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R T Zera

Publications and source records attributed to R T Zera.

At least 19 recordsLinked to original sources
PubMed2001

The impact of managed care and current governmental policies on an urban academic health care center.

BACKGROUND: Managed care and governmental policies have restructured hospital reimbursement. We examined reimbursement trends in trauma care to assess the impact of this market driven change on an urban academic health center. METHODS: Patients injured between January 1997 and December 1999 were analyzed for Injury Severity Score (ISS), length of hospital stay, hospital cost, payer, and reimbursement. RESULTS: Between 1997 and 1999, the volume of patients with an ISS less than 9 increased and length of stay decreased. In addition, overall cost, payment, and profit margin increased. Commercially insured patients accounted for this margin increase, because the margins of managed care and government insured patients experienced double-digit decreases. Patients with ISS of 9 or greater also experienced a volume increase and a reduction in length of stay; however, costs within this group increased greater than payments, thereby reducing profit margin. Whereas commercially insured patients maintained their margin, managed care and government insured patients did not (double- and triple-digit decreases). CONCLUSIONS: Managed care and current governmental policies have a negative impact on urban academic health center reimbursement. Commercial insurers subsidize not only the uninsured but also the government insured and managed care patients as well. National awareness of this issue and policy action are paramount to urban academic health centers and may also benefit commercial insurers.

Academic Medical Centers↗
PubMed2001

Atypical hyperplasia, proliferative fibrocystic change, and exogenous hormone use.

BACKGROUND: The association between breast cancer development and exogenous hormone use (EHU) is suggested by indirect clinical evidence. We undertook this study to better define the relationship that EHU has with proliferative fibrocystic change (PFC) and atypical hyperplasia (AH). METHODS: Women diagnosed with AH without associated carcinoma from January 1990 to December 1999 were compared with control subjects who underwent breast biopsy procedures during the same interval and who were diagnosed with either a proliferative fibrocystic change (PFC) or a nonproliferative fibrocystic change (NPFC). EHU was defined as the use of estrogen or progesterone taken together or separately within 3 months of biopsy. RESULTS: EHU was significantly higher in patients with AH compared with women with NPFC (P =.01). This observation was also significant if all proliferative change (both AH and PFC) was compared with NPFC (P =.03); it was not significant when PFC alone was compared with NPFC. No significant difference in EHU was demonstrated between women with AH and those with PFC. CONCLUSIONS: There is strong association between AH and EHU. These results support the theory that a continuum exists between hyperplasia and carcinoma and that EHU may influence the transition from one to the other in an undefined subset of women. We encourage our patients with AH to discontinue EHU.

Adult↗
PubMed2000

Academic practice groups: strategy for survival.

BACKGROUND: The mission of public academic health centers (puAHC) and their affiliated practice groups (APG) focuses on teaching, research, and the clinical care of at-risk populations. Resources to accomplish this mission, however, are becoming scarce. For puAHC to survive and remain competitive, innovative strategies will need to be developed by the APG. We hypothesized that the integration of a surgical academic practice of the APG with a nonacademic integrated health care delivery system (NAIDS) in a managed care environment would benefit all involved. METHODS: A surgical academic practice was integrated with a NAIDS in a 95% managed care market. Faculty alone provided care the first year, and third-year residents were added the following year. To assess outcome, we collected benefit and cost data for the 1-year period before integration and compared them with the two, 1-year periods after integration. RESULTS: In the second year of integration, revenues from the NAIDS referrals to the puAHC and APG increased 89% and 150%, respectively. The NAIDS' general surgical and endoscopy caseload increased by 25%. Additionally, there was a 92% reduction in operating room technician cost with no increase in operating time per case. Finally, the third-year resident experienced a caseload increase of 163%. CONCLUSIONS: In an environment where resources are diminishing and managed care consists of many large NAIDS that drive referrals and revenue, the integration of a surgical academic practice with a NAIDS benefits all shareholders. Academic practice groups that develop strategies that leverage their competitive advantage will have the best chance of surviving in today's turbulent health care market.

Academic Medical Centers↗
PubMed2000

Stapled versus hand sewn anastomoses in patients with small bowel injury: a changing perspective.

