The effects of formula feeding on physiological and immunological parameters in the gut of neonatal rats.

A unique model of formula feeding in the neonatal rat was utilized to investigate the effects of an enterally delivered artificial milk formula on clinically relevant immunological and biological characteristics in the gut, compared to naturally reared pups. Hooded Wistar rat pups were randomly allocated to two treatment groups: formula-fed (FF) or naturally suckled (NS). A flexible silastic intra-gastric cannula was surgically implanted into the FF pups, through which an artificial rat milk supplement was continuously delivered from day 4 to day 10 of life. Rat pups were sacrificed at 10 days of age. Body weight, small intestinal weight, mucosal CD8(+) cell numbers, and ileal lactase activity in FF animals were significantly decreased compared to their NS counterparts (P < 0.05). Numbers of eosinophils, mucosal mast cells, CD4(+) T-cells, ileal villus height and gastric emptying times were significantly increased in FF pups (P < 0.05). We have developed a new rat model of artificial feeding which possesses important immunological and biological similarities to the premature human infant.

Lactoferrin and desferrioxamine are ineffective in the treatment of Helicobacter pylori infection and may enhance H. pylori growth and gastric inflammation in mice.

AIMS: To evaluate the efficacy of bovine lactoferrin (BLf), recombinant human lactoferrin (rHLf) and desferrioxamine against Helicobacter pylori in vitro and in mice and also to determine whether BLf or rHLf alter gastric inflammation. METHODS AND RESULTS: In vitro: Broth dilution susceptibility tests were performed using different concentrations of desferrioxamine, BLf and rHLf. Murine trials: In the prevention trial, C57BL/6 female mice were treated with BLf or rHLF, and then infected with the SS1 strain of H. pylori. In the treatment trial, mice were gavaged with either BLf, rHLf or desferrioxamine. In addition, gastric myeloperoxidase activity (MPO) was measured to assess gastric inflammation. Desferoxamine was found to have a direct bactericidal effect, while BLf and rHLf only partially suppressed H. pylori growth in vitro. However, in both prevention and treatment trials all three forms of treatment failed to reduce H. pylori load in mice. Gastric MPO activity and H. pylori load were noted to be higher with lactoferrin treatments. CONCLUSIONS: Our study does not support the use of BLf or rHLF in the treatment of human H. pylori infection. Interestingly, H. pylori growth and gastric inflammation appear to be enhanced by lactoferrin treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: The mouse model is ideal for testing novel H. pylori eradicating agents.

A method for collecting breath samples from individual chickens for analysis of 13CO(2), H(2), and CH(4).

This study describes experiments using simple helmets to collect breath samples from individual birds for measurement of (13)CO(2), H(2), and CH(4), which form the basis for various diagnostic tests for intestinal dysfunction in humans. Peak enrichment in (13)C in breath CO(2) occurred between 5 and 30 min postingestion by 18-d-old chickens administered a gelatin capsule containing approximately 3.6 mg of (13)C-octanoic acid dissolved in vegetable oil. For 25-d-old chickens given 10 mL of homogenized cooked corn by oral gavage, peak enrichment occurred 60 to 90 min postingestion. In fully fed 25-d-old chickens, H(2) and CH(4) concentrations in breath ranged from 7 to 115 ppm and from 0 to 5.5 ppm, respectively. Following an overnight fast, H(2) and CH(4) concentrations in breath ranged from 0.5 to 7.5 ppm and 0 to 3.0 ppm, respectively, in the same chickens. Ranges in H(2) (1.0 to 56.5 ppm) and CH(4) (0 to 8.0 ppm) concentrations widened considerably 3 h after oral gavage with approximately 130 mg of lactulose (an indigestible disaccharide) dissolved in 5 mL of water. The results from these investigations indicate that collection of re-breathed air samples from chickens is plausible, which opens the way for development of noninvasive methods for evaluating gastrointestinal functions in chickens.

Immunobead-PCR: a technique for the detection of circulating tumor cells using immunomagnetic beads and the polymerase chain reaction.

The presence of tumor cells in the circulation may predict disease recurrence and metastases. We have developed a sensitive technique for the detection of carcinoma cells in blood, using immunomagnetic beads to enrich for epithelial cells and the polymerase chain reaction to identify a tumor marker. The colon carcinoma cell line SW480, homozygous for a K-ras codon 12 mutation, was used to establish optimal conditions. The SW480 cells were serially diluted in normal blood and incubated with immunomagnetic beads labeled with a monoclonal antibody specific for epithelial cells. Cells bound to the beads were retrieved using a magnetic field and the presence of K-ras codon 12 mutations determined by a polymerase chain reaction based analysis. SW480 cells could be detected in dilutions up to 1 SW480 cell/10(5) leukocytes in whole blood.

