Neuropathic pain in AIDS patients prior to antiretroviral therapy.

OBJECTIVE: To measure the prevalence, severity and morbidity of neuropathic pain in AIDS patients, prior to the initiation of antiretroviral (ARV) therapy. DESIGN: A prospective, cross-sectional and descriptive-analytical study. SETTING: The Kalafong Hospital HIV Clinic in Pretoria. SUBJECTS: All patients with confirmed AIDS who were referred to the Kalafong HIV clinic to be initiated on ARV therapy during the period August 2006 to March 2007. OUTCOME MEASURES: Data were collected regarding the presence and severity of neuropathic pain in each subject. Pain of predominantly neuropathic origin (POPNO) was identified using the Neuropathic Pain Diagnostic Questionnaire (DN4). Numerical rating scales (NRS), adapted from the Brief Pain Inventory, were used to measure pain severity and pain-related interference with six aspects of daily living. RESULTS: Of the 354 patients studied, 20.9% (95% confidence interval (CI) 16.8-25.2%) had POPNO. This pain was significantly more frequent in patients who were male, had lower CD4+ counts or higher viral load levels, and those on TB treatment. Eighty per cent of patients with POPNO experienced significant pain (worst pain severity > or =5 out of 10 on a NRS). Pain-related interference was highest for enjoyment of life, mood and ability to work. There was a significant positive correlation between severity of pain and pain-related interference for all domains of daily living evaluated. CONCLUSIONS: POPNO results in significant suffering and impaired functioning in patients with AIDS. It is therefore imperative that clinicians assess patients with AIDS for the presence and severity of neuropathic pain and manage it, using the most recent evidence-based guidelines.

Polycarnitine--a new biomaterial.

The natural product L-carnitine is--due to its biotechnological accessibility and specific properties--on the way to becoming an attractive biobased bulk product. L-carnitine is a natural betaine with vitamin properties. Carnitine is an essential part of the fatty acid metabolism of human beings and animals. Carnitine was first isolated in 1905 from meat extract and important recent developments include the biosyntheses of L-carnitine from L-lysine or gamma-butyrobetaine. Our synthesis routes are designed to maintain the primary structure and specific properties of carnitine, such as hydrophilicity and "stiffening" effects for polymeric structures and applications. L-carnitine is converted via lactonization or olefinization into polymerizable basic molecules. The properties and the applications of carnitine polymers are described.

The efficacy and safety of two oral moxifloxacin regimens compared to oral clarithromycin in the treatment of community-acquired pneumonia.

An international multi-centre, randomized, prospective, double-blind study compared oral moxifloxacin (200 mg or 400 mg once daily for 10 days) with oral clarithromycin (500 mg, twice daily for 10 days) in the treatment of community-acquired pneumonia (CAP). The clinical success rate in the evaluable population at the primary efficacy assessment, 3-5 days after the end of study treatment, was 93.9% in patients treated with 200 mg moxifloxacin; 94.4%, with 400 mg moxifloxacin; and 94.3%, with clarithromycin. Clinical success rates were maintained at follow-up, 21-28 days after the end of treatment: 90.7% (200 mg moxifloxacin), 92.8% (400 mg moxifloxacin) and 92.2% (clarithromycin). The 95% confidence intervals indicated that all three treatment regimens were equally effective in treating CAP. At follow-up, the 400 mg moxifloxacin dose had a slightly higher observed cure rate than the 200 mg moxifloxacin dose, but this was not statistically significant. The most frequently isolated pathogens were Streptococcus pneumoniae (42%), Haemophilus influenzae (19%), Haemophilus parainfluenzae (10%), Moraxella catarrhalis (6%), Klebsiella pneumoniae (5%) and Staphylococcus aureus (4%). The bacteriological success rate (eradication and presumed eradication) was 72.5% (29/40) for 200 mg moxifloxacin, 78.7% (37/47) for 400 mg moxifloxacin and 70.7% (29/41) for clarithromycin. The adverse event profile was comparable between the three treatment groups. Most adverse events, possibly or probably related to the study drug, were generally mild or moderate in severity and mostly related to the digestive system: diarrhoea, nausea and abdominal pain in 200 mg moxifloxacin patients; diarrhoea, liver function abnormalities and nausea in 400 mg moxifloxacin patients and liver function abnormalities, diarrhoea, nausea and taste perversion in clarithromycin patients. Study drugs were discontinued because of adverse events in 7/229 (3%) patients treated with 200 mg moxifloxacin, 11/224 (5%) with moxifloxacin 400 mg and 11/222 (5%) with clarithromycin. In all assessments, moxifloxacin was at least as effective clinically, and as well tolerated as clarithromycin in the treatment of CAP. Bacteriological success rates in moxifloxacin-treated patients were greater than those of clarithromycin. Moxifloxacin, given once daily, is free of many drug-drug interactions and requires no dosage adjustments in most renal hepatic deficient patients.

