1992 Distinguished Scientific Achievement Award Memorialization presented in memory of Marvin M. D. Williams.
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Awards and Prizes↗
Biomedical subjects
K L Nelson
Publications and source records attributed to K L Nelson.
Hysteretic behavior of the hepatic microsomal glucose-6-phosphatase system.
Carbamyl-P:glucose and PPi:glucose phosphotransferase, but not inorganic pyrophosphatase, activities of the hepatic microsomal glucose-6-phosphatase system demonstrate a time-dependent lag in product production with 1 mM phosphate substrate. Glucose-6-P phosphohydrolase shows a similar behavior with [glucose-6-P] less than or equal to 0.10 mM, but inorganic pyrophosphatase activity does not even at the 0.05 or 0.02 mM level. The hysteretic behavior is abolished when the structural integrity of the microsomes is destroyed by detergent treatment. Calculations indicate that an intramicrosomal glucose-6-P concentration of between 20 and 40 microM must be achieved, whether in response to exogenously added glucose-6-P or via intramicrosomal synthesis by carbamyl-P:glucose or PPi:glucose phosphotransferase activity, before the maximally active form of the enzyme system is achieved. It is suggested that translocase T1, the transport component of the glucose-6-phosphatase system specific for glucose-6-P, is the target for activation by these critical intramicrosomal concentrations of glucose-6-P.
Animals↗
Bioreactor and process design for large-scale mammalian cell culture manufacturing.
Good Manufacturing Practice for pharmaceuticals requires that the manufacturing processes be controlled and reproducible. The biological nature of cell culture-based processes lends them an inherently higher variability than is generally found for processes involving production of defined chemical entities. As one regulatory body has pointed out, this places a greater emphasis on in-process controls and adherence to GMPs in the manufacture of cell culture products. Design of bioreactors and associated process control systems is a key element in the successful implementation of a commercial-scale cell culture manufacturing process capable of meeting such high standards. It should be noted that reactor and control system designs for animal cell culture are still very much in a state of evolution from the modified bacterial fermentation systems that currently predominate, and it is difficult to predict how design strategies may change in the coming years. Having said this, however, it should be clear from the information presented here that satisfactory processes can be devised today using proven equipment configurations such as the stirred-tank reactor.
Animals↗
The prospective evaluation of Gd-DTPA in 225 consecutive cranial cases: adverse reactions and diagnostic value.
This prospective study evaluates two facets of gadopentetate dimeglumine (Gd-DTPA) enhanced MR imaging in 225 consecutive cranial cases in patients greater than 18 years of age: (i) patient and physician perception of adverse reactions, (ii) diagnostic value of the Gd-DTPA enhanced exam. The 225 cases included 173 head cases, 27 IAC cases, and 25 sella cases. Forty-six percent of the cases were abnormal excluding cases of mild atrophy and ischemic white matter disease judged to be related to aging and not pertinent to the patient's presenting complaint. Concerning adverse reactions, 83% of patients had no complaints. Five percent of the patients had reactions that were judged by the physician to be related to Gd-DTPA. All reactions were minor and required no therapy. In a subset of exams (115) that were blindly and independently interpreted by two board-certified, fellowship-trained radiologists, the Gd-DTPA-enhanced exam resulted in a change in diagnosis in 5%-8% of cases. Additionally, a major benefit of Gd-DTPA administration was the increased diagnostic confidence afforded by the addition of a contrast enhanced exam due to improved lesion characterization and exclusion of additional significant intracranial pathology. In 52%-69% of the abnormal cases, Gd-DTPA provided additional diagnostic information and in 26%-39% the absence of enhancement aided in interpretation. The Gd-DTPA-enhanced exam aids in the diagnosis and characterization of neoplastic disease, acoustic neuroma, subacute infarction, inflammatory disease (meningeal and parenchymal), and certain vascular abnormalities.
Brain Diseases↗
Gd DTPA: a review of clinical indications in central nervous system magnetic resonance imaging.
Since its approval for clinical use in mid 1988, Gd DTPA has found widespread application as a contrast agent in MRI. This paramagnetic metal ion chelate is used primarily for enhancement of head and spine lesions. Indications for contrast agent use in MRI are summarized drawing upon experience in more than 600 patients and a review of the literature. Enhancement improves both lesion detection and categorization. In head examinations, we recommend use of Gd DTPA for studies of the internal auditory canal, metastatic disease, infarction, infection, meningeal disease, and primary neoplastic disease. In spine examinations, contrast enhancement is employed both for detection of neoplastic disease and in the postoperative back for the differentiation of scar from recurrent disk herniation. Gd DOTA and Gd DO3A-R are new agents within this same class of contrast media.
