EEG operant conditioning in intractable epileptics.

Eight epileptic patients with mixed seizures refractory to medical control participated in a double-blind crossover study to determine the effectiveness of operant conditioning of the EEG as an anticonvulsant procedure. Baseline levels of seizures were recorded for four months prior to the beginning of treatment. Participants then received false (noncontingent) feedback for two months followed by an ABA-patterned training program lasting a total of ten months. Subjects were assigned to three treatment groups based on different schedules of EEG feedback. They were first trained (A1 phase) either to suppress slow activity (3 to 8 Hz), to enhance 12- to 15-Hz activity, or to simultaneously suppress 3- to 8-Hz and enhance 11- to 19-Hz activity. This was followed by a B phase, in which patients were trained to enhance slow activity (3 to 8 Hz). In the final phase (A2), the initial training contingencies were reinstated. Neuropsychological tests were performed before and after training, and changes in EEG activity as determined by Fast Fourier spectral analyses were analyzed. Five of eight patients experienced a decrease in their mean monthly seizure rate at the completion of feedback training as compared with their initial baseline level.

L-homoserine hydroxamic acid as an antitumor agent.

This report confirms the potent mutagenic and antitumor activity of L-homoserine hydroxamic acid in both in vitro and in vivo test systems. Its mutagenic potential is evident in the developing tadpoles of Xenopus laevis eggs exposed to the compound. Cytotoxic effects are demonstrated against human leukemia and melanoma cell lines proliferating in tissue culture and against xenografts of human breast cancer and sarcoma growing in nude mice. We propose that the mutagenic and antitumor activity are mediated through hydroxylamine, which is released from its stable carrier amino acid, homoserine, consequent to a reduction in pH occurring at the cellular level. The cytotoxic effects of L-homoserine hydroxamic acid are more intense than those of the D-isomer and are more evident in neoplastic than in normal cell lines.

Treatment of cerebrospinal fluid leaks and gram-negative bacillary meningitis with large doses of intrathecal amikacin and systemic antibiotics.

Six patients with cerebrospinal fluid (CSF) leaks and gram-negative bacillary meningitis (GNBM) were treated with large doses of intrathecal amikacin (20 to 40 mg daily) and systemic antibiotics. Bactericidal activity was measured in the CSF of each patient, and the dose of intrathecal amikacin was increased if bactericidal activity was absent. Five of six patients had no bactericidal activity with systemic antibiotics alone and/or low dose intrathecal amikacin. All six patients were cured, and three of four patients with vertebral lesions had cessation of CSF leaks within 72 hours of the start of intrathecal amikacin. Intrathecal treatment for 7 to 10 days was adequate for five patients; the CSF of all patients was sterile within 72 hours, and all had a 90% reduction of pleocytosis in the CSF within 96 hours. One patient had radicular back pain after each intrathecal injection, but other side effects were not observed. These findings indicate that CSF leaks associated with GNBM can be effectively treated with large doses of intrathecal amikacin plus systemic antibiotics.

Percutaneous restoration of a kinked shunt. Case report.

A thin-walled atrial catheter used in shunting for hydrocephalus may become curled or kinked in the neck after it has been in normal position and functioning for years. The usual cause is a bout of severe coughing. Such a case is described together with a percutaneous method of restoration of the shunt by transfemoral catheterization utilizing a wire loop.

The injudicious laminectomy.

This report is an attempt to point out a hazard of what would be otherwise competent treatment of acquired spinal stenosis, namely laminectomy and facetectomy, in a small group of patients who are osteoporotic and who also have a "minor" compression fracture in the area in which the surgery is contemplated. Three patients who had such laminectomies, with disastrous results, are presented, along with one patient who, instead, had internal fixation and fusion at the time of laminectomy with an excellent result. The latter approach is recommended in such cases.

Surgical correction of proximal femoral nerve entrapment.

