Polyphosphate kinase 1, a conserved bacterial enzyme, in a eukaryote, Dictyostelium discoideum, with a role in cytokinesis

Polyphosphate kinase 1 (PPK1), the principal enzyme responsible for reversible synthesis of polyphosphate (poly P) from the terminal phosphate of ATP, is highly conserved in bacteria and archaea. Dictyostelium discoideum, a social slime mold, is one of a few eukaryotes known to possess a PPK1 homolog (DdPPK1). Compared with PPK1 of Escherichia coli, DdPPK1 contains the conserved residues for ATP binding and autophosphorylation, but has an N-terminal extension of 370 aa, lacking homology with any known protein. Polyphosphate or ATP promote oligomerization of the enzyme in vitro. The DdPPK1 products are heterogeneous in chain length and shorter than those of E. coli. The unique DdPPK1 N-terminal domain was shown to be necessary for its enzymatic activity, cellular localization, and physiological functions. Mutants of DdPPK1, as previously reported, are defective in development, sporulation, and predation, and as shown here, in late stages of cytokinesis and cell division.     

Activity in a nephrology ward in 2009, Piemonte, Italy

The characteristics of patients hospitalized in nephrology wards in Italy have changed in recent years due to the aging Italian population and the increased immigration. We analyzed the demographic and clinical characteristics of patients hospitalized in our nephrology ward (17 beds) from 15 November 2008 to 15 November 2009. In this period there were 507 hospitalizations including 448 patients. The mean age was 64.4+/-18 years (range 16-96 years). Foreigners accounted for 10% of the total; their mean age was significantly lower than that of Italian patients (38.2+/-13.4 vs 67.4+/-15.9 years, p<0.01). 36.3% of patients were on dialysis, 10% were transplant recipients: the reasons for admission in these cases were internal medicine related; 18.15% were hospitalized because of emergency unit crowding without indications for admission to a nephrology ward. Hospitalization lasted a mean of 13+/-13 days. The most frequent diagnosis at discharge was acute renal failure (ARF) (28.9%) (prerenal 42.1%, obstructive 12.2%, drug induced 6.8%, other causes of ARF 38.7%). Patients with ARF were older than patients with other kidney conditions (67.05+/-16.98 vs 56.03+/-18.65 years, p<0.01). ARF resolved or improved in 86 patients (63.7%). Other diagnoses were cardiovascular disease 25.1%, glomerular disease 18.7%, acute pyelonephritis 10.6%, other 16.7%. Foreign patients presented infectionrelated diseases more often than Italian patients (39.2% vs 20.4%, p=0.02). 392 patients were discharged to their homes, 40 (7.9%) found a place in a long-term care facility or home for the elderly, 25 (4.9%) in other hospital units, and 50 patients died (9.8%). In conclusion, patients hospitalized in nephrology wards in 2009 were mostly elderly with a high frequency of cardiovascular disease and diabetes. The most frequent diagnosis was prerenal ARF. These data suggest the necessity of improving the prevention of this type of kidney disease. Moreover, the length of hospitalization, which is increasing because of difficult clinical and social situations, could be shortened if more nursing homes, convalescent homes and homes for the elderly were available in Italy.     

Montelukast, a leukotriene receptor antagonist, in combination with loratadine, a histamine receptor antagonist, in the treatment of chronic asthma

BACKGROUND: Montelukast sodium, a potent, oral, specific leukotriene-receptor antagonist, has demonstrated clinical efficacy in the treatment of chronic asthma. Loratadine, a selective histamine type 1 (H(1))-receptor antagonist, has demonstrated antiallergic properties. Leukotriene-receptor antagonists given concomitantly with H(1)-receptor antagonists have been shown to have additive effects in the prevention of bronchospasm in antigen-challenge models. OBJECTIVE: To determine whether montelukast plus loratadine provides improved efficacy to montelukast alone in the treatment of chronic asthma. METHODS: The efficacy of montelukast alone vs montelukast-loratadine was studied in a 10-week, multicenter, randomized, double-blind, 2 x 2 crossover study. After a 2-week placebo run-in period, patients received montelukast sodium (10 mg) plus loratadine (20 mg), or montelukast sodium (10 mg) plus placebo once daily for 2 weeks. After a 2-week placebo washout period, patients were crossed over to receive 2 weeks of the other active treatment regimen, followed by another 2-week placebo washout period. RESULTS: Montelukast given concomitantly with loratadine caused significant improvement in percentage of change from baseline in forced expiratory volume in 1 second (FEV(1)) compared with montelukast alone (13.86% vs 9.72%; P =.001). The average additional effect of loratadine (least square mean difference in percentage of change from baseline in FEV(1)) was 4.15% (95% confidence interval, 1.65%-6.65%). Key secondary end points (mean daily beta-agonist use, daytime and nighttime symptom scores, morning and evening peak expiratory flow rate, and the Patient Global Evaluation) all showed significant improvement with montelukast-loratadine (P<.05). CONCLUSION: Montelukast-loratadine significantly improved end points of asthma control during a 2-week treatment period.     

