Point of Care Ultrasound to Identify Diaphragmatic Dysfunction after Thoracic Surgery.

BACKGROUND: Postoperative diaphragmatic dysfunction after thoracic surgery is underestimated due to the lack of reproducible bedside diagnostic methods. We used point of care ultrasound to assess diaphragmatic function bedside in patients undergoing video-assisted thoracoscopic or thoracotomic lung resection. Our main hypothesis was that the thoracoscopic approach may be associated with lower incidence of postoperative diaphragm dysfunction as compared to thoracotomy. Furthermore, we assessed the association between postoperative diaphragmatic dysfunction and postoperative pulmonary complications. METHODS: This was a prospective observational cohort study. Two cohorts of patients were evaluated: those undergoing video-assisted thoracoscopic surgery versus those undergoing thoracotomy. Diaphragmatic dysfunction was defined as a diaphragmatic excursion less than 10 mm. The ultrasound evaluations were carried out before (preoperative) and after (i.e., 2 h and 24 h postoperatively) surgery. The occurrence of postoperative pulmonary complications was assessed up to 7 days after surgery. RESULTS: Among the 75 patients enrolled, the incidence of postoperative diaphragmatic dysfunction at 24 h was higher in the thoracotomy group as compared to video-assisted thoracoscopic surgery group (29 of 35, 83% vs. 22 of 40, 55%, respectively; odds ratio = 3.95 [95% CI, 1.5 to 10.3]; P = 0.005). Patients with diaphragmatic dysfunction on the first day after surgery had higher percentage of postoperative pulmonary complications (odds ratio = 5.5 [95% CI, 1.9 to 16.3]; P = 0.001). Radiologically assessed atelectasis was 46% (16 of 35) in the thoracotomy group versus 13% (5 of 40) in the video-assisted thoracoscopic surgery group (P = 0.040). Univariate logistic regression analysis indicated postoperative diaphragmatic dysfunction as a risk factor for postoperative pulmonary complications (odds ratio = 5.5 [95% CI, 1.9 to 16.3]; P = 0.002). CONCLUSIONS: Point of care ultrasound can be used to evaluate postoperative diaphragmatic function. On the first postoperative day, diaphragmatic dysfunction was less common after video-assisted than after the thoracotomic surgery and is associated with postoperative pulmonary complications.

The effect of plant sterol-enriched turkey meat on cholesterol bio-accessibility during in vitro digestion and Caco-2 cell uptake.

This study evaluated the effect of a plant sterol-enriched turkey product on cholesterol bio-accessibility during in vitro digestion and cholesterol uptake by Caco-2 monolayers. Turkey products, one plant sterol-enriched (PS) and one plant sterol-free (C), were produced in an industrial pilot plant. Before simulated digestion, matrices were spiked with cholesterol (1:5 weight ratio of cholesterol to plant sterol). Plant sterols were included at a concentration equivalent to the minimum daily intake recommended by the European Food Safety Authority (EFSA) for cholesterol lowering. After simulated digestion, the percentage of cholesterol micellarization and uptake by Caco-2 cells in the presence of PS meat were measured. Compared to C meat, PS meat significantly inhibited cholesterol micellarization on average by 24% and Caco-2 cell accumulation by 10%. This study suggests that plant sterols in meat can reduce cholesterol uptake by intestinal epithelia and it encourages efforts to make new PS-based functional foods.

Effect of growth factors and steroid hormones on heme oxygenase and cyclin D1 expression in primary astroglial cell cultures.

