Showing papers by "Mayo Clinic published in 1979"

A multiple testing procedure for clinical trials.

Abstract: A multiple testing procedure is proposed for comparing two treatments when response to treatment is both dichotomous (i.e., success or failure) and immediate. The proposed test statistic for each test is the usual (Pearson) chi-square statistic based on all data collected to that point. The maximum number (N) of tests and the number (m1 + m2) of observations collected between successive tests is fixed in advance. The overall size of the procedure is shown to be controlled with virtually the same accuracy as the single sample chi-square test based on N(m1 + m2) observations. The power is also found to be virtually the same. However, by affording the opportunity to terminate early when one treatment performs markedly better than the other, the multiple testing procedure may eliminate the ethical dilemmas that often accompany clinical trials.

Intestinal Calcium Absorption and Serum Vitamin D Metabolites in Normal Subjects and Osteoporotic Patients: EFFECT OF AGE AND DIETARY CALCIUM

Abstract: Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = -0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)(2)D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = -0.39, P < 0.01) and with serum 1,25(OH)(2)D (r = -0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)(2)D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 mug/d) of synthetic 1,25(OH)(2)D(3). In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH(2)-terminal assay) relative to age-matched controls, and mean serum phosphate was increased. The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)(2)D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH)(2)D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH)(2)D, analagous to that seen in aging rats, cannot be excluded.

Remission of seizures and relapse in patients with epilepsy.

Abstract: Summary: In a longitudinal study of patients with epilepsy in Rochester, Minnesota, we found that the probability of being in remission (at least 5 consecutive years seizure-free, and continuing) at 20 years after diagnosis was 70%. The rates for remission we encountered were generally higher than those previously reported. We believe that the better prognosis in our series results from inclusion of all incidence cases in a defined population, beginning at the initial diagnosis of epilepsy. Prognosis for remission of epilepsy is poor in patients with' associated neurologic dysfunction identified from birth. Patients with idiopathic seizures and survivors of postnatally acquired epilepsy have better prospects for eventual remission. The probability of remission is highest in patients with generalized-onset seizures diagnosed before 10 years of age. Prognosis is less favorable for those with partial complex seizures and adult-onset epilepsy. RESUME A L'occasion d'une etude longitudinale des malades Epileptiques de Rochester (Minesota) nous avons trouve que la probabilitye d'une remission (au moins 5 annees consecutives sans crises) 20 annees apres le diagnostic etait de 70%. Ce taux est plus eleve que ceux precedemment rapportes. Nous pensons que le meilleurs pronostic dans notre serie tient a ce que nous avons inclus tous les cas incidents dans une population definie, a partir du diagnostic initial d'epilepsie. Le pronostic concernant la remission est moins bon pour les patients qui presentent des troubles neurologiques associes d'origine obstetricale; il est meilleurs pour les patientsavec des crises idiopathiques ou ayant une epilepsie acquise apres la naissance. Ce pronostic est le meilleur pour les malades qui presentent des crises generalisees d'emblee diagnostiquees avant L';age de 10 ans; il est moins favorables chez ceux qui presentent des crises partielles a semiologie complexe et chez ceux dont L';epilepsie est survenue a L';age adulte. RESUMEN En un estudio longitudinal de enfermos con epilepsia realizado en Rochester, Minnesota, encontramos que la probabilidad de estar en remision (por lo menos 5 anos consecutivos sin ataques y continuar asi), 20 anos despues del diagnostico, era de un 70%. Las cifras de remisiones son generalmente mas elevadas que las publicadas previamente. Pensamos que el mejor pronostico de nuestras series se basa en la inclusion de todos los casos que inciden en una poblacion definida desde el momento del diagnostico de epilepsyia. El pronostico con respecto a la remision de la epilepsyia es pobre en los pacientes con disfuncion neurologica asociada identificada desde el nacimiento. Tienen mejor posibilidad de eventual remision aquellos enfermos con ataques idiopaticos y los supervivientes de epilepsyia adquirida en el periodo postnatal. La mayor posibilidad de remision la tienen los enfermos con ataques de comienzo generalizado diagnosticados antes de los 10 anos. El pronostico es menos favorable en los que presentan ataques parciales complejos y epilepsyia de comienzo en edad adulta. ZUSAMMENFASSUNG In einer Langzeitstudie uberPatienten mit Epilepsie in Rochester, Minnesota, fander wir das die Wahrs-cheinlichkeit einer Remission (mindestens 5 und mehr Jahre Anfallsfreiheit) 20 Jahre nach der Diagnosestel-lung bei 70% lag. Die Remissionsrate lag allgemein hoher als in fruheren Arbeiten angegeben wird. Wir glauben, das die bessere Prognose in unserer Gruppe dadurch zustande kommt, das, bei einer definierten Population, alle Falle mit dem Zeitpunkt der Diagnos-estellung Epilepsie in die Studie aufgenommen wur-den. Die Prognose bzgl. Anfallsfreiheit ist schlecht bei Patienten mit zusatzlich neurologischen Storungen, die seit Geburt bestehen. Sie ist besser bei Patienten mit idiopathischen Anfallen und bei uber-lebenden einer postnatal erworbenen Epilepsie. Die Wahrscheinlichkeit einer Remission ist besonders hoch bei Patienten mit generalisierten Anfallen, die vor dem 10. Lebensjahr diagnostiziert wurden. Weni-ger gunstig ist die Prognose bei Patienten mit parti-ellen Anfallen mit komplexer Symptomatik und Beginn im Erwachsenenalter.

