Reproductive Toxicity of Sulfamethazine in Swiss CD-1 Mice during Continuous Breeding

Sulfamethazine (SMZ) was evaluated for reproductive toxicityin Swiss CD-1 mice using a continuous breeding protocol. SMZwas administered in the diet at 0, 0.25, 0.5, or 1% (w/w), whichrepresented an average daily intake of 0, 313, 625, or 1250mg SMZ/kg/day, respectively. Exposure of F0 male and femalemice to 1% SMZ for 126 days resulted in a significant decreasein the mean number of live pups per litter and the number oflitters produced (task 2); the percentage pups born alive to1% SMZ females showed a nonsignificant decrease versus controlfemales. The effects on fertility were rapid to onset (1 to4 weeks) and cumulative in nature. F0 male and female body weightswere slightly depressed from 3 weeks to the end of the study.The crossover mating trial (task 3) revealed that the adverseeffect on ferility involved both treated partners in that littersize decreased when either 1% SMZ males were bred to controlfemales or 1% SMZ females were mated with control males. Afterapproximately 155 days of exposure of F0 mice to 1% SMZ, theterminal body weight of 1% SMZ females was significantly decreasedand that of 1% SMZ males showed a nonsignificant decrease. Inaddition, the liver weight to body weight ratio of the maleswas increased. Further, the prostate and seminal vesicle weightto body weight ratios were decreased in 1% SMZ males relativeto control males. No treatment-related gross or histopathologicallesions were noted for the pituitary or reproductive organsof either sex. Sperm assessment indicated no significant differencein the epididymal sperm concentration or percentage motile orabnormal sperm. In conclusion, SMZ was found to be a reproductivetoxicant in the male and female Swiss CD-1 mouse, albeit atrelatively high dietary intake (1250 mg/kg/day), and in thepresence of mild systemic toxicity.     

Phase II study of intravenous melphalan (NSC-8806) in the treatment of patients with advanced squamous carcinoma of the head and neck

The Illinois Cancer Center entered 25 patients on a phase II trial of intravenous melphalan treating patients with recurrent, metastatic or locally advanced and inoperable squamous cell carcinoma of the head and neck. All patients had bi-dimensionally measurable disease, at least a sixty day life expectancy, and adequate performance status (ECOG scale 2). All patients except one had received prior radiotherapy, chemotherapy or both. Melphalan dosage was 30 mg/m² every three weeks. Twenty-four patients were evaluable for response. One patient with laryngeal carcinoma had a clinical complete response of a nodal metastasis. Four patients had stabilization of disease for one to three months. There was formidable toxicity, including neutropenia (ANC < 1000/l 36%), and thrombocytopenia (< 50,000/l 32%). There were no drug-related deaths. Melphalan administered intravenously does not appear to be efficacious therapy in patients with previously treated advanced head and neck squamous carcinomas.     

Rarity of CDK4 germline mutations in familial melanoma

To date, two genes have been implicated in melanoma pathogenesis. The first, CDKN2A, is a tumour suppressor gene with germline mutations detected in 20% of melanoma-prone families. The second, CDK4, is an oncogene with co-segregating germline mutations detected in only three kindreds worldwide. We examined 16 American melanoma-prone families for mutations in all coding exons of CDK4 and screened additional members of two previously reported families with the Arg24Cys germline CDK4 mutation to evaluate the penetrance of the mutation. No new CDK4 mutations were identified. In the two Arg24Cys families, the penetrance was estimated to be 63%. Overall, 12 out of 12 invasive melanoma patients, none out of one in situ melanoma patient, five out of 13 dysplastic naevi patients, two out of 15 unaffected family members, and none out of 10 spouses carried the Arg24Cys mutation. Dysplastic naevi did not strongly co-segregate with the Arg24Cys mutation. Thus the phenotype observed in melanoma-prone CDK4 families appears to be more complex than just the CDK4 mutation. Both genetic and environmental factors are likely to contribute to the occurrence of melanoma and dysplastic naevi in these families. In summary, although CDK4 is a melanoma susceptibility gene, it plays a minor role in hereditary melanoma.     

Infant communicating hydroceles—do they need immediate repair or might some clinically resolve?

Purpose

Infant hydroceles that are communicating by history (fluctuation in size) or examination (reducible fluid) are often repaired soon after presentation. We have followed a series of infant boys with such hydroceles and reviewed their early natural history.

Materials and Methods

Since 1998, we have followed 174 infant boys presenting with an apparent communicating hydrocele without immediate surgical repair. All boys were initially seen before 18 months of age and most (168) by 12 months. Most had been full term at delivery, although 32 had been premature (<37 weeks' gestational age) and 11 extremely so (<32 weeks). Most boys (120) had bilateral hydroceles at presentation.

Results

Of the 110 boys followed to disposition, 69 (62.7%) had complete resolution without surgery by a mean age of 11.7 months. Forty-one patients (37.3%) underwent surgery for correction at a mean age of 14 months because of persistence in size or development of a hernia. Six developed a hernia during observation, none of whom had any episode of incarceration. Only 2 patients with apparent resolution subsequently had recurrence with a hernia. Age at presentation and gestational age at birth showed no effect on resolution. The hydroceles of 64 boys had improved in size after a mean follow-up of 13.9 months when last seen.

Conclusions

Many infant hydroceles that are communicating by history or examination do resolve clinically without surgery and deserve observation. Progression to hernia was rare in our experience and did not result in incarceration. Consequently, little risk is taken by initial observation.     

The radiologic evaluation of tinnitus

Tinnitus (“ringing in the ears”) is a prevalent symptom in the general population, and often brings patients to medical attention. Many causes of tinnitus are evident radiographically. The most frequently-encountered causes of tinnitus are discussed, and imaging recommendations are provided.