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Biomedical subjects

R J Baumann

Publications and source records attributed to R J Baumann.

At least 19 recordsLinked to original sources
PubMed1991

HMPAO scintigraphy, MRI, and CT of a vascular fibrous dysplasia of the craniofacial bones.

The authors present the case of a child with a predominantly unilateral craniofacial fibrous dysplasia and a substantial redirection of internal carotid blood flow to the dysplastic bone. The case illustrates the advantages of using multiple imaging modalities in the evaluation of this disorder. CT showed the diagnostic findings of fibrous dysplasia and demonstrated the extent of bony involvement. MRI showed the extent and vascularity of the intradiploic fibrous mass and best demonstrated the distortion of underlying cerebral structures. Tc-99m HM-PAO brain scintigraphy demonstrated adequate ipsilateral cerebral perfusion, thereby excluding any significant cerebral "steal."

Adolescent↗
PubMed1991

Suppression of Leishmania donovani by oral administration of a bis(benzyl)polyamine analog.

We reported previously that intraperitoneal administration of a bis(benzyl)polyamine analog, MDL 27,695, suppressed both pentavalent antimony (Sbv)-susceptible and -resistant Leishmania donovani in vivo. The present studies were performed to optimize parasite suppression by parenteral administration and to evaluate the efficacy of oral treatment with MDL 27,695. L. donovani infections in BALB/c mice were suppressed greater than 99% after intraperitoneal dosing for 20 days with a total dose of 150 mg of MDL 27,695 per kg of body weight or 560 mg of Sbv per kg. Suppression was not increased by a total dose of 400 mg of MDL 27,695 per kg given for 20 days. In mice treated for 2, 4, or 7 days with either MDL 27,695 or Sbv (total doses of 60, 120, and 210 mg/kg, respectively), more liver parasites were killed with MDL 27,695 than with Sbv. Assessment of livers posttreatment showed that parasite killing continued for at least 3 days in MDL 27,695-treated mice but not for longer than 1 day in Sbv-treated mice. Intramuscular administration of drugs resulted in 92% parasite suppression by MDL 27,695 (15 mg/kg three times per day for 5 days) and 64% suppression by Sbv (60 mg/kg once per day for 5 days). Dosing of mice by oral gavage with 100 mg of MDL 27,695 per kg twice per day for 14 days resulted in 99.7% parasite suppression, and the 50% effective dose was approximately 11 mg of MDL 27,695 per kg. MDL 27,695 represents an effective new drug potentially useful for oral or parenteral treatment of visceral leishmaniasis.

Animals↗
PubMed1991

In vitro and in vivo candicidal activities of 2-(p-n-hexylphenylamino)-1,3-thiazoline.

The 2-amino-1,3-thiazoline, 2-(p-n-hexylphenylamino)-1,3-thiazoline (MDL 20,245) killed 10(5) logarithmic or stationary phase Candida albicans/ml in less than 1 h. Miconazole killed logarithmic phase cells at that rate, but miconazole, clotrimazole or econazole killed stationary phase cells at a slower rate of 10(2)-10(4) cells/ml in 24 h. MDL 20,245 induced efflux of K+ and L[U-14C] lysine from C. albicans, indicating that the candicidal mechanism is to exert direct damage upon the cytoplasmic membrane. The activity of MDL 20,245 in vitro was antagonized by fatty acids, triglycerides and phospholipids. Topical application of MDL 20,245 ointment (10% w/v) twice per day for 4 days to rats suppressed C. albicans-induced vaginitis 100%. Single-dose regimens of MDL 20,245, miconazole or clotrimazole correlated with 97, 90 and 73% suppression, respectively. These data suggest that MDL 20,245 may be effective in the treatment of C. albicans-induced vaginitis in humans.

Administration, Topical↗
PubMed1991

Clinical features and magnetic resonance imaging in congenital and childhood stroke.

Fifty-three (5%) of 1064 consecutively imaged children showed an arterial vascular pattern on magnetic resonance images, accounting for 12% of all abnormal studies. Signal abnormalities on T2-weighted scans persisted years after the clinical stroke occurrence. Ipsilateral atrophy of the pons or midbrain was found in 25% of subjects and was strongly associated with congenital lesions. Most infarctions occurred before or during the neonatal period; only 31% were acquired later. We did not find the paucity of posterior circulation lesions or the marked excess of left middle cerebral artery lesions seen in other series. Cardiac disease and venous infarction had an unexpectedly low occurrence. All of the children with arterial border zone infarction had been resuscitated in the neonatal period, while 37% of the children with a single artery infarction had no clinical history of acute illness.

