[Advantage of conversion of a uretero-ileostomy to a continent reservoir]. The authors refer their own experience in conversion of incontinent urinary diversion to a continent one. In 6 patients with ureteroileostomy they constructed continent reservoir. Reservoirs were formed from isolated ileocecal segment of the intestine together with the previous ileal loop. Continence was ensured by construction of a valve by method of ileal intussusception. After operation patients were followed-up clinically, biochemically and urodynamically, their subjective feelings and objective findings were analysed. Serious early or late complications were not registered during follow-up.


[An uncommon cause of testalgia].

[An uncommon cause of testalgia]. Ten men aged 30-55 years suffered for many years from unilateral testalgia without subjective vertebrogenic complaints, and comprehensive urological examination did not reveal the cause of pain. Detailed functional examination of the spine revealed in all patients homolateral blocks of the Th-L transition, in nine men spasms of the musculus psoas, in five moreover a block of the SI synchondrosis on the same side. After a single or repeated release of the block the testalgias receded.


[A single-stage reconstruction in hypospadias using a vascularized preputial flap]. The authors submit an account of their experience with a modern method of reconstruction of hypospadias connected with the chorda. In 31 boys (10 months to 15 years) they used for reconstruction of the urethra a flap from the prepuce with a preserved vascular stalk, as described by Duckett. In the majority they transferred a double flap ("double face") where the outer sheath of the prepuce was used to cover the ventral side of the penis. In three boys the authors performed their own modification of this plastic operation. Complications developed in 12 boys (38.7%): stricture of the proximal anastomosis of the urethra (6), stricture of the meatus (1), necrosis of the skin cover (4), dehiscence (1). An open operation had to be made in the last five patients (16.1%). In all children excellent functional and aesthetic results were achieved. The above plastic operation is indicated in penile and penoscrotal hypospadias with chorda. It is a single stage operation. Due to the use of vascularized tissue and the microsurgical technique it is possible to perform a definite reconstruction of the external genitalia already by the age of one year.


[Drug-induced urolithiasis caused by N4-acetylsulfamethoxazole (Biseptol) and oxolinic acid (Desurol)]. The authors describe rare types of drug-induced urolithiasis in two female patients (N4-acetylsulfamethoxazole--a Biseptol metabolite and oxolinic acid--Desurol). To improve the diagnosis of drug induced urolithiasis the authors recommend a combination of microscopic methods and infrared spectroscopy. They findings are documented by photographs and infrared absorption spectra.


[Cystic lesions of the prostate--diagnosis, therapy and clinical significance]. The authors present an account of results of examinations in 162 patients with cancer of the prostate, benign hyperplasia of the prostate, inflammatory diseases of the prostate and patients with a normal finding on palpation of the prostate. The patients were subjected to clinical, laboratory, histopathological and transrectal ultrasonography of the prostate. In one patient a CT examination of the prostate was made. In the group were seven patients with cystic prostate lesions (4.3%). In the group of patients with inflammatory diseases of the prostate they observed cystic changes in five patients (14.2%). The most important group was formed by two patients with abscesses of the prostate and one patient with an ascended utriculus prostaticus. Transrectal ultrasonography of the prostate was the supreme method for the diagnosis of cystic prostate lesions.


[Ureteroscopy in the treatment of ureterolithiasis]. After establishment of endourological methods at our University Urological Department we have treated 36 ureteral stones in 34 patients since January 91 until April 92. Through retrograde (23) and antegrade (13) access we have successfully treated almost all calculi with the exception of one (where we hadn't been able to pass through reimplanted ureteral orificium). We have introduced double J stent in 90% patients after procedure and discharged them 3 days postoperatively on average. We have had no serious complication. Ureteroscopy with stone disintegration possibility has enabled us almost to leave open surgery in those cases, lower morbidity and shorten time spent in the hospital significantly.


[Seminal vesical abscess-diagnosis and therapy]. The authors present case-histories of two patients with abscesses of the seminal vesicles. They emphasize the asset of transrectal ultrasonographic examination for the early diagnosis of an abscess of the seminal vesicles. Antibiotic therapy, puncture of the seminal vesicles and evacuation of pus proved effective therapeutic methods.


[The effect of extracorporeal shock-wave lithotripsy on renal function]. Using the method of phase scintigraphy, the authors examined 48 patients who were treated by means of extracorporeal shock-wave lithotripsy. The authors proved at the 5% of significance that the development or deterioration of renal functions does not depend on the localization of the concrement and the number of shock-waves needed for disintegration. The authors confirmed the significant effect of the size of concrement on the lesion of renal function--all stones larger than 30 mm lead in 100% to a varying deviation, as compared with the examination made before extracorporeal shock-wave lithotripsy. Obesity has also a significant effect on the development or deterioration of lesions of renal function. From the total number of patients where after lithotripsy a lesion of renal function developed or deteriorated 70.6% were obese! After 24 months in two patients deterioration of the condition, as compared with the initial state, was proved.


[Giant cell arteritis of the arteries of the arm. Diagnosis, surgical indications and choice of procedure]. At autopsy, affection of the aortic arch and of the arm arteries is found in about 70% of patients with giant cell arteritis. Symptoms occur in only about 5% of them. Arteriography often shows typical spindle-shaped stenoses or tapered occlusions of the diseased vessels. Arterial stenoses are successfully treated with corticosteroids. In case of chronic occlusion, however, ischemia-induced symptoms may necessitate an operation. Endarterectomy should be preferred to bypass procedures. Subsequent long-term corticosteroid treatment should be instituted in order to treat the underlying disease, and to prevent reocclusions.


[Prognostic factors and results after the combined surgical and radiotherapy treatment of ependymomas]. Between 1978 and 1991, 31 patients with primary (n = 28) and recurrent (n = 3) ependymoma received external radiation after initial surgery. There were 26 cases of intracranial and five cases of spinal ependymoma. Histological grading revealed low-grade in 23 and high-grade tumors in eight patients. Craniospinal irradiation was given to 13 of 28 patients, whole cranial radiation with boost to posterior fossa in three and local treatment to twelve patients. Six of 28 patients received chemotherapy. Dose to the primary, tumor localisation, grading and extend of surgery did not significantly impact on survival and relapse-free survival. Age was a marginally significant prognostic factor for survival. In patients with intracranial ependymoma (n = 24) survival and relapse-free survival at five years were 54% and 42%, respectively. Patterns of recurrence showed a local recurrence alone in eight, a CNS-relapse with local recurrence in four and local recurrence with distant metastases in one case. Spinal seeding occurred in two of 13 after craniospinal irradiation and two of twelve patients after local treatment. The main problem in the treatment of ependymoma remains local control, the use of spinal irradiation does not seem to improve treatment results.


