Dog Days Research Articles

Gentamicin pharmacokinetics in diabetic dogs

Reduction of the prolonged terminal elimination phase of gentamicin may be caused by diabetes mellitus, irrespective of the model of diabetes. To test this hypothesis, five normal dogs, three dogs with alloxan-induced diabetes mellitus, and four dogs with naturally occurring diabetes mellitus (all of which were given exogenous insulin to control hyperglycemia) were given 4.4 mg/kg gentamicin intravenously. Serum pharmacokinetics were analyzed using non-compartmental pharmacokinetics assuming a sum of exponential terms. Gentamicin pharmacokinetics during the first 8 h were the same in normal and diabetic dogs. Over 7 days, MRT in normal dogs (5830 +/- 2970 min, mean +/- SD) was longer (P less than 0.01) than in diabetic dogs (136 +/- 164 min). In diabetic dogs, Cls was greater (3.01 +/- 0.86 ml/min/kg) than in normal dogs (1.45 +/- 0.11 ml/min/kg; P less than 0.01), whereas Vd(ss) was smaller in diabetic dogs (0.405 +/- 0.508 l/kg) than in normal dogs (8.56 +/- 4.48 l/kg; P less than 0.01). Serum gentamicin concentrations were less than 0.020 microgram/ml by 2 days in all of the diabetic dogs, but were 0.048 +/- 0.018 microgram/ml at 7 days in normal dogs. Thus, diabetes mellitus, either induced by alloxan administration or naturally occurring, abolished the terminal elimination phase of gentamicin disposition in a non-rodent species.

Periodicity of Dirofilaria immitis microfilariae in a dog from Muheza district, Tanzania

Dirofilaria immitis (the dog heartworm) microfilarial periodicity was determined hourly for five days in an infected dog from Kambai village in Muheza district Tanzania. Maximal microfilarial counts were found at 1100 h and minimal at 2200 h. This finding represents the first record of D. immitis microfilarial periodicity in Tanzania.

Methaemoglobin reductase deficiency in dogs

Erythrocyte methaemoglobin reductase deficiency is described in a toy Alaskan Eskimo dog, a miniature poodle dog and a cocker/poodle cross dog. Blood methaemoglobin contents ranged from 19% to 36% of total haemoglobin, with methaemoglobin reductase values between 13% and 33% of normal. There appeared to be a negative linear correlation between erythrocyte methaemoglobin content and methaemoglobin reductase activity. A single intravenous injection of methylene blue (1 mg/kg body weight) resulted in a dramatic decrease in methaemoglobin content within 1 hour when given to two of the deficient dogs in the present study. Following the disappearance of methylene blue from blood, methaemoglobin content increased linearly at 3.2% and 2.5% per day in these dogs, suggesting that about 3.0% of erythrocyte haemoglobin is normally oxidised to methaemoglobin each day in dogs, as has been estimated in humans. Oral riboflavin therapy was not effective in reducing blood methaemoglobin content in deficient dogs.

The pharmacokinetics of Casodex in laboratory animals

1. The pharmacokinetics of Casodex, a novel, non-steroidal antiandrogen, have been investigated following single oral and i.v. doses and during daily oral dosing to male and female rats and male dogs. 2. The binding of 14C-Casodex to rat, dog and human plasma proteins, determined by equilibrium dialysis, was high with values greater than 95%; in dog there was evidence for decreased binding at concentrations greater than 12 micrograms/ml. 3. Casodex was slowly absorbed over prolonged periods and its bioavailability decreased with increase in dose from 72% and 88% in male and female rats respectively at 1 mg/kg to 10% and 12% at 250 mg/kg; in dog bioavailability decreased from 100% at 0.1 mg/kg to 31% at 100 mg/kg. 4. Elimination of Casodex from plasma was slow with terminal elimination half-lives of about 1 day in rat and about 6 days in dog. On daily administration to rats Casodex accumulates slightly in plasma at 10 mg/kg but not at 250 mg/kg; in dog appreciable accumulation (9-12-fold), calculated from the ratio of trough plasma concentrations at steady state to those after a single dose, was observed at 2.5 and 10 mg/kg, but at 100 mg/kg the accumulation ratio was much lower (4-fold).

