[Occurrence of arterial hypertension in hospitalized children aged 3 days to 4 years].

Totally 510 measures of blood pressure were performed with sphygmo-oscillographic, ultrasound, and auscultation techniques. Sphygmo-oscillography was used for all measurements whereas ultrasound failed in 2.9% and auscultation in 48.2% of cases. Arterial hypertension was diagnosed in 24 children, i.e 11%.


[Sodium outflow rate through lymphocyte cell membranes, serum levels of sodium, potassium, aldosterone, total catecholamines, 6-keto- PGF2alpha and plasma renin activity in patients with primary arterial hypertension treated with captopril].

Sodium ions outflow rate through lymphocyte membranes, serum sodium, potassium, aldosterone, total catecholamines and 6-keto-PGE alpha levels, and plasma renin activity were studied in patients with mild hypertension associated with low and hugh plasma renin activity treated with captopril in a single dose of 12.3 mg and after the treatment with daily doses of 12.5 mg and 25 mg for 3 days. It was found, that captopril in hypertensive patients with high plasma renin activity decreases both systolic and diastolic blood pressure, decelerates heart rate, and decreases serum total catecholamines and plasma renin activity. Sodium ions outflow rate and serum sodium, potassium, aldosterone, and 6-keto-PGE alpha remain unchanged. Captopril in hypertensive patients with low plasma renin activity. The remaining parameters are unchanged. Moreover, it was noted that serum 6-keto-PGE alpha levels are lower in hypertensive patients with low plasma renin activity.


[Difficulties in the diagnosis of pheochromocytoma in children].

Pheochromocytoma was the cause of arterial hypertension observed in 0.9% of children treated in 1982-1989. Out of clinical features the most characteristic was sustained hypertension often complicated by the accelerated phase of malignant hypertension and encephalopathy. Sustained tachycardia was also found in all patients. Increased urinary excretion of catecholamines and its metabolites confirmed the diagnosis in all cases. The most sensitive and specific methods for tumor diagnosis were ultrasonography and computer tomography of the adrenals while scintigraphy with meta-iodobenzylguanidine+ labelled with iodine-131 radioisotope gave a high percentage of false negative results.


[Effectiveness of trimetazidine in patients with hypertension and the symptoms of coronary disease].

The investigations were aimed at the objective evaluating of trimetazidine efficacy in the treatment of 30 patients with arterial hypertension and ischemic heart disease carried out in non-invasive manner. It was found that trimetazidine complies with several requirements for the effective drug administered to the patients with hypertension associated with ischemic heart disease as it: (a) reduces peripheral resistance and exerts favourable effect on the walls tonus of larger arteries; (b) lowers specifically post-exercise arterial pressure and improves resting arterial pressure; (c) reduces demand for oxygen; (d) is safe, and well tolerated by 83% of the treated patients in daily dose of 60 mg.


[Hypertension in pregnancy with special reference to its treatment].

Definition and classification of the arterial hypertension in pregnancy are discussed. An emphasis is on the problems of differential diagnosis between pre-eclampsia and other forms of hypertension. Use of hypotensive drugs in pregnant patients with particular reference to emergencies is also discussed. The treatment of pregnant women with hypertension is still a problem which require close co-operation of both an obstetrician and internist. Follow-up after labour is GP duty to find out if the patient remains hypertensive. If so, etiology of the disease should be again searched.


[Abdominal resection of rectal cancer].

Preservation of anal sphincters in the surgical treatment of rectal cancer is often controversial as far as an extent of surgery, incidence of complications and an increase in mortality rate in perioperative period are concerned. The study was aimed at results of the retrospective analysis of patients, who undergone abdominal excision of the rectum for malignant tumours. Totally 136 patients were operated. Perioperative mortality rate was 5.14%. Totally 26.4% of patients survived for at least 5 years, including 80% of patients operated in A stage of cancer, according to Duke, and 43.3% of patients with tumour in B stage. An emphasis is on the necessity to leave a 2-centimeter margin of healthy tissues around the tumour, provided, that the result of intraoperative histological examination was negative. Such a margin is sufficient for anastomosis. Low anastomoses do not produce early complications and recurrences.


[Results and prognosis after highly selective vagotomy in the light of the mathematical theory of approximate sets].

Information system for 122 patients with peptic ulcer, who underwent highly selective vagotomy within 5 and 13 years earlier has been analysed with the use of technique based on the approximate sets theory. Cause-effect relationship between data describing the analysed patients before surgery and remote result of therapy (expressed in a 4-score Visick's scale) have been sought. Using a technique of the approximate sets, information system has been described from 11 to 5 significant and necessary preoperative data most closely related with the result of therapy. Models of the typical representatives of results classes have been constructed with the use of a/m data. Then, a decision algorithm has been made. Such an algorithm represents cause-effect relationship between significant data and the result of treatment. Models and decision algorithm for the favourable results of the treatment (I and II class in Visick's scale) constituted a base for the verification of indications to the highly selective vagotomy and construction of data base for computer-assisted system of the treatment of peptic ulcers with the highly selective vagotomy.


[Imipenem in the treatment of patients with severe surgical infection].

The clinical efficacy and safety of intravenously administered imipenem/cilastatin in the treatment of 45 patients with severe bacterial septicemia due to intra-abdominal abscesses, respiratory and urinary tract as well as skin, soft tissue and bone infections was studied in the prospective and open trial. The in vitro antimicrobial activity of imipenem has been assessed on the basis of 909 bacterial strains isolated from patients treated and non-treated with imipenem/cilastatin. Among them were 526 Gram-negative, 370 Gram-positive aerobic bacteria and 13 Gram-negative anaerobic bacteria (Bacteroides sp.). Pathogen susceptibility to imipenem was determined with a disc-diffusion technique using Merck, Sharp Dohme sensitive discs containing 10 mcg of imipenem. Highly sensitive to imipenem were 96.8% of Gram-negative 82.7% of Gram-positive aerobic bacteria and 100% of Bacteroides sp. All patients, in whom evident foci of infection e.g. intra-abdominal abscesses were discovered, were operated on. The dosage of imipenem/cilastatin ranged from 1.5 to 2.0 g/24 h. Clinical cure and bacteriological elimination was achieved in 39 (86.7%) of patients while 6 (13.3%) showed marked clinical improvement. Before and during therapy, aerobic and anaerobic cultures were taken from accessible sites. All specimens were worked up using conventional bacteriological techniques. Before during and after therapy, samples for hematology, biochemistry and urinanalysis were obtained. Adverse clinical effects were noted in 2 (4.4%) patients. One had nausea and vomiting which were probably related to rapid infusion and disappeared after increasing the administration time, and one had transient diarrhea. In conclusion, imipenem/cilastatin was a well tolerated and effective drug in the treatment of life-threatening surgical infections.


[Diagnosis of obstructive sleep apnea syndrome].

Symptoms and signs in 12 patients with severe obstructive sleep apnea (OSA) syndrome have been presented. The most common symptoms were snoring , increased motor activity during sleep and excessive daytime somnolence. The factors predisposing to OSA syndrome were obesity and anatomic abnormalities of the upper airway structure. In some cases the signs of OSA syndrome included hypertension, right heart failure, chronic alveolar hypoventilation and polycythemia. Polysomnography showed sleep fragmentation and the prevalence of light sleep stages. Obstructive sleep apneas repeated 73 +/- 23 times per hour of sleep. The mean apnea duration was 19 +/- 8 s. The mean arterial oxygen saturation during apnea was 72 +/- 14%.


[Plasma antithrombin III activity in patients with pulmonary thromboembolism].

A decreased plasma antithrombin III activity has been noted in 12 out of 20 patients. In 2 patients it was most probably congenital defect, whereas in the remaining 10 patients--acquired. The observed disorders in the activity of antithrombin III with particular reference to anticoagulant therapy have been discussed.


[Effect of misoprostol, a synthetic equivalent of prostaglandin E1, on bronchodilation in bronchial spasm].

A effect of a single dose 400 micrograms misoprostol (Cytotec-Searle) on a degree of the bronchospasm relief has been investigated in 8 patients, and the results have been compared with those produced by aminophylline i.v. infusion in the rate of 500 mg/hour. Prior to and 10, 20, 30, 60, 90, 120, 150 and 180 minutes after administration of both drugs, the following parameters of pulmonary ventilation have been determined: VC, VC%, FEV1, FEV1%, MVV, and MEFR. The results have shown that misoprostol given in a single oral dose of 400 micrograms to patients with bronchospasm has the bronchodilating activity which is statistically significant. However, this activity is rather weak and significantly lower than that of intravenous aminophylline infusion.


[IgE-containing immune complexes in bronchial asthma].

Level of circulating immunological complexes and their immunoglobulin content have been determined in 36 asthmatic patients, including 15 patients with atopic asthma and 21 patients with infectious asthma. A technique of staphylococcal protein A binding has shown, that the level of the circulating immunological complexes is increased in patients with infectious bronchial asthma. An amount of IgE in these complexes has been increased in both atopic and infectious bronchial asthma. However, a level of IgE-containing immunological complexes has been higher in the atopic asthma, then that in infectious form of the disease. An increased IgA content in the immunological complexes has been noted in the infectious asthma.


[Occurrence of early and late asthmatic reaction after provocation with antigen and the status of pulmonary ventilation in patients with hay fever after the pollination season].

Pulmonary ventilation and asthmatic reaction under laboratory conditions have been investigated in 23 patients with allergic rhinitis hypersensitive to grass pollen. Pulmonary ventilation has been assessed with the aid of VCin, FVC, FEV1, FEV1/VCin, PEF, MEF50, and MTT. Asthmatic reaction has been produced by an inhalation of allergens mixture with dose-response technique. An early reaction has been diagnosed, when FEV1 decreased by at least 20% or MEF50 by 30% within 10 minutes, and late reaction when the same parameters decreased after 6 or 24 hours. An early asthmatic reaction has been noted in 2 patients (8.7%), late--in 4 patients (17.4%), and double (both early and late) reaction in 2 patients (8.7%). Pulmonary ventilation has been normal in all examined patients, except two of them with peripheral airways obstruction (MEF50 less than 70% of the normal value). Results suggest, that asthmatic reaction may be provoked in the laboratory in patients with pollinosis and normal pulmonary ventilation after pollen season. Such a reaction may also be expected during a natural exposition to pollens.


