Diltiazem in the treatment of calcinosis in juvenile dermatomyositis.

Subcutaneous calcifications occur in a variety of diseases, including juvenile dermatomyositis. These calcifications cause disabling symptoms that do not always respond to immunosuppressant therapy. The calcium antagonist diltiazem reduces subcutaneous calcifications in CREST syndrome and in isolated cases of children with dermatomyositis. Our study was performed to determine the effects of diltiazem when used as adjunctive therapy in children with dermatomyositis.

Long-term tracheostomy ventilation in neuromuscular diseases: patient acceptance and quality of life.

Domiciliary assisted ventilation has been used to prolong life in patients with neuromuscular diseases. Although earlier studies suggest that the majority of patients are satisfied with their lives, the physician's perception of a patient's poor quality of life on assisted ventilation is a major reason for discouraging assisted ventilation. In this study, the quality of life was assessed in 19 patients with neuromuscular diseases on domiciliary tracheal intermittent positive-pressure ventilation for a mean duration of 54 months. An attempt was made to compare the quality of life of Duchenne muscular dystrophy patients with that of amyotrophic lateral sclerosis patients. More than two-thirds of patients were satisfied with their lives. Eighty-four percent thought they had made the right choice. Patients with amyotrophic lateral sclerosis were somewhat more negative or ambiguous toward assisted ventilation and had lower life satisfaction scores as compared with Duchenne muscular dystrophy patients. Financial stresses were significant. Assisted ventilation should be offered as a viable option to patients with neuromuscular diseases. Larger studies may be useful in influencing insurance companies to make expenses associated with assisted ventilation reimbursable.

Focal myositis presenting with radial nerve palsy.

Focal myositis is a rare inflammatory pseudotumor of skeletal muscle which usually has a benign course. We report a 56-year-old woman with a painful mass in the left arm with a radial nerve palsy. Magnetic resonance imaging (MRI) of the left arm showed a mass in the triceps muscle that was suggestive of a soft-tissue sarcoma. Electromyography showed a severe radial neuropathy involving both motor and sensory axons. An open biopsy showed focal myositis. Treatment with corticosteroids resulted in complete disappearance of the mass clinically and by MRI, without recurrence for more than 2 years. Radial nerve function also recovered completely. As a treatable cause of focal neuropathy, focal myositis should be included in the differential diagnosis of a muscle mass.

Tongue involvement in a patient with granulomatous myositis.

A 64-year-old woman had difficulty swallowing and talking, weakness of the tongue, and progressive muscle weakness that was proven to be caused by a granulomatous myopathy. This case resembled a motor neuron disease, indicating that granulomatous myopathy should be considered in patients with similar presentations, since it is a treatable condition with a more benign prognosis.

Solitary focal demyelination in the brain as a paraneoplastic disorder.

Solitary focal demyelination (SFD) in the brain is an uncommon and poorly understood disorder of uncertain etiology that may represent an intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis. In a few reported cases of SFD, the patient was briefly noted to have a nonneurological malignancy. We studied two patients who had solitary focal lesions in the brain. Utilizing magnetic resonance imaging and tissue biopsy, we found the characteristics of the brain lesions in these two patients to be those of SFD. In our combined experience over the past 10 years, we have encountered no similar brain lesions at our medical center. We found it remarkable that both of these patients also had malignancy outside of the nervous system. One had a seminoma, and the other a lymphoma. We conclude that some cases of SFD in the brain may occur as a paraneoplastic disorder associated with nonneurological malignancies.

Octreotide enhances positive calcium balance in Duchenne muscular dystrophy.

