Effect of supplementary dietary biotin on hoof growth and hoof growth rate in ponies: a controlled trial

The effect of dietary biotin supplementation, at a dose rate of 0.12 mg/kg bwt, on growth and growth rate of the hooves of 8 match-paired poines was investigated in a controlled feeding trial. Treatment animals had a mean hoof growth at the midline dead centre of the hoof capsule of 35.34 mm after 5 months of biotin supplementation compared to control animals 30.69 mm (P < 0.05). Comparison of regression analysis also showed that biotin supplementation produced a significantly higher (P < 0.02) growth rate of hoof horn in this trial. Treatment animals had a 15% higher growth rate of hoof horn and 15% more hoof growth at the midline dead centre, after 5 months of biotin supplementation compared to control ponies. No differences were found between feet for growth of horn, but the older animals in the trial had significantly lower hoof growth (P < 0.05) than the remaining poines.     

Vitamin D3 and ceramide reduce the invasion of tumor cells through extracellular matrix components by elevating protein phosphatase-2A

Increasing phosphorylation reactions by protein kinase A (PKA) or reducing dephosphorylation reactions of protein phosphatase-2A (PP-2A) increases the invasiveness of Lewis lung carcinoma (LLC) cells, as measured by their capacity to traverse extracellular matrix (ECM)-coated filters. Metastatic LLC-LN7 variants have reduced PP-2A activity when compared to nonmetastatic LLC-C8 variants. Immunoblotting showed that this reduced level of PP-2A activity was not due to reduced levels of the PP-2A catalytic (C) subunit. The cellular PP-2A activity could be stimulated by addition of C2-ceramide to LLC-LN7 lysates, or by incubating cells with either C2-ceramide or with a noncalcemic analog of vitamin D3, which has previously been shown to stimulate the release of ceramide. These treatments to elevate PP-2A activity in metastatic LLC-LN7 cells resulted in a decline in their capacity to invade through select (ECM) components, particularly through vitronectin and laminin. Underscoring the importance of PP-2A in limiting the invasiveness of tumor cells was the demonstration that LLC-LN7 cell transfectants overexpressing the PP-2A C alpha subunit were less invasive through ECM components than the wild-type cells. Invasion by these cells was further reduced by additionally increasing PP-2A activity by incubation with C2-ceramide or the vitamin D3 analog. These results suggest a role of a vitamin D3/ceramide/PP-2A pathway in limiting the invasiveness of tumor cells through select ECM components.     

A retroviral vector that directs simultaneous expression of alpha and beta T cell receptor genes

The transfer of alpha/beta T cell receptor (TCR) genes into T lymphocytes or their precursors could provide a means to increase frequency of tumor- or pathogen-specific cytotoxic T lymphocytes. To begin to address this possibility, we have used class I MHC-restricted alpha/beta TCR cDNAs to develop a retroviral TCR expression vector. Alpha- and beta-chain cDNAs were inserted into a derivative of the LN series of retroviral vectors, with the retroviral LTR directing expression of TCR-beta and an internal cytomegalovirus promoter/enhancer driving TCR-alpha expression. The variable region fragments can be replaced using unique restriction sites that have been introduced into the proximal constant regions. We have used this vector system to transfer two different pairs of alpha/beta TCR genes into an alpha- and beta-chain-deficient T cell hybridoma. TCR- hybridoma cells were transduced by coculture with pools of virus-producing cells, and fluorescence-activated cell sorting was used to enrich for cells expressing the transduced TCR. Transduction with either alpha/beta TCR restores stable, long-lived expression of the alpha/beta TCR complex. TCR-mediated signal transduction is also reconstituted, as demonstrated by the ability of transduced cells to secrete IL-2 following stimulation with Vbeta-specific antibodies. Our results suggest that alpha/beta T cell receptor gene transfer could provide a basis for new approaches to immunotherapy, and that further studies examining the in vivo fate of transduced TCR are possible.     

