PubMed Health⌕ Search

Biomedical subjects

H W Hann

Publications and source records attributed to H W Hann.

At least 19 recordsLinked to original sources

Biological aspects of neuroblastomas identified by mass screening in Quebec.

BACKGROUND: Neuroblastoma has several characteristics that suggest that preclinical diagnosis might improve outcome. Therefore, the Quebec Neuroblastoma Screening Project was undertaken from 1989 to 1994 to examine infants at 3 weeks and 6 months by measuring urinary catecholamine metabolites. PROCEDURE: Over the 5-yr period, 45 tumors were detected by screening, 20 were identified clinically prior to the third week, and 64 were identified clinically at a later time. We analyzed available tumors for Shimada histopathology, tumor ploidy, MYCN copy number and serum ferritin. RESULTS: Of the tumors detected by screening, only 2 of 45 tested had unfavorable histology, 2 of 45 had diploid or tetraploid DNA content, 0 of 43 had MYCN amplification, and 4 of 44 had elevated serum ferritin. All of these patients are alive and well. The 20 patients detected prior to the 3-week screen had similar biological characteristics. In contrast, of the patients detected clinically after 3 weeks of age, 19 of 51 testedhad unfavorable histology, 25 of 66 had diploid or tetraploid tumors, 12 of 56 had MYCN amplification, and 14 of 54 had elevated ferritin. CONCLUSIONS: The difference between the screened and clinically detected cases was highly significant for each biological variable. Preliminary data on other biological variables, such as neurotrophin expression and allelic loss on 1 p in these patients are consistent with the above findings. These data suggest that mass screening for neuroblastoma at or before 6 months of age detects almost exclusively tumors that have favorable biological characteristics, many of which might have regressed spontaneously. Thus, continued mass screening for neuroblastoma at 6 months is unlikely to accomplish its intended goal, and should probably be discontinued.

Age Factors↗

A multicenter study of lamivudine treatment in 33 patients with hepatitis B after liver transplantation.

Hepatitis B virus (HBV) infection after liver transplantation (LT) may lead to severe and rapidly progressive graft failure. Antiviral treatment may be of benefit in selected patients with recurrent hepatitis B post-LT. The aim of this prospective open-label study is to determine the safety and efficacy of lamivudine in 33 liver transplant recipients with active HBV infection. The median time from LT to study enrollment was 51 months, all patients were hepatitis B surface antigen positive, and 75% and 94% of subjects had detectable hepatitis B e antigen (HBeAg) and HBV DNA at entry, respectively. The median duration of lamivudine treatment on study was 85 weeks, during which time median HBV DNA levels became undetectable by 16 weeks and 9% of patients lost previously detectable HBeAg. Serum alanine aminotransferase (ALT) levels improved in most patients and normalized in 27% of patients with elevated values pretreatment. Serum bilirubin and albumin levels significantly improved in patients with abnormal values at entry (P <.05). Virological breakthrough was detected in 13 subjects after a median of 61 weeks of lamivudine treatment and was confirmed to be caused by YMDD mutants in all patients tested. None of the patients with virological breakthrough showed a complete loss of clinical response to lamivudine. Serum ALT and bilirubin levels in patients with and without virological breakthrough were not significantly different at last study follow-up. Study results show that lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B. However, the high rate of virological breakthrough with prolonged therapy indicates the need for further studies of combination antiviral therapy in this patient population. Our results and others further establish the improving long-term outcomes with LT for patients with hepatitis B through advances in prevention of reinfection, as well as the availability of safe and effective antiviral therapies to treat patients with HBV recurrence.

Adult↗

Lamivudine as initial treatment for chronic hepatitis B in the United States.

BACKGROUND AND METHODS: Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). RESULTS: Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs. 16 percent, P<0.001), and sustained normalization of serum alanine aminotransferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. CONCLUSIONS: In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were generally sustained after treatment.

Adolescent↗

Hepatocellular carcinoma: association with increased iron deposition in the cirrhotic liver at MR imaging.

