The role of scintigraphy in the evaluation of fever of unknown origin

Nuclear medicine imaging techniques are an important adjunct to other currently used modalities in the evaluation of patients with fever of unknown origin. Bone scanning performed with technetium-labeled phosphonate agents may identify osteomyelitis when plain radiography fails and may disclose sites of joint inflammation or unsuspected osseous tumor metastasis. Indium-labeled autologous leukocytes localize at sites of inflammation in the same manner as unlabeled leukocytes. Gallium citrate accumulates in areas of inflammation and in some tumors, most notably lymphomas. In most cases, scintigraphy is best used to determine the location of a lesion rather than to specifically identify the pathologic process.     

Functional role of hepatitis C virus chimeric glycoproteins in the infectivity of pseudotyped virus

The putative envelope glycoproteins of hepatitis C virus (HCV) likely play an important role in the initiation of viral infection. Available information suggests that the genomic regions encoding the putative envelope glycoproteins, when expressed as recombinant proteins in mammalian cells, largely accumulate in the endoplasmic reticulum. In this study, genomic regions which include the putative ectodomain of the E1 (amino acids 174 to 359) and E2 (amino acids 371 to 742) glycoproteins were appended to the transmembrane domain and cytoplasmic tail of vesicular stomatitis virus (VSV) G protein. This provided a membrane anchor signal and the VSV incorporation signal at the carboxy termini of the E1 and E2 glycoproteins. The chimeric gene constructs exhibited expression of the recombinant proteins on the cell surface in a transient expression assay. When infected with a temperature-sensitive VSV mutant (ts045) and grown at the nonpermissive temperature (40.5 degrees C), cells transiently expressing the E1 or E2 chimeric glycoprotein generated VSV/HCV pseudotyped virus. The resulting pseudotyped virus generated from E1 or E2 surprisingly exhibited the ability to infect mammalian cells and sera derived from chimpanzees immunized with the homologous HCV envelope glycoproteins neutralized pseudotyped virus infectivity. Results from this study suggested a potential functional role for both the E1 and E2 glycoproteins in the infectivity of VSV/HCV pseudotyped virus in mammalian cells. These observations further suggest the importance of using both viral glycoproteins in a candidate subunit vaccine and the potential for using a VSV/HCV pseudotyped virus to determine HCV neutralizing antibodies.     

Overshadowing and latent inhibition counteract each other: support for the comparator hypothesis

In 4 conditioned lick suppression experiments with rats, the combined effects of latent inhibition treatment followed by overshadowing treatment were assessed as a test of the comparator hypothesis's (R.R. Miller & L.D. Matzel, 1988) explanations of overshadowing and latent inhibition. Experiments 1 and 2 confirmed the prediction of the comparator hypothesis that combined latent inhibition and overshadowing treatments attenuate the response deficit produced by either treatment alone. Furthermore, consistent with the comparator hypothesis, posttraining changes in the associative status of the putative comparator stimulus altered responding to the target conditioned stimulus (Experiment 3), and switching contexts between latent inhibition and overshadowing treatments (Experiment 4) eliminated the interaction between the latent inhibition and overshadowing treatments.     

Synthesis and antiallergic activity of pyridothienopyrimidines

The synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC50 values in the range 2-25 microM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC50 = 9-25 microM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170-230%) and chemical (9e, 100-150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC50 = 0.1-0.2 microgram/mL) against P-388, A-549, HT-29, and MEL-28 tumor cell lines.     

CD4 cell counts of 200 x 10(6)/1 or below in natural history studies and surveillance: is one enough or are two better?

