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Biomedical subjects

K Hirsch

Publications and source records attributed to K Hirsch.

14 recordsLinked to original sources

Transmyocardial laser revascularization remodels the intrinsic cardiac nervous system in a chronic setting.

BACKGROUND: Prospective trials have demonstrated that transmyocardial laser revascularization (TMLR) imparts symptomatic relief to patients with refractory angina. Because peak clinical effectiveness of TMLR is usually delayed by several months, it has been proposed that ventricular denervation is one mechanism whereby TMLR imparts symptomatic relief. We have demonstrated that TMLR does not denervate the heart in the acute setting, nor does it modify the intrinsic cardiac nervous system (ICNS) in the acute setting. However, the long-term effects of TMLR on the ICNS remain unknown. METHODS AND RESULTS: A holmium:yttrium-aluminum-garnet laser created 20 channels through the anterolateral left ventricular free wall of 10 dogs. Four weeks later, the function of cardiac sensory inputs to the ICNS was studied by applying veratridine (7.5 micromol/L) to ventricular sensory fields. Chronotropic and inotropic responses elicited by cardiac sympathetic or parasympathetic efferent neurons stimulated electrically (10 Hz, 4 V, 4 ms) or chemically (nicotine 5 to 20 microgram/kg IV) were also assessed. Chemical activation of epicardial sensory neurites with veratridine elicited expected ICNS excitatory responses. Electrical stimulation of sympathetic and parasympathetic efferent neurons induced expected altered cardiac responses. In contrast, the responsiveness of the ICNS to systemically administered nicotine was obtunded. CONCLUSIONS: Although chronic TMLR does not affect cardiac afferent or extracardiac efferent neuronal function, it does "remodel" the ICNS so that its responsiveness to a known potent chemical agonist (ie, nicotine) becomes obtunded. Remodeling of the ICNS may account in part for the delayed symptomatic relief that TMLR imparts to patients with refractory angina.

Action Potentials↗

Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27(Kip1) in the cyclin E-cdk2 complexes.

Numerous studies have demonstrated the anticancer activity of the tomato carotenoid, lycopene. However, the molecular mechanism of this action remains unknown. Lycopene inhibition of human breast and endometrial cancer cell growth is associated with inhibition of cell cycle progression at the G(1) phase. In this study we determined the lycopene-mediated changes in the cell cycle machinery. Cells synchronized in the G(1) phase by serum deprivation were treated with lycopene or vehicle and restimulated with 5% serum. Lycopene treatment decreased serum-induced phosphorylation of the retinoblastoma protein and related pocket proteins. This effect was associated with reduced cyclin-dependent kinase (cdk4 and cdk2) activities with no alterations in CDK protein levels. Lycopene caused a decrease in cyclin D1 and D3 levels whereas cyclin E levels did not change. The CDK inhibitor p21(Cip1/Waf1) abundance was reduced while p27(Kip1) levels were unaltered in comparison to control cells. Serum stimulation of control cells resulted in reduction in the p27 content in the cyclin E--cdk2 complex and its accumulation in the cyclin D1--cdk4 complex. This change in distribution was largely prevented by lycopene treatment. These results suggest that lycopene inhibits cell cycle progression via reduction of the cyclin D level and retention of p27 in cyclin E--cdk2, thus leading to inhibition of G(1) CDK activities.

Adenocarcinoma↗

Adefovir dipivoxil for the treatment of lamivudine-resistant hepatitis B mutants.

Lamivudine has been shown to be an effective therapy for chronic hepatitis B, but resistance to this nucleoside agent is common after prolonged use. Five patients with chronic hepatitis B virus (HBV) infection developed resistance to lamivudine after 9 to 19 months of treatment. In 4 patients this occurred after liver transplantation and the remaining individual had stable cirrhosis. In each case, resistance was confirmed to be caused by one or more mutations in the HBV-DNA polymerase gene and was associated with active underlying liver disease. The patients were treated with adefovir dipivoxil in a dose of 5 to 30 mg daily. Two to 4 log(10) reductions in HBV-DNA levels were observed in 4 cases, and the fifth patient became negative by quantitative polymerase chain reaction (PCR) after retransplantation in conjunction with hepatitis B immunoglobulin (HBIg). Virologic improvement was associated with stable or declining serum alanine transaminase levels in 4 patients. HBV-DNA suppression has been sustained during a mean treatment period of 13 months (range 11 to 15 months), including 1 patient in whom lamivudine has been discontinued. Mild changes in renal function were observed during treatment in most cases but did not require early discontinuation of the drug. This study provides evidence that adefovir dipivoxil can be an effective treatment for lamivudine-resistant HBV mutants as well as wild-type HBV.

