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Drug courts provide what is often a final opportunity for justice-involved persons suffering from substance use disorders to avoid the criminogenic effects of incarceration and the severe h...

Introduction Obsessive Compulsive Disorder (OCD) following Cerebrovascular Accidents (CVA) is rare but people with CVA are at a higher risk of having OCD than the general population. Here, we present the case of a man who developed OCD after finding lacunar infarcts of the right hemisphere.This is one of the few case reports as this topic is in the early stages of research. Methods Patient was assessed and followed in outpatient psychiatry clinic.The case was reviewed and compared with relevant literature. Results This is a case report of a 73 year old man with history of Type 2 Diabetes and hypertension, no reported psychiatric history or developmental issues, who was referred to our psychiatry clinic after reporting a two year history of repeated daily checks and rituals in his home which were becoming more distressing and disruptive to his daily activities.On interview the patient reported frequently checking outlets, faucets, lights, and even his own clothes for dirt, and excessive hand washing. Patient reported that these checks took up to four hours per day causing him to frequently miss prior engagements and even awakens him at night. During the interview he cleaned the chair before sitting and asked the interviewer to check for stains on his coat. He described related nonspecific obsessive and intrusive thoughts that “something bad can happen” and was worried about contamination. He expressed relief of tension when performing these compulsions. Neurological examination was unremarkable and MMSE 28. CT scan of the brain without contrast, done two years prior to presentation, showed that the patient suffered from a lacunar infarct in the anterior limb of the internal capsule, extending into the putamen (basal ganglia). A diagnosis of Obsessive-Compulsive and Related Disorder due to Cerebral Infarction was made and he was started on an ongoing trial of Sertraline. Conclusions This case shows the rare development of OCD post cerebrovascular infarct in the right basal ganglia. Organic causes for late onset OCD should be considered when symptoms occur above age 50. Literature review suggests orbitofrontal cortex, basal ganglia and anterior cingulate cortex are most consistently implicated but not definitive. Review of cases shows that SSRI appear to be most effective in treating this rare disorder. Further studies on this topic is needed to provide additional details of the clinical features and structural/functional imaging finding. This research was funded by: NA

This manuscript stems from observations the authors made while teaching an environmental health course, which is part of a Master of Public Health (MPH) degree. Observations of student attitudes and patterns in course feedback prompted questions about how to pique interest in the course. Since research on motivation has shown that adult learners build new knowledge from what they believe they already know, we first sought to better understand this basis for learning. On the first day of class, students were administered an assignment prompting them to "define environment" in their own words; data were analyzed for content. Results characterize student conceptions of environment as being (1) beyond human influence and (2) individually-focused. The implications of these "alternative conceptions" of environmental public health for educators seeking to motivate adult learners are discussed. Restructuring coursework to reflect Transformative Learning Theory (TLT) is identified as a potential solution to student amotivation.

In 2011, the Office of the Executive Secretary of the Supreme Court of Virginia contracted with the National Center for State Courts to conduct a comprehensive, statewide evaluation of adult drug courts. The results provide evidence of the effectiveness and cost-efficiency of Virginia’s adult treatment drug courts. When compared to the business-as-usual alternative, drug courts saved taxpayers an average of $20,000 per participant. Further, programs employing Moral Reconation Therapy (MRT) produced significantly lower probabilities of recidivism, and those that employed written sanction guidelines reported significantly higher odds of graduation for participants with no prior felonies than programs that did not.

