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Biomedical subjects

E Lindh

Publications and source records attributed to E Lindh.

At least 19 recordsLinked to original sources
PubMed1999

Increased fracture rate in diabetes mellitus and females after renal transplantation.

BACKGROUND: Bone disease and fractures after organ transplantation pose severe clinical problems. About 20% of renal transplant patients have type 1 diabetes (IDDM). However, data are scarce in the literature about the occurrence of spontaneous fractures in IDDM patients posttransplantation. METHODS: In this cross-sectional study using a questionnaire and hospital records the prevalence of symptomatic bone disease was investigated in 193 renal transplanted patients with functioning renal grafts 6 months to 23 years after the transplantation. RESULTS: The frequency of IDDM was 18%. In the total group the rate of osteoporotic fractures posttransplantation was 17%, and the majority of fractures occurred within the first 3 years after the transplantation. A high rate of fractures, 40%, was noted in the diabetes group (P<0.001), compared with 11% in the nondiabetes group. Fractures seen in IDDM were often multiple and located mostly in the appendicular skeleton, i.e., in ankles and feet. Female gender was also associated with an elevated fracture rate, 23% (P<0.05). CONCLUSION: An increased incidence of osteoporotic fractures after renal transplantation was found in diabetic and female patients. The mechanism behind bone fragility in IDDM is multifactorial and despite a restored renal function bone disease may progress, and is probably enhanced by the immunosuppressive treatment.

Cross-Sectional Studies↗
PubMed1997

Reduced serum levels of the growth hormone-dependent insulin-like growth factor binding protein and a negative bone balance at the level of individual remodeling units in idiopathic osteoporosis in men.

Idiopathic osteoporosis in younger individuals could be related to reduced bone formation rather than increased bone resorption, and disturbances in GH or insulin-like growth factor (IGF)-I production could be involved in its pathogenesis. In the present study, men with idiopathic osteoporosis were compared with healthy men, with respect to bone histomorphometry and to serum levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-2 and IGFBP-3, and 24-h urinary excretion of GH. Mean wall thickness was reduced in the patients (48.3 +/- 7.2 vs. 61.7 +/- 5.4 microns, P < 0.001). Also, resorption depth was decreased, albeit to a lesser degree (54.4 +/- 3.8 vs. 60.7 +/- 5.3 microns, P < 0.01), thus creating a pronounced negative balance (-6.04 +/- 9.8 vs. 0.96 +/- 3.2 microns, P < 0.05). In the patients, serum concentrations of IGFBP-3 were reduced, compared with controls, with a 46% lower mean value; whereas levels of IGF-I, IGF-II, IGFBP-2, and GH were similar in the two groups. Thus, there was a significant negative balance caused by a pronounced decrease in wall thickness in men with idiopathic osteoporosis. The finding of low IGFBP-3 levels in these patients is interesting, in view of previous clinical and experimental findings, but its pathophysiological significance remains to be determined.

Adult↗
PubMed1997

Regulation of interleukin-6 secretion from mononuclear blood cells by extracellular calcium.

Interleukin-6 (IL-6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL-6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL-6 secretion from mononuclear blood cells. To investigate the underlying mechanism, we have studied the effect of calcium on IL-6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL-6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL-6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL-6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose-dependently increased IL-6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL-6 secretion was seen following treatment of the isolated mononuclear blood cells with PTH or calcitonin. These observations demonstrate that the plasma calcium concentration affects IL-6 secretion from mononuclear blood cells. The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.

Administration, Oral↗
PubMed1996

Effects of growth hormone and insulin-like growth factor I in men with idiopathic osteoporosis.

Injections with growth hormone (GH) or insulin-like growth factor I (IGF-I) have been proposed for anabolic therapy in osteoporosis. In a cross-over study, 12 men with idiopathic osteoporosis received daily subcutaneous injections of GH (2 IU/m2) or IGF-I (80 micrograms/kg) for 7 days with 12 weeks of wash-out. Serum levels of procollagen type I increased by 29% following treatment with GH (P < 0.001) and by 43% with IGF-I (P < 0.001 compared with pretreatment levels; P < 0.05 compared with GH injections), whereas both treatments rendered a 20% increase in osteocalcin concentrations (P < 0.001), indicating enhanced bone formation. There was also evidence of stimulated bone resorption, as the urinary levels of deoxypyridinoline increased by 44% following GH injections (P < 0.001) and by 29% following IGF-I (P < 0.001), and there were 28% higher serum concentrations of IGF-I after GH than after IGF-I injections. Although markers of bone metabolism increased under both treatments, comparison of the treatments suggests that IGF-I enhanced formation of collagen type I more than did GH. Furthermore, the stimulation of bone resorption was detected as soon as 4 days after the initiation of GH injections. Some of the differences might be dose-dependent, but could also indicate separate mechanisms at the cellular level.

