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Biomedical subjects

J D Miller

Publications and source records attributed to J D Miller.

At least 235 records · Page 13Linked to original sources

Chlamydosporol, a new metabolite from Fusarium chlamydosporum.

Extracts of rice on which an isolate of Fusarium chlamydosporum had been cultured were toxic to brine shrimps. The toxic fraction was purified by flash chromatography to give two compounds which were identified by UV, IR, NMR and mass spectroscopy at the 6 alpha and 6 beta isomers of 5-hydroxy-4-methoxy-6,8a-dimethyl-6,7-dihydro-2H, 8aH-pyrano[2,3-b]pyran-2-one. These lactones for which the name chlamydosporol is proposed have not been reported previously. When tested in brine shrimp and HeLa cell assays, the LC50 concentration for a mixture of the isomers was approximately 400 micrograms/ml in both systems.

Animals↗

A rodent model of infusion brain edema: methodology and pathophysiological effects of saline and protein infusions.

To evaluate the potency of putative secondary mediators of brain edema and their possible contribution to edema related brain dysfunction an infusion model of brain edema was developed in rats. 100 ul of fluid (saline, 20% nonautologous protein) was infused over one hour into the left forebrain white matter through a stereotaxically placed (+1.2 mm ant to bregma, 3 mm lateral and 2.9 mm depth) 25 G needle. Brain tissue hydraulic resistance (Rt), regional cerebral blood flow (rCBF), cortical somatosensory evoked potentials (SEPs) and intracranial pressure (ICP) (intraventricular needle) were monitored during the infusion and rCBF CO2 reactivity (hydrogen clearance), local brain water content (microgravimetry), BBB integrity (Evans Blue 2%) and brain histology (H & E. Solochrome-cyanin) were evaluated after the infusion. Saline infusates caused no physiological dysfunction despite ipsilateral expansion and vacuolation of the subcortical white matter, separation of axonal bundles and a significant decrease (p = 3.8 x 10(-5] in local subcortical tissue specific gravity. Cortical histology and specific gravity adjacent to the infusion locus were normal. Rt significantly decreased (p = 6.5 x 10(-4] during the infusion but there were only minor increases in ICP. Findings with 20% protein infusates were similar despite a focal 65% decrement in the rCBF CO2 reactivity adjacent to the infusion site. This study has shown that a simple and inexpensive model of infusion brain edema can be created in the rat and that it provides a useful model for assessing the physiological effects of mediator compounds in the infusate. Potential applications and methodological improvements for this model are discussed.

Animals↗

Voluntary emotional facial expressions in patients with focal cerebral lesions.

This study investigates the voluntary production of emotional facial expressions in 43 brain-damaged and 9 control subjects. The expressions of right- and left-hemisphere lesion groups did not differ significantly, but those of the anterior lesion group were impoverished relative to the posterior lesion and control groups. Deficits of voluntary expression were dissociable from impairments in "non-emotional" facial-motor functions, dysphasia, and unilateral neglect.

Aphasia↗

Lupron depot (leuprolide acetate for depot suspension) in the treatment of endometriosis: a randomized, placebo-controlled, double-blind study. Lupron Study Group.

The safety and efficacy of leuprolide acetate (LA) for depot suspension (Lupron depot; TAP Pharmaceuticals, North Chicago, IL), 3.75 mg versus placebo, in the treatment of pain associated with endometriosis was assessed in a randomized, double-blind, multicenter study involving 52 patients. Dysmenorrhea, pelvic pain, and pelvic tenderness all responded significantly to LA treatment in comparison with placebo. Menses were suppressed in all of the LA patients. Estradiol decreased significantly to menopausal levels in the LA group. There were small to moderate changes in a variety of laboratory parameters, but these were not clinically significant. The most common adverse event was vasodilatation, occurring significantly more frequently in the LA group. Lupron depot was shown to be safe and effective in inducing a hormonal and menstrual suppression in patients with endometriosis, resulting in alleviation of pain symptoms.

Adult↗

Ischemic brain damage in a model of acute subdural hematoma.

Ischemic brain damage is the most important neuropathological finding in humans who die after acute subdural hematoma; however, its causes are poorly understood. We have produced acute subdural hematoma in the rat by injecting 400 microliters of autologous blood (approximately 20% of intracranial volume) into the subdural space. Extensive areas of ischemic damage, involving 14 to 16% of the volume of the hemisphere, developed in this model at 4 and 24 hours after the lesion. The hematomas were associated with a brief peak in intracranial pressure (51 mm Hg), which remained at three times normal levels (14 mm Hg) for 3 hours. In this model, therefore, ischemic damage appears to be due to the local effects of blood overlying the cortex at 4 hours after the ictus, rather than to globally raised intracranial pressure. The implications for the pathophysiology of acute subdural hematomas in humans are discussed.

Animals↗

Spinal cord thromboplastin-induced coagulopathy in a rabbit model.

