Faculty Bibliography

Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of concentrations of anti-infective agents is limited. Advances in pharmacodynamics have pointed out the importance of understanding the profiles of drugs in the plasma and in specialized compartments in order to dose the drugs to obtain the best patient outcomes. Advances in population pharmacokinetic modeling hold the promise of allowing proper estimation of drug penetration into the vitreous (or other specialized compartment) with only a single vitreous sample, in conjunction with plasma sampling. We have developed a rabbit model which allows multiple samples of vitreous to be obtained without breaking down the blood-vitreous barrier. We have employed this model to test the hypothesis that robust estimates of vitreous penetration by the fluoroquinolone ciprofloxacin can be obtained from a traditional intensive plasma sampling set plus a single vitreous sample. We studied 33 rabbits which were receiving 40 mg of ciprofloxacin per kg of body weight intravenously as short infusions and from which multiple plasma and vitreous samples were obtained and assayed for ciprofloxacin content by high-performance liquid chromatography. Data were analyzed by the iterative two-stage population modeling technique (IT2S), employing the iterative two-stage program of Forrest et al. (Antimicrob. Agents Chemother. 37:1065-1072, 1993). Two data sets were analyzed: all plasma and vitreous samples versus all plasma samples and the initially obtained single vitreous sample. The pharmacokinetic parameter values identified were used to calculate the percent vitreous penetration as the ratio of the area under the concentration-time curve for the vitreous to that for the plasma. The values identified, 4% penetration for the full data set versus 3% penetration for the single vitreous sample data set, and their corresponding estimates were not statistically significantly different. We conclude that population modeling holds promise for the analysis of penetration of antimicrobiol agents into specialized spaces from which only single samples can be obtained, particularly for patients with whom robust plasma sampling can be performed.

The purpose of this study was to evaluate the pharmacokinetics of ofloxacin in serum and vitreous humor samples from albino and pigmented rabbits by using a recently described animal model which permits robust estimation of parameter values. The drug was administered to rabbits intravenously, multiple vitreous humor and serum samples were taken from each rabbit, and the vitreous humor and serum samples were assayed by high-pressure liquid chromatography. The pharmacokinetic parameters were determined with RSTRIP, an iterative, nonlinear, weighted, least-squares regression program. Eight New Zealand White rabbits and eight Dutch Belted rabbits (split into single-dose and multiple-dose groups) were investigated in this study. The value of penetration into the vitreous humor of albino rabbits (n = 6) was 32.6% +/- 2.12%, with terminal-elimination half-life values of 3.21 and 2.39 h, respectively, for vitreous humor and serum. In pigmented rabbits after a single dose (n = 3) and with a steady-state concentration of drug in serum (n = 4), penetration values were similar, at 30.4% +/- 2.98% and 30.0% +/- 4.12%, respectively (P > 0.10). Following a single dose of ofloxacin, pigmented animals had elimination half-life values from serum and vitreous humor of 2.64 and 4.32 h, respectively. After steady state was achieved, half-life values for serum and vitreous humor were 3.12 and 6.05 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The brachial plexus is a complex structure that arises from nerve roots in the neck and terminates by dividing into peripheral nerves in the axilla. Imaging the brachial plexus can be difficult because of this anatomy. MRI now is the imaging modality of choice in the evaluation of brachial plexopathy. T1-weighted axial and oblique coronal images supplemented by T-2 weighted or STIR images are a standard protocol. MRI can be used to diagnose nerve root avulsion, neuromas, tumor, and radiation fibrosis.

A woman with chronic hemoptysis as her only complaint had extensive testing and did not respond to antibiotic therapy. Radiologic examination of the sinuses identified a mass which, on surgical exploration, was found to be the result of a fungus, Pseudallescheria boydii. Although this fungus is known to be a cause of epistaxis, this is the first instance in which it has been reported to cause hemoptysis.

Successful prevention of bone loss in ovariectomized rats with 17 beta-estradiol (E2) at 10 micrograms/kg/d has been reported. Here we show that E2 dose twice that much is not enough to maintain PTH(1-34) mediated bone gain. Three-month-old female Wistar rats were ovariectomized and fed with regular rodent chow and water ad libitum. Three months later they were divided into 9 groups (5-8 per group) and treated cyclically with PTH(1-34) (20 micrograms/kg/d sc, 5d/w for 3w) and E2 (20 micrograms/kg/d sc, 5d/w for 4w). There were also a baseline group and five vehicle control groups. Cancellous bone volume (Cn.BV/TV) of distal femoral metaphyses was measured by computer-aided histomorphometry on trichrome stained thin sections, and 24-hour fasted urine was analyzed for pyridinoline/creatinine (PYR/CREA) by immunoassay. Histomorphometric results showed that PTH(1-34) progressively increased Cn.BV/TV but E2 failed to maintain them. Urinary PYR/CREA results showed that E2-treated groups had lower values. We conclude that E2 dose > 20 micrograms/kg/d is required to maintain the PTH mediated bone gain.

Lymphadenopathy and nasal obstruction are very common in the HIV-positive patient and may or may not reveal a nasopharyngeal tumor. Biopsy is warranted if there is evidence suggestive of lymphoma or other neoplastic disease. This would include progressive rapid enlargement observed on examination or CT scan, an asymmetric growth pattern, and evidence of invasion of normal anatomic boundaries. It is certain that not all cases of adenoid hypertrophy that occurs early in the course of HIV disease represent a malignancy. Further study is needed to determine the proper timing for nasopharyngeal biopsy in the HIV-positive population. As the life span of the HIV-positive patient increases, so may the incidence of malignant degeneration.

This is a case report of non-Hodgkin's lymphoma of the external auditory canal, and infratemporal fossa, which presented with multiple cranial nerve palsies. The diagnosis was achieved via biopsy of tissue from the external auditory canal, and treatment with radiation therapy led to improvement of the symptoms. The management of AIDS-related lymphoma of the skull base with cranial neuropathies is reviewed.