RS-61443—A NEW, POTENT IMMUNOSUPPRESSIVE AGENT

The immunosuppressive activity of RS-61443, a semisynthetic derivative of mycophenolic acid, was examined in 33 canine renal allografts. Initial studies established that triple therapy consisting of 20 mg/kg RS-61443 in combination with 5 mg/kg cyclosporine and 0.1 mg/kg methylprednisolone was the optimal combination to prevent graft rejection. The median survival time was 8.1 +/- 1.2 days in dogs without treatment (n = 5), 8.5 +/- 1.7 days in the treatment control group (CsA 5 mg/kg, MP 0.1 mg/kg; n = 6), 36.0 +/- 9.6 days with RS-61443 monotherapy (40 mg/kg; n = 6); and 122.4 +/- 38.75 days with triple therapy (n = 16). Graft prolongation was statistically significant when compared with controls (P less than 0.05 and 0.002, respectively). Six recipients in the triple therapy group survived over 150 days without major adverse effects. Long-term administration of RS-61443 (20 mg/kg/day) did not cause nephrotoxicity, hematotoxicity, or hepatotoxicity, with the exception of a slight elevation of the alkaline phosphatase levels. Gastrointestinal symptoms including gastritis, diarrhea, and anorexia were common, especially under 40 mg/kg RS-61443 monotherapy, and appeared to be dose-related. Despite its immunosuppressive activity, an increased susceptibility to bacterial or viral infections was not observed. Histological studies of the kidney grafts revealed slight interstitial cell infiltration without vascular or glomerular damage.

Letter from Chicago: Dog days

Letter from Chicago: Dog days

Lung Lavage Therapy to Lessen the Biological Effects of Inhaled 144 Ce in Dogs

To evaluate the therapeutic effects of removal of an internally deposited radionuclide on long-term biological effects, lung lavage was used to treat dogs that had inhaled 144Ce in a relatively insoluble form, in fused aluminosilicate particles. Either 10 lung lavages were performed between Days 2 and 56 after exposure or 20 lung lavages were performed between Days 2 and 84 after exposure. Approximately one-half of the 144Ce was removed by the lavages, resulting in a corresponding reduction in the total absorbed beta dose to lung. The mean survival time of the treated dogs was 1270 days compared to 370 days for untreated dogs whose initial pulmonary burdens of 144Ce were similar. Treated dogs died late from cancers of the lung or liver, whereas the untreated dogs died at much earlier times from radiation pneumonitis. Dogs treated with lung lavage but not exposed to 144Ce had a mean survival of 4770 days. We concluded that removal of 144Ce from the lung by lavage resulted in increased survival time and in a change in the biological effects from inhaled 144Ce from early-occurring inflammatory disease to late-occurring effects, principally cancer. In addition, the biological effects occurring in the treated dogs could be better predicted from the total absorbed beta dose in the lung and the dose rate after treatment rather than from the original dose rate to the lung. Therefore, we concluded that prompt treatment to remove radioactive materials could be of significant benefit to persons accidentally exposed to high levels of airborne, relatively insoluble, radioactive particles.

Pharmacokinetics, tolerance and serum thromboxane inhibition of carprofen in the dog

AbstractThe non‐steroidal anti‐inflammatory drug (NSAID) carprofen was administered to dogs as a mixed‐micelle solution at a dose rate of 0–7 mg/kg intravenously, as a palatable paste at a dose rate of 0–7 mg/kg orally, and as an oral tablet formulation at a dose rate of 0–7 mg/kg and 4‐0 mg/kg orally for pharmacokinetic studies. It was also administered as an oral tablet formulation at a dose rate of 9‐0 mg/kg orally daily for 14 days in a tolerance study. The pharmacokinetics following intravenous administration at a dose rate of 0–7 mg/kg indicate that carprofen has a small volume of distribution (Vd area = 0–09‐0‐25 litres), a slow systemic clearance (Cls = 1–34‐5‐57 ml/min) and an elimination half‐life of 3–20‐11‐77 hours. Both oral paste and tablet preparations were highly bioavailable and absorption was proportional to dose rate at 0–7 mg/kg and 4‐0 mg/kg bodyweight. Given once daily at dose rates likely to be used clinically it is unlikely to accumulate in the plasma. Carprofen administered as a palatable paste at a dose rate of 0–7 mg/kg did not inhibit serum thromboxane generation and this drug may therefore have a mode of action different from most NSAIDs. Carprofen was well tolerated when administered as an oral tablet formulation at a dose rate of 9.0 mg/kg daily for 14 days in healthy beagle dogs.

