Methotrexate treatment of idiopathic granulomatous hepatitis

OBJECTIVE: To test the efficacy and safety of low-dose oral pulse methotrexate therapy in patients with idiopathic granulomatous hepatitis who had complications of, did not respond to, or refused glucocorticoid therapy. DESIGN: Prospective case study. SETTING: Academic medical center hospital. PATIENTS: Seven patients with biopsy-proven, idiopathic granulomatous hepatitis who could not tolerate or were unresponsive to glucocorticoid therapy. INTERVENTION: Low-dose oral pulse methotrexate, 15 mg/wk. MEASUREMENTS: Temperature, symptoms, dose of concurrent glucocorticoids, biochemical tests of liver function, side effects of methotrexate, and assessment of liver biopsy specimens. RESULTS: All six febrile patients became afebrile within 3 months of starting methotrexate. Fatigue and anorexia improved in all patients. Glucocorticoid therapy was successfully discontinued within 6 months of starting methotrexate in four patients receiving prednisone at entry. Liver biopsy specimens were obtained again after methotrexate therapy and showed absence of granulomas in four of four patients. The minimum effective dose of methotrexate was 0.20 mg/kg body weight per week. No serious adverse effects and no failures to respond to methotrexate therapy were noted in this group of patients. In three patients, methotrexate therapy has been successfully tapered without signs or symptoms of recurrent disease. CONCLUSIONS: Low-dose oral pulse methotrexate was effective in treating patients with granulomatous hepatitis.     

Creutzfeldt-Jakob disease: neurophysiologic visual impairments

OBJECTIVE: The predictive value of electrophysiologic visual testing in Creutzfeldt-Jakob disease (CJD) was investigated, and the retinal pathologic findings in three cases are reported. BACKGROUND: The fatal prognosis of CJD, its transmissibility, and the lack of treatment make early diagnosis essential in averting human-to-human transmission. Electroretinogram and visual evoked potentials have been studied in few cases of CJD. METHODS: A visual electrophysiologic examination was performed in 41 consecutive patients referred with suspected CJD. The disease had been diagnosed in 24 patients (CJD group; 15 were confirmed neuropathologically and 9 by clinicolaboratory methods in accordance with diagnostic criteria). The remaining 17 patients were diagnosed with other neurologic disorders, and served as a control group. RESULTS: Flash electroretinogram revealed a significant decrease in the amplitude of the B1 wave (<60 microV) and the B/A ratio (<2) in the CJD group compared with those in the control group. Flash visual evoked potentials revealed no significant difference in latency, but amplitude was increased (>10 microV) in the CJD group, especially in patients with myoclonus. CONCLUSIONS: The visual electrophysiologic abnormalities provide an interesting noninvasive diagnostic tool in idiopathic CJD. The B1-wave decrease is closely correlated with the outer plexiform layer abnormalities observed on neuropathologic examination.     

Reflections on the Michigan splint and other intraocclusal devices

It seems obvious in retrospect that the treatment of disorders by interocclusal devices followed two paths: stabilization splints and functional orthopedic appliances. The dividing line between them is not always clear. Both have some function related to the position of the mandible. They may not differ significantly in their control of occlusal stability (e.g., telescoping devices anchored to stabilization splints). The stabilization splint, as well as other conservative measures, will play an increasing role in accepted therapy for TMD. The use of anterior repositioning devices for TMD, including MPD syndrome, will decrease. Research may provide answers that allow them to be used more specifically and predictably. Perhaps there will be but little change in their use where there is an association of TMD and Class II malocclusion. There will be an increase in the use of interocclusal devices for the treatment of snoring and obstructive apnea. Some additional directions seem to have emerged in the late 1980s and early 1990s: In the absence of pain and significant debilitation, treatment for TMD, if any, is to be reversible. Prevention or aggravation of TMD should be practiced to the extent possible during dental procedures. One long-term, well-designed, prospective study indicated that the incidence and severity of TMD could be reduced by appropriate occlusal adjustment. There is a small, but nevertheless important minority of patients with TMD who progress to persistent pain and/or dysfunction. Initial management of the vast majority of patents with TMD should be use of noninvasive reversible therapies. Surgery is indicated in only a relatively small percentage of cases of TMD. Research on interocclusal devices should not terminate simply because they are in part dental devices (i.e., biomechanical forms of treatment). The diagnosis and treatment of TMD has been called a dilemma, especially for those patients with chronic pain for whom no treatment has been effective. However, it would be ill-advised to abandon what treatment is already known to be effective by allowing those few but psychosocially important patients with chronic pain to determine what should be done for the vast majority of patients with TMD: reversible forms of treatment, including physiotherapy, pharmacologicals, and the stabilization occlusal bite plane splint.     

The role of gender in very old age: profiles of functioning and everyday life patterns

Older men and women have different life contexts as a function of differential longevity and socio-structural opportunities over the life course. The question is whether gender-related differences also occur in psychological and everyday functioning in older adults. Examined were 258 men and 258 women between the ages of 70 and 103 years (M = 85 years), participants in the Berlin Aging Study. Significant gender differences were observed in 13 of 28 aspects of personality, social relationships, everyday activity patterns, and reported well-being. Cluster analysis identified 11 subgroups whose profiles of life conditions and health and psychological functioning could be categorized as more or less desirable (functional). The relative risk of a less desirable profile was 1.6 times higher for women than for men. For older adults, gender as a variable carries differences in physical frailty and life conditions that likely have consequences for psychological functioning.     

