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J R Little

Publications and source records attributed to J R Little.

At least 37 records · Page 2Linked to original sources
PubMed1992

The effect of a mannose binding protein on macrophage interactions with Candida albicans.

A soluble mannose binding protein (MBP), obtained from rabbit serum, was found to inhibit phagocytosis of Candida albicans by bone marrow derived, cultured murine macrophages. During in vitro incubation of yeast with lymphocyte-free macrophage populations uptake of the yeast was significantly reduced at MBP concentrations of 5 micrograms/ml. A similar reduction in yeast phagocytosis was produced by dextrose, d-fucose, l-fucose, d-mannose and alpha-methyl-d-mannoside but required saccharide concentrations of 25-50 mg/ml. Inhibition of phagocytosis of the yeast also resulted from pretreatment of either the macrophages or the yeasts with MBP followed by washing. As expected, the addition of mannan to the assay medium blocked the inhibitory effect of MBP for uptake of C. albicans. These findings suggest that both cell bound and soluble mannose receptors may be important modulators of macrophage-Candida interactions.

Animals↗
PubMed1991

Perioperative management and outcome after surgical treatment of anterior cerebral artery aneurysms.

The authors present clinical experience with 28 cases of ruptured anterior cerebral artery (ACA) aneurysms managed personally during a 36 month period, and 10 unruptured ACA aneurysms. The cases included five giant aneurysms and four distal ACA aneurysms. Management strategy was uniform and included early operative intervention (except in the setting of deteriorating neurologic deficit, not attributable to hydrocephalus or hematoma), and vasospasm prophylaxis including calcium channel blockers and hypervolemic hemodilution and arterial hypertension. Modern diagnostic adjuncts including transcranial doppler were used as they became available. Good outcome (outcome grade 1 or 2) was observed at 6 months in 71% (20/28) of ruptured cases and in 90% (9/10) of unruptured cases; fair outcome (outcome grade 3) was observed in 14% (4/28) of ruptured cases and in 10% of unruptured cases; bad outcome (outcome grade 4 or 5) was observed in 14% (4/28) of ruptured cases. There were no instances of rebleeding after admission to the hospital. There was a single mortality in a patient moribund on admission. Delayed ischemic deterioration (DID) was documented in 46% (13 of 28) of the ruptured cases, and was a major source of morbidity in 7 of the 9 instances of fair or poor outcome in the series. Management outcome, including the occurrence of subtle neuropsychological difficulties commonly described in cases with ACA aneurysms, is discussed with relation to the incidence of DID, the clinical course of DID, and the possible impact of various therapeutic strategies.

Adult↗
PubMed1991

Surgical management of syringomyelia: a five year experience in the era of magnetic resonance imaging.

We summarize our experience with 59 consecutive surgically managed cases of syringomyelia (SM) over a 5 year period. All cases had magnetic resonance imaging (MRI) preoperatively and postoperatively. Twenty-eight patients presented with SM and the adult Chiari (Chiari I) malformation (SM-ACM), 6 patients had post traumatic syrinxes, 14 patients had syrinxes associated with an intramedullary neoplasm, 3 patients had syringomyelia associated with spinal arachnoiditis and 8 patients had idiopathic syringomyelia. Holocord syrinxes were more often associated with SM-ACM, while focal syrinxes were associated with posttraumatic, spinal arachnoiditis and neoplastic conditions. In all cases with neoplasms the MRI revealed parenchymal intramedullary signal abnormalities in addition to the syrinx cavity. Posterior fossa decompression with obex plugging (the Gardner operation) was the procedure of choice for SM-ACM and for idiopathic holocord syringomyelia. Exploration and drainage of the syrinx with or without shunting was carried out mainly for focal syrinxes associated with trauma and neoplasm. Patients with SM-ACM responded well to posterior fossa decompression with satisfactory results in 24/28 patients. Idiopathic SM is probably a forme fruste of SM-ACM and when treated with the Gardner procedure showed good results in all 8 patients. Posttraumatic and neoplastic SM had the least predictable results with surgery. The disappearance of the syrinx on postoperative MRI correlated well with a good surgical outcome.

Adolescent↗
PubMed1991

Importance of freezing time when iodoantipyrine is used for measurement of cerebral blood flow.