[Evaluation of selected personality factors in patients with bronchial asthma].

Psychological factors an important role in the development and clinical course of the bronchial asthma. Therefore, an effect of the selected personality features on the course of the bronchial asthma have been studied. The study included 91 asthmatic patients and 30 persons of the control group. Three psychological tests have been used: Wiskad-MMPI. Cattell's Self-Cognition Chart, and Eysenck's Personality Inventory translated by Chojnowski. The study has shown, that asthmatic patients are characterized by the high level of anxiety and marked emotional imbalance, especially female patients. Emotions are suppressed and neglected by the asthmatic patients. These attitude should be considered in psychotherapy of such patients.


[Results of surgical treatment of mediastinal neoplasms].

The results of radical and partial surgical treatment of 146 patients with mediastinal tumors have been assessed. All patients were operated at the Specialistic Hospital in Zakopane from the 1st January, 1967 to the 31st December, 1989. Hundred twenty one patients (82.9%) suffered from malignancy and 25 (17.1%) from non-malignant mediastinal tumors. Mortality rate was 2.0%. Late results have been expressed in terms of survival period, and they have been as follows: 44.4% of patients survived 20 years after surgery, 36.5% of patients survived 15 years, 42.9% of patients--10 years, and 56.1% of patients survived 5 years. More than 50% of operated patients resumed their previous work.


Nutrition in dystrophic epidermolysis bullosa.

In dystrophic epidermolysis bullosa (EB), a combination of diminished food intake and increased nutritional requirements commonly leads to malnourishment. Adequate nutrition in these patients could provide many benefits, including improved growth, accelerated healing, decreased susceptibility to infection, and enhanced well-being. We assessed nutrition status of children with dystrophic EB, and evaluated the benefits of nutritional advice in those who were considered malnourished. The majority of patients had inadequate intakes of a wide spectrum of nutrients, including those who appeared to be relatively mildly affected. We were unable to secure persisting substantial improvements in dietary intake despite thorough counseling. Adequate nutrition in patients with dystrophic EB depends on active nutritional support starting from birth. The need for more invasive techniques of nourishment, such as nasogastric and gastrostomy feeding, may have to be considered earlier than is currently the case.


[Hazards of antitubercular treatment--case report].

A case of the female caucasian patient with constricting tuberculous pericarditis is presented. The patient has been treated with tuberculostatics, which produced severe to ic liver damage, and ultimately the death. A risk of liver damage increases with patients' age and the jaundice onset in the period shorter than two months after the start of therapy. Prognosis is poor in case of HBs carrier state, alcohol abuse, therapy with benzodiazepines, and oral contraceptives. A moderate increase in transaminases activity does not require a cessation of the drugs but a reduction of the administered doses is necessary, especially in patients over 35 years of age. Patients of the height risk group require a careful selection of antitubercular+ agents. Patients with suspected chronic liver disease should be carefully examined, together with liver biopsy, before tuberculostatics are given.


Behavioral adjustment and self-concept of young children with hemangiomas.

This study was conducted to determine the behavioral responses and self-concepts of young children with self-limited but transiently disfiguring capillary hemangiomas involving the head and neck. Nineteen children with hemangiomas, age 3 to 5 years, and their parents were compared with an age-matched control group without lesions. Responses to a parental checklist, informal interview, and self-concept test showed few differences between young children with hemangiomas and those without this neoplasm.


Blister beetle dermatosis in Hawaii caused by Thelyphassa apicata (Fairmaire).

Members of the family Oedemeridae are known as false blister beetles. Although they have a worldwide distribution, oedemerid blister beetle dermatosis has been described only in the Pacific basin and the Caribbean. We report a case of the disorder in the Hawaiian Islands caused by Thelyphassa apicata (Fairmaire). To our knowledge this is the first case report described in that locale, and the first caused by this species.


Painful, plaque-like, pitted keratolysis occurring in childhood.

Pitted keratolysis is a superficial infection of the soles of the feet that is almost always asymptomatic. A painful variant of this disorder was reported to occur in adult males during military service. We report painful, plaque-like, pitted keratolysis in two children. Treatment with topical erythromycin was curative.


[Effect of environmental factors on the defense system of the respiratory tract].

Respiratory system due to its enormous surface is particularly prone to be penetrated by various exogenous factors. Therefore, this system is equipped with numerous local, specific and unspecific, cellular and humoral immunological mechanisms. This system includes: BALT (bronchial ++adeno-lymphatic tissue) producing secretory immunoglobulins, ciliary system, mucus which provides an extracellular surface for immunoglobulins, lysozyne, interferon, lactoferrin, and complement system activities. Moreover, alveolar macrophages, surfactant, neuropeptides, and inflammatory processes constitute other components of the whole defense system. A complex interactions increasing its efficiency take place between particular components. Unfavourable environmental factors attack this system in several ways. The most important are: recurrent bacterial and viral respiratory infections, air pollution, tobacco smoke, and unfavourable climate and microclimate.


Clinical, histologic, and ultrastructural findings in two cases of infantile systemic hyalinosis.

Two unrelated infants had stiff skin and painful joint contractures in the first few months of life. Other features included gingival hyperplasia, small papules on the face and trunk, perianal nodules, and bloody diarrhea. Hyaline material was evident in the papillary dermis and gut mucosa in both patients. Ultrastructural examination revealed a distinctive fibrillogranular appearance. These infants have the same clinical, histologic, and ultrastructural features as four infants we reported previously with infantile systemic hyalinosis. One of the patients described here demonstrated some features that overlap with those of juvenile hyaline fibromatosis.


[Normal values of peak expiratory flow in children from an environment with high degree of atmospheric air pollution].

Peak expiratory flow (PEF) has been measured with Vitalograph (in liters per minute) in 2,512 school-children aged between 7 and 15 years in Upper Silesian Industrial Region. Five hundred eighty one children from Zarki near Czestochowa served as a control group. The results have been analysed statistically. Determined PEF values for children from the Upper Silesian Industrial Region are considered as a biological reference values for assessment of PEF in both health and disease. PEF values calculated for children from Zarki were higher than those in the examined group, except the value for a 14-year old children.


Cutaneous mucinosis in a child with systemic lupus erythematosus.

Cutaneous mucinosis is rarely associated with systemic lupus erythematosus. A 13-year-old girl had a two-month history of numerous cutaneous mucinous papules and the new onset of systemic lupus erythematosus. The differential diagnosis and pathogenesis of this variant of cutaneous mucinosis are discussed. This is the first report of a child with this unusual entity.


Lipoid proteinosis: case report.

A 20-month-old Kuwaiti girl had manifestations of lipoid proteinosis, a rare autosomal recessive disorder seen more commonly in Caucasians. This condition is diagnosed based on clinical, histopathologic, and ultrastructural criteria. Its biochemical and genetic aspects are still poorly understood.


Acquired zinc deficiency in association with anorexia nervosa: case report and review of the literature.

Zinc deficiency, whether a result of an acquired or inherited abnormality of zinc metabolism, is associated with characteristic cutaneous findings. The inherited variety is known as acrodermatitis enteropathica. We present a case of zinc deficiency secondary to starvation induced by anorexia nervosa. Since the cutaneous stigmata of zinc deficiency and anorexia nervosa can initially be subtle and occasionally overlap, we believe that screening zinc levels in patients with anorexia nervosa with prominent cutaneous findings should be considered.


Neurothekeoma in a 15-year-old boy: case report.

A 15-year-old boy experienced a rapidly enlarging nodule on his left nose. Histologic findings and immunoperoxidase stains were consistent with the diagnosis of neurothekeoma. The patient was treated with local excision local excision without evidence of recurrence.


Halo dermatitis in children.

Halo dermatitis is a pruritic, eczematous eruption on pigmented nevi and halo nevi in young adults. It may be mistaken for nummular eczema, psoriasis, or fungal skin infection. Awareness of halo dermatitis will possibly reveal more cases in children, which have been reported only rarely.


Ultraviolet light burn: a cutaneous complication of visible light phototherapy of neonatal jaundice.

Visible light phototherapy is an easily administered and effective treatment for neonatal indirect hyperbilirubinemia. Reported cutaneous side effects include transient rashes and the uncommon bronze baby syndrome. A more hazardous side effect is ultraviolet burn. Two premature infants developed phototherapy-induced erythema, one associated with a second-degree burn, after exposure to fluorescent daylight bulbs inadvertently used without Plexiglass shields, thus allowing prolonged ultraviolet A (UVA) exposure. Premature infants, especially during the first two weeks of life, may be significantly susceptible to UVA-induced erythema. Plexiglass shields should always be in place during visible light phototherapy, and nursery staff should be made aware of their purpose.


Congenital miliaria crystallina: case report and literature review.

Generalized congenital miliaria crystallina occurred in a black newborn boy. Although miliaria crystallina occurring in infancy and beyond is well established, congenital occurrence is very rare. The pathogenesis of the disorder is not well understood. We discuss some hypotheses of pathogenesis in the context of our patient, as well as a differential diagnosis and a comparison with a previously reported case. Miliaria crystallina should be considered in the differential diagnosis of vesiculobullous eruptions in newborns.


Sweet syndrome in a neonate with aseptic meningitis.

A 7-week-old infant with antecedent otitis media, upper respiratory infection, and aseptic meningitis was diagnosed as having Sweet syndrome. Although this disease usually affects adults, it has been reported in 17 children. This is the youngest reported patient with the disorder to date, and the first in whom the syndrome was associated with aseptic meningitis.


Aplasia cutis congenita, cleft palate, epidermolysis bullosa, and ectrodactyly: a new syndrome?

Aplasia cutis congenita (ACC) is a skin disorder in which localized or widespread areas of skin are absent at birth. It has been associated with numerous anomalies and recognizable syndromes. We report a newborn infant with ACC of the scalp, multiple facial abnormalities including cleft palate but not cleft lip, hypoplasia of the distal phalanges of the hands, ectrodactyly of the feet, and epidermolysis bullosa of the extremities and lower trunk. Although this patient had some features that overlapped with ectrodactyly-ectodermal dysplasia-clefting syndrome, the absence of cleft lip and presence of additional skin abnormalities made that diagnosis unlikely. This could represent a newly recognized syndrome of numerous malformations in which ACC is associated with a constellation of previously undescribed structural anomalies.


