Phase Diagram for Light-Induced Superconductivity in κ-(ET)_{2}-X.

Resonant optical excitation of certain molecular vibrations in κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Br has been shown to induce transient superconductinglike optical properties at temperatures far above equilibrium T_{c}. Here, we report experiments across the bandwidth-tuned phase diagram of this class of materials, and study the Mott insulator κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Cl and the metallic compound κ-(BEDT-TTF)_{2}Cu(NCS)_{2}. We find nonequilibrium photoinduced superconductivity only in κ-(BEDT-TTF)_{2}Cu[N(CN)_{2}]Br, indicating that the proximity to the Mott insulating phase and possibly the presence of preexisting superconducting fluctuations are prerequisites for this effect.

Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study.

BACKGROUND: A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis. PATIENTS AND METHODS: A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2-4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2-3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2-5 after chemotherapy. RESULTS: Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137 M + D. Day 1 results were similar in both arms. On day 2-5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments. CONCLUSIONS: In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity. CLINICALTRIALSGOV NUMBER: NCT00869310.

Regulation of ATP-binding cassette transporters and cholesterol efflux by glucose in primary human monocytes and murine bone marrow-derived macrophages.

Individuals with type 2 diabetes mellitus are at increased risk of developing atherosclerosis. This may be partially attributable to suppression of macrophage ATP-binding cassette (ABC) transporter mediated cholesterol efflux by sustained elevated blood glucose concentrations. 2 models were used to assess this potential relationship: human monocytes/leukocytes and murine bone marrow-derived macrophages (BMDM).10 subjects (4 F/6 M, 50-85 years, BMI 25-35 kg/m²) underwent an oral glucose challenge. Baseline and 1- and 2-h post-challenge ABC-transporter mRNA expression was determined in monocytes, leukocytes and peripheral blood mononuclear cells (PBMC). In a separate study, murine-BMDM were exposed to 5 mmol/L D-glucose (control) or additional 20 mmol/L D- or L-glucose and 25 ug/mL oxidized low density lipoprotein (oxLDL). High density lipoprotein (HDL)-mediated cholesterol efflux and ABC-transporter (ABCA1 and ABCG1) expression were determined.Baseline ABCA1and ABCG1 expression was lower (>50%) in human monocytes and PBMC than leukocytes (p<0.05). 1 h post-challenge leukocyte ABCA1 and ABCG1 expression increased by 37% and 30%, respectively (p<0.05), and began to return to baseline thereafter. There was no significant change in monocyte ABC-transporter expression. In murine BMDM, higher glucose concentrations suppressed HDL-mediated cholesterol efflux (10%; p<0.01) without significantly affecting ABCA1 and ABCG1 expression. Data demonstrate that leukocytes are not a reliable indicator of monocyte ABC-transporter expression.Human monocyte ABC-transporter gene expression was unresponsive to a glucose challenge. Correspondingly, in BMDM, hyperglycemia attenuated macrophage cholesterol efflux in the absence of altered ABC-transporter expression, suggesting that hyperglycemia, per se, suppresses cholesterol transporter activity. This glucose-related impairment in cholesterol efflux may potentially contribute to diabetes-associated atherosclerosis.

Ankle-brachial index in a type 2 diabetic population with proliferative retinopathy: associated risk factors and complications.

AIM: The aim of this study was to analyse risk factors and complications associated with low ankle-brachial index (ABI) in a type 2 diabetic population with proliferative retinopathy. METHODS: This study included 181 subjects. ABI was measured with a Doppler device. Subjects with ABI <0.9 were diagnosed with peripheral vascular disease (PVD). The exclusion criterion was medial arterial calcification. RESULTS: The mean (± SD) age and diabetes (DM) duration were 65±9.7 years and 18.6±9.1 years, respectively. ABI <0.9 was associated with increasing age (P<0.001), DM duration (P=0.02), higher total (P=0.02) and LDL cholesterol (P=0.035), higher ESR (P=0.04), uric acid (P=0.004) vibration perception thresholds (VPT), and lower eGFR (P<0.001). BMI (P<0.001), waist index (P=0.01), FPG (P=0.013), HbA1c (P=0.005) and ALT (P<0.001) were significantly lower in patients with PVD. Multivariate analysis revealed age (P=0.04), high total cholesterol (P=0.038), low BMI (P=0.017), low VPT (P=0 031) and declining eGFR (p=0.006) to be independent predictors of PVD. CONCLUSION: Increasing age, total cholesterol levels, and VPT, together with declining renal function and lower BMI are independent predictors of PVD in a type 2 diabetic population with advanced microvascular disease. Knowledge of risk factors will help target preventive measures and treatment to subjects most susceptible to PVD.

