The effects of two progrestogen-only pills containing either desogestrel (75 microgram/day) or levonorgestrel (30 microgram/day) on carbohydrate metabolism and adrenal and thyroid function.

OBJECTIVE: To compare the effects of two progestogen-only pills, containing either desogestrel or levonorgestrel, on carbohydrate metabolism, and adrenal and thyroid function. METHODS: In a double-blind, randomized, multicenter study in Finland, 84 healthy female volunteers received either desogestrel 75 microg/day or levonorgestrel 30 microg/day for seven treatment periods of 28 days. The following laboratory parameters were measured at screening, and at treatment periods 3 and 7: carbohydrate metabolism (glucose, insulin, glycosylated hemoglobin (HbA1C)), adrenal function (total cortisol, cortisol binding globulin (CBG), dehydroepiandrosterone sulfate (DHEAS)), thyroid function (thyroid stimulating hormone, free thyroxine). RESULTS: Overall, the effect on carbohydrate metabolism was minimal with both study medications. There was a trend for higher glucose and insulin values for the levonorgestrel group at both treatment periods 3 and 7. None of the changes were thought to be clinically relevant. Both preparations had similar small effects on HbA1C values, indicating that carbohydrate metabolism was not affected. No effects were found on thyroid function parameters or DHEAS in either treatment group; however, total cortisol and CBG were slightly higher with desogestrel than with levonorgestrel. These changes were not considered to be clinically relevant. Both treatments were well tolerated. CONCLUSIONS: The effects of both progestogen-only pills on carbohydrate metabolism were minimal and considered to be clinically insignificant. With regard to adrenal and thyroid function, the effects of desogestrel were not significantly different from those of levonorgestrel.

Evaluation of self-reinforced polyglycolide membrane implanted in the subcutis of rabbits.

BACKGROUND: Self-reinforced absorbable implants have been developed recently to use in hard tissue reconstructive surgery. Polyglycolide is a biocompatible polymer from which the suture Dexon is made and widely used. AIMS: To study histologically the behaviour of self-reinforced polyglycolide membrane (SR-PGA) in rabbits' ears. MATERIAL AND METHODS: SR-PGA membranes, 0.4 mm thick, were implanted in the subcutis of the ears of 24 New Zealand white rabbits. Sham operations were carried out on the contralateral ear of each rabbit. The rabbits were followed-up for 4, 12 and 20 weeks. Attention was directed towards external macroscopic changes in the rabbits' ears. After sacrifice, the ears were taken as specimens, inspected for any evidence of infection, sinus formation or fluid accumulation and histological examination was carried out. RESULTS: No complications such as infection, fluid accumulation or sinus formation were observed. Histologically, the membranes induced a foreign-body reaction involving fibrous tissue encapsulation, macrophages and giant cells. Fibrous tissue and inflammatory cells were seen between the PGA fibres. The membranes underwent progressive degradation throughout the follow-up period. However, PGA material could be still seen 20 weeks postoperatively, with a small amount of fibrous tissue and macrophages and giant cells. The implant-cartilage interface comprised fibrous and fatty tissue. CONCLUSIONS: SR-PGA membranes are biocompatible when implanted in the subcutis of the ears of rabbits.

Histological evaluation of poly(L-lactide/epsilon-caprolactone) membrane implanted subcutaneously in rats.

BACKGROUND: Poly(L-lactide/epsilon-caprolactone) [P(L-LA/epsilon-CL)] 50/50 membranes is an absorbable membrane which has been developed recently for possible use in tissue engineering. AIMS: To look at histological tissue reactions to the membrane and its behaviour upon its in vivo implantation in rats. MATERIAL AND METHODS: P(L-LA/e-CL) 50/50 membranes, 0.4 mm thick, were implanted subcutaneously in the dorsal neck of 20 Wistar rats. The rats were followed-up for 1, 3, 6, 12 and 28 months. After sacrifice, subcutaneous tissues with implants were taken as specimens, inspected for any gross abnormality and histological examination was carried out. RESULTS: No significant macroscopic changes were noticed except for two implants that were grossly rounded. Histologically, the membranes had undergone cracking, fragmentation and progressive degradation. Cracks appeared initially at the periphery of the implant. Large cracks progressed mainly in longitudinal planes. Cracks occurred in the middle of implants and led to membrane bending in some cases. "Neomembrane" formation, comprised of fibrous tissue and the implant, was seen. The foreign-body reaction to the membrane involved macrophages and foreign-body giant cells. In one case an acute type of polymorphonuclear cell reaction was observed and in a second case a predominantly lymphocytic reaction was seen at three months. They were thought to be the results of infection. No other adverse effects were seen. CONCLUSIONS: P(L-LA/e-CL) 50/50 membrane was found to be biocompatible when implanted subcutaneously in rats. It was degraded to a great extent but not completely in 28 months.