Ethnopharmacological relevance Boophone disticha (Amaryllidaceae) is one of the most common bulbous plants used for medicinal purposes by the indigenous people of southern Africa. Its use as a narcotic substance by the Khoi/San tribes has been known for several centuries, while the Sotho, Xhosa and Zulu people are known to use the plant to treat a host of ailments, including inflammation, wounds, gynaecological conditions and psychosis. Aim of the study Much of the pharmacological work on the plant, such as affinity to the serotonin transporter, has been based on its reputed usage for narcotic purposes. However, its widespread use to treat wounds and infections has not been linked to a specific chemical entity. In this regard, Boophone disticha was here examined for its phytochemical composition which could shed light on the use of the plant for such purposes. Materials and methods The known crinane alkaloids buphanidrine and distichamine were isolated via column chromatography of the ethanolic extract of bulbs of Boophone disticha. Structural details of the compounds were determined by high field 2D NMR and mass spectroscopic techniques. Microbial activity against selected Gram-positive and Gram-negative bacteria was ascertained according to the micro-dilution assay. Results Both buphanidrine and distichamine were uncovered as novel, broad spectrum moderately active, antibacterial agents with the best MIC value detected at 0.063 mg/ml for Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae. MIC values for Bacillus subtilis were two-fold less than that observed for the other three bacteria, suggesting that the extract and pure compounds were selective in their interaction with the bacterial pathogens. Conclusion Phytochemical investigation of Boophone disticha has led to the identification of two known crinanes, buphanidrine and distichamine. Based on the reputed traditional use of the plant for wounds and infections, both compounds were screened for antibacterial activity which revealed them to be novel, broad spectrum antibacterial agents with the best MIC value set at 0.063 mg/ml. Their close structural similarity may have bearing on their similar activity profiles.

Globally, the commercialisation of plants as observed in their uses by many industries such as the cosmeceutical, nutraceutical and pharmaceutical ones is gaining more interest and popularity. Mondia whitei is a popular medicinal plant which is endemic to Africa. Since antiquity, M. whitei has been used by African people to treat various ailments. The roots were used for the treatment of anorexia, stress, bilharzia and sexual dysfunction as well as for general aches and pains. Researchers have evaluated the efficacy of most of these claims by screening the M. whitei for biological activities such as antimicrobial, anti-inflammatory and anthelmintic as well as aphrodisiac efficacy. Furthermore, M. whitei has horticultural, nutritional and other socio-cultural values as reported in countries such as South Africa, Nigeria, Zimbabwe, Kenya, Uganda and Malawi. As a result of its numerous uses across the African continent, we attempt to explore and assess the economic potential of M. whitei with emphasis on medicinal values. The root of M. whitei is the most popular organ used in traditional medicine; consequently, this has resulted in the species becoming rare or threatened with extinction in the wild. Several authors have suggested solutions such as plant or plant part substitution to overcome the over-harvesting problem. The application of biotechnology techniques such as micropropagation and hairy roots also remain viable options which are presently being utilised to a lesser extent. Nevertheless, the sustainable harvesting and feasible conservation strategy for the species remains a major challenge. It is strongly recommended that in as much as the economic potential of M. whitei should be exploited, more detailed attention and studies should be geared towards its conservation. In order to ensure sustainable use and to derive maximum economic benefits, it is necessary to have empirical information detailing its ethno-botanical values, conservation status and commercial potential.

Virginia has abolished parole and adopted truth-in-sentencing guidelines for persons convicted of felonies. As part of this reform, the Virginia Criminal Sentencing Commission developed a method for diverting 25% of nonviolent, prison-bound offenders into alternative sanction programs using risk assessment to identify the lowest risk offenders. This article describes an evaluation of the effectiveness of this instrument, used by judges at the time of sentencing. It serves to advance an understanding of the factors associated with recidivism and the policy implications of using risk assessment to divert offenders from incarceration at a time when states are facing fiscal challenges.

Objectives: The aetiology of the cognitive changes seen in Parkinson's disease (PD) is multifactorial but it is likely that a significant contribution arises from the disruption of dopaminergic pathways. This study aimed to investigate the contribution of the dopaminergic system to performance on two executive tasks using 18F-6-fluorodopa positron emission tomography (18F-dopa PET) in PD subjects with early cognitive changes. Methods: 16 non-demented, non-depressed PD subjects were evaluated with the Tower of London (TOL) spatial planning task, a verbal working memory task (VWMT) and 18F-dopa PET, all known to be affected in early PD. Statistical parametric mapping (SPM) localised brain regions in which 18F-dopa uptake covaried with performance scores. Frontal cortical resting glucose metabolism was assessed with 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET. Results: SPM localised significant covariation between right caudate 18F-dopa uptake (Ki) and TOL scores and between left anterior putamen Ki and VWMT performance. No significant covariation was found between task scores and 18F-dopa Ki values in either limbic or cortical regions. Frontal cortical glucose metabolism was preserved in all cases. Conclusions: These findings support a causative role of striatal dopaminergic depletion in the early impairment of executive functions seen in PD. They suggest that spatial and verbal executive tasks require integrity of the right and left striatum, respectively, and imply that the pattern of cognitive changes manifest by a patient with PD may reflect differential dopamine loss in the two striatal complexes.

