Prevalence of nephrotoxicosis associated with a four-hour saline solution diuresis protocol for the administration of cisplatin to dogs with naturally developing neoplasms

We evaluated the development of nephrotoxicosis in 64 dogs with malignant neoplasia given cisplatin during 4-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface area, IV, q 21 d) was given to 8 dogs once, 22 dogs twice, 9 dogs 3 times, and 25 dogs 4 times. For each treatment, cisplatin was given over a 20-minute period after saline (0.9% NaCl) solution was administered IV for 3 hours at a rate of 25 ml/kg/h. After cisplatin infusion, saline solution diuresis was continued at the same rate for 1 hour. Before each treatment with cisplatin, the dogs were evaluated by conducting a physical examination, CBC; and analysis of serum urea nitrogen and creatinine concentrations, and in most cases, serum phosphorus concentration and urine specific gravity were determined. Exogenous creatinine clearance also was evaluated in 8 dogs prior to 1 (n = 8), 2 (n = 8), 3 (n = 6), and 4 (n = 4) treatments. Five (7.8%) of 64 dogs developed clinically evident renal disease after two (n = 3) and three (n = 2) doses of cisplatin. Two of the 5 dogs had preexisting diseases of the urinary tract prior to the start of treatment. Survival time in dogs that developed renal disease (median, 114 days; range, 26 to 273 days) was similar to that of all dogs in this study (median, 145 days; range, 5 to 586 days), with 30 dogs still alive at the conclusion of the study. Three of the 5 dogs that developed renal disease were alive at the conclusion of the study, 1 died of tumor-related causes, and another died as a direct result of nephrotoxicosis. There was a significant (P < 0.05) decrease in median neutrophil counts and a significant (P < 0.05) increase in median creatinine concentrations prior to the third and fourth treatments, compared with pretreatment values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical diversity of pyruvate dehydrogenase deficiency

Clinical features, magnetic resonance, and biochemical studies are reported in 7 children with pyruvate dehydrogenase (PDH) deficiency. These findings confirm the diverse clinical presentation of this condition, although neurological abnormalities are consistent features. Imaging results are also varied. Six of the children were investigated with proton magnetic resonance spectroscopy and lactate was demonstrated in brain in all patients. Regional variation in the lactate signal was observed in those patients in whom 2 regions were examined. Advances in molecular genetics have provided some explanations for the clinical variation in pyruvate dehydrogenase deficiency.     

Isolation, characterisation and cell growth-regulatory properties of kumara (sweet potato) trypsin inhibitors

Locally grown kumara (sweet potato; Ipomea batatis) was used as the starting point for the purification of a proteinase inhibitor. The purified inhibitor was highly specific for trypsin, and much less effective as an inhibitor of chymotrypsin. Two 22kDa variants were present, closely homologous to each other and to sporamin A, but with a single amino acid substitution (proline in place of serine, the second residue in mature sporamin A). One variant had the same N-terminus as sporamin A, whereas the other had a tripeptide N-terminal extension, which may represent an intermediate in the proteolytic processing of the precursor protein. A larger variant was apparently a disulphide-linked dimer of the monomeric inhibitor. A rabbit polyclonal antiserum prepared against the trypsin inhibitor reacted with all of these variants, but did not cross-react with commercially-available soybean proteinase inhibitors. The purified inhibitor did resemble other proteinase inhibitors in having a biphasic effect upon the proliferation of human fibroblasts, with a mitogenic action at low concentrations, and an inhibitory effect at higher concentrations.     

Nucleation of hydroxyapatite by bone sialoprotein

Bone sialoprotein (BSP) and osteopontin, the major phosphorylated proteins of mammalian bone, have been proposed to function in the initiation of mineralization. To test this hypothesis, the effects of BSP and osteopontin on hydroxyapatite crystal formation were determined by using a steady-state agarose gel system. At low calcium phosphate concentrations, no accumulation of calcium and phosphate occurred in control gels or gels containing osteopontin. Gels containing BSP at 1-5 micrograms/ml, however, exhibited a visible precipitation band and significantly elevated Ca + PO4 contents. By powder x-ray diffraction, the precipitate formed in the presence of BSP was shown to be hydroxyapatite. These findings suggest that bone sialoprotein may be involved in the nucleation of hydroxyapatite at the mineralization front of bone.     

