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Biomedical subjects

D M Long

Publications and source records attributed to D M Long.

At least 73 records · Page 4Linked to original sources
PubMed1992

Hypoxia inhibits calcium influx in rabbit basilar and carotid arteries.

We examined the hypothesis that hypoxia inhibits Ca2+ influx in isolated rabbit common carotid, internal carotid, and basilar arteries. In arteries mounted for measurement of isometric tension and exposed to 122 mM K+ in Ca(2+)-free Krebs, cumulative addition of Ca2+ produced Ca(2+)-force relations that were right-shifted by hypoxia (PO2 approximately 15 Torr) with no decrease in maximum force attained. In arteries precontracted with 122 mM K+, exposure to hypoxia produced relaxations whose rates and magnitudes were enhanced by reductions in bath Ca2+ from 8.0 to 0.8 mM. Using an ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid method for 3-min 45Ca influx measurements, modified for use in rabbit basilar and carotid arteries, we found that resting levels of Ca2+ influx (mumol.min-1.kg dry wt-1) were significantly higher in basilar (67 +/- 1, n = 10) than in internal carotid (27 +/- 1, n = 12) or common carotid (33 +/- 1, n = 12) arteries. K+ stimulation increased Ca2+ influx more than two-fold compared with control in all three artery types, and hypoxia inhibited this increase by 74% in basilar, 49% in internal carotid, and 33% in common carotid arteries. Exposure to 10 microM serotonin and 100 microM uridine 5'-triphosphate (UTP) also increased Ca2+ influx, but these increases were less than observed during K+ contractions and averaged 10 (basilar), 31 (internal carotid), and 82% (common carotid) above control. Hypoxia completely inhibited serotonin- and/or UTP-induced increases in Ca2+ influx in basilar and internal carotid segments and inhibited 47% of this increase in the common carotid segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pregnancy-induced changes in ovine cerebral arteries.

We examined the effects of pregnancy on the ovine cerebral vasculature by comparing several characteristics of isolated endothelium-intact segments of three intracranial arteries including the middle cerebral (MCA), posterior communicating (PC), and basilar (BAS) arteries taken from pregnant sheep (138-143 days gestation, term approximately 145 days) and nonpregnant controls. For comparison, segments of the extracranial common carotid (COM) artery were also studied. With pregnancy, vessel water content increased (5.4-5.8%) in all arteries except the PC. Additionally, cellular protein content increased in all arteries (4.4-50.0%). Arterial stiffness, as determined by passive stress-strain determinations, was significantly decreased during pregnancy in the MCA but not in the larger arteries. Maximum contractile responses, when normalized to vessel wall cross-sectional area, were consistently greater in arteries from pregnant than in those from nonpregnant animals (10.1-49.7%). Relaxation to the endothelium-independent guanylate cyclase stimulator S-nitroso-N-acetyl penicillamine (SNAP) increased with pregnancy only in the distal MCA (approximately 17%). Endothelium-dependent relaxation to the calcium ionophore A23187 decreased only in the larger and more proximal COM (-39%). Thus pregnancy was associated with an increase in production of contractile force, a decrease in peripheral vascular stiffness, a decrease in the relaxant response to A23187 in the COM, and an increase in the relaxant response to SNAP in the MCA. Together, these findings indicate that pregnancy has widespread and important vessel specific cerebrovascular consequences that affect not only arterial composition, but also contractility and endothelial reactivity.

Analysis of Variance↗
PubMed1992

Preoperative risks predict neurological outcome of carotid endarterectomy related stroke.

