Preoperative carboplatin and paclitaxel-based chemoradiotherapy for esophageal carcinoma: results of a modified CROSS regimen utilizing radiation doses greater than 41.4 Gy.

Trimodality therapy for resectable esophageal and gastroesophageal junction cancers utilizing preoperative radiotherapy with concurrent carboplatin and paclitaxel-based chemotherapy is being increasingly utilized secondary to the results of the phase III CROSS trial. However, there is a paucity of reports of this regimen as a component of chemoradiotherapy in North America. We aim to report on our clinical experience using a modified CROSS regimen with higher radiotherapy doses. Patients with advanced (cT2-cT4 or node positive) esophageal or gastroesophageal junction carcinoma who received preoperative carboplatin/paclitaxel-based chemoradiotherapy with radiation doses of greater than 41.4 Gray (Gy) followed by esophagectomy were identified from an institutional database. Patient, imaging, treatment, and tumor response characteristics were analyzed. Twenty-four patients were analyzed. All but one tumor had adenocarcinoma histology. The median radiation dose was 50.4 Gy. Pathologic complete response was achieved in 29% of patients, with all receiving 50.4 Gy. Three early postoperative deaths were seen, due in part to acute respiratory distress syndrome and all three patients received 50-50.4 Gy. With a median follow-up of 9.4 months (23 days-2 years), median survival was 24 months. Trimodality therapy utilizing concurrent carboplatin/paclitaxel with North American radiotherapy doses appeared to have similar pathologic complete response rates compared with the CROSS trial, but may be associated with higher toxicity. Although the sample size is small and further follow-up is necessary, radiation doses greater than 41.4 Gy may not be warranted secondary to a potentially increased risk of severe radiation-induced acute lung injury.

Comparing mouse and human pluripotent stem cell derived cardiac cells: Both systems have advantages for pharmacological and toxicological screening.

Pluripotent stem cells offer an unparalleled opportunity to investigate cardiac physiology, pharmacology, toxicology and pathophysiology. In this paper we describe the use of both mouse (Nkx2-5(eGFP/w)) and human (NKX2-5(eGFP/w)) pluripotent stem cell reporter lines, differentiated toward cardiac lineage, for live single cell high acquisition rate calcium imaging. We also assess the potential of NKX2-5(eGFP/w) cardiac lineage cells for use toxicological screening as well as establish their sensitivity to a shift between low and high oxygen environments. Differentiated mouse Nkx2-5(eGFP/w) cells demonstrated a wide range of spontaneous oscillation rates that could be reduced by ryanodine (10µM), thapsigargin (1µM) and ZD7288 (10µM). In contrast human NKX2-5(eGFP/w) cell activity was only reduced by thapsigargin (1µM). Human cell survival was sensitive to the addition of trastuzumab and doxorubicin, while the switch from a low to a high oxygen environment affected oscillation frequency. We suggest that the human NKX2-5(eGFP/w) cells are less suitable for studies of compounds affecting cardiac pacemaker activity than mouse Nkx2-5(eGFP/w) cells, but are very suitable for cardiac toxicity studies.

INS(GFP/w) human embryonic stem cells facilitate isolation of in vitro derived insulin-producing cells.

