Circulating IL-17A Levels in Postmenopausal Women with Primary Hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common cause of secondary osteoporosis in postmenopausal women. Th17 lymphocytes and the released cytokine IL-17A play an important role in bone metabolism. Th17 cells have been shown to be activated by PTH, and peripheral blood T cells from patients affected with PHPT express higher levels of IL-17A mRNA than controls. AIM: To investigate circulating levels of IL-17A and the ratio RANKL/OPG, as markers of osteoclastogenesis, in 50 postmenopausal PHPT women compared with postmenopausal osteoporotic non-PHPT women (n = 20). RESULTS: Circulating levels of IL-17A were similarly detectable in most PHPT and non-PHPT osteoporotic women (12.9 (8.4-23.1) vs. 11.3 (8.3-14.3) pg/ml, median (range interquartile), P = 0.759), at variance with premenopausal women where IL-17A was undetectable. In PHPT women, any significant correlations could be detected between circulating IL-17A levels and PTH levels. Nonetheless, significant negative correlations between circulating IL-17A and ionized calcium levels (r = -0.294, P = 0.047) and urine calcium excretions (r = -0.300, P = 0.045) were found. Moreover, PHPT women were characterized by positive correlations between IL-17A levels and femur neck (r = 0.364, P = 0.021) and total hip (r = 0.353, P = 0.015) T-scores. Circulating IL-17A levels did not show any significant correlation with sRANKL, OPG, and sRANKL/OPG ratio in PHPT women. CONCLUSIONS: In postmenopausal PHPT women, circulating IL-17A levels were similar to those detected in postmenopausal non-PHPT women, showing a disruption of the relationship observed in postmenopausal osteoporosis among circulating PTH, sRANKL, OPG, IL-17A, and bone demineralization in postmenopausal PHPT women. The data support an osteogenic effect of IL-17A in postmenopausal PHPT women.

Clinical presentation and management of patients with primary hyperparathyroidism in Italy.

PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13  years), the remaining 38 (6.3%, age 41 ± 17  years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH-independent hypercortisolism.

OBJECTIVE: To evaluate if the parameters of hypothalamic-pituitary-adrenal (HPA) axis activity could predict the occurrence and duration of post-surgical hypocortisolism (PSH) in patients with Cushing's syndrome (CS) and with adrenal incidentaloma (AI). METHODS: We studied 80 patients (54 females, age 53.3 ± 11 years), who underwent adrenalectomy for CS (17 patients) or for AI (53 patients). Before surgery, we measured adrenocorticotroph hormone (ACTH), urinary free cortisol (UFC) and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST) levels. After surgery, all patients were given a steroid replacement therapy, and PSH was searched after 2 months by a low-dose (1 µg, iv) corticotropin stimulation test, that was repeated every 6 months in PSH patients for at least 4 years. RESULTS: The PSH occurred in 82.4 and 46% of CS and AI patients, respectively. In the whole sample and in AI patients separately considered, the PSH was independently predicted by the preoperative cortisol levels after 1 mg-DST, however, with a low (< 70%) accuracy. In AI patients the PSH occurrence was not ruled out even by the cortisol levels after 1 mg-DST lower than 1.8 µg/dL (50 nmol/L). In the 50% of CS patients and in 31% of AI patients the PSH lasted more than 18 months and in 35.7% of CS patients it persisted for more than 36 months. In AI patients, the PSH duration was not predictable by any parameter. However, a PSH duration of at least 12 months was significantly predicted before adrenalectomy (sensitivity 91.7%, specificity 41.2%, positive predictive value 52.4%, negative predictive value 87.5%, p = 0.05) by the presence of at least 2 out of low ACTH levels, increased UFC levels and cortisol levels after 1 mg-DST ≥ 3.0 µg/dL (83 nmol/L). CONCLUSION: The PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.

Non classical complications of primary hyperparathyroidism.

