Plasma oxytocin during the first and second stages of spontaneous human labour.

A technique for complete oxytocinase inhibition has been combined with a rapid serial sampling strategy to determine plasma oxytocin concentrations in twelve women during the early and late first stage and in eight women throughout the second stage of labour. The progress of labour is not related to an increase in oxytocin concentration, uterine contractions are not associated with changes in plasma oxytocin concentration and hypocontractile labour does not appear to be the result of a deficit of oxytocin. The majority of patients do not demonstrate an increase in plasma oxytocin concentration during the second stage of labour; however, a minority produce a large surge immediately before delivery. The results do not support a role for oxytocin during spontaneous labour unless uterine activity is controlled by extremely low plasma hormone concentrations or the uterus becomes sensitive to a constant oxytocin concentration.     

Role of Anger in Antral Motor Activity in Irritable Bowel Syndrome

There is considerable evidence indicating that patients with irritable bowel syndrome respond to emotional and environmental stimulation with increased colon motor activity. It has been suggested also that increased colon motor activity is not confined to the colon and may be representative of a broader disorder affecting the rest of the gastrointestinal tract in this population. The results of our current study suggest that anger may have a significant, although differential effect on antral motor activity in IBS patients compared to normal controls. We found that while antral motor activity did not differ significantly in our groups during rest, anger decreased antral motor activity in IBS patients and increased antral motor activity in normal controls. The difference was not attributable to a difference in anger levels since the groups did not differ in their response to the standardized anger stressor. Rather, the difference in the antral motor response appears to be qualitative and a possible marker for irritable bowel syndrome. Our data further suggest that increased colon motor activity in IBS patients during emotional stress is not a result of a rise in motor activity throughout the gastrointestinal tract, but a phenomenon that may be unique to the colon in this patient population.     

The alcoholic cardiomyopathies--genuine and pseudo.

Two types of genuine alcoholic cardiomyopathies can produce congestive heart failure, an acute fulminate hyperkinetic type with high cardiac output and a hypokinetic type with a low cardiac output, both of which respond to thiamine. When the chronic alcoholic develops a dilated cardiomyopathy with congestive heart failure without a history of significant malnutrition, then they do not respond to thiamine. This may be explained by a study in which mice given a myotropic virus plus alcohol developed more frequent and severe viral cardiomyopathies than those not fed alcohol. This suggests that a chronic dilated cardiomyopathy in an alcoholic may not be the direct result of the alcohol but secondary to a viral myocarditis. This suggests that the preferred terminology for a dilated cardiomyopathy in an alcoholic who does not respond to thiamine and good nutrition should simply be a dilated cardiomyopathy in an alcoholic. We should assume that the cardiomyopathy is possibly of viral etiology.     

Nadolol: evidence for sympathetic nerve inhibition by a beta blocker in essential hypertension

Although beta blockers' antihypertensive mechanisms have not been clearly delineated, their long-term effects may involve chronic reduction in systemic vascular resistance, which may be the result of sympathetic outflow inhibition. Although a central site of action has been advocated, we sought to identify a peripheral non-cardiac sympatholytic mechanism by studying autonomic function in a small group of nine hypertensive males during treatment with placebo and chronic oral nadolol, a noncardioselective hydrophilic beta blocker with little predicted brain penetration. Nadolol reduced blood pressure and heart rate (both P less than 0.005) while suppressing the blood pressure response to cold stimulus only after parasympathetic inhibition (P less than 0.05); the blunted response to cold stimulus did not correlate with the drug's overall blood pressure lowering effect. Baroreceptor sensitivities to phenylephrine and amyl nitrate stimuli were not enhanced. Several biochemical measures of sympathetic nervous system activity were not influenced by nadolol. Thus, nadolol, while not enhancing baroreflex sensitivity, does seem to have a peripheral non-cardiac sympatholytic effect, but this effect does not account entirely for the long term reduction in blood pressure observed in patients on the drug.     

Alcohol dependence—an illness with a treatment?

Unlike some countries, Britain may have experienced a rise rather than a fall in alcohol-related illness during a decade when consumption has not risen. Objections to the “illness concept” may impede our vision and the range of services we develop. It is possible to agree with objectors to the illness concept that a unidimensional view is unhelpful; that explanations are often only attributions; that the construct “illness” is not needed for help to be offered, its use could undermine self-mastery, and its misuse can breach civil fights. Learning can explain much over-drinking. However, the concept need not imply bimodality of drinkers; the syndrome of alcohol dependence has uses and does not imply a cause; physical and mental explanations are not incompatible; genetic and biochemical research has promise. Developments in treatment are still limited, but the mysteries of the free-will dilemma should not prevent us seeing physiological, psychological and social contributants of partners rather than rivals.     

