Patients requiring pediatric palliative care for advanced heart disease in France: A descriptive study.

INTRODUCTION: Pediatric palliative care (PPC) teams address unmet needs and improve the quality of life of patients with life-limiting conditions across pediatric subspecialties. However, little is known about the timing, reasons, and nature of PPC team interventions in advanced heart diseases (AHD). OBJECTIVES: Here we describe how, when, and why PPC teams interact with referred teams of children suffering from AHD. METHODS: We conducted a retrospective nationwide survey among PPC teams in France. All patients referred to participating PPC teams for a cardiologic disease in 2019 were studied. RESULTS: Among six PPC teams, 18 patients with AHD had a PPC consultation in 2019. Six of these patients had cardiomyopathy and 12 had congenital heart disease (CHD). The median age at referral was 0.9 months for CHD and 72 months for cardiomyopathy. An antenatal diagnosis had been made for six families with CHD, and two of them were referred to PPC before birth allowing for a prenatal palliative care plan. The main reason for referral was ethical considerations (50%) followed by organization for home-based palliative care (28%). PPC teams participated in ethical discussions when asked to but also provided family support (12/18), home-based PPC (9/18), coordination of care (5/18), support of the referred team (4/18), and symptoms management (3/18) CONCLUSION: The main reason for referral to PPC was ethical considerations, but PPC interventions followed a holistic model of care. Prospective outcomes measurement and partnerships should be further developed.

Use of an intragastric balloon for management of obesity in a dog.

While various bariatric surgeries are commonplace in obesity medicine for humans, these techniques have not been commonly used in veterinary medicine. A technique used in humans consists in endoscopically placing an intragastric balloon. The intragastric balloon takes volume in the stomach causing a feeling of satiety and reducing food intake. A 57.6 kg, 9-year-old neutered female Labrador dog with chronic hypothyroidism was presented for overweight management. Combined levothyroxine treatment and dietary management with specific alimentation for obesity had failed to control overweight. An intragastric balloon was placed endoscopically in the stomach to allow the reduction of the gastric capacity and resulted in effective weight loss. The dog weight decreased to 40.9 kg at the time of intragastric balloon removal 198 days after placement. Further research including a larger sample size and long term follow-up is required to establish safety and effectiveness of this procedure.

Analysis of radioprotection and antimutagenic effects of Ilex paraguariensis infusion and its component rutin.

DNA repair pathways, cell cycle checkpoints, and redox protection systems are essential factors for securing genomic stability. The aim of the present study was to analyze the effect of Ilex paraguariensis (Ip) infusion and one of its polyphenolic components rutin on cellular and molecular damage induced by ionizing radiation. Ip is a beverage drank by most inhabitants of Argentina, Paraguay, Southern Brazil, and Uruguay. The yeast Saccharomyces cerevisiae (SC7Klys 2-3) was used as the eukaryotic model. Exponentially growing cells were exposed to gamma rays (γ) in the presence or absence of Ip or rutin. The concentrations used simulated those found in the habitual infusion. Surviving fractions, mutation frequency, and DNA double-strand breaks (DSB) were determined after treatments. A significant increase in surviving fractions after gamma irradiation was observed following combined exposure to γ+R, or γ+Ip. Upon these concomitant treatments, mutation and DSB frequency decreased significantly. In the mutant strain deficient in MEC1, a significant increase in γ sensitivity and a low effect of rutin on γ-induced chromosomal fragmentation was observed. Results were interpreted in the framework of a model of interaction between radiation-induced free radicals, DNA repair pathways, and checkpoint controls, where the DNA damage that induced activation of MEC1 nodal point of the network could be modulated by Ip components including rutin. Furthermore, ionizing radiation-induced redox cascades can be interrupted by rutin potential and other protectors contained in Ip.

