Guanine nucleotide associated with the protein of the outer fibers of flagella and cilia.

Flagella from sperm of the sea urchin Strongylocentrotus droebachiensis and cilia from Tetrahymena pyriformis contain guanine nucleotides bound to the outer-fiber fraction in the ratio of one mole of nucleotide per mole of protein subunit.

Morphologic variations in graft endothelium.

The morphologic features of corneal endothelium were studied with clinical specular microscopy in 33 cases of clear corneal transplants. A complete morphologic profile of the corneal endothelium, which included cell density, mean cell area, and variation in cell size (polymegethism), was obtained with an automated, pattern-analysis system. Our observations demonstrated variation in all these parameters of graft endothelium with time, indicating that graft endothelium is in a state of transition during healing and that the end point to the healing process is still to be determined.

Evaluation of single- and multiple-dose pharmacokinetics of synthetic conjugated estrogens, A (Cenestin) tablets: a slow-release estrogen replacement product.

A multiple-dose, placebo-controlled, randomized pharmacokinetic study was performed in 15 early (i.e., 1-3 years) postmenopausal women to evaluate the single and steady-state pharmacokinetics of 0.625 mg Cenestin (Synthetic Conjugated Estrogens, A) tablets, administered once daily for 90 days. Plasma concentration-time profiles for both total (conjugated and unconjugated) estrone and equilin, two major estrogens in Cenestin, were nearly superimposable between Day 1 (single dose) and Day 90 (multiple dose), indicating equivalent drug exposure from one dose to the next. For total estrone, the mean estimates of Cmax and AUC0-24 were 2.5 ng/ml and 35.0 ng x h/ml for Day 1 and 3.0 ng/ml and 39.8 ng x h/ml for Day 90, respectively. Similarly, Cmax and AUC0-24 mean values for total equilin were 1.4 ng/ml and 17.4 ng x h/ml after Day 1 and 1.5 ng/ml and 17.3 ng x h/ml after Day 90, respectively. The mean tmax value for total estrone was 8.3 hours on Day 1 and 8.6 hours on Day 90, indicating a slower rate of absorption. The average estimate for observed drug accumulation index for the 24-hour dosing interval was calculated to be 1.1 for total estrone and 1.0 for total equilin. These data, taken together, indicate a slow and steady rate of absorption, minimal drug accumulation at steady state, and consistent drug exposure between Cenestin doses.

Idiopathic presenile cataract formation and galactosaemia.

Five hundred patients undergoing cataract surgery were prospectively examined, and 46 Caucasian patients were found to have strictly idiopathic cataracts severe enough to warrant surgery on or before age 55. In a masked fashion we determined the activity of galactokinase (GK) and galactose-1-phosphate uridyl transferase (GPUT) in these patients as well as on 53 age matched controls. With respect to GK no cataract patient had an enzyme level of less than 2 standard deviations below the control mean. However, 3 of 45 (6.7%) patients in the cataract group had a GPUT level less than 2 standard deviations below the mean for controls, and were presumably heterozygotes for this enzyme. In comparison with the expected population rate of 0.8% this is highly significant (p = 0.006). Abnormalities in galactose pathway enzymes may therefore predispose to development of presenile cataracts. In affected people there is a possibility of treating these patients clinically by dietary restriction of dairy products or by using aldose reductase inhibitors to prevent or reverse cataract formation.

Alternatives to splenectomy in adults after trauma. Repair, partial resection, and reimplantation of splenic tissue.

Splenectomy results in a lifelong risk of overwhelming infection in the adult as well as the child. This has prompted our current enthusiasm for splenic salvage in trauma patients. A number of alternatives to total splenectomy exist; however, the complications that result from splenic salvage must not exceed the risk incurred by loss of this organ. Splenorraphy can be performed safely in the majority of patients despite associated intraabdominal injuries. When splenectomy is necessary, reimplantation of splenic tissue is feasible. The efficacy of this technique is preventing postsplenectomy sepsis remains to be established.

Failure of splenic implants to protect against fatal postsplenectomy infection.

