Caffeine may disrupt the impact of real-time drowsiness on cognitive performance: a double-blind, placebo-controlled small-sample study.

Caffeine is widely used to promote alertness and cognitive performance under challenging conditions, such as sleep loss. Non-digestive modes of delivery typically reduce variability of its effect. In a placebo-controlled, 50-h total sleep deprivation (TSD) protocol we administered four 200 mg doses of caffeine-infused chewing-gum during night-time circadian trough and monitored participants' drowsiness during task performance with infra-red oculography. In addition to the expected reduction of sleepiness, caffeine was found to disrupt its degrading impact on performance errors in tasks ranging from standard cognitive tests to simulated driving. Real-time drowsiness data showed that caffeine produced only a modest reduction in sleepiness (compared to our placebo group) but substantial performance gains in vigilance and procedural decisions, that were largely independent of the actual alertness dynamics achieved. The magnitude of this disrupting effect was greater for more complex cognitive tasks.

Effect of ongoing inflammation in rheumatoid arthritis on P-wave dispersion.

It has been emphasized recently that there is a strong association between atrial fibrillation and inflammation. Rheumatoid arthritis (RA), characterized by ongoing inflammatory activity, can increase the risk of atrial arrhythmia. P-wave dispersion has been encountered as a risk factor for atrial fibrillation and the effect of inflammation on P-wave dispersion has not been studied thoroughly. The aim of this study was to examine the effect of ongoing inflammatory activity in RA on P-wave dispersion. The study comprised 82 patients diagnosed with RA and 41 healthy volunteers as controls. Systolic functions of all participants were evaluated by echocardiography. Maximum P-wave duration and dispersion were calculated and found to be significantly increased in the RA group compared with the healthy controls. These parameters were also significantly correlated with C-reactive protein levels. The findings of this study suggest that RA may be associated with increases in P-wave dispersion and maximum P-wave duration, and that this association may result from ongoing inflammation.

Estradiol/progesterone substitution in the luteal phase improves pregnancy rates in stimulated cycles--but only in younger women.

Innumerable studies have attempted to demonstrate that hormonal support of the luteal phase during ovulation induction cycles improves pregnancy rates. None has, however, so far been able to confirm the validity of such treatment conclusively, possibly because most studies only utilized progesterone substitution. Since luteal phase endometrium also requires estradiol support, this study attempted to investigate whether hormone substitution with progesterone and estradiol would be more successful in improving pregnancy rates. Amongst approximately 7500 consecutive ovulation induction cycles were identified prospectively which were characterized by a precipitous drop of luteal phase serum estradiol levels by more than 50% over a 48 hour period within 10 days from hCG administration. Those cycles were prospectively randomized to oral micronized estradiol substitution (Group I) or not (Group II), while both groups received routine progesterone substitution of the luteal phase. Cycles were then evaluated in regards to the occurrence of chemical, ectopic and clinical pregnancies. One hundred sixty-three Group I cycles resulted in 34 pregnancies (20.9%), which compared favorably to 21 pregnancies in 167 Group II patients (12.6%) (x2[1] = 4.06; p < 0.04). The advantage for Group I cycles (29/95 pregnancies, 31%) vs. Group II cycles (16/105, 15%) became even more pronounced when only women up to age 35 years were evaluated. Estradiol substitution maintained a significant advantage until age 38 (x2 [1] = 6.87; p < 0.009). While gravidity did not affect pregnancy success, estradiol substitution in Group I benefited nulliparous (23% pregnancy rate) over multiparous women (12% pregnancy rate) (x2 [2] = 6.86; p< 0.03). This association was, however, age-dependent. A combined estradiol and progesterone substitution of the luteal phase of ovulation induction cycles increases the overall pregnancy rate. Since estradiol substitution was initiated in this study only once a precipitous drop in serum estradiol levels had already taken place, an even larger improvement in pregnancy rates could conceivably be possible if earlier estradiol substitution of the luteal phase is initiated. A further expansion of investigations of similar protocols for routine ovulation induction and in vitro fertilization (IVF) cycles may be indicated, especially in women below age 38 years and in nulliparous females.

