A family exhibiting the cis-AB genotype

Studies on blood samples from a 30-year-old woman of Korean origin, her husband and children, showed the presence of the cis-AB genotype in the mother and one child. The cis-AB red cells showed abnormal reactions with both polyclonal and monoclonal anti-B reagents and an elevated level of H antigen. The serum contained weak anti-B that reacted with normal B antigen but not with that on cis-AB cells. Normal levels of A substance but reduced levels of B and H substances were present in the saliva. Conversely, the serum showed reduced A and normal B and H blood group transferase activity.     

Schedule dependent potentiation of antitumor drug effects by α-difluoromethylornithine in human gastric carcinoma cells in vitro

A clone of human gastric cancer cells (AGS-6) and the parental line (AGS-P) from which it was isolated were used in cell survival studies to determine whether pretreatment for 24, 48 or 72h with -difluoromethylornithine (DFMO, 5mM) would increase the cell's sensitivity to 5-Fluorouracil (5FU), Adriamycin (Adria), 1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea (MeCCNU), or Bleomycin (Bleo). Generally, the AGS parental cells were most sensitive to the anticancer agents after exposures to DFMO. However, there was no way to predict in advance from DFMO-induced changes in ornithine decarboxylase (ODC), polyamine or cell kinetics values, how long an exposure to DFMO was required before sensitization to an anticancer agent occurred. The degree of potentiation for a single drug was variable from time to time during exposure to DFMO, and broad differences in the sensitizations were demonstrated among the four anticancer drugs. The AGS-6 clone exhibited little or no increased sensitivity as a result of pretreatment with DFMO, even though the DFMO-induced reductions in ODC and polyamine values in these cells were similar to those produced in the more sensitive parental line.     

Pharmacological characterization of an α1A-adrenoceptor mediating contractile responses to noradrenaline in isolated caudal artery of rat

1. The α₁-adrenoceptor population mediating contraction of caudal artery of rat has been characterized by using quantitative receptor pharmacology.
2. Cumulative concentration-effect (E/[A]) curves to noradrenaline (NA) yielded a p[A]₅₀ of 5.56±0.05 (n=16). Prazosin caused concentration-dependent, parallel, dextral shifts of E/[A] curves to NA yielding a pK_b of 8.9 (Schild regression slope=1.0). RS-17053 (N-[2-(2-cyclopropyl methoxy phenoxy) ethyl]-5-chloro-α ,α-dimethyl -1H-indole- 3-ethanamine hydrochloride; 10–100 nM), a selective α_1A-adrenoceptor antagonist, produced non-parallel, biphasic, dextral shifts of E/[A] curves to NA, suggesting the involvement of more than one α₁-adrenoceptor subtype. Analysis of the high affinity component yielded an apparent pA₂ value of 9.2±0.3.
3. A-61603, a selective agonist at α_1A adrenoceptors behaved as a full agonist relative to NA and yielded monophasic E/[A] curves with a p[A₅₀] of 7.59±0.04 (n=15). Pretreatment of tissues with chloroethylclonidine (CEC; 100 μM for 20 min, followed by 40 min washout), which preferentially alkylates α_1B- and α_1D-adrenoceptors, did not alter E/[A] curves to A-61603. Prazosin (3–300 nM) caused concentration-dependent, parallel, dextral shifts of E/[A] curves to A-61603 yielding a pA₂ estimate of 9.2±0.2.
4. Experiments with α₁-adrenoceptor antagonists of varying subtype selectivities (RS-17053, SNAP 5089, tamsulosin, 5-methylurapidil, BMY 7378, HV 723 and REC 15/2739) revealed parallel dextral shifts of E/[A] curves to A-61603. Schild regression analyses yielded pA₂ estimates of 9.2, 9.3, 11.2, 9.0, 6.3, 8.7 and 10.0 for RS-17053, SNAP 5089, tamsulosin, 5-methylurapidil, BMY 7378, HV 723 and REC 15/2739, respectively, although deviations from unit slope (possibly reflecting a secondary involvement of another α₁-adrenoceptor) hindered estimations of pK_b for some antagonists. The antagonist affinity profile obtained reflects best that described for the α_1A-adrenoceptor.
5. In conclusion, caudal artery of rat contracts in response to NA via activation of at least two α₁-adrenoceptor subtypes. One of these subtypes displays the pharmacology of the α_1A-adrenoceptor, while the other remains to be defined. Use of the novel selective agonist, A-61603, allows for limited pharmacological isolation of the α_1A-adrenoceptor permitting characterization of the properties of selective antagonists.