Coagulopathy results from many diverse events, including several neurogenic causes. Using a rabbit model, we produced coagulopathy by injecting autologous spinal cord and extracted thromboplastin intravenously. Serial coagulation panels were performed to evaluate the activation of the thrombotic and fibrinolytic pathways. Group 1 animals (n = 4) received intravenous injections of homogenized spinal cord tissue. Coagulopathy was not produced with 36 mg of homogenized spinal cord tissue, but 50 mg or more resulted in death. Group 2 animals (n = 12) received intravenous injections of extracted rabbit cord thromboplastin, which contained approximately 60% activity of a commercially purified rabbit brain thromboplastin. Five animals receiving 2.5 to 5.5 mg of thromboplastin per kilogram of body weight survived with evidence of coagulopathy. Seven animals receiving 2.5 to 100 mg of thromboplastin per kilogram of body weight died. Group 3 (4 control animals) received normal saline injections without changes in clinical or laboratory status. The thrombotic pathway was activated in all animals as evidenced by decreased platelet counts and fibrinogen levels. Activation of the fibrinolytic system was demonstrated by increased concentrations of protamine sulfate and abnormal euglobulin clot lysis times. The most sensitive parameters were the platelet count, protamine sulfate concentration, and white cell count (margination), which became abnormal within 15 minutes after the injections and returned to normal within 1 hour.

Animals↗

Development of a traumatic intracranial hematoma after a "minor" head injury.

We have analyzed features of patients who had what appeared initially to be a minor head injury but who developed an acute traumatic intracranial hematoma. Over a 10-year period, 183 patients who were able to open their eyes spontaneously, were oriented to person, place, and time, and who obeyed commands when they were first seen at a hospital subsequently underwent operation for an acute intracranial hematoma. The hematoma was extradural in 54% of these patients. A history of altered consciousness or symptoms of headache and vomiting were present in 61% of the patients; 33% had a focal neurological deficit, and 43% had either focal deficit or signs of a basal skull fracture. A skull fracture was shown radiologically in 60% of patients, including 52% of those not clinically suspected of having an intracranial lesion. Six months after injury, 77% of the patients had made a moderate or good recovery. The possibility that a patient who has recently sustained a head injury might develop an acute intracranial hematoma can never be completely discounted, even when there are no abnormal clinical signs, and a skull x-ray retains a useful place in the investigation of selected patients with a minor head injury.

Acute Disease↗

Plosive/fricative distinction: the voiceless case.

Using only three measures of the waveform, the zero-crossing rate, the logarithm of the root-mean-square (rms) energy, and the derivative of the log rms energy with respect to time [termed rate of rise (ROR)], voiceless plosives (including affricates) can be distinguished from voiceless fricatives in word-initial, medial, and final positions. Peaks in the ROR contour are considered for significance to the plosive/fricative distinction by examining the log rms energy and zero-crossing rate. Then, the magnitude of the first significant peak in the ROR contour is used as the primary classifier. The algorithm was tested on 1364 tokens (720 word-initial tokens produced by four female and four male speakers; 360 word-medial tokens produced by two males and two females; 320 word-final tokens produced by two males and two females). Data from two male and two female speakers (360 word-initial tokens) were used as a training set, and the remaining data were used as a test set. The overall rate of correct classification was 96.8%. Implications of this result are discussed.

Algorithms↗

Norman Dott's contribution to aneurysm surgery.

Between 1926-36 Norman Dott managed 39 patients with suspected intracranial haemorrhage. During this period he established important principles of diagnosis and developed new methods for the medical and surgical treatment of aneurysmal subarachnoid haemorrhage. Dott performed the first intracranial operation to treat an aneurysm and the first angiogram to demonstrate an intracranial aneurysm. This article reviews Dott's early experiences of aneurysmal subarachnoid haemorrhage.

Cerebral Angiography↗

Aqueduct stenosis--presentation and prognosis.

In the 14-year period from 1974-1987 during which CT scanning was available in Edinburgh, 36 patients with benign, non-tumour related aqueduct stenosis were identified from a group of 342 patients with hydrocephalus. In terms of age at presentation, the patients separate into two groups, 9 cases diagnosed during the first year of life and 27 patients aged from 7 to 72 years. The presentation in the early cases was fairly acute, the diagnosis was secure and the operative treatment by ventricular peritoneal shunt was relatively free of complications. In the older patients, the first presentation was more chronic, and further investigation required a change of diagnosis in 5 of the 27 patients. More than half of the patients had recurrent symptoms which were much more acute and operative treatment was attended by a significant number of complications including death from intraventricular haemorrhage in one case.

Adolescent↗

The disposition of TCNU (tauromustine) in human malignant glioma: pharmacokinetic studies and clinical implications.