Intussusception in a private tertiary-care hospital, Bangkok, Thailand: a case series

This was a retrospective case series study of patients with intussusception at a private tertiary-care hospital in Bangkok, Thailand. The computerized hospital records of all 94 children aged 0-14 years diagnosed with intussusception from 2000 to 2005 were reviewed. About half (51.1%) were males, 23.4% were less than 1 year old. Most (78.7%) were Thai nationals. The highest case frequency was in August (n=12, Poisson means = 7.8, 95% confidence interval 6.3-9.6). Of these, none had the classical triad of vomiting, colicky pain, and mucous bloody stools. Only 12.8% had fever; abdominal mass was detected in 4.3%, and 4.3% had increased bowel sounds, while 34.0% had no specific signs. The most frequent site of intussusception was the ileocolic (62.6%). Stool cultures for bacteria and stool for rotavirus antigen obtained in some cases revealed no significant findings. Of the cases, 10 (10.6%) had spontaneous reduction, 84 (89.4%) underwent barium enema intervention, 10 of the latter (11.9%) required further surgical intervention. There were no mortalities during the observation period. There were 10 recurrent events in this series. The 7-day recurrence-free probability was 84.9% (95% CI 49.2, 96.3%). This study provides baseline data regarding intussusception in Thailand which may be useful for future epidemiological and/or clinical studies.     

Sclerosing mesenteritis, a rare mesenteric disorder, in a patient with ulcerative colitis

A 60-year-old female who had been ill with ulcerative colitis for more than ten years presented with upper abdominal pain. A flare-up of ulcerative colitis was unlikely, because she did not report rectal bleeding, altered bowel habit, and changes of stool form. A poorly defined mass with mild tenderness was palpable in the upper abdomen, with increased levels of serum pancreatic enzymes, leading us to suspect pancreatic disease. Although CT scan revealed no abnormalities in the pancreas, a well-defined, heterogeneous soft tissue mass was found in the small bowel mesentery. Although several different diagnoses were considered, characteristic features on CT strongly supported diagnosis of sclerosing mesenteritis. The symptoms resolved quickly without specific treatment. The mesenteric lesion has never changed and no unfavorable events have yet occurred.     

Eplerenone,a selective aldosterone blocker,in mild-to-moderate hypertension

BACKGROUND: Eplerenone, a selective aldosterone blocker (SAB) that is highly specific for the aldosterone receptor, has the potential to be efficacious in the treatment of hypertension. METHODS: This 8-week, multicenter, double-blind, placebo-controlled trial assessed the efficacy, safety, and tolerability of eplerenone in eligible patients randomized to eplerenone 50, 100, or 400 mg once daily; eplerenone 25, 50, or 200 mg twice daily; spironolactone 50 mg twice daily; or placebo. The primary efficacy variable was the adjusted mean change in baseline to final visit for seated diastolic blood pressure (DBP). RESULTS: Of 417 randomized patients, 409 were evaluated for efficacy. The adjusted mean change from baseline to final visit in seated and standing systolic blood pressure (SBP) and DBP was significantly greater (P < .05) in all eplerenone groups than in the placebo group. The adjusted mean change in 24-h ambulatory blood pressure monitoring (ABPM) measurements of SBP and DBP also documented a 24-h duration significantly greater (P < .05) than placebo in eplerenone-treated patients. For all measurements, the antihypertensive effect of eplerenone increased in a dose-response fashion. Eplerenone (100 mg) reduced BP by 75% compared with spironolactone (100 mg) and had an adverse events incidence rate similar to placebo. No antiandrogenic or progestational effects or clinically relevant safety issues were observed in eplerenone-treated patients. However, one spironolactone-treated patient reported menstrual irregularities. CONCLUSIONS: Eplerenone doses of 50 to 400 mg once daily are well tolerated and effective in reducing BP in patients with mild-to-moderate hypertension during a 24-h period.     

Bupivacaine,a long-acting local anesthetic,in anorectal surgery

Summary The long-acting local anesthetic, bupivacaine, was used in a series of 467 anorectal patients, both inpatients and outpatients. Bupivacaine was found to be safe and effective. Like other local anesthetics, it has none of the operative and postoperative complications frequently associated with general or spinal anesthetics. Its longer duration of action makes it extremely useful in anorectal operations on hospitalized and non-hospitalized patients. The potential hypertensive effects of using epinephrine in the local anesthetic solution appear to be negated by the calming, hypotensive effects of the intravenously administered sedatives in hospitalized patients. Read at the meeting of the American Society of Colon and Rectal Surgeons, San Francisco, California, May 4 to 8, 1975.     

