Risks to the offspring of women treated with hydantoin anticonvulsants, with emphasis on the fetal hydantoin syndrome

The fetal hydantoin syndrome is a variable pattern of altered growth and performance which includes unusual facies, distal phalangeal hyoplasia, and other defects occurring in some infants exposed in utero to hydantoins. A prospective study of 35 infants exposed prenatally to this class of anticonvulsants showed that 11% had sufficient features to be classified as having the fetal hydantoin syndrome. An additional 31% displayed some features compatible with the prenatal effects of hydantoins. A case-control study of 104 infants whose mothers received hydantoins during pregnancy supports these conclusions. Reduction of intellectual ability in infants with the fetal hydantoin syndrome is the area of greatest concern. Women being treated with hydantoin anticonvulsants should be told of the nature and magnitude of risks to the developing fetus before considering a pregnancy.     

A tilt and roll device for automated correction of rotational setup errors

A tilt and roll device has been developed to add two additional degrees of freedom to an existing treatment table. This device allows computer-controlled rotational motion about the inferior-superior and left-right patient axes. The tilt and roll device comprises three supports between the tabletop and base. An automotive type universal joint welded to the end of a steel pipe supports the center of the table. Two computer-controlled linear electric actuators utilizing high accuracy stepping motors support the foot of table and control the tilt and roll of the tabletop. The current system meets or exceeds all pre-design specifications for precision, weight capacity, rigidity, and range of motion.     

Regulation of neuronal nitric oxide synthase mRNA in lordosis-relevant neurons of the ventromedial hypothalamus following short-term estrogen treatment

OBJECTIVE: To determine the nature and extent of the release of prostate specific antigen (PSA) and its interaction with its plasma protein-derived inhibitors after transurethral resection of the prostate (TURP). MATERIALS AND METHODS: Twenty-three consecutive patients undergoing routine TURP for benign prostatic hyperplasia had blood samples taken pre-operatively and then post-operatively at 8-hourly intervals for 24 h. Further samples were obtained at 48 and 72 h post-operatively. Serum free and total PSA were determined by immunofluorometric assay. The major plasma protein inhibitors for PSA were also determined by immunoassay. RESULTS: The mean free and total PSA fractions increased significantly post-operatively with levels greatest immediately after surgery. There was also a gradual increase in the complexed PSA fraction, reaching a peak at 48 h. The concentration of the major serum inhibitors of PSA (alpha-1-antichymotrypsin and alpha-2-macroglobulin) also declined immediately after surgery. CONCLUSION: Increases of serum total PSA in patients after TURP are caused by increases in the free PSA fraction. The exponential decline in free PSA concentrations is consistent with the complexing of PSA with its protease inhibitors present in the plasma. The formation of this complex suggests that the free PSA released into the circulation at the time of TURP is the enzymatically active form.     

Experimental transmission of Ehrlichia canis (Rickettsiales: Ehrlichieae) by Dermacentor variabilis (Acari: Ixodidae)

Four trials were conducted in which laboratory-reared Dermacentor variabilis nymphs were exposed to Ehrlichia canis by feeding on experimentally infected dogs as soon as classical morulae were detected in peripheral blood monocytes. After molting 25, 50 or 90 adult tick pairs were permitted to feed on 7 Ehrlichia-naive dogs. Transmission occurred in trials 1 (1/1 dog), 3 (1/1 dog) and 4 (2/2 dogs) but not in trial 2 (0/3 dogs), with 4 of 7 dogs becoming infected. Successful transstadial transmission was demonstrated by detection of morulae in peripheral blood lymphocytes and by seroconversion to Ehrlichia canis 30 d post-exposure. Incubation periods ranged between 17 and 22 days (mean = 19). Clinical signs, typical of ehrlichiosis, included mucopurulent ocular discharge, lymphadenopathy and malaise with accompanying pyrexia, leukopenia and thrombocytopenia. Pyrexia, thrombocytopenia and erythrophagocytosis and vacuolization of the cytoplasm of monocytic cells were observed 1-4 d prior to detection of morulae. This is the first demonstration that a tick other than Rhipicephalus sanguineus is capable of transstadial transmission of this important pathogen of dogs.     

Barrels VI: Proceedings of a satellite symposium of the 1994 Society for Neuroscience Meeting

Recent neurophysiological studies have revealed the patterns of neuronal activity during the acquisition of goal-directed behaviors, both in single cells, and in large populations of neurons. We propose a model which helps three sets of experimental results in the monkey to be understood: (1) activity of single cells vary greatly and only population activities are causally related to behavior. The model shows how a population of stochastic neurons, whose behaviors vary widely, can learn a skilled conditioned movement with only local activity-dependent synaptic changes. (2) typical changes in neuronal activity occur when the rules governing the behavior are changed, i.e. when the relationship between cues and actions to reach a goal changes over time. There are two types of neuronal patterns during changes in reward contingency: a monotonic increasing pattern and a non-monotonic pattern which follows the change in the way the reward is obtained. Units in the model display these two types of change, which correspond to synaptic modifications related to the encoding of the behavioral significance of sensory and motor events. (3) These two patterns of neuronal activity define two populations whose anatomical distributions in the frontal lobe overlap with a gradient organized in the rostro-caudal direction. The model consists of two artificial neural networks, defined by the same set of equations, but which differ in the values of two parameters (P and Q). P defines the adaptive properties of processing units and Q describes the coding of information. The model suggests that a balance in the relative strengths of these parameters distributed along a rostro-caudal gradient can explain the distribution of neuronal types in the frontal lobe of the monkey.     