Analysis of radioprotection and antimutagenic effects of Ilex paraguariensis infusion and its component rutin

DNA repair pathways, cell cycle checkpoints, and redox protection systems are essential factors for securing genomic stability. The aim of the present study was to analyze the effect of Ilex paraguariensis (Ip) infusion and one of its polyphenolic components rutin on cellular and molecular damage induced by ionizing radiation. Ip is a beverage drank by most inhabitants of Argentina, Paraguay, Southern Brazil, and Uruguay. The yeast Saccharomyces cerevisiae (SC7Klys 2-3) was used as the eukaryotic model. Exponentially growing cells were exposed to gamma rays (γ) in the presence or absence of Ip or rutin. The concentrations used simulated those found in the habitual infusion. Surviving fractions, mutation frequency, and DNA double-strand breaks (DSB) were determined after treatments. A significant increase in surviving fractions after gamma irradiation was observed following combined exposure to γ+R, or γ+Ip. Upon these concomitant treatments, mutation and DSB frequency decreased significantly. In the mutant strain deficient in MEC1, a significant increase in γ sensitivity and a low effect of rutin on γ-induced chromosomal fragmentation was observed. Results were interpreted in the framework of a model of interaction between radiation-induced free radicals, DNA repair pathways, and checkpoint controls, where the DNA damage that induced activation of MEC1 nodal point of the network could be modulated by Ip components including rutin. Furthermore, ionizing radiation-induced redox cascades can be interrupted by rutin potential and other protectors contained in Ip.

Tuberculosis and noncommunicable diseases: neglected links and missed opportunities.

Globally, the incidence of tuberculosis (TB) is declining very slowly, and the noncommunicable disease (NCD) burden for many countries is steadily increasing. Several NCDs, such as diabetes mellitus, alcohol use disorders and smoking-related conditions, are responsible for a significant proportion of TB cases globally, and in the European region, represent a larger attributable fraction for TB disease than HIV. Concrete steps are needed to address NCDs and their risk factors. We reviewed published studies involving TB and NCDs, and present a review and discussion of how they are linked, the implications for case detection and management, and how prevention efforts may be strengthened by integration of services. These NCDs put patients at increased risk for developing TB and at risk for poor treatment outcomes. However, they also present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for both TB and NCDs. Hastening the global decline in TB incidence may be assisted by strengthening these types of activities.

TB contact investigations: 12 years of experience in the National TB Programme, Morocco 1993-2004.

We reviewed data collected from 1993 to 2004 as part of the routine activities of the national tuberculosis (TB) control programme (NTP) in Morocco. More than 1 million household TB contacts were identified in approximately 200,000 investigations. On average, 77% of identified contacts were screened every year; overall prevalence was 2.5%. The proportion of TB cases identified in household contacts of registered cases was 5.6%. This was significantly higher in children under 10 years and in patients registered and diagnosed with symptomatic primary complex. Performing TB contact investigations as part of the routine activities of NTP services is feasible in low-middle-income countries.

Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice.

TSAP6 (tumor suppressor-activated pathway 6), also known as Steap3, is a direct p53 transcriptional target gene. It regulates protein secretion, for example translationally controlled tumor protein (TCTP), which is implicated in tumor reversion. In keeping with the latter, we show herein that TSAP6 is a glycosylated protein present in the trans-Golgi network, endosomal-vesicular compartment and cytoplasmic membrane. To further investigate the physiological function of TSAP6, we have generated TSAP6-deficient mice. These mice exhibit microcytic anemia with abnormal reticulocyte maturation and deficient transferrin receptor downregulation, a process known to be dependent on exosomal secretion. Moreover, we provide direct evidence that exosome production is severely compromised in TSAP6-null cells. Finally, we show that the DNA damage-induced p53-dependent nonclassical exosomal secretory pathway is abrogated in TSAP6-null cells. Given the fact that exosomes are used as cell-free vaccines against cancer and that they could be involved in the biogenesis and spread of human immunodeficiency virus, it is important to understand their regulation. The results presented here provide the first genetic demonstration that exosome formation is a tightly controlled biological process dependent of TSAP6.

Role of routine blood cultures in detecting unapparent infections during continuous renal replacement therapy.