Prophylactic use of factor VIII: an economic evaluation

BACKGROUND: Since the introduction of exogenous factor VIII therapy, several studies have explored the clinical benefits of prophylactic use of factor VIII. Little research, though, has focused on the economic aspects of this regimen. We conducted a cost analysis using data from the Orthopedic Outcomes Study, a prospective, cross-national study of the clinical outcomes associated with different patterns of factor VIII utilization to examine the health care costs incurred and expenditures averted in patients receiving on-demand versus prophylactic use of factor VIII in hemophilia. METHODS AND ANALYSIS: 831 patients with severe hemophilia aged 1 to 31 years, from 19 centers around the world were included in the cost analysis. Patients were categorized into three groups according to the number of weeks during the study years in which they received prophylactic regimens of factor VIII. For each subject, we estimated the costs of hospitalization, surgery, days lost from school or work, and factor VIII utilization. Costs were then stratified by age and by joint score to assess confounding, and a multivariate model developed to determine the relationship between use of factor VIII prophylaxis and total costs, while controlling for potential confounders. RESULTS: Patients who received factor VIII episodically incurred substantially greater disability-related costs (days lost from school or work, days hospitalized due to hemophilia, surgery) than patients who received factor VIII prophylactically for some or all of the study period. For all treatment regimens, most disability-related costs were accounted for by hospitalization for hemophilia-related conditions. The cost of factor VIII itself was substantial in all treatment categories but was highest among patients who received year-round prophylaxis, exceeding the savings resulting from reduced disability and other health care expenditures. CONCLUSIONS: Reductions in non-factor health care costs and disability associated with prophylactic use of factor VIII in hemophilia were substantial and helped somewhat to offset the much higher costs of this regimen. For certain subgroups, frequent episodic treatment may be more expensive than full-time prophylaxis. However, because of the very high cost of year-round prophylactic use of factor VIII, total health care expenditures were highest among patients receiving this therapeutic regimen. However, because prophylaxis clearly offers important clinical benefits, this approach may be warranted on medical rather than economic grounds.     

An evaluation of transovarian uptake of metabolites using arterio-venous difference methods in dairy cattle

Arterio-venous (A-V) difference techniques were used in cattle to examine ovarian energy metabolism, cholesterol uptake and steroid hormone outputs. Catheters were inserted into the ovarian vein and facial artery, and Transonic flow transducers were placed around the ovarian A-V plexus. Further, in some cows, the effects of a challenge with GnRH were examined. Glucose uptake and lactate output were significant in most individual cows. Nonesterified fatty acids (NEFA) uptake were not significant in any cow in dioestrus. Ovarian uptake of beta-Hydroxy-butyrate (3-OHB) was significant in 4 cows in dioestrus. Cholesterol uptake was significant in only 1 cow. Oxygen uptake was significant in all cows at all stages of the oestrous cycle. All cows had significant output of progesterone and oestradiol-17 beta. These data show that the bovine ovary utilises significant amounts of glucose, and Respiratory quotient (RQ) estimates demonstrated that glucose was the primary fuel used by the ovary. The significant output of lactate suggested that anaerobic pathways were mainly used for glucose oxidation. The observed uptakes of 3-OHB indicated that the ovary utilises 3-OHB as a source of energy. Cholesterol uptake was not a rate-limiting factor for steroid hormone production in the ovary. Despite the high metabolic rate in the luteal ovary, the small difference in PO2 between arterial and ovarian venous blood indicated that the ovary consumes only a small proportion of available oxygen. GnRH had no significant effect on the uptake of metabolites and energy metabolism, but it increased OBF and the output of progesterone and oestradiol-17 beta. The use of A-V methods to determine the metabolic needs of the ovary is useful in understanding the means by which nutrition can influence fertility.     

The effects of an abusive primary partner on the condom use and sexual negotiation practices of African-American women

OBJECTIVES: This study examined the consequences of having a physically abusive primary partner on the condom use and sexual negotiation practices of young African-American women. METHODS: Interviews were conducted with 165 sexually active African-American women aged 18 through 29 in San Francisco, Calif. RESULTS: Women in abusive relationships were less likely than others to use condoms and were more likely to experience verbal abuse, emotional abuse, or threats of physical abuse when they discussed condoms. They were more fearful of asking their partners to use condoms, worried more about acquiring the human immunodeficiency virus (HIV), and felt more isolated than did women not in abusive relationships. CONCLUSIONS: HIV prevention programs for women should address domestic violence prevention strategies.     

Current airway clearance techniques

In recent times, airway clearance has become an increasingly important part of the treatment of patients with excessive bronchial secretions, especially those with cystic fibrosis. The number of airway clearance techniques available has also grown considerably, becoming increasingly more specific. This has allowed patients a greater choice of treatment techniques and has led to a subsequent rise in independence. This paper gives a brief overview of the methods of airway clearance currently being used by physiotherapists in New Zealand. To date, no one method has been shown to be more effective than another. It is imperative therefore, that those involved in respiratory care have a clear understanding of the airway clearance techniques available. This will allow us to provide out patients with the best possible treatment option.     

