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Biomedical subjects

G W Ellison

Publications and source records attributed to G W Ellison.

At least 55 records · Page 3Linked to original sources
PubMed1989

Surgical correction of concomitant cranioventral abdominal wall, caudal sternal, diaphragmatic, and pericardial defects in young dogs.

Seven puppies with concomitant congenital cranioventral abdominal wall, caudal sternal, diaphragmatic, and pericardial defects were treated surgically when they were between 10 and 12 weeks old. Three pups had ventricular septal defects that were not corrected. Diaphragmatic herniorrhaphy without extension of the diaphragmatic defect was performed in 6 pups. In one pup, paracostal extension of the diaphragmatic defect was necessary to decrease tension on the diaphragmatic closure. All pups were healthy at 6-month follow-up examinations, but 2 of 3 pups with ventricular septal defects had moderate generalized cardiomegaly evident on thoracic radiography. Early surgical correction of the congenital defects in these pups was usually simple because there were few or no thoracic adhesions, the dogs were small, the defects were small in 6 of 7 dogs, and the costal arch was pliable in each dog.

Abdominal Muscles↗
PubMed1989

Repair of sixth lumbar vertebral fracture-luxations, using transilial pins and plastic spinous-process plates in six dogs.

Transilial pins and paired plastic spinous-process plates were used to repair fracture-luxations of the sixth lumbar vertebra in 6 dogs. All dogs had signs of lumbar pain and variable lower motor neuron deficits to the hindquarters (including hind limbs, tail, and pelvic region). Lumbar pain was decreased or resolved the day after surgery in all dogs, and 3 dogs were able to walk without assistance. One dog initially deteriorated neurologically after surgery and 2 dogs with multiple concurrent orthopedic injuries had no improvement in neurologic function and remained nonambulatory. Pin migration associated with improper bending of the transilial pins and requiring early implant removal was the most common postoperative complication. Four dogs had no neurologic abnormalities 1 to 3 months after surgery. One dog had a resolving unilateral sciatic nerve deficit 9 months after surgery, and another dog was euthanatized 3 months after surgery because of continued paraparesis and urinary and fecal incontinence. These 6 cases illustrate the efficacy of plastic spinous-process plates in combination with transilial pins for the repair of fracture-luxation of the sixth lumbar vertebra.

Animals↗
PubMed1989

In vitro study of mediators of inflammation in multiple sclerosis.

Prostaglandin E levels have previously been demonstrated to be elevated in multiple sclerosis (MS). We have further investigated other products of activated macrophages related to inflammation. We report here on prostaglandin E and its relationship to interleukin 1, tumor necrosis factor, and leukotriene B4 produced by macrophages from blood and cerebrospinal fluid of MS patients and controls in vitro. Interleukin and tumor necrosis factor are elevated significantly after stimulation in MS, while leukotriene B4 production by blood macrophages is depressed compared to other neurological disease and normal healthy controls. In 40% of MS patients tested, peripheral blood macrophages spontaneously produced elevated levels of interleukin 1. All mediators of inflammation are produced in increased amounts by MS cerebrospinal fluid leukocytes after stimulation. Macrophages from MS blood are not as sensitive as controls to nonsteroidal inhibitors specific for lipoxygenase or cyclo-oxygenase pathways. Positive correlations of elevations in production of such mediators of inflammation as prostaglandin E, interleukin 1, and tumor necrosis factor in MS were significant. Elevated production of these mediators in combination with insensitivity to inhibitors of inflammation suggests a role for activated macrophages in the demyelination process.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Multiple sclerosis: why?

Multiple sclerosis is a chronic inflammatory demyelinating condition of the nervous system. Its etiology is obscure. Something in the environment strikes a susceptible host. Somehow the immune system produces central nervous system lesions. Magnetic resonance imaging scans show far greater "lesion" formation in the brain than was expected from clinical exacerbations. White blood cell changes suggest the disease is not entirely localized to the CNS. Some immunomodulatory treatments temporarily slow the rate of deterioration.

Humans↗
PubMed1989

A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis.

Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS.

Adolescent↗
PubMed1988

Medical and surgical management of multiple organ infarctions secondary to bacterial endocarditis in a dog.

