Diketo compounds with (trifluoromethyl)trimethylsilane: double nucleophilic trifluoromethylation reactions.

Reactions of various diketo compounds with (trifluoromethyl)trimethylsilane (Me3SiCF3) in the presence of catalytic amounts of cesium fluoride have been studied. gamma-Ketoesters, CH3COCH2CH2CO2R (R = Et, Bu), were reacted with 2 equiv of Me3SiCF3 at room temperature to give CH3C(OH)(CF3)CH2CH2COCF3 in good yield after hydrolysis. alpha-Diketones, R1COCOR2 (R1 = R2 = Ph; R1 = Ph, R2 = Me; R1 = R2 = Me; R1 = Me, R2 = Et), when reacted with Me3SiCF3, formed 1:1 or 1:2 addition products depending on the reaction conditions and stoichiometry used. Reactions of diones CH3COXCOCH3 (X = -CH2CH2-, -C6H4C6H4-, -CH2-) with Me3SiCF3 also led to the formation of the mono- or diaddition products depending on reaction conditions. With various kinds of substituted arylglyoxals, 2 equiv of Me3SiCF3 produced monoaddition products in 70-75% yield and diaddition products in 5-10% yield. One of the monoalcohols and two of the diols have been characterized by single-crystal X-ray analysis, and the presence of inter- and intramolecular hydrogen bonding has been confirmed.

Phase II North Central Cancer Treatment Group study of 2-cholorodeoxyadenosine in patients with recurrent glioma.

There is no standard treatment for patients with recurrent gliomas, and their prognosis remains poor. 2-Chlorodeoxyadenosine is a purine analogue that has significant activity in many low-grade lymphoproliferative disorders. The authors conducted a phase II study to determine the efficacy of 2-chlorodeoxyadenosine in patients with recurrent gliomas. Patients with a histologically confirmed primary brain tumor with evidence of progression after radiation therapy were eligible. Protocol treatment consisted of 2-chlorodeoxyadenosine 7.0 mg/m2 intravenously on days 1 through 5 every 28 days. For those with a history of prior nitrosourea therapy, the dose of 2-chlorodeoxyadenosine was reduced to 5.6 mg/m2 on days 1 through 5. Treatment was continued until progression or a maximum of 12 cycles. Fifteen patients with recurrent astrocytomas or oligoastrocytomas of all grades were entered in the study. Treatment was well tolerated. Major toxicities were myelosuppression and neurotoxicity. No responses were seen. The authors conclude that although 2-chlorodeoxyadenosine is well tolerated, no demonstrable activity in patients with recurrent gliomas was established.

Prospective evaluation of a chamomile mouthwash for prevention of 5-FU-induced oral mucositis.

BACKGROUND: Stomatitis has been found to be a major dose-limiting toxicity from bolus 5-fluorouracil-based (5-FU) chemotherapy regimens, despite the use of oral cryotherapy. Pursuant to preliminary data which suggested that a chamomile mouthwash might ameliorate this toxicity, a prospective trial was developed to test chamomile in this situation. METHODS: A Phase III, double-blind, placebo-controlled clinical trial was designed. Patients were entered into the study at the time of their first cycle of 5-FU-based chemotherapy. All patients received oral cryotherapy for 30 minutes with each dose of 5-FU. In addition, each patient was randomized to receive a chamomile or placebo mouthwash thrice daily for 14 days. Stomatitis scores were determined by health care providers and by patients themselves. RESULTS: There were 164 evaluable and well-stratified patients equally randomized to both treatment groups. There was no suggestion of any stomatitis difference between patients randomized to either protocol arm. There was also no suggestion of toxicity. Subset analysis did reveal unsuspected differential effects between males and females that could not be explained by reasons other than chance. CONCLUSION: The resultant data from this clinical trial did not support the prestudy hypothesis that chamomile could decrease 5-FU-induced stomatitis.

Inhibition of 5-fluorouracil-induced ocular irritation by ocular ice packs.

BACKGROUND: This clinical trial was developed to determine whether ocular ice pack therapy would decrease 5-fluorouracil (5-FU)-induced ocular toxicity. METHODS: Sixty-two patients who suffered from 5-FU-induced ocular toxicity, and were scheduled to receive another cycle of the chemotherapy that caused the ocular toxicity, were entered in this clinical trial. A randomized, crossover design was used, with patients documenting their ocular toxicity by the use of daily diaries. RESULTS: The results from the first cycle of treatment suggested that ocular ice pack therapy decreased 5-FU-induced ocular toxicity (P = 0.056). The 38 evaluable patients in the crossover analyses demonstrated decreased ocular toxicity with ocular ice pack therapy (p = .001). The ocular ice pack therapy was well tolerated by most of the study participants. CONCLUSION: Ocular ice pack therapy appears to lessen 5-FU-induced ocular toxicity to a clinically moderate degree. Better methods for decreasing 5-FU-induced ocular toxicity are necessary.

Results of innominate osteotomy in the treatment of Legg-Calvé-Perthes disease.