Atrial kinetics and left ventricular diastolic filling in the healthy elderly.

A delay of left ventricular isovolumic relaxation and decrease in myocardial compliance may result in a decline of measured early filling rates in elderly subjects. Previous studies of diastolic function, however, have not excluded coronary artery disease or addressed the contribution of atrial contraction to diastole. The present study evaluated radionuclide-derived diastolic variables in 13 healthy elderly volunteers aged 75 +/- 6 years without symptoms or risk factors for coronary disease who had normal findings on the stress electrocardiogram, stress gated blood pool imaging and two-dimensional echocardiogram. Results were compared with those of a group of 10 healthy young volunteers aged 26 +/- 5 years. High count, 32 frame, double-buffered gated blood pool acquisitions were obtained at rest in the left anterior oblique view with an RR interval variation less than 5%. Left ventricular time-activity curves were analyzed and flow-volume loops for each group were constructed. In the healthy elderly: peak early diastolic filling rate is decreased, time of peak early filling and time to first third of diastolic filling are delayed, and peak late left ventricular filling rate and percent of atrial filling volume are augmented, suggesting an adaptive response of the atria to diminished left ventricular compliance.

Short-term zinc supplementation attenuates Helicobacter felis-induced gastritis in the mouse.

BACKGROUND: Mucosal damage by H. pylori infection is mainly caused by neutrophils producing large quantities of reactive oxygen species (ROS). Metallothionein (MT) an intracellular, low-molecular, cysteine-rich protein, which is inducible by dietary zinc (Zn), has been implicated in sequestering ROS. This study examines the effects of Zn supplementation on Helicobacter colonisation and associated gastritis and the relationship with gastric MT levels. METHODS: C57Bl/6 mice were inoculated with either 10(8) H. pylori or H. felis and were infected for 4 weeks or 6 and 12 weeks, respectively. Mice infected with H. pylori (4 weeks) or H. felis (6 weeks) were treated with either Zn acetate (ZnA; 1 mg/ml), or Zn sulphate (ZnSO4; 5 mg/ml) for 2 weeks with 0.1 ml oro-gastric gavage twice daily. H. pylori load and H. felis colonisation density were determined by culture and microscopy, respectively. MT levels and H. felis-induced gastritis were also determined. RESULTS: Zn treatment showed no significant difference in Helicobacter load and gastric MT, however, ZnSO4 treatment showed a significant (p<0.05) increased in gastric MT in H. felis infected mice. Both Zn-treated groups showed a significant (p<0.05) difference in gastritis score in the antrum of the stomach within the basal and submucosal compartments compared to H. felis-infected controls. CONCLUSIONS: We found that H. felis-induced gastritis can be attenuated by short-term treatment of Zn. This observation suggests that Zn alone may be effective for the suppression of gastric mucosal inflammation induced by Helicobacter.

Psychiatry and the elderly: an overview.

The author notes that the elderly in our society have not been provided with treatment, research, and services commensurate with their needs. These needs are reflected in the increasing incidence of psychopathology, suicide, and poverty with increasing age. The psychiatric profession's therapeutic nihilism toward the elderly may reflect unresolved countertransference issues that result in a form of prejudice called "ageism." Many of the conditions labeled "senility" are actually manifestations of socioeconomic or medical problems that could be resolved with prompt, appropriate treatment. The author makes several recommendations--the creation of a multidisciplinary nongovernmental commission on mental health and illness of the elderly, reexamination by psychiatrists of their attitudes toward the elderly, and proportionate representation of older individuals in psychiatric services, training, and research.

Thoughts on aging.

Aging has not received attention in proportion to its effect on the life of every individual. Much of society's reluctance to deal with old age results from "ageism," a personal and cultural dread that stems from a view of aging that sees only the negative aspects. If we are to understand human development, we must learn about its outcome, old age. One means of doing this to listen to the reminiscences of old people. Psychiatrists can apply their special expertise in working to overcome ageism. Current and future legislative and research efforts can help identify and resolve some of the economic and physical problems of the elderly and thereby improve the quality of their lives.

Quality of life: can it be an endpoint? How can it be measured?