Prospective randomized trial comparing the outcome and cost of in vitro fertilization with that of a traditional treatment algorithm as first-line therapy for couples with infertility.

OBJECTIVE: To determine whether IVF or a standard infertility treatment algorithm results in better outcome and/or lower cost when used as first-line therapy for couples with infertility. DESIGN: Prospective, randomized clinical study. SETTING: University-affiliated infertility clinic. PATIENT(S): Couples with newly diagnosed infertility and no prior treatment. INTERVENTION(S): Couples were randomized to undergo either IVF (group 1, n = 46) or a standard infertility treatment algorithm (group 2, n = 50) as initial therapy for infertility. MAIN OUTCOME MEASURE(S): Pregnancy rates and costs per couple, per month of treatment, and per pregnancy. RESULT(S): Pregnancy rates were higher in group 2 than in group 1. Costs per couple were not statistically different, although a trend toward higher costs was apparent in group 1, reflected by a higher median cost per clinical pregnancy established and a higher cost per month of treatment. Whereas cost differences between the groups diminished over time, pregnancy rates remained the same. CONCLUSION(S): In vitro fertilization currently does not represent an appropriate first-line treatment option for couples with infertility. The use of a standard infertility treatment algorithm results in a higher pregnancy rate and lower cost and therefore should be the preferred treatment approach.

What is the radiation exposure to patients during a gynecoradiologic procedure?

OBJECTIVE: To evaluate the risk of radiation exposure to infertility patients during a gynecoradiologic procedure. DESIGN: Retrospective clinical study. SETTING: Medical school-affiliated infertility center. PATIENT(S): Three hundred thirty-two consecutive infertility patients undergoing a gynecoradiologic procedure. INTERVENTION(S): Patients underwent a gynecoradiologic procedure as part of their infertility workup and the fluoroscopic exposure time was analyzed. MAIN OUTCOME MEASURE(S): The fluoroscopic exposure (rad time) during gynecoradiologic procedures, including hysterosalpingogram (HSG), selective salpingography, tubal catheterization, and others. RESULT(S): The rad time (mean +/- SD) was 63 +/- 54 seconds for normal HSG (n = 94, range 17 to 404 seconds), 100 +/- 61 seconds for abnormal HSG (n = 53, range 28 to 272 seconds), 111 +/- 57 seconds for unilateral selective salpingography (n = 36, range 31 to 324 seconds), 142 +/- 74 seconds for bilateral selective salpingography (n = 87, range 40 to 430 seconds), 176 +/- 77 seconds for unilateral tubal catheterization (n = 27, range 70 to 342 seconds), and 239 +/- 82 seconds for bilateral tubal catheterization (n = 30, range 110 to 381 seconds). Five patients had other procedures, such as lysis of intrauterine adhesions (n = 2) and resection of an uterine septum (n = 3), for which the rad time was in a range of 180 to 300 seconds. CONCLUSION(S): The radiation exposure of patients during a gynecoradiologic procedure, using previously described standard techniques, is well within established margins of safety.

Elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis.

OBJECTIVE: To investigate the possible etiologies of elevated tubal perfusion pressures. DESIGN: Analysis of 48 consecutive female patients with infertility who underwent laparoscopy and a gynecoradiological investigation as part of their infertility work-up. SETTING: Academically affiliated infertility center. INTERVENTIONS: A gynecoradiological investigation was performed using a previously reported standardized contrast injection system. Laparoscopy was performed routinely. RESULTS: Patients who demonstrated by laparoscopy to have endometriosis showed a significantly increased incidence of tubal blockage during initial hysterosalpingography (HSG) (12/26, 46.1%) compared with controls (2/14, 14.3%). Patients with endometriosis also demonstrated significantly more frequently elevated tubal perfusion pressures (22/26; 84.6%) than women without disease (2/14, 14.3%) and significantly higher mean tubal perfusion pressures than women with normal pelvises (576 +/- 264 versus 450 +/- 268 mm Hg). CONCLUSION: Tubal blockage during initial HSG and elevated tubal perfusion pressures during selective salpingography are highly suggestive of tubal endometriosis. These data are the first evidence that tubal involvement with endometriosis may be more frequent than previously suspected. They also suggest that the performance of a gynecoradiological investigation, inclusive of selective salpingography, can greatly contribute to a presumptive diagnosis of endometriosis.