Comparison of self-reinforced poly-L-lactide and steel wire in fixation of sternotomy in rabbits.

BACKGROUND AND AIMS: To investigate the healing of sternotomies fixed with biodegradable self-reinforced poly-L-lactide (SR-PLLA) wire and comparing it with steel wire fixation. MATERIAL AND METHODS: Sixteen rabbits (15 Chinchilla and one New Zealand White rabbit) were operated on. Two parallel holes of 1.5 mm in diameter were drilled in the sternum at the level of the second and third rib and similar holes of 0.8 mm were drilled at the level of the third and fourth rib. A transverse sternotomy was created between both drill hole pairs. The sternotomy with larger drill holes was fixed with 1.1-mm thick SR-PLLA wire. The sternotomy between the smaller drill holes was fixed using 2.0 steel wire. The animals were sacrificed at 2, 7, 26 and 52 weeks postoperatively and specimens were taken, radiographed and studied by both light and scanning electron microscopy. RESULTS: One rabbit died at four months postoperatively as a result of gastrointestinal problems. No other complications were seen. The SR-PLLA wire was slowly degraded. There was no disturbance of bone healing. The implants were surrounded by a fibrous tissue capsule, which also contained chronic inflammatory cells. Both SR-PLLA and steel wires provided sufficient fixation security. No differences in the healing of the sternotomies were observed between SR-PLLA and steel wire fixation. CONCLUSIONS: SR-PLLA wires are biocompatible and useful for sternotomy fixation. They may be suitable for use in clinical applications.

Comparison of costs in ankle fractures treated with absorbable or metallic fixation devices.

The economic costs of ankle fractures treated operatively with self-reinforced polyglycolide acid (SR-PGA) screws, with self-reinforced poly-L-lactide acid (SR-PLLA) screws or with metallic implants was determined. All patients were divided into three groups according to the fixation material used. Open and otherwise complicated fractures were excluded. The total expense of operations in each group was taken into account. The average total cost of an ankle fracture fixed with SR-PGA screws was Pounds 3503. In the SR-PLLA group it was Pounds 3906, and in the metallic group it was Pounds 4514. Total expenses were Pounds 1011 higher in the metallic group than in the SR-PGA group, and consequently, expenses in the metallic group were Pounds 608 higher than in the SR-PLLA group. According to this study, it seems that absorbable fixation devices are more economical than metallic implants in operative treatment of ankle fractures though as part of the differences in total expense in this series is due to the age of the patients and other dissimilarities between these groups, the results have to be interpreted carefully.

Relationship of subjective disability with pain intensity, pain duration, pain location, and work-related factors in nonoperated patients with chronic low back pain.

OBJECTIVE: A cross-sectional study on patients with chronic low back pain to compare relationships between subjective disability and pain intensity, pain duration, pain location, and work-related factors. DESIGN AND SUBJECTS: One hundred and seven outpatients with low back pain, with or without radiation to the legs, of at least 3 months' duration, were administered a comprehensive back patient questionnaire. The questionnaire included the Pain Disability Index (PDI) for the assessment of overall perceived disability and assessments of pain intensity, duration, and location and two pretested short-form work questionnaires. None of the patients had undergone a back operation. SETTING: Tertiary care center. RESULTS: There was evidence of significant interrelationships between the PDI and pain intensity (low back pain, r = 0.53, p < 0.001; leg pain, r = 0.32, p < 0.01; and buttock pain, r = 0.36, p < 0.01), pain location (significantly higher scores with distal pain radiation), and work-related factors (a work load sum score of r = 0.31, p < 0.01; significantly higher scores in patients on sick leave). CONCLUSIONS: The results suggest that subjective disability in patients with chronic low back pain overlaps with both pain and work-related factors. The observations support the multidimensionality of low back disability.

Prevalence, morphology, and topography of blood vessels in herniated disc tissue. A comparative immunocytochemical study.

