Halothane hepatotoxicity and hepatic free radical metabolism in guinea pigs; the effects of vitamin E

Purpose

The aim of this study was to investigate the relation between halothane hepatotoxicity and hepatic free radical metabolism and to establish a possible protective role of vitamin E against halothane hepatotoxicity.

Methods

Twenty-eight guinea pigs were used in the experiments. Halothane (1.5% v/v) in oxygen (100%) was given to the animals for 90 min over three days. Livers from animals were then taken and prepared for the assays. In the enzymatic study, Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured. As a peroxidation index, the malondialdehyde (MDA) concentration was determined. Also, electron spin resonance (ESR) analysis and electron microscopy (EM) were performed. Results: Superoxide dismutase (1168.3 ± 78.2 U · mg^?1) and glutathione peroxidase (14.9 ± 6.2 mIU · mg^?1) activities were decreased, but catalase activity (1260.0 ± 250.6 lU · mg^?1) and malondialdehyde concentration (11.5 ± 1.8 ppb) were increased in liver tissues exposed to halothane compared with control values (1382.2 ± 91.8 U · mg^?1 for SOD, 27.8 ± 5.2 mIU · mg^?1 for GSH-Px, 840.2 ± 252.4 IU · mg^?1 for CAT and 10.0 ± 1.0 ppb for MDA). Electron spin resonance analysis revealed a peak of CF₃ CHCl radical in the exposed tissue. Electron microscopy indicated ultrastructural changes in the hepatic cells of both halothane groups with and without vitamin E treatment.

Conclusion

Halothane causes impairment in the hepatic antioxidant defense system and accelerates peroxidation reactions. As a result, some ultrastructural changes in hepatic tissues occur due to halothane treatment. Although vitamin E prevents peroxidative damage, it does not ameliorate ultrastructural changes caused by halothane treatment. This shows that halothane toxicity results not only from impaired hepatic antioxidant defense system but also from other, unknown causes.     

The effects of cyclosporine on antioxidant enzyme activities and malondialdehyde levels in rabbit hepatic tissues

Possible molecular mechanisms leading to cyclosporine-induced hepatotoxicity has not been cleared yet. Therefore, investigation of antioxidant status of hepatic tissues exposed to cyclosporine A (CsA) and of free radical involvement in the CsA-induced hepatotoxicity seems of importance. For this aim, 20 rabbits were used in the study. In each group (control, CsA, CsA plus vitamin and, vitamin only) there were 5 animals. CsA was given orally (25 mg/kg/day) for 10 days. Vitamins E (100 mg/kg/ day) and C (200 mg/kg/day) combination was injected intramuscularly. After 10th day, animals were killed, and livers were prepared for the enzymatic assays. Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and, malondialdehyde (MDA) levels were determined in the supernatant fractions. Lowered SOD, unchanged GSH-Px and, increased CAT activities and MDA levels were detected in hepatic tissues of rabbits treated with CsA as compared with controls. In the CsA plus vitamin group, SOD activity was found to be higher, GSH-Px and CAT activities unchanged and MDA levels lower than the CsA group. In the vitamin-treated group, all of the enzyme activities were higher than the controls but MDA levels were unchanged. Correlation analysis revealed some significant differences between the groups. Results suggest that cyclosporine impairs the antioxidant defense system and thus, leads to oxidant stress and peroxidation in rabbit hepatic tissues. It has been established that this process can be prevented by antioxidant vitamin supplementation.     

Hydroxyl radical formation during inhalation anesthesia in the reperfused working rat heart

Purpose

To determine whether isoflurane, sevoflurane and halothane influenced hydroxyl radical production in the ischemic rat heart.

Methods

Twenty-four male Wistar rats were divided into four groups; control (C), isoflurane 1.4% (I), sevoflurane 2.5% (S) and halothane 1% (H). The hearts were perfused with modified Krebs-Henseleit bicarbonate buffer by a working heart model for 10 min. Then, whole heart ischemia was induced by severely restricting coronary perfusion for 15 min. Reperfusion of the hearts after this ischemic period lasted for 20 min. The coronary effluent was collected before and during ischemia and at 1,5,10,20 min after reperfusion. At the end of reperfusion, hearts were removed and prepared for measurement. Hydroxyl radicals were identified by their reaction with salicylic acid to yield dihydroxybenzoic acids (DHBAs).