Isotretinoin for acne in Apert syndrome.

Apert syndrome is a congenital disorder consisting primarily of deformities of the skull, hands, and feet. These individuals are also prone to severe acne, particularly involving the upper arms and forearms. Conventional therapy is often ineffective. We report the successful use of isotretinoin for acne in a patient with Apert syndrome.


Instrumentation of a high-shear mixer: evaluation and comparison of a new capacitive sensor, a watt meter, and a strain-gage torque sensor for wet granulation monitoring.

A high-shear mixer was instrumented with a new capacitive sensor, a watt meter, and a strain-gage torque sensor. The output from the capacitive sensor was split into two channels, which monitor both resistive and capacitive changes during the granulation process. The outputs of the devices were related to properties of the wet granulation. The percentage moisture content related linearly to the amplitude channel response. Yield values provided a rheological property to relate with power consumption and torque measurement. Power consumption and torque furnished a similar map of the granulation process. The amplitude channel of the capacitive sensor appears to be more clearly differentiated between binder levels in hydrous lactose-HPMC granulations than either power consumption or torque measurement, based on particle size distributions.


Lymphatic targeting of polymeric nanoparticles after intraperitoneal administration in rats.

Following intraperitoneal administration, the lymphatic targeting of polyacrylic nanoparticles has been evaluated in thoracic duct cannulated rats. The dosage forms administered consisted of carbon-14 polyhexylcyanoacrylate nanoparticles (PHCA) and polymethylmethacrylate (PMMA) nanoparticles. The carbon-14 concentrations were much higher in the excreted thoracic lymph than in the blood for both types of particles. The most dramatic results were found in the mediastinal nodes since the carbon-14 concentrations of rats receiving PHCA and PMMA nanoparticles by the ip route were 70- to more than 2000-fold higher than in the corresponding nodes of animals treated by the intravenous route. This potential lymphatic targeting could prove valuable in cancerology to treat tumors that metastasize in the peritoneal cavity or via lymphatic pathways such as colon carcinomas.


Hydrogels for site-specific drug delivery to the colon: in vitro and in vivo degradation.

Novel hydrogels based on N,N-dimethylacrylamide, N-t-butylacrylamide, and acrylic acid cross-linked with azoaromatic compounds of varying length and electron density of the azo bond were synthesized. The cross-links are degradable by microbial azoreductases present predominantly in the colon, and the gels appear to be suitable for colon-specific drug delivery. The degradability in vitro and in vivo was found to be related to the degree of swelling of the gels. The higher the degree of swelling, the higher the degradability. However, structural and electronic factors were also shown to influence reduction of azo bonds.


The influence of liquid crystalline phases on drug percutaneous absorption. I. Development of a vehicle.

A phase diagram approach has been used to formulate topically applied vehicles containing liquid crystalline phases. The current paper describes the construction of a major portion of the polyoxyethylene(20)cetyl ether:dodecanol:water phase diagram. Known mixtures of the three components were equilibrated and centrifuged to separate the resultant conjugate phases. These were identified and analyzed quantitatively to determine phase boundaries in relevant portions of the phase diagram. Two isotropic liquid phases, several two- and three-phase regions, a solid surfactant phase, and at least three distinct liquid crystalline phases were identified. The determination of tie lines was undertaken in a two-phase region containing an aqueous isotropic micellar solution and a liquid crystalline gel. This information will be used to prepare a number of vehicles of known phase composition and concentration for a systematic evaluation of the effect of liquid crystalline phases on transdermal drug delivery.


The influence of liquid crystalline phases on drug percutaneous absorption. II. Permeation studies through excised human skin.

The influence of liquid crystalline (LC) phases on the percutaneous absorption of a model compound (ploxicromil; PXC) was studied with the use of the phase diagram for the surfactant, oil, and water comprising the vehicles. Two separate sets of vehicles, representing two different tie lines lying in the L1 + LC phase region, were prepared in which the concentration of LC was varied over the range 0 to 100% along each tie line. In vitro permeation studies of PXC from these systems were conducted using excised human skin and the flux values determined as a function of the percentage LC present in the vehicles. In virtually all cases, the flux reached a peak at 5-10% LC and then decreased significantly as the fraction of LC present increased further. The pattern of behavior observed is discussed in terms of current theories describing membrane-controlled and vehicle-controlled diffusion, none of which adequately model the results obtained.


Mixed micelles as proliposomes for the solubilization of teniposide.

The aqueous solubility of teniposide in detergent and phospholipid mixed micelles was investigated as functions of the detergents and lipids composing the mixed micelles, the molar ratio of detergent to phospholipid, and the total lipid concentration of the system. The polarity, the charge of the phospholipid, and its saturation affected the solubilization potential of the micelles. Physical chemical factors such as the pH, ionic strength, and temperature of the dispersion medium also altered the solubilization capacity of the system. The results are explained by the changes occurring in the critical micelle concentration and packing arrangements of the aggregates. The desired solubility of teniposide can be achieved by adjusting the studied parameters to the optimum values. Teniposide-containing mixed micelles were spontaneously converted to drug-containing vesicles upon aqueous dilution; therefore, the precipitation of the drug was totally eliminated. In conclusion, mixed micelles as proliposomes can be a suitable drug carrier system for insoluble compounds such as teniposide.


Determination of association constants in cyclodextrin/drug complexation using the Scatchard plot: application to beta-cyclodextrin-anilinonaphthalenesulfonates.

The appropriate Scatchard equation was developed for a system involving the formation of 1:1 and 1:2 substrate:cyclodextrin complexes. Simulation of this system was performed under the most common experimental conditions encountered in this type of study. The use of the equation allows for nonlinear least-squares estimation of the association constants. The interaction of the model compounds 1-anilino-8-naphthalenesulfonate (1,8-ANS) and 2(p-toluidinyl)-6-naphthalenesulfonate (2,6-TNS) with beta-cyclodextrin (beta-CD) was used to evaluate the theoretical model. Binding experiments were performed using either potentiometric titration or fluorimetric detection. The experimental data for 1,8-ANS/beta-CD fit well to the 1:1 binding model, with an association constant of 87 +/- 1 M-1. The association constants of the 1:1 and 1:2 2,6-TNS/beta-CD complexes utilizing direct potentiometry were 3737 +/- 6 and 149 +/- 2 M-1. It is shown that fluorimetry can give biased estimates for the association constants of the complexation 2,6-TNS/beta-CD, since the assumption of an equivalent quantum yield of bound species is not valid.


Percutaneous absorption enhancement of leuprolide.

Chemical enhancers and vehicles were tested for their ability to improve the percutaneous absorption of leuprolide, a nonapeptide (luteinizing hormone releasing hormone analogue; MW 1209.4). In vitro permeabilities in nude mouse, snake, and cadaver skin were evaluated in either Franz diffusion cells or a Bronaugh flow-through system using an HPLC assay. Skin irritation caused by the formulations was evaluated in the rabbit. The chemical enhancer systems investigated strongly enhanced skin penetration of leuprolide. Maximum permeability enhancement of leuprolide acetate can be achieved with a nonirritating formulation containing ethanol, menthol, camphor, methyl salicylate, urea, and hydrogel. The in vitro permeability in nude mouse skin was 10 or 100 times higher than that obtained in cadaver skin, depending on the type of enhancer that was used in the formulation. Snake skin was at least 10 times less permeable than cadaver skin in this study. However, the effects of chemical enhancers on skin permeability were highly dependent on the skin model. Further, the in vitro permeability of leuprolide in the base form was 10 times higher than in the acetate form with the enhancers.


Permeability characteristics of various intestinal regions of rabbit, dog, and monkey.

The in vitro permeability of a series of both hydrophilic and lipophilic compounds, as defined by the octanol/water partition coefficient, was measured in four segments of rabbit, monkey, and dog intestine using a side-by-side diffusion cell. A linear relationship was established for tissue resistance to hydrophilic compound diffusion in jejunum and colon among rabbit, monkey, and dog. The results suggest that rabbit jejunum is twice as permeable as monkey and dog jejunum. The colonic tissues of monkey, rabbit, and dog demonstrate similar permeabilities. Measuring the permeabilities of different tissues with compounds of similar physicochemical properties allows comparison of tissue restriction to transport. Thus, in vitro permeability measurements may be used to investigate physiological differences of various intestinal tissue segments that influence tissue permeability. Investigating the permeability of different intestinal segments from various species could allow the identification of an appropriate in vitro intestinal permeability model that will lead to the prediction of intestinal absorption in humans, eliminating the need for extensive and often misleading in vivo animal testing.


Influence of permanent cannulation of the jugular vein on pharmacokinetics of amoxycillin and antipyrine in the rat.

The effect of chronic cannulation of the rat jugular vein on the pharmacokinetics of amoxycillin and antipyrine administered by the i.v. and oral routes has been evaluated. Animals that received the i.v. dose of amoxycillin on the eighth day after jugular vein cannulation showed decreased clearance (4.0 +/- 0.3 ml/min) and steady-state volume of distribution (105 +/- 8 ml) compared to animals that received the i.v. dose on the fourth day (5.5 +/- 1.1 ml/min and 155 +/- 17 ml, respectively). Rats first dosed by the i.v. route showed an oral bioavailability of 54 +/- 12%, whereas for those first dosed by the oral route the calculated bioavailability was 31 +/- 6%. Antipyrine was administered to rats by the i.v. and oral routes on the first and fourth days after jugular vein cannulation. Animals intravenously dosed on the fourth day showed a decreased clearance (1.9 +/- 0.3 ml/min) compared to rats intravenously dosed on the 1st day (2.7 +/- 0.6 ml/min). Antipyrine bioavailability was larger in animals first dosed by the i.v. route than in animals first dosed by the oral route (173 +/- 43 and 74 +/- 15%, respectively). These results argue against the use of crossover studies in rats with permanently implanted cannulas since kinetic changes induced by cannulation can be larger than previously proposed.


Validation of different microdialysis methods for the determination of unbound steady-state concentrations of theophylline in blood and brain tissue.

