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Biomedical subjects

D Birt

Publications and source records attributed to D Birt.

At least 19 recordsLinked to original sources
PubMed1995

Immunologic effects of levamisole in mice and humans: evidence for augmented antibody response without modulation of cellular cytotoxicity.

Selected immunomodulatory effects of levamisole were studied in patients with asymptomatic metastatic colon cancer and in a preclinical model (CF1 female mice treated with methyl-azoxymethanol acetate) for colon tumors. In the patient population studied, there was no augmentation of cellular cytotoxicity or alteration in lymphocyte subpopulations that participate in these functions. An increase in Fc receptor binding on circulating monocytes was apparent at the 4-week timepoint; however, a corresponding increase in antibody-dependent cellular cytotoxicity was observed in only one of the six patients studied. In most patients, cellular cytotoxicity diminished with time. No significant effects on cellular immunity or carcinogenesis were observed in our murine studies. However, treatment with levamisole did increase circulating immunoglobulin levels and IgM response in mice immunized with the T-dependent antigen keyhole limpet hemocyanin. This parameter was not tested in the human trial. Failure to demonstrate antitumor effects on cellular immunity by levamisole in both human and murine studies suggests that these effects, if they do exist, may involve immunological parameters that were not tested using our methods or that may not be apparent in patients with more advanced malignancy.

Adenocarcinoma↗
PubMed1992

Changes in the activity of units of the cat motor cortex with rapid conditioning and extinction of a compound eye blink movement.

Patterns of spike activity were measured in the pericruciate cortex of conscious cats before and after development of a Pavlovian conditioned eye blink response. Unit activity was tested with presentations of a click conditioned stimulus (CS) and a hiss discriminative stimulus (DS) of similar intensity to the click. Unit discharge in response to the CS increased after conditioning, but not after backward conditioning when conditioned reflexes (CRs) were not performed. Rates of spontaneous, baseline discharge were not increased after conditioning with respect to rates of discharge measured in the naive state. It appeared that an increase in the ratio of CS-elicited discharge to background activity, together with an increase in the number of units responding to the CS after conditioning, supported discrimination of the CS from the DS and performance of the conditioned blink response. This is the first detailed characterization of patterns of a rapidly conditioned Pavlovian response. Activation of units by the CS preceded the onset of the CR, supporting the hypothesis that the activity played a role in initiating the conditioned eye blink movement. Extinction with retention of performance of the CR was associated with perseverance of the increased unit discharge in response to the CS. Extinction with substantially reduced performance of the CR was associated with diminution of the unit response to the CS below levels found with conditioning. Averages of patterns of spike activity elicited by the CS after conditioning showed components of discharge with onsets of 8-40 msec (alpha 1), 40-72 msec (alpha 2), 72-112 msec (beta), and greater than 112 msec (gamma), corresponding to each of four separate excitatory EMG components of the compound blink CR. Each component increased in magnitude after conditioning, relative to levels found in the naive state. The finding that long- as well as short-latency components of unit activation increased after conditioning supported the hypothesis that generation of both long- and short-latency blink CRs in normal animals may depend significantly on neural circuitry and mechanisms within the motor cortex.

Animals↗
PubMed1992

Increases in excitability of neurons of the motor cortex of cats after rapid acquisition of eye blink conditioning.

