Serum Fluoride Levels Research Articles

Fluoride and oxidative stress in postmenopausal women

–Fluorosis is a serious public health problem in many parts of the world where drinking water contains more than 1 ppm of fluoride. Higher intake of fluoride will result in dental and skeletal fluorosis and affect collagen synthesis and bone mineralization. Approximately 99% of the body burden of fluoride is associated with calcified tissues. The fluoride concentration in bone is not uniform. Fluoride concentration in bone is not uniform and higher fluoride levels in the body are associated with calcified tissues. The study was conducted on 100 subjects with their consent which consisted of control group of 50 nonpregnant women in their reproductive age group. Study group consisted of 50 women who had attained menopause either naturally or surgically, all residing in the endemic fluorotic area of Nalgonda district, Andhra Pradesh, India. 5 ml of venous blood was collected from both the groups. Serum fluoride levels (0.68  0.39; p<0.005) was statically significant when compared to the controls (0.45  0.28). Serum malondialdehyde, a lipid peroxidation product, was measured as an indicator of oxidative stress induced by fluorosis, was statistically significant (287.86  49.79; p<0.001). Keywords––Fluorosis, post menopausal women, malondialdehyde, oxidative stress, osteoporosis

Fluorotic cervical compressive myelopathy, 20 years after laminectomy: A rare event

Background:Spinal cord compression in flourosis is a common complication. These complications are mainly due to compression of the spinal cord by thickening and ossification of posterior longitudinal ligament and ligamentum flavum. Surgical decompression is the treatment of choice for fluorotic spinal cord compression. The recurrence of spinal cord compression after surgical decompression in flourosis is a rare event.Case Description:We are presenting a case of a 63-year-old man who belonged to Kanpur, an endemic fluorosis region in India, with symptoms of cervical cord compression cranial to the operative site, 20 years after laminectomy for cervical fluorotic myelopathy. Urinary and serum fluoride levels were elevated. The patient underwent a skeletal survey: computed tomography and magnetic resonance imaging of the cervical spine showed a postoperative defect of laminectomy, osteosclerosis, osteophyte formation, calcification of the intraosseus membrane in the forearm, thickening and ossification of the posterior longitudinal ligament at C1, thickening and ossification of the residual ligamentum flavum at C1/C2, and dural calcification at the C2 vertebral level and compressive myelopathy. The patient refused surgical decompression and was managed with tizanidine HCl (an antispasticity medicine), a sublingual single night dose, 8 mg for symptomatic relief.Conclusion:The recurrence of spinal cord compression in the fluorotic spine 20 years after laminectomy is a very unusual event and hence the patient should be kept under observation for a long duration. This case report contributes to the literature associated with the management of fluorotic spine.

Retraction: Serum Fluoride Level and Children's Intelligence Quotient in Two Villages in China.

The paper entitled "Serum Fluoride Level and Children's Intelligence Quotient in Two Villages in China" by Xiang Quanyong et al, which was published online on 17 December 2010, has been withdrawn.

Serum Fluoride and Sialic Acid Levels in Osteosarcoma

Osteosarcoma is a rare malignant bone tumor most commonly occurring in children and young adults presenting with painful swelling. Various etiological factors for osteosarcoma are ionizing radiation, family history of bone disorders and cancer, chemicals (fluoride, beryllium, and vinyl chloride), and viruses. Status of fluoride levels in serum of osteosarcoma is still not clear. Recent reports have indicated that there is a link between fluoride exposure and osteosarcoma. Glycoproteins and glycosaminoglycans are an integral part of bone and prolonged exposure to fluoride for long duration has been shown to cause degradation of collagen and ground substance in bones. The present study was planned to analyze serum fluoride, sialic acid, calcium, phosphorus, and alkaline phosphatase levels in 25 patients of osteosarcoma and age- and sex-matched subjects with bone-forming tumours other than osteosarcoma and musculo-skeletal pain (controls, 25 each). Fluoride levels were analyzed by ISE and sialic acid was analyzed by Warren's method. Mean serum fluoride concentration was found to be significantly higher in patients with osteosarcoma as compared to the other two groups. The mean value of flouride in patients with other bone-forming tumors was approximately 50% of the group of osteosarcoma; however, it was significantly higher when compared with patients of group I. Serum sialic acid concentration was found to be significantly raised in patients with osteosarcoma as well as in the group with other bone-forming tumors as compared to the group of controls. There was, however, no significant difference in the group of patients of osteosarcoma when compared with group of patients with other bone-forming tumors. These results showing higher level of fluoride with osteosarcoma compared to others suggesting a role of fluoride in the disease.

