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Biomedical subjects

M Holland

Publications and source records attributed to M Holland.

At least 55 records · Page 3Linked to original sources
PubMed1996

Use of a type-III trilateral external skeletal fixation device in three deer with comminuted fractures.

A type-III trilateral external skeletal fixation device was used to repair comminuted fractures of metacarpal and tibial bones in 3 deer. Mean weight of the deer was 25 kg, and mean age was 4 months. Mean interval from application until removal of the device was 6.5 weeks. All deer had complete function of their previously fractured limbs and had minimal complications during healing. Several factors should be considered when choosing a method of repair for wildlife with fractured limbs. Economic constraints and demeanor of the animal may limit the number of options. Analysis of results of our findings indicated that type-III trilateral external skeletal fixation devices can be used for the repair of comminuted fractures in young deer.

Animals↗
PubMed1996

Production, purification, and characterization of recombinant human hemoglobin rainier expressed in Saccharomyces cerevisiae.

Hemoglobin Rainier is a naturally occurring hemoglobin variant in which the beta 145 tyrosine is substituted with cysteine. The alpha and beta Rainier globin cDNAs were cloned in a high copy number vector and expressed in Saccharomyces cerevisiae under the control of galactose-regulated hybrid promoters. Using this system, we have expressed individual alpha and beta Rainier globin chains. Coexpression of both alpha and beta Rainier cDNAs resulted in the production of a functional hemoglobin molecule. Purification of the recombinant protein was accomplished by ion exchange chromatography. The N-termini of the alpha and beta chains were correctly processed, and the molecular mass, as determined by mass spectrometry, indicated amino acid composition identical to that of natural hemoglobin Rainier. The chromatographic properties of the recombinant hemoglobin Rainier were similar to human-derived hemoglobin A0. The purified recombinant hemoglobin molecule was shown to have an elevated oxygen affinity and a reduced cooperativity as previously reported for natural hemoglobin Rainier. Production of recombinant hemoglobin and especially hemoglobin variants like hemoglobin Rainier has the potential to facilitate use of hemoglobin as a blood substitute as well as in specific applications, such as for use as a therapeutic agent in the treatment of hypotension associated with septic shock.

Chromosome Mapping↗
PubMed1996

Effects of the BKCa channel activator, NS1619, on rat cerebral artery smooth muscle.

1. We have investigated the actions of NS1619, a putative activator of large conductance calcium-activated potassium channels (BKCa) by use of the patch-clamp technique on smooth muscle cells enzymatically isolated from the rat basilar artery. 2. Using whole cell current-clamp to measure membrane potential, addition of 30 microM NS1619 produced cellular hyperpolarization, moving the membrane potential towards the calculated equilibrium potential for potassium. This hyperpolarization was rapidly reversed by IbTX (100 nM), a selective inhibitor of BKCa. 3. In whole cell recordings made from cells voltage-clamped at 0 mV using the perforated-patch technique, addition of NS1619 (10-30 microM) activated an outward current, which reversed following washout of NS1619. 4. This outward current was unaffected by application of either glibenclamide (5 microM), an inhibitor of ATP-sensitive potassium channels, or apamin (100 nM), an inhibitor of small-conductance calcium-activated potassium channels. However, this current was almost completely abolished by iberiotoxin (IbTX; 50-100nM). 5. Depolarizing voltage steps activated small outward currents from cells held at -15 mV. Application of NS1619 (10-30 microM) increased the size of these currents, producing a shift to the left of the current-voltage (I-V) relationship. These currents were largely inhibited by IbTX (100 nM). 6. Measurements of the unitary amplitude of the single channels activated by NS1619 which could be resolved in whole cell recordings yielded a value of 5.6 +/- 0.14 pA at 0 mV. 7. NS1619 (10-30 microM) directly activated single channels contained in excised inside-out and outside-out membrane patches. In both configurations NS1619 (10-30 microM) rapidly increased the open probability of a large conductance calcium-dependent channel. The activation produced by NS1619 was calcium-dependent and inhibited by external IbTX (100 nM). The unitary current amplitude was unaffected by NS1619. 8. By use of conventional whole cell recording methods and conditions that suppressed BKCa openings, outward potassium currents were activated by depolarizing potentials positive to -35 mV from a holding potential of -65 mV. NS1619 (10-30 microM) inhibited this current in a concentration-dependent manner. This inhibition was reversed following washout of NS1619, recovering to 60-90% of control values within 2 min. 9. Ba2+ currents, measured by conventional whole cell recording, were activated by depolarizing voltage steps from negative holding potentials. NS1619 (1-30 microM) inhibited the evoked current in a concentration-dependent manner, yielding an IC50 value of 7 microM with a Hill coefficient approaching unity. This inhibition was reversible, with the currents recovering to 65-100% of control values after washout of NS1619 for 2 min. 10. NS1619 (0.3-100 microM) induced concentration-dependent relaxation of basilar artery segments contracted with histamine/5-HT (IC50 = 12.5 +/- 2.0 microM; n = 4). This relaxation curve was shifted to the right, but not abolished, when the tissue was treated with a blocker of BKCa channels (IbTX; 100nM). Additionally, NS1619 produced concentration-dependent relaxation of basilar artery contracted with a depolarizing, isotonic salt solution containing 80 mM K+. 11. Thus NS1619 produces hyperpolarization of basilar artery myocytes through direct activation of BKCa and also directly inhibits Ca2+ currents and voltage-activated K+ channels. We discuss the implications of these results for its vasorelaxant actions.