AIMS/HYPOTHESIS: We aimed to generate human embryonic stem cell (hESC) reporter lines that would facilitate the characterisation of insulin-producing (INS⁺) cells derived in vitro. METHODS: Homologous recombination was used to insert sequences encoding green fluorescent protein (GFP) into the INS locus, to create reporter cell lines enabling the prospective isolation of viable INS⁺ cells. RESULTS: Differentiation of INS(GFP/w) hESCs using published protocols demonstrated that all GFP⁺ cells co-produced insulin, confirming the fidelity of the reporter gene. INS-GFP⁺ cells often co-produced glucagon and somatostatin, confirming conclusions from previous studies that early hESC-derived insulin-producing cells were polyhormonal. INS(GFP/w) hESCs were used to develop a 96-well format spin embryoid body (EB) differentiation protocol that used the recombinant protein-based, fully defined medium, APEL. Like INS-GFP⁺ cells generated with other methods, those derived using the spin EB protocol expressed a suite of pancreatic-related transcription factor genes including ISL1, PAX6 and NKX2.2. However, in contrast with previous methods, the spin EB protocol yielded INS-GFP⁺ cells that also co-expressed the beta cell transcription factor gene, NKX6.1, and comprised a substantial proportion of monohormonal INS⁺ cells. CONCLUSIONS/INTERPRETATION: INS(GFP/w) hESCs are a valuable tool for investigating the nature of early INS⁺ progenitors in beta cell ontogeny and will facilitate the development of novel protocols for generating INS⁺ cells from differentiating hESCs.

Cryptosporidium parvum infection requires host cell actin polymerization.

The intracellular protozoan parasite Cryptosporidium parvum accumulates host cell actin at the interface between the parasite and the host cell cytoplasm. Here we show that the actin polymerizing proteins Arp2/3, vasodilator-stimulated phosphoprotein (VASP), and neural Wiskott Aldrich syndrome protein (N-WASP) are present at this interface and that host cell actin polymerization is necessary for parasite infection.

Hemodialysis.

Hemodialysis is a therapeutic procedure that uses the extracorporeal circulation of a patient's blood to ameliorate the azotemia, fluid, electrolyte, and acid-base abnormalities characteristic of the uremic syndrome. Hemodialysis is principally used for the management of acute and chronic renal failure that is refractory to conventional medical therapy. Additional applications include acute intoxications (e.g., ethylene glycol poisoning) and preoperative conditioning of renal transplant recipients. Hemodialysis is a technically demanding procedure that requires an extensive array of sophisticated delivery equipment and specifically trained and dedicated staff to perform, monitor, and ensure the integrity and safety of the procedure in critically ill patients. The advent of neonatal dialysis delivery equipment has ensured that hemodialysis is a feasible, efficacious, safe, and indispensable therapy for dogs and cats with life-threatening renal failure. Increased awareness and acceptance of hemodialysis as an effective renal replacement therapy coupled with increased owner demand guarantee a bright future for hemodialysis as a viable therapeutic modality.

Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5.

Heterozygous mutations in the cardiac homeobox gene, NKX2-5, underlie familial cases of atrial septal defect (ASD) with severe atrioventricular conduction block. In this study, mice heterozygous for Nkx2-5-null alleles were assessed for analogous defects. Although ASD occurred only rarely, atrial septal dysmorphogenesis was evident as increased frequencies of patent foramen ovale and septal aneurysm, and decreased length of the septum primum flap valve. These parameters were compounded by genetic background effects, and in the 129/Sv strain, septal dysmorphogenesis bordered on ASD in 17% of Nkx2-5 heterozygotes. In a proportion of neonatal heterozygotes, as well as in adults with ASD, we found that the size of the foramen ovale was significantly enlarged and altered in shape, potentially exposing the normally thin septum primum to excessive hemodynamic forces. Therefore, defective morphogenesis of the septum secundum may be one contributing factor in the generation of patent foramen ovale, septal aneurysm, and certain ASDs. Mild prolongation of P-R interval in females and an increased frequency of stenotic bicuspid aortic valves were also features of the Nkx2-5 heterozygous phenotype. Our data demonstrate that the complex effects of Nkx2-5 haploinsufficiency in mice are weaker but convergent with those in humans. As in the mouse, the phenotype of human NKX2-5 mutations may be modulated by interacting alleles.

Complications and outcomes associated with use of gastrostomy tubes for nutritional management of dogs with renal failure: 56 cases (1994-1999).