Actions by state prisoners have comprised a large and growing body of litigation in the U.S. federal courts over the past thirty years. State prisoners can challenge the validity of their state trial court convictions (habeas corpus petitions) and the constitutionality of the conditions of their confinement to state prisons and jails (Section 1983 lawsuits). Currently, one out of every five civil cases filed in the federal system is brought by a jail or prison inmate. When in the past did these cases begin to arise? What is the present trend? What does the future hold concerning the number of cases likely to be filed? These questions are at the heart of the current research. Care is needed in addressing these queries because it is neither easy nor obvious to know what propels the volume of litigation. Moreover, the future is especially difficult to predict in light of recent legislation adopted by the United States Congress to limit the number of habeas corpus petitions and the number of Section 1983 lawsuits filed each year. The unique contribution of the current research is threefold. First, an improved methodology is used to describe past patterns and to forecast future trends. Simply stated, prisoner litigation is hypothesized to be related to the number of prisoners. As the number of prisoners increases, the volume of litigation increases proportionately. What is not obvious about this relationship is that it has persisted over the past decades despite substantial changes in legal doctrines designed to affect the filing of the litigation. Second, the effects of two major congressional actions passed in 1996 to limit prisoner litigation are examined and assessed for their success in achieving their intended objectives. The first of these, the Antiterrorism and Effective Death Penalty Act, which sought to restrict habeas corpus petitions, is judged to have virtually no impact. The second piece of legislation, the Prisoner Litigation Reform Act, which sought to curtail lawsuits against correctional officials, appears to have lowered the volume of litigation in the short-term, but has not disrupted the underlying link between the number of prisoners and the number of lawsuits. Finally, estimates are made of the future volume of litigation and the corresponding number of federal judges needed to resolve prisoner litigation. These estimates have the advantage of being based on significant statistical relationships and accounting for the effects of recent congressional action.

Factors differentiating blended sentencing cases (Serious Youthful Offenders or SYOs) from conventional juvenile cases and cases transferred to the adult criminal court in Ohio were investigated using a two-stage probit. Conventional juvenile cases differed from cases selected for non-conventional processing (i.e., SYO or transfer) according to offense seriousness, number of prior Ohio Department of Youth Services placements, age and gender. Controlling for probability of selection for nonconventional processing, transfers differed from SYOs according to age, gender, and race. Minorities were significantly more likely than Whites to be transfers rather than SYOs, suggesting possible bias in the decision-making process. Objective risk and needs assessments should be used to identify the most suitable candidates for blended sentences and adult transfer and enhanced services should be provided to juvenile offenders given blended sentences.

Objective: To investigate the prevalence, outcome and multidisciplinary management of incontinence in patients with acquired brain injury. Design: Retrospective case notes review. Setting: Regional neurological rehabilitation unit. Subjects: Two hundred and thirty-eight patients with acquired brain injury. Main measures: Bladder and bowel subscores of the Barthel Index and Functional Independence Measure; number of multidisciplinary goals addressing bladder and bowel function. Results: Fifty per cent of patients (n=112) had impaired bladder or bowel subscores on admission. Significant improvement was seen at discharge but 36% of patients (n=77) still had some degree of impairment. Over 90% of patients were set multidisciplinary goals addressing self-care (n=213) and mobility (n=205) but only 3.5% (n=8) were set multidisciplinary goals addressing bladder and bowel function. Conclusions: Incontinence was common in patients with brain injury on a neurological rehabilitation unit. Significant improvement was seen following rehabilitation. Bladder and bowel management was not well incorporated into the multidisciplinary management process.

