Cytokines and the immunomodulatory function of the vagus nerve.

Cytokine synthesis and release is an essential component of the innate immune system, but inappropriate, excessive production results in a generalized systemic inflammatory response which damages distant organs. Recent research has identified an immunomodulatory function of the vagus nerve whereby activation of the efferent arm results in regulation of cytokine production. Termed the 'cholinergic anti-inflammatory pathway', this neuro-immune communication provides the host with a fast, discrete, and localized means of controlling the immune response and preventing excessive inflammation. Stimulation of the vagus nerve attenuates cytokine production and improves survival in experimental sepsis, haemorrhagic shock, ischaemia-reperfusion injury, and other conditions of cytokine excess and research is now underway in developing new and novel therapeutics aimed at stimulating the vagus nerve either directly or targeting specific components of the pathway.

Variation in the human lymphocyte sister-chromatid exchange frequency: results of a long-term longitudinal study.

The variation in lymphocyte sister-chromatid exchange (SCE) frequency as a function of time was investigated in nonsmokers and smokers. The smokers were divided into 3 groups depending on their smoking status. The group termed 'smokers' participated in a program to stop smoking but did not reduce or eliminate their use of tobacco; 'smoke enders' successfully completed the smokending program and remained free of tobacco for the duration of the study, while the 'variable' group stopped smoking for a limited time but then resumed smoking. 8 or more blood samples per person were obtained over a period of at least 12 months. The SCE frequencies for each of these groups were compared with each other and with those of two previous longitudinal study groups from our laboratory. The proportion of high-frequency cells (HFCs) was also determined for each sample. The results confirm our previous finding that SCE frequencies and the proportion of HFCs observed in separate samples from the same individual are more likely to be different as the time between samples increases. We also show that smokers have significantly more SCEs and HFCs than do nonsmokers, that SCE frequencies in smokers do not decline for at least 12 months when smoking is stopped, and that among smokers, significant seasonal variation in the SCE frequency occurs. These results provide useful information concerning the effects of smoking upon SCE frequencies, and will be helpful in designing and interpreting the results of long-term human population cytogenetic studies.

Prostatic disorders in the dog.

Common canine prostatic disorders include benign prostatic hypertrophy (BPH), prostatitis, prostatic cysts and prostatic adenocarcinoma. BPH is a spontaneous and age-related disorder of intact male dogs, which occurs in more than 80% male dogs over 5 years of age, and which is associated with clinical signs of sanguinous prostatic fluid, constipation and dysuria. BPH signs respond to castration or to finasteride treatment (0.1-0.5 mg/kg per os once daily), as finasteride inhibits conversion of testosterone to dihydrotestosterone, causing prostatic involution via apoptosis. BPH often occurs concurrently with prostatic infection, abscessation, cysts and neoplasia in the intact dog, and finasteride-induced prostatic involution may be beneficial in treatment of all of these conditions except neoplasia. Two studies suggest that risk of prostatic adenocarcinoma is increased in neutered, compared to intact male dogs. Although canine prostatic neoplasia, unlike human prostatic neoplasia, usually does not respond to androgen deprivation, recent reports of prostatic intraepithelial neoplasia (PIN) in a high percentage of older male dogs, with and without prostatic adenocarcinoma, suggests that PIN may be a precursor to adenocarcinoma in the dog as it is believed to be in man.

Diphallia in a mixed-breed dog with multiple anomalies.

Complete diphallia was detected in a six-month-old Poodle cross dog. Duplication of the urinary bladder, right renal hypoplasia, bifurcation of the descending colon and bilateral cryptorchidism were also present. The left urethra was patent, and emptied the left urinary bladder; the right urethra ended blindly at a point 2.5 cm from the tip of the right penis. The left urinary bladder was joined medially to a right urinary bladder with no interbladder communication; however, the right bladder opened caudally into a blind sac which drained into the left prostatic urethra. Pyelonephritis of the left kidney was present, and was suspected to be due to ascending bacterial infection of the right urinary bladder and the right segment of the bifurcated descending colon, which terminated at the apex of the right urinary bladder. Diphallia and associated urogenital anomalies are reviewed.

Radiographic assessment of laryngeal reflexes in ketamine-anesthetized cats.

