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Pediatric use of intravenous and intramuscular phenytoin: lessons learned.

First developed in 1950, parenterally administered phenytoin offered substantial advantages over parenterally administered phenobarbital and paraldehyde, which were the treatments for status epilepticus until the 1960s. During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight. Studies in the late 1970s and early 1980s established more appropriate dosing for neonates and children on a milligram-per-kilogram basis. Scientifically derived dosing guidelines have been available only for the past 12 years. Side effects associated with parenteral phenytoin, caused primarily by its high pH level and the propylene glycol content needed to increase its solubility, were frequently reported during the 1970s and 1980s, after 25 years of clinical use. Intravenous administration of phenytoin caused burning at the infusion site and was associated with severe local cutaneous reactions following infiltration into surrounding tissue, leading to a recommendation that intravenous phenytoin be avoided in young children and the elderly. The propylene glycol solvent was linked to seizures, arrhythmia, asystole, and hepatic and renal damage. When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site. Many of these side effects can be avoided in children with the use of fosphenytoin.

Anticonvulsants↗

Treatment of depression.

Depressions are the most common psychiatric diseases. For treatment, plant extracts have been used for thousands of years: examples are extracts from the (sleeping) poppy (opium), deadly nightshade (Atropa belladonna), Indian hemp (hashish), henbane (hyoscyamine), thorn apple (scopolamine), and St. John's wort (hypericum oil). In addition, psychotherapeutic measures, like playing music, dancing, playing theatre, and also the temple sleep, were used. In the 19th century, the introduction of brome (1826), codeine (1832), chloral hydrate (1869), and paraldehyde (1882), as well as the barbiturates (at the turn of the century) introduced significant improvements in pharmacotherapy. The modern thymoleptica therapy started in 1957 with the introduction of imipramine. Now about 40 active antidepressants are marketed. New drug developments should be characterized mainly by an improvement in tolerance.

Antidepressive Agents↗

Effects of fuchsin variants in aldehyde fuchsin staining.

Aldehyde fuchsin stains pancreatic B cell granules, hypophyseal basophils, goblet cell mucins, gastric chief cells, hyaline cartilage, and elastica. Neither the chemical structure of aldehyde fuchsin nor its staining mechanism is known. This study was undertaken to clarify the role of the fuchsin component of aldehyde fuchsin in its staining reaction. The major findings of this investigation include: 1) single N-methylation of the fuchsin molecule abolishes staining of unoxidized pancreatic B cells, although it does not prevent reaction of fuchsin with paraldehyde; 2) aldehyde fuchsin is probably a Schiff base condensation product of pararosaniline and acetaldehyde; 3) a Schiff base structure alone cannot account for aldehyde fuchsin staining of unoxidized pancreatic B cells; 4) a fully potent aldehyde fuchsin is possibly a Tris-Schiff base derivative of pararosaniline.

Animals↗

Rapid tranquillisation. A survey of emergency prescribing in a general psychiatric hospital.

Rapid tranquillisation--giving a psychotropic to control behavioural disturbances--is common in medical practice, yet few surveys describe its use in psychiatric populations. Over five months, 102 incidents, involving 60 patients, were retrospectively surveyed. Patients most often involved were young white men. The commonest diagnosis was affective disorder (manic phase) (39%) followed by schizophrenia (33%). Fifteen patients were involved in 57% of the incidents. The majority of incidents involved injury to people or damage to property. The most frequently used drugs were diazepam and haloperidol, alone or in combination. Droperidol, chlorpromazine, sodium amytal and paraldehyde were rarely used. Diazepam alone or in combination with haloperidol delivered intravenously was most rapidly effective and was associated with greatest staff satisfaction. Serious side-effects were rare.

Aggression↗

The torus longitudinalis in the gilthead seabream: an undescribed fiber tract link with the valvula cerebelli.

In this paper, we present a brief anatomical description of the torus longitudinalis and the valvula cerebelli in a percomorph fish, the gilthead seabream (Sparus aurata) based on the analysis of serial brain sections stained by paraldehyde fuchsin, Groat's hematoxylin-picroindigocarmin and cresyl violet. The existence of a small undescribed fiber tract directly bridging the ventral torus longitudinalis and the granular layer of the rostral valvula cerebelli is also reported. This small fiber tract was observed in its integrity on a few transverse sections providing that the angle of sectioning was appropriate. The existence of the anatomical link between the TL and the VC described in this paper might sustain the role of the TL as part of an ascending cerebello-tectal circuit, at least in gilthead seabream. However, these fibers might also represent fibers of passage originating from other brain structures.