Measurements were made of resting potentials, input resistance, and excitability to intracellularly applied, depolarizing current pulses in neurons of the pericruciate cortex of conscious cats before and after acquisition of a rapidly conditioned eye blink reflex (CR). Neuronal excitability increased after conditioning, and an increased input resistance was found to be correlated with the increased level of excitability. No associated changes were found in resting potentials as a consequence of conditioning. When cells were divided into groups according to the latency of spike activity elicited by a click conditioned stimulus (CS) in relation to four separate excitatory EMG components of the compound blink CR, excitability increases were found in cells with increased spike activity at alpha 1 (8-40 msec), alpha 2 (40-72 msec), beta (72-112 msec), and gamma (112-160 msec) latencies after delivery of the CS. Also, the proportion of cells with high excitability (less than 0.7 nA required for spike elicitation) was increased at each latency period after conditioning. Increases in later components of spike discharge could also be found in the cells with increases in earlier components of discharge and increased excitability. The findings suggested that excitability increases facilitated a responsiveness to the CS that supported production of long- as well as short-latency components of the blink CR. Many of the changes in neuronal properties found after rapid eye blink conditioning, such as the increases in excitability and resistance and in the proportion of CS-excitable cells, resembled changes found earlier after acquisition of a slowly developing Pavlovian blink CR, using the same click CS and tap unconditioned stimulus without addition of a hypothalamic stimulus. The possibility should be considered that the (10-100 times) more rapidly acquired form of eye blink conditioning does not represent a different form of conditioning, but instead a change in the rate of conditioning supported by the more rapid production of increases in neural excitability.

Animals↗
PubMed1991

Changes in membrane currents during Pavlovian conditioning of single cortical neurons.

Single electrode voltage clamp recordings were made during Pavlovian conditioning of single units of the motor cortex of cats. Units that developed a conditioned spike discharge in response to a click conditioned stimulus (CS) after pairing the click with glabella tap and local ionophoretic application of glutamate showed increases in input resistance and reductions of an early outward current induced by depolarizing commands and by return to holding potentials after hyperpolarizing commands. Changes in later currents were also found in some cells. Units that failed to develop a conditioned response did not show these changes. The decreases in membrane currents could contribute to an increased spike discharge in response to the CS as could the increased input resistance observed after conditioning. Conductance changes of this type may serve as engrams by which some forms of memory and learning are expressed across both vertebrate and invertebrate species.

Acoustic Stimulation↗
PubMed1990

MRI and neck metastases: a clinical, radiological, pathological correlative study.

In a previous report CT was shown to have no advantage over physical examination in the detection of metastatic neck disease. Therefore, a study was undertaken to evaluate whether MRI would show superiority to the CT in the diagnosis of neck nodes. A series of 35 patients with various head and neck tumors were evaluated clinically, radiographically and pathologically. Eight patients were excluded from the study because of various problems involving the MRI. Therefore, 27 patients with 30 neck dissections were analyzed. There was little advantage of MRI over clinical examination in the detection of metastatic neck disease. The present size criterion for the diagnosis of occult malignant nodes is not reliable. The soft tissue contrast resolution reported by MRI is inadequate to detect minimal morphological changes in lymph nodes involved by metastases, and MRI is difficult in patients who have airway or foodway obstruction.

Head and Neck Neoplasms↗
PubMed1989

Mandibulotomy in the irradiated patient.

Though the "mandibular swing," as an approach to certain upper aerodigestive tract malignancies, has been gaining popularity in recent years, there has been little reported as to the feasibility of this procedure in subjects who have received radical preoperative radiotherapy. We have recently reported the results of 23 such patients, and we now present an update. The results presented are of a retrospective analysis of 44 patients, 50% of whom received radical preoperative radiotherapy to fields including the osteotomy site. As in the previous study, there were no statistically significant differences between the complication rates in the irradiated and nonirradiated patient populations. All the patients were orally rehabilitated.

Adult↗
PubMed1988

AO/ASIF plate for mandibular reconstruction in tumor surgery: results in 20 cases.

Between May, 1983, and February, 1987, the authors performed mandibular reconstruction using an AO/ASIF plate in 20 patients. Apart from accurate modelling of the resected segment using a template, the key features of the technique include firm fixation and wrapping the plate with pectoralis major muscle. In 19 cases the plate was inserted at the same operation as the resection of a malignant neoplasm. In 10 cases the anterior mandibular osteotomy was placed on the far side of the midline, while in five the mandible was disarticulated through the temporomandibular joint. Eleven patients are alive (average survival 22 months) and nine have died (average survival 10 months). Two AO/ASIF plates have required removal because of exposure, while in three patients limited plate exposure was corrected with a minor surgical procedure. Seven patients had soft tissue complications that were managed conservatively. Nine of the patients had been irradiated previously. Five patients were fitted with dentures successfully. The authors believe that this technique provides a safe, rapid, functional and esthetically satisfactory method of mandibular reconstruction in the patient undergoing surgery for malignant disease.

