Thyroid profile during the alternative Sunitinib dosing 2/1 schedule in metastatic renal cell carcinoma.

PURPOSE: Hypothyroidism is a common side effect of Sunitinib (SUN) treatment in metastatic renal cell carcinoma (mRCC) patients. We aimed to evaluate thyroid profile during the alternative 2/1 SUN treatment schedule and to assess the predictive value of hypothyroidism in terms of survival. METHODS: We performed a prospective observational study enrolling 42 consecutive mRCC patients starting first-line alternative SUN dosing 2/1 schedule. Thyroid function was assessed at baseline and during the first three SUN cycles (1 cycle = 6 weeks = 2 ON/1 OFF + 2 ON/1 OFF), and then after 6 and 12 months. Thyroid ultrasound was performed at baseline and after 3, 6, and 12 months. RESULTS: Subclinical hypothyroidism developed in 24% of patients during the first cycle; in other 24% in the second cycle and in 14% in the third cycle. The highest TSH values were reached during the second cycle, ON phase (6.58 ± 5.74 µI U/l). We observed a reduction in thyroid size, in echogenicity and in parenchymal perfusion in all patients. Progression-free survival (PFS) tended to be longer in patients with TSH ≥ 5 µI U/ml during the second cycle (p = 0.069). TSH level was an independent risk factor for PFS in men (p = 0.009) but not in women (p = 0.285). CONCLUSIONS: This is the first study investigating functional and morphological effects on thyroid during the alternative 2/1 SUN schedule in mRCC patients. We detected an early onset of subclinical hypothyroidism, observing the association between TSH ≥ 5 µI U/ml and: (i) longer PFS in men; (ii) progressive decrease of thyroid size in absence of significant changes in autoimmune thyroid profile.

Combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy.

Introduction: With repeated courses of chemotherapy, chemotherapy-induced nausea and vomiting (CINV) becomes progressively more difficult to control. The aim of this study was to evaluate whether the antiemetic efficacy of the triple combination aprepitant, palonosetron and dexamethasone could be sustained for up to six cycles of highly emetogenic chemotherapy (HEC) (cisplatin ≥ 50 mg/m(2) ). Methods: Chemotherapy-naive patients receiving cisplatin-based HEC, were treated with palonosetron 0.25 mg/i.v., dexamethasone 20 mg/i.v. and aprepitant 125 mg/p.o. 1 h before chemotherapy. Aprepitant 80 mg/p.o. and dexamethasone 4 mg/p.o. were administered on days 2-3. The primary endpoint was complete response (CR, no vomiting and no use of rescue medication), over 5 days following HEC in up to six cycles. Secondary endpoints were emesis-free and nausea-free rates. Safety was also evaluated. Results: One hundred and fifty six lung cancer patients were included in the study; the median age was 64 years and 76.9% were men. The minimum cisplatin dosage was 75 mg/m(2) , and in most patients was combined with another drug (87.4%). CR ranged from 74.4% (first cycle) to 82% (sixth cycle). More than 90% and 60% of patients were emesis-free and nausea-free during all chemotherapy cycles. The most commonly reported side effects were constipation and headache. Conclusions: The triple combination of aprepitant, palonosetron and dexamethasone enhanced not only the antiemetic protection during the first cycle, but its efficacy was also sustained for up to six cycles of cisplatin-based HEC in lung cancer patients.

Ultrastructure of the male reproductive accessory glands in the medfly Ceratitis capitata (Diptera: Tephritidae) and preliminary characterization of their secretions.

The morphology and the ultrastructure of the male accessory glands and ejaculatory duct of Ceratitis capitata were investigated. There are two types of glands in the reproductive apparatus. The first is a pair of long, mesoderm-derived tubules with binucleate, microvillate secretory cells, which contain smooth endoplasmic reticulum and, in the sexually mature males, enlarged polymorphic mitochondria. The narrow lumen of the gland is filled with dense or sometimes granulated secretion, containing lipids. The second type consists of short ectoderm-derived glands, finger-like or claviform shaped. Despite the different shape of these glands, after a cycle of maturation, their epithelial cells share a large subcuticular cavity filled with electron-transparent secretion. The ejaculatory duct, lined by cuticle, has epithelial cells with a limited involvement in secretory activity. Electrophoretic analysis of accessory gland secretion reveals different protein profiles for long tubular and short glands with bands of 16 and 10kDa in both types of glands. We demonstrate that a large amount of accessory gland secretion is depleted from the glands after 30min of copulation.