Several studies suggested that the condition of primary hyperparathyroidism (PHPT) may be associated not only with the classical bone, kidney and gastrointestinal consequences, but also with cardiovascular, neuromuscular and articular complications, impaired quality of life and increased cancer risk. However, the only cardiovascular complications associated with PHPT, which seems to improve after parathyroidectomy, is left ventricular hypertrophy, while, data regarding the reversibility of hypertension, valve calcifications and increased vascular stiffness are inconsistent. Parathyroidectomy seems to ameliorate neuropsychological, cognitive disturbances and quality of life in moderate-severe PHPT, while data in mild PHPT are less clear. At variance, the effect of parathyroidectomy on neuromuscular and articular complications is still unknown, and no studies demonstrated a reduction of cancer risk after recovery from PHPT. Overall, to date, cardiovascular and neuropsychological evaluation are not recommended solely because of PHPT, nor cardiovascular disease, muscle weakness, and neuropsychological complications are indication for parathyroidectomy.

Lipid abnormalities in patients with adrenal incidentalomas: role of subclinical hypercortisolism and impaired glucose metabolism.

BACKGROUND: Subclinical hypercortisolism (SH) has been associated with metabolic complications such as type 2 diabetes mellitus, obesity and dyslipidemia. Scarce data are available regarding the lipid pattern abnormalities in SH, in relation to insulin resistance and impaired glucose metabolism (IGM). We aimed to evaluate the possible influence of SH on lipid pattern in relation to the presence/absence of impaired glucose metabolism. METHODS: In 338 patients with adrenal incidentaloma, the presence of SH, hypertension, dyslipidemia and IGM was evaluated. According to the presence of SH and IGM the patients were divided into 4 groups (IGM+SH+, IGM+SH-, IGM-SH+, IGM-SH-). We recruited 98 subjects without IGM (IGM-) and 100 with IGM (IGM+) as control groups. RESULTS: The prevalence of dyslipidemia was comparable among Group IGM+SH+, Group IGM+SH- and IGM+ controls (57.9, 58.4, 56%, P = NS). No difference in dyslipidemia prevalence among IGM- patients and IGM- controls was observed. The IGM+SH+ patients had a higher prevalence of dyslipidemia (57.9%) than IGM-SH+ ones (29.1%, P < 0.01). The IGM+SH- patients showed an increased prevalence of hypertension (76.6 vs 54.8%, P < 0.01) and dyslipidemia (58.4 vs 23.8%, P < 0.0001) as compared with IGM-SH- patients. Logistic regression analysis showed that only IGM was associated to dyslipidemia (OR 4.31, 95% CI 2.61-7.12, P = 0.0001) regardless of age, SH and gender. CONCLUSIONS: In the absence of alterations of glucose metabolism the presence of a subtle cortisol excess has no effect on lipid pattern. IGM seems to influence the lipid metabolism regardless of the presence of SH.

Factors associated with bisphosphonate treatment failure in postmenopausal women with primary osteoporosis.

UNLABELLED: Among 97 postmenopausal women with primary osteoporosis, adequate calcium and vitamin D supplementation, and good compliance to a 36-month bisphosphonate treatment, the 25.8% of patients are inadequate responders. Current smoking and a bone turnover in the upper part of the normal range increase the risk of treatment failure. INTRODUCTION: To evaluate the prevalence of the bisphosphonate treatment failure and its possible associated factors in women with primary osteoporosis (PO). METHODS: We studied 97 previously untreated postmenopausal women with PO and fragility fractures and/or a FRAX® 10-year probability of a major osteoporotic fracture ≥ 7.5%, before and after a 36-month treatment with alendronate or risedronate and adequate vitamin D supplementation with good compliance. At baseline and after 36 months, lumbar spine (LS) and femoral bone mineral density (BMD) were assessed by Dual X-ray absorptiometry and vertebral fractures by spinal radiographs. Spinal deformity index (SDI) was calculated. Treatment failure was defined by the presence of ≥ 2 incident fragility fractures and/or a BMD decrease greater than the least significant change. RESULTS: Bisphosphonate treatment failure was observed in 25.8% of patients. Age, body mass index, years since menopause, familiar history of hip fracture, number of falls, type of bisphosphonate used, 25-hydroxyvitamin D levels (25OHVitD), BMD, SDI, and FRAX® score at baseline were not different between responders and inadequate responders. Treatment failure was associated with current smoking (OR 3.22, 95% CI 1.10-9.50, P = 0.034) and baseline alkaline phosphatase total activity levels ≥ 66.5 U/L (OR 4.22, 95% CI 1.48-12.01, P = 0.007), regardless of age, number of falls, LS BMD, and baseline SDI. CONCLUSIONS: The 25.8 % of PO postmenopausal women inadequately responds to bisphosphonates, despite a good compliance to therapy and normal 25OHVitD levels. The current smoking and bone turnover in the upper part of the normal range are associated with the inadequate response to bisphosphonates.

Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics.

OBJECTIVE: The possible different prevalence of arterial hypertension (AH), type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and vertebral fractures (FX) between patients with bilateral and unilateral adrenal incidentalomas (BAI and UAI, respectively) with and without subclinical hypercortisolism (SH) is unknown. In this study we compared the prevalence of AH, T2DM, DL and FX in BAI and UAI patients in relation to SH. DESIGN: Prospective study. METHODS: In 175 UAI and 38 BAI patients, we evaluated BMI, spinal and femoral bone mineral density (LS and FN BMD, respectively) and the presence of AH, T2DM, DL and FX. SH was diagnosed in the presence of 2 of the following: urinary free cortisol levels >193 nmol/24 h, serum cortisol levels after 1 mg dexamethasone suppression test >83 nmol/l or ACTH levels <2.2 pmol/l. RESULTS: Age, BMI and cortisol secretion were comparable, while FN BMD was lower in BAI than in UAI patients (-0.45±0.86 vs 0.09±1.07, P=0.004). The prevalence of SH, AH, T2DM, and DL was comparable, while the prevalence of FX was higher in BAI than in UAI (52.6 vs 28%, P=0.007). The presence of FX was associated with BAI (odds ratio (OR) 2.6, 95% confidence interval (95% CI) 1.2-5.6, P=0.016), after adjusting for SH (OR 1.77, 95% CI 0.85-3.7, P=0.12), BMI (OR 1.06, 95% CI 0.98-1.13, P=0.1), age (OR 1.07, 95% CI 1.04-1.11, P=0.0001) and LS BMD (OR 1.31, 95% CI 1.03-1.67, P=0.03). CONCLUSION: BAI patients have an increased FX risk than UAI ones. Further studies should investigate the causes of bone involvement in BAI patients.

The role of salivary cortisol measured by liquid chromatography-tandem mass spectrometry in the diagnosis of subclinical hypercortisolism.

OBJECTIVE: The use of late-night salivary cortisol (LNSalC) for diagnosing subclinical hypercortisolism (SH) is debated. No data are available regarding the role of LNSalC as measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in SH diagnosis. The aim of this study was to evaluate the diagnostic accuracy of LNSalC measured by LC-MS/MS in SH. DESIGN: Cross-sectional prospective study of outpatients. METHODS: In 70 consecutive patients with adrenal incidentalomas (AI), without signs and symptoms of hypercortisolism, we diagnosed SH in the presence of at least two of the following: cortisol after 1 mg overnight dexamethasone suppression test (1  mg DST) >83  nmol/l, 24-h urinary free cortisol (UFC) >193  nmol/24  h, and morning ACTH <2.2  pmol/l. The LNSalC levels by LC-MS/MS at 2300  h (normal values <2.8  nmol/l) and the presence of hypertension, type 2 diabetes mellitus (T2DM), and osteoporosis (OP) were assessed. RESULTS: The increased LNSalC levels (>2.8  nmol/l) had an 83.3% specificity (SP) and a 31.3% sensitivity (SN) for predicting the biochemical diagnosis of SH. The increased LNSalC had an 85.2% SP and a 55.6% SN for predicting the presence of hypertension, T2DM, and OP, while the combination of LNSalC >1.4  nmol/l (cutoff with 100% SN) plus 1 mg DST >50  nmol/l had an 88.9% SN and an 85.2% SP (similar to SH criterion at enrollment). CONCLUSIONS: In AI patients, LNSalC measured by LC-MS/MS appears to be useful in combination with 1 mg DST for diagnosing SH, while it is not useful as a single criterion.

An antecedent diagnosis of refractory anemia with excess blasts has no prognostic relevance in acute myeloid leukemia of older adult patients.

