Recombinant polyketide synthesis in Streptomyces: engineering of improved host strains

OBJECTIVE: Among the high risk groups for complications from influenza and pneumococcal disease, individuals aged 65 and older hospitalized within the previous year represent the group at highest risk. Studies have demonstrated that targeting hospitalized patients aged 65 and older for immunization before hospital discharge can be successful. This study addressed the efficacy of such a program within a managed care organization to immunize this highest risk group. DESIGN: A cross-sectional study. SETTING: Oxford Health Plans, a major managed care organization in New York serving a large Medicare population. PARTICIPANTS: A total of 106 Primary Care Physicians caring for 153 patients aged 65 and older, who were hospitalized in one of 10 high volume hospitals during October and November of 1996. Nine of these facilities were located in New York and one was in New Jersey. INTERVENTION: Patients aged 65 and older admitted to any of the 10 hospitals were identified daily. A fax was sent to each patient's primary care physician explaining the program and requesting that he/she administer influenza and/or pneumococcal vaccine to his/her patient before hospital discharge. Literature references citing past successful programs were included in the fax. MEASUREMENTS: Measurements included medical record documentation of influenza and pneumococcal immunization, both ordered and given, for the individual member before discharge; patient age; sex; and primary and secondary diagnoses. Physicians were sent follow-up questionnaires to determine reasons for not vaccinating. RESULTS: A total of 206 patients were admitted during the eligible time period. One hundred fifty-three hospitalized patients (average age = 74 years) participated. The median length of stay among this study population was 5 days (range, 1-63 days). The distribution of the median length of stay for the 25th and 75th percentiles was 3 and 9 days. The rate for influenza and pneumococcal immunization, both ordered and given, before hospital discharge was 1.96% for the influenza vaccine (n = 3) and .65% for the pneumococcal vaccine (n = 1), respectively. Results of a follow-up survey mailed to all physicians (n = 106) with eligible members in the study indicated that the most frequent reasons for not vaccinating included: patients were vaccinated before admission, patients were not stable enough to be vaccinated before discharge, and the acute care setting is not appropriate for vaccination. Response rate of 58% (n = 61) was achieved with an initial mailing and one follow-up telephone call to all previous nonresponders. Some physician survey responses do not correlate with data obtained from retrospective patients' claims analysis. CONCLUSION: Well-coordinated and timely attempts to encourage primary care physicians to immunize patients 65 years and older before hospital discharge were unsuccessful in our study. Rather than working with physicians, it may be that managed care organizations should work directly with hospitals to implement influenza and pneumococcal immunization programs.     

Effect of an influenza vaccination campaign in the municipality of Copenhagen during the 1996-1997 season

In Denmark influenza vaccinations are usually paid for by the patients. In the autumn of 1996 Copenhagen City Council offered free influenza vaccinations to all residents aged 70 years or older. The impact of the campaign was evaluated in a questionnaire study of a random sample of the Danish population aged 70 years or older. In Copenhagen 81% (95% Confidence interval: 67-95%) of the elderly at risk were vaccinated compared to 51% (45-56%) outside Copenhagen. Offering free influenza vaccinations in a mass campaign is an effective way of improving coverage rate. However, no substantial difference was found in cost between the mass campaign and a targeted campaign with free vaccination in general practice.     