Astrocyte activity may be modulated by steroid hormones and GFs. This study investigates the interaction between glucocorticoids or estrogens and GFs on the expression of heme oxygenase-1 (HO-1) and cyclin D1 in astrocyte cultures at 14 days treated for 48 or 60 hr with dexamethasone (DEX) or 48 hr with 17ß-estradiol (E2) alone or with GFs added only in the last 12 or 24 hr. Twelve- or twenty-four-hour epidermal growth factor (EGF) treatment significantly enhanced HO-1 expression in astrocyte cultures pretreated for 48 hr with DEX. A highly significant increase in HO-1 expression was obtained after the last-12-hr EGF treatment in 48-hr E2-pretreated astrocyte cultures; this enhancement was particularly significant in 48-hr E2-pretreated cultures as well as in the last-12-hr insulin-treated ones pretreated for 48 hr with E2. Sixty-hour DEX-alone pretreatment as well as the last-12-hr EGF treatment in 60-hr DEX-pretreated astrocyte cultures showed a significant increase of cyclin D1 expression. A significant decrease of cyclin D1 expression in the last-12-hr insulin-like growth factor-I (IGF-1)-treated cultures pretreated for 60 hr with DEX was observed. A highly significant enhancement in cyclin D1 expression in 14 days in vitro astrocyte cultures pretreated with E2 alone for 48 hr and treated in the last 12 hr with IGF-1 in 48-hr E2-pretreated cultures was found. Finally, the data highlight an interactive dialogue between the growth factors and glucocorticoids or estrogens during the maturation of astroglial cells in culture that may control the HO-1 and cyclin D1 expression as well as proliferating astroglial cells during the cell cycle.

Effect of lipoic acid and α-glyceryl-phosphoryl-choline on astroglial cell proliferation and differentiation in primary culture.

Lipoic acid plays a crucial role as antioxidant and metabolic component of enzymes involved in glucose metabolism of different cell types. Choline alphoscerate (α-glyceryl-phosphoryl-choline [αGPC]) is a semisynthetic derivative of phosphatidylcholines representing, among acetilcholine precursors, a cholinergic drug. In the present study, we evaluated the expression of some proliferation and differentiation markers in 15 or 21 DIV astrocyte cultures treated with 50 µM (+)lipoic acid or (+/-)lipoic acid and/or 10 mM αGPC for 24 hr. In addition, we evaluated the possible genoprotective effect by analysis of DNA status detected by alkaline comet assay. The addition of single drugs [(+)lipoic acid, (+/-)lipoic acid, or αGPC] induced an "upward modulation" of the expression of biomarkers used in our study. On the contrary, the cotreatment with either (+)lipoic acid + αGPC or (+/-)lipoic + αGPC surprisingly showed no significant modification or even a downregulation of the above-mentioned biomarkers. This latter finding demonstrated no additional effect after the cotreatment with both drugs with respect to the single treatments alone. Further studies are necessary to clarify the specific mechanism evoked by the processing of these neuroprotective agents in our in vitro models. Finally, these preliminary findings may represent a good tool with which to clarify the antioxidant and metabolic roles played by lipoic acid in proliferating and differentiating astroglial cell cultures, during an interactive cross-talk between glial and neuronal cells, after brain lesions or damage correlated with oxidative stress that may occur in some degenerative diseases.

Methodological pipeline for monitoring post-harvest quality of leafy vegetables.

Plants are primary source of nutrients for humans. However, the nutritional value of vegetables tends to decrease once organ and tissue sinks are detached from the plant. Minimal processing of leafy vegetables involves cutting and washing before packaging and storage. These processing procedures result in stressful conditions and post-harvest disorders senescence-related can also occur. The aim of this work is to define a methodological pipeline to evaluate the "quality" changes of fresh cut leafy vegetables over their shelf-life. At this purpose, intra-species variability has been investigated considering two varieties of Lactuca sativa (var. longifolia and capitata), showing different susceptibility to browning. Since browning mainly depends on phenol oxidation, redox parameters as well as the activity of the enzymes involved in phenol biosynthesis and oxidation have been monitored over storage time. At the same time, the metabolic changes of the lettuce leaves have been estimated as response patterns to chemical sensors. The obtained sensor outputs were predictive of browning-related biological features in a cultivar-dependent manner. The integration of the results obtained by this multivariate methodological approach allowed the identification of the most appropriate quality markers in lettuce leaves from different varieties. This methodological pipeline is proposed for the identification and subsequent monitoring of post-harvest quality of leafy vegetables.

Absorbed dose evaluation of a blood irradiator with alanine, TLD-100 and ionization chamber.