Recombinant human granulocyte colony-stimulating factor accelerates hematopoietic recovery after DLA-identical littermate marrow transplants in dogs

We studied whether treatment of dogs with recombinant human granulocyte colony-stimulating factor (rhG-CSF), after 920 cGy total body irradiation (TBI) and transplantation of 3.3 +/- 1.0 x 10(8) bone marrow cells per kilogram from a DLA-identical littermate, accelerated hematopoietic recovery and influenced the incidence of subsequent marrow graft failure or graft-versus-host disease (GVHD). Ten animals were treated with 100 micrograms rhG-CSF/kg/d from days 1 through 10 after TBI. Results were compared with those of historical control of 14 dogs not administered rhG-CSF. Neither group of dogs received GVHD prophylaxis. The median time to recovery of 1,000 neutrophils/mm3 was 8 days for dogs administered rhG-CSF compared with 14 days in controls (logrank test: P less than .03). The median time to reach 100 monocytes/mm3 was 17 days in G-CSF-treated dogs compared with 49 days in controls (P less than .002). The median time to attain 500 lymphocytes/mm3 was 15 days versus 31 days, respectively (P less than .01). The median time to reach 20,000 platelets/mm3 was 26 versus 20 days (P = .68). Graft failure occurred in 1 of 10 G-CSF-treated dogs versus 2 of 14 controls (two-tailed Fisher's exact test: P = 1.00). GVHD was seen in 4 of 9 rhG-CSF-treated dogs compared with 1 of 12 controls (P = .12). Two G-CSF-treated dogs died of GVHD versus none of the controls (P = .17). No unusual toxicities were seen in dogs receiving rhG-CSF. In summary, rhG-CSF significantly accelerated recovery of neutrophils, monocytes, and lymphocytes after DLA-identical littermate marrow transplantation without altering platelet recovery. Graft failure was not seen more often than in controls, but there was a trend toward an increased incidence of GVHD.

Recombinant Human Granulocyte Colony-Stimulating Factor Accelerates Hematopoietic Recovery After DLA-Identical Littermate Marrow Transplants in Dogs

We studied whether treatment of dogs with recombinant human granulocyte colony-stimulating factor (rhG-CSF), after 920 cGy total body irradiation (TBI) and transplantation of 3.3 +/- 1.0 x 10(8) bone marrow cells per kilogram from a DLA-identical littermate, accelerated hematopoietic recovery and influenced the incidence of subsequent marrow graft failure or graft-versus-host disease (GVHD). Ten animals were treated with 100 micrograms rhG-CSF/kg/d from days 1 through 10 after TBI. Results were compared with those of historical control of 14 dogs not administered rhG-CSF. Neither group of dogs received GVHD prophylaxis. The median time to recovery of 1,000 neutrophils/mm3 was 8 days for dogs administered rhG-CSF compared with 14 days in controls (logrank test: P less than .03). The median time to reach 100 monocytes/mm3 was 17 days in G-CSF-treated dogs compared with 49 days in controls (P less than .002). The median time to attain 500 lymphocytes/mm3 was 15 days versus 31 days, respectively (P less than .01). The median time to reach 20,000 platelets/mm3 was 26 versus 20 days (P = .68). Graft failure occurred in 1 of 10 G-CSF-treated dogs versus 2 of 14 controls (two-tailed Fisher's exact test: P = 1.00). GVHD was seen in 4 of 9 rhG-CSF-treated dogs compared with 1 of 12 controls (P = .12). Two G-CSF-treated dogs died of GVHD versus none of the controls (P = .17). No unusual toxicities were seen in dogs receiving rhG-CSF. In summary, rhG-CSF significantly accelerated recovery of neutrophils, monocytes, and lymphocytes after DLA-identical littermate marrow transplantation without altering platelet recovery. Graft failure was not seen more often than in controls, but there was a trend toward an increased incidence of GVHD.