[Atypical fractionation in advanced squamous-cell carcinomas of the head-neck area]. From May 1990 to May 1991, 23 patients with advanced, inoperable squamous cell cancers, clinically staged as III or IV, were treated by unconventional fractionation radiotherapy. Treatment consisted of a continuous hyperfractionated accelerated radiotherapy, delivering a total dose of 55.3 Gy within 17 consecutive days. In ten patients radiation therapy was combined with chemotherapy; 20 mg mitomycin C/m2, administered by intravenous bolus injection on day 5 of treatment. Apart from a confluent mucositis, treatment tolerance was good. Haematological toxicity from mitomycin C was minor and did not require any specific therapy. The mucosal reaction lasted six weeks (median duration) and was not thought to be increased by additional chemotherapy. In twelve of 23 patients a complete remission of the primary tumour was seen, in patients with lymph node metastases there was a complete response in 14 out of 20 patients. After a median follow-up of 18 months, ten of 23 patients have survived (8/23 without evidence of disease). Eleven patients have died due to local tumour progression and one patient died with distant metastases, being without evidence of local tumour. The advantage of this unconventional fractionation, which takes the described short potential tumour doubling time for head and neck cancers into account, is discussed.


Advantage of three-dimensional treatment planning for localized radiotherapy of early stage prostatic cancer. Conventional two-dimensional (2-d) treatment planning was compared to three-dimensional (3-d) treatment planning for patients with prostatic carcinoma. Both types of treatment planning were performed for all ten patients with five fixed fields. In 3-d planning we used irregular shaped fields. For further evaluation we performed conventional planning in rotation technique in two patients. The target volume included prostate, seminal vesicles and a surrounding security margin of 2 cm. Using the MPR-version of the MEVAPLAN planning system, the three-dimensional dose calculations were performed. For the volumes of interest (VOI's) we discussed quality of the dose distribution concerning homogeneity in the target volume and isodose distribution in the organs at risk, which are the rectum and the urinary bladder. We defined the tumor encompassing reference isodose (ca. 95%) for the calculation of the involved rectum- and bladder volume. Using the five-field technique our results show a reduction of the radiation related rectum- and bladder volume concerning the tumor encompassing reference isodose (ca. 95%) for the rectum in between 9.5 and 36.6% (median: 19%, n = 10) and for the urinary bladder in between 15.7 and 47.8% (median: 28%, n = 10). Calculated for 80% of the reference isodose the difference for the rectum was 15.7 to 31.3% (median: 23%) and for the urinary bladder 24.5 to 56.7% (median: 42%). A significant reduction of radiation related side-effects concerning rectum and urinary bladder can be expected by a reduction of volume involvement and a consecutive dosage limitation.


Visualization of 3-D treatment plans with fast neutrons. The treatment planning for radiotherapy with fast neutrons requires modifications of the planning systems used for photons. The neutron- and photon-component of the treatment fields must be determined and can then be used for separate calculations. The corrections for inhomogeneities are performed by use of attenuation coefficients and the corresponding corrections for changes in the kerma. The treatment planning system MEVAPLAN (Siemens) was modified to follow these requirements. Thus treatment planning for 14 MeV DT-neutrons could be performed. The multiplanar option is used to calculate 3D-dose distributions based on up to 40 serial CT slices. The generated three-dimensional dose matrix and the CT data are transferred via magnetic tape to the visualization system VOXEL-MAN developed at the University Hospital of Hamburg. This system uses a ray casting algorithm based on the generalized Voxel-model to display detailed 3D-images of human anatomy together with the calculated dose distribution. Different treatment plans for neutrons and photons are calculated and visualized. Various manipulations of the data-sets are displayed to improve the critical examination of the simulated dose distribution and to discern the quality of treatment techniques.


[The improved determination of the dose rate in irregular photon fields]. A revised formula for calculation of dose per time or monitor unit ("dose rate") of irregular megavoltage photon beams is proposed. The formula considers additionally the shading by secondary shieldings of the plane source describing the scattered radiation in the head. Therefore, in addition to the primary output factor C(ac) as function of the equivalent square ac x ac of the collimator field size a secondary output factor S(as) is introduced denoted as function of the equivalent square as x as of the irregular field. S is determined using a satellite diaphragm formed of shielding blocks in combination with a totally opened collimator. In this definition, S includes both the effects of radiation scattered in tissue (phantom scatter factor PSF) and of missing photons from the plane source by the blocks (satellite diaphragm factor SAT). In the usual formula to calculate the "dose rate" (output) at reference point in depth t, PSF is replaced by S: D = D0 x C(ac) x [PSF(as)/PSF(ac)] x T x R(as,t). There T is representing the block tray factor and R(as,t) the tissue phantom ratio or relative depth dose, depending on the irradiation technique used. Thus the modified formula is given by D = D0 x C(ac) x [S(as)/S(ac)] x T x R(as,t). Measurements show that the revised formula provides an additional precision of up to 2% in the calculation of dose, depending on the type of accelerator respectively on the size of the plane source of scattered radiation.


[Radiobiological research to optimize high-dose-rate afterloading therapy with Ir-192 in extragenital tumors]. Since the introduction of the high-dose rate afterloading therapy a higher biological effectivity of this method has been well known in comparison with the low-dose contact therapy. This will practically taken into account by reducing the dose and more fractionating of the total dose. With our test we want: firstly to prove the influence of the therapy break on the duration of the radiation reaction. Secondly we want to prove the influence of the dose rate on the efficiency of the radiation reaction. We have tried to answer the question by the animal model guinea pig skin. We examined early reactions as well late reactions.


