Feeding increases dopamine metabolism in the rat brain.

Feeding induced by food deprivation is accompanied by an increased production of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the brains of rats. This neurochemical change occurs in the nucleus accumbens, the posterior hypothalamus, and the amygdala but not in other dopaminergic nerve terminal fields such as the corpus striatum. These results indicate that the release of dopamine from particular groups of central neurons is increased during feeding and suggest that anatomically distinct subgroups of central dopaminergic neurons serve different roles in the regulation of food intake.

Compartmentation of catecholamines in rat brain: effects of agonists and antagonists.

The subsynaptosomal distributions of dopamine (DA) in striatum and of norepinephrine (NE) in hypothalamus and cerebral cortex were examined. Isolated nerve-endings from each region were osmotically disrupted and subfractionated into a soluble cytoplasmic fraction (end supernatant, Se) and a synaptic vesicle fraction (P2V). DA and NE were measured in the crude homogenate and in subcellular fractions by a radioenzymatic assay. Levels of NE and DA were 3--5 times higher in the nerve-ending cytoplasm than in the synaptic vesicles, suggesting that catecholamines within the nerve-endings are predominantly in soluble form. Amphetamine increased DA levels in the tissue homogenate and in the nerve-ending cytoplasm but not in synaptic vesicles. Pargyline and gamma-butyrolactone (GBL) increased DA levels in all fractions with the greatest increase occurring in the cytoplasmic fraction. Both 6-hydroxydopamine (6-OHDA) and alpha-methyltyrosine (AMT) caused uniform DA decreases in all fractions. Hypothalamic levels of NE in the two nerve-ending compartments were also reduced to a similar extent after AMT. Reserpine produced uniform depletions of striatal DA in both nerve-ending fractions while the rate of DA repletion was more rapid in the vesicular compartment. Levels of hypothalamic NE were also uniformly depleted by reserpine at the times examined. The cytoplasmic storage compartment is discussed in terms of a possible anatomical correlate such as the smooth endoplasmic reticulum.

Long-term survival after out-of-hospital cardiac arrest: an 8-year follow-up.

Between 1988 and 1994, 441 patients were successfully resuscitated outside hospital in the city of Rotterdam, of whom 276 (63%) were discharged from hospital alive. Long-term survival was studied amongst those who were discharged alive. The duration of follow-up averaged 6.71 years. A survival rate of 88% after 1 year, 81% after 3 years, 77% after 5 years and 73% after 7 years was found. After multivariate analysis, age, diagnosis and gender were found to be independent and significant predictors of survival. No significant difference in survival was found in patients who had been resuscitated by emergency personnel, physicians and bystanders. Patients who were still alive were sent a EuroQol-questionnaire. No differences in outcomes between the four groups were found. Since long-term prognosis after out-of-hospital resuscitation is satisfactory, learning programmes for resuscitation should be continued.

Long-term survival after successful out-of-hospital resuscitation.

Between 1983 and 1989, 962 patients in Rotterdam were resuscitated outside hospital, of whom 240 (25%) could be discharged alive. A follow-up study was performed to determine prognosis in these patients. Of the 240 survivors of out-of-hospital resuscitation 80% survived after 1 year and 61% after 5 years. During the first year, 9% suffered from myocardial (re)infarction and 13% underwent coronary bypass surgery or angioplasty. Within the first 3 years after resuscitation 60% of the patients were readmitted to hospital. Permanent or temporary neurological deficits were observed in 30 patients (14%). Patients with a primary arrhythmia without myocardial infarction had a worse prognosis than patients with a cardiac arrest in the context of an infarct. Survival was better in patients in whom resuscitation was initiated by physicians or ambulance-nurses, than in patients resuscitated by lay-people. Multivariate analysis revealed that this difference could be explained by a larger proportion of patients with a primary arrhythmia in the latter group. Since long-term prognosis after out-of-hospital resuscitation is satisfactory, programmes for resuscitation courses should be stimulated. Such programmes should aim predominantly at relatives of patients with known heart disease, police officers and children.

Registered dietitian time requirements in the Modification of Diet in Renal Disease Study.

