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Biomedical subjects

M K Morgan

Publications and source records attributed to M K Morgan.

At least 37 records · Page 2Linked to original sources

Subacute and reproductive effects in mink from exposure to Fusarium fujikuroi culture material (M-1214) containing known concentrations of moniliformin.

This study was conducted to ascertain the subacute and reproductive effects in mink (Mustela vison) resulting from exposure to moniliformin, a toxic mycotoxin produced by Fusarium fungi. In a preliminary trial, adult mink were presented diets that contained targeted concentrations of 10, 20, 40, 80, 160, or 240 ppm moniliformin provided by F. fujikuroi culture material (M-1214). The mink fed diets that contained more than 40 ppm moniliformin refused to eat significant quantities of feed. Feeding adult mink diets that contained 8.1 or 17.0 ppm (wet weight) moniliformin, provided by F. fujikuroi culture material, in a 30-day subacute trial produced no significant adverse effects on feed consumption, body weights, hematologic parameters, or serum chemical values, and notable histologic changes in tissues that were examined. In the reproduction trial, female mink were exposed to the same dietary concentrations of moniliformin provided by F. fujikuroi culture material as in the subacute test from 2 weeks prior to the breeding season until their offspring (kits) were 8 weeks old. Consumption of the high-dose (17 ppm) diet resulted in significant neonatal mortality and reduced kit body weights at birth and at 8 weeks of age. Necropsy of 8-week-old kits from the control and high-dose groups revealed no gross or histologic lesions or alterations in liver, lung, or heart tissues that could account for the mortality observed in the kits exposed to the culture material. These results indicate that long-term (105-135 days) dietary exposure to F. fujikuroi culture material containing 17 ppm moniliformin is not lethal to adult female mink, but can have adverse effects on neonatal mink.

Animals↗

Combined endovascular stent implantation and endosaccular coil placement for the treatment of a wide-necked vertebral artery aneurysm: technical case report.

OBJECTIVE AND IMPORTANCE: We describe a case in humans of the combined application of endovascular stent placement and Guglielmi detachable coil packing in the management of a wide-necked intracranial aneurysm. CLINICAL PRESENTATION: A 56-year-old woman suffered a subarachnoid hemorrhage secondary to a large wide-necked left vertebral artery aneurysm. Because of the size of the neck of the aneurysm and the extent of its calcification evident on computed tomographic scans, it was deemed unsuitable for surgical intervention or for conventional endovascular coiling. Instead, a combined surgical and endovascular therapy was instituted. INTERVENTION: The left vertebral artery was surgically exposed and cannulated to allow for the placement of an endovascular stent across the neck of the aneurysm to act as a buttress against which Guglielmi detachable coils could be packed. The patient suffered no ill effects as a result of this procedure and made a slow but steady recovery. CONCLUSION: This report describes a case of a wide-necked intracranial artery aneurysm treated using a combination of endovascular stent implantation across an aneurysm neck and endosaccular coil placement to obliterate the aneurysm. The technique described provides another treatment to better manage the difficult entity of wide-necked intracranial aneurysms that may be unsuitable for clipping.

Angioplasty, Balloon↗

Detection of a novel strain of porcine circovirus in pigs with postweaning multisystemic wasting syndrome.

Swine infectious agents, especially viruses, are potential public health risks associated with the use of pig organs for xenotransplantation in humans. Therefore, there is a need for better characterization of swine viruses and for the development of diagnostic tests for their detection. We report here isolation of a novel strain of porcine circovirus (PCV) from pigs with postweaning multisystemic wasting syndrome (PMWS). Affected pigs exhibited severe interstitial pneumonia and lymphoid depletion. The complete nucleotide sequence (1,768 nucleotides) of the genome of the PCV isolate was determined and compared with the sequence of the PCV strain isolated from PK-15 cells. Sequence comparison revealed significant differences between the two PCV strains, with an overall DNA homology of 76%. Two major open reading frames (ORFs) were identified. ORF1 was more conserved between the two strains, with 83% nucleotide homology and 86% amino acid homology. ORF2 was more variable, with nucleotide homology of 67% and amino acid homology of 65%. PCR and in situ hybridization demonstrated abundant viral DNA in various organs of pigs with PMWS. In situ hybridization demonstrated that this strain of PCV targets multiple organs and infects macrophages, lymphocytes, endothelial cells, and epithelial cells.

Amino Acid Sequence↗

Meningeal carcinomatosis: an unusual cause of deafness.