Adult↗
PubMed1988

Mandibulotomy and radical radiotherapy: compatible or not?

The mandibular swing, as an approach to upper aerodigestive tract malignancies, has been gaining popularity in recent years. Little has been reported in the literature as to the feasibility of this procedure in subjects having received radical preoperative radiotherapy. The preliminary results of a retrospective analysis of 23 subjects, 70% of whom received radical preoperative radiotherapy, is presented. There was no statistically significant difference between the complication rates in the irradiated and nonirradiated subject populations. All subjects, ultimately, were orally rehabilitated.

Adult↗
PubMed1987

Pavlovian conditioning of discriminatively elicited eyeblink responses with short onset latency attributable to lengthened interstimulus intervals.

Conditioned eyeblink responses were obtained in cats by pairing click (CS) with glabella tap (US) and electrical stimulation of the hypothalamus (HS). Hiss was used as a discriminative stimulus (DS). Onset latencies of conditioned responses (CRs) of 20-56 ms were obtained by using an interstimulus interval (ISI) of 570-10 ms between CS and US-HS. Longer latency (90-320 ms) blink CRs were obtained with ISIs of 340-240 and 340-10 ms. The timing of associatively learned movements has been thought to increase with lengthening of the intervals between CS and US presentation. The production of shorter latency CRs of this type by lengthening the ISI is a novel result and one unexpected from widely held beliefs.

Acoustic Stimulation↗
PubMed1987

Observations on the size of the saccule in laryngectomy specimens.

Over 300 instances of the association of laryngocele with laryngeal carcinoma have been reported in Europe, but only seven in North America. In the present study, 353 serially sectioned total laryngectomy specimens were examined and the saccule measured with a steel ruler. Saccules extending superior or posterior to the thyroid cartilage were considered as large. Larynges were classified as "cancer" or "normal", the latter being uninvaded organs from patients with adjacent disease. Among the 242 cancer larynges, there were 43 specimens where the saccule exceeded thyroid cartilage dimensions, a laryngocele rate of 17.8%. Mean saccule height was significantly greater in cancer than in normal specimens in coronal sections (P = 0.04), and mean saccule length was significantly greater in cancer than in normal specimens in horizontal sections (P = 0.001). The incidence of large saccules showed a difference between cancer and normal larynges which was highly significant (P = 0.0002).

Adult↗
PubMed1985

An individualized approach to orbital decompression in Graves' orbitopathy.

With better understanding of the various techniques available for orbital decompression, the indications for surgical decompression in Graves' orbitopathy are now less rigid. Decompressions may be performed for (1) prolonged orbital congestion and pain, (2) orbital problems resistant to steroid treatment, (3) orbital problems where there have been steroid complications, (4) severe corneal exposure that cannot be treated with lid-lengthening surgery, and (5) the standard indication--Graves' optic neuropathy. Assessment of muscle size by computed tomographic scanning and ultrasound, as well as the measurement of orbital pressure, are important advances in the assessment of these patients. The lateral approach produces less strabismus and allows for exophthalmos reduction, especially if fascia temporalis is incised and if part of that muscle is removed. The inferomedial approach is advisable in patients with severe posterior optic neuropathy caused by apical crowding of the enlarged muscles, particularly the medial rectus. The two approaches may be combined in severe cases.

Female↗
PubMed1983

Laryngocele: a case report and review.

A 60 year old man had a symptomless mass in the neck for two years. Over two weeks he developed hoarseness and dysphagia and successfully underwent excision of a combined internal and external laryngocele. There is some disagreement in the literature as to when an enlarged saccule is a laryngocele and also as to whether laryngoceles result from chronic straining such as playing a wind instrument. Laryngeal carcinoma occasionally occurs in association with a clinical laryngocele. When sought for in laryngectomy specimens the incidence of laryngocele in patients with laryngeal carcinoma has been recorded at 18%.