     

Home is not where the heart is: looming problems of the home care industry

This analysis shows a definite trend of fiscal and social retrenchment policy by the government concerning in-home care service delivery (Tables 1 and 2). Ruggie (1990:164) notes that such shifts and changes in Medicare reimbursement patterns may be efforts of the government to realign itself to become the pivotal force in the provision or delivery of in-home care. Cost-containment pressures, although most needed in the health care industry, are the primary driving force behind retrenchment and the subsequent realignment of government. Such forces tend to impede the development of a comprehensive system for the provision of long-term care services. As noted, the movements and shifts in reimbursement patterns documented by this analysis can lead one to conclude that the same old features will continue to prevail instead of new and innovative delivery structures or public-private partnerships. In other words, the in-home care industry will become more like the nursing home industry--highly regulated and perpetually plagued by questions concerning quality of care. Although government is attempting to diminish its task as the prime provider of health services (i.e., through fiscal retrenchment) and the public's role as the dominant delivery system (i.e., social retrenchment), nevertheless the government has been unable to retrench politically in spite of its present direction of cost containment and fiscal restraint. Consequently, Ruggie (1990:147) notes that "the social welfare functions may continue to be performed" in spite of cost restraint policies. As a result, another "no care zone" is created and policy-makers will continue to develop "crisis policy" such as intense demands to hold unit costs low. The home care system has expanded many of the long-term care options and has emerged as a salient segment of our health and social service system (Applebaum and Phillips, 1990). Yet, policy-makers have not developed a comprehensive long-term care system, particularly one that defines a common policy for home care benefits and engenders the right kind of public-private partnership for the delivery of quality home care.     

Attitudes, knowledge, and behavior of family physicians regarding depression in late life.

OBJECTIVES: To assess self-reported knowledge, attitudes, and behaviors of practicing community family physicians regarding identification and management of depression in late life. DESIGN: We sent a 3-page "fax-back" survey to 768 active physician members of the Maryland Academy of Family Physicians, Baltimore. MEASUREMENTS: We asked physicians to rate how confident they felt in evaluating several common medical conditions of late life, including depression. The questionnaire included items related to knowledge and treatment practices for depression in older adults. RESULTS: Two hundred fifteen usable surveys were returned. In general, physicians took responsibility for diagnosing and treating depression. Few physicians reported that they routinely referred the older patient to a psychiatrist to treat depression, and only half thought that consultation was helpful. Physicians responding to the survey were generally aware of alternative presentations of depression in elderly persons, and were well informed about the duration of treatment with medications for depression. Most were using selective serotonin reuptake inhibitors as first-line agents to treat depression. Physicians though that medications for depression were as effective for older patients as for younger patients, but were less optimistic about the effectiveness of psychotherapy. The barriers to identifying and treating depression in older patients most often mentioned by physicians were related to the atypical presentation of depression in older adults. More than half of the physicians rated themselves as "very confident" in evaluating depression. There were few differences in the responses of physicians with and those without a Certificate of Added Qualifications in geriatrics. CONCLUSIONS: Depression in late life remains a difficult clinical challenge for primary care physicians. These findings are particularly relevant in the face of recent efforts to increase collaboration between primary care physicians and mental health professionals.     

Microbiological safety of drinking water: United States and global perspectives

Waterborne disease statistics only begin to estimate the global burden of infectious diseases from contaminated drinking water. Diarrheal disease is dramatically underreported and etiologies seldom diagnosed. This review examines available data on waterborne disease incidence both in the United States and globally together with its limitations. The waterborne route of transmission is examined for bacterial, protozoal, and viral pathogens that either are frequently associated with drinking water (e.g., Shigella spp.), or for which there is strong evidence implicating the waterborne route of transmission (e.g., Leptospira spp.). In addition, crucial areas of research are discussed, including risks from selection of treatment-resistant pathogens, importance of environmental reservoirs, and new methodologies for pathogen-specific monitoring. To accurately assess risks from waterborne disease, it is necessary to understand pathogen distribution and survival strategies within water distribution systems and to apply methodologies that can detect not only the presence, but also the viability and infectivity of the pathogen.     

Do women 'over-report' morbidity? Men's and women's responses to structured prompting on a standard question on long standing illness

It is frequently observed in contemporary industrialised societies that although women live longer than men, they are sicker than men in that they report higher rates of morbidity, disability and health care use. One common element of the explanation for women's higher rates of morbidity is that there are gender differences in the way that symptoms are perceived, evaluated and acted upon. It is widely assumed that women will be more ready to report illness and to seek help and that they have greater flexibility in their lives to accommodate illness. The few studies that have examined men and women with the same conditions or symptoms are contradictory, but lend little support to this hypothesised greater propensity, yet it is still widely believed. Here we compare men's and women's answers to a global, commonly used question about chronic illness and to a series of more specific prompts and classify the conditions reported by an externally defined categorisation of severity and International Classification of Disease chapter. Contrary to the common expectation that women report higher rates of morbidity and are more ready to report mental health problems, we found: no gender differences in the initial reporting of conditions; men reported a higher proportion of their conditions in response to the initial global question; and no evidence that women were more likely to report 'trivial' or mental health conditions in response to the initial question.