Fluoride-Related Bone Disease Associated With Habitual Tea Consumption

Acquired osteosclerosis is a rare disorder of bone formation but an important consideration in adults with sclerotic bones or elevated bone density results. In such patients, malignancy, hepatitis C, and fluorosis should all be considered when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted from chronic fluoride exposure due to excessive tea intake. Three of these patients had toxic serum fluoride levels (> 15 micromol/L). Although the clinical presentation of the patients varied, all 4 had an unexpectedly elevated spine bone mineral density that was proportionately higher than the bone mineral density at the hip. Other clinical features included gastrointestinal symptoms such as nausea, vomiting, and weight loss; lower extremity pain sometimes associated with stress fractures of the lower extremities; renal insufficiency; and elevated alkaline phosphatase levels. Readily available, tea often contains high levels of fluoride. Obsessive-compulsive drinking behaviors and renal insufficiency may predispose to excessive fluoride consumption and accumulation. The current cases show that fluoride-related bone disease is an important clinical consideration in patients with dense bones or gastrointestinal symptoms and a history of excessive tea consumption. Furthermore, fluoride excess should be considered in all patients with a history of excessive tea consumption, especially due to its insidious nature and nonspecific clinical presentation.

Fluoride-Related Bone Disease Associated With Habitual Tea Consumption

Acquired osteosclerosis is a rare disorder of bone formation but an important consideration in adults with sclerotic bones or elevated bone density results. In such patients, malignancy, hepatitis C, and fluorosis should all be considered when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted from chronic fluoride exposure due to excessive tea intake. Three of these patients had toxic serum fluoride levels (>15 μmol/L). Although the clinical presentation of the patients varied, all 4 had an unexpectedly elevated spine bone mineral density that was proportionately higher than the bone mineral density at the hip. Other clinical features included gastrointestinal symptoms such as nausea, vomiting, and weight loss; lower extremity pain sometimes associated with stress fractures of the lower extremities; renal insufficiency; and elevated alkaline phosphatase levels. Readily available, tea often contains high levels of fluoride. Obsessive-compulsive drinking behaviors and renal insufficiency may predispose to excessive fluoride consumption and accumulation. The current cases show that fluoride-related bone disease is an important clinical consideration in patients with dense bones or gastrointestinal symptoms and a history of excessive tea consumption. Furthermore, fluoride excess should be considered in all patients with a history of excessive tea consumption, especially due to its insidious nature and nonspecific clinical presentation. Acquired osteosclerosis is a rare disorder of bone formation but an important consideration in adults with sclerotic bones or elevated bone density results. In such patients, malignancy, hepatitis C, and fluorosis should all be considered when making a diagnosis. We describe 4 patients evaluated at our Metabolic Bone Disease Clinic from May 1, 1997, to July 1, 2006, whose bone disorders resulted from chronic fluoride exposure due to excessive tea intake. Three of these patients had toxic serum fluoride levels (>15 μmol/L). Although the clinical presentation of the patients varied, all 4 had an unexpectedly elevated spine bone mineral density that was proportionately higher than the bone mineral density at the hip. Other clinical features included gastrointestinal symptoms such as nausea, vomiting, and weight loss; lower extremity pain sometimes associated with stress fractures of the lower extremities; renal insufficiency; and elevated alkaline phosphatase levels. Readily available, tea often contains high levels of fluoride. Obsessive-compulsive drinking behaviors and renal insufficiency may predispose to excessive fluoride consumption and accumulation. The current cases show that fluoride-related bone disease is an important clinical consideration in patients with dense bones or gastrointestinal symptoms and a history of excessive tea consumption. Furthermore, fluoride excess should be considered in all patients with a history of excessive tea consumption, especially due to its insidious nature and nonspecific clinical presentation. CORRECTIONMayo Clinic ProceedingsVol. 82Issue 8PreviewIncorrect value: In the article by Wermers et al entitled “Fluoride-Related Bone Disease Associated With Habitual Tea Consumption,” published in the June 2007 issue of Mayo Clinic Proceedings (Mayo Clin Proc. 2007;82:719-724), an incorrect value was published on page 720, first full paragraph, right-hand column, third sentence, and in the last entry in Table 2 under the column heading “Reference range.” The sentence should read as follows: “A test of her specific brand of tea confirmed that she was consuming approximately 56 mg/d of fluoride, with the typical adult consumption being less than or equal to 2.5 mg/d. Full-Text PDF