Meningeal carcinomatosis is the diffuse infiltration of the meninges by metastatic carcinoma. Patients usually have a known underlying malignancy, but primary presentation can be with symptoms of meningeal involvement. The cases are reported of two patients who presented with sensorineural hearing loss. The roles of gadolinium-enhanced magnetic resonance imaging and cerebrospinal fluid cytology in reaching the diagnosis are discussed.

Adenocarcinoma↗

Oroantral fistula: a complication of transantral ligation of the internal maxillary artery for epistaxis.

Transantral ligation of the internal maxillary artery (IMAX) is a well-described option for surgical management of posterior epistaxis not controlled by anterior and posterior packing. Advocates for this procedure argue that it reduces the morbidity, length of hospital stay and financial cost associated with prolonged nasal packing. The procedure is carried out through a Caldwell-Luc approach and the IMAX is clipped in the pterygomaxillary fossa. Fashioning of a nasoantral window is optional and its inclusion usually depends on the integrity of the sinus ostium. The commonest complications of transantral IMAX ligation occur when local structures including the inferior orbital and anterior superior alveolar nerves are damaged. The incidence of oroantral fistula following IMAX ligation is very low but those cases reported have been associated with the failure to create a nasoantral drainage window. We report two cases of persistent oroantral fistula complicating transantral internal maxillary artery ligation. No nasoantral window was fashioned in either of these cases.

Adult↗

Chronic cerebral hypoperfusion: pathological and behavioral consequences.

OBJECTIVE: Although the effects of acute ischemic insults to the brain are well known, the effects related to chronic ischemia are poorly delineated. The pathological and behavioral changes induced by a chronic noninfarctional reduction in cerebral blood flow of 25 to 50% maintained for 6 months were assessed. METHODS: In each of 18 male Sprague-Dawley rats, an arteriovenous fistula was created in the neck via an anastomosis between the right external jugular vein and the right common carotid artery to induce cerebral hypoperfusion. Nineteen age-matched animals comprised a control group. Six months after surgery, the animals were examined using light and electron microscopic techniques, as well as via a battery of behavioral tests (motor, open field, and T-maze). RESULTS: Examination of the hippocampus by using light microscopy revealed disorganization of the CA1 sector with an increased number of astrocytes. Transmission electron microscopy of the CA1 region demonstrated neurons with increased lipofuscin pigment and central nucleoli and astrocytes with more numerous cytosolic mitochondria. Motor performance testing revealed no gross motor deficits, although open-field assessment demonstrated increased exploratory behavior in rats with fistulas. Finally, T-maze testing results suggested that errors in working memory were more common in rats undergoing chronic cerebral hypoperfusion (P < 0.05). CONCLUSIONS: These findings suggest that chronic reductions in cerebral blood flow of a magnitude previously thought to be harmless to neurons (i.e., reduced by 25-50%) do alter neuronal structure and affect whole animal behavior. Such a scenario may be responsible for a symptomatology secondary to arteriovenous steal and severe carotid stenoses. The mechanisms are still unknown.

Animals↗

Chronic cerebral hypoperfusion inhibits calcium-induced long-term potentiation in rats.

BACKGROUND AND PURPOSE: Long-term potentiation (LTP) in the rat hippocampus induced by tetanic stimulation is impaired by chronic cerebral hypoperfusion. The effects of chronic cerebral hypoperfusion on other forms of LTP are unknown. Such data could help delineate the pathways of cellular alteration caused by chronic cerebral hypoperfusion. The in vitro phenomenon of calcium-induced LTP was thus examined in rat hippocampal CA1 cells that had undergone chronic hypoperfusion with a reduction in cerebral blood flow of between 25% and 50% maintained for 26 weeks. METHODS: Ten Sprague-Dawley rats had a cervical arteriovenous fistula surgically constructed, and an additional 10 animals were used as age-matched controls. Hippocampal slices were prepared after 26 weeks of hypoperfusion, and in vitro extracellular field potential recordings were taken from the Schäffer collateral CA1 region. Properties of LTP induced through transient exposure to a hypercalcemic solution were analyzed. RESULTS: LTP was impaired in animals with an arteriovenous fistula (P < .05). Control animals demonstrated potentiation lasting for the entire 2 hours of recording, whereas fistula animals showed only transient potentiation (< 60 minutes) before returning to baseline values. CONCLUSIONS: Calcium-induced LTP is impaired by chronic cerebral hypoperfusion. This form of LTP is different from that induced by tetanic stimulation. It is the most sensitive test available for in vitro detection of the changes induced in neuronal function by chronic noninfarctional reductions in cerebral blood flow of 25% to 50% and may indicate that the most basic cellular parameters involving calcium homeostasis and metabolism are being altered. The precise mechanisms remain to be elucidated, and several postulates are discussed.