Irradiation of blood bags using X-ray irradiators and dosimetry services are required to ensure uniform dose levels in the range 25-50 Gy to prevent Transfusion Associated Graft versus Host Disease (TA-GvHD). An absorbed dose characterization of a Raycell MK2 X-Irradiator was performed using three different dosimetric systems. Results showed a dosimetric accuracy of the ionization chamber together with the Alanine dosimeter. TLDs measurements exhibited a small overestimation by 4% of the absorbed dose. The Dose Uniformity Ratio (DUR), between maximum and minimum dose levels in the canister, was in good agreement with the manufacturer specifications (≤1.5).

Principles and philosophies for speech and language therapists working with people with primary progressive aphasia: an international expert consensus.

PURPOSE: Primary progressive aphasia (PPA) is a language-led dementia associated with Alzheimer's pathology and fronto-temporal lobar degeneration. Multiple tailored speech and language interventions have been developed for people with PPA. Speech and language therapists/speech-language pathologists (SLT/Ps) report lacking confidence in identifying the most pertinent interventions options relevant to their clients living with PPA during their illness trajectory. MATERIALS AND METHODS: The aim of this study was to establish a consensus amongst 15 clinical-academic SLT/Ps on best practice in selection and delivery of speech and language therapy interventions for people with PPA. An online nominal group technique (NGT) and consequent focus group session were held. NGT rankings were aggregated and focus groups video recorded, transcribed, and reflexive thematic analysis undertaken. RESULTS: The results of the NGT identified 17 items. Two main themes and seven further subthemes were identified in the focus groups. The main themes comprised (1) philosophy of person-centredness and (2) complexity. The seven subthemes were knowing people deeply, preventing disasters, practical issues, professional development, connectedness, barriers and limitations, and peer support and mentoring towards a shared understanding. CONCLUSIONS: This study describes the philosophy of expert practice and outlines a set of best practice principles when working with people with PPA.Implications for rehabilitationPrimary progressive aphasia (PPA) describes a group of language led dementias which deteriorate inexorably over time.Providing speech and language therapy for people with PPA is complex and must be person centred and bespoke.This study describes the philosophy of expert practice and outlines a set of best practice principles for speech and language therapists/pathologists working with people with people with PPA.

Cholinergic precursors modulate the expression of heme oxigenase-1, p21 during astroglial cell proliferation and differentiation in culture.

Heme oxygenase-1 (HO-1) plays a crucial role in oxidative stress processes, apoptosis and cell differentiation. Further, some proteins related to cell cycle including cyclins and p21 are important markers of astrocyte cultures. Aim of investigation was to study the effects of cholinergic precursors (choline, CDP-choline, Acetylcholine and α-Glyceril-Phosphorylcholine) on HO-1 and p21 expression during astroglial cell proliferation and differentiation in primary cultures at 14 and 35 days in vitro (DIV) treated for 24 h with choline metabolites. Our results showed a slight reduction of HO-1 expression (data not statistical significant) in astroglial cell cultures treated with CDP-choline at 14 DIV and 35 DIV. On the contrary, ACh and choline induced a significant increase of HO-1 expression in 14 DIV astrocyte cultures. Surprisingly, choline and ACh dramatically reduced HO-1 expression at 35 DIV. A slight decrease not statistical significant was detectable for α-GPC at 14 DIV and particularly significant at 35 DIV. Data concerning p21 expression, a well known protein inhibiting cell cycle, evidenced a significant increase at 14 and 35 DIV after α-GPC treatment. CDP-choline treatment caused a high increase of p21 expression in 14 DIV astrocyte cultures, but no modification at 35 DIV. Instead, ACh treatment induced a marked increment of p21 expression at 35 DIV. Our data suggest that cholinergic precursors modulate HO-1 and p21 expression during astroglial cell proliferation and differentiation in culture and could be considered a tool to study the induced effects of ischemia and hypoxia diseases in some in vitro models to prevent and reduce its effects after treatment with cholinergic drugs.

Bye-bye chiro-inositol - myo-inositol: true progress in the treatment of polycystic ovary syndrome and ovulation induction.