Recovery From Skeletal Fluorosis (an Enigmatic, American Case)

A 52-year-old man presented with severe neck immobility and radiographic osteosclerosis. Elevated fluoride levels in serum, urine, and iliac crest bone revealed skeletal fluorosis. Nearly a decade of detailed follow-up documented considerable correction of the disorder after removal of the putative source of fluoride (toothpaste). Skeletal fluorosis, a crippling bone disorder, is rare in the United States, but affects millions worldwide. There are no data regarding its reversibility. A white man presented in 1996 with neck immobility and worsening joint pains of 7-year duration. Radiographs revealed axial osteosclerosis. Bone markers were distinctly elevated. DXA of lumbar spine (LS), femoral neck (FN), and distal one-third radius showed Z scores of +14.3, +6.6, and -0.6, respectively. Transiliac crest biopsy revealed cancellous volume 4.5 times the reference mean, cortical width 3.2 times the reference mean, osteoid thickness 25 times the reference mean, and wide and diffuse tetracycline uptake documenting osteomalacia. Fluoride (F) was elevated in serum (0.34 and 0.29 mg/liter [reference range: <0.20]), urine (26 mg/liter [reference range: 0.2-1.1 mg/liter]), and iliac crest (1.8% [reference range: <0.1%]). Tap and bottled water were negative for F. Surreptitious ingestion of toothpaste was the most plausible F source. Monitoring for a decade showed that within 3 months of removal of F toothpaste, urine F dropped from 26 to 16 mg/liter (reference range: 0.2-1.1 mg/liter), to 3.9 at 14 months, and was normal (1.2 mg/liter) after 9 years. Serum F normalized within 8 months. Markers corrected by 14 months. Serum creatinine increased gradually from 1.0 (1997) to 1.3 mg/dl (2006; reference range: 0.5-1.4 mg/dl). Radiographs, after 9 years, showed decreased sclerosis of trabeculae and some decrease of sacrospinous ligament ossification. DXA, after 9 years, revealed 23.6% and 15.1% reduction in LS and FN BMD with Z scores of +9.3 and +4.8, respectively. Iliac crest, after 8.5 years, had normal osteoid surface and thickness with distinct double labels. Bone F, after 8.5 years, was 1.15% (reference range, <0.1), which was a 36% reduction (still 10 times the reference value). All arthralgias resolved within 2 years, and he never fractured, but new-onset nephrolithiasis occurred within 9 months and became a chronic problem. With removal of F exposure, skeletal fluorosis is reversible, but likely impacts for decades. Patients should be monitored for impending nephrolithiasis.

Dose–effect relationship between drinking water fluoride levels and damage to liver and kidney functions in children

Although a dose–effect relationship between water fluoride levels and damage to liver and kidney functions in animals has been reported, it was not demonstrated in humans. To evaluate the effects of drinking water fluoride levels on the liver and kidney functions in children with and without dental fluorosis, we identified 210 children who were divided into seven groups with 30 each based on different drinking water fluoride levels in the same residential area. We found that the fluoride levels in serum and urine of these children increased as the levels of drinking water fluoride increased. There were no significant differences in the levels of total protein (TP), albumin (ALB), aspartate transamine (AST), and alanine transamine (ALT) in serum among these groups. However, the activities of serum lactic dehydrogenase (LDH), urine N-acetyl- β-glucosaminidase (NAG), and urine γ-glutamyl transpeptidase ( γ-GT) in children with dental fluorosis and having water fluoride of 2.15–2.96 mg/L and in children having water fluoride of 3.15–5.69 mg/L regardless of dental fluorosis were significantly higher than children exposed to water fluoride of 0.61–0.87 mg/L in a dose–response manner. In contrast to children with dental fluorosis and having water fluoride of 2.15–2.96 and 3.10–5.69 mg/L, serum LDH activity of children without dental fluorosis but exposed to the same levels of water fluoride as those with dental fluorosis were also markedly lower, but the activities of NAG and γ-GT in their urine were not. Therefore, our results suggest that drinking water fluoride levels over 2.0 mg/L can cause damage to liver and kidney functions in children and that the dental fluorosis was independent of damage to the liver but not the kidney. Further studies on the mechanisms and significance underlying damage to the liver without dental fluorosis in the exposed children are warranted.

