Inflammatory response to therapeutic gold bead implantation in canine hip joint osteoarthritis.

Inflammatory changes associated with periarticular pure gold bead implants were studied in dogs involved in a clinical trial investigating motor dysfunction and chronic pain owing to hip joint dysplasia and osteoarthritis. Gold beads were percutaneously implanted via a needle into different locations surrounding the greater trochanter of the femur. Nine dogs with implants were necropsied. In all examined animals, characteristic histologic lesions were observed in the tissue surrounding the gold implants--namely, a fibrous capsule composed of concentric fibroblasts intermixed with a variable number of inflammatory cells and a paucicellular innermost layer of collagen with a few fibrocyte-like cells in empty lacunae. Lymphocytes dominated the inflammatory infiltrate, with rarely observed macrophages present in close proximity to the implant site. No giant cells were observed. Immunohistochemistry showed mixed populations of lymphocytes, both CD3 positive (T cells) and CD79a positive (B cells), which in some cases formed lymphoid follicles. Diffuse inflammatory changes were present to a minor extent in the perimysium and surrounding fascia. The inflammation observed in dogs is similar to that observed with gold implants in humans. It is possible that the clinically beneficial effect of gold beads for chronic osteoarthritis depends on sustained localized inflammation with localized release of soluble mediators. The encapsulation of the implant by a paucicellular and poorly vascularized fibrous capsule may help prevent an exaggerated inflammatory reaction by sequestering the gold bead from the surrounding tissue.

Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary tumours.

The pharmacokinetic profile, tolerability and efficacy of benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) were studied in dogs with mammary cancer. A three-level response surface pathway designed trial was performed on seven dogs. At each level BP-C1 was administered subcutaneously daily for 7 days followed by a 7-day rest period in a dose escalating manner. Adverse events according to VCOG-CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two-compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half-life was 125 h. The maximum tolerated dose of BP-C1 was estimated to be above 0.46 mg kg-1 . A significant reduction in VCOG-CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.

Double-blind, placebo-controlled trial of the pain-relieving effects of the implantation of gold beads into dogs with hip dysplasia.

Seventy-eight dogs with pain due to hip dysplasia were studied in a controlled, double-blind clinical trial to evaluate gold bead implantation as a pain-relieving treatment. The dogs were randomly assigned to two groups, 36 in the gold implantation group and 42 in the placebo group. Both groups were treated equally regarding anaesthesia, hair clipping and penetration of the skin with the same type of needle. The gold implantation group had small pieces of 24 carat gold inserted through needles at five different acupuncture points and the placebo group had the skin penetrated at five non-acupuncture points so as to avoid any possible effect of stimulating the acupuncture points. A certified veterinary acupuncturist marked the points, and two surgeons performed the implantations according to a randomisation code made in advance. After 14 days, three months and six months, the owners assessed the overall effect of the treatments by answering a questionnaire, and the same veterinarian examined each dog and evaluated its degree of lameness by examining videotaped footage of it walking and trotting. The treatment was blinded for both the owners and the veterinarian. There were significantly greater improvements in mobility and greater reductions in the signs of pain in the dogs treated with gold implantation than in the placebo group. The veterinarian's and the owners' assessments corresponded well.

Internal radionuclide therapy of primary osteosarcoma in dogs, using 153Sm-ethylene-diamino-tetramethylene-phosphonate (EDTMP).

Fifteen dogs were referred because of a spontaneous bone tumor, lameness, and local pain. The osteosarcoma diagnosis was established by clinical examination, X-ray, bone scintigraphy, and histological examination of biopsy material. The tumors were located in the extremities (n = 12), scapula (n = 1), maxilla (n = 1), and the frontal bone (n = 1). The dogs were given one to four i.v. injections of 153Sm-labeled ethylene-diamino-tetramethylene-phosphonate (153Sm-EDTMP; 36-57 MBq/kg body weight). Three dogs had surgery in addition to the radionuclide treatment. Platelet and WBC counts showed a moderate and transient decrease. No other toxicity was observed. Average tumor doses after a single injection were approximately 20 Gy, considerably higher in some areas because of inhomogeneous uptake. Macroscopically distant metastases were detected in seven dogs at autopsy. One dog died from an intercurrent disease, free of cancer, 5 months after the radionuclide treatment. None of the dogs was cured. The median and mean survival times from the first treatment to death or euthanasia were 150 and 252 days, respectively. Nine of the dogs had obvious pain relief, and five of them seemed pain-free: one for 20 months and one for 48 months. It is concluded that high tumor doses may be deposited in dog osteosarcomas by 153Sm-EDTMP, and the ratio between tumor dose and the dose to surrounding tissues is favorable. The treatment gives pain relief and in some cases tumor growth delay. In combination with surgery, 153Sm-EDTMP may prolong life significantly and possibly cure the disease because the development of metastases are seemingly postponed. No serious side effects were observed.

