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Biomedical subjects

R Kaplan

Publications and source records attributed to R Kaplan.

At least 19 recordsLinked to original sources

Efficacy of bowel preparation with the use of a prepackaged, low fibre diet with a low sodium, magnesium citrate cathartic vs. a clear liquid diet with a standard sodium phosphate cathartic.

BACKGROUND: A colon free of faecal residue is required for accurate diagnostic colonoscopy. Patient tolerance of his/her colonoscopy cathartic regimen affects patient compliance and willingness to undergo repeated examinations. AIM: To determine whether a meal could be consumed during standard bowel preparation. METHODS: This was a randomized, endoscopists' blinded comparison of the tolerability and efficacy of a prepackaged, low-residue diet (NutraPrep) combined with the LoSo Prep bowel cleansing system, which contains magnesium citrate, bisocodyl tablets and a bisocodyl suppository (NP-LS regimen), compared with a clear liquid diet and a double-dose sodium phosphate (Fleet Phospho-soda) regimen (2F regimen). Outcome measures included efficacy of bowel preparation, patient preparation tolerability, side-effects and patient safety. RESULTS: A total of 506 patients completed the study, 222 randomized to 2F and 284 to NP-LS. The NP-LS regimen resulted in significantly better colon cleansing in terms of the proportion with good or excellent results (P = 0.025) and in significantly better patient tolerance and willingness to repeat the cathartic preparation (P < 0.01). CONCLUSION: The NP-LS regimen proved superior to the 2F regimen.

Bisacodyl↗

Gait velocity in senior people. An easy test for detecting mobility impairment in community elderly.

BACKGROUND: Functional assessment is an important part of the evaluation of elderly patients. Mobility problems detected by functional tests predict the development of more severe disability and injurious events such as falls and hip fractures. Several tests to evaluate mobility have been described, but most of them are difficult to perform by a primary care physicians or take much time in the ambulatory setting. PURPOSE: To evaluate different mobility test to detect mobility impairment in community senior people. Select an easier test to perform on the ambulatory ward by a GP with the hypothesis that gait velocity could be an easier test to detect early mobility impairment. METHODS: A cohort of 100 elderly subjects of 75 year and older were selected from our database and contacted by phone. The subjects were appointed and assessed by three geriatricians from January to May 2000. The measures including MMSE, Yesavage Test, ADL (Barhtel) and IADL (Lawton), the Get Up and Go test, the POMA, one leg balance test and the Gait Velocity (GV). A gait velocity of 0.8 m/s or lower was defined as a pathological gait velocity (PGV). RESULTS: 95 subjects, mean age 79.63 (+/- 4) ranged form 75 to 95. Women in 71.3%. The ADLs were normal on 85% of the patients and the MMSE was normal on 78%. There was a significant association between pathological gait velocity (<0.8m/sec) and impairment on Get up and Go (OR 2.20; 95% CI 1.44-3.34), incapacity to perform the one leg balance test (OR 2.20; 95%CI: 1.43 - 4.71) and abnormal POMA test (OR 4.60; 95 %CI 1.5-14.7). Only 15% of the subjects with normal gait velocity reported recurrent falls in the previous 6 months while 35% of subjects with pathological gait velocity did. (OR 0.32 CI95% 010-099 p < 0.044). CONCLUSION: The pathological gait velocity (<0.8m/sec) correlates with a pathologic performance of Get Up and Go test and POMA and with the incapacity to perform the One Leg Balance test. Also correlate with previous repeated falls in the last 6 (p <0.04). The gait velocity could be a test easy to perform, no time consuming, and an operative tool to apply in the ambulatory care to detect elderly patients with mobility impairment.

Accidental Falls↗

Reverse microdialysis of N-methyl-D-aspartic acid into the lateral hypothalamus of rats: effects on feeding and other behaviors.

The effects of reverse microdialysis of N-methyl-D-aspartic acid (NMDA) into the lateral hypothalamus (LH) on feeding and other behaviors were examined. Consistent with similar studies utilizing central microinjections, NMDA reverse microdialysed into the rat LH rapidly elicited a strong concentration-dependent stimulation of feeding. The minimum perfusate concentration of NMDA needed to elicit feeding with reverse microdialysis was 660 microM, a concentration 1/50 of that needed with pressure injections. Further, eating responses could be consistently elicited in sequential tests separated by 2-4 h in the same subject, and the magnitude of the eating in the first and second tests was highly correlated (r=0.87). Behavioral analysis revealed that the main response to NMDA consisted of eating without the concomitant hyperactivity produced by central microinjections of this agonist. The other behaviors exhibited during NMDA administration were those that normally occur during spontaneous feeding in rats. Also, rats precisely compensated for the increased food intake elicited by NMDA by reducing spontaneous feeding during the subsequent nocturnal phase, so as to maintain normal daily intakes. In contrast, N-methyl-L-aspartate (NMLA) reverse microdialysed in to the LH (660 microM) did not elicit feeding nor affect any other behaviors we examined. These data support a role for LH glutamate and NMDA receptors in the control of feeding.

