Poorly conserved ORFs in the genome of the archaea Halobacterium sp. NRC-1 correspond to expressed proteins.

MOTIVATION: A large fraction of open reading frames (ORFs) identified as 'hypothetical' proteins correspond to either 'conserved hypothetical' proteins, representing sequences homologous to ORFs of unknown function from other organisms, or to hypothetical proteins lacking any significant sequence similarity to other ORFs in the databases. Elucidating the functions and three-dimensional structures of such orphan ORFs, termed ORFans or poorly conserved ORFs (PCOs), is essential for understanding biodiversity. However, it has been claimed that many ORFans may not encode for expressed proteins. RESULTS: A genome-wide experimental study of 'paralogous PCOs' in the halophilic archaea Halobacterium sp. NRC-1 was conducted. Paralogous PCOs are ORFs with at least one homolog in the same organism, but with no clear homologs in other organisms. The results reveal that mRNA is synthesized for a majority of the Halobacterium sp. NRC-1 paralogous PCO families, including those comprising relatively short proteins, strongly suggesting that these Halobacterium sp. NRC-1 paralogous PCOs correspond to true, expressed proteins. Hence, further computational and experimental studies aimed at characterizing PCOs in this and other organisms are merited. Such efforts could shed light on PCOs' functions and origins, thereby serving to elucidate the vast diversity observed in the genetic material.

Role of transesophageal echocardiography in the evaluation of patients with retinal artery occlusion.

OBJECTIVE: To evaluate the role of transesophageal echocardiography (TEE) in detecting cardiac and thoracic aortic sources of retinal emboli. DESIGN: Retrospective observational case series. PARTICIPANTS: The study population consisted of 18 patients who were initially seen with retinal artery occlusion (7 central, 11 branch) and underwent TEE as part of the systemic evaluation. INTERVENTION: All patients underwent TEE, consisting of complete two-dimensional and Doppler color flow examinations. TEE was done immediately after transthoracic echo (TTE) examination. The medical records were reviewed. MAIN OUTCOME MEASURE: Detection of a possible cardiac or thoracic aortic source of retinal embolus. RESULTS: Cardiac or thoracic aortic pathologic conditions, which were a possible source of the retinal emboli, were detected by TEE in 13 of the 18 patients (72%). They included aortic arch atheroma (n = 7), mitral annulus calcification (n = 4), left atrial appendage thrombus (n = 2), valvular abnormalities (n = 5), left atrial smoke (n = 3), and patent foramen ovale (n = 3). In 11 patients (61%), at least one cardiac or aortic source of emboli detected by TEE was missed by TTE. Significant carotid artery disease (>or=40% stenosis) was present in 3 of 16 patients (17%). CONCLUSIONS: TEE is a potentially useful modality for detecting possible sources of retinal artery emboli and may be considered as an adjunct to the routine evaluation of affected patients.

Relationship between Helicobacter pylori CagA status and colorectal cancer.

OBJECTIVES: Infection with Helicobacter pylori, particularly with strains positive for CagA protein, increases the risk of gastric adenocarcinoma. Few studies have explored the possible association between H. pylori infection and colorectal cancer. This study evaluated whether the seroprevalence of CagA in H. pylori-infected patients affected risk for colorectal cancer independently of H. pylori status. METHODS: In this study, we tested serum IgG antibodies against H. pylori (ELISA) and CagA protein (Western blot assay) in 67 patients with colorectal adenocarcinoma, 36 with gastric adenocarcinoma, 47 with other malignancies (cancer controls), and 45 hospitalized for transesophageal echocardiography (TEE controls). Colonic cancer and gastric cancer patients with H. pylori infection were compared to each control group and to the pooled controls using simple and adjusted analyses. RESULTS: H. pylori infection was noted in 50 colon cancer patients, 31 gastric cancer patients, 31 cancer controls, and 32 TEE controls. In all, 41 (82%), 29 (94%), 11 (35%), and 13 (41%), respectively, of these H. pylori-positive sera expressed CagA reactivity (p < 0.001 for all pairwise comparisons between cases and controls). In the adjusted analysis, infection with H. pylori CagA+ compared to H. pylori CagA- was associated with increased risk for colorectal adenocarcinoma (odds ratio = 10.6; 95% CI = 2.7-41.3; p = 0.001) and gastric adenocarcinoma (odds ratio = 88.1; 95% CI = 6.3-1229.2; p = 0.001). CONCLUSIONS: Among patients infected with H. pylori, CagA+ seropositivity is associated with increased risk for both gastric and colonic cancer. This finding should stimulate additional research into the role of cagA+ H. pylori infection in the development of colorectal cancer.

Relevance of CagA positivity to clinical course of Helicobacter pylori infection in children.

