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Biomedical subjects

J Duff

Publications and source records attributed to J Duff.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pattern of liver, kidney, heart, and intestine allograft rejection in different mouse strain combinations.

With advances in microsurgery and molecular biology, the mouse model for organ transplantation has become increasingly popular. However, knowledge about these models is limited, as only a small number of centers have experience with murine models. In this study, we compared the rejection pattern after liver, kidney, heart, and small bowel transplantation in the three different mouse strain combinations: (1) C57BL/6 (H2b)-->BALB/c (H2d), (2) BALB/c (H2d)-->CBA (H2k), and (3) C57BL/6-->C3H/HeN (H2k). Our study demonstrated that mouse allograft survival varies depending on the organ graft and on the donor-recipient strain combinations. The majority of liver allografts were spontaneously accepted despite complete MHC disparity. A mixed pattern of acute rejection and acceptance occurred in kidney recipients depending on the donor-recipient strain combination. All the heart grafts developed rejection and all the intestinal grafts were rapidly rejected with no spontaneous acceptance. The criteria for rejection, the potential applications, and the limitations of each model are discussed. The models described in this article provide a number of useful choices for organ transplantation research.

Animals↗
PubMed1996

Small bowel transplantation. A life-saving option for selected patients with intestinal failure.

Thirty-seven patients were listed for small bowel transplantation; 16 were transplanted and 15 died while waiting for a donor. Cyclosporine (N = 6) or tacrolimus (N = 10) were used for immune suppression. Graft rejection rates were lower in the combined liver/small bowel grafts than the isolated intestinal transplants (1/7 vs 5/7; P < 0.01) All of the cyclosporine group have died; the median survival was 25.7 months with two patients living more than five years. The tacrolimus group had fewer infections and a shorter hospital stay. All but two are alive with a median survival of 13 months. Seven of eight long-term survivors are off intravenous feedings. We conclude that small bowel transplantation is a life-saving option for patients with intestinal failure who cannot be maintained on total parenteral nutrition.

Adolescent↗
PubMed1996

Limited usefulness of electroconvulsive therapy in progressive supranuclear palsy.

OBJECTIVE: To perform a pilot study of the efficacy of electroconvulsive therapy (ECT) in improving motor function in progressive supranuclear palsy (PSP). BACKGROUND: Few effective treatments are available for PSP. Tricyclic antidepressants and idazoxan (which increases central norepinephrine) have shown benefits in small clinical trials, and dopaminergic therapy has been reported, anecdotally, to be beneficial. ECT exerts effects on all of these transmitter systems, possibly by inducing increased receptor sensitivity. We postulated that by sensitizing dopaminergic and noradrenergic systems, ECT might improve motor symptoms of PSP. METHODS: Five patients with clinically diagnosed PSP were evaluated before and after nine ECT treatments using the Unified Parkinson's Disease Rating Scale (UPDRS) and an apomorphine challenge to assess dopaminergic responsiveness. RESULTS: No permanent side effects were seen. Transient side effects included confusion in all patients, worsening of speech and swallowing in two, and dystonic posturing of the foot in one. One patient experienced a dramatic response (going from a completely wheelchair-bound state to independent ambulation), two were mildly improved, and two were unchanged. CONCLUSIONS: Although ECT may ameliorate motor symptoms in PSP, the long hospitalization and the significant treatment-induced confusion limit the usefulness of this technique.

Aged↗
PubMed1996

The nurse's role in clinical trials.

Parkinson's disease (PD) is a chronic and progressive degenerative disorder of the central nervous system characterized by tremor, rigidity, slowness of movement (bradykinesia) and postural abnormalities. The cause is unknown, but the pathology shows that dopamine is profoundly reduced in the basal ganglia of patients with PD. When dopamine is replenished by the administration of levodopa, most of the symptoms of parkinsonism are reduced significantly. Levodopa is considered to be the most reliable and effective symptomatic drug treatment for keeping patients autonomous and functionally independent for as long as possible.

Antiparkinson Agents↗
PubMed1995

Effect of GPi pallidotomy on motor function in Parkinson's disease.

The major motor disturbances in Parkinson's disease are thought to be caused by overactivity of the internal segment of the globus pallidus (GPi), in large part due to excessive drive from the subthalamic nucleus. The excessive inhibitory activity of GPi is thought to "brake' the motor thalamus and the cortical motor system to produce the slowness, rigidity, and poverty of movement characteristic of parkinsonian states. To test the hypothesis that direct reduction of Gpi activity can improve motor function, we studied the effect of GPi pallidotomy in 14 patients. The location of the GPi nucleus was confirmed by microelectrode recording before lesion creation. Standardised videotape recordings before and after operation were randomised and scored by a "blinded' evaluator. 6 months after surgery, total motor score in the "off" state had improved by 30% and the total akinesia score by 33%. The gait score in the "off" state improved by 15% and a composite postural instability and gait score by 23%. After surgery there was almost total elimination of drug-induced involuntary movements (dyskinesias), with a 92% reduction on the side contralateral to the pallidotomy. No patient had visual or corticospinal complications. In these patients GPi pallidotomy enhanced motor performance, reduced akinesia, improved gait, and eliminated the neural elements responsible for levodopa-induced dyskinesias.

Activities of Daily Living↗
PubMed1995

Improved techniques for kidney transplantation in mice.