Overwhelming postsplenectomy infection is not a phenomenon confined to children. In all age groups, splenic trauma that requires surgery should be managed by splenorrhaphy if possible. Autoimplantation of splenic fragments into omental pockets has been performed in the few patients we have seen who required splenectomy. A case has been presented in which these small implants failed to protect a 61 year old woman from the development of fatal pneumococcal sepsis. The patient had received a pneumococcal vaccination, and her implants had shown activity on radionuclide scanning. Concerns about critical splenic mass, blood supply to the implant, and hepatic function require further study before this technique can be considered efficacious.

Controlled, multidose, pharmacokinetic evaluation of two extended-release carbamazepine formulations (Carbatrol and Tegretol-XR).

A major limitation of conventional carbamazepine (CBZ) formulations is their pharmacokinetics, which typically require q.i.d. dosing. Two extended-release formulations of CBZ have been developed recently to support b.i.d. dosing. One, Carbatrol (CBTL) uses immediate-, extended-, and enteric-release beads in a capsule. The other, Tegretol-XR (TXR), uses an osmotic pump (Oros tablet). To our knowledge, this is the first head-to-head comparison of the multidose pharmacokinetics of these two new formulations. The objective of the study was to evaluate the pharmacokinetics of carbamazepine (CBZ) and CBZ-10,11-expoxide (CBZ-E) after multidose b.i.d. dosing with CBTL or TXR. In this randomized, crossover study, 15 normal healthy adults received 400 mg of each formulation b.i.d. for 5 days. Blood samples for CBZ and CBZ-E analysis were obtained prior to morning doses on all days and hourly for 12 h after the Day 5 dose. There was a minimum interperiod washout of 9 days. For CBTL and TXR, the key CBZ pharmacokinetic measures of area under the curve of concentration versus time (AUC(0-tau)), maximum concentration (Cmax), and minimum concentration (Cmin) were bioequivalent. The ratio for CBTL-to-TXR was 98% (90% confidence intervals, 92-104%), 107% (96-118%), and 96% (89-104%), respectively. Similar ratios were also observed for CBZ-E: 102% (97-107%), 99% (92-107%), and 93% (83-109%), respectively. In conclusion, CBTL b.i.d. and TXR b.i.d. were bioequivalent in their pharmacokinetic parameters for CBZ and CBZ-E after 5 days of dosing.

A 12-week clinical trial determining the efficacy of synthetic conjugated estrogens, A (SCE), in the treatment of vasomotor symptoms in menopausal women.

OBJECTIVE: To compare the clinical effects of a new oral synthetic conjugated estrogens, A (SCE), versus placebo in a clinically relevant population on the reduction in the mean number of moderate to severe vasomotor symptoms. DESIGN: A total of 120 healthy pre- and postmenopausal women (72 active, 48 placebo) were enrolled into a randomized, placebo-controlled, double-blind, multi-center clinical trial. Women of all races were enrolled, using minimal inclusion and exclusion criteria. Each subject received either orally administered SCE, in doses of 0.3 mg, 0.625 mg or 1.25 mg per day, or placebo. Analysis of variance was performed on the primary efficacy variable (change from baseline to weeks 4, 8, and 12 in the mean number of moderate to severe vasomotor symptoms). RESULTS: Changes in moderate to severe vasomotor symptoms in the intent to treat population showed statistically significant differences between the active and placebo treatments at week 4 (P < .022), week 8 (P < .010), and week 12 (P < .010). By week 12, the mean percentage reduction in moderate to severe vasomotor symptoms was 81%, from an average baseline of 96.8, to 16.5 hot flashes per week for the active treatment group. The overall incidence of expected estrogen-related adverse effects was modest. Laboratory tests and vital sign measurements did not reveal clinically significant changes or abnormalities from screening to the final visit in either treatment group. CONCLUSIONS: The results of this study confirm the efficacy and safety of SCE in the treatment of moderate to severe vasomotor symptoms in menopausal women. In addition, the study also demonstrated that the use of more liberal entry criteria did not materially affect the efficacy outcome.

Fluoridation and the private practice of dentistry.