Gauged attenuation of congenital portosystemic shunts: results in 160 dogs and 15 cats.

Portosystemic shunts were ligated over a gauged stainless steel rod in 160 dogs and 15 cats, using a midline celiotomy. The diameter of the rod varied with the size of the shunt and the diameter of the portal vein cranial to the shunt. Shunts were narrowed to the smallest diameter that did not cause signs of portal hypertension such as cyanosis of the stomach, pancreas, and small intestine. A slight discoloration was accepted only if the heart rate, end-expiratory CO2%, or arterial blood pressure (if available) did not deviate more than 15% from the values that were recorded at the beginning of the surgical procedure. The perioperative mortality (0-30 days) was 29%. The most common cause of death was euthanasia because of hypoplasia of the portal vein cranial to the shunt. Animals with intrahepatic shunts had a significantly lower probability of survival than animals with extrahepatic portocaval or portoazygos shunts. In dogs, large breed and a high body weight were also significant risk factors for non-survival. Age had a significant effect on risk of non-survival, with an increased risk for older dogs, irrespective of the breed of the dog (large breed vs. small breed). The probability of survival without recurrence of hepatoencephalopathy (HE) after 1 and 4 years was 61.3% and 55.7%, respectively. The only variable that was significantly associated with non-recurrence of HE was the breed of the dog, there being a lower probability for large breeds. Among the animals that survived surgery for more than 30 days, there was a significant higher probability of recurrence of HE in cats than in dogs.

Effects of a branched-chain amino acid-enriched diet on chronic hepatic encephalopathy in dogs.

A decreased ratio of branched-chain amino acids (BCAA) to aromatic amino acids (AAA) is considered an important pathogenetic factor in hepatic encephalopathy (HE). A relationship between the deranged BCAA/AAA ratio and dopaminergic dysfunction through the formation of "false" neurotransmitters has been postulated. The intermediate lobe of the pituitary is more pronounced in dogs than in humans and because it is primarily under dopaminergic inhibitory influence, it may serve as an indicator of alterations in dopaminergic neurotransmission. We investigated the effects of a diet with a high BCAA/AAA ratio (HR) and an isonitrogenous diet with a low BCAA/AAA ratio (LR) on several physical and biochemical parameters including pituitary function in dogs with portocaval shunts and 40% hepatectomy and in sham-operated pair-fed controls, in a double-blind, randomized cross-over study. Portocaval-shunted dogs had hyperammonemia (33+/-3 microM (mean +/- SEM) before and 214+/-21 after surgery)) and signs of HE. Their BCAA/AAA ratio in plasma and CSF decreased from 4.3+/-0.3 and 2.3+/-0.3 before surgery to 1.3+/-0.1 and 0.5+/-0.1 after surgery, respectively. These parameters remained unaltered in the control dogs. The consumption of the LR diet was significantly higher than consumption of the HR diet. In the portocaval-shunted dogs, plasma ammonia concentration was higher on the HR diet than on the LR diet (344+/-52 v 246+/-45) and the HE grade was worse. The BCAA/AAA ratio remained abnormal in HE dogs during the feeding of both diets. The basal and haloperidol-stimulated release of alpha-melanotropin and cortisol in plasma were not significantly different between or within groups during any period. In contrast, urinary cortisol excretion was increased in the HE dogs after surgery (urinary cortisol:creatinine ratio (x10(-6)) 8.5+/-1.4 before and 30.4+/-8.9 after surgery). The basal plasma concentration of adrenocorticotropin in HE dogs was decreased after surgery (68.3+/-10.2 ng/L before and 40.8+/-4.4 after surgery). This indicates a non-pituitary-dependent hyperresponsiveness of the adrenals. We conclude from these results that chronic HE in dogs is not associated with an abnormal dopaminergic neurotransmission at least at the level of the pituitary, and that it is not the content of the dietary neutral amino acids but rather the total protein intake that may have a beneficial effect on HE.

