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Two species of prickly pears originally confined to America have been introduced into the Y.A.R.: Opuntia ficus-indicaL., naturalized round the Mediterranean Sea since more than 300years, was brought by the Turks and is called “turkish fig”. It is planted in North Yemen only because of its sweet fruits, and grows wild around many villages. Up to now its spineless variety is not cultivated as a fodder plant, whereas in other winter-dry countries it is successfully used.

This paper provides an overview of the role of data monitoring committees in ensuring patient safety and validity and scientific merit of the trial. This more formalized data monitoring approach tends to be used only in trials where there is a lot at stake. Use of data monitoring committees at the National Institutes of Health and results of a workshop held on the subject are covered.

This paper provides an overview of intent-to-treat analysis versus as-treated analysis. The first step in evaluating a therapy must be an unbiased intent-to-treat analysis. This is the only sure way to protect against potential bias. As-treated analyses, however, can be used in some situations, and methodology to provide objective secondary analyses should be pursued. A two-arm clinical trial of an active treatment versus placebo control will be used to illustrate the two procedures.

The indications of the speed of the present coastal changes were collected at two dozen of localities of Venezuela, Portugal and Spain by comparisons in a time period of 3, 5, or 9 years, respectively. The observations put in tabular form show that - flat shores may change continuously, but generally represent forms of an equal balance; - the estuaries may be subject to rhythmical changes without any quick disturbing of the former morphological structure; - steep coasts do not change continuously, but are formed episodically by small hazards, whereby these dynamic phases may be seperated by single years or decades.

• One or more nonfebrile seizures occurred between the ages of 1 month and 7 years in eight per 1000 white and in nine per 1000 black children enrolled in a large prospective study. We examined hundreds of prenatal and perinatal factors as predictors of childhood seizure disorders. Congenital malformations of the fetus (cerebral and noncerebral), family history of certain neurologic disorders, and neonatal seizures were the major predictors identified. Forty percent of children with postneonatal seizures and 68% of children with minor motor seizures had one or more of these risk factors compared with 21% of the seizure-free population. More than half of the children with minor motor seizures and a third of the infants with neonatal seizures had congenital malformations. Based on the prenatal and perinatal factors examined, prediction of postneonatal seizures carried a high rate of false-positive identification, indicating that our knowledge of the etiology of childhood seizure disorders is still very limited.(AJDC 1986;140:1053-1061)

• Birth weight and gestational age of single-born children with cerebral palsy (CP) and those with seizure disorders were compared with norms for 40,000 single-born children in the same prospectively identified population. Low birth-weight and short gestation were important risk factors for CP, but these characteristics were uncommon, and the majority of children with CP were of normal birth weight and term gestational age. Preterm children with CP by age 7 years tended to have been even smaller at birth than was appropriate for their short gestations. Among term infants with later CP, the birth weights of the majority were appropriate for dates, but a subgroup were noticeably small for dates at term. Low birth weight, preterm birth, and smallness for dates at term were not significantly related to the risk of seizure disorders in children free of CP.(Am J Dis Child 133:1044-1048, 1979)

In a prospective study, the risk of recurrence after a first postneonatal nonfebrile seizure was 61 by age 7 years. The risk of recurrence for nonsymptomatic seizures was considerably higher than for seizures attributed to immediate precipitating factors, Focal motor seizures were more likely than generalized motor seizures to recur. Children who had prior neonatal seizures were at greater risk for nonfebrile recurrence than children with no prior seizure. Family history and neurodevelopmental status were not significantly related to recurrence risk. Almost 90 of recurrences took place within 1 year, and 96 within 2 years.

To evaluate the postmarketing safety of recombinant hepatitis B (HB) vaccine given to neonates and infants in the US.

The Aequorea victoria green fluorescent protein (GFP) is widely recognized as a powerful tool in cell biology, serving as a vital reporter for monitoring localization and dynamics of intracellular proteins and organelles over time. GFP variants with shifted spectral characteristics have been described and offer enormous potential for double-labeling experiments and protein-protein interaction studies. However, most GFP variant combinations are not suitable for double-label, time-lapse imaging experiments because of either extremely rapid photobleaching of blue-shifted GFP variants or crossover of their excitation and emission spectra, which must then be computer corrected. Here, we describe the successful use of two photostable spectral GFP variants, W7 and 10C, in dual-color, timelapse imaging of fusion proteins in living cells using either wide-field or confocal microscopy. W7 and 10C were highly photostable during repetitive long-term imaging and were cleanly separated by their different excitation spectra alone with negligible crossover of fluorescence. We present time-lapse image sequences of COS-7 cells co-expressing both a marker of the Golgi complex (galactosyl transferase) fused to W7 and a marker of the nuclear envelope (lamin-B receptor) fused to 10C. To our knowledge, these image sequences provide the first simultaneous visualization of Golgi and nuclear envelope membranes in living cells.

