Vitamin D and bisphosphonate therapy in systemic lupus erythematosus patients who receive glucocorticoids: are we offering the best care?

OBJECTIVE: This study aimed to evaluate management practices for glucocorticoid (GC)-induced osteoporosis (GIOP) in systemic lupus erythematosus (SLE) patients using 2017 American College of Rheumatology guidelines as a gold standard. METHODS: We conducted a retrospective cohort study using a clinical database from the years 2011 to 2016. SLE cases with >90 days continuous prednisone use at doses of ≥7.51 mg daily were identified. Osteoporosis risk factors were assessed via chart review. The Fracture Risk Assessment (FRAX) score was estimated for patients > 40 years of age. Vitamin D, bisphosphonate prescriptions, and osteoporotic (OP) fractures were ascertained through chart review. A classification tree was used to identify the key patient-related predictors of bisphosphonate prescription. RESULTS: A total of 203 SLE patients met the inclusion criteria. The recommended dose of vitamin D supplement was prescribed to 58.9% of patients < 40 years of age and 61.5% of patients ≥ 40 years of age. Among patients aged ≥ 40 years, 25% were prescribed bisphosphonates compared to 36% who met indications for bisphosphonates per the ACR guidelines. Another 10% were prescribed a bisphosphonate, despite not having indication per the ACR guidelines, which was considered as overtreatment. Among patients aged ≥ 40 years, older age and a higher FRAX score for major OP fracture and hip fracture predicted bisphosphonate prescription. In a classification tree analysis, patients with FRAX scores (for major OP fracture) of ≥ 23.5% predicted bisphosphonate prescription in this SLE population. Among patients who had OP fractures in the follow-up period, nine (6.50%) were inpatients receiving appropriate GIOP care versus 12 (13.6%) who were inpatients not receiving ACR-appropriate care (p = 0.098). CONCLUSIONS: In clinical practice, fewer SLE patients with or at risk for GIOP are prescribed vitamin D and bisphosphonates than recommended by the 2017 ACR guidelines. Also, in this study, another 10% were prescribed a bisphosphonate, despite not having an indication per the ACR guidelines. Patients were most likely to receive a bisphosphonate prescription if they had a major OP FRAX score of > 23.5%.

Grazing management of mixed alfalfa bermudagrass pastures.

Rotational grazing management is commonly recommended to improve persistence of legumes interseeded into bermudagrass, but impacts on animal performance are poorly understood. Steers (n = 365, BW = 249 ± 22.9 kg) grazed mixed alfalfa (Medicago sativa L.)/bermudagrass (Cynodon dactylon [L.] Pers.) pastures (n = 10; 1.6-ha) with either continuous grazing (CONT) or rotational grazing (ROT) management over 3 yr. Initial stocking rate was set at 6.25 steers/ha. When forage allowance of CONT became limiting in mid-July each year, 2 randomly selected steers were removed from all pastures to maintain equal stocking rates in CONT and ROT. Rotational grazing pastures were divided into 8 paddocks with 3-d grazing and 21-d rest between grazing events. Initial, final, and interim (28-d) BW were collected following a 16-h removal from feed and water. Data were analyzed as a repeated measures experiment with completely random design using the mixed procedure of SAS (SAS Inst. Inc., Cary, NC) using pasture within treatment by year in the random statement. Across years, steer BW did not differ (P ≥ 0.47) at the midpoint or end of the grazing season. Daily BW gains during the early summer period tended (P = 0.10) to be 0.11 kg greater for CONT than ROT in yr 1, but did not differ (P ≥ 0.24) in yr 2 and 3. In the late summer, ADG was 0.15 kg less (P < 0.01) for CONT than ROT in yr 1, were not different (P = 0.23) in yr 2, and were 0.29 kg less (P < 0.01) for CONT than ROT in yr 3. Over the entire experimental period, ADG did not differ (P ≥ 0.67) in yr 1 or 2, but tended (P = 0.09) to be 0.10 kg greater for ROT than CONT in yr 3. Forage mass of ROT was greater (P < 0.01) than CONT throughout the grazing season. Because stocking rates were maintained at the same level, ROT pastures provided greater (P < 0.01) forage allowance during the grazing season than CONT explaining differences in ADG between treatments. Alfalfa stand percentage did not differ (P = 0.79) at the beginning of the experiment, but was less (P ≤ 0.03) for CONT than ROT at all other sampling dates. These data indicate that at equal stocking rates, ROT can maintain greater alfalfa persistence, forage nutritive quality, and forage allowance compared with continuous grazing and provided increased animal performance during the late summer when the alfalfa stand was reduced in CONT pastures.