Stratification, blinding and placebo effect in a randomized, double blind placebo-controlled clinical trial of gold bead implantation in dogs with hip dysplasia.

UNLABELLED: The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a randomized, placebo-controlled and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33 of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of the owners correctly guessed the treatment given, was found sufficient. Of those who guessed the treatment erroneously, 88% believed the treatment given was gold bead implantation. The treatment efficacy after six months in the blinded treatment group was found to be significantly larger compared to the efficacy obtained in the open study. A significant placebo effect was therefore detected. CONCLUSION AND CLINICAL RELEVANCE: The age of the dogs influenced the outcome of the CHD treatment, and is recommended as a stratification factor. A significant placebo effect has to be expected and an optimal blinding procedure is necessary in similar clinical studies.

Shortened duration of untreated first episode of psychosis: changes in patient characteristics at treatment.

OBJECTIVE: This study examined whether duration of untreated psychosis can be shortened in patients with first episodes of DSM-IV schizophrenia spectrum disorders and whether shorted duration alters patient appearance at treatment. METHOD: Two study groups were ascertained in the same Norwegian health care sector: one from 1993-1994 with usual detection methods and one from 1997-1998 with early detection strategies that included education about psychosis. RESULTS: Patients with early detection had a shorter median duration of untreated psychosis by 21.5 weeks than patients with usual detection. The number with psychosis was greater in the early detection group; the number with schizophrenia was less. Early detection patients had more substance abuse and were younger, better adjusted premorbidly, and less ill. CONCLUSIONS: Early detection can shorten duration of untreated psychosis and help more patients when they are less severely ill. Given the devastation of psychosis, this is a significant treatment advance.

A population-based case-control study of canine mammary tumours and clinical use of medroxyprogesterone acetate.

We investigated whether or not an association could be found between mammary tumours and prior clinical use of medroxyprogesterone acetate (MPA) in bitches. A population-based retrospective age-matched case-control study was designed based on interviews with the owners of the bitches. The proportion of bitches with diagnosed mammary tumours (group MT+, n = 98) that had received progestin injections was compared with the proportion in a control group without mammary tumours (group MT-, n = 98). In the case group 39%, and in the control group 21% of the bitches had been treated with MPA. A significantly higher number of bitches with mammary tumours had been exposed to progestins, compared with the control group without mammary tumours (odds ratio = 2.32, Chi-square = 7.01, p = 0.008). Bitches treated clinically with low doses of MPA to avoid oestrus were at a greater risk of developing mammary tumours, the majority of which were histologically malignant (91%).

Premorbid functioning versus duration of untreated psychosis in 1 year outcome in first-episode psychosis.

OBJECTIVE: This study examines 1year outcome in patients having first-episode non-affective psychosis, with emphasis on Duration of Untreated Psychosis (DUP) and premorbid functioning, in order to clarify how these factors interact. METHOD: Forty-three consecutively admitted patients were all rated on the Positive and Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning Scale (GAF), both upon hospitalization and at 1year follow-up. In addition, premorbid functioning, DUP, duration of hospitalization, and social functioning were rated. RESULTS: Fifty-six per cent were in remission, 18% suffered multiple relapses and 26% were continuously psychotic at 1 year follow-up. Both poor premorbid functioning and long DUP are significantly correlated with more negative symptoms and poorer global functioning at follow-up. Long DUP is also significantly correlated with more positive symptoms. Even when we control for other factors, including premorbid functioning and gender, DUP is a strong predictor of outcome. To a limited degree premorbid functioning and DUP interact, but DUP has an independent influence on outcome. CONCLUSIONS: these findings strengthen the rationale for establishing health service programs for early detection and treatment of first-onset psychosis

First-episode schizophrenia: I. Early course parameters.