Community-acquired pneumonia in the elderly. Clinical and nutritional aspects

Community-acquired pneumonia (CAP) in the elderly has a different clinical presentation than CAP in other age groups. Confusion, alteration of functional physical capacity, and decompensation of underlying illnesses may appear as unique manifestations. Malnutrition is also an associated feature of CAP in this population. We undertook a study to assess the clinical and nutritional aspects of CAP requiring hospitalization in elderly patients (over 65 yr of age). One hundred and one patients with pneumonia, consecutively admitted to a 1,000-bed teaching hospital over an 8-mo period, were studied (age: 78 +/- 8 yr, mean +/- SD). Nutritional aspects and the mental status of patients with pneumonia were compared with those of a control population (n = 101) matched for gender, age, and date of hospitalization. The main symptoms were dyspnea (n = 71), cough (n = 67), and fever (n = 64). The association of these symptoms with CAP was observed in only 32 patients. The most common associated conditions were cardiac disease (n = 38) and chronic obstructive pulmonary disease (COPD) (n = 30). Seventy-seven (76%) episodes of pneumonia were clinically classified as typical and 24 as atypical. There was no association between the type of isolated microorganism and the clinical presentation of CAP, except for pleuritic chest pain, which was more common in pneumonia episodes caused by classical microorganisms (p = 0.02). This was confirmed by a multivariate analysis (relative risk [RR] = 11; 95% confidence interval [CI]: 1.7 to 65; p = 0.0099). The prevalence of chronic dementia was similar in the pneumonia cohort (n = 25) and control group (n = 18) (p = 0.22). However, delirium or acute confusion were significantly more frequent in the pneumonia cohort than in controls (45 versus 29 episodes; p = 0.019). Only 16 patients with pneumonia were considered to be well nourished, as compared with 47 control patients (p = 0.001). Kwashiorkor-like malnutrition was the predominant type of malnutrition (n = 65; 70%) in the pneumonia patients as compared with the control patients (n = 31; 31%) (p = 0.001). The observed mortality was 26% (n = 26). Pleuritic chest pain is the only clinical symptom that can guide an empiric therapeutic strategy in CAP (typical versus atypical pneumonia). Both delirium and malnutrition were very common clinical manifestations of CAP in our study population.     

Effects of cocaethylene on dopamine and serotonin synthesis in Long-Evans and Sprague-Dawley brains

BACKGROUND: Primary liver cancer is an important health problem in Korea, where hepatitis B virus (HBV) infection is prevalent. The authors conducted a prospective cohort study to evaluate the protective effect of HBV vaccination against liver cancer in adults. METHODS: A total of 370,285 males aged > or = 30 comprised the study population. They were clinically free of liver diseases, and had not been vaccinated against HBV at enrolment. The results of HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) marker positivity and those of the vaccination programme which took place during 1985 were used for the construction of the cohort. About 5% (n = 18,914) were HBsAg positive, 78,094 were anti-HBs positive, and 273,277 were negative for both. Among the candidates for HBV vaccination (n = 273,277), 35,934 (13.2%) people had been vaccinated against HBV during 1985. Cases of liver cancer were ascertained by record linkage and from medical records covering 1986-1989. A multivariate log-linear model was used to test statistical significance and to estimate relative risks (RR). RESULTS: The total follow-up period was 1,404,566 person-years, with an average of 3 years and 10 months. A total of 302 incident cases were ascertained. The overall incidence rate of liver cancer was 21.7 per 100,000 person-years. With reference to the incidence level among the unvaccinated and uninfected, the RR of primary liver cancer among the chronically infected and that of the unvaccinated and infected was 18.1 (95% CI: 14.2-22.9) and 0.34 (95% CI: 0.19-0.60), respectively. The RR among the vaccinated group was 0.58 (95% CI: 0.31-1.09). CONCLUSIONS: This study suggested that artificial immunization through HBV vaccination, even in adulthood, reduces the risk of liver cancer. It might also offer a practicable means of primary prevention, especially in areas with hyperendemicity of HBV infection.     

Effects of influenza vaccination in HIV-infected adults: a double-blind, placebo-controlled trial

Annual influenza vaccine is recommended for persons with HIV infection. Recent reports indicate that immunizations may increase HIV replication in infected individuals. Forty-seven HIV-infected patients were randomized to influenza vaccine or saline placebo using a double blind study design. One month after vaccination, plasma HIV-1 RNA increased in the vaccinated but not placebo group (p = 0.029). At 3 months, CD4% dropped an average of 1.6 points in the vaccinated group compared to an increase of 0.1 points in the placebo group (p = 0.039). Patients on stable antiretroviral regimens had CD4% drop an average of 2.3 points in the vaccinated group at 3 months versus 0.1 points in the placebo group (p = 0.015). It is concluded that HIV-infected patients are at risk for increased HIV replication and decreases in CD4% following influenza vaccination. Since influenza has not been associated with significant morbidity in this population, further study of routine influenza vaccination for HIV-infected patients is warranted.     

