Association between Cowden syndrome and Lhermitte-Duclos disease: report of two cases and review of the literature

BACKGROUND: The authors describe 2 cases of dysplasic gangliocytoma of the cerebellum or Lhermitte-Duclos disease revealing Cowden disease or multiple hamartoma neoplasia syndrome. Cowden disease is a rare autosomal dominant disorder, now considered as a phakomatosis. Nevertheless, relationships between both conditions still remain unclear, since Lhermitte-Duclos disease can also be sporadic. CASE REPORTS: Two patients, 25 and 27 years old, were admitted to the emergency department for an acute intracranial hypertension. In both cases, magnetic resonance imaging (MRI) scan showed a mass in the cerebellar hemisphere. Pathological examination of surgical resection specimens concluded Lhermitte-Duclos disease. Because of the patients' previous personal and familial medical history, Cowden disease was suspected and confirmed by mutational analysis of the phosphatase and tensin homolog (PTEN) gene. In the first case, a nonsense punctual mutation in exon 8 was found. In the second one, a mutation was revealed in the exon 5, a mutational hot spot encoding the phosphatase catalytic core motif. CONCLUSION: Lhermitte-Duclos disease and Cowden disease can be associated. Germline mutations of PTEN gene are known to be implicated in Cowden disease. This gene, located at chromosome 10q23-3, is a tumor suppressor gene that encodes a protein with phosphatase activity. To date, more than 80 mutations have been reported in Cowden disease. When the diagnosis of either one of these two disorders is established, it is imperative to search for the other one to detect early malignant lesions that occur in Cowden disease. Finally, a long-term follow up of the patient is required and a thorough familial screening is necessary.     

Ghrelin,Leptin and Insulin Levels after Restrictive Surgery: a 2-Year Follow-up Study

Background: Ghrelin is a recently discovered orexigenic gastric hormone, whose production is induced by lack of food in the stomach. In morbidly obese individuals, ghrelin levels are low compared to lean persons. During dieting, plasma ghrelin levels increase, leading to an orexigenic signal, which could explain the lack of success of dieting in morbidly obese individuals. Morbid obesity is best treated with bariatric surgery, in which gastric bypass is reported to be more effective than restrictive surgery. A possible explanation could be the difference in plasma ghrelin levels after both operations for bariatric surgery. In this study, plasma ghrelin levels were investigated during a 2-year follow-up. Methods: 17 morbidly obese patients received gastric restrictive surgery. Plasma ghrelin, leptin and insulin levels were evaluated preoperatively and 1 year and 2 years postoperatively. Results: BMI decreased from 47.5 ± 6.2 kg/m² to 33.2 ± 5.8 kg/m² (P <0.001). Plasma ghrelin levels were significantly increased 1 year (P <0.05) and 2 years (P <0.02) postoperatively. Fasting plasma leptin and insulin levels were significantly lower at 2 years after surgery (P <0.001). Conclusion: After gastric restrictive surgery, ghrelin levels increased, in contrast to the reported fall in ghrelin levels after gastric bypass. This difference in ghrelin levels between these operations may be the k ey to understanding the superiority of gastric bypass in sustaining weight loss compared with restrictive surgery.     

Plasminogen kringle 5-engineered glioma cells block migration of tumor- associated macrophages and suppress tumor vascularization and progres- sion.

Angiostatin, a well-characterized angiostatic agent, is a proteolytic cleavage product of human plasminogen encompassing the first four kringle structures. The fifth kringle domain （K5） of human plasminogen is distinct from angiostatin and has been shown, on its own, to act as a potent endothelial cell inhibitor. We propose that tumor-targeted K5 cDNA expression may act as an effective therapeutic intervention as part of a cancer gene therapy strategy. In this study, we provide evidence that eukaryotically expressed His-tagged human K5 cDNA （hK5His） is exported extracellularly and maintains predicted disulfide bridging conformation in solution. Functionally, hK5His protein produced by retrovirally engineered human U87MG glioma cells suppresses in vitro migration of both human umbilical vein endothelial cells and human macrophages. Subcutaneous implantation of Matrigel-embedded hK5His-producing glioma cells in nonobese diabetic/severe combined immunodeficient mice reveals that hK5His indaces a marked reduction in blood vessel formation and signiticanfly suppresses the recruitment of tumor-infiltrating CD45（＋）Mac3（＋）Grl （-） macrophages. Therapeutically, we show ill a nude mouse orthotopic brain cancer model that tumor-targeted K5 expression is capable of effectively suppressing glioma growth and promotes significant long-term survival （〉120 days） of test animals. These data suggest that plasminogen K5 acts as a novel two-pronged anticancer agent, mediating its inhibitory effect via its action on host-derived endothelial cells and tumor-associated macrophages, resulting in a potent, clinically relevant antitumor effect.     

