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J W Weaver

Publications and source records attributed to J W Weaver.

8 recordsLinked to original sources

High-dose trimetrexate and minimal-dose leucovorin: a case for selective protection?

Our objective was to find the minimum dose of leucovorin (LV; 5-formyltetrahydrofolate) needed to potentially provide selective protection of normal tissue in patients with tumors resistant to methotrexate (MTX) by virtue of transport during prolonged therapy with high-dose trimetrexate (TMTX). Based upon the known daily requirement for folate, that tumors are often resistant to methotrexate via a transport-based mechanism, and that large doses of trimetrexate can be given with large doses of leucovorin for the treatment of patients with Pneumocystis carinii, a protocol was designed to find the minimum LV dose required to allow the administration of large doses of TMTX. Patients were treated in 28-day cycles consisting of 14 consecutive days of oral TMTX (45 mg/m2 every 12 h), followed by 14 days of rest. The dose of concurrent LV was started at 5 mg/m2 twice daily. Cohorts of patients received successive half doses of LV so long as three consecutive patients had less than or equal to grade 3 toxicity. Ten patients received 29 courses of therapy. The most common toxicities encountered were thrombocytopenia (38%), mucositis (14%), and neutropenia (10%). At a LV dose of 2.5 mg/m2, toxicities were consistently limited to less than or equal to grade 3 and only one episode of grade 4 hematological toxicity. Although there was marked interpatient variability, the minimally effective LV dose for selective protection seems to be 2.5 mg/m2. If tumors are resistant to methotrexate because of decreased transport of drug (and also folate), then the same pharmacological principle used to develop TMTX/LV for the treatment of P. carinii may be applied to treatment of some patients with cancer.

Adolescent↗

Effect of non-target cells on the sensitivity of the PCR for Escherichia coli O157:H7.

The sensitivity of a multiplex PCR for the virulence factors VT1, VT2 and eaeA specific for enterohaemorrhagic Escherichia coli (target cells, T) was adversely affected when non-pathogenic E. coli (non-target, NT) cells were present. In the absence of NT cells the sensitivity, obtained by decimally diluting the T cell culture, was T-10 (< 10 cfu ml-1) for eaeA and VT2, and T-5 (ca 10(4) cfu ml-1 T) for VT1 virulence factors. When approximately 10(9) cfu ml-1 NT cells (NT0 dilution) were present, the sensitivity dropped to T-1, T-3 and T-1 (ca 10(7), 10(6) and 10(8) cfu ml-1 T) for eaeA, VT2 and VT1, respectively. At NT-1 (ca 10(8) cfu ml-1 NT) or higher dilutions the sensitivity of eaeA and VT2 was the same as when no NT cells were present. In respect of VT1 the sensitivity gradually increased until at NT-4 the sensitivity was the same as when NT cells were completely absent. This work indicates that caution should be exercised when interpreting PCR results particularly when substantial non-target cell populations are suspected.

Adhesins, Bacterial↗

Webs of the lower esophagus: a complication of gastroesophageal reflux?

Seven patients with webs within 6 cm of the gastroesophageal junction were identified from 5109 barium studies of the esophagus covering a 10-year period (incidence, 0.14%). These webs were clearly distinct from the B-ring at the gastroesophageal junction itself. Demographic, social, and clinical factors for these patients are reviewed and compared with those of 26 cervical-web patients diagnosed in the same 10-year period, 26 control thoracic esophagogram patients and 26 control cervical esophagogram patients. Five of the seven patients with lower esophageal webs had gastroesophageal reflux.

Adult↗

Computed tomography of uterine papillary serous carcinoma.

We describe the CT appearances of a fairly commonly encountered "special variant" carcinoma of the uterine corpus called uterine papillary serous carcinoma ( UPSC ). UPSC closely resembles ovarian papillary serous carcinoma microscopically but CT with contrast can differentiate between these two entities. In addition CT in this patient clearly showed the characteristic spread mode of this particularly aggressive form of endometrial carcinoma. Because UPSC has a significantly higher relapse rate than other histologic types of endometrial carcinoma it is important to recognize it at the time of the CT staging procedure. The spread pattern of UPSC suggests the need for adjuvant irradiation or chemotherapy.

Aged↗