Autoimmune hepatitis: a study of 50 patients.

INTRODUCTION: Autoimmune hepatitis (AIH) is a well-defined entity in the West but there are sparse Indian data on this disease. AIM: To study the clinical profile and response to treatment of Indian patients with AIH. METHODS: This is a part retrospective and part prospective study of 50 patients (median age 48 years, range 11-82; 43 women) seen between 1995 to 2001, diagnosed to have AIH as per the revised scoring system. Clinical and laboratory profile, response to treatment, and complications of treatment were analyzed. RESULTS: AIH accounted for 6% of all patients with liver disease seen during the period. The presenting symptoms were gastrointestinal in 43 and non-gastrointestinal in 7, with median symptom duration of 6 months (range 2 weeks to 40 years). Forty patients (80%) had chronic liver disease. Associated illnesses were present in 28 patients. Twenty-six patients were classified as definite and the rest as probable AIH. Forty-nine patients had Type 1 AIH. Five patients had overlap syndrome. Forty-five patients (90%) received immunosuppressive therapy. Twelve of 18 patients receiving only prednisolone and 21 of 27 patients receiving prednisolone and azathioprine combination responded. Thirteen (26%) patients had therapy-related complications (infectious 5, non infectious 8) with two treatment-related deaths. CONCLUSION: Type 1 AIH was the predominant type of AIH. The majority of patients with AIH presented with chronic liver disease. There was good response to immunosuppressive therapy. Therapy-related complications occurred in one-fourth of patients.     

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

Differences in the abilities of human tau isoforms to promote microtubule assembly.

Three isoforms of human tau protein were compared for their abilities to induce microtubule assembly. The three isoforms, tau 3 (tau containing three microtubule-binding domains), tau 4 (tau containing four microtubule-binding domains) and tau 4L (tau containing four microtubule binding domains plus a 58-amino-acid insert near the N-terminus) were expressed in E. coli and purified using ammonium sulfate precipitation, ion exchange, and size exclusion chromatography. All three isoforms induced microtubule assembly at micromolar concentrations and showed similar critical concentrations for assembly of 0.4-0.45 microM. However, tau 4 induced microtubule formation at a rate five- to tenfold faster than either tau 3 or tau 4L. The rate of microtubule elongation seen with tau 4 was twofold greater than with tau 3 or tau 4L, suggesting that the faster rate of microtubule assembly seen with tau 4 was due, at least in part, to faster elongation. Tau 4 induced a greater number of microtubules to form at steady state than did tau 3 or tau 4L. The microtubules generated with each tau isoform had similar steady-state length distributions and were equally susceptible to cold-induced disassembly. These results indicate that the additional microtubule-binding domain in tau 4 enhances microtubule assembly, while the 58-amino-acid insert negates the stimulatory effect of the fourth microtubule-binding domain.     

Subacute cutaneous lupus erythematosus during PUVA therapy for psoriasis: case report and review of the literature

Lesions typical of subacute cutaneous lupus erythematosus developed in an elderly woman after 6 months of PUVA (8-methoxypsoralen and longwave ultraviolet light) therapy for psoriasis. Pancytopenia, antibodies to double-stranded DNA, and hypocomplementemia developed concurrently with the appearance of the cutaneous lesions. With discontinuation of photochemotherapy, the cutaneous lesions disappeared and the pancytopenia improved.     

Theory-based predictors of condom use among university students in the United States and South Africa.

This study compared the predictive value of the theory of planned behavior in university students in South Africa (N = 251) and the United States (N = 160) who completed an anonymous self-administered questionnaire. Multiple regression analyses revealed that condom use and intention were significantly predicted by positive condom attitude, subjective norm, self-efficacy, and attending university in South Africa. Significant interactions between country and predictors indicated that subjective norm predicted condom use and intention more strongly in the American sample than in the South African sample; attitude predicted intention more strongly in the American sample than in the South African sample; but self-efficacy predicted intention more strongly in the South African sample than in the American sample. The theory of planned behavior may provide a useful framework for interventions to reduce South African students' risk of HIV/and sexuality transmitted diseases. Such interventions should especially focus on building self-efficacy to use condoms.     