Three microdialysis methods, the "tritium" method, the "point-of-no-net-flux" method, and a method using the low perfusion rate of 0.1 microliter/min, were compared with respect to their ability to generate estimates of unbound steady-state concentrations (Cu(ss)) of the antiasthmatic drug theophylline in blood and brain tissue in anesthetized rats. Concomitantly, the influence of the perfusion flow rate on the estimated extracellular Cu(ss) obtained with the point-of-no-net-flux method was investigated. Theophylline was administered as a rapid intravenous bolus dose followed by constant intravenous infusion. Changes in perfusion flow rate from 2.0 to 0.75 microliter/min and, finally, to 0.25 microliter/min, using the point-of-no-net-flux method, had no significant effect on the estimated Cu(ss) of theophylline in blood and striatum. This observation, particularly in the case of brain tissue, is not consistent with the theory that the process of dialysis drains a significant amount of substance from the immediate vicinity of the dialysis probe. Similar estimates of Cu(ss) in blood as well as in brain tissue were obtained with all three methods. Their accuracy in estimating Cu(ss) in blood was further strengthened by observations of unbound fractions similar to those reported in the literature. Furthermore, all three methods gave striatum/blood ratios at steady state of approximately 0.5, indicating that there is active transport of theophylline from brain tissue. It is concluded that the tritium method, when validated, can be used to study the time course of unbound drug concentrations in blood and tissues.


Decreased systemic clearance of diltiazem with increased hepatic metabolism in rats with uranyl nitrate-induced acute renal failure.

The effect of uranyl nitrate (UN)-induced acute renal failure (ARF) on the pharmacokinetics of diltiazem (DTZ) was examined in rats through in vitro and in vivo studies. In vitro homogenate studies demonstrated that DTZ was metabolized to deacetyl diltiazem (DAD) predominantly in the liver. Metabolism in the small intestine, kidney, or blood pool was negligible compared with that in the liver. UN-induced ARF (UN-ARF) increased the in vitro hepatic clearance (CLvit) of DTZ 1.4-fold. In vivo pharmacokinetic studies following intravenous (iv) and portal venous (pv) administration revealed that UN-ARF increased the intrinsic clearance (CLi) of DTZ from 243.0 to 414.5 ml/min/kg but decreased its total plasma clearance (CLt) from 90.3 to 64.3 ml/min/kg. The increase in CLi was consistent with the increase in CLvit of the liver. The in vitro plasma free fraction of DTZ (fp) was decreased from 0.25 to 0.14 by UN-ARF, but the in vitro blood/plasma partition of DTZ (Rb) remained constant at unity. From the CLi and fp changes, the plasma intrinsic clearance for unbound DTZ (CLi') was calculated to be increased 2.7-fold, from 1104.5 to 2960.7 ml/min/kg, by UN-ARF. The fp decrease was also reflected in the steady-state distribution volume (Vdss) of DTZ, which was decreased significantly from 3595.5 to 2528.3 ml/kg. The absolute bioavailability of pv DTZ (Fpv) was decreased by UN-ARF from 37.5 to 15.5% but was still much higher than the reported oral bioavailability (6%), indicating poor absorption of DTZ from the GI tract. From the calculation based on a well-stirred pharmacokinetic model, DTZ was found to increase the hepatic blood flow (HBF) of the control rats more than twofold at doses of 3 mg/kg (iv) or 10 mg/kg (pv), possibly due to the vasodilating effect of DTZ. However, the effect of DTZ on HBF was not present in the UN-ARF rats. It is not clear at present whether this could be attributed to vasoconstricting effects of UN-ARF or blockade of the vasodilating effect of DTZ.


The bioinequivalence of carbamazepine tablets with a history of clinical failures.

The bioavailability of three lots of a generic 200-mg carbamazepine tablet, which had been withdrawn from the market, was compared to the bioavailability of one lot of the innovator product in 24 healthy volunteers. Fifty-three lots of the generic product had been recalled by the manufacturer because of concerns over reports of clinical failures for several of the lots. The three generic lots tested in this study exhibited a wide range of bioavailability, as well as large differences in the in vitro dissolution rates. The mean maximum carbamazepine plasma concentrations for two of the generic lots were only 61-74% that of the innovator product, while the third lot was 142% of the innovator. The mean areas under the plasma concentration-time curve for the three generic lots ranged from 60 to 113% that of the innovator product. The results clearly indicate a significant difference in the rate and extent of absorption of the generic products compared to the innovator, as well as among the generic lots. A good relationship was found between the in vivo parameters and the in vitro dissolution results for the four dosage forms.


Factors determining the intrinsic lymphatic partition rate of epitiostanol and mepitiostane.

Substitution of the steroid epitiostanol (EP) at position 17 with methoxycyclopentane yields the extremely liophilic mepitiostane (MP) with preferential partitioning into the lymph. Most of the MP in the lymph was associated with the core lipids of chylomicrons and very low-density lipoproteins (VLDL), as was also the case for EP. However, the dialysis velocity of EP and MP from lymph to plasma differed greatly; EP, but not MP, was transferred from the lymph to the plasma. This difference was attributed to differences in their unbound fraction in the lymph. Lymphatic transfer and the logP value of several tested steroids correlated well. Therefore, the oral EP prodrug, MP, partitioned into the lymph because of its superlipophilicity and resultant retention in the core lipids of chylomicrons and VLDL.


The effect of valproate on the metabolism of phenobarbital in the rat.

Valproate has been shown to interact with all major antiepileptic drugs. The interaction with phenobarbital is the most clinically significant. The mechanism of the interaction was evaluated in the in vivo rat and in vitro liver perfusion system. Phenobarbital and parahydroxyphenobarbital (PbOH) were administered with and without valproate treatment. In vivo, after administration of PbOH, valproate caused a significant inhibition of both the renal clearance of unchanged PbOH (40%) and the formation clearance (ClF) of its glucuronide conjugate (44%). When coadministered with phenobarbital, valproate caused a significant decrease in the total plasma clearance of phenobarbital (95.4 +/- 29.0 to 65.8 +/- 20.2 ml/hr/kg), with no apparent effect on the phenobarbital renal clearance or the ClF of PbOH. Valproate did cause a significant inhibition (50%) of formation of a minor metabolite, metahydroxyphenobarbital. The largest effect of valproate appears to be on unknown pathways of phenobarbital elimination. In the isolated perfused rat liver, the ClF of PbOH and its glucuronide conjugate were determined. Valproate caused a small (10%) but significant decrease in the ClF of PbOH. As seen in vivo, the most significant effect of valproate was on the ClF of the PbOH glucuronide (66% decrease). In conclusion, inhibition of PbOH formation by valproate cannot account entirely for the increased plasma concentrations of phenobarbital that occur when valproate is added to therapy. A complete understanding of the mechanism will require a complete accounting of the phenobarbital dose in rat or in humans.


Influence of age and gender on the plasma profiles of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity following multiple doses of lovastatin and simvastatin.

The effects of age and of gender on the plasma profiles of HMG-CoA reductase inhibitors following separate once-a-day dosage regimens (17 days) of lovastatin (80 mg/day) and simvastatin (40 mg/day) were studied in hypercholesterolemic patients. In general, plasma concentrations of active and total HMG-CoA reductase inhibitors were higher in elderly individuals (age, 70 to 78 years) and in females for both drugs. However, the Tmax of these inhibitors was not significantly affected by either age or gender. Following the last dose of lovastatin, the mean steady-stage plasma concentrations of total and active HMG-CoA reductase inhibitors were 30-60% higher in the elderly than in young individuals (age, 19 to 30 years). Also, the mean plasma concentrations were 20-50% higher in female than in male patients. Similarly, following the last dose of simvastatin, the mean plasma concentrations of HMG-CoA reductase inhibitors were 40-60% higher in the elderly than in young patients and were 20-50% higher in female than in male patients. These age- and gender-related differences do not appear to be large enough to warrant modification of dosage regimens, because plasma concentrations of these inhibitors are not necessarily indicative of efficacy and the therapeutic windows for lovastatin and simvastatin are broad.


Use of analytically defined estimates of aerosol respirable fraction to predict lung deposition patterns.

Analytical estimates of the respirable fractions on inhaled pharmaceutical aerosols are obtained by inertial sampling techniques. The respirable fraction may be defined as that portion of the particle size distribution less than a designated diameter. The diameter size below which particles were considered respirable in these studies was 6.4 microns. In clinical practice, a variety of particle size distributions may be related to a single respirable fraction. Herein, three respirable fractions were each defined by six particle size distributions. The deposition patterns of aerosols exhibiting these particle size characteristics were examined in a mathematical model. The analytically defined respirable fractions were compared with predicted lung deposition values. Under clearly defined breathing conditions, there is a correlation between the nominal respirable fraction and deposition. However, it was concluded that the variations which occur in breathing parameters within patient populations may not allow a single analytically derived respirable fraction to be appropriate for all individual subjects.


A high-performance liquid chromatographic method for the quantitative enantioselective analysis of mefloquine stereoisomers.

A rapid quantitative, enantioselective HPLC method for the analysis of the four stereoisomers, (+) and (-) erythro and (+) and (-) threo forms, of mefloquine has been developed using a Chiralpak Ad analytical column containing amylose tris-3,5-dimethylphenyl carbonate coated on silica gel and hexane/ethanol/diethylamine (96:4:0.1, v/v%) as the mobile phase. This method made it possible to quantitate small amounts of threo form in the presence of the erythro form of mefloquine, the form which is used as the active ingredient in commercial mefloquine tablets. Tablets from three sources were studied to estimate their optical purity, and it was found that tablets from one source contain 0.27 w/w% of the (-)-threo and 0.25 w/w% of the (+)-threo form, tablets from the second source contain 0.056 and 0.042 w/w% (-)- and (+)-threo, respectively, and tablets from the third source contain 0.052 w/w% (+)-threo, with the remainder erythro.


Mapping the ligand binding pocket of the human muscarinic cholinergic receptor Hm1: contribution of tyrosine-82.

