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Biomedical subjects

M A Cohen

Publications and source records attributed to M A Cohen.

At least 19 recordsLinked to original sources

Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity.

Fluoroquinolones are potent inhibitors of bacterial topoisomerase II (DNA gyrase). They can also inhibit eukaryotic topoisomerases, which could possibly lead to clastogenicity and/or cellular toxicity. Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the fluoroquinolones and the potential of these compounds to induce micronuclei, a genetic toxicity endpoint. In an effort to identify potent nontoxic quinolone antibacterials, we have examined the structural features of the fluoroquinolones associated with mammalian cell cytotoxicity. An investigation of a wide variety of substituents at the 1, 5, 7, and 8 positions of a quinolone nucleus was conducted. The results indicate that no one position has a controlling effect on the observed cytotoxicity. Instead, a combination of the various substituents contributes to the effects seen. Certain trends were apparent, such as the fact that compounds with pyrrolidines at the R-7 position were more cytotoxic than those with piperazines, and halogens at R-8 (X-position) were associated with more cytotoxicity relative to hydrogen. A general trend also existed between the cytotoxicity of the compounds and their Gram-positive antibacterial activity. A detailed comparison between the various groups and positional variations as they controlled the cytotoxicity and antibacterial activity is presented.

Animals

Exhaustive matching of the entire protein sequence database.

The entire protein sequence database has been exhaustively matched. Definitive mutation matrices and models for scoring gaps were obtained from the matching and used to organize the sequence database as sets of evolutionarily connected components. The methods developed are general and can be used to manage sequence data generated by major genome sequencing projects. The alignments made possible by the exhaustive matching are the starting point for successful de novo prediction of the folded structures of proteins, for reconstructing sequences of ancient proteins and metabolisms in ancient organisms, and for obtaining new perspectives in structural biochemistry.

Amino Acid Sequence

Interpretive criteria and quality control limits for testing susceptibility of Neisseria gonorrhoeae to enoxacin.

For testing the susceptibility of Neisseria gonorrhoeae to enoxacin, a proposed susceptibility category includes strains for which MICs are less than or equal to 0.5 micrograms/ml and zones of inhibition are greater than or equal to 32 mm in diameter. Because of the sparcity of resistant gonococci, a resistance category was not defined, but laboratory-selected resistant mutants were appropriately categorized by the proposed criteria. A review of clinical data confirmed the utility of a single 400-mg oral dose of enoxacin for treating gonorrhea caused by strains judged to be susceptible by the proposed criteria. For quality control purposes, for N. gonorrhoeae ATCC 49226 MICs should be 0.016 to 0.06 micrograms/ml and zones of inhibition should be 43 to 51 mm in diameter.

Enoxacin

Financing long-term care: a practical mix of public and private.

Congress is considering proposals to improve its financing of long-term care. The key issue is whether it should support a social insurance program or a program targeted to a population group defined by income and assets. Social insurance is expensive, costing between $15 and $20 billion. For the most part, it provides benefits--primarily asset protection--to middle- and upper-income individuals. An improved Medicaid program, costing about $8 billion, benefits lower-income individuals but does not protect those with higher incomes. These two options cannot be viewed independently from trends in the private market. Sales of private long-term care policies have grown and between 30 percent and 40 percent of the elderly can be considered potential buyers. If private alternatives are available for those individuals who need asset protection, the case for a more targeted public approach--along with reliance on the private sector--becomes more compelling. Congress should consider a program that enhances Medicaid; improves consumer education; assists states in regulating long-term care policies, so as to enhance consumer protection and confidence; and clarifies taxes on long-term care insurance to encourage workers and the elderly to protect themselves against catastrophic expenses.

Aged

Private outlets for public limitations: the rise of commercial health insurance in Israel.

In recent years, dissatisfaction with aspects of the Israeli health care system has grown. Labor conflict and unrest, long waits for elective surgery, increases in out-of-pocket payments for health care, and declining government investment have given rise to a new phenomenon: the increasing use of private services. This has led consumers to seek financing sources for their private care and created opportunities for commercial insurers and sick funds to offer new insurance packages to meet this demand. As a result, over the last five years more than twenty commercial health policies and four mandatory supplemental policies provided by the sick funds are currently on the market. The market for these policies is small but growing, with consequences for the cost and quality of care, access, the level and composition of national expenditures, and the allocation of resources to both the public and private health systems. As the balance between private and public financing changes, so too do the trade-offs between differing objectives. Greater private pluralism and competition at the financing level have many advantages but also make it more difficult for government to manage the tradeoffs that occur. Thus, a changed emphasis in government regulation and policy-making is required.

Adult

Estimating costs of traffic crashes and crime: tools for informed decision making.

Traffic crashes and crime both impose significant economic and social burdens through injury and loss of life, as well as property damage and loss. Efforts to reduce crashes and crime often result in competing demands on limited public resources. Comparable and up-to-date cost data on crashes and crime contribute to informed decisions about allocation of these resources in important ways. As a first step, cost data provide information about the magnitude of the problems of crashes and crime by allowing us to estimate associated dollar losses to society. More importantly, cost data on crashes and crime are essential to evaluating costs and benefits of various policy alternatives that compete for resources. This paper presents the first comparable comprehensive cost estimates for crashes and crime and applies them to crash and crime incidence data for Michigan to generate dollar losses for the state. An example illustrates how cost estimates can be used to evaluate costs and benefits of crash-reduction and crime-reduction policies in making resource allocation decisions. Traffic crash and selected index crime incidence data from the calendar year 1988 were obtained from the Michigan State Police. Costs for crashes and index crimes were generated and applied to incidence data to estimate dollar losses from crashes and index crimes for the state of Michigan. In 1988, index crimes in Michigan resulted in $0.8 billion in monetary costs and $2.4 billion in total monetary and nonmonetary quality-of-life costs (using the willingness-to-pay approach). Traffic crashes in Michigan resulted in $2.3 billion in monetary costs and $7.1 billion in total monetary and nonmonetary quality-of-life costs, nearly three times the costs of index crimes. Based on dollar losses to the state, the magnitude of the problem of traffic crashes clearly exceeded that of index crimes in Michigan in 1988. From a policy perspective, summing the total dollar losses from crashes or crime is of less importance than understanding the costs and benefits of various policy alternatives. This paper therefore concludes with an example of how our cost estimates can be used to compare the costs and benefits of competing policies.