Cytotoxic Properties of the Eosinophil Major Basic Protein

Abstract: Summary The eosinophil major basic protein (MBP) damages cells including those from organs whose dysfunction is associated with eosinophil infiltration. Concentrations of MBP in the toxic range were found in sputa from asthmatics, in pleural fluid and in sera. These findings suggest the hypothesis that the eosinophil produces damage to cells in disease.

Role of Glucagon, Catecholamines, and Growth Hormone in Human Glucose Counterregulation: EFFECTS OF SOMATOSTATIN AND COMBINED α- AND β-ADRENERGIC BLOCKADE ON PLASMA GLUCOSE RECOVERY AND GLUCOSE FLUX RATES AFTER INSULIN-INDUCED HYPOGLYCEMIA

Abstract: To further characterize mechanisms of glucose counterregulation in man, the effects of pharmacologically inducd deficiencies of glucagon, growth hormone, and catecholamines (alone and in combination) on recovery of plasma glucose from insulin-induced hypoglycemia and attendant changes in isotopically ([3-(3)H]glucose) determined glucose fluxes were studied in 13 normal subjects. In control studies, recovery of plasma glucose from hypoglycemia was primarily due to a compensatory increase in glucose production; the temporal relationship of glucagon, epinephrine, cortisol, and growth hormone responses with the compensatory increase in glucose appearance was compatible with potential participation of all these hormones in acute glucose counterregulation. Infusion of somatostatin (combined deficiency of glucagon and growth hormone) accentuated insulin-induced hypoglycemia (plasma glucose nadir: 36+/-2 ng/dl during infusion of somatostatin vs. 47+/-2 mg/dl in control studies, P < 0.01) and impaired restoration of normoglycemia (plasma glucose at min 90: 73+/-3 mg/dl at end of somatostatin infusion vs. 92+/-3 mg/dl in control studies, P<0.01). This impaired recovery of plasma glucose was due to blunting of the compensatory increase in glucose appearance since glucose disappearance was not augmented, and was attributable to suppression of glucagon secretion rather than growth hormone secretion since these effects of somatostatin were not observed during simultaneous infusion of somatostatin and glucagon whereas infusion of growth hormone along with somatostatin did not prevent the effect of somatostatin. The attenuated recovery of plasma glucose from hypoglycemia observed during somatostatin-induced glucagon deficiency was associated with plasma epinephrine levels twice those observed in control studies. Infusion of phentolamine plus propranolol (combined alpha-and beta-adrenergic blockade) had no effect on plasma glucose or glucose fluxes after insulin administration. However, infusion of somatostatin along with both phentolamine and propranolol further impaired recovery of plasma glucose from hypoglycemia compared to that observed with somatostatin alone (plasma glucose at end of infusions: 52+/-6 mg/dl for somatostatin-phentolamine-propranolol vs. 72+/-5 mg/dl for somatostatin alone, P < 0.01); this was due to further suppression of the compensatory increase in glucose appearance (maximal values: 1.93+/-0.41 mg/kg per min for somatostatin-phentolamine-propranolol vs. 2.86+/-0.32 mg/kg per min for somatostatin alone, P < 0.05). These results indicate that in man (a) restoration of normoglycemia after insulin-induced hypoglycemia is primarily due to a compensatory increase in glucose production; (b) intact glucagon secretion, but not growth hormone secretion, is necessary for normal glucose counterregulation, and (c) adrenergic mechanisms do not normally play an essential role in this process but become critical to recovery from hypoglycemia when glucagon secretion is impaired.

