Push-pull optical pumping of pure superposition states.

A new optical pumping method, "push-pull pumping," can produce very nearly pure, coherent superposition states between the initial and the final sublevels of the important field-independent 0-0 clock resonance of alkali-metal atoms. The key requirement for push-pull pumping is the use of D1 resonant light which alternates between left and right circular polarization at the Bohr frequency of the state. The new pumping method works for a wide range of conditions, including atomic beams with almost no collisions, and atoms in buffer gases with pressures of many atmospheres.

Intense, narrow atomic-clock resonances.

We present experimental and theoretical results showing that magnetic resonance transitions from the "end" sublevels of maximum or minimum spin in alkali-metal vapors are a promising alternative to the conventional 0-0 transition for small-size gas-cell atomic clocks. For these "end resonances," collisional spin-exchange broadening, which often dominates the linewidth of the 0-0 resonance, decreases with increasing spin polarization and vanishes for 100% polarization. The end resonances also have much stronger signals than the 0-0 resonance, and are readily detectable in cells with high buffer-gas pressure.

Mushroom poisoning--from diarrhea to liver transplantation.

Mushroom poisoning from the genus Amanita is a medical emergency, with Amanita phalloides being the most common species. The typical symptoms of nausea, vomiting, abdominal pain, and diarrhea are nonspecific and can be mistaken for gastroenteritis. If not adequately treated, hepatic and renal failure may ensue within several days of ingestion. In this case series, patients poisoned with Amanita virosa are described with a spectrum of clinical presentations and outcomes ranging from complete recovery to fulminant hepatic failure. Although there are no controlled clinical trials, a few anecdotal studies provide the basis for regimens recommended to treat Amanita poisoning. Use of i.v. penicillin G is supported by most reports. Silibinin, although preferred over penicillin, is not easily available in the United States. In those with acute liver failure, liver transplantation can be life saving.

ELISPOT analysis of hepatitis C virus protein-specific IFN-gamma-producing peripheral blood lymphocytes in infected humans with and without cirrhosis.

An improved ability to monitor hepatitis C virus (HCV)-specific T cell immunity in infected patients may provide novel information regarding the pathogenesis and prognosis of this infection. We used an ELISPOT assay to analyze a cross-section of HCV-infected humans. HCV-infected patients without cirrhosis, those with cirrhosis, and controls with other liver diseases were tested for recall responses to HCV Core and NS3 proteins. Peripheral blood lymphocytes (PBLs) from HCV-infected patients without cirrhosis responded to NS3 and Core proteins, producing predominantly IFN-gamma, with little IL-4 or IL-5. In contrast, PBLs from HCV-infected patients with cirrhosis responded to NS3, but not to the Core protein, suggesting a selectively altered immune state during cirrhosis. Our data provide support for the notion that HCV-specific IFN-gamma-producing immunity is important in the pathogenesis of progressing HCV-related disease.

Immune responses to hepatitis C and non-hepatitis C antigens in hepatitis C virus infected and HIV-1 coinfected patients.

OBJECTIVE: To characterize immune phenotype and function in hepatitis C virus (HCV) infection in the presence and absence of HIV-1 infection. DESIGN: Cross-sectional comparison among controls (group A), patients with HCV infection (group B), HCV-HIV-1 coinfected patients (group C), coinfected patients receiving treatment for HIV-1 (group D), and untreated HIV-1 infected patients (group E). METHODS: Flow cytometric analysis for lymphocyte phenotypes, lymphocyte proliferation and cytokine production by ELISPOT. RESULTS: HCV infected patients tended to have an increased percentage of activated (CD38, HLA-DR) CD8 cells (group A, 2+/-1.4%; group B, 6+/-3.9%; P=0.08). Proliferative responses to non-HCV antigens were comparable in group A and group B subjects. A greater proportion of group B patients had stimulation indices (SI) > 3 to the HCV protein NS3 compared to group C and D patients (67%, 0%, and 11% respectively; P < 0.003), but only two patients in group B had SI > or = 5. The SI to NS3 was significantly higher in group B patients [median, 4; interquartile range (IQR), 3-9) than in group C (median, 2; IQR, 1-3; P < 0.04) or group D (median, 1; IQR, 1-4; P < 0.009) patients. Plasma HCV RNA levels correlated directly with alanine aminotransferase levels (p, 0.52; P < 0.05) and inversely with the number of CD4 lymphocytes (rho, -0.55; P < 0.009) and proliferation to NS3 (p, -0.55; P < 0.009). CONCLUSIONS: Lymphocytes of HCV infected patients show weak proliferative responses to HCV antigens while responses to other antigens are preserved. Infection with HIV-1 potentiates this deficiency. Poor CD4 T cell responses to HCV are associated with and may determine the failure to control HCV propagation.

