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Biomedical subjects

R J Konkol

Publications and source records attributed to R J Konkol.

At least 19 recordsLinked to original sources
PubMed1997

Familial hemiplegic migraine with crossed cerebellar diaschisis and unilateral meningeal enhancement.

A 6-year-old boy with a family history of hemiplegic migraine had a hemiplegic migraine lasting for 6 days complicated by prolonged fever, lethargy, and two brief focal seizures. An acute single photon emission computerized tomogram (SPECT) demonstrated decreased blood flow in the symptomatic cerebral hemisphere as well as crossed cerebellar diaschisis not previously documented in migraine. Another unique finding was the MRI with enhancement of the meninges and pial vessels over the symptomatic cerebral hemisphere. These findings suggest cerebellar and extra-axial involvement as components of hemiplegic migraine.

Cerebellum↗
PubMed1996

Mobius syndrome: electrophysiologic studies in seven cases.

Mobius syndrome is characterized by congenital facial diplegia, frequent impairment of gaze, variable involvement of other cranial muscles, and various musculoskeletal anomalies. The site of dysfunction remains debatable. We performed detailed electrophysiologic studies in 5 children and 2 adults with Mobius syndrome to better delineate the pathophysiology of this disorder. Sensory and motor conduction studies were normal in the extremities. Facial compound muscle action potential amplitudes were reduced in all patients. The blink reflex R1 responses were unobtainable unilaterally in 2 patients and unobtainable bilaterally in 3 patients. Otherwise, R1 and R2 latencies were variably prolonged. The jaw jerk and masseter silent periods, tested in 2 patients, were normal. Detailed electromyographic studies of facial muscles revealed multifocal, chronic neurogenic changes. The findings indicate a brain stem process predominantly affecting the facial nuclei and their internuclear connections rather than a supranuclear or muscular site of involvement.

Action Potentials↗
PubMed1996

In vivo pharmacokinetics and in vitro production of cocaethylene in pregnant guinea pigs.

Simultaneous exposure to cocaine and ethanol results in the formation of cocaethylene, an active metabolite of cocaine. The concurrent abuse of both cocaine and ethanol is common during human pregnancy, but the kinetics of elimination and formation of this ethyl ester of cocaine have not been studied during pregnancy in any species. In the late gestation guinea pig (61 to 63 days), cocaethylene, at doses of 2 to 4 mg.kg-1, is rapidly eliminated with a half-life of 29 min and a total body clearance of 77 ml.min-1.kg-1. It is formed enzymatically by hepatic microsomal preparations from fetal, neonatal and maternal guinea pigs. The maximum rate of cocaethylene production (apparent Vmax) when either ethanol or cocaine are varied while the other substrate is held constant, increases with age, from the late fetal period (65 days gestation, term 70 days) to adulthood. However, the Michaelis-Menten constant (apparent KM) does not change with age. The rapid elimination of cocaethylene, coupled with the slow rate of formation (apparent Vmax of 140 pmol.min-1.mg microsomal protein-1) and the small amount of plasma analyzed most likely explains the inability to detect coacethylene in vivo after concomitant cocaine and ethanol administration.

Animals↗
PubMed1996

Effect of cocaine metabolites on behavior: possible neuroendocrine mechanisms.

The predominant cocaine metabolites were tested for central nervous system effects by intracerebroventricular (ICV) administration in rats. We found two types of responses: cocaine, norcocaine (NC), benzoylecgonine (BE), and benzoylnorecgonine (Nor BE) produced stimulatory effects, whereas ecgonine methyl ester (EME) and ecgonine (EC) resulted in no specific effect or sedation. A novel metabolite interaction was revealed when rats were pretreated with EME, which inhibited both analgesia and seizures by subsequently administered cocaine. Pretreatment with EC inhibited both cocaine and BE seizures and seizure-associated death. Direct injection of EME into the nucleus accumbens significantly suppressed systemic cocaine potentiation of intracranial electrical self-stimulation of the ventral tegmental area, whereas corticotropin releasing hormone injected ICV selectively potentiated BE-induced seizures and death. These results confirm multiple, metabolite-mediated activities in the central nervous system. Pharmacological interactions of the metabolites with each other and/or with neurohormones may help explain some of the pathophysiological effects seen in human chronic cocaine abuse.

Animals↗
PubMed1995

Cocaine and benzoylecgonine constrict cerebral arteries by different mechanisms.

This study was designed to determine possible mechanisms underlying the vasoconstrictor activity of cocaine and its principal metabolite, benzoylecgonine (BE) in cat isolated cerebral arteries. The arteries constricted significantly in response to single doses of cocaine, BE and norepinephrine (NE; (P < 0.05). After 6-OHDA treatment to remove adrenergic nerve endings, NE-induced constrictions were essentially unchanged from those before treatment. Denervated arteries exposed to cocaine dilated significantly (P < 0.05) but those exposed to BE constricted as much as before denervation. Following exposure to prazosin and yohimbine, arterial constrictions to NE and cocaine were significantly reduced from control (P < 0.05) but the BE-induced constriction was unchanged. Ryanodine eliminated the cocaine-induced contraction (P < 0.05) whereas verapamil eliminated the BE response (P < 0.05). These data suggest that while cocaine's vasoconstrictor action may be significantly mediated through adrenergic transmission, BE may act through a mechanism involving calcium (Ca2+) channels. Cocaine levels peak and decline in the body more rapidly than BE levels which can remain detectable for days. This study suggests there may also be different pharmacological mechanisms as well as temporal differences underlying the vasoreactivity of these two substances. Our findings may have implications for pharmacological management of cocaine-induced toxic vascular events.

