CMOS Amperometric Instrumentation and Packaging for Biosensor Array Applications.

An integrated CMOS amperometric instrument with on-chip electrodes and packaging for biosensor arrays is presented. The mixed-signal integrated circuit supports a variety of electrochemical measurement techniques including linear sweep, constant potential, cyclic and pulse voltammetry. Implemented in 0.5 µm CMOS, the 3 × mm(2) chip dissipates 22.5 mW for a 200 kHz clock. The highly programmable chip provides a wide range of user-controlled stimulus rate and amplitude settings with a maximum scan range of 2 V and scan rates between 1 mV/sec and 400 V/sec. The amperometric readout circuit provides ±500 fA linear resolution and supports inputs up to ±47 µA. A 2 × 2 gold electrode array was fabricated on the surface of the CMOS instrumentation chip. An all-parylene packaging scheme was developed for compatibility with liquid test environments as well as a harsh piranha electrode cleaning process. The chip was tested using cyclic voltammetry of different concentrations of potassium ferricyanide at 100 mV/s and 200 mV/s, and results were identical to measurements using commercial instruments.

Challenge model for Helicobacter pylori infection in human volunteers.

BACKGROUND: A reliable challenge model is needed to evaluate Helicobacter pylori vaccine candidates. METHODS: A cag pathogenicity island negative, OipA positive, multiple antibiotic susceptible strain of H pylori obtained from an individual with mild gastritis (Baylor strain 100) was used to challenge volunteers. Volunteers received 40 mg of famotidine at bedtime and 10(4)-10(10) cfu of H pylori in beef broth the next morning. Infection was confirmed by (13)C urea breath test ((13)C-UBT), culture, and histology. Eradication therapy was given four or 12 weeks post challenge and eradication was confirmed by at least two separate UBTs, as well as culture and histology. RESULTS: Twenty subjects (nine women and 11 men; aged 23-33 years) received a H pylori challenge. Eighteen (90%) became infected. Mild to moderate dyspeptic symptoms occurred, peaked between days 9 and 12, and resolved. Vomitus from one subject contained >10(3) viable/ml H pylori. By two weeks post challenge gastric histology showed typical chronic H pylori gastritis with intense acute and chronic inflammation. The density of H pylori (as assessed by cfu/biopsy) was similarly independent of the challenge dose. A minimal infectious dose was not found. Gastric mucosal interleukin 8 levels increased more than 20-fold by two weeks after the challenge. CONCLUSION: Challenge reliably resulted in H pylori infection. Infection was associated with typical H pylori gastritis with intense polymorphonuclear cell infiltration and interleukin 8 induction in gastric mucosa, despite absence of the cag pathogenicity island. Experimental H pylori infection is one of the viable approaches to evaluate vaccine candidates.

Antibiotic-resistant H. pylori infection and its treatment.

Helicobacter pylori infection causes progressive damage to gastric mucosa and results in serious disease such as peptic ulcer disease, MALT lymphoma, or gastric adenocarcinoma in 20% to 30% of patients. The current approach is to make a firm diagnosis, give combination antibiotic and antisecretory therapy, and confirm that the infection has been cured 4 to 6 weeks later. Antimicrobial resistance is largely responsible for treatment failures. Resistance to metronidazole can frequently be overcome by increasing the dose and duration of treatment with acid suppression. Clarithromycin is the most effective antibiotic against H. pylori but, unfortunately, resistance to it is increasing and can not be overcome by increasing the dose or duration of therapy with clarithromycin. The choice of therapy should be based on local susceptibility patterns. Re-treatment regimens for treatment failure should exclude antibiotics where acquired resistance is expected (i.e., clarithromycin and possibly metronidazole). Where available, treatment failure should prompt endoscopy and culture and susceptibility testing. Overall, higher doses and longer durations of treatment result in the best cure rates. When multiple treatment regimens fail, salvage therapy regimens such as bismuth or furazolidone quadruple therapy (a bismuth and tetracycline HCl 4 times a day along with a proton pump inhibitor twice a day, and either metronidazole 400 or 500 mg three times daily or furazolidone 100 mg three times daily for 14 days) can be used. Newer agents are needed to cope with the increasing prevalence of antibiotic resistance among H. pylori.

