Temperature alterations during embryogenesis have a sex-dependent influence on growth properties and muscle metabolism of day-old chicks and 35-day-old broilers.

Broiler eggs were either incubated at 37.8°C during the whole incubation period (control), or at higher (38.8°C, group H) and lower temperatures (36.8°C, group L) from embryonic day (ED) 7 up to ED 10 (ED 7 to 10) or from ED 10 up to ED 13 (ED 10 to 13). Before and after this temperature treatment the eggs were incubated at 37.8°C. The day-old chicks were weighted, sexed and fed up to day 35. On days 1 and 35 samples were taken from the breast and leg muscles for analyzing of the mitochondrial respiratory activity (MRA) and from the breast muscles for analysis of the cross-sectional areas (CSA) and the glycogen phosphorylase (GP), phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and cytochrome oxidase (COX) activities. Statistical analysis showed that treatment (control, group H, group L), sex and their interaction, but not the treatment period (ED 7 to 10; ED 10 to 13), significantly influenced the results. Group H chicks had lower (P⩽0.05) body and heart weights but higher (P⩽0.05) liver weights, CSA values, leg MRA as well as PFK, LDH, CS, GP and COX activities compared with the group L chicks. The results of the control chicks differ (P⩽0.05) from those of the group H (body, heart weight, COX), the group L chicks (liver weight, PFK, LDH, CS, GP) or the birds of both other groups (CSA). The group H broiler had higher (P⩽0.05) body and leg weights as well as LDH, CS, COX and GP activities than the group L broilers. The BWs and the LDH and GP results of the control broiler differ (P⩽0.05) from those of both other groups or from the results of the group H (CS) and group L broiler (COX). Female broilers had lower (P⩽0.05) body, breast and leg weights, but higher (P⩽0.05) CSA, LDH, CS and GP activities than the male animals. Analysis of treatment×sex interaction showed that group H hens had higher (P⩽0.05) body and breast weights, LDH and GP activities compared with the group L hens, whereas in the male broiler no effect of the interaction could be found, except for the lower (P⩽0.05) CSA values in the group H than group L cocks. The treatment effects are probably due to altered embryonic activity and related molecular mechanisms. The sex-related differences in the broiler indicate that these alterations already occur in the embryos and chicks, but become significant with the sexual dimorphism after hatch.

Comparative biochemical studies of fresh frozen plasma and pooled solvent/detergent-treated plasma (octaplasLG® ) with focus on protein S and its impact in different thrombin generation assay set-ups.

BACKGROUND AND OBJECTIVES: The solvent/detergent treatment enables effective and robust inactivation of all lipid-enveloped viruses, but also inactivates partly sensitive plasma proteins such as protein S. The aim of this study was to investigate the thrombin generation capacity of octaplasLG® , in particular focusing on the function of protein S in thrombin generation assay and the impact of assay settings. MATERIALS AND METHODS: Sixteen octaplasLG® batches and 32 units of single donor fresh frozen plasma (FFP) were investigated. For protein S, both functional activity and free antigen levels were measured. Thrombin generation assay was performed using two fluorogenic tests with different triggers. Finally, rotational thromboelastometry was performed. RESULTS: Mean protein S levels were lower in octaplasLG® , but a wider range of values was found for FFP. Clotting parameters and thrombin generation capacities overlapped between the two plasma groups as demonstrated using both thrombin generation assays and different triggers. Spiking studies with protein S-depleted plasma, human purified protein S or antibodies against protein S confirmed a correlation between protein S and thrombin generation capacity under specific assay conditions, especially in an assay with low tissue factor concentration. CONCLUSION: Correlation between protein S and thrombin generation capacity was demonstrated in the TGA. Due to higher variability in protein S content in the FFP group, overlapping haemostatic potentials of the two plasma groups were found.

Changing the incubation temperature during embryonic myogenesis influences the weight performance and meat quality of male and female broilers.