Polycystic ovary syndrome (PCOS) is a multifactorial syndrome affecting 10% of women in reproductive age. Insulin sensitizer agents are the best therapeutic option for PCOS patients; among which there is Inositol. Inositol is a polyalcohol existing as nine different stereoisomers, two of which have been shown to be insulin mediators: myo-inositol (MI) and D-chiro-inositol (DCI). So far only MI have been show to be present in the follicular fluid and in a direct comparison between MI and DCI only MI was able to improve oocyte and embryo quality. Therefore, Could we say "bye-bye D-chiro-Inositol" in the practice of clinical gynecology and reproductive medicine?

Comparison of CPAP and oxygen therapy for treatment of postoperative hypoxaemia in dogs.

OBJECTIVE: To compare 5 cmH2 O of continuous positive airway pressure with oxygen therapy in dogs recovering from general anaesthesia with low SpO2 values. continuous positive airway pressure is more effective than oxygen therapy in restoring normoxaemia (SpO2 ≥95%). MATERIALS AND METHODS: Prospectively, dogs recovering from anaesthesia, with SpO2 <95% after extubation (T0), were randomised and treated with continuous positive airway pressure (FiO2 0.21) or oxygen (O2 ; FiO2 0.35-0.40) therapy. Dogs were monitored with SpO2 every 15 minutes for 1 hour (T15, T30, T45, T60). Data from normoxaemic dogs (SpO2 >95%) were used as control (CTR). RESULTS: Of the 42 dogs enrolled, 34 completed the study. Eleven dogs were treated with O2 , 10 with continuous positive airway pressure and 13 were CTR. The SpO2 values at T0 were similar in the continuous positive airway pressure and O2 groups and were lower than in the CTR group. At T15, T30, T45 and T60, the SpO2 values in the continuous positive airway pressure group were higher than at T0; these were similar to those of the CTR group at the same time-points. In the O2 group, SpO2 values were significantly higher at T45 and T60 than at T0; 45.5% of dogs became normoxaemic at T45 and the remaining dogs became normoxaemic at T60. The average time to reach normoxaemia in the O2 group (53.1±7.3 minutes) was longer than in the continuous positive airway pressure group (15.0±0.0 minutes). CLINICAL SIGNIFICANCE: In dogs recovering from general anaesthesia with pulmonary gas exchange impairment, normoxaemia is restored more effectively and rapidly by using continuous positive airway pressure than by oxygen therapy.

Alpha-lipoic acid modulates GFAP, vimentin, nestin, cyclin D1 and MAP-kinase expression in astroglial cell cultures.

In the present study, we evaluated the expression of some proliferation and differentiation markers in 15 DIV astrocyte cultures pretreated or not with 0.5 mM glutamate for 24 h and than maintained under chronic or acute treatment with 50 µM R(+)enantiomer or raceme alpha-lipoic acid (ALA). GFAP expression significantly increased after (R+)enantiomer acute-treatment and also in glutamate-pretreated ones. Vimentin expression increased after R(+)enantiomer acute-treatment, but it decreased after raceme acute-treatment. Nestin expression drastically increased after acute raceme-treatment in glutamate-pretreated or not cultures, but significantly decreased after (R+)enantiomer acute and chronic-treatments. Cyclin D1 expression increased in raceme acute-treated cultures pretreated with glutamate. MAP-kinase expression slightly increased after (R+)enantiomer acute treatment in glutamate-pretreated or unpretreated ones. These preliminary findings may better clarify antioxidant and metabolic role played by ALA in proliferating and differentiating astrocyte cultures suggesting an interactive cross-talk between glial and neuronal cells, after brain lesions or damages.

MR-based artificial intelligence model to assess response to therapy in locally advanced rectal cancer.