Adolescent↗
PubMed1990

Antimalarial activity of a 4',5'-unsaturated 5'-fluoroadenosine mechanism-based inhibitor of S-adenosyl-L-homocysteine hydrolase.

A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl-L-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated with a large increase in the concentration of S-adenosyl-L-homocysteine (SAH) in the erythrocytes of the mice treated with MDL 28842. This increase in SAH was due apparently to inhibition of the mouse erythrocyte SAH hydrolase activity, because SAH hydrolase activity was undetectable in either P. berghei or P. falciparum isolated from infected erythrocytes, although enzyme activity was readily detected in mouse erythrocyte extracts. Therefore, MDL 28842 probably inhibits plasmodial growth indirectly by adversely changing the milieu of the host erythrocyte. SAH hydrolase represents a worthwhile target for the future development of potent inhibitors for the chemotherapy of malaria.

Adenosine↗
PubMed1990

Tc-99m HMPAO SPECT of the brain in the neonate.

A brain scan with Tc-99m hexamethylpropyleneamineoxime (HMPAO) performed on a neonate demonstrated normal localization only in the sensorimotor cortex, basal ganglia, and cerebellum. This pattern of localization is remarkably similar to previously published PET images of the neonate. Because Tc-99m HMPAO is readily available and has biochemical and physical characteristics that are suitable for perfusion imaging of the brain, it likely will become a major imaging agent in nuclear medicine. Normal scan findings in the neonatal age group with Tc-99m HMPAO have not been previously reported because of limited clinical use to date.

Brain↗
PubMed1990

Inhibition of epoxide hydrolase by valproic acid in epileptic patients receiving carbamazepine.

The effect of valproic acid (VPA) on the disposition of carbamazepine-10,11-epoxide (epoxide) was studied in five epileptic patients on chronic carbamazepine (CBZ) therapy. The individual pharmacokinetic parameters influencing epoxide disposition were determined in the presence and absence of VPA. VPA significantly decreased the clearance of unbound epoxide (an in vivo index of epoxide hydrolase activity), but did not appear to affect epoxide formation. VPA also increased the free concentrations of both CBZ and epoxide.

Adolescent↗
PubMed1990

Suppression of both antimony-susceptible and antimony-resistant Leishmania donovani by a bis(benzyl)polyamine analog.

It was recently demonstrated that a bis(benzyl)polyamine analog (MDL 27695; N,N'-bis(3-[(phenylmethyl)amino]propyl)-1,7-diaminoheptane) possessed potent antimalarial activity in vitro and in vivo (A. J. Bitonti, J. A. Dumont, T. L. Bush, M. L. Edwards, D. M. Stemerick, P. P. McCann, and A. Sjoerdsma, Proc. Natl. Acad. Sci. USA 86:651-655, 1989). We now report that MDL 27695 also has potent antileishmanial activity, eliminating 77 to 100% of Leishmania donovani amastigotes from mouse peritoneal macrophages in vitro at 1 microM. Administration of 15 mg of MDL 27695 per kg three times per day for 5 days to L. donovani-infected mice suppressed parasite burdens in liver, spleen, and bone marrow by 83 to 96, 90, and 87%, respectively, and by 99.9% in livers of mice given the same dose two times per day for 10 days. Liver parasites were suppressed 74% in L. donovani-infected hamsters treated three times per day for 4 days with 5 mg of MDL 27695 per kg. The 50% effective doses for MDL 27695 were 2.5 mg/kg in mice and about 1 mg/kg in hamsters. In hamsters, MDL 27695 was equally effective against both antimony-susceptible and antimony-resistant L. donovani, suggesting a different mechanism of action for the two types of drugs. Coadministration of N1,N4-bis(butadienyl)-butanediamine (MDL 72527) to mice to inhibit host polyamine oxidase, and hence the formation of oxidative metabolites of MDL 27695, did not affect the antileishmanial activity of MDL 27695. Thus, the mechanism of action of MDL 27695 does not appear to be related to its oxidation to toxic metabolites but may involve interference with DNA and RNA syntheses as found previously in Plasmodium falciparum (Bitonti et al., Proc. Natl. Acad. Sci. USA 86:651-655, 1989).