PURPOSE: To determine whether the frequency of hepatocellular carcinoma (HCC) in patients with cirrhosis is affected by hepatic iron deposition as detected with magnetic resonance (MR) imaging. MATERIALS AND METHODS: In a retrospective search of MR imaging and histopathology records, 196 patients with histopathologically proved cirrhosis and with (n = 80) or without (n = 116) HCC who underwent T2-weighted conventional or fast spin-echo and gradient-echo (GRE) (echo time > or = 6.0 msec) imaging were identified. MR images were qualitatively and quantitatively evaluated for diffuse hepatic iron deposition and siderotic regenerative nodules to assess their correlation with the presence of HCC. RESULTS: Hepatic parenchymal iron deposition was seen in 79 (40%) patients, and iron deposition in regenerative nodules was seen in 71 (36%) at MR imaging. The mean signal intensity ratio of GRE images in patients with hepatic iron deposition was significantly lower than that in patients without it (P < .001). The frequency of HCC in patients with iron deposition in regenerative nodules (52% [37 of 71 patients]) was significantly higher (P = .015) than that in patients without iron in regenerative nodules (34% [43 of 125 patients]). CONCLUSION: The occurrence of HCC may be associated causally with iron deposition in regenerative nodules in patients with cirrhosis. MR imaging can enable detection of iron deposition in regenerative nodules as a possible risk factor for the development of HCC.

Adult↗

Viral-induced cirrhosis: grading of severity using MR imaging.

OBJECTIVE: The purpose of this study was to determine whether MR imaging can be used to grade the severity of cirrhosis. MATERIALS AND METHODS: The MR examinations of 46 patients with cirrhosis were retrospectively reviewed independently by two radiologists and correlated with clinical severity assessed by Child-Pugh classification. MR imaging analysis by reviewers who were unaware of clinical status included comparison of volume indexes (computed as the product of three axis measurements) of the spleen and each segment of the liver, and changes in hepatic contour, iron or fat deposition, and presence of varices and collaterals. RESULTS: Volume index of the spleen and the presence of ascites and varices were significantly and positively correlated (p = .008, .002, .0001, respectively) with the clinical severity of cirrhosis (Child-Pugh classifications), and volume indexes of the posterior, medial, and lateral segments of the liver were significantly and inversely correlated (p = .001, .049, .041, respectively). On an MR scoring system based on four items (volume index of the spleen; volume index of posterior + medial + lateral segments; presence of ascites; and presence of varices and collaterals), averaged total MR scores were 2.5 +/- 0.3, 4.9 +/- 0.6, and 7.9 +/- 0.8 for Child-Pugh grades A, B, and C, respectively (p < .0001). The accuracy of MR scoring in distinguishing between clinical Child-Pugh grade A cirrhosis and further grades was 89%, the sensitivity was 93%, and the specificity was 82%. CONCLUSION: An MR scoring system can be used to grade the severity of cirrhosis.

Contrast Media↗

Interferon-alpha2b therapy is efficacious in Asian-Americans with chronic hepatitis B infection: a prospective controlled trial.

Chronic hepatitis B virus infection is endemic in Asian communities in the United States. The purpose of the current study was to compare the antiviral efficacy of interferon-alpha2b in a group of adult Asian patients chronically infected with hepatitis B with active replication compared to a control group of Caucasian patients treated with the same regimen. Patients with entry aminotransferase (ALT) levels greater than three times the upper limit of normal received interferon-alpha2b, 5 million units, subcutaneously daily for 16 weeks. Patients with pretreatment ALT levels 1.5-3 times the upper limit of normal received prednisone for a total of six weeks prior to interferon starting at 60 mg daily with reduction in dosage by 20 mg every two weeks with a two-week period between finishing prednisone and starting interferon-alpha2b. Eight (62%) of the 13 Asians and six (60%) of the 10 Caucasians cleared HBeAg and HBV DNA from serum (NS). By the end of one year of follow-up after therapy, four (67%) of six Caucasian responders but none of the Asian responders had cleared hepatitis B surface antigen from serum (P < 0.05). Loss of serum markers of active replication appeared less durable in the Asian responders compared to the Caucasians with reappearance of serum HBeAg in two (25%) of eight of the former but only one (17%) of the latter group. Three other Asian patients subsequently redeveloped HBeAg in serum. It is concluded that adult Asian-Americans have an identical initial response rate to antiviral therapy with interferon-alpha2b; however, the response may be less durable and does not usually lead to loss of HBsAg.

Adult↗

Progressive viral-induced cirrhosis: serial MR imaging findings and clinical correlation.