OBJECTIVE: Continuous renal replacement therapy (CRRT) is frequently employed in the management of renal failure in unstable intensive care patients. At some centers, blood cultures are performed routinely while on CRRT to monitor for occult bacteremia. We questioned the role of routine blood cultures (RBC) in diagnosing underlying infections in these often afebrile patients. DESIGN: Retrospective cohort study (1998-2003). SETTING: Medical, surgical and pediatric intensive care units in a tertiary care teaching hospital. METHODS/MEASUREMENTS: We undertook a retrospective chart review of all 101 episodes of CRRT performed in our hospital since 1998. The primary endpoint of the study was the number of positive cultures that changed patient management. For each positive result, documented infection and parameters of sepsis were noted. RESULTS: There were 101 treatments of CRRT in 98 patients. A total of 698 routine RBC bottles were drawn, a mean of 7.2+/-7 per patient; of those, 29 (4%) were positive in 17patients, documenting 11 bacteremias. Six positive cultures represented contaminants. In all but one case, infection was known or signs of sepsis were present prior to receipt of the culture result. CONCLUSIONS: For patients on CRRT, RBC are rarely positive, and do not detect occult infection in the absence of clinical evidence of infection for the majority of patients. Because routine cultures utilize significant resources, and can result in false-positive results, RBC should not be performed in these patients. Careful clinical monitoring, with blood cultures performed at the first clinical suggestion of an infection, should detect all clinically relevant infections.

Molineus torulosus (Nematoda, Trichostrongylina, Molineoidea) a parasite of Neotropical primates: new morphological and histological data.

Molineus torulosus (Molin, 1861) parasite of Cebus spp. from South America is redescribed in Cebus apella and C. olivecaeus (new host) from French Guyana with emphasis on the synlophe. During the maturation process, the larvae dwelt in the cysts carved alongside the external part of the small intestine. The turn-out of the mature worms and the laid eggs depended on the tissular organisation of cyst walls as the inflammatory process waned and fibrosis progressed to seal the cystic lumen. Adult worms entwine themselves in the cysts, live there permanently as their presence has never been evidenced in the intestinal lumen. They copulated, laid eggs, degenerated and died once entrapped by the fibrotic process. Laid eggs released in the intestinal lumen through a narrow channel ensured the continuation of the developmental cycle. However, erratic migration was possible via the vascular channels surrounding the cysts.

Leprosy chemoprophylaxis in Micronesia.

A programme of chemoprophylaxis was introduced as a component of the leprosy control programme in the Federated States of Micronesia (FSM), beginning in 1996. The entire population of the country was to be screened, and a single dose of 600 mg rifampicin, 400 mg ofloxacin and 100 mg minocycline (ROM) was to be administered to the entire population. Two rounds of screening the entire population were carried out, approximately 1 year apart, and chemoprophylaxis was administered at the time of each screening. Ninety percent of the population were screened at least once, and 55% were screened in both rounds; 87% of the population received at least one dose, and 54% received two doses. In the course of the first round, 322 new cases were detected, whereas only 80 new cases were detected during the second round, of whom only 12 had received chemoprophylaxis in the course of the first round. A third round of screening, confined to a small number of villages in both Chuuk and Pohnpei, in which states leprosy endemicity was high, was carried out approximately 2 years after the second. Only 16 new cases were detected during the third round of screening, whereas 102 new cases had been detected in this same population during the first round of screening, and 32 new cases during the second. Six of the 16 newly detected cases stated that they had been administered chemoprophylaxis at least once; however, this information may not be reliable.

[Antileprosy polychemotherapy in the member states of the OCCGE: a decade of implementation (1983-19930). The National Coordinators of the Leprosy Program of the 8 states of the OCCGE]. / La polychimiothérapie antilépreuse dans les Etats membres de l'OCCGE: une décennie de mise en oeuvre (1983-1993). Coordonnateurs Nationaux de Programme Lèpre des 8 Etats de l'OCCGE.

MDT for leprosy recommended by WHO in 1981 has been introduced and implemented in 8 Member States of OCCGE (an organization for leprosy control in francophone West Africa). This implementation from 1983 to 1993 can be divided in two phases: 1983-1987: introduction phase by pilot projects; 1988-1993: extension phase by national leprosy control programmes. During the ten years, MDT coverage rose to 68%, leprosy prevalence rate widely decreased (40.71 to 6.56 per 10,000), while annual detection rate weakly varied (1.89 to 1.26 per 10,000). Factors influencing this evolution of leprosy are brought out and recommendations are made about strategies to be developed for leprosy control up to year 2000.

