Biomedical subjects
Publications and source records attributed to E J Kosnik.
The technique of harvesting the ligamentum nuchae and its use in posterior fossa surgery are discussed. By using this technique the author has avoided postoperative cerebrospinal fluid leakage in more than 200 procedures.
Near the end of the data-collection phase of a case-control interview study of environmental factors and childhood brain tumors, an unusual space-time cluster was revealed. Not only had six genetically unrelated children been diagnosed with a primary intracranial tumor in a recent 2.4 year period in a rural county in Ohio, but each child had one parent employed by the same company (two mothers, four fathers). This represents an observed/expected ratio greater than 70 (p much less than 0.001). All tumors were microscopically confirmed, and all case parents worked at the facility in question for at least 1 year prior to conception, during the index pregnancy, and for at least 6 months after birth. The place of parental employment was an electronics firm (Standard Industrial Classification [SIC] group number 367, electronic components and accessories), where more than 100 chemical compounds are used by the company in a manufacturing process. Results of the cluster investigation are described, including a description of the case series. This cancer cluster is unique in that the index case series is composed of the offspring of workers, not the workers themselves.
The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations and safety of intravenous rifampin in pediatric patients undergoing shunt placement. Nine patients (mean age 5.6 y) received a single dose of rifampin, 20 mg.kg-1, administered intravenously 1 h prior to surgery. The peak serum concentrations ranged from 13.5-26.7 micrograms.ml-1; cerebrospinal fluid concentrations ranged from 0.12-3.0 (mean: 1.4) micrograms.ml-1. The mean total clearance, apparent distribution volume, and elimination half-life were 0.29 l.kg-1.h-1, 1.11.kg-1, and 2.8 h. The concentrations of rifampin achieved in the cerebrospinal fluid exceeded the minimum inhibitory concentrations by 100- to 1000-fold against Staphylococcus epidermidis. However, 5 of 9 patients developed cutaneous reactions during intravenous rifampin prophylactic therapy. Because of the high frequency of adverse effects and more than adequate rifampin concentrations achieved in the cerebrospinal fluid, rifampin doses lower than that used in this study may be evaluated in future studies.
Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but not pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 +/- 5.6 years) received three doses of intravenous nafcillin, 50 mg/kg every 6 h; the first dose was administered 1 h prior to surgery. Multiple blood samples were collected during and after surgery and the cerebrospinal fluid sample was obtained at the time of shunt insertion. Urine samples were collected for 24 h after initiation of nafcillin. Nafcillin was analyzed with an HLPC method. The peak serum concentrations ranged from 22 to 107 micrograms/ml; cerebrospinal fluid concentrations ranged from 0.02 to 0.30 (mean 0.16 +/- 0.11) micrograms/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.90 +/- 0.55 l/kg/h, 0.12 +/- 0.04 l/kg/h, 0.70 +/- 0.52 l/kg, and 0.5 +/- 0.1 h, respectively. 16% of total nafcillin dose was excreted in the urine. A 4-fold variability in total clearance and a 10-fold variation in cerebrospinal fluid concentrations of nafcillin was observed in these patients. Further, the concentrations of nafcillin attained in the cerebrospinal do not appear to be adequate, based on its minimum inhibitory concentration of 0.5 micrograms/ml against very susceptible staphylococci. These data, in addition to the fact that an increasing number of staphylococci are becoming resistant to nafcillin, question the usefulness of prophylactic nafcillin in pediatric patients undergoing shunt procedures.
Staphylococcus epidermidis has been established as the common pathogen causing cerebrospinal fluid shunt infections. In addition, clinical isolates of S. epidermidis from infected shunts are typically resistant to methicillin. Vancomycin is often used for neurosurgical prophylaxis due to its excellent in vitro activity against methicillin-resistant staphylococci. Limited data are available about the pharmacokinetics and cerebrospinal fluid concentrations of vancomycin in pediatric patients intraoperatively. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal fluid concentrations of vancomycin. Eight patients (mean age 8.3 +/- 7.0 years) received three doses of intravenous vancomycin, 15 mg/kg every 6 h. The first dose was administered 1 h prior to surgery. Blood samples were collected at 0, 0.5, 1, 2, 4, and 5 h after the end of the infusion. A cerebrospinal fluid sample was collected at the time of shunt insertion. Urine samples were collected over a 24-hour period. Vancomycin was measured with a fluorescence polarization immunoassay. The peak serum concentrations ranged from 15.6 to 33.7 micrograms/ml; cerebrospinal fluid concentrations ranged from less than 0.6 to 0.8 microgram/ml. The mean total clearance, renal clearance, apparent volume of distribution, and elimination half-life were 0.11 +/- 0.05 l/h/kg, 0.07 +/- 0.02 l/h/kg, 0.54 +/- 0.15 l/kg, and 4.8 +/- 4.0 h, respectively. Approximately 70% of total vancomycin dose was excreted in the urine. A 2- to 5-fold variation in total clearance and a 2.5-fold variability in renal clearance were observed. Low cerebrospinal fluid concentrations of vancomycin were present at the time of shunt insertion in these pediatric patients.(ABSTRACT TRUNCATED AT 250 WORDS)
The development of a new multidrug chemotherapy regimen for primary brain tumors was based upon the cellular heterogeneity within individual tumors, the Goldie-Coldman and Price-Goldie-Hill hypotheses, and known agonistic effects of certain drug combinations and sequences. Eight drugs (vincristine [VCR], hydroxyurea, procarbazine, CCNU, cisplatin, cytosine arabinoside [Ara-C] high-dose methylprednisolone, and either cyclophosphamide or dacarbazine) were administered within 12 hours in an attempt to minimize myelosuppression. Courses were repeated at 2- to 4-week intervals. The regimen was devised to include lipid and water soluble drugs, polar and nonpolar agents, phase-specific and cell-cycle independent agents, and antineoplastics with different mechanisms of action. More than 330 courses of the regimen were administered to 107 children with brain tumors whose tumor had recurred or had been incompletely resected at diagnosis. Tumor response according to protocol-specified criteria and independent review was evaluable in 78% of the patients. After just two cycles of chemotherapy and within a 4- to 6-week interval, 50% had an objective tumor response including 15.5% who had a complete response (CR). Nephrotoxicity and high-frequency hearing losses were noted after three to five courses of therapy in approximately half of the patients. Transfusions with red cells or platelets and use of antibiotics for fever and neutropenia were required in 10% to 25% of patients. The regimen appears satisfactory for preradiation chemotherapy in newly diagnosed patients with residual tumor after surgery, but it must be compared with standard therapeutic approaches in prospective controlled trials before its relative value can be established.