Albuminuria and glomerular filtration rate in type 2 diabetes mellitus.

AIM: The aim of this paper was to analyze the relation between glomerular filtration rate (GFR) and albumin excretion rate (AER) in subjects with type 2 diabetes. METHODS: Three hundred thirteen type 2 diabetic patients attending Diabetes Centre, Malta, were studied between 2008 and 2009. GFR was estimated using the Modified Diet Renal Disease (MDRD) formula while two spot measurements of urinary AER were used to determine albuminuria. RESULTS: Forty-nine patients were hyperfiltrating, of whom 69% were normoalbuminuric, 24% microalbuminuric, and 6% macroalbuminuric; 229 subjects had normal eGFR; of these 67% were normoalbuminuric, 27% microalbuminuric and 6% macroalbuminuric; 35 subjects had eGFR<60mL/min/1.73 m2, of whom 43% were normoalbuminuric, 37% microalbuminuric and 20% macroalbuminuric. No association was found between eGFR and AER in subjects with hyperfiltration (P=0.39); however eGFR was strongly correlated with AER in subjects with eGFR <60ml/min/1.73 m2 (r= -0.376; P=0.026). In multinomial logistic regression analysis, eGFR was significantly associated with albuminuria in non-hyperfiltrating, but not in hyperfiltrating, subjects. CONCLUSION: Our data suggests that hyperfiltration and albuminuria occur independently of each other in the early stages of DN, but the decline in eGFR and albuminuria follow a parallel course in later stages of DN suggesting that they may share common pathophysiological mechanisms or they may be causally linked.

Low efficacy of thalidomide in improving response after induction in multiple myeloma patients who are candidates for high-dose therapy.

Giving the impact of complete response (CR) on outcome of multiple myeloma patients addressed to high-dose melphalan, we explored the role of a pre-transplant intensification with 3 months thalidome plus dexamethasone therapy (Thal-Dex), after pulse-VAD induction. Seventy-four multiple myeloma patients (MM pts) uniformly treated, were retrospectively studied. The response rate after pulse-VAD were: CR 6%, VGPR 40%, PR 23%, MR 23%, and progression 8%. The response rate after Thal-Dex were similar: CR 11%, VGPR 39%, PR 17%, MR 9%, and progression 24%. Giving no advantage in terms of response rate with an additive toxicity, Thal-Dex does not seem useful for intensification before transplant.

5-year results of cisplatin-epirubicin-vinorelbine (PEV) combination as primary chemotherapy in T2-3, N0-2 breast cancer patients: a multicentre phase II study.

UNLABELLED: The aim this study was to assess the efficacy of cisplatin-epirubicin-vinorelbine, as primary chemotherapy, in reducing the tumour burden in T2-3 N0-2 breast carcinomas. Breast conservative surgery (BCS) rate, clinical and pathological complete response (pCR), toxicity and 5-year disease-free survival (DFS) and overall survival (OS) were evaluated. PATIENTS AND METHODS: Eighty-eight women with tumours > or =2.5 cm were treated with cisplatin (P) 50 mg/m2, epirubicin (E) 100 mg/m2 and vinorelbine (V) 25 mg/m2, every 3 weeks. RESULTS: Fifty-six out of the 88 patients (63.6%) underwent BCS, notably including 12/23 patients with initial tumours >5 cm. The overall clinical response was 72.8% (cCR=11.4%), pCR 20.5% and pTO+pNO 17%. No cardiac toxicity was observed. Grade 3/4 adverse events were leukopenia (9.4%), neutropenia (7.9%), nausea and vomiting (7.3%). After a median follow-up of 5 years, 24 patients (27.3%) had developed local or distant metastases. The mean DFS and OS were 51.7 (SE 2.38) and 57.02 (SE 1.98) months, respectively, and were significantly higher in pCR patients in comparison to the others (63.05 vs. 48.76, p<0.01 and 64.59 vs. 55.04, p<0.05, respectively). CONCLUSION: The PEV regimen was highly effective in reducing the tumour burden, especially for large tumours. The rate of pCR was similar to that obtained by other, including taxane-based regimens, and was well-tolerated. The study demonstrated the feasibility of such a regimen even in small centres, and being of low cost this combination could be of value in the application of primary therapy.