Brain Neoplasms↗
The straight and narrow path to good head and spine MRI.
The path to good head and spine images is narrow and treacherous. We have attempted to give the traveller a small but important set of basic rules, enabling him to cross with success. 1. Averaging can be used to achieve sufficient SNR for thin sections, but the cost in terms of scan time is high. Zooming the image (reducing the field of view) should generally be avoided, as the price in terms of SNR is very high. 2. Rectangular pixels and half-Fourier imaging are two methods for decreasing scan time. HFI, which produces high spatial resolution images, can be used when the SNR is not a limiting factor. Rectangular pixels improve the SNR, but decrease resolution. 3. To achieve good T1 contrast with spin echo imaging, set TE less than or equal to 20 msec. and TR less than or equal to 600 msec. For T2 weighted images, a TR between 2.0 and 3.0 sec. is preferred, typically with two echoes: for example, TEs of 25 and 90 msec. 4. Better slice profiles or gaps between slices can be used to combat slice-to-slice interference. This results in improved SNR on T1 weighted images and improved contrast on T2 weighted images. 5. Low bandwidth techniques may be used to improve the SNR on both T1 and T2 weighted images. Chemical shift artifact puts a finite limit on the extent to which this can be applied. 6. Motion compensating gradients are a tremendous boon to MRI and should be utilized in all possible head and spine applications. These reduce image degradation from CSF and vessel pulsation, as well as from involuntary motion. 7. Fast imaging techniques can be used in 2-D multislice mode to decrease scan time. Unfortunately the T2 contrast with this approach is far inferior to that of spin echo technique. 3-D FLASH, with 1 mm. sections, T1 contrast superior to spin echo technique, and the potential for high resolution reformatted images, may replace conventional 2-D, T1 weighted, spin echo imaging. Pulse techniques that combine all the advantages mentioned lie in the future. For example, one possible approach is a T2 weighted head screen that incorporates low bandwidth technique and HFI. This would produce high resolution images with reasonable SNR in approximately half the present scan time. Despite any further new developments, the trade-off between image quality and scan time will likely always remain.(ABSTRACT TRUNCATED AT 400 WORDS)
Head↗
FLASH: clinical three-dimensional magnetic resonance imaging.
Using 3-D FLASH, high resolution, very thin section T1 weighted images of the CNS, spine, and extremities can be obtained. From these single data sets, reformatted images whose resolution is equal to that of the original data set can be constructed in any desired plane. This approach may lead to the replacement of conventional T1 weighted spin echo imaging by 3-D FLASH techniques.
Brain↗
Surface shield: device to reduce personnel radiation exposure.
A simple device is described that can reduce personnel exposure from scatter radiation by up to 75%. The device consists of an oblong piece of shielding (0.75-mm lead equivalent) that is taped to the side of the patient during percutaneous renal stone removal and other interventional procedures. Contrary to other shields and barriers, this does not interfere with access to the patient. Scatter exposure data from phantom studies are presented and the rationale for surface shielding discussed.
Humans↗
Development of reversible hypertension during disulfiram therapy.
An alcoholic patient had a gradual increase of BP while he was treated with disulfiram. The BP returned to normal after the disulfiram was withdrawn. Increased BP should be considered a possible side effect of long-term disulfiram therapy, especially in the presence of alcohol-induced liver damage.
Alcoholism↗
Effect of acetaminophen on the leukocyte-labeling efficiency of indium oxine In 111.
The effect of acetaminophen on the labeling efficiency of leukocytes with indium oxine In 111 was studied. A blood sample was obtained from eight healthy men before and after they received acetaminophen 650 mg every four hours for 24 hours. After dividing the plasma from each sample into three portions, leukocytes were separated and labeled with indium oxine In 111. In an in vitro study, 200 ml of blood was obtained from one of the men, and the plasma was separated into four portions. Acetaminophen in 95% ethanol was added to three of the plasma fractions to produce acetaminophen concentrations of 4, 20, and 100 micrograms/ml; ethanol was added to the fourth fraction as a control. Each plasma fraction was then subdivided into three aliquots, and leukocytes were labeled as in the in vivo study. Mean leukocyte labeling efficiencies in both studies were calculated from the ratios of leukocyte radioactivity to initial radioactivity in the samples, expressed as percentages. Leukocyte labeling efficiencies before acetaminophen administration ranged from 79 to 85%; after administration, labeling efficiencies ranged from 70 to 87%. No significant differences in mean labeling efficiency before and after acetaminophen administration were noted in any of the subjects. Leukocyte labeling efficiencies in all in vitro plasma fractions were reduced, ranging from 54 to 63%, but no significant differences in labeling efficiency between any of the plasma fractions were found. Using the labeling procedures in this study, exposure of leukocytes from healthy men to acetaminophen in vivo or in vitro does not affect labeling efficiency with indium oxine In 111.
