Biomedical subjects
Publications and source records attributed to M Poisson.
A 56-year-old man had radiation necrosis of the optic pathways, hypothalamus and brainstem following irradiation of a pituitary adenoma at a conventional dose. Factors which predispose to this complication are discussed. Vascular risk factors appear to facilitate radiation induced necrosis, and a reduction of doses is suggested in these cases.
Diaziquone, a new alkylating agent which crosses the blood brain barrier, has shown a 20% response rate in phase II studies in heavily pretreated patients. We have treated 23 patients at our institution as part of a multicentric phase II European trial of diaziquone. All had histologically proven malignant glioma unequivocally progressing on CT scan. Prior therapy had consisted of surgical excision (13 patients), cobalt radiotherapy to CNS (13 patients), and chemotherapy with nitrosourea derivatives (11 patients). Six patients had no prior therapy. Median age was 42 years (range 22-69) and performance status was 3+ or better. They were treated with monthly courses of diaziquone 5.5 mg/m2 I.V. (10 min.) X 5 days. Dosage adjustments were made according to leucocyte and platelet nadirs. Thrombocytopenia was the dose limiting toxicity. Very mild gastrointestinal toxicity was observed. One patient developed hemolytic anemia. One complete response (clinical and CT scan), 7 partial clinical responses (3: greater than 50%, 4: 25-50%), and 1 disease stabilization (less than 25%) were documented. The longest response has now lasted over 26 months. These preliminary results show that chemotherapy with diaziquone can achieve a response rate as high as 35% in malignant glioma even in patients previously treated with a chemotherapy regimen including a nitrosourea (four of the seven objective responses were seen in such patients). Diaziquone is well tolerated and deserves further study in the management of malignant glioma.
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Our study was designed to confirm the potential effects of three aminoglycosides on the disposition of thyroid hormones. Twenty-seven patients diagnosed with either cellulitis (n = 19), chronic osteitis (n = 4), or an abscess (n = 4) were selected. Thirteen patients received tobramycin, 60 to 100 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; seven patients received netilmicin, 40 to 120 mg iv q. 8 h., plus cloxacillin, 1 gm iv q. 4 h.; and seven patients received either cloxacillin, 1.5 gm iv q. 4 h., or cefoperazone, 2 to 4 gm iv q. 12 h. for at least 7 days. Another group of six normal subjects received neomycin, 0.5 gm po q. 6 h. for 7 days. All these subjects had normal thyroid function before antibiotic dosing and none had thyroid function abnormalities. Tobramycin and cloxacillin/cefoperazone did not influence thyroid function. Netilmicin decreased the total serum concentrations of triiodothyronine (T3) from 114 +/- 9 to 75 +/- 7 ng/dl (P less than 0.01), probably because of increased clearance, as the T3 free fraction increased from 0.43% +/- 0.02% to 0.49% +/- 0.02% (P less than 0.05). Thyroxine (T4) and reverse T3 (rT3) levels were not affected. Neomycin decreased T3 levels from 104 +/- 8 to 92 +/- 7 ng/dl (P less than 0.05) and the serum concentrations of thyroglobulin from 17.3 +/- 2.0 to 11.7 +/- 2.0 ng/ml (P less than 0.001). Because T4 and rT3 levels did not change, our results suggest that neomycin may have directly affected the gland. We conclude that some aminoglycosides can alter the disposition of thyroid hormones.
Regression lines and error rate-bounded analyses were performed for correlating inhibitory zone diameters with the 30-micrograms aztreonam disk and aztreonam minimal inhibitory concentration for gram-negative aerobic clinical isolates. A correlation coefficient of -0.81 was found for the regression line. Preliminary proposed criteria to distinguish susceptible isolates from resistant ones are: susceptible greater than or equal to 22 mm (MIC less than or equal to 8 micrograms/ml), intermediate 16-21 mm (MIC = 16 micrograms/ml) and resistant less than or equal to 15 mm (MIC greater than or equal to 32 micrograms/ml). Using these criteria, the rates for false-susceptible and false-resistant isolates were zero.
A 42-year-old woman had a puerperal aseptic cerebral thrombophlebitis with repeated episodes of subarachnoid hemorrhage. Cerebrospinal fluid studies revealed a delayed, severe and lasting low sugar and high protein levels. The possible mechanisms of low sugar levels are discussed.