A 6-year-old male Doberman Pinscher developed multiple organ infarctions secondary to vegetative endocarditis. Clinical signs included fever, nystagmus, head-tilt, inappetence, dehydration, hematuria, and dysuria. The dog was azotemic and anemic and had a high WBC count and high liver enzyme activities. Disseminated intravascular coagulation was diagnosed on the basis of thrombocytopenia and prolonged activated clotting times. Vegetative mitral valvular lesions were evident on M-mode echocardiography. The dog underwent diuresis with physiologic saline solution and was treated parenterally with antibacterial and anticoagulant agents. Surgery was performed to remove an infarcted kidney and an infarcted spleen and to relieve urethral obstruction caused by a large blood clot. Gram-positive cocci were noticed in the biopsy specimens. Mortality associated with organ infarctions secondary to bacterial endocarditis is high, and combined medical and surgical therapy is rarely reported. This dog survived and was alive 38 months after surgery.

Animals↗
PubMed1988

Distracted cervical spinal fusion for management of caudal cervical spondylomyelopathy in large-breed dogs.

Using an autogenous bone graft (obtained from the iliac crest), 4-mm cancellous bone screws, and polymethylmethacrylate, a distracted cervical spinal fusion technique was performed on 10 dogs with myelographic evidence of caudal cervical spondylomyelopathy. All dogs had evidence of dynamic soft tissue spinal cord compression, as indicated by flexion, extension, and traction myelographic views. Of the 10 dogs, 4 previously had undergone surgery by use of ventral slot or cervical disk fenestration techniques, and their neurologic status had deteriorated after the original surgery. Preoperative neurologic status of the 10 dogs included nonambulatory tetraparesis (n = 5), severe ataxia with conscious proprioceptive deficits (n = 2), and mild ambulatory ataxia with conscious proprioceptive deficits (n = 3). Five dogs had signs of various degrees of cervical pain. Clinical improvement was observed in 8 of 10 dogs--either improved neurologic status or elimination of cervical pain. Implant loosening developed in 3 dogs; 2 of them were euthanatized because of lack of neurologic improvement. Radiographic evidence of bony cervical fusion was observed during a 9- to 24-week period in 6 of the 8 surviving dogs. The distracted cervical fusion technique appears to be a valid surgical procedure to manage cervical spondylomyelopathy in those dogs in which the lesions are limited to one cervical intervertebral disk space.

Animals↗
PubMed1988

Clinical experience with azathioprine: the pros.

We performed a randomized, placebo-controlled, double-blind, comparative clinical trial of 36 weeks of methylprednisolone and 3 years of azathioprine in 98 patients in the chronic progression phase of multiple sclerosis (MS). We demonstrated a trend in favor of the combination therapy for limiting progression. The relapse rate in the azathioprine recipients was half that of the control group, and visual evoked potential latencies were stabilized in those who received the combination. We think that a therapeutic trial of continuous use of the combination of adrenal steroids with azathioprine would be worthwhile if administered early in the course of the disease.

Azathioprine↗
PubMed1988

Alternatives to randomized clinical trials.

Data bases describing the natural history of patients with multiple sclerosis or the clinical course of patients treated with placebos might serve as "historical controls" in future clinical therapeutic trials. The results of clinical trials with such controls can be misleading. There is a strong tendency for the new treatment to appear efficacious when historical controls are the comparison group. Therefore, claims of efficacy deduced from trials using such controls should be closely questioned. Thus, such comparison groups probably would be useful for preliminary and early phase II (pilot) trials rather than in more definitive phase III (full) trials.

Clinical Trials as Topic↗
PubMed1988

Clinical drawbacks of total lymphoid irradiation: the cons.

Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS.

Humans↗
PubMed1987

Correlation of clinical and immunologic states in multiple sclerosis.