Influence of an n-3 long-chain polyunsaturated fatty acid-enriched diet on experimentally induced synovitis in horses.

Dietary n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation has previously been shown to modify joint-related inflammation in several species, although information in the horse is lacking. We investigated whether dietary supplementation with n-3 LCPUFA would modify experimentally induced synovitis in horses. Twelve, skeletally mature, non-pregnant mares were randomly assigned to either a control diet (CONT) or an n-3 long-chain fatty acid-enriched treatment diet (N3FA) containing 40 g/day of n-3 LCPUFA for 91 days. Blood samples taken on days 0, 30, 60 and 90, and synovial fluid collected on days 0 and 90 were processed for lipid composition. On day 91, joint inflammation was stimulated using an intra-articular (IA) injection of 100 ng of recombinant equine IL-1beta (reIL-1ß). Synovial fluid samples taken at post-injection hours (PIH) 0, 4, 8 and 24 were analysed for prostaglandin E2 (PGE2 ), matrix metalloproteinase (MMP) activity and routine cytology. Synovium and articular cartilage samples collected at PIH 8 were analysed for gene expression of MMP 1 and MMP 13, interleukin-1beta (IL-1ß), cyclooxygenase 2 (COX-2), tumour necrosis factor-alpha and the aggrecanases, a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5. A 90-day feeding period of n-3 LCPUFA increased serum phospholipid and synovial fluid lipid compositions of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) compared to CONT horses. The reIL-1ß injection caused an inflammatory response; however, there was no effect of dietary treatment on synovial fluid PGE2 content and MMP activity. Synovial tissue collected from N3FA horses exhibited lower expression of ADAMTS-4 compared to CONT horses. Despite the presence of EPA and DHA in the synovial fluid of N3FA horses, dietary n-3 LCPUFA supplementation did not modify synovial fluid biomarkers compared to CONT horses; however, the lower ADAMTS-4 mRNA expression in N3FA synovium warrants further investigation of n-3 LCPUFA as a joint therapy.

Additive effects of growth promoting technologies on performance of grazing steers and economics of the wheat pasture enterprise.