Deglutition Disorders↗
PubMed1982

Profile of malignant disease in the mouth clinic.

Between 1973 and 1981, 2,056 new patients were seen in the Mouth Clinic at Sunnybrook Hospital. Of these 109 proved to have malignant disease, with squamous cell carcinoma being the commonest type. Lower lip and floor of mouth were the most frequent sites. There was a high proportion of small tumors and local surgical excision was the most widely employed primary method of treatment. Radiation and combined treatment were used in larger lesions. Twenty-four patients have so far died of mouth cancer and the presence of enlarged lymph nodes at presentation was an ominous sign. Although containing the usual high proportion of heavy smokers and drinkers this group of patients at present exhibits a lower incidence of second primary malignancies than in some published series. It is concluded that surgery and radiotherapy have equivalent effectiveness in treating small primary lesions, where a policy of observation of the clinically negative neck appeared justified. The best treatment for large lesions and the most appropriate management of the clinically negative neck in intermediate size lesions has not been determined.

Adult↗
PubMed1981

Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to the human disease.

Syrian hamsters present a unique species for induction of pancreatic tumors that in many aspects resemble human pancreatic cancer. The specific response of Syrian hamsters, in contrast to may other rodents, for development of pancreatic ductal (ductular) tumors is not yet known. All pancreatic carcinogens thus far tested show certain common features. They are all nitrosamines that possess or can be metabolized to compounds with 2-oxopropyl- or 2-hydroxypropyl substituents. All but one, N-nitroso-methyl(2-oxopropyl)amine, occur or metabolize to nitrosamines with the ability to cyclize and form structures resembling glucose. Hence it is suggested that this cyclic structure may be responsible for the pancreatic carcinogenicity of these nitrosamines, as has been proposed for the pancreatotropic effect of streptozotocin. It is also of further interest that one pancreatic ductal (ductular) carcinogen, N-nitroso-2-methoxy-2,6-dimethylmorpholine, which possesses a totally cyclic structure, acts, like streptozotocin, as beta-cell cytotoxic and diabetogenic when given in a high single dose. Modification of pancreatic tumor induction has been demonstrated by specific procedures. A high fat diet significantly increases both the incidence and number of induced cancers. Methods for early diagnosis and therapy are being developed and their significance and applicabilities for clinical use will be of major importance. Compared with the other most common types of human cancer, pancreatic cancer has extraordinary characteristics, which make the disease one of the most mysterious of maladies. Consequently, pancreatic cancer represents a serious international problem and requires urgent resolution, especially with regard to its etiology, early diagnosis, prevention, and therapy.

Animals↗
PubMed1980

Diagnosis and management of long-standing benign oral ulceration.

The authors formed a Mouth Clinic at Sunnybrook Hospital in 1973 since when there have been 3025 patient visits. Those patients with chronic ulceration present a challenge, the diagnosis sometimes being difficult and therapy not rapidly effective. The differential diagnosis includes lichen planus, pemphigus vulgaris, benign mucous membrane pemphigoid, discoid lupus erythematosus, erythema multiforme, aphthous ulcers, Behcets disease, periadenitis mucosa necrotica recurrens, specific infections and iatrogenic causes. It is possible to reach a definite diagnosis in virtually every case by means of a good history and careful clinical examination supplemented by biopsies and in some cases direct and indirect immunofluorescent studies. Treatment emphasizes scrupulous attention to oral hygiene with baking soda mouthwashes and careful teeth cleaning to minimize the accumulation of dental plaque. Specific therapy includes topical steroids in lichen planus, intra muscular gold in benign mucous membrane pemphigoid, a previously unreported treatment which considerably improved seven out of ten patients, and tetracycline mouthwashes in aphthous ulcers.

Behcet Syndrome↗