The competence of the laryngeal closure reflexes of cats anesthetized with ketamine was assessed. Radiographic evaluations of the respiratory and digestive tracts were made after colloidal barium suspension was instilled into the pharynges of conscious and ketamine-anesthetized cats. There was a significant ketamine dose-related response of spread of contrast medium into the supraglottic laryngeal area and into the stomach 2 minutes after contrast medium was instilled into the pharynx (P less than 0.05). Cats did not aspirate contrast medium into the lower respiratory tract. Three ketamine-anesthetized cats aspirated contrast medium into the subglottic area of the larynx, and 2 of these cats also aspirated the material into the cranial part of the trachea. This material was coughed up and swallowed within 5 minutes. Transit time of contrast medium into the stomach seemed to be increased in 11 of the 15 cats given the larger dosages of ketamine (24, 36, 48 mg/kg of body weight), compared with that in conscious cats and those given ketamine at 12 mg/kg. Competent laryngeal protective reflexes in cats can be maintained with ketamine anesthesia. Contrast radiography could be used as a diagnostic aid in ketamine-anesthetized cats suspected of laryngeal reflex abnormalities.

Effects of urinary bladder distension on the length of the dog and cat urethra.

Urethral lengths were determined in male and female cats and in female dogs from positive contrast retrograde urethrocystograms at 2 levels of urinary bladder distension. Urethral lengths were longer on urethrograms obtained after urinary bladder distension in female cats and in 7 of 8 female dogs. The intrapelvic and penile urethra were longer after bladder distension in 4 of 6 male cats. In female cats, urethral lengths significantly increased (P less than 0.05) after urinary bladder distension.

Effects of urinary bladder distention on location of the urinary bladder and urethra of healthy dogs and cats.

Evaluation of the anatomic location of the distended and empty urinary bladders and urethras of healthy adult male and female dogs and cats by retrograde urethrocystography revealed substantial variations. In 15 dogs in lateral recumbency with empty bladder lumens, the caudal portion of the urinary bladder was within the pelvic canal in 5 of 7 male and 5 of 8 female dogs. In female dogs examined in ventrodorsal recumbency, only 4 of 8 had the empty urinary bladders in part within the pelvic canal. After luminal distention, 3 of 7 male and 3 of 8 female dogs, while in lateral recumbency, had the urinary bladders in part intrapelvically. However, when female dogs were placed in ventrodorsal recumbency, only 1 of 7 urinary bladders was in part within the pelvis. The urinary bladders of 14 cats were consistently within the abdominal cavity, irrespective of whether the bladder lumen was distended or empty. Urethral flexures occurred in dogs with intrapelvic bladders that were distended or empty. Urethral flexures were not found in cats. The urethras of dogs and cats in lateral recumbency were generally closer to the floor of the pelvis after urinary bladder distention than when the bladder was empty. The urethra of the dogs and cats in ventrodorsal recumbency was to the left or right of or on the midsagittal plane, whether the urinary bladder was empty or distended. A greater degree of lateral displacement was encountered in ventrodorsal recumbency after urinary bladder distention.

Feline renal ultrasonography: quantitative analyses of imaged anatomy.

Maximal kidney dimensions from serial ultrasonograms were measured in 10 healthy cats. Because clinical ultrasonographic examination is often performed in conjunction with excretory urography, the effect of radiographic contrast medium-induced diuresis on dimensional change also was evaluated. Although a slight, statistically significant increase in size was observed (compared with kidneys scanned without contrast medium), this increase could not be detected on the basis of visual image evaluation alone.

Renal ultrasonography in healthy cats.

Serial ultrasonographic examinations were performed on the kidneys of 10 healthy cats during normal hydration and after administration of contrast medium. Differences in the appearance of anatomic structures or in the echo intensity were not detected between kidneys during normal hydration and after contrast medium administration. The appearance of scanning images was influenced by mode, frequency, and focal range of the transducer, topography and mobility of the kidneys, and adequate sound conduction.

Effects of sterilized micropulverized barium sulfate suspension and meglumine iothalamate solution on the genitourinary tract of healthy male dogs after retrograde urethrocystography.