The ligand binding pocket of many G protein-coupled receptors is thought to be located within the core formed by their seven transmembrane domains (TMDs). Previous results suggested that muscarinic antagonists bind to a pocket located toward the extracellular region of the TMDs, primarily at TMDs 2, 3, 6, and 7. Tyrosine-82 (Y82) is located in TMD2 only one helical turn from the presumed membrane surface of Hm1, whereas a phenylalanine (F124) is found in the equivalent position of the closely related Hm3. In order to determine the contribution of Y82 to Hm1 ligand binding and selectivity versus Hm3, we constructed the point mutation Y82 F of Hm1 and measured binding affinities of various ligands, with 3H-N-methylscopolamine (3H-NMS) as the tracer. The Hm1 wild-type receptor and the Y82F mutant were transfected into human embryonic kidney U293 cells. Whereas the affinities of NMS, carbachol, and atropine were either unchanged (carbachol) or enhanced by less than twofold (atropine and NMS), the affinity of the Hm1-selective pirenzepine was reduced threefold by the Y82F mutation. These changes parallel affinity differences of Hm1 and Hm3, indicating that the Y82 F mutation affects the binding pocket and that Y82 contributes to the binding selectivity among closely related muscarinic receptors.


Drug delivery via ion exchange across a micromembrane.

The exchange of pharmaceutically significant amounts of dopamine across a micromembrane is reported, establishing the practical basis for such a drug delivery system. Drug release was accomplished with a commercially available device initially intended for use as a postcolumn reactor in ion chromatography. Release of other ionic drugs (e.g., methyldopate and piperacillin) was also achieved but with a lesser efficiency than was dopamine, presumably because of a size effect. The effect of releasing ion identification and concentration, the flow rate of the delivery solution and concentration of drug in the device reservoir on the drug release efficiency was examined. Under optimal conditions the efficiency approaches 80%, and 1 mg of drug is released/ml of delivery solution. Alternatively, operating conditions can be changed so that magnitude of release is optimized but absolute efficiency is sacrificed. Under such conditions the magnitude of dopamine release approaches 2 mg/ml but exchange efficiency is approximately 25%.


Effects of diethyl phthalate and other plasticizers on laurate hydroxylation in rat liver microsomes.

Diethyl phthalate (DEP) is used in pharmaceutical coatings, cosmetics, and plastic films to wrap foods. There is a health concern associated with the exposure to certain phthalate esters because they belong to a class of compounds referred to as peroxisome proliferators which have been shown to increase the incidence of liver tumors when administered to rats. In this study, we have compared DEP to four other commonly used plasticizers, 2-diethylhexyl phthalate (DEHP), dibutyl phthalate (DBP), 2-diethylhezyl adipate (DEHA), and acetyltributyl citrate (ATBC), for their ability to induce the cytochrome P450-mediated fatty acid omega-hydroxylation system, which is one of the initial cellular responses when animals are treated with peroxisome proliferators. The administration of DEHP, DBP, and DEHA to rats increased the specific activity of laurate 12-hydroxylase from 2.8 +/- 1.1 in control rats to 30.3 +/- 11.6, 14.5 +/- 4.1, and 9.7 +/- 1.9 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In contrast, laurate 12-hydroxylase activity in DEP- and ATBC-treated rats were 4.4 +/- 1.2 and 4.4 +/- 1.0 nmol 12-hydroxylaurate formed/min/nmol P450, respectively. In addition, whereas DEHP increased peroxisomal palmitoyl-CoA oxidation 6-fold, DEP increased this activity only 1.3-fold. Two protein bands, at 51 and 52 kDa, were found to increase 6- to 12-fold in microsomes of DEHP-, DBP-, and DEHA-treated rats, but these bands were increased only 2-fold in DEP- or ATBC-treated rats.


Viscoelastic properties of polyacrylic acid gels in mixed solvents.

The objective of this study is to investigate the viscoelastic properties of Carbopol 934P polymeric systems in a variety of mixtures of pharmaceutical solvents. Carbopol 934P neutralized with a 1:1 equivalent ratio of triethanolamine was dissolved in various binary or ternary solvent mixtures consisting of propylene glycol, glycerol formal, and water. Dynamic moduli G' and G'', complex viscosities, eta' and eta'', and loss tangent, tan delta, were examined over a frequency range of 10(-3) to 10 Hz using an oscillatory viscoelastic rheometer at 30 degrees C. The results indicated that for 0.5-1.5 wt% neutralized Carbopol in ternary mixtures, G' and G'' increased by 3-4 orders of magnitude and the phase angle decreased from 80 to 25 degrees when the water content in the solvent mixture increased from 10 to 80 wt%. These studies also indicated that the addition of water to nonaqueous Carbopol 934P polymer systems transforms them from low-viscosity solutions to gels with significant elastic behavior involving physical interaction and entanglement of polymer segments with solvents.


Formulation and optimization of a modified microporous cellulose acetate latex coating for osmotic pumps.

A cellulose acetate (CA) latex was modified for use as a microporous coating for osmotic devices. Potassium chloride core tablets were coated with a CA latex formulation containing a plasticizer (triacetin) and a pore-forming agent (urea). To promote the coalescence of the cellulose acetate latex beads into a film on the surface of the tablet, it was necessary to cure the coated tablets, hereafter referred to as devices, at elevated temperatures. The objectives were to determine the effect of four formulation variables (plasticizer level, pore former level, cure time, and cure temperature) on the in vitro KCl release rate and coat burst strength using a full 2(4) factorial experimental design. Burst strength was measured as the number of grams force a depleted device could support before bursting. The results indicated that urea content was the most important variable, followed by triacetin content and cure time. Cure temperature did not influence the results. Response surfaces generated with the experimental values were used to predict a formulation which would have both a high release rate and a high burst strength. This formulation was prepared and tested both in vitro and in vivo in dogs. The in vitro release rate and burst strength results agreed with those predicted by the model. The in vitro and in vivo release rates were not statistically significantly different as determined by ALQ analysis.


Chemoprevention of chemically induced skin tumor development by diallyl sulfide and diallyl disulfide.

Garlic and onion oil have been shown to inhibit chemically induced skin tumor development in mice. In the present study, the effects of diallyl sulfide and diallyl disulfide, oil-soluble constituents of garlic and onion, on 7,12-dimethylbenz(a)anthracene-induced and 12,O-tetradecanoylphorbol-13-acetate-promoted skin tumor formation were examined in SENCAR mice. Topical application of diallyl sulfide or diallyl disulfide significantly inhibited skin papilloma formation from the ninth week of promotion and significantly increased the rate of survival in the murine model. Our findings support earlier evidence that these naturally occurring compounds may be useful for the chemoprevention of certain types of tumors.


[Treatment of polycythemia vera with hydroxyurea or pipobroman. Efficacy and toxicity analysed from a protocol of 96 patients under 65 years of age. Le Groupe d'Etude des Polyglobulies].

Between 1980 and 1991, 96 patients with documented polycythemia vera were treated by hydroxyurea or pipobroman, according to a protocol including randomization, and maintenance therapy. Complete remission was induced in all cases. Two cases treated with hydroxy-urea had a very severe granulothrombocytopenia during the initial phase. Maintenance was generally satisfactory on pipobroman, but the platelet count often remained high (400 to 900.10(9)/l) on low-dosage hydroxy-urea, with a risk of vascular events. Progressive resistance to these drugs was observed in 5 cases. Digestive and cutaneous troubles were more frequent on pipobroman maintenance, sometimes enough to legitimate a therapeutic change. It may be concluded that such a treatment is less easy to use and to follow than is currently accepted. In the present series (397/years/patients follow-up, median 5-3 years), only one leukemia and one cancer were observed, which however only demonstrates the absence of any carcinogenic risk at short- but not at long-term.


[Schnitzler's syndrome. A new case].

A new case of Schnitzler's syndrome is reported in a 72-year old man hospitalized for severe deterioration of his general condition associated with recurrent ancient urticaria. Paraclinical examinations, which showed inflammatory syndrome, bone condensation and IgM monoclonal gammapathy, led to the diagnosis of Schnitzler's syndrome, first described in 1972. Twenty-two cases have now been published, characterized by vasculitic urticaria, osteosclerosis and IgM macroglobulinaemia. There is also severe inflammatory syndrome and the other immunological examinations are normal. Recent studies suggest the possibility of uncontrolled activity of interleukin-1 alpha. The condition is chronic and usually benign, but the fear of malignant transformation in the long term makes the therapeutic choice difficult.


[Familial amyloidosis].

Familial amyloidosis is characterized by its great clinical and genetic heterogeneity. The most frequent form is amyloidotic neuropathy which may be due to deposits of several amyloid proteins, such as transthyretin, apolipoprotein A1 and gelsolin. Other varieties include predominant lesions of another organ, such as kidney, heart, eye or skin. In most of these lesions, a punctual mutation affects the amyloid protein itself. In other varieties, the amyloid protein is not affected by mutation and, rarely, unknown. The advances achieved in our understanding of transthyretin deposition should improve our knowledge of amyloidosis in general.


[Characteristics of tuberculosis among children (data from a specialized hospital].

The results of analysis of 3076 case histories of patients who were studied in a specialized hospital of Leningrad in the period of 1984-1989 made it possible to give the present-day characteristic of tuberculosis infection in children aged up to 14 years. Study was conducted according to the accepted scheme and comprised analysis of a general composition of patients, clinical diagnosis structure, specific features of the different forms of tuberculosis, registration of complications, age, sex and territory factors and results of other investigations. Special emphasis was given to the characteristic of a group of children suffering from tuberculosis. The findings obtained give evidence on the unfavourable changes in the structure of clinical diagnosis of tuberculosis in children during the last five years.


[Current principles of diagnosis of cavitary formations in the lungs].

Tuberculosis, cancer or abscessed pneumonia were diagnosed in 141 (84%) of the 168 patients who had solitary cavities in the lungs in the absence of M. tuberculosis or cancer cells isolation. The most informative diagnostic signs in these cases are provided by sex, age, special features of the onset and course of the disease in the period between diagnosis establishment and patients' hospitalization, data obtained when fluorograms taken from archives were compared with the X-ray picture at the moment of disease detection as well as by the results of serological reactions such as tuberculous antigen detection and Mantoux test, and blood level fibrinogen determination. On the second stage of examination the supplementary signs were obtained in bronchoscopy, cytologic examination of the bronchial contents after prescription of irritating inhalations and prednisolone test and immunologic study. Correct diagnosis can be established in 99% of the cases in the presence of simultaneously five and more significant signs.


[Diagnosis of liver diseases in patients with pulmonary tuberculosis].

