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Biomedical subjects

F B Meyer

Publications and source records attributed to F B Meyer.

135 records · Page 8Linked to original sources

The incidence and prevention of meningitis after basilar skull fracture.

The survey of 1,077 consecutive skull fractures admitted to the Massachusetts General Hospital between July 1, 1969 and July 1, 1979 were reviewed. One hundred sixty-eight basilar skull fractures (15.6%) were diagnosed according to clinical and radiological criteria. In 128 patients with basilar skull fracture but without CSF leak, two out of 65 patients (3.1%) who received prophylactic antibiotics developed meningitis in contrast to none of 63 patients who were treated. Nine of 15 patients with otorrhea developed meningitis regardless of treatment. Of 18 patients with rhinorrhea, 13 were treated with prophylactic antibiotics and were free of meningitis but 2 of 5 patients not treated (40%) did develop meningitis. The overall incidence of CSF leak was 20.8%. There is no clear evidence to demonstrate that prophylactic antibiotics are effective in general in reducing the incidence of meningitis after basilar skull fracture with active rhinorrhea. However, the difference in the incidence of meningitis between the treated and the untreated group was noteworthy though not statistically significant. Meningitis can develop despite antibiotic prophylaxis. Additional investigation and therapy should be considered whenever the clinical situation warrants.

Adolescent↗

Calcium, neuronal hyperexcitability and ischemic injury.

Due to tight regulatory controls, a 10,000-fold concentration gradient exists between intracellular and extracellular free Ca2+ concentrations. With appropriate stimulus Ca2+ will rapidly flow into neurons through various types of membrane channels including voltage-dependent and receptor-operated channels. Intracellular Ca2+ concentrations are then quickly restored primarily through Ca2+-ATPase, Na+/Ca2+ exchange, and endoplasmic reticulum sequestration. It is well-known that Ca2+ is essential for neurotransmitter release. More recent investigations indicate that Ca2+ influx is essential for neuronal excitability independent from synaptic function. In fact, abnormal Ca2+ metabolism may play a dominant role in both the initiation and propagation of seizure discharge. Accordingly, Ca2+ channel blockers may represent a new therapeutic modality to treat epilepsy. Analyzed in this article are the major mechanisms by which neurons control Ca2+ fluxes and the evidence supporting the role of Ca2+ in seizure phenomena. Thereafter, an integrative theory for the role of calcium in neuronal hyperexcitability and ischemic cell death is constructed.

Animals↗

Effects of the dihydropyridine Ca2+ channel antagonist nimodipine on kainic acid-induced limbic seizures.

The effects of the dihydropyridine Ca2+ channel antagonist nimodipine on kainic acid-induced seizures were studied in 30 0.5% halothane anesthetized Sprague-Dawley rats. Each animal received low dose kainic acid 0.5 mg/kg i.v. to allow study of the progression of neuronal excitability and epileptiform activity. Preadministration of nimodipine 1.0 mg/kg i.p. increased the latency but did not prevent kainic acid-induced epileptic activity. For example, the latency from kainic acid administration to the appearance of the first seizure and status epilepticus was 75.6 +/- 9.1 min and 85.9 +/- 9.4 min in controls vs. 117.3 +/- 9.3 min and 128.0 +/- 8.7 min in the nimodipine group (P less than 0.005). It is hypothesized that nimodipine attenuated excitability by blocking Ca2+ influx through voltage-dependent L-channels secondary to kainic acid-induced membrane depolarization.

Animals↗

Pituitary carcinoma: an ultrastructural study of eleven cases.

Pituitary carcinomas are very rare. Defined as adenohypophysial tumors that undergo craniospinal and/or systemic metastasis, most are PRL- or ACTH-producing. Their ultrastructural features, particularly relative to benign adenomas of similar functional type, have not been sufficiently explored. Eleven cases of immunohistochemically characterized pituitary carcinoma with documented cerebrospinal and/or systemic metastases were collected from various institutions and studied by transmission electron microscopy. The tumors were surgically removed from 7 women and 4 men ranging in age between 28 and 74 years (mean, 50 years). All were endocrinologically functioning. Six tumors secreted PRL; three were ACTH-producing; one each was GH/PRL- and TSH-producing. The patients with the ACTH-producing tumors had all presented with Cushing's disease and two of them had undergone adrenalectomy (Nelson syndrome). In most cases significant cellular atypia and mitotic activity were observed. In terms of morphologic features of functional differentiation, electron microscopy revealed that in 9 cases the tumor cells maintained at least some ultrastructural markers of their basic phenotype. A unique feature in 2 ACTH carcinomas was the variable admixture of smooth endoplasmic reticulum with intermediate (cytokeratin) filaments. In 2 cases, both PRL-producing carcinomas, the cell type comprising the tumor could not be identified on an ultrastructural basis alone. Ultrastructural investigation of pituitary carcinomas confirms their endocrine nature and, in most but not all cases, reveals their functional differentiation. Despite the diagnostic utility of electron microscopy in the assessment of these rare tumors, the distinction of pituitary carcinoma from pituitary adenoma cannot be firmly made on ultrastructural grounds alone.

Adenoma↗

Suppression of pentylenetetrazole seizures by oral administration of a dihydropyridine Ca2+ antagonist.