Letale Intoxikation mit Zinkhexafluorosilikat (Flusssäure)

Die Intoxikation mit Flusssaure (Hexafluorosilikat) stellt eine seltene, meist letal verlaufende Intoxikation dar. Wir berichten uber eine Patientin, die in suizidaler Absicht ca. 30 ml Zinkhexafluorosilikat geschluckt hatte. Die Ubernahme erfolgte intubiert und beatmet mit Kreislaufschock. Neben einer schweren metabolischen Azidose waren massive Elektrolytentgleisungen (Hypokalzamie, Hypophosphatamie, Hypokaliamie, Hypomagnesiamie) auffallig. Des Weiteren trat eine schwere Verbrauchskoagulopathie auf. Die Fluoridspiegel im Serum betrugen 1,98 mg/l (Norm <0,03 mg/l). Trotz Korrektur der Elektrolytentgleisungen verschlechterte sich der Zustand, es kam zu wiederholtem Kammerflimmern, welches im Verlauf bei korrigiertem Elektrolythaushalt zunehmend schlechter auf Defibrillation ansprach. Die Patientin verstarb nach 12 h im therapierefraktaren kardiogenen Schock. Im Rahmen der Autopsie wurden zahlreiche Schleimhautveratzungen, Hyperamien im Bereich der Nierentubuli sowie Nekrosen der Herzmuskulatur beschrieben. Neben der ohnehin schlechten Prognose einer Intoxikation in dieser Dosis durfte vor allem das grose zeitliche Intervall zwischen Intoxikation und Auffinden der Patientin prognostisch limitierend gewesen sein.

Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats

Possible effects of long term exposure (6 months) to sodium fluoride (NaF) through drinking water on the morphology and biochemistry of myocardial tissue in second generation adult male rats were investigated. Wistar strain female and male rats were reared until the second generation of rats obtained, during which they were given 1, 10, 50 and 100 mg/L NaF in drinking water. Of the second generation, 28 male rats were divided into four groups and had the same treatment. All the second generation rats were sacrificed and autopsied at the end of the 6 months. In the samples of myocardial tissues, the levels of serum fluoride and the activities of principal antioxidant enzymes were determined, and a histopathological examination was conducted. Significant histopathological changes were found in the myocardial tissue of rats treated with 50 and 100 mg/L NaF. These were myocardial cell necrosis, extensive cytoplasmic vacuole formation, nucleus dissolution in myosits, swollen and clumped myocardial fibers, fibrillolysis, interstitial oedema, small hemorrhagic areas and hyperaemic vessels. Additionally, the increased activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and thiobarbituric acid-reactive substance (TBARS) levels were observed in the myocardial tissues of rats treated with 10 and 50 mg/L NaF. On the other hand, the activities of SOD, GSH-Px, and CAT decreased, but the TBARS levels increased in the myocardial tissues of rats treated with 100 mg/L. The present results revealed that prolonged ingestion of fluoride through drinking water, particularly with high doses, induced significant histopathological and biochemical changes leading to myocardial tissue damage.

Utility of check dams in dilution of fluoride concentration in ground water and the resultant analysis of blood serum and urine of villagers, Anantapur District, Andhra Pradesh, India