Familial factors in diabetic nephropathy: an offspring study.

AIMS: Familial clustering of diabetic nephropathy in patients with Type 2 diabetes suggests that inherited factors predispose to diabetic nephropathy, but the nature of these factors is uncertain. The aim of the study was to compare the prevalence of known risk factors for nephropathy in non-diabetic offspring of Type 2 diabetic patients with and without nephropathy and in control subjects. METHODS: Three groups of patients were recruited with 40 or 41 subjects in each group. These were subjects having one Type 2 diabetic parent with nephropathy (DN); subjects having one parent with Type 2 diabetes without nephropathy (DnoN), and non-diabetic unrelated control subjects with no personal or parental history of diabetes (Control subjects). RESULTS: The median (interquartile range) albumin/creatinine ratio (ACR) was 1.40 (0.96-2.90) mg/mmol in DN; 0.94 (0.50-1.46) mg/mmol in DnoN and 1.22 (0.66-1.83) mg/mmol in Controls (ANOVA: P = 0.03). ACR was higher in group DN than in DnoN (P < 0.006) and in Control subjects (P < 0.03), but there was no difference between DnoN and Control subjects. Twenty-four-hour ambulatory blood pressure monitoring showed mean daytime systolic blood pressure to be significantly higher in group DN than in DnoN (P < 0.02) or Control subjects (P < 0.01) (ANOVA: P = 0.004). Fasting insulin, HOMA-IR, interleukin-6 (IL-6) and C-reactive protein (CRP) were similar in the three groups. CONCLUSION: Our data provide further evidence that genetic factors are important in determining urinary albumin excretion and renal disease associated with Type 2 diabetes and suggest that genes that affect systemic arterial blood pressure but not those relating to insulin resistance or inflammation are likely to be implicated.

The prescription of psychotropic drugs in psychiatric residential facilities: a national survey in Italy.

OBJECTIVE: This paper reports the prescriptions of psychotropic drugs made to 2962 patients living in 265 residential facilities (RFs) in Italy. METHOD: Structured interviews were administered to RF managers and staff to obtain data on patients' sociodemographic and clinical characteristics; information about current drug prescriptions were obtained from clinical records. RESULTS: Polypharmacy was common: on average, each treated patient was taking 2.7 drugs (+/-1.1). The association of one atypical antipsychotic with one benzodiazepine represented the most common prescription profile. The variable most consistently associated with a higher likelihood of receiving polypharmacy was a history of admission to an acute general hospital psychiatric ward in the previous 12 months. Many prescriptions were loosely related to specific diagnoses. CONCLUSION: Psychotropic drug prescription patterns for severe patients living in RFs are characterized by substantial rates of polypharmacy. Specific guidelines may be helpful for long-stay patients living in RFs, who exhibit complex care needs.

Effects of apolipoprotein A-IV genotype on glucose and plasma lipoprotein levels.

The effects of apolipoprotein (apo) A-IV genotype on serum glucose, total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride and glucose concentrations were ascertained in a population of 373 men and 361 women with a mean age of about 57 years. Subjects were evaluated at entry into a lifestyle intervention program. Apolipoprotein A-IV genotype variations at residues 347 and 360 were examined, as these mutations affect the sequence of apo A-IV, a major protein constituent of intestinal triglyceride-rich lipoprotein and HDL. With regard to the apo A-IV 360 mutation, 16.4% of the females and 13.4% of the males carried the apo A-IV 2-allele, almost entirely in the heterozygous state. No effect of the apo A-IV 1/2 genotype was observed in either men or women on total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, the total cholesterol (TC)/HDL ratio, or on A-I, A-IV and apo B levels. This was also the case for the apo A-IV 347 mutation. However, women with the apo A-IV 360 1/2 genotype had significantly (p < 0.005) higher glucose levels (105.5 mg/dl) compared with the 1/1 wild-type (94.0 mg/dl). All analyses were also adjusted for age, body mass index, medications, alcohol use and cigarette smoking. The prevalence of the 347 mutation was somewhat higher than the 360 mutation, with 29% of the females and 32.0% of the males being heterozygous for this mutation, and 3.9% of the females and 5.4% of the males being homozygous for this mutation. These data are consistent with the concept that the apo A-IV 360 and 347 genotypes have no significant effect on apo A-IV levels and other lipid parameters in either gender. However, apo A-IV 360 1/2 genotype did have a significant effect on serum glucose levels in women.