We report 3 cases of severe syphilitic neuro-meningitis during the secondary stage: acute transverse dorsal myelitis with permanent paraplegia in a 17 year old teenager (case no. 1), uveo-meningitis with intracranial hypertension and diminished vision in a 52 year old woman (case no. 2), lower medulla lesion in a 46 year old man (case no. 3). The diagnosis was based upon highly positive serological tests for syphilis, associated with a compatible clinical context and meningitis in CSF specimens. Treatment was successful in cases nos. 2 and 3, unsuccessful in case no. 1 due to the irreversible character of the medullar lesions. Based on these 3 cases, the following points are discussed: the relatively atypical clinical character in the current context, the difficulties of the diagnosis, and the treatment regimens recommended for neurological syphilis. Despite the rarity of such cases, their extreme severity early in the secondary stage strongly implies the necessity for prevention by detecting and treating early syphilis. Attention is drawn upon the importance of doing serological tests for syphilis when presented with any atypical neurological situation.
Using a pharmacological model, the comparison between acetylsalicylic acid (ASA), administered orally, and a solution combining two salicylate derivatives (ethyl 5-methoxy-salicylate and 3-phenyl-propyl-salicylate), applied locally, demonstrated the value of the local application. Indeed, the pharmacological activity was highly significant and directly related to the tissue concentration of salicyl ions, which was higher after local application of the solution than after oral administration of ASA. The local solution also resulted in a lower plasma concentration of salicylate ions, allowing high plasma salicylate concentrations to be avoided.
The cases presented with psychic troubles and repeated somnolence episodes accompanied by dysarthria in 5 cases, myoclonic jerks in 4 cases and epileptic seizures in 1 case. In all cases the EEG was disturbed. It showed symetrical, paroxystic, bilateral, monomorph slow activity with more or less frequent paroxysms. The average serum aluminium level was at 407 microgram/l in the acute phase, at 161 microgram/l in the remission phase and at 123 microgram/l three months later. After interruption of oral and dialytic aluminium intake the remission is maintained. However in 2 cases the transitory readministration of aluminium gel was followed by reversible recurrency. The role of both aluminium gel and dialysate aluminium as the origin of encephalopathy is discussed.
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Report a typical case of dialytic dementia in a patient treated with aluminium gels. The course was fatal in fifteen months duration. Before interruption of aluminium gel intake, the aluminium blood level measured by atomic absorption spectrography was at 1300 microgram/l (normal less than 40 microgram/l). Cerebral aluminium was studied by the method of Le Gendre and Alfrey. On the three studied specimens of gray matter including, the parieto rolandic cortex, the thalamus, the cerebellar cortex, the mean aluminium concentration was seven times higher than the witness. The optic and electronic microscopy study showed important accumulation of lipofuscin. No neurofibrillary degeneration was observed. In contrast to the intensity of the clinical signs and the fatal course the cerebral lesions were slight.
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Forty-six patients with gliomas were introduced after surgery into a therapeutic programme of six cycles of combination chemotherapy with VM26 and CCNU, followed by delayed irradiation six months after surgery with an average dose of 5,800 rads. After irradiation the same preradiation chemotherapy was readministered for an average of four cycles. The results were compared to those from another group of 28 patients treated only by the same chemotherapy (CRC and C groups sucessively). Twelve patients (26%) died before irradiation in the CRC group, six patients (13%) had recurrences at the time of irradiation, and 28 patients (61%) had no clinical or radiological signs of recurrence at the time of irradiation. For the total of treated patients the median survival after surgery was 17 months, and 46% of the patients were surviving at 18 months. The percentage of survivors at 18 months was significantly more elevated in the group treated by combination chemotherapy and delayed irradiation than in a control group treated by the same combination chemotherapy alone. This result suggests that in approximately 50% of cases combination chemotherapy after surgery, and delayed irradiation six months after surgery, cumulated their effects on survival time.
34 patients operated on for malignant gliomas were successively treated by combination chemotherapy with VM26 and CCNU and conventional radiation therapy with an average dosage of 5,800 Rads, six months after surgery. The general and haematological tolerance of delayed irradiation after chemotherapy was satisfactory. Twelve patients developed neurological complications during or after irradiation. The complications were early in 10 cases, and delayed in 2. They were probably due to tumour growth in five cases, and secondary to irradiation in seven. In four of the seven cases the preradiation chemotherapy seemed to potentiate the radiation effect on the central nervous system.
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A case of encephalopathy with elevation of plasma aluminium level in a patient treated by maintenance hemodialysis is reported. Clinical symptoms were made of moderate impairment of intellectual functions and of intermittent drowsiness. EEG after 3 minutes of hyperpnea evidenced bisynchronous anteriorly dominant intermittent delta waves. Plasma aluminium level, determined by atomic absorption spectrophotometry, was initially at 300 microgram/l (normal range greater than 40 microgram/l). After interruption of aluminium gels, clinical and EEG symptoms slowly subsided in 9 months, plasma aluminium level came down to 145 microgram/l. This picture of encephalopathy could preceede irreversible dialysis dementia in chronic dialysis patients.
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