In a large prospective study, we investigated predictors of moderately low (1,501 to 2,500 g) and very low (<1,501 g) birth weight. Maternal age, height, and socioeconomic status, related to moderately low birth weight on univariate analysis, were not on multivariate analysis significant predictors for either low-birth-weight outcome. The leading predictors of very low birth weight were low weight (<2,000 g) of last live birth, fetal malformation, nonwhite race, early vaginal bleeding, cigarette smoking, and chorionitis. Some of these were also predictors of moderately low birth weight. About 20% of births under 1,501 g could be attributed to chorionitis, a characteristic of less than 3% of the births. Of the major predictors of low birth weight, only prolonged rupture of membranes, chorionitis, and congenital malformations contributed to the risk of cerebral palsy beyond their contribution to the risk of low birth weight.(JAMA 1985;254:1473-1479)

Both strength (ability to develop tension) and endurance (aerobic capacity as measured by V˙O2max) contribute to overall functional capacity. In the rehabilitation of individuals with major neuromuscular deficits such as paraplegia, primary emphasis is generally placed on strength training to develop functional independence. However, endurance training may also be important. To clarify the influence of paraplegia on the V˙O2, we studied 10 paraplegics between 2 to 12 weeks after injury to determine whether or not a deficit in arm V˙O2max was present before the inception of a conventional rehabilitation programme, and whether it persisted in three subjects after its completion. Cardiorespiratory responses to progressive multi-stage arm ergometry were measured using standard open circuit calorimetry. Ten paraplegic subjects demonstrated a low V˙O2max compared to control subjects. This deficit persisted when selected subjects (n = 3) were tested after completion of a conventional rehabilitation programme which emphasised strengthening exercises. Further research is needed to study the effects of complementary endurance training on the aerobic capacity as measured by V˙O2max, and to assess their value in the rehabilitation process.

Although diabetes plays a significant role in causing impotence in the diabetic male, its effects on female sexuality have only recently been studied. Surprisingly, no demonstrable effect on the capacity for sexual arousal or orgasm has been found in the diabetic female. This paper compares male and female anatomy, physiology, and neurology, and speculates about reasons for this sex difference.

Many woody and herbaceous plant species in different families have leaves with so-called “drip tips” (German: “Träufelspitzen” Fig. 1). These are most frequently found in the humid parts of the warmer zones (Fig. 2) but even here not at all everywhere. Since nearly 100 years the prominent tips often were supposed to promote the transpiration of the leaves and to prevent the growth of epiphyllic algae, lichens and mosses by draining off the water from the surface. However field observations as well as experiments with leaves or leaf models gave rise to doubts into the teleologic interpretation.

• The relationship of febrile seizures to later intellectual and academic performance was examined in a sibling-control study. Among 431 sibling pairs tested at the age of 7 years, the mean full scale IQ on the Wechsler Intelligence Scales for Children was not different for children who had febrile seizures as compared with siblings who were seizure-free. Neither recurrent seizures nor those lasting 30 minutes or longer were associated with IQ deficit.Poor academic achievement, defined as Wide Range Achievement Test performance more than one grade level below school placement in children with IQs of 90 or above, was equally frequent in index cases and control patients.Febrile seizures were not associated with a decrement in IQ or early academic performance, as judged by comparison of affected children with their siblings.

This paper is condensed from a lecture (given in May 1973 at Montpellier) which was honored by the presence of Josias Braun-Blanquet. The Andean Mountains and the adjacent lowlands, from Southern Colombia to Northern Chile and Argentina, offer an unique opportunity to study the variation of vegetation with the altitude as well as with the degree of humidity of climate within the tropics. In a series of diagrams this variation is represented schematically, using the number of arid months as horizontal and the altitudinal belts as vertical axis. Primary productivity is highest in the humid, not in the perhumid lowlands. More realistic graphs may give an idea of the structure of the zonal plant formation in a perhumid, in a semihumid to semiarid and in an arid climate. Climatic diagrams of the daily movement of air temperature and relative air humidity have been developed which show the more or less wet (hatched) and dry hours (dotted). Where possible, climatic diagrams with monthly average temperature and rain fall (according to Walter) are added. The abundance of vascular and cryptogamic epiphytes depends mainly on the degree of humidity at midday in the growing season, may this be caused by fog drift or frequency of rain fall. "Drip tips" of the leaves are lacking in the wettest forest climate (i. e. in the upper montanous belt) but are quite frequent where the average temperature is above 15° C, the whole growing season is humid, and the dry season is not longer than 4 months. Under these conditions, most leaves normally have no or only a thin and individual bud protection, and their tip is differenciated already when the lamina begins to be enlarged quickly, thus causing a curved transition to the tip. Most natural forest and woodland types have been partially or nearly totally replaced by grassland which was regularly burned and grazed since the Spanish conquest or even much longer. The best future land use, according to the author's experience and taking into account the different danger of soil erosion, is sketched in fig. 8 (lower part).