OBJECTIVE: To assess time expended by registered dietitians to conduct clinical and research activities during the Modification of Diet in Renal Disease (MDRD) Study. DESIGN: Two randomized, controlled clinical trials among persons with diminished levels of renal function using a factorial design to evaluate effects of dietary protein restriction and blood pressure control on progression of renal disease. In study A, subjects with moderate renal insufficiency were randomly assigned to a diet of usual protein (1.30 g/kg per day) or low protein (0.58 g/kg per day) and to either a usual or low blood pressure level. Study B involved subjects with advanced renal insufficiency who were randomly assigned to the low-protein diet or a very-low-protein prescription (0.28 g/kg per day) with a ketoacid-amino acid supplement (0.28 g/kg per day) and to either the usual or low blood pressure level. A time-log form designed by MDRD Study dietitians was completed for each participant at 36 monthly follow-up visits. SETTING: Fifteen clinical centers throughout the continental United States. SUBJECTS: Eight hundred forty adults aged 18 to 70 years with chronic renal diseases participated in the MDRD Study--585 in study A and 255 in study B. STATISTICAL ANALYSES: One-way analyses of variance and t tests were used to evaluate significant time requirement differences by diet groups, diagnosis, and sociodemographics. RESULTS: Mean total time for all participant visits declined from 183 +/- 1 minutes per visit during months 1 through 4 to 116 +/- 41 minutes per visit during months 25 through 36. Significantly more dietitian time was required for participants consuming the low-protein and very-low-protein diets than for those consuming the usual-protein diet. Age, gender, race, marital status, and renal diagnosis did not influence time requirements. A significant inverse association between education level and dietitian time was apparent. APPLICATIONS: The MDRD Study time-log data should be useful when determining staffing patterns for nutrition management in clinical and research settings.

A rapid method for the regional dissection of the rat brain.

A method is described for the rapid dissection of seventeen areas of the rat brain. Regions from fresh unfrozen brain tissue are dissected from coronal brain slices obtained with use of a cutting block. This method is applicable to pharmacological and behavioral studies which require the dissection of numerous brains during short time intervals.

[Long-term survival following successful resuscitation outside the hospital]. / Lange-termijnoverleving na succesvolle resuscitatie buiten het ziekenhuis.

Between 1983 and 1989, 962 patients in Rotterdam were resuscitated outside hospital, of whom 240 (25%) could be discharged alive. A follow-up study was performed to determine prognosis in these patients. Data were collected through the Municipal Health Service, Population Registries, the hospitals where the patients were admitted, and the general practitioners. Of these 240 survivors of out-of-hospital resuscitation 80% survived after 1 year and 61% after 5 years. During the first year, 9% suffered from myocardial (re)infarction and 13% underwent coronary bypass surgery or angioplasty. Within the first three years after resuscitation 60% of the patients were readmitted to a hospital. Permanent or temporary neurological deficits were observed in 30 patients (14%). Patients with a primary arrhythmia without myocardial infarction had a poorer prognosis than patients with cardiac arrest in the context of an infarct. Survival was better in patients in whom resuscitation was initiated by physicians or ambulance-nurses, than in patients resuscitated by lay-people. Multivariate analysis revealed that this difference was caused by a larger proportion of patients with a primary arrhythmia in the latter group. Since long-term prognosis after out-of-hospital resuscitation is satisfactory, programmes for resuscitation courses should be stimulated. Such courses should be aimed predominantly at relatives of patients with known heart disease, police officers and children.

[Analgetic ketamine feasible in ambulance emergency care]. / Analgeticum ketamine goed toepasbaar in de ambulancehulpverlening.

OBJECTIVE: To investigate if ketamine could be a feasible analgetic in ambulance trauma care. DESIGN: Prospective. SETTING: University Hospital of Rotterdam 'Dijkzigt'. METHODS: To 51 women and 87 men in the age of 9-95 years who suffered from pain due to trauma and needed pain relief during transport to the hospital, a low dose of ketamine was given according to protocol. Their pain was measured with a descriptive verbal pain scale every 5 minutes. RESULTS: Upon arrival in the hospital 125 (90.5%) out of the 138 patients had a relief of their pain. For 101 patients the pain was only minimal or had disappeared during transport. This was reached in 74 cases with only one dose of ketamine, in 26 cases a second dose was needed, a same number needed nitrous oxide in addition and 9 times a second dose and nitrous oxide was given. Side-effects were mostly of psychic origin, such as agitation (9%), disorientation (17%), sedation (27%), and hallucinations (5%). They never lasted longer than several minutes or hindered further investigation. CONCLUSION: A low dose ketamine seems a safe and feasible analgetic in ambulance trauma care. Further research which compares ketamine with other in the ambulance trauma care current analgetics seems of value.