The family Amaryllidaceae has a long history of usage in the traditional medicinal practices of the indigenous peoples of South Africa, with three of its species known to be used for cancer treatment. Furthermore, the Amaryllidaceae is widely recognized for its unique alkaloid constituents, several of which exhibit potent and selective cytotoxic activities. In this study, several crinane alkaloids derived from local Amaryllidaceae species were examined for cytotoxic effects against the human cervical adenocarcinoma cell line, of which distichamine was the most potent (IC50 2.2 μM).

A radioimmunoassay has been developed that employs a readily available radioligand 3 H-20 α -hydroxy-4-pregnen-3-one for the determination of pregnanediol glucuronide in urine. The unextracted steroid is assayed directly after dilution of urine with the use of an antiserum produced to a thyroglobulin conjugate of pregnanediol glucuronide. The assay has been validated, and the ability to assess luteal function by measurement of the concentration of pregnanediol glucuronide in early morning urine specimens has been demonstrated.

Antiprogesterone antiserum was entrapped within a polysiloxane copolymer prepared from a 3:1 mixture of tetraethoxysilane and 3-aminopropyltriethoxysilane monomers. 400 microliters of this monomer mixture entrapped 70 mg of the 140 mg of immunoglobulins which were added, and the protein could not be washed from the highly stable copolymer which formed. Approximately half of the entrapped antiprogesterone antiserum was found to retain progesterone binding capacity with an apparent Ka equal to that of free antiserum in solution and was insensitive to effects of pH between 3 and 7. These preliminary observations and the unique chemistry of polysiloxane polymer formation suggest that such polymers may be useful in the entrapment of proteins for a variety of applications.

Rat pituitary hormone radioimmunoassays (RIAs) are widely used in reproductive research, yet data on specificity and binding characteristics of many of the antisera are not widely available. This report characterizes one set of rat antisera supplied by the National Institutes of Health (USA). Rat follicle-stimulating hormone (FSH) and thyrotropin-stimulating hormone (TSH) antisera appear specific, but TSH exhibited significant competition in the rat luteinizing hormone (LH) assay. In addition, statistically significant nonparallelism was demonstrable in all three assay systems. This creates further problems in characterizing antisera cross-reactivity and may make potency estimates for pituitary standards inaccurate.

The concentrations of pregnanediol-3-glucuronide (PGD) and pregnanolone (PN) were measured in daily morning urine specimens from 66 infertile women (40 with varying degrees of endometriosis and 26 control subjects) and correlated with daily changes in basal body temperature (BBT) and with midluteal levels of serum progesterone (P). PN and BBT rose at midcycle in women with endometriosis, as expected, indicating secretion of some P at that time. However, PGD, the major endpoint of P metabolism, was delayed in its excretion. Endometrial biopsies were similarly delayed (out of phase) in women with endometriosis, and a significantly higher incidence of follicular luteinization was seen. It appears that while P secretion begins at midcycle, the bulk of P secretion is delayed, perhaps because of the process of follicular luteinization, and that a shortened functional luteal phase thus exists in women with endometriosis.

A highly specific antiprogesterone antiserum (APA) produced by immunization of sheep with an 11 α -hydroxyprogesterone hemisuccinate-thyroglobulin conjugate was purified, and the IgG fraction was entrapped within a polysiloxane matrix. The matrix immobilized APA but allowed penetration and binding of progesterone (P) to the APA. In this entrapped form APA implanted intraperitoneally in rats on the tenth day of pregnancy resulted in a decline in serum P from 50 to 12ng/ml within 12hours and to less than 2ng/ml within 36hours. Free serum P measured by equilibrium dialysis fell to less than 02ng/ml at 36hours. Concomitant with the decline in serum P was a rise in both serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and eventual fetal resorption.

Extension springs were placed across the elbow joints of mature but not senescent rabbits in a manner which produced compression but allowed the joint to move. Compression was maintained for from one to thirty-two days. Within the range of compression used, the severity of cartilage damage correlated with the duration rather than the magnitude of the compression. As the arthritic lesion developed, the cartilage matrix underwent fibrillation and eventually was eroded away entirely, while a proliferative response was evoked at the joint margin. The chrondrocytes became pyknotic and then, in the end stages, were compressed into linear masses devoid of internal structure.