BACKGROUND: Femoral nerve palsy is usually a result of trauma. Isolated femoral nerve palsy without external trauma is restricted to occasional case reports in various circumstances. CASE DESCRIPTION: Three cases of nontraumatic femoral nerve palsy are reported who presented with pain and weakness. Symptoms were relieved by transection of the iliopectineal arch. This is believed to be a newly described syndrome. An additional case of femoral nerve entrapment following vaginal hysterectomy is described. This case presented only as a pain syndrome. CONCLUSIONS: There is a syndrome of femoral nerve entrapment at the iliopectineal arch that can be easily relieved by sectioning of this arch, analogous to carpal tunnel syndrome. Several cases of femoral nerve palsy previously reported may be examples of this syndrome.

The lactam of alpha-guanidinoglutaric acid (1-amidino-2-pyrrolidone-5-carboxylic acid).

alpha-Guanidinoglutaric acid (alpha-GGA) has been reported to occur in the cerebral cortex after epileptic seizures. No physical characteristics of alpha-GGA have been given. A practical procedure for the preparation of alpha-GGA is reported here. alpha-GGA forms a lactam in aqueous solution at 80 degrees C. It is proposed to substitute this lactam, 1-amidino-2-pyrrolidone-5-carboxylic acid (pAGlu), for pyroglutamic acid (pGlu) at the N-terminal position in neuropeptides to modify their biological characteristics. L(+)-Glutamic acid was reacted with S-methylisothiourea (I) at pH 10 in aqueous solution to form L(-)-alpha-guanidinoglutaric acid: mp 165-168 degrees C, [alpha]22D = -22.7 (C = 4, 2 M HCl). alpha-GGA reacted promptly with excess reagent to form a salt, S-methylisothiourea-alpha-guanidinoglutarate: mp 209-210 degrees C, [alpha]22D = -13.0 (C = 4, 2 M HCl). I was removed from the salt with aqueous picric acid, since I readily formed an insoluble picrate, S-methylisothiourea picrate (mp 225-228 degrees C). Alternatively, the salt was added to a cation exchange column, and the alpha-GGA was eluted with molar ammonium acetate buffer, pH 9.5. Its lactam, 1-amidino-2-pyrrolidone-5-carboxylic acid, mp 248-249 degrees C, [alpha]22D = +2.1 (C = 4, 2 M HCl), formed a picrate (mp 196-199 degrees C).

Metabolic relationship between urea and guanidino compounds as studied by automated fluorimetry of guanidino compounds in urine.

In this automated system for assaying guanidino compounds, the compounds are resolved on an ion-exchange (Dowex 50) column, then reacted with phenanthrenequinone in alkaline solution. This mixture is then acidified and the resulting fluorescence is measured (lambda ex, 305 nm; lambda em, 395 nm). I applied the system to the analysis of urine from control rats and rats given L-canavanine, L-canavaninosuccinic acid, L-guanidinosuccinic acid, L-arginine, or urea, intraperitoneally. The recorder tracings are compared with those obtained for urine from healthy and uremic humans. After urea administration some guanidinosuccinate is excreted, along with substantial quantities of another substance that elutes just before guanidinosuccinate and so may be mistaken for it. Urine from uremic humans also shows this unidentified peak, but not urine from untreated rats or healthy humans. L-Canavanine gives rise, mainly, to guanidine and homoserine, apparently by reduction. Similarly, canavaninosuccinate is reduced to homoserine and guanidinosuccinate. Arginine gives rise to small quantities of guanidinosuccinate. Guanidinosuccinate is excreted mainly unchanged. When the guanidinosuccinate concentration is increased, excretion of guanidinoacetic acid is suppressed.

Early third ventriculostomy in meningomyelocele infants - shunt independence?

Percutaneous anterior and posterior third ventriculostomy utilizing a McKinney leukotome has been performed with fluoroscopic control in 9 newborn infants with meningomyelocele and hydrocephalus immediately following their shunt. The procedure was instituted in 1975, and there have been no shunt revisions in such patients since that time. Wider application of this or a similar technique in newborn meningomyelocele infants seems warranted.

Serum and erythocyte argininosuccinate lyase assay by NADH fluorescence generated from formed fumarate.

