VASOCONSTRICTION IN THE RENAL VASCULAR BED DURING EXERCISE: STUDIES IN CONTROL AND HEART FAILURE RABBITS

1. The effects of graded treadmill exercise on renal blood flow (RBF) were examined in seven rabbits, in which congestive heart failure (CHF) was produced by the administration of doxorubicin, 1 mg/kg, twice weekly for 8 weeks, and in seven controls. A third group of five rabbits underwent doxorubicin treatment with the addition of surgical section of the left renal sympathetic nerve. 2. During submaximal exercise, there was a small reduction in RBF in controls, which was greatly exaggerated in CHF. 3. In both control and heart failure rabbits, there was a precipitous fall in RBF as exercise fatigue developed. 4. Renal sympathectomy ablated these changes in RBF during exercise. 5. It is concluded that in heart failure there is an exaggerated, sympathetically mediated, diversion of blood flow away from the kidney. The onset of exercise fatigue in both normal and heart failure rabbits is accompanied by a marked intensification of this process.     

Thoracoscopic esophagomyotomy. Initial experience with a new approach for the treatment of achalasia.

The authors treated 17 patients with achalasia by a thoracoscopic (15 patients) or laparoscopic (2 patients) Heller myotomy. All patients had dysphagia and an upper gastrointestinal series demonstrating a dilated esophagus with a bird-beak deformity at the cardia. Manometry showed a mean lower esophageal sphincter (LES) pressure of 32 +/- 4 mmHg, incomplete sphincter relaxation on swallowing, and no primary esophageal peristalsis. After operation, mean LES pressure was 10 +/- 2 mmHg. Fifteen patients were fed on the second postoperative day. The average hospital stay was 3 days, and there were no deaths or major complications. In three early patients, the myotomy was not carried far enough onto the stomach, and dysphagia persisted until a second myotomy was performed (laparoscopically in two patients). The authors found that having an endoscope in the esophagus during the operation facilitated exposure and was vital to determine the appropriate length of the myotomy. With regard to dysphagia, final results were excellent in 12 patients (70%), good in two patients (12%), fair in two patients (12%), and poor in one patient (6%). Heller myotomy can be safely and reliably performed with minimally invasive techniques. Dysphagia is relieved, postoperative pain is minimal, hospital stay is short, and the patient can return quickly to normal activity.     

The efficacy and limitations of percutaneous endoscopic gastrostomy.

We analyzed 64 percutaneous endoscopic gastrostomy procedures performed by us between 1986 and 1990. Thirty patients had neurologic disease; 16 had head and neck cancers; eight had other malignancies; two had acquired immunodeficiency syndrome; and eight had other problems. Seven patients died within 30 days of complications (n = 4) or the primary illness (n = 3). Mean follow-up was 6 months; an additional patient died of aspiration and eight others died of their underlying illness. There were 19 complications (32%). Four wound complications occurred. Nine patients developed aspiration pneumonia within 3 days of the procedure, four of whom died in the hospital. Of the 24 patients with a history of aspiration, nine experienced aspiration during or after percutaneous endoscopic gastrostomy. Patients with a history of aspiration were more likely to have perioperative aspiration pneumonia, and patients who experienced aspiration were more likely to die.     

Gallstones Containing Bacteria are Biofilms: Bacterial Slime Production and Ability to Form Pigment Solids Determines Infection Severity and Bacteremia

