Long term management of duodenal ulcer in general practice: How best to use cimetidine?

Two hundred and sixty seven patients with duodenal ulceration were entered into a five year study of two strategies of treatment with cimetidine. Two thirds were treated continuously with 400 mg at bedtime supplemented by temporary increases in dosage if they had symptomatic relapses (group 1), and the remaining third were given intermittent “healing” doses for four to eight weeks if a symptomatic recurrence was judged to have occurred (group 2). Life table analysis showed that the probability of remaining free of clinically important symptoms five years after the start of treatment was 24% (95% confidence interval (CI) 15·5% to 32·6%) in group 1 compared with nil in group 2 (p<0·0001). The median values for the longest periods free from relapse for each patient were 108 weeks in group 1 and 32 weeks in group 2, respectively (p<0·0001; 95% CI of the median difference 36 to 76). Over the five years 10 patients suffered major complications, two requiring emergency surgery, while a further nine had elective surgery because of the failure of medical treatment. There were no deaths that could be attributed either to ulceration or to treatment with cimetidine.Medical management was therefore very satisfactory for most patients, though those treated continuously with cimetidine suffered considerably less from their ulcer symptoms. As 80% of patients studied relapsed during the two years after a healing course of cimetidine, continuous treatment will benefit many patients treated in general practice.     

Relation between Plasma Lignocaine Levels and Induced Haemodynamic Changes

Intravenous lignocaine (1 mg./kg. body weight) was found to produce insignificant haemodynamic changes, and in particular no reduction in myocardial contractility. A rate of 2 mg./minute infused intravenously is suggested for therapeutic purposes.In anaesthetized dogs an infusion of 13·5 mg./minute caused moderate haemodynamic depression and a maximum plasma level of 7 μg./ml. Massive injections of 200 and 400 mg. of lignocaine produced a maximum plasma level of 13·8 and 27·8 μg./ml., respectively, and in the latter failure of myocardial contraction in the presence of a normal E.C.G. ensued (“pump failure”). Lignocaine appears to alter the uptake of calcium by myocardial sarcoplasmic reticulum, and this may explain the negative inotropic effect of large doses.     

Impaired aerobic work capacity in insulin dependent diabetics with increased urinary albumin excretion

To assess whether decreased aerobic work capacity was associated with albuminuria in insulin dependent diabetics aerobic capacity was measured in three groups of 10 patients matched for age, sex, duration of diabetes, and degree of physical activity. Group 1 comprised 10 patients with normal urinary albumin excretion (<30 mg/24 h), group 2 comprised 10 with incipient diabetic nephropathy (urinary albumin excretion 30-300 mg/24 h, and group 3 comprised 10 with clinical diabetic nephropathy (urinary albumin excretion >300 mg/24 h). Ten non-diabetic subjects matched for sex, age, and physical activity served as controls. Oxygen uptake was similar in the four groups at rest and during a 75 W workload. Maximal oxygen uptake was also similar in the control subjects and group 1 (median 41·7, (range 29·1-53·0) ml/kg/min v 38·5 (26·6-59·2) ml/kg/min, respectively), but was significantly lower in group 2 (27·7 (13·9-44·3) ml/kg/min) and group 3 (26·8 (22·6-36·7) ml/kg/min). The difference in maximal oxygen uptake between groups 1 and 2 was 10·8 ml/kg/min (95% confidence interval 3·6 to 23·4 ml/kg/min) and between groups 1 and 3, 11·7 ml/kg/min (4·9 to 22·5 ml/kg/min). These differences were not explained by differences in metabolic control or the degree of autonomic neuropathy.Thus the insulin dependent diabetics with only slightly increased urinary albumin excretion had an appreciably impaired aerobic work capacity which could not be explained by autonomic neuropathy or the duration of diabetes. Whether the reduced capacity is due to widespread microangiopathy or another pathological process affecting the myocardium remains to be established.     

Androgen Function in “Psychogenic” and “Constitutional” Types of Impotence

Androgen function was studied in twenty-five physically healthy “primarily” impotent males classified on clinical criteria into “psychogenic” or “constitutional” groups. The mean urinary testosterone level in the former was significantly higher than in the latter group (P<0·005). Important variables associated significantly with higher urinary testosterone levels (P<0·05) were (a) “late onset” impotence, (b) shorter duration than two years, (c) stronger “sex drive,” and (d) an alternative sexual outlet to orgasm and ejaculation in the three months preceding referral; the last-mentioned appeared to be the single most important discriminatory feature.It is suggested that testosterone excretion patterns—namely, high, average, and low—may be one method of classifying impotence.     