STUDY DESIGN: Ninety disc herniations removed during surgery were studied by immunocytochemistry, using two different endothelial cell markers, to study the prevalence, morphology, and topography of blood vessels in disc herniations. OBJECTIVES: To increase the specific localization of even very small blood vessels present in disc herniations by using specific antibodies to endothelial cells; to study blood vessels comparatively with two different endothelial cell antibodies, comparing their prevalence; and to study blood vessel morphology and topographic relationships of blood vessels to other tissue elements, particularly disc cells. SUMMARY OF BACKGROUND DATA: In many previous macroscopic studies and in studies using conventional histologic methodology, blood vessels have been observed in degenerated and injured intervertebral discs. In a smaller patient sample, the authors previously observed blood vessels in approximately 80% of disc herniations by immunocytochemistry, the blood vessels co-localizing with macrophage cells. Many of these blood vessels are the product of very active neovascularization after disc tissue injury. The presence of such blood vessels has not, however, been studied in greater detail or in larger patient samples. Immunocytochemistry offers superior visualization and more specific localization and was thus used in the present study. METHODS: Thin frozen sections from 90 disc herniations were immunostained in parallel with von Willebrand factor and Ulex europaeus antibodies, both of which localize endothelial cells specifically. Indirect immunocytochemistry by avidin-biotin-peroxidase complex or alkaline phosphatase-antialkaline phosphatase were used for immunolocalization. Blood vessels were classified as being: +, abundant: (+), very few; or +, totally absent. RESULTS: The prevalence of blood vessels in disc herniations was found in 82 of 90 (91%) disc herniations with von Willebrand factor antibody and in 75 of 90 (83%) disc herniations with Ulex europaeus antibody. In 59 disc herniations (66%), blood vessels were observed with both antibodies in parallel, whereas they were observed with neither antibody in only six of 90 disc herniations. Furthermore, the ratio of abundant to very few blood vessels was 73:9 with von Willebrand factor antibody and 63:12 with Ulex europaeus antibody, further supporting the abundance of blood vessels in disc herniations. Blood vessels were most prevalent in sequestrated discs, but they were also observed in six of eight protrusions. Dense blood vessel networks were observed to penetrate the disc tissue, and blood vessels were also present in areas of inflammatory cell infiltration. Topographically, blood vessels were, on several occasions and with both antibodies, seen to pass close by or to surround disc cells. CONCLUSIONS: By immunocytochemistry with endothelial cell markers, blood vessels can be observed to be numerous, and their prevalence in herniated discs is very high, presumably as a result of a very intense neovascularization process after the disc injury. A close apposition to disc cells may suggest attempts to increase the nutrition of these cells and will influence the metabolism of the cells.

Immunocytochemical localization of immunoglobulins in disc herniations.

STUDY DESIGN: Disc herniation and control discs were studied for the presence of immunoglobulins immunocytochemically. OBJECTIVES: To study a possible presence of immunoglobulin complexes in herniated disc tissue and to locate them at the tissue level by immunocytochemistry; to compare immunohistologic findings with those obtained in control disc tissue; and to compare the prevalences of immunoglobulin M and immunoglobulin G. SUMMARY OF BACKGROUND DATA: In herniated disc tissue, high activity of inflammatory phospholipase A2 was previously demonstrated, and inflammatory cells were noted immunohistochemically. Immunoglobulins G and M were observed biochemically but have not been located at the tissue level. METHODS: Fifty-two disc herniations and three macroscopically normal fresh cadaver discs were managed by an identical immunocytochemical protocol, using monoclonal antihuman antibodies to immunoglobulins M and G. RESULTS: In 29 of 52 disc herniations (56%), immunoglobulin M deposits were observed, and in 18 of 52 disc herniations (35%) immunoglobulin G could be demonstrated. Almost all the disc herniations where immunoglobulin G was present also contained immunoglobulin M deposits (except for two). In the control discs studied, neither immunoglobulin could be observed immunohistochemically. The immunoglobulin deposits were noted in areas where blood vessels were also present. Morphologically, immunoglobulin immunoreactivity resembling immune complexes was observed. CONCLUSIONS: The results lend support to previous suggestions of inflammation and immune reaction in disc herniations, including previous biochemical studies suggesting immunoglobulin deposition. The exact role of the demonstrated immunoglobulins in disc tissue pathophysiology will have to be clarified further.

Immunohistochemical demonstration of sensory and autonomic nerve terminals in herniated lumbar disc tissue.

