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Biomedical subjects

T Steiniche

Publications and source records attributed to T Steiniche.

At least 19 recordsLinked to original sources

[Laparoscopic adrenalectomy. An alternative to open surgery of minor adrenal tumors].

In the period February 1994 to November 1995 11 laparoscopic adrenalectomies were performed at our institution (seven women, four men). A transperitoneal approach was used in both right- and left-sided operations. Results were collected retrospectively. Indications for surgery were: Conn's syndrome (four), Cushing's syndrome (two), phaecromocytoma (four), and incidentaloma (one). The operations took median 170 minutes (range 105-250 minutes). Median size of the tumour was 4 cm range 1(1/2)-5 cm). No significant peri- or postoperative complications were recorded. The patients were discharged from the surgical unit median two days after surgery. Laparoscopic operation emerges as an alternative to open operation when dealing with smaller adrenal tumours. Because of the small number of patients, these operations have to be restricted to a few centres where both internists, anaesthesiologists and surgeons with expertise in this field are found.

Adrenal Gland Neoplasms

Primary hyperparathyroidism: biochemical markers and bone mineral density at multiple skeletal sites in Danish patients.

Biochemical bone markers and bone mineral density (BMD) in spine, hip, and forearm were measured, before surgery, in 30 patients with mild to moderate primary hyperparathyroidism (PHP) (25 women and 5 men; mean age 54 +/- 12 years, range 26-73 years) and compared with normal controls. A group of 291 healthy adults (181 women and 110 men) served as controls for BMD. A smaller group of 30 normal individuals (25 women and 5 men; mean age 54 +/- 12 years; range 26-74 years) were used as matched normal controls. Parameters of bone formation (s-osteocalcin, s-alkaline phosphatase activity, and s-bone isoenzyme alkaline phosphatase activity) and bone resorption (s-type-1 collagen telopeptide) were considerably increased in patients with PHP compared with normal controls (p < 0.01 for all parameters). BMD was found to be reduced in the hip (trochanteric: 95.1 +/- 14.7% of expected, p < 0.05; intertrochanteric: 95.2 +/- 13.8% of expected, p < 0.05), and the forearm (proximal: 93.3 +/- 12.2% of expected, p < 0.05; mid: 91.8 +/- 11.6% of expected, p < 0.001; distal: 90.7 +/- 13.1% of expected, p < 0.001). Spine BMD was found significantly reduced in premenopausal (87.8 +/- 7.6% of expected, p < 0.05) but not in postmenopausal patients, and although normal women showed a decrease in spinal BMD with increasing age this was not found in the PHP women. Forearm BMD was reduced in both pre- and postmenopausal patients (distal forearm: 86.7 +/- 12.2% of expected, p < 0.05; 87.6 +/- 12.1% of expected, p < 0.01, respectively). It was concluded that Danish patients with mild or moderate PHP have only small reductions in BMD. The bone loss is mainly found in the appendicular skeleton.

Adult

Bone histomorphometry in the pathophysiological evaluation of primary and secondary osteoporosis and various treatment modalities.

In normal individuals, peak bone mass is reached at 25-35 years of age and thereafter a decrease with age occurs in both sexes. An acceleration in the bone loss is observed in normal women at menopause. Because of either a low peak bone mass or a more pronounced bone loss with age or during menopause, some individuals reach the fracture threshold for bone mass and suffer spontaneous fractures. To understand the mechanism behind age related bone loss, one must recognize that bone in adults is continually renewed through internal reorganization by which bone is turned over by localized osteoclastic resorption followed by osteoblastic formation (remodelling). A total reconstruction of the resorptive and formative phase can be performed by histomorphometric methods applied on iliac crest bone biopsies and thereby give a detailed description of resorptive and formative events. By the remodelling process bone may be gained or lost by 3 mechanisms: 1. Reversible bone loss depending on the magnitude of the remodelling space, which is the amount of bone resorbed and not yet reformed during the remodelling sequence. 2. Irreversible thinning of the trabeculae due to a negative balance at the remodelling site. 3. Irreversible loss of whole trabecular elements caused by deep resorption lacunae perforating the trabecular plates. Although the bone mass is significantly reduced by 20-30% in postmenopausal osteoporotic patients with vertebral fractures compared with normal controls a substantial overlap exists. Our study and several other studies have shown that beside the slight reduction in trabecular bone volume significant differences in microstructure exist between osteoporotic patients and normal controls. These changes in structure are probably a consequence of trabecular plate perforations. Although osteoporotic patients in term of remodelling (bone turnover) are a very heterogeneous group, with patients having a low, normal and even increased bone turnover, no signs in the ongoing remodelling process was found in our study that could explain why these patients had developed osteopenia and changes in the trabecular structure. The bone balance was in the patients slightly negative but no different from the balance found in normal controls. The cause of osteoporosis may therefore be factors occurring earlier in life, maybe long before the manifestation of the disease. Bone mass at any age is the result of two variables--the amount of bone achieved during growth and the subsequent rate of bone loss. Peak bone mass at maturity may be of great importance in determining the risk of developing symptomatic osteoporosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Recombinant human epidermal growth factor prevents sclerotherapy-induced esophageal ulcer and stricture formations in pigs.

