Biomedical subjects
Publications and source records attributed to W Lynch.
Bladder metastasis from breast cancer is rare. Patients with breast cancer, in particular patients with a lobular carcinoma subtype, who present with urinary symptoms including incontinence, hematuria, dysuria, and frequency should have the possibility of bladder metastases kept in mind and investigated with cystoscopy and imaging as necessary.
This research was conducted to determine whether elevated concentrations of metals in biosolids would result in increased accumulation of these metals in plants growing on an alkaline, artificial soil created by addition of municipal sewage biosolids to inorganic waste materials during reclamation of a filled lime settling basin. Accumulation of metals in vegetation growing on this alkaline, artificial soil was compared with accumulation in vegetation growing on a natural, reference soil that had not been amended by biosolids. Although the concentrations of Cd, Cr, Hg, Ni, Ag, and Zn were greater in the artificial soil than in the reference soil, only Cd was found at greater concentrations in vegetation growing on the artificial soil. These greater concentrations were only observed in wheat grass (Agropyron sp.), and not in orchard grass (Dactylis glomerata L.). Also, the accumulation ratio, which is the ratio of the metal concentration in plant tissue to that in the soil, for wheat grass was much lower than other published values. There were no differences in the concentrations of Ba and Pb in the two soils, but the concentrations of these two metals in orchard grass growing on the reference soil were greater than that in either grass on the artificial soil. The differences in plant uptake of metals appear to result from differences in soil pH between the artificial and reference soils. Many metals are generally more soluble and bioavailable at the lower pH of the reference soil (pH = 5.4-6.6) than at the higher pH of the artificial soil (pH = 7.8-8.2). As a result, transfer of metals to vegetation growing on the alkaline, artificial soil is less than that in vegetation growing on the reference soil despite the greater concentrations of metals in the artificial soil.
Northern pintail duck semen and sperm traits were characterized, and the fertility of cold-stored spermatozoa was investigated using artificial insemination. Excellent quality ejaculates containing high proportions of motile spermatozoa were collected from drakes within 20 s by a massage technique. Semen was collected in Beltsville poultry semen extender, pooled and cold-stored (4 degrees C) for 0, 24, 48 or 72 h. Hens were inseminated with 100 microl twice a week, and eggs were assessed for fertilization and hatch success. Fertilization success was similar (P > 0.05) for semen cold-stored for 0 (51.6%), 24 (51.5%), 48 (41.1%) and 72 h (22.3%; P > 0.05). Similar (P > 0.05) percentages of fertilized eggs hatched to live offspring (73.1, 71.4, 87.0 and 80.0%, respectively). Fresh semen was also equilibrated with 1 or 4% dimethylsulphoxide or glycerol, and cryopreserved at the following rates: (1) approximately 60 degrees C min(-1) (in liquid nitrogen [LN(2)] vapour) for 10 min; (2) 1 degrees C min(-1) to -20 degrees C, LN(2) vapour for 10 min; and (3) 1 degrees C min(-1) to -35 degrees C, all followed by immersion in LN(2). After thawing for 30 s at 37 degrees C or 20 min at 4 degrees C, sperm motility and viability were assessed. The highest numbers of motile spermatozoa were recovered after slow-fast freezing (2) and thawing at 0 degrees C (P < 0.05), but survival was inadequate to allow artificial insemination. Nonetheless, cold storage provides an effective means of short-term storage with no loss of fertility in this waterfowl species.
