Sildenafil relieves symptoms and normalizes motility in patients with oesophageal spasm: a report of two cases

Oesophageal spasm presents with dysphagia and chest pain. Current treatments are limited by poor efficacy and side effects. Studies in health and oesophageal dysmotility show that sildenafil reduces peristaltic pressure and velocity; however the clinical efficacy and tolerability in symptomatic oesophageal spasm remains uncertain. We provided open-label sildenafil treatment to two patients with severe, treatment resistant symptoms associated with oesophageal spasm. The effects of sildenafil on oesophageal function and symptoms were documented by high resolution manometry (HRM). Patients were followed up to assess the efficacy of maintenance treatment with sildenafil b.i.d. HRM revealed focal and diffuse spasm in the smooth muscle oesophagus that were associated with symptoms in both cases, especially on swallowing solids. Lower oesophageal sphincter function was normal. A therapeutic trial of 25-50 mg sildenafil suppressed oesophageal contraction almost completely for water swallows; however effective, coordinated peristalsis returned with reduced frequency of spasm for solid swallows. Dysphagia and chest pain resolved during the therapeutic trial and efficacy was maintained on maintenance treatment with 25-50 mg sildenafil b.i.d. without troublesome side effects. This report shows that sildenafil can improve oesophageal function and relieve dysphagia and chest pain in patients with oesophageal spasm in whom other treatments have failed.     

High propionic acid fermentations and mineral accumulation in the cecum of rats adapted to different levels of inulin

The digestive and metabolic effects of inulin (from chicory) were studied in rats adapted to semipurified diets containing 0, 5, 10 or 20% inulin (wt/wt). Moderate levels of inulin (5-10%) did not significantly affect food intake or body weight gain. Dietary inulin resulted in considerably greater cecal fermentation and a significantly greater intraluminal concentration of propionate (peaking at 58.4 mmol/L). A lower concentration of acetate (42.6 mmol/L) was observed in rats fed 20% inulin. Lactic fermentations were observed in rats fed the 10 or 20% inulin diets. The cecal pool of volatile fatty acids tended to reach a plateau in rats fed diets containing more than 10% inulin (up to 600-700 mumol), but volatile fatty acid absorption was a slightly hyperbolic function of the dietary inulin level. Butyrate absorption was proportionally lower than that of propionate. Inulin-containing diets induced an enlargement of the cecal pool of calcium, phosphate and (to a lesser extent) magnesium. There was also an enhanced absorption of these divalent cations. The cecal pool of bile acids was greater in rats fed inulin, and this oligosaccharide displayed a slight hypocholesterolemic effect, even in rats fed the 5% inulin diet. However, plasma triglycerides were depressed only in rats fed the 20% inulin diet. In conclusion, inulin seems very effective in promoting propionic fermentation and in enhancing the calcium content of the large intestine. However, high levels of inulin (greater than 10%) may affect growth in rats and lead to acidic (pH 5.65) cecal fermentation.     

Pharmacokinetics and pharmacodynamics of epidural and intrathecal morphine

Spinal opiate analgesia has opened an exciting new field of research and has also rapidly gained widespread clinical acceptance. This mode of administration has obvious and definite advantages over conventional pain therapy; however, the field is still at an early stage of development. More research is clearly needed to provide methods for coping with some of the drawbacks of this method of pain relief. Important areas for future research include (1) the CSF kinetics of opiates; (2) the physiological mechanisms underlying the rostral spread of drugs within the CSF compartment; (3) a search for safer and more selective drugs; and (4) an evaluation of the extent to which pain-modulating systems at different levels in the CNS can be regulated by opiates and drugs interfering with other neurotransmitters. In this context it is essential to emphasize the importance of simultaneous study of the pharmacokinetics and the pharmacodynamic/clinical effects in providing a rational basis for a better understanding of the mechanisms of actions underlying spinal opiate analgesia.     