The effect of endotoxin on preirradiated mice. Adult male mice were given a whole body irradiation with non-lethal doses of 2.5 or 5 Gy. Unirradiated animals served as controls. The animals (including controls) received a single injection of endotoxin (LPS from Salmonella abortus equi) with doses of 100, 200 or 400 micrograms one day up to one year after irradiation. Twelve, 24 or 48 hours after lipopolysaccharide (LPS) application the animals were killed and dissected. Animals which died spontaneously were also examined. Liver, lung, kidney, small intestine, and stomach were histologically investigated. The histological findings showed, that differences exist between irradiated and unirradiated mice and that the cause of death is also different for animals dying spontaneously. The investigations have shown that after irradiation phases of different degrees of sensitivity with regard to the endotoxin response exist. This behaviour can be observed by different lethality rates or in the light of the histological results. Moreover, the histological findings have shown, that distinct regenerative changes occur first of all in the liver, in the mucosa of small intestine, and the gastric mucosa, in which the number of differentiated cells compared with the mitotic active cells is reduced. It can be ascertained, that a whole body irradiation with 2.5 to 5 Gy enhances an additional injury by endotoxin weeks to months later. Contrary to this a preirradiation a few days before endotoxin application leads to a "protection" against the efficacy of endotoxin. These findings can be explained by modes of action described in literature, according to which endotoxins induce the formation of highly active mediators especially the tumor necrosis factor.


Post-irradiation protective effect of irsogladine maleate on intestinal crypt stem cells in mice. Radioprotective effect of irsogladine maleate, an anti-ulcer drug, on the intestinal crypt stem cell survival was studied in mice using a crypt microcolony assay. Irsogladine maleate was injected intraperitoneally immediately after irradiation and then, daily for three days. A successive administration of the drug following 10 Gy of irradiation increased the survival of intestinal stem cells with a clear dose-related trend. In order to estimate the D0, survival curves were determined for X-ray plus placebo and X-ray plus 10 mg/kg of irsogladine maleate. The D0, for X-ray plus the drug was 2.2 Gy while it was 1.9 Gy for X-ray plus placebo. These findings suggest that isogladine maleate can be applied for the alleviation of intestinal damages in heavily irradiated people by radiation accidents.


[Brain scintigraphy (SPECT) with thallium-201 in primary brain tumors]. We evaluated the role of thallium-201 single-photon emission-computed tomography (SPECT) in diagnosis, differential diagnosis and follow-up of 33 patients with primary brain tumors. 27 of 33 lesions were detectable by Tl-201 SPECT because only two of eight low-grade (grade 1 and 2) astrocytomas showed Tl-201 accumulation up to a tumor to nontumor ratio of 2.6. High grade (grade 3 and 4) astrocytomas showed Tl-201 accumulation in the range of 2.2 up to 13.0 and were different from low-grade astrocytomas. Noninvasive grading of astrocytomas is therefore possible, whereas differential diagnosis of oligodendrogliomas and astrocytomas or meningiomas was not possible with Tl-201. In the follow-up of six patients, we could demonstrate, that tumor progression is correlated with increasing and tumor regression with decreasing Tl-201 accumulations. This functional changing proceed morphological findings in CT. But vanishing of Tl-201 accumulation during therapy does not mean vanishing of tumor as could be demonstrated by follow-up.


The use of a bone lid to close the anterior wall defect after surgery in the maxillary sinus. Surgery was performed in the maxillary sinus with restoration of the surgical defect in the anterior wall with a resutured bone-lid, in 12 patients with an average age of 45 years, the technique is described and evaluated clinically and radiographically (computed tomography). During the followup time of 1-4 years, the condition of the maxillary sinus was normalized. It is our opinion that the bone-lid technique for maxillary sinus surgery is useful, especially when good overview and access is necessary.


Masticatory efficiency in individuals with natural dentition. 51 healthy dentate subjects aged between 20 and 60 years were evaluated with regard to their masticatory efficiency using a sieving test. A subjective evaluation of difficulty in chewing different kinds of food was also obtained by means of a questionnaire. The occlusal and restorative status were assessed using specific indices. The masticatory efficiency was shown to be lower with increasing age 20-39 years, mean = 39.8 and 40-60 years, mean = 27.1, respectively (p < 0.05). Males had a statistically significantly higher masticatory efficiency index than females. Multiple regression analysis showed that age, sex, the number of occluding teeth and the orthodontic treatment need index can predict half the variance in masticatory efficiency. It is concluded that it is more appropriate to describe masticatory efficiency with an average value for different age groups.


Pubertal growth and maturity pattern in early and late maturers. A prospective longitudinal study of Swedish urban children. Pubertal growth in height and the pattern of skeletal and pubertal development were studied in early and late maturers of each sex. The growth rate in height in relation to age at peak height velocity was found to be significantly greater in early maturers of both sexes from at least 7 years before to 2 years after PHV. The peak height was greater in early than in late maturers, the difference being statistically significant in boys only. The amount of growth during the pubertal growth spurt was significantly greater in the early maturers of each sex. The lag periods between the occurrence of maturity indicators of skeletal and pubertal development in relation to age at peak height velocity differed between early and late maturers. The maturity indicators occurred earlier in relation to PHV in the late maturer of each sex.


The validity of estimated age in rural Pakistani children based on interviews with mothers and tooth counts of primary teeth. Assessment of chronological age in children aged 6-30 months was made by obtaining information from uneducated rural Pakistani mothers and by means of counting the number of emerged primary teeth. There was found no statistically significant difference in the validity in age assessment between two methods. The average difference between true chronological age and perceived age was -0.8 months (SD 2.5 months) in boys, and 0.9 months (SD 3.9 months) in girls. The average difference between true chronological age and dental age was -0.4 months (SD 3.5 months) in boys, and 0.8 months (SD 4.8 months) in girls.


Conservative treatment methods in craniomandibular disorder. Conservative methods should be a basic treatment principle in CMD. In spite of similar signs and symptoms, the etiology may vary and treatment should, if possible, be directed towards the cause, but the management may often just be mitigating. Counselling may be crucial. Occlusal appliances of different design obviously influence the muscular activity significantly but equilibration may include a strong placebo effect. While relaxation is incompletely investigated, biofeedback seem possibly effective. The application of physical medicine procedures is almost entirely empirically based. Experience from other areas also motivates pharmacotherapy in CMD while intra-articular injections seem reasonably well founded. Investigations of pain-alleviating methods like TENS and acupuncture, though sometimes promising, are often uncontrolled. Manipulation, even if effective, may not necessarily be a "disc recapturing" manoeuvre. The results of conservative treatment for joint clicking seem unpredictable and long-term results of treatment with repositioning splints are not encouraging. A need for well-controlled, randomised clinical studies in diagnostic subgroups and controls has been expressed. Although most patients with CMD can be successfully treated with different conservative methods, often with remarkably similar results, other options must be considered for some.