INTRODUCTION: Recent studies indicate that trauma patients with hollow viscus injuries requiring anastomosis who are managed with stapling have a higher rate of complications than do those in whom a hand-sewn anastomosis is used. We undertook this study to determine whether this finding applied to patients with small bowel trauma at our institution. METHODS: Records of patients with small bowel injuries were retrospectively reviewed. Demographics, severity of injury, injury management, and outcome data were collected. RESULTS: Patients who had their small bowel injuries managed by hand-sewn repair versus resection and stapled anastomosis demonstrated a nonsignificant decrease in overall complication rate (35% vs. 44%) and rate of intra-abdominal complication (10% vs. 18%). Yet the rate of intra-abdominal abscess formation was significantly lower with hand-sewn repair than with resection and stapled anastomosis (4% vs. 13%). However, when hand-sewn primary repairs were excluded from the analysis and injuries that required resection and either stapled or hand-sewn anastomosis were compared, there was a similar overall complication rate (41% vs. 41%) and rate of intra-abdominal complications (17% vs. 21%). CONCLUSION: The rate of intra-abdominal complications did not differ significantly between patients requiring small bowel resection and reanastomosis managed by either a stapled or hand-sewn technique. In our experience, surgical stapling devices appear to be safe for use in repairing traumatic small bowel injury.

Abdominal Injuries↗
PubMed1999

Civilian rectal trauma: a changing perspective.

BACKGROUND: Recently the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma developed a Rectal Injury Scaling System (RISS). Little data exist regarding its clinical utility. METHODS: We retrospectively reviewed 45 patients with rectal injuries to assess the impact of the RISS on patient management and outcome. We compared RISS grade I patients (group I, partial-thickness injury) with patients with grades 2, 3, and 4 injuries (group II, full-thickness injury). RESULTS: Group II underwent distal rectal washout and repair of the injury twice as often and had a significantly higher rate of diversion of the fecal stream. This was associated with a 3-fold increase in complications. The only complications in group I were in patients managed with diversion of the fecal stream and distal rectal washout. CONCLUSIONS: Our data suggest that aggressive surgical management for RISS grade I injury may not be necessary. Implementation of therapy based on the RISS may improve outcomes of civilian rectal trauma.

Adolescent↗
PubMed1998

Differential chemoprotection against acetaminophen-induced hepatotoxicity by latentiated L-cysteines.

Novel thiazolidine prodrugs were prepared by the condensation of L-cysteine with aldose disaccharides. Using a disaccharide in prodrug construction allows for a terminal cyclic sugar moiety to be present on the prodrug, which may allow the delivery of the agent to specific receptors, such as the asialoglycoprotein receptor (ASGPR) of hepatocytes, that require specific structural motifs for recognition. Three L-cysteine prodrugs were synthesized with a pendant cyclic galactose moiety; two related glucose-bearing prodrugs were synthesized for comparison. The prodrugs were designed to release L-cysteine, which is then available to support glutathione (GSH) biosynthesis and provide cytoprotection against a variety of toxic insults. Protection studies in Swiss-Webster mice used acetaminophen (575 mg/kg), a well-documented hepatotoxin which depletes GSH at overdose. Three prodrugs performed exceptionally well against acetaminophen-induced hepatotoxicity, as measured by increased survival and improved histological profiles of liver tissue after 48 h. In further experimentation, two of the disaccharide-based prodrugs, prepared from alpha- and beta-lactose, were compared with the monosaccharide-based compound prepared from ribose. Co-administration of the selected prodrugs with a 400 mg/kg dose of acetaminophen to Swiss-Webster mice prevented the short-term depletion in hepatic GSH and also reduced hepatotoxicity as determined by histological damage and serum levels of alanine aminotransferase. A single dose of the prodrugs alone had no effect on hepatic drug metabolizing enzymes [glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase (QOR), UDP-glucuronosyltransferase (UGT), and cytochrome P450], but, concordant with the reduction of hepatotoxicity, the latentiated forms prevented the significant elevation in QOR activity and mRNA and GST mRNA elicited by acetaminophen itself. GST activity, UGT activity and mRNA, and cytochrome P450 concentration were all unaffected by acetaminophen or the prodrugs. These studies identified novel L-cysteine prodrugs with potentially useful hepatoprotective activity. However, no structure-activity relationships were obvious. In addition, the occurrence of targeted delivery to hepatocytes remains ambiguous.

Acetaminophen↗
PubMed1998

Assessment of the relationship between timing of fixation of the fracture and secondary brain injury in patients with multiple trauma.

