Peripheral neuropathic pain--a multidimensional burden for patients.

The present study was undertaken to assess the health-related quality of life (HRQoL) and burden of illness due to pain and its treatment for patients with peripheral neuropathic pain (PNP). It is the first step in finding reliable instruments/targets to evaluate treatment outcome in this patient population. Study population consisted of 126 patients suffering from neuropathic pain due to a peripheral nerve or root lesion, recruited from two multidisciplinary pain clinics. HRQoL was examined using Short Form 36 (SF-36) Health Survey and Nottingham Health Profile (NHP). Pain intensity in four categories (at rest and evoked by movement, touch and cold) was rated on a visual analogue scale (VAS). Degree of discomfort from pain and 25 symptoms related to pain and side-effects was also assessed. Reduction in workload due to pain was recorded, as was the pain relief from previous and current treatments and the reasons for discontinuing previous treatments. All dimensions in SF-36 and NHP were significantly impaired. SF-36 was a valid instrument for describing the impact of pain on the HRQoL of patients with PNP. NHP had a lower reliability but has other advantages that might be of importance. Many patients experienced poor pain relief from ongoing pain treatments. Most previous treatments were discontinued owing to lack of efficacy and/or severe side-effects. Many patients experienced a high intensity of at least one type of pain; median VAS for the highest pain intensity score of each patient (any type of pain) was 74/100. Besides pain, patients were most bothered by difficulty in sleeping, lack of energy, drowsiness, difficulty in concentrating and dry mouth. Employment status was reduced owing to pain in 52% of the patients. The intense pain, other troublesome symptoms, limited efficacy and tolerability of available treatments, together with the impaired health and reduced work status, amount to a substantial burden for patients with PNP.

A comparison of the SF-36 and Nottingham Health Profile in patients with chronic neuropathic pain.

The aim of this study was to evaluate and compare the psychometric properties of two generic health-related quality of life (HRQoL) instruments, the Short Form Health Survey (SF-36) and the Nottingham Health Profile (NHP) in a group of patients with chronic peripheral neuropathic pain (PNP). The sample consisted of 126 adults (56 men and 70 women) with PNP following a lesion of a peripheral nerve, spinal nerve or nerve root or patients with post-herpetic neuralgia. The battery of tests included visual analogue scales (VASs) for pain assessment and global rating of health and verbal rating scales of pain and other symptoms, as well as patient descriptors. The SF-36 had higher internal consistency reliability coefficients (alpha=0.79, range 0.70-0.90) than the NHP (alpha=0.68, range 0.49-0.79). Correlations between comparable dimensions of the two instruments were significant (range from -0.79 for the physical and mental dimensions to -0.29 for the social dimension) indicating a moderate degree of convergent validity. The study population had significantly worse scores on all dimensions of the two instruments when compared with the general population. Subjects with high VAS scores for pain on movement and those with low global health ratings had poorer scores on the both instruments. Overall, the SF-36 performed somewhat better on psychometric testing than did the NHP. However, the NHP contains dimensions such as sleep and more pain items which might be of particular importance in the PNP population. Since the instruments are short, both could be retained for continued testing in outcome studies of this population.

The effect of environmental pH on the proton motive force of Helicobacter pylori.

BACKGROUND & AIMS: Responses of the proton motive force (the driving force for protons) in Helicobacter pylori to varying medium pH may explain gastric colonization. The aim of this study was to determine the effect of external pH (pHout) on the proton motive force, the sum of the pH gradient, and the potential difference across the bacterial membrane. METHODS: Intracellular pH (pHin) was measured by bis-carboxyethyl-carboxy fluorescein fluorescence and transmembrane potential difference (PD) by fluorescent quenching of 3,3'-dipropyl thiadicarbocyanine iodide at differing pHout and was correlated with survival. RESULTS: PD was -131 +/- 0.36 mV (n = 3), and pHin was about 8.4 at loading pHout 7.0. PD increased as pHout was increased from 4.0 to 8.0, giving a constant proton motive force of about -220 mV. Outside these limits, PD collapsed irreversibly to zero. Addition of 5 mmol/L urea to weak buffer at pH 3.0 or 3.5 prevented irreversible collapse of PD by elevation of pHout caused by NH3 production. Urea addition to weak buffer at pH 7.0 collapsed the PD as urease activity increased the pHout to about 8.4. Survival was also limited to this range of pHout. CONCLUSIONS: H. pylori survives over the range of pHout where it maintains a proton motive force. The effect of urease activity on pHout, while allowing gastric survival in acidic media, may limit survival in nonacidic media.

Refinement of, and new applications for, Helicobacter pylori colonization in pig gastric biopsy specimens cultured in vitro.