Results

Before and after ischemia, there were no differences in coronary flow and heart rate among the four groups, but cardiac output and LV dP/dt maximum in the anesthetic groups were lower than in the control group. Hydroxyl radical products in the heart were significantly lower in the I group than the other groups (e.g. C vs I, 278.1 ± 24.3 vs 219.3 ± 14.4 μM· g^?1,P < 0.05). The concentrations of DHBAs in the coronary effluent at some points in the I and H groups were less than in the C and S groups.

Conclusion

These results indicate that isoflurane and halothane (to a lesser extent), reduce hydroxyl radical production in the ischémie heart, but sevoflurane does not.     

Oxidative stress in patients treated with continuous ambulatory peritoneal dialysis (CAPD) and the significant role of vitamin C and E supplementation

Purpose

Chronic renal failure patients undergoing peritoneal dialysis (PD) are characterized by increased oxidative stress (OS), which is associated with enhanced cardiovascular risk. Moreover, oxidative stress also contributes to peritoneal membrane changes and ultrafiltration failure. The aim of this study was to evaluate OS in PD patients and the effect of treatment with ascorbic acid and α-tocopherol.

Methods

Plasma, erythrocyte, urine, and peritoneal effluent samples from 20 patients on PD were evaluated for glutathione peroxidase and superoxide dismutase activity, total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, as well as protein carbonyl formation, before and after administration of vitamin C, alone or in combination with vitamin E, in comparison with 10 apparently healthy control individuals.

Results

All studied markers showed enhanced OS in the PD group, compared to controls. The supplementation of vitamin C and E resulted in improvements of all the OS markers, as indicated by increased erythrocyte antioxidant enzymes activity and TAC levels, as well as decreased MDA concentration and carbonyl compound formation.

Conclusions

The oral supplementation of antioxidant vitamins C and E, in combination, can lead to decreased OS, thus providing a useful and cost-effective therapeutic option in PD patients.     

Halothane and isoflurane enhance melanoma tumour metastasis in mice

Purpose

To investigate the incidence of tumour metastasis from B16 melanoma tumour cells in expenmental animals following exposure to equipotent concentrations of halothane or isoflurane, and to differentiate if exposure to one anaesthetic resulted in greater metastases than the other.

Methods

Experimental animals (C57B1 mice), were randomized to receive 1.3 MAC hours of halothane or isoflurane anaesthesia. The control group of animals received oxygen alone under identical conditions. Fifteen minutes after completion of anaesthesia, control and experimental groups were given 1 × 10⁵ B16 melanoma cells intravenously. After 21 days, all animals were autopsied, and the metastatic nodules in their lungs were counted. The difference in the numbers of metastatic nodules between control and expenmental groups of animals was analyzed for significance by the Mann Whitney “U test”.

Results

More metastases were observed in the animals exposed to halothane (37.28±5.08, P< 0.0001), or isoflurane anaesthesia (28.24±4.07, P< 0.0014) than in the control animals (12.22± 1.52).

Conclusion

Exposure to halothane or isoflurane anaesthesia increased the number of pulmonary metastases in C57B1 mice compared with the control groups but there was no difference in metastases among animals treated with halothane or isoflurane.     

Vitamin E Deficiency Begins within 6 Months after Gastrectomy for Gastric Cancer

Background

To clarify factors related to vitamin E malabsorption after gastric surgery, we evaluated serum vitamin E levels in patients who had undergone gastrectomy for gastric cancer.

Methods

We studied 39 patients (26 men, 13 women; mean age, 61.7 years) who underwent gastrectomy for early gastric cancer. Surgical procedures included 24 subtotal gastrectomies and 15 total gastrectomies. We measured serum levels of vitamin E before and 3, 6, 9, and 12 months after gastrectomy. A level of less than 0.75 mg/dl was defined as a low vitamin E level.

