Biomedical subjects
Publications and source records attributed to S L Cohan.
A patient with transient monocular rotary-vertical nystagmus demonstrated decreased gain of vertical pursuit and normal vestibulo-ocular reflex on electrooculogram. A supranuclear brain stem lesion, resulting in lack of monocular inhibition of oculomotor neurons, is postulated on the basis of these findings.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The effort to employ therapeutic drug monitoring in the management of patients with convulsive disorders has been extremely successful. Fortunately, the drugs used by the majority of these patients are readily measured in plasma, and in most cases the plasma concentration is a valid measure of the appropriateness of the dosage of drug administered. Monitoring also helps to ensure patient compliance to drug schedules and allows appropriate adjustment of dosage in patients who are taking concomitant drugs that influence anticonvulsant drug levels. Accurate and reliable quantitative methodology is available to all laboratories, with the method of analysis selected reflecting the technical capabilities of the laboratory personnel.
The efficacy of phenytoin sodium and chlorpromazine hydrochloride in the reduction of spasticity was evaluated in both open and controlled studies. In each study, the majority of patients exhibited both objective and subjective signs of improvement. Reduction of motor tone in spastic muscles, as well as improvement in functiional status, was observed. Most patients experienced greater benefit from the combination of phenytoin and chlorpromazine than from either drug alone. The use of the drugs in combination permitted decreased chlorpromazine doses and reduced unwanted side effects such as lethargy and somnolence. These drugs may exert their action by suppressing fusimotor efferent as well as afferent discharged from muscle spindles. The results suggest that the fusimotor system is an important pharmacologic target in the treatment of spasticity.
Tapetoretinal degeneration is described in two siblings in association with generalized major motor seizures and intellectual impairment. Neither of these patients have the characteristic dysmorphic features or biochemical abnormalities seen in previously described cases, which are reviewed. Inheritance was probably autosomal recessive.
Ten patients in stage IV hepatic encephalopathy who had not responded to conventional therapy for at least 48 hrs were treated with one or more 4 hr periods of hemoperfusion. Nine (90%) awoke, and 4 (40%) are alive to date, the survivors having acutely toxic and infective hepatic lesions. Biochemical changes that occurred were a reduction in blood ammonia of 23%, a rise in the ratio of branched chain to aromatic amino acids in blood (1.08 +/- 0.3 to 1.3 +/- 0.4), and cerebrospinal fluid (0.26 +/- 0.02 to 0.32 to 0.03), and a rise in cerebrospinal fluid cAMP from 2.3 +/- 0.7 ng/ml to 3.4 +/- 1.29 ng/ml with hemoperfusion. Administration of platelets and fresh frozen plasma restored the reduction of platelet counts of 29% towards pretreatment values.
An analytical method for the measurement of quaternary ammonium compounds in biological fluids has been developed. Samples are prepared by forming the corresponding iodides, which are extracted and isolated. The residue is taken into n-hexane or into water and part of the solution obtained is injected onto the gas chromatograph where thermal degradation takes place. The methyl iodide released is measured by a 63Ni electron capture detector. This method is quite sensitive and detects with good reliability and reproducibility as little as 10(-14) mole quaternary ammonium compound.
Mortality from severe poisoning remains excessively high in patients managed conservatively. In this report, charcoal hemoperfusion was used as a therapeutic aid to active drug removal in 10 patients (9 of whom were in Grade IV coma) intoxicated with a variety of drugs and a further 3 patients poisoned with the highly lethal herbicide, paraquat. All 10 patients who ingested drugs recovered. One of the 3 patients ingesting paraquat survived. The hemoperfusion treatments were associated with demonstrated drug removal. Complications associated with hemoperfusion were minor. Decreases in platelet levels were observed but were not accompanied by clinically important bleeding. The technique of hemoperfusion is simple and provides a therapeutic aid in the care of the severely poisoned patient.
Four patients with myasthenia gravis were under unsatisfactory control while receiving oral pyridostigmine. In each of these patients, the serum levels of this drug were below those observed in patients with myasthenia gravis who are well controlled. The strength of each of these patients improved when the serum pyridostigmine level was increased by intravenous administration of this agent. Furthermore, the rate of disappearance of pyridostigmine from the serum following intravenous administration was the same as that for control subjects and patients under good control. This demonstrates that failure to achieve adequate serum pyridostigmine levels following oral administration is due to malabsorption rather than to increased rates of tissue uptake, degradation, or excretion of the drug.
A simplified gas chromatographic method for measuring quaternary ammonium compounds has been developed and used to measure the serum concentration of pyridostigmine in human beings. Pyridostigmine is present in the serum within 1 hour after oral administration and reaches a peak at 2 hours. Results in several patients suggest that the serum concentration achieved is related to the size of the dose and that there is a relationship between serum concentration and clinical response.
A 25 year old man, with a family history of multiple sclerosis in two preceding generations, developed transient sensory changes and incoordination, initially on the left side, and then several months later on the right side in association with an elevated CSF gamma globulin. This was followed by an acute optic neuritis. During the latter episode he developed a positive brain scan which was unaccompanied by any clinical findings explained by a lesion in that area. Cerebral arteriography was normal and the brain scan returned to normal four weeks later, possibly as a result of blood brain barrier restoration. Abnormal brain scans appear to occur only during acute exacerbations of demyelinating disease, and multiple sclerosis should be part of the differential diagnosis of a positive brain scan in a person in the appropriate age range.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
An improved method is described for the collection of breath for the subsequent assay of acetaldehyde and other volatile components. Breath is collected in a Pyrex gas-collecting tube sealed at both ends with Teflon taps. Prior to collection or assay of the samples, this tube is heated to 72 degrees C; breath is sampled for assay by piercing a rubber septum on a sideport with the needle of a similarly heated gas-tight syringe, and injected into a gas chromatograph (GC). The advantages of this system are: (1) Avoidance of the artefacts encountered in the assay of acetaldehyde in the blood; (2) suitability for sample collection at a site remote from the GC laboratory; (3) avoidance of sample loss by leakage, contamination, or partitioning into water condensed from breath; and (4) compatibility with a "nondedicated" GC lacking any special gas-collecting circuitry. A typical study of a normal human volunteer is described, demonstrating the rise and fall of the concentration of acetaldehyde and ethanol in the breath following the ingestion of an oral dose of ethanol.