[Individual prospects of control over process of transfer of solid and liquid drugs inside the stomach]. / Individual'nye vozmozhnosti upravleniia protsessom fizicheskogo peremeshcheniia tverdykh i zhidkikh lekarstvennykh form vnutri zheludka.

It was discovered that patients with stomach ulcers take anti-ulcer drugs while standing, sitting, lying, or moving in the space. The overwhelming majority of them take drugs while sitting and keep the same position almost without any motion during one hour.

Genetic polymorphism in paraoxonase is a risk factor for childhood focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage renal failure (ESRF) in children. Our previous studies have shown that Arab children in Israel have a worse prognosis compared with Jewish patients despite similar clinical presentation and management. Progression of proteinuric glomerular diseases has been associated with alterations in lipid metabolism, and similarities have been drawn between the mechanisms underlying atherosclerosis and glomerulosclerosis. Paraoxonase (PON) is a high-density lipoprotein (HDL)-associated enzyme involved in preventing the oxidation of low-density lipoprotein (LDL), and an association has been shown between two genetic polymorphisms in PON1 and the risk of coronary artery disease. The aim of this study was to determine the frequency of these genetic polymorphisms in PON1 in Arab and Jewish children with FSGS and to determine any association with severity of outcome. Forty-seven children (21 Arab and 26 Jewish) with biopsy-proven FSGS and 274 healthy controls of matching ethnic origin were studied. The glutamine (A)-192-arginine (B) and the methionine (M)-55-leucine (L) polymorphisms were analyzed. The frequency of the A allele was similar in patients and controls (0.68 versus 0.71), as was that of the L allele (0.63 versus 0.6). When subgroups were analyzed, the prevalence of the LL genotype in Arab patients was significantly greater than in Jewish patients (57.1% versus 26.9%, P: < 0.05) and Arab controls (57.1% versus 28.9%, P: < 0.03). A trend in association was found between homozygosity for the L allele and progression of renal disease in Arab children. Homozygosity for the L allele is a risk factor for developing FSGS in Arab children and may be associated with a worse prognosis.

Genetic polymorphisms of the renin-angiotensin system and the outcome of focal segmental glomerulosclerosis in children.

BACKGROUND: The clinical course of primary focal segmental glomerulosclerosis (FSGS) in children is variable, with some patients having a much more rapidly progressing course than others. The purpose of our study was to compare the frequency of three polymorphisms of the renin-angiotensin system (RAS) in children with FSGS with that in healthy controls of matching ethnic groups, and to determine whether the clinical outcome of FSGS was associated with different RAS genotypes. METHODS: Three RAS genotypes were examined in 47 Jewish and Arab children with biopsy-proven primary FSGS and in a large control group: the ACE insertion/deletion polymorphism in intron 16, the M235T mutation in the angiotensinogen gene, and the A1166C in the angiotensin II type 1 receptor gene (AT1R). RESULTS: Arab patients showed a greater tendency towards progressive renal disease than their Jewish counterparts (12 of 21 vs. 9 of 26, P = 0.05) and were less likely to achieve remission (3 of 21 vs. 11 of 26, P < 0.04), despite similar clinical presentation, medical management and follow-up. The RAS allele prevalence was similar among patients and controls of matching ethnic backgrounds, and no difference in allele frequency was found between Arabs and Jews. Homozygotes for the ACE insertion genotype (II) were significantly less likely to have progressive renal disease than patients with the other genotypes (ID and DD; 0 of 6 vs. 21 of 41; P < 0.022). The other RAS polymorphisms were not associated with variations in the clinical course of childhood FSGS. CONCLUSIONS: Homozygosity for the ACE insertion allele may have a protective effect in children with FSGS and can serve as a positive prognostic indicator at diagnosis. The D allele may exert a detrimental dominant effect on outcome. Neither the ACE gene polymorphism nor the other RAS polymorphisms studied are associated with disease prevalence. The AT1R and angiotensinogen gene polymorphisms are not associated with progression of renal disease in FSGS. Ethnic differences in the clinical course of the disease are not linked to these polymorphisms.

Stab wounds associated with terrorist activities in Israel.