BACKGROUND: It has been suggested that early fixation of a fracture is deleterious to eventual neurologic outcome. We undertook this study to determine whether the timing of fracture fixation is correlated to neurologic outcome. METHODS: We retrospectively reviewed patients with severe head and orthopedic injuries requiring fracture fixation. Patients were divided into two groups: early fracture fixation (< 24 hours after injury) and late fracture fixation (> 24 hours after injury). RESULTS: One hundred twenty-three patients met entry criteria. During fracture fixation, the early group had a significant 2-, 3-, and 2-fold increase in crystalloid, blood infusion, and blood loss, respectively. There was no difference in oxygen saturation and systolic blood pressure or episodes of cranial hypertension or hypoperfusion. There was no difference in outcomes as measured by in-hospital complications, stay in the intensive care unit or hospital, mortality rates, hospital discharge or follow-up Glasgow Coma Scores, or long-term orthopedic or neurologic results. CONCLUSIONS: Patients undergoing fracture fixation with severe head injury mandate monitoring of intracranial pressure and perfusion and tailored fluid resuscitation to meet specific organ end points. Integrating end organ perfusion and pressure with meticulous fluid status during the definitive repair phase may reduce the exposure to secondary brain injury in patients undergoing early fracture fixation.

Adult↗
PubMed1997

Mastalgia. Tailoring treatment to type of breast pain.

Breast pain is a common, often distressing problem among women. After significant disease is ruled out, most patients respond to simple reassurance. Others, however, require treatment because symptoms interfere with their lifestyle. The authors offer practical suggestions for tailoring treatment for these patients according to type of pain--cyclical mastalgia, non-cyclical mastalgia, or chest wall pain.

Breast↗
PubMed1996

Preliminary biological evaluation of polyamidoamine (PAMAM) Starburst dendrimers.

PAMAM Starburst dendrimers are spherical macromolecules composed of repeating polyamidoamino units. They can be produced in successive "generations," each with a defined size, molecular weight, and number of terminal amino groups. Because of these well-defined characteristics, PAMAMs are finding utility in a variety of applications, many of which are biological in nature. Little is known, however, about the biological behavior of the PAMAMs, which is critical to their use in vivo. Generation 3 (G3; MW = 5,147; 24 terminal amines), 5 (G5; MW = 21,563; 96 amines), and 7 (G7; MW = 87,227; 384 amines) PAMAMs were studied in V79 cells or in Swiss-Webster, mice for a number of biological properties, including (1) in vitro toxicity, (2) in vivo toxicity, (3) immunogenicity, and (4) biodistribution. Potential biological complications were observed only with G7 at the highest level tested. No evidence of immunogenicity was seen. The biodistribution properties of the Starburst dendrimers were rather unusual. G3 showed the highest accumulation in kidney tissue (approximately 15% ID/g over 48 h); G5 and G7 appeared to preferentially localize in the pancreas (peak levels approximately 32% ID/g at 24 h, and approximately 20% ID/g at 2 h, respectively). In addition, G7 showed extremely high urinary excretion, with values of 46 and 74% ID/g at 2 and 4 h, respectively. In general, the dendrimers did not exhibit properties that would preclude their use in biological applications. Depending on the situation (desired endpoint, dose, and generation used), however, the biodistribution of biological preparations should be carefully studied.

Animals↗
PubMed1995

Efficacy of radioprotective agents in preventing small and large bowel radiation injury.

PURPOSE: A variety of adjuvant treatments and cytoprotective agents have been proposed to lessen the toxicity of radiation therapy. The following study was designed to evaluate the benefit of six agents or combinations using anastomotic bursting strength as a measure of transmural radiation injury. METHODS: The 40-Gy study consisted of the following. Seventy-two male Sprague-Dawley rats were divided into eight equal groups: nonradiated control, radiated untreated control, and six radiated treated groups. The radioprotective treatments included ribose-cysteine (Rib-Cys), WR-2721, glutamine, vitamin E, MgCl2/adenosine triphosphate, and RibCys/glutamine in combination. Radiated animals received 40 Gy to the abdomen. Two weeks after radiation, all animals underwent small bowel and colonic resection with primary anastomosis. Animals were sacrificed one week postoperatively, at which time anastomoses were evaluated and bursting strengths determined. The 70-Gy study consisted of the following. The same protocol was repeated for five groups of nine rats divided into nonradiated, radiated untreated, and three radiated treated groups receiving RibCys (8 mmol/kg), RibCys (20 mmol/kg), and WR-2721. All radiated animals received 70-Gy doses. RESULTS: In the 40-Gy group, there were 10 radiation-related deaths and 6 anastomotic leaks among 70 rats studied. None of the differences between groups were significant. Nonradiated control group small bowel and large bowel anastomotic bursting pressures were significantly elevated compared with all radiated groups. Compared with radiated controls, there were significant improvements in small bowel bursting strength in the RibCys, WR-2721, RibCys-glutamine, and vitamin E groups and significant improvement in colonic bursting strength in MgCl2/adenosine triphosphate, WR-2721, and RibCys groups. In the 70-Gy group, all nine nonradiated control rats survived. All eight untreated radiated control rats died, four of eight WR-2721 animals died (P = 0.03), all RibCys (8 mmol/kg) animals died (P = 0.03), and three of nine treated with RibCys (20 mmol/kg) survived (P = 0.08). CONCLUSIONS: WR-2721 and RibCys gave consistent protection against large and small bowel radiation injury. The lower incidence of treatment-related toxicity and potentially equal or greater radioprotective effects may make RibCys more clinically useful than WR-2721.

