Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors

Summary Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastromestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors.This investigation was supported by Pfizer Inc.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Intractable Diarrhea from Carbamazepine

Diarrhea has been reported as an early, mild, and uncommon complication of carbamazepine (CBZ) therapy. We report three cases of intractable diarrhea induced by CBZ necessitating discontinuation of the drug.     

Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.

Expression of the immediate early gene zif/268 (also termed NGFI-A, Krox 24, TIS8 and Egr-1) was investigated in awake rats following various long-term potentiation (LTP) induction protocols.zif/268 mRNA (Northern blots) and protein (immunohistochemistry) levels sharply increased following LTP, and followed a time course characteristic of other immediate early genes. When measured across 3 tetanization protocols known to produce differing degrees of LTP persistence,zif/268 induction was found to be more highly correlated with LTP duration than with the magnitude of initial LTP. These data support the hypothesis that the immediate early gene zif/268 plays a role as a third messenger in the cascade of cellular and nuclear events that govern the persistence of LTP.     

Vertically fused tracheal cartilage. An underrecognized anomaly.

Anterior vertical fusion of the tracheal cartilages with normal pars membranacea is a rarely described tracheal anomaly. We report four cases of this anomaly, three associated with craniosynostosis syndromes and one with Goldenhar's syndrome. The anomaly was documented at postmortem examination in one case, both endoscopically and at tracheotomy in two cases, and endoscopically in one case. Documentation from gross postmortem photographs, photomicrographs, and intraoperative endoscopic photographs is presented so that the anatomical aspects of this anomaly can be thoroughly understood and recognized. All four newborn patients developed recurrent lower respiratory tract infections, reactive airway disease, and chronically retained secretions attributable to this anomaly. Neither tracheal stenosis nor stridor was encountered. In the three surviving patients, the infections grew less frequent and less severe in later childhood. These observations suggest that this tracheobronchial anomaly may be associated with a variety of craniofacial syndromes and may alter airflow dynamics in a way that predisposes to retained secretions and chronic pulmonary disease.     

Laparoscopic partial fundoplication vs laparoscopic Nissen-Rosetti fundoplication

Background: Since 1992, all patients at our institution who have met standard accepted criteria for surgical intervention for complicated gastroesophageal reflux disease have been entered into a prospective sequential clinical study to evaluate outcomes of the laparoscopic approach to the Nissen-Rosetti procedure and a modified Toupet procedure. Methods: A standardized workup with upper GI series, esophagography, and endoscopy was used in all patients. Manometry, pH testing, and other special tests were used selectively. A measuring technique was used to determine wrap size without the use of dilators. The short gastric vessels were left intact in all patients. A cosurgeon approach was used, with technical factors described herein. Results: Some 226 of 231 cases were completed laparoscopically (98%)—125 patients in the Nissen-Rosetti group and 101 in the partial fundoplication group. There were no clinical failures in either group. The partial fundoplication group performed better than the Nissen-Rosetti group in all categories of comparison. Return to normal eating habits was much earlier in the partial wrap group (p < 0.0001). Postop distal esophageal sphincter pressures in the two groups were equal at 15 mmHg. Eight patients suffered significant dysphagia requiring endoscopy and dilatation, all in the Nissen-Rosetti group (p < 0.01). Minor complications occurred in 12% of the total group. There was a total surgical revision rate of 3%. There were no gastric or esophageal perforations. Average operative time was 30 min. Average hospital stay was 1.4 days. Hospital charges for the laparoscopic approach averaged $6,000 dollars compared to $12,000 for the open approach. Conclusion: Laparoscopic partial fundoplication is as effective as laparoscopic Nissen-Rosetti fundoplication, with a higher satisfaction rate and fewer side effects. Measuring for wrap and hiatus size eliminates the need for and risk of using stiff dilators. By utilizing cosurgeons and currently available technology, cost, operative time, hospital time, and complications can be reduced to a finite minimum. Received: 12 December 1995/Accepted: 12 August 1996     

Risk of periodontal defects after third molar surgery: An exercise in evidence-based clinical decision-making.