The goal of the present study was to determine effects of delay of freezing of the brain on distribution of [14C]iodoantipyrine in the brain. Blood flow to parietal cerebral cortex (CBF) and choroid plexus was measured with the indicator fractionation technique and quantitative autoradiography. After injection of iodoantipyrine, each rat was decapitated, and the head was immersed in chlorodifluoromethane (-40 degrees C). The brain was removed from the skull after it was frozen. In some rats, heads were immersed immediately after decapitation, and CBF was markedly heterogeneous. In another group, heads were frozen 3 min after decapitation. In this case, CBF was uniform in its distribution. Average CBF was similar in groups with immediate and delayed freezing (90-104 ml.min-1 x 100 g-1). In contrast, delays in freezing decreased blood flow to choroid plexus from 551 +/- 115 to 261 +/- 48 ml.min-1 x 100 g-1. Our findings indicate that immediate freezing of the brain after decapitation is necessary to prevent diffusion of iodoantipyrine from regions of high blood flow to regions of lower blood flow and underestimations of blood flow in regions with high blood flow.

Animals↗
PubMed1991

Amphotericin B selectively stimulates macrophages from high responder mouse strains.

Lymphoid cells from most inbred mouse strains respond to amphotericin B (AmB)-induced immunostimulation. However, C57BL/6 mice and related strains display low or absent lymphoid cell stimulation by AmB and enhanced susceptibility to AmB toxicity. Experiments reported here show that in vitro incubation with AmB can stimulate AKR (AmB-high responder strain) macrophage proliferation. Intraperitoneal injection of AKR mice with AmB also elicits a population of macrophages primed for enhanced oxidative burst activity after triggering by zymosan particles. Under the same experimental conditions, AmB elicits a population of very weakly responsive macrophages from C57BL/6 mice. The low responsiveness of C57BL/6 macrophages correlates with previous observations that AmB is a potent immunoadjuvant and B cell mitogen in most inbred strains, but it selectively lacks immunoadjuvant effects in C57BL/6 mice and it also fails to induce polyclonal B cell stimulation in their spleen cell suspensions. Similarly, in measurements of protein synthesis in vitro, high concentrations of AmB produce a greater inhibition of protein synthesis in C57BL/6 peritoneal macrophages than in parallel cultures of AKR macrophages. These findings support the hypothesis that the macrophage is an important target cell in the mediation of AmB-induced immunomodulation.

Amphotericin B↗
PubMed1991

Anticryptococcal activity of amphotericin B-stimulated macrophages.

Amphotericin B (AmB) and its methyl ester derivative (AME) are immunoadjuvants with macrophage stimulating properties. Cultures containing AmB and murine peritoneal macrophages showed synergistic anticryptococcal activity. The antifungal activity was associated with AmB-stimulated macrophages and with their culture supernatants. Photoinactivation of the residual AmB in the macrophage culture supernatant did not result in the loss of antifungal activity. AmB-stimulated macrophage culture supernatants inhibited the growth of C. neoformans in a dose responsive manner and the activity was destroyed by incubation at 100 degrees C but not at 60 degrees C.

Amphotericin B↗
PubMed1991

Natural history of the cavernous angioma.

The incidence and natural history of the cavernous angioma have remained unclear in part because of the difficulty of diagnosing and following this lesion prior to surgical excision. The introduction of magnetic resonance (MR) imaging has improved the sensitivity and specificity of diagnosing and following this vascular malformation. Seventy-six lesions with an MR appearance typical of a presumed cavernous angioma were discovered in 66 patients among 14,035 consecutive MR images performed at the Cleveland Clinic between 1984 and 1989. Follow-up studies in 86% of the cases over a mean period of 26 months provided 143 lesion-years of clinical survey of this condition. The most frequent presenting features were seizure, focal neurological deficit, and headache. While most lesions exhibited evidence of occult bleeding on MR imaging, there was overt hemorrhage in seven of the 57 symptomatic patients and only one overt hemorrhage occurred during the follow-up interval. The annualized bleeding rate was 0.7%. Analysis of the hemorrhage group revealed a significantly greater risk of overt hemorrhage in females. Pathological confirmation of cavernous angioma was obtained in all 14 surgical cases. This information assists in rational therapeutic planning and prognosis in patients with MR images showing lesions suggestive of cavernous angioma.