[Twelve year triage and thrombolysis treatment prior to hospitalization for myocardial infarction patients in the Rotterdam area of the Netherlands: outstanding short-term and long-term results]. / 12 jaar triage en trombolytische behandeling vóór ziekenhuisopname bij hartinfarctpatiënten in de regio Rotterdam: uitstekende korte- en langetermijnresultaten.

OBJECTIVE: To describe the results of thrombolysis prior to hospitalisation in patients with evolving myocardial infarction. DESIGN: Prospective cohort study. METHOD: The 'Reperfusion for acute infarcts Rotterdam' (Dutch acronym: REPAIR) programme aims to minimise treatment delay in patients with evolving myocardial infarction by the initiation of thrombolytic therapy prior to hospital admission. For patients with symptoms that indicate a developing myocardial infarction, treatment is initiated immediately by the ambulance personnel at the patient's home, once the diagnosis has been confirmed with the help of a portable 12-lead ECG system. The interval between the onset of symptoms and the thrombolysis infusion was recorded for all patients, as well as any complications which occurred during transportation. The long-term survival was determined using data from the municipal registration. RESULTS: In the period 1988-2000, 1487 patients were treated using the REPAIR protocol, 80% of these within two hours after the onset of symptoms. In 9 cases (0.6%) a thrombolytic treatment had been initiated, whereas the diagnosis 'myocardial infarction' was not confirmed at the hospital. During transport 40 patients (2.7%) experienced ventricle fibrillation, 25 (1.7%) severe hypotension, and 2 patients (0.1%) died. Mortality at 30 days and at one, five, and ten years was 4.9%, 7.3%, 16.2% en 30.1%, respectively. Patients treated within two hours after the onset of symptoms had lower mortality rates than those treated later: at one year 6.7% versus 9.7%, and at 5 years 14.0% versus 25.1% (Kaplan-Meier estimates; log rank test: p = 0.001). CONCLUSION: Immediate thrombolytic treatment of patients with a developing myocardial infarction which could be safely initiated by ambulance personnel, resulted in excellent short-term and long-term survival.

[Earlier treatment of acute myocardial infarction with administration of alteplase (rt-PA) before hospitalization]. / Snellere behandeling van het acute myocardinfarct door toediening van alteplase (rt-PA) vóór opname.

The gain in survival by thrombolytic therapy in patients with myocardial infarction is determined by the delay between coronary occlusion and reperfusion. The REPAIR study was designed to examine the feasibility and safety of prehospital thrombolysis with alteplase (rt-PA, Actilyse). Indications and contraindications are verified by general practitioner or ambulance nurse with a short questionnaire. A small portable ECG computer system is used to confirm the presence of a large evolving myocardial infarction 'on the spot'. Between June 1988 and May 1990, 150 patients were treated by the ambulance service. Therapy could be initiated within an average of 91 (+/- 40) minutes (sd) after the onset of symptoms, and within 23 (+/- 9) minutes after ambulance arrival. Three patients were defibrillated during transportation, in one of these therapy had to be discontinued because of cardiac massage. No other complications were observed. Five patients (3%) died after arrival in the hospital. The time gained by prehospital treatment averaged 47 (+/- 2) minutes in comparison with 220 patients who received thrombolytic therapy after hospital admission. The procedure allows rapid and safe initiation of thrombolytic therapy in selected patients, even in the absence of a physician.

Long-term mortality of chest pain patients managed according to a decision scheme that aims to avoid inappropriate hospitalisations.

OBJECTIVE: A triage decision scheme was developed to avoid unnecessary hospitalisations for suspected acute coronary syndromes. The current investigation aimed at evaluating the long-term survival of patients who were managed according to this scheme. SUBJECTS: Patients (n=964) with symptoms suggestive of acute cardiac pathology, who were seen by a general practitioner, and for whom a pre-hospital ECG was recorded by the ambulance service in 1993-1994. METHODS: During the year 2000 a follow-up of the entire cohort was performed, and the vital status of patients was determined via the civil registry office. Cox's multivariable regression analyses were performed to evaluate the relation between final (hospital discharge) diagnosis and long-term outcome. RESULTS: The median follow-up was 6.0 years (4.6-6.6). Six-year mortality of the entire cohort was 30%. Long-term mortality was significantly lower in patients identified to be at low risk, who are not hospitalised, than in hospitalised patients (six-year mortality 7.5% versus 33.1%; p<0.0001). Longterm outcome was strongly associated with the final hospital discharge diagnosis. CONCLUSION: Our data support the usefulness and appropriateness of the applied diagnostic scheme that aims to avoid unjustified hospital and CCU admissions in patients with acute chest pain.