Although quality of life is an elusive concept constantly in flux, it is possible to identify certain basic criteria whose presence or absence determines the degree of quality in an older person's life. It is possible through a variety of measures to improve quality of life on both a personal and societal level. Improvements will be even greater once the major diseases of old age are conquered. We can get closer to that goal with greater investments in research on aging.

The effect preloads of amino acid on shortterm satiety.

The effect of a preload of an amino acid preparation on food intake in man was assessed in eight subjects. Each subject was given a small dose of amino acids or placebo 1/2 h before being presented with a meal. This was done in a blind, randomized fashion on five occasions for each preparation to each subject. The mean food intake of the subjects when receiving the amino acid preparation was 10% (p less than 0.01) less than the intake when receiving the placebo. When the subjects were grouped according to their variation from ideal weight, a 22.5% reduction in food intake was observed in group I (n = 4) who were greater than 5% above the ideal weight for height ratio (p less than 0.001). A 1.75% increase (NS) was seen in group II (n = 4) whose weight was within 5% of their ideal weight. These results demonstrate a modulation of satiety by small caloric doses of amino acids in overweight subjects.

Economic and political implications of immunology and aging on tomorrow's society.

The historic development of immunology is associated with Eli Metchnikoff who introduced the term 'gerontology' in 1906. Metchnikoff also understood the impact of population aging on society as revealed in two remarkable books. The immune system is relevant to aging in so many ways immunesenescence, the potential role of immunological changes in the dementias, the interrelationship of immune resistance and bereavement, retirement and other life changes and transplantation biology and pathology. These are only a few examples of the interrelationships of immunology and aging. The economic and political implications of immunology and aging are rarely discussed. If we are not able to cure the disorders of longevity, we need to delay their onset and progression. Such an effort is enhanced by modern biology including recombinant DNA and Hybridoma technology. Many in society fear the growing numbers of older persons-can we afford old age? Will population aging lead to stagnation of society and will there be intergenerational conflicts? These gloomy notions are not entirely offset by enthusiasm for an extended high quality longevity. This presentation will discuss these various issues and offer positive solutions.

Mission of the National Institute on Aging.

The National Institute on Aging (NIA), the newest of the eleven National Institutes of Health, is dedicated to improving the quality of life of the old in America through biomedical, social, and behavioral research. Aging is reviewed as more than just decline and deterioration; it is also a process of continued development and accumulated knowledge. The NIA will encourage innovative research, but will not support the delivery of health services, as that is the domain of other agencies. In areas of overlap, such as diseases common to the old, the NIA will collaborate with other Institutes. A good target area for collaboration is senile dementia. Other areas of interest to the NIA are: encouraging the incorporation of geriatric medicine as a subspecialty, developing retirement test patterns, and investigating drug-drug and drug-age interactions, personality and social processes, and immunocompetence.

Non-steroidal anti-inflammatory drugs and apoptosis in the gastrointestinal tract: potential role of the pentose phosphate pathways.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely prescribed drugs, primarily for treatment of arthritis. NSAIDs can have two effects independent of their anti-inflammatory action. In the stomach and small bowel long term NSAID consumption can lead to ulceration, whereas in the colon NSAID use can regress existing tumours. In this review, we hypothesise that NSAID-induced damage occurs predominantly by promoting apoptosis, involving a number of mechanisms depending on the type and the redox state of the cell. In addition to inhibiting cyclooxygenase (COX) activity, this includes interfering with glucose metabolism through both arms of the pentose phosphate pathways and energy production via glycolysis and oxidative phosphorylation. Shifting the cellular balance from proliferation to apoptosis is probably the most important outcome by which NSAIDs exhibit their differing actions. Understanding how these different pathways can be reconciled and their contribution to the balance between cell birth and cell death is the challenge for the future. The pentose phosphate pathways may provide a pivotal point for understanding links between factors which alter proliferative activity (e.g. COXs), provide energy metabolism (particularly aerobic and anaerobic metabolism of glucose), and change the redox state of the cell leading to apoptosis.

First generation of pentazole (HN5, pentazolic acid), the final azole, and a zinc pentazolate salt in solution: A new N-dearylation of 1-(p-methoxyphenyl) pyrazoles, a 2-(p-methoxyphenyl) tetrazole and application of the methodology to 1-(p-methoxyphenyl) pentazole.