OBJECTIVE: To describe injuries resulting from terrorist-associated knife stabbings. DESIGN: Retrospective case series. SETTING: Israel (population 5.5 million). SUBJECTS: Israeli victims (N=154) of knife stabbings on nationalistic basis (the intifada) between July 1987 and April 1994. RESULTS: A total of 125 men and 29 women sustained stab wounds associated with terrorist activities. The median age was 28 years (range, 12-92 years), and 99 victims were aged 18 to 35 years. Seventy percent (108 patients) of the stabbing events occurred between 7 AM and 11 AM. The 154 victims sustained a total of 327 stab wounds, the median number of injuries was 2 per person (range, 1-28), and 68 individuals (44%) sustained more than 1 stab wound. The chest was the most commonly involved site (146 wounds), with the right posterior chest stabbed in 71 patients. The knife penetrated the heart in 20 patients and penetrated the peritoneal cavity in 29 patients. Overall, 29 patients (19%) had superficial injuries, 86 (56%) had internal organ injuries that mandated operative interventions, and 39 died (overall mortality, 25.3%). CONCLUSIONS: Unlike other civilian stabbings, wounds resulting from terrorist-associated stabbings represent severe and highly lethal injuries.

Erythropoietin stimulates atrial natriuretic peptide secretion from adult rat cardiac atrium.

Hypoxia is a powerful stimulus for erythropoietin (EPO) secretion from the kidney and for atrial natriuretic peptide (ANP) secretion from atrial myocytes. EPO is involved in the long term defense mechanism against hypoxia via stimulation of erythropoiesis. ANP is involved in the short-term defense mechanism against hypoxia via improved pulmonary and heart functions. We investigated a possible interaction between these two hormones. We tested the hypothesis that EPO may stimulate ANP secretion from the cardiac atrium. This hypothesis was tested in two in vitro models; isolated rate atrium and cultured adult atria rat myocytes. Recombinant human EPO (5-10 units/ml) enhanced ANP secretion from the isolated atrium (by approximately 2-fold) within 10 min in a concentration-dependent manner. To define whether the action of EPO on ANP secretion is direct, we examined the effect of EPO on ANP release from adult rat cultured atrial myocytes. EPO failed to stimulate ANP secretion from cultured atrial myocytes, suggesting that EPO-induced ANP secretion is an indirect effect. Cyclooxygenase products (e.g.,prostaglandins) and endothelin 1 were shown to be potent secretagogues of ANP from cardiac atrium. To test whether EPO-induced ANP secretion from isolated perfused atrium is mediated by cyclooxygenase products and/or endothelin, we used inhibitors of the enzyme cyclooxygenase (indomethacin or aspirin) and the endothelin receptor ETA subtype antagonist BQ123. EPO-stimulated ANP secretion was not affected by indomethacin (10(-4) M) or aspirin (10(-4) M), whereas BQ123 (10(-6) M) completely abolished EPO-stimulated ANP secretion from cardiac atrium. Our results expand our knowledge on the interaction between EPO and ANP hormonal systems and the possible role in the acute defense mechanism against hypoxia.

Water-soluble contrast material has no therapeutic effect on postoperative small-bowel obstruction: results of a prospective, randomized clinical trial.

BACKGROUND: Hyperosmotic water-soluble contrast materials have been fo und to be helpful diagnostic tools in postoperative small-bowel obstruction (POSBO); however, their therapeutic value remains controversial. PATIENTS AND METHODS: A prospective, randomized clinical study was conducted to examine the use of meglumine ioxitalamate as a supplement to the standard conservative treatment of POSBO. Patients with POSBO (n = 50) suitable for a conservative approach were randomized to receive standard conservative treatment with (n = 25) or without (n = 25) the addition of 100 mL of meglumine ioxitalamate via the nasogastric tube (patients with diffuse carcinomatosis and early POSBO were excluded). Both groups were compared for resolution of obstruction, need for surgical relief of obstruction, and complications. RESULTS: Seven (14%) patients required surgery: 3 in the contrast material group and 4 in the control group (P = not significant [NA]. Resolution of symptoms was achieved in nonsurgical patients within an average of 25.7 hours in the contrast material group and 28.7 hours in the control group (P = NS). There was no mortality in this study. In 2 (4%) patients (1 in each group), strangulated bowel was found during surgery, but only the 1 (2%) patient in the contrast material group required bowel resection. No difference was found in the length of hospital stay or rate of complications. There were no complications that could be attributed to the use of the contrast material itself. CONCLUSIONS: Although water-soluble contrast material is a safe and useful diagnostic tool, it offers no advantage as a supplement to the usual conservative treatment of POSBO.

Assessment of pain threshold and pain tolerance in women in labour and in the early post-partum period by pressure algometry.