This research was designed to evaluate the effect of monensin (Elanco Animal Health, Greenfield, IN) supplementation via mineral or pressed protein block with or without a growth-promoting implant on performance of steers grazing wheat pasture in Arkansas over 2 yr. Preconditioned steers (n = 360, BW = 238 ± 5.1 kg) grazed 15 1.6-ha wheat pastures in the fall (n = 60 steers each fall, stocking rate of 2.5 steers/ha) or 30 0.8-ha wheat pastures in the spring (n = 120 steers each spring, stocking rate of 5 steers/ha). Steers in each pasture were given free-choice access to nonmedicated mineral (CNTRL; MoorMan's WeatherMaster Range Minerals A 646AAA; ADM Alliance Nutrition, Inc., Quincy, IL), or were supplemented with monensin (Elanco Animal Health, Greenfield, IN) via mineral containing 1.78 g monensin/kg (RMIN; MoorMan's Grower Mineral RU-1620 590AR; ADM Alliance Nutrition, Inc.), or pressed protein block containing 0.33 g monensin/kg (RBLCK; MoorMan's Mintrate Blonde Block RU; ADM Alliance Nutrition, Inc.). Additionally, one-half of the steers in each pasture were implanted (IMPL) with 40 mg trenbolone acetate and 8 mg estradiol (Component TE-G with Tylan; Elanco Animal Health). There was no interaction (P ≥ 0.71) between supplement treatment and growth-promoting implants, and ADG for RMIN and RBLCK were increased (P < 0.01) over CNTRL by 0.07 to 0.09 kg/d, respectively. Implanting steers with Component TE-G increased (P < 0.01) ADG by 0.14 kg/d. The combination of these growth-promoting technologies are a cost-effective means of increasing beef production by 22% without increasing level of supplementation or pasture acreage. Utilizing ionophores and implants together for wheat pasture stocker cattle decreased cost of gain by 26%. Utilizing both IMPL and monensin increased net return by $30 to $54/steer for RMIN or $18 to $43/steer for RBLCK compared with UNIMPL CNTRL at Low and High values of BW gain, respectively.

Effects of two different dietary sources of long chain omega-3, highly unsaturated fatty acids on incorporation into the plasma, red blood cell, and skeletal muscle in horses.

The objective of this study was to examine the effects of different sources of dietary omega-3 (n-3) fatty acid supplementation on plasma, red blood cell, and skeletal muscle fatty acid compositions in horses. Twenty-one mares were blocked by age, BW, and BCS and assigned to 1 of 3 dietary treatments with 7 mares per treatment. Dietary treatments were: 1) control or no fatty acid supplement (CON), 2) 38 g of n-3 long chain, highly unsaturated fatty acid (LCHUFA) supplement/d provided by algae and fish oil (MARINE) containing alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA), and 3) 38 g of n-3 LCHUFA supplement/d provided by a flaxseed meal (FLAX) containing ALA. Each supplement was added to a basal diet consisting of hay and barley and was fed for 90 d. Blood samples and muscle middle gluteal biopsies were taken at d 0, 30, 60 and 90 of supplementation. Plasma, red blood cell and skeletal muscle fatty acid profiles were determined via gas chromatography. Plasma linoleic acid (LA) and ALA were at least 10 and 60% less (P < 0.01), respectively, in the MARINE compared with the FLAX and CON groups. Plasma EPA and DHA were only detected in the MARINE group, and EPA increased 40% (P < 0.001) from d 30 to 60, and DHA 19% (P < 0.01) from d 30 to 90. Red blood cell LA and ALA were not different among treatments. Red blood cell EPA and DHA were only detected in the MARINE group, where EPA increased 38% (P < 0.01) from d 30 to 60, and DHA increased 56% (P < 0.001) between d 30 and 90. Skeletal muscle LA was at least 17% less (P < 0.001) in the MARINE group compared with the other treatments. Skeletal muscle ALA was 15% less (P = 0.03) in the MARINE group compared with FLAX and CON groups. Skeletal muscle EPA was at least 25% greater (P < 0.001) in MARINE group compared with other treatments and increased (P < 0.001) by 71% from d 30 to 60. Skeletal muscle DHA was at least 57% greater (P < 0.001) in the MARINE group compared with other groups and increased (P < 0.001) by 40% between d 30 and 90. As far as the authors are aware, this is the first study to demonstrate that dietary fatty acid supplementation will affect muscle fatty acid composition in horses. Incorporation of n-3 LCHUFA into blood and muscle depends directly on dietary supply of specific fatty acids.

[Quality control and quality of life after uterine fibroid embolization: long-term results]. / Erfolgskontrolle und Lebensqualitat nach Myomembolisation: Langzeitergebnisse.

