The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats.

The ability of the growth hormone secretagogue (GHS) Ipamorelin to counteract the catabolic effects of glucocorticoid (GC) on skeletal muscles and bone was investigated in vivo in an adult rat model. Groups of 8-month-old female rats were injected subcutaneously for 3 months with GC (methylprednisolone) 9 mg/kg/day or GHS (Ipamorelin) 100 microg/kg three times daily, or both GC and GHS in combination. The maximum tetanic tension of the calf muscles was determined in vivo in a materials testing machine. The maximum tetanic tension was increased significantly, and the periosteal bone formation rate increased four-fold in animals injected with GC and GHS in combination, compared with the group injected with GC alone. In conclusion, the decrease in muscle strength and bone formation found in GC-injected rats was counteracted by simultaneous administration of the growth hormone secretagogue.

The frontotemporal peripheral nerves. Topographic variations of the supraorbital, supratrochlear and auriculotemporal nerves and their possible clinical significance.

The peripheral topography of the supraorbital (SON) and supratrochlear (STN) nerves and the superficial temporal branch of the auriculotemporal nerve (ATN) was investigated in 10 cadavers. The aim was to define the optimal locations for anaesthetic nerve blocks, as well as to help surgeons prevent nerve injuries. Specific measurements on the nerve "exits" in relation to defined landmarks are presented. The variability of the supraorbital notches and peripheral branching of the dissected nerves suggests several methods for anaesthetic blocks in cases of surgical and clinical head pain. The optimum injection site for a selective SON block is 20-30 mm from the midline (range 15-33 mm); reinjection at 30-50 mm from the midline might complete inefficient nerve block. For selective SON block the distance between the main SON and STN branches (mean 15.3 mm) should also be considered. The ATN is best blocked at a point located at the level with and 10-15 mm (range 8-20 mm) anterior to the upper origin of the helix. Separate exits for the medial and lateral SON branches were observed in eight of the 20 nerves examined. Twenty of the 28 exits were foraminae completed by bony or connective tissue. In many cases both the SON and STN ascended close to the associated artery: in six cases a tissue band covered the nerve and vessel at the orbital exit. Some of the observed structures associated with the nerve might be pain-generators, however the present study does not provide any evidence for such a hypothesis.

Growth hormone and mild exercise in combination increases markedly muscle mass and tetanic tension in old rats.

OBJECTIVE: A decline of skeletal muscle mass and strength is seen with aging and immobilization. Growth hormone (GH) has been shown to increase muscle mass. In the present study the effects of a combination of mild exercise and GH on skeletal musculature tetanic tension, dry defatted weight (DDW), volume, water, fat and collagen concentrations were investigated in old rats. DESIGN: Recombinant human GH (2.7mg/kg per day) was injected subcutaneously for 73 days in 21-month-old female rats. Exercised rats ran on a treadmill, 8 m/min for 1 h/day. The in vivo maximal tetanic tension of the calf musculature (m. soleus, m. plantaris, m. gastrocnemius together) was analysed in anaesthetized rats by stimulating the ischiadic nerve. RESULTS: The maximal tetanic tension was increased by 23% in GH-injected compared to saline-injected rats. Mild exercise + GH in combination resulted in a further 18% increase in maximal tetanic tension. The mild exercise by itself did not influence the maximal tetanic tension significantly when compared with saline injected rats. The GH administration and/or mild exercise did not change skeletal muscle endurance, measured as tetanic tension during 30s of stimulation. Serum IGF-I concentration was increased twofold in GH-injected rats. CONCLUSION: The increased muscle mass induced by GH + mild exercise was associated with a corresponding increase in maximal tetanic tension. Combination of GH + mild exercise resulted in a substantial further increase of muscle mass and maximal tension compared with GH injections alone in these old rats.

Growth hormone and mild exercise in combination markedly enhance cortical bone formation and strength in old rats.

