Safety of Complete and Sustained Prophylaxis Withdrawal in Patients Liver-transplanted for Hepatitis B Virus-related Cirrhosis at Low Risk of Hepatitis B Virus Recurrence.

BACKGROUND: HBV (hepatitis B virus) reactivation after liver transplantation may be related to persistence of covalently closed circular (ccc) DNA. We investigated the safety of HBV prophylaxis withdrawal in selected HBV transplanted patients. METHODS: Thirty patients transplanted 64-195 months earlier (23 males, median age 56 years), HBsAg-positive, HBeAg, and HBV-DNA-negative at transplant (43% HCV/HDV coinfected), with undetectable intrahepatic total and ccc-DNA were enrolled. All patients underwent HBIg withdrawal and continued lamivudine with monthly HBsAg and HBV-DNA monitoring and sequential liver biopsies. Those with confirmed intrahepatic total and ccc-DNA undetect-ability 24 weeks after stopping HBIg also underwent lamivudine withdrawal and were followed up without prophylaxis. RESULTS: Twenty-five patients did not exhibit signs of HBV recurrence after prophylaxis withdrawal (median follow-up 28.7 months, range 22-42). Five patients became HBsAg-positive: one early after HBIg withdrawal, the other four after HBIg and lamivudine withdrawal. None of these patients experienced clinically relevant events. In the first patient, HBIg were reinstituted with prompt HBsAg negativization. Of the other four, one remained HBsAg-positive with detectable HBV-DNA and mild alanine transaminase elevation and was successfully treated with tenofovir. In the remaining three, HBsAg positivity was transient and followed by anti-HBs se-roconversion; thus no antiviral treatment was needed. CONCLUSION: Patients with undetectable HBV viremia at transplant and no evidence of intrahepatic total and ccc-DNA may safely undergo cautious weaning of prophylaxis, showing the low rate of HBV recurrence after a 2-year follow-up. Undetectability of intrahepatic ccc-DNA may help to identify patients at low risk of recurrence; yet studies with longer follow-up are needed.

Neonatal estradiol exposure alters mouse mammary estrogen receptor alpha expression.

The rate of prepubertal ductal morphogenesis as well as the incidence of hyperplastic growth in the adult mouse mammary gland is enhanced by 5 days of neonatal estradiol exposure. It is unknown whether estradiol acts through its nuclear receptor to affect growth in the neonatal gland. Immunohistochemical analysis indicates that estrogen receptor alpha (ER) is present in both the mammary epithelium and stroma before estradiol exposure is initiated at day 1. By 7 days of age, the frequency of ER-positive epithelial and stromal cells is significantly reduced in mammary glands of estradiol-exposed mice compared to controls. Coincident with this decrease in mammary ER is growth inhibition of the estradiol-exposed gland. At day 21, the exposed glands exhibit precocious epithelial outgrowth while significantly fewer stromal cells express ER compared to controls. By day 35, the exposed epithelium fills the fat pad while the exposed stromal cells express significantly more ER. To study the function of mammary ER, we have established mammary epithelial cell lines from oil and estradiol treated mice. Two cell lines from oil-treated and two from estradiol-exposed glands maintain ER expression in culture. Transient transfection of these ER-positive cell lines with a reporter vector containing an estrogen response element (ERE) demonstrates that the immunodetected ER is functional as a transcription factor in response to 100 nM estradiol. The in vitro transcriptional activity in response to estradiol is anti-estrogen sensitive, requires the presence of the ERE, and is independent of neonatal treatment in vivo. Our data indicate that neonatal estradiol exposure alters ER expression and mammary growth, but does not alter ER function.

Plasma creatine kinase responses of 18- to 30-yr-old African-American men to eccentric exercise.

PURPOSE: The primary aim was to describe the response of plasma creatine kinase (CK) activity in a sample of African-American men after a bout of eccentric exercise. The study also described signal intensity changes detected by MR in the musculature of the right lower leg. METHODS: Subjects were 20 male volunteers of African descent (age = 24 +/- 4 [mean +/- SD] yr). Each walked backward for 60 min at 3 km x h(-1) down a 23% grade. Venous blood was sampled before exercise, immediately (0 d) after and 1, 2, 4, and 7 d after exercise for plasma CK assay. Soreness in the plantar flexor muscles was evaluated in 18 subjects at selected times during the 7 d postexercise. Injury to the plantar flexor muscles was evaluated by magnetic resonance imaging (MRI). RESULTS: The subjects had high baseline plasma CK activity (187 +/- 127 IU x L(-1); 163 +/- 70 IU x L(-1) with one outlier excluded) compared with typical clinical norms. As a group, CK activity was increased (P < 0.05) 4 d (980 +/- 1331 IU L(-1)) and 7 d (1022 +/- 1031 IU L(-1)) postexercise, compared with preexercise. Eleven (55%) of the subjects had large, delayed increases in plasma CK activity ("hyperresponses"). As a group, the plasma CK response was similar to responses of comparison Caucasian subjects. All subjects reported delayed muscle soreness; there was no association between soreness and plasma CK. Every subject showed MRI evidence of injury to plantar flexor muscles postexercise but varying in degree and time course. Plasma CK activity correlated to MRI signal intensity (rho = 0.445). CONCLUSION: Results suggest that changes in plasma CK activity and skeletal muscle injury in African-American men after eccentric exercise do not differ from the responses of Caucasians.

Computerized hand diagnostic/rehabilitation system using a force feedback glove.