A potential virulence determinant of Helicobacter pylori is the cagA gene product. To determine the relevance of the expression of CagA to the clinical picture and outcome of H. pylori infection in children, we examined 104 consecutive children diagnosed with H. pylori infection. Serum samples were collected to test for the presence of immunoglobulin G (IgG) anti-CagA antibodies. Forty-five patients (43%) had antibodies to the CagA protein (group I), and 59 did not (group II). Seropositive patients had a longer prediagnostic history of abdominal pain (P = 0.02), more severe abdominal pain (defined as ulcer pain) (P = 0.05), a higher prevalence of duodenal ulcer (38 versus 7%; P<0.01), more active chronic gastritis (82 versus 32%; P<0.001), and a higher titer of serum IgG anti-H. pylori antibodies (P<0.001). Ninety percent of the patients were monitored for 27+/-18 months. On multivariate analysis, CagA-negative patients had a 3.8-fold-higher chance of achieving a disease-free state than CagA-positive patients (95% confidence interval, 1.5- to 9.5-fold). We conclude that infection with CagA-producing strains of H. pylori is a risk factor for severe clinical disease and ongoing infection.

Prediction of mortality in patients with bacteremia: the importance of pre-existing renal insufficiency.

Pre-existing renal insufficiency serves as a common risk factor in the development of acute renal failure. Acute renal failure is a common finding in patients with bacteremia and is associated with poor prognosis. A total of 2722 consecutive patients 18 years old or older, fulfilling strike criteria of bacteremia or fungemia were prospectively evaluated to establish the prognostic importance of pre-existing renal insufficiency in bacteremic patients. They were classified according to serum creatinine levels upon admission into three groups. 915 patients had normal creatinine levels (< or = 1.0 mg/dL), 1528 had mild to moderate renal failure (creatinine 1.1-3 mg/dL) and 279 patients had severe renal failure upon admission (creatinine > 3.0 mg/dL). Mild to severe renal failure upon admission was associated with old age, male gender, diabetes mellitus, ischemic heat disease, hypertension and congestive heart failure. The serum albumin in patients with severe renal failure was significantly low, with a mean of 2-9 mg/dL. Urinary tract infections were more prevalent in patients with mild to severe renal failure, while intravenous line infections, bacterial endocarditis and soft and skin tissue infections were more common in patients with normal renal function. In the 279 patients with severe renal failure the mortality rate was significantly higher (50%) compared to patents with mild to moderate renal failure and patients with normal renal function (21% and 26% respectively, p = 0.0001). Multiple regression analysis revealed that pre-existing serum creatinine > 3 mg/dL was significantly associated with death attributable to bacteremia (OR = 1.7, 95% CI 1.0-2.7). In conclusion, adult bacteremic patients with pre-existing serum creatinine above 3 mg/dL upon admission are at increased risk of mortality due to bacteremia than patients with normal or mild to moderate renal failure.

Fecal and oral shedding of Helicobacter pylori from healthy infected adults.

CONTEXT: Helicobacter pylori commonly infects humans; however, its mode of transmission remains unknown. OBJECTIVE: To determine how humans-the primary host for H pylori-shed the organism into the environment. DESIGN: Controlled clinical experimental study conducted from February through December 1998. SETTING: Clinical research unit of a hospital in northern California. PATIENTS: Sixteen asymptomatic H pylori-infected and 10 uninfected adults. INTERVENTION: A cathartic (sodium phosphate) and an emetic (ipecac) were given to all infected subjects and an emetic was given to 1 uninfected subject. MAIN OUTCOME MEASURE: Confirmed H pylori isolates cultured from stool, air, or saliva before and after catharsis and emesis and from vomitus during emesis. Isolates were fingerprinted using repetitive extragenic palindromic (REP) polymerase chain reaction and species identity was confirmed by sequencing the 16s ribosomal RNA gene. RESULTS: All vomitus samples from infected subjects grew H pylori, often in high quantities. Air sampled during vomiting grew H pylori from 6 (37.5%) of the 16 subjects. Saliva before and after emesis grew low quantities of H pylori in 3 (18.8%) and 9 (56.3%) subjects, respectively. No normal stools and only 22 (21.8%) of 101 induced stools grew the organism, although 7 (50.0%) of 14 subjects had at least 1 positive culture (2 stool culture samples were contaminated by fungus and were not included). Fingerprints of isolates within subjects were identical to one another but differed among subjects. No samples from uninfected subjects yielded H pylori. CONCLUSIONS: Helicobacter pylori can be cultivated uniformly from vomitus and, occasionally, from saliva and cathartic stools. The organism is potentially transmissible during episodes of gastrointestinal tract illness, particularly with vomiting.

Acute stroke after coronary angiography associated with protruding mobile thoracic aortic atheromas.

We describe two patients who developed acute embolic stroke immediately after coronary catheterization for unstable angina. Transesophageal echocardiography (TEE) and spiral CT of the chest revealed protruding floating atheromas within the aortic arch. These cases of stroke immediately after coronary catheterization suggest that protruding floating atheromas of the thoracic aorta place patients at risk for stroke. TEE or CT might predict a risk of stroke in such patients.

Effect of ammonia starvation on hydroxylamine oxidoreductase activity of Nitrosomonas europaea.

