Ventilation practices in the neonatal intensive care units in Saudi Arabia, survey of the utilization of volume-targeted ventilation among practicing neonatologists.

OBJECTIVE: To assess the current practice in using volume-targeted ventilation among neonatologists working at the Neonatal Intensive Care Units (NICU) of Saudi Arabia. METHODS: The questionnaire was provided electronically to 153 practicing Neonatologists working in 39 NICUs. The survey's results were received and statistically analyzed. RESULTS: One hundred nineteen (119) responses were received with, a 78% response rate. Volume Targeted Ventilation (VTV) was used routinely by 67.2%, whereas 21.8% still use only pressure control (PC)/pressure limited (PL) mode. During the acute phase of ventilation support, Assist Control was the most popular synchronized mode, whereas Synchronized Intermittent Mandatory Ventilation (SIMV) with pressure support (PS) or PSV were the two most common modes during the weaning phase, 31.8%, and 31% respectively. The majority of the neonatologists used a tidal volume of 4 ml/kg as the lowest and 6 ml/kg as the highest. The major reasons for not implementing VTV were the limited availability of ventilator devices that have an option of VTV, followed by lack of experience. CONCLUSION: VTV is the predominant ventilation practice approach among neonatologists working in the KSA. Limited availability and lack of experience in using are the main challenges. Efforts to equip NICUs with the most advanced ventilation technology, enhance practitioners' experience and sufficient training in its use are warranted.

Ochromobactrum intermedium: an emerging opportunistic pathogen-case of recurrent bacteraemia associated with infective endocarditis in a haemodialysis patient.

We describe the first clinical case report of infective endocarditis related to Ochrobactrum intermedium infection. The case involved a 23-year-old man receiving dialysis via an internal jugular long-term haemodialysis catheter. He improved with a prolonged course of meropenem and minocycline. Ochrobactrum spp. are recognized as rare emerging opportunistic pathogens.

Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis.

Dendritic cells (DCs) play a key role in the induction and regulation of antigen-specific immunity. Studies have shown that, similar to infection, cellular necrosis can stimulate DC maturation. However, the ability of necrotic cell death to modulate DC cytokine secretion has yet to be explored. We investigated the regulation of interleukin (IL)-12 secretion by human DCs in response to tumour cell necrosis in an in vitro culture model. Two human tumour cell lines (K562 and JAr) were induced to undergo necrosis using heat injury and repeated cycles of freezing and thawing. Both types of tumour cells tested in this study, when injured, induced secretion of monomeric IL-12p40 by monocyte-derived DCs. Furthermore, priming DCs with necrotic cells augmented IL-12p70 secretion significantly in conjunction with CD40 cross-linking. This was physiologically relevant because cell death-pulsed DCs were more potent than non-pulsed DCs at stimulating T cells to proliferate and secrete interferon (IFN)-gamma. The Toll-like receptor 4 (TLR4) played a role in mediating the DC response to heat-killed, but not freeze/thaw-killed necrotic cells. For both methods of injury, proteins contributed to the effect of necrosis on dendritic cells, whereas DNA was involved in the effect of freeze/thawed cells only. These findings indicate that necrotic tumour cell death is not sufficient to induce bioactive IL-12p70, the Th1 promoting cytokine, but acts to augment its secretion via the CD40/CD40L pathway. The results also highlight that the mode of cell death may determine the mechanism of dendritic cell stimulation.

Angiogenin and vascular endothelial growth factor in pregnancies complicated by preeclampsia.