Human epidermal growth factor (EGF), a naturally occurring protein, has been implicated in the protection of gastrointestinal mucosal integrity. The efficacy of EGF in the prevention of sclerotherapy-induced esophageal lesions was investigated in 18 minipigs with surgically induced portal hypertension. The animals underwent five weekly sessions of sclerotherapy with polidocanol 2% and were concomitantly treated with either placebo or EGF administered either paravenously or subcutaneously. EGF significantly (P < 0.05) reduced esophageal ulcerations, stricture formations, and mucosal histological damage associated with sclerotherapy. The drug was well-tolerated with no overt toxicity. These results suggest a potentially important clinical value of EGF as an adjunctive treatment with the sclerotherapy.

Animals

Changes in bone histomorphometry after long-term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis.

Intermittent, cyclic etidronate therapy (400 mg/day for 2 weeks followed by 13 weeks free from study drug administration) resulted in a significant increase in lumbar bone mineral content and a significant decrease in the rate of new vertebral fractures in patients with postmenopausal osteoporosis. To investigate the effect of the treatment on bone histomorphometry, transiliac crest bone biopsy samples were obtained in this study before treatment and after 60 and 150 weeks of treatment with either intermittent, cyclic etidronate (n = 33) or placebo (n = 33). After 60 weeks of etidronate therapy, significant decreases in activation frequency (from 0.55 to 0.09 year,-1 P < 0.01) and resorption depth (from 53.2 to 37.8 microns, P < 0.05) were observed, leading to a positive balance per remodeling cycle. In the placebo group, no significant changes were seen. The 150 week bone biopsy samples were suboptimal for analysis, probably as a result of a regional acceleratory phenomenon. Our results suggest that, as a result of reductions in both activation frequency and resorption depth, intermittent, cyclic etidronate therapy may protect the trabecular network against fortuitous perforations and thereby maintain the strength of the bony tissue.

Aged

Reconstruction of the formative site in trabecular bone by a new, quick, and easy method.

Ordinary measurements of the wall thickness (the end result of the osteoblastic work) of trabecular bone packets (completed remodeling sites) describe the average thickness of walls formed during the previous two to three years. If the bone biopsy is obtained shortly after onset of disease or initiation of treatment, only a few of the measured sites will represent walls formed under the new conditions. With a reconstruction of the formative site true information of the performed osteoblastic work can be obtained, since it is based upon observations of the actual formative events and not the end result (completed walls). Previously published methods have the disadvantage of being time consuming and technically difficult. Furthermore, the method by Eriksen et al. includes rather complicated mathematical calculations. In the present study a new method for reconstruction of the formative phase is presented, which can be performed from measurements normally obtained in a routine histomorphometric analysis and from paired values of osteoid thicknesses and uncompleted wall thickness. The method does not introduce a new time consuming step in the histomorphometric analyses of the bone biopsy. Furthermore, calculations needed to reconstruct the events of the formative phase can easily be performed using a personal computer and a spread-sheet. The new method for reconstruction presented in this paper gives growth curves for matrix and bone mineral, which are virtually identical with the growth curves previously published by Eriksen et al. for the same 20 normal individuals.

Adult

Primary hyperparathyroidism: iliac crest trabecular bone volume, structure, remodeling, and balance evaluated by histomorphometric methods.