This study was performed in order to evaluate the changes in uterine fibroid symptoms and their impact on the quality of life after uterine fibroid embolization (UFE). The patients source of information about this novel treatment and their reasons for choosing UFE were also studied. Health-related quality of life and the status of uterine fibroid symptoms were assessed in 44 patients before and after treatment using a validated questionnaire. After 33.5 months on average, a significant change in symptoms of -60.4% and a change in health-related quality of life of +74.39% were reported. Over 50% of patients had heard about UFE for the first time through the media, and 62.9% of patients had opted for this form of treatment because it enabled them to keep their uterus; 91.5% of patients would recommend it. UFE is a novel, effective and minimally invasive alternative to more invasive, open or laparascopic treatment procedures in cases of uterine fibroid symptoms.

Does usefulness of potassium supplementation depend on speed?

REASONS FOR PERFORMING STUDY: Electrolyte mixtures given to counter sweat loss usually contain abundant potassium. However, increases in plasma [K+] occur with exercise and supplementation may further increase plasma levels, potentially increasing the risk of neuromuscular hyperexcitability and development of adverse clinical sequellae. This proposition requires study. OBJECTIVES: To compare effects of a K-rich electrolyte supplement (EM+K) to a K-free one (EM-K) on plasma [K+], [Ca++] and acid-base status during an endurance incremental exercise test on the treadmill. METHODS: The test consisted of 3 bouts (simulating loops in an endurance race) of 12 km performed at 6, then 7, then 8 m/sec with 25 min rest stops (S1, S2) between loops on 13 endurance trained Arabian horses (7 EM-K, 6 EM+K). Electrolytes were supplied orally 60 mins before exercise (Pre) and at each stop. Blood samples were taken before exercise and during exercise, each S and 120 mins of recovery (R). Blood was analysed for pH, PCO2, packed cell volume (PCV), plasma [Na+], [K+], [Cl-], [Ca++], glucose, and lactate [La-]; plasma [H+] and osmolality (osm) were calculated. The dietary cation anion difference (DCAD) was calculated to be -27 meq/dose EM-K and 109 meq in EM+K, respectively. RESULTS: Plasma [H+] decreased during the 6 and 7 m/sec loops, increased during the 8 m/sec loop, and returned to Pre at S1, S2 and R. Plasma [K+] was higher at 8 m/sec and plasma [Ca++] was overall lower in the EM+K group compared to EM-K. Other findings included higher overall PCV, overall glucose, and [La-] during the 8 m/sec loop (P<0.040) in EM+K compared to EM-K horses. CONCLUSIONS: EM+K supplementation leads to higher plasma [K+] increasing the risk of neuromuscular hyperexcitability during exercise. Acute effects of a lower DCAD in EM-K may have led to higher plasma [Ca++]. Potassium-rich electrolytes may have triggered the release of epinephrine, contributing to higher PCV, glucose release and increased lactate production. POTENTIAL RELEVANCE: Lower plasma [K+] and higher plasma [Ca++] with EM-K supplementation may help reduce the risk of conditions associated with neuromuscular hyperexcitability occurring especially during higher speeds in endurance races.

Antioxidant supplementation and subsequent oxidative stress of horses during an 80-km endurance race.

This study tested the development of oxidative stress and the effects of antioxidant supplementation in an 80-km ride. A precompetition survey revealed that no competitor would participate without vitamin E supplementation; therefore, 46 horses were paired for past performances and randomly assigned to two groups of 23 each for 3 wk of supplementation before the ride. One group (E) was orally supplemented with 5,000 IU of vitamin E per day; the other group (E+C) received that dose of vitamin E plus 7 g/d of vitamin C. Blood samples, temperature, and heart rate were taken the day before the race, at 21 and 56 km during the ride, at completion, and after 20 min of recovery. Plasma was assayed for lipid hydroperoxides, alpha-tocopherol, total ascorbate, albumin, creatine kinase (CK), and aspartate aminotransferase (AST). Total glutathione and glutathione peroxidase activity were determined in red blood cells and white blood cells. Thirty-four horses completed the race, 12 horses (six in E and six in E+C) did not finish for reasons including lameness, metabolic problems, and rider option. Plasma ascorbate was higher (P = 0.045) in the E+C group than in the E group. Other than ascorbate, neither antioxidant status nor CK and AST activities were affected by supplementation with E+C vs. E. Red blood cell glutathione peroxidase, white blood cell total glutathione, lipid hydroperoxides, CK, and AST increased, and red blood cell total glutathione and white blood cell glutathione peroxidase activity decreased with distance (P < 0.001). Positive correlations were found for plasma lipid hydroperoxides on CK (r = 0.25; P = 0.001) and AST (r = 0.33; P < 0.001). These results establish an association between muscle leakage and a cumulative index of oxidative stress.

