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K M Fitzgerald

Publications and source records attributed to K M Fitzgerald.

29 records · Page 2Linked to original sources

Experimental autoallergic sialadenitis in the LEW rat. III. Role of CD4+ T cells in EAS induction.

Experimental autoallergic sialadenitis (EAS) in the LEW rat is an induced autoimmune disease of the salivary tissues. EAS is characterized by a lymphocytic infiltration that consists of both CD4+ (helper/inducer T-cell subset) and CD8+ (cytotoxic/suppressor T-cell subset) T cells and results in the immune-mediated destruction of the exocrine salivary glands. To investigate the role that each of the T-cell subsets may have in the pathogenesis of EAS, LEW rats sensitized with WF SMG homogenate were injected with monoclonal antibodies to deplete or inactivate, in vivo, the CD4, CD5 (OX19; pan T lymphocyte), CD8, or RT6 (70% of peripheral T cells) T-cell populations. Treatment with the OX8 (CD8), OX19 (CD5), or W3/25 (CD4) only partially reduced in vivo the respective splenic or lymph node T-cell subsets when analyzed on Day 14, while treatment with DS4.23 (anti-RT6) resulted in greater than 95% depletion of RT6+ spleen and lymph node T cells. EAS incidence and severity was significantly reduced in the W3/25 (CD4) treatment group (11% incidence rate; histologic score 1.0) as compared to medium-injected controls (88% incidence rate; histologic score 2.9). Although the incidence and severity of EAS in the OX19 (71%; histologic score 1.7), OX8 (55%; histologic score 1.7), and RT6 (67%; histologic score 1.6) treatment groups appeared decreased, the reduction was not statistically significant. These results provide evidence that CD4+ T cells have an important role in EAS induction and demonstrate that in vivo treatment with anti-CD4 can ameliorate and/or prevent EAS in the LEW rat.

Animals↗

Comparative analysis of retroperitoneal and transperitoneal aortic replacement for aneurysm.

Transabdominal aortic replacement is the most widely accepted surgical approach in the treatment of infrarenal abdominal aortic aneurysms (AAA) with an enviable mortality rate of 2 to 5 per cent. This approach, however, is attended by significant intraoperative loss of fluid and subsequent translocation as well as impaired postoperative pulmonary function and ileus. Although the retroperitoneal exposure of the aorta was used for the first repair of an AAA by Dubost and has been championed more recently by others, it has not been widely accepted. Experience suggests, however, that the exposure is as good and that postoperative morbidity is significantly less than that with the transperitoneal approach. In the past five years, we have surgically treated 299 AAA, 106 by the transabdominal route and 193 by the extended retroperitoneal approach. In 133 of the 193 patients upon whom the retroperitoneal approach was used, the aneurysm was left intact after division of the infrarenal aorta for an end to end proximal anastomosis of an aortoaortic to iliac to femoral bypass. There has been a significant reduction in the intraoperative replacement of fluid and blood, in postoperative respiratory support, in length of time in the intensive care unit and in occurrence of postoperative ileus when compared with the transabdominal endoaneurysmorrhaphy approach. Furthermore, the exposure, particularly upon the obese patient, is superior. Findings from this experience using the retroperitoneal approach for repair of AAA indicate that it results in less over-all physiologic disturbance of the patient.

Aged↗

Durability of the tibial artery bypass in diabetic patients.

Infrapopliteal bypass in diabetic patients has been associated with lower rates of patency and limb salvage than in nondiabetic patients. We prospectively compared the patency and limb salvage rates of in situ tibial artery bypass in diabetic and nondiabetic patients. Of 681 in situ bypasses performed for limb salvage over a 7 year period, 387 (57 percent) were carried out in diabetic patients and 294 (43 percent), in nondiabetic patients. Indications for operation most commonly included gangrene or ulceration (74 percent of the diabetic group and 49 percent of the nondiabetic group). Otherwise, the two patient groups were similar. Cumulative patency rates at 1 and 5 years were similar (91 and 74 percent for diabetic patients and 90 and 76 percent for nondiabetic patients, respectively). Limb salvage rates were also not significantly different (96 and 86 percent at 1 and 5 years, respectively, for diabetic patients and 99 and 94 percent, respectively for nondiabetic patients). Despite the unfavorable pattern of atherosclerosis in diabetic patients, the results of tibial arterial reconstructions showed patency and limb salvage rates similar to those seen in nondiabetic patients.

Amputation, Surgical↗

Understanding cohort differences in cross-generational, self, and peer perceptions.

Thirty adolescent, middle-aged, and elderly people participated in a study exploring (a) their self-, inter- and intra-cohort perceptions; (b) ascribed social distance; (c) knowledge of aging; and (d) the relationships among these phenomena. Data were gathered using a Social Distance Scale, Goals of Life Index, Facts on Aging Quiz, and Aging Semantic Differentials. In general, elderly adults were the most devalued and middle-aged adults the most favored cohort. Unfavorable attitudes toward elderly people were predicted more by age-related social distance and societally induced biases than differential investments in psychosocial life tasks. Appraising one's member cohort more favorably than those outside it was paralleled by a tendency to view the self more favorably than peers. The discrepancy between societal and older individuals' views of aging suggests that the social breakdown syndrome itself may be breaking down: Older adults are moving away from a characterization of themselves as ineffective and dependent. A similar view might be engendered in younger cohorts if social distance were reduced and more attention paid to assertions of elderly adults rather than to societally induced stereotypes.