OBJECTIVE: To determine whether patients with detrusor instability (DI) were more likely to have bacterial cystitis or significant bacteriuria on the urodynamic-test day than were women with a stable bladder. PATIENTS AND METHODS: A catheter specimen of urine was cultured (overnight in air) from 862 consecutive women at the time of urodynamic testing. The upper urinary tract was imaged, with cystoscopy when indicated, to exclude upper tract lesions or malignancy. The percentage of patients with pure idiopathic DI and those with mixed DI/genuine stress incontinence (GSI), in whom the urine culture was positive, was compared with the percentage who had a stable bladder (pure GSI or urodynamically normal) and a positive urine culture, both for the entire dataset and for women aged > or <65 years. Data were also analysed to detect the converse relationship; in those women found to have bacterial cystitis, the relative risk of being found urodynamically unstable or stable was determined. RESULTS: The likelihood of bacterial cystitis occurring in patients with idiopathic DI (5.6%) was significantly greater than that in patients with GSI (1.1%; P = 0.009, Fisher's exact test). The proportion of patients with DI and significant bacteriuria (15. 4%) was significantly greater than that in patients with GSI (7.9%; P = 0.02). In patients with combined pure and mixed DI, bacterial cystitis was significantly more likely to occur (6.3%) than in GSI (P < 0.001), but bacteriuria was no more likely (12.5%, P = 0.09). Conversely, of those women found to have bacterial cystitis, the relative risk of having an unstable bladder was increased (+1.56), but for those with bacteriuria the relative risk of detrusor instability was not increased. CONCLUSION: There was a significant association between idiopathic DI and bacterial cystitis, and we suggest that in some women with an unstable bladder, urinary infection may enhance detrusor contractility. Nevertheless, large-scale studies are needed of the temporal relationship between the onset of bacterial cystitis and the onset of DI.
This study characterized seasonal changes in circulating LH and testosterone and in semen production and quality in the Northern pintail duck. Plasma LH and testosterone were measured in blood samples collected weekly throughout the year from eight males exposed to natural fluctuations in day length and temperature. Semen quality was evaluated weekly in these same males from April-June, the months when spermatozoa were produced. Semen quality (based on sperm concentration and normal morphology) peaked 0-2 weeks after sperm production onset and decreased sharply before sperm production cessation in late June. Nadir LH concentrations were measured in July and August with peak LH observed in May and November. There were clear seasonal patterns in circulating testosterone with July-September values being less (P<0.05) than October-December which, in turn, were less (P<0.05) than January-March. Maximal circulating testosterone (P<0.05) occurred during April-June, coincident with semen production. Weekly circulating LH during the breeding season was directly related to testosterone concentrations (P<0.01), but was not correlated to any specific semen or sperm trait (P>0.05). Testosterone concentrations throughout the breeding season were correlated (P<0.05) to total numbers of spermatozoa produced (volume x cell concentration) and percent normal sperm morphology. In summary, the Northern pintail experiences seasonal hormone fluctuations, with maximum circulating testosterone coinciding with peak ejaculate quality reflected by the production of high numbers of morphologically normal spermatozoa.
BACKGROUND: The use of extracorporeal life support (extracorporeal membrane oxygenation [ECMO]) as a direct bridge to heart transplant in adult patients is associated with poor survival. Similarly, the use of an implantable left ventricular assist device (LVAD) to salvage patients with cardiac arrest, severe hemodynamic instability, and multiorgan failure results in poor outcome. The use of LVAD implant in patients who present with cardiogenic shock who have not been evaluated for transplantation or who have sustained a recent myocardial infarction also raises concerns. ECMO may provide reasonable short-term support to patients with severe hemodynamic instability, permit recovery of multiorgan injury, and allow time to complete a transplant evaluation before long-term circulatory support with an implantable LVAD is instituted. After acquisition of the HeartMate LVAD (Thermo Cardiosystems, Inc), we began using ECMO as a bridge to an implantable LVAD and, subsequently, to transplantation in selected high-risk patients. METHODS AND RESULTS: From October 1, 1996, through September 30, 1998, 32 adult patients who presented with refractory cardiogenic shock (cardiac index <2.0 L. min(-1). m(-2), with systolic blood pressure <100 mm Hg and pulmonary capillary wedge pressure >/=24 mm Hg and dependent on >/=2 inotropes with or without intra-aortic balloon pump) were evaluated and accepted as candidates for mechanical assistance as a bridge to transplant. Of the 32 patients, 14 (group I) had a cardiac arrest or severe hemodynamic instability (systolic blood pressure </=75 mm Hg) with evidence of multiorgan failure (defined as serum creatinine level >3 mg/dL or oliguria; international normalized ratio >1.5 or transaminases >5 times normal or total bilirubin >3 mg/dL; and needing mechanical ventilation). Group I patients were placed on ECMO support; 7 underwent subsequent LVAD implant and 1 was bridged directly to transplant. Six patients in group I survived to transplant hospitalization discharge. The remaining 18 patients (group II) underwent LVAD implant without ECMO support; 12 survived to transplant hospitalization discharge and 2 remained alive with ongoing LVAD support and awaited transplant. One-year actuarial survival from the initiation of circulatory support was 43% in group I and 75% in group II. One-year actuarial survival from the time of LVAD implant in group I, conditional on surviving ECMO, was 71% (P=NS compared with group II). CONCLUSIONS: In appropriately selected high-risk patients, the rate of LVAD survival after initial ECMO support was not significantly different from the survival rate after LVAD support alone. An initial period of resuscitation with ECMO is an effective strategy to salvage patients with extreme hemodynamic instability and multiorgan injury. Use of LVAD resources is improved by avoiding LVAD implant in a very-high-risk cohort of patients who do not survive ECMO.
