Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study

Background Botulin toxin (BTX) has been proposed as a potential obesity treatment.Methods In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35–57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m²; range 38.2–56.7 kg/m²) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region.Results No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism.Conclusions BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely.     

Losartan treatment and left ventricular filling during volume loading in patients with dilated cardiomyopathy

Background Patients with mild heart failure show a reduction in preload reserve mechanism during volume expansion. At this time, the effects of volume expansion on left ventricular (LV) diastolic filling in this subset of patients have not been well characterized. Methods We evaluated the effects of acute volume loading on Doppler parameters of LV filling in 10 healthy control subjects and in 12 patients with idiopathic dilated cardiomyopathy (DCM). In patients with DCM, the effects of losartan on diastolic adaptation to volume load were also investigated. Results During volume loading, the healthy control subjects showed a decrease in isovolumic relaxation time (F = 5.3, P < .05) but an increase in the LV peak filling rate (F = 52.9, P < .001) and velocity time integral of both systolic (F = 72.8, P < .001) and diastolic (F = 4.6, P < .05) pulmonary venous flow. In patients with DCM, isovolumic relaxation time decreased more than in control subjects (F = 8.1, P < .01), and the deceleration time of the early mitral wave was reduced (F = 26.3, P < .001). Furthermore, the duration of pulmonary venous flow reversal exceeded that of mitral flow at atrial contraction (F = 28.5, P < .001). After treatment with losartan, the deceleration time of early mitral wave remained unchanged, and the duration of pulmonary venous flow reversal at atrial contraction did not exceed that of mitral flow; thus, a significant treatment effect was detectable (F = 5.6, P < .05; and F = 6.6, P <.05, respectively). Conclusions Control subjects respond to volume load with enhancement in early LV filling, whereas patients with DCM show an increase of LV filling pressure. Diastolic adaptation to volume load improves in patients with DCM after treatment with losartan. (Am Heart J 2002;143:433-40)     

Absence of somatic mutations in natriuretic peptide receptor type A gene in human aldosterone-secreting adenomas

Somatic mutations of genes codifying for key regulatory proteins are the cause of different types of hormone-secreting adenomas. Natriuretic peptides (NP) are the strongest inhibitors of aldosterone secretion but aldosterone-secreting adenomas (aldosteronomas) are resistant to this inhibition and have reduced binding sites for NPs. The objective of this study was to sequence the entire coding region of the NP receptor type A (NPRA, codified by the Npr1 gene) to find loss-of-function somatic mutations. Total RNA was extracted from eight aldosteronomas and cDNA was synthesized. NPRA mRNA expression was evaluated by Northern blot analysis and compared with beta-actin mRNA as the housekeeping gene. Twelve primer couples were designed on the basis of the Npr1 gene organization to amplify, by PCR, all 22 coding exons of the gene. The two strands of amplified DNAs were purified and directly sequenced by automated capillary sequencer. NPRA mRNA expression did not differ among aldosteronomas. Npr1 open reading frame sequences obtained from eight aldosteronomas did not contain any mutation. The coding sequences of all 22 exons were identical in all samples and identical to published sequences. In the 3'-untranslated region (3'-UTR) a new length difference 3C/4C polymorphism was found at position 15 129 (three adenomas were 3C/4C and two were 3C/3C). Such a 3C/4C polymorphism was present in genomic DNA from 80 control subjects (25, 4C/4C; 40, 3C/4C; 15, 3C/3C). Mutations in the coding exons of the Npr1 gene do not appear to be a common cause of aldosteronomas. Moreover, the exons of Npr1 encoding for the translated portion of mRNA do not appear to be prone to polymorphisms. The polymorphism identified in the 3'-UTR might affect mRNA stability resulting in lower receptor synthesis, but it is not likely to confer a predisposition to the development of aldosteronomas.     

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

A Psychoneuroendocrino-immune approach in the nursing treatment of anorexia and bulimia nervosa

Recent clinical reports have shown an increasing number of patients afflicted by eating disorders in the western world. There are numerous causes and mechanisms leading to eating disorders that affect the psychoneuroendocrinoimmune system. In this study, we define a novel psychoneuroendocrinoimmune nursing approach for anorexic and bulimic patients&rsquo; treatment. According to the specific diagnostic items deriving from the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases, and clinical guidelines in eating disorders formulated by the National Institute for Clinical Excellence, we carried out a qualitative study on the nursing treatment chosen by 210 international centers considered as a sample. This study was based on a no structured interview via e-mail to better understand the nursing approach in anorexia and bulimia nervosa. Thanks to the selected centers&rsquo; answers, four different levels of nursing care were identified, that include:

1. the nursing role analyzing the spectrum of patients&rsquo; problems;

2. the nursing intervention in inpatient care;

3. the nursing intervention in outpatient care;

4. the day hospital treatment.