The impact of a media campaign on public action to help maltreated children in addictive families

Developed because of the need to promote public understanding of the link between addictions and child maltreatment, a multimedia campaign helped to increase by 62% the average monthly number of people who called a telephone service for information about how to aid abused and neglected children. The campaign was supported by market research and professional experience that indicated the campaign should focus on easy action a citizen could take, avoid inducing fear or blame, and target third party helpers and younger families-at-risk. Campaign exposure was promoted through the support of corporate partners. A random household survey found that 61% of the general population had seen or heard the campaign slogan. The average monthly calls to the child maltreatment information service regarding alcohol and other drug abuse tripled and the requests regarding at-risk children almost doubled. An auxiliary project provided interprofessional education to increase the probability that people seeking help would get it when referrals were made. The project yielded several lessons for future public awareness campaigns: focus on helping action rather than the problem; use of client-based market research; a strategic plan to assure necessary exposure; reliance on public-private-nonprofit sector partnerships; preparation of the service system; promotion of personal ways of helping.     

Novel methods for molecular dynamics simulations

HYPOTHESIS: Monovalent measles vaccine can be administered to children 6 to 11 months of age during an outbreak. Efficacy and effectiveness of this control measure still have to be assessed. METHODS: During and outbreak of measles, monovalent measles vaccine was administered as part of outbreak control to children aged 6 to 11 months. Active surveillance was used to detect cases of measles occurring during the following month. Children who did not develop measles were tested for measles antibody before their revaccination at 15 months of age. RESULTS: Of 81 children 6 to 11 months of age, 56 were vaccinated and two received immunoglobulins; the latter were excluded from the analysis. Measles occurred in 15 of the 79 children during and after the vaccination campaign, for an overall attack rate of 19%. The attack rate among unvaccinated children was 39% (9 of 23), compared with 11% (6 of 56) among those vaccinated (relative risk = 3.6, 95% confidence interval [CI] = 1.5 to 9.1). All of those who sustained measles in the vaccinated group developed the disease within 10 days after vaccination. The overall vaccine effectiveness was 73% (95% CI = 32% to 89%) when children were classified as vaccinated as soon as they were given measles vaccine. It rose to 96% (95% CI = 72% to 99%) when children were considered vaccinated 1 week postimmunization. Nineteen infants who were vaccinated and who did not develop measles during the outbreak were tested for measles antibody status at 15 months of age before revaccination. All had plaque reduction neutralizing antibody titers greater than 120. CONCLUSION: This study confirms that measles vaccination of infants aged 6 to 11 months is an effective intervention measure during measles outbreaks.     

Dermal application of lisuride on parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the common marmoset and on cases with Parkinson''s disease

BACKGROUND: Follow-up study of patients with surgical repair of aneurysmal subarachnoidal hemorrhage (SAH), looking for clinical outcome predictors. PATIENTS AND METHODS: Sixty two patients consecutively admitted to a teaching hospital, from January 1992 to December 1995 were included in the study. We studied preoperative, intraoperative and postoperative features looking for their relationship with the outcome. The ultimate outcome was evaluated by means of Glasgow Outcome Scale on discharge and 6 months later. RESULTS: Smoking (p = 0.0001) and arterial hypertension (AHT) (p = 0.0186) were more frequent in these patients than in general population, but without relationship to the outcome as with the age of the clinical status on admission. The greatest statistical relationship was found between the level of consciousness on postoperative awakening (measured by the Hunt and Hess scale), and the outcome (p = 2.53 x 10(-8). From our results we made an algorithm that correctly assigned 92% of studied patients to their outcome. CONCLUSIONS: All patients admitted on with aneurysm SAH deserve intensive care treatment besides their clinical grade. The level of consciousness on postoperative awakening was a good outcome predictor.     