Failure of adefovir 20 mg to improve suboptimal response in lamivudine‐resistant hepatitis B patients treated with adefovir 10 mg and lamivudine

Summary. Nine patients with lamivudine‐resistant chronic hepatitis B infection who had been treated with adefovir 10 mg/day and had had a suboptimal response but did not have genotypic resistance to adefovir were treated with high‐dose adefovir (20 mg/day). The response to the increased dose of adefovir was compared with the response in 15 patients with a suboptimal response who did not receive an increase in the dose of adefovir. The increase in the dose of adefovir did not lead to a significant reduction in hepatitis B DNA when compared with patients maintained on the standard dose. These data suggest that increasing the dose of adefovir in patients with a suboptimal response does not lead to an improved response.     

Diabetes and Employment

Uncomplicated diabetes does not require any adjustment regarding employment, but those with complications should undergo detailed assessment to determine safety and effectiveness to perform duties. Though there is no such guidance in India, the American Diabetes Association (ADA) adopted a position statement that any person with diabetes, whether insulin treated or non-insulin treated, should be eligible for any employment for which he/she is otherwise qualified. Patients suffering from diabetes should be assessed individually, and after reviewing medical and treatment history, medical fitness to the job should be assigned. Maintenance of proper medical documentation and use of screening guidelines are a must. For this to be implemented properly, one needs state and national laws. A health care professional (HCP) treating the employee though preferred should have expertise in treating diabetes. If there is a disagreement between the opinions of physicians, an independent opinion from a HCP with clinical expertise in diabetes should be taken. An employer should not enquire about an employee’s condition till a job has been offered and can only do so if it is not safe or poses a threat to his health and also if expert opinion and medical documentation suggest so. Screening guidelines, though not used in India but regularly used in Western countries, can be used in evaluation. Safety risks should be assessed individually—recurrent hypoglycemia, not a single episode, may pose a risk whereas hyperglycemia and chronic complications though may not pose immediate risk should be assessed separately. Periodic safety assessments should be done. Jobs requiring operating firearms or running dangerous machinery may have safety concerns with patients having severe hypoglycemia or those on insulin or secretagogues. Hypoglycemia usually can be effectively prevented or self-treated by ingestion of glucose. Severe hypoglycemia requiring assistance may pose a risk; even if it is a single incidence, one has to be followed up properly and investigated to find out its cause. In recurrent severe hypoglycemia, as episodes cannot be explained, it is a risk for the employee himself as well as the public. Hyperglycemia leading to chronic complications is only relevant when it interferes with the performance in actual jobs. Self-monitored blood glucose measurements over a period of time give actual information and should be evaluated by a HCP with expertise in diabetes. Multiple incidents of severe hypoglycemia may pose a problem in high-risk occupations, and the factors responsible should be properly evaluated. Hypoglycemia unawareness increases the risk of a sudden episode of severe hypoglycemia and should be treated with changes in diabetes management. Chronic complications may pose a risk in some jobs, but if not present, possible future development should not be taken into consideration. The tools that do not accurately reflect the current state of diabetes like urine glucose and HbA1C should not be used. The term uncontrolled diabetes should also not be used as it is not well defined. A few accommodations are required at a job for diabetes patients to be able to perform their work responsibilities effectively and safely: testing blood glucose at regular intervals, administering insulin as and when required with proper storage facilities, access to snacks, and a flexible work schedule to accommodate needs and modifications if required for chronic complications.     

Use of automated irrigation pumps improves quality of bowel preparation for colonoscopy

AIM: To evaluate the effectiveness of automated irrigation pumps(AIPs) in improving the quality of the bowel preparation and the yield of colonoscopy.METHODS: A retrospective observational study was conducted at a single medical center. Outpatient colonoscopies performed during a 4-mo time period when AIPs were not in use, were compared to colonoscopies performed during control period. The main outcomes measured were quality of bowel preparation, procedures aborted due to poor preparation, recommendations to repeat at short interval due to suboptimal bowel preparation and adenoma detection rates.RESULTS: One thousand and thirty-seven colonoscopies were included. A higher proportion of cases did not achieve a satisfactory bowel preparation when AIPs were not used(24.4% vs 10.3%, P < 0.01). The number of procedures aborted due to inadequate preparation was not significantly different, however a repeat procedure at a short interval was recommended in a higher proportion of cases when AIPs were not used(21.3% vs 6.9%, P < 0.01). Good or excellent preparation was 2.91(95%CI: 2.04-4.15) times more likely when AIPs were used. Detection of polyps and adenomas was not significantly different.CONCLUSION: AIP use during colonoscopy results in a higher proportion of colonic preparation rated as satisfactory, although polyp detection rate is not significantly affected. Recommendations for repeat colonoscopy at shorter interval significantly decrease with the use of AIPs. This study supports the use of the irrigation pumps in endoscopy units to improve the quality of colonoscopy.     

Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy： Endoscopic findings, clinical management and outcome

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P=0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.     

Beliefs, risk perceptions, and gaps in knowledge as barriers to colorectal cancer screening in older adults

OBJECTIVES: To assess beliefs and perceptions of risk about colorectal cancer (CRC) and gaps in knowledge about screening in adults aged 65 to 89.
DESIGN: A population-based survey.
SETTING: United States.
PARTICIPANTS: A total of 1,148 respondents with no history of CRC, representing an estimated population of 31.6 million persons, who were stratified according to screening behavior (up to date (n=457) vs not up to date (n=691)) and age (65–74 vs 75–89).
MEASUREMENTS: The Health Information National Trends Survey (2003) questionnaire.
RESULTS: An estimated 25% of adults aged 65 to 89 had not heard of the fecal occult blood test, 17% had not heard of sigmoidoscopy or colonoscopy, and 42% were not up to date with either screening modality. Not visiting a healthcare provider in the previous year, not knowing about tests available for colon cancer, perceiving the arrangements to be checked for detecting colon cancer to be difficult, and not having an opinion about it and its cost, were significantly associated with not being up to date (each P <.03). Persons who were not up to date were frequently unaware of the importance of CRC screening, and often reported lack of a provider's recommendation to be screened (>75%). Lack of knowledge and awareness were more prevalent in those aged 75 to 89 than those aged 65 to 74.
CONCLUSION: Lack of knowledge and awareness and the absence of a physician's recommendation to be tested might explain not being up to date with CRC screening in adults in these age groups. These findings suggest a potential value for better communication between older adults and their providers regarding screening for CRC, when appropriate.     

A comparison of the refractory periods induced by hypertonic airway challenge and exercise in bronchial asthma

We have compared the changes in FEV1 of 10 asthmatic patients who were subjected in random order to paired challenges with different combinations of exercise and aerosolized hypertonic 3.6% saline. The challenges were separated by 60 min when the FEV1 values had returned to within 10% of baseline values. Four patients were refractory to exercise-induced asthma (EIA) after an initial exercise task, and these patients also demonstrated a refractory period to hypertonic-saline-induced bronchoconstriction after an initial hypertonic challenge. Furthermore, hypertonic challenge produced refractoriness to EIA in the patients, and exercise rendered them refractory to hypertonic-saline-induced asthma. Six subjects were not refractory to EIA after an initial exercise task, and they were also not rendered refractory by an initial hypertonic challenge to asthma induced by hypertonic saline or by exercise. Histamine-induced bronchoconstriction in the 4 refractory subjects did not induce a refractory period to EIA, indicating that the refractory periods developing after hypertonic saline challenge and exercise were not due to the bronchoconstriction alone. Inhalation of isotonic saline in the same volumes as those used for hypertonic challenges did not induce a refractory period, indicating that the refractory period caused by the inhalation of hypertonic saline was not due to the volumes of fluid inhaled. Thus, exercise and aerosolized hypertonic saline induced refractoriness interchangeably, suggesting that airway hypertonicity and exercise produced a refractory period through a very similar, if not identical, final common pathway.     

Circulating endogenous opioids and ventilatory response to CO2 and hypoxia

The role of endogenous opioids in the control of breathing is not yet well defined. Radioimmunoassays that measure beta-endorphin (BE) and met-enkephalin (MET) having recently become available, we decided to evaluate the possible relation between the blood levels of these two opioids and different hypercapnic and hypoxic ventilatory responses observed in a group of normal subjects. Ventilatory response to hypercapnia (n = 9) and to hypoxia (n = 7) were determined by classical rebreathing methods. A voluntary isocapnic normoxic hyperventilation test was used as a control. Basal levels of BE and MET did not correlate with the magnitude of the ventilatory response to either hypercapnia or hypoxia. Moreover, BE and MET levels measured repeatedly up to 30 min after each test did not change significantly. We conclude that circulating endogenous opioids do not play a role in the control of breathing in normal humans. These results do not rule out a possible role for these substances as locally released mediators.     