Phenotypic and genotypic characterization of prolyliminopeptidase-negative Neisseria gonorrhoeae isolates in Denmark

In the study presented here 26 recent Danish clinical isolates of prolyliminopeptidase (PIP)-negative Neisseria gonorrhoeae were phenotypically and genotypically characterized to investigate whether one or more PIP-negative strains are circulating in the Danish community. The profiles of these isolates were compared with those of three isolates from a recent outbreak of PIP-negative N. gonorrhoeae infection in the UK. Twenty-five of the Danish isolates and all three UK isolates had similar antibiograms and were designated serovar IB-4. Genotypic characterization by pulsed-field gel electrophoresis, porB1b gene sequencing, and opa-typing revealed that these isolates were indistinguishable or closely related. The results indicate that at least one PIP-negative N. gonorrhoeae strain is currently circulating in the Danish community, and this strain is indistinguishable from the one that caused an outbreak in the UK.An erratum to this article can be found at     

Functional development of the visual system in normal and protein-deprived rats. IX. Visual evoked response in young rats

Changes in latencies of the visual evoked response (VER) during early post-natal development were examined in protein-deprived (PD) rats. The evoked response to light-flash stimulation was recorded in the dorsal lateral geniculate nucleus (dLGN) and on the surface of the visual cortex. In control rats, latencies of the cortical VER decreased rapidly up to 20 days and slowly thereafter. In PD rats, the latencies of the cortical VER were increased by 10-15 ms at 17 days; the developmental decrease was delayed by approximately 3 days. After 20 days, PD rats also went into a phase with slow decrease of the latencies, and the onset latency of the cortical VER was still increased by some 10 ms at 26/27 days. At this age, PD rats showed an increase in the latencies of the VER in the dLGN which was of similar magnitude to that in the cortical VER, indicating that alterations were more marked in the peripheral parts of the visual system at this stage of development. The findings are in agreement with previous studies indicating that there is a delay of visual system development in PD rats before 20 days. A maturational event which turns rapid into slow development at approximately 20 days in both C and PD rats turns this delay into a distortion of development. The delays and distortions of visual system development may be one causative factor for the functional deficit present in the visual cortex of adult PD rats.     

Functional development of the visual system in normal and protein-deprived rats. IV. Latencies in the specific visual pathway of adult rats

It was recently shown that an increase in latency of the cortical visual evoked response (VER) seen in young malnourished animals persists in adult rats given a low protein diet. In the present paper the VER latencies of the specific visual pathway were measured in order to establish the level at which the latency increase occurs in protein-deprived rats. The VER in the dorsal lateral geniculate nucleus (dLGN) showed no significant differences to onset or peak latencies between control (C) and the protein-deprived (PD) rats. The dLGN activity was higher in C rats than in PD rats. Late components differed in median values between the two groups, but the individual variations were large. Generally, the VER of the dLGN in PD rats was more stereotype compared with the C rats. Intracortical VER at a depth of 0.4-0.5 mm showed a small negative component of short onset latency in both C and PD rats. This component preceded the onset of the initial positivity recorded from the cortical surface by 1-2 ms in C rats and by 3-6 ms in PD rats. Following electrical stimulation of the dLGN, no differences in onset latency of the first cortical activity (monosynaptic response) were recorded between C and PD rats, whereas later activity was significantly delayed in PD compared with C rats. The laminar potential pattern was less distinct in PD compared with C rats, and the late components of the evoked response from deep cortical layers were markedly attenuated or lacking.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contribution of sensitivity, volume and tone to visceral perception in the upper gastrointestinal tract in man: emphasis on testing

Abstract  Upper gastrointestinal (GI) symptoms occur frequently in the general population, making them among the most common indications responsible for patients consulting the healthcare system. Consequently, understanding and characterization of the upper GI symptoms is important for the diagnosis and assessment of organ dysfunction. In practice, assessment of clinical symptoms is difficult and it is still to a large extent unclear how sensitivity, volume and tone contribute to visceral perception in the upper GI tract. The goal of advanced research in upper GI symptoms is to obtain a better understanding of the mechanisms involved in transduction, transmission, and perception under normal and pathophysiological conditions. An important step towards this goal is understanding the information provided by and the inherent limitations of the currently available measuring techniques. This article focuses on the sensory testing of the oesophagus, and methods and concepts used to assess the relation between gastric volumes or tone and upper GI symptoms. It also summarizes the contributions of these techniques towards identifying the components responsible for the generation of upper GI symptoms.     

Treatment of horizontal root‐fractured maxillary incisors – a case report

Abstract – Traumatic dental injuries often occur to the teeth and their supporting tissues and they are the main reasons for emergency visit to a dental clinic. Management of a fracture depends on its position and the extent of root involvement. Horizontal root fractures are not seen frequently and the treatment consists of reduction and long‐term rigid fixation of the coronal segment. The present case demonstrates the successful management of two horizontally fractured maxillary central incisors with a follow‐up period of 9 months.