Comparison of Effect of Two Induction Doses of Methohexitone on Infants Delivered by Elective Caesarean Section

Observations were made on 26 infants delivered by elective caesarean section under general anaesthesia. A standard anaesthetic technique was employed using a methohexitone, relaxant, nitrous oxide-oxygen sequence with regulated ventilation and the administration of papaveretum after clamping the umbilical cord. In 12 patients the induction dose of methohexitone was 1·4mg/kg and in 14 it was reduced to 1·0 mg/kg. There were no significant differences between the two groups in the clinical status of the mothers, in operative technique and timing, or in the value of PO₂, PCO₂, and pH in the umbilical cord venous blood.The infants whose mothers received the lower dose of methohexitone were in better condition, as assessed by the number needing assisted ventilation, the time taken to establish regular respiration, the Apgar score, and the “Apgar minus colour” score.     

Long-Term Treatment of Clonidine,Atenolol, Amlodipine and Dihydrochlorothiazide,but Not Enalapril,Impairs the Sexual Function in Male Spontaneously Hypertensive Rats

This study was designed to investigate the impact of representative antihypertensive drugs of 5 classes on the sexual function in male spontaneously hypertensive rats (SHR) at doses that achieved similar blood pressure (BP) reduction. The experiment was performed in 6 groups of male SHR. The dose are 20 μg/kg/day for clonidine, 3 mg/kg/day for enalapril, 20 mg/kg/day for atenolol, 2 mg/kg/day for amlodipine, and 10 mg/kg/day for dihydrochlorothiazide. SHR were treated for 3 months, and then the penile erection and sexual behavior were detected. After BP recording, SHR were killed to evaluate the organ-damage, weight of accessory sex organs and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone in serum. Five drugs had the similar efficacy on BP reduction. All drugs except of enalapril, significantly prolonged the mount latency, and decreased the mount frequency (P<0.05). Clonidine also reduced the conception rate (45% vs. 80% in control group, P<0.05). Amlodipine and dihydrochlorothiazide significantly increased the testosterone level (0.79±0.30, 0.80±0.34 vs. 0.49±0.20 in control group, unit: ng/dl, P<0.05). Enalapril, atenolol and amlodipine also significantly decreased the BP variability (systolic, 8.2±2.5, 7.6±1.8, 8.9±2.0 vs. 12.2±3.8 in control group, unit: mm Hg). All these drugs significantly decreased the organ-damage (P<0.05). In conclusion, long-term treatment with 5 common antihypertensive drugs possessed obvious organ protection in SHR. Clonidine, atenolol, amlodipine and dihydrochlorothiazide, but not enalapril, impair sexual function.     

Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia

Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO₄) is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB) disruption and neuroinflammation that lowers seizure threshold. Further, MgSO₄ decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP) was combined with a high cholesterol diet (HC) to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg) required to elicit seizure in RUPP+HC±MgSO₄ and compared to normal pregnant controls (n = 6/group; gestational day 20). RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼65% lower vs. control (12.4±1.7 vs. 36.7±3.9 mg/kg PTZ; p<0.05) that was reversed by MgSO₄ (45.7±8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC). BBB permeability to sodium fluorescein, measured in-vivo (n = 5–7/group), was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9±1.0 vs. 12.2±0.3 counts/gram ×1000; p<0.05) and was unaffected by MgSO₄ (15.6±1.0 counts/gram ×1000; p<0.05 vs. controls). In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35±2% of microglia being active compared to 9±2% in normal pregnancy (p<0.01; n = 3–8/group). MgSO₄ treatment reversed neuroinflammation, reducing microglial activation to 6±2% (p<0.01 vs. RUPP+HC). Overall, RUPP+HC rats were in a state of augmented seizure susceptibility potentially due to increased BBB permeability and neuroinflammation. MgSO₄ treatment reversed this, increasing seizure threshold and decreasing neuroinflammation, without affecting BBB permeability. Thus, reducing neuroinflammation may be one mechanism by which MgSO₄ prevents eclampsia during severe preeclampsia.     