The association between use of oral contraceptives (OC) and death from myocardial infarction (MI) in young women was investigated in a collaborative case-control study conducted in the five largest metropolitan areas in the US. Potential cases were identified from computer tapes of the National Center for Health Statistics. Controls were selected from among women who died from, or were hospitalized for, acute conditions other than heart disease or from accidents, and were matched to cases on age, geographic area, and year of death. Information on cause of death, personal characteristics, OC use, and the presence of conditions predisposing to MI was obtained from interviews with relatives and abstracts of hospital, clinic and physician records. Odds ratios as approximations to relative risks for fatal MI in relation to OC use, and the associated 95% confidence limits, were calculated overall and for subgroups determined by demographic and health history characteristics. Odds ratios in the total study population were not significantly different from one. However, odds ratios significantly different from one were found when attention was restricted to white subjects without contraindications to OC use, andincluding only those cases whose deaths were attributed to MI with the greatest degree of certainty. Smoking was found to be a significant risk factor for fatal MI.

Deaths of 338 women at ages 15-44 years attributed to myocardial infarction (MI) on death certificates during an 18-month period in five metropolitan areas were investigated. Evidence of recent MI or evidence that death occurred suddenly was obtained for about half (163) from records of hospitals or medical examiners or from relatives. A case-control study (involving one deceased control, and one hospitalized living control) of risk factors for heart attack was then conducted using interviews with relatives and abstracts of records of hospitals and physicians identified by the relatives as sources of medical care. Information was obtained on history of prior MI, other heart disease, diabetes, thromboembolism, stroke, hypertension, high cholesterol, obesity, oophorectomy, oral contraception and cigarette smoking. Data are presented on the prevalence of these potential risk factors for the case group and each control group, and for subsets of cases consisting of those without prior heart disease, definite MI only, sudden death only, and white women only. Multivariate analyses identify somewhat different sets of risk factors and different levels of risk for the various subgroups. In general, the risk factors are those that have been reported for men, despite the major difference in level of mortality.

The entity of diabetic neuropathy has been recognized for many years. With increasing experience and recognition of this complication of diabetes, a broader appreciation of its clinical manifestations has taken place. Unfortunately, however, a basic confusion in diagnosis still exists. This results from the fact that the neurological syndromes are so numerous that almost any condition may be simulated. Nervous system involvement is frequently diffuse and disseminated and may present a bizarre picture. Further, the etiology, pathology, and treatment remain essentially unknown. The symptoms may indicate involvement of the peripheral nerves, the spinal roots, the spinal cord, the cerebrum, or any combination thereof.The most frequent clinical picture is characterized by involvement of the nerves of the lower extremities, most often bilaterally symmetrical and predominantly sensory.1 However, unilateral involvement may be present2; there may or may not be pain3; there may be severe pain, with a minimum

A number of conditions generally recognized as complications of diabetes mellitus frequently occur before the characteristic findings of hyperglycemia, glycosuria, polyuria, and polyphagia. As a result, the complications appear as the presenting symptoms that lead to the diagnosis. The characteristic retinopathy, for example, occasionally causes impairment of vision before glycosuria is found. This fact, that characteristic disorders can involve the eye, the skin, the nervous and vascular systems, the kidney, and the reproductive functions before the characteristic disorder of carbohydrate metabolism becomes manifest, means that diabetes mellitus is a complex disease. It should no longer be thought of as meaning simply hyperglycemia and glycosuria. An alert clinician has the opportunity to recognize the disease more promptly, begin its management at an earlier stage, and solve some obscure clinical problems.