Preferential benefit of implementation of a statewide trauma system in one of two adjacent states

BACKGROUND: Implementation of Oregon's trauma system was associated with a reduction in the risk of death for hospitalized injured patients. An alternative explanation for improved outcome, however, is favorable concurrent temporal trends, e.g., new technologies and treatments. PATIENTS AND METHODS: To control for temporal trends, seriously injured hospitalized patients in Oregon and Washington were compared before either state had a trauma system (1985-1988) and when only the Oregon trauma system had been implemented (1990-1993). The study group consisted of hospitalized injured patients aged 16 to 79 years with one or more index injuries in six body regions, i.e., head, chest, spleen/liver, femur or pelvis fracture, and burns. Hospital discharge claims data were analyzed, converting International Classification of Diseases, Ninth Revision, Clinical Modification, discharge diagnosis codes to Abbreviated Injury Scale scores and Injury Severity Scores using a conversion algorithm. Multivariate logistic regression models were used to estimate the differential risk-adjusted odds of death in Oregon compared with Washington after adjustment for demographics, injury type, and injury severity. RESULTS: Findings indicated no difference in the risk-adjusted odds of death between Oregon and Washington while both states functioned under an ad hoc trauma system (1985-1988). A significant reduction in the risk of death, however, was noted in Oregon for patients with an index injury and an Injury Severity Score > 15 compared with Washington (adjusted odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.70-0.91) after trauma system implementation in Oregon (1990-1993). Specifically, reductions in the risk of death were demonstrated for patients with head injuries (adjusted OR = 0.70, 95% CI = 0.59-0.82) or liver/spleen injuries (adjusted OR = 0.73, 95% CI = 0.54-0.99). CONCLUSION: Assuming that the two states demonstrated similar concurrent temporal trends, the findings support the conclusion that improved outcomes among injured patients in Oregon may be attributed to the institution of a statewide trauma system.     

Dose equivalence and bronchoprotective effects of salmeterol and salbutamol in asthma

BACKGROUND: Salbutamol is the most widely prescribed short acting beta 2 agonist and salmeterol is the first long acting inhaled beta 2 agonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio. METHODS: The bronchoprotection afforded against repeated methacholine challenge by inhaled salmeterol 25 micrograms and 100 micrograms and salbutamol 100 micrograms and 400 micrograms was compared in a randomised, double blind, placebo controlled, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of > or = 65% predicted, screening concentration provoking a fall in FEV1 of 20% (PC20FEV1) of < or = 8mg/ml, and a shift in PC20FEV1 of more than two doubling concentration steps following inhalation of salbutamol 400 micrograms. On five separate occasions subjects underwent methacholine challenge before and 30 and 120 minutes after drug administration. PD20FEV1 was calculated for each challenge. FEV1 at 90 minutes after drug administration was also recorded. RESULTS: Bronchoprotection afforded by salmeterol was increased at 120 minutes compared with 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 micrograms at 30 minutes but significantly greater at 120 minutes. FEV1 at 90 minutes was significantly greater after salmeterol 100 micrograms than after placebo, but there were no other significant differences between treatments. Maximal observed protection was equivalent for salmeterol 100 micrograms and salbutamol 400 micrograms. CONCLUSIONS: The data are compatible with a weight-for-weight dose ratio for salmeterol:salbutamol of < or = 1:4.     

Hb Malm? [beta-97(FG-4)His-->Gln] leading to polycythemia in a Dutch family

We have examined six individuals from a two-generation Dutch family for a suspected hemoglobin (Hb) abnormality. The propositus presented with polycythemia and complained of persistent weakness, headache, and epistaxis. All family members initially showed a normal Hb-electrophoretic pattern, but on isoelectric focusing, three of them displayed a fast-moving band associated with high packed red cell volumes (PCV) and increased red blood cell count. The Hb mutant was analyzed at the DNA level by specific gene fragment amplification (PCR), followed by direct DNA sequencing, and the mutation was confirmed by restriction enzyme analysis. We found a C-->G transversion (CAC-->CAG) at codon 97 of the beta-chain, which corresponded to the His-->Gln amino acid substitution previously described as Hb Malm?. We report here the clinical history of the patient, the effects of phlebotomy treatment, and the effect of subnormal iron conditions on the erythropoietic recovery after phlebotomy. The mechanism responsible for the induction of the higher oxygen affinity is discussed, as are some aspects concerning the occurrence, pathology treatment, and the genetic risk of Hb variants with high O2 affinity.