Incidence of spontaneous pneumothorax in Olmsted County, Minnesota: 1950 to 1974.

Abstract: Between 1950 and 1974, 318 cases of initial pneumothorax were diagnosed among the residents of Olmsted County, Minn. Seventy-five cases were due to trauma, and 102 were iatrogenic. One hundred forty-one cases were spontaneous in onset, of which 77 were primary and 64 secondary to a specific underlying pulmonary disease. The age-adjusted incidence of primary spontaneous pneumothorax was 7.4/100,000/yr for males and 1.2/100,000/yr for females. For secondary spontaneous pneumothorax, the incidence was 6.3 and 2.0/100,000/yr for males and females, respectively. The ratio of male-to-female incidence was 6.2:1 for primary and 3.2:1 for secondary spontaneous pneumothorax. The differences between the incidence rates for primary and secondary pneumothorax by sex or in total were not significantly different.

Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia

Abstract: A single intrathecal injection of capsaicin depletes substance P from primary sensory neurons and causes a prolonged increase in the thermal and chemical pain thresholds of the rat but no apparent change in responses to noxious mechanical stimuli.

Biomechanical study of the elbow following excision of the radial head.

Abstract: The extent of proximal migration of the radius in thirteen patients who had had the radial head excised for fracture was 1.9 millimeters. After an average of twenty years there was minimum loss of motion of the elbow and forearm but strength was moderately decreased. The patients often had degenerative arthritis at the elbow that generally was not severe but correlated with the amount of pain. It correlated poorly with the severity of arthritis, loss of strength, motion, or pain. Over-all, the patients did well following resection of the radial head and there was no deterioration of results with time. An instrumented method for functional evaluation provided an objective and sensitive quantitative means to assess the need for and effectiveness of reconstructive procedure.

Atypical lipoma, atypical intramuscular lipoma, and well differentiated retroperitoneal liposarcoma: a reappraisal of 30 cases formerly classified as well differentiated liposarcoma.

Abstract: Thirty cases formerly diagnosed as Grade I lipogenic liposarcoma (well differentiated liposarcoma) were reviewed. The basic histologic pattern in all was that of adult fat modified by the presence of cells with enlarged, hyperchromatic nuclei; in most cases there was also a component of myxoid and/or fibrous tissue. The length of follow-up ranged from two to 30 years. Nine of the tumors were located in the subcutaneous layer. None of these recurred after excision, not even those which were simply "shelled out," and none metastasized. The term "atypical lipoma" is proposed for this group. Thirteen were located within or between muscles of the limbs, limb girdles, and head and neck. Nine of these recurred at least one, but there were no metastases and no deaths due to tumor. These were designated "atypical intramuscular lipoma." The remaining eight originated in the retroperitoneum. Although none of these patients developed metastases, five suffered inoperable recurrence and three died as a result of the neoplasm. It is suggested that the term "well differentiated retroperitoneal liposarcoma" be retained for cases of this type.

