ARS Presidential Address: Estrogen therapy: a causal role in endometrial cancer?

Publicity associated with recent reports of a greater frequency of adenocarcinoma of the endometrium among women who take exogenous estrogens has created confusion among physicians and fear among patients. An objective review of available data on estrogen effects and current epidemiologic evidence suggests that estrogen may play an indirect role in the development of endometrial carcinoma. Until definitive data are available, physicians should exercise caution in prescribing estrogens, monitoring the status of the endometrium at regular intervals by sampling and pathologic analysis.     

Cyclic changes of cervical mucus enzymes related to the time of ovulation. I. Alkaline phosphatase

The concentration of alkaline phosphatase in cervical mucus was serially determined during a menstrual cycle in five normal ovulatory women and correlated with the time of ovulation as monitored by the basal body temperature and radioimmunoassay of serum lutenizing hormone (LH), progesterone, and estradiol. The activity of alkaline phosphatase decreased significantly at midcycle just prior to the LH surge and began to rise after ovulation. Self-detection of cervical mucus alkaline phosphatase may provide a practical method of ovulation prediction.     

Crystallization of Mesoscopic Colloids into 3D Opaline Lattices in Packing Cells Fabricated by Replica Molding

Replica molding against an elastomeric mold has been used to fabricate packing cells to be used for the crystallization of mesoscopic, spherical colloids into three‐dimensionally ordered arrays over relatively large areas. The capability and feasibility of this method have been demonstrated by the production of homogeneous, opaline lattices of 255 or 467 nm polystyrene beads over areas as large as ∼0.5 cm². These 3D crystalline lattices of mesoscopic colloids are useful for fabricating new types of diffractive optical components, for producing porous materials, and for generating photonic bandgap structures. We believe the demonstration of a replica molding procedure for the fabrication of the packing cells should make the crystallization method more useful to those who have no direct access to clean‐room facilities.     

Comparison of fluconazole pharmacokinetics in serum, aqueous humor, vitreous humor, and cerebrospinal fluid following a single dose and at steady state

The objective of this study was to characterize the pharmacokinetic parameters and penetration of fluconazole following a single dose in the serum, aqueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacokinetic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, vitreous humor and CSF samples were taken 15 minutes after the initial intravenous injection and hourly thereafter for six hours. Fluconazole concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concentrations were noted in all compartments. While mean concentrations in each anatomical compartment were similar in animals receiving a single dose or among those at serum steady state, the mean concentrations achieved in the serum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times higher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetration of fluconazole into the noninflamed aqueous and vitreous humors and CSF were > or = 70%. The CSF and ocular pharmacokinetic parameters closely resembled each other, so that either could be used as a surrogate for the other.     

Effects of elevated concentrations of prostaglandin F2 alpha on pregnancy rates in progestogen supplemented cattle

An experiment was performed to determine the effect of elevated prostaglandin F2 alpha (PGF2 alpha) on pregnancy rates of progestogen-treated bred cows in the presence or absence of luteal tissue. Ninety-one beef cows were bred (Day 0) and assigned randomly to receive either 3 mL saline (CON), 15 mg PGF2 alpha, or 15 mg PGF2 alpha + lutectomy (P + L) administered intramuscularly (i.m.) at 8 h intervals on either Days 5-8, 10-13, or 15-18 postbreeding. Lutectomies were performed by transrectal digital pressure before initiation of treatment on Day 5, 10, or 15 for the respective treatment groups. All cows were fed 4 mg/day of melengesterol acetate from two days prior to initiation of treatment until Day 30 postbreeding. Mean concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) were increased in cows administered PGF2 alpha and P + L treatments (398 +/- 23 and 413 +/- 22 pg/ml, respectively; p < 0.01) compared to the CON group (80 +/- 29 pg/ml) regardless of treatment group. Mean concentrations of oxytocin (OT) were increased in cows given PGF2 alpha on Day 10 and 15 (p < or = 0.0001) and tended to be increased on d 5 when compared to CON and P + L treatment groups on Day 5. Pregnancy rates were reduced (p < or = 0.03) in the PGF2 alpha treatment group (23%) and by Day 5-8 compared to CON (72%). Lutectomy tended to improve pregnancy rate in P + L (5-8; 55%) compared to PGF2 alpha (5-8; p = 0.1). Pregnancy rates tended (p < or = 0.07) to increase in the PGF2 alpha treatment groups on Days 5-8 treatment (23%, 50%, and 60% for Days 5-8, 10-13, and 15-18, respectively). The later the treatments were initiated pregnancy rates did not differ between treatments given on Days 10-13 and 15-18. In conclusion, the most susceptible period of embryonic growth to the negative effects of PGF2 alpha was during morula to blastocyst development. Removal of luteal tissue diminishes the negative effects of PGF2 alpha through interruption of the luteal oxytocin-uterine PGF2 alpha feedback loop.     

Effect of the extramitochondrial adenine nucleotide pool size on oxidative phosphorylation in isolated rat liver mitochondria

We report a long-term follow-up of abduction-extension osteotomy of the first metacarpal, performed for painful trapeziometacarpal osteoarthritis. Of a consecutive series of 50 operations, 41 thumbs (82%) were reviewed at a mean follow-up of 6.8 years. Good or excellent pain relief was achieved in 80%, and 93% considered that surgery had improved hand function, while 82% had normal grip and pinch strength, with restoration of thumb abduction. Metacarpal osteotomy was equally successful in relieving symptoms of those with early (grade 2) and moderate (grade 3) degenerative changes. This simple procedure provides lasting pain relief, corrects adduction contracture and restores grip and pinch strength, giving good results with few complications.     

Endotoxin release and cytokine production in acute and chronic meningococcaemia

Muscle activity produces an electrical signal termed the myo-electric signal (MES). The MES is a useful clinical tool, used in diagnostics and rehabilitation. This signal is typically stored in 2 bytes as 12-bit data, sampled at 3 kHz, resulting in a 6 kbyte s-1 storage requirement. Processing MES data requires large bit manipulations and heavy memory storage requirements. Adaptive differential pulse code modulation (ADPCM) is a popular and successful compression technique for speech. Its application to MES would reduce 12-bit data to a 4-bit representation, providing a 3:1 compression. As, in most practical applications, memory is organised in bytes, the realisable compression is 4:1, as pairs of data can be stored in a single byte. The performance of the ADPCM compression technique, using a real-time system at 1 kHz, 2 kHz and 4 kHz sampling rates, is evaluated. The data used include MES from both isometric and dynamic contractions. The percent residual difference (PRD) between an unprocessed and processed MES is used as a performance measure. Errors in computed parameters, such as median frequency and variance, which are used in clinical diagnostics, and waveform features employed in prosthetic control are also used to evaluate the system. The results of the study demonstrate that the ADPCM compression technique is an excellent solution for relieving the data storage requirements of MES both in isometric and dynamic situations.