A device was constructed to assess two-point discrimination in the plantar skin of younger, middle-aged, and older adults. The device consisted of paired filaments, each delivering a tip force of 4.56 log units (equivalent to 3.63 g), at a fixed distance apart. Statistical analysis showed significant differences in two-point discrimination accuracy between these groups of subjects. Younger subjects showed greater accuracy of plantar two-point discrimination than either middle-aged or older subjects, with an apparent inverse linear relationship between subject age and plantar two-point discrimination ability. A model to assess age-related changes in two-point discrimination is presented.
BACKGROUND: Androgen receptor blocking agents have become an established form of therapy for men with disseminated prostate carcinoma. The purpose of this study was to evaluate markers of bone turnover and to measure bone mineral densities (BMD) in men with disseminated prostate carcinoma treated with combined androgen blockade prior to and after 6 months of intermittent cyclic etidronate therapy. METHODS: Twelve consecutive men with disseminated prostate carcinoma were evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropin-releasing hormone agonist (goserelin acetate) and an androgen antagonist (flutamide). During the 6-12 month period, patients were treated with adjuvant intermittent cyclic etidronate therapy and calcium supplementation. Lumbar spine BMD was measured by spinal quantitative computed tomography (QCT) and femoral neck BMD by dual energy X-ray absorptiometry (DXA). RESULTS: Combined androgen blockade resulted in all men achieving serum free testosterone concentrations of <2.2 pmol/L (normal range, 38-114 pmol/ L). The mean serum prostate specific antigen activities decreased from 130.8+/-46 to 6.9+/-4.4 ng/mL (P < 0.05). Although serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measurements remained unchanged, serum bone Gla-protein concentrations and urinary deoxypyridinolene excretion rates increased significantly (P < 0.01, respectively). Mean lumbar spine QCT decreased by 6.6+/-1.5% from 76.5 mg/cm3 (95% confidence interval [95% CI, 57-96 mg/cm3) to 73.9 mg/cm3 (95% CI, 55-93 mg/cm3) (P < 0.001) and mean femoral neck DXA decreased by 6.5+/-1.3% from 0.94 g/cm2 (95% CI, 0.81-1.07 g/cm2) to 0.91 g/cm2 (95% CI, 0.79-1.04 g/cm2) (P < 0.001). After treatment with adjuvant intermittent cyclic etidronate, mean lumbar spine QCT increased by 7.8+/-3.7% to a final value of 75 mg/cm3 (95% CI, 48.7-101 mg/cm3) (P=0.001 compared with the initial 6 months without intermittent cyclic etidronate therapy). Significant increases in BMD also were observed in the femoral neck and Ward's triangle. CONCLUSIONS: Androgen receptor blocking agents have an established role in the treatment of disseminated prostate carcinoma. However, combined androgen blockade in elderly men with disseminated prostate carcinoma results in high bone turnover with significant cancellous bone loss. The results of this study show that adjuvant therapy with intermittent cyclic etidronate may prevent these changes and decrease the risk of spinal fractures.