We previously demonstrated that the dihydropyridine calcium channel blocker, nimodipine, is an effective anticonvulsant in experimental seizures when administered parentally. Reported now are the results for the oral administration of nimodipine in pentylenetetrazole (PTZ)-induced seizures in the rabbit. Twenty rabbits were randomly assigned into 10 controls and 10 treated with nimodipine 5 mg/kg/day orally for 5 days. All animals received increasing doses of the convulsant PTZ intravenously (i.v). The epileptogenecity of this agent was assessed in all animals (mg/kg) by four electrocorticographic criteria: first seizure greater than 5 s, two seizures within 5 min, epileptiform activity for 1 h, and status epilepticus. In all four categories, nimodipine increased the seizure threshold by 50-60%. The dose of PTZ required to produce the first seizure was 27.0 +/- 5.4 mg/kg in controls and 49.6 +/- 9.9 mg/kg in treated animals (p less than 0.001). Similar values were obtained for the other three electrocorticographic categories. There were no observable adverse side effects. The results confirm our previous findings that calcium influx is critical for seizure induction, and that selective central nervous system (CNS) calcium channel blockers may emerge as a new class of anticonvulsants.

Administration, Oral↗

Anticonvulsant effects of dihydropyridine Ca2+ antagonists in electrocortical shock seizures.

The dihydropyridine calcium antagonists nimodipine (NMD), PN200-110, and nicardipine were compared with phenytoin (PHT) as potential anticonvulsants in electrocortical shock (ECS)-induced seizures in the white New Zealand rabbit. Before treatment, seizure duration ranged from 43.8 +/- 5.1 to 49.6 +/- 5.2 s with an ECS stimulus of 10-V, 100-Hz, 0.1-ms pulses for 5 s. Each drug was administered into the right internal intracarotid artery 2 min before the ECS. A cumulative nimodipine dose of 440 micrograms/kg decreased seizure discharge to 6.6 +/- 5.0 s (p less than 0.001), whereas a total dose of 1.0 mg/kg PN200-110 was required to achieve a similar effect. Nicardipine was ineffective. A cumulative dose of 7 mg/kg phenytoin was required to suppress seizure discharge. These results indicate that Ca2+ channels modulated by dihydropyridines play a facilitating role in ECS-induced seizures. We propose that the anticonvulsant effects of nimodipine and PN200-110 are due to inhibition of neuronal calcium L-channels. Dihydropyridine Ca2+ antagonists that penetrate the blood-brain barrier (BBB) and bind to neuronal tissue may emerge as a novel class of anticonvulsants.

Animals↗

Effects of magnesium sulfate on pentylenetetrazol-induced status epilepticus.

The use of magnesium sulfate (MgSO4) as an anticonvulsant is controversial. Status epilepticus was induced in 0.5% halothane-anesthetized Wistar rats with a threshold (90 mg/kg) or suprathreshold (200 mg/kg) dose of intravenous (i.v.) pentylenetetrazol (PTZ) under stereotactic hippocampal depth electrode monitoring. Fifteen minutes after seizure induction, the maximum hemodynamically tolerated dose of MgSO4 (10 mg/kg/min in 22 min) was administered i.v. MgSO4 was ineffective in altering seizure discharge. A subgroup of nine animals received hypertonic mannitol before MgSO4 to open the blood-brain barrier (BBB) to facilitate Mg2+ CNS penetration. Again MgSO4 was ineffective in attenuating epileptic activity. These results support the contention that MgSO4 is not an effective treatment for status epilepticus. We hypothesize that because Mg2+ blocks Ca2+ influx into the neuron through the N-methyl-D-aspartate (NMDA) receptor-operated calcium channel in a voltage-dependent manner it would be ineffective in neurons that are continuously depolarizing as in status epilepticus.

Animals↗

Pediatric transseptal transsphenoidal pituitary surgery.

The use of the transseptal transsphenoidal approach to the pituitary gland has gained acceptance as a safe, relatively atraumatic means of removing pituitary tumors. The outcome in adult patients has been successful; however, the outcome in pediatric patients whose noses may still be developing is not well described. We reviewed the outcomes in 41 patients younger than age 18 years who underwent transseptal transsphenoidal pituitary surgery at our institution between 1986 and 1997 (20 boys and 21 girls; age, 3 to 17 years; mean age, 13.4 years). The most common diagnosis was prolactin-secreting adenoma (14 patients), followed by craniopharyngioma (7 patients). Presenting symptoms included headache (20 patients), galactorrhea (13 patients), and menstrual irregularities (11 patients). The most common early complication was transient diabetes insipidus (20 patients). No patient experienced serious bleeding at pack removal and no patient developed a cerebrospinal fluid leak postoperatively. Follow-up ranged from 3 months to 12.7 years, with 7 patients experiencing recurrent or residual disease between 6 days and 2 years after their original transseptal procedure. The most common long-term surgical complication was nasal obstruction in 5 patients, 3 of whom also complained of seasonal allergies. Four patients complained of recurrent sinus infections, and 4 patients noted an external nasal deformity as a result of the surgery.

Adolescent↗

Endoscopic transnasal pituitary surgery: report on 180 cases.

The endoscopic transnasal approach is an evolving technique for treating lesions in the sella turcica. Since this method was introduced at our institution 4 years ago, the majority of transsphenoidal procedures are performed with it. The records of all patients having endoscopic transnasal hypophysectomy at the Mayo Clinic during the last 4 years were reviewed retrospectively. The criteria analyzed were safety, functional and cosmetic outcome, and complications. During the 4-year period, the operative procedure was modified to improve operative exposure and safety. The results of our review showed a significant decrease in length of hospital stay, reduced operative time, reduced need for nasal packing, and elimination of a sublabial incision. The complication rate was equivalent to that reported for the traditional transseptal transsphenoidal approach. As the neurosurgeons at our institution gained experience with this approach, an increasing number of pituitary microadenomas were resected safely and successfully. In addition, because of the limited septal dissection, this approach is particularly helpful for revision operations. This approach also can be used for the full range of pituitary lesions and in conjunction with adjunctive techniques, including frontal craniotomy and gamma-knife irradiation. Currently, the endoscopic transsphenoidal approach is the method preferred for surgically treating pituitary lesions in adults at our institution.

Adenoma↗