The paper deals with the results of detection of liver diseases in 868 patients who underwent examination at the department of pulmonary tuberculosis surgery of the St. Petersburg research institute of phthisiopulmonology. The rate of carriage of hepatitis B surface antigen was 11.05%, while Al/At activity was increased in 30.41% of the cases. Signs of chronic liver disease were diagnosed in 84 patients. Morphological examination verified the diagnosis of chronic hepatitis in 53% of the cases, including 44% of virus etiology; in the rest of patients medicamentous and alcoholic forms were found. Specific liver affections were detected in 16% of the patients, dystrophic and cirrhotic changes in 25%, mainly of medicamentous and alcoholic etiology; in 8% the cause of liver affection remained +non-established.


[Problem of differential diagnosis of tuberculosis of peripheral lymph nodes and malignant neoplasms].

A total of 386 patients admitted with the diagnosis of tuberculous lymphadenitis were subjected to a differential diagnosis of tuberculosis of peripheral lymph nodes and malignant tumours. A histological examination of the removed lymph nodes demonstrated malignant tumours in 22 (5.7%) patients. Difficulties encountered in differentiating between tuberculous lymphadenitis and malignant tumours are due to changes in the clinical course of the process which are manifested in the enlargement of one or several nodes in 80% of patients in the absence of intoxication, which is also typical of primary malignant tumours of the lymph nodes. Histological and bacteriological studies of the removed nodes proved to be more informative for the differential diagnosis of tuberculous lymphadenitis and malignant tumours.


[Diagnosis and treatment of pleural lesions in sarcoidosis of the respiratory organs].

Among the 2775 respiratory sarcoidosis patients who were examined over the last ten years 278 (10%) had pleural affections: thickening of interlobular pleura and pleural deposits (98.2%), exudative pleurisy (1.1%) and spontaneous pneumothorax (0.7%). The most common pleural affection was found in sarcoidosis of stages II and III (16.8 and 70.8%, respectively). The clinical manifestations in all forms of this pathology had poor symptoms. Complex therapy proved to be highly effective. It included use of corticosteroids, antioxidants and immunomodulators; massive exudative pleurisy was managed by pleural puncture and removal of exudate.


[Magnetic resonance tomography in the diagnosis of tuberculous spondylitis in children].

The experience of using magnetic++-resonance tomography to diagnose tuberculous spondylitis in 15 children admitted to a hospital for surgical treatment is described. The method proved to be highly effective for evaluating the condition of the spine and spinal medulla and for establishment of early diagnosis of the attendant neurotrophic changes in healthy vertebrae. The examination findings serve to determine the volume of surgical intervention, character of postoperative restorative management and allow the prognosis of treatment outcome. In this respect, magnetic++-resonance tomography is a valuable supplementary diagnostic method.


[Hemostatic changes in patients with pulmonary tuberculosis in the postoperative period in relation to the volume of surgical blood loss].

Hemocoagulation changes were studied in 71 pulmonary tuberculosis patients in the postoperative period. Red blood parameters and graphic coagulogram were determined. A moderate hypercoagulation syndrome was found in patients with operative blood loss of 500 g in the early and immediate postoperative period. With a rise in the operative blood loss volume and hemodilution degree changes appeared indicating a tendency to hypocoagulation shifts. In patients having moderate blood loss (501-1500 g) the hypocoagulation syndrome was associated with dilution coagulopathy. In larger blood loss (over 1500 g) the hypocoagulation syndrome was aggravated both by hemodilution coagulopathy and the expenditure of blood coagulation factors with the increase in fibrinolytic blood activity. These cases require therapy aimed at the prevention and management of arising hemocoagulation disorders.


[Central and peripheral hemodynamics in patients with tuberculous spondylitis and spinal cord disorders].

The results of study of central and peripheral hemodynamics in 79 tuberculosis spondylitis patients are presented. The rate and degree of central and peripheral hemodynamic disorders were dependent on the presence and severity of cerebrospinal disturbances. It is recommended that the body's integral rheography, rheovasography and thermovision be used as a diagnostic means for early detection of cardiovascular disorders as well as the determination of their manifestation degree and control of treatment effectiveness.


[Stage-by-stage pneumonectomy in pleural empyema].

Staged pneumonectomy tactics in complication of the main lung affection by pleural empyema was described. Surgery was based on an open treatment of empyema cavity before and after the principal surgical stage--pneumonectomy, which was completed by closed treatment using the method of early pleural cavity filling with curative solutions. Use of staged surgical treatment tactics makes it possible to prevent serious postoperative complications such as empyema recurrence and bronchial fistulas. Full clinical effect was achieved in 11 of the 56 operations of staged pneumonectomy in the presence of empyema.


[Atelectasis after segmental resection of the lungs in patients with tuberculosis].

Study of 219 tuberculosis patients who underwent segmental resections showed that the rate of atelectasis development constituted 16.4%. In the right-sided operations atelectases developed 3 times more frequently than those in the left-sided ones (27.5 and 7.5%, respectively) and were mainly segmental (atelectasis of the anterior segment after excision of the ++apico-posterior segment), while in the left-sided intervention they were total in the majority of patients. The character of atelectasis in the right- and left-sided operations was determined by specific features of bronchial structure of the right and left lungs. As a result of therapeutic measures all total atelectases were relieved within 3-5 days, while segmental atelectases persisted for a long time; in 6 patients they still remained by the time of discharge.


[Medico-social aspects of epidemiology of tuberculosis in the Extreme North].

Tuberculosis is still of top priority in health care of the not numerous peoples of the Extreme North and will preserve its importance as a prevalent infection for the nearest ten years. All aborigines must be included in high-risk groups of tuberculosis and the system of its control should be based on a state status, which supposes the immediate solution of socio-economic and medico-biological problems. It is advisable to organize the interdepartmental committee for tuberculosis at the Association of northern peoples and envisage additional assignments, including foreign currency, to be spent on research work, fluorographic++ technology, diagnostic means and equipment and medicaments. Under conditions of a new economic mechanism and market economy assignments aimed at anti-tuberculosis aid should include donations brought by the leading industrial branches; separate enterprises and state structures.


[Determining dehydrogenase activity as a method of accelerated indication of the viability of Mycobacterium tuberculosis].

A comparative effectiveness of mycobacterial dehydrogenase activity (DHA) determination was studied with the help of the following stains: methylene blue, malachite green and tetrazole derivative--triphenyl tetrazole chloride (TTC). Best result were obtained with TTC tests which allowed a reliable registration of M. tuberculosis culture viability. On the basis of indication of M. tuberculosis viability by DHA, accelerated techniques were developed to determine mycobacterial drug resistance to the main antituberculous preparations and blood bacteriostatic activity. These techniques are available for practical laboratories, economical and safe in work.


[Status of the peroxidation-anti-oxidation system in patients with sarcoidosis of the respiratory organs].

Parameters of lipid peroxidation (LPO) and of the antioxidant system (AOS) were analysed according to the level of diene conjugates (DC) and blood serum antiradical activity (ARA), respectively. Study included 115 patients with active respiratory sarcoidosis. The DC level was found to be significantly increased in 89-97% ot the examined patients. At the same time, the ARA changes had a differently directed pattern. The DC/ARA coefficient was estimated which was also increased in most patients providing evidence on the peroxide-antioxidant system imbalance in active sarcoidosis patients. It was found that the parameters were dependent on the process duration. They were studied in dynamics against the background of combined therapy in 2-4-6 months and in the remote periods (1-2 years). Dynamic changes in the biochemical parameters had the unidirectional pattern with manifestation of the clinical and X-ray process dynamics. There was a significant difference in the rate and degree of changes in the LPO-AOS parameters depending on the activity degree of sarcoidosis process and treatment effectiveness. It is believed that the antioxidant therapy is necessary in all sarcoidosis forms at the early stages of treatment and that its duration should be no less than 4 months in the acute process while the protracted course requires a longer period of time.


[Characteristics of immunity in patients with destructive pulmonary tuberculosis].

Parameters of systemic immunity, activity of cation proteins of neutrophilic granulocytes and individual blood serum proteins were studied in two groups of patients: with newly diagnosed (83) and chronic destructive pulmonary tuberculosis (105). Four levels of T-lymphocytes were established per their absolute content in 1 ul of the peripheral blood, which had different interconnection with cell response intensity to mitogenic PHA stimulation and the values of the lysosomal cation++ test in both groups of patients. Indications for the prescription of immune active preparations based upon the T-cell level and, when necessary, supplemented by information related to the values of BTR with PHA and BTR with PPD were developed for both groups of patients independently of hereditary consolidated serum proteins.


[Immunologic status of patients with pulmonary tuberculosis and pneumonia].

A combined immunologic examination included 67 patients with concurrent lung pathology (tuberculosis with pneumonia), 64 with tuberculosis and 71 with pneumonia. The relation of the immune status to the pattern of the process was demonstrated proceeding from the findings. Pneumonia in the abatement phase had no influence on the immunologic parameters of a tuberculosis patient. Acute pneumonia combined with tuberculosis was marked by suppressed T-lymphocyte functional and specific activity, increased counts of T-suppressors and the presence of antituberculous antibodies. It was found that the newly developed diagnostic tables can be used effectively for differentiating the combined pathology from the uncomplicated tuberculosis and pneumonia.


[Effect of plasmapheresis on the course of experimental tuberculosis and the tolerance of chemotherapy by patients with renal tuberculosis].

A plasmapheresis (PA) model was developed to be used in chronic rabbit experiments. Test results obtained in 96 generalized tuberculosis animals demonstrated a more benign tuberculosis process in animals subjected to plasmapheresis, which was confirmed by parameters of the coefficients of mass and indices of animals' organ affecting, findings of the cation-lysosomal test and peptide molecules content in the peripheral blood. Rabbit studies involving registration of bromsulphalein half-life, hepatic blood flow and relative parenchymatous clearing showed that the isoniazide and rifampicin action significantly decreased under the PA influence. Studies in a hospital accommodating 90 patients with different renal tuberculosis forms and poor tuberculostatic tolerance showed that PA promoted restoration of tolerance to specific preparations and renal function improvement. PA was found to be practicable and safe method which relieves side effects of antituberculous preparations and contributes to tuberculosis treatment efficiency.


[Characteristics of prevention of tuberculosis in the conditions of low prevalence of tuberculous infection].