A retrospective cohort study was performed to examine the extent and clinical significance of misclassification associated with using the current United States AIDS case defining category of an initial CD4 count < or = 200 cells x 10(6)/l (< or = 200) compared with a definition requiring two consecutive counts below this level. The main outcomes examined were the probability of subsequent CD4 counts > 200 x 10(6)/l (> 200) and progression times to AIDS and death. Of the 2025 predominantly male homosexual HIV-positive patients attending two hospital based HIV clinics with initial CD4 cell counts < or = 200, 1524 (75%) subsequently had consecutive counts < or = 200, but only half did so at the next CD4 count. Ten per cent had either no further or only non-consecutive counts < or = 200, and 15% had only one CD4 count available for analysis. The cumulative proportion of patients with a CD4 count > 200 at one year after a first count of < or = 200 was about twice (39%) that observed among the subgroup with at least two consecutive counts < or = 200 (19%). The times from the initial counts of < or = 200 to AIDS and death were also shorter by six months and two months, respectively, in the subgroup with two or more consecutive counts < or = 200. A significant proportion of patients will be prematurely classified as having a CD4 cell count < or = 200 if a single CD4 count below this level is accepted. A definition of two consecutive counts < or = 200 should be adopted in preference to a single count < or = 200 for natural history studies and clinical trials, in which precise estimates of the time to or from a defined CD4 threshold are important. In surveillance programmes, however, such an approach may be impractical because of missing or infrequent serial CD4 counts, although adjustments can be made based on these estimates of premature misclassification.     

Myelination in cerebellar slice cultures: development of a system amenable to biochemical analysis

Myelin deposition and maintenance are critical to proper function of the mammalian nervous system. Previous investigations of myelination in the central nervous system (CNS) were hampered by the lack of an in vitro system that can faithfully reproduce in vivo events yet is amenable to biochemical investigation. We have developed a procedure, based on organotypic cultures, which permits efficient preparation of large numbers of cerebellar slice cultures that can be easily manipulated. Cultures have been examined to document myelination biochemically (by incorporation of [35S]sulfate into sulfolipids), immunohistochemically (by labeling the myelin components myelin basic protein and galactocerebroside), and morphologically (by both light and electron microscopy). We tested the effects of biologically active peptides and antibodies on myelination in the thin slices. The results indicate that the cultures provide an in vitro system that can be used to examine specific cellular events that occur during CNS myelination.     

Mental health services in the public and private sectors

Analysis of data on mental health service providers indicates that in 1971 the private sector accounted for 34% of inpatient days, 86% of outpatient visits, 44% of expenditures by source of funds, and 51% of expenditures by receipt of funds. The author believes that mental health professionals must familiarize themselves with the economic interests influencing national health insurance proposals and with public policy making processes if they are to help preserve appropriate roles for the public and private sectors in mental health service delivery.     

Clival chordoma

Chordomas are uncommon tumors arising from embryonic remnats of the fetal notochord. The spheno-occipital and sacrococcygeal regions account for over 90 per cent of cases, the remaining 10 per cent occurring anywhere along the vertebral axis. A case of chordoma arising from the clivus is presented with a view to discussing management. The ability to obtain reasonable survival times associated with a useful and meaningful quality of life is emphasized. This may be accomplished by repeated, judicious surgical intervention with surprising ease and little morbidity to the patient in spite of its intracranial location.     

Correlation of the production of gonadotropic and sex hormones in boys and girls during sex maturation

There is an early period of puberty in boys at the age of 10 to 13, accompanied by an increase in the level of follicle stimulating hormone and a low secretion of luteinizing hormone and testosterone, with no secondary sexual signs. The beginning of an increase in the luteinizing hormone and testosterone concentration in boys coincides with the development of secondary sexual signs. The stabilization of the level of luteinizing hormone takes place in boys already at the 2nd degree of the sexual development. The secretion of luteinizing hormone at this point corresponds already to the normal level in adult men. The level of testosterone in the blood continues to increase and does not reach its definitive level until after the age of 17, or at the 5th degree of sexual development. Like in boys, the increase of the follicle stimulating hormone in girls precedes the increase of the luteinizing hormone secretion. The beginning of the increase in the follicle stimulating hormone coincides with an increase in the level of estrogens and testosterone in the blood, and with the appearance of secondary signs of sexual maturation. The increase of the luteinizing hormone secretion takes place later in girls than in boys and is accompanied by a new and significant increase in the level of estrogens in the blood. At the 2nd degree of sexual development, the level of testosterone in the blood of girls is substantially higher than at the other stages.