Effects of apolipoprotein A-I genetic variations on plasma apolipoprotein, serum lipoprotein and glucose levels.

The present authors investigated the individual and combined associations of the apolipoprotein (apo) A-I -75 bp and +83 bp polymorphisms with plasma lipid, lipoprotein and apolipoprotein levels in 734 Caucasian men and women. The frequency of the A allele at position -75 bp (G-->A) was 0.14 in women and 0.17 in men. The frequencies for the rare M2 allele at position +83 bp and/or 84 bp (C-->T and G-->A, respectively) were 0.04 and 0.05 in women and men, respectively. In women, the A allele was associated with significantly higher levels of apo B (P = 0.016), total cholesterol (TC) (P = 0.005), low-density lipoprotein cholesterol (LDL-C) (P = 0.018) and TC:high-density lipoprotein (HDL) ratio (P = 0.026) compared to the G/G subjects. In men, no significant associations were detected between the -75 bp polymorphism and any lipid trait examined. The M2 allele for the +83 bp polymorphism was significantly associated in men with higher levels of apo A-I (P = 0.002) and TC (P = 0.046). In women, a significant effect was observed for TC (P = 0.036), with M2+/- subjects having lower levels than M2+/+ subjects. Significant linkage disequilibrium (P = 0.037) between the apo A-I -75 bp and +83 bp polymorphisms was detected. Women carrying both rare alleles (G/A M2+/-) had significantly higher TC:HDL ratios (P = 0.031) compared to the other haplotypes. In men, significant differences were observed for apo A-I (P = 0.021) and TC (P = 0.044), with carriers of the G/G M2+/- haplotype having the highest values compared to other genotype combinations. In conclusion, the -75 bp (G/A) polymorphism appears to have a significant effect on levels of apo B, plasma TC and LDL-C in women, while the +83 bp polymorphism seems to affect the apo A-I levels in men, and the plasma cholesterol levels in both genders.

Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a rare recessive autosomal disease caused by mutations of the sterol 27-hydroxylase gene. Clinically, CTX is characterized by tendon xanthomas, cataracts and progressive neurological deficits. Because of the disruption of the 27-hydroxylase activity, CTX patients have elevated plasma levels of cholestanol, a by-product of abnormal bile acid synthesis. The present authors describe a female patient with CTX. The proband in this study presented with elevated cholestanol levels, markedly reduced mitochondrial 27-hydroxylase activity and altered bile acid composition. The 27-hydroxylase gene was analysed for mutations by polymerase chain reaction amplification of the exons and the splice-junction regions of the gene. The proband was found to be a compound heterozygote for two different mutations which have not been previously described: (1) a G --> A transition at nucleotide 455 that is responsible for converting a glycine to a glutamic acid residue at amino acid position 112 (G112E); and (2) a five-nucleotide deletion in exon 5 (from nucleotide 965 to 969) that is responsible for a shift in the reading frame and the insertion of a premature codon at position 296, and consequently, the synthesis of a truncated protein lacking the heme-binding and andrenodoxin-binding domains. Long-term (18-year) treatment of the proband with chenodeoxycholic acid (750 mg day-1) has been effective in preventing any progression of the disease.

Adjuvant chemotherapy in gastric cancer: 5-year results of a randomised study by the Italian Trials in Medical Oncology (ITMO) Group.