OBJECTIVE: To evaluate complications and outcomes associated with use of gastrostomy tubes in dogs with renal failure. DESIGN: Retrospective study. ANIMALS: 56 dogs. PROCEDURE: Medical records were reviewed for dogs with renal failure that were treated by use of gastrostomy tubes. RESULTS: Mean +/- SD BUN concentration was 134 +/- 79 mg/dl and mean serum creatinine concentration was 9.0 +/- 3.8 mg/dl. Low-profile gastrostomy tubes were used for initial placement in 10 dogs, and traditional gastrostomy tubes were used in 46 dogs. Mild stoma-site complications included discharge, swelling, erythema, and signs of pain in 26 (46%) of dogs. Twenty-six gastrostomy tubes were replaced in 15 dogs; 11 were replaced because of patient removal, 6 were replaced because of tube wear, and 3 were replaced for other reasons. Six tubes were replaced by low-profile gastrostomy tubes. Gastrostomy tubes were used for 65 +/- 91 days (range, 1 to 438 days). Eight dogs gained weight, 11 did not change weight, and 17 lost weight; information was not available for 20 dogs. Three dogs were euthanatized because they removed their gastrostomy tubes, 2 were euthanatized because of evidence of tube migration, and 1 died of peritonitis. CONCLUSIONS AND CLINICAL RELEVANCE: Gastrostomy tubes appear to be safe and effective for improving nutritional status of dogs with renal failure.

Effect of hemodialysis on plasma amino acid concentrations in healthy dogs.

OBJECTIVE: To characterize the effect of maintenance hemodialysis on plasma amino acid concentrations and to quantitate free amino acid losses into the dialysate during hemodialysis in healthy dogs. ANIMALS: 8 healthy adult dogs. PROCEDURE: Five dogs received hemodialysis treatments 3 times per week for 4 weeks. Plasma amino acid concentrations were evaluated once per week for 4 weeks in each of the 5 dogs prior to hemodialysis (time 0), 90 minutes during hemodialysis, and immediately after hemodialysis (180 minutes). Total free amino acid concentrations and plasma amino acid concentrations (time 0, 90 minutes, and 180 minutes) in the dialysate were evaluated in 3 dogs that received 1 hemodialysis treatment. RESULTS: Significant time versus week interactions with any plasma amino acid were not detected; however, significant decreases in all plasma amino acid concentrations measured were detected at the midpoint of dialysis (46 +/- 2%) and at the end of each dialysis session (38 +/- 2%). Mean (+/- SEM) total free amino acid loss into the dialysate was 2.7 +/- 0.2 g or 0.12 g/kg of body weight. CONCLUSIONS AND CLINICAL RELEVANCE: Hemodialysis is associated with significant alterations in plasma amino acid concentrations and loss of free amino acids into the dialysate. Loss of amino acids into the dialysate, coupled with protein calorie malnutrition in uremic patients, may contribute to depletion of amino acid stores.

Reliability of history and physical examination findings for assessing control of glycemia in dogs with diabetes mellitus: 53 cases (1995-1998).

OBJECTIVE: To evaluate the reliability of history and physical examination findings for assessing control of glycemia in insulin-treated diabetic dogs. DESIGN: Retrospective study. ANIMALS: 53 insulin-treated dogs with diabetes mellitus. PROCEDURE: Medical records of insulin-treated diabetic dogs from June 1995 to June 1998 were reviewed, and information on owner perception of their dog's response to insulin treatment, physical examination findings, body weight, insulin dosage, and concentrations of food-withheld (i.e., fasting) blood glucose (FBG), mean blood glucose (MBG) during an 8-hour period, blood glycosylated hemoglobin (GHb), and serum fructosamine was obtained. Owner's perception of their dog's response to insulin treatment, physical examination findings, and changes in body weight were used to classify control of glycemia as good or poor for each dog. The FBG, MBG/8 h, blood GHb, and serum fructosamine concentrations were compared between well-controlled and poorly controlled insulin-treated diabetic dogs. RESULTS: Presence or absence of polyuria, polydipsia, polyphagia, lethargy, and weakness were most helpful in classifying control of glycemia. Mean FBG and MBG/8 h concentrations, blood GHb concentrations, and serum fructosamine concentrations were significantly decreased in 25 well-controlled diabetic dogs, compared with 28 poorly controlled diabetic dogs. Most well-controlled diabetic dogs had concentrations of FBG between 100 and 300 mg/dl, MBG/8 h < or = 250 mg/dl, blood GHb < or = 7.5%, and serum fructosamine < or = 525 mumol/L, whereas most poorly controlled diabetic dogs had results that were greater than these values. CONCLUSIONS AND CLINICAL RELEVANCE: Reliance on history, physical examination findings, and changes in body weight are effective for initially assessing control of glycemia in insulin-treated diabetic dogs.