Concepts and definitions pertaining to the early course of schizophrenia are reviewed, along with recent illustrative studies of first-episode schizophrenia. Early course parameters of a Norwegian first-episode sample are presented. This sample (n = 43) demonstrated strong gender differences, with male patients having significantly higher frequency of single marital status, lower educational status, schizophrenia, early age at onset, and lower Global Assessment of Functioning scores the last year before hospitalization. The duration of untreated psychosis (DUP) was long (mean = 114 weeks), as in other studies. Longer DUP was associated with poorer work, social, and global functioning in the year before admission, with more insidious onset of psychosis, and with more negative symptoms at first clinical presentation. Longer DUP was not associated with the age at onset of psychosis. These findings were mostly gender independent. The data help to frame questions about why patients can be psychotic for so long before getting help. Finally, suggestions are offered for the definition and measurement of early course parameters for schizophrenia.

Renal microcystic tubular lesions in two 1Year-old dogs - an early sign of hereditary renal cystadenocarcinoma?

As a part of a study of early renal changes in renal cystadenocarcinoma (RC), a 5-year-old German shepherd dog and two 1-year-old German shepherd mixed-breed dogs were examined. All three animals had bilateral, microscopic renal cysts, and the 5-year-old dog also had RC. Microscopical examination showed papillary hyperplastic tubular epithelial cells lining the inner wall of the renal cysts in all dogs. These cells showed strong reactivity with a monoclonal antibody against a broad-spectrum type of cytokeratin. The dam of the young dogs had suffered from autosomal dominant inherited RC and nodular dermatofibrosis (ND) syndrome. It is likely that the microscopic renal cystic lesions seen in the young dogs represented an early renal change in the RC/ND syndrome. This suggests that the diagnosis of RC can be made on suspected carriers by microscopical examination of renal biopsies as early as 1 year of age, i.e., before the dogs are used for breeding.

Estimation of glomerular filtration rate in dogs with 99M-Tc-DTPA and iohexol.

The glomerular filtration rates (GFR) of 18 dogs of different breeds were estimated by simultaneously comparing the plasma decay curves of 99M-Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) and the contrast medium iohexol. Nine of the dogs were clinically healthy, and nine had renal disease. After the intravenous injection of the two substances, nine to 12 blood samples were taken during the first six hours and in some cases up to 24 hours. The total clearance of the substances was determined by one- and two-compartment models. Individual GFRiohexol values, estimated by using a two-compartment model in 16 of the dogs, ranged from 39.0 ml min-1 m-2 to 84.3 ml min-1 m-2 and for GFRTc-DTPA from 41.1 ml min-1 m-2 to 106.6 ml min-1 m-2. The GFRiohexol values estimated by using a one-compartment model in the 18 dogs ranged from 4.52 ml min-1 m-2 to 105 ml min-1 m-2 and for GFRTc-DTPA from 5.4 ml min-1 m-2 to 118.9 ml min-1 m-2. The agreement between the two methods was good, as shown by a limits of agreement plot. The ratio of GFRTc-DTPA/GFRiohexol was 1.15 throughout the range of measurement (SD = 0.085). The study indicates that the iohexol method is a valid measure of GFR in the dog. The practical aspects make it a useful tool in small animal practice.

Calculation of urinary enzyme excretion, with renal structure and function in dogs with pyometra.

The urinary enzyme markers of renal damage, alkaline phosphatase (AP), gamma-glutamyl transferase (GGT) and N-acetyl-beta-glucosaminidase (NAG), glomerular filtration rate (GFR) and renal biopsies were studied to evaluate renal status in dogs with pyometra. After ovariohysterectomy, urinary enzymes were measured daily for 12 days in 55 dogs, and again at a later follow-up visit. Thirteen dogs had high levels of at least one enzyme at initial presentation. Seventeen dogs had a transient increase in urinary enzyme values between one and five days after surgery. Enzyme values usually declined to low activities within 12 post-operative days. Renal biopsies demonstrated tubular abnormalities in many dogs. Mean GFR was 2.4 and 2.0 ml min(-1) kg(-1), respectively on day 1 post-operatively and at the follow-up visit 1-4 months later. High urinary enzyme values often reflected extensive lesions in renal proximal tubular cells and sometimes reduced GFR.

