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Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed. This paper considers tools (both those available and others that may be required) to achieve and maintain malaria elimination. New diagnostics are needed to direct treatment and detect transmission potential; new drugs and vaccines to overcome existing resistance and protect against clinical and severe disease, as well as block transmission and prevent relapses; and new vector control measures to overcome insecticide resistance and more powerfully interrupt transmission. It is also essential that strategies for combining new and existing approaches are developed for different settings to maximise their longevity and effectiveness in areas with continuing transmission and receptivity. For areas where local elimination has been recently achieved, understanding which measures are needed to maintain elimination is necessary to prevent rebound and the reestablishment of transmission. This becomes increasingly important as more countries move towards elimination., David Kaslow and colleagues examine the progress in reasearch for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication and propose a research agenda.

The authors, both of whom are involved in providing support services to university students with learning disabilities, describe some of the current issues and challenges faced by students, staff, and faculty. Programs and initiatives in some Canadian institutions that have proven to be successful are described, such as a sequential five-step procedure model that directed the delivery of services at the university. Resource and reference lists are also provided.

Audiometric hearing tests were conducted at the Mayo Clinic in Rochester at the beginning of the 1930s. The list price for one of its audiometers at that time was 3,500 dollars, which translates into approximately 37,000 dollars in 2003 currency. Physicians and residents in training were responsible for conducting hearing tests in the 1930s and 1940s. In the early 1940s a registered nurse was trained as an audiometrist to assist for some of the audiometric testing. The first "consulting audiologist" at the Mayo Clinic in Rochester was hired in 1949, early in the development of audiology as a profession. Growth in demand for audiologic services for larger numbers of patients and in the variety of services provided to them led to marked increases in personnel, space, and specialization over the years.

Erythema gyratum repens is a rare cutaneous marker for internal malignancy and the association with other paraneoplastic syndromes is not unusual.We report the case of a 54 year-old man with a three-month history of erythroderma which evolved into erythema gyratum repens; a bronchial carcinoma was discovered. Erythema gyratum repens was associated with acquired ichthyosis, hyperkeratosis of the ears and eosinophilia. Improvement of the paraneoplastic dermatosis was achieved by treatment of the underlying carcinoma with chemotherapy, surgery and radiation. However, the lesions relapsed when metastases appeared. Another regimen of chemotherapy improved the carcinoma and the dermatosis.The parallel course of the carcinoma and the cutaneous eruption strongly supports the diagnosis of a cutaneous paraneoplastic syndrome. Three months prior to erythema gyratum repens, the patient developed a scaling erythroderma. This unusual early manifestation is misleading. Our case highlights the possible association of different paraneoplastic syndromes: initially scaling erythroderma, followed by erythema gyratum repens associated with acquired ichthyosis, hyperkeratosis of the ears and eosinophilia.

Bullous pemphigoid is the most frequent autoimmune blistering dermatologic disease. Induction of pemphigoid has been observed after administration of certain drugs but also after various irradiation procedures. We report a case of pemphigoid strictly confined to the irradiated area.A 66-year-old woman had been irradiated 16 years before because of a breast carcinoma. She presented with a blistering rash strictly confined to the irradiated area. The diagnosis of pemphigoid was confirmed with pathologic examination, direct immunofluorescence, direct immunofluorescence of sodium chloride-separated skin, electron microscopy and immunoelectron microscopy. Indirect immunofluorescence and serum immunoblot were also positive. The patient was successfully treated with topical steroids.The location on the area of radiotherapy and the limited character of lesions were unusual. A few cases of pemphigoid strictly localized to the area of radiotherapy have been published. However, in our case, only direct immunofluorescence and immunoelectron microscopy reliably confirmed the diagnosis. The unusual location of this pemphigoid is not due to the regional variation in the expression of the antigen. Other hypotheses concerning the pathogenesis of localized pemphigoid should be examined.

Cutaneous cryptococcosis is a systemic fungal disease; it is commonly observed in immunocompromised patients.We report the case of a cryptococcal whitlow in an HIV positive patient. The mycologic culture of the cutaneous lesion was positive for Cryptococcus neoformans serotype D. The detection of the blood antigen was positive but there was no pulmonary nor central nervous system involvement. The lesions cured with fluconazole (400 mg/day during 2 months and 200 mg/day after).This unusual clinical presentation of cutaneous cryptococcosis has never been reported in an HIV positive patient. As the dermatologic manifestations of cryptococcosis are polymorphous mycologic examination of skin lesions is very important.