PURPOSE: To develop and validate an Artificial Intelligence (AI) model based on texture analysis of high-resolution T2 weighted MR images able 1) to predict pathologic Complete Response (CR) and 2) to identify non-responders (NR) among patients with locally-advanced rectal cancer (LARC) after receiving neoadjuvant chemoradiotherapy (CRT). METHOD: Fifty-five consecutive patients with LARC were retrospectively enrolled in this study. Patients underwent 3 T Magnetic Resonance Imaging (MRI) acquiring T2-weighted images before, during and after CRT. All patients underwent complete surgical resection and histopathology was the gold standard. Textural features were automatically extracted using an open-source software. A sub-set of statistically significant textural features was selected and two AI models were built by training a Random Forest (RF) classifier on 28 patients (training cohort). Model performances were estimated on 27 patients (validation cohort) using a ROC curve and a decision curve analysis. RESULTS: Sixteen of 55 patients achieved CR. The AI model for CR classification showed good discrimination power with mean area under the receiver operating curve (AUC) of 0.86 (95% CI: 0.70, 0.94) in the validation cohort. The discriminatory power for the NR classification showed a mean AUC of 0.83 (95% CI: 0.71,0.92). Decision curve analysis confirmed higher net patient benefit when using AI models compared to standard-of-care. CONCLUSIONS: AI models based on textural features of MR images of patients with LARC may help to identify patients who will show CR at the end of treatment and those who will not respond to therapy (NR) at an early stage of the treatment.

Physiological effects of a lung-recruiting strategy applied during one-lung ventilation.

BACKGROUND: One-lung ventilation (OLV) affects respiratory mechanics and ventilation/perfusion matching, reducing functional residual capacity of the ventilated lung. While the application of a lung-recruiting manoeuvre (RM) on the ventilated lung has been shown to improve oxygenation, data regarding the impact of RM on respiratory mechanics are not available. METHODS: Thirteen patients undergoing lung resection in lateral decubitus were studied. During OLV, a lung-recruiting strategy consisting in a RM lasting 1 min followed by the application of positive end-expiratory pressure 5 cmH(2)O was applied to the ventilated lung. Haemodynamics, gas exchange and respiratory mechanics parameters were recorded on two-lung ventilation (TLV(baseline)), OLV before and 20 min after the RM (OLV(pre-RM), OLV(post-RM), respectively) and TLV(end). Haemodynamics parameters were also recorded during the RM. RESULTS: The PaO(2)/FiO(2) ratio was 358+/-126 on TLV(baseline); it decreased to 235+/-113 on OLV(pre-RM) (P<0.01) increased to 351+/-120 on OLV(post-RM) (P<0.01 vs. OLV(pre-RM)), and remain stable thereafter. During the RM, CI decreased from 3.04+/-0.7 l/m(2) OLV(pre-RM) to 2.4+/-0.6 l/m(2) (P<0.05), and returned to baseline on OLV(post-RM) (3.1+/-0.7 l/m(2), NS vs. OLV(pre-RM)). The RM resulted in alveolar recruitment and caused a significant decrease in static elastance of the dependent lung (16.6+/-8.9 cmH(2)O/ml OLV(post-RM) vs. 22.3+/-8.1 cmH(2)O/ml OLV(pre-RM)) (P<0.01). CONCLUSIONS: During OLV in lateral decubitus for thoracic surgery, application to the dependent lung a recruiting strategy significantly recruits the dependent lung, improving arterial oxygenation and respiratory mechanics until the end of surgery. However, the transient haemodynamic derangement occurring during the RM should be taken into account.

Analysis of volatile organic compounds: an innovative approach to heart failure characterization in older patients.

BACKGROUND: Analysis of exhaled volatile organic compounds (VOCs) may be applied for diagnostic purposes in some chronic diseases, but there are no data on their role for discriminating people with congestive heart failure (CHF), particularly in older patients where natriuretic peptides have lower accuracy. We evaluated whether VOCs analysis can discriminate patients with or without CHF, stratify CHF severity and predict the response to therapy of decompensated CHF. METHODS AND RESULTS: We recruited 89 subjects admitted to an acute care ward with acutely decompensated CHF, 117 healthy controls and 103 chronic obstructive pulmonary disease (COPD) controls. CHF patients performed echocardiography. VOCs were collected using the Pneumopipe® and analyzed with the BIONOTE electronic nose. Partial least square analysis was used to evaluate the discriminative capacity of VOCs. Accuracy in discrimination of CHF versus healthy and COPD controls was 81% and 69%, respectively; accuracy did not decrease in a sensitivity analysis excluding subjects younger than 65 and older than 80 years. In CHF patients VOCs pattern could predict with fair precision ejection fraction and systolic pulmonary arterial pressure, but not changes in weight due to therapy. CONCLUSIONS: VOCs pattern is able to discriminate older CHF patients from healthy people and COPD patients and correlates with cardiac function markers.

