Biomedical subjects
Publications and source records attributed to J Kauffman.
The synthesis and in vitro Class III antiarrhythmic activity of several 4-aroyl (and aryl)-1-aralkylpiperazine and piperidine derivatives are described. Among several potent compounds identified in the series, RWJ-28810 (3), with its EC20 of 3 nM, ranks as one of the most potent (in vitro) compounds reported.
Chronic pain patients who have limited access to opioids may be redirected to methadone maintenance centers for management of their pain. Unfortunately, little information exists on the incidence and characteristics of methadone maintenance patients with chronic pain. The aim of this study was to survey individuals at methadone maintenance centers in order to determine the prevalence of chronic pain and to explore differences between patients with and without pain in this treatment setting. Of 248 participants interviewed at three centers, 152 (61.3%) reported chronic pain. Compared with patients without pain, those with pain reported significantly more health problems (P < 0.001), more psychiatric disturbance (P < 0.05), more prescription and nonprescription medication use (P < 0.001), and greater belief that they were undertreated (P < 0.001); 44% of those with pain believed that opioids prescribed for their pain had led to an addiction problem. Most of the methadone maintenance patients stated that they had always required some substance (alcohol or opioids) to feel normal. These results raise many questions about chronic-pain treatment policies and resources for persons with a history of substance abuse. Further investigations are needed to define the needs of this population and to improve their access to effective pain management.
Interference with polyamine transport and biosynthesis has emerged as an important anticancer strategy involving polyamine analogues and specific inhibitors of key biosynthetic enzymes. Because the prostate gland has a high polyamine content, by using the polyamine transporter for selective uptake into cancer cells, alkylating polyamines are likely to be highly effective against prostatic tumors. We have recently synthesized a novel class of spermine analogues, the lead compound of which has efficacy against human cancer cells (P. S. Callery et al., U. S. patent, 5,612,239, Issued March 17, 1997.). In this study, to investigate the potential therapeutic efficacy of the lead spermine analogue 1,12-diaziridinyl-4, 9-diazadodecane (BIS), against advanced prostate cancer, we examined the in vitro effect and in vivo efficacy of the compound in two androgen-independent human prostate cancer cell lines, PC-3 and DU-145. BIS exhibited a dose-dependent cytotoxic effect against prostate cancer cells via induction of apoptosis. Treatment of cells with BIS (1 microM) for 24 h resulted in a significant induction of apoptosis (24%). Exposure of BIS-treated PC-3 prostate cancer cells to gamma-irradiation resulted in a significant increase in the number of cells undergoing apoptosis and a subsequent decrease in the IC50. Furthermore, BIS treatment led to a significant enhancement of loss of clonogenic survival in irradiated prostate cancer cells (both PC-3 and DU-145). In vivo efficacy trials demonstrated a significant antitumor effect of BIS against both PC-3 and DU-145 tumor xenografts in severe combined immunodeficient mice in a dose-dependent pattern at maximally tolerated doses. Terminal transferase end-labeling analysis indicated that BIS-mediated tumor regression in vivo occurs via induction of apoptosis among prostatic tumor cells. These results suggest that the novel spermine analogue BIS: (a) has a potent antitumor effect against prostatic tumors via induction of apoptosis; and (b) increases the radiosensitivity of human prostate cancer cells by decreasing the apoptotic threshold to radiation. This study may have important clinical implications for the manipulation of this antitumor activity of the polyamine analogue for the optimization of the therapeutic efficacy of radiation in patients with advanced prostate cancer.
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Despite recent advances in its understanding and treatment, addiction remains a difficult challenge for clinicians within medical settings such as the general hospital. The use of single, traditional paradigms (disciplinary, therapeutic, educational, or libertarian) for approaching addiction-related problems have often failed to embrace the complexity of the patients' motivation to change. Prochaska and DiClemente's [7] stage of change model offers a realistic, practical, and broadly applicable means by which clinicians can facilitate behavioral change from the stage of denial (precontemplation) through that of sustained recovery (maintenance). Clinicians can help addicted individuals to move from precontemplation to contemplation by enhancing their ambivalence; from contemplation to preparation by considering their history of change; from preparation to action by flexibly intervening based on this understanding; and from action to maintenance by evaluating the outcomes of these interventions. A stage of change model is also useful in understanding the process of change in clinicians' own approaches to patients with substance use disorders.
Seasoned board members from two dynamic health systems--Centura Health and Crozer-Keystone Health System--point to the CEO's commitment to the system and its mission as the critical element in keeping the board focused.
