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Biomedical subjects

William F Chandler

Publications and source records attributed to William F Chandler.

8 recordsLinked to original sources
PubMed2006

The role of endogenous growth hormone-releasing hormone in acromegaly.

CONTEXT: Some indirect evidence suggests hypothalamic control of GH secretion in acromegaly. OBJECTIVE: The objective of the study is to examine whether GH secretion in acromegaly is dependent on endogenous GHRH. PATIENTS AND STUDY DESIGN: We studied eight patients with untreated acromegaly due to a GH-producing pituitary tumor. All patients received an iv infusion of normal saline for 24 h and GHRH-antagonist (GHRH-ant) at 50 microg/kg x h for 7 d. GH was measured every 10 min for 24 h during the normal saline infusion and on the last day of the GHRH-ant infusion. A group of nine different patients with untreated acromegaly served as the control group and underwent blood sampling for GH every 10 min for two 24-h periods to assess the day-to-day variability of GH secretion. SETTING: The study was set in a university referral center. MAIN OUTCOME MEASURE: Twenty-four-hour mean GH was the main outcome measured. RESULTS: In six of eight subjects treated with GHRH-ant, 24-h mean GH decreased by 5.8-30.0% during iv GHRH-ant and, in three subjects, the change in the 24-h mean GH was greater than the upper limit of the 95% confidence interval of the spontaneous day-to-day variability of the mean GH in patients with acromegaly. Based on the binomial distribution, the probability of this magnitude of change to occur in three of eight subjects by chance alone is 0.0008. CONCLUSION: In some patients with acromegaly due to a pituitary adenoma, GH secretion is under partial control by endogenous GHRH.

Acromegaly↗
PubMed2006

Changes in the utilization of spinal fusion in the United States.

OBJECTIVE: Several reports suggest that spine surgery has experienced rapid growth in the past decade. Limited data exist, however, documenting the increase in spinal fusion. The objective of this work was to quantify and characterize the contemporary practice of spinal fusion in the United States. METHODS: Clinical data were obtained from the Nationwide Inpatient Sample for the years from 1993 to 2003. All patients with International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) procedure codes indicating cervical fusion, thoracolumbar fusion, lumbar or unspecified fusion were identified (n = 471,990). Primary ICD-9-CM diagnosis codes were used to determine the rationale for surgical fusion. Population-based utilization rates overall and for each procedure were calculated from United States census data. Rank order of spinal fusion compared with other inpatient procedures from the Nationwide Inpatient Sample was reported for the years 1997 to 2003. RESULTS: Overall utilization increased during the time period for cervical, thoracolumbar, and lumbar fusions by 89, 31, and 134%, respectively. Patients aged 40 to 59 years experienced the rapid rise in utilization for cervical fusions (60-110 per 100,000) and lumbar fusions (35-84 per 100,000). For patients 60 years and older, utilization also increased for cervical (30-67 per 100,000), thoracolumbar (4-9 per 100,000), and lumbar (42-108 per 100,000). Spinal fusion rose from the 41st most common inpatient procedure in 1997 to the 19th in 2003. CONCLUSION: Cervical, thoracolumbar, and lumbar spinal fusion have experienced a rapid increase in utilization in isolation and compared with other surgical procedures in contemporary practice. These changes are most pronounced for patients over 40 years of age, and degenerative disc disease seems to account for much of this increase.

Adult↗
PubMed2005

Phase II study of 9-nitro-camptothecin in patients with advanced chordoma or soft tissue sarcoma.

PURPOSE: The purpose of this trial was to assess the objective clinical response, toxicity, and time to progression of treatment with 9-Nitro-Camptothecin (9-NC) in patients with advanced chordoma, soft tissue sarcoma (STS), and gastrointestinal stromal tumor (GIST). PATIENTS AND METHODS: Patients with locally advanced and/or metastatic chordoma, STS, or GIST received 9-NC 1.25 mg/m2 orally for 5 consecutive days followed by 2 days of rest. Patients continued on therapy until disease progression, uncontrollable toxicity, or withdrawal of consent. RESULTS: From January 2000 to May 2003, 51 patients (15 chordoma, 23 STS, 13 GIST patients) enrolled. One patient (7%) with chordoma and one patient (4%) with STS had an objective response. Median time to progression was 9.9, 8.0, and 8.3 weeks for chordoma, STS, and GIST patients, respectively. Three- and 6-month progression-free survival rates were 47% and 33% for chordoma patients, 26% and 22% for STS patients, and 31% and 23% for GIST patients, respectively. Ten patients (10%) stopped study drug before disease progression secondary to toxicity. Common adverse events included anemia (42 patients, seven with grade 3/4 toxicity), leukopenia (33 patients, nine with grade 3/4 toxicity), fatigue (30 patients, three with grade 3/4 toxicity), nausea (34 patients, six with grade 3/4 toxicity), and diarrhea (28 patients, five with grade 3/4 toxicity). CONCLUSION: 9-NC has modest activity in delaying progression in patients with unresectable or metastatic chordoma. 9-NC is associated with moderate toxicity and shows little benefit in patients with advanced STS and GIST.