OBJECTIVE: To investigate the role of the angiogenic factors, vascular endothelial growth factor (VEGF) and angiogenin in the pathophysiology of preeclampsia and how their concentrations correlate with the severity of the disease and fetal outcome. PATIENTS AND METHODS: A prospective study was carried out on 71 pregnant patients with preeclampsia and 20 pregnant normotensive controls. Maternal serum levels of VEGF and angiogenin were determined in all cases by enzyme immunoassay. Assessment of fetal well-being using the Biophysical Profile Score (BPS), umbilical and uterine artery Doppler velocimetry, and infant birthweight were carried out. RESULTS: Maternal serum VEGF and angiogenin levels were significantly increased in cases of mild and severe preeclampsia compared to controls. Their increase was positively correlated with elevated systolic and diastolic blood pressure, as well as poor BPS, abnormal Doppler velocimetry, and low birthweight. CONCLUSION: Elevated levels of both VEGF and angiogenin could confirm the existence of vascular reactivity and endothelial disturbance in preeclampsia. Measurement of these angiogenic factors in maternal serum may be a useful as biomarkers for the assessment of the severity of the disease and of fetal outcome.

Cyclooxygenase-2 expression in Barrett's esophagus.

Barrett's epithelium is a recognized premalignant condition for esophageal adenocarcinoma. Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the relative risk of colon cancer in humans and the esophageal tumor load in carcinogen-treated mice. Previous studies provided conflicting results for COX-2 activity in Barrett's mucosa. Pinch mucosal biopsies were collected from Barrett's and adjacent normal esophageal mucosa from 17 patients with Barrett's esophagus. Low-grade dysplasia was found in seven patients. COX-2 protein was undetectable in normal esophageal mucosa. COX-1 protein expression did not vary between normal and Barrett's epithelium. Increased COX-2 protein was detected in Barrett's epithelium in seven patients (41%) but did not differ with or without dysplasia (43% vs 40%). In conclusion, COX-2 protein is increased in 41% of patients with Barrett's epithelium compared to normal esophageal mucosa but did not differ with or without dysplasia. COX-2 induction may be an early event in the development of Barrett's esophagus.

Cclooxygenase-2 (COX-2) Protein Expression by Western Blotting.

Most epidemiological studies (1-7) support a protective role of aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) against colorectal cancer. People who (by their report) take aspirin regularly have about a 50% decrease in the incidence (3,4) and mortality (1,2) from colorectal cancer compared to those who reported no aspirin use. In addition, hospital-based case control studies suggest a protective effect of aspirin use on the development of large-bowel adenomas (5-7). On the other hand, the Physician's Health Study failed to detect any protective effect for aspirin against the subsequent development of colorectal cancer over 12 years of follow up, although this may be due to the short period of follow up (8,9).

Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis.

Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2/IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day of indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. Imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.

Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis.

Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2:IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS-induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. An imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.

Renal cell carcinoma metastatic to the pituitary gland: clinical manifestations and successful treatment with transsphenoidal resection.

OBJECTIVE: To describe two cases of metastatic involvement of the pituitary gland by renal cell carcinoma (RCCA) and review the medical literature regarding this entity. METHODS: We present two case reports and discuss the published literature to illustrate the clinical findings, radiographic features, and recommended management of RCCA metastatic to the pituitary gland. RESULTS: During a 12-month period, we encountered two patients, one with visual deficits and both with anterior pituitary dysfunction, who had large sellar lesions that were histologically proved to be RCCA. Both patients were successfully treated with transsphenoidal surgical resection of the lesion, one of whom is alive and well more than 2 years later. A pituitary metastatic tumor is an uncommon complication of RCCA; it may be difficult to diagnose and potentially fatal. Anterior pituitary dysfunction and visual disturbances are more common initial features than is diabetes insipidus, in contrast to pituitary metastatic involvement from other tumors. CONCLUSION: Transsphenoidal resection is a safe and effective method of treatment of RCCA metastatic to the pituitary gland.

Mutations in the Chediak-Higashi syndrome gene (CHS1) indicate requirement for the complete 3801 amino acid CHS protein.

