Different effects of 4-aminopyridine on sensory and motor fibers: pathogenesis of paresthesias.

Mammalian motor and sensory fibers respond differently to the potassium channel-blocking agent, 4-aminopyridine (4-AP). The action potentials of the motor fibers increase in duration after 4-AP, while the sensory fibers respond with bursts of action potentials after a single stimulus. These differences may account for the paresthesias reported by patients with multiple sclerosis following treatment with 4-AP.

Myelin sheath remodelling in regenerated rat sciatic nerve.

Adult rat sciatic nerves were subjected to a crush lesion and allowed to survive during 2 weeks-11 months. Segments of regenerated nerve were removed from exsanguinated animals and subjected to physiological analysis and light microscopic examination of teased fibres. Application of the potassium channel blocking agent 4-aminopyridine (4-AP) to regenerated nerve segments had marked effects on action potential waveform and recovery properties.

Depressive behavior and hyperactive adrenocortical function.

This study examined relationships between depressive subtypes, clinical-behavioral characteristics, and hypothalamic-pituitary-adrenocortical (HPA) function in 132 hospitalized depressed patients. There were significant positive correlations between several pre- and postdexamethasone plasma cortisol measures and anxiety, psychomotor disturbance, distressed expression, and sleep disturbance. Few significant relationships were seen between illness severity and HPA function.

The effect of age on salicylate-induced nephrotoxicity in male rats.

The administration of 500 mg/kg sodium [14C]salicylate to 3- and 12-month-old male rats produced proximal tubular necrosis in the older animals but only mild nonspecific cellular changes in the younger group. The onset of renal damage was similar for both 3- and 12-month-old rats but recovery time was prolonged in the older rats. Covalent binding of salicylate equivalents was present in renal cortices from all rats and was largely confined to the mitochondrial fraction; however, older rats displayed five times more binding to this organelle than younger rats.

Reduced sensitivity of lymphocyte beta-adrenergic receptors in patients with endogenous depression and psychomotor agitation.

It has been suggested that there are altered levels of norepinephrine or other neurotransmitters at functionally important receptors in patients with depressive disorders. This hypothesis is difficult to study in the human central nervous system. However, noradrenergic function can be assessed indirectly with peripheral-blood lymphocytes used as a model of the beta-adrenergic receptor complex.

Mosaic Turner's syndrome and pituitary microadenoma.

A case of a 25-year-old woman with amenorrhoea-galactorrhoea syndrome and microprolactinoma is reported. The 45 XO/46 XX chromosome aberration did not cause complete ovarian failure. The presence of a pituitary microadenoma was demonstrated by thin layer pluridirectional x-ray tomography of the sella and the pathologically high prolactin reserve capacity of the pituitary.

Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects.

The authors took multiple serum samples for measurement of melatonin between 4:30 p.m. and 7:30 a.

Cerebrospinal fluid levels of amitriptyline, nortriptyline, imipramine and desmethylimipramine. Relationship to plasma levels and treatment outcome.

Fifty-five (55) depressed patients were treated with amitriptyline (AMI) or imipramine (IMI). Concentrations of AMI, IMI, and their metabolites, nortriptyline (NT) and desmethylimipramine (DMI), were measured in cerebrospinal fluid (CSF) and plasma at steady state by gas chromatography mass spectrometry (GC/MS). Highly significant correlations between CSF and plasma levels of AMI, NT, IMI, and DMI were found (r greater than 0.

Peripheral edema associated with trazodone: a report of ten cases.

Ten depressed patients treated with trazodone developed edema and weight gain that was promptly reversed by reduction or discontinuation of trazodone. This suggests a dose-dependent effect. None of the patients had an active medical problem that might predispose to edema formation.

Differences between mammalian ventral and dorsal spinal roots in response to blockade of potassium channels during maturation.

Differences in potassium channel organization between motor and sensory fibres have been described in amphibians but have not previously been examined in mammals. In the present investigation, we studied whole nerve and single axon responses following pharmacological blockade of potassium conductance in rat ventral and dorsal spinal roots during maturation. Our results indicate a differential sensitivity in maturing mammalian motor and sensory fibres which is most apparent in younger roots.

4-Aminopyridine leads to restoration of conduction in demyelinated rat sciatic nerve.

Whole nerve and single axon recordings were obtained in vitro from rat sciatic nerve demyelinated with lysophosphatidyl choline. Compound action potentials recorded across the lesion site were attenuated in amplitude, and showed conduction slowing and temporal dispersion. Application of the potassium channel blocker 4-aminopyridine (4-AP), markedly enhanced the response recorded through the lesion demonstrating both an increase in amplitude and duration of the response.

Ligature-induced injury in peripheral nerve: electrophysiological observations on changes in action potential characteristics following blockade of potassium conductance.

The effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on action potential properties were studied in chronically injured rat sciatic nerves. In normal, mature myelinated fibers, application of 4-AP does not lead to any significant change in action potential waveform or firing pattern in response to single stimuli. In contrast, application of 4-AP to nerves injured by the placement of loose ligatures results in the appearance of late rippled components in the compound action potential.

Aminopyridine-sensitivity of spinal cord white matter studied in vitro.

Sections of dorsal columns of the spinal cord were removed from rats of various ages and studied in a sucrose gap chamber. The potassium channel blocking agent, 4-aminopyridine (4-AP), led to a pronounced increase in the area of the compound action potential of immature dorsal column axons. During the course of maturation this effect was attenuated but not lost.

Efficacy and feasibility of high dose tricyclic antidepressant treatment in elderly delusional depressives.

It is unclear why delusional depressives respond poorly to usual doses of tricyclic antidepressants alone. Seventeen elderly, delusional depressives were treated with high doses of imipramine or desmethylimipramine while monitoring plasma levels in an open study. Four of seven patients who received an adequate trial responded, but over half of the total sample had to be dropped due to intolerable side effects or worsening clinical condition.

Adenosine selectively blocks parallel-fiber-mediated synaptic potentials in rat cerebellar cortex.

Electrophysiological techniques were used to study the efficacy of adenosine in modulating synaptic transmission mediated from convergent parallel- and climbing-fiber inputs to Purkinje cells. Our results indicate that adenosine application leads to selective blocking of parallel fiber-mediated synaptic activity but not of climbing fiber activity. Adenosine does not alter the action-potential excitability properties of the parallel fibers.

Retrograde impulse activity and horseradish peroxidase tracing of nerve fibers entering neuroma studied in vitro.

Neuroma formation was induced in rat sciatic nerve by tight ligature. At various times after placement of the ligature, the nerves were excised, desheathed, split longitudinally proximal to the neuroma, and studied in vitro in a nerve chamber. Stimulation of one of the arbitrarily formed proximal branches was found to generate impulse activity in the other branch.

Dexamethasone suppression in major depression.

Overnight 1 mg dexamethasone suppression tests were performed on 37 hospitalized patients with unipolar major depression and 13 psychiatric controls: 62% of the depressives and 38% of controls failed to suppress below 6 micrograms/dl of plasma cortisol at least once on the day after dexamethasone. Specificity for depressive diagnosis was only 62% but rose to 100% when a plasma cortisol value of 10 micrograms/dl was used as the criterion for normal suppression. Depressed patients were significantly more likely to show normal suppression if they were under age 65 (56% vs.

Sudden death and antipsychotic drugs.

Antipsychotic drug use may be associated with clinically significant cardiovascular side effects and rare instances of sudden death. The authors review case reports of patients who suddenly died while taking these drugs and examine possible mechanisms involved. Clinical recommendations for prevention are made and include attention to predisposing medical factors and avoidance of risky drug combinations.