A randomized prospective comparison between intrauterine insemination and fallopian sperm perfusion for the treatment of infertility.

OBJECTIVE: To determine if the pregnancy rates (PRs) in infertile women could be improved with fallopian sperm perfusion in comparison with IUI. DESIGN: Randomized prospective analysis. SETTING: Academically affiliated infertility center. PATIENTS: Consecutive patients undergoing controlled ovarian hyperstimulation (COH). INTERVENTIONS: After hCG administration, patients were randomized to either IUI or fallopian sperm perfusion. MAIN OUTCOME MEASURES: Pregnancy rates with the two treatment modalities. RESULTS: Of 240 COH cycles, those randomized to IUI included 44 clomiphene citrate (CC) (group I) and 76 gonadotropin (group III) cycles. Patients receiving fallopian sperm perfusion included 44 cycles of CC (group II) and 76 cycles of gonadotropin (group IV) treatment. The overall PRs per cycle (10.8% versus 10.8%) were similar for IUI and fallopian sperm perfusion, respectively. The PRs were also similar when compared for ovulation induction with CC (6.8% versus 9.1%) and gonadotropins (13.2% versus 11.8%). CONCLUSION: We conclude that fallopian sperm perfusion offers no advantage over IUI. Because the process of fallopian sperm perfusion is more time consuming and more costly (because of increased media usage), fallopian sperm perfusion does not seem indicated as a routine infertility therapy and should not replace IUI.

Gynaecoradiological uterine resection.

We assessed the feasibility of performing uterine surgery under fluoroscopic control in an ambulatory setting that does not require operating room time and general anaesthesia. Four uterine septae were resected and two cases of Asherman's syndrome were treated using fluoroscopically guided scissors. All six surgical procedures were successfully completed. Gynaecoradiological uterine resection (GUR) procedures, utilizing fluoroscopy guided scissors, are promising new techniques, which may allow the successful performance of uterine surgery in a cost effective ambulatory setting with no requirement of general anaesthesia.

The desire for multiple births in couples with infertility problems contradicts present practice patterns.

Paradoxically, the attitude of infertility patients towards multiple births has never been investigated. We therefore generated a survey by questionnaire, which was sent to 3800 consecutive unselected couples with infertility problems: 582 responses were received (15% response rate) and analysed. The percentage distribution of the responses to 21 questions, addressing attitudes towards and knowledge about the risk of multiple gestations, was the main outcome. Worry about multiple births was expressed, independent of the number of multiples, although fear about multiple conceptions was rejected by a large majority (64%). The risk of a twin birth was not strongly perceived, but the perception of risk increased with increasing numbers of multiples: triplets (50-62%), quadruplets or more (71-72%). A desire for the conception of twins was expressed by 67-90% of couples, a desire for the conception of triplets was equally expressed and rejected, and for a multiple gestation beyond triplets was rejected by 73-82% of couples. Patients were educated about the risks of selective embryo reduction and responded in a bimodal fashion to the option of utilizing this procedure, with equal numbers being willing to consider or reject it. Age, parity and length of infertility did not affect the couples' worry or fear about multiples. The desire for twins and triples, however, was correlated significantly with age (twins, P = 0.032; triplets, P = 0.03); there was no such correlation for larger multiples. The length of infertility was correlated with a positive attitude towards multiples beyond triplets (P = 0.029) but was not correlated with a desire for twins or triplets. Prior parity did not affect the attitude towards multiples at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the human gonadotroph free alpha-subunit secretory pools by administration of gonadotropin hormone-releasing hormone into normal subjects at different phases of the ovarian cycle.