Chediak-Higashi syndrome (CHS) is a rare, usually fatal, autosomal recessive disorder characterized by severe immunologic defects, reduced pigmentation, progressive neurologic dysfunction and a bleeding diathesis. The hallmark of CHS is giant organelles and giant granules in many different cell types, most likely the result of defective trafficking of specific organellar and granular proteins necessary for the normal genesis, structure or function of these cytoplasmic components. The CHS1 gene has recently been identified and shown to be homologous to the beige locus of the mouse; however, there has been disagreement as to the length of the functional CHS1 mRNA and protein. Here we report homozygous CHS1 gene mutations in two of the original probands we used to map the gene to 1q42-q44. One of these, a frameshift at codon 3197, supports our assertion that the functional CHS protein is a predicted 3801 amino acid polypeptide encoded by a 13.5 kb mRNA.

Henna (Lawsonia inermis Linn.) inducing haemolysis among G6PD-deficient newborns. A new clinical observation.

Over a 10-year period, 15 glucose-6-phosphate dehydrogenase (G6PD)-deficient male newborns were admitted to Al-Jahra Hospital with acute haemolysis a few days after applying henna dye over the body, which is a unique Bedouin tribal practice to celebrate the arrival of the first-born boy. Laboratory investigations revealed significant anaemia, reticulocytosis and indirect hyperbilirubinaemia among the index newborns as compared with controls (p < 0.001). The mean (SD) haemoglobin concentration in index patients was 113.4 (13.4) g/l vs 171.2 (11.2) g/l in controls, reticulocytic count 13.8% (4.2%) vs 1.4% (0.74%), and indirect bilirubin 382.8 (58.7) mumol/l vs 63.7 (61.4) mumol/l. G6PD-deficient newborns with haemolysis linked to henna application had delayed age at presentation and a higher reticulocytic count and hyperbilirubinaemia compared with non-henna-induced haemolysis (p < 0.05). Percutaneous henna absorption is well recognized and clinical findings support the harmful effect of henna on G6PD-deficient red blood cells. A local health education programme has been established to prevent the use of henna dye in infancy.

Homozygosity mapping of the gene for Chediak-Higashi syndrome to chromosome 1q42-q44 in a segment of conserved synteny that includes the mouse beige locus (bg).

Chediak-Higashi syndrome (CHS) is an autosomal recessive disorder characterized by hypopigmentation or oculocutaneous albinism and severe immunologic deficiency with neutropenia and lack of natural killer (NK) cell function. Most patients die in childhood from pyogenic infections or an unusual lymphoma-like condition. A hallmark of the disorder is giant inclusion bodies seen in all granule-containing cells, including granulocytes, lymphocytes, melanocytes, mast cells, and neurons. Similar ultrastructural abnormalities occur in the beige mouse, which thus has been suggested to be homologous to human CHS. High-resolution genetic mapping has indicated that the bg gene region of mouse chromosome 13 is likely homologous to the distal portion of human chromosome 1q. Accordingly, we carried out homozygosity mapping using markers derived from distal human chromosome 1q in four inbred families or probands with CHS. Our results indicate that the human CHS gene maps to an 18.8-cM interval in chromosome segment 1q42-q44 and that human CHS therefore is very likely homologous to mouse bg.

Hypertension prevalence, awareness, treatment, and control in Egypt. Results from the Egyptian National Hypertension Project (NHP). NHP Investigative Team.

This report from the Egyptian National Hypertension Project presents national estimates of the prevalence of hypertension and the extent to which high blood pressure is being detected, treated with medications, and controlled in the Egyptian population. The results are based on findings from a national probability survey of adults > or = 25 years of age conducted in six Egyptian governorates. With the use of a stratified multistage probability design, 6733 people (85% response rate) were examined. Hypertension was defined as systolic pressure > or = 140 mm Hg, and/or diastolic pressure > or = 90 mm Hg, and/or reported treatment with one or more antihypertensive medications. Overall, the estimated prevalence of hypertension in Egypt was 26.3%. Hypertension prevalence increased progressively with age, from 7.8% in 25- to 34-year-olds to 56.6% in those 75 years or older. Hypertension was slightly more common in women than in men (26.9% versus 25.7%, respectively). Overall, 37.5% of hypertensive individuals were aware that they had high blood pressure, 23.9% were being treated with antihypertensive medications, and 8.0% were under control (systolic pressure < 140 mm Hg and diastolic pressure < 90 mm Hg). Hypertension prevalence as well as awareness, treatment, and control rates varied by region, with Cairo having the highest prevalence (31.0%) and the Coastal Region having the highest control rate (15.9%). Rates of awareness, treatment, and control tended to be lowest in areas of lower socioeconomic status. Our results indicate that hypertension is highly prevalent in Egypt and that the rates of hypertension is awareness, treatment, and control are relatively low.(ABSTRACT TRUNCATED AT 250 WORDS)