Animals↗

Propranolol versus diazepam in the management of the alcohol withdrawal syndrome: double-blind controlled trial.

Thirty-seven male alcoholics admitted electively for detoxification were randomized to treatment with either diazepam or propranolol. Subjects were comparable both in age and in duration and quantity of alcohol consumed. Admission laboratory parameters did not distinguish between the groups. Eleven subjects required no medication to control withdrawal signs/symptoms. Both groups showed improvement in blood pressure, pulse, and withdrawal tremor. None of the subjects randomized to diazepam manifested withdrawal seizures or hallucinations. By contrast, one subject in the propranolol group had a single withdrawal seizure. Another subject manifested increasing withdrawal that required parenteral paraldehyde treatment. Thus, this study confirms that a significant number of subjects admitted electively for alcohol withdrawal can be managed without medication. Minor tranquilizers still remain the "gold standard" for management of the withdrawal syndrome.

Adult↗

Polystyrene embedding: a new method for light and electron microscopy.

Polystyrene embedments of histological specimens can be obtained with a solution of 1:14 polystyrene-toluene, 5% benzyl alcohol and 1% dibutyl phthalate, allowing the solvent to evaporate in polyethylene containers for 2-3 days at 58 C. The resulting blocks are easily cut into truncated pyramids, each containing a piece of tissue, which are then glued to a Plexiglas support. Drying is completed at 80 C for 20 hr. The pyramids can then be sectioned to produce thick sections with a steel knife or to produce semi- or ultrathin sections with a glass knife. A 10% paraldehyde solution is used to mount the light microscopy sections on a slide heated on a hot plate to 80 C; these can be treated with the same techniques used with paraffin sections. The results are of high quality. Semithin sections of tissues fixed for electron microscopy can be stained directly after mounting, or by a wider range of stains once the polystyrene has been removed by organic solvents. In electron microscopy, the ultrathin sections obtained with the usual techniques are highly electron beam-resistant and given acceptable results.

Animals↗

Reduction of cellular energy requirements. Screening for agents that may protect against CNS ischemia.

Protection of the brain and spinal cord against ischemia is a goal of vast clinical importance. One approach to this objective is to reduce the tissue's functional activity in order to preserve energy for the metabolic processes that are essential to viability. Experiments to explore ways of reducing function-related energy demands were performed on isolated rabbit retina, a well-characterized model of organized adult mammalian central nervous system (CNS) tissue. The retina was maintained in a nearly physiological state in a miniature "heart-lung" apparatus. Energy metabolism (oxygen consumption and glycolysis) and electrophysiological function (determined by electroretinogram) of the in vitro retina were monitored, and their responses to a series of agents that may reduce energy requirements were determined. Large reversible reductions in O2 consumption, glycolysis, and electrophysiological function were seen in response to mild hypothermia (-3 degrees to -6 degrees C), phenytoin (Dilantin, 100 to 200 mg/kg), chlordiazepoxide (Librium, 200 microM), lithium (1 to 4 mM), Mg++ (6 to 20 mM), strophanthidin (0.15 to 0.25 microM), CO2 (25% to 30%), 2-amino-5-phosphonovaleric acid (APV, 500 microM), amiloride (1 mM), and dantrolene (1 mM). One retina was exposed simultaneously to a combination of six of these agents, which reduced its oxidative and glycolytic metabolism to less than 50% of the control level. The retina recovered metabolic and electrophysiological function after a 2 1/2-hour exposure period. Other agents tested (diphenhydramine, midazolam, nifedipine, nimodipine, and quercetin) had effects on energy metabolism and electrophysiological function that were poorly reversible. Surprisingly little effect was seen in response to general anesthetic agents (thiopental and Althesin) and other CNS depressants (chlorpromazine, ethanol, lidocaine, paraldehyde, valproic acid, and baclofen). The presumed mechanisms through which these agents reduce cellular energy requirements, as well as their potential roles in the treatment of CNS ischemia, are discussed.