BACKGROUND: The aim of this study was to determine the efficacy of the EAP regimen (etoposide, adriamycin and cisplatin) followed by the Machover schedule (fluorouracil and folinic acid) given as adjuvant treatment to patients with poor prognostic factors (N+ or T3/4). PATIENTS AND METHODS: Before randomisation, the subjects were stratified on the basis of node involvement (N+ or N-) and the time from surgery to randomisation (< or = 21 days or > 22 days). The surgical procedures for sub-total or total gastrectomy with D2 dissection were standardised among the participating centres. RESULTS: Between December 1992 and December 1997, 274 patients were enrolled: 137 in the treatment arm and 137 in the control arm. The majority of the patients (90%) were N+. After a median follow up of 66 months (range 2-83), the 5-year overall survival (OS) was 52% in the treatment arm and 48% in the control arm [hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.65-1.34]; the 5-year disease-free survival (DFS) was 49% and 44%, respectively (HR: 0.83; 95% CI 0.59-1.17). Among the patients with N-/N+ (1-6), the 5-year OS was 61% in the treatment group and 60% in the control group; in those with N+ (1-6), it was 42% and 22%. The treatment was completed by 87% of patients. Drug-related grade 3/4 WHO toxicities included leukopenia (21%), nausea and vomiting (14%), mucositis (9%), neutropenia (3%) and thrombocytopenia (2%). There were two deaths due to sepsis. CONCLUSIONS: Although our results are not statistically significant, there was a limited relative risk reduction in the patients receiving adjuvant therapy (17% in DFS and 7% in OS). The data suggest that D2 surgery may have a favourable impact on OS.

ACE gene polymorphism as a prognostic indicator in patients with type 2 diabetes and established renal disease.

OBJECTIVE: To investigate whether the DD genotype is a predictor of mortality and of the decline in renal function in patients with type 2 diabetes and established nephropathy. RESEARCH DESIGN AND METHODS: A total of 56 such patients of Maltese Caucasian descent were recruited, and their ACE genotype was determined. Serum creatinine was estimated approximately every 4 months. The glomerular filtration rate (GFR) was calculated according to the Cockroft-Gault formula, and rate of change was determined by regression analysis. RESULTS: The rate of change in calculated GFR was -7.76 ml.min(-1).year(-1) in those with the DD genotype (n = 31) and -1.17 ml. min(-1). h(-1) in those with the ID or II genotype (n = 25) (P < 0.01). The 3-year mortality was 45.2% in the DD group compared with 20.0% in the ID/II group (P < 0.05). CONCLUSIONS: The DD genotype of the ACE gene polymorphism is associated with a more rapid decline in renal function and higher mortality in type 2 diabetic patients with established nephropathy.

A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01).

Sequential administration of the association of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel could be better tolerated than the association of an anthracycline and paclitaxel while having a similar antitumour effect. 69 patients with advanced breast cancer previously untreated with anthracyclines or paclitaxel entered a phase II multicentre study in which FEC was followed by paclitaxel. Both regimens were administered 4 times every 21 days. The median follow-up is 20 months and 38/69 patients have died. Grade III-IV toxicity was acceptable. Leukopenia occurred in 26% of patients, thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred in 9% and 4% of patients, respectively and one patient had respiratory hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy because of: treatment refusal (n = 1), cardiac toxicity (n = 1), early death during FEC chemotherapy (n = 1), major protocol violations (n = 4), hypersensitivity reaction (n = 1) and early death during paclitaxel chemotherapy (n = 1). The overall response rate was 65% (95% CI = 53-76), and 7% of patients had stable disease. Therapy was defined as having failed in 28% of patients because they were not evaluable (13%) or had progressive disease (15%). The median time to progression and survival are 13.2 and 23.5 months, respectively. Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic breast cancer who have not been previously treated with anthracyclines and/or taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour effect.

Sequential docetaxel and vinorelbine for patients with advanced breast cancer previously treated with anthracyclines: a phase II study.