Chronic hepatitis C infection in patients with end stage renal disease: characterization of liver histology and viral load in patients awaiting renal transplantation.

OBJECTIVES: Hepatitis C virus (HCV) is common in patients with end stage renal disease (ESRD) awaiting renal transplantation (RT). However, few data are available on the liver histology and viral titer in these patients relative to patients with HCV and normal renal function. The aims of this study were to assess liver histology, quantitative HCV-RNA titer, and alanine aminotransferase (ALT) levels in patients with ESRD awaiting RT, and to identify clinical predictors of histological progression to advanced bridging fibrosis and/or cirrhosis. METHODS: A total of 50 consecutive patients (mean age 42 yr, 62% male) with ESRD and HCV, who were awaiting RT, underwent liver biopsy. Two HCV populations, one with persistently normal ALT and another with elevated ALT, both with normal renal function, served as controls. HCV-RNA titer was assessed by quantitative PCR. RESULTS: Of the patients with ESRD, 94% had normal ALT. Log HCV RNA titer was significantly higher in patients with ESRD (5.8+/-0.3) than in either normal ALT (5.4+/-0.1) or elevated ALT (5.3+/-0.1) controls (p < 0.05). Knodell Histological Activity Index (HAI) in patients with ESRD was similar to that observed in control patients with normal ALT (4.8+/-0.4 vs 4.9+/-0.4) but significantly less (p < 0.05) than that observed in control patients with elevated ALT (8.4+/-0.5). The percentage of patients with bridging fibrosis or cirrhosis was similar in patients with ESRD and controls with persistently normal ALT (22% vs 13%) but significantly less (p < 0.001) than that observed in control patients with elevated ALT (48%). No significant differences in ALT, HCV-RNA titer, duration on hemodialysis, or time from first possible exposure was observed between ESRD patients with advance fibrosis (n = 11) and those with mild disease (n = 39). CONCLUSIONS: Our data suggest that liver biopsy is necessary to exclude significant liver pathology in patients with HCV and ESRD, and to help define those patients in whom interferon treatment might be helpful.

Resolution of hepatitis B viremia in a renal transplant recipient treated with alpha-2b interferon.

A renal transplant patient developed symptomatic hepatitis after withdrawal from corticosteroids. Tests for hepatitis B e antigen and hepatitis B viral DNA were both positive prior to treatment with 1 million units alpha interferon three times weekly for 3 weeks followed by an increase to 3 million units alpha interferon three times weekly for a total of 16 weeks. At the end of treatment, hepatitis had clinically resolved with conversion to a hepatitis B e antibody positive and hepatitis B e antigen and viral DNA negative state. The renal allograft function remained excellent throughout the course of therapy with interferon.

Resolution of spur cell anemia with liver transplantation: a case report and review of the literature.

Spur cell anemia is an acquired hemolytic anemia, characterized by an increased percentage of abnormally shaped erythrocytes that are known as acanthocytes. The erythrocytes have numerous spicules irregularly distributed over the cell surface. Spur cell anemia has been described to occur in several conditions, including cirrhosis. We present an unusual case of a young patient with hemochromatosis, alcohol abuse, decompensated cirrhosis, and spur cell anemia who had a spontaneous resolution of the spur cell anemia after orthotopic liver transplantation. This finding suggests that the diseased liver may contribute to transformation of the erythrocyte to the spur cell.