Controlled transperitoneal percutaneous cecostomy as a therapeutic alternative to the endoscopic decompression for Ogilvie's syndrome

Acute colonic pseudo-obstruction, the so-called Ogilvie's syndrome, results in massive colonic dilation without mechanical obstruction. In most cases, a conservative treatment with or without endoscopic decompression is sufficient. In rare cases of relapses or failures, a cecostomy has to be performed. A surgical cecostomy is associated with high morbidity and mortality. However, a percutaneous cecostomy could be an interesting alternative treatment. We report the case of a 67-yr-old male with colonic pseudoobstruction for which both the conservative and the endoscopic treatments were unsuccessful. A percutaneous cecostomy was performed, and for the first time in this indication, a transperitoneal access was used with the help of nylon T-fasteners.     

Mechanosensory transduction of vagal and baroreceptor afferents revealed by study of isolated nodose neurons in culture

Changes in arterial pressure and blood volume are sensed by baroreceptor and vagal afferent nerves innervating aorta and heart with soma in nodose ganglia. The inability to measure membrane potential at the nerve terminals has limited our understanding of mechanosensory transduction. Goals of the present study were to: (1) Characterize membrane potential and action potential responses to mechanical stimulation of isolated nodose sensory neurons in culture; and (2) Determine whether the degenerin/epithelial sodium channel (DEG/ENaC) blocker amiloride selectively blocks mechanically induced depolarization without suppressing membrane excitability. Membrane potential of isolated rat nodose neurons was measured with sharp microelectrodes. Mechanical stimulation with buffer ejected from a micropipette (5, 10, 20 psi) depolarized 6 of 10 nodose neurons (60%) in an intensity-dependent manner. The depolarization evoked action potentials in 4 of the 6 neurons. Amiloride (1 microM) essentially abolished mechanically induced depolarization (15 +/- 4 mV during control vs. 1 +/- 2 mV during amiloride with 20-psi stimulation, n = 6) and action potential discharge. In contrast, amiloride did not inhibit the frequency of action potential discharge in response to depolarizing current injection (n = 6). In summary, mechanical stimulation depolarizes and triggers action potentials in a subpopulation of nodose sensory neurons in culture. The DEG/ENaC blocker amiloride at a concentration of 1 microM inhibits responses to mechanical stimulation without suppressing membrane excitability. The results support the hypothesis that DEG/ENaC subunits are components of mechanosensitive ion channels on vagal afferent and baroreceptor neurons.     

High-titer measles vaccination before 9 months of age and increased female mortality: do we have an explanation?

In 1989, high-titer (HT) Edmonston-Zagreb measles vaccine with a titer more than 10(4.7) plaque-forming-units was recommended by the World Health Organization for use in areas with a high incidence of measles in children younger than 9 months. In 1992, the recommendation was rescinded following reports from Guinea-Bissau, Senegal, and Haiti showing an increased incidence of female mortality occurring after administration of HT Edmonston-Zagreb vaccination. We reviewed 9 studies of HT measles vaccines that reported data on mortality. These reports included 4 randomized trials comparing HT vaccine administered to children younger than 9 months with standard-titer (ST) vaccines (10(3.0) to 10(4.0) plaque-forming-units) given at 9 months of age. Five studies from Zaire, Haiti, Senegal, Rwanda, and Zaire had no control group receiving ST vaccine at 9 months of age, but investigators were able to examine the female-to-male mortality ratio within these HT studies. Investigators have hypothesized that HT vaccine had caused immune suppression similar to that of measles infection. The present review suggests first that the HT vaccine itself is unlikely to be the cause because the effect was not found in all studies. Second, the increased mortality started only after 9 to 10 months of age when controls received ST measles vaccine, and HT groups received the "control vaccine." It was not found in the studies that provided another measles vaccine instead of control vaccine. Third, because the HT studies with excess mortality rates showed increased female mortality rates, we need to find environmental or contextual conditions associated with increased female mortality rates in some studies to explain the problem associated with HT measles vaccination.     