Epidemiologic factors, clinical findings, and vaccination status of rabies in cats and dogs in the United States in 1988

Summary Despite the availability of rabies vaccination through private veterinarians and government-sponsored rabies control programs, rabies was reported in an average of 338 cats and dogs per year from 1980 through 1987 in the United States. Information was collected on 90% of the 183 cats and 97% of the 119 dogs that were reported to have rabies in the continental United States in 1988. The median age of rabid cats and dogs was 1 year, and 81% were from rural areas. Compared with rabid cats, rabid dogs were more likely to have been male (66 vs 42%, odds ratio = 2.6), to have been kept as pets (84 vs 43%, odds ratio = 6.8), and to have had reported contact with wildlife before onset of illness (38 vs 14%, odds ratio = 3.8). Rabid cats accounted for a greater proportion of human rabies postexposure prophylaxis, bites to people, and exposures to other animals than did rabid dogs. Although the clinical signs of rabies varied, rabid cats were more likely than dogs to have had aggressive behavior (55 vs 31%, odds ratio = 2.8). In contrast, rabid dogs were more likely than cats to have had an illness consistent with a paralytic process. The median period between onset of illness and death was 3 days (range, < 1 to 10) in rabid cats and dogs that were allowed to die of rabies. Vaccine failures were documented in 3 (1%) rabid animals (2 cats and 1 dog). All animals had received only a single dose of vaccine in their lifetime and were vaccinated when they were between 3 and 6 months old.

1/f fluctuations in arterial pressure and regulation of renal blood flow in dogs

To determine whether renal blood flow is regulated against spontaneous fluctuations in arterial pressure and to estimate the frequency band of the regulation, we measured arterial pressure and renal blood flow continuously over several days in conscious dogs. Mean arterial blood pressure showed broad band fluctuations and behaved as a 1/f process, indicating that the blood pressure record is a fractal curve and therefore scale invariant. The fluctuations in arterial pressure caused attenuated fluctuations in renal blood flow; the gain was about -6.5 +/- 0.5 dB through all sampled frequencies greater than or equal to 4 cycle/day. The kidney did not attenuate the blood pressure signal at the lowest frequencies. The results show that renal blood flow is better regulated against fluctuations in pressure at frequencies greater than or equal to 4 cycle/day than it is at lower frequencies. Although there are no direct tests of the underlying regulatory mechanisms, we argue that the responses are generated locally and can be identified with renal autoregulation.

Control of arterial pressure and renal function during chronic renin inhibition

The aim of this study was to determine whether the renin inhibitor CP-71362 (Pfizer Central Research, Groton, Connecticut, USA) is capable of inducing sustained reductions in arterial pressure in sodium-depleted dogs and to examine the changes in renal function associated with chronic renin inhibition. In addition, we also examined the chronic effects on renal function and blood pressure of the angiotensin converting enzyme (ACE) inhibitor enalaprilat. Infusion of CP-71362 (1.1 micrograms/kg per min, intravenously) for 7 days decreased mean arterial pressure from 87 +/- 3 to 75 +/- 2 mmHg, while causing no significant changes in sodium excretion, the glomerular filtration rate, or effective renal plasma flow. Plasma renin activity was suppressed to undetectable levels throughout the 7 days of CP-71362 infusion. Infusion of enalaprilat (4 mg/kg per day) for 7 days in sodium-depleted dogs decreased mean arterial pressure (from 85 +/- 2 to 64 +/- 3 mmHg) and renal vascular resistance, and increased effective renal plasma flow and sodium excretion, but caused no significant changes in the glomerular filtration rate. Thus CP-71362 is a potent inhibitor of dog plasma renin, and we observed no waning of this inhibitory effect of CP-71362's hypotensive actions over 7 days. The mechanisms responsible for the differences in the blood pressure and renal responses to CP-71362 and ACE inhibition are not clear, but may be dose-related or due to differences in the distribution of these compounds to various tissues, including the kidney.