Action Potentials↗

Normal perfusion pressure breakthrough: the role of capillaries.

Excision of human cerebral arteriovenous malformations (AVMs) can be complicated by postoperative edema and hemorrhage in adjacent brain tissue, despite the complete excision of the malformation. Various theories have purported to explain the hemodynamic basis for this predisposition, including disordered autoregulation causing "normal perfusion pressure breakthrough" and obstruction of venous drainage leading to "occlusive hyperemia." This study did not evaluate the arterial or venous circulations in this scenario, but rather examined the capillaries in adjacent brain parenchyma for any structural deficiencies that would predispose the brain to the postoperative formation of edema and hemorrhage. Arteriovenous fistulas (AVFs) were created surgically in the necks of 10 male Sprague-Dawley rats, which caused chronic cerebral hypoperfusion with a reduction in cerebral blood flow of between 25% and 50%. Ten age-matched animals were used as controls. Twenty-six weeks after AVF formation the animals were killed and perfusion fixed. Their brain tissue was prepared for light microscopic studies by staining for glial fibrillary acidic protein or for transmission electron microscopy. In the CA1 pyramidal cell region of the hippocampus, it was found that in the animals with AVFs there was increased capillary density and absent astrocytic foot processes in some of these vessels. It was concluded that these vessels had developed as a result of neovascularization in response to chronic cerebral ischemia and that their anatomical configuration made them prone to mechanical weakness and instability following the increase in perfusion pressure that occurs in adjacent brain parenchyma after AVM excision. The authors believe that this study pinpoints a structural accompaniment to the hemodynamic changes that occur in brain tissue in the vicinity of cerebral AVMs that predispose these areas to the formation of edema and hemorrhage after AVM excision.

Animals↗

Surgery for cerebral arteriovenous malformation: risks related to lenticulostriate arterial supply.

The aim of this study was to compare complications of surgery in arteriovenous malformations (AVMs) supplied by the middle cerebral artery (MCA) with and without a lenticulostriate arterial contribution. Ninety-two consecutive surgical resections of AVMs with an angiographically demonstrated MCA supply were performed between January 1989 and July 1996. Ten of these cases had a significant lenticulostriate arterial contribution. The cases were graded according to the Spetzler-Martin classification. There were no deaths and 4.3% of cases developed new major neurological deficit by the 3-month follow-up examination. All cases had angiographically confirmed obliteration of the AVM. There were no complications in 16 patients with Spetzler-Martin Grade I AVMs, one case of complications in 40 patients with Grade II AVMs, eight cases of complications in 26 patients with Grade III AVMs, and seven cases of complications in 10 patients with Grade IV and V AVMs. The supply of blood from lenticulostriate branches was associated with complications in eight of the 10 cases. The effect of the presence of a lenticulostriate arterial supply was most apparent in cases of Grade III AVMs: complications were experienced in three of 20 patients whose AVMs were not supplied by the arteries and in five of six patients whose AVMs were fed by the lenticulostriate arteries. This difference is significant (p < 0.0001). The conclusions drawn from this study are that for Grade III AVMs, the presence of a lenticulostriate arterial supply can be considered a factor predictive of an increased risk of surgical complications.

Adolescent↗

Dietary fumonisins disrupt sphingolipid metabolism in mink and increase the free sphinganine to sphingosine ratio in urine but not in hair.

This study was conducted to investigate the effects of dietary Fusarium moniliforme culture material (M-1325) containing known concentrations of fumonisins B1, B2 and B3 on sphingolipids in urine and hair of mink (Mustela vison) for use as potential, non-invasive biomarkers of exposure to fumonisins in this species. Feeding mink diets containing 86, 22, and 7 ppm or 200, 42, and 12 ppm of fumonisins B1, B2 and B3, respectively, yielded marked increases in urinary free sphinganine (Sa) and free sphingosine (So) concentrations, and free Sa/free So ratios (2 to 11-fold) within 7 d, compared to controls. Free Sa and free So concentrations and Sa/So ratios in hair samples from mink fed the control or high dose fumonisin diets for 100 days were similar and were not apparently altered by exposure to these mycotoxins. These results suggest that Sa/So ratios in urine, but not in hair of mink can serve as an early indicator of exposure to fumonisins in this species.