PURPOSE: To determine which magnetic resonance (MR) imaging findings of cirrhosis change as disease severity progresses. MATERIALS AND METHODS: Seventy-six abdominal MR imaging studies in 38 patients (two per patient) with Child-Pugh grade A cirrhosis were retrospectively reviewed. All patients were followed up clinically and with MR imaging for 12 months or longer. MR images were used to determine volume indexes of the spleen and of each liver segment, as well as changes in hepatic contour, iron or fat deposition, and presence of varices and collateral vessels. RESULTS: During follow-up in patients with progressive cirrhosis (n = 13), the volume indexes of the anterior, posterior, and medial segments of the liver decreased significantly (P = .011, .013, .002, respectively), and the number of varices and collateral vessels increased significantly (P = .018). In patients with stable cirrhosis (n = 25), the volume indexes of the spleen, caudate lobe, and lateral segment increased significantly (P = .032, .018, .003, respectively). The atrophic index was significantly greater in progressive cirrhosis than in stable cirrhosis (P = .009). CONCLUSION: Progressive atrophy of the right hepatic lobe and the medial segment correlated with progression of clinical severity of cirrhosis, whereas increasing size of the caudate lobe and the lateral segment correlated with stability.

Adult↗

Compensated cirrhosis due to viral hepatitis: using MR imaging to predict clinical progression.

OBJECTIVE: The goal of our study was to determine the relative value of multiple MR features in predicting clinical progression of disease in patients with compensated cirrhosis. MATERIALS AND METHODS: The MR examinations of 23 patients with compensated cirrhosis (Child A) were retrospectively reviewed independently by two radiologists and correlated with clinical progression after follow-up of all patients for more than 12 months each (12-87 months: average, 39 months) by the same experienced hepatologist. Clinical progression was defined as an increase of the Child grade or the Pugh score by at least two points (5- to 15-point scale). In the initial MR study of each patient, the following MR findings were assessed by each radiologist independently: volume indexes of the spleen and each segment of the liver (based on three-axis measurements), nodular surface, regenerative nodules, ascites, iron or fat deposition, and varices or collaterals. RESULTS: The volume index of the spleen was the most accurate predictor of clinical progression (p = .001), the next most accurate was the number of sites of varices or collaterals (p = .002), and the third most accurate was the ratio of caudate lobe to right lobe volume index (p = .02). Other MR findings failed to correlate with clinical progression. CONCLUSION: As revealed on MR imaging, the volume index of the spleen, the severity of varices, and the volume index ratio of caudate lobe to right lobe can be used to help predict clinical progression of disease in patients with compensated cirrhosis.

Adult↗

Early hepatocellular carcinoma that develops within macroregenerative nodules: growth rate depicted at serial MR imaging.

PURPOSE: To assess by means of magnetic resonance (MR) imaging the growth rate of early hepatocellular carcinoma (HCC) that develops within macroregenerative nodules. MATERIALS AND METHODS: Serial MR imaging was performed in five patients with six macroregenerative nodules that demonstrated a "nodule-within-nodule" pattern (small intranodular focus). The diameter and volume increases of the internal foci at different time intervals were estimated. Average doubling time (DT) was then calculated. RESULTS: The tiny foci within macroregenerative nodules exhibited rapid growth, with average DTs of 29 weeks for diameter and 9.5 weeks for volume. HCC was proved histopathologically in all five patients. CONCLUSION: HCC, which manifests initially as a small focus within a macroregenerative nodule, has the potential for rapid growth. This growth rate should be considered when plans are formulated for follow-up and/or treatment.

Aged↗

Rapid development of lymphoma following liver transplantation in a recipient with hepatitis B and primary hemochromatosis.

We report a case of a posttransplant lymphoproliferative disorder (PTLD) which presented in a liver allograft shortly after transplantation. The patient, who had been transplanted because of cirrhosis due to primary hemochromatosis and chronic hepatitis B infection (HBV), developed early recurrent HBV in the graft, and 2 months after transplantation, liver biopsies showed a malignant large-cell lymphoma. The neoplastic cells demonstrated Epstein-Barr virus DNA by in situ hybridization. The patient died 3.5 months posttransplant due to liver failure. At autopsy, the liver showed nodules of malignant lymphoma, massive hepatic necrosis, and iron overload, but no evidence of rejection. This report suggests that the grafted liver can be the site of PTLD in recurrent HBV and hemochromatosis.