Adenosine Triphosphate↗
PubMed1993

Objective evaluation of endoscopy skills during training.

OBJECTIVE: To evaluate the number of supervised gastrointestinal endoscopic procedures required to achieve initial competency using a simple objective grading system. DESIGN: Prospective, cross-sectional study. SETTING: A gastroenterology and surgical training program at a large, university-affiliated county hospital. PARTICIPANTS: Seven gastroenterology fellows and five fourth-year surgery residents. INTERVENTIONS: Trainees were graded postprocedure using a microcomputer program. Grading criteria for esophagogastroduodenoscopy included entering the esophagus (esophageal intubation), traversing the pylorus into the duodenum, and recognizing whether the upper gastrointestinal tract was abnormal. Criteria for colonoscopy were traversing the splenic flexure, intubating the cecum, and recognizing whether the colon was abnormal. RESULTS: When presented with a case mix representative of practice, esophageal intubation did not reach 90% until more than 100 procedures had been done. Cecal intubation remained at only 84% after 100 procedures. CONCLUSIONS: More than 100 supervised upper gastrointestinal endoscopies or colonoscopies are necessary to achieve technical competence in gastrointestinal endoscopy.

Clinical Competence↗
PubMed1993

Comparison of bursting pressure of sutured, stapled and BAR anastomoses.

The study was undertaken to compare anastomotic bursting pressure (ABP) of colorectal canine anastomoses using three different anastomotic techniques. Biofragmentable anastomotic ring (BAR), stapled, and sutured colon anastomoses were sequentially placed in each of 48 dogs following division of the colon at three equally spaced sites. Four groups of 12 dogs were sacrificed either on day 0, 3, 7, or 28 and ABP and bursting wall tension were determined. The data revealed that BAR anastomoses have the greatest strength on the day of surgery, sutured anastomoses are the strongest on the third day and all are comparable by the 7th day. Bursting pressures for all groups by day 28 approach normal colonic bursting pressure, with any differences likely to be a reflection of variation in anastomotic fibrosis and other factors.

Anastomosis, Surgical↗
PubMed1993

Protective effect of RibCys following high-dose irradiation of the rectosigmoid.

UNLABELLED: Ribose-cysteine (RibCys) is a prodrug of L-cysteine that stimulates glutathione biosynthesis. Increased glutathione levels have been shown to have a protective effect against radiation-induced injury and oxidative stress. Surface oximetry has previously been used successfully to predict anastomotic leakage. PURPOSE: The following study was done to evaluate the protective effect of RibCys and the predictive value of PtO2 determinations in a swine model. METHODS: Domestic swine were divided into three groups: Group A served as a nonradiated control; Group B received 6,000 to 6,500 rad to the rectosigmoid; and Group C received RibCys (1 g/kg) prior to receiving 6,000 to 6,500 rad. Radiated animals and controls underwent rectosigmoid resection after a three-week rest period. Intraoperative anastomotic PtO2 was checked with a modified Clark electrode. Anastomoses were evaluated radiographically at three and seven days; animals were sacrificed, and bursting strength was recorded at 10 days. RESULTS: Mean bursting pressures were 243.8 +/- 59.4, 199.5 +/- 37.8, and 209.5 +/- 54.9 mmHg (NS) for Groups A, B, and C, respectively. Anastomotic PtO2 ranged from 19 to 98 mmHg and could not be correlated with anastomotic leaks or bursting pressure. There were 11/15 radiation-related deaths and leaks (eight deaths and three leaks) in the radiated group and 4/12 radiation-related deaths and leaks (three deaths and one leak) in the group receiving radiation and RibCys (P < 0.04). CONCLUSIONS: 1) RibCys protected animals against radiation-related deaths and anastomotic leaks following high doses of pelvic irradiation; 2) anastomotic PtO2 levels did not correlate with anastomotic healing in this model.

Anastomosis, Surgical↗
PubMed1992

Protection against acetaminophen hepatotoxicity by ribose-cysteine (RibCys).