Animals↗

Teratogenic potential of atrazine and 2,4-D using FETAX.

The teratogenic potential of commercial formulations of atrazine (40.8%) and 2,4-D was evaluated using FETAX (frog embryo teratogenic assay--Xenopus). Because these herbicides have been detected in ground and surface water, this study was designed to determine the adverse effects in buffer and natural water for both herbicides. All treatments showed a significant concentration-response effect on exposed embryos, except for the 2,4-D natural water sample. Atrazine (solubility of the commercial formula used 70 mg/L at 20 degrees C), compared to 2,4-D (solubility = 311 mg/L at pH = 1 and 25 degrees C), had a significantly greater teratogenic effect in both the buffer (atrazine EC50 = 33 mg/L, LC50 = 100 mg/L, TI = 3.03; 2,4-D EC50 = 245 mg/L, LC50 = 254 mg/L, TI = 1.04) and natural water samples (atrazine EC50 < 8 mg/L, LC50 = 126 mg/L; 2,4-D EC50 and LC50 > 270 mg/L). The 2,4-D EC50 and LC50 values for the buffer were similar at 245 mg/L and 254 mg/L. These similar values and the teratogenic index (TI) of 1.04 suggested that 2,4-D was more embryotoxic than teratogenic to frog embryos at high concentrations. Atrazine in natural water demonstrated a significantly greater EC50 (100% abnormality at 8 mg/L, the lowest test concentration) to frog embryos than the buffer experiment (EC50 = 33 mg/L). The extrapolated lowest observable adverse effect concentration (LOAEC) for the natural water experiment was 1.1 mg/L. These results suggest that atrazine toxicity is enhanced by the synergistic or additive effects of some component of the water or atrazine was already present in the sample. In contrast to atrazine, 2,4-D was less toxic in natural water than buffer. These results suggest that both atrazine and 2,4-D pose little threat, since their embryotoxicity and teratogenicity to frog embryos occur at high concentrations approaching their maximum solubility levels in water.

2,4-Dichlorophenoxyacetic Acid↗

Fluid dynamics of the cerebral aqueduct.

Despite a multitude of theories describing the mechanics of the intracranial spaces in diseases such as hydrocephalus, little is known about the mechanics of normal CSF flow. A pressure difference is required to drive CSF flow. Knowing that the pressure difference driving fluid through the aqueduct is beyond the resolution of clinically used pressure transducers, a computational fluid dynamics program was used to analyze flow through an aqueduct shape. Flow through this duct was compared with that through a cylinder and through a double hourglass. Both steady and oscillating flows were tested, revealing that only 1.1 Pa of pressure is required to move CSF through the aqueduct. This suggests that normally less than 5% of the total resistance to CSF flow within the CSF pathways occurs in the aqueduct.

Cerebral Aqueduct↗

Chronic cerebral hypoperfusion in the rat: temporal delineation of effects and the in vitro ischemic threshold.

Acute reductions in cerebral blood flow of up to 50% do not affect neuronal function although it has been shown that reductions of a similar magnitude maintained for 26 weeks do induce neuronal changes. In vitro rat hippocampal LTP was evaluated after 10 weeks of cerebral hypoperfusion. An assessment was also made of the possible 'robustness' of hippocampal CA1 pyramidal neurons to combined in vitro hypoxic/ischemic insults because of previously shown differences in hemodynamic autoregulatory curves. No differences were found between controlled and chronically hypoperfused animals in either study. It is concluded that the changes in neuronal function induced by reductions in cerebral blood flow of less than 50% take time to develop and do not induce adaptive changes in affected neurons. The mechanism for these changes remains to be elucidated.

Animals↗

Delayed referral of patients with aneurysmal subarachnoid haemorrhage.

OBJECTIVE: To determine the outcome of patients with subarachnoid haemorrhage and whether delays in their diagnosis and referral have been reduced over a 15-year period. DESIGN: A 15-year retrospective study of patients admitted to a tertiary neurosurgical unit between 1977 and 1992. SETTING: The Royal North Shore Hospital, Sydney. PATIENTS: 511 patients admitted with subarachnoid haemorrhage from ruptured intracranial aneurysms. RESULTS: Of 486 patients with at least a six-month follow-up, 66% made a good recovery and 19% died. Outcome was significantly influenced by the neurological condition of the patient at admission (P < 0.0001). There was no significant difference in the relative proportions of patients transferred late (three or more days after onset of symptoms) when those admitted before and after 1986 were compared. CONCLUSION: Delayed diagnosis and referral remain the major preventable problems in the management of patients with aneurysmal subarachnoid haemorrhage.