Immunologic screening was used for examining children of five St. Petersburg regions (4155 subjects) and workers of two industrial enterprises (7700 subjects). Tuberculosis infection level in children living together with subjects of groups I, II, Va, Vb and VII dispensary record and tuberculin sensitivity in adults were determined. New risk groups of tuberculosis development have been suggested which include children from the families of subjects with residual changes of past respiratory tuberculosis with a high risk of its reactivation and adults having hyperergic tuberculin sensitivity. BCG revaccination postponement in adults aged 27-30 years is valid in conditions of low tuberculosis prevalence.


[Optimal methods for the detection of tuberculosis in not easily accessible regions of the Extreme North by bacteriological screening].

The results of bacteriological study of 2210 residents of the Extreme North are presented. The author's complex many factorial system of bacteriological screening is discussed, whose use will enable one to raise the detection parameter of bacilli excretors up to 2.93% in the preliminary detected population groups.


[Biotransformation of aza-3-chalcol in the rat: isolation and structural analysis of seven metabolites].

The azachalcol 3-phenyl-1-(3-pyridinyl)prop-2-en-1-ol S-1 has been used to investigate the metabolic profile in rat. Seven metabolites and the unchanged substance were isolated from urine. The biotransformation products were extracted and purified by chromatography (LC, CTLC, HPLC) and identified by comparison with some synthetic reference compounds or by spectroscopic analysis (UV, IR, 1H, 13C NMR and MS). A scheme of potential metabolic pathway is proposed. It appears that three specific targets of the parent molecule are extensively oxidized. Thus the aromatic heterocycle yields three N-oxides (M-4, M-5, M-7). The deshydrogenation of the secondary alcoholic group to the ketone is also observed (M-2). Finally, the ethylenic double bond is a favored site for hydroxylation (M-7, M-8) as well as reduction (M-3, M-4, M-6).


In vitro and in vivo evaluation of macrofilaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl: a diglyceride prodrug.

A new therapeutic target has been identified from the filaria Molinema dessetae: the gabaergic system. gamma-aminobutyric acid (GABA) itself showed antifilarial effect in vitro and a macrofilaricidal action in vivo at high dose by intraperitoneal route (10(-2) M). Nevertheless, no action was observed by oral route. The study we report here consists to obtain an antifilarial effect by oral route using a diglyceride prodrug. Such a strategy is based on the triglycerides metabolism. A diglyceride prodrug of gamma-aminobutyric acid has been synthesized and its filaricidal activity compared with that of GABA, in vitro on adults of Molinema dessetae and in vivo on Molinema dessetae infected Proechimys oris. In vitro, GABA at 2.5 x 10(-3) M induced a temporary paralysis and the ester drug at the same concentration was fully active on adults. In vivo, no significant activity was observed by oral administration of a daily dose of GABA (10(-2) M). A five day course of GABA at 10(-2) M via the intraperitoneal route induced a significant reduction of male and female worms. We did not find any activity of the prodrug in vivo, either by the oral route (10(-2) M) or after an intraperitoneal administration (10(-3) M). The interest of GABA and GABA derivatives as potential filaricidal drugs was discussed.


Sulphydryl-containing agents: a new approach to the problem of refractory peptic ulceration.

Refractory peptic ulceration is the term applied to those gastric and duodenal ulcers which remain unhealed despite active treatment for at least 3 months. Sulphydryl-containing agents stimulate the formation of gastrointestinal mucus, bind the oxygen-derived free radicals that mediate tissue damage and play an important role in protein synthesis. This is the first report which suggests that these agents stimulate the healing of refractory gastric and duodenal ulceration without any adverse events.


Pharmacodynamics and kinetics of loss of tolerance and physical dependence on morphine induced by pellet implantation in the rat.

The decay characteristics of tolerance and physical dependence on morphine induced by a pellet implantation procedure were determined in male Sprague-Dawley rats. Rats were implanted subcutaneously with 6 morphine pellets during a 7-day period. The pellets were removed, and at various times thereafter tolerance to the analgesic and hyperthermic effects of morphine was measured by determining the response in rats implanted with morphine and placebo pellets. Similarly, the physical dependence was assessed by monitoring withdrawal signs following an injection of naloxone. A high degree of tolerance developed to the analgesic and hyperthermic effects of morphine. Similarly, a high degree of physical dependence also developed as evidenced by a high incidence of jumping response, teeth chattering and production of fecal boli induced by injections of naloxone. In addition, loss of body weight and body temperature also occurred. The analgesic and hyperthermic response to morphine recovered very gradually. There was no significant difference in the analgesic and hyperthermic responses to morphine on day 4 after the pellet removal in rats implanted with morphine and placebo pellets. The decay of tolerance was linear with time for the analgesic effect (r = 0.98) and for the hyperthermic effect (r = 0.93). The change in symptoms of physical dependence on morphine with time depended on the specific symptom monitored. The average number of jumps and teeth chattering decreased with time in a linear fashion with r values of 0.98 and 0.99, respectively. However, the number of fecal boli and wet dog shakes increased linearly with time (r = 0.97). The recovery of loss of body weight was also linear with time. Thus, it is clear that fecal boli and wet dog shakes, which increase in number as the dependence decays, are signs of a low degree of dependence. The results suggest that different central or peripheral mechanisms may be operating in different withdrawal symptoms. These studies may prove to be useful when studying the mechanisms involved in the induction and reversibility of tolerance and dependence processes, and in long-term effects of opiates at a time when the tolerance and physical dependence is no longer evident.


Effects of nonsteroidal antiestrogens in the in vitro rat uterus.

We have studied the effect of nonsteroidal antiestrogens on rat uterine contractions induced by oxytocin (8 nmol/l), methacholine (10 mumol/l), prostaglandin F2 alpha (1 mumol/l), KCl (60 mmol/l) and CaCl2 (6 mmol/l). In a concentration-dependent way, the antiestrogens tamoxifen, clomiphene, nafoxidine and ethamoxytriphetol inhibited the amplitude and frequency of the oxytocin-induced contractions and the contraction produced by CaCl2. At a concentration of 30 mumol/l the four drugs inhibited the contractions induced by methacholine and prostaglandin F2 alpha. They also relaxed the tonic contraction to KCl in a concentration-dependent way. This action was partially counteracted by CaCl2 (0.1-10 mmol/l). Bay k 8644 (0.3 nmol/l to 3 mumol/l) only partially reversed the inhibition by ethamoxytriphetol (0.1 mmol/l) of CaCl2 (6 mmol/l)-induced contractions. The steroidal antiestrogen, ICI 164,384, which lacks agonist activity, had an inhibitory effect (44 +/- 4%, n = 7) on KCl-induced contractions only at a concentration of 0.1 mmol/l. However, the quaternary analogue of tamoxifen (tamoxifen ethyl bromide) produced 86 +/- 3% relaxation of the KCl-induced contracture (IC50 1.52 +/- 0.1 mumol/l, n = 10) and this effect was counteracted by addition of CaCl2. Taken together the results indicate that the inhibitory effects of nonsteroidal antiestrogens on rat uterine contractions could be mediated by an action to block Ca2+ entry through an agonist action on extracellular estrogen receptors.


Articulatory phonology: an overview.

An overview of the basic ideas of articulatory phonology is presented, along with selected examples of phonological patterning for which the approach seems to provide a particularly insightful account. In articulatory phonology, the basic units of phonological contrast are gestures, which are also abstract characterizations of articulatory events, each with an intrinsic time or duration. Utterances are modeled as organized patterns (constellations) of gestures, in which gestural units may overlap in time. The phonological structures defined in this way provide a set of articulatorily based natural classes. Moreover, the patterns of overlapping organization can be used to specify important aspects of the phonological structure of particular languages, and to account, in a coherent and general way, for a variety of different types of phonological variation. Such variation includes allophonic variation and fluent speech alternations, as well as 'coarticulation' and speech errors. Finally, it is suggested that the gestural approach clarifies our understanding of phonological development, by positing that prelinguistic units of action are harnessed into (gestural) phonological structures through differentiation and coordination.


Mobile community treatment in inner city and suburban Sydney.

Intensive and assertive community based treatment was provided to 27 inner city and 45 suburban severely and chronically mentally ill patients in Sydney. The teams use assertive outreach methods to address the needs of these most difficult to treat patients who have only sporadically complied with outpatient treatment and who frequently required hospitalisation. The staff-patient ratio at 1:10 on both teams is much higher than in the conventional mental health centres. Preliminary outcomes indicate that the number of hospital bed days of the suburban patients dropped by 67%, that stability in accommodation for inner city patients increased, and that functioning improved significantly for patients treated by both teams.


Adult lifetime prevalence of firesetting behaviors in a state hospital population.

Hospital records of all patients under age 65 years old on the census of Worcester State Hospital (WSH) on October 25, 1988 (n = 279) were reviewed for indications of firesetting behaviors during the individuals' adult lifetime. The prevalence of firesetting behaviors was found to be 27.2%. The prevalence of firesetting episodes, a subset of firesetting behaviors, was found to be 17.6%. A stepwise discriminant function analysis was used to determine whether any factors significantly differentiated the members of the firesetting behavior group from the remainder of the population. This analysis revealed that the number of WSH admissions, the number of admissions to other inpatient facilities, and a history of injurious behavior to self are significant positive predictors of membership in the firesetting behaviors group. The results of the WSH analysis are very similar to those found at Northampton State Hospital in 1983. These high prevalence rates have implication for treatment, education, record keeping, and liability.


Who repeats? A follow-up study of state hospital patients' firesetting behavior.

The authors report on a population of psychiatric patients who were studied over a 6.75 year period to determine the occurrences of firesetting behavior noted in their psychiatric inpatient records. Two groups of 50 patients each were drawn from an earlier study and were matched by sex, age, and diagnoses. One group of patients had prior firesetting behavior; the other did not. Firesetting behavior was found not only in patients originally identified as having previously engaged in this behavior, but also in those with no documented history of this act prior to the period of the study. Patients having firesetting behavior in their past psychiatric record set more actual fires. Total number of episodes of firesetting behavior, however, was not significantly different between the two groups. Results are discussed in terms of the communicative function of firesetting and the dilemma of clinical prediction.


Family management of schizophrenia: a comparison of behavioral and supportive family treatment.

