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Biomedical subjects

K Ricker

Publications and source records attributed to K Ricker.

At least 55 records · Page 3Linked to original sources
PubMed1991

Confirmation of linkage of hyperkalaemic periodic paralysis to chromosome 17.

Linkage studies were performed in six European families with hyperkalaemic periodic paralysis (PPII) with myotonia, an autosomal dominantly inherited disorder characterised by episodic weakness. The weakness is caused by non-inactivating sodium channels of reduced single channel conductance of the muscle fibre membrane. Recently, portions of the gene coding for the alpha subunit of the sodium channel of the adult human skeletal muscle (h-Na2) have been cloned and localised on chromosome 17q with no recombinants to the human growth hormone locus (GH1). Linkage between these two chromosome 17 markers and the disease was shown in our families (Z = 7.14, 0 = 0.00). These results, combined with the linkage data of a single large American family, suggest that the disease is caused by dominant mutations of the adult sodium channel, and that it is probably a genetically homogeneous disorder. Hyperkalaemic periodic paralysis is the first non-progressive myotonic disorder to be localised on the human genome.

Chromosomes, Human, Pair 17↗
PubMed1990

Myotonia fluctuans.

Autosomal-dominantly inherited nondystrophic myotonic disorders are an interesting group of muscle diseases that provide considerable opportunity for future molecular genetic studies to identify the genes responsible for specific membrane functions. A family with such a myotonic disorder is described with features that are distinctly different from myotonia congenita and paramyotonia congenita. Five members were affected in three generations. The myotonia fluctuated to an unusual degree. It did not worsen with cold but increased markedly with potassium loading. Muscle weakness never occurred. Analysis of the contraction force of the flexor digitorum muscle showed a unique type of myotonia, namely, exercise-induced delayed-onset myotonia. Microelectrode studies done on one muscle biopsy specimen revealed a normal chloride conductance of the muscle fiber membrane.

Adult↗
PubMed1990

Autosomal dominant cramping disease.

A family was studied in which four generations (16 of 41 members) suffered from painful recurrent muscle cramping. A clear pattern of autosomal dominant inheritance was noted. The cramping first developed during adolescence or early adulthood. Electromyographic analysis indicated a neurogenic origin. The cramps seemed to be due to dysfunction of the motor neurons. The mechanisms underlying this alteration are unclear and require further investigation.

Adolescent↗
PubMed1990

Borrelia burgdorferi myelitis presenting as a partial stiff man syndrome.

Eight weeks after a tick bite, a 33-year-old male patient presented with stiffness of one leg together with spasmodic painful jerks resembling stiff man syndrome. Isolated myelitis of lumbosacral segments of the spinal cord, apparently confined to the grey matter, was diagnosed and its spirochaetal aetiology confirmed by serology and CSF findings. Oligoclonal IgG bands in CSF specific for Borrelia burgdorferi were found. Thus, there is evidence that B. burgdorferi ist able to cause a localized myelitis, probably of spinal interneurons, presenting as a partial stiff man syndrome.

Adult↗
PubMed1989

Rippling muscle disease.

Six patients from two families with an autosomal dominantly inherited disease, apparently a myopathy, are described. Their major complaint was muscle stiffness, primarily in the legs. The muscles displayed an unusual sensitivity to stretch, manifested by rippling waves of muscle contraction. These rippling contractions were not accompanied by muscle fiber action potentials. Nonspecific, mild abnormalities were seen on muscle biopsy. These findings raise the possibility that there is an intracellular derangement in the muscle fiber responsible for the muscle rippling; further studies are necessary to establish the underlying pathophysiologic condition.

Adult↗
PubMed1989

Adynamia episodica hereditaria: what causes the weakness?

The cause of weakness was investigated in a patient with adynamia episodica hereditaria without myotonia. A pattern of exercise and rest produced episodes of hyperkalemic periodic paralysis. In addition, local muscle weakness was induced by forearm cooling. Investigations on isolated intercostal muscle demonstrated that a high potassium concentration in the bathing solution triggered a noninactivating membrane current causing depolarization of the muscle fibers. This current was carried by sodium as it could be inhibited by tetrodotoxin. The abnormal sodium conductance led to an increase of sodium within the fibers. This was demonstrated directly by intracellular recordings. Weakness induced by rest after exercise and cold-induced weakness appeared to have different pathomechanisms. In the cold, the muscle fibers retained a normal resting potential, but their excitability was reduced and their mechanical threshold was increased. These findings also provide evidence that the mechanism of cold-induced weakness in adynamia episodica is distinctly different from the cold-induced weakness that occurs in paramyotonia congenita.