Several antifungal agents, at concentrations of 10 µg/ml, were shown to suppress ATP concentrations very rapidly in intact cells and spheroplasts of Candida albicans. The highest ATP-suppressing activity was shown by the highly lipophilic imidazole derivatives difonazole, clotrimazole, econazole, isoconazole, miconazole, oxiconazole and tioconazole, which all caused a reduction of cellular ATP content of more than 50% in 10 min. Relatively hydrophilic imidazole derivatives such as ketoconazole were essentially inactive in the test, as were the triazole derivatives fluconazole, ICI 153066, itraconazole and terconazole, and 5-fluorocytosine. Amphotericin B and terbinafine possessed intermediate ATP-suppressing activity, and the dose-response and pH-response curves for these compounds suggested their mechanism of ATP suppression differed from that of the active imidazole derivatives. ATP suppression by azole antifungals did not involve leakage of ATP from the cells and the effect was entirely abrogated by th...

The Main Donegal Granite is described in its regional setting and details are given of the envelope of Dalradian metasediments and the relation to the earlier members of the granite complex. A separation is made into the Main Granite Proper and the structureless Trawenagh Bay Granite, covering areas of 140 and 20 square miles respectively. The Main Granite Proper is a biotite-granite showing a medium-grained, grey, apparently marginal type in the south-east of its outcrop, and a coarser, lighter-coloured variety in the north and west. Pegmatite forms a roof facies in the south-west. Flow structures are shown by mineral orientation and a perfect banding ; the latter is produced by granites of varying grain and biotite content, the finer-grained biotite-richer type being of earlier consolidation and possibly constituting a roof phase. Banding is everywhere steep and along the NE.–SW. length of the Main Granite Proper. Within the Granite, perfectly aligned trains of free-swimming rafts of country rocks, seen to be derived from roofs or walls, extend for some dozen or more miles in the Granite and agree perfectly with its flow pattern. The contact-zones of the Main Granite Proper show marked sheeting by granite and, in these zones, high-grade contact schists are produced with staurolite and garnet—deformation, and heating have acted together. The marginal parts of the Granite and the adjacent contact-zones show an intense shoar structure, lineation and mullioning, the planar structures running vertically NE.–SW. and the linear elements plunging gently north-eastwards in the north-eastern part of the outcrop and south-westwards in the south-western. The production of these structures was contemporaneous with that of the contact schists and is related to the emplacement of the Main Granito Proper. The phenomena shown by the Main Granite Proper and by its roof and walls are consistent with the almost horizontal flow, from north-east to south-west, of viscous magma in a long narrow body beneath a pronged roof and between steep walls. A broad divergence of raft-trains as they are followed into the granite shows that it cannot be of replacement origin, nor can the room problem be solved by major stoping. The authors propose that lateral magmatic wedging is the mechanism of emplacement this great granite body.

The important excavations conducted at Numantia by Dr. Schulten represent one of those rare cases in which the work of the archaeologist is brought into direct connexion with that of the historian. The patient and methodical exploration of the Celtiberian stronghold and the Roman siege-works surrounding it has yielded results which are not interesting merely to the specialist in Roman military history, but add largely to our knowledge of an important historical event and furnish a topographical commentary to our literary records. In view of these facts it is somewhat surprising to find that in a recent English history of the Roman republic, both detailed and elaborate, Dr. Schulten's work is ignored and the site of Numantia is said to be only known by conjecture.

PATENT practice has changed with time and use—responding somewhat to changing needs. Yet, the changing needs and new forces of today appear to be considerably greater and more critical than those of earlier times when the trade and commerce of the land did not depend so heavily upon scientific research, particularly in the chemical and related fields. Thus, patent practice, as a dynamic thing, well deserves the attention of the inventing public and the patent bar. Patent practice may be defined as the unwritten rules followed by the Patent Office and by the present bar relating to patent prosecution. This practice is based on precedent, custom, and interpretations of written rules, statutes, and court cases. The term has a broader meaning, but for the present purpose it may be characterized as changeable and flexible. The patent system, on the other hand, has remained more or less firmly upon its constitutional foundation for over a century. ...