Animals↗

Depression and/or potentiation of cortical responses after status epilepticus in immature rats.

Lithium-pilocarpine status epilepticus (SE) resulted in delayed changes of single cortical interhemisperic (transcallosal) responses in immature rats. Low-frequency stimulation inducing depression and/or potentiation was studied to analyze possible dynamic changes in cortical responses. Status was elicited in 12-day-old (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of the sensorimotor region of the cerebral cortex 3, 6, 9, 13, or 26 days after status. A series of 5 biphasic pulses with intensity equal to twofold threshold were used for stimulation. The interval between pulses was 100, 125, 160, 200 or 300 ms, eight responses were always averaged. Peak amplitude of the first positive, first negative and second positive waves was measured and responses to the second, third, fourth and fifth pulse were compared with the first one. Animals after status epilepticus as well as lithium-paraldehyde controls exhibit a frequency depression at nearly all the intervals studied. An outlined increase of responses in SE rats in comparison with the controls three days after SE stayed just below the level of statistical significance. In addition, animals in the SE12 group exhibited potentiation of responses at this interval after SE. With longer intervals after SE, the relation between SE and control animals changed twice resulting in a tendency to lower amplitude of responses in SE than in control rats 26 days after SE. Rats in the SE25 group exhibited higher responses than controls 13 days after status, but this difference was not present at the longest interval after SE. Low-frequency stimulation did not reveal increased cortical excitability as a long-lasting consequence of status epilepticus induced in immature rats. In addition, the outlined differences between SE and control rats changed with the time after SE.

Animals↗

Injection-induced sciatic nerve injury in Nigerian children.

OBJECTIVES: A retrospective study of all children with a diagnosis of sciatic nerve injury managed at the University College Hospital, Ibadan, Nigeria over a 12 year period was carried out in order to determine predisposing factors to the nerve injury and highlighting practical preventive measures. DESIGN: The necessary data was collected from the case files of children seen at the hospital with a diagnosis of sciatic nerve injury, from 1988 to 1999. RESULTS: There were 27 children aged five months to 12 years with a diagnosis of sciatic nerve injury. Twenty (74%) of the children were aged five years or less. While seven patients (26%) presented within two weeks of development of foot drop consequent on intramuscular (i.m.) injection given on the buttock, 20 patients (74%) presented much later. Fever was the most common complaint for which the injection had been given. The identity of the drugs given was not known in 10 patients. In the remaining 17 patients drugs administered were specified and included Chloroquine, Novalgin, Paraldehyde, Procaine penicillin, and Sulfadoxine-Pyrimethamine. Most of the patients had received the injections in privately owned medical facilities where staff with minimal training are often allowed to administer i.m. injections. CONCLUSION: It is suggested that the i.m. route for injection be strongly discouraged when a drug can be given by other routes. Only trained staff should be allowed to administer i.m. injections. Giving i.m. injections at sites other than the buttock maybe advantageous in children particularly those aged five years and below.

Child↗

The effect of disinfecting alginate and addition cured silicone rubber impression materials on the physical properties of impressions and resultant casts.

Four commercially available disinfectants were tested and the dimensional stability and detail reproduction of impressions and their resultant casts were measured according to ANSI/ISO specifications. Results showed that alginate impressions immersed in chlorhexidine exhibited considerable dimensional change if not poured immediately. Moreover, alginate impressions soaked in a paraldehyde agent (Virkon) for more than 2 minutes produced casts of inferior surface quality whilst those sprayed and left in contact with phenol derivatives (C&J Spray) for 30 minutes resulted in casts which demonstrated statistically and clinically significant dimensional changes. Addition cured silicone impressions exhibited minimal dimensional change regardless of the disinfection regime employed and the resultant casts were accurate with acceptable surface quality.

Alginates↗

Peripheral nerve injuries from intramuscular injection of drugs.

17 patients who were treated at the University of Nigeria Teaching Hospital for peripheral nerve paralysis resulting from intramuscular injection of drugs are analyzed. Ten of them were below the age of 5 years. Sciatic nerve was affected in 16 patients and only one patient had median nerve paralysis. Penicillin, ampicillin, tetracycline, paraldehyde and optalgin were some of the offending drugs. The prognosis was poor as only three patients achieved a partial recovery of function in the paralyzed nerves. With determination and public education, this iatrogenic tragedy could be eradicated.