Speed associated with plasma pH, oxygen content, total protein and urea in an 80 km race.

To test the hypothesis that endurance performance may be related quantitatively to changes in blood, we measured selected blood variables then determined their reference ranges and associations with speed during an 80 km race. The plan had 46 horses in a 2 x 2 factorial design testing a potassium-free electrolyte mix and a vitamin supplement. Blood samples were collected before the race, at 21, 37, 56 and 80 km, and 20 min after finishing, for assay of haematocrit, plasma pH, pO2, pCO2, [Na+], [K+], [Ca++], [Mg++], [Cl-], lactate, glucose, urea, cortisol, alpha-tocopherol, ascorbate, creatine kinase, aspartate amino transferase, lipid hydroperoxides, total protein, albumin and creatinine, and erythrocyte glutathione and glutathione peroxidase. Data from 34 finishers were analysed statistically. Reference ranges for resting and running horses were wide and overlapping and, therefore, limiting with respect to evaluation of individual horses. Speed correlations were most repeatable, with variables reflecting blood oxygen transport (enabling exercise), acidity and electrolytes (limiting exercise) and total protein (enabling then, perhaps, limiting). Stepwise regressions also included plasma urea concentration (limiting). The association of speed with less plasma acidity and urea suggests the potential for fat adaptation and protein restriction in endurance horses, as found previously in Arabians performing repeated sprints. Conditioning horses fed fat-fortified and protein-restricted diets may not only improve performance but also avoid grain-associated disorders.

Activation of plasma coagulation by retransfusion of unwashed drainage blood after hip joint arthroplasty: a prospective study.

Twelve patients undergoing cementless hip joint arthroplasty were retransfused with unwashed drainage blood collected postoperatively. Global coagulation parameters, coagulation factors (factor V:C, factor VIII:C, activated factor XII, and factor XIII) and markers of thrombin generation (F1+2 Fibrin split products, thrombin-antithrombin complexes), fibrin generation (fibrinogen and fibrin degradation products), and fibrinolysis (D-dimers, thrombin degradation products, plasminogen) were determined. High levels of factor XIIa, thrombin and fibrin generation markers, and markers of fibrinolysis were present in the shed blood. After retransfusion (mean, 433 mL), increased levels of these markers together with decreased values for factor XIII and plasminogen were indicative of renewed clot formation and fibrinolysis in the circulation. These changes were highly significant compared with preretransfusion values. The unwashed drainage blood contained high levels of procoagulation material and induced an activation of the plasma coagulation pathway with renewed clot formation and fibrinolysis in the patients.

The selective removal of phosphorus from soil: is event size important?