The following inscription has been kindly communicated to me, at the suggestion of Mr. D. G. Hogarth, by Mr. Henry Reitlinger, to whom I am very much indebted for permission to publish it in the Journal of Roman Studies.Mr. Reitlinger informs me that the inscription, which was engraved upon one side of a block of grey limestone, apparently an altar, about two feet high by one foot six inches broad, was discovered by some Circassian peasants among the ruins of Gerasa, in the Syrian Decapolis, two days before he himself arrived on the site at the end of November, 1913. The altar, which was still in its original position, stood about 67 yards north-east of the propylaea, which gives access from the main street to the great temple of the Sun. The stone, it may be hoped, is still in existence, since it was given into the charge of the Turkish commandant, who promised to do his best to save it from being used as building material.

Eucomis species having considerable horticultural potential are used in African traditional medicine to treat various ailments. The effects of environmental and physiological parameters on the initiation and growth of bulblets using leaf explants were investigated. These included the effect of temperature (10, 15, 20, 25 and 30 °C), photoperiod (8 h light, 16 h light, continuous light and continuous dark), carbohydrates (sucrose, fructose and glucose) at different concentrations and combinations as well as various plant growth regulators; gibberellic acid (GA 3 ), indole-3-butyric acid (IBA), napthaleneacetic acid (NAA), N 6 -benzyladenine (BA), zeatin and others. Liquid shake and liquid static cultures versus solid cultures were investigated. Maximum number of bulblets per leaf explant was obtained at 20 °C, with an average of 3 bulbs per leaf explants and a bulblet mass of 57 mg. An 8 h light cycle produced 1.38 bulbs per leaf explant, at a mass of 42 mg. Fructose at 3% produced an average of 1.18 bulbs per leaf explant, 3.39 mm wide and weighing 56.6 mg. Of the plant growth regulators, 4.90 µM IBA was found to be the optimum treatment for bulblet induction, with an average bulb diameter of 4.36 mm and a mean bulblet mass of 79.07 mg. Liquid shake cultures exhibited poor growth while bulblet, leaf and root growth was improved in liquid static cultures. Successful micropropagation from leaf explants established that leaf explants can be used as an alternative explant source to bulbs. This protocol allows for the fast and economic mass propagation of Eucomis plants.

A 30-year-old patient with primary infertility had a history of recurrent oral and perineal rashes that appeared just prior to the midcycle rise in basal body temperature and subsided with the onset of menses. The rashes did not appear during periods of treatment with oral contraceptives or danazol, and were suppressed by administration of cortisol. Sera obtained during the follicular and luteal phases of her cycle were found to contain a progestin-binding component with high affinity for 17-hydroxyprogesterone and a somewhat lower affinity for progesterone. Analysis of these sera showed the progestin-binding component to have properties of IgG, with an apparent binding affinity for 17-hydroxyprogesterone of 2 X 10(10) M-1. This report is the first characterization of an antibody to an endogenous steroid in human serum.

The concentrations of pregnanediol-3-glucuronide (PGD) and pregnanolone (PN) were measured in daily morning urine specimens from 66 infertile women (40 with varying degrees of endometriosis and 26 control subjects) and correlated with daily changes in basal body temperature (BBT) and with midluteal levels of serum progesterone (P). PN and BBT rose at midcycle in women with endometriosis, as expected, indicating secretion of some P at that time. However, PGD, the major endpoint of P metabolism, was delayed in its excretion. Endometrial biopsies were similarly delayed (out of phase) in women with endometriosis, and a significantly higher incidence of follicular luteinization was seen. It appears that while P secretion begins at midcycle, the bulk of P secretion is delayed, perhaps because of the process of follicular luteinization, and that a shortened functional luteal phase thus exists in women with endometriosis.