Evaluation of ammonia measurements in dogs with two analysers for use in veterinary practice.

The measurement of ammonia in biological fluids is the only way to diagnose and evaluate hepatic encephalopathy, but samples for ammonia measurement cannot be stored or sent by post. Two analysers for use in veterinary practice have recently become available, the VetTest and the Blood Ammonia Checker II; the reliability of ammonia measurements in canine blood with these two analysers has been evaluated by comparing the results with a standard automated enzymatic assay. Blood samples from 39 dogs, with a range of ammonia concentrations from 5 to 589 microM, were used simultaneously in the three assays. The blood samples were placed immediately on ice, and the measurements were made in duplicate. The intra-assay coefficients of variation were 13.7 per cent for the VetTest, 4.7 per cent for the Blood Ammonia Checker, and 2.8 per cent for the enzymatic assay. The correlation coefficients over the entire range of concentrations were 0.79 between the VetTest and the enzymatic assay, and 0.98 between the Ammonia Checker and the enzymatic assay. The ammonia concentrations recorded in the enzymatic assay were divided into 12 samples within the normal range (0 to 50 microM), 18 samples with moderately increased concentrations (51 to 150 microM), and nine samples with concentrations above 150 microM. No correlation or a poor correlation was found between the results from the VetTest and those from the enzymatic assay from 0 to 50 microM (R = 0.27) and from 50 to 150 microM (R = 0.51; P = 0.05). The results from the VetTest were only reliable in samples with the highest concentrations (R = 0.93; P < 0.05). In contrast, the results from the Ammonia Checker correlated well with the results from the enzymatic assay over all the ranges: R = 0.79 (P < 0.05) from 0 to 50 microM, R = 0.86 (P < 0.05) from 50 to 150 microM, and R = 1.00 (P < 0.05) in samples exceeding 150 microM.

Progressive remission of portosystemic shunting in 23 dogs after partial closure of congenital portosystemic shunts.

The congenital portosystemic shunts in 23 dogs were closed partially in 18 and completely in five with a single silk ligature. The clinical results were studied and the degree of portosystemic shunting was measured by a scintigraphic method, the results being expressed as the shunt index (SI). In 17 of the dogs, the mean (sd) SI decreased from 0.92 (0.16) before surgery to 0.34 (0.25) during surgery after the attenuation of the shunt, and then to 0.10 (0.12) one month later. The dogs' venous ammonia concentration decreased from 203 (122) microM before surgery to 36 (18) one month after surgery. At the same time the clinical scores improved significantly. There were positive correlations between the SI and the general evaluation of the dogs' well-being by their owners (rs = 0.60), the ammonia concentration (rs = 0.86), and the diameter of the shunt (rs = 0.86). In the other six dogs, the intraoperative and/or postoperative SI was high. In two of them the shunt was further attenuated during a second operation, which resulted in lower SI values; in two a second small shunt was responsible for the high SI; in one multiple portosystemic shunts were found postmortem; and one dog was lost to follow-up.

Fast resolution of hypercortisolism in dogs with portosystemic encephalopathy after surgical shunt closure.

The aim of this study was to investigate whether hypercortisolism in dogs with congenital portosystemic shunts disappeared after surgical closure of the shunts concomitantly with recovery from hepatic encephalopathy. We examined 22 dogs before and four weeks after partial surgical closure of a single, large congenital portosystemic shunt (PSS). Parameters measured to characterise the basal activity of the pituitary-adrenal axis were the cortisol:creatinine (c/c) ratio in home-sampled urine and total and free cortisol in plasma. The binding characteristics of cortisol binding globulin (CBG) in pooled pre- and postoperative plasma were also determined. Ammonia and bile acid concentrations were measured in plasma to characterise the liver perfusion and function. Clinical symptoms relevant to liver function, cortisol excess, and hepatic encephalopathy were recorded semiquantitatively using a standardized questionnaire. The dogs had hypercortisolism before surgery, which had normalized four weeks later. The pre- and postoperative concentrations (means +/- SEM) were, respectively, 238+/-45 nM and 126+/-19 nM for total cortisol, 15.5+/-2.6 nM and 8.4+/-1.3 nM for free cortisol in plasma, 13.4+/-4.3 x 10(-6) and 3.9+/-0.4 x 10(-6) for c/c in urine. The pre- and postoperative Bmax values of CBG were 41 and 79, and Kd values were 3.8 and 5.5. The concentrations of ammonia were 217+/-23 microM and 32+/-3.1 microM, and of bile acids 1 10+/-33 and 11.1+/-2.0 microM, respectively. We conclude that there is a close relation between portosystemic encephalopathy and hypercortisolism in dogs with PSS and that both deviations resolve completely within four weeks of closure of the shunt.