Data from the Woburn Erosion Reference Experiment (Bedfordshire, UK) were used to test the hypothesis that losses of phosphorus (P) in small erosion events are as great as those in infrequent large events, and to examine the effect of storm characteristics on the selective enrichment of P in eroded sediment. For almost every plot event in the period 1988 to 1994, the clay-sized fraction of the sediment was enriched compared with the soil of the plots. There was more variation in clay enrichment for smaller erosion events than for larger ones. The clay and P contents of the sediment were strongly correlated (p < 0.01), and there was a wider range of P concentrations in the sediment derived from small events than in that from large events. However, individual events resulting in small soil losses (< 100 kg) did not account for greater P losses than larger events (> 100 kg). The greater frequency of smaller events, combined with the likelihood of higher P concentrations in the sediment, therefore accounted for a greater proportion of the P lost over the 6-yr period than the infrequent large events. Phosphorus concentrations generally increased with increasing peak discharge and decreased with increasing event duration. For the same return period, P losses were generally greater from plots cultivated up and down the slope than from those cultivated across the slope. Overall, our results suggest that small erosion events should be controlled to prevent P contamination of surface waters and that the most effective means of doing this are by the introduction of minimal tillage techniques and across-slope cultivations.

[MRI in chronic inflammatory bowel disease]. / MRT chronisch entzündlicher Darmerkrankungen.

Chronic inflammatory bowel disease is diagnosed and monitored by the combination of colonoscopy and small bowel enteroklysis. Magnetic resonance imaging has become the gold standard for the imaging of perirectal and pelvic fistulas. With the advent of ultrafast MRI small and large bowel imaging has become highly attractive and is being advocated more and more in the diagnostic work up of inflammatory bowel disease. Imaging protocols include fast T1-weighted gradient echo and T2-weighted TSE sequences and oral or rectal bowel distension. Furthermore, dedicated imaging protocols are based on breath-hold imaging under pharmacological bowel paralysis and gastrointestinal MR contrast agents (Hydro-MRI). High diagnostic accuracy can be achieved in Crohn's disease with special reference to the pattern of disease, depth of inflammation, mesenteric reaction, sinus tract depiction and formation of abscess. In ulcerative colitis, the mucosa-related inflammation causes significantly less bowel wall thickening compared to Crohn's disease. Therefore with MRI, the extent of inflammatory changes is always underestimated compared to colonoscopy. According to our experience in more than 200 patients as well as the results in other centers, Hydro-MRI possesses the potential to replace enteroklysis in the diagnosis of chronic inflammatory bowel disease and most of the follow-up colonoscopies in Crohn's disease. Further technical improvements in 3D imaging will allow interactive postprocessing of the MR data.

Interactions of bacteria and microflagellates in sequencing batch reactors exhibiting enhanced mineralization of toxic organic chemicals.

Community level interactions were studied in non-axenic sequencing batch reactors (SBRs) being used to treat 2,4-dinitrophenol (DNP). Increasing the influent DNP concentrations from 1 to 10 µg ml(-1) eliminated large predatory organisms such as rotifers and ciliated protozoa from the SBRs. Under steady-state conditions at a DNP concentration of 10 µg ml(-1), supplemental additions of glucose enhanced DNP degradation and led to the establishment of a microbial community consisting of five species of bacteria and a variety of microflagellates. The bacteria and flagellates exhibited oscillating population dynamics in this system, possibly indicating predator-prey interactions between these two groups. Only two of the five bacteria isolated from this system could utilize glucose as a growth substrate, and one of these two species was the only organism that could mineralize DNP in the system. The other three bacteria could grow using metabolic by-products of one of the glucose-utilizing strains (Bacillus cereus) found in the reactors. Supplemental glucose additions increased the average size of bacterial floc particles to 172 µm, compared with 41 µm in SBRs not receiving glucose. It is theorized that the enhanced mineralization of DNP in this non-axenic system was attributable to increased community interactions resulting in increased bacterial flocculation in SBRs receiving supplemental glucose additions.

Supplemental substrate enhancement of 2,4-dinitrophenol mineralization by a bacterial consortium.