L-glutamine and L-asparagine stimulate ODC activity and proliferation in a porcine jejunal enterocyte line.

We studied the effect of L-glutamine (Gln), the principal intestinal fuel, on proliferation of a porcine jejunal cell line, IPEC-J2. In cells synchronized by serum deprivation for 4 h, Gln stimulated ornithine decarboxylase (ODC; EC 4.1.1.17) in a dose- and time-dependent manner, with maximal effects at 10 mM in 3 h (P < 0.01). Similar effects were seen for the structurally related amino acid L-asparagine and serum. The Gln effect on ODC was specific, as isosmolar mannitol, glucose, methyl-beta-D-glucoside, L-phenylalanine, ammonia, and aminoisobutyric acid were ineffective. The alanine aminotransferase inhibitor aminooxyacetate (AO) inhibited the ODC stimulation by Gln in a dose-dependent manner (half-maximal inhibitory concentration = 0.5 mM). AO was not toxic to cells, as determined by propidium iodide uptake into nuclei. In addition, Gln stimulated a twofold increase of cellular 24-h [3H]thymidine incorporation above rates of control cells bathed in standard media (P < 0.01); this effect was also blocked by AO. Gln and phorbol 12-myristate 13-acetate stimulated ODC in a synergistic manner. The Na+/H+ exchange inhibitor methylisobutyl amiloride blocked the enhancement of ODC by Gln. Gln also induced the mRNA of the immediate-early gene c-jun. Gln stimulates proliferation in a porcine jejunal cell line through a mechanism requiring transamination and intact Na+/H+ exchange. This stimulation of enterocyte proliferation by Gln suggests that therapeutic Gln administration could facilitate epithelial recovery in the injured small intestine.

Oral transforming growth factor-alpha enhances jejunal mucosal recovery and electrical resistance in piglet rotavirus enteritis.

A randomized, investigator-masked trial determined the effects of oral recombinant human transforming growth factor-alpha (TGF alpha) on jejunal mucosal recovery in 75 piglets with rotavirus diarrhea. Rotavirus inoculation of artificially reared piglets induced subtotal (approximately 50%) villus atrophy and watery diarrhea. Dietary TGF alpha was associated with significant restoration of villus surface area by 4 d postinoculation (p.i.) and complete restoration by 8 d p.i., whereas saline-treated animals required 12 d for recovery. Jejunal segments from clinically recovered TGF alpha-treated piglets showed an increase in electrical resistance across the epithelial barrier in vitro which was proportional to villus height. TGF alpha treatment for 12 d also produced a 30-50% increase in jejunal mucosal mass (protein content and wet weight), compared with the corresponding values in saline-treated piglets and in uninfected controls. However, oral TGF alpha did not hasten the resolution of diarrhea, enhance the specific activities of jejunal mucosal digestive enzymes, or increase jejunal glucose-stimulated Na+ absorption in vitro. We conclude that dietary TGF alpha stimulates jejunal mucosal hypertrophy, improves barrier function, and enhances regrowth of villi in rotavirus enteritis; however, it does not facilitate the restoration of functional activity or mucosal digestive enzymes. Oral TGF alpha can facilitate intestinal epithelial recovery in diseases associated with mucosal damage.

Tumour necrosis factor alpha changes porcine intestinal ion transport through a paracrine mechanism involving prostaglandins.