Adenine↗

Effect of purified allicin, the major ingredient of freshly crushed garlic, on cancer cell proliferation.

The diverse health benefit effects of garlic include its anticancer activity. However, very little is known about such activity of isolated garlic compounds, among which allicin (the major ingredient of crushed garlic) has been the least studied. The aim of this work was to determine whether pure allicin exhibits the antiproliferative effect reported for garlic in in vitro models. Allicin, but not its precursor alliin, inhibited proliferation of human mammary (MCF-7), endometrial (Ishikawa), and colon (HT-29) cancer cells (50% inhibitory concentration = 10-25 microM). Two of three tested primary lines of human fibroblasts displayed a similar response to allicin (50% inhibitory concentration = 16-40 microM), whereas the third line was almost unaffected by this compound. The pure allicin and water extract of garlic powder with equivalent allicin concentrations displayed a similar potency, suggesting that allicin is responsible for the antiproliferative effect of the extract. The growth inhibition was accompanied by accumulation of cells in the G0/G1 and G2/M phases of the cell cycle (MCF-7 cells) and not by a significant increase in cell death. Allicin caused a transient drop in the intracellular glutathione (GSH) level, the magnitude and kinetics of which significantly varied depending on cell type. The extent of the decrease in GSH levels correlated well (r = 0.75) with the growth inhibitory activity of allicin. On the basis of these findings, we suggest that allicin plays a major role in the antiproliferative effect of water-soluble garlic preparations and that this effect may be attributed to the ability of allicin to transiently deplete the intracellular GSH level.

Antineoplastic Agents, Phytogenic↗

Surgeon-patient communication in the treatment of pancreatic cancer.

BACKGROUND: Effective physician-patient communication has been correlated with patient satisfaction and improved outcome. Pancreatic cancer (PC) is a disease with an overwhelmingly poor prognosis that requires a complex level of communication and emotional support. Since the treatment of PC is often surgical, surgeons play a central role in the care of these patients. OBJECTIVES: To assess the quality of long- and short-term surgeon-patient communication. To assess the role of the surgeon in the emotional support of patients with PC. DESIGN: Combined mail and telephone survey of a case series of patients who had undergone a pancreatic resection for PC. SETTING: Urban tertiary cancer referral center. PATIENTS: Forty-eight patients who underwent pancreatic resection for PC. INTERVENTION: Pancreatic resection. MAIN OUTCOME MEASURE: Patient satisfaction. RESULTS: Forty-eight patients completed surveys for a response rate of 70%. Patients were extremely satisfied with the information provided by their surgeon before surgery and while in the hospital. However, 21% of patients reported an unexpected outcome of their operation and 27% had questions about their disease at the time of the survey. Patients were largely satisfied with the emotional support they had received while in the hospital and after discharge. The attending surgeon was the most commonly desired source of additional emotional support. CONCLUSIONS: While surgeon-patient communication was extremely effective before surgery and during hospitalization, patients developed long-term questions and dissatisfaction after discharge from the hospital. Strategies to improve long-term support and communication would benefit a significant number of patients with operable PC. Surgeons play an important role in the emotional support of patients with operable PC.

Adult↗

Blunt abdominal trauma in children: risks of nonoperative treatment.

This retrospective study includes 203 children who had intraabdominal injuries after blunt trauma, mainly bicycle accidents and falls. Of 145 patients with splenic injury, seven underwent surgery. There was a 100% splenic salvage rate. Twenty-nine children had hepatic injury and four underwent laparotomy. One patient who was initially treated conservatively had a complicated clinical course with rebleeding that led to two laparotomies. Three of 10 pancreatic injuries were operated on; one of them 4 weeks after the trauma because of a pseudocyst. Nineteen patients had gastrointestinal tract injuries. Of seven intramural hematomas, five were treated nonoperatively. Twelve patients had gastrointestinal perforations. Seven underwent laparotomy without delay. Three patients underwent surgery 24 hours after admission because of severe abdominal rigidity or pneumoperitoneum. There was one case of severe in-hospital delay in which splenic and hepatic injuries were thought to account for the physical findings. At laparotomy 36 hours after admission, a jejunal rupture and necrosis of the transverse colon were found. Nonoperative management of blunt abdominal trauma has been very successful regarding splenic ruptures. Conservative management of hepatic injuries is more hazardous, and treatment of pancreatic injuries is a matter of controversy. Gastrointestinal-tract perforations are difficult to diagnose and important to bear in mind while keeping a conservative attitude toward abdominal trauma.