Tauromustine (TCNU), 130 mg/sq m, was administered intraoperatively by nasogastric tube to 10 patients with malignant glioma (seven glioblastomas and three anaplastic astrocytomas). High-performance liquid chromatography analysis of 32 tumor specimens for TCNU revealed that tissue concentrations ranged from 0 to 554 ng/gm: TCNU was not detected in necrotic regions of the tumor. Levels of TCNU in brain adjacent to tumor were similar to those recorded within the gliomas (range 0 to 635 ng/gm). The variability in the tissue level of TCNU was partly attributable to variable absorption of the drug, since peak plasma TCNU levels ranged from 164 to 3333 ng/ml. There were close quantitative and temporal relationships between the times of peak plasma levels (median 456 ng/ml at 45 minutes after administration), peak tumor levels (median 250 ng/gm tissue at 55 minutes), and brain adjacent to tumor levels (median 256 ng/gm tissue at 50 minutes). Linear regression analysis of the ratio between tissue and plasma TCNU levels at particular times after drug administration suggest that plasma concentrations can be used to estimate tissue concentrations. This study demonstrates that TCNU enters malignant glioma. In view of the activity of TCNU against a range of tumors, a full clinical evaluation of this new nitrosourea in malignant glioma seems justified.

Adult↗

Systems analysis of cerebrovascular pressure transmission: an observational study in head-injured patients.

In an observational study in head-injured patients, cerebrovascular pressure transmission was investigated using a systems analysis approach whereby the blood pressure (BP) waveform was used as a measure of an input stimulus to the cerebrovascular bed (CVB) and the intracranial pressure (ICP) waveform as the response to that stimulus. The transfer function is a measure of how much pressure is transmitted through the CVB at a given frequency and is calculated using Fourier analysis of the pressure waveforms. The transfer function allows quantification of the pressure transmission performance of the CVB, thus providing a basis for comparison between normal and abnormal function. Fifteen hundred samples of ICP and BP waveforms were collected from 30 head-injured patients via microcomputer. Off-line spectral analysis of the waveform database revealed four main classes of transfer function: those with an overall flat transfer function (curve type 1); those with an elevated low-frequency response (curve type 2); those with an elevated high-frequency response (curve type 3); and those exhibiting both an elevated low- and high-frequency response (curve type 4). Curve types 2 and 4 were most often associated with raised ICP (greater than 20 mm Hg), whereas curve types 1 and 3 were most often affiliated with ICP less than 15 mm Hg. Studies of this type may provide insight into the pathophysiology of the CVB and ultimately aid in the prediction and treatment of raised ICP.

Adolescent↗

Leuprolide acetate in the management of ureteral obstruction caused by endometriosis.

Endometriotic ureteral obstruction is a serious event commonly diagnosed late and therefore associated with a major risk of hydronephrotic renal atrophy. The standard therapy is surgical. However, medical treatment has been reported using danazol, progestins, and estrogen-progestin combinations, although solid documentation of the effect of hormonal therapy against ureteral endometriosis is lacking. Gonadotropin-releasing hormone (GnRH) agonist treatment of endometriosis has yielded good results but has not been adequately reported in patients with ureteric involvement. We report three patients treated with a GnRH agonist, leuprolide acetate, for 6-9 months as a preoperative course. One patient had bilateral and two had unilateral obstruction. The preoperative course relieved the obstruction in the patient with bilateral disease and in one with unilateral changes. The failure occurred in a patient with intrinsic ureteric endometriosis. This early experience suggests a place for GnRH agonist therapy for patients with ureteric obstruction due to endometriosis, probably, but not necessarily, in conjunction with a planned surgical procedure. If medical therapy is attempted, close surveillance of renal function is mandatory.

Adult↗

Postoperative rehydration.

Oral rehydration therapy (ORT) by the enteral route was compared with intravenous ORT in a group of patients undergoing cholecystectomy. Rehydration was successfully accomplished in both groups; however, enteral rehydration was more comfortable, more economical, and caused fewer complications than the intravenous infusion. When the study was expanded to patients undergoing colonic surgery, the results were encouraging; enteral ORT in patients undergoing gastric or duodenal surgery was less successful.

Digestive System Surgical Procedures↗

14C-2-deoxyglucose uptake in the ground squirrel brain during entrance to and arousal from hibernation.

Neuronal activity underlying various phases of the mammalian hibernation cycle was investigated using the 14C-2-deoxyglucose (2DG) method. Relative 2DG uptake (R2DGU) values were computed for 96 brain regions across 7 phases of the hibernation cycle: euthermia, 3 body temperature (Tb) intervals during entrance into hibernation, stable deep hibernation, and 2 Tb intervals during arousal from hibernation. Multivariate statistical techniques were employed to identify objectively groups of brain regions whose R2DGU values showed a similar pattern across all phases of hibernation. Factor analysis revealed that most of the variability in R2DGU values for the 96 brain regions across the entire cycle could be accounted for by 3 principal factors. These factors could accurately discriminate the various phases of hibernation on the basis of the R2DGU values alone. Three hypothalamic and 3 cortical regions were identified as possibly mediating the entrance into hibernation because they underwent a change in R2DGU early in entrance into hibernation and loaded strongly on one of the principal factors. Another 4 hypothalamic regions were similarly identified as possibly causally involved in the arousal from hibernation. These results, coupled with characteristic changes in ordinal rank of the 96 brain regions in each phase of hibernation, support the concept that mammalian hibernation is an active, integrated orchestration of neurophysiological events rather than a state entered through a passive process.

Animals↗