Eggs of broilers were initially incubated at 37.8°C, then at 38.8°C (group H) and 36.8°C (group L) between embryonic days 7 to 10 (time A) and days 10 to 13 (time B) and further incubated at 37.8°C until hatching. The chicks were fattened until day 35 and then slaughtered. The effect of treatment, time, and sex and their interactions on carcass and meat quality traits were determined. No significant impact of the "treatment time" was analysed, but "treatment" and "sex" and their interactions influenced (P < 0.05) the different parameters. After hatching, group L broilers were heavier (P < 0.05), followed by slower growth compared to group H chicken. At slaughter day, body, carcass, and leg weights of group H broiler were higher (P < 0.05) and yield results lower (P < 0.05) compared to group L animals. pH, drip loss, shear force, and lightness values of group H broiler breast muscles were higher (P < 0.05) and grill loss and redness values lower (P < 0.05) compared to group L Musculus pectoralis superficialis (MPS). Body, carcass, MPS, and leg weights, leg yields and grill loss and lightness values of the male broiler were higher (P < 0.05) and drip loss results lower (P < 0.05) than the female birds. Male group H broiler showed lower (P < 0.05) carcass and MPS yields compared to the control and group L males, whereas females group H birds had higher (P < 0.05) carcass and MPS weights and lower leg yields (P < 0.05) than the female group L animals. The study shows that an increasing incubation temperature during early embryogenesis positively influences the growth and carcass traits of the broilers, accompanied with a partly negative impact on meat quality (drip loss, shear force, lightness). The growth effects were sex-dependent, as significant weight differences could be only found in female broilers. The results indicate that incubation temperature alteration influences molecular mechanisms in the muscle and other tissues with an impact on growth after hatch.

Physico-chemical and microbiological properties of raw fermented sausages are not influenced by color differences of turkey breast meat.

It has been suggested that the color of turkey breast meat influences both physico-chemical and microbiological properties of raw fermented sausages. In this study, raw fermented sausages were produced with turkey breast meat in 3 different colors (pale, normal, or dark), which were obtained from 2 fast-growing-genetic-line toms at 2 slaughterhouses. Prior to the sausage production, the breast muscles were sorted into color groups according to the lightness values determined at 24 h postmortem. This meat was subsequently processed to raw fermented sausages using 1.5 or 2.5% curing salt (CS). The pale meat had higher lightness, electrical conductivity, and drip loss, whereas the dark meat showed a darker color only. The physico-chemical (pH, water activity), visual (lightness, redness), and microbial (total plate count) properties of the sausages were not influenced by the color of the turkey breast meat. The sausage made with 2.5% CS had lower aw and higher ash and hardness values than the sausages produced with 1.5% CS. In conclusion, processing of differently colored turkey meat to raw fermented sausages does not influence the quality characteristics of the products. Based on these findings, there is no reason for the sausage producer to separate turkey breast muscles by color before producing raw fermented sausages.

Serum procalcitonin levels in the postmortem diagnosis of sepsis.

Procalcitonin is regarded as a valuable marker for sepsis in living persons and even in post-mortem investigations. At the Institute of Legal Medicine, 25 autopsy cases with suspected bacterial infectious diseases or sepsis were examined using the semi-quantitative PCT-Q(®)-test (B.R.A.H.M.S., Germany) in 2010 and 2011. As controls, 75 cadavers were used for which there was no suspicion of a bacterial infectious disease or sepsis. Femoral blood was cultured from the cases and from controls, and samples from the brain, heart, lungs, liver, spleen and kidneys were examined histologically for findings seen in sepsis. Twelve cases in the sepsis/infectious disease group (48%) were classifiable as sepsis following synopsis of PCT levels, autopsy results, and histopathological and microbiological findings. This study shows that the semi-quantitative PCT-Q(®)-test is a useful supplementary marker in routine autopsy investigations, capable of classifying death as due to sepsis.