Predicting age at menopause

Macrophages in the tissues have been shown to express receptor for urokinase-type plasminogen activator (uPAR) on their cell surface which plays an important role in cell invasion and attachment. We examined the effects of inflammatory mediators on the expression of uPAR employing U937 cells which have monocyte/macrophage-like characteristics. U937 cells were incubated with various mediators such as interleukins (IL), tumor necrosis factors (TNF), dexamethasone, thrombin, fibrin fragment D, bradykinin, complement C5a, and components of the extracellular matrix. The uPAR expression on the cell surface was then analyzed by radio-ligand binding assay using 125I-scuPA. The strongest enhancement of uPAR was observed in the cells stimulated by TNF alpha and TNF beta. IL-1 beta, IL-6, and C5a also increased the uPA binding sites with various patterns of affinity change. Dexamethasone decreased the uPA binding sites without changing the affinity. Fibrin fragment D and IL-3 reduced the affinity without changing the number of receptors. These findings suggest that the expression of uPAR in inflammatory cells could be modulated by various inflammatory mediators.     

Adenosine analogues as antimetabolites against Plasmodium falciparum malaria

Analogues of purine nucleosides and deoxynucleosides were tested for toxicity against the intraerythrocytic parasite Plasmodium falciparum in vitro culture. Sangivamycin (7-deaza-7-amido-adenosine) (IC37 of 0.3 microM), tubercidin (7-deaza-adenosine) (IC37 of 0.7 microM), 6-methylamino-deoxyadenosine (IC37 of 10 microM), 8-aza-2-amino-deoxy-adenosine (IC37 of 11 microM) and 2-chloro-adenosine (IC37 of 11 microM) were found to be the most toxic towards the parasite. Structure-activity analysis suggested that alteration of the purine ring at the 7 or 8 position significantly increased the toxicity of the compound against P. falciparum. Analysis by HPLC of parasite lysates which had been subjected to the cytotoxic compounds confirmed that alterations in the flux of the purine salvage pathways of the parasite had occurred. Comparison of the toxicity of these compounds against P. falciparum with the toxicity against a similar intraerythrocytic parasite, Babesia bovis, or human melanoma cell lines indicated a differential toxicity, in that many of the compounds toxic towards P. falciparum were relatively non-toxic towards human melanoma cell lines or B. bovis and vice versa. The mechanism of toxicity of the deoxyadenosine and adenosine analogues, whose normal metabolism involves transport, metabolism and incorporation into nucleic acids appears to vary significantly between P. falciparum, B. bovis and mammalian cells.     

Disposition of intramuscular cefonicid in elderly patients

OBJECTIVE: To examine the disposition of intramuscular (IM) cefonicid in elderly patients with bacterial pneumonia. DESIGN: Pharmacokinetic study. SETTING: A 620-bed university-affiliated long-term care institution with its own 39-bed acute care unit. PATIENTS: Nine consecutive elderly patients with bacterial pneumonia treated with IM cefonicid. MEASUREMENTS: Blood samples were collected on the seventh day of therapy over a 24-hour period and analyzed by high performance liquid chromatography. Pharmacokinetics parameters (volume of distribution, half-life, and clearance) and protein binding were calculated. Clinical outcome of IM cefonicid therapy was also noted. RESULTS: The estimated creatinine clearance (CIcr) ranged from 32 to 145 mL/min. Peak cefonicid serum concentrations occurred at 0.5-1.5 hours, with a mean value of 118 +/- 41 micrograms/mL. Cefonicid concentrations declined monoexponentially to 57 +/- 16 micrograms/mL at 12 hours and 28 +/- 14 micrograms/mL at 24 hours. The mean apparent distribution volume was 0.2 +/- 0.07 L/kg, and the mean apparent total clearance was 15 +/- 12 mL/min. The half-life ranged from 3.1 to 38 hours. A linear correlation was noted between Clcr and cefonicid clearance (r = 0.99). CONCLUSIONS: Cefonicid absorption was variable among these patients, and the serum half-life was longer than previous values noted in younger patients with similar degree of renal dysfunction. Pharmacokinetic and clinical outcome data from our study group indicate the potential role of IM cefonicid in treating elderly patients with bacterial pneumonia.     

Characterization of Aspergillus isolates by pyrolysis mass spectrometry

Pyrolysis mass spectrometry (PYMS) is a useful typing method for many bacterial and Candida species. We attempted to type Aspergillus spp. by PYMS. Four distinct A. fumigatus isolates could not be distinguished from each other, whereas one A. niger and one A. terreus could. Poor reproducibility was shown using multiple identical cultures of a single A. fumigatus isolate and several isolates of the same DNA type. PYMS is obviously an unsuitable typing method for Aspergillus spp.     

Association of periampullary diverticula with primary choledocholithiasis but not with secondary choledocholithiasis

The precision and the diagnostic performance of the Boehringer Mannheim CEDIA DAU LSD assay was evaluated. The assay was performed in the semi-quantitative mode on a Hitachi 917 analyzer. Within-run coefficients of variation (CVs) of the semiquantitative values for 0.25 and 1.0 ng/mL were 11.2 and 6.2%, respectively. Day-to-day CVs for the same concentrations were 12.6 and 8.6%. We analyzed 318 urine samples by CEDIA, DPC Coat-A-Count RIA and Behring EMIT II. Confirmation was performed by GC-MS, after extraction on Bond Elut Certify columns. Two hundred sixty-three samples were negative by all methods. Twenty-five samples were positive by all immunoassays, 19 of which were confirmed by gas chromatography-mass spectrometry (GC-MS). One sample was falsely negative by CEDIA. Three samples were positive by EMIT and CEDIA, but negative by RIA and GC-MS. Twenty-six samples were positive by EMIT alone, but they were not confirmed by GC-MS. The LSD CEDIA assay seems to be less specific than DPC RIA but more specific than the EMIT LSD assay.