Iliac bone biopsies from 69 patients (48 females, 21 males; median age 58 years; range 17-79 years) with primary hyperparathyroidism (PHP) were examined, and static histomorphometric parameters compared to 30 age- and sex-matched normal controls. The control group for the dynamic parameters constituted 20 sex-matched younger normal controls. Fractional volume of trabecular bone was normal, but the trabeculae were thinner (p less than 0.05) in PHP. The structural parameters marrow space star volume, intertrabecular distance, and mean trabecular plate density were not significantly different in PHP patients compared to normal controls, but the age-related increase, for females, in marrow space star volume and decrease, for both sexes, in mean plate density observed in the controls were not noticed in the PHP group. Trabecular bone remodeling was found significantly increased in the PHP patients reflected by increased extension of eroded (p less than 0.001), osteoid (p less than 0.001), and labeled surfaces (p less than 0.05). The activation frequency was increased by approximately 50% (p less than 0.001). Neither PHP patients nor controls showed age-related decrease in trabecular thickness, and accordingly in both groups the bone balance per remodeling cycle was very close to and not significantly different from zero. Normal postmenopausal women (age greater than or equal to 50 yr) had lower trabecular bone volume (p less than 0.001) and higher intertrabecular distance than normal pre-menopausal women (age less than 50 yr).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The effects of etidronate on trabecular bone remodeling in postmenopausal spinal osteoporosis: a randomized study comparing intermittent treatment and an ADFR regime.

Thirty-seven patients were randomized to receive intermittent cyclic etidronate (400 mg/day oral for 2 weeks, followed by 13 weeks off treatment) or an ADFR treatment (100 micrograms/day oral triiodothyronine for 7 days, followed by 400 mg/day etidronate for 2 weeks and 12 weeks off treatment). Supplemental calcium (120 mg/day) and vitamin D3 (400 IU/day) were given throughout the study period to all patients. Biochemical analyses, iliac-crest bone biopsies, and lumbar bone mineral content (BMC) measurements were performed before and during 60 weeks of treatment. Sixteen patients in the intermittent cyclic etidronate group and 15 in the ADFR group completed 60 weeks of treatment. Serum alkaline phosphatase decreased from 185 (43) (mean, (SD] to 144 (35) (p less than 0.001) and from 221 (69) to 156 (43) (p less than 0.002) during intermittent cyclic etidronate treatment and ADFR treatment, respectively, without any significant changes in renal hydroxyproline excretion. Final resorption depth, trabecular bone activation frequency, and bone formation rate decreased significantly from 51.5 (48.4/60.0) microns (median (25%/75% quartiles] to 44.0 (39.6/46.2) microns (p less than 0.04), from 0.30 (0.17/0.62) year-1 to 0.10 (0.02/0.19) year-1 (p less than 0.03) and from 0.035 (0.020/0.081) microns3/microns2/day to 0.015 (0.002/0.025) microns3/microns2/day, p less than 0.03 respectively, during intermittent cyclic etidronate treatment, but were unchanged during ADFR treatment. No significant changes in trabecular bone volume, bone balance per remodeling cycle, or BMC were noted in either treatment group; no evidence of osteomalacia was found. Intermittent cyclic etidronate treatment may be effective in preventing bone loss and in decreasing the risk of trabecular plate perforation, and thereby maintaining the integrity of bone architecture, in postmenopausal osteoporosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Bone disorder in men with chronic alcoholism: a reversible disease?

Disturbances in bone metabolism and histology have been recognized in chronic alcoholism. It has not been established whether they are reversible and the cause remains unclear. We studied various serum and urine variables (including serum PTH, calcium, D-vitamins, and osteocalcin concentrations), bone mineral content, and bone histomorphometrics in men who at present abused alcohol and compared the results to those from men who previously had abused alcohol but who had abstained from alcohol for at least 2 yr and from normal men. No significant differences were found in bone mineral content at the two measuring sites (distal forearm, lumbar spine) between drinkers, abstainers, and controls though a considerable proportion of both current drinkers and abstainers had subnormal values. Bone formation rate and turnover (expressed by the activation frequency) was significantly reduced in the current drinkers who also had lower serum PTH, 1,25-dihydroxycholecalciferol, and osteocalcin concentrations. Men who had abstained from alcohol consumption for at least 2 yr had results similar to those from normal men, suggesting that the disturbances in bone metabolism in men abusing alcohol are reversible. The decrease in bone turnover in the drinkers may be explained by the observed reduction in plasma PTH concentration or a direct toxic effect of ethanol on bone tissue leading to a deficient recruitment of osteogenic cells.

Alcoholism

Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis.

