Influence of standing estrus before an injection of GnRH during a beef cattle fixed-time AI protocol on LH release, subsequent concentrations of progesterone, and steriodogenic enzyme expression.

Beef cows that exhibit estrus before fixed-time AI have been reported to have increased pregnancy success and increased concentrations of progesterone during the subsequent estrous cycle. Therefore, these experiments were conducted to evaluate if initiation of standing estrus before an injection of GnRH during a fixed-time AI protocol affected LH pulses, subsequent concentrations of progesterone, and luteal steroidogenic enzyme expression. In Experiments 1 and 2, cows were treated with the CO-Synch protocol (100 µg GnRH day -9, 25 mg PGF(2α) day -2, and 100 µg GnRH day 0) and allotted to one of two treatments: 1) cows that initiated estrus before GnRH on day 0 (estrus; n = 5) or 2) cows that did not initiate estrus and were induced to ovulate by the GnRH on day 0 (no estrus; n = 5). In Experiment 1, blood samples were collected at 15-min intervals from 0 to 6 (bleed 1), 12 to 20 (bleed 2), 26 to 34 (bleed 3), and 40 to 48 (bleed 4) h after GnRH. Daily blood samples were collected for 17 d. Initiation of estrus before the GnRH injection had no effect on LH release or the pattern of progesterone increase; however, cows detected in estrus had overall increased (P = 0.002) concentrations of progesterone compared with cows not in estrus. In Experiment 2, estrus was detected with the HeatWatch system. Location and size of the ovulatory follicle was determined on day 0 by transrectal ultrasonography at time of injection with GnRH. Blood samples were collected on days 3, 4, 5, 7, and 9; luteal tissue was collected on day 10 (n = 4 estrus and n = 9 no estrus) from corpus luteum (CL) originating from similar-sized follicles (13.0 to 16.0 mm). Total cellular RNA was extracted, and relative mRNA levels were determined by real-time reverse transcription PCR and corrected for GAPDH. There was no effect of estrus on CL weight or concentrations of progesterone. In addition, there was no effect of estrus, follicle size, or CL weight on luteal expression of LH receptor, StAR, CYP11A1, or 3ßHSD. However, there was a correlation between follicle size and CL weight (P = 0.01; R(2) = 0.43); for every increase of 1 mm in follicle size, CL weight increased by 1.5 g. In summary, estrus did not influence release of LH, CL weight, progesterone concentrations, or expression of steriodogenic enzymes. However, as follicle size increased, CL weight increased; therefore, both follicle size and CL weight were associated with progesterone concentrations.

Influence of inducing luteal regression before a modified controlled internal drug-releasing device treatment on control of follicular development.

At the initiation of most controlled internal drug-releasing (CIDR) device protocols, GnRH has been used to induce ovulation and reset follicular waves; however, its ability to initiate a new follicular wave is variable and dependent on stage of the estrous cycle. The objectives of the current studies were to determine 1) if inducing luteal regression before the injection of GnRH at time of insertion of a CIDR resulted in increased control of follicular development, and 2) if removing endogenous progesterone by inducing luteal regression before insertion of the CIDR decreased variation in LH pulse frequency. In Exp. 1 and 2, Angus-cross cycling beef heifers (n = 22 and 38, respectively) were allotted to 1 of 2 treatments: 1) heifers received an injection of PGF(2α) on d -3, an injection of GnRH and insertion of a CIDR on d 0, and a PGF(2α) injection and CIDR removal on d 6 (PG-CIDR) or 2) an injection of GnRH and insertion of a CIDR on d 0 and on d 7 an injection of PGF(2α) and removal of CIDR (Select Synch + CIDR). In Exp. 3, Angus-cross beef heifers (n = 15) were assigned to 1 of 3 treatments: 1) PG-CIDR; 2) PGF(2α) on d -3, GnRH on d 0, and PGF(2α) on d 6 (PG-No CIDR); or 3) Select Synch + CIDR. Follicular development and ovulatory response were determined by transrectal ultrasonography. Across all experiments, more (P = 0.02) heifers treated with PG before GnRH initiated a new follicular wave after the injection of GnRH compared with Select Synch + CIDR-treated heifers. In Exp. 1, after CIDR removal, interval to estrus did not differ (P = 0.18) between treatments; however, the variance for the interval to estrus was reduced (P < 0.01) in PG-CIDR heifers compared with Select Synch + CIDR heifers. In Exp. 3, there was a tendency (P = 0.09) for LH pulse frequency to be greater among PG-CIDR and PG-No CIDR compared with the Select Synch + CIDR, but area under the curve, mean LH concentrations, and mean amplitude did not differ (P > 0.76). In summary, induction of luteal regression before an injection of GnRH increased the percentage of heifers initiating a new follicular wave. Removal of endogenous progesterone tended to increase LH pulse frequency, and the modified treatment increased the synchrony of estrus after CIDR removal.