Prevalence of pituitary tumors among diabetic cats with insulin resistance.

OBJECTIVE: To determine prevalence of pituitary tumors, detectable by means of computed tomography or magnetic resonance imaging, in cats with insulin resistance suspected to have acromegaly or hyperadrenocorticism versus cats with well-controlled diabetes mellitus. DESIGN: Case series. ANIMALS: 16 cats with insulin resistance that were also suspected to have acromegaly (n = 12) or pituitary-dependent hyperadrenocorticism (4) and 8 cats with well-controlled diabetes mellitus. PROCEDURE: Computed tomography was performed on all 16 cats with insulin resistance and 2 cats in which diabetes mellitus was well-controlled. The remaining 6 cats in which diabetes mellitus was well-controlled underwent magnetic resonance imaging. Images were obtained before and immediately after i.v. administration of contrast medium. RESULTS: Computed tomography revealed a mass in the region of the pituitary gland in all 16 cats with insulin resistance. Maximum width of the masses ranged from 4.4 to 12.7 mm; maximum height ranged from 3.1 to 12.6 mm. Results of computed tomography performed on 2 cats with well-controlled diabetes and magnetic resonance imaging performed on the remaining 6 cats were considered normal. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that cats with insulin resistance suspected to have acromegaly or pituitary-dependent hyperadrenocorticism are likely to have a pituitary mass detectable by means of computed tomography or magnetic resonance imaging.

Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface.

Cryptosporidium parvum is an intracellular protozoan parasite that causes a severe diarrheal illness in humans and animals. Previous ultrastructural studies have shown that Cryptosporidium resides in a unique intracellular compartment in the apical region of the host cell. The mechanisms by which Cryptosporidium invades host intestinal epithelial cells and establishes this compartment are poorly understood. The parasite is separated from the host cell by a unique electron-dense structure of unknown composition. We have used indirect immunofluorescence microscopy and confocal laser scanning microscopy to characterize this structure. These studies indicate that host filamentous actin is assembled into a plaque-like structure at the host-parasite interface during parasite invasion and persists during parasite development. The actin-binding protein alpha-actinin is also present in this plaque early in parasite development but is lost as the parasite matures. Other actin-associated proteins, including vinculin, talin, and ezrin, are not present. We have found no evidence of tyrosine phosphorylation within this structure. Molecules known to link actin filaments to membrane were also examined, including alpha-catenin, beta-catenin, plakoglobin, and zyxin, but none was identified at the host-parasite junction. Thus, Cryptosporidium induces rearrangement of the host cell cytoskeleton and incorporates host cell actin and alpha-actinin into a host-parasite junctional complex.

Comparison of serum fructosamine and blood glycosylated hemoglobin concentrations for assessment of glycemic control in cats with diabetes mellitus.