The aim of this study was to determine if preoperative risk factors are predictors of poor stroke outcome after carotid endarterectomy. In addition, the effect of other stroke risk factors on stroke severity was determined. A retrospective review of carotid endarterectomy results spanning 10 years, encompassing 561 patients, and reporting the combined results of all surgeons at our institution was performed. Patients were assigned to one of four groups. There were 227 patients with no preoperative risks (Group 1), 61 with angiographic risks (Group 2), 196 with medical risks with or without angiographic risks (Group 3), and 77 with neurological risks with or without medical/angiographic risks (Group 4). Other risks associated with stroke occurrence were recorded including: intraoperative risks (cross-clamp time, use of shunt, use of glucose solutions), surgical complications (carotid occlusion/thrombus or ligation), and medical complications (hypoxia, myocardial infarct). Stroke incidence was 5% with 2% (11 patients) and 3.4% (19 patients) having good and poor outcomes, respectively. Stroke incidence was highest in Groups 2 and 4 (10 and 14%, respectively), and Group 4 had the highest incidence of poor-outcome stroke (12%). Cross-clamp time, intraoperative shunt placement, and intraoperative glucose administration were similar among preoperative risk groups and were not primary determinants of stroke severity. The most common medical complication was myocardial infarction, which had the highest incidence in Groups 3 and 4 (6.1 and 5%, respectively). The highest incidence of surgical complications occurred in Groups 2 and 4, carotid thrombosis being the most common event (16 patients). Surgical complications were more commonly associated with stroke than were medical complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Effect of emulsion concentration on biodistribution of perflubron in tumor-bearing mice.

Perflubron (perfluoroocytlbromide, PFOB) emulsion concentrations of 100%, 90%, or 60% w/v were administered to mice with and without 3 types of murine malignant tumor implants, and the distribution in blood, tumor, lung, liver and spleen were studied 48 hours after a dose of 10 or 3 g/Kg of PFOB. The most important changes were seen in the blood where the PFOB concentration [PFOB] was decreased in tumor bearing mice (TBM). Blood [PFOB] was also decreased in TBM and normal mice (NM) that received the 60% emulsion. Liver [PFOB] was increased in TBM. Lung [PFOB] was directly proportional to the emulsion concentration with the 10g/Kg dose. No major differences were seen in the biodistribution between the 100% and 90% emulsions using 10g/Kg, in spite of differences in composition and manufacturing history.

Animals↗
PubMed1992

Cyclooxygenase inhibition with ibuprofen: effect on biodistribution of perflubron emulsions in mice with mammary tumor.

The biodistribution of Perflubron (perfluorocytylbromide, PFOB) was studied by infusing 10 or 3 g/Kg doses of 90% and 100% w/v emulsions into Balb C mice with and without malignant mammary tumor implants. PFOB concentrations were measured in blood, liver, spleen, lung and tumor, and X-rays were taken 48 hours after infusion. Ibuprofen (IBU) was given intraperitoneally 10 mg/Kg dialy for 3 days to study the effects of cyclooxygenase blockade. The results showed that the blood [PFOB] in tumor-bearing mice (TBM) was only 3.6% of that measured in normal mice (NM), and the liver [PFOB] was increased by 59%. The lung [PFOB] increase with IBU therapy in NM was highly significant. IBU therapy resulted in a 98% and 468% increase in blood [PFOB] in normal and TBM, respectively. Smaller but statistically significant changes occurred in blood [PFOB] with saline and sham injections. Tumor [PFOB] was lower by 17% (P = .028) in mice treated with IBU. Smaller decreases were seen with saline and sham injections but did not achieve statistical significance. In conclusion, the presence of this malignant tumor resulted in changes that might influence the usefulness of PFOB as a contrast agent and as an adjuvant for radiation and chemotherapy. This study shows that cyclooxygenase inhibition significantly modified the pharmacodynamics of PFOB emulsions in blood, tumor and lung. The changes seen in the saline placebo and sham category were attributed to stress from procedures.

Animals↗
PubMed1992

Decision making in lumbar disc disease.

When a patient presents with an acute pain syndrome suggestive of a herniated lumbar disc, nonoperative treatment is almost always the rule. Urgent surgery is undertaken for intractable pain, significant or progressive neurological deficit, and abnormalities of bowel, bladder, or sexual function. Evaluation of the patient is not needed in typical cases until nonoperative care has failed. The decision to evaluate and treat by intervention is made after a reasonable time, usually a minimum of 1 month and a maximum of 3 for the patient who is not making progress. Slow recoveries can be monitored for even longer if agreeable with the patient. The decision for intervention is almost never warranted in the face of normal imaging studies. Several interventions are possible. Traditional surgery, with or without magnification, is followed by an excellent outcome. Chymopapain injection is a reasonable alternative for those expert in its use. Percutaneous discectomy is a possibility but remains to be proved by acceptable clinical studies. Lumbar disc surgery is highly successful and complications are extremely unusual. They do occur however, and can be extremely serious. Unexpected postoperative complications should be investigated immediately. Recovery from disc surgery usually is uneventful, and no rehabilitation is required. Some patients, particularly those who do heavy work, can be helped by a rehabilitation program that stresses return to normal function. Rarely will a patient develop a serious neurological deficit following surgery. Unexpected serious deficits require urgent reevaluation. Most patients return to work promptly without assistance. For those who cannot, referral to a multidisciplinary rehabilitation program to assist with return to function through general management of comorbidities can be useful. It is a rare patient who is disabled by a back disorder, and the decision that a patient is disabled should be made only after thorough evaluation and adequate rehabilitative therapy.