BACKGROUND: Conflicting results have been reported about the prognostic relevance of antecedent myelodysplastic syndrome (MDS) in acute myeloid leukemia (AML) of older adults. PATIENTS AND METHODS: Data from 87 intensively treated AML patients (median age 69 years) were analyzed, with the aim of comparing therapeutic results and toxicity between de novo and AML secondary to a previous MDS (s-AML). Rate of CD34+ cells mobilization and feasibility of autologous stem cell transplantation (ASCT) were also compared. RESULTS: Complete remission rate, death in induction and primary resistance were not statistically different between the two groups. Median time for neutrophil recovery was similar, while s-AML patients required a longer time for platelet recovery (P = 0.04). There was no difference as to eligibility for consolidation as well as for mobilization and feasibility of ASCT. S-AML had negligible impact on overall survival (OS) and disease-free survival (DFS). In the multivariate analysis the only parameter significantly related to either OS or DFS duration was adverse karyotype (P = 0.02 and 0.04, respectively). CONCLUSIONS: A diagnosis of s-AML does not represent a clinically relevant prognostic factor in elderly AML patients treated with aggressive therapy. Furthermore, s-AML patients can be mobilized and autografted with comparable results as opposed to de novo cases.

Continuous infusion idarubicin and oral busulfan as conditioning for patients with acute myeloid leukemia aged over 60 years undergoing autologous stem cell transplantation.

There is growing interest in autologous stem cell transplantation (ASCT) for elderly patients with acute myeloid leukemia (AML). While mortality and toxicity from ASCT have been reduced, relapse rate is still high. In a prospective study, we investigated the feasibility of a new conditioning regimen consisting of high-dose idarubicin plus busulfan in AML patients aged over 60 years undergoing ASCT. A total of 14 patients (median age: 64 years) received 2 days continuous infusion of idarubicin at 20 mg/m2/day, followed by 3 days of oral busulfan (4 mg/kg/day) as conditioning. No case of transplant-related mortality occurred. The median number of days to neutrophil ( > 0.5 x 10(9)/l) and platelet ( > 20 x 10(9)/l) recovery was 11 and 12, respectively. Cardiac toxicity was absent, while 12 patients (86%) had grade 3-4 mucositis. After a median follow-up of 9 months from ASCT, nine of 14 patients are alive in continuous complete remission (CR), four have relapsed at 3, 6, 8 and 9 months, and one died in CR1 from gastric cancer. Our data demonstrate the feasibility of a conditioning regimen based on high-dose idarubicin plus busulfan in elderly AML patients. Results concerning reduction of relapse rate need confirmation in a larger series with longer follow-up.

Rituximab: a useful drug for a repeatedly relapsed hairy cell leukemia patient.

We describe a case of complete response in a patient with hairy cell leukemia, relapsed after treatment with interferon-alpha, 2'-deoxycoformicin, and 2-chlorodeoxyadenosine, and then successfully treated with rituximab. A fourfold reduction of leukemic cells was observed concomitantly with restoration of normal blood count and differential.

Vincristine as treatment for recurrent episodes of thrombotic thrombocytopenic purpura.

The clinical course of thrombotic thrombocytopenic purpura has dramatically improved after the introduction of plasma-based therapy, including plasma exchange and plasma infusion. However, a considerable number of patients still experience relapse after initial successful treatment. In this study, vincristine (VCR) was given as salvage treatment in 12 episodes of recurrent thrombotic thrombocytopenic purpura in seven patients, concomitantly with short-term plasma infusion. Complete remission (CR) was defined by normal platelet, hemoglobin, and serum lactic dehydrogenase (LDH) values as well as by absence of clinical signs. Of 12 patients, 12 achieved CR following therapy with VCR. The median duration of CR was 15 months (range: 2-16). Toxicity was mild consisting of paresthesias in three cases, leukopenia in one case, and autonomic neuropathy leading to paralytic ileus in one case. We conclude that VCR is remarkably effective for recurrent thrombotic thrombocytopenic purpura with acceptable toxicity.

Aggressive salvage treatment is not appropriate for the majority of elderly patients with acute myeloid leukemia relapsed from first complete remission.