Effects of GnRH treatment on initiation of pulses of LH, LH release, and subsequent concentrations of progesterone.

Progesterone is essential for establishment and maintenance of pregnancy. One proposed method to increase progesterone is administering GnRH at insemination. However, this method has resulted in conflicting results. Therefore, 2 experiments were conducted to evaluate how administering GnRH at insemination affected pulses of luteinizing hormone (LH) and subsequent progesterone. In Experiment 1, cows were allotted to 2 treatments: (1) GnRH (100 microg) given approximately 12h after initiation of estrus (n=5); and (2) Control (n=5). Blood samples were collected at 15-min intervals for 6h at 12 (blood sampling period 1), 26 (blood sampling period 2), 40 (blood sampling period 3), 54 (blood sampling period 4), and 68 (blood sampling period 5) h after onset of estrus. Daily blood samples were collected for 17 d. In Experiment 2, cows were allotted into 2 treatments: GnRH administered 10 to 11h (n=10) or 14 to 15 h (n=10) after onset of estrus. Daily blood samples were collected for 17 d. Cows treated with GnRH tended (P

Chronic heart failure. Examining consensus recommendations for patient management.

In the mid 1990s, various organizations published guidelines for the management of chronic heart failure. Subsequent advances in pharmacologic treatment, however, warranted the release of recommendations that accounted for the new developments. Hence the publication in 1999 of the "Consensus recommendations for the management of chronic heart failure." Although there are measures patients can take to help prevent development of heart failure, the recommendations focus primarily on pharmacologic treatment of left ventricular systolic dysfunction. The discussion includes examination of the role of diuretics, ACE inhibitors, beta blockers, cardiac glycosides, as well as alternate agents such as angiotensin II receptor blockers. All of these agents can be used to help achieve a key management goal: decrease disease progression and thereby decrease the risk of hospitalization and death.

Urinary incontinence. A primary care guide to managing acute and chronic symptoms in older adults.

Loss of urinary control is closely linked with loss of independence. Most cases of urinary incontinence can be improved using behavioral and pharmacologic interventions. Several factors--including reluctance by physicians and patients to discuss and investigate symptoms--prevent patients from obtaining effective clinical management. In 1996, the Agency for Healthcare Research and Quality published a guideline for the management of acute and chronic urinary incontinence in adults. In addition to educating healthcare providers and patients about urinary incontinence, the guideline's mission includes improving the reporting, diagnosis, and treatment of the condition. The guideline offers a thorough discussion of urinary incontinence symptoms and subtypes, techniques for identifying and evaluating the condition, and treatment approaches.

Clinical practice guidelines. Finding and appraising useful, relevant recommendations for geriatric care.

Practicing effective evidence-based medicine in the geriatric setting depends on routine review of the current literature and critical analysis of its relevance to the patient and condition in question. Clinical guidelines facilitate this approach and are readily available from an array of print and electronic resources. The recent growth in the number of published guidelines by medical associations, government agencies, and healthcare organizations makes determining their validity and applicability a challenging proposition. The Internet provides one of the most effective tools for quickly finding evidence-based guidelines. Appraisal involves several fundamental steps that can aid in determining whether the guidelines are valid--based on "best evidence"--and clinically relevant.

The baccalaureate degree in nursing as an entry-level requirement for professional nursing practice.

The education of professional nurses must take place in institutions of higher learning with a bachelor of science in nursing degree required for beginning professional practice. Nurses educated in these academic settings should be socialized as professionals with a philosophical and value system that is compatible with this role. This education should be flexible, diverse, and directed toward providing the nurse with a solid base for general, professional nursing practice. Nursing as a profession is a social institution and must present itself as a strong, unified profession to survive the inevitable changes occurring on the health care front. By tracing the evolution of the entry-into-practice dilemma, a systems archetype and two mental models that currently drive nursing and jeopardize its potential to meet the demands of the emerging health care market are identified. The authors offer a high-leverage solution to the entry-into-practice dilemma that they believe will strengthen the nursing profession.

