Drug resistance mutation profile and accumulation kinetics in human immunodeficiency virus-positive individuals infected with subtypes B and F failing highly active antiretroviral therapy are influenced by different viral codon usage patterns.

The major human immunodeficiency virus type 1 subtype circulating in Brazil is B, followed by F and C. We have genotyped 882 samples from Brazilian patients for whom highly active antiretroviral therapy failed, and we found subtype B and the unique recombinant B/F1 forms circulating. Due to codon usage variation, there is a significantly lower incidence of the substitutions L210W, Q151M, and F116Y in subtype F1 isolates than in the subtype B counterparts.

Anterior cervical discectomy with and without interbody bone graft.

Fifty-one patients with symptomatic cervical disc disease refractory to conservative management were allocated at random to one of two treatment groups. The standard anterior approach devised by Cloward was used for 25 patients, and radical discectomy and foraminotomy for the other 26. All patients were followed for 6 months or longer with interview, physical examination, and radiographic evaluation. There was no difference in the success rate between the two groups. The large majority (92%) of patients in both groups were pleased with results of their operation. Because of technical factors related to operative exposure of the spinal canal and nerve roots, we prefer the Cloward procedure for patients symptomatic from advanced spondylosis and reserve discectomy without bone graft insertion for those with minimal spondylosis or soft disc herniations.

Blood flow and oxygen consumption of the focally traumatized monkey brain.

The exposed left superior frontal gyrus of the anesthetized macaque brain was focally traumatized by a jet of compressed air. Focal blood flow in tissue around the lesion and total cerebral blood flow was determined before and during the 4 hours after trauma by the hydrogen clearance technique. Blood flow fell in tissue adjacent to the injured brain but the reduction was not statistically significant. Total cerebral blood flow, blood flow in the right superior-frontal gyrus, and oxygen consumption of the brain was unaffected by the trauma. The authors conclude that neither spreading ischemia within uninjured tissue surrounding focally traumatized brain nor posttraumatic diaschisis is readily provoked in the anesthetized brain of the monkey.

Local spinal cord blood flow in experimental traumatic myelopathy.

Focal blood flow was measured in the lateral funiculus and center of the spinal cord in the rhesus monkey both before and after a 600 gm-cm injury at T-10. Measurements made by the hydrogen clearance technique showed that blood flow in the lateral funiculus more than doubled within 4 hours after injury, returned to normal by 8 hours, and remained in the normal range for 24 hours. At no time was a hypoperfusion in the lateral funiculus present. Blood flow in the center of the spinal cord, at the level of the lesion, began to fall within 1 hour following injury and continued to fall for 4 hours. These data challenge the notion that spreading ischemia of the white matter is an important factor in the pathophysiology of experimental spinal cord injury.

Double-blind evaluation of chemonucleolysis for herniated lumbar discs. Late results.

Sixty-six patients with symptomatic herniated lumbar discs refractory to the usual conservative management were allocated at random into one of two treatment groups according to a double-blind protocol: 31 received chymopapain intradiscally (chemonucleolysis) and 35 received a placebo intradiscally. Symptoms remained significantly improved 1 year or more after injection for 55% of those treated with chymopapain and for 46% of those treated with placebo. The difference is not statistically significant. However, to discard chemonucleolysis on the basis of this one small clinical trial may be premature. Since continuing controversy has re-established a climate in which another double-blind study of chemonucleolysis is ethically feasible and scientifically desirable, we favor additional clinical trials under a tightly controlled protocol to help resolve the issue.

Intracanalicular meningioma with normal tomography. Case report.

A middle-aged woman presented with the typical symptoms and signs of a compressive optic nerve lesion. Plain skull films, tomography of the optic canals, and selective angiography with magnification and subtraction were normal. Computerized transaxial tomography clearly showed the tumor, which was a meningioma of the optic nerve sheath. At surgery the tumor was found within the optic canal with intracranial and orbital extensions. It was strictly intradural and did not involve the surrounding bone at any point. This case documents the fact that an intracanalicular meningioma may be associated with normal tomograms of the optic canal.

Experimental delayed radiation necrosis of the brain. Part 1: Effect of early dexamethasone treatment.

The authors have designed an experiment to detect a hitherto unrecognized interaction between high doses of the glucocorticoid, dexamethasone, and brain irradiation. Eighteen juvenile male rhesus monkeys received 1800 rads to the whole brain in 8.5 minutes. For 1 1/2 days before and 10 1/2 days after the irradiation, nine animals received approximately 2.9 mg/kg/day of dexamethasone intramuscularly in addition to irradiation, while the remaining nine animals served as the control group and received saline. All animals eventually developed a progressive neurological syndrome, and died of delayed radiation necrosis of the brain. The two groups were compared with regard to latency to onset of clinical signs, survival time, and number, distribution, and location of lesions of radionecrosis. Large doses of desamethasone did not alter the susceptibility of the primate brain to delayed radiation necrosis. Detailed morphological study of the radionecrotic lesions supports the hypothesis that most, if not all, of the lesions develop as the consequence of injury to blood vessels.