Results

Serum vitamin E levels decreased to less than 0.75 mg/dl in 6 (15.4 %) of the 39 patients within 6 months after gastrectomy and in 7 (17.9 %) of the 39 patients within 1 year after gastrectomy. The proportion of patients with a low serum vitamin E level was significantly higher in the total gastrectomy group (p = 0.002). A low vitamin E level was significantly associated with a low total cholesterol level. Total cholesterol levels in low vitamin E levels patients were lower than normal vitamin E levels patients. None of the patients with a low vitamin E level had neuropathy.

Conclusions

The type of operation performed (total vs. subtotal gastrectomy) may be the major cause of vitamin E malabsorption after gastrectomy for gastric cancer. Vitamin E deficiency probably begins within 6 months after gastrectomy for gastric cancer.     

Pattern of ventilation during halothane anaesthesia in infants less than two months of age

Purpose

To examine the breathing pattern of infants aged less than two months in order to understand better the effect of halothane on ventilation in infants.

Methods

The inspiratory flow waveform, the CO₂ waveform and occluded inspiratory pressure waveform were recorded at different inspired concentrations of halothane using a washout of halothane in two groups of infants undergoing elective herniorrhaphy. Data were analyzed for minute ventilation (Vi) and tidal volume (Vt), parameters of timing of the breath [Total time (Ttot), Inspiratory time (Ti), and the ratio of the occluded to unoccluded inspiratory time (Ti^occ/Ti)/, parameters of Amplitude of the neural output /mean inspiratory flow (Vt/Ti)] and parameters of the Shape of the inspiratory breath profile [the inspiratory flow centroid (Ci/Ti), the inspiratory duty cycle (Ti/Ttot)]. The airway was occluded at end expiration and the slope of the initial 100 msec of occlusion (dP/dt) together with the maximal negative pressure (PMAX) and occluded inspiratory time (Ti^occ) were obtained. We studied ten infants <48 wk post-conceptional age (PCA) and ten infants > 48 wk. PCA Flow (V), pressure (Pao) and carbon dioxide tension (PCO₂) were recorded at three concentrations of inspired halothane (FiH): 0%, 1% and 2% which corresponded to an end-tidal halothane concentration of about 0.2%, 0.8% and 1.2% respectively.

Results

In both groups Vi,Vt andVt/Ti decreased whereas dP/dt, did not, suggesting that the respiratory pump was impaired. The parameters of breath Shape did not change. Importantly the parameters of Timing showed different tendencies. In infants > 48 wk PCA Ti^occ/Ti decreased. In infants <48 wk PCA, Ti^occ/Ti did not change.

Conclusions

The different response in the timing parameter Ti^occ/Ti is consistent with a different effect of halothane on parameters of ventilatory timing in infants <48 wk PCA and this may represent a maturational effect.     

The effect of vitamin E or vitamin A on the prevention of renal scarring in children with acute pyelonephritis

Background

Numerous factors may contribute to renal tissue injury after urinary tract infection. We have evaluated the effects of vitamins A or E supplementation in combination with antibiotics for the prevention of renal scarring in acute pyelonephritis.

Methods

A simple non-blind randomized clinical trial was conducted on 61 children aged 1 month to 10 years between 2004 and 2006. The inclusion criteria were positive urine culture, clinical findings, and 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy-based evidence in favor of acute pyelonephritis. The children were randomized into three treatment groups: 10-day treatment with only antibiotics (control group; n?=?25) and 10-day treatment with supplements of vitamin A (n?=?17) or vitamin E (n?=?18) in addition to antibiotics during the acute phase of infection. The final analysis was performed after excluding male patients. Each patient was evaluated twice by 99mTc-DMSA scintigraphy performed at least 6 months apart. P?<?0.05 was considered to be statistically significant.

Results

The analysis included 108 kidney units. The frequency of inflammation at the beginning of therapy was not significantly different in the three groups (63.3 % in vitamin A, 61 % in vitamin E, and 76.2 % in the control group). A worsening of lesions, based on the second 99mTc-DMSA scan, was observed in 42.5, 0, and 23.3 % of the control, vitamin E, and vitamin A patients, respectively (LR?=?26.3, P?<?0.001).

Conclusion

Vitamins A or E supplements were effective in reducing renal scarring secondary to acute pyelonephritis.     