This paper reports a comparison of behavioral and supportive family treatment for family management of schizophrenia. The family project applied two psycho-educational approaches to a highly "treatment resistant" population of young adults afflicted with chronic mental illness. The study compares and contrasts the effects of behavioral and supportive family management programs on clinical outcomes. Clinical improvements were associated with both family interventions. Discussion is provided on the relevance of this work to the growing body of evidence concerning the efficacy of psychoeducational family intervention for the management of schizophrenia.


HIV prevention among psychiatric inpatients: a pilot risk reduction study.

An HIV prevention program was piloted on an acute inpatient admission ward. Patients who volunteered to participate had significantly higher rates of histories of substance use than non-participants, suggesting that patients participated based on rational concerns about past HIV risk behavior. The program consisted of 75 minute sessions once a week for seven weeks and was co-led by an HIV counselor and the ward's social worker. Each session focused on a specific topic and included a short presentation of informational material, viewing of an educational videotape, a discussion, and role play and other educational games. In spite of a wide range in functioning among the participants, discussion was lively and participation was good. The pilot program demonstrates that chronic mentally ill patients can engage in, and benefit from, risk reduction programs and that frank and explicit discussion of sexual issues is well tolerated. Recommendations for improvement in the program are discussed.


Long-term hospital treatment: a 25-year study.

Findings from a 25-year study of admissions to a single long-term private psychiatric inpatient facility document a sharp decline in average age and an increase in concurrent diagnoses of substance abuse and personality disorders. In this case, long-term private inpatient care has survived the significant changes in mental health policy and funding practices of the past quarter century, but has shifted its focus from a more general psychiatric caseload to the seriously disturbed adolescent or young adult patient. There are numerous factors which determine every aspect of hospital treatment. Though some are easily determined, many are dimly defined and difficult to measure. At present, their effect on patient progress is obscure. These factors, discussed in some detail, may be internal and peculiar to an institution itself. A dialogue is initiated for the insight it furnishes about the changes that have occurred in hospital treatment.


The insanity verdict, the psychopath, and post-acquittal confinement.

Automatic post-acquittal confinement, an almost inevitable concomitant of a verdict of not guilty or not responsible by reason of insanity has for many acquittees been nothing more than punishment in disguise. Replacement of the insanity defense by statutes that provide for expert witness testimony to show that the defendant lacked the state of mind required as an element of the offense charged, has been found by two state supreme courts to be in accord with constitutional requirements. Procedures can be implemented, with due regard for public safety, so that all offenders, mentally disordered or otherwise, may be dealt with in an ethical, effective and humane manner. The 1992 decision of the Supreme Court of the United States in the case of Foucha v. Louisiana, holding that the Constitution does not permit the continued confinement of a still dangerous, but no longer mentally ill, insanity acquittee, makes it all the more necessary that the insanity defense be abolished and that an offender's mental illness be considered primarily in the context of mitigation, disposition and sentencing, rather than exculpation.


The hypomanic personality of Wilkins Micawber: a Dickensian case study.

The concept of hypomanic personality has historically been viewed with ambivalence. However, by replacing cyclothymic personality with cyclothymic disorder, DSM III doomed this entity into oblivion. The author examines the Dickensian portrayal of Mr. Micawber in light of existing descriptions of hypomanic personality in order to justify its inclusion in future psychiatric classifications.


Assessment of therapeutic relationship of community-agency workers.

This article reports on the ratings of the personal and professional characteristics of community-based workers for children and adolescents who had recently been released from a psychiatric inpatient service. The child/adolescent's family members/caregivers and the community workers both responded to the same items of a questionnaire. Families/caregivers rated the community workers with whom they were the most and the least satisfied. Community workers rated themselves in relation to these study children and/or their families. Findings indicate that both family members/caregivers and the community workers themselves saw community workers performing relatively well in the areas of providing information and offering support to families. Likewise, both assessed the service providers as having the greatest deficits in the area of teaching skills for child/adolescent home management. Suggestions for meeting the needs of the families and for ensuring that a system of care for child/adolescents is child-centered and family-focused are discussed.


The development of de-institutionalization in Europe.

In this article movements from institutional to community care for psychiatric patients in various European countries are discussed. Programs considering the welfare of afflicted persons, diminution of psychopathology and improvements of functioning, as well as the costs of deinstitutionalization are reviewed. The review first deals with the prevention of admissions prior to referral to inpatient facilities, looking at the role of general practitioners and ambulatory services in preventing admissions. Secondly, alternatives for hospital care are considered. Thirdly, consideration is given to the possibilities of shortening the time patients stay in hospitals. Next, experiences in discharging long stay patients to alternatives for continued care in psychiatric hospitals are reported. Finally, the advantages are shown of integrating all regional mental health services under one administration. Selected national policies are described as well as the success of present programs are discussed. With few exceptions only European studies are reported.


The closing of a state hospital: what is the quality of patients' lives one year post-release?

The closing of a state psychiatric facility afforded an opportunity to assess the quality of life of a cohort of patients who were released. Patients were interviewed a month after release and again a year later. Patients spent about half their time in mental health programs, but few were engaged in community activities or in employment. Cohort members mainly turned to mental health workers and case managers for support and problem resolution, as they had limited supports to turn to otherwise. Patients desired assistance in such areas as money management. In a number of areas of daily living, cohort members desired assistance a year after discharge, more so than upon release. Despite this, a year after release patients appeared to be quite positive toward themselves and their quality of life.


Quantitative electroencephalographic effects of caffeine in panic disorder.

It has been demonstrated that patients with panic disorder are more sensitive than normal control subjects to the anxiogenic effects of caffeine. The underlying physiologic basis for this difference is unclear. We examined the electroencephalographic (EEG) activity of seven patients with panic disorder and seven normal control subjects during the randomized double-blind, placebo-controlled administration of oral caffeine (7 mg/kg). EEG data were collected on-line from 28 electrodes; artifact-free epochs were selected manually for off-line Fourier transformation. Caffeine was associated with a significant increase in peak occipital alpha frequency and significant decreases in occipital alpha amplitude, central beta amplitude, and central theta amplitude. Despite the observation that caffeine increased anxiety more in the patients with panic disorder than in the normal control subjects, the two groups did not differ in their EEG responses to caffeine.


Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging.

Magnetic resonance images were used to measure the volume of the head of the caudate nucleus in 20 patients with obsessive-compulsive disorder and 16 normal control subjects. The obsessive-compulsive patients showed a significant increase in the volume of the right side of the head of the caudate nucleus compared with that of control subjects. This finding was not correlated with demographic, psychopathological, or clinical characteristics.


MRI in psychiatry: 731 cases.

The frequency of brain pathology found in the 731 patients who underwent MRI scans in the present study was higher than expected on the basis of reports in the literature (Owens et al., 1980). This underlines the value of a simple MRI examination as an effective diagnostic complement in the investigation of patients with psychiatric symptoms that may have an underlying organic basis.


Artifact processing in topographic mapping of electroencephalographic activity in neuropsychopharmacology.

Mapping of the electroencephalogram (EEG) has been found to be a valuable method in clinical neuropsychopharmacology. It is evident that careful treatment of artifacts is of utmost importance for EEG data processing, as artifacts that contaminate the EEG data can lead to spurious results. The artifact-processing method described in this article splits signal analysis into a preprocessing step, yielding individual electro-oculographic (EOG) regression factors for EOG minimization, and into a processing step, yielding target variables. The combination of avoiding, minimizing, and identifying artifacts, as well as visual checking of face validity, will help remove artifactual effects from the EEG.


Noise, noise sensitivity and psychiatric disorder: epidemiological and psychophysiological studies.

Noise, a prototypical environmental stressor, has clear health effects in causing hearing loss but other health effects are less evident. Noise exposure may lead to minor emotional symptoms but the evidence of elevated levels of aircraft noise leading to psychiatric hospital admissions and psychiatric disorder in the community is contradictory. Despite this there are well documented associations between noise exposure and changes in performance, sleep disturbance and emotional reactions such as annoyance. Moreover, annoyance is associated with both environmental noise level and psychological and physical symptoms, psychiatric disorder and use of health services. It seems likely that existing psychiatric disorder contributes to high levels of annoyance. However, there is also the possibility that tendency to annoyance may be a risk factor for psychiatric morbidity. Although noise level explains a significant proportion of the variance in annoyance, the other major factor, confirmed in many studies, is subjective sensitivity to noise. Noise sensitivity is also related to psychiatric disorder. The evidence for noise sensitivity being a risk factor for psychiatric disorder would be greater if it were a stable personality characteristic, and preceded psychiatric morbidity. The stability of noise sensitivity and whether it is merely secondary to psychiatric disorder or is a risk factor for psychiatric disorder as well as annoyance is examined in two studies in this monograph: a six-year follow-up of a group of highly noise sensitive and low noise sensitive women; and a longitudinal study of depressed patients and matched control subjects examining changes in noise sensitivity with recovery from depression. A further dimension of noise effects concerns the impact of noise on the autonomic nervous system. Most physiological responses to noise habituate rapidly but in some people physiological responses persist. It is not clear whether this sub-sample is also subjectively sensitive to noise and whether failure to habituate to environmental noise may also represent a biological indicator of vulnerability to psychiatric disorder. In these studies noise sensitivity was found to be moderately stable and associated with current psychiatric disorder and a disposition to negative affectivity. Noise sensitivity levels did fall with recovery from depression but still remained high, suggesting an underlying high level of noise sensitivity. Noise sensitivity was related to higher tonic skin conductance and heart rate and greater defence/startle responses during noise exposure in the laboratory. Noise sensitive people attend more to noises, discriminate more between noises, find noises more threatening and out of their control, and react to, and adapt to noises more slowly than less noise sensitive people.(ABSTRACT TRUNCATED AT 400 WORDS)


Dimensions of neurosis.

Factor analyses of the General Health Questionnaire have attempted to interpret the factors as measuring anxiety, depression and social functioning. Data from two large community surveys were used to conduct an unrotated principal components analysis of the 30-item General Health Questionnaire. A general factor, indicating overall severity of psychiatric disorder, accounted for around 30% of the variance. The next most important factor, accounting for about 8% of the variance, was bipolar with the positive ('less than usual') items of the General Health Questionnaire having positive coefficients and the negative ('more than usual') items having negative coefficients. It is suggested that the concepts of positive and negative mental health derive empirical support from the results and may prove to be a useful classification of dimensions of mental health in the community.