Biomedical subjects
Publications and source records attributed to R Hammond.
The cervical screening programme has had a dramatic impact on the incidence of invasive cervical cancer and preinvasive disease can be effectively treated in the majority of cases. However, recurrent abnormalities after treatment pose management dilemmas which are considered in this overview of the topic.
BACKGROUND AND PURPOSE: There are a variety of embolization applications for non-adhesive, liquid agents. We reevaluated the potential microvascular angiotoxicity of superselective infusions of dimethyl sulfoxide (DMSO) using very long infusion rates in a previously described animal model. METHODS: Twenty-six swine underwent percutaneous femoral puncture for superselective catheterization of the artery of the rete while being continuously monitored for ECG and intraarterial pressure. Two volumes (0.5 or 0.8 mL) and three durations (30, 60, and 90 seconds) of superselective infusion of DMSO were used to evaluate the effect of a single-dose rate within an ipsilateral rete. Contralateral control infusions of normal saline were also administered. Acute hemodynamic and angiographic outcomes were assessed. After recovery, follow-up angiography and sacrifice were performed at either 10 or 28 days. Brains and retia were harvested for gross and microscopic histopathologic evaluation. RESULTS: No significant hemodynamic alterations occurred acutely. Twenty-three of the 24 infused retia showed variable acute vasospasm that typically was mild to moderate in severity and transient (10 to 20 minutes). Follow-up angiography at sacrifice always showed normal retial arterial anatomy. No adverse clinical sequelae were noted. Gross inspection of brains showed no evidence of infarction or subarachnoid hemorrhage. Microscopic histopathologic examination of retia showed mostly nonspecific changes in both exposed and control samples. Possible causal histotoxicity was seen in four retia (three of four exposed to higher dose rates), in which involvement was limited to one to three retial arteries. CONCLUSION: Lower total dose and dose rates of superselective infusion of DMSO into the retial microarterial network resulted in substantially less angiotoxicity than that found in a previous study, as defined by clinical, angiographic, gross, and histopathologic criteria.
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The cervical smear and biopsy results were reviewed for 141 patients who were referred for colposcopy with either a technically unsuitable smear or with cervical smear abnormalities less severe than dyskaryosis. The number of referrals due to minor smear abnormalities more than doubled from 8.6% to 22.3% of the total colposcopy referrals over the 4 year period studied. The minor smear abnormalities were only associated with cervical intraepithelial neoplasia (CIN) in patients aged < 50 years. In 19 (13.5%) of the 141 patients high-grade lesions (CIN II or CIN III) were diagnosed. There were no cases of invasive cancer. Furthermore, the increased number of patients being referred for colposcopy with minor cervical smear abnormalities highlights the increasing pressures on colposcopy services, with prolonged waiting times for all patients.
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Vibrio vulnificus infections are highly lethal and associated with consumption of raw shellfish and exposure of wounds to seawater. V. vulnificus infections were reported to the Centers for Disease Control and Prevention from 23 states. For primary septicemia infections, oyster trace-backs were performed and water temperature data obtained at harvesting sites. Between 1988 and 1996, 422 infections were reported; 45% were wound infections, 43% primary septicemia, 5% gastroenteritis, and 7% from undetermined exposure. Eighty-six percent of patients were male, and 96% with primary septicemia consumed raw oysters. Sixty-one percent with primary septicemia died; underlying liver disease was associated with fatal outcome. All trace-backs with complete information implicated oysters harvested in the Gulf of Mexico; 89% were harvested in water >22 degrees C, the mean annual temperature at the harvesting sites (P < .0001). Control measures should focus on the increased risk from oysters harvested from the Gulf of Mexico during warm months as well as education about host susceptibility factors.