Five-year mortality in elderly French subjects from the PAQUID epidemiologival survey: the burden of diabetes

We describe the 5-year mortality and its risk factors in a cohort of elderly people with and without known diabetes mellitus. The PAQUID cohort was representative of the population older than 65 living in Gironde, south-west France. Potential mortality risk factors were collected during a baseline evaluation, using a health questionnaire, from 68.9% of a randomly selected sample of over-65s in 1988. A total of 237 subjects (8.5%) had diabetes. Annual review occurred for 5 years and cause of any death was ascertained from family doctors. After 5 years, 623 people (22.3%) had died, of whom 576 were non-demented; 30.0% of the diabetic group versus 20.3% of the non-diabetic group had died. Survival of the known diabetic group was lower than that of the non-diabetic group (p < 0.001), although this excess mortality was significant only in the 65 to 75 age range (relative risk 1.8; 95% confidence interval 1.2 to 2.8, p = 0.04). Cardiovascular mortality rate did not differ between the diabetic and non-diabetic groups (RR 1.2 [0.8-2.0]). Death related to neoplasia was significantly higher in the known diabetic group (RR 2.2 [1.2-3.3], p = 0.01). In the final model, integrating diabetes as a mortality risk factor in the total cohort, known diabetes at the baseline examination was an independent risk factor for mortality (RR 1.4 [1.0-1.8], p = 0.01), in addition to tobacco use, hypertension and functional dependency. These results confirm suggestions that diabetes increases mortality in the over-65 age group, perhaps with an adverse interaction with other pathology.     

Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients

To examine the nature of asthma in the elderly, we compared older (group 1: 65 years or older, n = 50) with younger patients (group 2: <40 years, n = 99) and to determine the influence of long-standing disease, elderly asthmatics with early onset (group A: onset before 40, n = 22) were compared with patients developing symptoms later in their lives (group B: onset after 40, n = 22). Blood eosinophilia and IgE value >/=100 IU/l were more frequent in younger patients. Short symptom-free periods were more frequent among older asthmatics (78.5 vs. 45.4%, p < 0.001). Only 31.2% of older patients had only mild symptoms. Requirement of systemic steroids was higher in the elderly population. The worst FEV1 was lower in older patients (54.4 +/- 17.3 vs. 71.8 +/- 18.5%, p 相似文献   

Prostaglandin-induced iris color darkening. An experimental model

In the 80s it was established that atherosclerotic renal artery stenosis (ARAS) is a leading cause of renal insufficiency and that this condition ranks among the rare etiologies of chronic renal failure amenable to improvement or stabilization particularly in the white. Nephroangiosclerosis (NAS) is an increasing cause of ESRD in the western countries, especially in blacks. Epidemiological data on the vascular nephropathies leading to ESRD are still rare. In this study, we compare annual incidence of ESRD due to ARAS and NAS during two five-year periods: period A = 1982-1986, period B = 1992-1996. The region of the survey comprised 410,664 inhabitants (99.6% of Caucasians), of whom 100,230 were aged over 60 years. Diagnosis of ARAS required arteriography and that of NAS a renal biopsy. Undetermined vascular nephropathy was diagnosed when ESRD patients had had previously no arteriography or no histological examination. Major results were as follow (A vs B, incidence = n/million inhabitants): 1) Increasing incidence of ESRD due to all causes: 76 vs 95 per million, mean age at ESRD 56 vs 62 yrs, percentage of patients over 65 yrs 28 to 59% (p < 0.001). 2) Increasing incidence of ESRD due to vascular nephropathies: 5.5 vs 27.5 per million (p < 0.0001) in general population and 22 vs 110 per million (p < 0.0001) in population aged over 60 years, mean age at ESRD 68 vs 73 yrs. 3) Increasing incidence of different types of ischemic renal diseases leading to ESRD: ARAS 2.5 vs 15 per million (p < 0.0001) in general population and 10 vs 60 per million (p < 0.001) in those aged over 60 yrs, mean age 69 vs 74 yrs, NAS: 1 vs 8 and 4 vs 32 per million (p < 0.001), mean age 67 vs 72 yrs, undetermined VN 0.5 vs 2.5 and 2 vs 10 per million, 65 vs 73 yrs. Our study demonstrates that ischemic renal diseases 1) have become the most frequent causes of ESRD (27% of all patients and 43% of those aged over 6C years) in the Caucasian elderly. 2) are the only cause of increasing incidence of ESRD in this French region.     