The changes in the pressure pain threshold (PPThr) and pressure pain tolerance (PPTol) in 41 parturients have been studied during the active phase of labour and in the early post-partum period. The sensitivity to pressure stimuli was examined with an electronic pressure algometer placed on the sternum during the interval between painful contractions, after extradural analgesia and 24 h after childbirth. Prior to extradural analgesia, mean (+/- SD), PPThr and PPTol were 4.9 +/- 1.6 kg 0.25 cm-2 and 6.9 +/- 1.8 kg 0.25 cm-2, respectively. Similar values were recorded 1 h after induction of the extradural block when the pain of labour was abolished. At 24 h post-delivery, a significant decrease in both PPThr and PPTol was noted (P < 0.001). The lack of influence of extradural analgesia on pressure algometry values, and the elevated sensitivity to pain in the early post-partum period, may be related to the influence of pregnancy and labour on the appreciation of pain.

Antley-Bixler syndrome and esophageal atresia in a patient with trisomy 21.

The Antley-Bixler syndrome (ABS) is characterized by craniofacial, skeletal and urogenital anomalies. While most patients with ABS die of severe respiratory complications in their first months, long-term survivors have been reported. We report an infant girl, born to a consanguineous couple, with craniofacial and skeletal anomalies, consistent with ABS, in addition to atresia of the esophagus and trisomy 21.

Antitumor necrosis factor antibodies reduce hepatic steatosis during total parenteral nutrition and bowel rest in the rat.

BACKGROUND: In previous studies, we demonstrated the overgrowth of gram-negative bacteria in the gut and an enhanced release of tumor necrosis factor (TNF) by peritoneal macrophages, suggesting that endotoxin, TNF, or both, may act as hepatotoxins to produce hepatic steatosis during total parenteral nutrition (TPN) and bowel rest. The present study attempts to better define the role of each of these two mediators. The first part examines the LD50 for various doses of endotoxin in TPN-treated rats compared with free-feeding and free-feeding saline-infused rats. In the second part we repeatedly administered anti-TNF monoclonal antibodies to rats subjected to TPN and bowel rest. METHODS: In the first set of experiments, 87 male Sabra rats were randomized into three groups: free-feeding, infused with normal saline, and infused with TPN. On day 7 of the experiment, all rats received an IV injection of endotoxin at various doses (1.5, 2.5, 5.0, 7.5, and 10 mg/kg). The LD50 in the three groups and at the various doses of lipopolysaccharide tested was determined at 24 hours postinjection. In the second set of experiments, 38 male Sabra rats were randomized into three groups: infused with normal saline and fed rat food ad libitum, infused with TPN, and infused with TPN but also receiving monoclonal antibodies against TNF. RESULTS: Lower endotoxin doses were required to achieve LD50 in the two IV-infused groups (2.5 to 5.0 mg/kg) compared with the free-feeding group (7.5 mg/kg) (p < .03). These findings suggest a moderate increase in susceptibility to the lethal effect of endotoxin in IV-treated rats. The total hepatic fat and triglyceride levels, which were markedly increased in TPN rats, were significantly reduced by using anti-TNF antibodies. Enhanced TNF production by peritoneal macrophages during TPN was completely eliminated by anti-TNF antibodies, probably the result of suppressed TNF production. CONCLUSIONS: The continuous translocation of endotoxin from gram-negative bacterial overgrowth in the gut during TPN and bowel rest results in enhanced release of TNF by macrophages. TNF causes hepatic dysfunction, portrayed in the present experimental model as hepatic steatosis. TPN-induced hepatic steatosis was significantly reduced by the administration of monoclonal antibodies against TNF-alpha.

A pitfall in the technique of jejunal tube insertion, resulting in jejunal perforation.

Enteral feeding by a jejunostomy tube is a reliable and cost-effective method for both long- and short-term nutritional support in selected patients, although a high complication rate has been reported in some series. The authors report on jejunal perforation in an infant, caused by a kinked jejunostomy tube, and emphasize this possible pitfall as a warning to others.

Altered gut barrier function to Candida during parenteral nutrition.