Animals↗
PubMed1996

Varicocele in prepubertal boys. Evaluation of clinical Doppler and hormonal findings.

Hormonal, clinical and scrotal Doppler findings were assessed in 16 prepubertal patients having unilateral varicocele. As already described in pubertal patients, Doppler studies made it possible to detect patterns of prolonged, intermittent or permanent reflux. An LH-RH test and an hCG test measuring LH, FSH and testosterone (T) were performed in all cases. Patients with varicocele showed (median and range): LH B (mlU/ml): 0.40 (0.40-2.1); LH Mx.: 3.7 (1.1-15); FSH B (mlU/ml): 1.95 (0.40-4.5); FSH Mx.: 4.9 (3.1-10); T B (ng/ml): 0.2 (0.1-1.5); T Post.: 2.25 (0.82-11.5). The control group showed: LH B (mlU/ml): 0.40 (0.4-0.85); LH Mx.: 2.15 (0.63-12) FSH B (mlU/ml): 1.45 (0.4-3); FSH Mx.: 4.25 (2.6-5.9); T B (ng/ml): 0.1 (0.1-0.3); T Post.: 3.26 (1.0-5.6). No significant differences were found between the hormonal results of the different groups classified according to the scrotal findings. Basal LH and FSH in grade 3 varicoceles were found to be significantly higher (p < 0.05) than those of the control group. Basal T, as well as the maximal response of both gonadotropins to LH-RH, and T response to hCG showed no significant differences with reference to the control group. Our findings provide indirect support to the notion that the gonadal damage would become detectable from puberty onwards.

Adolescent↗
PubMed1995

Growth hormone neurosecretory disfunction in major depressive illness.

Neurotransmitter impairments in MDI can also affect hormonal neuroregulation. Therefore, we decided to study the integrated concentration of growth hormone (IC-GH) and its 24-h secretory profile in this pathology. Ten women with major depressive illness (MDI) (three premenopausal and seven postmenopausal) and four normal matched controls (one premenopausal and three postmenopausal) were evaluated. Samples were obtained every 30 min using a constant withdrawal pump. Growth hormone (GH) pulses were analysed by Cluster System. Twenty-four hour IC-GH was evaluated as area under the curve (AUC) and the following results were found: depressed (D) = 429.15 +/- 367.9 vs. controls (C) = 1281.07 +/- 379.77 (p < .008); nocturnal IC-GH: D = 220 +/- 274.0 vs. C = 739.52 +/- 378.15 (p < .02). No statistically significant differences were found between D and C in diurnal IC-GH or in the number of nocturnal or diurnal pulses. Adrenal (cortisol at 0800h, 2300h and post-suppression with 1 mg of dexamethasone) and thyroid (T3, T4, 0800h and 1700h TSH) evaluations did not show statistically significant differences between D and C women. In conclusion, patients with MDI present a decrease in total GH secretion at the expense of the nocturnal period, probably due to changes in the neurotransmitters that would be involved in depression.