Unilateral cricothyroid contraction and glottic configuration

The outpatient population using the emergency department (ED) is increasing and so is the risk of not admitting people who need it. There is, thus, one important question: are the services delivered appropriate to the needs of these ED outpatients? Follow-up of non-admitted patients after a visit to the ED is a prerequisite for the evaluation of these health services. A multicentric follow-up study was thus performed in order to assess the possibility of contacting outpatients after a visit to the ED. Three randomized follow-up methods were compared: (1) telephone call 1 week after the emergency department visit; (2) telephone call 2 weeks after the visit; (3) telephone call 4 weeks after the visit. The follow-up rate did not change depending on whether patients were contacted at 1, 2 or 4 weeks after the visit. The success rate was 78.6%, 85.6% and 74% respectively (NS). In each strategy, 50% of patients were contacted at the first telephone call, 20% at the second telephone call and 10% by mail. Thus, in a group of outpatients who gave their consent to be called, the follow-up was found to be feasible with a high success rate whatever the time between the visit and the phone recall.     

Thrombolysis following myocardial infarct. European Secondary Prevention Study

For evaluation of the management of patients with acute myocardial infarction, all cases of ten Zurich hospitals (278, 184 men and 94 women) in the period from 1 January to 31 March 1993 were analyzed retrospectively. 223 patients were released from hospital, 55 died. A follow-up was done 6 months after the patient's discharge by means of a questionnaires to the family doctor (return rate: 65.9%). 48.5% of patients were referred to hospital within the first 6 h. after onset of symptoms, 64% within the first 12 h. 28% (n = 76) of the patients received a thrombolytic therapy, of which 91% (n = 69) got streptokinase and 9% (n = 7) got tissue plasminogen activator. In 81% of the cases the thrombolytic therapy was done within the first hour in hospital, in accumulated 97% of the cases within two hours. In the age group under 65 years (39% of the patients, n = 109), 48 patients received thrombolysis (odds ratio [OR] = 1.0). In the age group between 65 and 74 years (24.5 % of the patients, n = 68), 19 patients received thrombolysis (OR: 0.49; 95% CI: 0.42-0.99; p < 0.05), and in the age group over 74 years (36.5% of the patients, n = 101), 9 patients were received thrombolysis (OR: 0.12; 95% CI: 0.05-0.28; p < 0.0001). 31% of the patients (n = 46) received a coronary angiography, 15% (n = 22) had coronary angioplasty, and 11% (n = 1) received coronary bypass surgery. There is evidence that there should be more importance attached to early hospitalization, if acute myocardial infarction is suspected. Thereby age alone should be considered as a contraindication for thrombolytic therapy. The issue of assumed underuse of thrombolytic therapy should be investigated all over Switzerland.     

Vaccination in elderly patients in rehabilitation: a missed opportunity?

BACKGROUND: Immunization against influenza is recommended for elderly persons in Switzerland, but no national guidelines are currently available regarding immunization of the elderly against pneumococcus and tetanus. In addition, almost no data are available regarding immunization rates of the elderly in the general population. In this study we explored the immunization status for influenza, tetanus and pneumococcus of a selected elderly population admitted to a Swiss rehabilitation facility. POPULATION AND METHODS: The study population (n = 145) were patients admitted to a rehab facility during 3 consecutive winter months. Data on demographics, immunization, previous functional status (BADL, IADL), cognitive (MMSE) and affective status (GDS) were collected upon admission. RESULTS: Subjects' mean age was 79.4 years, 32.4% were male, 42.8% had BADLs dependencies and 81.9% IADLs dependencies. Most patients had normal MMSE and GDS scores. Vaccination rates were 39.3% for influenza, 12.4% for tetanus and only 2.1% for pneumococcus. In univariate analyses, people immunized against influenza were older than those who were not (p = 0.01). This relationship remained in multivariate analyses, controlling for gender, functional, cognitive and affective status. Subjects aged 80 and over were 2.5 times (95% CI 1.2-5.5, p = 0.02) more likely to be immunized against influenza, but were less likely to be immunized against tetanus (OR 0.3, 95% CI 0.1-0.9, p = 0.04). Functional status was not significantly associated with any vaccination status. CONCLUSIONS: Immunization rate for influenza in this selected population is similar to those described in US surveys. The positive association between older age and flu vaccination is surprising and needs further investigation. These results also indicate a need to educate patients and physicians in order to increase vaccination use, especially against pneumococcus.     