STUDY DESIGN: Thirty-five lumbar disc herniations removed at surgery were studied by indirect immunocytochemistry. OBJECTIVES: To localize immunohistochemically both sensory and autonomic nerve terminals in disc herniations. SUMMARY OF BACKGROUND DATA: Using various more or less specific histologic and histochemical methods, investigators have reported the presence of free nerve terminals in disc tissue. However, very few studies have, to date, convincingly demonstrated nerve terminals in disc tissue that morphologically resemble the tiny nerve terminals of sensory and autonomic nerve fibers. METHODS: Amplification of the peroxidase reaction product in avidin-biotin-peroxidase complex immunostaining by the glucose oxidase-diaminobenzidine-nickel sulfate method was used to visualize small punctate nerve terminals at high magnification. Thin frozen sections from disc herniation tissue prefixed in Zamboni fixative were incubated with antibodies to synaptophysin to visualize nerve terminals in general, and with antibodies to substance P and C-flanking peptide of neuropeptide Y to further characterize nerve terminals as either sensory or sympathetic. RESULTS: Nerve terminals could be demonstrated in 29 (83%) of the 35 disc herniations. They were observed with the synaptophysin antibody in 17 of 35 (49%) disc herniations, with substance P in 16 of 35 (46%) disc herniations, and with C-flanking peptide of neuropeptide Y in 13 of 35 (37%) disc herniations. Morphologically, the nerve terminals were seen as tiny immunoreactive dots. Some of the nerve terminals were observed close to disc cells, possibly suggesting direct interaction. CONCLUSIONS: Small nerve terminals in disc herniations, both sensory substance P endings and sympathetic C-flanking peptide of neuropeptide Y endings, could be involved in mechanisms of discogenic pain, disc tissue neurogenic inflammation, tissue repair processes after injury, and control of local blood circulation in the newly formed blood vessels. Disc cells may be directly affected by the neuropeptides released from nearby nerve terminals.

Posterolateral lumbosacral fusion with transpedicular fixation: 63 consecutive cases followed for 4 (2-6) years.

We analyzed the clinical, vocational and radiologic outcomes of 63 consecutive posterolateral lumbosacral fusions performed with transpedicular fixation. The indication for surgery was long-standing intractable lumbar and/or radiating pain with spondylolysis-olisthesis in 31 cases, degenerative disc disease and/or facet joint arthrosis in 23 cases and pain after laminectomy/decompression in 9 cases. Radiographic union was finally achieved in 30 out of the 63 cases. Fixation device-related complications, such as screw misplacement, breakage, bending and loosening, occurred in 33 cases. 15 patients underwent refusion. 43 patients obtained good pain relief. There was no correlation between bony healing and a good clinical outcome. 28/49 preoperatively employed patients returned to work. There was no correlation between relief of pain and return to work. 20 patients retired on a full disability pension. The clinical results were best in the spondylolysis-olisthesis group. Only 2/15 patients with markedly reduced spondylolisthesis maintained the reduction. In 3 patients, progressive disc degeneration above the level of fusion was observed. We conclude that posterolateral lumbosacral fusion with transpedicular fixation provides a satisfactory clinical outcome in patients with spondylolysis-olisthesis, but the high incidence of complications related to the fixation device in the other indications studied is a serious drawback of the method.

Osteolysis around uncoated polyethylene acetabular cups : A seven- to nine-year follow-up of 79 hips.

From 1983 to 1985, we performed 105 primary hip replacements in 92 osteoarthritic patients, using a non-cemented uncoated RM polyethylene cup. After a follow-up of 8.2 (7.0-9.0) years, 12 patients had died, five sockets had been revised for loosening and three for dislocation, three patients had been lost to follow-up, and three had been excluded due to severe general illnesses.The remaining 66 patients with 79 hip replacements were reviewed clinically and by radiography, which showed osteolytic foci, mean size 13×18 mm, around 17 acetabular sockets mostly around the superior dome of the cup. Osteolytic foci were also seen around 10 femoral stems, and they were significantly more frequent in the 12 cases, where the socket had migrated.After an exclusion of 11 patients due to a loose stem (one revised) and eight for other illnesses, an excellent or good overall functional outcome was seen in 51% of the remaining 61 hips, a fair outcome in 20% and a poor outcome in 29%. The influence of acetabular pathology on pain and function seemed to be slight.The non-cemented uncoated polyethylene socket involves over time, a high rate of osteolysis and migration, which also endangers the fixation of the stem. These phenomena do not necessarily give symptoms. Regular radiographic reviews are therefore essential. The socket should be exchanged if the stem is revised.

Generation of cartilage from auricular and rib free perichondrial grafts around a self-reinforced polyglycolic acid mould in rabbits.