Delayed Appearance of Lactobacilli in the Intestines of Chicks Reared in a “New” Environment

Male chicks (1 day old; Vantress × Arbor Acre) were fed a basal folic acid-deficient diet, a 5% uric acid-containing diet with and without 5 mg/lb (453.5 g) of bacitracin and 20 mg/lb of sodium penicillin G, the basal diet supplemented with only the antibiotics, and the basal diet plus 500 μg/lb of folic acid. The chicks were reared in a room which had not been used previously for housing chickens (“new” environment). Bacteriological analyses of the contents of the small intestine revealed a decrease in numbers of streptococci and “anaerobic” bacteria in the chicks receiving dietary antibiotics. No persistent changes were seen in the numbers of coliform bacteria. Lactobacilli were not detected in any of the groups until 3 weeks after feeding.     

Assessment of Intraocular Measurements in Neonatal Foals and Association with Gender,Laterality, and Body Weight: A Clinical Study

Objective of this study was to describe intraocular measurements in newly born foals (1–7 days of age) and assess the association between globe measurements and gender, laterality, and body weight. B-scan ultrasonographic biometry was performed on both eyes of 22 healthy foals (44 eyes) ages 1–7 days using a 10-MHz transducer. Intraocular measurements (anterior chamber depth, central lens thickness, vitreous chamber depth, axial globe length, longitudinal globe length, lens poles distance) were carried out using the ultrasound internal calipers. The influence of gender (male or female), laterality (right or left eye), and body weight (“light” <48 kg; “heavy” ≥48 kg) on ocular measurements was analysed by the Student t test. Values of P<0.05 were accepted as significant for all analyses. Mean anterior chamber depth was 2.2±0.5 mm (Standard Deviation); central lens thickness was 9.9±0.8 mm; vitreous chamber depth was 15.5±1.1 mm; axial globe length was 27.6±1.6 mm; longitudinal globe length was 35.8±1.2 mm, and lens poles distance was 16.4±1.0 mm. Intraocular measurements were not influenced by gender, laterality nor body weight. This study provides reference values for intraocular measurements in neonatal foals and may be useful in the diagnosis and treatment of congenital and acquired pathologies involving the globe.     

Interpretation of Serum Calcium in Patients with Abnormal Serum Proteins

Two hundred consecutive specimens received in this laboratory for “liver function tests” showed a wide range of abnormal protein concentrations. Calcium concentration correlated closely with albumin (r = 0·867) but less closely with total protein (r = 0·682). A simple formula for adjusting calcium concentration was derived from the regression equation of calcium on albumin. Adjusted calcium = calcium - albumin + 4·0, where calcium is in mg/100 ml and albumin in g/100 ml.Low calcium concentrations were found in 49 (24·5%) and raised concentrations in six (3%) of the 200 blood specimens taken for liver function tests. After adjustment, the 95% limits of the observed range were identical with the 95% limits of the normal range determined in this laboratory. Unlike adjustments based on total protein or specific gravity, the adjustment on albumin in 39 specimens which showed hypergammaglobulinaemia on electrophoresis gave normal calcium concentrations.     

RELIABILITY AND VALIDITY OF AN ACCELEROMETRIC SYSTEM FOR ASSESSING VERTICAL JUMPING PERFORMANCE

The validity of an accelerometric system (Myotest©) for assessing vertical jump height, vertical force and power, leg stiffness and reactivity index was examined. 20 healthy males performed 3ד5 hops in place”, 3ד1 squat jump” and 3× “1 countermovement jump” during 2 test-retest sessions. The variables were simultaneously assessed using an accelerometer and a force platform at a frequency of 0.5 and 1 kHz, respectively. Both reliability and validity of the accelerometric system were studied. No significant differences between test and retest data were found (p < 0.05), showing a high level of reliability. Besides, moderate to high intraclass correlation coefficients (ICCs) (from 0.74 to 0.96) were obtained for all variables whereas weak to moderate ICCs (from 0.29 to 0.79) were obtained for force and power during the countermovement jump. With regards to validity, the difference between the two devices was not significant for 5 hops in place height (1.8 cm), force during squat (-1.4 N · kg⁻¹) and countermovement (0.1 N · kg⁻¹) jumps, leg stiffness (7.8 kN · m⁻¹) and reactivity index (0.4). So, the measurements of these variables with this accelerometer are valid, which is not the case for the other variables. The main causes of non-validity for velocity, power and contact time assessment are temporal biases of the takeoff and touchdown moments detection.     