The effects of a combination of mild exercise and GH injections on bone were studied in old female rats. Biosynthetic human GH, 2.7 mg/kg/day, was injected s.c. for 73 days. Exercised rats ran 8 m/min on a treadmill for 1 h/day. All rats (age 21 months old) were labeled with a tetracycline injection 56 days and a calcein injection 11 days before killing. The GH injections resulted in an 11-fold increase in femoral middiaphyseal bone formation rate and a 12% increase in cross-sectional area compared with the saline-injected group. The mild exercise doubled the mineralizing surface but did not influence the bone formation rate significantly. The combination of GH injections plus exercise, however, resulted in a further increase of 39% in bone formation rate, primarily at the anterolateral aspects, and an increase of 5% in cross-sectional area compared with the group injected with GH only. The femur ultimate breaking load was increased by 37% and the stiffness by 42% in the group injected with GH compared with the saline-injected group. Exercise alone did not influence the femur mechanical properties. The combination of GH injections plus exercise induced a 4% further increase in ultimate breaking load and 7% further increase in stiffness compared with the group injected with GH alone. The GH injections induced a 117% increase in serum insulin-like growth factor I. The GH-insulin-like growth factor I axis stimulates recruitment of osteoblast precursor cells, resulting in increased bone formation at the periosteal surface. GH injections and mild excercise in combination modulate and increase further the formation and strength of cortical bone in old female rats.

Two oral contraceptives, efficacy, serum proteins, and lipid metabolism. A comparative multicentre study on a triphasic and a fixed dose combination.

A triphasic, combined oral contraceptive containing 30 - 40 - 30 micrograms ethinyloestradiol (EE), and 50 - 75 - 125 micrograms levonorgestrel was compared with a fixed dose combination containing 30 micrograms EE and 150 micrograms desogestrel in a randomized multicentre trial in 193/199 women and 1 063/1 073 cycles, respectively. The duration of the trial was six months. Eleven centres in Denmark, Sweden, and Norway participated. Contraceptive reliability, bleeding control and side effects were evaluated. Influence on serum sex hormone binding globulin (SHBG) and transcortin was assayed as well as lipid metabolism. Three pregnancies occurred in the group using the triphasic regimen but none in the fixed dose regimen. Two of the three pregnancies were considered drug failures and the third a possible interaction. Possible reasons for the triphasic contraceptive failure are discussed with special reference to a British report on eight pregnancies. Bleeding control appeared to be equally good for the two preparations. However, the number of cycles with spotting, breakthrough bleeding and missed withdrawal bleeding were above the levels reported earlier on the triphasic regimen. About 80 per cent of the women completed the planned six months on either combination. Side effects were generally mild and in accordance with earlier reports on low dose oral contraceptives. Metabolically the triphasic levonorgestrel combination increased SHBG 100 per cent versus 200 per cent for the fixed desogestrel combination. Transcortin rose about 98 and 110 per cent, respectively. Both preparations induced similar changes in the levels of lipids and lipoproteins with the exception of a significant increase in the arachidonic content of cholesterol during treatment with the desogestrel-containing preparation.

The effect of general anesthetic agents, ouabain, and aldosterone on striated muscle contraction in toad.

Na+ and K+ transport, resting potentials, action potentials, and muscle contraction are interrelated in the excitation-contraction coupling process. Since anesthetics affect the electrogenic Na+ transport mechanism in the toad bladder model and the coupled Na+, K+ transport in muscle, the authors tested the hypothesis that the effects of inhalation anesthetics on ion transport and muscle contraction are parallel. In this study, the effects were assessed of 4 inhalation anesthetics and, for comparison, the effects of ouabain and aldosterone, on contractions of toad sartorius muscle. Cyclopropane, N2O, ether, and halothane, as well as ouabain and aldosterone, increased twitch height in low concentrations. Halothane, ether, and ouabain decreased twitch height in high concentrations. The effect of cyclopropane and N2O, oubain, and aldosterone on muscle contraction closely paralleled their action on electrogenic Na+ transport. This observation supports the hypothesis that the influence of these agents on muscle contraction is linked to the effect on active ion transport or that both effects are equally sensitive to anesthetic agents.

The effect of corrective surgery on pulmonary function in scoliosis.

Pulmonary function was studied in thirty-five patients before, during, and immediately after major orthopaedic operations. One group of twenty patients had corrective procedures for idiopathic scoliosis. Fifteen patients had operations involving the extremities. In the patients with scoliosis were found that pulmonary mechanics, as expressed by flow resistance and elastic compliance, deteriorated during the operation; that pulmonary right-to-left shunting increased and arterial oxygen tension on air decreased immediately postoperatively; and that vital capacity was greatly reduced after the operation. No significant changes took place in the rest of the patients. We concluded that corrective operations for idiopathic scoliosis are associated with major reductions of pulmonary function in the immediate postroperative period, so that postoperative respiratory failure would be a risk in patients who had compromised pulmonary function preoperatively. We therefore recommend pulmonary function testing preoperatively and outline one approach to this problem.