Teriparatide increases the maturation of circulating osteoblast precursors

Summary

This study shows that teriparatide promotes the circulating osteoblast (OB) precursor degree of maturation in patients affected by postmenopausal osteoporosis.

Introduction

Anabolic treatment with teriparatide has proven effective for the therapy of postmenopausal osteoporosis and significantly reduces the risk of non-vertebral fragility fractures. The aim of this study was to investigate the effect of teriparatide on circulating OB precursors.

Methods

We evaluated by flow cytometry and real-time PCR the expression of OBs typical markers in peripheral blood mononuclear cells during treatment with teriparatide plus calcium and vitamin D, raloxifene plus calcium and vitamin D or calcium and vitamin D alone at various time points. Serum bone alkaline phosphatase and osteocalcin (OC) were measured as markers of bone turnover.

Results

Our results show that circulating OB precursors are more numerous and more immature in patients affected by fragility fractures than in osteoporotic patients without fractures. We also show that teriparatide treatment increases the expression of alkaline phosphatase and of OC in OB precursors; thus, it increases their degree of maturation.

Conclusions

We suggest that teriparatide acts as anabolic agents also by promoting the maturation of OB precursors.     

Ca2+ channel modulation alters halothane-induced depression of ventricular myocytes

Purpose

This study examined the direct myocardial depressant effect of halothane and determined whether an L-type Ca²⁺ channel agonist and antagonists altered the myocardial depression induced by halothane in cultured rat ventricular myocytes.

Methods

Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase and then cultured for 6 to 7 days. The myocytes were stabilized in a serum-free medium, and the spontaneous beating rate and amplitude were measured. To assess the halothane-induced conformational changes in L-type Ca²⁺ channel, receptor binding study was performed using a dihydropyridine derivative, [³H] PN 200-110, in cardiac membrane preparation.

Results

Halothane (1%, 2%, 3%, 4%) decreased the beating rate and amplitude in a concentration-dependent manner (P < 0.05). The myocardial depressant effects of halothane were potentiated by nifedipine or verapamil (P < 0.05). Bay K 8644, an L-type Ca²⁺ channel agonist, completely prevented the halothane-induced depression in amplitude (P < 0.05), but affected the beating rate less. Adding halothane (2%) decreased (P < 0.05) the maximum binding site density for [³H] PN 200-110 (from 198.6 ± 23.7 fmol·mg^?1 protein to 115.3 ± 21.6 fmol·mg^?1 protein) but did not affect binding affinity (from 0.461 ± 0.077 nM to 0.307 ± 0.055 nM).

Conclusion

The reduction of Ca²⁺ current via sarcolemmal L-type Ca²⁺ channel, probably due to conformational changes in dihydropyridine binding sites, plays an important role in halothane-induced myocardial depression in living heart cells.     

Optimal sutures for use in the abdomen: an evaluation based on the formation of adhesions and abscesses

Purpose

This study explored the optimal suture materials for use in the peritoneal cavity based on the formation of adhesions and abscesses under clean and contaminated conditions.

Methods

The parietal peritoneum and muscle layer of rats were incised. The incision was followed by interrupted suturing in the clean group. A suspension of E. coli (1.0 × 10⁶) plus Bacteroides fragilis (1.0 × 10⁵) was sprayed onto the incision in the contaminated group, followed by interrupted suturing. Four types of sutures were used: nonabsorbable multifilament silk, absorbable multifilament Polyglactin 910 (Vicryl^®), absorbable monofilament Polydioxanone (PDS^®), and Poliglecaprone 25 (Monocryl^®). The rats were killed at 2, 4 or 8 weeks after the surgery.

Results

The incidence of adhesions in the clean group was low with Polyglactin 910. The incidence of adhesions was 96 % or higher regardless of the suture type in the contaminated group. The incidence of severe adhesions was low with Polyglactin 910 and Poliglecaprone 25 and significantly higher with Polydioxanone in the contaminated group. The incidence of abscess formation around the silk was significantly higher than the other three types of sutures in the contaminated group.

Conclusion

Polyglactin 910 was less likely to form adhesions than the other three types of sutures under both conditions, suggesting that Polyglactin 910 may be the optimal type of suture to use in the peritoneal cavity.     