High levels of fluoride (beyond 1.5 ppm) in ground water as source of drinking water are common in many parts of Andhra Pradesh, India, causing fluorosis. The study carried out in endemic Nalgonda District, Andhra Pradesh, has indicated that the fluoride-rich ground water present in the wells located down stream and close to the surface water bodies is getting diluted by the low-fluoride surface water. Encouraged by this result, check dams were constructed upstream of the identified marginally high fluoride bearing ground water zones in Anantapur District to reduce fluoride levels as an alternate solution for safe drinking water. In this paper, an attempt is made to study the utility and effect of these check dams in dilution of fluoride concentration in drinking water and its resultant impact on the health aspects of certain villagers of Anantapur District through the analysis of their blood serum and urine. Ground water samples from three fluoride-affected villages, blood and urine of males and females from the same villages were collected and analyzed for fluoride using ion selective electrode method. The results indicated that the fluoride levels in blood serum and urine of males in the age group of 5-11 years are found to be the highest. The concentration of fluoride in ground water is directly proportional to the concentration of fluoride in blood serum and urine. The concentration of fluoride in ground water with depth of the aquifer is a function of lithology, amount and duration of rainfall, rate of infiltration, level of ground water exploitation in the area etc. The construction of check dams upstream of the identified marginally high fluoride waters will not only cause additional recharge of ground water but also reduces the fluoride concentration eventually improving the health of the villagers.

Lethal intoxication with hydrofluoric acid

Intoxication with hydrofluoric acid is a very rare but mostly lethal clinical condition. It is mainly caused by dermal exposure, with ingestion extremely rare. Hydrofluoric acid is one of the strongest acids known that has a strong lipophilic ability. Ingestions of more than 20 mg/kg body weight are considered a lethal dose. Even after dermal exposure, the fatal prognosis is caused by severe electrolyte disturbances, especially hypocalcemia. We report on a 50-year-old female with endogenous depression who swallowed approximately 30 ml hexafluorosilicate (hydrofluoric acid) during a night-time attempt to commit suicide. In the early morning, the woman was found somnolent in a condition of circulatory shock. She complained of severe abdominal pain. She had to be intubated by the emergency doctor and was admitted to the hospital. Physical examination of the mechanically ventilated patient only revealed conjunctival irritation. Laboratory investigations showed severe electrolyte disturbances (hypokalemia, hypocalcemia, hypophosphatemia decreased magnesium levels) as well as severe metabolic acidosis. Within the next few hours, disseminated intravascular coagulation and hyopalbuminemia developed. Serum fluoride levels were 0.099 mmol/l or 1.98 mg/l (normal values 0.0005–0.02 mmol/l or 0.1–0.4 mg/l). Urine fluoride levels were 1.94 mg/l (normal values <1.0 mg/l). Gastroscopy showed necrotic gastric mucosa without signs of bleeding. Topical instillation of calcium was not performed due to the long time interval from burn to treatment but intravenous calciumgluconate was substituted immediately. Despite fluid resuscitation, correction of the electrolyte abnormalities, stabilisation of coagulation and substitution of albumin, the clinical condition worsened. The patient had to be defibrillated due to ventricular fibrillation about 30 times. Later on, these episodes of ventricular fibrillation were becoming less responsive to defibrillation although the electrolyte threshold had already been corrected. After 12 hours, the patient died under cardiopulmonary resuscitation. On autopsy, severe burns were found in the esophageal and gastric mucosa, hyperemic lesions were seen in the renal tubular system as well as necrotic lesions in the cardiac musculature. Besides the poor prognosis of a fluoride intoxication in this dosis, the long time interval until treatment could be started seems to be the main reason for the fatal outcome of this case.

Prevention and control of brick-tea type fluorosis—a 3-year observation in Dangxiong, Tibet

To evaluate the effects of preventing and controlling brick-tea type fluorosis, we carried out a 3-year field observation and assayed the total daily fluoride intake, urinary and serum fluoride level, and dental fluorosis prevalence and index in a boarding school in Dangxiong, Tibet, in students aged 8–15. We replaced the traditional brick tea with low-fluoride brick tea (LFBT). Reduction in the traditional brick-tea consumption decreased the total daily fluoride intake among the children, which still remained within the level of chronic intoxication but at a safe level. The study suggests that the LFBT is effective in the prevention and control of endemics of brick tea type fluorosis, although further improvement of the LFBT is required.

Serum fluoride levels in a group of Egyptian infants and children from Cairo city.