This paper describes recent results of a unified computerized system for hand diagnosis and rehabilitation. Automatic diagnosis data collection and Virtual Reality rehabilitation exercises are the main characteristics of the system. The diagnosis subsystem includes a tactile sensing glove in addition to standard devices such as electronic dynamometer, pinchmeter and goniometer. Three standard rehabilitation exercises were simulated in a Virtual Reality environment, using the WorldToolKit graphics library. The first two exercises (ball squeezing and DigiKey) allow measurement of finger forces exerted during the rehabilitation routine. The third exercise (Peg board) involves the patient's visual-motor coordination. The rehabilitation subsystem uses a VPL DataGlove retrofitted with Rutgers Master (RM-I) and its interface. The exercises involve manipulation of objects with different stiffnesses and geometry. Grasping forces were modeled and fed back using the Rutgers Master worn on patient's hand. Data is gathered in real time from both diagnosis and rehabilitation subsystems. Finger specific forces recorded during rehabilitation exercises allow better diagnosis of the patient impairment. An ORACLE database is used to store and manipulate patients' records. Proof of concept trials were performed in a clinical environment. Some results of patient records analysis are presented in this paper. A new version of the system using an RM II haptic interface is presently under consideration.

Neurofibromatosis type 1: pathologic substrate of high-signal-intensity foci in the brain.

PURPOSE: To investigate a correlation between pathologic and radiologic findings with regard to the characteristic high-signal-intensity foci seen on long repetition time (TR) magnetic resonance (MR) images of the brain in patients with neurofibromatosis type 1 (NF-1). MATERIALS AND METHODS: Three girls with NF-1 and abnormal hyperintensities on long TR images of the brain underwent pathologic examination at autopsy. RESULTS: Two 10-year-old girls had classic, focal hyperintensities in the internal capsules and globus pallidus regions, which have been associated with NF-1. The third patient, a neonate, had diffuse hyperintensity of the supratentorial and infratentorial white matter on T2-weighted MR images. Findings at histopathologic examination revealed spongiotic change in the tissue sections that correspond to the high-signal-intensity foci demonstrated on T2-weighted images. CONCLUSION: Hyperintense foci seen on T2-weighted MR images appear to correspond to pathologic findings of areas of vacuolar or spongiotic change. The resultant fluid-filled vacuoles explain the occurrence of high signal intensity demonstrated on T2-weighted images.

Solitary cortical tubers.

We report two cases of solitary cortical tubers not associated with tuberous sclerosis and having an appearance simulating neoplasm in two patients presenting with seizures. CT showed solitary, hyperdense frontal lobe lesions in both patients. MR revealed a lesion hyperintense on both T1- and T2-weighted images in one patient and a heterogeneous mass with a target appearance in the other. Histologically, the lesions were consistent with cortical tubers.

A linoleate-enriched cheese product reduces low-density lipoprotein in moderately hypercholesterolemic adults.

OBJECTIVE: To test the effect of substituting a modified-fat cheese product into the diets of hypercholesterolemic adults. DESIGN: A 4-month, randomized, double-blind, crossover substitution trial. SETTING: General community outpatient study. PARTICIPANTS: Twenty-six healthy adult volunteers (17 men, 9 women) with moderate hypercholesterolemia (total cholesterol > 5.69 mmol/L but < 7.24 mmol/L). INTERVENTION: Daily substitution of 100 g of cheese, either partial skim-milk mozzarella or modified-fat (vegetable oil) mozzarella cheese product, into participants' normal diets. Participants consumed an assigned cheese for 2 months, at which time they crossed over to consume the other study cheese. MAIN OUTCOME MEASURES: Plasma lipid and apolipoprotein levels were measured at baseline and at 2 and 4 months after initiation of the study. Compliance was assessed by body weight and by biweekly dietary records and interviews. RESULTS: No differences in weight or in the amount or type of calories consumed were found during the study. No statistically significant changes in lipid values resulted from consumption of mozzarella cheese. Modified-fat cheese substitution resulted in a decreased low-density lipoprotein cholesterol level when compared with levels at both baseline (-0.28 mmol/L; 95% Cl, -0.14 to -0.42 mmol/L) and during consumption of the skim-milk mozzarella cheese (-0.38 mmol/L; 95% Cl, -0.2 to -0.70 mmol/L). Findings for total cholesterol were similar. High-density lipoprotein cholesterol, plasma triglyceride, and apolipoprotein A-l and B-100 levels were unaltered. Both sexes responded similarly. CONCLUSIONS: A linoleate-enriched cheese product, in the absence of any other changes in diet or habits, substituted into the normal diets of hypercholesterolemic adults reduced low-density lipoprotein and plasma cholesterol levels.

A comparative analysis of Giliberty, Bateman, and Universal femoral head prostheses. A long-term follow-up evaluation.

This study compares four different types of bipolar hip prostheses used from 1977 to 1984. The devices studied were the Giliberty I and II hip prostheses, the Bateman I prosthesis, and the Universal Hip Replacement (UHR) prosthesis. The surgical indications for prosthetic hip replacement in all cases were displaced subcapital hip fractures (Garden Types 3 and 4). Postoperative evaluation included D'Aubigne's hip rating system and roentgenograms to assess prosthetic placement, dislocation, disassembly of the components, and the presence of inner and outer bearing motion of the prostheses. Results of the study revealed intact inner bearing motion in all of the devices investigated in the immediate postoperative period. The UHR prosthesis demonstrated a statistically significant lower incidence of dislocation and no incidence of prosthesis disassembly. This study demonstrates the superiority of the bipolar prosthesis when compared to published results of the so-called unipolar prosthesis and also suggests superiority of the design and function of the UHR prosthesis when compared to the Bateman I and Giliberty prostheses. Longer follow-up evaluation is needed to assess the effects of a functioning bipolar prosthesis on acetabular wear.