Objective Gallstone bacteria provide a reservoir for biliary infections. Slime production facilitates adherence, whereas β-glucuronidase and phospholipase generate colonization surface. These factors facilitate gallstone formation, but their influence on infection severity is unknown. Methods Two hundred ninety-two patients were studied. Gallstones, bile, and blood (as applicable) were cultured. Bacteria were tested for β-glucuronidase/phospholipase production and quantitative slime production. Infection severity was correlated with bacterial factors. Results Bacteria were present in 43% of cases, 13% with bacteremia. Severe infections correlated directly with β-glucuronidase/phospholipase (55% with vs 13% without, P < 0.0001), but inversely with slime production (55 vs 8%, slime <75 or >75, P = 0.008). Low slime production and β-glucuronidase/phospholipase production were additive: Severe infections were present in 76% with both, but 10% with either or none (P < 0.0001). β-Glucuronidase/phospholipase production facilitated bactibilia (86% with vs 62% without, P = 0.03). Slime production was 19 (±8) vs 50 (±10) for bacteria that did or did not cause bacteremia (P = 0.004). No bacteria with slime >75 demonstrated bacteremia. Conclusions Bacteria-laden gallstones are biofilms whose characteristics influence illness severity. Factors creating colonization surface (β-glucuronidase/phospholipase) facilitated bacteremia and severe infections; but abundant slime production, while facilitating colonization, inhibited detachment and cholangiovenous reflux. This shows how properties of the gallstone biofilm determine the severity of the associated illness. Presented at the annual meeting of the Society for Surgery of the Alimentary Tract, held May 20–24, 2006 in Los Angeles, California.     

Cardiac dysrhythmias in the acute setting: pathophysiology or anyone can understand cardiac dysrhythmias

Cardiac dysrhythmias are easy. Unlike the lung (which has formidable neuroendocrine, metabolic, and respiratory responsibilities), the heart is simple. It is an innervated muscular pump. A resting Purkinje or ventricular muscle cell membrane maintains a charge of about 90 millivolts. The five phases of a cardiac action potential are similar to the action potential in skeletal muscle, however, the cardiac action potential lasts a hundred times longer. When sodium specific "fast" channels and calcium specific "slow" channels open, positive ions rush into the myocardial cell, thus causing rapid membrane depolarization. In order to produce an action potential, some stimulus must decrease the membrane potential from -90 millivolts to "threshold" or -60 millivolts. Purkinje fibers do not have a stable phase for diastolic potential. These fibers continuously depolarize during diastole. Hypoxemia or hypokalemia may exacerbate this diastolic depolarization, thus promoting "hyperexcitability" or "automatic" ectopy. When myocardium is damaged, characteristically with myocardial ischemia, rapid conduction of cardiac impulses may be slowed dramatically. Very slow impulses may course through muscle such that by the time the activation wave front returns to the initiating site, this origin has had a chance to repolarize. This is the basis for re-entrant dysrhythmias. All cardiac dysrhythmias are automatic, re-entrant or both.     

Family planning increase in some African countries

Governments in sub-Saharan Africa, recognizing the economic and health benefits of slower population growth, have begun to adopt explicit policies aimed at reducing growth rates. More countries also are providing support to family planning programs. In 1985, more than 70% of the 402 million people living in sub-Saharan Africa lived in countries which have government-supported family planning programs. Yet, the coverage of many of these programs has been and remains limited. Reflecting low demand as well as problems in supplying contraceptive services, results from national-level surveys conducted in 10 countries between 1977-82 as part of the World Fertility Survey (WFS) program showed that approximately 5% of the currently married women aged 15-49 in these countries were using contraceptive methods. More encouraging are the results of surveys conducted in Botswana, Kenya, and Zimbabwe in 1984 as part of the international Contraceptive Prevalence Survey (CPS) program which demonstrate that family planning programs in Africa can be very successful. The CPS data show that substantial proportions of currently married women aged 15-49 in all 3 countries are currently practicing family planning. The level of current use of contraception reported in the CPSs in Botswana, Kenya, and Zimbabwe lay to rest the myth that women in sub-Saharan Africa are unwilling to use family planning. The majority of current users in all 3 countries use modern contraceptive methods. Most nonusers in the 3 countries know at least 1 family planning method. Male approval of family planning also seems to be common, although men are reported to be somewhat more likely than their wives to disapprove of family planning. Despite the fact that there is relatively widespread adoption of modern contraceptive method in Zimbabwe and Botswana as well as an increasing reliance on family planning methods in Kenya, the CPS results show that women in these 3 countries continue to have and want large families. The mean number of children ever born to women aged 45-49 ranges from 6.8 children in Botswana to 8.2 children in Kenya. Interest in planning their families is widespread among women in the 3 countries despite the high fertility expectations.     