BACKGROUND: Skeletal muscle ventricles have been shown to provide effective aortic diastolic counterpulsation in an experimental model. Construction has included full ligation of the thoracic aorta. The authors sought to determine if these muscle pumps could function effectively without fully ligating the aorta. METHODS: Skeletal muscle ventricles were constructed in two groups of dogs. Group 1 had their aortas fully ligated (n = 10) while group 2 had their aortas narrowed by 50% (n = 10). The animals were followed for 10 weeks. RESULTS: There was no significant difference in femoral diastolic augmentation at implant or at 10 weeks (19.1% +/- 9.9% in group 1 [full ligation] versus 16.3% +/- 10.2% in group 2 [half ligation] p = 0.502). Survival to 10 weeks was significantly better in group 1 (full ligation). Nine of 10 animals in this group survived versus 4 of 10 in group 2 (p = 0.019). Two animals survived in the half ligation group with effective augmentation and without thrombus formation. CONCLUSION: Both models produce effective diastolic counterpulsation. Survival was decreased in this model using half ligation, and survival without complication was observed in 2 of 10 animals. Currently the overall results are better with the full aortic ligation model. However, design modifications will probably result in an effective model of diastolic counterpulsation without full aortic ligation.
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Viroids are non-translatable, autonomously replicating circular RNAs that infect only plants. An important component of the viroid infection process is cell-to-cell movement; however, there is virtually no information available about the pathways and mechanisms of this process. In this study, potato spindle tuber viroid (PSTVd) has been used as a model system to investigate the mechanism of viroid cell-to-cell transport. Infectious RNA transcripts were produced from PSTVd cDNA clones in vitro, labeled with the nucleotide-specific fluorescent dye TOTO-1 iodide, and used for micro-injection. When injected into symplasmically isolated guard cells of mature tomato and tobacco leaves, PSTVd remained in the injected cells; in contrast, PSTVd injected into symplasmically connected mesophyll cells moved rapidly from cell to cell. A 1400 nt RNA containing only vector sequences was unable to move out of the injected mesophyll cells, but when PSTVd was fused to this transcript, the fusion RNA moved from cell to cell. At the DNA level, PSTVd cDNA also appears able to mediate cell-to-cell movement of plasmid DNA. These data indicate that (i) PSTVd moves from cell to cell via plasmodesmata, and (ii) this movement may be mediated by a specific sequence or structural motif.
Two intravenous doses of romlfidine (40 and 80 micrograms/kg) and a placebo were compared as premedicants for anaesthesia induced with thiopentone and maintained using halothane in oxygen. Romifidine significantly and linearly reduced the induction dose of thiopentone; placebo-treated dogs required 15.1 +/- 3.6 mg/kg, while dogs treated with 40 micrograms/kg and 80 micrograms/kg romifidine required 6.5 +/- 1.6 and 3.9 +/- 0.3 mg/kg thiopentone, respectively. Romifidine also significantly and linearly reduced the end tidal halothane concentration necessary to maintain a predetermined level of anaesthesia; placebo-treated dogs required 1.6 +/- 0.3 per cent halothane, while dogs treated with 40 micrograms/kg and 80 micrograms/kg romifidine required 1.3 +/- 0.4 and 0.8 +/- 0.2 per cent, respectively. Romifidine produced a significant shortening in the recovery from anaesthesia, and the higher dose of romifidine significantly improved the overall quality of anaesthesia.
PURPOSE: To compare the toxicity, pharmacokinetics, and efficacy seen in ovarian cancer patients treated with escalating doses of intraperitoneal (I.P.) interleukin-2 (IL-2) by two different infusion schedules. PATIENTS AND METHODS: Forty-five patients were sequentially entered onto a phase I/II study in groups of four at fixed dosage tiers of 6 x 10(4), 6 x 10(5), 6 x 10(6), and 3 x 10(7) IU/m2/d in either of two schedules: (A) intermittent weekly infusions of 24 hours' duration; or (B) alternating continuous 7-day infusions followed by 7-day intervals without therapy. Eligibility criteria included > or = six courses of prior platinum-based chemotherapy and laparotomy-confirmed persistent or recurrent ovarian cancer. RESULTS: Forty-one eligible patients received I.P. IL-2 and were assessable for toxicity, but six patients were not assessable for response, which left 35 patients assessable for response. Significant locoregional dose-limiting toxicity was seen with the 7-day infusions (including bowel perforation), with 600,000 IU/m2 as the maximum-tolerated dose (MTD), but catheter infection was the only significant complication seen with the 24-hour infusions, for which an MTD was not established. Among 35 assessable patients, there were six laparotomy-confirmed complete responses (CRs) and three partial responses, for an overall response rate of 25.7% (nine of 35). The median survival time of the cohort was 13.7 months and the overall 5-year survival probability was 13.9%. For the nine patients who demonstrated responses (six on the 24-hour infusion and three on the 7-day infusion), the median survival time has not been reached (range, 27 to 90+ months). CONCLUSION: I.P. IL-2 is better tolerated as a weekly infusion as compared with a 7-day infusion and demonstrates evidence of possible long-term efficacy in a modest number of patients. A randomized trial is indicated to determine if the prolonged survival seen in this study is a due to I.P. IL-2 therapy or other factors that cannot be controlled for in a single-arm study.