The incidence of ovulation was studied in a group of 33 normal young women by means of changes in basal body temperature (BBT) and by the pattern of pregnanediol glucuronide and LH concentrations in morning urine specimens. Blood was also drawn for progesterone and LH assays on 10 consecutive days of one cycle in each of 15 of these women. Perceived stress and hours of sleep were recorded daily. Ovulation occurred by hormonal criteria in only 22 of 33 cycles studied, and only 14 of the ovulatory cycles had a detectable midcycle rise in BBT. Anovulatory subjects had significantly less sleep than subjects in the ovulatory groups. The frequency of ovulation was not influenced by the stress of blood withdrawal, nor was it related to the level of perceived stress. However, the perception of stress was significantly reduced during the luteal phases of ovulatory cycles in subjects having a clear rise in BBT.

A radioimmunoassay has been developed that employs a readily available radioligand 3H-20alpha-hydroxy-4-pregnen-3-one for the determination of pregnanediol glucuronide in urine. The unextracted steroid is assayed directly after dilution of urine with the use of an antiserum produced to a thyroglobulin conjugate of pregnanediol glucuronide. The assay has been validated, and the ability to assess luteal function by measurement of the concentration of pregnanediol glucuronide in early morning urine specimens has been demonstrated.

Women who had a history of regular menstrual cycles and who had not participated in a regular exercise or sports program for at least six months were recruited for a study of the effects of initiation of an exercise program on ovulation. After a control menstrual cycle during which basal hormone levels and the occurrence of ovulation were assessed, exercise on a treadmill was begun on the first day of the second menstrual cycle; exercise was continued at 85% of maximum heart rate for three sessions per week of from 15 to 30 minutes. The effect of this program on ovulation, luteal function, and on levels of Cortisol, testosterone, prolactin and growth hormone measured 10 minutes after cessation of exercise was studied during the month of exercise and at the same times of day in pre- and postexercise control months. Initiation of the exercise program resulted in a shortening of the follicular phase of the menstrual cycle with no effect on luteal phase length or on progesterone levels or pregnanediol excretion during the luteal phase. Testosterone and growth hormone were significantly elevated after exercise by comparison with values obtained during the control months, but Cortisol and prolactin were not. Cortisol levels may have been measured too soon after exercise began to detect an elevation. However, the complete absence of a prolactin elevation may be the reason for the failure of the brief exposure to exercise of this intensity to affect ovulation.

A highly specific antiprogesterone antiserum (APA) produced by immunization of sheep with an 11 alpha-hydroxyprogesterone hemisuccinate-thyroglobulin conjugate was purified, and the IgG fraction was entrapped within a polysiloxane matrix. The matrix immobilized APA but allowed penetration and binding of progesterone (P) to the APA. In this entrapped form APA implanted intraperitoneally in rats on the tenth day of pregnancy resulted in a decline in serum P from 50 to 12 ng/ml within 12 hours and to less than 2 ng/ml within 36 hours. Free serum P measured by equilibrium dialysis fell to less than 0.2 ng/ml at 36 hours. Concomitant with the decline in serum P was a rise in both serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and eventual fetal resorption.

The concentrations of luteinizing hormone (LH), pregnanediol-3-glucuronide (PGD), and estriol-16-glucuronide (E 3 G) were measured in daily morning urine specimens from 53 infertile women. In 26 of 29 women with various degrees of proven endometriosis, two distinct midcycle peaks of LH were found 2 or 3 days apart. Patients with LH peaks separated by 3 days had significantly more severe endometriosis than those with a single peak. Maximum concentrations of E 3 G were found to be delayed until after the first LH peak in these patients, and PGD concentrations did not rise until the time of the second LH peak, making actual luteal function of shorter duration than normal. From the data on LH, it appears that an inappropriate hormonal feedback mechanism is operative in endometriosis.