Ceric ammonium nitrate (CAN) in methanol-water gave a new N-dearylation of a series of substituted 1-(p-methoxyphenyl) pyrazoles and a 2-(p-methoxyphenyl)tetrazole producing p-benzoquinone and the parent azole in a mole for mole ratio. Application of this reaction to 1-(p-methoxyphenyl) pentazole at -40 degrees C produced p-benzoquinone. 15N NMR spectra suggest that pentazole, HN5, was also produced and held in solution as N5- with Zn2+ ion. The 15N signal from N5- was -10.0 +/- 2.0 ppm in agreement with calculated values.

A new tricyclic ring and a nitrogen-sulfur analogue of the tri-pentagon bowl. Substituted 5,6,7,7a-tetrahydropyrrolo[2,1-b]-1,3,4-thiadiazole- endo-6,7-dicarboxyimides.

The first examples of a bowl-shaped tricyclic nitrogen-sulfur analogue of the tri-pentagon bowl are reported; substituted 5,6,7,7a-tetrahydropyrrolo[2,1-b]-1,3,4-thiadiazole-endo-6,7-dicarboxyimides are synthesised by a relatively simple route.

Injury-control education in six U.S. medical schools.

PURPOSE: To assess knowledge, attitudes, and formal instruction related to injury control among fourth-year medical students. Injury is the leading cause of death among Americans aged 1 to 44 years. METHOD: The authors conducted a cross-sectional survey of fourth-year students at six U.S. medical schools, four of which maintain federally funded injury prevention research centers. Main outcome measures included injury-related knowledge scores, three attitude measures, and self-reported exposures to injury prevention education. RESULTS: Six hundred and thirty-five fourth-year medical students (73% of those eligible) participated. The responding students were, on average, unable to correctly answer half of the questions testing injury-related knowledge. They rated medical problems more important and more preventable than injury problems, and they felt more comfortable asking their patients about risk factors for medical problems. These findings may be explained, in part, by the students' reported minimal exposure to injury control education in medical school. The students encountered the topic more frequently on rotations in pediatrics (84%), family medicine (73%), and preventive medicine (66%) than on rotations in emergency medicine (47%), internal medicine (41%), or obstetrics and gynecology (34%). Injury control was encountered least often on rotations in psychiatry (23%) and surgery (14%). CONCLUSIONS: These findings suggest that injury control is given limited coverage in the curricula of U.S. medical schools. As a result, students have little understanding of the principles and benefits of injury control.

Therapeutic goals: quality and quantity of life.

The elderly population is projected to increase from the present 11 per cent of the overall population to 20 per cent by the year 2020. The efforts of the medical community are directed toward extending the quantity of life. However, economic necessity and technologic advance in medicine will dictate the health care delivery to the elderly, as quality of life becomes a major factor in therapeutic decision making.

Hearing and age: research challenges and the National Institute on Aging.

Just as the ear trumpet once symbolized the elderly, so do contemporary approaches to hearing loss in the aged reflect many of the major themes in geriatrics and gerontology today. This paper begins by describing the National Institute on Aging (NIA) with particular emphasis on activities relevant to hearing in the elderly. Next, several areas of research interest, including the typology of presbycusis and related conditions, the epidemiology of auditory impairment in old age, the design of testing and research, and the rehabilitation of the hearing-impaired elderly, are addressed. The NIA and the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) are coordinating their efforts to stimulate investigation of these and related topics.

Late-life depression: when and how to intervene.

Late-life depression ranges from mild to severe and can lead to significant physical and social limitations. Up to one-third of patients with medical disorders also suffer from depressive symptoms. Differential diagnosis of depression is often confounded by medical conditions that impair cognitive functioning, such as Alzheimer's disease and vascular dementia. Depression is a modifiable risk factor for suicide in old age. Once diagnosed, depression is a highly treatable disease. Treatment modalities include psychotherapy, antidepressants, and electroconvulsive therapy for intractable cases. Many patients are now being treated in primary care settings, due to managed care limits on referrals and to patient reluctance to seek psychiatric care.

Love and sex after 60: how to evaluate and treat the impotent older man. A roundtable discussion: Part 2.

In the medical evaluation of older men with erectile dysfunction, obtain a detailed history to determine whether the dysfunction is organic or psychogenic. Determine if there are underlying pathologic processes--most notably vascular diseases--or other factors responsible for the dysfunction, such as medications or nerve or arterial damage from surgery. Lifestyle changes in mid-life (regular exercise, a low-fat diet, and smoking cessation) increase a man's chances of remaining potent as he grows older. Treatments for impotence include injection therapy, vacuum devices, and implants. Each therapy has advantages and disadvantages, and the informed patient plays an important role in choosing the therapy that is right for him.