Volatile anaesthetics attenuate hypocapnia-induced constriction in isolated dog cerebral arteries

Purpose

Hypocapnia causes cerebral arterial constriction, whereas volatile anaesthetics cause dilatation. The purpose of this study was to compare the direct effects of halothane, isoflurane and sevoflurane on hypocapniainduced constnction of isolated cerebral arteriesin vitro.

Methods

Basilar and middle cerebral arteries of mongrel dogs (n= 11) were cut into nngs and mounted for isometnc tension recording in organ baths containing Krebs’ bicarbonate solution, aerated with CO₂ 5% and O₂ 95% at 37°C. After constnction with 20 mM KCl, hypocapnia was induced by replacing the aerating gas with CO₂ 2.5% and O₂ 97.5% in the presence or absence of anaesthetics.

Results

Exposure of cerebroartenal rings to the hypocapnic gas produced sustained vasoconstnction (418 ± 19 mg), reaching a plateau within 10 to 15 min. Halothane (0.5, 1, 2 MAC) attenuated the hypocapnia-induced constnction (P< 0.05). In contrast, isoflurane and sevoflurane attenuated this constriction only at 2 MAC (P< 0.05). Attenuation by halothane was greater than that by isoflurane or sevoflurane at each concentration(P< 0.05). N^G-nitro-L-arginine (3 × 10^?5 M) did not alter the contractile response to hypocapnia. When a similar degree of constnction was induced by addition of 10 mM KCl, halothane (1 and 2 MAC) preferentially attenuated the constriction induced by hypocapnia to a greater extent than that induced by 10 mM KCl (P< 0.01)

Conclusion

Hypocapnia-induced vasoconstnction of isolated dog cerebral arteries precontracted with KCl is more susceptible to halothane than isoflurane or sevoflurane. This may account for the greater increase in cerebral blood flow dunng halothane than isoflurane or sevoflurane anaesthesia.     

Perphenazine decreases vomiting by children after tonsillectomy

Purpose

To test the hypothesis that perphenazine decreases the incidence of vomiting by children after tonsillectomy.

Methods

Healthy children (n = 260) aged 2–12 yr undergoing elective tonsillectomy on a day care surgical basis were studied in this randomised, stratified, blocked, double-blind investigation. General Anaesthesia was induced intravenously with propofol or by inhalation with halothane and N₂O. Perphenazine 70 μg·kg^?1 up to 5 mg or placebo iv was administered before surgery. Management of perioperative fluids, emesis and pain were all standardised.

Results

The groups were similar with respect to demographic data. There was less vomiting after perphenazine during the first 24 hr after surgery 42% (95% CI = 34%–50%) vs 57% (95% CI = 48%–66%, placebo), P < 0.01. On the day of surgery, both in and out-of hospital emesis were decreased by perphenazine. The perphenazine treated patients required fewer rescue antiemetics than the control group, P < 0.05. Each episode of in-hospital vomiting delayed discharge by 20 ± 7 min (mean ± SD). P = 0.007.

Conclusion

The prophylactic administration of perphenazine decreases vomiting by children after tonsillectomy.     

Low bone density and bone metabolism alterations in Duchenne muscular dystrophy: response to calcium and vitamin D treatment

Summary

Boys with Duchenne muscular dystrophy often have reduced bone mass and increased fracture risk. In this prospective study on 33 patients, calcifediol (25-OH vitamin D₃) plus adjustment of dietary calcium to the recommended dose reduced bone resorption, corrected vitamin D deficiency, and increased bone mass in about two-thirds of cases.

Introduction

Low BMC and BMD and bone metabolism alterations are frequent in boys with Duchenne muscular dystrophy (DMD), especially now that long-term glucocorticosteroid (GC) treatment is the standard of care. This prospective study was designed to evaluate the effects of a first-line treatment (25-OH vitamin D₃ [calcifediol] plus adjustment of dietary calcium to the recommended daily dose) on bone.

Methods

Thirty-three children with DMD on GC treatment were followed for 3?years: one of observation and two of treatment. Main outcome: spine and total body BMC and BMD increase; secondary outcome: changes in bone turnover markers (C-terminal [CTx] and N-terminal [NTx] telopeptides of procollagen type I; osteocalcin [OC]).