Community-living older people’s interpretation of the Norwegian version of older people’s quality of life (OPQOL) questionnaire

The aim of this study is to investigate how community-living older people interpret the Norwegian version of Older People's Quality of Life (OPQOL) questionnaire. The original OPQOL questionnaire was translated based on guidelines for cross-cultural translation. The Three-Step Test-Interview instrument was adopted to investigate how community-living older people interpreted the questionnaire. Data were collected from 14 participants (72–89 years). The questionnaire was filled in under observation. Semi-structured interviews were then conducted to clarify the observational data and elicit the participants’ experiences and opinions. Lastly, data were analysed using a hermeneutic interpretation approach. Our findings indicate that most of the participants managed to complete the OPQOL questionnaire without problems. The data analysis resulted in four primary themes: relevance & applicability, formulation, consistency & accuracy and subjectivity. The questionnaire covered all aspects related to the participants’ quality of life. However, statements related to religion were found to be irrelevant to their quality of life. Most of the participants thought that religion, philosophy and culture should be separate rather than included in the same statement. The participants missed the option of ‘not applicable’ when the statements were irrelevant to them. The statements are formulated in both positive and negative ways, which was sometimes confusing to them. The participants perceived phases such as “around me” “local,” and “things” as ambiguous, and thus they raised concerns about whether the OPQOL questionnaire could capture consistent data regarding their quality of life. The results of this study pinpoint the issues that community-living older people faced when interpreting and answering the Norwegian version of OPQOL questionnaire. These issues were mostly caused by sociocultural differences. Our work provides an overview of the changes that must be made in the questionnaire in order to address these sociocultural differences while using the OPQOL questionnaire in the Norwegian context.     

The behavioral genetics ofCaenorhabditis elegans

Caenorhabditis elegans, a small free-living soil nematode, is an ideal organism for the genetic dissection of simple behaviors. Over 150 genes required for normal behavior have been identified. We review here the neural and genetic pathways underlying four of the best-studied C. elegans behaviors: locomotion, response to gentle touch, egg-laying, and chemotaxis. Mutations affecting these behaviors have identified genes which specify neuronal cell lineage, neuronal cell fate, and the formation of cell matrix cues involved in axonal guidance. Molecular analysis of genes required for normal behavior offers the prospect of characterizing functionally important nervous system proteins, regardless of their abundance or biochemical role.     

Nitric oxide-mediated neurotransmission is attenuated in the anococcygeus muscle from diabetic rats

Summary The effect of STZ-induced diabetes of 8-weeks duration was examined on nitric oxide-mediated neurotransmission in the rat anococcygeus muscle. In the presence of noradrenergic blockade and raised tissue tone, relaxant responses to nerve stimulation (0.5–5 Hz, for 10 s), sodium nitroprusside (5 and 10 nmol/l) and nitric oxide (1 and 3 mol/l) were significantly reduced in anococcygeus muscles from diabetic rats compared to responses from control rats (p <0.05). In contrast, relaxations to papaverine (3 and 10 mol/l were not reduced in tissues from diabetic rats. The nitric oxide synthesis inhibitor NOLA (100 mol/l) abolished relaxant responses to nerve stimulation but had no effect on responses to any of the relaxant agents used. Exposure to NOLA at 10 mol/l reduced stimulation-induced relaxations; this reduction was significantly greater in tissues from the diabetic group than from the control group (p <0.05), probably as a consequence of the smaller relaxant responses in muscles from diabetic rats. Contractile responses to nerve stimulation (1–10 Hz, for 10 s), but not noradrenaline (0.03–30 mol/l), were significantly greater in anococcygeus muscles from diabetic rats than from control rats (p <0.05). NOLA (100 mol/l) significantly enhanced stimulation-induced contractions (p <0.05), however the enhancement was significantly less in tissues from diabetic rats (p <0.05). The results suggest that STZ-induced diabetes impairs smooth muscle reactivity to nitric oxide in the rat anococcygeus muscle.Abbreviations STZ Streptozotocin - NOLA N^G-nitro-l-arginine - NANC nonadrenergic noncholinergic - ANOVA analysis of variance