Although receptors for somatostatin are found in bone cells, the effect of somatostatin analogs on calcium metabolism is unknown. The authors studied, in a metabolic ward, the effect of octreotide (a long-acting somatostatin analog) and a placebo in two 6-day calcium balance periods in 8 children with Duchenne muscular dystrophy. As expected, octreotide (2 micrograms/kg, subcutaneously, every 8 hours) reduced serum growth hormone and somatomedin (IGF-1) to levels found in growth hormone deficiency. Octreotide enhanced calcium retention by 30% (96 mg daily [P < 0.04]) in 7 boys for whom complete data (diet, urine, and fecal calcium) were available. In 6 children with urinary calcium excretion (Uca) greater than 50 mg daily, octreotide markedly lowered Uca, from 114 +/- 23 mg daily to 61 +/- 9 mg daily (P < 0.03). Calcium retention occurred in patients with or without initial hypercalciuria, but the higher the basal Uca, the greater was the inhibition by octreotide (r = 0.79; P < 0.03). Inactive, nonambulatory patients had a more pronounced response of Uca to octreotide (P < 0.02). Octreotide caused a mild, nonsignificant reduction in fecal calcium, with no major changes in serum calcium, phosphorus, parathyroid hormone, urinary excretion of sodium and potassium, or in creatinine clearance. Based on the current observations and the presence of receptors for somatostatin in bone cells, this hormone may have, at least on a short-term basis, an anabolic effect on calcium, perhaps favoring its deposition in bone.

Muscle hypertrophy secondary to the tethered cord syndrome.

Segmental muscle enlargement occurs in a variety of neurogenic conditions. We present a case with calf hypertrophy, likely produced by partial denervation and continuous neuromuscular irritability, which was caused by a tethered spinal cord that was demonstrated by MRI. Muscle MRI correlated with muscle biopsy findings in which atrophy and hypertrophy were accompanied by rimmed vacuoles.

Immunohistochemical analysis of the distribution of MyoD1 in muscle biopsies of primary myopathies and neurogenic atrophy.

The expression of the myogenic determination gene MyoD1 plays a primary role in the commitment of primitive mesenchymal cells to a striated muscle lineage and is down-regulated during later stages of differentiation. To determine the potential role of this gene in myopathic conditions, we examined its expression by means of immunohistochemical analysis, using a series of muscle biopsies from 14 patients with a variety of primary myopathies and neurogenic disorders. Utilizing the avidin-biotin-complex technique, cryostat sections were stained with monoclonal antibody 5.8 A, which we have previously described as having a high level of specificity for tumors with rhabdomyoblastic differentiation. Of special interest was the observation in 4 of 8 cases of neurogenic atrophy of varying levels of cytoplasmic positivity of muscle fibers, appearing to correlate with their degree of atrophy, in addition to weak nuclear staining. Muscle biopsies from 2 patients with Duchenne's muscular dystrophy and 2 patients with autoimmune inflammatory myopathies demonstrated various levels of nuclear positivity in scattered foci that appeared to correlate with areas of regeneration. A biopsy from a single case of neurogenic atrophy secondary to infantile spinal muscular atrophy (Werdnig-Hoffmann's disease) demonstrated diffuse but relatively weak staining of myofiber nuclei, in contrast to sections of normal striated muscle and muscle biopsies from patients with unexplained myoglobinuria, which exhibited only minimal amounts of staining. These data are compatible with observations that MyoD1 expression is related to electrical activity and muscle regeneration.

An evaluation of automated defibrillation and manual defibrillation by emergency medical technicians in a rural setting.

We show that automated external defibrillation training of emergency medical technicians (EMTs) is less time consuming than manual defibrillation training, and hypothesize that both improve survival from sudden cardiac death. Data on 91 cardiac arrests over 27 months among five basic life support services was collected before EMT-defibrillation (EMT-D) training. Subsequently, seven BLS services were trained in EMT-D using either manual difibrillation or automated external defibrillation technology, and 55 sudden cardiac death patients were entered after training. Manual defibrillation required 11 more hours per student in initial training. Survival to hospital discharge improved from two of 91 patients (2.2%) in the series before EMT-D training to nine of 55 patients (16.4%) after EMT-D training (P = .001). Improved survival was correlated with shorter prehospital defibrillation times, 8.84 minutes, when EMTs performed defibrillation versus 16.3 minutes before training when EMTs awaited advanced life support defibrillation (P < .001). To enhance equipment familiarity we allowed EMTs to apply three-lead electrode monitors to all medical/cardiac patients during transport (surveillance). There were six emergency medical service-witnessed "surveillance" arrests and three arrests survived to hospital discharge (50% survival). This group represented 33% of all survivors in the series. We recommend automated external defibrillation training for EMTs. Improved survival in sudden cardiac death cases in well-run emergency medical service systems should result from EMT-D training. Finally, we recommend that routine "surveillance" of high-risk patients during transport by defibrillation-capable EMTs be considered in EMT-D programs, rather than limiting EMT-D only to units capable of rapid "man-down" response.