A sufficient quantity of 30% w/v sterile barium sulfate suspension was infused into the caudal portions of urinary tracts of 12 young adult healthy male Beagles to induce vesicoureteral reflux. A control group of dogs was infused with a 7.5% solution of meglumine iothalamate. The dogs were radiographed at 1, 6, 13, and 29 days later. Three dogs from each group were euthanatized and necropsied (1 each) after radiography at each of these times. In some dogs, radiopacity in the prostate, urinary bladder, and renal pelvic diverticula due to barium persisted throughout the 30-day observation period. Opacity at or beyond 24 hours was not found in dogs infused with iothalamate. Light microscopy revealed barium either free or within macrophages in the submucosa of the bladder, in glandular and stromal areas of the prostate, and in the kidney. Renal barium was limited to pelvic diverticula (3 dogs), in a medullary tubule (1 dog), and in cortical tubules (2 dogs). Significant lesions attributable to barium were not seen in kidneys of dogs in the barium group. Iothalamate induced focal to multifocal inflammatory responses in some prostates; barium was phagocytosed by macrophages. Focal transient inflammatory and ulcerative lesions induced by bladder distention were observed in the bladder and urethral mucosa in both groups.

Maximum-distention retrograde urethrocystography in healthy male dogs: occurrence and radiographic appearance of urethroprostatic reflux.

Urethroprostatic reflux was found during retrograde urethrocystography in 21 of 24 mature healthy Beagles. Minimal parenchymal-positive contrast " blushes " near the urethra were identified, but no massive accumulations of contrast medium within the prostate were found. A particulate contrast medium, sterilized barium sulfate, was used in 12 of the dogs. After retrograde urethrocystography, the barium particles were found in the secretory (acinar) portion of the prostatic parenchyma, confirming that urethroprostatic reflux extended beyond the prostatic duct system that directly empties into the urethral lumen.

Maximum-distention retrograde urethrocystography in healthy male dogs: occurrence of vesicoureteral reflux.

Twenty-four healthy, mature male Beagles were examined radiographically for vesicoureteral reflux (VUR) by maximum-distention retrograde urethrocystography. Bilateral VUR was observed in 9 dogs and unilateral VUR was observed in 3 dogs. The VUR occurred when the bladder was full or nearly full when maximum bladder filling was defined by trigonal-prostatic urethral dilation. The refluxed contrast medium reached the renal pelves in all but 3 of the 21 affected ureters.

Effects of prolonged distention of retention catheters on the urethra of dogs and cats.

The effects of inflation of a balloon-tipped catheter in the distal part of the urethra of clinically healthy male and female dogs and cats were evaluated. Tissues were evaluated at 1 and 14 days after balloon inflation. Macroscopic and microscopic lesions were limited to the distal part of the urethra occupied by the inflated balloon in animals which were euthanatized 1 day after balloon inflation. The lesions were characterized by submucosal urethral hemorrhage. This investigation indicates that balloon inflation for 15 minutes duration in the distal part of the urethra of dogs and cats results in a mild reversible inflammatory reaction.

Complications of retrograde contrast urethrography in dogs and cats.

Urinary bladder lesions varying histologically from a focal hemorrhagic cystitis to a diffuse transmural fibrinonecrotic cystitis were encountered in 11 of 14 dogs and cats euthanatized 1 day after retrograde urethrography. Focal-to-diffuse hemorrhagic urethritis was histologically encountered in 14 of 14 dogs and cats euthanatized 1 day after retrograde urethrography. Lesions in the urinary bladder and urethra were not reversible within 14 days and were evident histologically in 10 of 15 urinary bladders and 11 of 15 urethras of dogs and cats euthanatized 14 days after retrograde urethrography. During urethrography, iatrogenic mural leakage of contrast media into the bladder wall or bladder wall rupture was encountered radiographically in 6 of 15 dogs and 3 of 14 cats. However, macroscopic evidence of bladder rupture was encountered in only 1 male dog at necropsy. Immediately after retrograde urethrography, macroscopic hematuria occurred in 12 of 15 dogs and 9 of 14 cats. Microscopic hematuria was not encountered in dogs or cats euthanatized 14 days after urethrography. Pyuria was encountered less frequently and was present in only 2 cats euthanatized 14 days after urethrography. One day after urethrography, urinary tract infection characterized by urine cultures with greater than 10(5) microbes/ml was encountered in 4 of 29 dogs and cats. All animals with urinary tract infection were female dogs or cats. At day 14, only 1 female cat had a positive urine culture. Seemingly, the technique of retrograde urethrography was the cause of the encountered lesions.

Orthovoltage radiation of normal canine nasal passages: assessment of depth dose.