Adolescent↗

Prophylactic antibiotics in uncomplicated appendicitis during childhood--a prospective randomised study.

544 children operated upon for uncomplicated appendicitis were randomised into three groups. Group I received no antibiotics, patients in Group II were administered one single pre-operative dose of metronidazole (10 mg/kg) and patients in Group III received both both metronidazole (20 mg/kg) and cefuroxime (50 mg/kg) in a single preoperative dose. The rate of infectious complications in Group I was 6.3% but only 2.1 and 2.3 in Groups II and III, respectively. Among patients with a normal appendix or patients with simple appendicitis there was no difference in the rate of post-operative infections between the three different groups. However, in patients with gangrenous appendicitis the rate of postoperative infections was significantly lower in the two groups who received preoperative antibiotics (1.8% and 3.0% respectively) than in the group receiving no prophylactic antibiotics (infection rate 14%). It is concluded that a single preoperative dose of metronidazole significantly decreases the rate of postoperative infectious complications in children with appendicitis. No further improvement could be demonstrated if cefuroxime against aerobic organisms was added.

Adolescent↗

Optimization of irradiation conditions for photon activation analysis of biological and environmental samples using a high power electron accelerator.

Using the bremsstrahlung flux density data of Tanaka et al. (1983), the PHOTAC code has been developed to calculate the activity induced in a sample during photon activation as a function of the geometrical arrangement of the electron energy and the beam profile. Some results are given for sample volumes from 1 to 1000 cm3 and sample distances from 1 to 10 cm at 25 MeV. Examples for the application of the PHOTAC code to estimate the maximum activity output and to minimize the heating up of the sample during irradiation are discussed.

Activation Analysis↗

[Stress-induced changes in blood glucose level in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) aged 13-14 and 26 weeks].

In normotensive WKY-rats and spontaneously hypertensive rats relations were investigated between the general stress related behaviour of adaptation and the blood glucose level under fasting condition. In respect to the level of blood glucose differences were existent specifically depending on age and strain. Compared with WKY-rats, spontaneously hypertensive rats on the same age had shown a higher stress related increase of blood glucose level. Furthermore an age depending increase of blood glucose level was found in both SHR and WKY-rats. These differences depending on strain and age are discussed including the further results about the influence of peptides on catecholamins and blood pressure regulation.

Animals↗

Carcinoma within urethral diverticula.

Because diagnosis of urethral diverticulum is often elusive the presence of a tumor within the diverticular cavity may be overlooked until it has grown beyond the confines of the diverticulum. A search of the medical records from 1940 to 1975 at the University of California Medical Center in San Francisco and Alta Bates Hospital in Berkeley has revealed only 3 cases of carcinoma within a urethral diverticulum. Two are presented here and the third was reported by Hinman in 1960. The paucity of cases in the literature reflects the rarity of such location for the tumor--or, perhaps, rather its evasive diagnostic nature. Undoubtedly, many cases are unreported but the important message for the clinician is that he suspect a urethral diverticulum (with the possibility of underlying neoplasm) in any patient with unexplained persistent irritative symptoms of the lower genitourinary tract.

Adenocarcinoma↗

The fate of retained gallstones following laparoscopic cholecystectomy in a prairie dog model.

BACKGROUND AND OBJECTIVES: Reported complications of retained gallstones following laparoscopic cholecystectomy (LC) are increasing. This study was undertaken to evaluate the effects of retained gallstones following LC in a prairie dog model. METHODS: Twenty-seven prairie dogs with diet-induced gallstones were divided into three groups of nine. Group I (control) had LC with removal of stones. Group II had LC followed by return of native stones intra-abdominally. Group III had LC followed by return of infected stones (stones dipped in Escherichia coli) intra-abdominally. Animals were euthanized at two months and the character and extent of intra-abdominal adhesions were scored. RESULTS: Adhesions were present in 56% of animals in Group I, 89% in Group II, and 100% in Group III. The character and extent of adhesions in groups II & III were significantly greater than the control group (p < 0.03). Group III exhibited the highest degree of adhesions when compared to control (p < 0.007). Histopathology revealed evidence of micro-abscess formation, foreign body giant cell reaction, and fat necrosis adjacent to retained stones. CONCLUSION: Retained intra-abdominal gallstones, especially if infected, are associated with increased adhesions and inflammatory response in this LC model. Further investigation into the long-term consequences of this entity is warranted.

Animals↗