Outcomes of immediate perforator flap reconstruction after skin-sparing mastectomy following neoadjuvant chemotherapy.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.

Effect of ß-carotene supply during close-up dry period on the onset of first postpartum luteal activity in dairy cows.

The aim of this study was to examine the effect of ß-carotene supply during the close-up dry period on the onset of first postpartum luteal activity in dairy cows. Twelve cows were supplied with 2000 mg of ß-carotene (20 g Rovimix(®) ß-Carotene containing 10% ß-carotene; DSM Nutrition Japan K.K., Tokyo, Japan) by oral administration daily from day 21 before expected calving date to parturition. Fourteen cows (control) did not receive ß-carotene supplementation. Blood samples were obtained on days 21, 14 and 7 before expected calving date and on days 1, 7, 14, 21 postpartum. When the plasma progesterone concentration exceeded 1 ng/ml by day 21 postpartum, luteal activity was assumed to have been initiated. The result showed that serum ß-carotene concentrations in the ß-carotene cows were higher than in the control cows during the experimental period (p < 0.01). The number of cows with the onset of luteal activity by day 21 postpartum was 9/12 in the ß-carotene cows and 4/14 in the control cows (p < 0.05). Retinol, certain metabolic parameters and metabolic hormones concentrations did not differ between ß-carotene and control cows. In addition, serum retinol concentration in ß-carotene cows without luteal activity was lower than in ß-carotene cows with luteal activity (p < 0.05), and serum gamma-glutamyl transpeptidase concentration in ß-carotene cows with luteal activity (p < 0.05) and control cows without luteal activity (p < 0.01) was higher than in control cows with luteal activity. In conclusion, ß-carotene supply during the close-up dry period may support the onset of luteal activity during early lactation in dairy cows.

Generation of lipid peroxyl radicals from edible oils and their biological activities: a need for consideration for anti-radical components and purification processing.

Lipid hydroperoxides (LOOH or oxidized oils) are known as unfavorable food components. Molecular details of the fate and mechanisms of LOOH to exert adverse effects in vivo are, however, little understood. In the present study, we demonstrated that LOOH generated alkylperoxyl radical (LOO*) after reaction with various heme compounds such as myoglobin, cytochrome c, hemin, hematin, etc., but little formation of other radical species was noticed such as L* or LO*. It was also shown that LOO* thus formed exhibits cytotoxicity and caused DNA damages including strand breakage and abasic site formation. This highly toxic LOO* is effectively scavenged by hot water extracts of vegetable (soup), flavonoids, polyphenols as well as tocopherols. Another important finding is that crude vegetable oils are rich in potent-LOO* scavenging activity, which exhibits potent anti-oxidant activity as well; whereas highly purified oils are scanty in such components and LOO* scavenging activity. These findings imply that a considerate processing in the refining of oils should be needed to retain such potent endogenous anti-oxidative radical scavenging-components.

Lipid peroxyl radicals from oxidized oils and heme-iron: implication of a high-fat diet in colon carcinogenesis.

A diet high in fat and iron is known as a risk factor in cancer epidemiology. However, the details of the molecular mechanism remains to be elucidated. We examined the possible implication of lipid peroxyl radicals generated from fatty acids and heme-iron in DNA damage, and hence in the possibility of colon cancer. F344 female rats were given N-nitroso-N-methylurea six times during a 2-week period and then fed diets containing different amounts of safflower oil and hemoglobin (rich in iron) for 36 weeks; the occurrence of colon cancer was determined by H&E staining. In this animal model, simultaneous feeding of a fat diet and heme-iron produced a significant increase (P < 0.05) in the incidence of colon cancer compared with a diet without hemoglobin. Electron paramagnetic resonance and chemiluminescence studies revealed that oxidized refined vegetable oils, particularly safflower oil, readily generated lipid peroxyl radicals in the presence of various heme compounds, and the peroxyl radicals did effectively cleave DNA. Unpurified native vegetable oils contain a high amount of peroxyl radical scavengers, whereas conventional refining processes seem to reduce the levels of many valuable anti-peroxyl radical compounds abundant in plant seeds. In conclusion, lipid peroxides and heme components generate peroxyl radical species that exert DNA-cleaving activity. A plausible explanation is that lipid peroxyl radicals thus generated, which originated from routine dietary components such as fat and red meat, may contribute, at least in part, to the high incidence of colon cancer.

Transient late neonatal hypocalcemia with high serum parathyroid hormone.

We report two patients with transient late neonatal hypocalcemia. Serum examination showed low calcium (Ca), high phosphorus, high parathyroid hormone (PTH), normal 25-hydroxyvitamin D and low or normal 1,25-dihydroxyvitamin D (1,25(OH)2vitD) levels. PTH infusion test revealed normal cyclic AMP production. In these patients, 1,25(OH)2vitD production by PTH, or Ca mobilization from bone and Ca absorption from intestine by PTH and 1,25(OH)2vitD might have been disturbed transiently due to developmental immaturities. This is a new type of transient late neonatal hypocalcemia with high serum PTH levels.

Effect of growth hormone (GH) therapy on parathyroid hormone metabolism in a girl with GH deficient short stature and chronic renal failure.

During GH treatment of a 14 year-old girl with chronic renal failure and short stature, she developed hyperparathyroidism which was successfully treated by the oral agent 26,27-F6-1, 25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2vit D3). It is hypothesized that the elevation of serum PTH level was induced either by the rise in phosphorus levels induced by GH or by a direct stimulatory effect of IGF-I on PTH production. This seems to be the first report of this kind.