Animals↗
PubMed1994

Childhood stroke and lupus anticoagulant.

Despite extensive evaluation, the cause of many childhood ischemic strokes remains unexplained. Two children are reported with stroke and lupus anticoagulant. Both had family members with features of the antiphospholipid antibody syndrome. Children with unexplained ischemic stroke should be evaluated for lupus anticoagulant and anticardiolipin antibodies.

Antiphospholipid Syndrome↗
PubMed1994

Infantile spasms in children with Down syndrome.

The authors retrospectively identified 17 children with Down syndrome who developed infantile spasms, and analysed their etiology, EEG findings, response to medication, development and prognosis. Compared with symptomatic infantile spasms in the general population, which have a poor prognosis, these patients had a relatively benign outcome with regard to seizure control: only three of 16 survivors currently have seizures and seven of the 16 currently receive anticonvulsants. Developmental outcome was poorest in those with a superimposed hypoxic insult and in those who regressed developmentally at the onset of the spasms and did not regain developmental milestones. The overall neurological prognosis for children with Down syndrome and infantile spasms appears to be better than for children with infantile spasms in the general population.

Adolescent↗
PubMed1994

Cocaine metabolites in the neonate: potential for toxicity.

Recent reports indicate that cocaine metabolites have biologic activity and could be toxic. To explore this possibility, two studies were initiated. The first study aimed to define the distribution of cocaine species by quantifying levels of cocaine and its metabolites norcocaine, benzoylecgonine, and benzoylnorecgonine in newborn cord blood and meconium. The second study sought to determine whether they produced a clinical effect. Compared to cord blood, meconium had a greater number of metabolites and a higher concentration of cocaine metabolites, including the previously undetectable norcocaine and benzoylnorecgonine derivatives. Benzoylecgonine was the most common species found in both sources and was usually lower in concentration in blood. An inverse relation existed between meconium benzoylecgonine levels and the serum catabolic enzyme pseudocholinesterase, implying genetic variability in cocaine metabolism. To determine whether cocaine and/or its metabolites could be linked to a distinct clinical state, a second study focusing on newborn behavior was performed with an independent large cohort of cocaine-exposed infants. Neonates with increased signs of "neuroexcitation" had benzoylecgonine and no cocaine in urine, whereas lethargic neonates had detectable urinary cocaine. These findings support the hypothesis that cocaine metabolites, especially benzoylecgonine, may play a role in altering newborn behavior and produce a clinical syndrome distinct from that related to the parent compound.

Butyrylcholinesterase↗
PubMed1994

Normal high-resolution cerebral 99mTc-HMPAO SPECT scans in symptomatic neonates exposed to cocaine.

Vascular constriction is said to account for a variety of clinical effects of cocaine. High-resolution 99mTc-hexamethylpropylene amine oxime single photon emission computed tomographic (SPECT) scans, which measure cerebral blood flow, were used to determine whether neonatal brain perfusion deficits are present in newborns with confirmed cocaine exposure. Normal, age-appropriate SPECT scans were found in 21 babies. Conventional neuroimaging was also performed when possible. All but one of the 14 magnetic resonance imaging (MRI) scans and one computed tomographic scan were normal. One MRI showed a mild delay in myelination. All but four neonates had behavioral or electroencephalographic abnormalities, and microcephaly was found in five of 21. The normal neonatal SPECT scans contrast with findings in adult cocaine users, which typically report abnormal findings of cerebral hypoperfusion. This study identifies a unique lack of corresponding cerebral vascular pathology in symptomatic neonates. It raises the possibility that many of these children can escape significant ischemic injury.

Brain↗
PubMed1993

Quantitation of benzoylnorecgonine and other cocaine metabolites in meconium by high-performance liquid chromatography.

A method for simultaneous extraction of cocaine and metabolites benzoylnorecgonine, benzoylecgonine and norcocaine from meconium was developed. The procedure uses solid-phase extraction columns with both cation-exchange and hydrophobic properties after vortex-mixing meconium with methanol. Chromatography utilizes reversed-phase high-performance liquid chromatography with a C18 column and phosphate buffer-acetonitrile as mobile phase. The method is specific and sensitive to 50 ng/g meconium for all compounds. Standard curves are linear from 0.05 to 5.0 micrograms/g (r2 > or = 0.989). Intra-assay coefficients of variation were < or = 6.9%. Meconium from infants exposed to cocaine in utero contained varying combinations of the four drugs.

Chromatography, High Pressure Liquid↗
PubMed1993

New subform of the late infantile form of neuronal ceroid lipofuscinosis.