Salicylates have been used in the treatment of acute articular rheumatism for some sixty years, but there remain wide differences of opinion with regard to their usefulness and mode of action. Yet the use of the drug persists, and studies of its clinical applications are still being published. In the United States, clinical practice largely restricts the use of salicylates to the relief of acute rheumatic arthritis. In Europe, particularly in France, the salicylates are regarded as valuable measures in the treatment of the cardiac manifestations of rheumatic fever.A number of careful studies made in this country beginning with one by Miller1 in 1914 and continuing to that of Master and Romanoff2 in 1932 show that the administration of salicylates does not reduce the frequency of cardiac complications of patients with rheumatic fever. Wyckoff, DeGraff and Parent3 demonstrated by electrocardiographic studies that the conduction disturbances which

Clinic records of 27 of 44 freshmen who visited a college mental health service suggested a psychiatric disturbance during the students' high school years. Of the remaining 17 students, 15 were seen in follow-up interviews four to five years after their clinic visits. Twelve of the 15 were judged to have significant psychiatric difficulties extending well beyond the freshman year. The authors take issue with the notion that the typical student visiting the college mental health clinic is well and undergoing only transient situational or developmental problems.

The development of a simple procedure1to determine both thiamin and the pyrimidines in human urine permits the investigation of the possible relationship between the two.Schultz, Atkins and Frey showed that the rate of glucose fermentation by a yeast is directly proportional to the concentration of thiamin present. In addition to thiamin, the pyrimidines give mol for mol stimulation effect on the rate of fermentation. Such pyrimidines are found normally in human urines. Since the pyrimidine nucleus constitutes an integral part of the thiamin molecule, it is of interest to determine the relationship between thiamin and urinary pyrimidine.The total fermentation is a measure of thiamin and pyrimidine in the urine. The fermentation after oxidation of the free thiamin is a measure of the pyrimidines; the difference represents the free thiamin. This technic combines the gas method with the initial steps of the thiochrome procedure.The urinary excretion of the thiamin and pyrimidine of a group of patients was studied under various conditions. Three patients were given a diet completely deficient in B1for 10 days. Two of these were normal and one had ileo-jejunitis. Fig. 1 and 2 and Table I illustrate that complete deprivation of dietary thiamin for a period of 10 days changed the thiamin-pyrimidine ratio from approximately 9:1 to 1:9. During this 10-day deprivation period, the absolute amount of pyrimidine excreted remained at approximately the same level, while the free thiamin disappeared almost completely. It becomes apparent, then, that the determination of free thiamin in the urine is an index of the dietary intake immediately preceding the measurement, since the urinary excretion of thiamin decreases so rapidly on deprivation. Therefore, low values for free thiamin need not necessarily indicate a state of chronic insufficiency with respect to this vitamin since the same values are obtained with temporary, acute deprivation.

The widespread clinical application of vitamin B1 therapy has been stimulated by the availability of the crystalline substance. Estimates as to dosage and duration of therapy have had to be approximated on the basis of gross clinical changes. The use of this vitamin as a therapeutic test in various confusing syndromes has been expensive to both patient and physician. Furthermore, the negative response to vitamin B1 in many of these syndromes may discourage its use where it is really indicated.If a test were available by means of which one could estimate the state of nutrition in a person with respect to vitamin B1 rapidly and inexpensively, then the clinical application could be placed on a more rational basis.The methods available up to recently have been long and cumbersome. Schultz, Atkins and Frey developed a method which is comparatively simple and lends itself to clinical investigations.

Virus antibody levels were determined for multiple sclerosis patients and matched controls from three different locations. For rubeola, several different antigen preparations were used. Measles antibody titers were significantly elevated in multiple sclerosis patients in Washington, DC, increased in the patients in Minneapolis, and somewhat elevated in the patients in Vermont. In the Vermont series, the trend for high measles antibody levels only became apparent when sibling controls were excluded from the analysis. Antibody levels for respiratory syncytial virus, adenovirus, mumps, and varicella were also increased among multiple sclerosis patients in individual groups, but this was not consistent for all three groups.

A LTHOUGH bladder involvement in diabetes was alluded to over 100 years ago 1 and established as a diabetic neuropathic manifestation 30 years ago,2 it still remains a comparatively obscure clinical entity. The lack of appreciation of its relative frequency, the unfamiliarity with its clinical picture, the urgent indication for available remedial therapy, and the dire consequences of neglect prompt this paper. Our series consists of 27 cases collected within a relatively short period of time and is the largest such series to be reported. TERMINOLOGY. —The term neurogenic vesical dysfunction describes the pathogenesis of the clinical syndrome in diabetes and should replace the term "chord bladder" which includes many pathologically and clinically unrelated entities.3 CLINICAL PICTURE. —The outstanding feature is the insidious nature of onset and progresssion of the bladder paralysis and urinary retention. The interval between voidings gradually increases until urine is passed only once or

A Correction to this paper has been published: https://doi.org/10.1038/s41586-021-03287-8.

Supplemental Digital Content is available in the text.