Adult↗
PubMed1989

Potassium uptake in muscle during paramyotonic weakness.

Previous studies have suggested that an abnormal release of potassium from muscle may accompany attacks of paramyotonic weakness. We investigated 3 patients with paramyotonia congenita before and after the induction of forearm muscle weakness by exercise in cold water. Two of these patients had paralysis periodica paramyotonica and the 3rd had paramyotonia congenita. At the time of paramyotonic weakness there was a marked increase in the arterialized-venous concentration difference of potassium across forearm muscle. This indicated a significant uptake of potassium by forearm muscle in all 3 patients. Normal controls showed a slight release of potassium both at rest and after exercise in cold water. These results suggest that (1) the sodium-potassium pump of the muscle fiber is operating efficiently during paramyotonic weakness; and (2) there is a different mechanism responsible for the generalized weakness that occurs in hyperkalemic periodic paralysis.

Adult↗
PubMed1988

Hypertrophy of the calf with S-1 radiculopathy.

Occasionally, chronic denervation is associated with enlargement rather than atrophy of muscle tissue. We studied seven patients with S-1 radiculopathy who developed ipsilateral enlargement of the calf. On the basis of results of calf muscle biopsies, it seems likely that the enlargement was due to muscle fiber hypertrophy and atrophy combined with an increase in connective tissue. Computed tomograms of the legs revealed no evidence of tumor. Surgical decompression of the involved S-1 nerve root had no obviously beneficial effect in reducing the calf enlargement. More information is needed to define the natural course of the calf enlargement and to clarify the pathophysiologic processes involved.

Adult↗
PubMed1988

Transient weakness and altered membrane characteristic in recessive generalized myotonia (Becker).

The isometric force of arm and leg muscles was studied in five unrelated patients with recessive generalized myotonia (Becker). The symptom of myotonia was present mainly in the legs, whereas transient weakness was the prominent symptom in the arms. Tocainide improved both symptoms, although it improved the stiffness more than the weakness. A specimen of intact muscle fibers was excised from the external intercostal muscle of one of the patients. The resting potential of the fibers was normal, but on injection of depolarizing current the fibers responded with repetitive action potentials. In normal interstitial fluid the current-voltage relationship was N-shaped, with a region of negative slope between -70 and -55 mV. Replacement of chloride by an impermeant anion changed this relationship very little, suggesting an abnormally small chloride conductance. The potassium current through the inward-going rectifier was larger than normal. The force of tetanic contractions of a rested bundle was not sustained but fell quickly to a plateau that increased with repeated stimulation. The relaxation of a rested tetanus was slow and accompanied by spontaneous electrical activity. In subsequent contractions the relaxation became faster and electrical after-activity decreased. However at 23 degrees C the speed of relaxation was always high despite a large amount of electrical after-activity. The electrical instability of the membrane and the transient weakness can be explained on the basis of the N-shaped membrane characteristic.

Action Potentials↗
PubMed1987

Adynamia episodica hereditaria with myotonia: a non-inactivating sodium current and the effect of extracellular pH.

To study the mechanism of periodic paralysis, we investigated the properties of intact muscle fibers biopsied from a patient who had adynamia episodica hereditaria with electromyographic signs of myotonia. When the potassium concentration in the extracellular medium, [K]e, was 3.5 mmol/l, force of contraction, membrane resting potential, and intracellular sodium activity were normal, but depolarizing voltage clamp steps revealed the existence of an abnormal inward current. This current was activated at membrane potentials less negative than -80 mV, reached a maximum within 50 msec, and was not inactivated with time. The inward current was completely and reversibly blocked by tetrodotoxin, which indicates that it was carried by sodium ions. In a solution containing 9 mmol/l potassium, normal muscle would depolarize to -63 mV and yet be capable of developing full tetanic force upon stimulation. The muscle from the patient depolarized to -57 mV and became inexcitable, i.e., it was paralyzed. A contracture did not develop. Lowering of the extracellular pH did not influence the resting potential, but it effectively antagonized or prevented the paralytic effect of high [K]e by changing the inactivation characteristics of the sodium channels. Hydrochlorothiazide, which had a therapeutic effect on the patient, did not prevent paralysis in vitro. An abnormal rise of the intracellular sodium activity was recorded when the extracellular potassium concentration was raised to 10 mmol/l.

Adult↗
PubMed1987

Membrane defects in paramyotonia congenita (Eulenburg).