Acetaminophen↗
High-dose gadoteridol in MR imaging of intracranial neoplasms.
Twelve patients with a high suspicion of brain metastases by previous clinical or radiologic examinations were studied in a phase III investigation with magnetic resonance (MR) imaging at 1.5 T after a bolus intravenous injection of 0.1 mmol/kg gadoteridol followed at 30 minutes by a second bolus injection of 0.2 mmol/kg gadoteridol. All lesions were best demonstrated (showed greatest enhancement) at the 0.3-mmol/kg (cumulative) dose, with image analysis confirming signal intensity enhancement in the majority of cases after the second gadoteridol injection. More lesions were detected with the 0.3-mmol/kg dose than with the 0.1-mmol/kg dose, and more lesions were detected with the 0.1-mmol/kg dose than on precontrast images. In this limited clinical trial, high-dose gadoteridol injection (0.3-mmol/kg cumulative dose) provided improved lesion detection on MR images specifically in intracranial metastatic disease.
Adult↗
MR imaging detection of cerebral metastases with a single injection of high-dose gadoteridol.
The utility of a single high-dose (0.3 mmol/kg) injection of gadoteridol, a gadolinium chelate, in the detection of brain metastases on magnetic resonance images was studied. Patients (n = 29) with a high suspicion for brain metastases at clinical examination and by history were imaged on two occasions--separated by more than 24 hours and less than 7 days--with a 0.1 mmol/kg contrast agent dose used for the first study and a 0.3 mmol/kg dose for the second. In patients (n = 15) with confirmed brain metastases by clinical, radiologic, and/or histologic criteria, 40 lesions were detected at the 0.3 mmol/kg dose by a single reader blinded to contrast agent dose, compared with 33 lesions at 0.1 mmol/kg, a 21% increase. Three of 15 patients (20%) demonstrated an increase in the number of lesions detected at the higher dose. Region-of-interest analysis of signal intensity measurements showed that lesion contrast (relative to normal brain) improved from 54% at 0.1 mmol/kg to 92% at 0.3 mmol/kg. A 0.3 mmol/kg dose of gadoteridol, administered in a single injection, permits identification of brain metastases not detected at 0.1 mmol/kg. Such information can influence the choice of therapy.
Adolescent↗
Linguistic analysis to assess medically related posttraumatic stress symptoms.
The authors examined the presence of posttraumatic stress symptoms (PTSS) in 20 patients requiring ventilation after acute respiratory distress. The subjects completed a semistructured interview about their ventilation experience that was subject to content and linguistic analysis. Subjects also completed two self-report measures to assess PTSS and socioemotional adjustment. Subjects who endorsed PTSS were more likely to use a narrative style suggesting emotional involvement in their recall of the stressful event. The authors indicate that the presence of PTSS is a common consequence of traumatic medical experiences and that denial of distress may be an adaptive short-term coping strategy.
Adaptation, Psychological↗
Metastatic lesions involving the cerebellopontine angle.
PURPOSE: To evaluate the clinical and MR findings of metastatic lesions involving the cerebellopontine angle (CPA), which may be useful in differentiating them from the more commonly occurring benign CPA lesions. METHODS: Clinical and MR findings of 14 patients with clinical/radiologic (seven) or pathologic (seven) diagnoses of CPA metastasis were retrospectively reviewed. RESULTS: Useful clinical findings included acute onset and rapid progression of cranial nerve symptoms, especially 7th and/or 8th cranial nerve deficits (92.9%). Cranial nerve symptoms could be unilateral (50%) and frequently involved multiple cranial nerves (64.3%). MR findings showed significantly more extensive disease than suggested by clinical presentation, with 100% of patients having multiple cranial nerve involvement and 85.7% bilateral. Useful MR findings included small and/or bilateral CPA-enhancing lesions with relative isointensity to brain parenchyma on precontrast MR, with associated findings of multiple and/or bilateral cranial nerve and/or leptomeningeal lesions. CONCLUSIONS: These associated findings suggest that cerebrospinal fluid dissemination and/or leptomeningeal extension may be an important pathway for metastatic spread to the CPA. Because the CPA metastasis may be the initial or only site of metastasis, and may occur many years after the initial diagnosis of malignancy, MR findings with clinical correlation are not only useful for the detection of CPA metastases, but also for their differentiation from the more common benign CPA tumors.
Adult↗