Adolescent↗

Transcutaneous flow measurements in in-situ bypasses: an assessment of duplex scanning.

Measurement of laminar flow using an ultrasound scanner was shown to have a high degree of correlation with quantified timed flows (r = 0.98, p less than or equal to .001). Sixty-one in-situ bypasses had flow assessed both proximally and distally. Mean fistula flow (proximal-distal flows) for time periods 1-8 weeks, 3 to 8, and 9+ months were 108, 85, and 16mls respectively. Distal bypass flow remained constant despite a significant decrease in fistula flow between the later time periods (p less than or equal to .001) (unpaired t-test). There was no evidence from the study that proximal flow through fistulas of varying resistances adversely affected the distal bypass flow.

Arteriovenous Fistula↗

Sex differentiation of t-e circadian system in the golden hamster.

The effect of estradiol benzoate (EB) on free-running circadian activity rhythms was studied in gonadectomized hamsters maintained in constant dim illumination. EB shortened the period (tau) of the female, but not of the male circadian activity rhythm. Responsiveness of the circadian system to EB was subject to sexual differentiation. The circadian period of wheel running by female hamsters given a single injection of testosterone propionate on the day of birth did not shorten in response to EB in adulthood. This failure to respond to EB also was observed in normal male hamsters, and was different from the response shown by normal females. Preliminary data suggest that tau of the activity rhythm of males castrated on the day of birth is shortened during EB treatment in adulthood. The differential effects of estradiol on tau are related to anatomic differences between the sexes in neural connections of the substrate for circadian rhythms.

Animals↗

Estradiol shortens the period of hamster circadian rhythms.

Continuous administration of estradiol benzoate by means of subcutaneously implanted capsules shortened the free-running circadian period of locomotor activity of blind hamsters (Mesocricetus auratus) that had had their ovaries removed. Estradiol also advanced the phase of the wheel running of sighted female hamsters without ovaries that were entrained to a photoperiod with 12 hours of light and 12 of darkness. These results, and findings from hamsters undergoing natural estrous cycles, indicate that endogenous estradiol is involved in the regulation of circadian periodicity.

Animals↗

Duchenne/Becker muscular dystrophy: correlation of phenotype by electroretinography with sites of dystrophin mutations.

The dark-adapted electroretinogram (ERG) of patients with Duchenne and Becker muscular dystrophy (DMD/BMD) shows a marked reduction in b-wave amplitude. Genotype-phenotype studies of mouse models for DMD show position-specific effects of the mutations upon the phenotype: mice with 5' defects of dystrophin have normal ERGs, those with defects in the central region have a normal b-wave amplitude associated with prolonged implicit times for both the b-wave and oscillatory potentials, and mice with 3' defects have a phenotype similar to that seen in DMD/BMD patients. The mouse studies suggest a key role for the carboxyl terminal dystrophin isoform, Dp260, in retinal electrophysiology. We have undertaken a systematic evaluation of DMD/BMD patients through clinical examination and review of the literature in order to determine whether the position-specific effects of mutations noted in the mouse are present in man. We have found that, in man, a wider variation of DMD defects correlate with reductions in the b-wave amplitude. Individuals with normal ERGs have mutations predominantly located 5' of the transcript initiation site of Dp260. Our results suggest that the most important determinant in the ERG b-wave phenotype is the mutation position, rather than muscle disease severity. Forty-six per cent of patients with mutations 5' of the Dp260 transcript start site have abnormal ERGs, as opposed to 94% with more distal mutations. The human genotype-phenotype correlations are consistent with a role for Dp260 in normal retinal electrophysiology and may also reflect the expression of other C-terminal dystrophin isoforms and their contributions to retinal signal transmission.

Dystrophin↗

Electroretinography in congenital idiopathic nystagmus.

Ganzfeld electroretinograms were recorded from 105 consecutive patients clinically believed to have congenital idiopathic nystagmus. Retinal disease causing congenital nystagmus was diagnosed in 59 patients (56%). Electroretinographic evaluation of children with nystagmus and apparently normal eyes has both diagnostic and prognostic value. In patients with congenital nystagmus with a normal ocular examination, a diagnosis of congenital idiopathic nystagmus cannot be inferred without electroretinographic evidence of normal retinal function.

Adolescent↗

The fate of extremities with flat lower calf pulse volume recordings.

The prognosis of patients with a flat (Class 5) or nearly flat (Class 4) pulse volume recording was studied in relation to the signs and symptoms of vascular disease in 517 patients. Within one year of follow up, 97.9% of 96 patients with jeopardized limbs and flat tracings required surgery, whereas 72.4% of 29 patients with no or minimal symptoms required reconstruction (p less than 0.001); 85.7% of patients with Class 4 tracings and jeopardized limbs required surgery, whereas 41.9% of those with minimal symptoms and Class 4 recordings developed need for reconstruction (p less than 0.001). The requirement for surgery Class 5 patients is significantly higher than in those with Class 4 tracings. The general trend of pulse volume recording amplitude to correlate with ankle systolic blood pressure was confirmed. One year mortality in Class 5 patients was 43.2%. The majority of patients with severely abnormal pulse volume recordings eventually come to surgical reconstruction. The timing of surgery is based on the clinical status of the jeopardized limb, not solely on the presence of a pulse volume tracing abnormality.

Blood Pressure↗