The teriparatide in the treatment of severe senile osteoporosis.

The osteoporosis is a systemic disease of multicausal etiopathogenesis. A progressive bone loss and qualitative alterations in the macro- and micro-architecture of the remaining bones, resulting in a loss of strength of bones to such an extent that even very modest traumas will cause fractures characterize it. Three forms are defined (i) postmenopausal appearing after the menopause, (ii) senile appearing with advancing age, and (iii) the idiopathic forms. Severe osteoporosis is declared when the patients suffer vertebral or femoral fractures without any trauma during a treatment with anti-reabsorptive medicines of at least 1-year. The treatment of osteoporosis is based on various categories of pharmaca, such as bisphosphonates, selective estrogen receptor modulators (SERMs), diaminobutyric acid (DABA), parathyroid hormone (PTH), estrogens and non-hormonal drugs. The teriparatide, the recombinant human (rh)PTH(1-34), is identical in amino acid sequence until the 34th (N-terminal) amino acid of the endogenous, human PTH. It is produced in E. coli using the recombinant DNA technology. It is a pharmacon having a strong trophic-anabolic action on the bone tissue, assuring both the inhibition of the bone loss, and the formation of new bones of good quality. It acts as a stimulant of the osteoblast functions, and at the same time, increases the absorption of calcium from the intestine, and also the renal reabsorption of calcium, and decreases the excretion of phosphates in the kidney. This study summarizes our own experience with the use of rhPTH(1-34) in the treatment of senile patients with severe osteoporosis. Our sample consisted of 40 elderly women of the mean age of 78+/-5 years, having severe osteoporosis. They displayed a columnar T-score>-3.5 and femoral T-score>-2.5, had been under antireabsorptive treatment since at least 12 months. In particular, 15 patients were treated with Alendronate (70 mg/week), 10 of them with Risedronate (35 mg/week), and 15 of them with Raloxifene (60 mg/day). These patients in our study were treated for 1 year with 20 microg/day of rhPTH (1-34), injected subcutaneously, and supplemented also with a daily dose of 1g of calcium and 800 IU of Vitamin D, per os. At start of this treatment (time t(0)), after 6 months (time t(6)) and after 12 months (time t(12)) patients underwent a bone mineral density (BMD) analysis (Dexa-Lunar-DPX-P) on the lumbar vertebral column, (L1-L4 zone), as well as a femoral BMD. We applied also quality of life (QoL) questionnaire of the European Foundation for Osteoporosis (QUALEFFO), and evaluated also the use of non-steroidal anti-inflammatory drugs (NSAIDs). Our final considerations are that the teriparatide therapy increases significantly the bone mass density, expressed in terms of T-Score, reduces the occurrence of new fractures, improves the QoL, and decreases also the consumption of NSAIDs.

The inflammatory abdominal aortic aneurysm and coronary artery disease. Case report and review.

Inflammatory abdominal aortic aneurysm (IAAA) is defined as an unusually thickened aneurysmatic wall, encircled by a wide dense perianeurysmal and/or retroperitoneal fibrosis with adjacent tissues adhesion, and is now considered as an extreme shape of the common phlogistic process involved in atherosclerotic plaque formation. Latest studies demonstrated that inflammation plays an important role in coronary disease and in other atherosclerosis manifestations. We introduce the clinical case of a patient with IAAA who developed an acute myocardial infarction 6 months after the surgical procedure on the aorta. Through a literature review about IAAA we stress the clinical usefulness of the inflammatory markers as independent predictors in management of patients with coronary disease and we present the hypothesis, related to the introduced case, of an advanced coronary disease, aggravated or clinically revealed after the cytokine storm related to important localized inflammatory engagements or great vascular surgery treatments.

Quality of deli-style turkey enriched with plant sterols.