Results

During the observation year, BMC and BMD decreased in all patients. At baseline and after 12?months, serum CTx and urinary NTx were higher than normal; OC and parathyroid hormone at the upper limit of normal; 25-OH vitamin D₃ significantly lower than normal. After 2?years of calcifediol and calcium-rich diet, BMC and BMD significantly increased in over 65% of patients, and bone metabolism parameters and turnover markers normalized in most patients (78.8%). During the observation year, there were four fractures in four patients, while during the 2?years of treatment there were two fractures in two patients.

Conclusions

Calcifediol plus adequate dietary calcium intake seems to be an effective first-line approach that controls bone turnover, corrects vitamin D deficiency, and increases BMC and BMD in most patients with DMD. Lack of response seems related to persistently high bone turnover.     

Halothane inhibition of acetylcholine-induced relaxation in rat mesenteric artery and aorta

Purpose

T1he effect of halothane was compared on acetylcholine (ACh)-induced relaxation of the mesentenc artery and the aorta in rats

Methods

The responses of isolated rat aortic and mesentenc artenal nng segments precontracted with phenylephnne to ACh (10^?8– 10^?5M), in the presence of halothane 0–3%. were compared using isometric force tension recordings. Effects of N^G -nitro-l-arginine (L-NOARG, 3 × 10^?5), methylene blue (MB, 5 × 10^?6 M), oxyhaemoglobin (OxyHB, 10^?7 M), and vanous potassium channel inhibitors; tetraethylammonium (TEA, 10^?5 M. 10^?3 M), apamin (AP, 10^?7 M), charybdotoxin (ChTx, 10^?7M) and glibenclamide (GC, 10^?5M) on ACh-induced relaxation in mesentenc artery were tested. Using radioimmunoassay, ACh (10^?6M)-induced guanosine 3′:5′-cyclic monophosphate (cGMP) accumulation of mesentenc arterial rings pretreated with L-NAORG were also measured.

Results

L-NOARG partially inhibited ACh-induced relaxation in mesentenc arterial rings (P < 0.05. maximum relaxation reduced by approximately 50%), whereas it abolished them in aortic rings. The remaining relaxation resistant to L-NOARG in mesentenc artenal rings was insensitive to additional MB or OxyHB, and was not accompanied by increases in cGMP contents of rings. Halothane inhibited endothelium-dependent relaxation in aorta and mesentenc artenal rings. This inhibitory effect was larger in aorta. Halothane also inhibited NO independent EDHF-dependent relaxation in the mesentenc arterial rings.

Conclusion

Despite a similar inhibitory effect on the EDHF relaxing pathway, halothane has a larger effect on endothelium-dependent relaxation in the aorta (NO dependent mainly) than in the mesenteric rings (NO and EDHF dependent).     

Detecting wakefulness in anaesthetised children

Purpose

To investigate the suitability of the isolated forearm technique in detecting wakefulness in children aged 5 to 16 yr.

Methods

Forty-one healthy English speaking children were enrolled. Following intravenous induction of anaesthesia with 5–7 mg·kg^?1 thiopentonen. but before administration of 1–1.5 mg·kg^?1 succinylcholine a pneumatic toumiquet was inflated to 50 mmHg above systolic pressure in order to isolate the non-cannulated forearm. Thereafter, anaesthesia was maintained with halothane 1.5–2.5% in nitrous oxide and oxygen. Following the muscle relaxant the patient was instructed to move the unparalyzed arm. Movement was checked at 30 sec intervals and if present on command, identified as wakefulness.

Results

Movement of the isolated forearm to command was observed in 19.5% of children. The youngest child to respond was five years old.

Conclusion

The isolated forearm technique can be used to detect wakefulness during and immediately following tracheal intubation in children from the age of five years.     

Health risks and benefits from calcium and vitamin D supplementation: Women's Health Initiative clinical trial and cohort study

Summary

The Women's Health Initiative (WHI) double-blind, placebo-controlled clinical trial randomly assigned 36,282 postmenopausal women in the U.S. to 1,000 mg elemental calcium carbonate plus 400 IU of vitamin D₃ daily or placebo, with average intervention period of 7.0 years. The trial was designed to test whether calcium plus vitamin D supplementation in a population in which the use of these supplements was widespread would reduce hip fracture, and secondarily, total fracture and colorectal cancer.