Effect of dietary iron content on hematologic and other measures of iron adequacy in dogs

Summary Eighteen 9- to 10-week old Beagles were fed casein-based diets (4,710 kcal of metabolizable energy /kg of body weight) containing either 12, 80, or 160 mg of iron/kg of diet. Growth and feed consumption were monitored throughout the 47-day study. Hematocrit (Hct), hemoglobin (Hb) concentration, mean corpuscular volume (mcv), mean corpuscular hemoglobin (mch), mean corpuscular hemoglobin concentration (mchc), rbc numbers, erythrocyte protoporphyrin (ep) concentration, serum iron concentration, serum total iron-binding capacity (tibc), and serum ferritin concentration were determined weekly. Growth rate and feed efficiency were not significantly influenced by dietary iron content. At 14 days, Hb concentration, Hct, mcv, mch, rbc numbers, and serum iron concentration were significantly (P < 0.05) lower in dogs fed the 12 mg/kg diet, and remained significantly low for the remainder of the study. Erythrocyte protoporphyrin concentration increased significantly (P < 0.05) by 14 days in dogs fed the basal diet, and remained significantly high relative to that in dogs of the other dietary groups for the remainder of the study. Serum ferritin concentration decreased in dogs of the group fed the basal diet, with a significant (P < 0.05) difference beyond day 42. Differences in Hct, mch, mcv, or hemoglobin, serum iron, serum ferritin, or ep concentration were not found between groups fed 80 and 160 mg of iron/kg of diet. Liver nonheme iron content was significantly (P < 0.05) affected by dietary iron content.

Excretion and tissue distribution of 14C-labelled 8-methoxypsoralen in beagle dogs and miniature pigs

Male beagle dogs and miniature swine were given 14C-labelled 8-methoxypsoralen (8-MOP) as a single oral dose (10 mg/kg body weight). In dogs, there appeared to be wide variability in 8-MOP absorption as indicated by the broad range of percentages of radioactivity recovered from urine and faeces over a 4-day period (3.6–24.7% in urine; 47.3–94.9% in faeces); mean recovery values were 13.6% in the urine and 68.6% in the faeces. In pigs, considerable variability in absorption was also evident, but not to the extent of that seen in dogs. Based on the fraction of the dose recovered in the urine, the absorption of 8-MOP was greater in pigs; the proportion of the dose recovered in urine over a 7-day period ranged from 25.8 to 57.8%. Faecal recovery ranged from 15.4 to 49.0% of the dose. Mean recovery values in pigs were 45.4% in urine and 35.6% in faeces. Most of the 8-MOP was cleared from the bodies of dogs and pigs in a few days, and little 8-MOP residue was sequestered in any of the tissues examined in either species. Small amounts of an 8-MOP-related substance remained in the liver and blood for as long as 4 days in dogs and 7 days in pigs.

AUR memorial award--1988. MRI enhancement of perfused tissues using chromium labeled red blood cells as an intravascular contrast agent.