Mitochondrial respiratory and antioxidative enzyme activities in turkey meat.

Meat quality and (anti)oxidative metabolism of m. pectoralis superficialis (MPS), m. gastrocnemius (MG) and m. iliotibilialis lateralis (MIL) from turkey toms were analysed. After slaughter, pH of MPS and MG decreased and electrical conductivity of the MPS increased. The MG had generally higher pH values. The meat lightness (L) and redness (a) increased in MG and MPS after slaughter. The MPS always had higher L and lower a values. Mitochondrial respiratory activities (MRA) were higher in the MIL than the MPS. The activities of superoxide dismutase (SOD) and glutathione peroxidase, analysed in the MPS, increased and the glutathione reductase activity decreased after slaughter. Meat samples with lower pH24 h p.m. had higher drip loss and L values. The MRA were tendentially lower and the SOD activities higher in these samples. These results indicate a relation between the meat quality, the antioxidative metabolism and mitochondrial respiration.

Serious head injury in young children: birth trauma versus non-accidental head injury.

Birth injury of the skull and central nervous system can be a complication of a difficult delivery, especially following forceps or vacuum-assisted delivery. Birth trauma of the head can also mimic the appearance of a non-accidental head injury and is therefore an important differential diagnosis. We report on two young infants with serious head injuries. The difficult differential diagnosis birth trauma versus non-accidental head injury is discussed and the necessity for cooperation between clinicians, forensic doctors and specialized neuroradiologists is emphasized.

Aortic dissecting aneurysms--histopathological findings.

Acute aortic dissection is a life-threatening disease with a high rate of mortality. At the Institute of Legal Medicine of the Hanover Medical School, 30 cases with aortic dissections were found during autopsy and examined histologically between 2006 and 2009. The grade of medial alterations in the form of cystic medial necrosis, elastin fragmentation, fibrosis and medionecrosis were estimated semi-quantitatively. In order to assess the normal aging process, samples of the aortic wall of 25 decedents without dissecting aneurysms were analyzed histologically. This study demonstrates that there are partly quantitative differences, particularly with a statistically significant increase in cystic medial necrosis (p<0.001) and elastin fragmentation (p<0.001), between aortas from dissecting aneurysms and the normal aging aorta, which may help to identify genetically predisposed relatives of patients with a dissection of the aorta.

Color values and other meat quality characteristics of breast muscles collected from 3 broiler genetic lines slaughtered at 2 ages.

Broilers from the lines Ross 308, Ross 708, and Cobb 700 were slaughtered at 28 and 41 d of age at a commercial abattoir. After slaughter, the carcass, breast, and leg weights as well as the breast and leg yields were determined. Further investigations analyzed the color [lightness (L*), redness (a*), and yellowness (b*)], pH at 24 h postmortem, electrical conductivity (EC), drip loss, grill loss, and shear force values as well as the muscle fiber cross-sectional areas of the breast muscles. The 41-d-old broilers had higher carcass, breast, and leg weights than the 28-d-old birds. The breast yield values were higher and the leg yields were lower in the 41-d-old broilers. The fiber cross-sectional area values were also higher in the older birds. Within the younger birds the slaughter characteristics were approximately comparable among the lines. The EC, L*, grill loss, and shear force values increased but the drip loss and a* values decreased with the age of the broiler. The genetic lines differed within the 28-d-old broilers with regard to EC, grill loss, and shear force values and within the 41-d-old broilers with regard to the EC, L*, grill loss, and shear force values. The pH correlated negatively with the EC, L*, b*, drip loss, and shear force values. During storage, L* and b* values of the breast muscles increased and a* values decreased in all genetic lines, whereas the L* values were generally higher in the older broilers and the a* and b* results were generally higher in the breast muscles of the younger broilers. In conclusion, the carcass and meat quality characteristics of broilers changed with age with positive (carcass and breast muscle weight, drip loss) but also negative (L*, a*, grill loss) effects. The effect of the genetic line was rather low. Despite the age-related changes of meat quality parameter, the pH values remained unchanged, indicating muscle structural influences on the muscle-to-meat-transition with increasing age of the broiler.