Introduction

This study further examines the health benefits and risks of calcium and vitamin D supplementation using WHI data, with emphasis on fractures, cardiovascular disease, cancer, and total mortality.

Methods

WHI calcium and vitamin D randomized clinical trial (CT) data through the end of the intervention period were further analyzed with emphasis on treatment effects in relation to duration of supplementation, and these data were contrasted and combined with corresponding data from the WHI prospective observational study (OS).

Results

Among women not taking personal calcium or vitamin D supplements at baseline, the hazard ratio [HR] for hip fracture occurrence in the CT following 5 or more years of calcium and vitamin D supplementation versus placebo was 0.62 (95 % confidence interval (CI), 0.38–1.00). In combined analyses of CT and OS data, the corresponding HR was 0.65 (95 % CI, 0.44–0.98). Supplementation effects were not apparent on the risks of myocardial infarction, coronary heart disease, total heart disease, stroke, overall cardiovascular disease, colorectal cancer, or total mortality, while evidence for a reduction in breast cancer risk and total invasive cancer risk among calcium plus vitamin D users was only suggestive.

Conclusion

Though based primarily on a subset analysis, long-term use of calcium and vitamin D appears to confer a reduction that may be substantial in the risk of hip fracture among postmenopausal women. Other health benefits and risks of supplementation at doses considered, including an elevation in urinary tract stone formation, appear to be modest and approximately balanced.     

Malondialdehyde and CA II autoantibody levels are elevated in children with undescended testes

Purpose

In the pathogenesis of sub-fertility/infertility and testicular cancer related to undescended testes, oxidative stress, inflammation and autoimmunity are important factors. Therefore, the present study was designed to determine serum oxidative stress markers and carbonic anhydrase (CA) II autoantibodies in boys with undescended testes (UDT), and to investigate the relationship between these parameters.

Methods

Serum CA II autoantibody titers, malondialdehyde (MDA), ischemia modified albumin (IMA), protein carbonyl content and soluble CD40 ligand (sCD40L) levels were measured in 59 boys with UDT and 30 healthy subjects.

Results

MDA levels were significantly higher in the UDT group compared with the control group (p = 0.003). There was no significant difference between serum IMA, sCD40L or protein carbonyl levels. CA II autoantibody titers in the UDT group were significantly higher compared with those of the control group (p = 0.048). A weak positive correlation was determined between anti-CA II antibody titers and MDA and IMA levels (p = 0.041, p = 0.005, respectively).

Conclusions

MDA is the most reliable and decisive biochemical marker displaying oxidative damage in undescended testes, and an autoimmune response may be triggered by oxidative stress against CA II during the UDT process.     

A Novel Technique for Assessing Antioxidant Concentration in Retrieved UHMWPE

Background

Antioxidants added to UHMWPE to prevent in vivo oxidation are important to the long-term performance of hip and knee arthroplasty. Diffused vitamin E antioxidant polyethylene raised questions about potential in vivo elution that could cause inflammatory reactions in periprosthetic tissues and also potentially leave the implant once again prone to oxidation. Currently, there is no information on the elution, if any, of antioxidants from implant polyethylene materials in vivo.

Questions/purposes

(1) Do antioxidants, especially diffused vitamin E, elute from antioxidant polyethylene in vivo? (2) Can extraction of the retrieved antioxidant polyethylene (to remove absorbed species from the in vivo environment near the articular and nonarticular surfaces) improve the identification of antioxidant content? (3) Can actual antioxidant content be estimated from calculated antioxidant indices by accounting for ester content (from absorbed species) near the articular and nonarticular surfaces?