Animals↗
PubMed1988

Outcome of neonatal strokes.

We examined the clinical outcome of 17 children, 1 to 11 years of age, who experienced major cerebral artery infarctions (strokes) as neonates. Nine of the 17 children had left middle cerebral artery (MCA) infarctions, five had right MCA infarctions, two had bilateral MCA infarctions, and one had a left posterior cerebral artery infarction. Fourteen of the 17 children developed seizures as neonates. Most of these children who developed seizures were neurologically abnormal as neonates, became seizure free and neurologically normal early in the first year of life, and their anticonvulsant therapies were discontinued. After a seizure-free period of one to eight years, three of the 14 patients again required anticonvulsant therapy for seizure control. Two of the 16 surviving children continue to be severely handicapped while 11 of the 16 are making apparently normal developmental progress. One of the two children presently attending school has cognitive deficits appropriate to the site affected by the original infarction. Most children with neonatally diagnosed strokes appear to have a good short-term outcome, but later onset of seizures and subsequent recognition of cognitive deficits may not be uncommon.

Blindness↗
PubMed1988

Inhibition of Escherichia coli growth and diaminopimelic acid epimerase by 3-chlorodiaminopimelic acid.

The diaminopimelic acid (DAP) analog, 3-chloro-DAP, was synthesized and tested as the racemic acid for antibacterial activity and for inhibition of DAP epimerase. 3-Chloro-DAP was a potent inhibitor of DAP epimerase purified from Escherichia coli (Ki = 200 nM), and it is argued that 3-chloro-DAP is converted to a tight-binding transition state analog at the active site of this enzyme. Furthermore, 3-chloro-DAP inhibited growth of two E. coli mutants. In one of the mutants known for supersusceptibility to beta-lactams, inhibition was not seen until the mid-log phase of growth, while in the other mutant, a DAP auxotroph, inhibition occurred much earlier. Growth inhibition was reversed by DAP in both strains. In the auxotroph, the reversal was specific for meso-DAP, indicating that DAP epimerase was the target for 3-chloro-DAP. Thus we suggest a novel mechanism of bacterial growth inhibition which depends on DAP epimerase inhibition by a DAP analog.

Amino Acid Isomerases↗
PubMed1987

Neurologic complications of the epidermal nevus syndrome.

The epidermal nevus syndrome is a neurocutaneous disorder characterized by distinctive skin lesions and often serious somatic and central nervous system (CNS) abnormalities. We observed four cases of this disorder with epidermal nevi and neurologic manifestations, including mental retardation, seizures, ophthalmologic abnormalities, intracranial aneurysm, and porencephalic cyst. A review of 60 reported cases of the epidermal syndrome and our experience suggest that CNS complications are more likely to be associated with epidermal nevi on the head and that the CNS abnormalities are most often ipsilateral to the skin lesion.

Adolescent↗
PubMed1987

Patterns of cerebral arterial injury in children with neurological disabilities.

We reviewed the data from 215 consecutively imaged children who were referred because of neurologic disease. We specifically looked for evidence of cerebral arterial infarction in the form of focal brain damage in an arterial vascular distribution. Twenty-eight showed an arterial infarction pattern. All the major cerebral arteries were involved: middle cerebral artery, 17/28; posterior cerebral artery, 7/28; anterior cerebral artery, 2/28; carotid, 2/28; and vertebro-basilar, 1/28. Six of the 28 subjects had disorders reported to be associated with cerebrovascular damage. Another 13 subjects had other associated disorders, including perinatal distress and presumed anoxia, closed head trauma, hydrocephalus, and dehydration with electrolyte imbalance. Despite a careful search of medical records, we were unable to find any evidence of an adverse event or associated illness for more than one third of the children. These data suggest that cerebral arterial infarction is a more common lesion in the static neurologic disabilities of childhood than previously thought.

Adolescent↗
PubMed1986

Frontal lobe lesions and cognitive function in craniopharyngioma survivors.