Multifocal hepatic lesions in AIDS: an unusual presentation of steatosis.

Patients infected with HIV frequently have abnormal results on liver tests, leading to radiographic evaluation for hepatic lesions. The etiology of these lesions in patients infected with HIV is most often secondary to infections or tumors. Occasionally, focal abnormalities in the liver are identified in asymptomatic patients. The etiology and clinical course in this subset of patients are not known. However, because of concerns of tumor, an evaluation is usually warranted. We report an unusual case of multifocal hepatic steatosis presenting as multiple liver lesions in an HIV-positive patient with cutaneous Kaposi's sarcoma. This case emphasizes the importance of obtaining a tissue diagnosis in this patient population.

Clinical variables associated with colorectal cancer on colonoscopy: a prediction model.

OBJECTIVES: We prospectively evaluated the ability of various indications for colonoscopy to predict colorectal cancer. METHODS: Indications and findings were prospectively recorded for 1223 consecutive colonoscopies performed during an 18-month period at a University Hospital. Colonoscopies performed on 981 patients for indications which included colorectal cancer in the differential diagnosis were included in the study. A group of 653 patients was randomly selected to derive a model predictive of colorectal cancer at colonoscopy; the remaining 328 patients were used to validate the model. RESULTS: Colorectal cancer was found in 44/981 patients (4.5%). Univariate analysis of the derivation set showed that age > 55, occult bleed, anemia, iron deficiency, weight loss, and abnormal CT scan were associated with finding colorectal cancer at colonoscopy in the derivation set, p < 0.05. History of polyps was negatively associated with finding colorectal cancer. Stepwise selection was used to develop a predictive model by using three independent variables-age > 55, iron deficiency, and weight loss. Assigning a score of 1 to each variable, cancer was present in 0% [95% confidence intervals (CI), 0-0.6%], 5.3% (95% CI, 2.3-8.3%), and 17.9% (95% CI, 4.8-31%) of patients in the validation sample with a score of 0, 1, and > or = 2, respectively (p < 0.001 by chi2 for trend). The model was predictive of finding colorectal cancer at colonoscopy, independent of the location or stage of the cancer. CONCLUSIONS: Age, iron deficiency, and weight loss are important independent predictors of colorectal cancer in patients referred for colonoscopy.

Risk of extraesophageal malignancy in patients with adenocarcinoma arising in Barrett's esophagus.

OBJECTIVES: It has been suggested that the presence of Barrett's mucosa is a marker for potential malignancy in other organs. Our objective was to study subjects with adenocarcinoma of the esophagus arising in Barrett's epithelium. METHODS: We reviewed the medical records of patients with esophageal adenocarcinoma, with esophageal squamous cell carcinoma, and with no esophageal pathology and recorded the occurrence of extraesophageal malignancies and the heavy use of tobacco and alcohol. RESULTS: The prevalence of extraesophageal malignancies was not higher in patients with esophageal adenocarcinoma (15%) than in patients in either control group (14% each). Patients with either type of cancer of the esophagus had higher rates of tobacco and alcohol use than normal controls (tobacco: p = 0.02 and p < 0.01 for adenocarcinoma and squamous cell carcinoma, respectively, vs. normal controls; alcohol: p < 0.01 for each esophageal malignancy vs. normal controls). The rate of tobacco and alcohol use was higher in patients with esophageal squamous cell carcinoma than in those with adenocarcinoma, but only the difference in alcohol consumption was statistically significant (p < 0.01). CONCLUSION: Patients with adenocarcinoma of the esophagus are not at higher risk for development of extraesophageal malignancy. This observation applies to both those with and without underlying Barrett's epithelium. Alcohol and tobacco use appear to be related to the malignant transformation of esophageal epithelium.

Cytochrome P-450 levels of immature rat ovaries during early follicular development: quantification, cellular and subcellular distribution, enzymatic activity and response to FSH in vivo and in vitro.

