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Biomedical subjects

John F Madden

Publications and source records attributed to John F Madden.

5 recordsLinked to original sources

Bradykinin receptor subtype 1 expression and function in prostate cancer.

Kinins exert multiple pathophysiological functions, including vascular permeability and mitogenesis, by activating their cognate receptors, bradykinin subtype 1 receptor (B1R) and bradykinin subtype 2 receptor (B2R), which belong to the superfamily of G protein-coupled receptors. Tissue-specific expression pattern or contribution of the individual kinin receptors to pathological prostate cell growth is not known. We report here the differential expression of B1R and B2R in human benign and malignant prostate specimens. Whereas B2R is ubiquitously expressed, the B1R is detected only in prostatic intraepithelial neoplasia and malignant lesions and not in benign prostate tissues. Using androgen-insensitive prostate cancer PC3 cells, we show that specific stimulation of endogenous B1R promotes cell growth, migration, and invasion. These findings identify B1R as an early marker for pathological growth of the prostate and suggest its potential utility as a drug target effective for the treatment of prostate cancer.

Biopsy↗

Liposarcoma presenting as an intraluminal ureteral mass.

An 86-year-old woman with a previous excision of a large retroperitoneal low-grade liposarcoma presented with a 4-month history of persistent left flank discomfort. Workup revealed left hydronephrosis secondary to obstruction, which was caused by a recurrent liposarcoma in the intraluminal ureter. She underwent a left nephroureterectomy for symptomatic palliation. Pathologic study revealed high-grade liposarcoma. Despite negative surgical margins, the tumor rapidly recurred, leading to death only 4 months after surgery. This case highlights the aggressive nature of liposarcoma.

Aged↗

Laser Doppler flowmetric determination of ureteral blood flow after ureteral access sheath placement.

BACKGROUND AND PURPOSE: The ureteral access sheath has positively impacted ureteroscopy by decreasing operative times and increasing success rates. However, as previous studies have suggested that large-caliber endoscopes may cause ureteral ischemia, concern has been raised about the impact of access sheath insertion on ureteral blood flow. We sought to determine whether the access sheath compromises ureteral blood supply and, if so, causes ischemic damage to the ureter during ureteroscopic procedures. MATERIALS AND METHODS: Using a swine animal model, ureteral blood flow was measured with a laser Doppler flowmeter. Eleven ureteral units were randomized into four study groups: those dilated with 10F-12F, 12F-14F, and 14F-16F access sheaths (N = 3 per group) and an undilated control group (N = 2). Blood flow measurements were obtained from the proximal ureter via laser Doppler flowmetry for 70 minutes at 5-minute intervals. Hemodynamic variability was controlled for through intraoperative heart rate and oxygen saturation monitoring, as well as a second Doppler probe that was placed on the animal's skin, from which readings were also taken every 5 minutes. Results were correlated with histopathologic findings. RESULTS: The control group demonstrated little ureteral blood flow variability over the course of 70 minutes. The study groups that were dilated with sheaths, however, all showed a decrease in ureteral blood flow after access sheath insertion, with the flow in animals dilated with 12F-14F and 14F-16F sheaths dropping below 50% of baseline. This initial drop in blood flow was followed by a gradual increase from nadir toward baseline values over the course of the study. On average, the 14F-16F group reached nadir more quickly and took longer to restore its ureteral blood flow. All animals remained hemodynamically stable throughout the study, showing only minimal variability in heart rate, oxygen saturation, and skin blood flow over the 70-minute experiment. Histologically, there was no evidence of ischemic damage in any of the study groups at 72 hours. CONCLUSIONS: In this animal model, the access sheath does cause a transient decrease in ureteral blood flow. Nonetheless, compensatory mechanisms of the ureteral wall restore blood flow to near-baseline rates and preserve urothelial integrity, suggesting that use of the ureteral access sheath remains a safe adjunct to flexible ureteroscopy. Because the chronic effects of the access sheath have yet to be elucidated, care must be taken in selecting an appropriate-size sheath for each individual case. Preventive measures may be available to help avoid sheath-related ureteral injury in those patients identified as high risk.

Animals↗

Emergency department personnel use seatbelts almost all the time: what do they know that average Delawareans don't?

A survey was sent to each emergency department in Delaware and each county Emergency Medical Service (EMS) Advanced Life Support (paramedic) service asking seven questions on risk-taking behavior. Within the survey were the following four questions regarding seatbelt use: a) Do you wear a seatbelt while driving? b) Do you require others in your car to wear seatbelts? c) When you are a passenger in a car, do you wear a seatbelt? d) Has the seatbelt law in Delaware impacted your seatbelt use? The three possible responses were "never," "sometimes," and "always." The remaining three questions were confouders and asked about cigarette smoking and driving under the influence of alcohol. Replies were divided into the following job categories: 1) emergency physician (EP), emergency department (ED) physician assistant (PA) or nurse practitioner (NP), 2) emergency nurse, 3) paramedic, or 4) ED clerk, respiratory therapist (RT), or other emergency support personnel. A total of 313 surveys was returned by 78 physicians, NPs and PAs; 115 paramedics; and 115 clerks, RTs, and other support personnel. Overall, 86 percent of respondent stated that they always wear seatbelts with 99 percent of EPs/PAs and NPs responding always. Overall, 83 percent stated that they require others to wear seatbelts in their automobiles. Eighty-four percent wear seatbelts while a passenger in someone else's car. The physician, PA, and NP group had the greatest "always" response rate as compared to the other groups.

Allied Health Personnel↗

Lithium toxicity: two case reports.

Lithium has many medical and psychiatric uses. These include cluster and migraine headaches, alcoholism, impulsive behavior, and bipolar disorder. Toxicity from lithium can occur by overdose (intentional or accidental) or, more commonly, from alteration in its clearance by the kidney. We present two cases of lithium toxicity. The first is a 57-year-old male who presented with confusion, ataxia, and lethargy. The second case involves a 52-year-old female with bizarre behavior who was unable to care for herself. Both patients received dialysis and recovered without sequelae.

Female↗