Effects of Salbutamol and Isoprenaline Phenylephrine in Reversible Airways Obstruction

Ventolin (salbutamol) and Medihaler-Duo (isoprenaline/phenylephrine combination) standard pressurized inhalers were used to administer doses of two or six “puffs” to 16 patients with known reversible airways obstruction. The doses were administered in random order over two days. Both the Ventolin and Medihaler-Duo inhalers substantially increased FEV₁, but in the doses used salbutamol was more effective than isoprenaline/phenylephrine (P < 0·01). There was no significant difference between two and six puffs of salbutamol, though there seemed to be an advantage of six puffs of isoprenaline/phenylephrine over two puffs (P < 0·05). Adrenaline (1/1,000) 0·5 ml and atropine 0·6 mg produced similar increases in FEV₁ to those produced by salbutamol.The Pao₂ fell more than 5 mm Hg in three patients after salbutamol and in three after isoprenaline/phenylephrine. There was no significant fall in mean Pao₂ in any of the treatment groups. It is concluded that the Ventolin inhalant, administered in the conventional dose of two puffs, is as effective a bronchodilator as subcutaneous adrenaline and atropine, is more effective than the Medihaler-Duo, and is without detectable side effects.     

Synchronization of follicular wave emergence does not improve embryonic yield in superovulated ewes

The present study aimed to investigate the effects of a combination of progesterone with different doses of E-17β on following end points: (1) ovarian follicular dynamics and emergence of a new follicular wave, and (2) superovulatory response and embryo yield. In Experiment 1, 28 ewes were randomly divided into four groups (n = 7) to receive either 2.0 mg, 1.0 mg, 0.5 mg or none E-17β one day after insertion of a progesterone device. The different doses of estradiol similarly delayed the moment of follicular emergence (overall mean = 3.1 ± 1.0 days vs. control group = 0.86 ± 1.0 days; P < 0.01), but the emergence of the new wave showed greater synchronization with the 0.5 mg dosage of E-17β. In Experiment 2, sixty-two donor ewes received an internal progesterone release device (day -1) for 7 d and 1 d after the insertion of this device (day 0) were allocated randomly to receive 0.5 mg of E-17β or only the vehicle (control group). Superstimulation was initiated on day 3 with the administration of 133 mg of pFSH in eight decreasing doses. Contrary to expectations, the protocol with the administration of 0.5 mg E-17β did not improve the percentage of donors with > 2 CL, the number of CL and the production of embryos (P > 0.05). It was concluded that the combination of progesterone and 0.5 mg E-17β was more efficient in synchronizing the emergence of the new follicular wave, however this approach seems to be unnecessary in ewe’s superovulation programs.     

Changes in Extremely Hot Summers over the Global Land Area under Various Warming Targets

Summer temperature extremes over the global land area were investigated by comparing 26 models of the fifth phase of the Coupled Model Intercomparison Project (CMIP5) with observations from the Goddard Institute for Space Studies (GISS) and the Climate Research Unit (CRU). Monthly data of the observations and models were averaged for each season, and statistics were calculated for individual models before averaging them to obtain ensemble means. The summers with temperature anomalies (relative to 1951–1980) exceeding 3σ (σ is based on the local internal variability) are defined as “extremely hot”. The models well reproduced the statistical characteristics evolution, and partly captured the spatial distributions of historical summer temperature extremes. If the global mean temperature increases 2°C relative to the pre-industrial level, “extremely hot” summers are projected to occur over nearly 40% of the land area (multi-model ensemble mean projection). Summers that exceed 5σ warming are projected to occur over approximately 10% of the global land area, which were rarely observed during the reference period. Scenarios reaching warming levels of 3°C to 5°C were also analyzed. After exceeding the 5°C warming target, “extremely hot” summers are projected to occur throughout the entire global land area, and summers that exceed 5σ warming would become common over 70% of the land area. In addition, the areas affected by “extremely hot” summers are expected to rapidly expand by more than 25%/°C as the global mean temperature increases by up to 3°C before slowing to less than 16%/°C as the temperature continues to increase by more than 3°C. The area that experiences summers with warming of 5σ or more above the warming target of 2°C is likely to maintain rapid expansion of greater than 17%/°C. To reduce the impacts and damage from severely hot summers, the global mean temperature increase should remain low.     