The specificity of a monoclonal antibody RIA for the measurement of free alpha-subunit in plasma is presently documented. This RIA was used to explore the pituitary gonadotroph free alpha-subunit reserve in normal ovulating women stimulated with gonadotropin hormone-releasing hormone (GnRH). RIA specificity was established by means of competitive inhibition curves with various glycoprotein hormone preparations, and Sephadex G-100 exclusion chromatography of purified hFSH (1-2), hLH (LER 960) and pituitary extract. The 3.8% and 5.5% crossreactivities of hFSH 1-2 and hLH LER 960 were shown by exclusion chromatography to result in part from free alpha-subunit contamination in these purified preparations. Pituitary extract chromatography indicated hFSH and hLH cross-reactivity below 2.5% and 1.5%, respectively. Normal females were stimulated with GnRH throughout the cycle: 3 tests were performed on Day 7, 1 test on Day 13, 16, 17 and 22, respectively, and 2 tests on Day 24. GnRH stimulation consisted of an initial 100 micrograms bolus (time 0) followed at 2 h by a 12.5 micrograms/h constant infusion, and a second 100 micrograms bolus at 5 h. In all subjects, baseline free alpha-subunit values were below 2 ng/ml. Total free alpha-subunit secretion was markedly enhanced in subjects Day 13 and 16, in concert with total hLH and hFSH secretion. In the three subjects Day 7, free alpha-subunit was released only after the second GnRH bolus. In periovulatory subjects, free alpha-subunit secretion became apparent after the initial bolus and with constant GnRH infusion. In the three subjects Day 22 and 24, peak levels of free alpha-subunit were obtained after the second GnRH bolus.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of cryosurgery in the treatment of intraepithelial neoplasia of the uterine cervix.

Six hundred five women with varying degrees of intraepithelial neoplasia of the uterine cervix were treated with 4 different modalities: 315 patients were treated with cryosurgery, 43 with electrocautery, 127 with conization, and 120 with hysterectomy. Of the patients undergoing cryosurgical treatment, 83 had cervical intraepithelial neoplasia (CIN) I (mild dysplasia), 172 had CIN II (moderate dysplasia), and 60 had CIN III (severe dysplasia and carcinoma in situ). Patients undergoing electrocautery all had either CIN I or II. Of 247 patients undergoing conization and hysterectomy, all had CIN III except for 2 with CIN II. A follow-up study revealed a failure rate of 5.5% in CIN I or II and of 15.5% in CIN III among patients with cryosurgical treatment. Following conization for CIN III, 12.5% of patients had treatment failure; no treatment failure was reported among patients who underwent hysterectomy for CIN III. Cryosurgery and conization were equally successful in treating CIN III. Cryosurgical therapy of CIN is therefore an effective means of treatment, but a precise diagnosis must be established by colposcopy and colposcopically directed biopsy before therapy. Also, restricted criteria should be used with regard to the geographic extent of the disease, and endocervical curettage should be performed as part of the evaluation of patients with CIN undergoing cryotherapy.

Effects of mating on serum LH, FSH, and prolactin and accessory tissue weight in male rats.

The literature reveals contradictory data regarding whether or not male release LH acutely following coitus. Since it has been shown that repeated mating increases accessory sex organ weight, suggesting induction of gonadotrophin release, it seemed of interest to reinvestigate the issue. Male rats were divided into two groups: the mated group was provided with frequent mating ("experiencing") trials; the unmated group served as cage controls which received no sexual contact throughout the entire experiment. All rats were provided with chronic jugular cannulae. One set of serum samples was taken from each rat at 85 days, the second set at 115 days. On the two evening when sampling took place the mated rats were subdivided into three groups: "chamber" (placed in mating arena alone), "mount" (allowed two to five mounts, but no intromission), and "ejaculation" (mated through entire copulatory sequence). Serum sampling took place every 15 min during the hour following completion of mating (defined in the "ejaculation" group). On the day following the second sampling, autopsies were performed, and terminal serum samples were taken. LH, FSH, and prolactin were measured by radioimmunoassay. There were no significant differences in any hormone among the groups during the hour following mating nor in the terminal sample. However, the mated rats showed significantly greater seminal vesicle and ventral prostate weights than the cage controls at autopsy. Several hypotheses are offered to account for the latter findings.