OBJECTIVE: The object of this study was to apply evidence-based principles to answer the question, What is the risk of having periodontal defects on the distal aspect of the mandibular second molar (M2) following third molar (M3) removal? STUDY DESIGN: To identify relevant articles for review, we completed a computerized literature search of Medline. The inclusion criteria for articles included prospective cohort studies or randomized clinical trials with follow-up periods of 6 months or more, and preoperative and postoperative measurements of periodontal probing depths (PDs) or attachment levels (ALs). RESULTS: Eight articles met the inclusion criteria. Overall, the reported mean changes in ALs or PDs on the distal of M2 6 months after M3 removal were clinically insignificant, ie, less than 2 mm. Six months after M3 removal, 52% to 100% of subjects had no change or improvement in ALs or PDs. Given periodontal disease present preoperatively, the number needed to treat (NNT) ranged from 3 to 10. Given healthy periodontal status preoperatively, 48% had worsening of their periodontal measures after M3 removal and the number needed to harm (NNH) was 2. CONCLUSION: Commonly, the second molar periodontal probing depth or attachment levels either remain unchanged or improve after third molar removal. For subjects with healthy second molar periodontium preoperatively, the indication for third molar removal needs to be evaluated carefully as these subjects have an increased risk for worsening of probing depths or attachment levels after third molar removal.     

Molecular cloning of a cDNA for rat diabetes-inducible cytochrome P450RLM6: hormonal regulation and similarity to the cytochrome P4502E1 gene.

1. A polyclonal, monospecific antibody to a constitutive, diabetes-inducible and insulin-reversible cytochrome P-450 isozyme (RLM6) was used to screen a male rat liver cDNA library in lambda gt 11. Six clones harbouring the RLM6 cDNA insert were isolated initially from the expression library and three of these were further plaque-purified and sub-cloned. A 1.1 Kb cDNA insert, representing approximately 65% of the expected full length cDNA was characterized by restriction endonuclease mapping and sequenced by the dideoxy chain-termination method. Comparison of the nucleotide sequence of RLM6 cDNA to that of ethanol-inducible P4502E1 rat cDNA showed the two cDNAs to be identical, the RLM6 cDNA corresponding to nucleotides 310-1402 of the P4502E1 sequence. 2. RLM6 cDNA probe was used in Northern blot and RNA dot blot hybridization analysis to demonstrate that both streptozotocin-induced diabetes and fasting significantly elevated the steady-state level of RLM6 mRNA in male rat liver. Increased RLM6 mRNA level in the diabetic rat resulted in increased RLM6 apoprotein synthesis when polysomal RNA was used in a cell-free, protein-synthesizing system, indicating that the elevated RLM6 level observed in diabetic rats was correlated directly with the increased RLM6 mRNA concentration. 3. Daily insulin treatment of diabetic rats reversed the diabetes-dependent increase in RLM6 mRNA in a time-dependent manner, returning to control values after approximately 2 weeks of continuous insulin treatment. This insulin-dependent decrease of the RLM6 mRNA level was paralleled by a similar time-dependent decrease in serum acetone concentration. 4. Treatment of the male diabetic rat with testosterone also resulted in a decrease in both RLM6 mRNA and in vitro translated apoprotein. 5. Modulation of RLM6 mRNA level in the diabetic rat by insulin and testosterone, and the nucleotide sequence similarity with that of P4502E1 confirms that diabetes-inducible P450RLM6 and ethanol-inducible P4502E1 are coded for by the same gene.     

Emergency surgery for haematoma-forming aneurysmal haemorrhage

Patients with intracerebral haematomas (ICH) secondary to aneurysmal bleeds usually have a poor prognosis or die if treated conservatively. Younger patients with rupture of a middle cerebral artery (MCA) aneurysm and temporal haematomas have the potential to return to useful life. They should be assessed separately from other subarachnoid haemorrhage (SAH) patients and considered for emergency surgery. Seven such cases are presented, five made an acceptable recovery. The experience of other units as represented in the literature is considered.