Histopathological types of cardiac fibrosis in myocardial disease

Abstract: Myocardial fibrosis is a frequently observed pathologic finding. It is a common practice to differentiate macroscopic scarring and microscopic scarring, but there has been little attempt to distinguish the various types of interstitial fibrosis, and to determine their prevalence in different cardiac disorders. In this study, we have semiquantitatively assessed microscopic scarring, interfibre and perivascular fibrosis and a distinctive type of plexiform fibrosis. We examined ten hearts with congestive cardiomyopathy, ten with hypertrophic cardiomyopathy, ten with severe valvular aortic stenosis and ten normal hearts. Perivascular and interfibre fibrosis were quantitatively closely linked and most marked in the congestive cardiomyopathy and the valvular aortic stenosis groups. Plexiform fibrosis occurred maximally in the hypertrophic obstructive cardiomyopathy group, closely associated with myocardium exhibiting muscle fibre disarray. Our study demonstrates that although different types of interstitial fibrosis have particular associations with certain disease entities, the associations are not specific. The recognition of the prevalence of one or more types of interstitial fibrosis may, however, assist in the histopathologic diagnosis of certain myocardial disorders.

The declining incidence of stroke

Abstract: A major decline in the incidence of stroke occurred in the population of Rochester, Minnesota, during the period 1945 to 1974. For every 100 first episodes of stroke that occurred per unit of population during the period 1945–49, only 55 occurred in the period 1970–74. Although the decline was present in both sexes and in all age groups, the reduction in rates was more pronounced in the elderly. There was no major change in age at onset. Analysis of cohorts born during successive five-year periods from 1865 to 1915 confirmed the decreasing incidence rate in all age groups. (N Engl J Med 300:449–452, 1979)

Organization of trigeminothalamic tracts and other thalamic afferent systems of the brainstem in the rat: Presence of gelatinosa neurons with thalamic connections†

Abstract: Thalamic projections from trigeminal and certain other nuclei of the brainstem of the rat have been investigated using the technique of retrograde transport of horseradish peroxidase (HRP). The pattern of trigeminothalamic projections is very specifically related to the individual subnuclei of the complex. The Main Sensory Nucleus (MSN) provides profuse cross connections to the ventrobasal thalamus (VB); these arise exclusively from medium and small-sized neurons, but never from the large cells. In addition to these crossed connections, a small ipsilateral dorsal trigeminothalamic tract arises from the dorsal third of the most rostral part of the MSN; this is the only ipsilateral connection to VB found in the trigeminal complex. Subnucleus Oralis has no projections to the thalamus; it is suggested that it may be concerned primarily with reflex activation of the facial nucleus, with which it is co-extensive in the rostro-caudal axis. Subnucleus Interpolaris has a well-defined crossed projection of moderate size which arises from the large, medium and some of the small neurons. Subnucleus Caudalis has a sparse output to the thalamus and differs in its projections from rostral to caudal. At the most rostral level, all layers (marginal, transitional gelatinosa and magnocellularis) contain neurons which project to the thalamus; particularly conspicuous in this respect are the marginal neurons, most of which are strongly labelled. The presence of gelatinosa neurons projecting to the thalamus emphasizes a point made in earlier reports, that these neurons do not form an homogeneous population. At caudal levels, the marginal neurons are the major source of thalamic projections, while connections to the thalamus form deeper lying neurons are infrequent. With a single exception, the medullary reticular nuclei contained no neurons with thalamic connections; a small number of reticulo-thalamic neurons were found in the ventral pontine area. Marked labelling of the medial cuneate nucleus and moderate labelling of the gracilis and lateral cuneate nuclei occurred contralaterally to the injection site. A small numebr of medial cuneate and gracile neurons project to the ipsilateral thalamus. Projections from the solitary nucleus were always ipsialteral. The boundaries of individual subnuclei of the lateral sensory trigeminal complex in the rat have been redefined on the basis of cytological criteria; these are in good accord with the corresponding thalamic projection patterns.

The decreasing incidence of primary intracerebral hemorrhage: a population study.