Assessment of a structured in-hospital educational intervention addressing breastfeeding: a prospective randomised open trial

Objective To determine whether a single one-to-one in-hospital education session could increase the rate of breastfeeding at 17 weeks.
Design A prospective, randomised, parallel group, open trial.
Setting A level two maternity hospital in France.
Sample Breastfeeding mothers who were employed outside the home prenatally and were delivered of a healthy singleton.
Intervention A structured one-to-one in-hospital education session.
Methods One hundred and six mother–infant pairs were allocated to the intervention group and 104 to the control group (receiving usual verbal encouragement). A total of 93 mother–infant pairs in the intervention group and 97 in the control group provided complete data for final evaluation of efficacy.
Main outcome measure Rate of breastfeeding at infant age of 17 weeks.
Results There was no significant difference between the two groups in the rate of any breastfeeding (34.4% in the intervention group vs 40.2% in the control group, relative risk = 0.86 [0.52–1.40]), and in the rate of exclusive breastfeeding (14.0% in the intervention group vs 14.4% in the control group, relative risk = 0.97 [0.42–2.22]).
Conclusion Our findings suggest that a single in-hospital educational intervention has no effect on the breastfeeding rate at four months. Guidance provided by maternity staff should be reinforced by a long term multifaceted support programme in countries with a low to intermediate rate of breastfeeding.     

Sexuality after sigmoid colpopoiesis in patients with Mayer-Rokitansky-Kuster-Hauser Syndrome

OBJECTIVE: To assess the functional outcome and sexuality of patients after creation of a sigmoid neovagina. DESIGN: Clinical study performed between 1992 and 2002, with a mean follow-up of 3.3 years (range, 6 months to 9 years). SETTING: Tertiary care center. PATIENT(S): Sixteen consecutive patients with Rokitansky syndrome. INTERVENTION(S): Creation of a neovagina with an antiperistaltic (n = 13) or isoperistaltic (n = 3) sigmoid graft and colovestibular anastomosis by interrupted suture (n = 11) or PCEEA forceps (n = 5). All patients had a neovaginal vault suspension (n = 16). MAIN OUTCOME MEASURE(S): Functional results were evaluated in patients 6 or more months after the operation (n = 12) by using the standardized Female Sexual Function Index (FSFI). This index assesses four domains of sexual dysfunction: desire disorder, arousal disorder, orgasm disorder, and sexual pain disorder. Lubrification and "sexual" quality of life was also evaluated. Normal patients had a mean full FSFI score of 30 +/- 5 of 36. RESULT(S): The mean full FSFI score was 28 +/- 5 (range: 22-34). Seventy-two percent of patients had vaginal intercourse at least once a week; in this subset, the mean full FSFI score was 30 +/- 3 (range: 25-34). CONCLUSION(S): Sigmoid neovagina allowed a normal sexual life in patients who had sexual relations.     

Delayed visual maturation in Karen refugee infants

Thirty-eight babies born to Karen mothers living in camps for displaced persons in north-western Thailand have delayed visual maturation (DVM type 1) that recovers within 6 months. Vitamin A concentrations were deficient in 16% of breast-milk samples from lactating mothers and vitamin B(1) concentrations were deficient in 60% of plasma samples. Infantile beriberi was common in this population. The levels of fatty acids in plasma and milk in Karen women were excellent at birth and in the postpartum period. The degree of deficiencies in these vitamins and the concentration of essential fatty acids in cord blood and maternal breast-milk did not correlate significantly with visual impairment in the infants. DVM might be caused by nutritional deficiency or toxic effects during critical periods of gestation that lead to delayed cortical myelination or structural defects which impinge on parietal cortex function.