Investigation of the use of the CAMCOG in the visually impaired elderly.

OBJECTIVE: To determine the effect of decreased visual acuity due to cataract on tests of cognitive function in the elderly. METHOD: Patients at a precataract surgery assessment clinic were screened to exclude cognitive impairment. The CAMCOG was completed by 42 subjects, and the visual acuity for each eye assessed. RESULTS: There was a significant correlation between visual acuity and the CAMCOG score, which was abolished when simple modifications were made to the CAMCOG. Although 5 subjects scored below the cut-off point, 3 with worse visual acuity scored within the cut-off. CONCLUSIONS: Visual impairment has a significant effect on the scoring of the CAMCOG. However, the effect may not only be due to decreased visual acuity but also to other factors such as contrast sensitivity, which may be affected by cataract.

BioPrep. A premedical program for rural high school students.

To address physician maldistribution in Alabama and the Southeast region. The University of Alabama established the Biomedical Sciences Preparation Program (BioPrep) in five rural high schools. Its purpose is to help rural, disadvantaged high school students develop academically and socially so that they will be motivated and able to enroll in and progress successfully through college, specifically in pre-health professional curricula. It aims to develop their desire to return eventually to rural areas of Alabama as professionals. Project students are compared with two control groups. Performance on the American College Testing Program college entrance examination revealed significantly higher achievement by the project students. The project students also chose professional careers earlier and more frequently than matched high school students not receiving this special program, but similar to medical students and premedical students. The implications of the project for increasing the size of the rural, disadvantaged student applicant pool are discussed.

Integrating personal computers into family practice: a comparison of practicing physicians and residents.

A survey was used to assess levels of experience with personal computers and interest in learning personal computer applications among Alabama family practice physicians and residents in 1994. The study compared responses of 272 physicians and 77 residents as well as responses of physicians and residents in a sample of respondents thirty-eight years old or younger, including 77 physicians and 73 residents. Almost 25% of physicians reported never having used a computer, compared to 7.9% of residents. Respondents had learned computer skills through various combinations of methods, with over half of each group claiming to be self-taught through reading and hands-on experience. More than 86% of both groups expressed interest in learning more; interest increased in the population thirty-eight years or younger. Respondents, especially physicians, reported using professional applications less often than personal applications. Overall, there was a high level of interest in learning various practice-related applications; however, a significantly larger proportion of residents reported interest in each type of application than did physicians.

First year residency stress: sources and mediators.

This study expands on previous research on stress in the internship year by identifying potential sources of stress in the training requirements and faculty contacts of first year family practice residents. All first year residents completed the Profile of Mood States (POMS) and the Zung Self-Rating Depression Scale (SDS) once a month throughout the year. It was shown that specific training demands, such as the number of beeper calls, the number of nights on call, the amount of sleep, etc., correlated with the POMS and the SDS only in the early rotations. The residents' ratings of commitment to teaching, availability, and sensitivity of the faculty on each service, however, were consistently related to the residents' moods regardless of time of year. When residents rated faculty as low on these characteristics, they scored higher on the stress indicators, whereas when residents rated faculty as high on these characteristics, their stress scores were significantly reduced.

Effect of chronic human recombinant erythropoietin therapy on antibody responses to immunization in chronic hemodialysis patients.