Prostaglandins stimulate electrogenic anion secretion and inhibit sodium chloride absorption in cryptosporidium induced pig diarrhoea. Because tumour necrosis factor alpha (TNF alpha) is an early mediator of inflammation and stimulates prostaglandin secretion, we investigated its effect on intestinal ion transport. Cryptosporidium infected pig ileum showed higher macrophage infiltration and tissue TNF alpha-like activity than uninfected tissues (p < 0.05, n = 4 and p < 0.05, n = 12, respectively). TNF alpha treatment of control porcine ileal mucosa increased the short circuit current (Isc), a measurement of net anion secretion in this model (p < 0.001, n = 23). This effect was blocked by 10(-6) M indomethacin and Cl- replacement. Neither acute treatment nor preincubation of colonic intestinal epithelial cell monolayers (T84) with TNF alpha stimulated the Isc. However, co-mounting of TNF alpha preincubated pig jejunal fibroblasts (P2JF) monolayers back to back with untreated T84 monolayers dose-dependently induced an indomethacin sensitive increase in Isc compared with values in untreated co-mounted monolayers (p < 0.001, n = 11). These data suggest that in infectious diarrhoea, TNF alpha may induce Cl- secretion through a paracrine mechanism involving prostaglandin release from subepithelial cells, for example fibroblasts.

[Doppler echocardiographic evaluation of functional parameters of mechanical and biological valve prostheses]. / Valutazione tramite ecocardiografia-Doppler dei parametri funzionali di protesi valvolari meccaniche e biologiche.

We studied and compared functional parameters in 314 valvular prostheses. The following parameters have been calculated: mean transvalvular gradients for aortic and mitral prostheses and functional area by Pht (pressure half time) for mitral prostheses. All patients with important depression in myocardial function, tachycardia or malfunctioning prostheses were excluded. 173 prostheses were in aortic position and 141 in mitral position. Mitral prostheses were: 31 biological and 110 mechanical. We subdivided mechanical prostheses in monoleaflet (Omnicarbon, Sorin-Carbocast and Allcarbon, Medtronic, Bjork-Shiley) and bileaflet (Sorin-Bicarbon, St. Jude). These three groups were compared: mean transvalvular gradients and area showed no differences. Aortic prostheses were: 33 biological and 140 mechanical; mechanical prostheses were subdivided in two groups: monoleaflet (Sorin Allcarbon e Carbocast, Bjork-Shiley, Medtronic, Omnicarbon) and bileaflet (Sorin-Bicarbon, St. Jude). Mean transvalvular gradients of these three groups were compared within each group for every size: bileaflet prostheses demonstrated inferior gradients than biological and monoleaflet for 19-21 and 23 sizes; in superior sizes there were no significant differences. Further analysis showed a significant correlation among gradients and body surface area in the 21 size prostheses (p = 0.004). Bileaflet prostheses in this subgroup showed less increase in mean gradient with surface area than mechanical and biological ones.

Marked resistance of normal subjects to tube-feeding-induced diarrhea: the role of magnesium.

The tolerance of healthy subjects to increasing rates of tube feeding was studied to better understand the etiology of diarrhea among tube-fed patients. Five volunteers were fed Osmolite HN by continuous duodenal infusion beginning at 314 kJ (75 kcal).kg body wt-1 x d-1 and progressing each 24 h until no longer tolerated. The five subjects were able to tolerate maximum 24-h infusions of 331-511 kJ.kg-1 x d-1 (198-340 mL/h). Diarrhea developed in only three subjects. Compared with nondiarrheal stools, the high-speed supernatant of the diarrheal stools had significantly higher concentrations of magnesium (192 +/- 22 mmol/L vs 139 +/- 17 mmol/L, P = 0.005), lower concentrations of potassium and phosphorus, and similar concentrations of calcium. The mean carbohydrate, fat, and nitrogen contents were not significantly different. We conclude that normal adult males are remarkably tolerant to duodenal infusion of this typical, isotonic tube-feeding product. The diarrhea that occurred in three of the volunteers at very high infusion rates appeared to be osmotic and attributable predominantly to magnesium.