Pharmacokinetic aspects of measurement of glomerular filtration rate in the dog: a review.

Glomerular filtration rate (GFR) is estimated by means of clearance, defined as the volume of plasma that has been cleared of a particular substance per unit time. Glomerular filtration rate may be estimated by measuring the renal clearance of a filtration marker using data from both urine and plasma or by plasma clearance using only plasma data. Several alternative pharmacokinetic models are used for the calculation of clearance using various filtration markers with slightly different pharmacokinetic properties. The purpose of this article is to discuss how the choice of marker and pharmacokinetic model may influence estimated GFR values and to elucidate commonly used methods and reported GFR values in the dog.

The relationship between some plasma clearance methods for estimation of glomerular filtration rate in dogs with pyometra.

The purpose of the present study was to compare different pharmacokinetic models for estimation of glomerular filtration rate (GFR) in 50 dogs with pyometra. GFR was estimated by plasma clearance (CLplasma) of iohexol by four 1-compartment methods (CL1c), a 2-compartment method (CL2c), and the trapezoidal method (CLtr). Regression analysis was performed to establish correction formulas for prediction of CLtr from the CL1c values and to find optimal times of sampling. Standardization of clearance values to body weight (kg), body surface area (m2) and extracellular fluid volume (ECFV) was compared by ranking of values. CLtr and CL2c values were similar, whereas CL1c overestimated CLtr. CLtr could be predicted from 2 samples at 2 and 3 hours after injection, using the formula CLtr = 4.52 + 0.84CL1c - 0.00080(CL1c)2 (R2 = .97). Similar relationships were found when sampling at 2 and 4 hours or at 2, 3 and 4 hours after injection, whereas predictions from the 3- and 4-hour estimates were not optimal (R2 = .79). The 2-sample methods for calculating GFR/ECFV generally produced unreliable predictions of the complete curve GFR/ECFV values. For some dogs, the choice of standardization procedure substantially changed the apparent level of renal function relative to other dogs in the study. We conclude that by applying an appropriate correction formula, GFR may be estimated using 2 blood samples at 2 and 3, or 2 and 4 hours after injection of iohexol when renal function is normal or moderately reduced. The method of standardizing the analysis with respect to body size may influence interpretation of the results substantially.

A retrospective study of conservative treatment of gastric dilatation-volvulus in the dog.

A retrospective study of 103 dogs with gastric dilatation-volvulus (GDV) treated conservatively during the period 1985-1989 was performed. The date and number of recurrences, and the date and cause of death along with breed, age and sex were collected from clinic records and from a questionnaire sent to the owners (77% response). The treatment consisted of emptying the stomach with a stomach tube, gastrocentesis if necessary and treating shock. All of the affected dogs were from moderate to large sized breeds and the study showed that particular breeds appear to be predisposed to GDV. The average age was 7.2 years and there was no gender predisposition. Sixty-six per cent of the dogs survived the initial treatment and 50% of the dogs were still alive 1 month after treatment. Thirty-nine dogs (71%) received recurrence between 5-760 days after initial treatment. Fifty-six per cent had recurrence within 3 months and all except 2 dogs, within 1 year. Data for the time of death, regardless of cause, was available for 68 dogs. Of these 59 (81%) died within a year after initial treatment. Conservative treatment was found to be an adequate life-saving procedure in the acute stage of GDV, but could not alone prevent recurrence of the disease.

Comparison of two surgical treatments of gastric dilatation-volvulus in dogs.

The purpose of this randomized clinical study was to compare the effect of 2 surgical methods in the treatment of gastric dilatation-volvulus (GDV) in dogs. One group of dogs (group A) was treated with and one group (group B) without fixation of the stomach. Group A consisted of 21 cases (including 2 dropouts) and group B of 10 cases. The dogs in group A received decompression, anatomical repositioning of the stomach and a circumcostal gastropexy and the dogs in group B (the control group) received the same treatment without gastropexy. Supportive treatment was the same for both groups. The randomization of the dogs in groups A and B was successful with only small differences between the 2 groups in the breed, age, sex and initial decompression methods. At the end of the study (censoring time), the median survival times were significantly different between group A and group B, respectively 549 and 107 days. There were no recurrences in group A while in group B 3 dogs (50%) experienced a recurrence within 6 months. The overall death rates within the first year were 32% in group A and 80% in group B. The death rates caused by GDV and GDV related causes only, after one year of follow-up, were 19% and 71% for groups A and B, respectively. This study shows that treatment that included circumcostal gastropexy significantly reduced the recurrence of GDV and prolonged the postoperative survival time compared with treatment that did not include fixation of the stomach.