There are multiple lines of evidence suggesting that human recombinant erythropoietin (rEPO) could influence immune responses by direct effects of rEPO on T or B cells. The present study tested this hypothesis by measuring antibody responses after immunization to tetanus toxoid (TT, a T cell dependent antigen) or pneumococcal capsular polysaccharide antigen (PA, a T cell independent antigen). The patients chosen for this prospective study were chronic hemodialysis patients receiving chronic rEPO therapy, and a comparable group of chronic hemodialysis patients not receiving rEPO therapy. We found that the patients immunized with PA and receiving rEPO therapy (N = 15) had IgG anti-PA responses comparable to that of those not receiving rEPO therapy (N = 15). In contrast, in the patients immunized with TT, those receiving rEPO (N = 15) developed significantly higher IgG anti-TT levels than those not receiving rEPO (N = 14) (time-group interaction P = 0.005). The peak difference between these groups was at two weeks, where the rEPO-treated patients developed a 4.1-fold mean increase in IgG anti-TT level and those not receiving rEPO developed only a 1.4-fold mean increase in IgG anti-TT level (P < 0.01). The difference in immune response to TT in the rEPO compared to the non-rEPO-treated patients could not be explained by differences between the groups in any of the parameters measured at baseline or during the post-immunization period. In conclusion, rEPO therapy increased immune response to TT but not PA, which suggests that rEPO enhances immune response to T cell dependent antigens.

Ultraviolet radiation enhances both the nodular and ulcerative forms of Mycobacterium ulcerans infection in a Crl:IAF(HA)-hrBR hairless guinea pig model of Buruli ulcer disease.

BACKGROUND: Ultraviolet radiation (UV) pre-exposure enhances intracellular mycobacterial infections, however, its effect upon the pathogenesis of the extracellular Mycobacterium ulcerans parasite had not been previously examined. The hypothesis tested was that UV pre-exposure enhances both the nodular and ulcerative forms of M. ulcerans infection in the Crl:IAF(HA)-hrBR hairless guinea pig. METHODS: Groups of five animals were exposed to total cumulative UV doses of 0 (control), 3 or 30 kJ/m2 followed 3 days later by subcutaneous infection with 3 x 10(4) CFU of M. ulcerans in order to induce the nodular form of the disease. The resultant nodules were then measured for the next 22 days. The experiment was then repeated using intradermal infection with 2 x 10(6) CFU in order to induce the ulcerative form of the disease. The resultant ulcers were measured for the next 30 days. In both experiments, the animals were tested for delayed-type hypersensitivity (DTH) reactivity to Burulin-S as a marker of the onset of the reactive phase of the disease. RESULTS: Following low inoculum subcutaneous infection, distinct, well-demarcated, subcutaneously situated skin nodules were present at infected skin sites between 7 and 22 days post-infection. Between days 14 and 21, the mean nodule diameters of the UV irradiated groups were significantly (P < 0.03) greater than that of the control group. UV pre-exposure resulted in significant (P < 0.035) suppression of DTH responses to Burulin-S challenge. High inoculum intradermal infection resulted in the development of ulcerative lesions. Between 10 and 30 days post-infection, the mean lesion diameters and mean ulcer development times of UV irradiated groups were significantly (P < 0.05) greater than those of the controls. However, UV irradiation did not affect DTH responses to Burulins in the high inoculum experiment. In both experiments, the lesions were histologically consistent with human Buruli ulcer disease. These results demonstrate that UV pre-exposure results in enhanced M. ulcerans infection in the hairless guinea pig model of Buruli ulcer disease and suggest that UV exposure may be a relevant factor in the pathogenesis of human forms of the disease.

Dietary protein restriction, blood pressure control, and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group.

In the Modification of Diet in Renal Disease Study, a follow-up (mean, 2.2 yr) of 200 study participants with autosomal dominant polycystic kidney disease (ADPKD) was conducted to determine the effect of lowering protein intake and blood pressure on the rate of decline in GFR. The rate of decline was faster in participants with ADPKD than in persons with other diagnoses, reflecting, in part, faster disease progression in the ADPKD group. Baseline characteristics that predicted a faster rate of decline in GFR in persons with ADPKD were greater serum creatinine (independent of GFR), greater urinary protein excretion, higher mean arterial pressure (MAP), and younger age. In patients with initial GFR values between 25 and 55 mL/min per 1.73 m2, neither assignment to a low-protein diet group nor assignment to a low blood pressure group significantly reduced the rate of decline of GFR in ADPKD participants. Similarly, the decline in GFR was not related to achieved protein intake or MAP. In participants with GFR values between 13 and 24 mL/min per 1.73 m2, assignment to the low MAP group led to a somewhat more rapid decline in GFR. However, the more rapid decline in GFR did not appear to be due to a detrimental effect of low blood pressure or the antihypertensive agents used to reach the low blood pressure goal. Lower protein intake, but not prescription of the keto acid-amino acid supplement, was marginally associated with a slower progression of renal disease.