We hypothesize that catheter-related sepsis with Candida during total parenteral nutrition (TPN) is caused by Candida translocation from the gut. Fifty male Sabra rats weighing 330 +/- 40 g were randomized into four groups and put into metabolic cages: group 1 (n = 16), nonoperated free-feeding controls; group 2 (n = 10), infused with normal saline and free feeding; group 3 (n = 14), infused with TPN solution for a total of 36 kcal and 1.5 g g protein.100 g-1 body wt.day-1;group 4 (n = 10), same TPN regimen as group 3 but also receiving oral and intravenous antibiotics. On day 7, all animals received 1.5 x 10(10) viable Candida albicans CBS 562 cells by gavage, and 24 h later, the number of Candida colony-forming units in blood, mesenteric lymph nodes, and kidneys was determined. No growth of Candida was detected in group 1 or group 2. Positive Candida cultures were found in the blood, mesenteric lymph nodes, and kidneys of groups 3 and 4, although levels reached statistical significance only for mesenteric lymph nodes in group 3. Because Candida growth occurred exclusively in groups receiving TPN and bowel rest, we conclude that altered gut-barrier function to Candida occurs during TPN and speculate that Candida sepsis during TPN might be the result of Candida translocation from the gut due to the combination of high-density Candida colonization and favorable local conditions in the gut induced by TPN and bowel rest.

The effect of heat load and dehydration on hypertonic saline solution treatment of controlled hemorrhagic shock.

Small volume hypertonic saline solution has been suggested for initial effective resuscitation of hemorrhagic shock. The effect of hypertonic saline solution in controlled hemorrhagic shock was studied in rats subjected to dehydration or heat, or both. The rats were randomly divided into four groups--group 1 (n = 19), normal rats; group 2 (n = 21), water deprivation for 12 hours; group 3 (n = 20), heating at 37 degrees C. for five hours, and group 4 (n = 19), water deprivation for 12 hours and heating at 37 degrees C. for five hours. Controlled hemorrhagic shock was induced in all rats by arterial bleeding of 15 milliliters per kilogram and the rats were divided into three treatment subgroups--group a was untreated, group b was treated with 5 milliliters per kilogram 0.9 percent NaCl and group c was treated with 5 milliliters per kilogram 7.5 percent NaCl. Arterial bleeding of 15 milliliters per kilogram in group 1 resulted in decrease in mean arterial pressure (MAP) to 44 +/- 2 millimeters of mercury (p < 0.001) and pulse rate to 280 +/- 13 per minute (p < 0.01). A similar decrease in MAP and pulse rate was observed in all four groups. Infusion of hypertonic solution (HTS) in group 1c was followed by an increase in MAP to 89.0 +/- 9.7 milliliters of mercury (p < 0.01) in 15 minutes. This was significantly higher than infusion of normal saline solution in group 1b (p < 0.01) or untreated group 1a (p < 0.01). This difference remained significant also after 45 minutes from infusion (p < 0.05 and p < 0.05, respectively). The increase in MAP in response to HTS in group 1c after 15 minutes was significantly higher than the rise in groups 2c (p < 0.05), 3c (p < 0.05) and 4c (p < 0.05). This difference in response to HTS remained significant 45 minutes from infusion in groups 3c (p < 0.05) and 4c (p < 0.05), but not in dehydrated rats in group 2c. Arterial bleeding did not alter serum sodium significantly in all four groups. Infusion of HTS in group 1c was followed by an increase in serum sodium from 149.1 +/- 1.4 to 161.1 +/- 2.4 milliequivalent per liter (p < 0.001), while infusion of HTS in group 4c, where serum sodium was initially elevated to 157.1 +/- 3.0 milliequivalent per liter, did not further elevate the serum sodium level.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypertonic saline infusion in hemorrhagic shock treated by military antishock trousers (MAST) in awake sheep.