Progressive bone loss in osteoporosis results from bone resorption in excess of bone formation. We conducted a double-blind study in 66 women with postmenopausal osteoporosis of therapy with etidronate, a diphosphonate compound that reduces bone resorption by inhibiting osteoclastic activity. The patients were randomly assigned in equal numbers to receive oral etidronate (400 mg per day) or placebo for 2 weeks, followed by a 13-week period in which no drugs were given. This sequence was repeated 10 times, for a total of 150 weeks. Daily oral supplementation with calcium and vitamin D was given throughout the study to both groups. Vertebral bone mineral content was measured by dual-photon absorptiometry; spinal radiographs were assessed to identify new vertebral fractures. Vertebral bone mineral content increased significantly (P less than 0.01) after 150 weeks of etidronate therapy (5.3 percent; 95 percent confidence interval, 2.0 to 8.6; n = 20) but decreased with placebo (-2.7 percent; 95 percent confidence interval, -7.3 to 1.9; n = 20). The difference between groups was 8.0 percentage points (P less than 0.01; 95 percent confidence interval, 2.4 to 13.6). The rates of fracture were significantly different for the period from week 60 to week 150 between the etidronate and placebo groups (6 vs. 54 fractures per 100 patient-years; P = 0.023). No adverse clinical, biochemical, or bone histomorphometric effects of treatment were observed. We conclude that at the end of nearly three years, etidronate therapy for postmenopausal osteoporosis results in significant increases in vertebral bone mineral content and, after approximately one year of treatment, a significant decrease in the rate of new vertebral fractures.

Administration, Oral

Primary hyperparathyroidism: changes in trabecular bone remodeling following surgical treatment--evaluated by histomorphometric methods.

Iliac bone biopsies from 11 patients who underwent successful surgery for primary hyperparathyroidism were examined before and median 7 months after surgical treatment. Trabecular bone volume increased (p less than 0.05) and eroded (p less than 0.005) and osteoid covered surfaces decreased (p less than 0.005) in the postoperative period. Also, a decline in tetracycline labeled surfaces was noticed (p less than 0.02). Osteoid thickness, mineral appositional rate and mineralization lag time were unchanged. Bone formation rate at the level of the basic multicellular unit (BMU) was unaffected, but at the tissue level bone formation rate diminished (p less than 0.02). The surgical cure of primary hyperparathyroidism was found accompanied by a change in bone metabolism as the trabecular bone remodeling decreased from a high turnover to a low turnover state. The spongy bone mass increased after parathyroidectomy but the clinical significance of this finding was not clear.

Aged

[Treatment of Paget's osteitis deformans].

Specific treatment of osteitis deformans (OD, Paget's disease of bone) is indicated when symptoms are associated with signs (biochemical or by bone scintigraphy) of active disease. OD in the base of the skull and osteolytic lesions in weight-bearing bones should be treated irrespective of symptoms. The effect of calcitonin (CT) on symptoms and skeletal blood-flow is achieved rapidly and healing of osteolytic lesions may occur. However, CT is only effective in approximately 60%, is discontinued due to side effect in 20% of patients, and must be administered parenterally. EHDP (Etidronate) is administered orally but the use of even small doses carries a risk of mineralisation defect and possibly fracture. EHDP should, therefore, be given intermittently and should not be used in osteolytic lesions of weight-bearing bones. Second-generation bisfofonates are devoid of this side effect and are very effective in OD. The effect of mithramycin is only transient and because of the risk of serious side effects the use should be restricted to severe cases of OD resistant to the other lines of treatment.

Adenosine Diphosphate

[Paget's osteitis deformans. Epidemiology and clinical picture].

Osteitis deformans is a focal disease of the osteoclasts characterised by increased bone resorption subsequently followed by increased bone formation leading to abnormal bone. A viral etiology seems increasingly probable, but remains unproven. 5-30% of the patients present with symptoms such as pain, deformity and fracture. Hearing loss, nerve- or root-compression, arthrosis and hyperuricaemia may complicate the disease while malignant degeneration, hypercalcemia and high output cardiac failure are rare. The diagnosis is based on X-ray findings but biopsy may be necessary in selected cases. The extent of the disease is revealed by bone scintigraphy and the activity of the disease reflected by urine hydroxyproline excretion and serum alkaline phosphatase.

Adult

A randomized study on the effects of estrogen/gestagen or high dose oral calcium on trabecular bone remodeling in postmenopausal osteoporosis.