We performed neuropsychological testing using the Luria-Nebraska Neuropsychological Battery, computed tomography, and magnetic resonance imaging (MRI) in four patients one to 15 years after surgery and radiation therapy for childhood craniopharyngioma. Of three patients with impairment of frontal lobe-mediated cognitive function, two had extensive areas of prolonged spin-lattice and spin-spin relaxation times in the frontal lobes demonstrated by MRI, and one had a lipid accumulation in the anterior horn of the right lateral ventricle and beneath a burrhole defect in the skull. One patient with minimal cognitive dysfunction had no abnormality in imaging studies. We believe assessment of neuropsychological status is an important aspect of the evaluation of children with craniopharyngioma. We have found the Luria-Nebraska Neuropsychological Battery and MRI to be particularly useful in this evaluation.

Adolescent↗
PubMed1985

Brain biopsy in cases of neonatal herpes simplex encephalitis.

Neonatal herpes simplex encephalitis (HSE) can represent a difficult diagnostic problem when it occurs without concomitant mucocutaneus lesions and usually requires brain biopsy for diagnosis. Asymptomatic for the initial 2 to 4 weeks of life, the three infants we describe with localized HSE came to medical attention only because they developed persistent seizures and other nonspecific symptoms. Lumbar spinal fluid obtained from these children at clinical presentation showed an encephalitic pattern. Radionuclide brain scans revealed focal uptake of isotope in a variety of cortical areas, and electroencephalograms (EEGs) demonstrated repetitive, high amplitude, polyphasic sharp waves arising from analogous regions. Computed tomography (CT) showed nonspecific ill-defined areas of low density or contrast enhancement that did not correlate well with radionuclide, EEG, or clinical findings in two neonates. No infant had predominant temporal lobe involvement. Because these data suggested a multifocal, encephalitic process, all three infants underwent brain biopsy. A widespread infiltration of leukocytes and macrophages was observed in each specimen, and abundant intranuclear inclusions were present. Electron microscopy revealed abundant herpesvirus particles, and herpes simplex virus (HSV) was subsequently isolated from each sample. From our observations and our review of the literature, we propose the following criteria as indications for brain biopsy: Brain biopsy is warranted to rule out HSE when a neonate presents with seizures, cerebrospinal fluid mononuclear pleocytosis with a negative gram stain, and focal, cortical disease on EEG and radionuclide scan.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1979

Extending neurologic services to rural children.

The University of Kentucky provides neurologic services to rural children by a traveling clinic. In 1978, 438 children (including 231 new patients) made 646 clinic visits. The primary diagnoses were appropriate for a neurology clinic; epilepsy was the most common (74 of 231) among new patients. A community survey of school-age children found the clinic serving 45 percent of "active epileptics." Clinic patients had a higher seizure frequency and came from a more disadvantaged background that nonclinic patients. These data show that an urban-based traveling clinic can identify and care for rural children with neurologic disorders.

Child↗
PubMed1978

Juvenile amaurotic idiocy (neuronal ceroid lipofuscinosis) and lymphocyte fingerprint profiles.

Lymphocytes from 3 children with a form of juvenile amaurotic idiocy (characterized by retinal blindness, progressive dementia, and extrapyramidal motor disturbance) were studied by electron microscopy. Numerous fingerprint profiles (FP) were found in vacuolated lymphocytes from all 3 patients and an asymptomatic younger sibling of 1 patient who subsequently became symptomatic. We propose that the combination of this clinical picture and vacuolated lymphocytes with FP is sufficiently distinctive for clinical and research purposes until the biochemical defect is discovered. Wider utilization of ultrastructural study of lymphocytes should increase the number of children diagnosed and allow detection of asymptomatic patients.

Adolescent↗
PubMed1978

Lactic acidosis associated with cerebellar vermal atrophy and cardiomyopathy.

The association of fluctuating neurological signs and congestive cardiomyopathy with chronic lactic acidosis is described in a 5 1/2 year-old-boy who ultimately succumbed to congestive heart failure. The autopsy findings included severe atrophy of the anterior cerebellar vermis and a hypertrophied heart with left sided endocardial fibroelastosis. Skeletal and cardial muscle calcification was prominent and probably due to the effect of intracellular metabolic alterations associated with lactic acidosis. A review of the literature shows that the combination of cardiomyopathy, isolated atrophy of cerebellar vermis and muscle fiber calcification have not been reported in association with idiopathic lactic acidosis previously.

Acidosis↗