Origin, distribution, and morphology of serotonergic afferents to the cat superior colliculus: a light and electron microscope immunocytochemistry study.

We have studied the serotonergic (5-HT) projection to the cat superior colliculus (SC) using serotonin antibody immunocytochemistry and retrograde transport of peroxidase-conjugated wheatgerm agglutinin (WGA-HRP). In 3 experiments, the two labels were combined in order to double label cells with both anti-5-HT and WGA-HRP. In the remaining experiments, the two labels were examined separately. Serotonin-like immunoreactive fibers were found throughout all layers of SC, but were most densely distributed within the zonal and upper superficial gray layers. Most 5-HT fibers were thin and had characteristic varicosities and terminal swellings. At the EM level, immunoreactive terminals and varicosities were found to contain small agranular vesicles and occasionally large granular vesicles (LGVs). Conventional synaptic densities were only rarely observed. Injections of WGA-HRP into SC resulted in labeling of neurons throughout the dorsal raphe nucleus and surrounding ventrolateral periaqueductal gray. Only a few cells were found in the raphe medianus and raphe pontis and none within the raphe magnus or other medullary raphe nuclei. Cells in the dorsal raphe giving rise to the SC projection varied in shape, size, and morphology and must represent more than one cell type. The morphology of these cells was indistinguishable from that of cells in the dorsal raphe which were double labeled by anti-5-HT and WGA-HRP. We conclude that the 5-HT innervation of the superior colliculus varies in density in different laminae, arises from several different cell types, and originates primarily from the dorsal raphe nucleus with minor projections from raphe medianus and raphe pontis.

Computer-generated reports for monitoring variances in the drug budget.

A computerized pharmaceutical-purchasing cost-management system that can be used to monitor variances in the drug budget is described. Variance reports on inflation, volume of drugs used, and changes in inventory are generated monthly to determine whether the pharmacy is operating within its budget. The reports are processed on an IBM personal computer with the use of a dBASE-III management software package. The price and quantity of each drug, as specified in the standard drug budget, are entered into the system; using approximately four hours per month is required for entry of the quantities and prices of drugs received as noted on the invoice. Variances in the budget are reviewed, and drug-use data are assessed to determine trends. Demand intensity (use per 1000 cases) is also tracked to determine the effects of educational programs on the proper use of drugs. Variance reports generated by a computerized budget-monitoring system provide the pharmacy with timely cost data that can be used to monitor the effects of drug-use guidelines and educational programs on the budget.

Quantitative comparison of retinal synapses in the dorsal and ventral (parvicellular) C laminae of the cat dorsal lateral geniculate nucleus.

Three physiological classes of retinal ganglion cell project to the cat dorsal lateral geniculate nucleus (DLGN). The dorsal laminae A, A1, and magnocellular C receive X and Y retinal input, whereas the ventral parvicellular laminae C1 and C2 receive predominantly W input. We have compared quantitatively the retinal synaptic terminals of the dorsal and ventral laminae to determine whether there are morphological differences in the terminals that correspond to their different response properties. Anterogradely labeled retinal synaptic terminals in all laminae contained pale mitochondria and large, round synaptic vesicles. However, retinal terminals with pale mitochondria varied in size and synaptic organization in different laminae. The terminals in the A laminae were, on average, quite large and made numerous contacts with conventional dendritic profiles and with profiles that themselves contained synaptic vesicles (F2 profiles). The terminals in lamina C that contained pale mitochondria had a smaller overall mean area. Terminals with pale mitochondria in C1 and C2 were almost all small and synapsed with F2 profiles less frequently than did terminals in the A laminae or in lamina C. These results provide quantitative evidence that visual areas receiving W-type retinal input contain smaller retinal terminals and have a different synaptic organization from that of laminae receiving X and Y input.

[The chemoselective fluorescence labeling of alpha-chymotrypsin]. / Untersuchungen zur chemoselektiven Fluoreszenzmarkierung von alpha-chymotrypsin.