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Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, patients were initially treated with weekly brequinar, in combination with an every-three-week administration of cisplatin. Due to toxicity, the schedule was modified to a 28-day cycle with brequinar given on days 1, 8, 15, and cisplatin on day 1. A total of 24 patients (16 male, 8 female; median age 57; median performance status 1) received 69 courses of therapy. Six dose levels were explored, with cisplatin/ brequinar doses, respectively, of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2. The serum concentration versus time curves for brequinar were biphasic. A comparison of the pharmacokinetic results after the first and third doses of brequinar indicate that the presence of 50, 60, and 75 mg/m2cisplatin did not change the protein binding and the pharmacokinetics of brequinar in any of the three brequinar-dose groups. Total cisplatin plasma pharmacokinetic followed a triphasic-shape curve and unbound cisplatin decayed at a very rapid rate. Since pharmacokinetic parameters for total cisplatin in this study were similar to those reported in the literature, the presence of brequinar is unlikely to alter the pharmacokinetics of cisplatin. Main dose-limiting toxicities included myelosuppression (including neutropenia and thrombocytopenia) and mucositis. Cisplatin/brequinar doses of 50/500, 50/650, 50/860, 60/860, 75/650, and 75/860 mg/m2, were associated with dose limiting toxicity in 0/3, 1/3, 1/3, 1/3, 2/4, 2/5, and 4/6 patients, respectively. This study shows that co-administration of brequinar and cisplatin does not affect the pharmacokinetic properties of either drug and that the MTDs of cisplatin/brequinar combinations are 60/860 mg/m2 or 75/650 mg/m2. From this study, we conclude that full dose of 75 mg/m2 cisplatin (day 1) can be administered with 650 mg/m2 brequinar (days 1, 8 and 15) without significant modifications of individual drug pharmacokinetic parameters.
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The importance of definition and post-discharge wound surveillance on reported wound infection rates have been studied, using data taken from a prospective, randomized, placebo-controlled, double-blind trial of the effect of whole body disinfection on postoperative wound infection rates. All patients admitted for an elective clean or potentially contaminated surgical procedure over a 32-month period were recruited into the study. Of the 3733 patients recruited, 3466 completed the study. Wound infection (which is defined for this study) is the main outcome that was examined. The effect of careful post-discharge follow-up of patients to look for wound infections was analysed for age, wound type and presence or absence of a drain. Sixty percent of postoperative wound infections occurred after discharge. A rising wound infection rate with increasing age was observed in the in-hospital cohort whereas the incidence of outpatient wound infections declined with age. This finding is attributed to the longer in-hospital stay encountered in patients above 50 years old (median, 3 vs. 5 days, P < 0.00001). Although clean operations had a significantly lower in-hospital infection rate, potentially contaminated procedures had a lower outpatient infection rate. A similar picture was observed in other subgroups of operations including horizontal versus vertical wounds and use of drains. When assessing reported wound infection rates, the definition of wound infection used and the extent of follow-up must be known to enable accurate assessment of the results.
The characteristics of two types of intraperitoneal (i.p.) soilage sepsis models, autologous fecal inoculum (FEC) and a pure culture of Escherichia coli (EC), were studied in 26 male Yucatan minipigs (20-30 kg). Early (1-4 h) and late (24-72 h) changes were different between the two groups. The EC group was characterized early by hypotension, low cardiac output, and increased systemic and pulmonary vascular resistances, along with leukopenia, hypoglycemia, lactacidemia, and elevated blood urea nitrogen. Of the pigs in the EC group that survived the early effects, there were few significant differences in physiological parameters, compared to control pigs, that would indicate ongoing pathological processes. In contrast, the FEC group pigs demonstrated early hypotension, but with increased cardiac output and reduced systemic vascular resistance. Other parameter changes were similar to those seen in the EC pigs, but to a lesser degree, with the exception of elevations in serum lactate dehydrogenase. Also in contrast to the EC group, most of the changes in the FEC group persisted in later days, and FEC pigs demonstrated leukocytosis. There were also greater elevations in circulating lipopolysaccharide (LPS) concentrations in the EC group that returned later to baseline levels. In the FEC group, there were persistently elevated LPS concentrations over 72 h. These observations suggest that pigs challenged with intraperitoneal E. coli demonstrated an initial acute peritonitis and damaging physiologic effects of high levels of circulating LPS. Survivors in this group improved and were physiologically stable after 24 h. Pigs that received i.p. autologous feces developed an early acute peritonitis phase with lower levels of circulating LPS, and later developed pronounced peritoneal reaction as demonstrated by multiple abdominal abscesses, pyogenic granuloma formation, and adhesions with physiological evidence of developing sepsis over 72 h. These observations indicate that i.p. EC models evoke a systemic response not unlike intravenous administration of LPS or EC, however, the FEC model produced a systemic response akin to a slower developing septic process.