An analytical procedure for simultaneous determination of codeine and morphine In urine Is described. The detection of codeine and morphine Is based on liquid-liquid extraction and derlvatlzatlon to the scetylated compounds. The acetylated codeine and morphine are separated by capillary gas chromatography and Identified mass apectrometrlcally by selected Ion monitoring (SIM). Quantitative determination was carried out by SIM using nalorphlna as Internal standard. Excellent Ilnserlty was obtained over a concentration range of 25 to 800 ng/mL. The overall recovery for codeine and morphine In the extraction was found to be 58% and 40%, respectively. The on-column sensitivity for both compounds was 2 ng at a peak-to-noise ratio of 5:1. The derivatives, acetylcodelne, dlscetylmorphlne, and dlacetylnalorphlne were stable at room temperature for 72 hr. ing procedures including silylation 09,26,29,30), pentafluorobenzylation (27), trifluoroacetylation (27,28,36), pentafluoropropionylation (20,25,31), heptafluorobutyrylation (21,22), and acetylation (12,23) are being used. The perfluoroesters are unstable in the presence of moisture (22,28,32,35) due to the strong negative inductive effects of fluorine atoms in the molecule. Therefore, the preparation and handling of these derivatives require anhydrous conditions. The trimethylsilyl derivatives are also known to be moisture sensitive. In addition, abnormal silylation at the double bond in the allylic alcohol moiety of codeine has been reported (29). Such unusual silylation is also expected in other opiate compounds having that functionality. An acetylation procedure with detection of products utilizing a packed GLC column and flame ionization detection is known (12,23). Possible overlapping of undesirable compounds having the same retention time as that of acetylcodeine and diacetylmorphine must be considered. Therefore, a method is described here to separate and identify codeine and morphine in urine by capillary column gas chromatography and electron impact (EI) selected ion monitoring (SIM) mass spectroscopy.

Five drug-free male subjects ingested marijuana-laced brownies in a double-blind crossover study designed to test for behavioral effects, physiologic effects, and urinary cannabinoid metabolites produced as a result of consumption of marijuana plant material cooked in foodstuff. On three separate occasions, each subject consumed two brownies which contained 1.6 g of marijuana plant material. Placebo marijuana plant material (0% THC) was mixed with marijuana plant material (2.8% THC) so that each subject ingested equivalent marijuana plant material of 0, 1, and 2 marijuana cigarettes (2.8% THC). Subjects scored significantly higher on behavioral measures after consumption of brownies containing THC than with placebo; however, the effects were slow to appear and variable. Peak effects occurred 2.5 to 3.5 h after dosing. Modest changes in pulse and blood pressure also were noted. Urinalyses by EMIT d.a.u. assay and Abuscreen RIA for cannabinoids and GC/MS assay for THCCOOH indicated that substantial amounts of marijuana-related metabolites were excreted over a period of 3 to 14 days. No positives were produced as a result of ingestion of placebo brownies.

SUMMARY A case is described of livedo reticularis and nodules, resembling polyarteritis nodosa but shown to be due to emboli of cholesterol crystals.

Anesthesia for the patient with heart disease has become increasingly safer with the passage of years due to a better knowledge of the physiology of heart disease and of the pharmacologic action of anesthetic agents themselves. There are few statistics to support the clinical impression that patients with cardiac disease tolerate anesthesia and surgery well but reports are not lacking. The difficulty in gathering statistics lies in an inability to compare results in comparable groups of patients. Anesthesia is but a small part of the total operative experience. The patient with serious heart disease usually undergoes a relatively long period of preoperative preparation. When ready, he is given preanesthetic medication and is subjected to the administration of an anesthetic. The surgical operation is superimposed on these preliminary events. Subsequently, convalescence with its many physiologic adjustments completes the surgical experience. Anesthetic problems may originate in any of the aforementioned phases of the operative experience. These problems have been briefly reviewed. The most important factor in minimizing the problems of anesthesia itself is the skill and knowledge with which the anesthetic agents are chosen and administered rather than the actual pharmacologic and physiologic effects of the agents themselves. On a background of thorough medical preperation safe anesthesia for the patient with heart disease consists of the careful selection of preanesthetic medication, flawless technic, and use of minimal quantities of anesthetic agents and adjuncts. Despite the attainment of these goals, circulatory and respiratory problems will be encountered. These may be related to the heart disease itself, to medical preparation, pharmacologic side effects, and to a multitude of undesirable respiratory and circulatory reflexes. The latter in turn reside in anesthetic and surgical manipulation. Knowledge of these factors enables the internist to understand the problems of anesthesia and to prepare the patient for the operative experience.

This study examined the inter-judge and intra-judge reliability of interpreting the presence or absence of averaged evoked responses. There is considerable variability on both of these measures. The only conclusion which can be made based on the data in this study is that the judges used in this study are not able to be reliably objective about the responses. If this conclusion is correct and can be generalized, the procedure as described in this study should be used with extreme caution. It would further appear that the procedure lacks a great deal of objectivity when conducted without specific objective criteria.