BACKGROUND: Although performing mouth-to-mouth resuscitation (MMR) during cardiopulmonary resuscitation (CPR) is an effective lifesaving procedure, both the general public and physicians are often unwilling to perform CPR. Fear of contracting infectious diseases, especially AIDS, is often stated as the reason for this reluctance. However, the likelihood of saving a life usually outweighs the chance of contracting an infectious disease, especially when victims are considered to be at low risk for being HIV+ and are in communities with low incidences of HIV antibodies. METHODS: The entire housestaff (58 residents) in the Department of Internal Medicine of a suburban hospital responded to a questionnaire of hypothetical cardiac arrest scenarios in both inpatient and outpatient settings. Their responses were compared to those previously obtained from the housestaff (82 residents) of a hospital in a large metropolitan area with a high incidence of HIV positive patients. RESULTS: The willingness of the suburban housestaff (residents) to perform MMR in the inpatient scenario of a patient with an unknown risk for communicable infections was 43%, with trauma was 12%, with a perceived high risk for being HIV+ was 14%, and in the elderly was 29%, compared to 45, 16, 7 and 39%, respectively of the house staff of the metropolitan hospital. In outpatient scenarios, the willingness of the suburban housestaff to perform MMR on a victim with an unknown risk for communicable infections was 50%, with trauma was 33%, with a perceived high risk for being HIV+ was 34%, in the elderly was 26%, and in a child was 86%, compared to 54, 36, 21, 65, and 99%, respectively, of the metropolitan residents. Overall, the suburban male residents were more likely to be willing to perform MMR than the female ones, as were residents actively practising a religion or having graduated from medical schools in the United States. Suburban residents under 30 years of age seemed more willing to perform MMR in the majority of the scenarios than those over 30 years of age. Of the 31 suburban residents that stated they would be unwilling to perform MMR in at least one of the given scenarios, all stated that their unwillingness was due to fear of becoming infected with HIV or other infectious agents. In 1994, the percentage of known HIV positive individuals admitted to the suburban hospital was approximately five times less than that of the metropolitan hospital whose house staff was interviewed (P < 0.001). CONCLUSIONS: Patients perceived to be at high risk for HIV were less likely to receive MMR than those at low risk. The reluctance of house staff to perform MMR in a suburban community hospital with a low incidence of HIV+ patients is similar to that of house staff in a large metropolitan community with a much higher incidence of infected patients. This reluctance, which was largely due to fear of contracting HIV infections, is not influenced by frequent contact with patients infected with HIV but is based on perceived rather than actual risks of contracting HIV. To increase the willingness of physicians, other medical personnel, and the lay public to perform MMR on victims of cardiac and respiratory arrests, the negligible risk of contracting infectious diseases while performing MMR should be emphasized. Use of portable barrier masks while performing MMR and an increase in their availability would decrease the minimal risks even further, and is recommended by the authors.
OBJECTIVE: Medical house staff are required to perform cardiopulmonary resuscitation (CPR) as part of their job responsibilities. Previously it has been shown that house staff are reluctant to perform mouth-to-mouth resuscitation (MMR) in an out of hospital setting. Therefore, whether reluctance to perform MMR extends to the inpatient setting, and, if so, the reasons for this reluctance were investigated. DESIGN: All 74 internal medicine house officers of a large metropolitan hospital responded to presentations of hypothetical inpatient cardiac arrest scenarios to assess their willingness to perform MMR. SETTING: A 1200 bed university-affiliated teaching hospital in Los Angeles, California. SUBJECTS: All categorical internal medicine house officers at this hospital. INTERVENTIONS: This study is a survey which concerns whether the house officer would perform mouth-to-mouth resuscitation in different hypothetical cardiac arrest scenarios. RESULTS: Forty-five percent would perform MMR on an unknown patient and 39% would perform MMR in the elderly patient scenario. Only 16% would do MMR on a patient with a small amount of blood on his lips and only 7% would perform MMR on a patient with presumed acquired immunodeficiency syndrome. Medical housestaff were much more reluctant to perform MMR on elderly, trauma, or presumed immunodeficient patients in an inpatient setting than in an outpatient setting. All house staff that indicated their unwillingness to perform MMR cited fear of human immunodeficiency virus infection as their reason. CONCLUSION: Medical housestaff are quite reluctant to perform MMR in an inpatient setting. Thus, educating the medical house staff about the percent of patients that survive inpatient cardiac arrest and the actual risks of contracting infectious diseases, especially HIV infections, from MMR and preventative measures, such as effective barrier masks, should result in an increased willingness of physicians to perform MMR or mouth-to-mask ventilation on inpatients.