Frozen heads of 9 clinically normal dogs were irradiated with orthovoltage x-rays. Surface doses and nasal cavity depth doses were measured, and the percentage of surface dose (depth dose) was calculated at random depths from the dorsal cutaneous surface in transverse planes through the medial and lateral canthi. Depth dose of 2 orthovoltage x-ray beams having half-value layers of 1.5 mm of Cu (96 keV) and 2.6 mm of Cu (134 keV) were compared with and found to resemble that reported in depth dose tables based on soft tissue equivalent material. Any differences (identified graphically) in depth dose, compared with that described using a uniform (soft tissue equivalent) phantom, were explained by the variations in tissue composition and the presence of air within the normal nasal and paranasal cavities.

Effects of intravesical hydrostatic pressure and volume on the distensibility of the canine prostatic portion of the urethra.

Positive-contrast retrograde urethrocystograms were obtained serially on 12 male dogs weighing 11.4 to 23.2 kg before, during, and after the injection of contrast medium until the urinary bladder neck and prostatic and membranous portions of the urethra remained open and distended as viewed by fluoroscopy. Correlations of intravesical volumes and pressures required to achieve maximum distension of the midprostatic portion of the urethra with body weight and surface area were not significant. Because of the variability in intravesical volumes and pressures encountered at maximum distension of the prostatic portion of the urethra, a dose of contrast material expressed relative to body weight or surface area could not be determined for consistently providing maximum distension of the prostatic portion of the urethra.

Two-dimensional, gray-scale ultrasonography for assessment of hepatic and splenic neoplasia in the dog and cat.

An analysis was made of 17 cases of microscopically proven hepatic and splenic neoplasms, with the objective of describing the ultrasonographic findings and determining how interpretation of these findings contributed to the diagnosis and prognosis of these cases. The ultrasonographic appearance of these tumors ranged from focal, large (6 to 20 cm diameter) mixed hyperechoic/hypoechoic masses to multifocal (0.5 to 2.0 cm diameter) hypoechoic masses. The ultrasonographic appearance was not specific for the microscopic cell-type of the neoplasm. When the combined clinical, hematologic, serum chemical, and ultrasonographic findings were interpreted, neoplasia was always the primary consideration, but microscopic confirmation was mandatory. The uses of ultrasonography in these cases were: (1) to characterize the internal architecture of a mass identified radiographically, (2) to confirm the organ of origin of the mass, (3) to define the extent of disease in or around an affected organ, (4) to evaluate palpable abdominal mass(es) in the presence of poor abdominal radiographic contrast, and (5) to identify previously undetected or unsuspected metastases. Three interpretive errors were found, but only one would have influenced the prognosis for that specific patient.

Urogenital blastomycosis in a dog.

Blastomycosis was diagnosed in a dog by finding the causative organism in preputial exudate and urine. Prostatic involvement was confirmed by transrectal biopsy. The dog was not treated, and, after it was euthanatized, a complete necropsy was performed. The only other sites where organisms were found were the iliac lymph nodes and the lungs. Although organisms were not found in any other part fo the genitourinary tract, both kidneys had diffuse glomerulonephritis and tubular degeneration.

Vesicoureteral reflux induced by manual compression of the urinary bladder of dogs and cats.

Vesicoureteral reflux caused by manual compression of the urinary bladder performed to obtain urine samples was evaluated by contrast radiography in 10 sedated, clinically normal male and female dogs and in 10 sedated, clinically normal male and female cats. Vesicoureteral reflux occurred in 50% of the dogs and in 40% of the cats. Application of digital pressure to the urinary bladder for a prolonged period to initiate urine voiding was associated with a greater occurrence of reflux than was application of digital pressure for a transient period. Contrast material refluxed into the prostate gland of 3 of 6 male dogs.

Vaginal septa in dogs: 15 cases (1983-1992).

Medical records of 15 dogs with vaginal septa, examined between April 1983 and December 1992, were reviewed. Overall prevalence of vaginal septation at the hospital during the study period was 0.03%. Thirteen breeds were represented; mean age at the time of initial examination was 2.4 years. Owners' original complaints included inability to breed naturally, dysuria, urinary incontinence, infertility, recurrent vaginitis, ambiguous external genitalia, and dystocia. One dog did not have clinical signs associated with the vaginal septum. In 11 of the 15 dogs, the septum could be palpated during digital vaginal examination. The septum could be seen in 6 of the 7 dogs in which vaginoscopy was performed. Twelve of the 15 dogs underwent positive-contrast vaginography; in all 12, the septum could be easily seen. Four of the 15 dogs underwent removal of the septum, with or without episiotomy, and 4 others were ovariohysterectomized. One dog was bred by means of artificial insemination and became pregnant. The remaining 6 dogs were lost to follow-up.