The generative potential of free perichondrial grafts from rabbit auricular and rib cartilage around a self-reinforced polyglycolic acid (SR-PGA) rod was examined in eight growing rabbits. A 15 x 15 mm perichondrial graft was dissected away from the posterior side of each auricular cartilage. One graft was wrapped around a 1.1 x 10 mm SR-PGA rod and the other served as a control and was shaped into a tube without an implant. Fifth rib cartilages were then resected subperichondrially on both sides. The remaining perichondrium on the other side was wrapped around a 1.1 x 10 mm SR-PGA rod, while the other served as a control and was shaped into a tube without an implant. All the grafts were placed inside pectoralis major muscles. Grafts were biopsied six weeks postoperatively. Neocartilage formation was seen in all grafts with one exception on both the implant and control sides. It formed a tube-like structure around the implant in four cases after grafting of auricular perichondrium and in three cases after grafting of rib perichondrium. New bone formation was also observed. SR-PGA implants did not seem to disturb the generative potential of perichondrium.

Results of the surgical treatment of Morton's neuralgia in 58 operated intermetatarsal spaces followed over 6 (2-12) years.

In 45 patients (52 feet), 58 intermetatarsal spaces were operated on for Morton's neuralgia. The procedure included dorsal incision, division of the deep intermetatarsal ligament, and resection of the common digital nerve including the neuroma. The outcome of the operation was excellent in 13 clefts good in 20, fair in 14, and poor in 11 after a mean follow-up period of 6 years. Five clefts were reoperated, with improvement in four. The feet with Morton's neuralgia displayed a significantly higher rate of other foot pathologies than feet in a randomly selected control group. The results show the efficacy of the surgical treatment of Morton's neuralgia over a long follow-up period, with an improvement in 80% of cases.

Polylactide and polyglycolic acid-reinforced coralline hydroxy-apatite for the reconstruction of cranial bone defects in the rabbit.

The possibility of using coralline hydroxy-apatite in combination with polylactide and polyglcycolic acid instead of a bone graft in the skull region is examinated. Coralline hydroxy-apatite blocks strengthened with a membrane made of a combination of polylactide and polyglycolic acid were inserted into bony defects created in 12 rabbit skulls. The blocks were observed during a follow-up of 12 months. They became fixed to the surrounding bone and no adverse effects or harmful reactions in the nearby tissues could be detected.

Perivascular sympathectomy does not remove adrenergic nerves from distal vessels. The effect of various denervations on the rat saphenous bundle: a histochemical study.

It has been claimed earlier that perivascular sympathectomy removes distal adrenergic innervation of the vessels. Based on preliminary results suggesting the contrary, the purpose of this work was to reconsider the denervation effect of perivascular sympathectomy. We operated on 40 rats using different denervation methods mainly to test the effects of perivascular sympathectomy on the distal saphenous vessels of the leg. The operations were performed on the right leg, while the left leg was used as a control. Samples were taken 2 days after the operations for glyoxylic acid-induced fluorescence examination for the histochemical demonstration of adrenergic nerves. Perivascular sympathectomy seemed to remove the adrenergic innervation only from the operated segment of the vessel. There was a short segment of diminished innervation a few millimeters in length just distal to the perivascular sympathectomy while the more distal adrenergic nerves around the vessels appeared to be normal. When the saphenous nerve was cut the adrenergic innervation seemed to disappear for 1 cm and to continue to be diminished at the medial malleolus site. Lumbar sympathectomy did not seem to remove the distal adrenergic nerves around the vessels, but caused only a slight decrease in innervation. It can be concluded that the peripheral adrenergic innervation is apparently normal after perivascular sympathectomy and that the operation does not have the previously assumed denervation effects.

Shaped regeneration of rabbit ear perichondrium.

The neocartilage that regenerated from the ear perichondrium in 18 growing rabbits was shaped using biodegradable implants. The animals were divided into two groups according to the operation used. In group 1 a self-reinforced polyglycolic acid (SR-PGA) rod was placed inside a perichondrial pocket on the dorsum of the ear and surrounded by blood clot, and in group 2 a flap of ear perichondrium was shaped around an SR-PGA rod. Samples were taken for histological examination six weeks after the operation. Active growth of neocartilage was seen in both groups and the SR-PGA rod had successfully guided the perichondrial regeneration in most of the animals.

The role of polyglycolic acid rods in the regeneration of cartilage from perichondrium in rabbits.

The role of polyglycolic acid (PGA) rods in the regeneration of cartilage from perichondrium was investigated in 12 growing rabbits. The fifth rib cartilage was resected subperichondrially from both sides. A 10 X 1.5 mm self-reinforced polyglycolic acid (SR-PGA) rod was inserted on one side to replace the resected cartilage and the retained perichondrium was sutured around the implant. On the control side the perichondrium was shaped into a tube without an implant. Samples were taken 4, 12, and 20 weeks after operation. Pronounced neocartilage formation was seen on both sides, and had grown to form a tube around the implant. Also new bone formation was seen in 12 and 20 weeks. Foreign body reaction was seen inside the implants in every animal.