In this study, the authors investigated fluoride levels in the serum of infants and children (n = 296) and in the breast milk from nursing mothers (n = 60) in Cairo city. Their goal was to evaluate the necessity and safety of implementing a fluoride supplementation program. The authors used an ion-selective electrode to assay fluoride by direct potentiometry. Also, 2- to 12-yr-old participants underwent clinical dental examinations to detect caries and/or fluorosis. The serum fluoride levels of infants were significantly lower than levels found in preschoolers and school-age children. Serum fluoride correlated positively with age; it was significantly lower during the 1st than 2nd yr of infancy (p = 0.005). Breast or formula feeding did not influence serum fluoride status; the fluoride levels in mothers' milk reflected the serum levels of their own infants. Dental examinations revealed that 81% of the children had caries, whereas there was no evidence of fluorosis. Serum fluoride levels did not vary with the presence or absence of dental caries and did not correlate with the number of decayed, missing, or filled teeth. Gender did not influence serum fluoride expression, and the percentile values were unrelated to height, weight, or head circumference. These findings suggest the necessity and safety of improving the fluoride consumption levels of infants and children in Cairo city. Wider-scale studies are needed to obtain better insight into the problem.

Fluoride causing abnormally elevated serum nitric oxide levels in chicks

Serum fluoride, nitric oxide (NO), malondialdehyde (MDA) contents and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities were determined in chicks treated with graded doses of sodium fluoride. Compared with chicks in the control group, in the groups treated with fluoride, serum NO and MDA levels largely increased, and the activities of SOD, GSH-Px, and CAT decreased, most of which changed significantly ( P<0.05). Serum fluoride levels significantly and positively correlated with serum NO, MDA levels, respectively ( P<0.05), and significantly and negatively with serum SOD, GSH-Px, CAT activities, respectively ( P<0.05). The results indicated fluoride was associated with the elevated NO levels and the decreased activities of antioxidant enzymes and the deposit of lipid peroxides (LPO). We suggest the mechanism of fluoride injuring soft tissues as follows: fluoride causes excessive production of NO, LPO and oxygen free radicals, which can damage seriously the structure and function of soft tissues.

Calcium preventing locomotor behavioral and dental toxicities of fluoride by decreasing serum fluoride level in rats

Spontaneous motor activity, rota-rod performance (motor co-ordination), body weight gain, food intake, activities of total cholinesterase (blood) and acetylcholinesterase (brain), and dental structure were determined in adult female rats treated with a very high dose of sodium fluoride (500 ppm in drinking water) alone and in combination with calcium carbonate (50 mg/kg body weight by oral intubation) for 60 days. The concentration of fluoride and calcium were measured in the serum of these animals. Administration of sodium fluoride with drinking water produced both behavioural and dental toxicities and not lethality in the present study. A suppression of spontaneous motor activity, a shortening of rota-rod endurance time, a decreased body weight gain and food intake, a suppression of total cholinesterase and acetylcholinesterase activities and dental lesion were observed in test animals. Serum fluoride concentration was raised markedly and that of calcium was decreased in these animals. The effects of sodium fluoride were prevented significantly when animals received calcium carbonate along with sodium fluoride. Serum fluoride content was decreased and that of calcium was restored to control level in these animals. These results indicate that calcium prevents not only fluoride-induced hypocalcemia but also the locomotor behavioral and dental toxicities of fluoride by decreasing bioavailability of fluoride.

Correlation Between Renal Function and Pharmacokinetic Parameters of Inorganic Fluoride Following Sevoflurane Anesthesia

We studied the correlation between renal function and pharmacokinetic parameters of inorganic fluoride following sevoflurane anesthesia. In 30 neurosurgical patients aged 40–70 years, anesthesia was induced with midazolam and sevoflurane and maintained with sevoflurane and nitrous oxide in oxygen. Serum and urine inorganic fluoride (F−) levels and β2-microglobulin (BMG), blood urea nitrogen (BUN), and serum creatinine (Cr) were measured during and after anesthesia. The decrease rate of serum F− level and the area under the curve (AUC) of serum F− were calculated. Correlations among sevoflurane dosage, duration of administration, peak serum F− level, AUC, the decrease rate of serum F− level, and the maximum values in BUN, Cr, and urine BMG during the study were investigated. Urine BMG increased significantly after surgery but returned to the preoperative level in a week. BUN, Cr, and serum BMG remained within normal ranges during the study. Sevoflurane dosage and duration of administration were significantly correlated with AUC and the maximum value of urine BMG, but not with the peak serum F− level or the decrease rate of serum F−. AUC was significantly correlated with the maximum value of urine BMG. In sevoflurane anesthesia, sevoflurane dosage, duration of administration, and AUC affected urine BMG level, but not peak serum F−.