Adolescent↗

What's new in cerebral palsy.

Among new researches bearing on cerebral palsy are the growth of brain cells in tissue cultures for experimentation; the use of polysaccharides to prevent the formation of a glial barrier to nerve growth after injury; observation of changes in reactions of neurons at various stages of development; the finding of hypernatremia and hyperchloremia in lesions of the frontal lobe and the thalamus; stimulation of cerebral blood flow by injection of sodium bicarbonate and retardation with ammonium chloride; and studies of serial sections of brains of palsied children who died. Study of development in the early months of life has made possible the detection of significant abnormalities in behavior early in life. Loss of hearing may be tested in very young children by measuring minute variations in electrical resistance of the skin upon auditory stimulation of the sympathetic nervous system. Conditions which have been described as having been confused with cerebral palsy are dislocation of a cervical vertebra, hereditary spastic paraplegia, transverse myelopathy, injury to the spinal cord or cauda equina by anomalous growths of the spine, and also encephalitis and meningitis. Sedation has proved a valuable adjunct to electroencephalographic study of cerebral palsy. Better criteria for abnormality in the young child should be determined and the application of them more clearly standardized. Simple exercises are useful for early training of palsied children to stimulate development. "Crossed laterality"-the dominant eye being contralateral to the preferred hand-has been counteracted by special training with great success in eliminating emotional and behavior problems and accelerating development.Recent studies indicate that only 50 per cent of cerebral palsy patients have normal or better intelligence. Subluxation of the hip joint, a common deformity associated with cerebral palsy, can sometimes be corrected by operation if detected at an early stage. Radical ablation of epileptogenic foci in the cortex is also being done in young patients if drug control of seizures fails. Frontal topectomy, cingulate gyrectomy or prefrontal labotomy may be advisable in cases in which proper response to drug therapy is not obtained. Improvement in behavior as well as control of seizures may follow the use of Benzedrine,(R) Dexedrine,(R) Dilantin(R) sodium, Mebaral(R) and phenobarbital. Alcohol, paraldehyde and chloral hydrate have been effective as relaxants.

Cerebral Palsy↗

[Drug-induced acid-base disorders].

Drug-induced acid-base disorders may be classified into four categories with respect to the mechanism. 1. Metabolic acidosis is induced by a large acid loads incurred from exogenous sources (e.g. NH4Cl, or toxin ingestion) or endogenous acid production (e.g. generation of ketoacids or lactic acids by alcohol or phenformin) or base loss (e.g. abuse of laxatives). 2. Metabolic alkalosis results from exogenous bicarbonate loads (e.g. milk-alkali syndrome) or effective extracellular fluid contraction, potassium depletion plus hyperaldosteronism (e.g. vomiting, diuretics, or licorice). 3. Renal tubular acidosis is induced by the drugs which mainly impair proximal and/or distal tubules (e.g. vitamin D, NSAID, acetazolamide or amphotericin B). 4. Respiratory acidosis or alkalosis results from drug-induced respiratory center depression or neuromuscular impairment (e.g. anesthetic, sedative overdosage or curare) or hyperventilation (salicylates, paraldehyde, epinephrine, or nicotine).

Acid-Base Imbalance↗

The morphological and histochemical neurosecretory magnocellular system in the rat after administration of chlorpromazine.

The effect of chlorpromazine (CPZ) on the neurosecretory action of the hypothalamo- hypophyseal system was investigated in 72 male rats. The experimental animals received CPZ in a dose of 0.4 mg, 4.0 mg and 20.0 mg/kg b.w. for 30 days. The rats were sacrificed by decapitation at 24 h and 7 days after the last dose of the drug. The neurosecretory material was stained with paraldehyde fuchsin in the supraoptic nucleus, paraventricular nucleus, eminentia mediana and neurohypophysis, the tigroid was stained with toluidine blue and the acid phosphatase activity was evaluated histoenzymatically. It was found that CPZ reduced the content of the neurosecretory material after 24 h, while an increase was observed 7 days after the last drug administration.

Acid Phosphatase↗

Effects of a free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on short-term recovery of immature rats after status epilepticus.