Salivary levels of lactobacilli, buffer capacity and salivary flow rate related to caries activity among adults in communities with optimal and low water fluoride concentrations. In several human studies, scientists have sought to elucidate the connection between caries activity, high levels of lactobacilli, low buffer capacity and a low salivary flow rate, separately or in combinations. The aims of the study were to investigate if there was a difference in caries activity among adults in optimal versus low fluoride areas. It was further investigated if this difference was related to high lactobacilli levels, low buffer capacity and low salivary flow rate, separately or in combination. Finally, it was analysed if the lactobacilli levels were lower in an area with optimal fluoride water concentration. The study is based on clinical examinations of 30-40 year olds who all their lives had drunk water with a fluoride concentration representative for the community. 260 individuals living in the optimal fluoride area and 236 from the low fluoride area are included in the study. The results show a caries activity significantly lower among those in the optimal fluoride area. It is also shown that these differences can not be explained by differences in lactobacilli levels, buffer capacity and salivary flow, neither separately nor in combination. The fluoride concentration in the drinking water is wholly decisive. No difference in lactobacilli levels between optimal and low fluoride areas were demonstrable in this study.


An individual training programme for speeding up prolonged oral sugar clearance in hospitalized elderly patients. A pilot study. The aim of this pilot study was to evaluate an individual programme for speeding up prolonged oral sugar clearance in hospitalised elderly patients. Six patients at a university hospital for geriatric medicine, aged 67-85 years, completed a 6-week study. Every second week one of the authors gave: 1) information on the importance of oral sugar clearance for oral health, 2) instruction in oral hygiene, and 3) professional tooth cleaning. Moreover, the staff responsible for each patient provided 1) massage and training of the lips, cheeks and tongue shortly before each main meal, 3 times daily, 2) supervision of chewing on a sugar-free chewing gum for at least 20 min, 4 times daily, and 3) support and encouragement of the patients throughout the day. Salivary glucose clearance was measured both sublingually and vestibularly in the lower jaw after chewing a glucose tablet and after a mouth rinse with 10% glucose solution. There was a clear tendency that the oral sugar clearance was reduced after the 6-week period and some of the reductions in the clearance variables were statistically significant. All patients, especially those suffering from cerebral haemorrhage, reported an improved ability to chew while proceeding with the programme, which was also confirmed by the staff. The main conclusion from this pilot study is therefore that it might be possible to speed up prolonged oral sugar clearance in elderly hospitalised patients using an individual training programme.


Some factors influencing the quantity of prosthodontic treatment performed by general practitioners in public dental service. For general dentists in public dental service, Orebro county, the numbers of artificial crowns, pontics, RPD:s and CRD:s produced in 1989 were studied in relation to some background factors. The dentist-related factors were: gender, time in profession, working time per week, and place of graduation. Factors related to dental clinics were: location of the clinic, general prosthodontic activity at the clinic. Multiple regression analyses were used. Two different patterns were found; one for fixed prosthodontics, another for removable prosthodontics. Prosthodontic activity at the clinic, the male sex, and (inversely) time in profession were significantly associated with high production of artificial crowns and pontics. The regression models for removable prosthodontics showed no significance.


Mutans streptococci, lactobacilli and caries prevalence in 15 to 16-year olds in Göteborg. Part II. During the fall of 1987 one hundred and fifty-five 15 to 16-year-olds were examined with regard to caries prevalence, saliva secretion rate and salivary numbers of mutans streptococci and lactobacilli. In 15% of the subjects no mutans streptococci were detected, while 17.7% carried > 10(6) colony forming units (cfu) per ml saliva. The median value was 1.8 x 10(5) cfu per ml saliva. No lactobacilli were detected in 19% of the subjects and 14.3% had > 10(5) cfu per ml saliva. The mean caries prevalence was 21.0, of these 14.1 were incipient lesions. Increased numbers of mutans streptococci and lactobacilli were associated with increasing caries prevalence. Subjects with high numbers of both microorganisms showed about 4 times higher mean caries prevalence than those with low numbers. Streptococcus sobrinus carriers (15%) had both higher mean caries prevalence and a higher proportion of subjects with > 10(6) cfu mutans streptococci per ml saliva than was found in the whole group.


Both phasic sensory stimulation and tonic pharmacological activation increase Fos-like immunoreactivity in the rat locus coeruleus. Neuronal activation increases levels of Fos protein, the product of the early immediate gene c-fos. Since most studies used stimuli that evoke sustained elevations in activity; the present study examined Fos-like immunoreactivity (Fos-LI) in the nucleus locus coeruleus (LC). Halothane-anesthetized rats were given either footshock to elicit phasic activation of LC neurons or yohimbine (10 mg/kg, i.p.) to induce a tonic increase in firing. Both treatments markedly increased Fos-LI in a subpopulation of LC neurons. These results demonstrate that c-fos induction does not require high tonic levels of neuronal activity and that Fos-LI may underestimate the proportion of LC neurons neurophysiologically activated by a given stimulus and suggest that factors beyond neuronal activity per se contributes to c-fos expression.


