Testing the tyrosine/catecholamine hypothesis of oral contraceptive-induced psychological side-effects: a controlled study on triphasil.

BACKGROUND: This study was conducted to probe the existence of oral contraceptive (OC)-induced psychological side effects that might be undetectable by psychometric testing. METHODS: Triphasil was administered during six complete menstrual cycles to young never-OC-users. Plasma Tyr and Trp/Sigma-respective competitor neutral amino acids (NAA) ratio and concentrations of other amino acids (AA), known to be involved in the functioning of the central nervous system (CNS) and the synthesis of neurotransmitters, in particular, were used as biochemical markers to assess this likelihood. Factors known to influence plasma AA concentrations such as cortisol and pyridoxal phosphate (PLP, active form of vitamin B6), both modulators of AA intestinal absorption, were examined. RESULTS: Dietary supply of amino acid substrates (precursors) and blood levels of coenzyme/cofactor (vitamin B6 and iron) involved were adequate in both groups and were kept constant throughout the treatment. The rise in plasma cortisol, known to be stimulated under the action of estrogen, was significant (p < 0.05) after the first menstrual cycle and remained higher (although not significantly) than mean baseline and reference normal values at the end of the 6-month OC treatment. Plasma Trp/Sigma-specific competitor NAA ratio remained unchanged whereas Tyr/Sigma-specific competitor NAA ratio was significantly (p < 0.02) reduced after the sixth artificial menstrual cycle. CONCLUSION: Although plasma AA biochemical markers cannot accurately assess CNS activity, they seem to be more sensitive than a comprehensive psychometric testing (MMPI) in assessing OC-induced psychological changes.

Nutritional and psychological status of young women after a short-term use of a triphasic contraceptive steroid preparation.

The present study was aimed to assess the psychological status of young healthy women after the administration of a triphasic contraceptive steroid preparation for six complete menstrual cycles. Subjects had never used oral contraceptives (OC) and had neither a familial history of depression nor psychological disturbances. OC-induced psychological disturbances were interpreted for years as evidence of pyridoxine (vitamin B6) deficiency. Other nutritional deficiencies, namely in cobalamin, folate and iron, can disturb the functioning of the central nervous system. In addition, a deficiency of any of these nutrients can lead to several anemia-induced symptoms that are highly susceptible to influence the psychological status. For ample evidence, nutritional status was then evaluated in parallel to psychological testing. Blood iron and vitamin levels of interest were found to be adequate and could not have biased the response to a psychological test (MMPI). This study showed that a 6-month Triphasil treatment did not modify significantly the psychological status of subjects. To our knowledge, this is the first psychological study on young never OC-users taking an identical triphasic contraceptive steroid preparation to investigate early psychological side-effects due to OC, at a similar time of the menstrual cycle, when nutritional status was also evaluated.

Early effect of a low dose (30 micrograms) ethinyl estradiol-containing Triphasil on vitamin B6 status. A follow-up study on six menstrual cycles.

The objectives of the study were to follow-up six artificial menstrual cycles induced by Triphasil in order to determine: 1) the time of apparition of B6 metabolic side-effects, in the eventuality they occur, and 2) the existence or non-existence of a normalization process and if so, when it is initiated. The choice of this triphasic OC preparation was based on its current popularity among modern gynecologists. Among the selected twenty-three young women who had never used oral contraceptives (OC), fourteen consented to try a new contraceptive method. Their nutritional status including anthropometric, hematologic, biochemical and dietetic (including vitamin B6 intake) parameters was found to be adequate. A functional enzymatic test coupled to a direct measurement of vitamin B6 was employed to obtain a complete assessment of their vitamin B6 status. By using both approaches, only one case (7%) of deficiency due to OC was evidenced. This well-controlled study revealed that a short-term use of a relatively low dose estrogen-containing OC (30 micrograms) did not alter PLP concentrations in plasma and erythrocytes in the majority of our young subjects consuming adequate diets. However, a disturbance in vitamin B6 metabolism was detected. PL levels in both blood components have increased steadily and did not subside to pretreatment values at the end of the experiment. In conclusion, the single use of the PLP vitamer can be misleading as demonstrated by other investigators. To assess B6-status during oral contraception, in addition to a functional enzymatic test, it may be necessary to include the other aldehydic form of vitamin B6, to fully establish and comprehend hormone-induced adverse effects on this metabolism, particularly those of progesterone/progestin that have not yet been explored.

Operations management approach to hospitals.

