The use of pigs as an animal model to evaluate the efficacy, potency and specificity of two growth hormone releasing factor analogues.

In 1982, Guillemin et al reported the isolation of the human (h) growth hormone (GH) releasing factor (GRF) from a pancreatic tumour in an acromegalic patient. Since then, work to develop potent GRF analogues has been widespread and the rat has been the main animal model used. The aim of the present study was to compare the efficacy, potency and specificity of two GRF analogues with those of the native GRF(1-29)NH(2)using pig (p) as the animal model. Two analogues, Al ([His(1), D-Ala(2), Ala(8,9,15,17), D-Arg(29)] hGRF(1-29)NH(2)) and A2 ([D-Ala(2), Ala(8,9,15,17), D-Arg(29)] hGRF(1-29)NH(2)) were compared with the h or pGRF(1-29)NH(2). Five studies were designed using 28-48 kg BW growing barrows. Results showed that the two GRF analogues were more potent than the native GRF molecule, were highly specific, were active for long periods of time and were able to induce changes in body composition similar to those reported with GH or other GRF analogues. Because of the similarity between swine and human species with respect to the amino acid sequence of GRF and to the physiology, secretion and effects of GH, it can be proposed that the pig could be used as a pre-clinical animal model to study and test new GRF molecules over short and long periods of time.

Chiropractic management of a professional hockey player with recurrent shoulder instability.

OBJECTIVE: To describe the clinical management of recurrent shoulder instability in a professional hockey player by using chiropractic management and rehabilitation exercises. CLINICAL FEATURES: A 23-year-old professional hockey player with recurrent left shoulder pain and instability. He had two previous unsuccessful shoulder operations to correct the instability. He reported that the shoulder "slips out" in positions of abduction and external rotation or when the left arm is moved suddenly above shoulder height. The patient was still playing hockey professionally at the time of the initial visit and did not want to have to take time off for another surgery, so he chose to attempt a conservative approach. INTERVENTION AND OUTCOME: The patient had undergone strength training for rehabilitation after each of the previous two shoulder operations and had very strong rotator cuff and scapular musculature. Proprioceptive testing revealed a poor response in the left shoulder compared with the right shoulder. Two subjective outcome measures were used to determine the effectiveness of the treatment protocol in reducing the symptoms of recurrent shoulder instability. Much of the treatment focused on proprioceptive training, soft tissue mobilization, and improving joint function. CONCLUSION: This case demonstrates the potential benefit of chiropractic management and proprioceptive exercises to decrease the symptoms of recurrent shoulder instability.

Isometric back extension endurance tests: a review of the literature.

OBJECTIVE: To review the literature that describes and evaluates the use of isometric back extension endurance tests. DATA COLLECTION: Relevant articles in English were retrieved through a search of MEDLINE and the Index to Chiropractic Literature. Key search terms were back muscle endurance, isometric back endurance, trunk extensors, back muscle performance, and Sorensen test. DATA SYNTHESIS: The principal criterion for inclusion was as follows: any study that discussed or tested an isometric type of back endurance extension test. Studies that were excluded did not use an isometric testing protocol. Thirty-seven of the initial studies are included in this review. RESULTS: Six different types of isometric back extension endurance testing methods were found. Three of these procedures require special testing devices. Much of the research on this topic has centered on a procedure known as the Sorensen test. Normative databases have been established for the Sorensen test and 2 other test types. Validity and reliability have been assessed for some of the procedures. CONCLUSIONS: The influence of motivation and effort exerted by the subject are limiting factors in all of the tests reviewed. These psychologic factors warrant further research. On the basis of the literature reviewed, we determined that the Sorensen is probably the most clinically useful of these tests; it is easy to perform, requires no special equipment, and enjoys the most support from the literature.

Lumbosacral transitional segments: classification, prevalence, and effect on disk height.

OBJECTIVE: To determine the rate of lumbosacral transitional segments among chiropractic practice settings and to determine if this anomaly would affect the height of the lumbosacral disk. STUDY DESIGN: Retrospective review of radiographs. SETTING: Los Angeles College of Chiropractic outpatient clinic and a private chiropractic office. SAMPLES: A total of 20 lumbar series with lumbosacral transitional segments from a private chiropractic office, 47 lumbar series with lumbosacral transitional segments, and 60 age- and sex-matched control series from a college clinic. RESULTS: A total of 2.3% of 882 lumbar series at the private chiropractic office and 6.5% of 786 lumbar series at the Whittier Health Center showed lumbosacral transitional segments of types II, III, or IV. The L5-S1 intervertebral disk height was significantly smaller in patients with lumbosacral transitional segments compared with those without (ie, 11% vs 19% of total lumbar disk height, respectively). When bilateral bony fusion of L5 to the sacrum was present, the L5-S1 disk height was significantly smaller than that without bony fusion (ie, 8% vs. 12% to 14% of total lumbar disk height, respectively). CONCLUSIONS: We conclude that the rate of occurrence of lumbosacral transitional segments is low in chiropractic practice. In the presence of lumbosacral transitional segments, especially when there was bony fusion, the lumbosacral intervertebral disk was significantly narrower than the upper lumbar disks, which should not be considered as disk degeneration or displacement. The type of lumbosacral transitional segment present also showed a significant effect on the height of the lumbosacral disk.

Oxaliplatin with high-dose leucovorin and 5-fluorouracil 48-hour continuous infusion in pretreated metastatic colorectal cancer.

Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m2 as a 2-h infusion on day 1; leucovorin 500 mg/m2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m2 for two cycles and increased to 2 g/m2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity > or = grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.

How is leghemoglobin involved in peribacteroid membrane degradation during nodule senescence?

An increase in the rate of succinate and glutamate uptake by isolated symbiosomes from French bean nodules was observed in the presence of iron plus H2O2. The lipid bilayer, and not proteins involved in transport, seems to be the major target of radical attack. Leghemoglobin in the presence of a 6-fold excess of H2O2 (where heme breakdown and iron release occurred) provoked also an increase in peribacteroid membrane permeability. In contrast, this hemoprotein in the presence of a 2-fold excess of H2O2 (where a protein radical was generated) was without effect. We suggest that in vivo the release of heme iron may constitute the major process concerning the involvement of leghemoglobin in the degradation of the peribacteroid membrane during nodule senescence.

Comparative physiological disposition of some anthraquinone glycosides and aglycones.

The in vitro microbial degradation and the urinary excretion and biliary secretion in rats of two anthraquinone glycosides (sennosides A and B) and four aglycones (sennidins A and B, rhein, and danthron) were studied using a high performance liquid chromatographic system with gradient elution and amperometric detection. Microbial degradation of sennosides A and B occurred almost exclusively in the presence of mice caecum inoculae and was associated with the release of sennidins A and B. Rhein and danthron were indiscriminately metabolized by bacteria sampled from all regions of mice intestine, whereas sennidins lacked stability in biological media. The fraction of the dose administered orally to rats and recovered as aglycones or as glucuronides in bile and urine after 48 hours was five times greater for rhein (15 per cent) and danthron (13.4 per cent) than for sennosides A (1.8 per cent) and B (2.8 per cent) excreted or secreted as sennidins. These results support the concept that anthraquinone glycosides are less likely to enter the systemic circulation and, thus, are able to exert their laxative effect at lower doses than aglycones.