Adult↗
PubMed1995

Hormonal regulation of serum lipoprotein(a) levels. Contrasting effects of growth hormone and insulin-like growth factor-I.

In response to treatment with growth hormone, serum levels of lipoprotein(a) increase, while those of LDL cholesterol decrease. To establish if increased levels of insulin-like growth factor-I may be of importance for these changes, we analyzed serum lipoprotein concentrations in 11 male patients with idiopathic osteoporosis who were treated with growth hormone (2 IU.m-2.d-1) or insulin-like growth factor-I (80 micrograms.kg-1.d-1) in a randomized, double-blind, cross-over study. LDL cholesterol was reduced by 0.7 mmol/L (P < .01) during growth hormone treatment but was not affected when the same patients received insulin-like growth factor-I. In contrast, mean lipoprotein(a) levels increased from 519 to 571 mg/L (P < .03) in response to growth hormone but were reduced from 538 to 478 mg/L (P < .04) during treatment with insulin-like growth factor-I. These results indicate that growth hormone exerts its effects on lipoprotein metabolism independent of insulin-like growth factor-I. Furthermore, the results suggest that treatment with insulin-like growth factor-I may reduce lipoprotein(a) levels.

Adult↗
PubMed1995

Carbon dioxide laser miniconization for treatment of human papillomavirus infection associated with cervical intraepithelial neoplasia.

BACKGROUND: The effect of the carbon dioxide laser miniconization for treatment of cervical intraepithelial neoplasia with concomitant human papillomavirus infection was evaluated. MATERIAL AND METHODS: One hundred and eighteen women with cytologically proven cervical intraepithelial neoplasia stage 1 and/or 2 were investigated with repeat vaginal smear, colposcopy and human papillomavirus DNA sampling. Seventy-five out of 118 women were subjected to laser miniconization or punch biopsy and cervical curettage. RESULTS: Out of 118 patients 37 proved to have positive human papillomavirus DNA with one or more oncogenic types (31.4%). Of these, 32 women were miniconized and five subjected to punch biopsy or cervical curettage. On the first follow-up after miniconization all 32 patients were HPV negative. With follow-up up to five years no recurrences of HPV or dysplasia were seen. CONCLUSION: A miniconization procedure with carbon dioxide laser for treatment of cervical intraepithelial neoplasia proved useful also for simultaneous therapy of concomitant human papillomavirus infection of the uterine cervix.

Carbon Dioxide↗
PubMed1995

Lead intoxication caused by skeletal disease.

BACKGROUND: Inorganic lead is accumulated in the skeleton, which harbors more than 90% of the body burden of lead. If rapidly mobilized, this pool may constitute a health risk. However, clear evidence of this theory has been lacking. HISTORY: A previously healthy 36-year-old Swedish man with more than 10 years of work-related lead exposure developed headache, musculoskeletal pain, and paresthesia of both arms. Two months after the cessation of exposure, the lead level in his blood (B-Pb) was 5.5 mumol.l-1, and treatment with chelating agents was started. Shortly after the treatment period, he had an accident causing a fracture of the right collum femoris. The B-Pb was fairly stable around 1.5 mumol.l-1 for about two years after the end of exposure (95th percentile 0.6 mumol.l-1 for occupationally unexposed Swedish men). The examination showed that the patient had high skeletal turnover and clearly reduced bone density, as well as signs of tubular dysfunction. He was given the diagnosis idiopathic osteoporosis. His moderately raised bone lead concentration (about 20 micrograms.g wet weight-1; normal level in Sweden 4 micrograms.g-1) can only partly explain the raised B-Pb, remaining for years after the cessation of exposure. Instead, the main explanation is probably the increased skeletal turnover. CONCLUSIONS: A combination of a moderately increased bone lead pool and skeletal disease seems to increase the risk for lead poisoning.

Adult↗
PubMed1994

Effects of infusion of parathyroid hormone and primary hyperparathyroidism on formation and breakdown of type I collagen.