A Janthinobacterium sp. and an actinomycete, both capable of mineralizing 2,4-dinitrophenol (DNP), were used to construct a consortium to mineralize DNP in nonaxenic bench-scale sequencing batch reactors (SBRs). Average K(m) values for DNP mineralization by pure cultures of the Janthinobacterium sp. and the actinomycete were 0.01 and 0.13 mug/ml, respectively, and the average maximum specific growth rate (mu(max)) values for them were 0.06 and 0.23/h, respectively. In the presence of NH(4)Cl, nitrite accumulation in pure culture experiments and in the SBRs was stoichiometric to initial DNP concentration and the addition of nitrogen enhanced DNP mineralization in the SBRs. Mineralization of 10 mug of DNP per ml was further enhanced in SBRs by the addition of glucose at concentrations of 100 and 500 mug/ml but not at 10 mug/ml. Possible mechanisms for this enhanced DNP mineralization in SBRs were suggested by kinetic analyses and biomass measurements. Average mu(max) values for DNP mineralization in the presence of 0, 10, 100, and 500 mug of glucose per ml were 0.33, 0.13, 0.42, and 0.59/h, respectively. In addition, there was greater standing biomass in reactors amended with glucose. At steady-state operation, all SBRs contained heterogeneous microbial communities but only one organism, an actinomycete, that was capable of mineralizing DNP. This research demonstrates the usefulness of supplemental substrates for enhancing the degradation of toxic chemicals in bioreactors that contain heterogeneous microbial communities.

Time pattern of allergic reactions to drugs.

Generalized, allergic reactions to drugs show time patterns different from those based on pharmacological concepts. We distinguish three types of reactions: acute reactions (reaction time (RT): 0-60 minutes), subacute reactions (RT: 1-24 hours) and reactions of the latent type (RT: 1 day to several weeks). In this study, allergic reactions in the strict sense are supplemented by reactions considered to be based on intolerance or idiosyncrasy to aspirin, pyrazolones, paracetamol, NSAIDs, quinidine, iodine-containing contrast media and some as yet not understood reactions to local anaesthetics. Out of a total of 23,935 drug monitoring patients with 32,317 hospitalizations in the clinical divisions of internal medicine at three Swiss hospitals during the 1974-1987 period, 951 patients with 1,040 probably or definitely drug-related events of the selected type were recorded. Ultimately, 287 patients with 310 adverse drug reactions (ADRs) fulfilled our selection criteria and were classified into six groups of syndromes (Table 1). (Of the reactions described as maculopapular rash, unspecified rash and special exanthema, only the 159 reactions from the 1985-1987 period out of a total of 889 reactions of this type observed during the whole study period were included in our secondary evaluation.) The total number of 310 reactions (100%) showed the following RT distribution: 36 (11.6%) were of the acute type, 13 (4.2%) of the latent type, 12 (3.9%) could be interpreted as two distinct possible types of reaction to different drugs, and for 3 (1.0%) reactions, the type of reaction was indeterminable. The majority of reactions, 246 (79.4%), were of the subacute type starting within 24 hours of the last drug exposure. Among the 36 reactions of the acute type, 7 events of acute severe dyspnoea were observed which seemed to be as life-threatening as anaphylactic or anaphylactoid shock. These hospital-epidemiological data are of interest for focusing basic research and developing further principles of drug safety.

Incorporation of aluminium and effect of removal in experimental osteomalacia and fibro-osteoclasia.

Osteomalacia (OM) and fibro-osteoclasia (FO) was induced in growing rats by feeding a low calcium, low phosphorus, vitamin D poor diet or a low calcium diet respectively. After two weeks, Al Cl3 was supplemented up to a content of 0.1% of elemental Al and feeding continued for another two weeks, when half of the animals were sacrificed and the rest treated with desferrioxamine. In spite of similar blood aluminium concentrations, OM rats retained more Al in bone than FO rats. Desferrioxamine (DFO) treatment resulted in a significant decrease of Al in OM rats and tended to decrease Al in FO rats. Simultaneously the per cent mineral weight of the bone increased. We conclude that the preexisting bone pathology (OM or FO) is related to aluminium uptake and removal by DFO, which results in rapid mineral uptake.