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Biomedical subjects

D C Martin

Publications and source records attributed to D C Martin.

At least 73 records · Page 4Linked to original sources

Pain and infertility--a rationale for different treatment approaches.

Endometriosis may result in pain and/or infertility in some patients, while others may remain asymptomatic. The disease appears to progress and regress somewhat unpredictably, making it difficult to determine the appropriate treatment. Progression of the disease can be altered by medical and surgical treatments used according to general guidelines but selected for the individual. Coagulation, medical suppression and observation are frequently the first approaches to infertility or pain resulting from endometriosis. Deep dissection and excision may be indicated with deep disease, persistent pain or persistent tenderness.

Disease Progression↗

Evaluation of outpatient geriatric assessment: a randomized multi-site trial.

OBJECTIVE: To evaluate the process and outcome of outpatient consultative geriatric assessment compared with traditional community care. DESIGN: Randomized, controlled clinical trial, with 12-month follow-up. SETTING: Four hospital-based ambulatory geriatric assessment clinics and community physicians' offices. PARTICIPANTS: 442 recruited older adults with a health problem or recent change in health status. INTERVENTION: Outpatient consultative geriatric assessment or usual physician assessment. MAIN OUTCOME MEASURES: Identification of health problems, mortality, nursing home admissions, health status, health services utilization, satisfaction with care, and caregiver well-being. RESULTS: Geriatric assessment, in comparison with usual community care, resulted in the identification of a significantly greater number of patients with cognitive impairment (P < .0001), depression (P = .0004) and incontinence (P < .0001). The group receiving a geriatric assessment had greater improvement in anxiety levels at 1 year (P = .036). Caregivers of participants in the geriatric assessment group had less caregiver stress at 1 year (P = .002). No outcome differences in mortality, nursing home admissions, cognitive health, functional health, or health services utilization were observed. Some evidence of greater patient satisfaction with respect to qualities of the physician was found for the geriatric assessment group. CONCLUSIONS: Consultative outpatient geriatric assessment led to significantly improved diagnosis of the common health problems of cognitive impairment, depression, and incontinence, to psychological and emotional benefits for patients, and to reduced levels of caregiver stress. Even with limited follow-up care and control of treatment, outpatient geriatric assessment has potential for significant positive effects.

Aged↗

Immunoresponsiveness in endometriosis: implications of estrogenic toxicants.

Endometriosis is a reproductive disease characterized by the growth of endometrial cells at sites outside the uterus. This disease is a serious disorder associated with chronic pain and infertility, which may be present in 6 million women in this country. Traditional medical therapy has consisted of hormonal regimens that limit the action of endogenous estrogen. The etiology of endometriosis is unknown, but studies suggest that soluble factors known as cytokines play a role in disease pathogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is an environmental toxicant that alters the action of estrogen in reproductive organs and adversely affects immunocompetence. The incidence of endometriosis was determined in rhesus monkeys that were chronically exposed to dioxin for a period of approximately 4 years. Ten years after termination of dioxin treatment, the presence and severity of endometriosis was assessed by surgical laparoscopy. The incidence of endometriosis correlated with dioxin exposure and disease severity was dependent upon the dose administered. Moderate to severe endometriosis was not found in control animals but was documented in three of seven animals exposed to 5 ppt dioxin (43%) and in five of seven animals exposed to 25 ppt dioxin (71%). The frequency of spontaneous disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys with no history of dioxin exposure. This study indicates that endometriosis may be associated with dioxin exposure in the rhesus. In view of overwhelming evidence that cytokines participate in the mediation of reproductive-endocrine phenomena and regulation of endometrial growth, future assessment of the effects of environmental toxicants on reproductive health may depend upon our understanding of the bidirectional cytokine network between the immune and endocrine systems.

Animals↗

Ethanol augments pre-emptive analgesia produced by nitrous oxide in the formalin test in the rat.

Experimental evidence suggests that the introduction of analgesia prior to a painful stimulus can reduce the subsequent pain (preemptive analgesia). Using the formalin test model, previous studies have demonstrated that general volatile anesthetics reduce the pre-emptive analgesia produced by nitrous oxide administration in the rat. The present study compared the influence of halothane and ethanol on the response to formalin injection in rats previously exposed or not exposed to nitrous oxide. Nitrous oxide decreased second phase licking behavior by approximately 70% from controls. Halothane decreased second phase licking by 37% from sham animals and, when administered with nitrous oxide, mitigated the suppression of licking seen with nitrous oxide alone. Ethanol reduced the licking response in both early and late phases following formalin injection. In contrast to halothane, ethanol failed to attenuate the analgesia produced by nitrous oxide administration alone. Thus, ethanol provides apparent analgesia following formalin injection and, unlike halothane, augments the preemptive analgesia produced by nitrous oxide.