Mitochondrial respiratory and antioxidative enzyme activities in broiler meat in relation to age and gender of the animals.

Colour is an important quality parameter of broiler meat influencing the consumer buying behaviour. The alterations of the colour after slaughter are related to the oxidative status of the tissue. This in turn is influenced by an interaction between the mitochondria and the antioxidative enzymes. In this study, breast muscles were collected from hens and cocks of a commercial line slaughtered at the ages of 28 and 41 day. Analysis of the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) was performed with samples obtained 20 min and 48 h after slaughter (post mortem, p.m.), whereas the mitochondrial respiratory activity was analysed in permeabilised breast muscle fibres collected 20 min p.m. The carcass characteristics of breast muscle and leg weight as well as breast yield were significantly higher, and the leg yields lower, in the 41-day-old broiler. The 28-day-old hens and cocks had comparable carcass characteristics (P > 0.05), whereas 41-day-old cocks had significantly higher carcass, breast and leg weight in comparison to the hens. The pH20 min p.m. and the L*48 h p.m. were significantly higher, and the a* and b* values of the 20 min and 48 h p.m. samples as well as the drip loss were significantly lower in the 41-day-old broiler. Mitochondrial respiratory rates were comparable (P > 0.05) between the 28- and 41-day-old cocks and hens. The same result could be found with regard to the activities of the SOD, GPx and GR except for lower activities of the SOD20 min p.m. and higher of the GR48 h min p.m. in the 41-day-old broiler. The concentrations of thiobarbituric acid-reactive substances were generally higher in the breast muscles of the 41-day-old broiler. Assorting the data according to their mean pH20 min p.m. indicates a positive influence of higher pH values (>6.34) on the mitochondrial function, whereas a low pH20 min p.m. results in tendentially and significantly higher activities of the antioxidative enzymes and drip loss values. These results indicate a relation between the meat quality and the oxidative metabolism as well as antioxidative capacity of the meat.

[The unrecognized myocardial infarction]. / Der nicht erkannte Myokardinfarkt.

BACKGROUND AND OBJECTIVES: despite the improved quality of diagnostic technology, myocardial infarction still belongs to the diseases that are most frequently overlooked. Especially asymptomatic patients or patients with atypical symptoms are more common to be misdiagnosed. Failure to correctly diagnose is the leading cause of malpractice claims. It was the aim of this study to evaluate the records of patients who died from myocardial infarction and to analyse whether medical malpractice had occured in those who had undergone a medical examination shortly before their death. METHODS: in the years 2008 and 2009 myocardial infarction had been diagnosed in 109 auotopsies performed at the Institute of Legal Medicine of the Hanover Medical School. The records of these patients who had died from myocardial infarction were retrospectively analysed with particular emphasis on an antemortem medical consultation, reported symptoms and diagnostic measures. RESULTS: in 38 persons (34.9 %) an antemortem medical consultation or hospitalisation has taken place, whereby in five persons the diagnosis of myocardial infarction was suspected. In 33 persons, a myocardial infarction could not be diagnosed antemortem. In two cases an additionally cardiologic assessment was recommended to estimate if medical malpractice was present and in another two cases with insufficient diagnostic measures medical malpractice was reproached from forensic pathologists. CONCLUSION: autopsy give the most accurate diagnostic information. On the other hand, it may provide an effective defence against medical malpractice litigation.

Safety of glucose-containing solutions during accidental hyperinfusion in piglets.