Delayed radiation necrosis of the brain.

The cases of six patients are presented to delineate the clinical profile of delayed radiation necrosis of the brain. In five the diagnosis was verified histologically. Symptoms most often begin 9 months to 2 years after radiotherapy. Progressive visual impairment and dementia are common following perisellar irradiation, while hemispheric signs predominate following irradiation of the cerebrum. Cerebrospinal fluid protein may be elevated. Focal delta slowing is usually present on electroencephalography. The necrotic brain may appear on radionuclide brain scan as an area of abnormal uptake and also act as an avascular space-occupying lesion. With computerized tomography, radiation necrosis appears as an intracerebral area with diminished absorption coefficient that is often enhanced with intravenous contrast medium. The syndrome may be sufficiently characteristic to eliminate the need for surgical exploration and biopsy in some cases. Cumulative experience suggests that the risk-to-benefit ratio of radiotherapy becomes increasingly unfavorable for most patients with benign intracranial neoplasms when the standard brain tumor dose of 5000 to 7000 rads is fractionated at greater than 200 rads per day.

Effect of intracisternal phentolamine on cerebral blood flow after subarachnoid injection of blood.

The hydrogen clearance method was used to measure total and focal cerebral blood flow (CBF) in the monkey before and for 5 hours after a simulated subarachnoid hemorrhage (SAH). Some monkeys also received 0.2 to 1.0 mg/kg phentolamine intracisternally 3 hours after SAH. Results show that SAH did not change cerebrovascular resistance, but as cerebral perfusion pressure decreased, CBF fell transiently. Phentolamine injected intracisternally 3 hours after SAH produced a significant fall in arterial blood pressure; cerebrovascular resistance did not change but CBF decreased significantly. These data indicate that intracisternal phentolamine cannot be considered potentially useful to treat ischemic encephalopathy after SAH.

Double-blind evaluation of intradiscal chymopapain for herniated lumbar discs. Early results.

The authors report 66 patients with signs, symptoms, and a myelographic abnormality of herniated lumbar disc, who were not responsive to conservative treatment. The discs were injected at random with either chymopapain or a placebo. Neither patient nor surgeon knew which agent was used until after the results had been tabulated. Unless early laminectomy was necessary for intractable pain, all patients were followed for 2 months or more. There was no statistically significant difference in incidence or quality of improvement between the two groups: chymopapain was successful in 58% while placebo was successful in 49% (p = 0.15). Early results from this study indicate that most, if not all, of the putative effectiveness of chemonucleolysis probably derives from a placebo effect.

Evidence for adrenal medulla involvement in cold adaptation of preoptic-lesioned rats.

The cold-adaptation process was examined in preoptic-lesioned (PO, 18 rats) and adrenaldemedullated-preoptic-lesioned rats (ADPO, 16 rats). PO rats and ADPO female Wistar rats were cold acclimatized to 5 degrees C for 2 operated and then treated exactly like the lesioned rats. Lesions in the PO region caused a decrease in the ability to maintain normal body temperature in a cold environment (5 degrees C for 2 h). Their colonic temperature fell even by the end of the 2nd h of cold exposure (-1.1 degrees C for PO rats and -1.25 degrees C for ADPO rats, P less than 0.01). However, after 2 weeks of cold acclimation the PO rats, but not the ADPO rats were able to thermoregulate in the cold and showed a normal increase in interscapular brown adipose tissue weight (79%, P less than 0.01). These data suggest that the PO is not an essential link for cold adaptation when a mild cold-adaptation method is used. Furthermore, the data show that increased adrenal medullary activity is required for the cold adaptation process in PO rats.

Surgically correctable lesions detected by CT in 143 patients with chronic epilepsy.

CT findings justified surgical intervention in four young patients who had suffered from intractable epilepsy for many years. Previous non-invasive and invasive neurodiagnostic procedures with these patients had failed to show focal cerebral lesions amenable to surgical treatment. All four patients achieved significant relief from seizures after the operations.

Autoregulation of spinal cord blood flow.

The response of SCBF to changes in pACO2 was tested in Rhesus monkeys under normotensive conditions. A sigmoid shaped response was demonstrated. At a pACO2 of 10 to 50 mm. Hg, SCBF remained constant and in the normal range. As the pACO2 was raised from 50 to 90 mm. Hg, SCBF increased. Further increases in the pACO2 above 90 mm. Hg failed to effect further changes in SCBF. We conclude from these data that SCBF is somewhat less responsive than CBF to changes in pACO2. Next, the effect of changes in MAP on SCBF was studied under normocapnic conditions. SCBF remained constant and in the normal range with an MAP of 50 to 135 mm. Hg. Above 135 mm. Hg, SCBF rose with further increases in MAP. With decreases in MAP below 50 mm. Hg, SCBF fell passively. It is our conclusion that autoregulation exists in the lateral white matter of the spinal cord and follows a pattern similar to that suggested for the cerebrum.