An operations management systems approach can be a useful tool for coordinating and planning in a complex organization. The authors argue for adapting such an approach to health care from the manufacturing industries in order to facilitate strategy formulation, communication and implementation.

Hindgut dysgenesis as a cause of constipation with delayed colonic transit.

In a patient complaining of constipation since birth, delayed transit time in the ascending colon was related to a congenital malformation of the hindgut, different from Hirschsprung's disease. This was associated with absence of the left lobe of the liver. There was no propagating electrical muscular activity in the distal bowel.

[Constipation caused by colonic inertia and distal obstruction: electromyographic study]. / Constipation par inertie colique et obstruction distale: étude électromyographique.

Colonic motility was evaluated in 15 patients with chronic constipation and 12 healthy subjects by both measuring the transit time of 20 radiopaque markers and recording the colonic myoelectric signals by means of a silastic tube equipped with 4 ring contact electrodes. The tube was introduced by flexible sigmoidoscopy so as the electrodes be located at 50, 40, 30 and 20 cm from the anal verge. Constipation resulted from colonic inertia in 7 patients, the markers being delayed over the whole length of the colon. In the 8 other patients, constipation was due to distal obstruction, the markers accumulating electively in the rectum. The myoelectric tracings showed in the control subjects, on one hand rhythmical stationary spike potentials that occurred at only one electrode site at a mean rate of 10 per minute; on the other hand sporadic (non-rhythmic) spike potentials that were either propagating over the colonic segment (sporadic propagating potentials) or not (sporadic non-propagating potentials). In the constipated patients, the following changes were observed: 1) the number of sporadic propagating potentials was significantly decreased in colonic inertia (2.5 +/- 1.3 bursts of spikes per hour) compared to the controls (8.5 +/- 1.1 bursts/h) or distal obstruction (7.9 +/- 1.3 bursts/h); 2) sporadic propagating potentials usually moved aborally; however, 19.8 +/- 0.9 p. 100 moved orally in colonic obstruction, while 4.6 +/- 0.2 p. 100 in the controls and 4.7 +/- 0.1 p. 100 in colonic inertia.(ABSTRACT TRUNCATED AT 250 WORDS)

Constipation with colonic inertia. A manifestation of systemic disease?

Transit of radiopaque markers was delayed in the ascending colon of 51 females and 3 males treated for severe idiopathic constipation. Onset of symptoms was between age 10 and 20 in more than half of the patients. Eighteen percent had previously undergone unnecessary laparotomy for large bowel pseudoobstruction. Stool frequency ranged from 1 stool every three days to 1 every 2 months. Twenty-six percent suffered from fecal incontinence. In addition, 30% had orthostatic hypotension and 15% galactorrhea of idiopathic origin. Patients had a higher than normal anal pressure (P less than 0.001). They all had a rectoanal inhibitory reflex, but it was abnormal in 76%. In the upper esophageal sphincter, resting pressure was higher (P less than 0.02), and coordination poorer (P less than 0.05) than in normal control subjects. Incidence of spontaneous tertiary contractions in the body of the esophagus was greater than normal (P less than 0.03). In the lower esophageal sphincter, resting pressure was lower (P = 0.001) and gastroesophageal gradient weaker (P = 0.05). Closing pressure of the sphincter was lower (P less than 0.001) and coordination less adequate (P less than 0.02). After subcutaneous injection of 0.035 mg/kg bethanechol, urinary bladder intraluminal pressure increased by over 15 cm H2O in 31% of patients but never did in controls, and average maximal pressure was greater (P less than 0.025). Time taken to reach peak pressure was shorter (P less than 0.01). This study provides evidence that patients who suffer from constipation with colonic inertia also have abnormal function in other hollow viscera.(ABSTRACT TRUNCATED AT 250 WORDS)

Ischemic fecal incontinence and rectal angina.

In 36 patients who consulted for fecal incontinence or rectal pain, or both, there was grossly visible scarring of the rectum and biopsy revealed mucosal atrophy and fibrosis. A steal from the hemorrhoidal arteries to the iliac vessels was demonstrated in 3 subjects. Maximum tolerable volumes within a rectal balloon were smaller than in control subjects, both in men (192 vs. 273 ml) and in women (142 vs. 217 ml) (p less than 0.01). The rectoanal inhibitory reflex was abnormal in all but 1 patient. Specific abnormalities were a decreased amplitude or a prolonged duration of the reflex. It was totally absent in 2 patients. This study is compatible with the hypothesis that chronic ischemia of the rectum may cause fecal incontinence or rectal pain.