Disability Evaluation↗
PubMed1992

Non-glial tumors of the brain: tumors of the cerebellopontine angle and meningiomas.

The principal non-glial tumors of the brain are meningiomas and acoustic schwannomas. Advances in the management of meningiomas have included endovascular techniques for embolization to reduce blood loss, radical surgical approaches, and the recognition of the high recurrence rate of these tumors. Advances in the management of acoustic tumors have been in preservation of VIIth nerve function, improved preservation of hearing, and the availability of stereotactic radiosurgical techniques as an alternative. There is still a substantial discussion concerning the route of surgery for acoustic tumors and not all agree that hearing preservation is a reasonable goal at present.

Cerebellopontine Angle↗
PubMed1991

Clivus chordoma: a report of 12 recent cases and review of the literature.

Twelve patients with histologically confirmed clivus chordoma were treated at the Johns Hopkins Hospital between 1971 and 1989. Eight of the patients were men and four were women. The mean age at first operation was 51 years (range, 10 to 80). The most common presenting symptoms were headache, diplopia, dysphagia and dysarthria, and facial sensory changes. Computed tomography, with and without contrast enhancement, proved adequate for tumor identification and localization. Magnetic resonance imaging and angiography were occasionally employed to localize the tumors further and to define tumor vascular supply and proximity to vascular structures. Twenty-two resections were performed in 11 patients, and another patient underwent biopsy only. Seven were also treated with radiation therapy. Tumors recurred in eight patients, six of whom underwent further operations. The mean time to first recurrence was 22 months (range 8 to 36 months). Six of the patients are still alive, with a mean follow-up of 31 months (range, 3 to 89 months) from first surgical resection. The mean survival time from first treatment was 31 months (range, 4 to 62 months) among those patients who died. There was no operative mortality. The 5-year cumulative survival rate was 20%. Six patients with long follow-up have had fair to good results, being free of recurrences for at least a year. However, none of the patients returned to their premorbid baseline of activities. Five of the patients had tumors with the histologic diagnosis of chondroid chordoma. Three of these patients are still alive. The mean age at first treatment was 44 (compared with 62 for typical chordomas). The mean time from symptoms to diagnosis was 29 months (typical chordomas, 18 months). The mean length of survival and time to tumor recurrence were not significantly different between chondroid and typical chordomas.

Journal Article↗
PubMed1991

Spinal cord compression complicating subarachnoid infusion of morphine: case report and laboratory experience.

The intraspinal administration of morphine has been employed increasingly in the management of intractable pain of malignant as well as benign origin. We have encountered a previously unreported clinical complication: spinal cord compression by an inflammatory tissue mass surrounding a subarachnoid infusion catheter administering morphine, leading to paraplegia. The patient was referred to our institution after catheter and pump implantation for chronic, intractable pain associated with pre-existing lumbar arachnoid fibrosis, after multiple myelograms and surgeries. The patient may, therefore, have had an underlying propensity to foreign body reactions. We have encountered a similar phenomenon, however, in a canine laboratory model. The pathological features in both our patient and our laboratory preparation, with inflammatory tissue masses around the tip of the catheter but not around proximal subarachnoid segments, suggest an effect related to infusion, as opposed to infection or the presence of the catheter. We review the pathological features in both settings and the pertinent literature.

Adult↗
PubMed1991

Iohexol cervical myelography in adult outpatients.

The incidence of adverse reactions following standard film or screen cervical myelography with iohexol in 32 adult outpatients was reported. Iohexol at a dose of 1,080-3,000 mg of iodine was administered via a lateral C1-C2 approach in 26 patients and via a lumbar route in 6 patients. All 32 patients underwent postmyelographic cervical spine computed tomography and were discharged after the procedure was completed. No adverse reactions occurred in 53.1% of patients. The most common adverse reaction was headache (31.3%); other minor adverse reactions included exacerbation of pre-existing pain (12.5%), neck stiffness (9.4%), and vomiting (6.3%). Good to excellent technical quality was seen on all myelograms and computed tomographic scans. Outpatient cervical myelography with iohexol appears to be a safe and cost-effective alternative to inpatient examination.