Prolonged Sevoflurane Inhalation Was Not Nephrotoxic in Two Patients with Refractory Status Asthmaticus

Prolonged Sevoflurane Inhalation Was Not Nephrotoxic in Two Patients with Refractory Status Asthmaticus

Drug therapy for vertebral fractures in osteoporosis: Evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy

The conventional belief is that osteopenia is the major cause of vertebral fractures and that drug therapy must induce a substantial increase in vertebral bone mineral density (BMD) before the vertebral fracture rate (VFR) is decreased. We hypothesized that the increased bone turnover in osteoporosis also is a major cause of vertebral fractures because of its adverse effects on the microarchitecture of the vertebrae and, thus, that normalization of bone turnover by antiresorptive drug therapy will decrease VFR substantially. This hypothesis is supported by our reanalysis of data from previous clinical trials with fluoride and with estrogen therapy in postmenopausal osteoporotic women. As evident from computer-generated three-dimensional graphic plots of data from osteoporotic women treated with placebo, VFR increased as bone turnover increased or as vertebral BMD decreased. Estrogen therapy decreased the bone turnover rate to normal and eliminated the relationship between VFR and bone turnover, whereas the inverse relationship with vertebral BMD persisted. In osteoporotic women treated with fluoride, VFR decreased as vertebral BMD increased, provided that patients with high (toxic) serum fluoride levels were not included in the comparison. Over the range of values in the data set, increased vertebral BMD and decreased bone turnover had approximately equal effects in decreasing VFR. Thus, both formation-stimulating and resorption-inhibiting drugs can substantially decrease VFR but do so by different mechanisms.

Sevofluran oder Halothan bei inhalativ eingeleiteten Narkosen im Kindesalter An�sthesiequalit�t und Serum-Fluoridspiegel*

Due to its low blood:gas partition coefficient (0.69) and its neutral odor, sevoflurane (S) is suitable for inhalational induction of anaesthesia. At the moment halothane (H) is preferentially used for this purpose due to its non-irritating odor and the smoothness of anaesthetic action. However, experience is limited with the use of S in children, and concern exists about potential renal toxicity of its metabolite, i.e. fluoride. Therefore, we compared S and H in an open, randomized phase III trial. With approval of the ethics committee and written informed parental consent, 40 children (age 1-10, mean 5.3 years, ASA class I and II) had anaesthesia induced without premedication (fresh gas flow 6 l/min, N2O/O2 = 65/35). Concentration of volatile anaesthetics was increased every 3-5 breaths (S: 0.8...3.2 vol%, H: 0.4...1.6 Vol%). The ciliary reflex was tested until it disappeared. Airway reflexes and excitation were quantified using a score. Upon venipuncture, relaxation and intubation, anaesthesia was maintained with S (Fi: 2.4 vol%) or H (Fi: 1.2 vol%) in N2O/O2 (3 l/min, etCO2 35-38 mm HG). Alfentanil was supplemented in repeated doses of 20 micrograms/kg. ECG, NIBP, SpO2, Fi and Fet of CO2 and volatile anaesthetics were continuously recorded. At the end of surgery anaesthetics were terminated abruptly and fresh gas flow was increased to 6 l/min O2. Time to the first purposeful movement was registered. Serum fluoride levels were determined immediately after venipuncture, at the end of surgery and 70 min later. Time to possible discharge from the PACU was quantified using a modified Aldrete score. Data were analysed with descriptive methods, Student's t-test or non-parametric tests as appropriate. Groups did not differ with respect to age, weight, sex, or type of surgery. Total dose of anaesthetics was 1.60 MACxh for S and 1.77 MACxh for H (p = 0.68). Table 6 shows the essential data. Mean arterial blood pressures and heart rate remained within +/- 20% of age-related normal values (Table 7). Mean serum fluoride level was 23.1 +/- 1.2 mumol/l at the end of surgery and decreased to 18.6 +/- 0.970 min later (Fig. 3). Sevoflurane is an alternative to halothane in pediatric inhalational anaesthesia, with a comparable, low incidence of airway irritation and smoothness of induction. Because of the significantly faster induction and recovery it seems superior to halothane. With the fluoride levels measured, an impairment of renal function is unlikely.