Twenty-seven patients with Legg-Calve-Perthes disease were treated by innominate osteotomy. Satisfactory results were achieved in 96% of the patients, with a mean follow-up period of 9.3 years. Eleven patients included in assessment seven years previously were reassessed. Ten of these 11 patients showed improvement with continued growth in the shape of the affected femoral heads. A preoperative center-edge angle of less than 20 degrees is of prognostic importance. The presence or absence of a subchondral fracture before and at the time of surgery has not been found to influence the long-term results significantly.

Growth disturbance in Legg-Calvé-Perthes disease and the consequences of surgical treatment.

Seventy-two patients with Legg-Calvé-Perthes disease were studied to assess the interference with proximal femoral growth as a result of the disease itself and of surgical treatment. Twenty-five patients were treated nonoperatively, 20 were treated by femoral varus derotation osteotomy, and 27 by innominate osteotomy. All patients were studied clinically for evidence of abductor weakness and leg-length discrepancy. They were also studied roentgenographically for evidence of femoral head deformity and trochanteric overgrowth. The overall results showed a 6% incidence of leg-length discrepancy greater than 2 cm after both operative and nonoperative treatment. The articulo-trochanteric distance (ATD) was less than +5 mm in 23% of patients, of which 43% had a positive Trendelenburg sign. A significantly lower mean ATD was found in patients treated by femoral varus osteotomy, which should be avoided in patients over eight years of age. The study also demonstrated a strong association between coxa magna and growth disturbance of the proximal femoral physis manifesting itself as either a leg-length discrepancy or as a low ATD. The significant effects of growth disturbance after treatment must be considered, as well as the sphericity of the healed femoral head, in the final assessment in Legg-Calvé-Perthes disease.

Three-dimensional imaging of a juvenile Tillaux fracture.

The juvenile Tillaux fracture is an injury involving the articular surface of the ankle joint. The fracture sometimes requires open reduction and internal fixation. The decision to adopt an operative or nonoperative policy in each case can only be made with precise imaging of the anatomy which can be provided by three-dimensional reformation of computed tomography (CT) scanning.

Incidence of Vibrio cholerae from estuaries of the United States West Coast.

The incidence of Vibrio cholerae in shellfish, sediment, and waters of California, Oregon, and Washington was determined during the summer of 1984. Samples from 24 distinct estuaries were analyzed qualitatively. V. cholerae non-O1 was found in 23 estuaries and in 44.6% of the 529 samples examined. V. cholerae O1 Inaba was isolated from water samples in Morro Bay, Calif. Vibrio mimicus was found in 2.3% of the samples. Cholera enterotoxin was not found in cell-free filtrates of the 100 isolates tested in the Y-1 mouse adrenal cell assay, but heat-labile cytotoxic activity was observed with 3% of the isolates.

Virulent strains of Vibrio vulnificus isolated from estuaries of the United States West Coast.

Vibrio vulnificus was isolated from United States West Coast estuaries at a low frequency (5.9%) from 529 samples of water, shellfish, and sediment. Four strains tested with iron-treated mice had 50% lethal dose values ranging from 7.6 to 360 CFU, compared with a 50% lethal dose of 4.9 CFU for a clinical isolate that caused the death of a septicemic patient. The presence of this pathogen may be a hazard to users of marine beaches and consumers of raw shellfish on the West Coast, especially to persons most susceptible to V. vulnificus septicemia. Species-specific antiflagellar serum and a gene probe for cytotoxin-hemolysin production were useful for screening these environmental isolates.

Hepatic injury after whole-liver irradiation in the rat.

Radiation-induced hepatic injury in rats, which is characterized by marked ascites accompanied by liver necrosis, fibrosis, and vein lesions, is described in this study. These adverse sequelae are produced within 30 days after irradiation if there is surgical removal of two-thirds of the liver immediately after whole-liver irradiation. The LD50/30 day and median survival time after liver irradiation and two-thirds partial hepatectomy is 24 Gy and 17 days, respectively. Death is preceded by reduction in liver function as measured by [131I]-labeled rose bengal clearance. Prior to death, liver sepsis and endotoxemia were detected in most irradiated, partially hepatectomized animals. Pretreatment of the animals with endotoxin and/or antibiotic decontamination of the GI tract, which increase the host resistance to infection and endotoxemia, resulted in increased survival time, but no irradiated, partially hepatectomized animal survived beyond 63 days. The combination of these treatments resulted in additive effects leading to 38% survival at 100 days. These treatments did not, however, prevent the eventual development of radiation-induced liver pathology. This suggests that sepsis and endotoxemia resulting from the bacteria in the intestine are the immediate cause of death after 30-Gy liver irradiation and partial hepatectomy. It is concluded that the hepatectomized rat model is an economical and scientifically manageable experimental system to study a form of radiation hepatitis that occurs in compromised human livers.

Alpha heavy-chain disease presenting as goiter.

A patient with alpha heavy-chain disease (alpha HCD) originally had presented with a goiter from an extramedullary plasmacytoma. Alpha HCD was diagnosed by both standard laboratory procedures and high-resolution two-dimensional gel electrophoresis. The fragment of the alpha chain had a molecular weight of 38,000 and consisted of seven major charge forms, with an isoelectric point range of 5.2-5.6. Since alpha HCD usually involves the gastrointestinal tract, the thyroidal involvement in this case is unusual.