Several antifungal agents, at concentrations of 10 micrograms/ml, were shown to suppress ATP concentrations very rapidly in intact cells and spheroplasts of Candida albicans. The highest ATP-suppressing activity was shown by the highly lipophilic imidazole derivatives difonazole, clotrimazole, econazole, isoconazole, miconazole, oxiconazole and tioconazole, which all caused a reduction of cellular ATP content of more than 50% in 10 min. Relatively hydrophilic imidazole derivatives such as ketoconazole were essentially inactive in the test, as were the triazole derivatives fluconazole, ICI 153066, itraconazole and terconazole, and 5-fluorocytosine. Amphotericin B and terbinafine possessed intermediate ATP-suppressing activity, and the dose-response and pH-response curves for these compounds suggested their mechanism of ATP suppression differed from that of the active imidazole derivatives. ATP suppression by azole antifungals did not involve leakage of ATP from the cells and the effect was entirely abrogated by the presence of serum. Intact cells and spheroplasts of yeast-form and hyphal-form C. albicans were generally equally sensitive to ATP suppression, but stationary-phase cells of both morphological forms were less sensitive than exponential-phase cells. The extent of ATP suppression was significantly reduced in stationary-phase yeast cells of a C. albicans strain with known resistance to azole antifungals, but exponential-phase cells of resistant and susceptible strains were equally sensitive. The effect is tentatively ascribed to membrane damage caused directly by the antifungals.

Fluconazole is a novel triazole antifungal intended for oral treatment of superficial and systemic mycoses. In tests done in standard mycological media, the compound had minimal inhibitory concentrations against pathogenic Candida species that were usually in excess of 100 mg/l. By contrast, its 'relative inhibition factors' against Candida species (calculated from areas under the antifungal dose-response curves) were of the same order as those of other imidazole and triazole antifungal agents. Against pathogenic Aspergillus species and dermatophytes, the mean relative inhibition factors were the highest so far recorded for an azole antifungal, indicating a relatively weak inhibitory activity against these fungi. Fluconazole inhibited branching and hyphal development in C. albicans at concentrations as low as 10(-6) M (0.3 mg/l), but miconazole and ketoconazole were still active in these tests at concentrations 100 times lower than this. The new antifungal did not suppress ATP concentrations in C. albicans spheroplasts, in common with other weakly lipophilic azole antifungals. This overall poor activity of fluconazole in vitro corresponds badly with its high activity in animal models of mycoses in vivo, and provides more evidence for the unreliability of tests with azole antifungals in vitro as predictors of potential efficacy in vivo.

A high affinity antiprogesterone antibody (APA) was tested in both pseudopregnant and pregnant rats for its ability to alter serum and ovarian concentrations of total and free progesterone and serum gonadotropins and for contragestational effects. APA injected ip on the sixth day of pseudopregnancy resulted in rapidly increased levels of total progesterone in serum, but no detectable change in free progesterone as measured by equilibrium dialysis. Serum gonadotropins similarly increased after APA injection. Progesterone concentrations in various body tissues indicated an initial increase in progesterone production followed by a marked decrease apparently in response to induce luteolysis. Similar levels of hormones were obtained in pregnant rats after ip administration of APA on day 10 of gestation. Fetal resorption followed in all animals and was complete within 96 h. The effect of APA on fetal loss appears to be a combination of a direct reduction of uteroovarian progesterone concentration and a negative feedback of progesterone on the pituitary release of gonadotropins, thus resulting in luteolysis and a further reduction in available progesterone.

The following inscriptions from the Roman colony of Antioch in Pisidia, which form part of the fruits of expeditions made in 1912 and 1913, have been kindly communicated to me by Sir W. M. Ramsay. I am indebted to him and to Mr. J. G. C. Anderson for helping me to elucidate several of the points discussed below, and I have also to thank Mr. W. M. Calder for suggestions made at a later stage.

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ANY businessman today who departs from past procedure in running his business faces a vital and growing patent problem—that of negative patent protection. He needs protection against others patenting his own improvements and discoveries. Under present practice he can't get it unless he goes through all the motions required by regular patent routine, a laborious and expensive method. To protect his minor improvements upon which he wants no monopoly, he is placed in the absurd position of having to apply for a patent—a thing for which in itself he has no need except to forestall lawsuits and headaches from interfering patents possessed by others. Why shouldn't he be permitted to obtain protection by merely challenging the priority of ideas? If he could file in the Patent Office an application for the purpose of challenging priority only, the resulting elimination of cost and labor should be welcome to everyone concerned. Applications for Interference Only I propose ...