Maintenance of intragastric pH > 4 with famotidine in duodenal ulcer patients: factors influencing drug requirements.

The gastrojet, a closed loop pH feedback infusion pump capable of maintaining intragastric pH at a target value by infusing H2 blockers at variable rates, was used to assess factors influencing the quantity of famotidine required to maintain intragastric pH above 4 for 24 hours in 34 fed patients with duodenal ulcers. The following factors were considered: sex, age, duration of the disease, previous bleeding, previous poor response to H2 blockers (ulcer unhealed at six weeks, or recurrence within three months during maintenance treatment), activity of the ulcer disease, smoking habits, cirrhosis. The patients had taken no antisecretory drugs for the 15 days before the study. Two standardised meals were given during the study period (from 1000 to 1000). Fifty ml of famotidine (4 mg/ml) was loaded into infusion bags and the pump was programmed to deliver the drug intravenously at 11 rates varying from 0 to 40 microliters/min. The target pH was 4. Mean famotidine use was 111 mg (range 33 to 200), the 23 hour median pH was 5.3, and the mean time during which pH was above 4 was 75.4%. There was a negative correlation (p < 0.001) between famotidine delivery and the inhibition of gastric acidity. Statistical analysis showed that only cirrhosis significantly influenced drug delivery, median pH, and the time during which pH was above 4. Mean drug delivery in the cirrhotic and non-cirrhotic patients was 135 v 97 mg (p < 0.04), 23 hour median pH was 4.7 v 5.6 (p < 0.01), and the mean time at pH > 4 was 65.9 v 81.6% (p < 0.01). There were large interindividual variations in famotidine requirements, but not only cirrhosis was predictive of dose requirement. These results suggest that the appropriate amount of famotidine to treat duodenal ulcer in cirrhotic patients is probably higher than the usually recommended dose.

[Surgery of pulmonary metastasis from malignant melanoma. Results and criteria of surgical excision]. / Chirurgie des métastases pulmonaires du mélanome malin. Résultats et critères d'opérabilité.

Lung metastases from malignant melanoma are frequent and they often inaugurate the metastatic stage. Exceptionally, they present as one or a few nodules, and in the absence of any other secondary lesion these cases raise the problem of surgical eradication. A retrospective multicentre study was carried out in a series of 38 patients and its results were compared to the data obtained from a review of 435 published cases in order to assess the value of surgery in terms of survival and to delimit its indications as closely as possible. Our series of 38 patients comprised 20 men and 18 women aged from 22 to 93 years (mean 51 years, median 55 years). The primary tumour was located in the trunk in 47 p. 100 of the cases; it was nodular in 33 p. 100 and superficial but extensive in 37.5 p. 100. The time elapsed before the metastases appeared varied from 0 to 108 months (median 40 months). Surgery had been radical in 70 p. 100 of the patients and usually limited, tumorectomies and segmentectomies accounting for 51 p. 100 of the operations. RESULTS. In this series the duration of survival varied between 2 and 144 months (mean 26 months, median close to 15 months), with a 20 p. 100 probability of survival at 5 years (fig. 1). Disease free survival varied from 0 to 144 months (mean 22.5 months, median 10.5 months) (fig. 2, curve 1). The parameters of response as regards patients, primary tumour, metastases and treatment were analysed. Response was uninfluenced by sex and slightly influenced by age, with a difference of borderline significance between subjects under and over 50. The primary tumour characteristics did not affect survival, and the features of metastases were of extremely varied importance. The number of operable metastases was not determinant. On the other hand, the presence of mediastinal lesions, either isolated or associated with lung lesions, worsened the prognosis of terms of survival and much more significantly so in terms of remission (fig. 3 and 4). The evaluation of evolutive characteristics, such as date of appearance and tumour doubling time, was inconclusive. Survival was of the same duration after wide and limited surgery, so that tumorectomy or segmentectomy should preferably be performed. The results of surgical treatment were determinant, with a highly significant difference in survival between radical and incomplete surgery (fig. 5 and fig. 2, curve 2). DISCUSSION. The median survival of patients operated upon for lung metastases is diversely evaluated in the literature as 8 to 29 months (table V), the mean figure of 16 months being virtually the same as that of our series. In this, as in most of the previously published series, the maximum duration of survival was beyond 8 to 10 years. The mean survival rate at 5 years is very close to the one we have recorded (20 p. 100) (table V). Compared with other treatments of lung metastases, surgery may be considered as capable of prolonging survival by 6 months; this is not much unless we add the possibility of a 5-year survival in 1 out of 5 operated patients and the possibility of a survival exceeding 8 or 10 years in 2 to 5 p. 100 of the cases. Some prognostic factors seem to constitute positive or negative criteria of operability. This is the case with mediastinal lesions which may consist of a metastasis of metastasis or of a lymph node invasion associated or not with the lung lesion, but in any case correspond to the involvement of more than one site. Mediastinal lesions must be systematically looked for and treated as contraindications of surgery, as shown by the differences in survival recorded in our series. Opinions differ as regards the value of evolutive parameters of the metastasis. For some authors, a more than 5 years interval before the metastasis appears is associated with a good chance of prolonged survival, whereas a less than 6 months or 1 year interval reflects a steadily high progressiveness and in practice precludes surgery. The value of the