BACKGROUND: Errors in fluid management can lead to significant morbidity in children. We conducted an experimental animal study to determine the margin of safety in accidental hyperinfusion of different glucose and electrolyte containing solutions. METHODS: Fifteen piglets [bodyweight 12.1 (sd 2.0) kg] were randomly assigned to receive either 100 ml kg⁻¹ of balanced electrolyte solution with glucose 1% (BS-G1), hypotonic electrolyte solution with glucose 5% (HE-G5), or glucose 40% solution (G40) over 1 h. Blood electrolytes, glucose, and osmolality and intracranial pressure (ICP) were measured before, during, and after fluid administration. RESULTS: Hyperinfusion of BS-G1 led to moderate hyperglycaemia [baseline 3.4 (sd 1.3) mmol litre⁻¹, study end 12.6 (1.8) mmol litre⁻¹], but no other relevant pathophysiological alterations. Hyperinfusion of HE-G5 produced marked hyperglycaemia [baseline 3.9 (1.2) mmol litre⁻¹, study end 48.6 (4.3) mmol litre⁻¹, P < 0.05] and hyponatraemia [baseline 136.4 (1.3) mmol litre(-1), study end 119.6 (2.1) mmol litre⁻¹, P < 0.05], whereas osmolality remained stable during the course of the study. Hyperinfusion of G40 induced acute hyperglycaemic/hyperosmolar decompensation with an extreme decrease in serum electrolytes [e.g. sodium baseline 138 (1.1) mmol litre⁻¹, 30 min 87.8 (6.4) mmol litre⁻¹, P < 0.01], leading to cardiac arrest after infusion of 50-75 ml kg⁻¹. ICP remained within a physiological range in all groups. CONCLUSIONS: In an animal model of accidental hyperinfusion, BS-G1 showed the widest margin of safety and can therefore be expected to enhance patient safety in perioperative fluid management in children; HE-G5 proved significantly less safe; and G40 was found to be outright hazardous.

Comparative study of the quality of broiler and turkey meat.

1. An experiment was conducted to compare different meat quality parameters, especially colour development, in the breast muscle of turkeys and broilers. 2. A total of 160 broilers (Ross 308) with a mean age of 32 d and 120 turkeys (BUT Big 6) with a mean age of 147 d were slaughtered at 4 (broilers) or three (turkeys) dates at two commercial abattoirs and the slaughter characteristics (slaughter and breast weight, breast yield) were determined. 3. The Musculus pectoralis superficialis (MPS) was collected and different meat quality parameters (pH, electrical conductivity (EC), colour (L * a * b*), grill loss, shear force) were analysed 24 h after slaughter; the colour development during cold storage of the MPS was also analysed. 4. The turkeys had greater carcase and breast weights as well as breast yields. The pH was significantly lower and the EC as well as the grill loss significantly higher in the MPS of the turkey, whereas the shear force values were comparable. 5. Considering the colour of the breast muscle the broiler MPS had significantly higher L* and b* but lower a* values. During cold storage the L* and b* values of the MPS increase in both investigated poultry species, whereas a* increased in the turkey but decreased in the broiler birds. The L* and b* of the broiler and turkey MPS thereby increased in parallel. 6. From the results of this and previously published studies that investigated only broilers or turkeys it can be concluded that chemical (or biochemical) differences between these poultry species exist that specifically influence the muscle-to-meat transition process after slaughter.

Smooth muscle cell migration promoting activity of plasma predicts restenosis in patients with peripheral arterial occlusive disease undergoing angioplasty.