Abstract: This population study describes the experience with primary intracerebral hemorrhage (PIH) in residents of Rochester, MN, for the 32-year period from 1945 through 1976. The average annual age-adjusted incidence rate for PIH was 12.1 per 100,000 population, and the incidence for all cases of spontaneous intracerebral hemorrhage was 15.2 per 100,000. The PIH rates were higher for males than for females, and they increased steadily with age. When patients on long-term anticoagulant therapy were excluded, there was a steady decrease in the average annual age-adjusted incidence rate for PIH in each succeeding 8-year interval since 1945. Prehemorrhage hypertension, present overall in 89% of patients, was much more frequent and severe in the earlier years of the study. The frequency and severity of prehemorrhage hypertension also varied inversely with age in the population with PIH. The median age at the onset of PIH increased from 65 years for the period 1945 through 1952 to 71 years for 1969 through 1976.

Ultrastructural localization of the terminal and lytic ninth complement component (C9) at the motor end-plate in myasthenia gravis.

Abstract: The terminal and lytic complement component (C9) was localized at the motor end-plate in acquired autoimmune myasthenia gravis (MG) by the immunoperoxidase method, with adequate preservation of fine structure and negligible background staining. C9 was localized on short segments of the postsynaptic membrane on degenerated fragments of the junctional folds shed into the synaptic space, and on disintegrating junctional folds. An inverse relationship was noted between the structural integrity of the junctional folds and the abundance of C9 at a given end-plate region. Destruction of junctional folds by complement may induce relocation of the nerve terminal and increased spatial separation of end-plate regions on the muscle fiber. Destruction of junctional folds by the complement membrane attack complex is a cause of the acetylcholine receptor deficiency at the MG end-plate, but antibody-dependent modulation of the receptor may also contribute to deficiency of the receptor. In certain disorders other than autoimmune MG, pathological mechanisms other than complement-mediated lysis may affect the structural integrity of the postsynaptic region.

Different gastric, pancreatic, and biliary responses to solid-liquid or homogenized meals.

Abstract: We have compared responses to an ordinary solid-liquid (S) meal and to a homogenized (H) meal of identical composition (sirloin steak, bread, butter, ice cream with chocolate syrup, and water) by measuring simultaneously postprandial gastric, pancreatic, and biliary functions by marker-perfusion techniques Responses to each (S or H) meals differed strikingly both in magnitude and pattern S meals elicited a stronger early gastric secretory response (acid, pepsin, and volume) which compensated for faster initial emptying and resulted in higher gastric acidity and volume than after H meals Further, nutrients ingested with S meals were emptied at a slower rate than H (as evidenced by a more gradual decline in intragastric buffer and osmolality, as well as time required for complete emptying of the meal) This, in turn, prolonged pancreatic and biliary responses since stimulation of these organs continued for as long as meal was delivered into the duodenum However, early biliary outputs (gallbladder response) were less after S than H, probably because nutrients entered the duodenum more slowly and were initially diluted by rapidly emptying water The physical characteristics of each meal (encompassing appearance, taste, and form of ingestion) probably accounted for early differences in digestive responses Later, interactions between gastric (motor and secretory), pancreatic, and biliary functions played a major role Our findings suggest that gastric, pancreatic, and biliary responses to liquid test meals introduced into the stomach may differ substantially from the presumably more physiological response to ordinary solid-liquid meals

Cardiac involvement in polymyositis: a clinicopathologic study of 20 autopsied patients.

Abstract: Cardiac involvement in polymyositis was investigated in 20 autopsied cases. Clinically, 13 of 18 patients had abnormal electrocardiograms, and 9 of the 20 patients had previous evidence of congestive heart failure. Histologically documented myocarditis was detected in 6 patients (4 with congestive heart failure and 2 without), 4 of whom also had small vessel disease of the myocardium. Patients with polymyositis may have a cardiopathy in the absence of overt myocardial inflammatory disease.

Cutaneous angiosarcoma of the head and neck.