It has been demonstrated that chromium (Cr) labeling significantly decreases the relaxation times of packed red blood cells (RBCs). In this study, the spin-lattice relaxation time (T1) of human red cells was shortened from 836 ms to 29 ms and the spin-spin relaxation time (T2) shortened from 134 ms to 18 ms, when the cells were labeled at a Cr incubation concentration of 50 mM. Labeling of canine cells at 50 mM resulted in a T1 of 36 ms and a T2 of 26 ms. A labeling concentration of 10 mM produced similar relaxation enhancement, with uptake of 47% of the available Cr, and was determined to be optimal. The enhancement of longitudinal and transverse relaxation rates (1/T1,-1/T2) per amount of hemoglobin-bound Cr are 6.9 s-1 mM-1 and 9.8 s-1 mM-1 respectively, different from those of a pure Cr+3 solution. Labeling cells at 10 mM decreased the survival half-time in vivo from 16.6 days to 4.7 days in dogs. No difference in red cell survival was found with the use of hetero-transfusion versus auto-transfusion of labeled RBCs. Significant shortening of the T1 (912 ms to 266 ms, P = .03) and T2 (90 ms to 70 ms, P = .006) of spleen and the T1 (764 ms to 282 ms, P = .005) and the T2 (128 ms to 86 ms, P = .005) of liver occurred when 10% of the RBC mass of dogs was exchanged with Cr labeled cells. Liver and spleen spin density changes (P greater than 0.23) and muscle spin density and relaxation changes (P greater than 0.4) were insignificant. The in vivo T1 of a canine spleen which had been infarcted did not change following transfusion with labeled cells, where the T1 of liver did shorten. We believe this preliminary study suggests that Cr labeled red cells may have the potential to become an intravascular magnetic resonance imaging contrast agent.

Natriuretic and diuretic effects of infusion of atrial natriuretic factor in conscious dogs

We studied the effects of 30-min infusions of the synthetic 25-amino acid atrial natriuretic factor [ANF-(102-126)] and the 28-amino acid ANF-(99-126) at 0.1 and 0.3 micrograms.kg-1.min-1 on urine flow rate, sodium excretion, and arterial pressure in conscious dogs. Each dose was administered on a separate day following a 1-h stabilization period. We also compared the effects of 60-min infusions of ANF, 0.01 micrograms.kg-1.min-1, or water infusion on separate days in conscious dogs. Arterial pressure was reduced in a dose-dependent fashion, reaching statistical significance at a dose of 0.3 micrograms.kg-1.min-1. During the 0.01-micrograms.kg-1.min-1 infusion, the plasma concentration of ANF rose approximately threefold (from 68 +/- 7 to 207 +/- 14 pg/ml), with no change in urine flow rate, sodium excretion, or arterial pressure. At a dose of 0.1 micrograms.kg-1.min-1, urine flow increased (P less than 0.05) by 0.41 +/- 0.15 ml/min, and sodium excretion rose by 72 +/- 24 mu eq/min, but not significantly, whereas plasma ANF levels rose to 1,236 +/- 229 pg/ml. At the highest dose of ANF (0.3 micrograms.kg-1.min-1) urine flow rose by 0.62 +/- 0.16 ml/min, P less than 0.05, and sodium excretion rose by 139 +/- 30 mu eq/min, P less than 0.05, whereas plasma levels of ANF rose to 2,436 +/- 320 pg/ml. In contrast, volume loading with dextran increased urine flow by 3.5 +/- 1.3 ml/min, P less than 0.05, and sodium excretion by 439 +/- 147 mu eq/min, P less than 0.05, whereas ANF rose to only 320 +/- 69 pg/ml. These results suggest that, in the conscious dog, ANF does not cause significant diuretic or natriuretic effects until plasma levels are markedly above those observed in physiological conditions. A possible explanation for the difference between this and previous studies is that the renal effects of ANF, at physiological plasma levels, are indirect and thus dependent on autonomic and hormonal (angiotensin, vasopressin, and aldosterone levels) factors governing the renal function of the animal.

Therapy for osteosarcoma in dogs with intravenous injection of liposome-encapsulated muramyl tripeptide.

Canine osteosarcoma is a spontaneous malignancy in dogs, characterized by micrometastasis to pulmonary and extrapulmonary tissues at the time of diagnosis. Standard treatment involves amputation of the affected leg, but median survival time is 3-4 months with death due to metastasis. A randomized double-blind trial was conducted to evaluate liposome-encapsulated muramyl tripeptide-phosphatidylethanolamine (liposome/MTP-PE) as a treatment for metastasis in dogs undergoing amputation for osteosarcoma. Fourteen dogs were treated with liposome/MTP-PE, and 13 were treated with empty liposomes. Median survival time was 222 days for dogs treated with liposome/MTP-PE, compared to 77 days for dogs treated with empty liposomes (P less than .002). In the liposome/MTP-PE-treated group there were still four dogs alive and free of metastasis at greater than 1 year post surgery. Treatment was well tolerated; no significant toxic effects were noted except for mild elevations in body temperature (1-2 degrees C) for 2-6 hours post injection.