Adult↗

Antitumor effect of deferoxamine on human hepatocellular carcinoma growing in athymic nude mice.

BACKGROUND: Iron is essential for the growth of all living cells. One of the important intracellular roles for iron is in the activation of ribonucleotide reductase, the enzyme that catalyzes the first step in DNA synthesis. Thus, the intracellular iron level may serve as a regulator of cell growth. The authors tested the hypothesis that lowering body iron concentration inhibits the growth of human-derived hepatocellular carcinoma (HCC) cells by depleting these cells of iron. Deferoxamine (DFO), an iron-chelating agent, was used to lower intracellular iron level. METHODS: HCC cells, PLC/PRF/5 (7 x 10(6) cells/mouse), were transplanted subcutaneously into athymic nude mice. When tumors reached 200-300 microliters in size, mice with comparable tumor sizes were paired; one was treated with DFO (300 mg/kg body weight/day, 5 days/week) intraperitoneally while the other received no treatment. RESULTS: Eight pairs of mice with HCC were observed for 5-18 weeks. Mean tumor growth rates (TGR) (mean +/- standard error) for the untreated and treated mice were 30.5 +/- 3.7 microliters/week and 11.9 +/- 1.5 microliters/week. The difference was significant (P < 0.02). In the second set of studies, DFO treatment was begun when the tumor size was smaller (100-200 microliters). Four pairs of mice were observed for 4-15 weeks; mean TGR for the four untreated mice was 18.1 +/- 5.1 microliters/week. In two mice treated with DFO, tumors regressed completely by the seventh week after initiation of treatment. The two remaining mice on DFO therapy had much slower growing tumors, with a mean TGR of 1.8 +/- 0.5 microliters/week. CONCLUSIONS: Thus, our results suggest that (1) reduction of intracellular iron concentration by DFO may be useful as antitumor therapy in HCC and (2) the favorable effects of DFO treatment are best seen when treatment is begun when the tumor is small.

Animals↗

Mass-like hepatic hypertrophy: MRI findings with histologic correlation.

Hepatic parenchyma may hypertrophy following asymmetrical injury. The histologic characteristics of hypertrophic hepatic parenchyma are more similar to normal hepatic parenchyma than is the more severely damaged liver. We present four cases where large hypertrophic masses resembled neoplasm on other imaging modalities or at surgery, but had MRI signal characteristics similar to those of normal liver.

Adult↗

Iron enhances tumor growth. Observation on spontaneous mammary tumors in mice.

Iron is essential for the growth of all cells, including tumor cells. The authors previously reported that a variety of transplantable tumors grew faster and larger in mice that were on an iron-rich diet compared with those on an iron-deficient diet. In this study the authors examined the relationship between iron in the diet and development of tumors in mice that are known to develop spontaneous tumors--C3H/HeN-MTV+(C3H-MTV+) mice that were congenitally infected with mammary tumor virus. These mice have a greater than 96% chance of developing mammary tumors between the ages of 7.2 and 9.2 months. Fifteen C3H-MTV+ weanlings were given a low-iron diet (5 mg iron/kg diet), and 15 were given diets with normal amounts of iron (180 mg Fe/kg diet). Thirteen of the 15 mice from the low-iron group and all 15 mice from the normal-iron group developed tumors. The average tumor growth rate in the normal-iron group was 112%/wk, compared with 62%/wk for the low-iron group. The difference in tumor growth rate between the two groups was significant (P = 0.02 by Student's t test). In this study, low iron intake did not prevent tumor development, but the results confirm the authors' previous report that iron nutrition of the host affects tumor growth; tumors grow better in an iron-rich environment. High levels of iron in the diet may enhance tumor growth, and this should be considered when treating patients with cancer.

Animals↗

Chromosome abnormalities in peripheral blood cells of hepatitis B virus chronic carriers.

Cytogenetic analysis of metaphase chromosome spreads from peripheral blood cells of hepatitis B virus (HBV) chronic carriers and HBV-negative individuals of the same ethnic origin revealed a significantly higher incidence of chromosome breaks and other mitotic aberrations in the HBV chronic carriers. The highest incidence of chromosome breaks was found in chronic carriers who evidenced circulating HBV. Such an association between HBV and these genetic lesions assumes importance in light of the known correlation between HBV chronic carrier status and the high risk of hepatocellular carcinogenesis, where a mutagenic effect of HBV cannot be excluded.