Urorectodynamic evaluation of healthy volunteers.

Twelve female and 8 male healthy volunteers underwent urorectodynamic evaluation. Mean bladder capacity was 594 ml. and mean maximal vesical pressure 12.5 cm. water (H2O). Maximal bladder pressure correlated significantly with maximal mural tension (r = 0.96) but did not correlate well with bladder capacity (r = 0.20). Mean bladder volume at first desire to void was 32 per cent of mean bladder capacity. The bladder volume at the first desire did not correlate significantly with the capacity. Mean bladder pressure at 100 ml. volume was 2.9 +/- 0.4 cm. H2O (X +/- SEM). After bethanechol injection, the bladder pressure at 100 ml. volume increased by 8.8 +/- 1.2 cm. H2O (X +/- SEM) at twenty minutes. In only 1 subject did bladder pressure rise higher than 15 cm. H2O (5 per cent). Rectal pressure increased from 1.4 +/- 0.3 to 14.1 +/- 2 cm. H2O (X +/- SEM) at sixteen minutes. Electromyogram (EMG) of the external and sphincter did not follow regular pattern with vesical filling or attempt of voiding. The data obtained in these normal subjects may serve as a basis for comparison in the interpretation of data obtained in patients.

Urorectodynamics in patients with colonic inertia.

Sixteen female patients with colonic inertia and 12 control women underwent manometric evaluation of their bladder and rectal cavities. After subcutaneous injection of 0.035 mg./Kg. bethanechol, bladder intraluminal pressure increased by over 15 cm. water in 5 patients (31 per cent) and in none of the control group; maximal pressure after injection was 11.5 +/- 1.6 cm. H2O (mean +/- SE) in patients and 8.5 +/- 1 in controls (p less than 0.025). The intraluminal rectal pressure reached 23 +/- 4 cm. H2O in patients and only 11.9 +/- 1.4 in controls (p less than 0.0025). Time taken to reach a peak pressure was faster in patients both in bladder (17.4 +/- 0.7 vs. 19.8 +/- 1.2 minutes; p less than 0.01) and in the rectum 914.6 +/- 0.8 vs. 16.3 +/- 1.2; p less than 0.025). These findings and the clinical presentation suggest an autonomic neuropathic lesion in this group of patients.

Traumatic constipation.

In 4 patients, trauma to the lumbosacral area produced abnormalities similar to those seen after resection of the nervi erigentes. Mechanisms of the resulting constipation and fecal incontinence for liquid stools included a prolonged transit time through the entire colon, a low rectal pressure, spasticity of the anal canal, and abnormal anal reflexes. Previous trauma to the lower spine must be considered in the differential diagnosis of chronic constipation.

Some parameters of large bowel motility in normal man.

This study presents normal values of bowel habits, colonic transit times of radioopaque markers, and anorectal pressure obtained from 114 normal subjects. Their stool frequency ranged from 3 to 11 per 7 days, whereas their diet contained an average of 14.4 g of crude fibers. Radioopaque markers progressed regularly along the large bowel and a range of transit times was established for its different segments. Manometric studies included measurements of anal pressure at rest, amplitude and duration of the rectoanal inhibitory reflex, anal inflation reflex, and amplitude of rectal contraction in response to rectal distension. Normal ranges were established. Amplitude, duration and magnitude (as measured by planimetry) of anal relaxation elicited by rectal distensions were related to rectal distending volume (P less than 0.001). The incidence of spontaneous variations of anal pressure at rest and of overshoot of pressure after the inhibitory reflex was also established. These data obtained on normal subjects may be compared to those obtained in patients with constipation in order to define the symptoms and to understand pathophysiological mechanisms. This has been done in a companion study.

Mechanisms of idiopathic constipation: outlet obstruction.

Anorectal myectomy was performed in 62 patients suffering from symptoms attributed to ineffective colonic motility. Indications for surgery rested on the presence of one or more of the following three criteria: abnormally reduced stool frequency, prolonged transit of radioopaque markers, and abnormal anorectal manometry. One year after myectomy in the 50 patients with less than three stools per week the average number of stools per week increased from 1.2 to 4.2 (P less than 0.001). The remaining 12 patients, who had more than three stools per week, were completely relieved of their symptoms. In all cases with improved symptoms, myectomy acclerated the transit of radioopaque markers through the large bowel. Organic constipation amenable to surgical treatment is more frequent than previously thought. Idiopathic constipation may result from colonic inertia or outlet (anorectal) obstruction.