The covalent fixation of the phosphinoyl residues in the active site of alpha-chymotrypsin is proved by the application of the fluorescent phosphinoyl fluorides 1 [( 5-(dimethylamino)-1-naphthyl]phenylphosphinoyl-fluoride) or 4 [(5-methoxy-1-naphthyl)phenyl-phosphinoylfluoride]. The differences in the rates of the phosphinoylation of alpha-chymotrypsin and "methyl-alpha-chymotrypsin" as compared to 1 agree with model reactions. In both enzymes the serine-OH in the active site is phosphinoylated. The non-fluorescent 4-nitrophenyl [5-(dimethylamino)-1-naphthyl]phenylphospinate (3) and the corresponding non-fluorescent 5-methoxynaphthyl derivative 5 inhibit alpha-chymotrypsin far more slowly than the corresponding fluorides 1 and 4. The phosphinoyl residues of the nitrophenyl esters 3 and 5 are covalently linked in a yield of 80% to the active site of the enzyme with evolution of fluorescence. 20% of the nitrophenyl ester inhibits the enzyme by adsorption.

[Inhibition of acetylcholinesterase using fluorescence-labeled inhibitors]. / Untersuchung der Inhibierung der Acetylcholinesterase mit Hilfe fluoreszierender Inhibitoren.

The inhibition of acetylcholinesterase with fluorophores type II and III linked with the OH-selective fluorophosphonoyl groups is kinetically investigated by comparing the changes in activity and fluorescence. The hydrolysis of the fluorescent phosphonoylfluorides 1 and 4 to 7 in aqueous buffer solutions does not interfere with the inhibition kinetics. The inhibition constants of the investigated compounds are unexpectedly high (10(6) to 10(8) S-1M-1). They increase with increasing spacer length, but arrive at an optimal value with four methylene groups in the inhibitor 6. The fluorescence is quenched by the interaction of 6 and acetylcholinesterase. This fact can be used for the determination of acetylcholinesterase by fluorescence titration (Fig. 9). Fluorescence once more increases slowly during the aging process, leading to the degradation products 9, 11 and 12. In acetylcholinesterase inhibited by 1, a sensitized fluorescence is observed, produced by tryptophane intrinsically linked to the esterase. In the presence of quaternary ammonium salts like acetylcholine chloride or gallamine triethochloride 15, the decrease of fluorescence is lower. Acetylcholinesterase inhibited in this way is reactivated quantitatively by toxogonine. No reactivation is possible with acetylcholinesterase inhibited in the absence of the above mentioned quaternary ammonium salts. As a result of the investigation using fluorescent inhibitors the conclusion can be drawn that not only the active site of acetylcholinesterase is blocked by phosphonoylation. The conformation too seems to be influenced by interactions of the inhibitors with the hydrophobic areas of the enzyme.

Retinal synapses of the cat medial interlaminar nucleus and ventral lateral geniculate nucleus differ in size and synaptic organization.

The retinal terminals of the medial interlaminar nucleus (MIN) and ventral lateral geniculate nucleus ( VLG ) have been examined quantitatively to determine if there are morphological differences in their synaptic ultrastructure which reflect their distinctive physiologies . The cross-sectional area and density (number per unit area) of synaptic contact zones with conventional and presynaptic dendrites (F2 profiles) were measured for each retinal terminal. The densities of F2 presynaptic dendrites and F1 flattened vesicle axon terminals were also measured. Retinal terminals in MIN were often large (mean size = 2.7 micron2 area) and had a high density of synaptic contacts (0.14 per micron surface area) with conventional dendrites, presynaptic dendrites, and dendritic spines. A high density of F2 presynaptic dendrites (0.08 per micron2 area) was found in MIN. F1 axon terminals were also found frequently (0.04 per micron2). MIN retinal terminals were often organized in glomeruli like those of the dorsal lateral geniculate nucleus. The retinal terminals in VLG were almost always small (mean size = 0.94 micron2 area), although they also had a high density of synaptic contacts (0.17 per micron surface area). They frequently synapsed on small dendrites and dendritic spines and less frequently on large dendrites. Unlike MIN, retinal terminals in VLG rarely contacted F2 presynaptic dendrites which were much less frequent in VLG (0.01 per micron2 area). Like MIN, VLG contained numerous F1 axon terminals (0.06 per micron2 area). No typical retinal glomeruli were found in VLG . These results show that MIN, which contains many Y cells, has a population of large retinal terminals and many F2 presynaptic dendrites. VLG , which apparently has only W cells, contains only small retinal terminals and has fewer F2 presynaptic dendrites. Both have a high density of F1 flat vesicle axon terminals.