The S. cerevisiae CLU1 and D. discoideum cluA genes are functional homologues that influence mitochondrial morphology and distribution.

The cluA gene, encoding a novel 150 kDa protein, was recently characterized in Dictyostelium discoideum; disruption of cluA impaired cytokinesis and caused mitochondria to cluster at the cell center. The genome of Saccharomyces cerevisiae contains an open reading frame (CLU1) that encodes a protein that is 27% identical, 50% similar, to this Dictyostelium protein. Deletion of CLU1 from S. cerevisiae did not affect cell viability, growth properties, sporulation efficiency, or frequency of occurrence of cells lacking functional mitochondria. However, in clu1Delta cells the mitochondrial reticulum, which is normally highly branched, was condensed to one side of the cell. Transformation of cluA- Dictyostelium mutants with the yeast CLU1 gene yielded amoebae that divided normally and had dispersed mitochondria. The mitochondria in cluA- Dictyostelium cells complemented with CLU1 were not as widely scattered as in cluA+ Dictyostelium cells, but formed loose clusters throughout the cytoplasm. These results indicate that the products of the CLU1 and cluA genes, in spite of their limited homology, are functional homologues.

Spray-freezing freeze substitution (SFFS) of cell suspensions for improved preservation of ultrastructure.

Some unicellular organisms present challenges to chemical fixations that lead to common, yet obvious, artifacts. These can be avoided in entirety by adapting spray-freezing technology to ultrarapidly freeze specimens for freeze substitution. To freeze specimens, concentrated suspensions of cells ranging in diameter from 0.5-30 pm were sprayed with an airbrush at 140-200 kPa (1.05-1.5 torr; 20.3-29.0 psi) into a nylon mesh transfer basket submerged in liquid propane. After freezing, the mesh basket containing the frozen sample was lifted out of the chamber, drained and transferred through several anhydrous acetone rinses at 188 K (-85 degrees C). Freeze substitution was conducted in 1% tannic acid/1% anhydrous glutaraldehyde in acetone at 188 K (-85 degrees C), followed by 1% OsO4/acetone at 277 K (4 degrees C). Freeze substitution was facilitated using a shaking table to provide gentle mixing of the substitution medium on dry ice. High quality freezing was observed in 70% of spray-frozen dinoflagellate cells and in 95% of spray-frozen cyanobacterial cells. These could be infiltrated and observed directly; however, overall ultrastructural appearance and membrane contrast were improved when the freeze-substituted cells were rehydrated and post-fixed in aqueous OSO4, then dehydrated and embedded in either Spurr's or Epon resin. Ultrastructural preservation using this ultrarapid freezing method provided specimens that were consistently superior to those obtainable in even the best comparable chemical fixations.

Dopamine transporters decrease with age.

UNLABELLED: Postmortem studies have documented degeneration of dopamine cells with age, but the changes that occur in healthy aging individuals is less clear. The purpose of this study was to evaluate the extent to which age-induced changes in dopamine transporters occur in subjects with no evidence of motor impairment. METHODS: We evaluated 23 right-handed healthy volunteers (age range 20-74 yr) using PET and [11C]d-threo-methylphenidate. The ratio of the distribution volume for [11C]d-threo-methylphenidate in striatum to that in cerebellum was used as model parameter for dopamine transporter availability (Bmax/Kd + 1). RESULTS: Dopamine transporter availability was significantly lower in subjects > 40 yr of age than in those < 40 yr. Estimates of dopamine transporter availability showed a significant negative correlation with age both for the putamen (r = -0.72, p < 0.0001) and the caudate (r = -0.74, p < 0.0001). Dopamine transporter availability was higher in the left than in the right putamen but did not differ between the left and right caudate. CONCLUSION: This study documents a 6.6% decrease per decade of life in striatal dopamine transporters of healthy volunteers.

Geriatric education. Part I: Efficacy of a mandatory clinical rotation for fourth year medical students.