The present study examined the effects of a free radical scavenger, N-tert-butyl-alfa-phenylnitrone (PBN) on lithium-pilocarpine-induced status epilepticus (SE) and its short-term consequences in rats 12 (P12) or 25 (P25) days old. PBN (2 x 100 mg/kg i.p.) was injected according to the following schedules: 1) PBN-pretreated animals received the first dose 30 min prior to pilocarpine, the second dose was given 1 min after SE onset, and 2) PBN-treated animals received the first dose of PBN 1 min after SE onset and the second one 60 min later. Paraldehyde was administered to decrease mortality. Effects of PBN were highly age-dependent. In P25 group, PBN-pretreatment increased latency to SE onset and significantly suppressed the severity of motor manifestation of SE. Both PBN pretreatment and treatment improved recovery after SE. In contrast, administration of PBN in P12 animals did not affect SE pattern or recovery after SE. Administration of PBN had no effects on the motor performance of animals 3 and 6 days after SE. Neuronal damage was examined 24 h and 7 days after SE using Fluoro-Jade B staining. Mild neuroprotective effects of PBN in hippocampal fields CA1 and CA3 occurred in P25 rats in both experimental schedules. In contrast, administration of PBN aggravated neuronal injury in the hippocampus in P12 rats. Administration of PBN to intact rats did not induce neurodegeneration in either age group.

Age Factors↗

Status epilepticus. Recent experience at the Port-of-Spain General Hospital, Trinidad.

In this retrospective study, experience in status epilepticus (SE) over an 18-month period at the Port-of-Spain General Hospital is reported. Sixty-three episodes in 41 patients were studied. Fifty-one per cent of patients were under 10 years of age. Fifty-one per cent of patients were classified as remote symptomatic, 29% idiopathic, 15% acute symptomatic and 5% febrile. Bolus doses of diazepam were used in 62 of 63 episodes, phenytoin in 18, diazepam infusion in 9, paraldehyde in 12 and phenobarbitone in 9. Seizures were controlled within half-hour of starting treatment in 55 episodes (87%). In 3 episodes in 2 patients (5%), control was poor and exceeded 18 hours. No deaths were recorded. Two neurological deficits and 8 other morbid events were recorded. Mean hospital stay was 2.9 days. No patient was ventilated or admitted to the Intensive Care Unit. Current drug therapy is highly effective in SE even in institutions where modern intensive care technology is limited. Prognosis is excellent in patients in whom the underlying aetiology is benign.

Adolescent↗

The treatment of sleep disorders.

Narcolepsy is clinically associated with cataplexy, sleep paralysis and hypnagogic hallucinations. It is treated by reassurance (that there is no physical disease) and by stimulants such as ephedrine and amphetamine on an intermittent basis. The special tricyclic antidepressant clomipramine is also used, and mono-amine oxidase inhibitors (MAOIs) are useful in theory. Obstructive sleep apnoea is an important and often unrecognised cause of daytime somnolence. It is treated by weight reduction (pickwickian syndrome), hormones, or recently, with continuous positive pressure apparatus. Night terrors (pavor nocturnus) and sleepwalking typically occur during deep sleep (stage 3 and 4 throughout the episode) in children. In a night terror the child sits up with a scream, with eyes open, but inaccessible. He eventually falls asleep calmly. Sleepwalking, too, shows the features of inaccessibility and subsequent amnesia for the episode. Both conditions are normally treated with reassurance (to the parents) but may occasionally warrant benzodiazepines. Enuresis usually occurs in non-rapid eye movement (NREM) sleep, especially stages 3 and 4. The reason for the efficacy of tricyclic antidepressants is not precisely known. Delirium tremens (DT) is treated as a rebound excess of REM sleep, with benzodiazepines and other drugs. It is the withdrawal syndrome (with or without major seizures) to the barbiturate-alcohol group of drugs, which includes alcohol, chloral, paraldehyde, glutethimide, methylprylone, ethchlorvynol, meprobamate and meprobamate-diphenhydramine. Insomnia may be treated by the above drugs, by analgesics, antidepressants, major tranquillisers (neuroleptics) and miscellaneous other compounds. For the majority of patients, however, the most suitable group seems to be the benzodiazepines. The benzodiazepines are much safer than their predecessors, in both acute and chronic usage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