Accidents, Traffic

Treatment decisions in end-stage bladder cancer. Bilingual liaison rounds.

A bilingual conference was held in order to assist a Spanish-speaking patient and her physicians in planning for her care. The patient spoke only Spanish and her oncologists were primarily English-speaking. Her daughter, who was bilingual, did not attend the conference. One of the authors translated and served as interpreter and liaison between the patient and her other physicians. The patient was severely depressed and terminally ill with end-stage bladder cancer. Her depression and hopelessness complicated her care.

Carcinoma, Squamous Cell

AIDS education and a volunteer training program for medical students.

The process of AIDS education poses exceptional challenges for teachers and students. Medical students are in a unique position in the health care system. They are young enough to be ideal role models for high school and college students. They are mature enough to be responsible educators. We describe a special program designed and implemented by a medical student to train other medical students to become AIDS educators. This student-run program provides education for student volunteers who are able to educate other students and members of the community. The program is designed to educate a generation of physicians who will be well-equipped to combat the HIV epidemic and who can serve the community as AIDS educators while still in medical school.

Acquired Immunodeficiency Syndrome

In vitro antibacterial activities of PD 131628, a new 1,8-naphthyridine anti-infective agent.

PD 131628 is a new aminopyrrolidine-substituted fluorocyclopropyl naphthyridine quinolone which possesses high in vitro activity against a wide spectrum of bacterial species. The MICs for greater than or equal to 90% of strains were 0.125 to 0.25 microgram/ml for staphylococci, Streptococcus pyogenes, and S. pneumoniae; 0.5 micrograms/ml for S. agalactiae and Enterococcus faecalis; 0.125 micrograms/ml for members of the family Enterobacteriaceae and Acinetobacter spp.; 0.5 micrograms/ml for Pseudomonas aeruginosa; and less than or equal to 0.03 micrograms/ml for Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Neisseria gonorrhoeae. In these in vitro comparisons with ciprofloxacin, PD 131628 is more active against gram-positive organisms, approximately equivalent against gram-negative organisms, and, like most other quinolones, relatively inactive against gram-negative anaerobes. In most instances, the in vitro potency of PD 131628 exceeded those of widely used compounds: ciprofloxacin, imipenem, ampicillin, penicillin G, oxacillin, cefazolin, ceftazidime, cefoxitin, cefsulodin, aztreonam, piperacillin, amikacin, spectinomycin, doxycycline, erythromycin, metronidazole, and vancomycin.

Anti-Bacterial Agents

Apathetic hyperthyroidism in middle age.

Apathetic hyperthyroidism was first described in the medical literature by Lahey in 1931. It is a form of hyperthyroidism found principally in the elderly population. In this disorder the usual hyperkinetic presentation of thyrotoxicosis is replaced by apathy and inactivity, often leading to an erroneous psychiatric diagnosis. Although there is a paucity of literature on apathetic hyperthyroidism, it has been described in the elderly and as an extremely rare complication of hyperthyroid disorder in children. It was described only rarely in middle age. The following case highlights the diagnostic and therapeutic dilemmas encountered in a middle-aged patient who presented with dementia and apathetic hyperthyroidism.

Antithyroid Agents

How can we combat excess mortality in Harlem: a one day survey of substance abuse in adult general care.

Our hypothesis was that a one-day survey of all patients hospitalized on Adult General Care would demonstrate a need for expanded addiction services in a municipal teaching hospital in East Harlem. We interviewed 276 patients in Adult General Care on February 16, 1990 to assess whether they abused drugs or alcohol or were hospitalized for reasons related to substance use. Of the 276 patients interviewed, 18 percent used alcohol alone, 14 percent used drugs alone, 17 percent used both drugs and alcohol and 2 percent were hospitalized for reasons related to substance use. One hundred forty or 51 percent of all patients were admitted because of substance use and its sequelae or as a result of violence associated with the buying or selling of drugs. The percentage was highest on one medical floor where 89 percent of the patients were substance users and on medical floors in general where the average was 60 percent. Forty patients or 14 percent were known to be HIV seropositive. Given the high mortality in Harlem, the results of our one-day survey indicate a need for expanded addiction services.

Acquired Immunodeficiency Syndrome

[Splenectomy for chronic thrombocytopenic purpura].

During the period 1985-1989, 49 patients underwent splenectomy for chronic idiopathic thrombocytopenic purpura in our department. A correct follow-up was available for 39 patients. All patients had been previously treated with corticosteroids. We evaluated the platelet count one year after the operation and the relation between this count and several preoperative and postoperative factors. We observed a favourable prognosis when the preoperative study of platelet sequestration showed splenic destruction, when the duration of symptoms was less than one year and when there was a rapid increase in the platelet count during the first week after the operation.

Adrenal Cortex Hormones