Adrenal Cortex Function Tests↗
PubMed1995

Lessons in cooperation: four hospital consortia relate their quality improvement experiences.

BACKGROUND: In 1989, The Robert Wood Johnson Foundation launched a demonstration project to test a consortium approach to quality improvement. As part of this project, four hospital consortia in various parts of the United States are currently sharing quality resources (for example, training) and collaborating on various improvement efforts. The purpose of the project is to demonstrate that hospitals can take on more difficult problems and accomplish more in cooperation with each other than on their own. CASE STUDIES: The Institute for Quality Healthcare (Iowa City, Iowa) has built a comparative database so that 40 member hospitals can make meaningful comparisons on various aspects of performance; The Vermont Program for Quality in Health Care has lowered the postoperative infection rate in Vermont by monitoring compliance with consensus guidelines; Interwest Quality of Care, Inc, which has member organizations in Utah, Wyoming, and Idaho, has adapted and disseminated guidelines for diabetic care; and The Public Hospital Institute, in Berkeley, California, has worked with the Joint Commission on Accreditation of Healthcare Organizations to develop a written guide to help surveyors understand the unique operational traits of public hospitals. LESSONS LEARNED: Projects such as those with champions in several member organizations and comparative data analysis lend themselves more easily to cooperative work than others. They also provide some strategies for collaboration, such as continually reinforcing the principles of collaboration, obtaining a fully informed commitment, beginning with initiatives that are likely successes, and being serious and vocal about the commitment to confidentiality. CONCLUSIONS: Collaborators in quality improvement gain important resources, such as better information, more relevant reference databases, colleagues and support for quality improvement specialists, and economies of scale in education programs, training materials, and interaction with vendors. However, the difficulties in collaboration are great. Hospitals must continually consider not only "What's in this for me," but also "What can we accomplish as a group that is greater than what each of us can do alone?"

California↗
PubMed1995

Oesophageal cancer: outcome of modern surgical management.

Many clinicians still associate oesophagectomy for oesophageal carcinoma with low cure rates, poor palliation and prohibitive peri-operative mortality. Surgical advances have rendered such perceptions inaccurate. A prospective study of all patients undergoing surgery for oesophageal cancer in an Australian teaching hospital between 1979 and 1993 has been undertaken. Selection, staging, pre-operative preparation, surgical technique and postoperative care were all carefully controlled. One hundred and thirty-seven patients were explored. Twenty-one were inoperable. One hundred and sixteen underwent resection with intent to cure. Hospital mortality for oesophagectomy was 1.7%. There were no cases of clinical anastomotic leakage. Eighty-nine per cent achieved excellent to good swallowing. The median survival for all cases was 14 months and the 5 year survival was 18%. Median survival for resected cases was 18 months and the 5 year survival was 26%. The long-term survival was related to postoperative stage of the disease but not to tumour type. Oesophagectomy for oesophageal cancer will restore good swallowing in 90% of cases. Operative mortality should be less than 5% and the overall 5 year survival 20-30%. Early tumours can often be cured (ca in situ 100%, stages I and II 50-60%), indicating the benefits of early detection. Poor survival in advanced disease (stage III 15%, stage IV 0%) on a background of low surgical mortality indicate the need for better staging and more effective adjuvant therapies.

Adenocarcinoma↗
PubMed1995

Neonatal genistein chemoprevents mammary cancer.

We have investigated the potential of genistein, an estrogenic component of soy, when administered neonatally, to manifest a protective effect against chemically induced mammary cancer. Female Sprague-Dawley rats were treated on Day 2, 4, and 6 postpartum with genistein or dimethylsulfoxide (vehicle). To induce mammary carcinogenesis, all animals were subsequently exposed on Day 50 postpartum to dimethylbenz(a)anthracene. Animals treated neonatally with genistein had increased latency and reduced incidence and multiplicity of mammary tumors compared with vehicle-treated animals. Cell differentiation studies in mammary whole mounts revealed that neonatal genistein treatment resulted in decreased numbers of terminal end buds and increased numbers of lobular structures. A precocious maturation of undifferentiated terminal end buds to more differentiated lobules may account for neonatal genistein treatment protecting against chemically induced mammary cancer.

9,10-Dimethyl-1,2-benzanthracene↗