Animals↗

Volume-outcome relation for physicians and hospitals performing angioplasty for acute myocardial infarction in New York state.

BACKGROUND: An inverse relation exists between the number of coronary angioplasty procedures performed by physicians or hospitals and short-term mortality. It is not known, however, whether a similar relation holds for physicians and hospitals that perform primary angioplasty for acute myocardial infarction. METHODS AND RESULTS: We analyzed data from the 1995 New York State Coronary Angioplasty Reporting System Registry to determine the relation between the number of primary angioplasty procedures performed by physicians and hospitals and in-hospital mortality. Patients who underwent angioplasty procedures within 23 hours of onset of acute myocardial infarction without preceding thrombolytic therapy were included (n=1342). In-hospital mortality was reduced 57% among patients who underwent primary angioplasty by high-volume as opposed to low-volume physicians (adjusted relative risk 0.43; 95% CI 0.21 to 0.83). When patients with acute myocardial infarction were treated with primary angioplasty in high-volume hospitals rather than low-volume institutions, the relative risk reduction for in-hospital mortality was 44% (adjusted relative risk 0.56; 95% CI 0.29 to 1.1). Compared with patients treated at low-volume hospitals by low-volume physicians, patients treated at high-volume hospitals by high-volume physicians had a 49% reduction in the risk of in-hospital mortality (adjusted relative risk 0.51; 95% CI 0.26 to 0.99). CONCLUSIONS: Among hospitals in New York State, a higher volume of primary angioplasty procedures performed by physicians and/or hospitals was associated with a lower mortality rate.

Angioplasty, Balloon, Coronary↗

Dual mechanisms of ABCA1 regulation by geranylgeranyl pyrophosphate.

ATP-binding cassette transporter A1 (ABCA1) mediates an active efflux of cholesterol and phospholipids and is mutated in patients with Tangier disease. Expression of ABCA1 may be increased by certain oxysterols such as 22(R)-hydroxycholesterol via activation of the nuclear hormone receptor liver X receptor (LXR). In searching for potential modulators of ABCA1 expression, we have studied the effects of various mevalonate metabolites on the expression of ABCA1 in two human cell lines, THP-1 and Caco-2 cells. Most of the tested metabolites, including mevalonate, geranyl pyrophosphate, farnesyl pyrophosphate, and ubiquinone, failed to significantly change the expression levels of ABCA1. However, treatment with geranylgeranyl pyrophosphate resulted in a dose- and time-dependent reduction of ABCA1 expression. Geranylgeranyl pyrophosphate appears to reduce ABCA1 expression via two different mechanisms. One of these mechanisms is by acting directly as an antagonist of LXR since it reduces the interaction between LXR alpha or -beta with nuclear coactivator SRC-1. Another mechanism appears to involve activation of the Rho GTP-binding proteins since treatment of Caco-2 cells with inhibitors of geranylgeranyl transferase or the Rho proteins significantly increased the expression and promoter activity of ABCA1. Further studies showed that mutations in the DR4 element of the ABCA1 promoter completely eliminate the inducible activities of these inhibitors. These data indicate that activation of the Rho proteins may change the activation status of LXR.

ATP Binding Cassette Transporter 1↗

Measuring the incremental cost of clinical cancer research.