Opium has been used for the relief of pain at least as far back as records go. Morphine was separated from the mixture of opium alkaloids in 1806, and synthesis was accomplished in 1952. From an over-all viewpoint, morphine is still the most satisfactory narcotic analgesic, but certain untoward effects have fostered the search for a better compound, a goal still to be achieved. This review of the narcotic analgesics will deal with the clinical pharmacology of these substances with reference to morphine and meperidine, the best known substitutes, as yardsticks. A discussion of the general actions and uses of these drugs will be followed by a more detailed consideration of the commonly used compounds. It should be understood that few of the drugs have been studied satisfactorily in their entirety. This deficiency relates largely to the difficulty in determining drug effects on man under controlled conditions and to the haste in presenting new substances for clinical use before thorough study.

With the recent development and distribution of hearing aids incorporated into eyeglasses, there has come an automatic reawakening of interest in providing binaural sound amplification for hard of hearing persons. Although the effort to achieve a practical binaural hearing aid has been long and persistent, it is only in the eyeglass models that many disadvantages and problems seem to have been minimized or eradicated. Mere logical reasoning seems basis enough for the thought that binaural hearing is more satisfactory than monaural; and if one were to give total credence to the claims and inferences of certain hearing aid manufacturers, it would seem that every person suffering from a binaural hearing loss should profit from sound amplification received in both ears. In recent months rather impressive testimonials have been appearing in trade journals supported by hearing aid manufacturers and dealers. 1,2,10,13 Among other things, binaural amplification is reputed to achieve the

IN three patients extremely prolonged renal failure developed after exposure to methoxyflurane (Penthrane). Their course and biopsy findings were unusual and similar enough to suggest a distinct syndrome. Renal failure persisted for several months to over a year on dialysis despite the absence of cortical necrosis. A number of renal abnormalities, ranging from an unusual diuresis to acute renal failure, are well documented as complications of methoxyflurane.1 Prolonged, acute renal failure has also been suggested,2 but this unusual – and extremely important – complication has not been documented in detail. Case Reports Case 1 (PBBH 9–67–09). A 53-year-old man was . . .

A patient with bilateral pneumothorax is presented in whom staged, bilateral pleural abrasions were planned. Following the removal of Webs from one lung, postoperative IPPV produced a tension lung cyst in the opposite lung causing compression of the lung and mediastinum, requiring emergency operation on the opposite thorax and resection of a giant bullae. The case is an unusual complication of IPPV therapy in a patient with chronic obstructive lung disease.

ALTHOUGH expected to be increasingly rare, death and a considerable morbidity still follow the aspiration of gastric contents into the lungs in the anesthetic period. The exact rate of occurrence cannot be ascertained, for the accident is not officially reportable except perhaps to obstetric mortality commissions. Every physician probably will recall at least 1 such death in his practice. It is urgent, therefore, to call attention to the problem as being to a large extent preventable, and to narrate the anesthetic experience so far as it may pertain to other fields of medicine. Aspiration occurs in the comatose patient, in . . .

ANESTHESIA for obstetrics is well over a century old, but a review of methods used reveals few innovations in the past fifty years. Nevertheless, progress has been made through increased knowledge ...

In two separate studies, 5 drug-free male volunteers with a history of marijuana use were passively exposed to the sidestream smoke of 4 and 16 marijuana cigarettes (2.8% delta-9-tetrahydrocannabinol [THC]) for 1 h each day for 6 consecutive days. A third study was similarly performed with 2 marijuana-naive subjects passively exposed to the smoke of 16 marijuana cigarettes. Passive smoke exposure was conducted in a small, unventilated room. Room air levels of THC and CO were monitored frequently. All urine specimens were collected and analyzed by EMIT d.a.u. assay, Abuscreen radioimmunoassay and GC/MS. The studies show that significant amounts of THC were absorbed by all subjects at the higher level of passive smoke exposure (eg., smoke from 16 marijuana cigarettes), resulting in urinary excretion of significant amounts of cannabinoid metabolites. However, it seems improbable that subjects would unknowingly tolerate the noxious smoke conditions produced by this exposure. At the lower level of passive marijuana-smoke exposure, specimens tested positive only infrequently or were negative. Room air levels of THC during passive smoke exposure appeared to be the most critical factor in determining whether a subject produced cannabinoid-positive urine specimens.

Chemical substances migrate outwards from within the body to the skin surface by diffusion from cutaneous capillaries across the epidermis. Heretofore, study of transepidermal chemical emissions have been restricted to substances which are in the vapor phase at skin surface temperature. We have investigated outward transcutaneous chemical migration of nongaseous chemicals by devising an occlusive transcutaneous chemical collection system, consisting of a tape-encased plug of gelled saline in which activated carbon is dispersed. Investigations of nine chemicals in ‘fuzzy’ rats, rhesus monkeys, and man provide data which are consistent with a general theory of outward transcutaneous chemical migration. This noninvasive continuous transcutaneous sampling technique provides a new method for investigating skin permeability in vivo and may provide a basis for convenient diagnosis and monitoring of chemical exposure.