Immunohistochemical characterization of gastrinomas with antibodies specific to different fragments of progastrin.

The characterization of the tumors and their metastasis in patients with the Zollinger-Ellison syndrome is currently based on the immunohistochemical identification of gastrin cells. However, sometimes tumoral cells fail to react with common C-terminal gastrin antibodies. In order to clarify this failure, we carried out morphologic, morphometric and immunocytochemical analyses performed on light and electron microscope levels of 6 pancreatic and 1 metastatic gastrinomas, using antibodies raised against various sequences of human progastrin. On the basis, in light microscopy, of qualitative analysis of immunostaining within cells and of immunostained cell numbers, gastrin 34 residue seemed to be the prominent form in 2 of the tumor tissues, G-17 in 1 tumor which was not responsive with C terminus progastrin and N terminus G-34 antisera, and progastrin in the metastatic tissue that did not contain typical gastrin (G-like) cells. Two tumors failed to react with all antisera used. At the electron microscope level, immunogold staining revealed that progastrin was present only in the progranules and gastrin 34 in both progranules and intermediate granules. Quantitative studies performed on 3 tumors showed that, within a given tumoral cell, about 25 percent of progranules contained progastrin while 75 percent contained gastrin 34. We concluded that different forms of gastrin can be immunodetected in a gastrinoma tissue, depending on the regions, and that the distribution of progastrin fragments is variable from tumor to tumor. So, specific antibodies to different fragments of progastrin may help to the characterization of gastrinomas.

[Long-term efficacy and tolerability of omeprazole in 20 patients with severe Zollinger-Ellison syndrome]. / Efficacité et tolérance à long terme de l'oméprazole chez 20 malades présentant un syndrome de Zollinger-Ellison sévère.

Omeprazole efficacy and tolerance were evaluated in 20 patients with longstanding Zollinger-Ellison syndrome (ZES) committed to long-term antisecretory therapy. The study included 13 men and 7 women, aged 53 (30-74) years (median and range). Nineteen patients presented with epigastric pain, 14 with vomiting, and 9 with diarrhea. All patients had gastroduodenal ulcerations, associated with esophagitis in 9 cases. Median and extreme values for basal acid output (BAO) and serum gastrin (SG) levels before omeprazole treatment were 41 (3.7-80) mmol H+/h and 413 (111-11,490) pg/ml, respectively. In 18 patients, omeprazole treatment was initiated because of resistance to H2-antagonists, and in 2 patients because of carbothioamide RP 40749 discontinuation. Initial doses of omeprazole were 60 mg per day in 10 patients and ranged from 80 to 160 mg per day in the others. Esophagogastrectomy was performed in one patient at day 15 because of esophageal stenosis. In the remaining 19 patients, median duration of treatment was 16 (7-54) months and median doses of omeprazole were 70 (20-160) mg per day during the survey. Omeprazole therapy was highly effective in inducing rapid disappearance of clinical abnormalities in 18 of 19 patients. Twenty-two days after initiation of treatment, median BAO was 4 (0-14) mmol/h and ulcerations had healed in 17 of 19 patients. Median BAO was less than 5 mmol/h during follow-up. However, asymptomatic ulcer recurrence was noted in 4 patients, but disappeared quickly after omeprazole doses were increased. Median basal gastrin level was 700 (116-36.625) pg/ml at the least determination and was statistically higher than pretreatment values (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric endocrine cell behavior in Zollinger-Ellison patients upon long-term potent antisecretory treatment.