OBJECTIVE: To correlate serum fructosamine concentrations with established measures of glycemic control and to compare serum fructosamine and blood glycosylated hemoglobin (GHb) concentrations as a means for assessing glycemic control in diabetic cats. DESIGN: Longitudinal cohort study. ANIMALS: 26 healthy cats, 5 cats with stress-induced hyperglycemia, 15 untreated diabetic cats, and 36 treated diabetic cats. PROCEDURE: Control of glycemia was classified and monitored and serum fructosamine and blood GHb concentrations were measured for 12 poorly controlled diabetic cats before and after improving glycemic control, 8 well-controlled treated diabetic cats before and after glycemic control deteriorated, and 5 cats with diabetes mellitus before and after onset of stress-induced hyperglycemia. RESULTS: Mean serum fructosamine and blood GHb concentrations were significantly higher in untreated diabetic cats, compared with healthy cats, and in 24 poorly controlled diabetic cats, compared with 12 well-controlled diabetic cats. Mean serum fructosamine and blood GHb concentrations decreased significantly in 12 poorly controlled diabetic cats after improving glycemic control and increased significantly in 8 well-controlled diabetic cats after glycemic control deteriorated. A significant stress-induced increase in mean blood glucose concentration was evident 12 hours after insulin administration, but not in 5 docile diabetic cats that became fractious. CLINICAL IMPLICATIONS: Serum fructosamine and blood GHb concentrations are clinically useful tools for monitoring control of glycemia in cats with diabetes mellitus.

Cobalt 60 irradiation of pituitary gland tumors in three cats with acromegaly.

Acromegaly was diagnosed in 3 cats with insulin-resistant diabetes mellitus (DM) on the basis of history and physical examination findings, which ruled out other causes of insulin-resistant DM, and by documenting high plasma concentrations of growth hormone. Computed tomography revealed a mass in the area of the pituitary gland in each cat. Pituitary gland tumors were irradiated with cobalt 60, and none of the cats developed complications to radiotherapy. Each cat received a total dose of 48 Gy of cobalt 60 during 12 treatments. After completion of radiotherapy, insulin requirements were less for all cats, although in 1 cat, this improvement was transient. Diabetes mellitus resolved in 2 of 3 cats. After treatment, decreases in insulin requirements correlated with decreases in plasma growth hormone concentrations in 2 of 3 cats in which DM resolved. On the basis of these findings, irradiation of pituitary gland tumors appears to be a treatment option for cats with acromegaly.

Divergent roles for NK-2 class homeobox genes in cardiogenesis in flies and mice.

Recent evidence suggests that cardiogenesis in organisms as diverse as insects and vertebrates is controlled by an ancient and evolutionarily conserved transcriptional pathway. In Drosophila, the NK-2 class homeobox gene tinman (tin) is expressed in cardiac and visceral mesodermal progenitors and is essential for their specification. In vertebrates, the tin homologue Nkx2-5/Csx and related genes are expressed in early cardiac and visceral mesodermal progenitors. To test for an early cardiogenic function for Nkx2-5 and to examine whether cardiogenic mechanisms are conserved, we introduced the mouse Nkx2-5 gene and various mutant and chimeric derivatives into the Drosophila germline, and tested for their ability to rescue the tin mutant phenotype. While tin itself strongly rescued both heart and visceral mesoderm, Nkx2-5 rescued only visceral mesoderm. Other vertebrate 'non-cardiac' NK-2 genes rescued neither. We mapped the cardiogenic domain of tin to a unique region at its N terminus and, when transferred to Nkx2-5, this region conferred a strong ability to rescue heart. Thus, the cardiac and visceral mesodermal functions of NK-2 homeogenes are separable in the Drosophila assay. The results suggest that, while tin and Nkx2-5 show close functional kinship, their mode of deployment in cardiogenesis has diverged possibly because of differences in their interactions with accessory factors. The distinct cardiogenic programs in vertebrates and flies may be built upon a common and perhaps more ancient program for specification of visceral muscle.

Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users.