LHRH neurons in the medial septal-diagonal band-preoptic area do not project directly to the hippocampus: a double-labeling immunohistochemical study. While neurons containing immunoreactive luteinizing hormone-releasing hormone (LHRH) are scattered primarily in the medial septal-diagonal band of Broca-medial preoptic area (mS-dbB-PO) complex, autoradiographic studies have demonstrated dense concentrations of LHRH receptors in the hippocampus. The route by which LHRH is transported to its hippocampal receptors is unknown. The present study was designed to test the hypothesis that LHRH-containing neurons in the mS-dbB-PO complex project to hippocampal sites containing LHRH receptors, thereby serving as a source of innervation to these receptors. Large (0.10 microliters) or small (0.02 microliters) volumes of the retrograde tracer wheat germ agglutinin (WGA) were injected unilaterally into four separate hippocampal locations in six ovariectomized female rats. In an additional five females, a 0.15 microliter volume of the retrograde tracer fluorogold (FG) was similarly injected. After a five day survival period, the animals were sacrificed. Vibratome sections of the brain were stained for both WGA and LHRH with a dual immunohistochemical technique. Since FG is a fluorescent chromagen, brains of animals injected with FG only required processing for LHRH immunofluorescence. As a positive control, some sections containing retrogradely labeled cells filled with either WGA or FG were processed for choline acetyltransferase (CHAT) immunoreactivity. The WGA and FG injections covered targeted hippocampal sites and neurons containing retrogradely transported WGA or FG were found in abundance in the mS-dbB-PO complex. In accord with previous reports, many CHAT-positive and fewer LHRH-positive neurons were found in this complex. Approximately 5-10% of the CHAT-positive neurons also contained WGA or FG; however, no neurons were found to co-localize LHRH and either of the retrograde tracers. The results indicate that LHRH neurons in the mS-dbB-PO complex do not project directly to hippocampal sites containing LHRH receptors.


Distribution of cocaine recognition sites in monkey brain: II. Ex vivo autoradiography with [3H]CFT and [125I]RTI-55. CFT [WIN 35,428, 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane] and its 4-iodinated analog RTI-55 have been proposed as imaging probes for cocaine recognition sites and for dopamine transporters. The central and peripheral distribution of radiolabeled forms of these compounds was studied 30 minutes after intravenous administration in squirrel monkey (Saimiri sciureus). Quantitative ex vivo autoradiography of brain tissue sections from animals receiving [3H]CFT (2.5 nmol/kg) revealed radioligand distribution primarily in dopamine-rich brain regions, and treatment with cocaine or mazindol substantially reduced [3H]CFT accumulation. The caudate nucleus, putamen, and nucleus accumbens/olfactory tubercle accumulated the highest levels of [3H]CFT, and within the caudate nucleus, medial-to-lateral and anterior-to-posterior gradients were observed. Low levels of [3H]CFT were found in the cortex, thalamus, hypothalamus, and background levels in white matter and in the cerebellum (striatal:cerebellar ratio > 3). The in vivo distribution of [3H]CFT closely paralleled its in vitro distribution (Synapse, 9:177-187). Although [125I]RTI-55 (0.2 nmol/kg) also distributed to dopamine-rich brain regions (striatal: cerebellar ratio of 3.6), high levels also were detected in cortex, thalamus, and in midbrain/brainstem structures. In the periphery, [125I]RTI-55 accumulation, measured as percent of administered dose, was higher than [3H]CFT in liver and lung, respectively. Of the radioactivity detected in soluble extracts of striatum, liver, and lung, greater than 90% comigrated with [3H]CFT or [125I]RTI-55 standards. The results support the hypothesis that dopamine-rich brain regions may be relevant to the effects of cocaine, and that both CFT and RTI-55 may be suitable imaging probes for these sites.


Reduction of GABAB inhibitory postsynaptic potentials by serotonin via pre- and postsynaptic mechanisms in CA3 pyramidal cells of rat hippocampus in vitro. The action of serotonin (5-HT) on GABAergic synaptic transmission was investigated with intracellular recordings in CA3 pyramidal cells of rat hippocampal slices. Local application of 5-HT (500 microM) hyperpolarized CA3 pyramidal cells, decreased cellular input resistance, and reduced slow afterhyperpolarizations. Serotonin attenuated the late (GABAB) component of polysynaptic inhibitory postsynaptic potentials (IPSPs; 47% of control) without affecting the early (GABAA) component. During bath application of the excitatory amino acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (20 microM) and 2-amino-5-phosphonovalerate (AP-5) (40 microM), 5-HT similarly decreased the amplitude of the late (GABAB) component (17% of control) of monosynaptic IPSPs but did not affect the early (GABAA) component. The mean reversal potentials of poly- and monosynaptic IPSPs were unaffected by 5-HT. The conductance increases associated with the late component of poly- and monosynaptic IPSPs were reduced by 5-HT. Hyperpolarizing responses evoked in CA3 pyramidal cells by somatic applications of gamma-aminobutyric acid (GABA) were unaffected by 5-HT. During bath application of bicuculline (20-50 microM), hyperpolarizing responses elicited by dendritic GABA application were reduced by 5-HT (71% of control). The effect of 5-HT on these direct GABAB hyperpolarizations (29% decrease in response) does not appear sufficient to fully account for the effect of 5-HT on late GABAB IPSPs (53-83% decrease in response). Therefore, 5-HT may reduce GABAB IPSPs in CA3 pyramidal cells 1) by a postsynaptic action on pyramidal cells and 2) by a selective presynaptic action on GABAergic interneurons mediating the GABAB IPSP. This presynaptic action of 5-HT does not appear to involve excitatory afferents onto inhibitory interneurons.


Involvement of the nigrotectal and nigrothalamic pathways in kappa opioid-induced circling. The relationship between kappa opioid-induced movement and output stations of the substantia nigra pars reticulata (SNpr) was examined using the rodent circling model. Contralateral rotation produced by intranigral microinjection of the kappa opiate U50,488 was lower in animals with ibotenic acid lesions of either the ipsilateral ventromedial thalamus or superior colliculus than in control animals without lesions. These results suggest that endogenous kappa opioids in the SNpr may influence movement through actions on the nigrothalamic and nigrotectal pathways. In contrast, animals with ipsilateral lesions of the striatum showed an increase in circling relative to controls, possibly due to kappa receptor supersensitivity in the SNpr.