Water fluoridation holds an important place in the history of Grand Rapids. This paper recounts the firsthand professional experiences of a dentist before and after he joined his father's established dental practice in Grand Rapids, only two years after fluoridation of the city's water supply began. The benefits of water fluoridation are documented through a review of office records. The prevalence of dental caries in patients who were born in Grand Rapids after water fluoridation began is low, and no case of a missing first permanent molar was found. Quadrant dentistry is no longer practiced. Children of parents born in Grand Rapids after the start of water fluoridation experience less decay than their parents, suggesting that factors in addition to water fluoridation have played a role in the downward trends in caries. The complete destruction of mouths of patients seen in this practice 50 years ago no longer happens, providing evidence of the benefits of water fluoridation, the most important advance ever in dentistry.

Inadequacy of APUD concept in explaining production of peptide hormones by tumours.

The amine precursor uptake and decarboxylation (APUD) system of cells has been claimed to derive from the embryological neural crest. This assertion has been uncritically accepted. There is much contradictory evidence, especially about the origin of the gastrointestinal and respiratory APUD cells. There is further evidence that the embryological derivation of a particular cell does not relate to the possibility of ectopic peptide hormone synthesis by malignant tumours arising from that cell type. There are many reports of APUD activity by endodermally and mesodermally derived tumours, and of "APUDomas" with endodermal microscopic features. It seems that the concept of dedifferentiation explains the observed data much more satisfactorily and that the presence of double minute chromosomes may denote gene amplification and cellular production of peptides.

Patient, revenue and cost analyses for medical practices.

Authors Robert Stevens and Thomas Chatham write that revenue and cost analysis can be performed by medical groups from historical data they maintain. Such analysis provides the administrator with a data base for developing realistic objectives and identifying areas which should be more fully developed or even eliminated.

The public's image of doctors, dentists, and pharmacists.

The basic purpose of this study was to evaluate the public's image of three health professions. Q questionnaire was administered by telephone to a random sample of 150 residents of a southern metropolitan area. Respondents were asked to evaluate seven professions on (1) social standing (prestige), (2) honest and ethical standards, (3) importance to society and nation, and (4) interesting and challenging occupation. Overall findings indicate that doctors rated significantly higher than dentists, and pharmacists in all areas except honest and ethical standards. The three groups were rated equally on this factor. Cross tabulations of respondents by income, age, education, and sex revealed that there were no significant differences in the ratings of these groups on the basis of socio-economic characteristics of respondents except for pharmacists. Male respondents rated pharmacists significantly lower than female respondents.

Segmenting the mental health care market.

The authors report the results of a segmentation study of the mental health care market. A random sample of 387 residents of a western city were interviewed by telephone. Cluster analysis of the data identified six market segments. Each is described according to the mental health care services to which it is most sensitive. Implications for targeting the segments are discussed.

Dissecting health care markets: large versus small businesses.

This article reports the results of a mail survey of businesses in Tulsa, Oklahoma (population 377,900 in the city and 745,300 in the surrounding metropolitan area). The purpose of the research was to analyze differences in health care provision and perspectives between large and small businesses. The survey of 3,200 members of the city's chamber of commerce yielded 640 responses. Analysis of the data revealed distinct differences between the two segments of the health care industry. The findings suggest that market opportunities exist for the development of health care delivery system programs aimed at small businesses.

Feasibility analysis for medical services.

Feasibility analysis is an important aspect of business planning. A feasibility study is a study of the impacts of revenues, cost, and returns on a decision. It helps answer the questions of "What share of total sales can be attained?" "What revenues will be generated?" "What costs will be incurred?" "What will be the return on investment?" The discipline of going through a systematic approach to analyze market demand, cost requirements, and return on investment will improve business decisions by eliminating risk and increasing the possibility of successful ventures.

Segmenting health care markets: large versus small businesses.

What differences exist between provision of health care benefits, cost containment measures, and health care concerns between large and small companies? This issue of DRG Monitor examines these differences through the analysis of responses to a survey and suggests strategies that hospitals and other health care providers may employ to target both markets.

The nature of physician's services: marketing implications.

A specific system for classifying services is applied to physicians' services in an attempt to better understand those services. Other services organizations are identified that are similar to these services along each of the dimensions suggested by the classification system. In addition, marketing insights and implications are offered for marketing physicians' services.