Urinary cyclic nucleotides and the cytopathology of human uterine cervical dysplasias.

Blinded urinary assays for cyclic guanosine 3':5'-monophosphate (cGMP) and cyclic adenosine 3':5'-monophosphate (cAMP) were performed on 49 subjects with documented abnormal cervical cytology and 21 control subjects with normal cytology. A significant difference in the mean cGMP:cAMP ratios between the case and control groups was found. A significantly greater proportion of women with cytological abnormalities had a cGMP:cAMP ratio above the 0.2 level (p less than 0.001). Cases treated surgically for severe dysplasia or carcinoma in situ of the cervix revealed a significant postsurgical fall in the cGMP:cAMP ratios (p less than 0.025). The possibility of utilizing urinary ratios of cyclic nucleotides as an objective index in the detection, monitoring of progression, and therapy of preneoplastic cervical lesions is discussed.

Influence of vitamin A on cervical dysplasia and carcinoma in situ.

A case-control study was undertaken to determine the dietary intake of vitamin A in women having abnormal uterocervical cytology. The study groups (87 cases and 82 controls) were drawn from a population of women who received a screening Pap test in the ambulatory health care section of a large municipal hospital center. A subset of cases (with abnormal cytology) were matched to controls for age, ethnicity, socioeconomic status, and parity. Nutrient intake and retinol binding protein concentrations were determined; epidemiological data were also obtained. It was found that the subset of cases with severe dysplasia or carcinoma in situ (CIS) were more likely to have a total dietary vitamin A intake below the pooled median (3,450 IU) and/or a beta-carotene intake below the pooled median (2,072 IU) than were normal controls (p less than 0.05 and p less than 0.025, respectively). Odds ratios revealed approximately a 3-fold greater risk for severe dysplasia or CIS in women with lowered vitamin A or beta-carotene intake. In addition, retinol binding protein was either absent or undetectable in 78.8% of the dysplastic tissue samples, versus 23.5% of the normal tissue samples (p less than 0.005).

Retinoids and the prevention of cervical dysplasias.

Women with abnormal cytology were matched with normal control subjects for age, parity, ethnicity, and socioeconomic class and participated in a blind case-control study focused on the role of nutrition in cervical dysplasia. Sucrose gradient ultracentrifugation studies for determination of the presence and concentration of the binding proteins for retinol and retinoic acid were performed on colposcopic biopsy tissue specimens. The nutritional survey revealed statistically significant differences for vitamins A and C and beta carotene. Retinol binding protein was absent or minimally detectable and inversely related to the severity of the dysplasia. It is proposed that a double-blind clinical trial be conducted to evaluate whether retinoids may pharmacologically inhibit, arrest, or reverse cervical dysplasia.

Plasma vitamin C and uterine cervical dysplasia.

Plasma concentrations of vitamin C were determined in a case-control study of women (n = 80) who had sought a Papanicolaou test in the Bronx Municipal Hospital Center. Controls (n = 34) were women having negative cytologic tests, negative colposcopic findings, and no known gynecologic dysfunction. Cases (n = 46) were defined as women who had either one positive or two consecutive suspicious Papanicolaou smears in a 12-month period. The mean concentration of vitamin C in the plasma was significantly lower in the cases than in the controls (0.36 versus 0.75 mg/dl, p less than 0.0001). Cases were further stratified according to the histopathologic diagnosis. The data direct attention to a possible etiologic association of vitamin C in human cervical epithelial abnormalities. A clinical trial with vitamin C intervention is suggested.

Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain.

We conducted a study of the safety of controlled-release (CR) oxycodone tablets (OxyContin Tablets) administered chronically to patients with cancer-related pain in a usual clinical setting. These patients had participated in 1 of 2 double-blind, active-control studies. Our study was an open, 3-month treatment study that included 87 patients. Patients received CR oxycodone tablets every 12 hr in a manner that reflected typical clinical practice. Supplemental immediate-release (IR) oxycodone was available PRN for breakthrough pain. Patients recorded medication use, adverse events, and evaluations of pain intensity and acceptability of therapy in a daily diary. Forty-four patients (51%) completed all 12 weeks of study; 43 patients (49%) discontinued participation. At baseline and throughout the study period, the overall mean pain-intensity score was slight to moderate. A comparison of initial and final doses showed a significant but modest increase in total daily CR oxycodone dose. An increase or decrease in titration of the oxycodone dose occurred for 66 patients (84%) at least once during the 12-week study period, primarily for increased pain. Forty-four patients (56%) did not undergo dose titration when the latter was indicated. Half of the patients used IR oxycodone rescue almost daily; the mean number of rescue doses per day was 1.5. Despite stable pain control and an increasing total daily CR oxycodone dose, the percentage of patients reporting common opioid-related adverse events decreased over the course of the study. CR oxycodone tablets administered every 12 hr were successfully used to manage cancer pain over a 12-week period. Importantly, side effects diminished over time without a concomitant change in efficacy.