Sigma receptors are associated with cortical limbic areas in the primate brain. Putative sigma receptors are a current target for antipsychotic drug development. Novel antipsychotic agents which possess selective and high affinity for sigma binding sites may serve as an alternative to the principal neuroleptic drugs currently in clinical use which mediate extrapyramidal side effects and dyskinesias through their blockade of dopamine receptors. We have used in vitro autoradiography to localize putative sigma receptors labelled with (+)-[3H]-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [(+)-[3H]-3-PPP] in the brain of the rhesus macaque. The binding characteristics of (+)-[3H]-3-PPP in the primate brain were comparable to those previously described in the rodent. Saturation analysis demonstrated a single class of sites in cerebellar and hippocampal membranes with a Kd value of 28 nM. Sigma receptors labeled with (+)-[3H]-3-PPP in the primate brain displayed the appropriate rank order of potency and stereoselectivity in competition binding assays. Haloperidol displaced (+)-[3H]-3-PPP binding in the low nanomolar range, and the (+) isomer of pentazocine was 50-fold more potent than (-) pentazocine. Computerized densitometric analysis of the autoradiograms demonstrated a striking enrichment of sigma binding sites over the paralimbic belt cortices, including the orbitofrontal, cingulate, insular, parahippocampal, and temporopolar gyri. Peak densities of sigma receptors were seen over the medial and central nuclei of the amygdala and were widely distributed within the hippocampal formation. Sigma binding sites densities were elevated over the suprachiasmatic and supraoptic nuclei of the hypothalamus. Moderate sigma receptor densities were observed over the ventromedial sectors of the caudate and the putamen. Sigma receptors were also elevated over autonomic relay nuclei of the brainstem, including the nucleus of the solitary tract and the dorsal motor nucleus of the vagus. The distribution of sigma receptors in the primate brain suggests that the paralimbic belt cortices, amygdala, hippocampus, hypothalamus, and autonomic relay nuclei of the brainstem may be interrelated by a topographic chemical linkage. The autoradiographic visualization of sigma receptor distributions in the primate brain provides further support for a role of sigma receptor mechanisms in the functions of the limbic system.


Systemic and microiontophoretic administration of morphine differentially effect ventral pallidum/substantia innominata neuronal activity. In vivo electrophysiological recording techniques were employed to examine responses of ventral pallidum/substantia innominata (VP/SI) neurons to systemic and local administration of morphine. Using a cumulative dosing protocol, intravenous administration (0.1-30 mg/kg i.v.) produced a suppression of firing in 82% of neurons tested. The suppression was dose-related and blocked by the opioid antagonist, naloxone. In contrast, microiontophoretic applications of morphine resulted in current-related suppression (32% of neurons tested) or excitation (26%). Concurrent application of naloxone attenuated or blocked both effects of local morphine application. It was demonstrated that acute tolerance did not develop with repeated morphine exposures following either systemic or local administration. The present findings establish the sensitivity of VP/SI neurons to morphine and provide functional relevance at the level of a single neuron for opioid peptides and their receptors in this region. As reported for most other opioid-receptive brain areas, neuronal rate suppression was the predominate response observed, and it is proposed that excitations to iontophoresed morphine reflect a disinhibitory phenomenon. The differential morphine-induced rate changes, and number of responding neurons, observed with systemic vs. iontophoretic morphine administration suggest that extra-VP/SI regions that also are opioid sensitive can subsequently direct neuronal responsiveness to opioids within the VP/SI.


Comparative PET studies of the kinetics and distribution of cocaine and cocaethylene in baboon brain. Recent studies have suggested that cocaethylene, an active metabolite of cocaine found in blood and postmortem brain of individuals self-administering cocaine and alcohol, may play a role in the increased toxicity seen when coadministering these 2 drugs. We have used positron emission tomography (PET) and carbon-11 (t1/2:20.4 min) labeled cocaine and cocaethylene to compare the short-term kinetics of cocaine and cocaethylene in baboon brain. The regional uptake of [11C]cocaine cocaethylene in baboon brain. The regional uptake of [11C]cocaine ([11C]COC) and [11C]cocaethylene ([11C]CE), 5-8 mCi and 4-6 micrograms, in baboon brain (n = 7) were similar but clearance from whole brain (global, GL) and from striatum (SR), thalamus (TH), and cerebellum (CB) was slower for cocaethylene. Steady-state distribution volumes (DV) were not significantly different in the striatum but were greater for cocaethylene in the thalamus, cerebellum, and whole brain. Debenzoylation of cocaethylene proceeded at about one-third the rate of cocaine, as determined by in vitro incubation of labeled cocaethylene and labeled cocaine with baboon plasma and with purified horse butyryl-cholinesterase (EC 3.1.1.8). Even though the slower clearance of cocaethylene could lead to longer tissue exposures and potentially accentuated or different physiological effects relative to cocaine, the difference between the 2 drugs is not large. Thus it is more likely that the direct actions of cocaine and alcohol on some organs, rather than cocaethylene, account for this enhanced toxicity.


Alcohol intoxication does not change [11C]cocaine pharmacokinetics in human brain and heart. There is increasing evidence that the combined use of cocaine and alcohol produces enhanced behavioral and toxic effects. We have used PET and tracer doses of [11C]cocaine in 7 normal human volunteers to assess if the distribution and clearance of cocaine are altered by alcohol intoxication. Each subject received 2 PET studies with [11C]cocaine (3-11 micrograms), one before and one during alcohol intoxication (1 g/kg). Regions of interest included the brain (n = 3) and heart (n = 4). Arterial plasma was assayed for unchanged cocaine and for labeled cocaethylene, a metabolite of cocaine found in individuals using cocaine and alcohol in combination (Hearn et al., 1991a). Alcohol intoxication did not change uptake and clearance or the steady-state distribution volume of [11C] cocaine in brain (striatum, thalamus, and cerebellum) or in heart. Moreover, labeled cocaethylene was not detected in the 10 minute plasma sample. These results suggest that the acute enhancement of behavior and toxicity associated with the combined use of cocaine and alcohol is not due to an alteration in cocaine's organ distribution or to cocaethylene formation but may be related to an additive effect resulting from the direct actions of each of these drugs.


In vivo studies of [125I]iodobenzamide and [11C]iodobenzamide: a ligand suitable for positron emission tomography and single photon emission tomography imaging of cerebral D2 dopamine receptors. Iodobenzamide (IMB) labeled with either [11C] or [125I] was studied in mice and baboons. Pharmacological studies demonstrated an in vivo binding profile compatible with D2 dopamine receptors. Mouse biodistribution studies with both [11C]IMB and [125I]IMB showed a similar brain distribution of radioactivity. Mouse [125I]IMB studies with amphetamine and reserpine pretreatment suggested that IMB may be less susceptible to endogenous dopamine competition for D2 receptor binding in vivo as compared to raclopride. Preliminary baboon studies showed haloperidol competition for IMB binding sites.