Adolescent↗
PubMed1991

Symptomatic Chiari malformation in adults: a new classification based on magnetic resonance imaging with clinical and prognostic significance.

Thirty-five consecutive adults with Chiari malformation and progressive symptoms underwent surgical treatment at a single institution over a 3-year period. All patients underwent magnetic resonance imaging scan before and after surgery. Images of the craniovertebral junction confirmed tonsillar herniation in all cases and allowed the definition of two anatomically distinct categories of the Chiari malformation in this age group. Twenty of the 35 patients had concomitant syringomyelia and were classified as Type A. The remaining 15 patients had evidence of frank herniation of the brain stem below the foramen magnum without evidence of syringomyelia and were labeled Type B. Type A patients had a predominant central cord symptomatology; Type B patients exhibited signs and symptoms of brain stem or cerebellar compression. The principal surgical procedure consisted of decompression of the foramen magnum, opening of the fourth ventricular outlet, and plugging of the obex. Significant improvement in preoperative symptoms and signs was observed in 9 of the 20 patients (45%) with syringomyelia (Type A), as compared to 13 of the 15 patients (87%) without syringomyelia (Type B). Postoperative reduction in syrinx volume was observed in 11 of the 20 patients with syringomyelia, including all 9 patients with excellent results. Magnetic resonance imaging has allowed a classification of the adult Chiari malformation in adults based on objective anatomic criteria, with clinical and prognostic relevance. The presence of syringomyelia implies a less favorable response to surgical intervention.

Adult↗
PubMed1990

Intracranial hypertension associated with unruptured cerebral arteriovenous malformations.

Only 6 patients with intracranial hypertension associated with unruptured cerebral arteriovenous malformations have been reported. We report 6 additional patients seen at the Cleveland Clinic during the past 10 years. The average age was 28 years (range, 19-44 years); 4 were women. Symptoms and signs included papilledema (6 patients), headache (6), transient nonepileptic focal symptoms (4), visual obscurations (3), ipsilateral carotid or ocular bruits (3), abnormal visual fields (3), focal seizures (2), and progressive visual loss (1). Enhanced computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated the malformations in all 6 patients. The malformations were large, supplied by the branches of the middle and anterior cerebral arteries, with the posterior cerebral artery contributing in 3 patients, and all drained into the superior sagittal sinus. Associated venous obstruction was seen in 2 patients. Four patients underwent excision of the arteriovenous malformation, with resolution of papilledema in all 4. Measurements of cortical arterial and venous pressures during surgery in 3 patients showed decreased feeding artery pressures and elevated draining vein pressures, which normalized after removal of the malformation. Treatment in the 2 remaining patients consisted of medical therapy (acetazolamide, furosemide, steroids) alone in 1 patient, and in conjunction with proton beam radiation in the other. Papilledema resolved in the former patient, but the patient receiving proton beam radiation still had papilledema 2 years later. Intracranial hypertension associated with unruptured cerebral arteriovenous malformations occurs in young patients with high flow malformations that drain into the superior sagittal sinus, and is likely the result of increased cortical venous and superior sagittal sinus pressure. Excision of the malformation effectively reduces the intracranial pressure.

Adult↗
PubMed1990

Intracranial dural arteriovenous malformations: factors predisposing to an aggressive neurological course.

The natural history of cranial dural arteriovenous malformations (AVM's) is highly variable. The authors present their clinical experience with 17 dural AVM's in adults, including 10 cases with an aggressive neurological course (strictly defined as hemorrhage or progressive focal neurological deficit other than ophthalmoplegia). Two of these 10 patients died prior to surgical intervention and a third was severely disabled by intracerebral hemorrhage. Six patients underwent surgical resection of their dural AVM, with preparatory embolization in two cases. One patient received embolization and radiation therapy without surgery. Six of the seven cases without an aggressive neurological course were treated conservatively, and the seventh patient underwent embolization of a cavernous sinus dural AVM because of worsening ophthalmoplegia. In order to clarify features associated with aggressive behavior, a comprehensive meta-analysis was performed on 360 additional dural AVM's reported in the literature with sufficiently detailed clinical and angiographic information. The location and angiographic features of 100 aggressive cases were compared to those of 277 benign cases. No location of dural AVM's was immune from aggressive neurological behavior; however, an aggressive neurological course was least often associated with cases involving the transverse-sigmoid sinuses and cavernous sinus and most often associated with cases at the tentorial incisura. Contralateral contribution to arterial supply and rate of shunting (high vs. low flow) did not correlate with aggressive neurological behavior as defined. Leptomeningeal venous drainage, variceal or aneurysmal venous dilations, and galenic drainage correlated significantly (p less than 0.05) with aggressive neurological presentation. The latter three angiographic features often coexisted in the same dural AVM. It is concluded that these features significantly increase the natural risk of dural AVM's, and warrant a more vigilant therapeutic strategy.