A selective LC/RIA for dexamethasone and its prodrug dexamethasone-21-isonicotinate in biological fluids.

A combined LC/RIA procedure is described for the selective determination of dexamethasone (DEX) and its prodrug dexamethasone-21-isonicotinate (DIN) in plasma. The low affinity of the employed dexamethasone antiserum for DIN (cross-reactivity less than 0.5%) allowed the direct determination of DEX in plasma extracts. For the determination of DIN, both substances of interest were separated by LC, the DIN containing fraction was collected, hydrolysed and the generated DEX was consequently assayed by radioimmunoassay. The assay detection limits were 0.1 ng ml-1 for DEX and 0.75 ng ml-1 for DIN. For both substances, inter- and intra-day variabilities (RSDs) were 6 and 12%, respectively.     

Analysis of the interbeat interval increment to detect obstructive sleep apnoea/hypopnoea.

The prevalence of obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is underestimated and its diagnosis is costly and restricted to specialised sleep laboratories. The frequency component of interbeat interval increment (III) has been proposed as a simple and inexpensive diagnostic tool in OSAHS. In a set of 150 patients with clinically suspected sleep-related breathing disorder, the actual predictive accuracy of the power spectral density of the III of the very low frequencies (%VLFI) was analysed by comparing with the apnoea/hypopnoea index (AHI), as assessed by synchronised polysomnography. OSAHS was defined in 100 patients according to an AHI>or=15 events.h(-1). Receiver operator characteristic curves built for %VLFI confirmed that this variable was able to separate OSAHS positive from OSAHS negative with statistical significance. Using an appropriate threshold (>4%), %VLFI demonstrated a positive predictive value of 80%. Misclassification of false-positive subjects occurred when the patient presented significant sleep discontinuity and sleep fragmentation (sleep fragmentation index>or=50 events.h(-1)) related to insomnia or periodic limb movements. A power spectral density of the interbeat interval increment of very low frequencies>4% allowed correct classification of obstructive sleep apnoea/hypopnoea syndrome when the clinical history suggested sleep-related breathing disorders and when moderate-to-severe cases are considered. Higher power spectral density of the interbeat interval increment of very low frequencies may also indicate disrupted sleep in the absence of clear clinical symptoms of sleep apnoea/hypopnoea syndrome.     

Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Spatiotemporal modeling of cerebral evoked magnetic fields to median nerve stimulation.

We measured somatosensory evoked magnetic fields during median nerve stimulation in 6 normal subjects. We applied multiple dipole models to study the spatiotemporal structure of early somatosensory evoked magnetic fields (SEFs), as well as the number, 3-dimensional location and time activity of their underlying neuronal sources. Two dipole sources were necessary to model the first 40 msec of SEFs explaining 85% of the data variance. Source 1 was located deeper than source 2, showed primarily a tangential orientation, and accounted for a larger part of the variance; source 2 showed no consistent orientation across subjects. Both sources showed biphasic time activities corresponding to the previously described N20-P30 and P25-N35 components. Spatiotemporal modeling could identify sources which could not be modeled consistently above noise by single moving dipoles (P25 component), revealed small latency differences of the two sources in some subjects suggesting parallel activation of these sources, and allowed separation of sources overlapping considerably both in space and time. We conclude that spatiotemporal modeling of SEFs may be useful to study functional anatomy of human sensorimotor cortex non-invasively.     

Chemical composition and cytotoxic activity of the leaf essential oil of <Emphasis Type="Italic">Eugenia zuchowskiae</Emphasis> from Monteverde,Costa Rica

The leaf essential oil of Eugenia zuchowskiae from Monteverde, Costa Rica, has been obtained by hydrodistillation and analyzed by GC–MS. The principal constituents of E. zuchowskiae leaf oil were α-pinene (28.3%), β-caryophyllene (13.2%), α-humulene (13.1%), and α-copaene (8.1%). The leaf essential oil of E. zuchowskiae showed pronounced in-vitro cytotoxic activity against MCF-7, MDA-MB-468, and UACC-257 human tumor cell lines. The major components showed cytotoxic activities comparable to doxorubicin (LC₅₀ 14–70 μg/ml).