Nasal colonization plays an important role in the pathogenesis of Staphylococcus aureus infections. To identify characteristics associated with colonization, we studied a cross-section of a well-described cohort of HIV-seropositive and -seronegative active and former drug users considered at risk for staphylococcal infections. Sixty percent of the 217 subjects were Hispanic, 36% were women, 25% actively used injection drugs, 23% actively used inhalational drugs, 23% received antibiotics, and 35% were HIV-seropositive. Forty-one percent of subjects had positive nasal cultures for S. aureus. The antibiotic susceptibility patterns were similar to the local hospital's outpatient isolates and no dominant strain was identified by arbitrarily primed polymerase chain reaction (AB-PCR). Variables significantly and independently associated with colonization included antibiotic use (odds ratio [OR] = 0.37; confidence interval [CI] = 0.18-0.77), active inhalational drug use within the HIV-seropositive population (OR = 2.36; CI = 1.10-5.10) and female gender (OR = 1.97; CI = 1.09-3.57). Characteristics not independently associated included injection drug use, HIV status, and CD4 count. The association with active inhalational drug use, a novel finding, may reflect alterations in the integrity of the nasal mucosa. The lack of association between HIV infection and S. aureus colonization, which is contrary to most previous studies, could be explained by our rigorous control for confounding variables or by a limited statistical power due to the sample sizes.

Growth and morphological transformations of Helicobacter pylori in broth media.

Helicobacter pylori, a cause of peptic ulcer disease and certain types of gastric cancers, has usually been cultured on diverse agar-based media, resulting in a requirement for 2 to 4 days of growth at 37 degrees C. We have developed a novel broth medium consisting of a base medium supplemented with 2% newborn calf serum, Mg2+, Cu2+, Fe2+, Zn2+, Mn2+, and 1 mg of lysed human erythrocytes per ml. This medium supports rapid growth of H. pylori, with a doubling time of about 50 min. Optimal growth was obtained in a pH range higher than that supporting most other gram-negative bacteria (at pH 8.5). H. pylori cultured in this supplemented broth retains the spiral morphology seen in both histological sections and cultures from agar-based media and also retains a high urease activity. After 18 h in this broth, H. pylori transforms to a coccal form with a complete loss of urease activity. Previously these cocci have been reported to be senescent, since they could not be subcultured on agar medium. Our experiments suggest that some of the cocci can revert back to the spiral morphology with full recovery of urease activity when subcultured in fresh microaerobic broth medium.

Extracellular matrix heparan sulfate modulates endothelial cell susceptibility to Staphylococcus aureus.

The ability of extracellular matrix heparan sulfate to alter the susceptibility of human endothelial cells to S. aureus was investigated. Endothelial cells grown on extracellular matrix synthesized by S. aureus-infected endothelial cells were more susceptible to subsequent staphylococcal infection than endothelial cells grown on the extracellular matrix synthesized by untreated endothelial cells. Endothelial cells were more susceptible to S. aureus infection when 1) grown on heparitinase-treated extracellular matrix that removed heparan sulfate chains, 2) grown on extracellular matrix produced by chlorate-treated endothelial cells that reduced sulfation in the matrix heparan sulfate proteoglycans, 3) grown on heparan sulfate purified from extracellular matrix elaborated by infected endothelial cells, and 4) endothelial cells were chlorate-treated and therefore expressed desulfated cellular heparan sulfate proteoglycans. Extracellular matrix produced by S. aureus-infected endothelial cells contained heparan sulfate proteoglycans with reduced sulfation. The altered extracellular matrix with reduced sulfated heparan sulfate proteoglycans signalled the uninfected endothelial cells to produce under sulfated cellular heparan sulfate proteoglycans that increased S. aureus adherence to the endothelial cells.

Glycosylated hemoglobin concentrations in the blood of healthy dogs and dogs with naturally developing diabetes mellitus, pancreatic beta-cell neoplasia, hyperadrenocorticism, and anemia.