Analgesics↗

Morphology and primary crystal structure of a silk-like protein polymer synthesized by genetically engineered Escherichia coli bacteria.

The morphology and primary crystal structure of SLPF, a protein polymer produced by genetically engineered Escherichia coli bacteria, were characterized. SLPF is a segmented copolymer consisting of amino acid sequence blocks modeled on the crystalline segments of silk fibroin and the cell attachment domain of human fibronectin. Wide angle x-ray scattering (WAXS), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and molecular simulations were used to analyze the primary crystal structure of SLPF. TEM experiments conducted on SLPF droplets cast from formic acid on amorphous carbon film demonstrated that these protein films have a microstructure formed of woven sheaves. The sheaves are composed of well-defined whisker crystallites. The width of the whiskers, 11.8 +/- 2.2 nm, may be correlated to the length of the silk-like segment in SLPF as predicted by molecular simulations. WAXS data, TEM images, SAED, patterns, molecular simulations, and theoretical diffraction patterns all were consistent with the crankshaft model proposed for Silk I by Lotz and Keith.

Amino Acid Sequence↗

Volatile anesthetics inhibit NMDA-stimulated 45Ca uptake by rat brain microvesicles.

We have previously shown that volatile anesthetics inhibit glutamate-stimulated [3H]MK-801 binding to the ionophore of NMDA receptor complexes in rat brain. In the present study, we examined the influence of enflurane and halothane on NMDA-stimulated 45Ca uptake by a microvesicle fraction isolated from rat brain. NMDA stimulated 45Ca uptake (30 sec) by rat brain microvesicles by up to 70% with an EC50 of 1.4 +/- 0.5 microM. The NMDA-stimulated 45Ca uptake was inhibited by MK-801 and D-AP-5 with IC50's of approximately 10 microM. Enflurane and halothane inhibited 45Ca uptake stimulated by 100 microM NMDA by as much as 60-80% with IC50's of 0.2-0.3 mM, concentrations achieved during routine clinical use. Basal 45Ca uptake measured in the absence of agonist was not affected by the anesthetics. Glycine did not affect the level of NMDA-stimulated 45Ca uptake, but markedly reduced the inhibition of uptake caused by enflurane and halothane. Preincubation of microvesicles with NMDA resulted in a desensitization of NMDA-stimulated 45Ca uptake, with a t1/2 of approximately 20 sec. Enflurane and halothane diminished both the extent and rate of development of this desensitization, as did glycine. These findings support the idea that volatile anesthetic interference with neurotransmission at NMDA receptor complexes contributes to the development of the anesthetic state.

2-Amino-5-phosphonovalerate↗

A computerized intervention to improve timing of outpatient follow-up: a multicenter randomized trial in patients treated with warfarin. National Consortium of Anticoagulation Clinics.

OBJECTIVE: To evaluate a computerized scheduling model that employs nonlinear optimization to recommend optimal follow-up intervals for patients taking warfarin. DESIGN: Randomized trial. SETTING: 5 anticoagulation clinics. PATIENTS/PARTICIPANTS: 620 patients expected to receive warfarin for > or = 6 weeks. INTERVENTIONS: Computer-generated recommendations for scheduling the next visit were presented to or withheld from practitioners. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were the follow-up interval scheduled by the provider, the interval at which the patient actually returned to clinic, and the quality of anticoagulation control (computed as the absolute difference between the measured and target prothrombin times [PTRs] or international normalized ratios [INRs]). Follow-up intervals scheduled for the patients whose practitioners received computer-generated recommendations were significantly longer than those for control patients (mean, 4.4 vs 3.5 weeks, p < 0.001), despite the fact that the practitioners modified the suggested return interval by > 1 week on 40% of the visits. The interval at which the intervention group actually returned to clinic was also longer (mean, 4.4 vs 4.1 weeks, p < 0.05), even though the control patients tended to return at longer intervals than were scheduled by their practitioners. Control of anticoagulation was nearly the same among experimental and control patients. Life-threatening complications occurred in the care of three experimental patients and one control patient, while other serious complications occurred in the care of 16 experimental patients and 17 control patients. CONCLUSIONS: Recommendations based on nonlinear optimization prompted clinicians to schedule less frequent follow-up for patients taking warfarin, with no deterioration in anticoagulation control. This approach to scheduling can potentially reduce utilization while maintaining quality of care for patients who require long-term monitoring.