Inhibition by triptoquinone-A of LPS- and IL-1 beta-primed induction of NO synthase in rat thoracic aorta.

We investigated the effect of triptoquinone-A (TQA), an active principal of Triptergium wilfordii, on the induction of nitric oxide synthase (NOS) promoted by endotoxin (LPS) and interleukin-1 beta (IL-1 beta). Prophylactic application of TQA selectively prevented LPS-primed initiation of L-arginine (Arg)-induced relaxation, and cGMP formation of rat thoracic aorta, and LPS-stimulated nitrite production by cultured aortic smooth muscle cells, which appear to be mediated by NOS expressed by LPS in vascular smooth muscle. TQA also prevented IL-1 beta-triggered initiation of Arg-induced relaxation and nitrite accumulation. These results suggest that TQA prevents LPS-or IL-1 beta-promoted induction of NOS in vascular smooth muscle, thus inhibiting development of Arg-induced vasorelaxation.

The pathogenic role of the NMDA receptor in hyperthermia-induced seizures in developing rats.

Hyperthermia-induced seizures (HS) in rats have been used as a model of febrile seizures. Activation of the N-methyl-D-aspartate (NMDA) receptor by increased extracellular glutamate (Glu) in the cortex during hyperthermia may be involved in the induction of HS and HS kindling. To confirm this hypothesis, the effects of a potent blocker of the NMDA receptor, MK-801, on the threshold and pattern of HS were evaluated. The threshold temperatures for rats given 0.1 (low dose) and 0.5 (high dose) mg/kg MK-801 (i.p.) for the first time were 41.6 degrees C (39.7-42) (median, range) and 42.0 (41.2-42.0), respectively, which were significantly higher than the 40.5 (39.4-41.2) for rats without MK-801 administration (P < 0.01). The recurrent occurrence of HS suppressed the increase in the threshold temperature with age, and changed the seizure from partial to generalized seizures (HS kindling), whereas these effects of recurrent HS on the threshold and pattern of HS were inhibited by the high dose (0.5 mg/kg) of MK-801. MK-801 blocks HS and HS kindling. The activation of the NMDA receptor during hyperthermia plays an important role in the induction of HS and HS kindling.

[Pharmacokinetical and clinical study of cefpirome in children].

This study describes the pharmacokinetic characteristics and clinical usefulness of cefpirome (CPR) in children. Mean half-lives of 20 mg/kg and 40 mg/kg of CPR injected intravenously in one shot were 1.18 and 1.34 hours, respectively, and their mean recovery rates into urine were 69.8 and 72.2%, respectively. Minimum inhibitory concentrations of CPR against Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli and Haemophilus influenzae were the same as or lower than those of ceftazidime. CPR was clinically effective in 14/15 of patients with bacterial infections; 8/9 of pneumonia, 2/2 of bronchitis, 1/1 of pharyngitis, 1/1 of tonsillitis, 1/1 of osteomyelitis, 1/1 of urinary tract infection. No clinically overt side effects of CPR were found, while an increase of eosinophils in blood was observed in 2 cases, and an increase of platelet in blood in 1 case and an elevation of serum GPT activity in 1 case were also observed. These findings indicate that CPR is useful for the treatment of bacterial infections in children.

Role of change in vitamin D metabolism with age in calcium and phosphorus metabolism in normal human subjects.

This study describes the age-related changes of vitamin D metabolism and its related hormones, immunoreactive PTH (iPTH) and calcitonin (CT) in normal human subjects. The objective was to assess their roles in the changes in metabolism of calcium and phosphorus with age. Serum calcium and phosphorus levels declined linearly with age from newborn infants to older adults (r = -0.385, P less than 0.01; r = -0.568, P less than 0.01). The serum calcium and phosphorus levels in adults of 51 yr of age or more were significantly lower than those in children and younger adults of 50 yr of age or less (P less than 0.025, P less than 0.01), whereas the calcium and phosphorus levels in cord blood were significantly higher than those in children and younger adults (P less than 0.025, P less than 0.01). The serum concentration of 1 alpha,25-dihydroxyvitamin D (1 alpha,25-(OH)2-Vit D) did not change in children and younger adults, being 42.0 +/- 1.4 (SE) pg/ml, but it significantly decreased to 31.4 +/- 1.9 pg/ml in older adults (P less than 0.01). There were no significant age-related changes in the serum concentrations of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D, or vitamin D-binding protein (DBP) among children, younger adults and older adults. The concentrations of all vitamin D metabolites and DBP in cord serum were significantly lower than those in children and younger adults (P less than 0.01). Serum iPTH levels were higher in older adults (P less than 0.05) and lower in cord blood (P less than 0.1), compared with those in children and younger adults, whereas the serum CT level was higher in cord serum (P less than 0.01). No sex differences were found in the serum concentrations of calcium, phosphorus, vitamin D metabolites, DBP, iPTH, and CT. The serum concentration of calcium or phosphorus did not correlate significantly with that of 1 alpha 25-(OH)2-Vit D by simple correlation analysis. Multivariate analysis, however, showed that the change in the serum concentration of 1 alpha,25-(OH)2-Vit D, as well as iPTH and CT, contributed to their correlation with the change in the serum concentrations of calcium and phosphorus. These data indicate that change in vitamin D metabolism might play some role in the age-related change of serum calcium and phosphorus levels in children and adults, but that calcium and phosphorus metabolism in the fetus might be regulated by some mechanisms other than vitamin D metabolism.