The influence of chronic and acute exposure to parathyroid hormone (PTH) on formation and breakdown of type I collagen, using two recently developed radioimmunoassays for serum PICP (the carboxyterminal propeptide of type I procollagen) and serum ICTP (the carboxyterminal telopeptide of type I collagen), have been evaluated. Fasting morning values were obtained from 18 women with primary hyperparathyroidism (HPT) and an equal number of age-matched, healthy controls. A 24-hour infusion of synthetic human parathyroid hormone (PTH 1-38) was performed in 14 healthy females. The patients with HPT had higher values for serum ICTP than the controls (6.0 +/- 3.0 and 4.1 +/- 2.1 micrograms/liter; P < 0.05), whereas the serum PICP concentrations were not different (170 +/- 72 and 151 +/- 65 micrograms/liter; n.s.). During infusion of PTH in healthy subjects, there was an increase of the serum ICTP concentrations (from 3.6 +/- 1.3 to 4.4 +/- 1.8 micrograms/liter; P < 0.001) whereas those of serum PICP decreased (from 185 +/- 78 to 118 +/- 42 micrograms/liter; P < or = 0.0001). The increase of serum ICTP during infusion of PTH was positively related to the increase of serum calcium and other indices of bone resorption, i.e., fasting urinary excretions of hydroxyproline and calcium. The decrease of serum PICP was also related to the changes of serum ICTP and hydroxyproline in urine, serum calcium, and alkaline phosphatase but not to osteocalcin, an established marker of osteoblastic activity. The findings support the fact that serum ICTP is a valuable method for evaluating bone resorption and is also easy to perform.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Circulating levels of insulin-like growth factor-I and -II, and IGF-binding protein-3 in inflammation and after parathyroid hormone infusion.

In order to assess if the anabolic action of PTH is related to changes in circulating levels of insulin-like growth factor-I and -II (IGF-I and -II), and IGF binding protein 3 (IGFBP-3), 24 h of PTH infusion was performed in healthy women and in patients with rheumatoid arthritis (RA), a state where both bone metabolism and PTH secretion is influenced by the inflammatory activity. The patients with RA had lower basal levels of both IGF-I and -II than the healthy controls (P < 0.05). In neither group did the IGFs change after 24 h of PTH administration, while IGFBP-3 was significantly increased in the healthy controls (4600 +/- 1200 to 5750 +/- 2200 micrograms/l, P < 0.05). IGFBP-3 was not affected by PTH infusion in patients with RA when the disease had high activity, but when inflammation had subsided they responded with a similar increase in IGFBP-3 as the control group and basal IGF-I and -II levels were normalised. Since IGFBP-3 can enhance the anabolic action of IGF-I, increased IGFBP-3 levels after PTH infusion may reflect a mechanism by which PTH is anabolic for bone. Inflammation may inhibit bone formation via decreased serum levels of IGFs and blocked IGFBP-3 response to PTH.

Adult↗
PubMed1993

Formation of neutralizing antibodies after treatment with human calcitonin.

PURPOSE: Calcitonin is used for the treatment of Paget's disease of bone, hypercalcemia, and postmenopausal osteoporosis. The formation of antibodies against heterologous calcitonins, such as salmon calcitonin (sCT), has been described frequently. Neutralizing effects of these antibodies have been demonstrated in many cases. As far as antibody formation against human calcitonin (hCT) is concerned, only a single case has been reported in the literature; however, investigations concerning the biologic activity of the antibodies were not performed. We have now assessed the sera of 33 patients treated with hCT for postmenopausal osteoporosis for a period of at least 12 months to evaluate the occurrence of hCT-binding and hCT-neutralizing antibodies. PATIENTS AND METHODS: Binding antibodies were detected by incubation of patient sera with 125I-labeled hCT; neutralizing activity was assessed in an in vitro bioassay that measured the impairment of the hCT-induced cyclic adenosine monophosphate (cAMP) formation in the human breast cancer cell line T47D. RESULTS: Prior to hCT treatment, none of the patients showed evidence of the presence of either binding or neutralizing antibodies. During the course of treatment, binding antibodies occurred in a single patient. These antibodies had a neutralizing activity characterized by 15% impairment of cAMP formation after 6 months and 27% impairment after 12 months of treatment compared with pretreatment control values. The neutralizing effect observed in this particular patient was comparatively mild compared with the effects seen after the formation of neutralizing antibodies against sCT, so major clinical sequelae were not expected in this patient. This may be due to the lower antigenicity of hCT as compared with sCT. CONCLUSION: Although antibody formation against hCT is a rare phenomenon, we nonetheless recommend monitoring of postmenopausal osteoporosis patients treated with sCT or hCT for neutralizing antibody formation in order to evaluate the therapeutic effect of treatment.

Aged↗
PubMed1993

Patients with various types of human papillomavirus: covariation and diagnostic relevance of cytological findings in Papanicolaou smears.