All four prove to be especially useful in the nursing practice.     

EphA2-mediated mesenchymal–amoeboid transition induced by endothelial progenitor cells enhances metastatic spread due to cancer-associated fibroblasts

Tumor progression is deeply influenced by epigenetic changes induced by tumor stroma. Cancer-associated fibroblasts (CAFs) have been reported to promote epithelial–mesenchymal transition in cancer cells, thereby enhancing their aggressiveness and stem-like properties. As CAFs are able to recruit endothelial progenitor cells (EPCs) to tumor site, we aim to investigate their interplay for prostate carcinoma progression. Both prostate CAFs and cancer cells actively recruit EPCs, known to affect tumor progression through increased vasculogenesis. EPCs synergize with CAFs to further promote epigenetic plasticity of cancer cells, through a mesenchymal-to-amoeboid transition. Indeed, after fibroblasts have engaged epithelial–mesenchymal transition in cancer cells, a further shift towards amoeboid motility is promoted by EPCs through contact-mediated triggering of the bidirectional ephrinA1/EphA2 signaling. The activation of ephrinA1 reverse pathway enhances EPC-induced neo-vascularization, thus promoting tumor growth, while EphA2 forward signaling elicits mesenchymal–amoeboid transition in cancer cells, favoring their adhesion to endothelium, transendothelial migration, and lung metastatic colonization. We therefore underscore that the metastatic advantage given by tumor microenvironment embraces different motility strategies and propose EphA2-targeted tools as useful adjuvants in anti-metastatic treatments.     

A volumetric prediction model for postoperative cyst shrinkage

Clinical Oral Investigations - With only limited information available on dimensional changes after jaw cyst surgery, postoperative cyst shrinkage remains largely unpredictable. We aimed to propose...     

Angiotensin-converting enzyme activity in stools of healthy subjects and patients with celiac disease

Angiotensin-converting enzyme (ACE) is a dipeptidylcarboxypeptidase that occurs in three types of cells: endothelial, epithelial, and neuroepithelial. ACE activity is present in plasma, urine, and vascular endothelium. High levels of ACE are found in the brush border of human small bowel. The aim of this study was to evaluate ACE activity in human stools and to find a correlation with the intestinal loss of epithelial cells. Fifteen healthy subjects (HS) (8 males, 7 females; age range 6–56 years), 20 patients with celiac disease (CD) (11 males, 9 females; age range 15–53 years), and 18 patients with CD in remission after a gluten-free diet (CD-GFD) (8 males, 10 females; age range 14–54 years) were enrolled in the study. The fecal ACE activity was measured in all groups. Fecal samples were kept at –20°C for a subsequent test. In HS, fecal ACE activity was 21.03±16.17 nmol/min/100 g (mean ±sd). In patients with CD with subtotal mucosa atrophy, ACE activity was significantly higher (113 ± 88.94) than in HS and CD on GFD (36.65±23.9). We have demonstrated ACE activity in human stools. ACE activity in stools seems to derive from the microvilli of the intestinal mucosa, thus suggesting the potential usefulness of ACE determination as an index of enterocyte damage.     

Solitary fibrous tumor of the liver

We report a new case of benign solitary fibrous tumor (SFT) of the liver. A 65‐year‐old man presented to our unit with upper right abdominal discomfort. On examination abdominal distension was present and palpation showed a large firm mass in the right hypochondrium and epigastrium. The patient's past medical history was not significant and laboratory tests were normal. Ultrasonography and computed tomography showed a large tumor, 20 cm in diameter, in the right lobe of the liver. An extended right hepatectomy was performed. The tumor measured 30 × 28 × 14 cm and weighed 4725 g. Microscopic evaluation showed a benign SFT of the liver with tumor cells typically positive for vimentin and CD34. The postoperative course was uneventful, and the patient is alive 30 months after surgery. This is a rare neoplasm of mesenchymal origin that occasionally involves the liver in adult patients. Most SFTs are benign, but some may have malignant histological features and recur locally or metastasize. Because of their rarity, overall experience has not been significant and little has been published concerning this tumor, Including the present one, 28 cases have been reported in the English literature. Surgery is the mainstay of treatment. Little can be said about the benefits of adjuvant radiochemotherapy in these patients. As SFT of the liver is often a benign neoplasm, chemotherapy or radiotherapy should not be necessary, and should be reserved for when resection is incomplete and/or histological examination reveals features of malignancy. Surgeons must be aware of SFT of the liver, and this neoplasm should be included in the differential diagnosis of a single large hepatic mass.