Ambulatory Care↗
PubMed1991

Effect of light/dark cycles on expression of nitrate assimilatory genes in maize shoots and roots.

The level of nitrate reductase (NR) and nitrite reductase (NiR) varied in both shoot and root tissue from nitrate-fed Zea mays L. grown under a 16-hour light/8-hour dark regime over a 10-day period postgermination, with peak activity occurring in days 5 to 6. To study the effect of different light regimes on NR and NiR enzyme activity and mRNA levels, 6-day-old plants were grown in the presence of continuous KNO(3) (10 millimolar). Both shoot NRA and mRNA varied considerably, peaking 4 to 8 hours into the light period. Upon transferring plants to continuous light, the amplitude of the peaks increased, and the peaks moved closer together. In continuous darkness, no NR mRNA or NR enzyme activity could be detected by 8 hours and 12 hours, respectively. In either a light/dark or continuous light regime, root NRA and mRNA did not vary substantially. However, when plants were placed in continuous darkness, both declined steadily in the roots, although some remained after 48 hours. Although there was no obvious cycling of NiR enzyme activity in shoot tissue, changes in mRNA mimicked those seen for NR mRNA. The expression of NR and NiR genes is affected by the light regime adopted, but light does not have a direct effect on the expression of these genes.

Journal Article↗
PubMed1991

Developmental changes in ovine cerebral artery composition and reactivity.

We have examined age-related changes in segments of common carotid (Com), basilar (Bas), posterior communicating (PC), and middle cerebral (MC) arteries taken from 14 near-term fetal lambs, 62 newborn lambs 3-7 days old, and 42 adult nonpregnant sheep. Transition from fetal to newborn life was associated with a decreased water content in all arteries ranging from 0.6% (Com) to 2.3% (Bas), no change in the relative content of cellular protein, an increase in wall thickness ranging from 4% (MC) to 26% (Com), an increase in maximum contractile tension ranging from 18% (MC) to 82% (Com), an increase in stiffness, an increase in the maximum active stress ranging from 6% (Bas) to 43% (Com), a decrease in the amine-to-potassium ratio (calculated as the maximum response to 10 microM serotonin with 20 microM histamine divided by the maximum response to 122 mM K+) ranging from 8% (Bas) to 51% (Com), and a decrease in the norepinephrine-to-potassium ratio ranging from 2.1% (Bas) to 56% (Com). Thus developmental changes associated with the transition from fetal to newborn life were much more pronounced in the larger, more proximal Com than in the smaller, more distal cerebral arteries, suggesting that, at term, the cerebral arteries are more mature both functionally and structurally than the Com arteries. Similarly, the transition from newborn to adult life was associated with much greater changes in Com characteristics than with those of the cerebral arteries. These studies demonstrate that the effects of aging vary considerably along the cerebrovascular tree and that conclusions based on developmental studies of large systemic arteries cannot be freely extrapolated to the smaller arteries of the circle of Willis.

Aging↗
PubMed1991

Fifteen years of transcutaneous electrical stimulation for pain control.

Transcutaneous electrical stimulation was reintroduced into medical practice in the early 1970s. Since that time, numerous studies, both controlled and uncontrolled, have suggested its utility for the treatment of pain related to acute musculoskeletal injury, postoperative pain, pain of peripheral vascular origin, pain of myocardial ischemia and chronic pain of a variety of causes. Pain of labor in delivery is affected equivocally. Pain complicating cancer has not been reliably relieved. A small number of controlled studies fail to demonstrate benefit, but the preoponderance of evidence suggests that electrical stimulation of the peripheral nervous system is a useful adjunct in the management of many pain states. Most studies indicate that the resultant analgesia is not opioid-dependent. Pain threshold and perception both appear to be reduced. The physiological mechanism by which pain is affected is not defined; local neural blockade, branch block in the dorsal horn and activation of a central inhibitory system have all been postulated.

Analgesia, Obstetrical↗
PubMed1991

Dorsal root ganglionectomy for failed back surgery syndrome: a 5-year follow-up study.