Adult↗
PubMed1990

Vascular pressures and cortical blood flow in cavernous angioma of the brain.

This study was designed to investigate the hemodynamic characteristics of cavernous angiomas of the brain. Five adult patients with a cavernous angioma underwent local cortical blood flow studies and vascular pressure measurements during surgery for the excision of the cavernous angioma. Clinical presentation included headache in four patients, seizures in four patients, and recurring diplopia in one patient. Magnetic resonance imaging demonstrated the cavernous angiomas in all patients and revealed an associated small hematoma in two. Four patients with a cerebral cavernous angioma were operated on in the supine position and the remaining patient, whose lesion involved the brain stem, was operated on in the sitting position. Mean local cortical blood flow (+/- standard error of the mean) in the cerebral cortex adjacent to the lesion was 60.5 +/- 8.3 ml/100 gm/min at a mean PaCO2 of 35.0 +/- 0.6 torr. Mean CO2 reactivity was 1.1 +/- 0.2 ml/100 gm/min/torr. The local cortical blood flow results were similar to established normal control findings. Mean pressure within the lesion in the patients undergoing surgery while supine was 38.2 +/- 0.5 mm Hg; a slight decline in cavernous angioma pressure occurred with a drop in mean systemic arterial blood pressure and PaCO2. Mean pressure in the cavernous angioma in the patient operated on in the sitting position was 7 mm Hg. Jugular compression resulted in a 9-mm Hg rise in cavernous angioma pressure in one supine patient but no change in the patient in the sitting position. Direct microscopic observation revealed slow circulation within the lesions. The hemodynamic features demonstrated in this study indicate that cavernous angiomas are relatively passive vascular anomalies that are unlikely to produce ischemia in adjacent brain. Frank hemorrhage would be expected to be self-limiting because of relatively low driving pressures.

Adult↗
PubMed1989

Bimodal treatment with nimodipine and low-molecular-weight dextran for focal cerebral ischemia in the rat.

We compared the effects of intravenous treatment with combined low-molecular-weight dextran and nimodipine (n = 9), or placebo (n = 10), on local cerebral blood flow after occlusion of the left middle cerebral and common carotid artery in the rat. Treatment for a total of 4 hours with low-molecular-weight dextran (5 mg/kg/min) and nimodipine (0.25 microgram/kg/min) produced a decrease in hematocrit from 46 +/- 1 to 33 +/- 1% at the end of the study and a statistically significant increase in local cerebral blood flow, when compared to the control group, in 6 regions of interest: the territories of the right middle (p = 0.01), right anterior (p = 0.007), and left anterior cerebral arteries (p = 0.001); the superior (p = 0.03) and inferior border zone (p = 0.003); and white matter in the right hemisphere (p = 0.04). The ischemic volume, defined as brain volume with a cerebral blood flow of less than the critical level of 25 ml/min/100 gm was determined as a percentage of total brain volume for the control and treatment groups. The group treated with low-molecular-weight dextran and nimodipine showed a 31% decrease in ischemic volume (p = 0.03). These results indicate that a bimodal approach with low-molecular-weight dextran and nimodipine can be safely used in a model of acute stroke and has a beneficial effect on local cerebral blood flow and ischemic volume when compared with control subjects. After 4 hours, the potential exists that this treatment is therapeutic, assuming that the ischemic volume progresses to infarction.

Animals↗
PubMed1989

Clindamycin enhances murine delayed-type hypersensitivity and anti-candidal activity.