With respect to their association, sequential non-cross-resistant cytostatics could be better tolerated and allow a similar antitumor effect. From January, 1998 to July, 1999, 42 consecutive patients with metastatic breast cancer (MBC) previously treated with anthracyclines as adjuvant- or first-line therapy entered a phase II multicenter study where docetaxel (TXT, 100 mg/m2/3 weeks/4 times) was followed by vinorelbine (VNR, 25 mg/m2/10 days/8 times). Median follow-up is 21 months and 22/42 patients have died. Four patients did not complete therapy due to early death, grade 3-4 gastrointestinal mucosytis (2 patients) and grade 3 neurotoxicity during TXT therapy. Overall response rate was 57%, and 5% of patients had stable disease. There were 38% of therapy failures due to non-evaluability (10%) or progressive disease (28%). Median time to progression and survival are 10.1 and 17.1 months. Sequential TXT-VNB is a suitable strategy for MBC patients previously treated with anthracyclines. It avoids haematologic toxicity and allows a good antitumor effect. Careful monitoring of intestinal mucosytis is required.

Adult height and proteinuria in type 2 diabetes.

BACKGROUND: Short stature has been shown to be associated with proteinuria in type 1 diabetes, but no data exist with respect to type 2 diabetes. The objective of the study was to investigate the relationship between final adult height and macroproteinuria in type 2 diabetic patients. METHODS: One hundred and forty-four consecutive type 2 diabetic patients (84 males, 60 females) with macroproteinuria were recruited into the study. For every patient, three diabetic controls matched for age, gender, and duration of diabetes were randomly selected. Height was measured in patients and controls to the nearest 0.5 cm. RESULTS: The mean height in men with macroproteinuria (n = 84) was 164.4 cm (SD 6.74) compared to 166.6 cm (SD 6.64) in controls (n = 252) (P < 0.01). The mean height in women with macroproteinuria (n = 60) was 150.6 cm (SD 5.20) compared to 152.5 cm (SD 5.78) in controls (n = 180) (P < 0.02). CONCLUSION: Short stature is associated with an increased risk of macroproteinuria in type 2 diabetic patients. We postulate that common genetic or environmental factors that affect final adult height might also predispose to the development of nephropathy.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) is an effective regimen for peripheral blood stem cell collection in multiple myeloma.

DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) has proved to be an effective salvage therapy for refractory-relapsed MM patients. Little is known, however, about its potential as mobilizing therapy. The aim of this study was to evaluate the efficacy of DCEP in mobilizing PBSC and to define its toxicity. Fifty-five MM patients received DCEP followed by G-CSF as part of high-dose programs including autologous transplantation. At the time of mobilization, 40 patients had previously received VAD only, and 15 alkylating agents. Mobilization was successful (minimum number of CD34(+) cells 2 x 10(6)/kg) in 48/55 patients (87%), and 41/55 patients (75%) collected >4 x 10(6)/kg CD34(+) cells. Of the seven patients who did not mobilize stem cells, five (71%) had been previously exposed to alkylating agents. The median number of CD34(+) cells harvested was 5.8 x 10(6)/kg (range 2.1-22.4). There was no treatment-related mortality. The side-effects of DCEP were always tolerable. No neutropenia <1000/microl nor thrombocytopenia <50,000/microl were observed. No patient required transfusion as a consequence of therapy, or hospitalization for septic complications. In conclusion, DCEP, in addition to its demonstrated anti-tumor activity, is an effective regimen for mobilizing peripheral blood progenitor cells in myeloma patients, with little or no side-effects. These properties render DCEP a useful regimen for the debulking and mobilization phase of high-dose programs for multiple myeloma.

Complete and selective estrogenic effects on lipids and cardiovascular disease.

Observational studies have shown a protective effect of estrogen replacement on risk of cardiovascular disease in postmenopausal women. The estrogen protection is thought to be mediated by mechanisms acting at different levels, including a beneficial effect on plasma lipid concentrations. Selective estrogen receptor modulators (SERM) share with estrogen the ability to reduce plasma levels of atherogenic lipoproteins like low-density lipoproteins and lipoprotein(a). The recent publication of the first randomized, placebo-controlled trial of estrogen/progestin replacement (HERS), which failed to show a reduced number of cardiovascular events in women randomized to estrogen treatment as compared with placebo, has cast some doubts on the protective role of estrogen. Other large randomized studies on the effect of estrogen and other compounds with estrogenic activity (eg, SERM) on cardiovascular disease risk are currently underway and will provide more definite answers to both clinicians and postmenopausal women.