A community mental health center established a group lithium clinic to introduce a medical model of treatment for manic-depressive patients and to reduce staff time in caring for these patients. Clinical maintenance consisted of a monthly group meeting with a psychiatrist and a social worker; the social worker led general discussions on symptomatology, the toxic side-effects of lithium, and the importance of medication compliance, while the psychiatrist reviewed the effectiveness of the pharmacotherapy with each patient individually. Drug compliance was good, and patients seemed pleased to discuss their problems with others having similar diagnoses. Most patients ended or reduced visits to their therapists, and staff time spent on lithium-taking patients was greatly reduced.

• We investigated whether infants weighing over 2500 g who had experienced one or more of 14 late pregnancy or birth complications, but who were free of certain signs in the nursery periodod were at increased risk of cerebral palsy (CP). The signs evaluated were decreased activity after the first day of life, need for incubator care for three or more days, feeding problems, poor suck, respiratory difficulty, or neonatal seizures. More than 90% of the infants weighing over 2500 g had none of these signs. In asymptomatic Infants with one or more birth complications, the rate of CP by 7 years of age was 2.3/1000; among asymptomatic infants whose births were uncomplicated, the rate of CP was 2.4/1000. The risk for CP rose with number of abnormal neonatal signs, and children with sustained neonatal abnormalities were at higher risk than those whose abnormalities were transient. Most children with CP did not derive from groups at increased risk. The full-term infant whose birth was complicated but who was free of certain abnormal signs in the newborn period was not at increased risk of CP.(AJDC 1987;141:1333-1335)

The discussion from “Methodological Issues in Pivotal Trials,” Session 2 of the DIA Workshop “Clinical Trials in Biotechnology: Planning to Prevent the Pitfalls,” is presented. This is an unusual offering for the Drug Information Journal, but the comments are important enough to merit publication.

Tolbutamide (Orinase), a sulfonylurea derivative, is an orally given hypoglycemic agent which has recently been added to the therapy of diabetes mellitus. The introduction of any new drug into the therapeutic armamentarium necessarily requires careful observation to detect any toxic manifestations. This applies even more to tolbutamide, since, in addition to being a new drug, it is chemically related to the sulfonamides which have many known undesirable side-effects, the site and mode of action are not clearly defined, its use requires a prolonged period of administration, and it is a substitute for insulin, a known nontoxic agent which has been used safely and successfully for the past 25 years. On the other hand, it is equally important not to attribute to a drug undesirable but coincidental clinical phenomena that are inherent in the course of the disease under treatment and, hence, unrelated to any injurious effects of the medicament per

Sebrell and Butler1 in their classic discussion described the criteria for the diagnosis of ariboflavinosis in the human being. Among the signs pointed out by them were certain changes in the mucous membranes of the lips and the skin at the angles of the mouth, which they called a cheilosis. More specifically, there was a maceration in each angle of the mouth, the lips were reddened along the line of closure and the mucosa appeared thin, shiny and denuded. In addition to the lesions on the lips there was also a scaly, greasy desquamation in the nasolabial folds, on the alae nasi in the vestibule of the nose and in a few instances on the ears and eyelids. These lesions disappeared in twenty days or less when the patients were given from 0.025 to 0.075 mg. of riboflavin per kilogram of body weight.In addition to the cheilosis, Kruse,

A test designed to measure the individual patient's saturation with respect to Vitamin Bi would have a wide clinical application. Experiments have been carried out in an attempt to develop such a procedure. The validity of such a test depends upon, among other things, the accuracy of the method of assay for the Vitamin B1. The assay methods fall into two categories—chemical and biological. The chemical methods on the whole are specifically for pure thiamin. Among the biological methods the Schultz, Atkins and Fry technic which employs the rate of fermentation of glucose by a yeast is the most suitable for clinical investigation. This method measures not only the thiamin but the pyrimidines as well. The pyrimidines present in the urine may be considered for practical purposes as originating from the members of the B complex. The actual test in its present form employed in this laboratory is summarized as follows:Patients were injected with 1 mg of thiamin hydrochloride intramuscularly in the fasting state. The urine was collected for a 4-hour period following the injection. The Vitamin B1activity of this collected urine was assayed by means of the Schultz, Atkins and Fry yeast fermentation method. Fig. 1 shows the tabulation of the results of the test on 349 unselected patients. The distribution curve of the results indicates that an excretion of 180 gammas or more in the 4-hour period represents the average normal. Patients excreting less than 180 gammas may be considered as below average saturation. This group of patients represents the population of hospitals and dispensaries and cannot be considered a representative cross section of the population. Fig. 2 shows the tolerance test on 35 normal, healthy students, instructors and physicians.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.