2(RS)-D-ribo-(1',2',3',4'-Tetrahydroxybutyl)thiazolidine-4(R)-carb oxylic acid (Ribose-Cysteine, RibCys), a latent form of L-cysteine, releases the sulfhydryl amino acid in vivo by non-enzymatic ring opening and solvolysis. The liberated L-cysteine then stimulates hepatic glutathione biosynthesis. In the present studies, the efficacy of hepatoprotection by RibCys was evaluated to explore its potential utility as an acetaminophen (APAP) antidote. Protection was evaluated in the Swiss-Webster mouse model both by survival data as well as by quantitative histological criteria of hepatic damage. A dose-response study showed increased protection with increased intraperitoneal doses of RibCys ranging from 0.5 to 8.0 mmol/kg. RibCys administration 30 min. prior to and up to four hours after the APAP dose showed varying degrees of protection; however, the best protection was seen when RibCys was given shortly after APAP administration. A single RibCys dose given by the intraperitoneal or intravenous route gave better protection than when administered orally; however, RibCys given in three doses, one hour apart, regardless of the mode of administration, offered the best protection after an LD90 dose of APAP. Overall, RibCys continues to exhibit promising protective capabilities against APAP hepatotoxicity, which may be capitalized upon in clinical overdose situations.

Acetaminophen↗
PubMed1991

L-cysteine prodrug protects against cyclophosphamide urotoxicity without compromising therapeutic activity.

2(R,S)-D-ribo-(1',2',3',4'-Tetrahydroxybutyl)-thiazolidine-4(R)-ca rboxylic acid (RibCys) is a prodrug of L-cysteine that releases the sulfhydryl amino acid after nonenzymatic ring opening and hydrolysis. The L-cysteine then elevates glutathione (GSH) levels by stimulating its biosynthesis. RibCys was investigated for its ability to protect CDF1 mice from the potent urotoxicity of cyclophosphamide (CTX) without compromising the therapeutic utility of the drug. RibCys induced a significant reduction in weight loss of the animals and in bladder inflammation at 48 h after CTX administration; however, bladder tissue remained inflamed as compared with that in controls. Bladder histology also showed some pathological changes in the presence of RibCys. In contrast, all parameters of toxicity (body weight loss, bladder inflammation, and pathological abnormalities) had been virtually reversed by day 21 after administration. In tests against L1210 leukemia, RibCys did not interfere with CTX anticancer activity. From these preliminary studies, RibCys appears to be a likely candidate for protecting against long-term CTX toxicity, perhaps reversing the original damage caused by a very high dose, without compromising the therapeutic utility of the alkylating agent.

Animals↗
PubMed1987

Prodrugs of L-cysteine as protective agents against acetaminophen-induced hepatotoxicity. 2-(Polyhydroxyalkyl)- and 2-(polyacetoxyalkyl)thiazolidine-4(R)-carboxylic acids.

Eight prodrugs of L-cysteine (1a-h) were synthesized by the condensation of the sulfhydryl amino acid with naturally occurring aldose monosaccharides containing three, five, and six carbon atoms. The resulting 2-(polyhydroxyalkyl)thiazolidine-4(R)-carboxylic acids (TCAs) are capable of releasing L-cysteine and the sugars by nonenzymatic ring opening and hydrolysis. Thus, when added to rat hepatocyte preparations in vitro, these TCAs (1.0 mM) raised cellular glutathione (GSH) levels 1.2-2.1-fold relative to controls. On the basis of this finding, the cysteine prodrugs were tested as protective agents against acetaminophen-induced hepatotoxicity in a mouse model. The TCA derived from D-ribose and L-cysteine (RibCys, 1d) showed the greatest therapeutic promise of the series, with a 100% (12/12) survival profile compared to 17% without treatment. However, the degree of stimulation of GSH production in rat hepatocytes by these prodrugs did not correlate with the extent of protection afforded in mice, suggesting that pharmacokinetic parameters must supervene in vivo. To evaluate the effect of increased lipid solubility, we prepared prodrugs 2a-c by using peracetylated aldehydic sugars in the condensation reaction. These compounds, however, displayed acute toxicity to mice, possibly due to liberation of the acetylated sugars themselves. Nevertheless, the efficacy of the unacetylated TCAs, and RibCys (1d) in particular, suggests that the prodrug approach for the delivery of L-cysteine to the liver represents a viable means of augmenting existing detoxication mechanisms in protecting cells against xenobiotic substances that are bioactivated to toxic, reactive metabolites.

Acetaminophen↗