Methods

An institutional review board-approved retrieval laboratory received 39 antioxidant polyethylene hip and knee retrievals at revision from 25 surgeons with in vivo time of 0.02 to 3.6 years (median, 1.3 years). These consecutive antioxidant polyethylene retrievals, received between May 2010 and February 2016, were made from three different antioxidant highly crosslinked polyethylene materials: diffused vitamin E, blended vitamin E, and hindered phenol antioxidant pentaerythritol tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)] propionate (here and after referred to as PBHP). Retrievals were analyzed using Fourier transform infrared (FTIR) spectroscopy. Absorbed ester index (1725–1740 cm^?1 normalized to 1365–1371 cm^?1), and vitamin E index (1245–1275 cm^?1) and PBHP index (1125–1150 cm^?1), normalized to 1850–1985 cm^?1, were defined. Microtomed thin sections of PBHP and vitamin E retrievals were hexane-extracted to remove absorbed species from the in vivo environment in an effort to improve identification of antioxidant content. Paired Student’s t-tests were used to compare as-retrieved articular antioxidant index with expected antioxidant index (the bulk value for blended antioxidants where constant antioxidant content is expected throughout and the extrapolated original vitamin E concentration at the articular surface based on the as-manufactured vitamin E concentration gradient). Linear regression was used for each of the retrievals to evaluate the correlation of antioxidant index to ester content with the goal of extrapolation to the antioxidant index at zero ester content.

Results

On average, vitamin E index at the articular surface (0.04 ± 0.03) was reduced compared with expected vitamin E index (0.09 ± 0.04; 95% confidence interval [CI] of the difference, 0.04-0.07; p < 0.001), and PBHP index at the articular surface (0.06 ± 0.02) was elevated compared with the average PBHP index from the bulk (0.03 ± 0.00; 95% CI of the difference, 0.03-0.05; p < 0.001). Extraction returned the PBHP index at the articular surface (0.03 ± 0.00) to bulk values (95% CI of the difference, -0.001 to 0.004; p = 0.326); diffused vitamin E was removed by extraction. Crossplots of vitamin E index and PBHP index with ester index showed significant (p < 0.001 for 32 of the 35 retrievals with sufficient data) linear trends (r ≥ 0.89) that allowed extrapolation of the articular surface antioxidant indices at zero absorbed ester index.

Conclusions

Absorbed esters from time in vivo caused erroneous values of antioxidant index to be calculated. However, hexane extraction to remove absorbed species also removed diffused vitamin E. Correlating antioxidant indices with ester content, measured by FTIR in unextracted antioxidant retrievals, provides a nonaltered method for estimating actual articular surface vitamin E index and demonstrates that there was no measurable elution in these short-term retrievals.

Clinical Relevance

Assessing antioxidant content in retrieved polyethylene inserts is important to determine how much of the antioxidant remains in place to prevent oxidation of the polyethylene over time in vivo. Retrieval analyses reporting antioxidant content must account for absorbed species to be valid. Because standard hexane extraction removes both absorbed species and vitamin E from diffused vitamin E retrievals, the correlation method presented in this study is the recommended analysis alternative.

     

Subhypnotic propofol does not treat postoperative vomiting in children after adenotonsillectomy

Purpose

To investigate the efficacy of a subhypnotic dose of propofol to treat vomiting in children after adenotonsillectomy.

Methods

Two hundred and fifty-two children, aged 2–12 yr, underwent a standardized anaesthetic opioid administration, and postoperative care after adenotonsillectomy, adenoidectomy or tonsillectomy. A prospective, double-blinded, placebo-controlled study was performed in 70 of the patients who retched or vomited after surgery and who had intravenous access. Patients were assigned randomly to receive either 0.2 mg-kg propofol (n = 35). or placebo (intralipid 10%, n = 35).

Results

The overall incidence of vomiting during the first 18–24 hr was 50%. Of those who had received propofol after the fust episode of vomiting, 63% relapsed requiring a rescue antiemetic compared with 57% of those who had received intralipid (P=NS). Of the children who received propofol, 54% expenenced pain on injection and 46% were mildly sedated compared with 3% and 11%, respectively, in the placebo group (P< 0.003).

Conclusion

We conclude that an intravenous bolus of 0.2 mg·kg^?1 propofol is not effective in the treatment of postoperative vomiting in children after adenotonsillectomy when a standardized anaesthetic with thiopentone, halothane. nitrous oxide, and 1.5 mg·kg^?1 codeine phosphate is used, but it does cause sedation and pain on injection.