Primary screw fixation of a Type II odontoid fracture or non-union is an attractive alternative to posterior atlanto-axial arthrodesis in that normal cervical motion can be maintained. Eight cervical cadaver spines, ranging in age from 17-90 years, were used for study. Type II fractures of the dens were created using an osteotome. Simulated fractures were fixed using one or two 3.5-mm bone screws. After testing each screw fixation technique, the screws were removed and a posterior C1-C2 brooks sublaminar wiring was performed using four 18-gauge wires with wooden blocks to simulate bone graft. No significant differences were found between bending and torsional stiffnesses for the one-screw and two-screw specimens. No significant differences were found between one- and two-screw fixation when compared with primary C1-C2 wiring in torsion. One- or two-screw fixation was as stiff as primary C1-C2 wiring in bending. One or two screws offers similar stability for fixation for a dens fracture. One- and two-screw fixation is at least as stiff as primary C1-C2 wiring in torsion and one- or two-screw fixation is stiffer than primary C1-C2 wiring in bending.
A total of 3482 general surgical patients entered a trial in which they had a chlorhexidine or placebo detergent shower three times before elective clean wound or potentially contaminated surgery. Patients who showered with a chlorhexidine detergent (N = 1744) had a significant reduction in skin flora compared with those who showered with a placebo detergent (N = 1738). The majority of wound infections occurred outside hospital (312 outpatient infections vs. 201 inpatient infections). Wound infection rates were similar in the chlorhexidine and placebo groups (5.79% vs. 5.75% for inpatient infections and 8.54% vs. 9.38% for outpatient infections). The average hospital cost of both non-infected and infected patients was higher in the chlorhexidine group. The average cost of a non-infected chlorhexidine patient was 847.95 pounds as opposed to 804.60 pounds for a non-infected placebo patient, whilst the average cost of an infected patient was 1459.70 pounds (chlorhexidine) and 1414.22 pounds (placebo). A cross-match comparison of patients undergoing vascular surgery revealed no statistical significance in the difference between the two experimental groups. Patients were matched for age, sex, type of operation and surgeon. We conclude that preoperative whole-body disinfection with a chlorhexidine detergent is not a cost-effective treatment for reducing wound infection.
This study compares the utilization costs of ceftazidime therapy with those of gentamicin in combination with other antibacterial drugs. The results show that the relatively high purchase cost of ceftazidime compared to combinations is more than counterbalanced by the additional materials used for drug administration and serum antibiotic assays, even when other drugs were combined with ceftazidime. The average drug and equipment costs were 230.13 pounds for ceftazidime regimens and 253.94 pounds for gentamicin regimens. It is also shown that ceftazidime therapy is associated with a reduction in personnel time compared to gentamicin regimens. The average times per patient for administration and assay were 1 h 43 min for ceftazidime and 4 h 57 min for gentamicin regimens. We conclude that ceftazidime regimens are cheaper than gentamicin regimens when all drug and equipment costs are quantified. Moreover, the use of ceftazidime will release staff time for other purposes.
Seventeen patients with advanced melanoma and no prior exposure to chemotherapy were treated with brequinar sodium as first-line chemotherapy. Brequinar was given at a median weekly dose of 1200 mg/m2 intravenously. In 14 patients evaluable for efficacy, there were no objective responses. The toxicity was moderate. We conclude that, at this dose and schedule, brequinar has no activity in advanced melanoma.
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