Prediction of inherited portosystemic shunts in Irish Wolfhounds on the basis of pedigree analysis.

OBJECTIVE: To test validity of prediction for inherited portosystemic shunts (PSS) in Irish Wolfhounds, using nonselective clinical findings and a computerized database containing 5-generation pedigrees. ANIMALS: 613 dogs in the first and 396 dogs in the second cohort. PROCEDURE: Preprandial venous ammonia concentration was measured at 6 to 8 weeks in all pups born between Jan 1, 1988 and Jan 1, 1997 Portosystemic shunts were confirmed in hyperammonemic pups, using radioisotope shunt index measurement, and diagnosis of shunting was confirmed at abdominal surgery or necropsy. Findings in dogs of the first cohort (born before Jan 1, 1992) were used to predict shunting in their offspring of the second cohort. Common ancestors of first-cohort dogs with shunts were tested for positive associations with the disease. Risk for a shunt in all second-cohort dogs was predicted on the basis of relatedness with founders and was compared with outcome of clinical screening. RESULTS: Prevalence of shunts in first and second cohorts was 3.1 and 2.3%, respectively. Fifteen highly related associated founders could be identified. Second-cohort dogs were classified into 6 groups of increasing predicted risk. Mean number of dogs per class was 60; number of clinically diagnosed cases ranged from 0 in the class with the lowest risk to 4 in the highest risk class. CONCLUSIONS: Genetic risk for reproducing a PSS in Irish Wolfhounds was accurate, using the described method. CLINICAL RELEVANCE: Risk estimation provides a tool for genetic counseling, does not require knowledge of the mode of inheritance, and may be valid for any inherited disease.

Renal dysplasia in three young adult Dutch kooiker dogs.

Chronic renal failure as consequence of renal dysplasia was diagnosed in three young adult Dutch kooiker dogs (Dutch decoy dogs). Two animals were anorectic from an early age and were thinner than healthy dogs of the same breed. All three were presented because of apathy and weakness. Laboratory examination revealed anaemia and uraemia. One dog was presented with severe dehydration and died during emergency treatment. One dog was euthanatised because of a poor prognosis, and one was given a low-protein diet. This dog survived for 7 months after the diagnosis of chronic renal failure. At necropsy all three animals had shrunken, pale, and firm kidneys that showed microscopical lesions characteristic of canine renal dysplasia, such as asynchronous differentiation of nephrons, persistent immature mesenchyme, persistent metanephric ducts, and adenomatoid proliferation of the tubular epithelium. Secondary degenerative and inflammatory changes consisted of interstitial fibrosis and predominantly lymphocytic/plasmacytic inflammation. This is the first report of renal dysplasia in the Dutch kooiker dog. The disease should be included in the differential diagnosis in young Dutch kooiker dogs with signs of chronic renal failure. The presentation of three cases of this rare disease in this breed, which is based on a rather small gene pool, suggests that it is a familial or hereditary nephropathy.

Improvement of chronic hepatic encephalopathy in dogs by the benzodiazepine-receptor partial inverse agonist sarmazenil, but not by the antagonist flumazenil.