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This review of pediatric neck injuries includes patients admitted to Children's Hospital of Columbus, Ohio, during the period 1969 to 1979. The 122 patients with neck injuries constituted 1.4% of the total neurosurgical admissions during this time. Forty-eight patients had cervical strains; 74 had involvement of the spinal column; and 27 had neurological deficits. The injuries reached their peak incidence during the summer months, with motor-vehicle accidents accounting for 31%, diving injuries and falls from a height 20% each, football injuries 8%, other sports 11%, and miscellaneous 10%. There is a clear division of patients into a group aged 8 years or less with exclusively upper cervical injuries, and an older group with pancervical injuries. In the younger children, the injuries involved soft tissue (subluxation was seen more frequently than fracture), and tended to occur through subchondral growth plates, with a more reliable union than similar bone injuries. In the older children, the pattern and etiology of injury are the same as in adults. The entire cervical axis is at risk, and there is a tendency to fracture bone rather than cartilaginous structures.
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A 14-year-old boy with anophthalmia presented evidence of hypothalamic dysfunction. He was found to have a third-ventricular germinoma, probably pineal. This case is interesting in view of a previous case report of the association of anophthalmia and a germ-cell tumor (teratoma), and suggests a possible causal relationship between this malformation and germ-cell neoplasms, bith of which probably arise early in development.
Ventricular tumors of tuberous sclerosis are almost always hamartomas or benign tumors occurring predominantly in children or young adults. No clear gross or histological distinctions between the ventricular "candle gutterings" and "tumors" have been identified. The clinical presentation may be acute, with the sudden onset of increased intracranial pressure and possible serious morbidity (visual impairment) or death. When these tumors are surgically removed or decompressed, the prognosis for life seems to be quite good. Malignant change in these lesions is very rare.
A series of 18 primitive neuroectodermal tumors in children (15 cerebral and three spinal) is reported. These are highly malignant neoplasms, both histologically and clinically. They are rapidly growing tumors, with a brief duration of symptoms and a rapidly progressive course. Forty percent of the patients were alive at 6 months, only 10% at 1 year, and all patients had died within 2 years following diagnosis.
A 62-year-old hypertensive woman had bilateral intracranial arterial aneurysms associated with persistent trigeminal artery. The presenting symptom of this patient was painless ophthalmoplegia. We review embryologic development of the circle of Willis as an explanation for the occurence of the trigeminal artery. We also discuss the high incidence of associated vascular malformations with these vessels.
One of the unusual signs of sudden increase in intracranial pressure is central neurogenic pulmonary edema. This pulmonary edema produces a capillary-aveolar block resulting in hypoxia complicating the underlying neurologic condition. Good success in treating this problem has been obtained with controlled ventilation and positive end expiratory pressure respiration.
A series of stereotaxic percutaneous third ventriculostomies has been carried out on 46 shunt-dependent hydrocephalic children. The technique and results are presented. The advantages of this procedure over the open craniotomy type are discussed. There has been low morbidity and one mortality. The necessity of preoperative shunting to provide a 'slack brain' is emphasized.
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An unusual case is presented of an intradiploic encephalocele surrounding a cerebrospinal fluid cyst. The relationship of this developmental anomaly to the more commonly encountered midline encephalocele and isolated reports of temporal bone encephaloceles are discussed.
Elevation of systemic arterial pressure in seven patients with intracranial arterial aneurysms has been shown to be effective in alleviating ischemic symptoms attributed to cerebral vasospasm. Autoregulation is at least partially lost in patients with cerebral hemodynamic crisis. Blood volume expansion was used to augment vasopressors in maintenance of systemic hypertension. The management of these cases is discussed. Caution in the use of this technique is advised, since the regimen is not without risk.