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The sedative and physiological effects of intravenous romifidine at 0, 20, 40, 80 and 120 micrograms/kg were investigated in five clinically normal adult male beagle dogs in a blind study using a Latin square design. Following the injection of romifidine, the dogs became ataxic and stood with a wide-based stance, they exhibited signs of skeletal muscle relaxation and their heads were lowered. All the dogs became recumbent and there was a reduction in the heart and respiratory rates. Increasing the dose from 20 to 40 micrograms/kg, or higher, produced a significant reduction in heart rate. There was am increase in the sedation score following even low doses of romifidine, and although measures of sedation showed no differences among romifidine doses, subjectively, the higher doses produced a more consistent effect. Dogs given lower doses of romifidine regained a standing position more rapidly than following the higher doses, although this effect was not significantly different. A second blind study compared the sedative effects of intravenous romifidine, at 40 and 80 micrograms/kg, with medetomidine at 10 micrograms/kg in six adult beagles. The cardiopulmonary and sedative effects were not significantly different between all regimens, although medetomidine at 10 micrograms/kg appeared to be intermediate in effect between romifidine at 40 and 80 micrograms/kg. The sedative and physiological effects of romifidine in dogs appear to be similar to other alpha2-adrenoceptor agonists. Intravenous administration provided sedation which might be clinically useful.
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OBJECTIVE: The neuropathologic mechanisms of the ovine fetal brain in response to several hours of sustained hypoxemia with variable degrees of metabolic acidemia was investigated in both the preterm and near-term ovine fetus. STUDY DESIGN: Three groups of fetuses were studied in each of the near-term and midgestation groups: a hypoxic group, a control group, and an uninstrumented control group. Histopathologic studies were performed after a 40-hour recovery period after experimentation. RESULTS: Pathologic findings consisted of predominately white matter damage with some adjacent cortical necrosis but no selective neuronal injury. In the near-term group the hypoxia group fetuses demonstrated significantly higher white matter injury scores than did control group fetuses (p < 0.05). Periventricular white matter injury was the predominant pattern seen in the midgestation group. CONCLUSIONS: In spite of normalization of biophysical and biochemical parameters after hypoxemia both midgestation and near-term fetuses sustained pathologic changes. Presence or extent of injury did not correlate with the degree of hypoxemia or metabolic acidosis achieved.
Periodontal bone defects were established in four dogs, with one proximal lesion and one furcation lesion in each quadrant. These defects were treated with the implantation of collagen membranes, collagen sponge or a combination of membrane and sponge, inserted between the mucoperiosteal flaps and the bone defects. Control sites were treated in a similar surgical manner to the experimental sites, but no collagen was inserted. Substantial amounts of new bone formed in those cases treated with the collagen products, especially those treated with the membrane either with or without the sponge. The membranes limited the infiltration of small round cells, whereas in the control sites, inflammatory cells infiltrated to the bone surface. New connective tissue attachment was established in experimental situations, especially with the use of the membranes alone or in conjunction with sponge.
During a 10-year period from January 1, 1979, 59 patients out of a total of 203 undergoing definitive treatment for epithelial ovarian cancer were managed with primary adjuvant whole abdominal radiotherapy after initial cytoreductive surgery. The median survival of this group was 53 months. The serious morbidity rate was approximately 8% with 4 laparotomies for bowel complications and 1 death following radiation related liver failure. This form of adjuvant therapy in appropriately selected patients with minimal residual disease merits further evaluation against other forms of therapy such as systemic or intraperitoneal chemotherapy.