BACKGROUND: Physicians and nurses constitute a major part of citizen cardiopulmonary resuscitation responders and serve as educators and resource personnel concerning cardiopulmonary resuscitation. We decided to determine if fear of infectious disease has dampened physician and nurse response to perform mouth-to-mouth resuscitation (MMR). METHODS: Four hundred thirty-three internists and one hundred fifty-two medical nurses responded to presentations of mock cardiac arrest scenarios. RESULTS: Forty-five percent of the physicians and 80% of the nurses would refuse to do MMR on a stranger. Between 18% and 25% of nurses and attending internists would not do MMR on a child. Being born in the United States or white racial background decreased the reluctance of the respondents to perform MMR. Only 15% of the respondents would do MMR on a stranger in a gay neighborhood. All respondents that would not do MMR stated that their reason involved fear of contracting communicable diseases, especially acquired immunodeficiency syndrome. CONCLUSIONS: Internists and medical nurses are highly reluctant to perform MMR. We recommend that the teaching of MMR should emphasize performance on children and family members where willingness to perform MMR is high. We urge public education along with widespread availability of effective barrier masks to resuscitate MMR itself.
In 1987, a patient presented with pulmonary sarcoidosis and progressive renal failure. Percutaneous renal biopsy showed focal glomerular sclerosis (FGS). Over the subsequent 4-year period, her renal failure progressed to require hemodialysis. During this time, her pulmonary sarcoidosis was treated with daily corticosteroid therapy and she remained in clinical remission. The patient received a one-haplotype-identical living-related renal transplant from her mother. The patient is now 25 months posttransplant with a serum creatinine of 106 mumol/L (1.2 mg/dL). Her sarcoidosis continues to be in clinical remission. In this report, we review the rare association of a primary glomerular lesion causing renal failure in patients with sarcoidosis. In addition, we detail the first successful renal transplant in such a patient.
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Experiments were carried out in pregnant nephrectomized rabbits to determine the relationship between uterine blood flow and uterine renin secretion. Uterine blood flow was measured by the percentage distribution of radioactive microspheres injected into the left ventricle which lodged in uterus and placenta, and cardiac output was measured by dye dilution. In 40 animals, 24 hr after nephrectomy, uterine blood flow was 4.7+/-0.4% of cardiac output and absolute flow 32.4+/-3 ml/100 g per min. Plasma renin activity (PRA) in uterine vein, 994+/-182 ng/100 ml per hr, was higher than in carotid artery, 832+/-143 (P < 0.025). With reduction of uterine blood flow from 4.7+/-0.5 to 1.95+/-0.3% of cardiac output and absolute flow from 30.8+/-4.6 to 8.8+/-2 ml/100 g per min, uterine vein PRA rose from 1434+/-234 to 4430+/-300 (P < 0.001), and carotid artery PRA from 1009+/-200 to 2300+/-350 (P < 0.01). Hemorrhagic hypotension caused uterine vein PRA to increase from 913+/-293 to 3638+/-1276 (P < 0.001) and carotid artery PRA from 774+/-252 to 1730+/-433 (P < 0.01). Uterine blood flow expressed as a percentage of cardiac output remained constant after hemorrhage, 5.5+/-0.9 and 6.3+/-0.8%, although absolute flow fell from 37+/-7.7 to 29+/-3.6 ml/100 g per min because of the large fall in cardiac output which occurred.Angiotensin, 10 ng/kg per min, caused no significant change in blood pressure or cardiac output but increased uterine blood flow from 4.1+/-0.6 to 8.4+/-1% (P < 0.005) of cardiac output with absolute flow increasing from 37.4+/-7 to 73.2+/-10 ml/100 g per min (P < 0.001). The increase in uterine blood flow during angiotensin was abolished by the prior administration of propranolol. Isoproterenol, 0.5 mu/min, increased uterine blood flow from 3.5+/-0.6 to 6.4+/-1.2% of cardiac output (P < 0.02) with absolute flow increasing from 25+/-5 to 51+/-12 ml/100 g per min (P < 0.05). Norepinephrine, 500 ng/min, caused no significant change in uterine blood flow. These findings suggest that uterine renin might be involved in regulating uterine blood flow, secretion being increased in response to a reduction in flow with the resultant rise in circulating or local angiotensin, through beta adrenergic stimulation, increasing uterine blood flow.
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