Adult↗
PubMed2005

Clinically silent somatotropinomas may be biochemically active.

The diagnosis of acromegaly is suspected based on the typical clinical presentation and is subsequently confirmed biochemically by elevated GH and IGF-I concentrations. We report three female patients with pituitary tumors who presented without any signs or symptoms of acromegaly but with elevated IGF-I levels. Plasma GH was measured every 10 min for 24 h, and an oral glucose tolerance test was performed. All patients had abnormally elevated mean and trough plasma GH levels as well as post-glucose nadir GH concentrations. All patients had magnetic resonance imaging scans revealing pituitary tumors and underwent transsphenoidal surgery. Histologically, they had GH-producing pituitary tumors. Plasma IGF-I levels returned to normal in two patients after surgery. Some pituitary adenomas are true GH-secreting tumors despite not being accompanied by obvious clinical stigmata of acromegaly. Natural history of this disease is unknown because of the small number of reported patients and inconsistent results of biochemical testing. Based on the results of this and previous reports, we propose that all patients with known pituitary tumors, especially younger women with normal or mildly elevated prolactin level, be evaluated for GH excess.

Acromegaly↗
PubMed2004

The role of radiation therapy after surgical resection of nonfunctional pituitary macroadenomas.

OBJECTIVE: Radiotherapy after aggressive surgical resection of nonfunctional macroadenoma (NFA) of the pituitary remains controversial. Historically, immediate postoperative radiotherapy has been recommended to decrease risk of recurrence. With the availability of high-resolution imaging, most neurosurgeons now withhold radiation until recurrence. There is relatively little evidence to support this practice, however. This study reviews postoperative results in a large number of patients with NFA, the majority of whom did not undergo prophylactic radiation. METHODS: Of the 258 patients who underwent surgery from 1979 to 1999 for NFA, medical records were available for 176. Forty-four patients were treated with immediate postoperative radiotherapy after tumor resection, and the remaining 132 patients were followed up with serial imaging studies and treated with radiotherapy only when a recurrence was documented by follow-up imaging. RESULTS: Patients in the group that received immediate postoperative radiotherapy at time of initial diagnosis and surgery did not differ significantly with respect to age or sex from those in the group that was observed. Five- and 10-year recurrence rates were 2.3 and 2.3%, respectively, for patients who received immediate postoperative radiotherapy, as compared with 15.2 and 50.5%, respectively, for patients who were followed up and did not receive radiotherapy unless there was evidence of recurrence or progression. No patient had symptomatic recurrence in the group that was observed if consistent follow-up was performed. Of the 26 patients who received radiotherapy at time of tumor recurrence or progression, 18 had adequate follow-up, and in all cases, the tumors either remained stable or regressed. CONCLUSION: Withholding radiotherapy after a high-percentage resection of NFA leads to a higher recurrence rate, but it avoids exposing all patients to the risks of radiation. Deferring radiotherapy for patients with complete or near-complete resection seems to be a safe and prudent approach, as our data suggest that recurrences may be detected early with high-resolution imaging and treated effectively with radiation at time of recurrence. Therefore, immediate postoperative radiotherapy may be eliminated for patients with complete or near complete resection of NFA and who agree to undergo close follow-up for a long period.

Adenoma↗
PubMed2003

Management options for persistent functional tumors.

This article describes in detail the current management of patients with functional pituitary tumors that demonstrate persistent function after surgical intervention. After providing a clear definition of "persistent function" for each specific type of tumor, the medical, surgical, and radiation options for each type are provided. Functional tumors include those that produce growth hormone, adrenocorticotrophic hormone, prolactin, and thyroid stimulating hormone.

Growth Hormone-Releasing Hormone↗
PubMed2002

Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up.

The biochemical diagnosis of acromegaly is conventionally based on elevated plasma GH levels that fail to suppress after an oral glucose load. We studied 16 newly diagnosed patients with acromegaly with normal mean plasma GH but elevated age and gender-adjusted plasma IGF-I concentrations (476 +/- 29 microg/liter, mean +/- SE). Plasma GH was sampled every 10 min for 24 h, and an oral glucose tolerance test was performed. The control group included 46 healthy subjects. All patients had 24-h mean GH values that overlapped with those of the healthy controls. Mean plasma GH was less than 2.5 microg/liter in 12 patients. Patients had higher 24-h nadir GH values than healthy controls (P < 0.001). During the oral glucose tolerance test, nadir plasma GH was less than 1 micro g/liter in eight patients. Plasma IGF-I normalized in 11 of 14 patients after transsphenoidal surgery. Four patients with normal IGF-I after transsphenoidal surgery were restudied. Mean and nadir GH decreased in all of them. In our experience in many patients with acromegaly, the diagnosis could be missed if only the existing GH-based criteria are used. Revised GH criteria in combination with plasma IGF-I should be used for the diagnosis and follow-up of acromegaly.

Acromegaly↗