BACKGROUND: As we have previously reported, pig gastric biopsy specimens cultured in vitro are a highly useful model for studies of Helicobacter pylori growth and adhesion. The aim of this study was to further refine the model in terms of mucosal specificity, culture time, bacterial adhesion, and drug delivery. METHODS: H. pylori-inoculated antral and corporeal pig gastric specimens were cultured for up to 96 h. Biopsy viability, bacterial growth, and adhesion were determined every 24 h. Bismuth subcitrate and omeprazole were added to the top of the specimens via a bio-adhesive gel. RESULTS: Corporeal and antral specimens could be cultured for 72 h and 96 h, respectively, without affecting the viability. In parallel experiments from the same pig the percentage adhesion and total number of adhering H. pylori was higher in corporeal than in antral specimens at 72 h (28% and 4 x 10(5) versus 15% and 4 x 10(4), respectively). Removal of loosely attached H. pylori by rinsing at 24 h doubled the percentage H. pylori adhered during the subsequent 48 h. Bismuth subcitrate had a dose-dependent inhibitory effect on H. pylori; when added to the mucosal side, omeprazole had no effect. CONCLUSION: The pig in vitro biopsy model can be used for detailed H. pylori adhesion studies and for the screening of drugs added to the mucosal or serosal side.

Helicobacter colonization of biopsy specimens cultured in vitro is dependent on both mucosal type and bacterial strain.

BACKGROUND: Colonization by Helicobacter pylori is strictly tissue-specific. We have previously reported on an in vitro adhesion model for pig and human gastric mucosa, in which biopsy specimens were successfully infected and cultured for 72h. The aim of this study was to compare H. pylori colonization of different mucosae and by different Helicobacter strains. METHODS: Specimens from pig, rabbit, and rat antrum, pig urinary bladder, and pig duodenum were inoculated with two H. pylori strains and one H. mustelae strain. Four additional strains, including one mutant lacking flagella, were compared on pig antral specimens. RESULTS: The viability of all mucosae was comparable at 48h of culture. The percentage adhering bacteria increased with time in all mucosae, reaching 17%, 11%, and 2% in pig, rabbit and rat antral mucosa, 11% in pig bladder, and 3% in duodenum at 48h. The type of H. pylori strain was a strong determinant for adhesion in pig antrum. Strain SVA40 had the highest adhesion; the mutant lacking flagella colonized very poorly. H. mustelae adhered to all types of mucosae in a more unspecific manner. CONCLUSIONS: On the basis of tissue viability, bacterial colonization, and adhesion, pig antral mucosa is clearly superior. H. pylori strains differ in their ability to adhere to and colonize cultured mucosa.

Acid, protons and Helicobacter pylori.

The anti-ulcer drugs that act as covalent inhibitors of the gastric acid pump are targeted to the gastric H+/K+ ATPase by virtue of accumulation in acid and conversion to the active sulfenamide. This results in extremely effective inhibition of acid secretion. Appropriate dosage is able to optimize acid control therapy for reflux and peptic ulcer disease as compared to H2 receptor antagonists. However, clinical data on recurrence show that Helicobacter pylori eradication should accompany treatment of the lesion. These drugs have been found to synergize with many antibiotics for eradication. The survival of aerobes depends on their ability to maintain a driving force for protons across their inner membrane, the sum of a pH and potential difference gradient, the protonmotive force (pmf). The transmembrane flux of protons across the F1F0 ATPase, driven by the pmf, is coupled to the synthesis of ATP. The internal pH of H. pylori was measured using the fluorescent dye probe, BCECF, and the membrane potential defined by the uptake of the carbocyanine dye, DiSC3 [5] at different pHs to mimic the gastric environment. The protonmotive force at pH 7.0 was composed of a delta pH of 1.4 (-84mV) and a delta potential difference of -131mV, to give a pmf of -215 mV. The effect of variations in external pH on survival of the bacteria in the absence of urea correlated with the effect of external pH on the ability of the bacteria to maintain a pmf. The effect of the addition of 5 mM urea on the pmf was measured at different medium pH values. Urea restored the pmf at pH 3.0 or 3.5, but abolished the pmf at pH 7.0 or higher, due the production of the alkalinizing cation, NH3. Hence H. pylori is an acid-tolerant neutrophile due to urease activity, but urease activity also limits its survival to an acidic environment. These data help explain the occupation of the stomach by the organism and its distribution between fundus and antrum. This distribution and its alteration by proton pump inhibitors also explains the synergism of proton pump inhibition and antibiotics such as amoxicillin and clarithromycin in H. pylori eradication.

13C-urea breath test for diagnosis of experimental Helicobacter pylori infection in barrier born pigs.

Previous studies with Helicobacter pylori infected barrier born pigs indicate that the infection has a patchy distribution, resulting in false negative culture results on endoscopic biopsy specimens. This study aimed to adapt the 13C-urea breath test as used in humans to diagnose H pylori infection in barrier born pigs. The breath test was also performed after bismuth as a single treatment and after triple therapy (bismuth, ampicillin, metronidazole). In control pigs the median excess of 13CO2 in expired air was 2.2 (range 0-12 n = 22) ppm. The infected pigs (n = 4) showed consistently high values (median 23 range 14-43) when examined on four occasions (n = 16) four to 10 weeks after inoculation. Biopsy specimens for culture had lower sensitivity than the breath test. No reduction in excess 13CO2 was seen after three days' single bismuth treatment, but after two weeks' triple therapy the breath test results had returned to normal. This suppression was temporary only, however, as the breath test was positive again four weeks after stopping treatment. In conclusion, the 13C-urea breath test is a simple and reliable test for determining H pylori infection and monitoring treatment effects in barrier born pigs. Because the test can be performed in awake pigs anaesthesia and gastroscopy are unnecessary.