Thirty-seven patients with postmenopausal crush fracture osteoporosis were randomized to oral cyclic estrogen/gestagen (n = 20) or oral calcium (2000 mg elemental calcium per day) (n = 17). Fourteen in each group completed 1 year of treatment. Iliac crest bone biopsies were obtained after intravital double labeling with tetracycline before and after treatment in 10 patients on estrogen/gestagen and 11 patients on calcium. In the estrogen/gestagen group the activation frequency in trabecular bone decreased from 0.52 + 0.11 (SEM) year-1 to 0.27 + 0.08 year-1 (p less than 0.01). No significant changes were found in resorption or formation periods. The osteoid surfaces and the mineralizing surfaces decreased (p less than 0.05), whereas the decrease in eroded surfaces was insignificant. Furthermore, no significant changes were observed in final resorption depth, wall thickness or bone balance per remodeling cycle. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.002), whereas the lumbar bone mineral content (BMC) increased (p less than 0.01). In the calcium group the extent and thickness of osteoid surfaces decreased (p less than 0.05) without significant changes in activation frequency. Serum alkaline phosphatase and renal hydroxyproline excretion decreased during treatment (p less than 0.02). No significant changes were observed in lumbar BMC or the other histomorphometric parameters. The study supports that the positive effect of estrogen/gestagen on BMC can be explained by a reduction in the activation frequency of new remodeling cycles leading to a decreased remodeling space and an increase in mean bone age. There is no evidence of a positive balance per remodeling cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Structural and histomorphometric studies of iliac crest trabecular and cortical bone in autosomal dominant osteopetrosis: a study of two radiological types.

Cylindrical iliac crest biopsies were obtained from 16 patients with autosomal dominant osteopetrosis after intravital double labeling with tetracycline, and compared with normal age- and sex-matched controls. Ten patients had the radiological type I (5 women, 5 men, aged 17-62 years, mean 42) characterized by diffuse, symmetrical osteosclerosis and enlarged thickness of the cranial vault. Six patients had type II (2 women, 4 men, aged 22-44 years, mean 36), where "Rugger Jersey Spine" and endobone are characteristic findings. Structural studies of cortical and trabecular bone were performed, and trabecular bone resorption and formation rates were studied using dynamic histomorphometry. The total biopsy length (C. Wi) were increased in type I (p less than 0.05), and unchanged in type II. Both types showed increased cortical width (Ct. Wi) (p less than 0.01 and p less than 0.05, respectively), and decreased fractional width of cancellous bone (Cn.Wi/C.Wi) (p less than 0.01 and p less than 0.05). The fractional trabecular bone volume (BV/TV) and trabecular thickness (Tb. Th) were both significantly increased in type I (p less than 0.05), while resorptive and formative indices of trabecular bone remodeling were normal. No difference was found in trabecular bone balance, which was slightly positive in both patients and controls. In type II osteopetrosis the eroded surfaces (OS/BS) were significantly increased (p less than 0.01), as was the total resorptive period RP) (p less than 0.05). The resorption depth (R.D.) was normal, while the resorption rate (MRR) was insignificantly decreased. Many big multinucleated osteoclasts were seen in this type suggesting defective resorptive function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Histomorphometric analysis of bone in idiopathic hypercalciuria before and after treatment with thiazide.

Twenty-seven normocalcemic patients aged 11-69 yrs with recurrent renal stone formation and idiopathic hypercalciuria were studied before and after treatment with hydrochlorthiazide (TD) 50 mg twice a day for 6 months. Hypercalciuria was defined as a 24 h renal calcium excretion of more than 7.5 mmol for males and 6.3 mmol for females. Quantitative histomorphometric analysis of iliac crest bone biopsies were performed before and after treatment. TD treatment increased the adjusted serum calcium level (p less than 0.01), whereas no significant effects on the serum levels of phosphorous, alkaline phosphatase or iPTH were found. The urinary calcium/creatinine ratio decreased (p less than 0.01) during TD treatment, whereas no change in the urinary phosphorous/creatinine ratio was found. The histomorphometric analysis revealed a reduction in the extent of eroded surfaces (p less than 0.05) and bone formation rate (p less than 0.05) as well as a decrease in the osteoid thickness (p less than 0.05) during TD treatment. No effect on the trabecular bone volume was found. A reduction in the activation frequency of new remodeling sites and thereby a reduced bone turnover during TD treatment can explain the observed histomorphometric changes. The decrease in osteoid thickness may be related to the increased serum calcium concentration leading to better conditions for mineralization.

Adult