Clonally related penicillin-nonsusceptible Streptococcus pneumoniae serotype 14 from cases of meningitis in Salvador, Brazil.

Active hospital-based surveillance in the city of Salvador, Brazil, from December 1995 through October 1998, identified 221 patients with confirmed pneumococcal meningitis. Of these 221 patients, 29 (13%) had isolates with intermediate-level resistance to penicillin. Infection with these penicillin-nonsusceptible isolates was significantly associated with age of <2 years (P<.0019), previous antibiotic use (P<.0006), and coresistance to trimethoprim-sulfamethoxazole (P<.0000). Serotype 14 was the most prevalent serotype (55.2%) of penicillin-nonsusceptible isolates. Strain typing by repetitive element BOX polymerase chain reaction (PCR) analysis showed that penicillin-nonsusceptible serotype 14 isolates had closely related BOX PCR patterns, whereas penicillin-susceptible serotype 14 isolates each had distinct, unrelated patterns. Penicillin-nonsusceptible serotype 14 isolates from Salvador and other Brazilian cities had similar BOX PCR patterns. These observations indicate that in Brazil a large proportion of cases of penicillin-nonsusceptible pneumococcal meningitis appear to be caused by a closely related group of serotype 14 strains that may have disseminated to widely separate geographic areas.     

Role of epinephrine in the development of hypertension in Dahl salt-sensitive rats

The present experiments were designed to test the hypothesis that adrenal epinephrine contributes to the development of hypertension in the Dahl salt-sensitive (DS) rat. All studies were carried out in conscious male DS and Dahl salt-resistant (DR) rats weighing 200-240 g. An indwelling femoral arterial catheter was placed for blood sampling and measurement of blood pressure. After 5 days of either a high salt (7% NaCI) or a normal salt (1% NaCl) dietary regimen, DS and DR rats were subjected to an acute stress paradigm (graded electrical footshock). There were no differences in basal plasma catecholamine concentrations or in the acute pressor responses to graded footshock between the four substrain/diet groups. However, in both DS and DR rats, plasma epinephrine responses to acute footshock were greater on a 7% than on a 1% NaCl diet. Additional groups of DS rats were treated with an inhibitor of adrenal phenylethanolamine N-methyltransferase, SK&F 29,661 (1-2 g/kg body wt/day) or with vehicle. Three days after placement of an arterial catheter, rats were placed on a 7% NaCl diet, and blood pressure was measured daily for an additional 3 weeks. Although SK&F 29,661 treatment was effective in reducing adrenal epinephrine content and apparent release by approximately 80%, treatment did not alter the time course of salt-induced changes in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lithium chloride: protective and antisecretory properties in rats

Lithium chloride was evaluated as a potential protective agent against ethanol-induced hemorrhagic gastritis in rats. Rats received lithium chloride intragastrically (30, 60, or 90 mg/kg i.g.) or subcutaneously (3, 5, 10, 15, 20, 30, 60, or 90 mg/kg s.c.), or a placebo (H2O i.g. or 0.9% NaCl s.c.). Ninety minutes later 1 cm3 of 95% ethanol was administered intragastrically. After 30 min, the rats were killed and their stomachs were removed and visually scored for gross hemorrhagic gastritis. Lithium chloride at all doses less than 3 mg/kg significantly improved hemorrhagic gastritis when compared with the placebo. Moreover, rats treated with lithium chloride intragastrically had significantly less hemorrhagic gastritis than those treated subcutaneously even though serum lithium levels were similar. To determine if lithium's protective properties related to acid inhibition, pylorus-ligated and gastric fistula rats were studied. The median effective dose for lithium chloride was 20-30 mg/kg and the nonantisecretory dose was 3 mg/kg. No difference in hemorrhagic gastritis was noted between controls and animals receiving the nonantisecretory dose. However, at higher doses (LiCl 30, 60, and 90 mg/kg), lithium's protective properties persisted in spite of adding 150 mM HCl to the intragastrically administered ethanol (p less than 0.001). To determine further if lithium chloride stimulated endogenous prostaglandins, indomethacin, a prostaglandin inhibitor, was administered. Indomethacin did not alter lithium chloride's protective properties. In fact, when compared with exogenously administered 16,16-dimethyl prostaglandin E2 (5 and 500 micrograms/kg), high-dose LiCl (30, 60, or 90 mg/kg) resulted in significantly more protection against ethanol-induced injury (p less than 0.001). In contrast, when both nonantisecretory doses were compared, 16,16-dimethyl prostaglandin E2 (5 micrograms/kg) gave significantly better protection than LiCl (3 mg/kg). These data indicate that LiCl is a potent gastric antisecretory and protective agent. The protective properties of LiCl appear to be related to acid inhibition and be independent of endogenous prostaglandins, although other protective mechanisms may be present at higher LiCl doses. Additionally, this study indicates that LiCl may have clinical application in protecting the gastric mucosa against hemorrhagic gastritis.     