OBJECTIVES: To determine the effect of military antishock trousers (MAST) combined with hypertonic saline in controlled hemorrhagic shock in an awake sheep model. DESIGN: Prospective, randomized, controlled study. SETTING: University research laboratory. SUBJECTS: Healthy adult sheep (21 to 33.5 kg) were studied in four experimental groups. INTERVENTIONS: Sheep underwent cannulation of the jugular vein and the carotid artery. An indwelling catheter was also inserted into their bladders. Mean arterial, pulmonary arterial, pulmonary artery occlusion, and central venous pressures, cardiac and stroke volume indices, systemic and pulmonary vascular resistances, PaO2 and PaCO2, and serum lactate and hemoglobin concentrations were measured at baseline, after induction of hemorrhagic shock, and subsequently during resuscitative treatments of normal saline, MAST, hypertonic saline, and the combination of MAST and hypertonic saline. MEASUREMENTS: Controlled hemorrhagic shock was induced by arterial bleeding of 40 mL/kg in all animals. The sheep were randomized into four groups. In group 1 (n = 5), controlled hemorrhagic shock was treated by 5 mL/kg sodium chloride 0.9% (isotonic saline). In group 2 (n = 6), controlled hemorrhagic shock was treated by 5 mL/kg sodium chloride 7.5% (hypertonic saline). In group 3 (n = 5), controlled hemorrhagic shock was treated by MAST inflated to 40 mm Hg followed by 5 mL/kg sodium chloride 0.9%. In group 4, controlled hemorrhagic shock was treated by MAST (40 mm Hg) followed by 5 mL/kg of hypertonic saline. MAIN RESULTS: Arterial bleeding was followed by significant decreases in mean arterial pressure (87 +/- 1 to 41 +/- 4 mm Hg; p < .001), cardiac index (4.6 +/- 0.4 to 2.0 +/- 0.2 L/min/m2; p < .001), and urine output (102 +/- 30 to 13.0 +/- 7 mL/hr; p < .001), and an increase in systemic vascular resistance (1517 +/- 130 to 2601 +/- 370 dyne.sec/cm5; p < .001). MAST inflation in group 3 increased systemic vascular resistance to 3018 +/- 399 dyne.sec/cm5 (p < .05) and mean arterial pressure to 79 +/- 5 mm Hg (p < .05), while cardiac index, urine output, and lactate concentration remained unchanged. Infusion of hypertonic saline after MAST inflation (group 4) resulted in an increase in mean arterial pressure to 99 +/- 4 mm Hg (p < .001), an increase in cardiac index to 4.1 +/- 0.4 L/min/m2 (p < .001), an increase in urine output to 221 +/- 93 mL/hr (p < .001), and a decrease in systemic vascular resistance to 1847 +/- 175 dyne.sec/cm5 (p < .005). CONCLUSIONS: In hemorrhagic shock, the combination of MAST and hypertonic saline increases mean arterial pressure, improves cardiac output and tissue perfusion during the application of MAST, and also prolongs for > 2 hrs the short beneficial effect of hypertonic saline on mean arterial pressure.

Regional versus general anesthesia for bone marrow harvesting.

STUDY OBJECTIVE: To compare regional versus general anesthesia for bone marrow harvesting. DESIGN: Retrospective study. SETTING: Inpatients at a bone marrow transplantation unit of a university medical center. PATIENTS: One hundred sixty-two donors: 63 healthy patients donating heterologous marrow, 99 patients donating autologous marrow. INTERVENTIONS: Anesthesia and patient charts from 1986 to 1990 were reviewed. MEASUREMENTS AND MAIN RESULTS: Regionally anesthesized patients required less transfused blood in the perioperative period, even though more bone marrow was aspirated. This group also required less postoperative analgesia. We found no difference between the groups with regard to length of hospitalization or amount of colloid required in the perioperative period. CONCLUSIONS: Our data suggest that both modes of anesthesia can be safely administered. Further investigations should be carried out to determine whether the two types of anesthesia, regional and general, are equivalent.

How conservatively can postoperative small bowel obstruction be treated?

Although postoperative adhesion ileus is the most common cause of small bowel obstruction in adults, its management remains controversial. We retrospectively studied 297 admissions of 227 patients over a period of 14 years to evaluate our conservative approach in managing adhesion ileus. We found that nonoperative therapy of up to 5 days' duration can be used safely for the majority of patients who present with postoperative intestinal obstruction, including those with complete obstruction. In those patients, who responded to conservative treatment, the obstruction resolved within a mean of 22 hours and a maximum of 5 days. A trial of more than 5 days' duration proved ineffective. The conservative approach resulted in a 73% resolution of obstruction with no significant increase in mortality or in the rate of strangulated bowel.

Feeding jejunostomy for post-operative nutritional support.

Enteral feeding by tube jejunostomy, inserted during definitive surgery, was used in 19 adult patients operated upon in a 24 month period. Jejunostomy feeding was associated with a low rate of minor complications enabling delivery of adequate caloric and protein input shortly after major abdominal operations and up to 9 months later. We feel that the insertion of a regular size jejunostomy tube during surgery is a simple, brief and safe procedure which offers efficient and inexpensive nutritional support, and thus has an important role in the post-operative management of selected patients. It is also easily used in the home setting if needed.