The effect of isoferritins on granulopoiesis

The evidence for a regulatory role of acidic isoferritins on hemopoiesis is not entirely consistent with our knowledge of ferritin biochemistry, and no clear picture of this phenomeonon has emerged. In the present study, we have been unable to confirm a consistent effect of purified heart (acidic), spleen (basic), or serum (glycosylated) isoferritins on CFU-GM colony formation in vitro. Inhibition of colony formation by cell extracts or conditioned media does not relate to the presence of acidic isoferritins, nor is this effect neutralized by a monoclonal antibody to acidic isoferritins. The composition of ferritin preparations previously described as inhibitory to CFU-GM colony growth could not be confirmed, and they were not found to be predominantly acidic in nature. Our data do not support a role for acidic isoferritins as inhibitors of granulopoiesis.     

Regional alterations in intestinal sucrase expression in streptozocin-treated chronically diabetic rats

In ad libitum-fed diabetic rats, sucrase specific activities in jejunum and ileum were significantly increased two- to threefold compared to controls, a response unaltered by pair-feeding. Gradients of sucrase activities along the ileal villus-to-crypt axis were readily measured in crypt regions in diabetic, but not in nondiabetic, rats. Changes in sucrase activities were commensurate with increases in sucrase immunoreactivity and not a result of altered functional activity. Insulin treatment reversed these effects, although insulin-deficiency, studied in food-deprived, nondiabetic rats, did not affect sucrase expression. We conclude that chronic diabetes significantly stimulates sucrase expression along the proximal-to-distal and villus-to-crypt axes of rat small intestine. In ileum, these changes suggest marked alterations in phenotypic development of enterocytes along the villus-to-crypt axis. Alterations in sucrase expression do not appear to correlate with insulin states and are not a consequence of altered functional activity.     

Effect of levamisol on tissues of Ascaris lumbricoides.

Levamisol which is highly effective against Ascaris infections, was shown to produce degenerative changes in the intestine and the reproductive system of the worm. Worms that were not expelled by treatment produced only nonviable eggs which could not develop in vitro. Levamisol is thus shown to be not only a highly curative drug, but a compound of significant epidemiological importance.     

Effects of a Practicum with Well Elderly on Physical Therapy Students' Attitudes Towards Older People and Their Intention to Work with the Elderly

A physical therapy course incorporating a practicum in which students provide health promotion services at senior centers was evaluated to determine its effect on the students' attitude towards older people for students participating in the course. The amount of improvement was not significantly different from that of a comparison group. There was not a significant difference in the amount of time the students intended to work with older clients after graduation. The correlation between attitude towards older people and intention to work with older clients was significant at the beginning of the first and second years in the physical therapy curriculum, but not significant during the third year. This suggests that by the end of the professional training program some other factor or factors become more more important in choosing whether or not to practice geriatrics. Preference for a humanistic versus a scientific approach is discussed as a possible factor in deciding whether to practice geriatrics.     

Penicillamine in rheumatoid arthritis: clinical pharmacology and biochemical properties.

The current status of the clinical pharmacology of penicillamine was reviewed. Its indications in the therapy of RA were defined, and current principles of dosage were presented. The autoimmune side effects were discussed in the light of their possible implication with regard to a locus of action of the drug on the immunological system. A comparison was presented of the biochemical properties of penicillamine and 5-thiopyridoxine, another mercaptan compound which appears to demonstrate a penicillamine-like action in patients with RA. It was found that 5-thiopyridoxine did not possess copper chelating properties, it failed to form a mixed disulfide with cystine, it did not induce dermolathyrism in the weanling rat, and it was not a vitamin B6 antagonist. If both of these compounds do work by a common mechanism in RA, then the aforementioned biochemical properties of penicillamine must be presumed to be not relevant to its fundamental action in this disease.     

A case of hemoglobin Indianapolis [beta 112(G14) Cys----Arg] in an individual from Cordoba, Spain

Hemoglobin Indianapolis was first described by Adams et al (1,2) as a very unstable variant with a phenotype similar to severe beta-thalassemia. We have also characterized this variant, but there are several differences in the clinical expression of the variant described in our report and those described in the original case. We found Hb Indianapolis to be unstable, but not to the extent that it could not be detected by routine testing. The four family members heterozygous for the variant were not anemic, showed normal hematologic values, and did not exhibit any severe clinical disadvantages, although there was slight reticulocytosis. The variant could not be resolved from Hb A on cellulose acetate (pH 8.4), but isoelectric focusing showed a double band in the region of Hb A that is probably the variant and Hb A. However, the variant chain was clearly evident by globin chain analyses in acid and alkaline buffers. The condition of additional blood samples did not allow us to determine the oxygen dissociation properties of the variant or the rates of globin chain synthesis.