Estimation of glomerular filtration rate in normal sheep by the disappearance of iohexol from serum.

The aim of the study was to establish reference values for glomerular filtration rate (GFR) in healthy sheep from the clearance of iohexol in serum. Fifteen healthy sheep were tested twice with 14 to 21 days between tests. No side-effects were observed after iohexol injections and all the sheep were clinically normal during and after the study. The mean clearance of iohexol estimated by the two-compartment method was 1.8 ml/min per kg (95% CI = 1.6-2.0) in the first trial and 1.7 ml/min per kg (1.5-1.9) in the second trial. The mean GFRiohexol estimated by a one-compartment method was 1.9 ml/min per kg (1.7-2.2) in the first trial and 1.8 ml/min per kg (1.6-2.0) in the second. The GFR values were similar to those reported for the inulin method. The results indicate that the iohexol method is valid for estimating GFR in sheep, and it is easier to perform than the inulin method.

Hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis in 51 German shepherd dogs.

The clinical findings in German shepherd dogs with hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis are presented. Between 1978 and 1996, 51 cases were examined. Eight cases were detected after being offered a clinical examination because the disease was present in a parent. The remaining 43 dogs were diagnosed after an unsolicited visit to a clinic because of a specific problem. Skin lesions were the main reason (37 per cent) the owners presented their dog for examination. The mean age at diagnosis of renal cystadenocarcinomas and nodular dermatofibrosis was 8.2 years. The male-to-female ratio was 1.1, while the corresponding figure for a reference population was 1.25. Enlarged and abnormally shaped kidneys were palpated in 60 per cent of the dogs and were detected by radiography in 86 per cent of cases. The renal lesions, including metastases, were the main reason for euthanasia and death. The mean age at death was 9.3 years, and the mean age at the first detection of nodular dermatofibrosis was 6.4 years.

Maxillectomy and targeted radionuclide therapy with 153Sm-EDTMP in a recurrent canine osteosarcoma.

An eight-year-old dog with a local relapse of an osteosarcoma was treated with partial maxillectomy and systemic radionuclide therapy that involved two injections, 43 and 45 megabecquerels per kg bodyweight of the bone-seeking agent samarium-153-ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP), 15 weeks apart. A transient drop in white blood cell count and platelet count was observed following each 153Sm-EDTMP treatment. Follow-up 21 months after surgery revealed no evidence of local recurrence or metastases. The dog was in excellent condition, suffering only minor sequelae from the surgical procedure. Compared with historical controls treated with surgery alone, the combination of surgery and systemic radionuclide therapy seems a promising strategy for the treatment of canine osteosarcoma.

Breed differences in the proportional morbidity of testicular tumours and distribution of histopathologic types in a population-based canine cancer registry.

Histologically verified tumours submitted to the Norwegian Canine Cancer Register from 1990 to 1998 were studied (n=14,401). The proportion of testicular tumours (n=345) was 2.4%, and the breakdown of histological tumour diagnoses is presented. The frequency of the most common histopathological types was 33% interstitial (Leydig), 26.4% Sertoli and 33.9% seminomas/germ cell tumours. The average age at diagnosis was 10 years, but was significantly lower for Sertoli cell tumours (8.6 years) than for the other tumour types. Following a histopathological re-evaluation, 22.5% of the original tumor diagnoses were modified. Proportional morbidity ratios were calculated and individuals from the breeds Shetland sheepdog and Collie were five times more likely to have testicular tumours than the overall average for the registry. Breed differences in the distribution of histopathologic types were observed. Shetland sheepdog and Collie were most commonly diagnosed with Sertoli cell tumours, while all tumours from Norwegian elkhound in this material were seminomas.