Cyclophosphamide was administered to 14 patients with chronic progressive multiple sclerosis on an intermittent escalating dosage schedule adjusted to maintain numbers of peripheral blood B lymphocytes and helper/inducer (CD4) T cells below the fifth percentile of the normal population. Peripheral blood B cells, T cells, suppressor/cytotoxic (CD8) T cells, CD4 cells, and FcR+-bearing cell numbers and percentages were monitored at one-week to two-week intervals. Clinical status was assessed by neurologic examinations at approximately four-week intervals. Regression analysis revealed a statistically significant correlation between changes in immunologic status and changes in clinical state. The immunologic changes preceded the neurologic changes. Increases in percent of CD8 cells and decreases in percent of CD4 cells forecast improved clinical course. These findings, coupled with other studies, strongly suggest a pathogenetic role for helper and suppressor T cells in the production of clinical signs of multiple sclerosis.

B-Lymphocytes↗
PubMed1987

Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial.

To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.

Adult↗
PubMed1987

Increased spontaneous immunoglobulin secretion associated with cyclophosphamide-induced immune suppression.

Spontaneous immunoglobulin (Ig) secretion by cells from multiple sclerosis (MS) patients (in the progressive phase) treated with monthly pulse doses of cyclophosphamide (CY) (1000-1600 mg/M2) was measured using the protein A plaque assay, to evaluate the effect of CY treatment on B-cell function. Surprisingly, an increase, rather than a decrease, in Ig-secreting cells was seen following CY treatment. CY-treated MS patients averaged 1380 +/- 535 spontaneous total (IgM + G + A) Ig plaque-forming cells (PFC) per 1 X 10(6) peripheral blood mononuclear cells (MNC), measured at 15-22 days after monthly CY administration, while healthy adults had 280 +/- 47 Ig PFC/10(6) MNC, and MS patients not treated with CY had 300 +/- 43 Ig PFC/10(6) MNC. The observed increase was due to an increase in IgG and IgA PFC. PFC levels remained elevated for 4 weeks following CY treatment, decreasing to control levels by 7-8 weeks post-CY. A small increase in serum IgG level was noted after greater than 12 months of pulse CY therapy; no increase was seen in CSF IgG levels. A preferential decrease in the number of CD4+ T cells was also seen in the CY-treated MS patients. We propose that the observed increase in the number of spontaneous Ig PFC was due to the CY-induced disruption of the CD4+ T cell-mediated control of in vivo activated B cells.

Antibody-Producing Cells↗
PubMed1987

Administration of monthly-pulse cyclophosphamide in multiple sclerosis patients. Effects of long-term treatment on immunologic parameters.

Eleven patients with chronic progressive multiple sclerosis received monthly pulses of cyclophosphamide (CY) for approximately one year. During the final 9 months the monthly dose ranged between 1000 mg/m2 and 2000 mg/m2. This resulted in a marked (47% or greater) reduction in CD4 (T helper/inducer) cells a less striking (22%) decrease in CD8 (T suppressor/cytotoxic) cells and a decline in the CD4/CD8 ratio. The magnitude of the decrease in CD4 cells correlated with the total dose received (r = 0.88, P less than 0.05). B cells were reduced 50% and FcR+ lymphocytes were reduced 48% without comparable reduction in natural killer cells or antibody-dependent cellular cytotoxicity. Proliferative responses to PHA were suppressed. Two patients improved, seven stabilized and two continued to worsen. Monthly pulses of CY can achieve substantial and differential reduction in immune parameters and appear to slow the disease progression in some MS patients.

Cyclophosphamide↗
PubMed1987

Administration of monthly pulses of cyclophosphamide in multiple sclerosis patients. Delayed recovery of several immune parameters following discontinuation of long-term cyclophosphamide treatment.

Recovery of various components of the immune system was followed in eight patients with multiple sclerosis who had received monthly pulses of cyclophosphamide (CY) for approximately one year. CD8 cell numbers and NK and ADCC functions recovered in 1-2 months; B cells and FcR+ cell numbers recovered in 2-4 months. The recovery of CD4 cells and total T cell numbers, CD4/CD8 ratio and proliferative responses to PHA took more than 4 months. The impaired proliferation was not attributable to low IL-2 receptor expression. Once immunosuppression has been achieved pulse administration of CY at 2- to 4-month intervals may be feasible for long-term maintenance treatment.

Antibody-Dependent Cell Cytotoxicity↗