BACKGROUND AND OBJECTIVES: The prognosis of acute myeloid leukemia (AML) in the elderly is still poor because of different reasons, including a high incidence of relapse. The aim of this study was to investigate whether aggressive salvage chemotherapy (CHT) results in an actual survival advantage in elderly patients with relapsed AML, as well as to compare hospitalization and load of supportive treatment between patients receiving aggressive management or only palliation. DESIGN AND METHODS: One hundred and fifty consecutive patients with relapsed AML (median age 66 years) were analyzed. At relapse, 99 (66%) were treated with CHT, and 51 had palliative management. RESULTS: Second complete remission (CR2) was achieved in 36/99 patients (36%) receiving CHT, while no CR was observed in the other group (p<0.001). Induction death rate was 22%, while 41% were resistant to CHT. The median survival from relapse was 4 months for the whole patient population; according to management, it was 5 months and 3 months for CHT and palliation, respectively (p=0.01). As to patients given CHT, a CR1 duration of more than 12 months was the only parameter significantly related to a better clinical outcome (survival from relapse: 8 vs. 4 months, p=0.002; CR2 duration: 11 vs. 5 months, p=0.001, respectively). Finally, patients managed with palliation required less hospitalization and less supportive therapy as compared to the CHT group. INTERPRETATION AND CONCLUSIONS: Aggressive chemotherapy results in an actual survival advantage only for a minority of elderly patients with relapsed AML, i.e. those with CR1 lasting for more than 12 months.

High-dose idarubicin and busulphan as conditioning for autologous stem cell transplantation in acute myeloid leukemia: a feasibility study.

INTRODUCTION: Between 30 and 50% of patients with acute myeloid leukemia still relapse after autologous stem cell transplantation. We investigated the feasibility of a new conditioning regimen consisting of high dose IDA plus oral busulphan in patients undergoing autologous transplantation. MATERIALS AND METHODS: Patients (n = 13) were given three days continuous infusion IDA, followed by four days conventional dose oral busulphan as conditioning. Peripheral blood stem cells were used in all cases. Eleven patients were in CR1. Patients with t(8;21) and inv(16) as well as those with acute promyelocytic leukemia were excluded from the study. The median of CD34+ cells infused was 6.2 x 10(6)/l (2.6-16.1). RESULTS: No case of transplant-related mortality occurred. The median number of days to neutrophil (>0.5 x 10(9)/l) and platelet (>20 x 10(9)/l) recovery was 10 (7-21) and 20 (9-26), respectively. Patients needed a median of 3 platelet units (1-6) and 3 blood units (0-12), respectively. Left ventricular ejection fraction remained unmodified after ASCT. Twelve out of 13 patients (92%) had variable grade of mucositis (two grade 2, five grade 3 and five grade 4). Total parenteral nutrition was needed in nine patients (69%). After a median follow-up of 14 months from ASCT, 11 patients out of 13 (85%) are alive in continuous CR; the other two patients experienced relapse at 12 and 14 months. CONCLUSION: Our data demonstrate the feasibility of a conditioning regimen based on high-dose IDA plus Busulphan in AML. Results concerning antileukemic efficacy are promising, but need confirmation on larger series with longer follow-up.

In vitro antiproliferative activity of isothiocyanates and nitriles generated by myrosinase-mediated hydrolysis of glucosinolates from seeds of cruciferous vegetables.

A comparison of the effect of isothiocyanates and nitriles derived from some glucosinolates, namely, epi-progoitrin, sinalbin, glucotropaeolin, glucocheirolin, and glucoraphenin, on human erythroleukemic in vitro cultured cells was studied. Many studies have in fact evidenced that a consumption of vegetable containing glucosinolates could reduce the development of colorectal cancer. In the experimental conditions used, the production of isothiocyanates and nitriles from glucosinolates is almost quantitative as confirmed by HPLC or GC-MS analysis. The obtained results demonstrated that in general nitriles are considerably less potent than the corresponding isothiocyanates in inhibiting cancer cell growth. Particularly, the isothiocyanates inhibitory activity on K562 cells growth is higher in the case of products derived from epi-progoitrin, glucotropaeolin, glucoraphenin, and glucocheirolin; while for nitriles the higher activity in inhibiting K562 cells growth is showed by sinalbin-derived product. Considering the antiproliferative activity found for isothiocyanates and nitriles, further studies will be aimed to the possible application of glucosinolate-derived products as chemopreventive cancer agents for the reduction of colorectal cancer.