Dilly Beans

RITA SIMS QUILLEN, Hilton, Virginia, is the author of Looking for Native Ground: Contemporary Apppalachian Poetry. JEANNIE REED, native of Virginia, is making her second appearance in Appalachian Heritage . HARRY ROBIE teaches in the Department of English at Berea College. SHELBA COLE ROBISON, Laguna Beach, California, is Professor of Creative Writing at Saddleback College in Mission Viejo, California. JENNIFER E. SMITH resides in Washington, D.C., and does freelance writing. The Reverend Davidson The preacher from the next farm slowed his truck beside me on the hot grey road, and, as I climbed in, we stretched our faces in greeting. "Are you married, are you happy?" he asked in one jovial gasp, to which I answered, "Well, I'm happy..." leaving the statement open like the fields where we pastured our horses and where I danced like a mare foal. I couldn't explain the exquisiteness of tall timothy and of the thorny sweetness of blackberries in the summer heat from which he had been kind enough to rescue me in an air-conditioned pickup. -Diana R. Olsen MICHAEL THOMPSON is a Porcelain Restoration Artist in Berea. RAY TURNER, librarian for the Southeast Kentucky Area Health Education Center in Hazard, Kentucky, teaches children's literature for Alice Lloyd College, Pippa Passes, Kentucky . TOM R. WALTERS, Leesburg, Florida, had his Clay County Cemetery Records, Vol.1 published last year and hopes to follow with Vol. II soon. MIRIAM L. WOOLFOLK, past president of Kentucky State Poetry Society, has appeared in regional and international publications. DiIIy Beans (for my sister) On the last dog day, frantic last-minute phone calls in search of dillweed. Violently red co-op cayenne pepper. The smell of hot vinegar, the imported generosity of garlic. I return from a walk to find them already canned, the Blue Lakes I helped plant and pick: green columns in brine, sunken cities, crunchy fingerbones I will snap delightedly between my teeth on those lucky winter evenings I am home and my sister chooses to dole them out. This August afternoon we sit about the kitchen smiling, lifting our gin and tonics to abundance, to Ball jar autonomy, waiting for the seals to pop. -Jeff Mann 79 ...

STUDIES OF THE EFFECTS OF FK506 ON RENAL ALLOGRAFTING IN THE BEAGLE DOG

The immunosuppressive activities of a newly discovered macrolide extracted from Streptomyces tsukubaensis, FK506, were examined using 38 renal allografts in the beagle dog. The median survival time was 15.5 days in dogs without treatment, 61 days with a dose of 0.08 mg/kg/day and 176 days with a dose of 0.16 mg/kg/day of intramuscularly administered FK506. Prolongation of survival was statistically significant when compared with controls (P = 0.02, 0.0044, respectively). None of 6 recipient dogs receiving the agent at a dose of 0.16 mg/kg/day encountered rejection during the treatment course. Three of them survived over 200 days. Oral administration of FK506 at a dose of 0.32 mg/kg/day did not prolong the median survival time (20.5 days) compared with the placebo treated control (16.5 days), but oral treatment with 1.0 mg/kg/day resulted in all of the recipient dogs surviving over 130 days. Histological studies of 7 kidney graft biopsy specimens of the dogs surviving over 3 months revealed no cell infiltration or only some degree of reversible interstitial cell infiltration, but vascular and glomerular changes were not observed in any of the specimens. Irregularity of nuclear shape and cytoplasmic vacuolation of the pars recta of the proximal tubules were observed in one dog each. Liver biopsy specimens showed no consistent evidence of hepatocellular damage. Three dogs died of intussusception 2-3 weeks posttransplant. The dogs treated intramuscularly with 0.32 mg/kg/day suffered from anorexia. Two dogs receiving oral treatment at a dose of 1.0 mg/kg developed papilloma of the skin around day 60, but the tumors disappeared by day 120. We conclude that FK506 is a powerful immunosuppressant in the dog with tolerable side effects.