Histological changes over time around the site of sustained release naltrexone-poly(DL-lactide) implants in humans.

In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.     

Dysphagia aortica

Three patients with dysphagia caused by compression of the distal esophagus by a tortuous nonaneurysmal atherosclerotic aorta are described. All three patients were elderly women; systemic hypertension and cardiomegaly were present in two patients. Barium studies of the esophagus showed displacement and compression of the distal esophagus by the thoracic aorta. Debilitating dysphagia was treated surgically in one patient. The other two patients had milder symptoms and were managed conservatively. Esophageal manometry in these three patients showed superimposed pulsations and elevated intraluminal pressure just proximal to the lower esophageal sphincter. To evaluate the significance of these manometric findings and their correlation with clinical symptoms, we reviewed manometric tracings in 47 normal subjects. Ten of these subjects had an elevation of baseline intraluminal esophageal pressure as a result of superimposed vascular pulsations. We conclude that (1) compression of the distal esophagus by a tortuous atherosclerotic aorta in the appropriate setting can lead to clinically significant dysphagia and (2) a manometric finding of vascular compression of the esophagus does not necessarily correlate symptomatic dysphagia.     

Quality of object relations versus interpersonal functioning as predictors of therapeutic alliance and psychotherapy outcome

The purpose of the study was to compare an interview measure of quality of object relations to questionnaire and interview measures of recent interpersonal functioning with respect to the prediction of therapeutic alliance and psychotherapy outcome. The sample consisted of 64 patients who had received approximately 20 sessions of short-term individual psychotherapy within a controlled, clinical-trial investigation. Ratings of therapeutic alliance were provided independently by the patient and the therapist after each session. Outcome measures, which were provided by three sources (patient, therapist, and independent assessor), covered the areas of interpersonal functioning, psychiatric symptomatology, self-esteem, and life satisfaction. Quality of object relations, which characterizes the patient's lifelong pattern of relationships, was the best predictor. It was significantly related to patient-rated and therapist-rated therapeutic alliance and to patient improvement of both general symptomatology and specific target problems. The study also replicated previous studies that have reported significant relationships between therapeutic alliance and therapy outcome. The advantages of pretherapy predictors of therapy outcome, such as quality of object relations, are discussed.     

Distinct Membrane Effects of Spinal Nerve Ligation on Injured and Adjacent Dorsal Root Ganglion Neurons in Rats

Background: Painful peripheral nerve injury results in disordered sensory neuron function that contributes to the pathogenesis of neuropathic pain. However, the relative roles of neurons with transected axons versus intact adjacent neurons have not been resolved. An essential first step is identification of electrophysiologic changes in these two neuronal populations after partial nerve damage.

Methods: Twenty days after spinal nerve ligation (SNL), intracellular recordings were obtained from axotomized fifth lumbar (L5) dorsal root ganglion neurons and adjacent, intact L4 neurons, as well as from control neurons and others subjected to sham-SNL surgery.

Results: Pronounced electrophysiologic changes were seen only in L5 neurons after SNL. Both A[alpha]/[beta] and A[delta] neuron types showed increased action potential duration, decreased afterhyperpolarization amplitude and duration, and decreased current threshold for action potential initiation. A[alpha]/[beta] neurons showed resting membrane potential depolarization, and increased repetitive firing during sustained depolarization developed in A[delta] neurons. The afterhyperpolarization duration in neurons with C fibers shortened after axotomy. In contrast to the axotomized L5 neurons, neighboring L4 neurons showed no changes in action potential duration, afterhyperpolarization dimensions, or excitability after SNL. Depolarization rate (dV/dt) increased after SNL in L4 A[alpha]/[beta] and A[delta] neurons but decreased in L5 neurons. Time-dependent rectification during hyperpolarizing current injection (sag) was greater after SNL in A[alpha]/[beta] L4 neurons compared with L5. Sham-SNL surgery produced only a decreased input resistance in A[alpha]/[beta] neurons and a decreased conduction velocity in medium-sized cells. In the L5 ganglion after axotomy, a novel set of neurons, consisting of 24% of the myelinated population, exhibited long action potential durations despite myelinated neuron conduction velocities, particularly depolarized resting membrane potential, low depolarization rate, and absence of sag.     

Gastric emptying disorders. Tests and treatments

Tests to measure the volume of gastric contents are necessary to determine the nature of a gastric emptying disorder. The conditions that can affect gastric emptying are as varied as peptic ulcer disease, achlorhydria, viral and bacterial infections of the stomach, diabetes, scleroderma, anorexia nervosa, and CNS lesions; some patients experience gastric emptying problems after surgery for peptic ulcer disease. The future of electrical pacing of the stomach and perhaps the gastrointestinal tract in general is very exciting, as is the future use of antiarrhythmic drugs.     

Update on trauma care in Canada. 5. Trauma and hypothermia

Trauma may be accompanied by hypothermia in all climates. Because of the associated increased death rate due to hypothermia (core body temperature less than 35 degrees C), traumatized patients must be protected from it. The body maintains heat balance by hypothalamic regulation of endogenous heat generation and heat loss. Decreased core temperature causes generalized physiologic deceleration and homeostatic disturbances in all organ systems. To prevent hypothermia in polytraumatized patients a number of methods may be used: warming crystalloid, increasing ambient temperature, the use of warming devices, irrigation of body cavities with warmed fluids, heating of inspired gases and, in severe cases when there is circulatory instability, the use of extracorporeal membrane oxygenation.     

Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with parkinson's disease

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0–3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 ± 6.4% retention of isotope 2 h after the meal compared with 37.0 ± 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.     

Metronidazole susceptibility testing for Helicobacter pylori: comparison of disk, broth, and agar dilution methods and their clinical relevance.

Since the methods for metronidazole susceptibility testing of Helicobacter pylori have not been standardized or validated, we compared three methods that are used to test the metronidazole susceptibilities of 25 isolates of H. pylori. Specifically, we examined the methods of Steer's replicator agar dilution, tube broth microdilution, and modified Kirby-Bauer disk diffusion. The metronidazole disk zone sizes obtained by the disk diffusion method correlated well (r = 0.74) with the MICs obtained by the agar dilution method. Afterward, the disk diffusion method was used to characterize the metronidazole susceptibilities of 44 isolates of H. pylori. Dual therapy (bismuth and metronidazole) proved to be highly effective against metronidazole-susceptible strains (81.6% eradication rate) but fared poorly against resistant strains (16.7% eradication rate; P < 0.01). Using agar dilution testing, we validated the modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of H. pylori and conclude that it is practical, accurate, and clinically applicable.