Clinicopathological studies of a series of nine children with a new subform of Jansky-Bielschowsky disease or late infantile neuronal ceroid lipofuscinosis (LINCL) is presented. The onset of this subform is between 2.5-3.5 years of age with initial neurological symptoms of abnormal motor skills caused by cerebellar and extrapyramidal signs. Soon after dementia, myoclonic seizures are followed. Visual impairment is more clearly seen after the age of 5 or 6 years. The ultrastructural studies of the skin and/or buffy coat showed abundant lysosomal storage of curvilinear profiles, rarely intermixed with fingerprint profiles. The MRI of the head performed in seven cases, showed initially enlargement of the ventricles that is secondary to basal ganglia atrophy and presence of cerebellar and cerebral atrophy. In 4 of 7 cases (Cases 1, 5, 6, 8) abnormalities in the deep white matter showing increased signals of T2-weighted imaging in the periventricular areas of the fronto-parietal region, internal capsule, tracks of the brainstem, and white matter of cerebellum were seen. These abnormalities were also observed by post-mortem neuropathological studies in three cases (nos. 7-9). The MRI in Cases 7 and 9 was not performed. The electrophysiological abnormalities (EEG, ERG, VER) are similar as described in the classical LINCL. Neuropathological studies done in 3 of 9 cases showed generalized brain atrophy and unique type of neuronal cytoplasmic inclusion body in the basal ganglia, brainstem, dentate nuclei, and rarely, cerebral cortex. These large, round neuronal cytoplasmic inclusions were pink in hematoxylin (HE), violet in cresyl violet, and dark blue with Klüver-Barrera method.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Ganglia↗
PubMed1993

Seizure exacerbation related to beta-lactam antibiotics in a child with cerebral dysgenesis.

A three-year-old boy with right hemimegalencephaly, developmental delay and left hemiparesis had well-controlled left focal seizures. Occasionally he had generalized seizures if he was given beta-lactam antibiotics. An EEG with simultaneous penicillin injection was performed to examine this apparent association: a secondarily generalized seizure was documented within two minutes of intravenous administration of the penicillin. This procedure confirmed the suspicion of a causal link between antibiotic treatment and seizures. The factors increasing susceptibility to beta-lactam antibiotic-induced seizures are reviewed.

Anti-Bacterial Agents↗
PubMed1993

An unusual cause of cerebral venous thrombosis in a four-year-old child.

BACKGROUND AND PURPOSE: Inherited protein S deficiency has been associated with an increased risk of thromboembolic disease. It is possible that such a coagulopathy could predispose children to the development of strokes by permitting clot formation in response to stimuli that ordinarily would be insufficient to cause thrombus formation. CASE DESCRIPTION: We evaluated a previously well 4-year-old boy who developed cerebral venous thrombosis after suffering minor head trauma. Crossed-immunoelectrophoresis of his plasma showed a marked decrease of the free, active form of protein S. Family studies revealed that the patient's father and other paternal relatives had a similar abnormality of protein S. CONCLUSIONS: We suggest that the cerebral venous thrombosis in this child was initially precipitated by minor head trauma and pathological thrombus formation was then potentiated by inherited protein S deficiency. This case extends the clinical spectrum for protein S deficiency and emphasizes the importance of evaluating family members to establish a specific diagnosis and therapeutic intervention.

Blood Coagulation↗
PubMed1993

Möbius syndrome: evidence for a vascular etiology.

We report five infants with restricted lateral gaze, facial diplegia, feeding difficulty, and/or respiratory disorders without significant pulmonary disease. Viral studies were negative in all patients. Two children had radiologic findings that included brain-stem hypoplasia and symmetric calcification in the dorsal tectum at the junction of the midbrain and pons. Autopsy of one of these two children demonstrated capillary telangiectasia in the mesencephalon and pons. The other three children had normal computed tomographic (CT) scans. However, their autopsies revealed focal brain-stem necrosis with calcifications but without vascular malformation. We suggest that the capillary malformations in one of our patients directly resulted in a vascular-induced necrosis and the manifestation of Möbius sequence. The similarity of symmetric neuropathologic findings in the three other patients and the CT scan in the one surviving patient suggest focal hemodynamic changes restricted to the posterior circulation, indirectly supporting a vascular theory of embryopathogenesis.

Brain Diseases↗
PubMed1992

Effects of benzoylecgonine on the behavior of suckling rats: a preliminary report.

A major metabolite of cocaine, benzoylecgonine, causes behavioral activation that progresses to seizures when given intraventricularly to 2-week-old rats. The seizures are characterized by running, hopping, and vocalizing and are mixed with shorter-duration tonic episodes. Pretreatment with haloperidol, at a dose aimed at blocking stereotyped behavior, did not suppress these behaviors. In contrast, seizures were prevented by antiepileptic drugs, with the order of potency being diazepam greater than phenobarbital greater than phenytoin. We hypothesize that the long-lasting cocaine metabolite, benzoylecgonine, contributes to the infant cocaine intoxication syndrome.

Animals↗