Expression of the double-stranded RNA-dependent protein kinase (p68) in squamous cell carcinoma of the head and neck region

OBJECTIVE: p68 is an interferon-inducible protein kinase that is believed to be an important factor in the regulation of both viral and cellular protein synthesis. We have previously shown that p68 expression correlates with differentiation in a variety of tumors, including squamous cell carcinoma of the head and neck region. The current study aims to identify the prognostic significance of p68 expression in squamous cell carcinoma of the head and neck. DESIGN: Archival material from a cohort of 75 patients with primary squamous carcinomas of the head and neck was immunostained for p68 with the monoclonal antibody TJ4C4. Overall scores for p68 expression were tabulated based on staining intensity and percentage of immunoreactive tumor cells. Clinical information including tumor grade, stage, site, treatment, disease-free, and total survival was tabulated and compared by p68 expression group. SETTING: Veterans Administration Lakeside Medical Center and outpatient clinics (Northwestern University and Veterans Administration Lakeside Medical Center, Chicago, Ill). PATIENTS: Seventy-five consecutive patients with primary squamous cell carcinoma of the head and neck (excluding the esophagus), with tissue blocks available for study, a known primary site, no history of prior carcinoma, and demographic and follow-up information available. MAIN OUTCOME MEASURED: Disease-free and overall survival rates. RESULTS: While there was a wide range of outcomes within each group, as a group, high levels of p68 expression correlated with a lower incidence of recurrent or residual disease and longer disease-free and total survival times compared with groups with lower levels of p68 expression. These differences could not be explained on differences in patient age, tumor grade, and TNM stage. CONCLUSIONS: High-level p68 expression is associated with prolonged disease-free and overall survival in a series of patients with squamous cell carcinoma of the head and neck region. Additional study is needed to monitor changes in p68 expression with treatment or tumor progression.     

Personal continuity and the care of patients with epilepsy in general practice

BACKGROUND: So far no study has shown that patients with a chronic illness benefit from seeing the same doctor in general practice although many believe this to be so. AIM: Epilepsy was chosen as an example to test the hypothesis that if patients see the same doctor more often in general practice they are more likely to discuss personally important aspects of their illness. METHODS: In this cross-sectional survey 99 patients aged 15-84 years with active epilepsy were interviewed at home and then their records were reviewed. The patients came from four large Southampton group practices, one with a strict personal list system and three with combined lists. Outcome measures included reported discussion of feelings about stopping medication, stigma and concealment and the patient's relationship with practice doctors. Continuity was assessed from the records. RESULTS: Discussion of epilepsy was not significantly associated with continuity of doctor but was significantly associated with ease of talking to one or more doctors. CONCLUSION: Encouraging patients with epilepsy to see the same doctor may be less important than improving doctors' communication skills and paying specific attention to the psychosocial aspects of epilepsy as well as to seizure control. It is recommended that a simple checklist including these items is used when a patient's care is reviewed.     

Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole

OBJECTIVE: To determine the effect of standard-dose trimethoprim-sulfamethoxazole on serum potassium concentration in hospitalized patients. DESIGN: Prospective chart review. SETTING: Community-based teaching hospital. PATIENTS: 105 patients with various infections were hospitalized and treated. Eighty patients treated with standard-dose trimethoprim-sulfamethoxazole (trimethoprim, < or = 320 mg/d; sulfamethoxazole, < or = 1600 mg/d) composed the treatment group; 25 patients treated with other antibiotic agents served as the control group. MEASUREMENTS: Serum sodium, potassium, and chloride concentrations; serum carbon dioxide content; anion gap; blood urea nitrogen level; and serum creatinine level. RESULTS: The serum potassium concentration in the treatment group (mean +/- SD) was 3.89 +/- 0.46 mmol/L (95% CI, 3.79 to 3.99 mmol/L), and it increased by 1.21 mmol/L (CI, 1.09 to 1.32 mmol/L) 4.6 +/- 2.2 days after trimethoprim-sulfamethoxazole therapy was initiated. Blood urea nitrogen levels increased from 7.92 +/- 5.7 mmol/L (CI, 6.67 to 9.16 mmol/L) to 9.2 +/- 5.8 mmol/L (CI, 7.9 to 10.5 mmol/L), and serum creatinine levels increased from 102.5 +/- 49.5 mumol/L (CI, 91.4 to 113.6 mumol/L) to 126.1 +/- 70.7 mumol/L (CI, 110.3 to 141.9 mumol/L). Patients with a serum creatinine level of 106 mumol/L (1.2 mg/dL) or more developed a higher peak potassium concentration (5.37 +/- 0.59 mmol/L [CI, 5.15 to 5.59 mmol/L]) than patients with a serum creatinine level of less than 106 mumol/L (4.95 +/- 0.48 mmol/L [CI, 4.80 to 5.08 mmol/L]). Patients with diabetes had a slightly higher peak potassium concentration (5.14 +/- 0.45 mmol/L [CI, 4.93 to 5.39 mmol/L]) than did patients without diabetes (5.08 +/- 0.59 mmol/L [CI, 4.93 to 5.23 mmol/L]), but the difference was not statistically significant. The serum potassium concentration in the control group was 4.33 +/- 0.45 mmol/L (CI, 4.15 to 4.51 mmol/L), and it decreased nonsignificantly over 5 days of therapy. CONCLUSIONS: Standard-dose trimethoprim-sulfamethoxazole therapy used to treat various infections leads to an increase in serum potassium concentration. A peak serum potassium concentration greater than 5.0 mmol/L developed in 62.5% of patients; severe hyperkalemia (peak serum potassium concentration > or = 5.5 mmol/L) occurred in 21.2% of patients. Patients treated with standard-dose trimethoprim-sulfamethoxazole should be monitored closely for the development of hyperkalemia, especially if they have concurrent renal insufficiency (serum creatinine level > or = 106 mumol/L).     

Phase I evaluation of mitoxantrone alone and combined with whole body hyperthermia in dogs with lymphoma

The maximum tolerated dose of mitoxantrone (MX) administered alone or combined with whole body hyperthermia (WBH) was determined in this nonrandomized, prospective study in dogs with lymphoma. MX was administered to 53 dogs every three weeks for a total of six treatments unless progressive disease or persistent, severe toxicity developed. Fifty dogs were evaluable (MX alone n = 30, MX/WBH n = 20). MX was administered as a 1 h infusion at the onset of the plateau phase of WBH in dogs treated with combined therapy. Dogs were evaluated weekly between treatments for the first four treatments with physical examination and complete blood counts to define acute and cumulative toxicity. Dogs were evaluated every three weeks for tumour response until relapse. The maximum tolerated dose (MTD) was defined as that dose in each group that resulted in a 50% incidence of moderate or severe toxicity as estimated from logistic regression analysis of the toxicity data. Myelosuppression was the only toxicity observed. Neutropenia was equal in frequency and severity between treatment groups. Thrombocytopenia was not observed in any dog receiving MX/WBH but occurred in 13% of dogs treated with MX alone. The MTD for MX +/- WBH was 6.1 +/- 0.6 and 6.5 +/- 0.8mg/M2 respectively. A steeper dose response relationship was observed in dogs receiving combined therapy compared to dogs treated with MX alone suggesting WBH may improve the uniformity of patient response to chemotherapy. We concluded that MX may be administered without dose reduction to dogs undergoing WBH and that MX should be evaluated more thoroughly in future thermochemotherapy studies.