Intrahepatic cholestatic syndromes: pathogenesis, clinical features and management.

Intrahepatic cholestasis is characterized by a decrease in bile flow in the absence of overt bile duct obstruction, resulting in the accumulation of bile constituents in the liver and blood. Various etiological factors have been incriminated including drugs, total parenteral nutrition, sepsis, pregnancy, graft-versus-host disease and systemic disorders such as sarcoidosis, amyloidosis and Hodgkin's disease. The pathogenesis of cholestasis is unclear and several mechanisms have been hypothesized, without convincing evidence that any of these play a role in clinical cholestasis. Despite the uncertainty about the pathophysiology of intrahepatic cholestasis, several forms of therapy have been employed. Ursodeoxycholic acid may relieve pruritus and lethargy, and in some cases may modify disease progression. If cholestasis persists, supportive therapy is important to maintain optimal physical and nutritional well-being. In patients with advanced liver disease associated with hepatocellular failure, liver transplantation is the only viable option.

Long-term endoscopic management of variceal bleeding.

Recurrent hemorrhage from esophageal varices is a major source of morbidity and mortality in patients with portal hypertension. Esophageal sclerotherapy (EST) and more recently esophageal band ligation (EVL) can obliterate varices in 3-6 treatment sessions. Multiple band ligators make the use of overtubes unnecessary and make the procedure faster and more tolerable for the patient. EVL has several advantages, including fewer complications, fewer treatment sessions to obliteration, lower rebleeding rates, and lower mortality as compared to EST; the other advantages of EVL make it the treatment of choice for bleeding varices and long term management. The recommendations and rational for long term EST and EVL are presented and combination therapy and EUS guided EVL are discussed.

Diagnosis and management of Helicobacter pylori infection.

Helicobacter pylori infects more than half of the world's population, making it one of the most prevalent infections. H pylori is now accepted as the most common cause of histologic gastritis and is responsible for the majority of cases of peptic ulcer disease and gastric cancer. Approximately 1 in 6 (17%) persons with H pylori infection will develop peptic ulcer disease, and each year 1% to 2% of these will experience a major or life-threatening complication, such as bleeding, perforation, or gastric outlet obstruction. Peptic ulcer disease should no longer be regarded as a chronic, recurring, lifelong disease, but rather as a curable infectious disease. The diagnosis and therapy of this common infectious disorder have become increasingly straightforward. In this article, we discuss the possible outcomes of long-standing infection, the various diagnostic tests available, including whom and when to test, and the combination drug regimens approved for cure.

Systemic ehrlichiosis presenting as progressive hepatosplenomegaly.

A 42-year-old white man had headache, fever, chills, abdominal pain, nausea and vomiting, night sweats, and dark urine for 3 days before admission; he had history of a tick bite 6 weeks earlier. Progressive systemic deterioration, heralded by progressive hepatosplenomegaly and pancytopenia, occurred despite doxycycline therapy. Subsequent recovery was preceded by progressive resolution of hepatosplenomegaly. Progressive hepatosplenomegaly has not been previously reported in association with systemic monocytic ehrlichiosis.

Acute bleeding from peptic ulcers. How to restore hemostasis and prevent recurrence.

Prompt resuscitation is the cornerstone in management of acute upper gastrointestinal bleeding. Endoscopy has become the diagnostic procedure of choice because it offers the chance for hemostatic therapy. For patients in whom endoscopy reveals actively bleeding peptic ulcers or nonbleeding peptic ulcers or nonbleeding ulcers with visible vessels, endoscopic therapy decreases the likelihood that the patient will bleed further, require surgery, or die. Patients with critical illnesses requiring intensive care should receive prophylaxis against stress ulcers. Long-term management of bleeding peptic ulcer disease includes educating patients to quit smoking, avoid non-steroidal anti-inflammatory drugs, and comply with maintenance therapy with a histamine2 receptor antagonist.

An unusual complication of paracentesis.

Paracentesis is an important and commonly performed procedure in patients with ascites. It is a safe procedure when carried out in the midline below the umbilicus, with a complication rate of less than 1%. We report an instance in which a large midline varix was entered during paracentesis. The utility of different imaging techniques in detecting such anomalies in the portal hypertensive patient with portal hypertension and ascites is discussed. The approach and management of this complication are outlined.