Abstract: Between 1920 and 1970, 13 patients (7 men and 6 women) with cutaneous angiosarcomas of the head or neck were treated at the Mayo Clinic; the mean age of the patients was 66 years. Three clinical patterns were noted: a superficial spreading type, a nodular type, and an ulcerating type. There were no predisposing benign lesions; however, in one patient, angiosarcoma developed in an area of previously irradiated skin. Three modes of therapy were used: surgery alone, radiation alone, and surgery with postoperative irradiation. Of the 13 patients, 2 survived more than 5 years and 2 were alive within 1 year of therapy. Because cervical lymph node spread is common, lymph node clearance is recommended for patients with lateralized lesion or with palpable lymphadenopathy at presentation.

Radiotherapy of intracranial astrocytomas: analysis of 417 cases treated from 1960 through 1969.

Abstract: In a review of 417 intracranial astrocytomas treated radiotherapeutically at the Mayo Clinic from 1960 through 1969, the well-known correlation of tumor grade with survival was verified. Totally unexpected was the finding that age was fully as important a discriminant as tumor grade. Another unexpected finding was that patients treated with biopsy only followed by radiation therapy did as well as or slightly better than those subjected to resection followed by postoperative radiotherapy. We could not verify the importance to survival of either large dose or large volume radiotherapy, which has been emphasized by some. Patients receiving less than 1400 rets did just as well as or slightly better than those receiving more than 1400 rets. With low grade astrocytomas, survival beyond 4 years was significantly worse (higher death rates) in the group receiving more than 1400 rets. This suggested the possibility of radiation damage with delayed manifestations. We also could not verify an increased effectiveness for the generally accepted use of total brain irradiation for high grade gliomas.

Catechol-O-methyltransferase: thermolabile enzyme in erythrocytes of subjects homozygous for allele for low activity

Abstract: Low catechol-O-methyltransferase (COMT) activity (less than 8 units per milliliter) in the human erythrocyte is inherited as an autosomal recessive trait (COMTL). The average half-life of COMT in erythrocyte lysates incubated at 48 degrees C was significantly shorter in lysates from three subjects with low enzyme activity than in lysates from three subjects with high enzyme activity (12.5 +/- 0.9 minutes compared with 21.2 +/- 1.4 minutes, P less than .01). When the ratios of COMT activities in lysates heated at 48 degrees C for 15 minutes to enzyme activities in unheated samples were used as a measure of enzyme thermostability in blood samples from 316 randomly selected subjects, the ratios were significantly less for subjects with low enzyme activity than for subjects with higher enzyme activity. The presense of thermolabile COMT in blood of individuals homozygous for COMTL raises the possibility that the locus COMT may represent the structural gene for the human enzyme.

The natural history of peripheral neuropathy in primary systemic amyloidosis

Abstract: The records of 31 patients with primary systemic amyloidosis and peripheral neuropathy seen during a 17-year period were analyzed to define the natural history of the neuropathy. Patients tended to be older men with a painful, distal, symmetrical sensorimotor neuropathy and prominent autonomic features. Loss of pain and temperature sensation was frequently more striking than loss of mechanoreception. Renal, cardiac, hematological, and gastrointestinal dysfunction often overshadowed the neuropathy. Clinical, neurophysiological, and histopathological studies pointed to axonal degeneration with predominant but not exclusive involvement of small myelinated and unmyelinated fibers. The neuropathy was progressive in all patients with or without treatment, but death was typically due to supervening medical complications.

Do anticonvulsants reduce the efficacy of oral contraceptives

Abstract: Women in our area with epilepsy who were also taking oral contraceptives were identified. Of 82 patients taking oral contraceptives, 41 had used both anticonvulsants and oral contraceptives for a total of 955 months. Three documented oral contraceptive (pill) failures occurred during this period, whereas the expected number of 0.12 (relative risk, 25; 95% confience interval, 5 to 73). No pill failures were observed in 2,278 months among women with epilepsy who were taking oral contraceptives but who were not taking anticonvulsants at this time. Thus our data support the suggestion that there is an increased rate of pill failure among women taking anticonvulsants. In view of this diminished effectiveness, the advisability of using oral contraceptives rather than one of the other forms of contraception when anticonvulsant medication is being used concurrently may need to be reevaluated.