A technique for detection of the activity of hydroxylamine oxidoreductase (HAO) involving denaturing SDS-polyacrylamide gels was developed. The activity of HAO of Nitrosomonas europaea was assayed using this technique, which revealed a single active band of 140 kDa. The HAO activity of other ammonia-oxidizers was also resistant to SDS, the molecular weights being identical to that of N. europaea. N. europaea cells starved of ammonia for up to 72 h retained a considerable amount of HAO, as detected on Western blot analysis, and a significant level of its activity, as found on assaying at the end of the starvation period. Only after 4 h incubation of starved N. europaea cells with 2.0 mM ammonia was some increase in the HAO level observed. The results indicate that HAO remains highly stable during ammonia starvation of N. europaea.

Candida tropicalis multifocal endophthalmitis as the only initial manifestation of pacemaker endocarditis.

PURPOSE: To document a case of Candida tropicalis endophthalmitis as the only manifestation of pacemaker endocarditis. METHODS: We examined a 75-year-old man with diabetes mellitus who was initially examined for bilateral multifocal endophthalmitis complicating endocarditis 2 years after a permanent pacemaker for sick sinus syndrome was implanted. RESULTS: Transesophageal echocardiography showed a large vegetation with a 3-cm diameter attached to the pacing electrode in the right ventricle. Six consecutive blood cultures grew C tropicalis. CONCLUSIONS: Ocular involvement, including multifocal endophthalmitis, may occur as the only manifestation of C tropicalis endocarditis, complicating an intravenous permanent pacemaker.

Double-blind randomized study of 1 g versus 2 g intravenous ceftriaxone daily in the therapy of community-acquired infections.

In a multicentre, double-blind, randomized study involving four general hospitals in Israel, the efficacy and safety of ceftriaxone 1 g/day i.v. was compared to that of 2 g/day i.v. in the treatment of moderate to severe community-acquired infections requiring hospitalization. Two hundred and twenty-two patients were enrolled; 112 received intravenous ceftriaxone 1 g/day, and 110 received 2 g/day. The two groups were matched demographically, and their mean APACHE II score (10 points) and mean duration of successful therapy (7 days) were identical. The sites of infection in the 1 g and 2 g groups respectively were lower respiratory tract in 57 versus 51 patients, urinary tract in 31 versus 40 patients, and soft tissue in 24 versus 19 patients. There were no significant differences in clinical outcome between the 1 g and 2 g groups, the outcome being cure in 91% versus 86% of patients, improvement in 3% versus 3% of patients, failure in 3% versus 8% of patients, and relapse in 3% versus 3% of patients. The findings of this study indicate that ceftriaxone 1 g/day is as effective as 2 g/day in the treatment of moderate to severe community-acquired infections. The low-dose form is a more economical means of treating these infections.

Pelger-Huët anomaly mimicking 'shift to the left'.

A case report is presented of an 83-year-old male patient with respiratory distress, body temperature of 38.5 degrees C, bilateral white infiltrates on chest X-ray and ECG showing acute myocardial infarction. Clinical evaluation led to the suspicion of severe infection accompanying lung congestion due to the infarction, mostly because his white blood cell differential count showed a persistent severe 'shift to the left'. Re-examination of his blood smear showed that the 'shift to the left' did not consist of band forms but of a 'Pelger-Huet' anomaly of the granulocytes. Recognition of this anomaly in the light of rapid clinical and radiological improvement precluded the administration of antibiotics for the diagnosis of severe infection with pulmonary involvement, which responded to diuretic therapy alone.

Management of congestive heart failure: neuroendocrine approach.

The term heart failure is a complex of clinical syndromes caused by "neuroendocrine" compensatory responses that are renal, neural, hormonal and hemodynamic in nature. Activation of these multiple systems--as a result of renin, angiotensin II and the action of circulatory catecholamines--causes the release of norepinephrine vasopressin and aldosterone. These responses contribute to the arteriolar constriction and salt and water retention that promote central pooling with an increase in pre- and afterload of the already failing heart, causing deterioration of the congestive heart failure (CHF). Therapy for this clinical syndrome is aimed at reducing both pre- and afterload with vasodilators, which produce a profoundly favorable effect on left ventricular performances. Beta blocking agents, which inhibit the increased sympathetic mediated vasoconstriction, up-regulate beta receptors and thus restore responsiveness to the failing heart. Inotropic agents, such as digitalis and amrinone/milrinone are reserved for patients with dilated failing heart and impaired systolic function; recently a synthetic atrial natriuretic factor has been developed for potential use in CHF. Ultrafiltration is also used in refractory preoperative CHF with cardiac abnormalities. Neuroendocrine responses to CHF are treated today directly by improving central hemodynamic imbalance in these patients.

Seven years of left ventricular pacing due to malposition of pacing electrode.

The case report is presented of a patient in whom an uncomplicated left ventricular transvenous pacing produced right bundle branch block (RBBB). A diagnostic echocardiography, confirmed by cine cardiovascular computed tomography, showed that there was no rupture of the right ventricle and diagnosed a left ventricular pacing, due to malposition of the pacing electrode. The patient was treated with aspirin and dipyridamole during the last 6 years of follow-up, without any complications, including 1 year of pacing, prior to admission.