Structural organization of the copulation site in the medfly Ceratitis capitata (Diptera: Tephritidae) and observations on sperm transfer and storage.

The copulation site of the medfly Ceratitis capitata was investigated at anatomical and ultrastructural levels. It consists of the anterior vagina, with a ventral fertilization chamber and a dorsal insemination pocket into which the two spermathecal ducts open. The fertilization chamber is an organ comprised of a number of alveoli that in virgin females are filled with a filamentous secretion, whereas in mated females contain sperm bundles. Through study of the internal morphology of the aedeagus, its position in the anterior vagina, and the direct observation of sperm transfer and storage, we confirmed that sperm are ejaculated through two gonopores at the top of the distiphallus and another at the base of the genital rod. The sperm flow dorsally into the insemination pocket and ventrally into the fertilization chamber. During copulation, the two spermathecae and the fertilization chamber are progressively filled with spermatozoa.

Preliminary results of nuclear magnetic resonance studies of healthy human saliva.

Relaxation times T1 and T2 of water protons for stimulated and unstimulated parotid and submandibular saliva from healthy patients were measured in the conventional way using the Bruker PC 20 Minispec. Some measurements of dispersion were also carried out. An interpretation of the average values for T1 and T2 observed in the 20 MHz range is proposed for these types of saliva in relation to biochemical composition (total proteins, amylase activity, sialic acids and hexosamins) and viscosity. For parotid saliva T2(-1)-T1(-1) correlates significantly with amylase activity. In the submandibular saliva T2(-1)-T1(-1) correlates significantly with both mucins and alpha-amylase activity.

Proton NMR-relaxation dispersion in meconium solutions and healthy amniotic fluid: possible applications to medical diagnosis.

In order to show that for a possible application in medical diagnosis NMR-relaxation experiments at low Larmor frequencies (v0 less than or equal to 20 kHz) are more sensitive than the up to now done high field measurements in the MHz-range, we present dispersion curves (v0 = 50 Hz to 50 MHz) of the proton longitudinal relaxation time T1 and values of the transversal relaxation time T2 for the example of amniotic fluids. Only for Larmor frequencies below congruent to 100 kHz the relaxation times for healthy amniotic fluid and pathological meconium solutions are significantly different, whereas at high Larmor frequencies, i.e. in the conventional MHz-range, the observed changes are rather small.

Estimating meconium (fetal feces) concentration in human amniotic fluid by nuclear magnetic resonance.

Measurements are reported of NMR relaxation times (T2) on hydrogen in water of isotonic NaCl solutions and of normal human amniotic fluid in which known concentrations of meconium (fetal feces) were dissolved. Magnetic fields for resonance of 23.5 X 10(3) and 0.6 oersteds were used. From the measured T2 values, reliable estimates of meconium concentrations could be obtained that might be considered estimates of fetal distress. Observed minor variation of T2 values was probably due to the mucopolysaccharides comprising 80% of the meconium weight. Advantages of this technique for possible clinical use in obstetrics include small volume of sample required (0.1 ml), lack of necessity for sample filtration or centrifugation, and shortness of time required for analysis (less than 30 min).

Low field topical nuclear magnetism apparatus in a hospital area.

We describe the technique and the measure of the relaxation time T2 for the free precession of protons in the earth field. In vitro and in vivo experiments on human physiological fluids, including blood coagulation, are reported. We put forward the evident interest of this technique to study the meconium in the amniotic liquid and small quantities of oscite observed in situ.

[Diagnosis of the presence of meconium in amniotic fluid by dispersion curves of the longitudinal relaxations of protons]. / Diagnostic de la présence de méconium dans le liquide amniotique par dispersion de la relaxation longitudinale des protons.

Dispersion curves of the longitudinal relaxation T1 of protons in healthy amniotic fluid in a meconium solution are distinct at low Larmor frequencies (V0 less than 100 kHz). We are thus able to distinguish these fluids by T1 measurements in this range.