Improving telephone follow-up after ambulatory surgery

BACKGROUND: An increasing proportion of patients attended at hospital emergence departments (HED) are elderly people. OBJECTIVES: a) To check the reliability of the usual medical assessment to detect the cognitive deterioration in elderly people attended at HED, compared with that performed systematically by means of an evaluation test of cognitive functions; b) to study the applicability of such a test in HED, on the basis of the time necessary for its administration, and c) to describe the deterioration prevalence in that group of patients and identify the possible associated risks for its detection in patients. PATIENTS AND METHODS: Prospective study including patients aged > or = 60 years attended at a HED, using the orientation, memory and concentration test (OMC) to perform the cognitive assessment. RESULTS: A total of 352 patients who had no exclusion criteria out of the 536 attended during the study period were included. Cognitive deterioration was not detected in 111 patients (31.5%); it was mild in 147 (41.8%), moderate in 71 (20.2%) and severe in 23 (6.5%). In patients with moderate-severe deterioration according to the OMC test, such a deterioration was detected by the usual medical evaluation in 7% of cases. The mean time in completing the test was 2.6 +/- 0.9 minutes. An age > or = 80 years was associated with an increased relative risk for detecting moderate-severe cognitive deterioration (1.98; 95% CI, 1.42-2.78; p < 0.001), whereas the discharge diagnosis of respiratory disease was associated with a decrease of the relative risk (0.41; 95% CI, 0.19-0.89; p < 0.05). No association was observed with other factors, such as gender, home residence or final destination from the emergency department. CONCLUSIONS: The prevalence of cognitive deterioration in elderly people attended at HED is high and increases with age. The OMC test can be administered at HED to detect cognitive deterioration, which is not frequently detected by the usual medical assessment.     

Effects of a TV mental health campaign 1992

A 1992 one-Sunday fund-raising TV-show was broadcasted by the Norwegian Broadcasting Corporation. The six-hour TV-show included information on mental health intermingled with entertainment and money-counting results. The mass media had covered the forthcoming TV-show extensively. The campaign has been evaluated through a stratified random sample of the population who were questioned before (n = 1,191) and after (n = 644) the campaign. Almost 94% were aware of the campaign and more than 60% watched the campaign day TV-show. Nearly 70% had read about psychiatric disorders and 45% had discussed the campaign topic with others. The proportion who were aware that suicide takes more lives than traffic accidents, and the proportion with an open attitude to mental illness had increased significantly after the campaign (p < 0.001). After the campaign, a higher proportion would recommend a person with a minor mental disorder to visit a general practitioner (p < 0.001). Through its penetrating effect the Norwegian Mental Health Campaign put mental health issues on the cultural agenda, and succeeded in changing people's knowledge and attitudes.     

Cortisol induces apoptosis in activated B cells, not in other lymphoid cells of the common carp, Cyprinus carpio L.

Two-hundred and 31 patients with a newly diagnosed multiple myeloma first seen and admitted to 17 hospitals located in the North-East of Italy between 1987 and 1992, were registered for a prospective study on the course of the disease. Median age was 68 years (range 41-90). Fifty-one per cent were in stage I, 9% in stage II and 40% in stage III. The presenting features and the survival of the 61 (26%) patients who were first admitted to a division of Hematology of a University Hospital (group HEM) were compared with those of the 170 (74%) patients who were referred to 16 divisions of Internal Medicine at General and County Hospitals (group INT). In the latter group, the patients were older (p = 0.002), had a poorer performance status ( p = 0.0001 ), a higher frequency of renal failure (p = 0.006) and anemia (p = 0.02) and higher beta2 microglobulin levels (p = 0.01). Median survival of group HEM patients did not differ significantly from group INT patients, if all stages were considered, but stage II and III patients of group INT had a significantly shorter median survival than advanced stage patients of group HEM (12 vs. 35 months, p = 0.01). If those older than 65 years or with unfavourable prognostic factors at presentation were excluded, prolonged survival of group INT patients was observed and the curves of the two groups did not differ significantly anymore. These results show that the patients recruited by a specialized centre may represent a selected population with better prognostic factors and younger age and this may affect analysis of clinical trials. Participation of minor centres in clinical trials may considerably contribute in improving interpretation of results of therapy in myeloma and be more representative of the entire population.