Improved microsurgical techniques for kidney transplantation in the mouse are described. Left renal transplantation is performed with end-to-side anastomoses of the donor renal vein to the inferior vena cava and the donor aortic cuff to the aorta. Urinary tract reconstruction is accomplished by suturing the donor ureter with a bladder patch to the recipient bladder. With these modifications, it is possible to achieve success rates as high as 90%. This stable and reproducible model provides a useful tool to study the immunological mechanisms of kidney allograft rejection at the molecular level.

Anastomosis, Surgical↗
PubMed1995

Remoxipride in Parkinson's disease: differential response in patients with dyskinesias fluctuations versus psychosis.

Remoxipride is a novel substituted benzamide that more effectively blocks mesolimbic than striatal D2 dopamine receptors. We used remoxipride in the management of nine patients with Parkinson's disease (PD) who were experiencing visual hallucinations due to dopaminergic therapy. Remoxipride was begun in a dose of 25 mg three times daily and gradually increased to 75-225 mg/d (mean 161 mg). The psychiatric status improved in eight patients. Little or no change in the severity of parkinsonism was noted in five, a mild increase in two, and a moderate increase in two. Because one patient with moderately severe levodopa-induced dyskinesias experienced a reduction in the abnormal movements without a substantial increase in parkinsonism, we began a trial of remoxipride for disabling peak-dose dyskinesias. The trial was abandoned after every one of the first four patients entered experienced an immediate, severe, and prolonged increase in off periods with single 10- to 25-mg doses. This striking differential response to an atypical neuroleptic with weak striatal D2 antagonist properties indicates that different states of postsynaptic dopamine receptor sensitivity or synaptic dopamine levels may be associated with various disease- and treatment-related problems found in late-stage PD.

Aged↗
PubMed1994

Timing of surgery in relation to the menstrual cycle in premenopausal women with operable breast cancer.

Recent studies have suggested that the timing of surgery in relation to the menstrual cycle might influence survival of premenopausal women with operable breast cancer. The data of 96 premenopausal patients who underwent primary surgery for operable breast carcinoma between 1975 and 1988 were analysed. At 10 years, disease-free and overall survival rates of patients whose initial surgery was 1-12 days after the starting date of the last menstrual period (follicular phase) were significantly poorer compared with survival of those who underwent operation more than 12 days after the last menstruation (luteal phase) (disease-free survival rate 40 versus 72 per cent, P = 0.002; overall survival rate 40 versus 79 per cent, P = 0.001). These differences in survival remained significant in a second analysis based on the menstrual phase at the time of both initial and definitive operation. Menstrual phase had the greatest impact on the survival of patients with positive axillary nodes (P = 0.009). Prospective studies are required to elucidate the relationship between the timing of all surgical procedures during the menstrual cycle and survival.

Adult↗
PubMed1994

Timing of surgery influences survival in receptor-negative as well as receptor-positive breast cancer.

Analysis of oestrogen and progesterone receptor (ER, PR) status was interpreted in relation to menstrual phase at the time of surgery and survival in 84 women diagnosed with breast cancer between 1975 and 1988. We showed previously (Br J Surgery 1994, 81, 217-220) that long-term survival was significantly poorer when surgery was performed during the follicular phase of the menstrual cycle compared to luteal phase; we now demonstrate that this effect on survival is at least as important in receptor-negative as receptor-positive patients. At 10 years, overall survival (OS) of ER-positive patients who had their biopsy during the follicular phase was significantly poorer than for those whose biopsy was performed during the luteal phase of their menstrual cycle (52 versus 88%, P = 0.02). OS for the ER-negative follicular phase group was also significantly poorer than that for the ER-negative luteal phase group (33 versus 76%, P = 0.009). The OS difference between the PR-positive follicular phase group and PR-positive luteal phase group was of borderline significance (60 versus 87%, P = 0.06), while the difference in OS between the PR-negative follicular phase group and that of the PR-negative luteal phase group was highly significant (13 versus 76%, P = 0.001). Disease-free survival for these groups followed a similar trend. The survival differences in receptor-negative women suggest that hormonal fluctuations at the time of surgery may have complex indirect effects on tumour growth and metastasis. The mechanism, if indeed independent of the tumour steroid receptors, could also apply in other cancers.

Adult↗
PubMed1993

Development of a mouse intestinal transplantation model.

We have recently developed a mouse intestinal transplantation model. The proximal segment of donor jejunum is transplanted into the recipient in a heterotopic position. End-to-side anastomoses are performed between donor aorta and recipient aorta and between donor portal vein and recipient inferior vena cava. Mortality rates were initially high due to shock, arterial thrombosis, and postoperative sepsis. Refinements in surgical techniques reduced these complications, resulting in a high rate of success. Important technical factors included (1) minimizing ischemic injuries to the graft in both the donor and the recipient, (2) using an aortic patch and elliptical aortotomy for anastomosis, (3) administering large volumes of crystalloid to maintain normal blood pressure during the donor and recipient surgeries, and (4) using broad-spectrum antibiotics as postoperative prophylaxis. The mice with isografts had normal intestinal function and histology when they were sacrificed 1 month after surgery. This new model of small bowel transplantation will be a useful tool to study the immunology of intestinal grafting at the molecular level.

Anastomosis, Surgical↗