Isolation of the epithiospecifier protein from oil-rape (Brassica napus ssp. oleifera) seed and its characterization.

The epithiospecifier protein (ESP) is a myrosinase (MYR) cofactor, which is necessary to drive the MYR-catalyzed hydrolysis of some specific glucosinolates towards the production of cyanoepithioalkanes instead of isothiocyanates and nitriles. ESP was isolated from Brassica napus seeds by anionic exchange and gel filtration chromatography. ESP showed a molecular weight of about 39 kDa and pI 5.3. The amino acid sequence of several tryptic peptides of ESP (accounting for about 50% of the total sequence) made it possible to establish the high similarity (81% identity) with a hypothetical 37 kDa protein (TrEMBL data base accession number Q39104) and several jasmonate-inducible proteins from Arabidopsis thaliana. This observation suggests that ESP is likely to be involved in jasmonate-mediated defence and disease resistance mechanisms.

A cytoskeletal localizing domain in the cyclase-associated protein, CAP/Srv2p, regulates access to a distant SH3-binding site.

In the yeast, Saccharomyces cerevisiae, adenylyl cyclase consists of a 200-kDa catalytic subunit (CYR1) and a 70-kDa subunit (CAP/SRV2). CAP/Srv2p assists the small G protein Ras to activate adenylyl cyclase. CAP also regulates the cytoskeleton through an actin sequestering activity and is directed to cortical actin patches by a proline-rich SH3-binding site (P2). In this report we analyze the role of the actin cytoskeleton in Ras/cAMP signaling. Two alleles of CAP, L16P(Srv2) and R19T (SupC), first isolated in genetic screens for mutants that attenuate cAMP levels, reduced adenylyl cyclase binding, and cortical actin patch localization. A third mutation, L27F, also failed to localize but showed no loss of either cAMP signaling or adenylyl cyclase binding. However, all three N-terminal mutations reduced CAP-CAP multimer formation and SH3 domain binding, although the SH3-binding site is about 350 amino acids away. Finally, disruption of the actin cytoskeleton with latrunculin-A did not affect the cAMP phenotypes of the hyperactive Ras2(Val19) allele. These data identify a novel region of CAP that controls access to the SH3-binding site and demonstrate that cytoskeletal localization of CAP or an intact cytoskeleton per se is not necessary for cAMP signaling.

Formation of glucoraphanin by chemoselective oxidation of natural glucoerucin: a chemoenzymatic route to sulforaphane.

A new semi-synthetic way to produce glucoraphanin (2), the bio-precursor of the potential anticarcinogen sulforaphane (3), has been developed. Starting from glucoerucin (1), isolated from ripe seeds of Eruca sativa, glucoraphanin was obtained through chemoselective oxidation. Controlled myrosinase-catalysed hydrolysis of this precursor quantitatively afforded sulforaphane.

Complete remission of refractory anemia following a single high dose of cyclophosphamide.

We describe a case of stable complete remission in a patient with refractory anemia complicated by severe autoimmune hemolytic anemia, achieved with a single high dose (4 g/m2) of cyclophosphamide (cyclo). Concomitantly, an effective mobilization of CD34-positive cells was induced. Other immunosuppressive approaches including high-dose methylprednisolone, high-dose immunoglobulin, and cyclosporine had been ineffective. This finding suggests that, in selected cases, an immunologic mechanism may mediate cytopenia in myelodysplastic syndromes (MDS). In addition, it demonstrates that successful mobilization of peripheral blood stem cells can be induced with high-dose cyclo in MDS.

Prenatal diagnosis of aortic insufficiency.

The prenatal diagnosis of various forms of left ventricular outflow tract obstruction has been reported in detail. However, the appearance and the characteristics of fetal aortic insufficiency have been described only in association with complete absence of the value. We report here a case of aortic insufficiency associated with severe aortic stenosis. Features characteristic of insufficiency were severe cardiomegaly due to left ventricle dilatation and the hypocontractility of the myocardium. The aortic root was enormously dilated and the semilunar valve showed thick and dysplastic cusps. On color Doppler, the retrograde high-velocity regurgitant jet was clearly visible.