Low-fat meat products could be excellent carriers for plant sterols, known for their cholesterol-lowering properties. In this study, we developed a protocol for the manufacture of a deli-style turkey enriched with plant sterols (S) at a level sufficient to deliver the maximum plant sterols amount recommended for cholesterol reduction by the European Food Safety Authority (3 g of plant sterols per day) in a 70 g portion. We investigated the stability of the plant sterols and the effects of their addition on the product quality. Plant sterols remained stable during the seven-day storage period. The addition of plant sterols significantly affected some texture parameters, shear force, lipid oxidation, L values and water-holding capacity compared with control (C). Sensory analysis was carried out by an untrained panel (32) using the difference-from-control test between C and S samples to evaluate first the extent of the overall sensory difference and then the extent of sensory difference on colour, texture and flavour. Results indicated that panellists considered the intensity of the difference between C and S samples to be 'small'. Plant sterols could be used as a potential health-promoting meat ingredient with no effect on plant sterol stability but with some effects on texture and sensory characteristics.

Vinorelbine and paclitaxel as first-line chemotherapy in metastatic breast cancer.

PURPOSE: To evaluate the efficacy and toxicity of a combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy in metastatic breast carcinoma (MBC). PATIENTS AND METHODS: Between August 1995 and August 1997, 49 patients with untreated MBC received a regimen that consisted of VNB 30 mg/m2 in a 20-minute intravenous (IV) infusion on days 1 and 8 and PTX 135 mg/m2 in a 3-hour IV infusion (starting 1 hour after VNB) on day 1. Cycles were repeated every 28 days. The median age of the patients was 52 years, and 59% of patients were postmenopausal. Median performance status was 1. Dominant sites of disease were soft tissue in 6%, bone in 29%, and viscera in 65%. RESULTS: Objective responses were recorded in 27 of 45 assessable patients (60%; 95% confidence interval, 46% to 74%). Complete remissions occurred in three patients (7%), and partial remissions occurred in 24 patients (53%). No change was recorded in 12 patients (27%), and progressive disease occurred in six patients (13%). The median time to treatment failure was 7 months, and median survival duration was 17 months. The limiting toxicity was myelosuppression, mainly leukopenia in 49 patients (100%) (grade 1 to grade 2, four patients; grade 3, 30 patients; and grade 4, 15 patients). Neutropenia was observed in 100% of patients (grade 1 to grade 2, three patients; grade 3, 11 patients; grade 4, 35 patients). Two treatment-related deaths due to febrile neutropenia were observed in patients with massive liver involvement. Peripheral neurotoxicity developed in 33 patients (67%) (grade 1, 25 patients; grade 2, eight patients); there were no grade 3 or grade 4 episodes. CONCLUSION: The combination of VNB-PTX showed significant activity as first-line chemotherapy for patients with MBC. Myelosuppression was the dose-limiting side effect, whereas neurotoxicity was mild to moderate.

A quantitative immunofluorescent study of the endocrine cell populations in the developing human pancreas.

The immunofluorescent cell content of the pancreas of 8--40-wk fetuses and of 1.5--5-mo Caucasian infants was quantitatively evaluated using anti-insulin, anti-glicentin, anti-glucagon, anti-somatostatin, and anti-pancreatic polypeptide antisera. The most significant findings are: (1) the pancreas of 8--10 wk fetuses contains a sizable population of endocrine cells reacting exclusively to anti-glicentin antiserum. This cell population decreases and disappears in later stages and is replaced by the adult type glucagon/glicentin immunoreactive cell; (2) the pancreatic polypeptide-rich region shows a lower relative endocrine cell content as compared with the glucagon-rich region and its islets appear smaller; (3) in the total pancreas, the relative (volume density) and absolute (microliter) insulin cell content increases regularly with age, while the relative volume of glucagon cells peaks in fetal life (wk 17--20) to decrease in infants, although remaining at higher levels than in adults; the relative and absolute volumes of somatostatin cells are elevated in fetal and infant stages studied where they represent the second most abundant cell type, while pancreatic polypeptide cells appear to least abundant cells during prenatal and infant life. These data show several differences with the pattern of the respective endocrine cell populations in the adult pancreas.