Effects of beta-blocker therapy on ventilatory responses to exercise in patients with heart failure

BACKGROUND: Ventilatory efficiency is the increase in ventilation relative to carbon dioxide production during exercise. Congestive heart failure (CHF) is associated with decreased ventilatory efficiency. beta-blockers improve hemodynamics, prolong survival, and improve functional class in patients with CHF, though peak exercise performance may not improve. We hypothesized beta-blockers increase ventilatory efficiency in patients with CHF. METHODS AND RESULTS: The study group comprised 614 subjects with left ventricular ejection fraction < or = 40% referred for cardiopulmonary exercise testing. Clinical and exercise data were reviewed and recorded. For comparison, subjects were divided into those treated with beta-blockers (n = 195) and those not treated (n = 419). Subjects on beta-blockers had lower minute ventilation (12 +/- 4 versus 14 +/- 4 L/min, P < .001) at rest, which remained lower during submaximal and maximal exercise, by 4 and 6 L/min, respectively (P = .001). Ventilatory efficiency was increased in subjects treated with beta-blockers at submaximal (32 +/- 6 versus 34 +/- 7, P = .002) and maximal (34 +/- 7 versus 37 +/- 10, P = .005) exercise. Differences between treatment subgroups remained significant by covariate analysis; beta-blockers were also independently associated with decreased minute ventilation by multiple regression. CONCLUSION: Beta-blockers may be associated with increased ventilatory efficiency in CHF patients, which may contribute to improved functional class and quality of life.     

The ETO domain is necessary for the developmental abnormalities associated with AML1-ETO expression in the hematopoietic stem cell compartment in vivo

Translocation of the ETO gene on human chromosome 8 with the AML1 gene on chromosome 21 (AML1-ETO) is a recurrent cytogenetic abnormality associated with approximately 12% of acute myelogenous leukemia (AML) cases. To understand the contribution of the t(8;21) to AML, we transduced purified hematopoietic stem cells (HSC) with a retroviral vector that coexpressed AML1-ETO or just the AML1 portion (AML1d) of the translocation along with a green fluorescent protein reporter gene. Animals reconstituted with AML1-ETO-expressing cells exhibited many of the hematopoietic developmental abnormalities seen in the bone marrow of human patients with the t(8;21), although the animals did not develop acute leukemia. We noted a gradual increase in primitive myeloblasts that accounted for approximately 10% of bone marrow by 10 months posttransplant. Consistent with this observation was a 50-fold increase in myeloid colony-forming cells in vitro. In addition, accumulation of late stage metamyelocytes was observed in bone marrow along with an increase in immature eosinophil myelocytes that showed abnormal basophilic granulation. There was also a gradual increase in both the frequency and absolute number of AML1-ETO-expressing HSC so that by 10 months posttransplant, there were 29-fold greater HSC numbers than in transplant-matched control mice. These phenotypes were not observed in animals reconstituted with cells expressing only the DNA-binding domain of AML1, suggesting that the ETO domain is necessary to establish the developmental abnormalities associated with AML1-ETO expression in HSC.     

Renal ultrasonographic correlates of acute pyelonephritis.

To determine the frequency and clinical significance of ultrasonographically detectable alterations in renal volume and anatomy that are associated with acute pyelonephritis, 25 women underwent renal ultrasonography during the acute phase of their illness, and 21 of these patients underwent the procedure after receiving antimicrobial therapy. One patient had a predisposing anatomic abnormality (4%; 95% confidence interval, 0-12%), and one patient each (8%; 95% confidence interval, 0-19%) experienced focal complications (an intrarenal mass and perinephric fluid collection). The kidneys of the 21 evaluable patients were acutely swollen (mean, 20%; P = .0001); one or both kidneys were enlarged by greater than or equal to 15% in 17 (81%). Acute renal enlargement was associated with protracted pretherapy symptoms (P less than .01), leukocytosis (P less than .01), focal infectious complications (P less than .01), and prolonged hospitalization (P less than .05). Thus, ultrasonographically demonstrable renal swelling characteristically occurs in women with acute pyelonephritis but is usually apparent only in retrospect. The degree of swelling correlates with selected clinical parameters, and the frequency of underlying anatomic abnormalities and focal infectious complications is low.     

Effects of aminoglutethimide on luteinizing hormone and steroid secretion, and ovulation in the hen, Gallus domesticus

Two experiments were conducted: 1) to assess the ovulation-blocking ability and steroidogenesis-inhibiting activity of aminoglutethimide in the laying hen; and 2) to determine whether LHRH or progesterone (P4) administration can overcome the ovulation-blocking effect of aminoglutethimide. Aminoglutethimide inhibited ovulation and suppressed the secretion of P4 and testosterone (T) in a dose-related fashion. In the absence of any increase in plasma P4 and T, there was no preovulatory increase in plasma LH. These results indicate that the preovulatory surge of LH is initiated by an increase in steroid. The effectiveness of P4 and LHRH to stimulate LH release and overcome the ovulation-blocking effect of aminoglutethimide was tested in the second experiment. Administration of 500 micrograms P4 (im) to aminoglutethimide-treated hens resulted in a significant and sustained release of LH [peak, 3.08 +/- 0.62 (+/- SEM) ng/ml; 120 min after injection] and induced ovulation in the absence of any increase in plasma T or estrogen. In contrast, injection of 20 micrograms LHRH (iv) failed to overcome the blocking effect of aminoglutethimide and caused an attenuated (peak, 2.17 +/- 0.37 ng/ml; 60 min after injection) and short-lived increase in plasma LH. These results are consistent with the model for a true positive feedback mechanism in which P4 initiates and sustains the preovulatory LH surge of the hen.     