Aneurysm, Ruptured↗

The use of intraarterial papaverine in the management of vasospasm complicating arteriovenous malformation resection. Report of two cases.

The authors report two cases of treatment by intraarterial papaverine of cerebral vasospasm complicating the resection of an arteriovenous malformation (AVM). Both cases had successful reversal of vasospasm documented on angiography. In the first case sustained neurological improvement occurred, resulting in a normal outcome by the time of discharge. In the second case, neurological deterioration occurred with the development of cerebral edema. This complication was thought to be due to normal perfusion pressure breakthrough, on the basis of angiographic arterial vasodilation and increased cerebral blood flow. These two cases illustrate an unusual complication of surgery for AVMs and demonstrate that vasospasm (along with intracranial hemorrhage, venous occlusion, and normal perfusion pressure breakthrough) should be considered in the differential diagnosis of delayed neurological deterioration following resection of these lesions. Although intraarterial papaverine may be successful in dilating spastic arteries, it may also result in pathologically high flows following AVM resection. However, this complication has not been seen in our experience of treating aneurysmal subarachnoid hemorrhage by this technique.

Adult↗

Chronic cerebral hypoperfusion and impaired neuronal function in rats.

BACKGROUND AND PURPOSE: Studies in acute cerebral ischemia have shown that reductions in cerebral blood flow of up to 50% do not lead to infarction or alterations in neuronal electric activity. Little is known about the effects of chronic reductions in cerebral blood flow. The purpose of this study was to evaluate neuronal electrophysiological function in brain that had been subjected to a chronic reduction of cerebral blood flow of less than 50%. Based on existing knowledge of thresholds of cerebral ischemia, neuronal electrophysiological function should be unaffected by hypoperfusion of this magnitude. METHODS: An arteriovenous fistula model in the rat was used to induce chronic cerebral hypoperfusion with reductions of cerebral blood flow of 25% to 50% as measured previously by 14C-labeled autoradiography. Using in vitro electrophysiological brain slice techniques, long-term potentiation in hippocampal CA1 neurons was examined extracellularly after 6 months of chronic noninfarctional cerebral hypoperfusion. Brains were also examined histologically at this time for evidence of cerebral infarction. RESULTS: There was no evidence of cerebral infarction. Long-term potentiation was produced in 9 of 12 control animals and only 2 of 8 hypoperfused animals. This difference was significant (P < .05) and demonstrated that long-term potentiation was impaired in animals with chronic hypoperfusion. CONCLUSIONS: Noninfarctional reductions in cerebral blood flow of up to 50% do impair neuronal function in chronic cerebral ischemia, a result quite distinct from that seen in acute ischemia. The threshold for neuronal dysfunction in chronic cerebral hypoperfusion is lower than that found in acute cerebral ischemia, suggesting that duration as well as severity of ischemic insult determines cellular viability. Chronic hypoperfusion may lead to a noninfarctional state with impaired neuronal function, a category of chronic cerebral ischemia not previously identified.

Action Potentials↗

Successful treatment of an acute thrombosis of an intracranial vertebral artery endarterectomy with urokinase.

This is a case report of a 47-year-old man admitted with a 7-month history of disequilibrium, multiple reversible vertebrobasilar ischemic attacks, and one submaximal completed stroke in the left posterior inferior cerebellar artery distribution. Vertebrobasilar ischemic attacks continued despite anti-coagulation, and orthostatic symptomatology suggested a significant hemodynamic component contributing to the posterior circulation ischemia. Angiography confirmed bilateral high-grade stenoses of the intracranial vertebral arteries. A right intracranial vertebral artery endarterectomy was performed with electroencephalographic and somatosensory evoked potential monitoring and protection with barbiturate infusion. The arteriotomy was closed with a vein patch. Postoperatively, the endarterectomy site thrombosed. This thrombosis was completely reversed with 220,000 U of urokinase selectively infused intra-arterially at the site of thrombosis. This procedure was not complicated by hemorrhage or distal embolization. The vertebral artery was confirmed to be patent 24 hours and 7 days after the urokinase injection. The patient sustained a borderzone infarction in the right cerebellar hemisphere without neurological deficits and was discharged home well.

Blood Vessel Prosthesis↗