Pancreaticojejunal anastomosis, using a stent tube, in pancreaticoduodenectomy

We report our technique for pancreaticojejunostomy, using a stent tube, and examine the literature with regard to the use of a stent tube in pancreaticojejunostomy. The total number of stitches in the anastomosis of the pancreatic parenchyma and seromuscle layer of the jejunum should be more than 20, and there should be more than 8 stitches in the anastomosis of the pancreatic duct and parenchyma and all layers of the jejunal wall, even in a normal-sized main pancreatic duct. There is no dead space between the cut end of the pancreatic parenchyma and the jejunal wall. None of the 114 consecutive patients who underwent pancreaticoduodenectomy in our series died. We use a stent because this makes it easier to perform anterior wall anastomosis of the pancreaticojejunostomy. It is easy to find the pancreaticojejunal anastomosis at the anterior wall anastomosis. We never stitch the posterior wall of the anastomosis with a stent tube in place at the anterior wall anastomosis. If the anastomosis leaks, the massive flow of pancreatic juice around the anastomosis is prevented because of the pancreatic juice flowing out of the pancreatic tube.     

No deterioration after 13 years in a stability study of a rabbit brain, plain, thromboplastin, RBT 1010, in rubber-stoppered ampoules

RBT 1010, a rabbit brain thromboplastin, plain, was prepared at the Thrombosis Reference Centre, Withington Hospital, Manchester, in 1989. The batch has been stored at -20 degrees C, in rubber-stoppered ampoules, for 13 years. The material was unchanged after this time. This was confirmed in a stability study, in which the reagent was used to test the prothrombin times of a panel of plasmas stored in liquid nitrogen, one from a normal volunteer and two from stable anticoagulated patients. RBT 1010 was also tested in calibrations, according to World Health Organization recommendations, against the reference thromboplastin preparations CRM 149S and RBT 90.     

Effects of enalapril, a new angiotensin-converting enzyme inhibitor, in a controlled trial in heart failure

Angiotensin-converting enzyme inhibitors are effective vasodilators in the treatment of congestive heart failure. Enalapril, a new angiotensin-converting enzyme inhibitor, or placebo, in addition to digoxin and diuretic drugs, were given to 17 patients with chronic congestive heart failure who were followed up for 12 weeks. In random double-blind fashion, nine patients received enalapril and eight received placebo. Cardiac dimensions and function improved slightly but insignificantly in both groups. Treadmill exercise duration increased from a mean value (+/- standard deviation) of 9.1 +/- 3.2 to 12.0 +/- 3.5 minutes during enalapril administration (p less than 0.025) and was unchanged during placebo administration (10.1 +/- 3.7 versus 11.1 +/- 5.2 minutes). Maximal oxygen consumption also increased during enalapril therapy (15.8 +/- 3.4 to 18.4 +/- 4.4 ml/min per kg, p less than 0.05) and remained unchanged during placebo treatment (16.0 +/- 6.4 versus 17.0 +/- 4.6 ml/min per kg). Clinical functional class (Yale scale) improved 3.1 +/- 1.9 points (p less than 0.01) during enalapril treatment but not during placebo treatment (0.8 +/- 3.5 points, no significant difference). No significant side effects were observed. Thus, enalapril appears to be a clinically effective and useful new angiotensin-converting enzyme inhibitor for the management of chronic congestive heart failure.     

Adrenomedullin, a new peptide, in patients with insulinoma

BACKGROUND: It has been demonstrated that adrenomedullin, a newly discovered peptide, affects the release of insulin from pancreatic islets cells, suggesting a role in the insulin-regulating system. OBJECTIVE: To investigate whether adrenomedullin secretion is modified in patients with insulin-secreting islet cell tumours. DESIGN: The study was performed in nine patients with surgically treated insulinoma. Circulating adrenomedullin was assayed using a specific radioimmunoassay and its localization and distribution in the tumour were determined by means of immunohistochemistry. RESULTS: Adrenomedullin concentrations were significantly greater in patients with insulinoma (6.6 +/- 3.2 fmol/ml) than in controls (2.1 +/- 1.1 fmol/ml). In six patients monitored before and after surgery, plasma adrenomedullin decreased from 6.3 +/- 2.9 fmol/ml to 3.0 +/- 1.6 fmol/ml. Immunoreactive adrenomedullin was localized exclusively in the tumours cells, whereas stroma, surrounding pancreas parenchyma and major ducts were negative for the peptide. CONCLUSIONS: Our findings indicate that circulating adrenomedullin is increased in insulinoma and that this increase is related to the neoplastic phenotype.