Appointments and Schedules↗

Mechanisms of unresponsiveness associated with pretransplant blood transfusion-cyclosporine-induced mixed lymphocyte chimerism.

Multiple pretransplant blood transfusions while under limited daily cyclosporine cover (PTBT-CsA) induce extensive rat renal allograft survival and antigen-specific non-responsiveness. The underlying mechanisms of this extensive allograft survival are not yet fully understood. We hypothesized that one of the potential contributing mechanisms to tolerance induction in PTBT-CsA-treated kidney recipients is the development of stable mixed chimerism, putatively due to the proliferation of stem cells capable of haematopoiesis in the transfused blood. BN rats served as whole blood and kidney donors. LEW rats served as recipients of the PTBT-CsA protocol and BN kidney transplants. Three weekly transfusions were given under concomitant limited CsA cover. Following these multiple primary sensitizations, antigen-specific splenic cellular responsiveness in vivo was normal in comparison with naive animals. However, these experimental splenocytes were non-specifically suppressed against third-party allodeterminants. At 100 days post-transplantation (T100) following tolerance induction to kidney allografts (secondary challenge), in vivo adoptive transfer experiments demonstrated the existence of potent splenic suppressor cells. In vitro suppressor cell assays confirmed that these cells were non-specific suppressor cells. However, following chimerism stabilization at T130, splenic antigen-specific suppressor cells became exclusively expressed in the tolerant animals, replacing the non-specific suppressor cells. At this time, splenic microchimerism was at peak levels and remained stable from T100 to T130. In conclusion, these findings demonstrate that sequential mechanisms of suppressor cell network expression are induced within a chimeric environment by blood-CsA immune modulation. Stable mixed lymphocyte chimerism and related immunomodulatory mechanisms may, therefore, play an important tolerogenic role in blood-CsA-induced non-responsiveness and in the beneficial effect of blood transfusion.

Animals↗

The effect of matching on the power of randomized community intervention studies.

Currently, there is considerable interest in studies that use the community as the experimental unit. Health promotion programmes are one example. Because such activities are expensive, the number of experimental units (communities) is usually very small. Investigators often match communities on demographic variables in order to improve the power of their studies. Matching is known to improve power in certain circumstances. However, we show here that if the number of communities is small, the matched design will probably have less power than the unmatched design. This is due primarily to the loss of degrees of freedom in the matched design, which outweighs the benefits of matching on any but the strongest correlates of changes in behaviour. In the community intervention situation, even small differences in sample size between the matched and unmatched analyses can have expensive consequences.

Bias↗

Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The incidence of the reproductive disease endometriosis was determined in a colony of rhesus monkeys chronically exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) for a period of 4 years. Ten years after termination of dioxin treatment, the presence of endometriosis was documented by surgical laparoscopy and the severity of disease was assessed. The incidence of endometriosis was directly correlated with dioxin exposure and the severity of disease was dependent upon the dose administered (p < 0.001). Three of 7 animals exposed to 5 ppt dioxin (43%) and 5 of 7 animals exposed to 25 ppt dioxin (71%) had moderate to severe endometriosis. In contrast, the frequency of disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys housed at The Harlow Primate Center with no dioxin exposure. This 15-year study indicates that latent female reproductive abnormalities may be associated with dioxin exposure in the rhesus. Therefore, the effects of this toxin may be more diverse than previously recognized.

Animals↗

Buttonhole ulceration and perforation of the rectum.

Three laparoscopies were performed with treatment of cul-de-sac endometriosis near the rectum Two patients had a subsequent laparotomy for rectal perforation. The bowel damage appears to have been from a combination of failure to appreciate the position of the bowel with anatomy distorted by endometriosis, dissecting into healthy tissue with a carbon dioxide laser, desiccating healthy tissue with bipolar electrosurgery, and thermal spread into healthy tissue from the desiccated endometriotic tissue. Gynecologists must be aware of this potential complication when treating endometriosis near the rectum.

Adult↗

Test-tube equilibration of volatile anaesthetic concentrations.

We have measured concentrations of volatile anaesthetics after injection into test-tube assay solutions. In non-agitated tubes, aqueous anaesthetic concentrations decreased significantly throughout 40 min of incubation. Agitation (20-s vortex) of the tubes decreased the aqueous anaesthetic concentration by approximately 80% from concentrations in non-agitated tubes and resulted in more stable liquid anaesthetic concentrations over time. A decrease of less than 15% occurred between 10 and 50 min of incubation.

Enflurane↗