Therapeutic modulation of the increased GABAergic tone in chronic hepatic encephalopathy (HE) by the benzodiazepine receptor (BR) antagonist flumazenil (F) has led to conflicting results in humans and animal models for HE. The BR inverse agonist sarmazenil (S) has only been used in animal models of acute HE. Therefore we investigated the effects of intravenous injection of F and S in dogs with chronic HE 8 to 12 weeks after placement of a portocaval shunt and 40% hepatectomy (n=7), compared to sham-operated pair-fed controls (n=7). The HE dogs had hyperammonemia (298 +/- 48 microM v 33 +/- 3 before surgery (mean +/- SEM)) and signs of HE at the start of the experiments (0.9 +/- 0.1 (scale 0-4)). Three (S3) and 8 (S8) mg/kg of S resulted in a significant improvement of encephalopathy (grade 0.9 +/- 0.2 immediately before v 0.5 +/- 0.1 after injection (S3) and 0.7 +/- 0.1 v 0.3 +/- 0.1 (S8)) and increase in mean dominant frequency of the EEG (MDF; 9.1 +/- 0.7 Hz v 11.1 +/- 0.3 (S3) and 8.9 +/- 0.5 v 11.0 +/- 0.3 (S8)) in HE dogs, whereas 15 mg/kg of S, 3 and 8 mg/kg of F, and the vehicle had no significant effects. The efficacy of S in these dogs is consistent with an increased GABAergic tone in the pathogenesis of chronic HE. The lack of effects of F makes a role for endogenous benzodiazepines herein unlikely.

Polyuria and polydipsia and disturbed vasopressin release in 2 dogs with secondary polycythemia.

In dogs, secondary polycythemia (SP) may be associated with polyuria and polydipsia (PU/PD). The pathogenesis of this PU/PD has not yet been explained. We hypothesized that hyperviscosity and increased blood volume in SP might affect vasopressin (VP) release, resulting in PU/PD. This hypothesis was tested in 2 dogs with SP caused by renal neoplasia and PU/PD. Osmoregulation of VP release was studied by a modified water deprivation test and by investigating the VP response to hypertonic saline infusion. Water deprivation test results were consistent with an inability to produce concentrated urine despite increasing plasma osmolality. During hypertonic saline infusion, the osmotic threshold of VP release was markedly increased in both dogs, resulting in a delayed VP response to increasing plasma osmolality. The sensitivity of VP release was low normal in both dogs. We conclude that blood hyperviscosity and increased blood volume led to impaired VP release and polyuria.

Destructive polyarthritis in a dog with leishmaniasis.

The clinical history and diagnosis of a dog with leishmaniasis involving both elbow joints and the skin is described. The dog, a female, five-year-old crossbreed, had been imported from Majorca (Balearic Islands, Spain) four years before the diagnosis was made. For two years, the dog had had bilateral forelimb lameness. Physical examination revealed swollen, painful and crepitating elbow joints. Furthermore, an ulcerating dermatitis was found on the concave surface of the left pinna and necrotising margins on both ears. Radiographs of the elbow joints revealed complete destruction of the joint surfaces with dislocation of the radius and the ulna, compatible with severe osteolytic arthritis. The diagnosis of leishmaniasis was confirmed by a direct agglutination test.

Transient metabolic hyperammonaemia in young Irish wolfhounds.

Inherited portosystemic shunts occur in 2 to 3 per cent of Irish wolfhounds and are associated with high venous ammonia concentrations and signs of hepatic encephalopathy. Moreover, the vast majority of Irish wolfhound pups without signs of hepatic encephalopathy have moderate hyperammonaemia. The aim of this study was to investigate whether the increased ammonia levels in these clinically healthy dogs are caused by low-grade portosystemic shunting, and whether the hyperammonaemia persists in adulthood. The fasting venous ammonia concentration and the fraction of portal blood by-passing the liver, expressed as the shunt index (SI) were measured in 42 Irish wolfhound pups, and the dogs with high SI values were examined post mortem. The ammonia concentration was also measured in 25 adult Irish wolfhounds in which it had been measured when they were seven to eight weeks old. Eleven of the 42 pups had a portosystemic shunt, as evidenced by a high SI (mean 0.82, range 0.12 to 1.00, normal range 0.01 to 0.05) and by post mortem examination. Their mean ammonia concentration was 249 mumol/litre (range 121 to 350). The 31 pups with a normal SI (mean 0.025, range 0.00 to 0.05) had a mean ammonia concentration of 93 mumol/litre (range 51 to 125). In the 25 dogs in which the ammonia concentration was measured twice, the mean concentration at seven to eight weeks of age was 77 mumol/litre (range 47 to 115) and in the adults it was 17 mumol/litre (range 6 to 27) at a mean age of 3.1 years (range 1.0 to 8.9). These results show that Irish wolfhounds with ammonia concentrations > 125 mumol/litre had a portosystemic shunt, whereas the hyperammonaemia in dogs with ammonia concentrations < 120 mumol/litre was transient and of metabolic origin.