Assortative mating and grandparental transmission facilitate the persistence of a sign language. Conditions for the persistence (i.e., protection from loss) of a sign language are investigated assuming monogenic recessive inheritance of deafness, assortative mating for deafness or hearing, and cultural transmission of the sign language to deaf individuals from their deaf parents and deaf maternal grandparents. A new method is introduced to deal with the problem of grandparental transmission in which the basic variables are the frequencies of triplets comprising a mother, a father, and their daughter of permissible phenogenotypes. Usual stability analysis is then done on the system of linear recursions in the frequencies of these triplets, derived on the assumption that signers (users of the sign language) are rare. It is shown that assortative mating is the most important factor contributing to persistence, but that grandparental transmission can also have a significant effect when assortment is as strong as observed in England and the United States.


Survival enhancement through food sharing: a means for parental control of natal dispersal. The value of food sharing among relatives is analyzed for a situation where fitness equals survival. In seasonal environments the minimum food abundance may set a limit to group living. Delayed dispersal is predicted to be linked to relaxed winter competition and high parental survival. Enhanced survival for the offspring when parents share food could be a sufficient reason to delay dispersal, while early dispersal in advance of food shortage periods may be induced by a competitive relationship. At low resource abundance dominant parents do best by being competitive and retaining all resources. For food abundance higher than the expected requirements food sharing with independent offspring is possible, although it has a non-zero cost. Food sharing parents still retain most of resources to themselves, but the resource share given to subordinate offspring gradually gets larger when food abundance increases. Except for at very low food abundance, where subordinates may adopt a "suicidal" behaviour and cede their resources to the dominant, there is a conflict over how to share the resources.


Some threshold and stability results for epidemic models with a density-dependent death rate. Most classical models for infectious diseases assume that the birth and death rates of individuals and the meeting rates between susceptible and infected individuals do not depend on the total number of individuals in the population. While these assumptions are valid in some situations they are less valid in others. For example, for diseases in animal an insects populations competition for scarce resources might well mean that the death rate depends on the number of individuals. The present paper examines two epidemic models where the death rate is density dependent. For each model the possible equilibrium levels of disease incidence are determined and the stability of these equilibrium levels to small perturbations is discussed. The biological interpretation of these results is presented together with the results of some numerical simulations.


National survey of notifications of tuberculosis in England and Wales in 1988. Medical Research Council Cardiothoracic Epidemiology Group. A survey was undertaken to determine the distribution of tuberculosis in England and Wales and, by comparison with the findings of similar surveys in 1978-9 and 1983, to study trends in the incidence of the disease by ethnic group over the decade. The survey included all cases of tuberculosis in England and Wales newly notified to the medical officers for environmental health during the six months from 2 January to 1 July 1988. Notification rates were calculated from population estimates from the 1988 Labour Force Survey. Clinical details were obtained from the clinician for 2149 (99.4%) of the 2163 newly notified and previously untreated patients. Over 90% were either white (53%) or of Indian, Pakistani, or Bangladeshi ethnic origin (39%). The notification rate in the white population was 4.7/100,000/year, a decline of 7.2% per year since 1978. The rate was 134.6/100,000/year in the population of Indian ethnic origin, and 100.5/100,000/year in that of Pakistani or Bangladeshi ethnic origin, a decline of 6% a year since 1978 for the two groups combined (standardised for age, country of birth, and length of time in the UK). In all ethnic groups rates of disease were much higher in the elderly than in the young. Bacteriological results were available in 1161 (80%) of the 1443 pulmonary cases. In 939 (81%) Mycobacterium tuberculosis was cultured; 614 cases (53%) also had positive smears, of which 424 (69%) were from white patients. Notification rates for tuberculosis in England and Wales declined over the decade, but major differences remained between ethnic groups.


Does a positive Heaf test reaction in Asian schoolchildren predict later breakdown of tuberculosis? Some authorities advise giving prophylactic antituberculosis treatment to those with a grade 3 or 4 reaction to Heaf tests performed as part of the schools' BCG programme. This is not done in Leicestershire, which because of its large Asian population would require considerable resources to do so. A calculation of the "breakdown" rate, and thus the potential value of chemoprophylaxis, in these children would therefore be valuable. Lists of names of Asian children who had a grade 3 or 4 Heaf test reaction in 1982 and 1983 were compared with lists of notifications for the five years 1983 to 1987. Those who were on both lists were considered to have tuberculosis that had "broken down." Of the 760 children with positive Heaf test reactions, only four were on the subsequent notification lists. The chest radiograph obtained because of the Heaf test result showed evidence of active tuberculosis in only three of these. Only one child had infection that "broke down" later. The benefit of chemoprophylaxis seems likely to be limited in these Asian children, most of whom had received BCG early in life.


Nucleolar organiser regions as a marker of growth rate in squamous cell carcinoma of the lung. The numbers of nucleolar organiser regions (AgNORs) per cell has been considered as an indicator of the cellular proliferative activity. A study was carried out to examine whether AgNOR numbers relate to the growth rate in squamous cell carcinoma of the lung. AgNORs were stained by a one step silver method, and examined in representative paraffin sections from 45 cases of squamous cell carcinoma of the lung treated by surgical resection of the primary tumour. The mean (SD) AgNOR numbers per cell in squamous cell carcinomas (5.3 (0.9)) were significantly higher than those in normal bronchial epithelium (1.2 (0.1)). There was no statistical difference among tumours of different post-surgical stages (stage I = 5.2 (0.8), II = 5.9 (1.4), III A = 5.5 (1.3)). The tumour volume doubling time in these cases ranged from 74 to 208 days (120.7 (40.4)). There was a high inverse correlation between the AgNOR numbers and doubling time. The AgNOR numbers were related to the growth rate of squamous cell carcinoma of the lung. Thus the AgNOR count could be used as a useful marker for investigating the cellular proliferative activity.