PURPOSE: To summarize evidence on the costs of treating patients in clinical trials and to describe the Cost of Cancer Treatment Study, an ongoing effort to produce generalizable estimates of the incremental costs of government-sponsored cancer trials. METHODS: A retrospective study of costs will be conducted with 1,500 cancer patients recruited from a randomly selected sample of institutions in the United States. Patients accrued to either phase II or phase III National Cancer Institute-sponsored clinical trials during a 15-month period will be asked to participate in a study of their health care utilization (n = 750). Costs will be measured approximately 1 year after their trial enrollment from a combination of billing records, medical records, and an in-person survey questionnaire. Similar data will be collected for a comparable group of cancer patients not in trials (n = 750) to provide an estimate of the incremental cost. RESULTS: Evidence suggests insurers limit access to trials because of cost concerns. Public and private efforts are underway to change these policies, but their permanent status is unclear. Previous studies found that treatment costs in clinical trials are similar to costs of standard therapy. However, it is difficult to generalize from these studies because of the unique practice settings, insufficient sample sizes, and the exclusion of potentially important costs. CONCLUSION: Denials of coverage for treatment in a clinical trial limit patient access to trials and could impede clinical research. Preliminary estimates suggest changes to these policies would not be expensive, but these results are not generalizable. The Cost of Cancer Treatment Study is an ongoing effort to provide generalizable estimates of the incremental treatment cost of phase II and phase III cancer trials. The results should be of great interest to insurers and the research community as they consider permanent ways to finance cancer trials.

Clinical Trials as Topic↗

Multifocal carcinoid tumor resembling a solitary tumor: report of a case.

A laparotomy was performed on a 44-year-old male patient with an acute abdomen who had findings suggestive of acute appendicitis and a periappendicular abscess. A histopathological examination revealed a carcinoid tumor infiltrating the intestinal serosa. The distal ileum and cecum were infiltrated with more than 40 multifocal tumors, with the largest measuring 1 cm in size. The distal ileum and cecum were resected. We failed to find any distant metastases either peroperatively or during postoperative scintigraphic tests. In addition, the patient had no symptoms of carcinoid syndrome either before or after surgery. No recurrence was experienced. We thus conclude that primary multifocal carcinoid tumors may act as a solitary carcinoid tumor, and the largest tumor tends to indicate the overall clinical outcome.

Adult↗

Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light.

BACKGROUND: Aminolevulinic acid hydrochloride (ALA, Levulan) applied topically to actinic keratoses (AKs) leads to accumulation of the photosensitizer protoporphyrin IX, which, when activated by exposure to light, eradicates AKs. OBJECTIVE: We examined the safety and efficacy of photodynamic therapy using topical 20% ALA in a solution formulation and varying blue light doses to treat multiple AKs on the face and scalp. METHOD: This is a multicenter, investigator-blinded, randomized, vehicle-controlled study. RESULTS: Thirty-six patients with clinically typical AKs were treated with 20% ALA; 14 to 18 hours later, they were irradiated with a nonlaser fluorescent blue light source. With the optimal light dose of 10 J/cm(2), 88% of the AKs completely cleared 8 weeks after a single photodynamic treatment, compared with 6% after treatment with vehicle and light. CONCLUSION: Topical ALA PDT using a nonlaser, blue light source is an effective treatment for multiple AKs.

Administration, Topical↗

The effect of the menstrual cycle on acne.

Acne is a common disease with an underlying hormonal basis; however, there has never been a study to determine the ways in which the different stages of the menstrual cycle affect acne in women. Four hundred female participants, aged 12 to 52 years, were questioned whether their acne got worse before, during, or after their menstrual period and also asked whether it was unrelated to the menstrual period. Their age, severity of acne, ethnicity, and oral contraceptive use were also recorded. Overall 177 of 400 (44%) of those interviewed experienced premenstrual flares of their acne. Severity of acne, ethnicity, and oral contraceptive use did not affect the premenstrual flare rate. Women older than 33 years had a higher rate of premenstrual flares relative to women aged 20 to 33 years (P =.03 by chi(2) analysis). We concluded that almost half of all women experience premenstrual flares of their acne. Premenstrual flares may be more common in older women.

Acne Vulgaris↗

Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element.

Diesel exhaust particles (DEP) contain organic chemicals that contribute to the adverse health effects of inhaled particulate matter. Because DEP induce oxidative stress in the lung and in macrophages, effective antioxidant defenses are required. One type of defense is through the expression of the antioxidant enzyme, heme oxygenase I (HO-1). HO-1 as well as phase II detoxifying enzymes are induced via antioxidant response elements (ARE) in their promoters of that gene. We show that a crude DEP total extract, aromatic and polar DEP fractions, a benzo(a)pyrene quinone, and a phenolic antioxidant induce HO-1 expression in RAW264.7 cells in an ARE-dependent manner. N-acetyl cysteine and the flavonoid, luteolin, inhibited HO-1 protein expression. We also demonstrate that the same stimuli induce HO-1 mRNA expression in parallel with the activation of the SX2 enhancer of that gene. Mutation of the ARE core, but not the overlapping AP-1 binding sequence, disrupted SX2 activation. Finally, we show that biological agents, such as oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, could also induce HO-1 expression via an ARE-dependent mechanism. Prior induction of HO-1 expression, using cobalt-protoporphyrin, protected RAW264.7 cells against DEP-induced toxicity. Taken together, these data show that HO-1 plays an important role in cytoprotection against redox-active DEP chemicals, including quinones.