OBJECTIVES: To describe the curriculum of a mandatory, fourth-year geriatrics clerkship and assess its impact on medical students' knowledge of geriatric medicine and attitudes toward the elderly. DESIGN: One group, before/after trial. SETTING: Mount Sinai School of Medicine of the City University of New York. PARTICIPANTS: Entire fourth year class of medical students (n = 127). INTERVENTION: Four-week-long clinical geriatrics clerkship. MEASUREMENTS: Pre- and post-rotation: test of knowledge; Aging Semantic Differential (ASD) attitude scale; Modified Maxwell-Sullivan attitude scale; questionnaire. MAIN RESULTS: Seventy percent of students found the rotation to be educationally valuable; however, only one-third of students would have taken the clerkship had it not been required. Mean geriatric knowledge score increased by 18.7% (P less than 0.001). Mean ASD attitude score did not change significantly (130.5 +/- 19.2 pre-rotation versus 126.6 +/- 18.8 post-rotation, P = 0.15), but students started the rotation with a neutral attitude. Over 90% of students agreed they would welcome elderly into their future practice. CONCLUSION: If a national curricular goal is to improve medical students' knowledge of geriatric medicine, required rather than elective rotations may be in order.

Geriatric education. Part II: The effect of a well elderly program on medical student attitudes toward geriatric patients.

OBJECTIVE: To assess impact of exposure to healthy elderly on medical students' attitudes toward the elderly. DESIGN: Prospective, randomized, controlled intervention trial. SETTING: Community-based Well Elderly Program. PARTICIPANTS: Ninety-three fourth year medical students on a required Geriatric Medicine clerkship who were assigned to either a tertiary care university medical center or a teaching nursing home. INTERVENTION: Thirty-five students were randomly assigned to participate in a Well Elderly Program and were compared to a control group of 58 students at equivalent sites who did not participate. MEASUREMENTS: Pre- and post-rotation, students were given the Aging Semantic Differential (ASD), a validated geriatric attitudinal scale. MAIN RESULTS: By repeated measures analysis of variance, the difference between pre- and post-rotation ASD scores were most significant for students who participated in the Well Elderly Program; site did not exert a significant interaction effect. CONCLUSION: These results underscore the importance of exposure to healthy older people on effecting positive attitude changes among medical students on geriatrics rotations.

Usefulness of the Neurobehavioral Cognitive Status Examination in the hospitalized elderly.

A prospective pilot study compared the Neurobehavioral Cognitive Status Examination (NCSE) to the Folstein Mini-Mental State Examination (MMSE) to determine the usefulness of the NCSE as a cognitive screen in a geriatric inpatient population. All patients directly admitted to the geriatric evaluation and treatment unit (GETU) of a university teaching hospital over a two-and-a-half-month period were eligible for the study, in which 42% participated. Within 72 hours of admission, patients were given the MMSE and the NCSE in a nonrandom order by a trained psychologist and a structured interview by a psychiatrist. The ability of the NCSE to detect global cognitive impairment was compared to the MMSE and psychiatrist's assessment. Differences in sensitivity were examined by discordant pair analysis. The psychiatrist's determination of the presence of cognitive impairment was used as the criterion standard. Comparisons of the MMSE and NCSE, respectively, revealed the following: sensitivity 83% versus 100%; specificity 78% versus 11%; positive predictive value 83% versus 43%; and negative predictive value 78% versus 100%. Seven patients who were cognitively impaired by the NCSE were not impaired by the MMSE (p less than 0.05 by discordant pair analysis). The time of administration for the two tests was significantly shorter for the MMSE (14.75 +/- 5.7 minutes) than for the NCSE (38.9 +/- 12.9 minutes). The NCSE was found to be more sensitive than the MMSE in detecting cognitive impairment among geriatric inpatients, but its specificity and positive predictive values were lower. Beyond this pilot study, additional work examining the utility of the NCSE in other geriatric settings and for different purposes (e.g., as part of comprehensive assessment) needs to be performed.

History-taking in the elderly: obtaining useful information.

Although the medical history in the average adult can approach a diagnostic yield of 90%, its utility in geriatric patients is often much lower. Potential barriers to communication with the elderly include cognitive, behavioral, and physical problems. This article suggests techniques the primary care physician can use to overcome these obstacles and get the maximum diagnostic information from the patient history.

Special considerations in the physical exam of older patients.

For diagnostic utility, aspects of the standard physical examination are modified for elderly patients. Special attention is paid to problems that interfere with function, such as gait disorders, incontinence, and hearing and visual loss. Certain findings in cardiac and pulmonary examinations of the elderly require different interpretations. The examination should include the head and neck, chest, back, abdomen, breasts and pelvic area in women, prostate in men, extremities, and skin, as well as mental status. A number of diagnostic maneuvers are used to distinguish changes of normal aging from those associated with disease.