Measurement of argininosuccinase (I; EC 4.3.2.1) activity is useful in following the course of disease in hepatitis and in screening for the genetic defect, argininosuccinic aciduria. Methodology is proposed for a novel procedure for the determination of I in serum and erythrocytes. In the procedure, fumarate, generated in the reaction, is assayed by conversion to malate with fumarase, determining the malate enzymatically with malate dehydrogenase, and estimating the NADH formed spectrofluorometrically. By this procedure, the enzyme activity in serum from normal individuals is less than 11 mumol/liter of erthrocytes/per hour. The correlation coefficient between results by this method and by the colorimetric method, which measures the arginine generated in the reaction, is +0.97 for serum and +0.98 for erythrocytes. The proposed procedure has a relatively low initial blank, requires less serum, and is completed faster.

Hepatic synthesis of canavaninosuccinate from ureidohomoserine and aspartate, and its conversion to guanidinosuccinate.

This study continues the exploration of the mechanism for the formation of guanidinoacetate and guanidinosuccinate in the human [Clin. Chem. 21, 235 (1975)]. In this report we describe the formation of canavaninosuccinate from ureidohomoserine and aspartate by a human or bovine liver extract that had high argininosuccinate synthetase (EC 6.3.4.5) activity, and the subsequent formation of guanidinosuccinate by reductive cleavage. In the presence of ATP the optimum pH for the synthetic reaction is 8.4. This reaction can be carried out in either a tris(hydroxymethyl)aminomethane or borate buffer. Subsequent addition of dithiothreitol in the presence of Fe2+ resulted in the cleavage of some of the synthesized canavaninosuccinate to form guanidinosuccinate and homoserine. Synthesis of canavaninosuccinate was strongly inhibited by added argininosuccinate, less so by canavaninosuccinate, arginine, canavanine, glycine, or 2,3-dimercaptopropanol. The Km values for the substrates of the synthetic reaction are 3.6 X 10(-4) mol/liter for aspartate, 1.6 X 10(-3) mol/liter for ureidohomoserine, and 2.92 X 10(-5) mol/liter for ATP. These values are higher than those obtained when the synthesis of argininosuccinate was studied, except for ATP, which yielded a lower value. All of the reactions in the proposed mechanism have now been demonstrated except for the synthesis of canaline from aspartate.

Afibrinogenemia with intracerebral hematoma. Report of a successfully treated case.

A patient with congenital afibrinogenemia underwent removal of an intracerebral hematoma following specific therapy with fibrinogen-containing concentrates. We believe the successful neurosurgical intervention in a life-threatening complication of this unusual coagulation disorder to be unique.

Improved staining characteristics of serum lipids after halogenation and esterification of thin-layer chromatograms.

We describe a procedure for treatment of thin-layer chromatographic serum lipid patterns so that they may be stained by dyes for evaluation by densitometry. After development of the chromatogram [Clin. Chem. 18, 384 (1972)] the plates are dried and sprayed with butyryl chloride. This esterifies the free cholesterol. After drying, the plate is treated with iodine monobromide, to add iodline to the double bonds. The triacylglycerols (triglycerides), cholesterol esters, free cholesterol, and phospholipids are now all in the form of esters with no unsaturated double bonds. The free fatty acids are also now saturated. The chromatogram is now stained with basic fuchsine in acetate buffer (0.1 mol/liter, pH 5.0). Excess stain is removed with a buffered solution of guanidine hydrochloride. Erythrosine B may also be used. With basic fuchsine the background will be a uniform pink. With erythrosine B the background is white, but the stain tends to be washed out of the free fatty acids. The chromatograms are evaluated by densitometry, with use of a 540-nm filter for basic fuchsine and a 520-nm filter for erythrosine B. The stained chromatograms and densitometric scans accurately represent the relative concentration of the various lipid fractions as compared to that of an internal standard, and correlate with the nature of the disease being explored.

Delayed CSF seeding of benign oligodendroglioma.

We report the case of a man who at 42 years of age had right frontal lobectomy for removal of a benign oligodendroglioma. Seventeen years later, at age 60, he had resection of a fourth ventricular vermian lesion, which was found to be histologically identical to the original lesion. A further lesion in the left occipital lobe was not biopsied but was treated with radiation therapy. We suggest that these subsequent two neoplasms represent CSF spread of the original tumor. This case emphasizes the need for indefinite longitudinal surveillance for these patients.