Human papillomavirus (HPV) infection in the genital tract is associated with a number of cytological changes which are accepted as standard criteria for a cytological diagnosis. We evaluated the covariation and diagnostic accuracy of these criteria in 210 patients, i.e. 150 cases who were positive for HPV types 6, 11, 16, 18, 31, 33 or 35, and 60 cases who were HPV-negative by simultaneous Southern blot analysis. This was done by re-examining cervical smears obtained at the same time, without knowing the results of the Southern blot analysis, for the presence of koilocytosis, dyskeratosis-parakeratosis, nuclear smudging, hyperchromasia, binucleation, multinucleation, karyorrhexis and macrocytosis. We found that all these cytological changes correlated with the presence of an HPV infection. However, analysis of variance showed that koilocytosis, dyskeratosis-parakeratosis and karyorrhexis were of particular diagnostic value, while the other features provided little or no additional information. By omitting these features and making the diagnosis when two out of three of the key criteria, i.e. koilocytosis, dyskeratosis-parakeratosis and karyorrhexis were present, we diagnosed HPV infection with a specificity of 100% in 36% of the 150 cases, which were positive by Southern blot analysis. The various HPV types produced different morphological patterns which may reflect differences in action on the host cell. In the individual patient, however, such differences in cytology do not provide a sound basis for distinguishing between viral types.

Adult↗
PubMed1993

The risk of hip fractures in patients with primary hyperparathyroidism: a population-based cohort study with a follow-up of 19 years.

OBJECTIVE: To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip fractures. DESIGN: A population-based, record-linked, prospective study with a mean observation time of 17 years (women) and 16.5 years (men). SETTING: A cohort obtained from a register of hospital admissions in the Uppsala Health Care Region, Sweden, 1965-1983. PARTICIPANTS: All patients (1373 women and 551 men) who were admitted to hospital with the diagnosis of HPT during the period. Comparisons were made with the entire background population. MEASUREMENTS: Cohort subjects were followed with regard to a first instance of hip fracture prior to or after the diagnosis of HPT. The observed number of cases was compared with that expected on the basis of person-years of observation and incidence rates in the background population. Analyses were made for cervical and trochanteric fractures, and for patients operated and not operated for HPT. MAIN RESULTS: (i) Women. During 23,341 person-years of observation, 67 cases of first hip fractures occurred, yielding a relative risk (RR) of 0.93 (95% confidence interval [CI] 0.72-1.19). The RR for cervical fractures was 0.77 (CI 0.54-1.06), and for trochanteric fractures 1.33 (CI 0.88-1.93). Operation for HPT did not influence the risk of hip fracture. (ii) Men. The total person-years was 9091. Eleven fractures were observed--compared with the expected 7.90 (RR 1.39; CI 0.69-2.50). Men operated for HPT had an increased risk for cervical hip fractures (RR 2.73; CI 1.18-5.39). Owing to the few fractures in this group (n = 8) the relevance of this is uncertain. CONCLUSIONS: This study indicates that HPT is not a risk factor for hip fractures in women.

Aged↗
PubMed1993

Parathyroid hormone is able to enhance cyclic adenosine monophosphate formation without causing an increase in cytoplasmic Ca2+ in osteoblasts.

There are several reports indicating that parathyroid hormone (PTH), besides inducing the formation of cyclic adenosine monophosphate (cAMP), also causes an increase in cytoplasmic free Ca2+ ([Ca2+]i) in osteoblasts, and it has been speculated that both of these second messengers are necessary to mediate PTH-induced bone resorption. In the osteoblastic cell line MC3T3-E1, bovine PTH 1-34 (10 nmol/l-1 mumol/l) stimulated cAMP formation but did not cause an increase in [Ca2+]i in adherent single cells (basal [Ca2+]i = 151 +/- 5 nmol/l, mean +/- SEM; N = 98). In contrast, subsequent addition of bradykinin (1 mumol/l) resulted in a transient increase in [Ca2+]i from a basal level of 155 +/- 11 nmol/l to a peak value of 351 +/- 60 nmol/l (N = 14). When the PTH challenge was followed by the addition of thrombin (10 U/ml), the latter induced a transient rise in [Ca2+]i from a basal level of 173 +/- 12 nmol/l to a peak at 341 +/- 33 nmol/l (N = 20). Primary cultures of human osteoblasts were obtained from trabecular bone. These cells were also PTH-responsive in terms of cAMP formation. On the other hand, human PTH 1-34 (100 nmol/l) did not affect [Ca2+]i in the isolated human osteoblasts, while bradykinin (1 mumol/l) caused a transient increase in [Ca2+]i (from a basal value of [Ca2+]i at 154 +/- 10 nmol/l to a peak value of 757 +/- 147 nmol/l within 30 s; N = 16).(ABSTRACT TRUNCATED AT 250 WORDS)

Bradykinin↗