Littre’s hernia in newborn infants: report of two cases

Littres hernia was originally defined by Reinke in 1841 as the presence of a Meckels diverticulum in any hernial sac. It is generally difficult to differentiate from other types of hernia until complications arise. It is a rare and accidental finding at any age, but it is absolutely exceptional in neonates. To our knowledge, only one case under the age of 1 month has been reported in the literature. Herein two cases treated in the first 20 days of life are reported.     

Growth and adult height in atypical coeliac patients, with or without growth hormone deficiency

OBJECTIVE: To evaluate the effect of a gluten-free diet on growth and adult height, when available, in coeliac children without gastrointestinal symptoms. PATIENTS AND METHODS: Sixty-one coeliac children without gastro-intestinal symptoms were included in the study. The age at diagnosis was 9.50 +/- 3.3 years. Thirty-eight had short stature at diagnosis (< 10th percentile) and 23 had normal stature. Thirty-seven reached adult height. RESULTS: After beginning the diet an increase in growth velocity was seen in 30 patients (responders) (20 with initial short stature), while in 31 patients (18 with short stature) there was no catch-up growth (non-responders). Bone age at diagnosis was significantly more delayed in the responders than in the non-responders. Target height was significantly higher in children with normal stature at diagnosis than those with short stature. Growth hormone (GH) deficiency was found and confirmed after 6-12 months of diet in 12 of the 38 patients (32%) with short stature. In the group of the 30 'short' patients who attained final height, target height was attained or improved in 12 patients (40%): in eight of the 16 (50%) responders and in four of the 14 (29%) non-responders; in eight (all responders) out of 22 (36%) without GH deficiency, and in four out of eight (50%) patients with GH deficiency treated with GH (all non-responders). CONCLUSIONS: In children in whom coeliac disease is diagnosed because of short stature, a gluten-free diet will be successful if at diagnosis there is a delay of bone age and in the first year of diet there is an evident catch-up growth. When this does not occur, i.e. in half of the patients (18 out of 38), it may be because of an associated and transient GH deficiency. In these patients a period of GH replacement therapy as well as a gluten-free diet may improve their final height.     

Genotype/phenotype correlation in glycogen storage disease type 1b: a multicentre study and review of the literature

We studied the genotype/phenotype correlation in a cohort of glycogen storage disease type (GSD) 1b patients. A total of 25 GSD1b patients, 13 females and 12 males, age range: 4.3–28.4 years, mean:14.6±6.8 years; median: 15 years, representing the entire case load of Italian GSD1b patients, were enrolled in the study. Molecular analysis of the glucose 6-phosphate translocase (G6PT1) gene was performed in all patients. We analysed the presence of a correlation among both the clinical features associated with GSD1b (neutropenia, frequency of admission to the hospital for severe infections) and the presence of systemic complications (liver adenomas, nephropathy, bone mineral density defect, polycystic ovaries, short stature, inflammatory bowel disease) and the mutations detected in each patient. Nine patients were homozygous or compound heterozygous for mutations causing stop codons. In particular, three patients were homozygous for the same mutation (400X); of these patients, one showed chronic neutropenia with severe and frequent infections and severe inflammatory bowel disease, another patient cyclic neutropenia associated with rare bacterial infections and mild bowel involvement and the last one normal neutrophil count. Two patients were homozygous for the mutation 128X; one of these patients did not show neutropenia, whereas the other one had severe neutropenia needing frequent hospital admission and was under granulocyte-colony stimulating factor treatment. In three patients no mutations were detected. Conclusion:no correlation was found between individual mutations and the presence of neutropenia, bacterial infections and systemic complications. These results suggest that different genes and proteins modulate neutrophil differentiation, maturation and apoptosis and thus the severity and frequency of infections. The absence of detectable mutations in three patients could suggest that a second protein plays a role in microsomal phosphate transport.     

Aging: functional metabolic balance among cAMP, cGMP and reactive oxygen intermediate generation by human granulocytes

BACKGROUND: The nature of the aging process has been the subject of considerable speculation. It has been reported that in the aging process several components of the signal transduction pathways, including phosphoinositide, protein kinase C, protein kinase A and reactive oxygen intermediate (ROI) generation, are altered. OBJECTIVE: The aim of our study was to evaluate the functional metabolic balance among cAMP, cGMP and ROI generation by human neutrophils in relation to age. METHODS: The age-induced ROI generation was studied in healthy subjects ranging in age from 20 to 80 years old, divided into 6 age groups: 20-29, 30-39, 40-49, 50-59, 60-69 and 70-80 years old. The oxidizing cellular generation was quantified in a luminol-dependent (ROI production) chemiluminescence assay and the results expressed as relative light units per minute. RESULTS: Our results show a differential functional metabolic balance of cAMP and cGMP in relation to age from 50 years on. This phenomenon is reflected by the increase in ROI generation by neutrophil stimulation with cGMP at all ages and a simultaneous lack of effect of cAMP on cGMP from 50 years old. The same results were observed when neutrophil reacted with endogenous contents of cGMP (levamisole, an inhibitor of cGMP phosphodiesterase) or cAMP (aminophylline, an inhibitor of cAMP phosphodiesterase). Our results show that the lack of modulation of the endogenous or exogenous contents of cAMP or cGMP on ROI generation altered the age-related functional metabolic balance. CONCLUSIONS: This altered functional metabolic balance in cAMP, cGMP and ROI generation of neutrophils may certainly have consequences on host defenses, mainly on inflammatory processes, in healthy subjects from 50 years old. However, the exact consequences of this phenomenon on the aging process remain unknown.     