Serum Gastrin in Chronic Gastritis

Fasting gastrin levels in serum were measured in 49 patients with different types of chronic gastritis and in matched controls. In 15 patients with established pernicious anaemia the mean (± S.E. of mean) level of gastrin was greatly raised (699 ± 99 pg/ml). In 17 patients with chronic atrophic gastritis, seropositive for parietal cell antibody but with adequate vitamin-B₁₂ absorption, the level was also raised (476 ± 74 pg/ml). By contrast, in “simple” atrophic gastritis seronegative for parietal cell antibody the gastrin levels were significantly lower for both diffuse atrophic gastritis (129 ± 31 pg/ml) and multifocal gastritis (14 ± 4 pg/ml). These levels were similar to those in the controls (46 ± 7 pg/ml).The mechanism of the raised gastrin levels remains uncertain, but neither achlorhydria nor in vivo action of the parietal cell antibody wholly accounted for the hypergastrinaemia.We conclude that hypergastrinaemia is characteristic of gastritis associated with autoimmune reactions to gastric antigens and pernicious anaemia and that a raised serum gastrin is a useful marker of the type of gastritis that tends to progress to the gastric lesion of pernicious anaemia. The findings suggest that this type of gastritis is an essentially different disease from “simple” atrophic gastritis, and the differences in gastrin levels may be due to sparing of the antral mucosa in the autoimmune type but not in “simple” gastritis.     

The Control of Growth Habit of Marquillo x Kenya Farmer Wheat Dwarf I by Temperature

The Marquillo × Kenya Farmer 1 “grass-clump” dwarf selection of Triticum aestivum L. was grown under continuous 2000 foot candle light and several regimes of alternating 16° and 26° temperatures combined in total cycle lengths of 6, 12, 24, or 48 hr. Plants at 26° grew as normal wheat. Those exposed to 0.25 to 2 hr of 16° per cycle showed typical “grass-clump” dwarf characteristics which were independent of the cycle length. Treatments with 16° exposures of 4 to 8 hr per 24 hr and 12 to 16 hr per 48 hr exhibited vegetative “grass-clump” dwarfness for 40 days but later displayed extensive reproductive development. Longer 16° treatments killed the plants at a very early stage of vegetative development before floral initiation. The data supported an hypothesis that all 4 growth habits were related to the temperature sensitivity of the vegetative meristem. The cessation of meristem development was possibly due to the accumulation of a stable inhibitory substance produced at low temperatures.     

Chronic Bronchitis: Method of Cigarette Smoking

Male volunteers for mass radiography examination, aged 40 or more, were questioned about their sputum production, smoking habits, and, when applicable, their method of smoking cigarettes.Of 5,438 cigarette smokers 460 (8·4%) smoked their cigarettes without removing the cigarette from the mouth between puffs (“drooping” cigarette smokers) whereas the rest smoked in the normal manner.Persons who admitted to producing sputum from their chests on most days of the year or on most days for at least three months of the year for a minimum of two years were classified as chronic bronchitics in the absence of other causative disease.The rate of chronic bronchitis among the “drooping” cigarette smokers (41·5%) was considerably greater than that among those smoking cigarettes in the normal manner (33·6%). The same pattern was maintained when age and cigarette consumption were standardized, though “drooping” cigarette smokers had a slight bias towards plain as distinct from filter cigarettes and towards a lower social class this was not sufficient to account for the excess of chronic bronchitis among those using this method of smoking.     

Ecdysteroids: A novel class of anabolic agents?

Increasing numbers of dietary supplements with ecdysteroids are marketed as “natural anabolic agents”. Results of recent studies suggested that their anabolic effect is mediated by estrogen receptor (ER) binding. Within this study the anabolic potency of ecdysterone was compared to well characterized anabolic substances. Effects on the fiber sizes of the soleus muscle in rats as well the diameter of C2C12 derived myotubes were used as biological readouts. Ecdysterone exhibited a strong hypertrophic effect on the fiber size of rat soleus muscle that was found even stronger compared to the test compounds metandienone (dianabol), estradienedione (trenbolox), and SARM S 1, all administered in the same dose (5 mg/kg body weight, for 21 days). In C2C12 myotubes ecdysterone (1 µM) induced a significant increase of the diameter comparable to dihydrotestosterone (1 µM) and IGF 1 (1.3 nM). Molecular docking experiments supported the ERβ mediated action of ecdysterone. To clarify its status in sports, ecdysterone should be considered to be included in the class “S1.2 Other Anabolic Agents” of the list of prohibited substances of the World Anti-Doping Agency.     

Experience with Coeliac Axis Compression Syndrome

Seven patients with “coeliac axis compression syndrome” are reported. Five were treated surgically, but only two did well. A survey of 200 healthy adults showed epigastric bruits in 6·5%; only one of these had dyspepsia, though dyspepsia was present in 12·5% overall.Caution is urged in attributing a causal relationship between coeliac axis compression and pain and in proceeding to arteriography when compression is suspected on clinical grounds.