Serum gastrin and gastric endocrine cell numerical densities were examined in 22 patients with long-standing Zollinger-Ellison syndrome who were receiving either ranitidine, omeprazole, or other antisecretory drugs (SMS 201-995 or pirenzepine with or without ranitidine) for long periods of time. Fifteen patients had iterative biopsies. Twenty-one subjects with normal endoscopy, serum gastrin, and acid secretion served as controls. Individual fundic argyrophil cell density was above the highest control value in 77% of the patients, whatever the treatment. Argyrophil cell densities tended to be higher in women than in men. During the survey, fundic carcinoids developed in one ranitidine- and in one omeprazole-treated patient. Fundic argyrophil cell densities were correlated with serum gastrin levels (r' = 0.730, p less than 0.001). Antral somatostatin cell density was not modified in any patients as compared with controls, nor was antral gastrin cell density except in omeprazole-treated patients. In these patients, gastrin cell density and gastrin to somatostatin cell ratio were significantly higher than in all other patients or controls. Such increases may indicate true gastrin cell hyperplasia in relation to drug-induced profound acid inhibition.

Gastrin processing in primary culture of gastrinoma cells.

There is a general agreement on the cell specificity of gastrin processing. In order to investigate this processing in Zollinger-Ellison (ZE) patients, we have studied in two primary gastrinoma cultures (one from a pancreatic tumor, the other from a liver metastasis) the proportion of progastrin fragments using immunochemical and immunohistological methods. In tumor extracts as well as in sera, the predominant gastrin form differed between the two patients (i.e. being G17 and G34, respectively). In the two gastrinoma cultures, RIA determinations and electron microscopic observations indicated that the proportion of progastrin increased with time while that of G17 and G34 decreased. On the other hand, as the culture time extended, an increasing proportion of nonimmunostained secretory granules was observed suggesting the presence of other gastrin precursors (e.g. Gly-extended progastrin). From these findings, we suggest that gastrinoma culture cells could be a valuable tool in the biochemical approach to gastrin processing in ZE tumors.

Gastrin secretion by gastrinoma cells in long-term culture.

Gastrinoma cells from surgical specimens of a primary pancreatic tumor and an hepatic metastasis in two patients with a Zollinger-Ellison syndrome were grown and subcultured for 7 mo. Cultured cells displayed a strong reactivity to heptadecapeptide gastrin antibody and maintained an ultrastructural appearance resembling that of the original tumor cells with the presence of secretory granules of variable size and electron density. Cultured cells also showed the ability to secrete immunoreactive gastrin, and this secretion was further concentration-dependently stimulated by secretin (10(-10)-10(-6) M), carbachol (10(-6) M), and bombesin (10(-10)-10(-6) M). The latter peptide was the more potent stimulant with a maximal effect at 10(-9) M (460 +/- 20% of basal release; P less than 0.05). This stimulation occurred in the absence of extracellular Ca2+ and was potentiated by the addition of dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-3) M) into the culture medium. The somatostatin analogue, somatostatin-(201-995), did not alter basal gastrin release but inhibited secretin, carbachol, and bombesin stimulation. Moreover, DBcAMP (10(-3) M) and Ca2+ (1-3 mM) stimulated gastrin release; Ca2+ ionophore A23187 (6 micrograms/ml) enhanced gastrin response to Ca2+ in the early time intervals of incubation. Furthermore the phorbol ester derivative, 12-O-tetradecanoyl phorbol-13-acetate, dramatically stimulated gastrin release (10 times the basal value). We conclude that gastrinoma cells can be cultured over an extended period with maintenance of their capacity to secrete gastrin in response to various hormones and mediators.(ABSTRACT TRUNCATED AT 250 WORDS)