The contact sensitivity response of mice to dinitrofluorobenzene (DNFB), as determined by an epicutaneous painting and subsequent ear challenge assay, was enhanced by clindamycin administration. The optimal augmentation effect of clindamycin required its simultaneous administration at the time of DNFB skin sensitization. Clindamycin also was found to boost both in-vitro and in-vivo murine response to experimental infection with Candida lusitaniae. Intraperitoneal injection of 1-2 mg of the drug increased the clearance of yeast from organs after intravenous inoculation of mice. Clindamycin at concentrations of as low as 12.5 mg/l also increased the ability of cultured murine macrophages to kill the yeast without an increase in phagocytic activity.

Animals↗
PubMed1989

Internal carotid artery occlusion for cavernous segment aneurysm.

We review our recent experience with occlusion of the cervical internal carotid artery (ICA) in 15 patients with symptomatic aneurysms of the cavernous segment. All the patients were women and ranged in age from 38 to 74 years. Ten patients sought treatment initially for ophthalmoplegia, 9 for retro-orbital pain, 8 for facial paresthesia, and 3 for loss of vision. Two patients had symptoms of transient ocular or brain ischemia. The diameter of the aneurysm was greater than 3 cm in 10 patients. Ten patients underwent gradual occlusion of the ICA by Selverstone clamp under anticoagulation and monitoring of neurological status. One patient underwent ligation of a severely stenotic ICA under general anesthesia and electroencephalographic monitoring. Four patients underwent trapping of the aneurysm (after attempts at direct obliteration) under electroencephalographic and cerebral blood flow monitoring. Two patients with incompetent circle of Willis collaterals underwent prophylactic superficial temporal artery to middle cerebral artery bypass surgery prior to ICA occlusion. There was no postoperative clinical change in 9 patients. Ophthalmoplegia improved in 2 patients, and facial pain improved in 3. Three patients developed new extraocular muscle palsies within hours of ICA occlusion; these resolved in all patients by 1 week postoperatively. No change in aneurysm size was documented by serial postoperative computed tomographic or magnetic resonance imaging scans. After a follow-up of 5 to 6 years (range, 6 months-9 years), 11 patients have remained neurologically stable. Two patients experienced delayed transient worsening of visual or facial symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of Histoplasma capsulatum on murine macrophage functions: inhibition of macrophage priming, oxidative burst, and antifungal activities.

Histoplasma capsulatum yeast cells fail to trigger an oxidative burst response in normal murine macrophages. The results of this study, in which an in vitro assay of macrophage antifungal effects was used, extend these findings. During 18 h of incubation, unprimed elicited murine macrophages inhibited H. capsulatum growth only when macrophages were present in great excess. Gamma interferon (IFN-gamma)-primed macrophages showed enhanced fungal growth inhibition but a similar requirement for an excess of phagocytes. Macrophages containing heat-killed H. capsulatum exhibited diminished antifungal effects toward viable H. capsulatum and Saccharomyces cerevisiae cells. Parallel experiments showed no comparable effect of ingested latex particles on macrophage antifungal activity. Using chemiluminescence as a measure of the oxidative burst, we found that macrophages primed in vitro with IFN-gamma alone failed to exhibit a significant response to triggering by H. capsulatum yeast cells unless a second priming agent (tumor necrosis factor alpha or bacterial lipopolysaccharide) was added to IFN-gamma. Furthermore, macrophage priming with single agents was blocked by the prior ingestion of heat-killed H. capsulatum. These studies provide evidence that ingestion of H. capsulatum yeast cells can induce a prompt and enduring deactivation of murine macrophages.

Animals↗
PubMed1989

New fluorescence assay for the quantitation of fungi.

Quantitative determination of fungal mass is easily achieved with a new procedure that detects particle epifluorescence. Fungi are detected after exposure to a fluorescent stain (Fungiqual; CIBA-GEIGY Corp., Summit, N.J.) by using a fluorescence particle concentration analyzer. This report describes a simple fluorescence method for quantitation of either yeast or mycelial forms of fungi. The nature of the staining reaction was studied, and a practical application of this procedure for determination of fungal susceptibility to an antifungal agent is presented.

Amphotericin B↗