Absolute values of cytochrome P-450 (cyt. P-450) content were determined by dual beam spectrophotometry in mitochondrial and microsomal fractions of granulosa cells and stroma (theca and interstitial cells) obtained from ovaries of immature rats treated with diethylstilbestrol (DES) or with DES and FSH. Cholesterol side-chain cleavage activity and aromatase activity were also measured in relevant cell fractions. The cyt. P-450 content in the granulosa cell mitochondria was significantly increased in FSH-treated animals (cyt.P-450 in nmols/mg protein, mean +/- SE: DES-treated 0.027 +/- 0.00213, N = 9; DES/FSH-treated 0.0668 +/- 0.0120, N = 13, P = 0.014). The increased cyt. P-450 content was associated with an increase in cholesterol side-chain cleavage activity confirming the functional relevance of the spectrophotometric measurements. The increase in cyt. P-450 content in stroma after FSH treatment was not statistically significant but there was a significant increase in cholesterol side-chain cleavage activity. The cholesterol side-chain cleavage activity of intact granulosa cells from secondary follicles of DES-treated rats was significantly stimulated by in vitro exposure to FSH during 2 hr assay incubations. A significant cyt. P-450 content was detected in the microsomal fraction of granulosa cells from DES-treated rats which was not associated with aromatase activity. Granulosa cell microsomal cyt. P-450 content was not significantly altered by in vivo FSH treatment despite a dramatic increase in aromatase activity of such microsomal preparations.

Colectomy in patients with inflammatory bowel disease and primary sclerosing cholangitis.

PURPOSE: The aim of this study was to assess risk factors for early postoperative death in patients with primary sclerosing cholangitis who are undergoing colectomy. METHODS: The charts of 24 patients with primary sclerosing cholangitis who underwent colectomy between 1972 and 1990 at the Cleveland Clinic Foundation were reviewed. Clinical and laboratory data were collected and compiled to determine preoperative factors that might be helpful in predicting early postoperative death. RESULTS: The only factor that predicted a poor outcome was cirrhosis at the time of surgery. Three of 8 patients with cirrhosis and 0 of 16 patients without cirrhosis had an early postoperative death (P < 0.05, Fisher's exact test). CONCLUSION: We conclude that establishing whether or not patients with inflammatory bowel disease and primary sclerosing cholangitis have cirrhosis is helpful in determining the risk of colectomy.

Prevalence of colonic neoplasia in patients with Barrett's esophagus.

Recent reports have suggested that there might be an increased risk of colonic adenomas and cancer in patients with Barrett's esophagus. We conducted a controlled prospective study investigating the risk of colonic neoplasia in 17 patients with Barrett's esophagus. Six additional patients with previous colonoscopy were considered separately. The prevalence of colonic neoplasia in these patients was compared with that in a group of 25 asymptomatic subjects participating in a screening colonoscopy study. There were three adenomas (17.6%) in the Barrett's group and 11 (44%) in the control group. Including the six Barrett's patients with previous colonoscopy, the rate was 30.4%. No cancers were found in either group. We conclude that the rate of colonic adenomas is no higher in a group of patients with Barrett's esophagus than in a group of matched asymptomatic subjects. The presence of Barrett's esophagus does not justify a special colonoscopic surveillance program.

Crohn's disease of the gallbladder.

In a 57-year-old woman, Crohn's disease involving the gallbladder and duodenum caused biliary tract obstruction and necessitated surgery. The patient's symptoms did not improve postoperatively until corticosteroids provided rapid resolution. Inflammatory bowel disease often involves the hepatobiliary tree, yet the gallbladder is rarely involved directly. This patient highlights a rare complication of Crohn's disease.

Acute colonic pseudo-obstruction associated with interleukin-2 therapy.

In this case report, we present a patient with metastatic gastric carcinoma who developed massive colonic dilatation during treatment with recombinant interleukin-2. The spectrum of gastrointestinal symptomatology associated with interleukin-2 therapy is broad. However, colonic pseudo-obstruction, to our knowledge, has never before been reported. We review therapy for colonic pseudo-obstruction and a proposed mechanism of interleukin-2 toxicity. We report this case to heighten awareness of the potential for the development of this complication in patients undergoing interleukin-2 immunotherapy.