Morbidity during hospitalization: can we predict it?

Physicians use the concept of stability to estimate the likelihood that a patient will deteriorate during a hospitalization. To determine whether physicians can accurately predict a patient's risk of morbidity, 603 patients admitted to the medical service during a one month period were rated prospectively as to how stable they were. Overall, 15% of patients had deterioration of already compromised systems, while 17% had new complications, such as sepsis. Eight percent of patients had both. Twelve percent of stable patients experienced morbidity; 39% of the somewhat unstable and 61% of the most unstable. When all of the demographic and clinical variables were taken into account including the reason for admission and comorbid diseases, the residents' estimates of the patient's stability was the most significant predictor of morbidity (p less than 0.001). The judgment that a patient was stable had an 87% negative predictive accuracy, while the judgment unstable had a 46% positive predictive accuracy.

Reversibility of cognitive impairment in medical inpatients.

To determine outcomes of patients admitted to the hospital with global cognitive impairment and to identify factors that might predict improvement, we screened all medical ward admissions over a one-month period with Folstein's Mini-Mental State Examination. Of 115 patients, 23 (20%) scored less than 24, indicating that they were cognitively impaired. Nineteen patients survived to discharge and were followed up for three months; three additional patients died in this period. Nine (47%) of the 19 patients significantly improved their Mini-Mental State scores. Five (26%) of the 19 improved to normal. They scored better on the initial Mini-Mental State Examination and lower (less dementia) on Blessed's Dementia Rating Scale. Age, severity and stability of medical illness, presence of neurologic abnormalities, clinical course, extensiveness of medical evaluation, and psychiatric criteria for delirium did not predict improvement.

Cognitive impairment. Can it predict the course of hospitalized patients?

All patients admitted to three medical services at the New York Hospital during a one-month period were screened with Folstein's Mini-Mental State Examination. The prevalence of cognitive impairment was 19.8% (23 of 116). Cognitively "impaired" patients, ie, those with a Folstein score less than 24, were older, sicker, and less physiologically stable than the cognitively "intact." The in-hospital mortality (17 versus 5%) and morbidity (39 versus 18%) rates were higher for the cognitively "impaired" patients; these differences could be explained by the greater severity of illness, instability, and comorbidity found in these patients. Cognitively "impaired" patients were particularly susceptible to respiratory complications. Cognitively "impaired" patients had longer lengths of hospital stay, spent more time in hospital awaiting placement, and were more likely to be discharged to a nursing home or require home assistance than their cognitively "intact" counterparts. Three-month mortality rates were also higher for the cognitively "impaired" patients (30 versus 15%). These findings suggest that cognitive impairment on admission may be regarded as a marker for patients with poorer prognoses.

Resuscitation: how do we decide? A prospective study of physicians' preferences and the clinical course of hospitalized patients.

Physicians have to address the question of the measures to be employed in the event that a patient's condition deteriorates after admission to the hospital. To identify the information that physicians use in making such decisions, all 604 patients admitted to the medical service during a one-month period were studied. The patient's age and residents' estimates of the patient's long-term prognosis and ability to function were the three primary factors that correlated with intervention preferences. When illness severity, the reason for admission, comorbidity, and poor function were taken into account, mortality and morbidity rates did not differ between patients for whom full vs not-full intervention was favored. Apart from differential rates of admission to critical care units, there were no important differences in the care, course, or mortality of patients for whom less than full intervention was initially favored. Suggestions that physicians should discuss resuscitation with all or most patients who may die are unrealistic. A more prudent strategy is to discuss the issue with patients whose hospital course is marked by a steady deterioration.

KIE: A study was undertaken to identify the determinants of physicians' decisions about the treatment status of all patients admitted to the medical service of the New York Hospital-Cornell Medical Center during a one-month period. It was found that the patient's age, prognosis, and functional status were the main factors considered in assigning "full" vs. "not-full" intervention. Within prognostically similar groups, there was no significant difference in mortality rates between "full" and "not-full" intervention patients. Except for admission to intensive care units the level of care was not lower for "not-full" intervention patients. The investigators conclude that, because most severely ill patients survive and patient participation in resuscitation decisions is psychologically stressful, the optimal strategy is to limit initiation of such discussions to those patients whose hospital course is marked by a steady deterioration.