Dorsal root ganglionectomy has been suggested as a method for the treatment of chronic intractable radicular pain, with theoretical advantages over dorsal rhizotomy, which does not interrupt ventral root afferents. The indications for these procedures in patients with persistent pain following lumbosacral spine surgery are not well established. Long-term results have been reported infrequently, and no published series has a mean follow-up period of more than 30 months. The authors have reviewed their experience with a series of 13 patients with failed back surgery syndrome, in whom dorsal root ganglionectomy was performed. Patients were selected on the basis of clinical presentation and diagnostic root blocks suggesting a monoradicular pain syndrome. Follow-up data were obtained at a mean of 5.5 years following dorsal root ganglionectomy. Follow-up interviews to assess outcome were conducted by a disinterested third party. Treatment "success" (at least 50% sustained relief of pain and patient satisfaction with the result) was recorded in two patients at 2 years after surgery and in none at 5.5 years. Equivocal success (at least 50% relief, without clearcut patient satisfaction) was recorded in one patient at 2 and at 5.5 years postoperatively. Improvements in activities of daily living were recorded in a minority of patients. Loss of sensory and motor function was reported frequently by patients. A minority of patients had reduced or eliminated analgesic intake. These results suggest that dorsal root ganglionectomy has a limited role in the management of failed back surgery syndrome, and that methods to select patients to receive this procedure should be refined or alternative approaches should be considered.

Activities of Daily Living↗
PubMed1991

Interstitial delivery of dexamethasone in the brain for the reduction of peritumoral edema.

Controlled-release polymers have facilitated the interstitial delivery of drugs within the central nervous system. In the present study, dexamethasone was incorporated into ethylene-vinyl acetate polymers, which were then implanted adjacent to a 9L gliosarcoma in the brain of Fischer 344 rats. The effect of interstitial delivery of dexamethasone on peritumoral edema was assessed and compared to the effect of dexamethasone delivered systemically. Eighty-five rats underwent intracranial implantation of the 9L gliosarcoma. Five days later, the animals were randomly assigned to one of four treatment groups: Group 1 received intracranial implantation of controlled-release polymers containing dexamethasone; Group 2 received intraperitoneal implantation of controlled-release polymers containing dexamethasone; Group 3 received serial intraperitoneal injections of dexamethasone; and Group 4 received sham treatment. The animals were sacrificed 3 days after initiation of therapy and their brains were removed for measurement of the water content (edema) in the tumor-bearing and contralateral hemispheres. Brain and plasma samples were analyzed by reverse-phase high-performance liquid chromatography to determine the tissue and plasma concentrations of dexamethasone. Measurement of the release kinetics of dexamethasone from the ethylene-vinyl acetate polymers in an in vitro system showed that the drug was released in a controlled, tapering fashion. During the first 3 days of controlled release in vitro, 330 micrograms of a total content of 7.5 mg of dexamethasone was released into the medium. Analysis of tissue for drug levels demonstrated, however, that the interstitial delivery of this fractional amount of dexamethasone within the brain resulted in levels 19 times higher than those achieved by administering the full dose of 7.5 mg systemically over a 3-day period. Conversely, the systemic administration of dexamethasone resulted in plasma levels 16 times higher than those measured in the interstitial delivery of dexamethasone in the brain. Brain-water content determinations showed that the interstitial controlled release of the fractional amount of dexamethasone within the brain was as effective in controlling peritumoral edema as systemic administration of the full dose by serial intraperitoneal injections. The study demonstrates the following: 1) controlled-release polymeric carriers deliver biologically active dexamethasone in a sustained fashion; 2) very high concentrations of dexamethasone in brain tissue can be achieved using interstitial polymer-mediated drug delivery while minimizing plasma concentrations of this drug which are sometimes associated with serious systemic side effects; and 3) peritumoral brain edema can be effectively treated by the interstitial delivery of dexamethasone directly within the tumor bed.

Animals↗
PubMed1991

The Johns Hopkins Hospital.

The role of The Johns Hopkins University as an innovative school with a basic mission of scientific research is discussed. Its principle that research is best performed by faculty and students at a graduate level gave birth to the revolutionary concept of a research university. Against this background, the hospital and later the medical school were founded. The innovations that emerged from this medical education structure are touched on.

Baltimore↗