Synthesis and characterization of a new 5-thiol-protected deoxyuridine phosphoramidite for site-specific modification of DNA

A new nucleotide analogue was developed for site-specific incorporation of a reactive thiol group into DNA. This creates a unique site for the post-synthetic modification of that nucleotide with a variety of molecular tags, such as photo-cross-linkers and fluorescent or spin-label moieties. 5'-O-(4,4'-Dimethoxytrityl)-5-[S-(2,4-dinitrophenyl)thio]-2'-deoxyuridin e 3'-O-(2-cyanoethyl N,N'-diisopropylphosphoramidite) was synthesized and incorporated at internal positions in several oligonucleotides using automated DNA synthesis and standard phosphoramidite chemistry. The coupling yield of the analogue was comparable to the coupling yield for a standard phosphoramidite, and no significant differences were observed in the overall yields of the dinitrophenyl-labeled oligonucleotides compared to the corresponding unmodified oligonucleotides. Characterization of the dinitrophenyl-modified oligonucleotides included enzymatic degradation, HPLC chromatography, and gel electrophoresis. Deprotection of the mercaptan group with beta-mercaptoethanol yielded an oligonucleotide containing 5-mercaptodeoxyuridine which was then selectively modified, without purification, by reaction with 5-(iodoacetamido)fluorescein. Incorporation of the dinitrophenyl-modified oligonucleotide into double-stranded DNA was achieved using the polymerase chain reaction. CHaracterization of the dinitrophenyl-labeled product by immunodetection with anti-dinitrophenyl antibodies confirmed the stability of the protecting group to the thermocycling and thus established the use of this thiol-protected mercaptodeoxyuridine phosphoramidite for preparation of site-specifically modified DNA.     

Chi recombination activity in phage lambda decays as a function of genetic distance

In Escherichia coli, chi is a recombination hotspot that stimulates RecBCD-dependent exchange at and to one side of itself. chi activity is highest at chi and decreases with distance from chi. The decrease in chi activity may be a simple property of the physical distance over which chi can stimulate recombination. Alternatively, the decay in chi activity with distance may reflect the high likelihood that chi-stimulated recombination occurs in a single chi-proximal act, to the exclusion of additional chi-stimulated exchanges more distal to chi. To test the models, we determined if chi activity decreases as a function of physical distance (i.e., DNA base pairs) or genetic distance (homologous DNA base pairs). Our results indicate that chi activity decays as a function of genetic distance. In addition, we found that the sbcB gene product (exonuclease I, a 3'-->5' ssDNA exonuclease) modulates the distance over which chi can act. In contrast, the recJ gene product (a 5'-->3' ssDNA exonuclease) does not alter the decay of chi activity.     

Correlates of fatigue in older women with heart failure

OBJECTIVE: To examine the relative contribution of psychologic factors and physical symptoms to the variance in fatigue in older women with heart failure. METHODS: Eighty women who had been hospitalized in the previous 12 months for heart failure were interviewed. Fifty-seven women completed second interviews 18 months after the first interview. RESULTS: Fatigue was the most frequently occurring physical symptom at both measurement times, and it significantly increased with time. Other physical symptoms contributed uniquely to the variance in fatigue at both measurement times, but psychologic factors did not. At time 1, sleep difficulties, chest pain, and weakness each explained unique variance in fatigue. At time 2, dyspnea was the only variable that explained unique variance in fatigue (9%). Dyspnea also explained a significant portion of the variance (7%) in time 2 fatigue, when time 1 fatigue was controlled. CONCLUSIONS: Fatigue in older women with heart failure is related more to other physical symptoms than psychologic factors.     

Expression and cellular distribution of baculovirus-expressed bovine herpesvirus 1 (BHV-1) glycoprotein D (gD) sequences

Glycoprotein D (gD) of bovine herpesvirus 1 (BHV-1), a homolog of herpes simplex virus gD, represents a major component of the viral envelope and is a dominant immunogen. To study the antigenic properties of the different regions of gD, we have expressed the full-length gD encoding gene and overlapping fragments spanning various regions of the gD open reading frame in a baculovirus (Autographa californica nuclear polyhedrosis virus)--insect cell (Spodoptera frugiperda, SF-9) system. Maximum levels of expression for all proteins were obtained 48 to 72 h post infection of SF-9 cells by recombinant viruses. Full-length and truncated recombinant gD proteins reacted specifically with anti-gD monospecific serum as determined by immunoprecipitation and immunoblotting, indicating that the proteins retained their antigenicity. However, based on the reactivity with a panel of gD-specific monoclonal antibodies (Mabs), the full-length recombinant gD lacked proper expression for two highly neutralizing linear epitopes identified by Mabs R54 and 9D6. The rest of the epitopes appeared to be preserved and antigenically unaltered. Immunofluorescence studies of recombinant baculovirus infected SF-9 cells using gD monospecific serum, revealed no direct correlation between cellular localization of the expressed proteins and their amino acid sequences.     

Effects of gonadectomy in infancy and adulthood on handedness in male and female Mongolian gerbils

When assuming a species-typical tripodal posture, female Mongolian gerbils most often rest on their left forepaws and hold their right forelimbs aloft; male gerbils most often do the reverse. This experiment examined effects of gonadectomy, both in infancy and in adulthood, on the sexually dimorphic asymmetry in forelimb use by Mongolian gerbils when maintaining a tripodal stance. In adulthood, both male and female gerbils that had been gonadectomized at birth reversed their forelimb use while in a tripodal stance: Gonadectomized males used their forelimbs as did sham-operated females, and gonadectomized females used their forelimbs as did sham-operated males. Gonadectomy in adulthood abolished the sexual dimorphism in forelimb use seen in sham-operated subjects. It was concluded that gonadal hormones have organizational as well as possible activational effects on adult patterns of forelimb use by gerbils.