of tumor-suppressor genes. In some studies, amplification of either c-myc, c-erbB2, or int-2 has been found to have a significant association with high risk of relapse or poor survival. The current status of these mutations as potentially useful prognostic indicators for the management of the disease is controversial and points to the need for further research in this area.

Animals↗

Innervation of the gastrointestinal canal of the toad Bufo marinus by neurons containing 5-hydroxytryptamine-like immunoreactivity.

The gut of the toad, Bufo marinus, was examined for evidence of enteric neurons containing 5-hydroxytryptamine-like immunoreactivity. Such neurons were absent from the stomach. They were present in the small intestine, with processes confined to the myenteric plexus. Immunoreactive nerve cell bodies lay on branches of the pelvic nerves supplying the large intestine; fibres were found in the submucosa of the posterior large intestine and in the muscularis external of the anterior large intestine. It is concluded, on morphological grounds, that the neurons in the small intestine are interneurons, whereas those in the large intestine are postganglionic parasympathetic motoneurons.

Animals↗

Distribution of substance P in the enteric plexuses of the small intestine of the platypus, Ornithorhynchus anatinus.

A study was made of substance P-like-immunoreactive nerves within the small intestine of platypus, an Australian prototherian mammal. Both immunoreactive nerve cell bodies and fibers were present. No immunoreactive fibers were found in mesenteric nerves or on intramural blood vessels, suggesting that extrinsic sensory neurons containing substance P do not innervate platypus ileum. This was further supported by the result of in vitro experiments. Although applied substance P (10(-9) M-3 x 10(-8) M) caused contraction of the longitudinal muscle, neither mesenteric nerve stimulation nor application of capsaicin caused contractions.

Animals↗