Acetylcysteine↗

The role of a mitochondrial pathway in the induction of apoptosis by chemicals extracted from diesel exhaust particles.

We are interested in the cytotoxic and proinflammatory effects of particulate pollutants in the respiratory tract. We demonstrate that methanol extracts made from diesel exhaust particles (DEP) induce apoptosis and reactive oxygen species (ROS) in pulmonary alveolar macrophages and RAW 264.7 cells. The toxicity of these organic extracts mimics the cytotoxicity of the intact particles and could be suppressed by the synthetic sulfhydryl compounds, N-acetylcysteine and bucillamine. Because DEP-induced apoptosis follows cytochrome c release, we studied the effect of DEP chemicals on mitochondrially regulated death mechanisms. Crude DEP extracts induced ROS production and perturbed mitochondrial function before and at the onset of apoptosis. This mitochondrial perturbation follows an orderly sequence of events, which commence with a change in mitochondrial membrane potential, followed by cytochrome c release, development of membrane asymmetry (annexin V staining), and propidium iodide uptake. Structural damage to the mitochondrial inner membrane, evidenced by a decrease in cardiolipin mass, leads to O-*2 generation and uncoupling of oxidative phosphorylation (decreased intracellular ATP levels). N-acetylcysteine reversed these mitochondrial effects and ROS production. Overexpression of the mitochondrial apoptosis regulator, Bcl-2, delayed but did not suppress apoptosis. Taken together, these results suggest that DEP chemicals induce apoptosis in macrophages via a toxic effect on mitochondria.

Air Pollutants↗

A titrated morphine analgesic regimen comparing substance users and non-users with AIDS-related pain.

To compare morphine dosage and effectiveness in AIDS patients with/without prior substance use and pain, a prospective, open-label case series lasting 3-18 days was conducted in both outpatients and inpatients at major pain service teaching programs. Forty-four patients, 13 with prior drug use history, who had pain associated with HIV infection or its treatment were administered sustained-release morphine (SRM) every 12 hours. The dose was titrated to pain relief for a period of > or =3 consecutive days (associated with < or =2 immediate-release morphine tablets per 24 hours), or until the patient discontinued from the study or completed 18 study days. Forty-four patients were enrolled (13 with a prior drug use history). Forty were evaluable for an intent-to-treat analgesia, including 11 with a drug use history. Twenty-four (6 users) completed this study. Former users and non-users were similar in demographics, baseline pain intensities, causes of pain, discontinuation, quality of life, and acceptability of therapy. Pain intensity decreased by > or =50% in both groups (P < or = 0.0001). To identify a stable dose, the dose of SRM more than doubled in former users and rose by 31% in non-users (mean final dose 177.4 mg and 84.9 mg, respectively) (P = 0.0018). Immediate-release morphine decreased in both; former users required more (P = 0.0006). These data suggest the utility of morphine for AIDS-related pain. Patients with a prior drug use history benefited but required substantially more morphine.

Acquired Immunodeficiency Syndrome↗

Allergic reaction to spinal cord stimulator.

OBJECTIVE: The objective was to report on the possibility of allergic reaction to the components of a spinal cord stimulator. DESIGN: We describe a severe allergic reaction after the insertion of a spinal cord stimulator in a patient with complex regional pain syndrome type 1. SETTING: The patient was being followed in an office-based pain management practice. PATIENT: The patient is a 41-year-old woman with complex regional pain syndrome type 1, posttrauma. INTERVENTION: Insertion of a cervical and lumbar spinal cord stimulator. OUTCOME MEASURES: The outcome measures were a numerical scale of pain intensity and the ability to perform the activities of daily living. RESULTS: Adequate pain control complicated by allergic reaction. CONCLUSIONS: There exists a possibility that a patient may experience an allergic reaction to spinal cord stimulator components. Recognition of such contact sensitivity is important for physicians implanting such devices. Patients may be misdiagnosed as having infections, which can delay appropriate management; definitive diagnosis can be confirmed with a patch test. Treatment consists of removal of such devices.

Adult↗