Pain on common bile duct injection during ERCP: does it indicate sphincter of Oddi dysfunction?

The reproduction of a patient's biliary-type pain upon initial injection of contrast material into the common bile duct during diagnostic ERCP is a dramatic experience for both patient and physician. The significance of this phenomenon is not clear, but it is touted by some to be a provocative test for sphincter of Oddi dysfunction. Sphincter of Oddi manometry was performed on 224 consecutive patients referred over a 2-year period for evaluation of post-cholecystectomy syndrome and suspected sphincter of Oddi dysfunction. All patients received only intravenous diazepam as premedication for ERCP. Delayed drainage time (greater than 45 min), bile duct dilation (greater than or equal to 12 mm), and a basal sphincter of Oddi pressure of greater than 40 mm Hg (mean +/- 3 SD) were considered elevated. We observed a reproduction of pain in 15 of 224 patients (6.7%) immediately following contrast injection. There was no correlation between pain on contrast injection and elevated basal sphincter of Oddi pressure, delayed common bile duct drainage, bile duct dilation, or abnormal liver enzymes. Therefore, we feel that reproduction of the patient's biliary-type pain associated with contrast injection of ERCP is not a provocative test for sphincter of Oddi dysfunction.     

An assessment of the management of acute bleeding varices: a multicenter prospective member-based study

OBJECTIVE: Bleeding from esophagogastric varices is a major complication of portal hypertension. Despite recent practice guidelines for the management of bleeding esophageal or gastric varices, the widespread application of these measures by gastroenterologists has not been evaluated. The purpose of this study was to continue the concept of membership-based research within diverse practice settings by expanding the American College of Gastroenterology (ACG) GI Bleeding Registry to assess the management and outcome of acute variceal bleeding. METHODS: All ACG members (domestic and foreign) were invited to participate during the 1997 Annual Fall meeting and by mail. Data were collected over 12 months. Information obtained included physician training, practice demographics, patient demographics, disease etiology and severity, clinical presentation, medications, transfusion needs, therapy, complications, and rebleeding within 2 wk. RESULTS: A total of 93 physicians/centers (79.6% domestic, 26.9% university and affiliated, 3.2% Veterans Affairs) participated. Complete demographic data were available for 725 of the 741 patients enrolled with index bleeding. The median age of these 725 patients was 52 yr and 73.3% were male. The most common single etiology for portal hypertension was cirrhosis (94.3%). The most common causes of cirrhosis were alcohol (56.7%), hepatitis C virus (30.3%), and hepatitis B virus (10.0%). Hemodynamic instability was noted in 60.7% of the patients (22.3% tachycardic, 9.7% orthostatic, 28.7% hypotensive). Index interventions included banding (40.8%; median five bands), sclerotherapy (36.3%), combination banding/sclerotherapy (6.2%), octreotide (52.6%; median 3 days), balloon tamponade (5.5%), transjugular intrahepatic portosystemic shunt (TIPS) (6.6%), liver transplantation (1.1%), surgical shunt (0.7%), and embolization (0.1%). Transfusion of packed red blood cells, fresh frozen plasma, and platelets was given in 83.4%, 44.7%, and 24.6% of the patients with index bleeding, respectively. Median transfusion was four units of packed red blood cells, three units of fresh frozen plasma, and 1.5 units of platelets. Rebleeding occurred in 92 of the 741 patients (12.6%) at a median of 7 days (mean 11 days) and was treated by banding (18.5%; median six bands), sclerotherapy (30.4%), octreotide (63%; median 2 days), balloon tamponade (17.4%), TIPS (15.2%), and surgical shunt (3.3%). Complications from the index bleeding and rebleeding within 2 wk included ulceration (2.6%, 2.2%), aspiration (2.4%, 3.3%), medication side effects (0.8%, 0%), dysphagia (2.3%, 0%), odynophagia (2.2%,0%), encephalopathy (13%,17.4%), and hepatorenal syndrome (2.4%, 2.2%), respectively. After the index bleeding, 46.2% of patients were treated with beta-blockers and 8.2% with nitrates. The majority of patients with index bleeding had Child's B cirrhosis (61.5%). Patients presenting with recurrent bleeding had mostly Child's B (46.7%) or Child's C cirrhosis (44.6%). The overall short-term mortality after index bleeding was 12.9%. CONCLUSIONS: Acute variceal hemorrhage occurs more often in patients with Child's B and C cirrhosis. Endoscopic banding is the most common single endoscopic intervention. Adjunctive pharmacotherapy is prevalent acutely and after stabilization. Both morbidity and mortality may be lower than reported in previous studies.