Preoperative criteria of incomplete resectability of peritoneal carcinomatosis from non-appendiceal colorectal carcinoma

OBJECTIVE: To analyse the causes of non resectability of peritoneal carcinomatosis (PC) of non-appendiceal colorectal carcinomas, discovered only at the time of the laparotomy. SUMMARY BACKGROUND DATA: The combination of a maximal cytoreductive surgery (resecting tumor deposits > 1 mm in diameter) with intraperitoneal chemohyperthermia results in cure a significant number of patients. Complete resection of the PC is the determining factor of this time-consuming and resource-consuming therapy. Unfortunately, it has not been possible, so far, to safely predict complete resectability before carrying out the laparotomy. METHODS: All patients with colorectal PC who had undergone a laparotomy in order to receive this new treatment, but who finally presented a non completely resectable PC were included in our study. Their preoperative parameters were retrospectively studied and compared to matched number of patients who had successfully undergone this treatment. RESULTS: 29 patients had incomplete resection PC at laparotomy. They were compared with 29 matched patients who underwent a complete resection of the PC. The factors predicting non resectability were, in decreasing order of frequency: presence or persistence of an ascitis just before the laparotomy (P = 0.0008), progression of the PC while on neo-adjuvant chemotherapy (P = 0.01), abnormal CT- imaging (P = 0.03), and sub-occlusive syndrome (P = 0.05). These parameters were partially inter-related. CONCLUSION: The persistence of ascitis and any progression of the disease while on chemotherapy are important predictive factors of incomplete resectability of non-appendiceal colorectal PC.     

Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25+ regulatory T cells

We analyzed the serum and cerebrospinal fluid (CSF) leptin secretion and the interaction between serum leptin and CD4(+)CD25+ regulatory T cells (T(Regs)) in naive-to-therapy relapsing-remitting multiple sclerosis (RRMS) patients. Leptin production was significantly increased in both serum and CSF of RRMS patients and correlated with IFN-gamma secretion in the CSF. T cell lines against human myelin basic protein (hMBP) produced immunoreactive leptin and up-regulated the expression of the leptin receptor (ObR) after activation with hMBP. Treatment with either anti-leptin or anti-leptin-receptor neutralizing antibodies inhibited in vitro proliferation in response to hMBP. Interestingly, in the RRMS patients, an inverse correlation between serum leptin and percentage of circulating T(Regs) was also observed. To better analyze the finding, we enumerated T(Regs) in leptin-deficient (ob/ob) and leptin-receptor-deficient (db/db) mice and observed the significant increase in T(Regs). Moreover, treatment of WT mice with soluble ObR fusion protein (ObR:Fc) increased the percentage of T(Regs) and ameliorated the clinical course and progression of disease in proteolipid protein peptide (PLP(139-151))-induced relapsing-experimental autoimmune encephalomyelitis (R-EAE), an animal model of RRMS. These findings show an inverse relationship between leptin secretion and the frequency of T(Regs) in RRMS and may have implications for the pathogenesis of and therapy for multiple sclerosis.     

3D structure of eukaryotic flagella in a quiescent state revealed by cryo-electron tomography

We have used cryo-electron tomography to investigate the 3D structure and macromolecular organization of intact, frozen-hydrated sea urchin sperm flagella in a quiescent state. The tomographic reconstructions provide information at a resolution better than 6 nm about the in situ arrangements of macromolecules that are key for flagellar motility. We have visualized the heptameric rings of the motor domains in the outer dynein arm complex and determined that they lie parallel to the plane that contains the axes of neighboring flagellar microtubules. Both the material associated with the central pair of microtubules and the radial spokes display a plane of symmetry that helps to explain the planar beat pattern of these flagella. Cryo-electron tomography has proven to be a powerful technique for helping us understand the relationships between flagellar structure and function and the design of macromolecular machines in situ.     

Impairment of Response Inhibition Precedes Motor Alteration in the Early Stage of Liver Cirrhosis: A Behavioral and Electrophysiological Study

Abnormality in movement initiation may partially explain psychomotor delay of cirrhotic patients, even in the absence of overt hepatic encephalopathy (HE). Therefore, the aim of this study was to determine the mechanisms of psychomotor delay observed in patients with cirrhosis in the absence of overt HE. Fourteen patients with nonalcoholic cirrhosis and 12 healthy matched control subjects underwent the lateralized readiness potential (LRP) measurement elicited by a visuospatial compatibility task (Simon task). Stimulus-triggered LRPonset reflects the time in which response is selected, while response-triggered LRP onset reflects motor execution. Cirrhotic patients showed delayed reaction times (RTs) compared to controls, particularly those with trial-making test A (TMT-A) or electroencephalogram (EEG) alterations. Stimulus-triggered LRP onset was found to be delayedin cirrhotic patients compared to controls, with a significant Group-versus-Condition interaction, showing a reduced cognitive ability to cope with interfering codes, even in patients without minimal HE (MHE). Response-triggered LRP was found to be delayed only in the patients with TMT-A or EEG alterations. In conclusion, cirrhotic patients without overt HE display a psychomotor slowing, depending firstlyon response inhibition and only later accompanied by impaired motor execution.