Membrane potentials, current-voltage relationships, and component conductances were determined in resting excised external intercostal muscle fibers from five patients with paramyotonia congenita. At 37 degrees C all investigated parameters were normal. At 27 degrees C the resting potentials decreased to about -40 mV, and the fibers were inexcitable. At this stage the membrane currents were much larger than in normal fibers owing to increases in the membrane conductances for Na and Cl ions. The earlier finding that in the cold the Na permeability is abnormally large was confirmed. The Cl permeability was shown to be normal even in the cold. The decrease of the resting potential and the changes in the current-voltage relationship at 27 degrees C could be prevented by the use of the Na channel blocker tetrodotoxin (TTX) or by bathing the fibers in a Na-free solution. Our previous conclusion that the Cl conductance at 27 degrees C was also increased when TTX was present was not confirmed. Exposure of a muscle bundle to 7 mmol/l potassium did not lead to excessive depolarization and paralysis.

Biopsy↗
PubMed1986

Muscle stiffness and electrical activity in paramyotonia congenita.

To investigate the pathomechanism of paramyotonic stiffness, the mechanogram of isometric finger force and the electromyogram of the flexor digitorum muscle were simultaneously recorded in five unrelated paramyotonia congenita patients. Cooling of the forearm provoked "spontaneous" electrical activity, but the accompanying force was less than 5% of the maximal voluntary isometric contraction amplitude. The relaxation of maximal voluntary contractions executed in the cold had a normal first phase and a very slow second phase. The force amplitude at the beginning of the slow phase was up to 80% of the maximal contraction amplitude; the duration of the slow phase was up to several minutes. It was concluded that the slowed muscle relaxation is more important as a factor contributing to paramyotonic stiffness than spontaneous force generation. Involuntary electrical activity recorded during the slow relaxation phase was too low to account for the force. Intercostal muscle biopsies obtained from four patients showed similar phases of slow relaxation when stimulated to give isometric twitches or tetani in the cold. Extracellular recording with electrodes designed to pick up all activity from the small bundles clearly showed that the slow relaxation phase was not caused by spontaneous action potentials. One possible explanation for the slowed relaxation is a long-lasting depolarization-induced contracture of the muscle fibers following activation in the cold.

Adult↗
PubMed1986

Adynamia episodica and paralysis periodica paramyotonica.

We studied hyperkalemic attacks in one family with adynamia episodica (AE) and one family with paralysis periodica paramyotonica (PPP). Under exercise, serum potassium increased as in healthy subjects. Thiazide did not affect this increase. Thirty minutes after exercise, a second potassium increase occurred, but could be prevented by thiazide and not by mexiletine. After cooling, muscle relaxation time was normal in AE but increased up to 100 times in PPP; this cooling effect was prevented by mexiletine. Although hyperkalemic attacks are similar in AE and in PPP, the membrane defect in PPP seems more complex.

Adult↗
PubMed1985

In vivo P-NMR spectroscopy: muscle energy exchange in paramyotonia patients.

Using phosphorus nuclear magnetic resonance spectroscopy, we studied the muscle metabolism in four patients with paramyotonia congenita as reflected in the PC/Pi and PC/ATP ratios. At normal body temperature, all results were indistinguishable from controls. After cooling to 29 degrees C muscle temperature and a single 2-sec maximum contraction, the forearm muscles were stiff. At this stage, no decrease in the ATP content could be detected. In greater than 50% of the experiments with patients, an additional peak occurred transiently at the resonant frequency for monophosphates. After a working period at 29 degrees C muscle temperature, the paramyotonic muscles were paralyzed, but displayed spectra similar to those obtained at normal body temperature and full working capability. Intracellular pH was close to 7 in paramyotonic muscle under all conditions examined.

Adenosine Triphosphate↗
PubMed1984

Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters.

To study the mechanism of attacks in familial hypokalemic paralysis, we recorded resting membrane potentials, action potentials, current-voltage relationships, and isometric forces in intercostal muscle fibers from three patients. In normal extracellular medium, the resting potential was reduced, but membrane conductance was not different from control. Excitability was reduced and the action potentials had no overshoot. On exposure to a 1-mM potassium solution, with or without insulin, the cells depolarized to about -50 mV, and became inexcitable. Over the tested membrane potential range from -120 to -40 mV, the slope conductance in the 1-mM potassium solution was not different from that of control fibers in a 1-mM potassium solution. In particular, the potassium component conductance was not reduced. Depolarized fibers could not be completely repolarized by returning to a 3.5-mM potassium solution. An experimentally induced transient shift of the chloride equilibrium potential to a highly negative value caused stable repolarization. Paralysis could also be induced by replacement of extracellular chloride with an impermanent anion, a treatment which causes myotonia in healthy fibers. It was concluded that the basic defects are a reduced excitability and an increased sodium conductance, and that these defects are aggravated on reduction of the extracellular potassium concentration.

Adult↗