Available methods for determining PCP use are based on the presence of the parent drug in urine. PCP, however, is very potent and is extensively metabolized; it is therefore present in urine in only small quantities. This work was undertaken to determine whether an amino acid metabolite of PCP, 5-(N-(1'-phenylcyclohexyl)amino)pentanoic acid, can be used to determine PCP use. A solid phase adsorption technique was developed to extract the amino acid metabolite from urine. Recovery averaged 93%, and subsequent GC/MS analysis was free from interference. Analysis of 67 urine samples demonstrated that the amino acid metabolite exists in human urine in significant quantities.

A procedure for detection and quantitation of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid, a major metabolite of delta-9-tetrahydrocannabinol in urine, has been described. Since the metabolite is present in both conjugated and unconjugated forms, hydrolysis of urine was carried out to increase the sensitivity of detection. The acidic metabolite was isolated by strongly basic anion exchange resin, and subsequently derivatized to methyl 1-dehydroxy-1-methoxy-11-nor-delta-9-tetrahydrocannabinol-9-carbox ylate (1a) by methyliodide in the presence of tetramethylammonium hydroxide. The derivatized product was separated in a capillary column gas chromatograph, and finally detected by a mass spectrometer under electron impact mode. Confirmation of the product was carried out by monitoring three ions that represent the major portions of the molecule and comparing their relative abundances to that of a standard. Quantitation was based on 5'-2H3-11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid as internal standard. Excellent linearity was obtained over the range of 2 to 1000 ng/mL. The overall yield of extraction using the anion exchange resin was 50 to 60%. This extraction process is rapid and suitable for a large number of sample analyses. The methylated product (1a) is stable for at least 72 hr at room temperature.

An infarct in the left middle cerebral artery territory in a 9 months old girl occurred in the course of Kawasaki's disease which in addition had induced a coronary aneurysm and a myocardial infarct. Embolism from the myocardial infarct was likely to have provoked the cerebral infarction. Neurological symptoms and signs are unusual in Kawasaki's disease.

Experience with patient-controlled audiometers in a clinical setting suggests that group testing can be accomplished satisfactorily with most adult subjects. Some of the findings and a comparison of results obtained with automatic and conventional audiometry are presented as a basis for evaluating this means of auditory screening. Generally, the findings justify the use of automatic screening audiometry as one means of handling large numbers of patients with relative convenience and economy. Certain problems inherent in the procedure appear to make it impractical for some clinical patients.

P HYSIOLOGIC and metabolic changes of varying complexity accompany the use of the heart-lung machine in man. These changes relate to many factors, such as the design of the apparatus, the ventilating gas, the pH of the priming blood, the rate and duration of perfusion, the body temperature and the need for and manner of producing cardiac arrest. Many of the changes in acid-base balance, blood volume and myocardial function are difficult or impossible to duplicate in the laboratory. For these reasons this study presents circulatory and respiratory data obtained during cardiopulmonary bypass in 50 adults undergoing operation for a variety of congenital and acquired diseases of the heart. It attempts to integrate the hemodynamic responses, to indicate some unusual responses, and to present technics that have been found helpful in avoiding serious abnormalities.

Resembling certain members of the animal species, more than a few new drugs, while demonstrating admirable familial traits, also indulge in streaks of abnormal behavior. The volatile inhalation anesthetics provide no exception to this rule although early in the history of use, their deviations are apt to be concealed in the complications of surgery. Over the last 15 years chemists have concentrated on the synthesis of new halogen-substituted hydrocarbons in an effort to eliminate undesirable features of the primordial anesthetics. The result has been the introduction into clinical anesthesia of several compounds incorporating the most wanted characteristic — inertness, therefore . . .

A method of anesthesia, essentially amnesia, for patients undergoing cardioversion has been presented. A review of the administration of anesthesia in 150 cases has indicated the safety of the method and the absence of complications in this group of patients presenting with cardiac arrhythmias.

In the light of recent investigations I have undertaken to re-examine the thesis that prolonged anaesthesia may be shocking Discussion was confined to the pharmacological properties and manner of administration of anaesthetics, although it is recognized that many effects cannot be distinguished from those produced by operation Not only may anaesthetics alter physiology intra-operatively, but their physical properties suggest that retention in the body can extend untoward effects into the postoperative period As an example of postanaesthetic shock the instance was cited of postoperative hypotension refractory to vasopressor drugs Some of the common abnormalities underlying this condition were enumerated, and each subsequently exammed for possible anaesthetic complicity