OBJECTIVE: To characterize glycosylated hemoglobin (GHb) concentrations in the blood of dogs with disorders that may affect serum glucose or blood GHb concentrations, and to determine whether changes in GHb concentration correlate with changes in control of diabetes in dogs. DESIGN: Prospective study. ANIMALS: 63 healthy dogs, 9 dogs with anemia, 24 dogs with untreated hyperadrenocorticism, 12 dogs with pancreatic beta-cell neoplasia, 23 dogs with newly diagnosed diabetes mellitus, and 77 diabetic dogs treated with insulin. PROCEDURE: Control of diabetes in dogs treated with insulin was classified as good or poor on the basis of history, physical examination findings, changes in body weight, and measurement of serum glucose concentrations Sequential evaluations of control were performed and GHb concentration in blood was measured, by means of affinity chromatography, for 5 untreated diabetic dogs before and after initiating insulin treatment, for 10 poorly controlled diabetic dogs before and after increasing insulin dosage, and for 5 diabetic dogs before and after pancreatic islet cell transplantation. RESULTS: Mean (+/-SD) GHb concentration was 3.3 +/- 0.8% in the blood of healthy dogs. Compared with results from healthy dogs, mean GHb concentration was significantly lower in the blood of dogs with anemia and pancreatic beta-cell neoplasia and significantly higher in the blood of untreated diabetic dogs. Mean GHb concentration was significantly higher in the blood of 46 poorly controlled diabetic dogs, compared with 31 well-controlled diabetic dogs (7.3 +/- 1.8 vs 5.7 +/- 1.7%, respectively). Mean GHb concentration in blood decreased significantly in 5 untreated diabetic dogs after treatment (8.7 +/- 1.9 vs 5.3 +/- 1.9%). Mean GHb concentration in blood also decreased significantly in 10 poorly controlled diabetic dogs after control was improved and in 5 diabetic dogs after they had received a pancreatic islet cell transplant. CLINICAL IMPLICATIONS: Measurement of GHb concentration in blood may assist in monitoring control of diabetes in dogs.

Glycosylated hemoglobin concentration for assessment of glycemic control in diabetic cats.

Blood glycosylated hemoglobin (GHb) concentration was quantified in 84 healthy cats, 9 cats with stress-induced hyperglycemia, 37 cats with newly diagnosed diabetes mellitus, and 122 diabetic cats treated with insulin or glipizide. Diabetic control was classified as good or poor in insulin-treated or glipizide-treated cats based on review of history, physical examination findings, changes in body weight, and measurement of blood glucose concentrations. Blood GHb concentration was determined using an affinity chromatography assay. Mean blood GHb concentration was similar for healthy normoglycemic cats and cats with transient, stress-induced hyperglycemia, but was significantly (P < .001) higher in untreated diabetic cats when compared with healthy normoglycemic cats. Mean blood GHb concentration was significantly (P < .001) higher in 84 cats with poorly controlled diabetes mellitus when compared with 38 cats in which the disease was well controlled. Mean blood GHb concentration decreased significantly (P < .01) in 6 cats with untreated diabetes mellitus after insulin and dietary treatment. A similar significant (P < .01) decrease in mean blood GHb concentration occurred in 7 cats with poorly controlled diabetes mellitus after diabetic control was improved by an increase in insulin dosage from 1.1 +/- 0.9 to 1.4 +/- 0.6 U/kg/ 24 h and by feeding a diet containing increased fiber content and in 6 cats with transient diabetes mellitus 8.2 +/- 0.6 weeks after discontinuing insulin treatment. There was a significant (P < .01) stress-induced increase in mean fasting blood glucose concentration and mean blood glucose concentration for 12 hours after administration of insulin or glipizide but no change in mean blood GHb concentration in 5 docile diabetic cats 12.2 +/- 0.4 weeks after the cats became fractious as a result of frequent hospitalizations and blood samplings. Results of this study suggest that evaluation of blood GHb concentration may be a clinically useful tool for monitoring glycemic control of diabetes in cats.