Carcinoma, Hepatocellular↗

Parenchymal versus reticuloendothelial iron overload in the liver: distinction with MR imaging.

Parenchymal iron deposition occurs in hemochromatosis, while iron is deposited in reticuloendothelial (RE) cells after blood transfusions or rhabdomyolysis. Magnetic resonance images of patients with decreased liver signal intensity on T2-weighted images at 1.5 T were blindly compared in an effort to distinguish these conditions. In each of five patients with hemochromatosis, the pancreas had low signal intensity, but splenic signal intensity was decreased in only one. In contrast, only three of the 16 patients with RE iron overload had low pancreatic signal intensity, while all of these patients either had low splenic signal intensity (n = 14) or previously underwent splenectomy (n = 2). Distinction among these causes of iron deposition is clinically important because parenchymal iron overload from hemochromatosis may produce significant tissue damage, while the RE iron of transfusions and rhabdomyolysis is of little clinical consequence.

Adolescent↗

Prognostic importance of serum transferrin and ferritin in childhood Hodgkin's disease.

The relationship of iron-binding proteins to prognosis was studied in 50 children at the Children's Hospital of Philadelphia, newly diagnosed with Hodgkin's disease (HD). There were five patients with Stage I, 18 with Stage II, 14 with Stage III, and 13 with Stage IV. Initial serum ferritin, transferrin, iron, hemoglobin (Hb), erythrocyte sedimentation rate (ESR), and A or B symptoms were analyzed for their association with progression-free survival (PFS). There was a linear increase of mean and median ferritin levels and a decrease of mean and median transferrin levels with advancing stages. Also, there was a significant inverse correlation between ferritin and transferrin (P less than 0.001). In univariate analyses, high ferritin (greater than 142 ng/ml) (P = 0.02) and low transferrin (less than or equal to 250 mg/dl) (P = 0.008) were significantly associated with poor PFS. Serum iron, Hb, ESR, and A or B symptoms were not associated with PFS. Stepwise proportional hazards regression analysis of all factors showed that transferrin was the only factor significantly associated with PFS. These preliminary results suggest that serum transferrin can also be used as a prognostic factor in addition to serum ferritin and that it may be helpful to assay both serum ferritin and transferrin as prognostic factors in childhood HD. Further testing of large groups of patients is needed to determine whether they are independent of tumor bulk and other established prognostic factors.

Adolescent↗

Effect of iron and desferoxamine on cell growth and in vitro ferritin synthesis in human hepatoma cell lines.

To investigate the effects of iron supplementation on hepatoma cell growth, cells from a human hepatoma cell line, PLC/PRF/5, were grown in RPMI 1640 supplemented with 0, 10 and 20 micrograms/ml of FeSO4 and harvested weekly. At the end of 6 wk culture, cell mass measured 9.6, 14.7 and 13.2 gm, respectively. Amounts of ferritin from these cell masses were 0 (undetectable), 0.89 and 2.27 micrograms/gm of cells. To study the effects of iron deprivation of hepatoma cells, three human hepatoma cell lines (PLC/PRF/5, Hep G2 and Hep 3B) were incubated in tissue culture medium mixed with graded amounts of an iron-chelating agent, desferoxamine, for 48 to 96 hr at 37 degrees C with 5% CO2. Over 50% cell death in PLC/PRF/5 cells and 30% to 50% cell death in Hep G2 and Hep 3B cells were observed 48 to 72 hr after exposure to desferoxamine. Addition of ferric citrate partially reversed the cytotoxic effect of desferoxamine. On the other hand, viability of control cells, human diploid cell line (WI 38), was not affected by desferoxamine. Even after 96 hr exposure to desferoxamine, cell death was only 2% to 4%. These results suggest that (a) iron enhances tumor cell growth, (b) iron induces increased ferritin synthesis by tumor cells in vitro and (c) iron depletion causes tumor cell death but has little effect on normal human diploid cells. These findings should be considered when designing treatment of patients with hepatoma. Iron oversupply in patients with cancer might enhance tumor growth and adversely affect cancer therapy. Iron chelation with desferoxamine might have a place in the treatment of patients with hepatoma in conjunction with other anticancer agents.

Antineoplastic Agents↗