BACKGROUND: Efficacy of percutaneous transluminal angioplasty (PTA) is limited by restenosis occurring in a large proportion of patients. Smooth muscle cell (SMC) migration is a major pathomechanism of restenosis. We studied SMC migration inducing activity of plasma from patients with peripheral arterial occlusive disease (PAOD) undergoing PTA. METHODS AND RESULTS: SMC migration was determined in a two-dimensional assay system after addition of 1/25 plasma dilutions. Mean increase in migration area was 65.5 +/- 33.8% in normal controls and 67.7 +/- 53.2% in patients with PAOD. 6 hours after PTA, plasmatic migration inducing activity was largely unchanged. In 19/30 patients with restenosis (6 months after PTA) migration promoting activity (82.7 +/- 60.0) was significantly higher than in 11/30 patients with patent vessels (41.8 +/- 21.0; p = 0.03). No correlation of clinical risk factors with outcome was observed. A weak correlation was found between plasmatic migration promoting activity and levels of epidermal growth factor and transforming growth factor-beta. CONCLUSION: The capacity of human plasma to stimulate SMC migration in tissue culture can be used to assess the risk for restenosis after PTA in patients with PAOD.

Changes in the fibrinolytic system in patients with peripheral arterial occlusive disease undergoing percutaneous transluminal angioplasty.

We have investigated fibrinolytic parameters in 33 patients with peripheral arterial occlusive disease (PAOD) before and 6, 24, and 48 hours after percutaneous transluminal angioplasty (PTA) as well as in 35 gender-matched healthy controls, whose mean age was not significantly different from the mean age of the patients. PAOD patients had significantly higher plasma levels of t-PA antigen (12.0+/-4.9 vs. 9.2+/-5.5 ng/ml), PAI-1 antigen (34.8+/-22.1 vs. 27.2+/-23.6 ng/ml), PAI-1 activity (10.0+/-6.5 vs. 8.0+/-8.0 U/ml), PCI (188.2+/-55.6 vs. 134.1+/-75.5% as compared with normal human plasma), and fibrinogen (420.2+/-92.6 vs. 261.9+/-32.7 mg/dl) as compared with controls. After angioplasty, fibrinolytic parameters and fibrinogen levels increased, reaching higher than preintervention levels 24 and 48 hours after the intervention. Six months after initially successful PTA, restenosis was demonstrated in 14 out of 33 patients (42%). Patients with late restenosis had significantly higher levels of PAI-1 activity 24 and 48 hours after PTA, as compared with patients with late patency (24 hours: 16.1+/-8.0 vs. 10.0+/-7.4; 48 hours: 16.5+/-7.9 vs. 12.0+/-7.0; p<0.05 for both time points). The results suggest that impaired fibrinolysis early after PTA might be a cause or marker of a disturbed repair process of vascular injury, leading to restenosis.

Immunohistochemical detection of adhesion molecule CD44 splice variants in lymph node metastases of cervical cancer.

Expression of specific cell adhesion molecule CD44 isoforms (splice variants) has been shown to be associated with poor prognosis in human cervical cancer. We used 3 different variant exon sequence-specific murine monoclonal antibodies (MAbs) to epitopes encoded by exons v5, v6 and v7-v8 of human variant CD44 to study the expression of CD44 splice variants in 35 primary squamous-cell carcinomas of the cervix and pelvic lymph node metastases by means of immunohistochemistry. Primary tumors showed expression of CD44 splice variants CD44v5, CD44v6 and CD44v7-8 in 93%, 73% and 33% of cases, respectively. Lymph node metastases expressed CD44v5, CD44v6 and CD44v7-8 in 83%, 53% and 21% of cases, respectively. Tumors with expression of CD44v6 in pelvic lymph node metastases showed metastatic spread to 2 or more pelvic lymph nodes significantly more often compared to patients without expression of splice variant CD44v6. Patients suffering from tumors with lymph node metastases expressing splice variant CD44v6 had a poorer recurrence-free survival compared to patients without CD44v6 expression in lymph node metastases, but this trend was not statistically significant. Expression of CD44 splice variants containing epitopes encoded by exon v6 in primary tumors and pelvic lymph node metastases of cervical cancer patients is consistent with a prominent role of CD44 in the process of metastasis formation.

Direct evidence of a parathyroid related protein gradient between the mother and the newborn in humans.

