beta-lactam antibiotics. II. Structure-activity relationships of 6-[alpha-(alpha'-ureido-acylamino) acylamino] penicillanic acids.

The influence on the structure-activity relationships (S.A.R.) of the stereochemistry and various alkyl, aryl, aralkyl and heterocyclic substituents at the two chiral centres in the dipeptide side-chain of a new series of penicillins was examined. In many cases the effects of these changes had a pronounced influence on the degree of activity against Gram-positive and especially Gram-negative bacteria. Several compounds indicated that the size, shape and spatial disposition of a substituent were the parameters of importance in influencing activity, rather than it lipophilic or electronic character. The most active homologues in the series provided broad-spectrum penicillins which in terms of their in vitro antibacterial properties showed improvements over certain of the marketed penicillins. Thus 6-[D-alpha(alpha'-ureidoacyl-amino)acylamino]penicillanic acids were found which had a carbenicillin-like profile, with improvements against Pseudomonas aeruginosa, Klebsiella aerogenes, sensitive and beta-lactamase-producing Gram-positive cocci.     

Health risk changes with a low-cost individualized health promotion program: effects at up to 30 months

BACKGROUND AND PURPOSE. Health promotion programs are increasingly important components of health care in an era of predominantly chronic illness preceded by identified health risk behaviors. We report a large and relatively long experience with a low-cost intervention delivered through the mail and using sequential time-oriented risk appraisal and personalized recommendations, each six months, together with self-management materials. METHODS. We performed a prospective, longitudinal, observational study of 103,937 consecutive program participants observed for at least six months and up to 30 months. The primary study endpoint is overall health risk score, with secondary analysis of individual risk behaviors. A concurrent comparison group utilizes the initial scores of new participants by calendar time over the study period. RESULTS. Strong overall positive effects were observed, with improvement in computed health risk scores over 18 months of 14.7% (p less than .0001) in those 65 and over and 18.4% (p<.0001) in those under 65. At 30 months, improvement was 18.8% (p less than .0001) and 25.7% (p less than .0001), respectively. There was improvement in self-report scores for all targeted health risk behaviors, except for pounds over ideal weight, including smoking; dietary fat, salt, and fiber; alcohol; exercise; cholesterol; and reported stress. There was progressive improvement approximating 5% each six-month period. Results were consistent across age groups 16-35, 36-50, 51-65, and over 65 and over different educational level. Results could not be accounted for by sequential changes in initial health habits of participants over time. DISCUSSION.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Wentworth Center for Clinical Engineering: a collaborative and interactive venture

A program has been developed in Boston to bring together hospital and industrial biomedical engineers, BMETs, CEs, nurses, physicians, the Massachusetts Medical Devices Society, academic engineering technologists, and students. This program is headquartered at the Center for Clinical Engineering at the Wentworth Institute of Technology, and is designed to serve and support the interests of the participants for educational, professional, networking and interdisciplinary activities. Because of the availability of engineering technology programs at Wentworth, and the willingness of local professionals to participate, a comprehensive and unique program has been developed to train BMETs and CEs. This program emphasizes hands-on electronic technology, biomedical lectures and laboratories, management lectures and in-hospital preceptorships under the supervision of BMETs, CEs, biomedical directors and nurses.     

Social health maintenance organizations' service use and costs, 1985-89

Presented in this article are aggregate utilization and financial data from the four social health maintenance organization (S/HMO) demonstrations that were collected and analyzed as a part of the national evaluation of the S/HMO demonstration project conducted for the Health Care Financing Administration. The S/HMOs, in offering a $6,500 to $12,000 chronic care benefit in addition to the basic HMO benefit package, had higher start up costs and financial losses over the first 5 years than expected, and controlling costs continues to be a challenge to the sites and their sponsors.     

A new vibrotactile stimulator for functional MRI

Presenting various stimuli in an MRI scanner can be difficult due to the high magnetic field associated with the scanner. Mechanical vibration stimuli are difficult to deliver to subjects in the MRI environment because most vibration devices contain internal circuitry that can adversely interact with the high magnetic field. Piezoelectric ceramics can provide a solution to this problem since they do not require any internal circuitry to vibrate. Piezoceramics are nonmagnetic and they can be made to vibrate if supplied with an alternating current from a straight wire. We designed a piezoceramic vibrotactile stimulator that is safe and effective in functional MRI experiments. The stimulator was tested in an fMRI experiment at 35 and 150 Hz. The results yielded activation sites in the primary sensory cortex and Brodmann area 40 at both frequencies.     

Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment.

PURPOSE: Invasive mucinous carcinoma of the ovary (mucinous epithelial ovarian cancer [mEOC]) is a histologic subgroup of epithelial ovarian cancer (EOC). Chemotherapy for mEOC is chosen according to guidelines established for EOC. The purpose of this study is to determine whether this is appropriate. PATIENTS AND METHODS: Women with advanced mEOC (International Federation of Gynecology and Obstetrics stage III or IV) who underwent first-line platinum-based chemotherapy were compared with women with other histologic subtypes of EOC in a case-controlled study. RESULTS: Eighty-one patients (27 cases, 54 controls) treated with platinum-based regimens were analyzed. The response rates for cases and controls were 26.3% (95% CI, 9.2% to 51.2%) and 64.9% (95% CI, 47.5% to 79.8%), respectively (P=.01). The odds ratio for complete or partial response to chemotherapy for mEOC was 0.19 (95% CI, 0.06 to 0.66; P=.009) compared with other histologic subtypes of EOC. Median progression-free survival was 5.7 months (95% CI, 1.9 to 9.6 months) versus 14.1 months (95% CI, 12.0 to 16.2 months; P<.001) and overall survival was 12.0 months (95% CI, 8.0 to 15.6 months) versus 36.7 months (95% CI, 25.2 to 48.2 months; P<.001) for cases and controls, respectively. The hazard ratio for progression and death was 2.94 (95% CI, 1.71 to 5.07; P<.001) and 3.08 (95% CI, 1.69 to 5.6; P<.001), respectively, for mEOC patients as compared with controls. CONCLUSION: Patients with advanced mEOC have a poorer response to platinum-based first-line chemotherapy compared with patients with other histologic subtypes of EOC, and their survival is worse. Specific alternative therapeutic approaches should be sought for this group of patients, perhaps involving fluorouracil-based chemotherapy.     

Thyroid function in a population of children with attention deficit hyperactivity disorder

To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated.

Method:

Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed.

Results:

The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%.

Conclusion:

Routine thyroid hormone screening is not indicated in children with non-familial ADHD.