Umbilical cord plasma has increased parathormone (PTH)-like bioactivity in comparison with that in maternal plasma, but suppressed PTH levels. Previous attempts to detect elevated levels of PTHrP(1-34) in the umbilical cord were unsuccessful, whereas PTHrP was detected by immunohistochemistry in both fetal parathyroid glands and placental membranes. At the time of delivery, plasma samples were drawn simultaneously from 47 normal mothers (mean age, 26 years) and from the umbilical cord of 25 female and 22 male newborns and assessed for calcium adjusted for albumin, magnesium, creatinine, intact PTH and PTHrP. PTHrP was measured using a new 2-site immunoradiometric assay recognizing separately 1-40 and 60-72 residues with a sensitivity of 0.3 pmol/l. Mean (+/- S.D.) plasma calcium values were 2.35 +/- 0.10 in the mothers versus 2.63 +/- 0.12 mmol/l in the newborns (P < 0.001). PTH values were significantly higher in the mothers, as expected (22.3 +/- 14.8 vs. 6.2 +/- 0.9 pg/ml). In contrast, PTHrP values were significantly higher in the newborns (1.50 +/- 0.39 versus 0.84 +/- 0.28 pmol/l, P < 0.001). Only 1/47 mother had a PTHrP level higher than her child (0.9 vs. 0.8 pmol/l). Only 10/47 mothers had PTHrP higher than 1 pmol/l whereas only 1/47 newborn had a value below 1 pmol/l. There was no correlation between Ca and PTHrP in either group. Serum creatinine values were all within the normal range. Serum magnesium levels were not different between the mothers and the children.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of clodronate treatment on bone scintigraphy in metastatic breast cancer.

Because of their high affinity for bone, bisphosphonates are used both in the treatment of benign and malignant bone disease and in radiopharmaceutical bone imaging. A prospective study was undertaken to evaluate whether intravenous clodronate (dichloromethylene bisphosphonate) therapy might affect the results of bone scintigraphy with 99mTc-labeled methylene diphosphonate (MDP). In 11 female patients with breast cancer and metastatic bone disease, quantitative bone scans were obtained using a region of interest (ROI) method on Days 0 and 22. After intravenous clodronate therapy from Day 1 to Day 21, all metastatic bone lesions were still detectable, and median ROI ratios did not differ to a statistically significant extent from baseline values. Serum calcium levels decreased (p = 0.0449), whereas parathyroid hormone concentrations showed an increase (p = 0.0053). Mean serum levels of creatinine, inorganic phosphorus, osteocalcin, gamma glutaminyl-transpeptidase and alkaline phosphatase remained unchanged. However, a more than twofold rise in the serum activity of alkaline phosphatase was measured in three patients. We conclude that 3 wk of intravenous clodronate treatment did not impair the sensitivity of 99mTc-MDP bone scintigraphy in detecting bone lesions in patients with metastatic breast cancer.

[Pamidronate in the treatment of tumor-associated hypercalcemia]. / Pamidronat in der Behandlung der tumorassoziierten Hypercalcämie.

After a 48-hour rehydration period 28 of 31 patients with cancer-associated hypercalcemia (serum calcium greater than or equal to 2.8 mmol/l) were treated intravenously with the bisphosphonate pamidronate. In three patients fluid repletion with 0.9% saline solution had already normalized serum calcium levels. Pamidronate was given in a single infusion on day 0, the dose of pamidronate adapted to the severity of hypercalcemia. If the serum calcium concentration was greater than or equal to 2.8 mmol/l on day 3, application of pamidronate was repeated. In all patients normocalcemia was restored; mean serum calcium decreased from 3.2 +/- 0.35 on day 0 to 2.15 +/- 0.32 on day 12. Hypercalcemia recurred in 11 patients, seven of these underwent pamidronate treatment according to the same therapeutical regimen. Normal calcium levels were attained in five cases. Side effects were of minor gravity: brief hyperthermia occurred in four patients and transient, asymptomatic hypocalcemia was noticed in nine cases.