Portable liquid oxygen and exercise ability in severe respiratory disability. The development of portable liquid oxygen systems, capable of delivering high flow rate oxygen for long periods, justifies reassessment of the value of supplemental oxygen to aid exercise tolerance in patients with chronic respiratory insufficiency. The type of exercise test and the low oxygen flow rates previously used may account for the variable and often poor responses to supplemental oxygen reported in earlier studies. The walking tolerance of 30 patients with severe respiratory disability was measured while they were breathing air and increasing doses of supplemental oxygen (2, 4, 6 1/min) by using both the standard six minute walking test and an endurance walking test. To assess the initial learning effect and repeatability of the walking tests, three six minute walks and three endurance walks were performed on day 1 and a single walk of each type on days 2, 3, and 14. In addition, oxygen dosing studies were performed on days 2 and 3 after the initial baseline walking tests. Each dosing study comprised four endurance walking tests or four six minute walking tests with patients breathing either air at a flow rate of 4 1/min from a portable cylinder or supplemental oxygen at a flow rate of 2, 4 or 6 1/min from a portable liquid oxygen supply. The order of the tests was randomised. Walking distance with each flow rate of oxygen was compared with walking distance with patients carrying cylinder air and for the initial unburdened walks. Breathlessness was assessed by visual analogue scoring on completion of each walk. Exercise ability and breathlessness were significantly improved with supplemental oxygen and this benefit outweighed the reduction in performance resulting from carrying the portable device. Supplemental oxygen at flow rates of 2, 4, and 6 1/min increased mean endurance walking distances by 37.9%, 67.7% and 85.0% and six minute walking distances by 19.2%, 34.5%, and 36.3% by comparison with distances when the patient was carrying air with a flow rate of 4 1/min. The additional work of carrying the portable gas supply reduced endurance walking distance by 22.2% and six minute walking distance by 14.1% by comparison with a baseline unburdened walk. Comparison of supplemental oxygen at 2, 4, and 6 1/min with the baseline unburdened performance showed increased endurance walking distances of 7.3%, 30.4%, and 43.9% and six minute walking distances of 2.3%, 15.5%, and 17.0%. Walking distance was increased by more than 50% by comparison with an unburdened walk in seven patients with the endurance walking test but in only three patients with the six minute walking test. The benefit was similar in patients with obstructive and with interstitial lung disease. Individual responses were variable and only desaturation during the baseline walk in patients with obstructive lung disease had any predictive value for benefit with oxygen. As there was no clear relation between response to oxygen therapy and the patients' characteristics, assessment for supplemental oxygen therapy will depend on exercise testing. It is suggested that portable oxygen should be considered only if a patient shows a 50% improvement in exercise ability with high flow rate oxygen (4-6 1/min) by comparison with an unburdened walk.


Quantification of right to left shunt at rest and during exercise in patients with pulmonary arteriovenous malformations. Current treatment of patients with pulmonary arteriovenous malformations requires serial embolisations by means of steel coils or balloons. Measurement of right to left shunt is the most specific index of response to treatment. A new method of measuring shunt has been developed that is less invasive than traditional methods. Right to left pulmonary shunt (expressed as percentage of cardiac output) was measured at rest in 19 patients with pulmonary arteriovenous malformations and six normal subjects by using intravenously injected albumin microspheres labelled with technetium-99m. The technique was compared with a simultaneous shunt measurement in subjects breathing 100% oxygen while they rested. The microsphere technique was adapted to measure the right to left shunt during exercise in 12 patients and five normal subjects with a new method of quantification. The mean (SD) shunt at rest as measured by the microsphere method was 23.2% (15.6%) in the patients and 2.7% (1.2%) in the normal subjects. When these values were compared with those of the 100% oxygen method the difference in mean values was 1% and the limits of agreement between the two methods -32% to +45%. The microsphere method is less invasive (arterial blood gas sampling is not required), quicker, and more comfortable for patients than the 100% oxygen method. In five of the normal subjects the mean (SD) 99mTc microsphere shunt increased from 2.9% (1.3%) at rest to 5.1% (2.9%) during exercise. In the 12 patients studied during exercise the shunt increased from 33.7% (12.7%) at rest to 41.7% (13.3%) during exercise in eight but decreased from 22.6% (2.4%) at rest to 17.6% (2.2%) during exercise in four. Arterial desaturation during exercise correlated with change in the size of the right to left shunt during exercise (r = +0.80). The microsphere method allows measurement of right to left shunt at rest and during exercise. Serial measurements at rest provide a simple, safe assessment of the physiological response to embolisation in patients with pulmonary arteriovenous malformations.


Inhaled frusemide and exercise induced asthma: evidence of a role for inhibitory prostanoids. Inhaled frusemide protects subjects with asthma against a wide range of bronchoconstrictor challenges, including allergen, exercise and inhaled sodium metabisulphite. An investigation was designed to determine whether this protection is related to the production of inhibitory prostaglandins, such as prostaglandin E2 (PGE2), by studying the effect of the cyclooxygenase inhibitor indomethacin on the protection afforded by inhaled frusemide against exercise induced asthma. In a double blind crossover study 10 subjects with mild asthma were pretreated with indomethacin (50 mg thrice daily) or placebo capsules for three days; they then inhaled frusemide (40 mg) or placebo 10 minutes before an exercise test previously shown to cause a 20-30% fall in forced expiratory volume in one second (FEV1). After inhalation of placebo exercise caused a similar maximum fall in FEV1 whether pretreatment was with placebo (26%) or indomethacin (25.2%). After inhalation of frusemide the maximum fall in FEV1 was reduced to 14.3% after placebo pretreatment and to 21.8% after indomethacin pretreatment; the difference between placebo and indomethacin pretreatment was significant (mean difference 7.5%, 95% limits 0.6%, 14.4%). The inhibitory effect of frusemide on the response to exercise, assessed as change in FEV1 over 30 minutes, was significantly greater with placebo (62%) than indomethacin (13%) pretreatment. These findings support a role for inhibitory prostanoids, such as PGE2, in the beneficial effects of frusemide as a protection against exercise induced asthma.


Circadian rhythm of peak expiratory flow in children passively exposed and not exposed to cigarette smoke. Because airway calibre shows a circadian rhythm and since exposure to passive smoking reduced lung function this study was undertaken to investigate whether passive smoking affects the circadian rhythm of peak expiratory flow (PEF) in schoolchildren. Twenty schoolchildren (12 boys and 8 girls, aged 10-11 years) exposed to passive smoking were matched for sex, age, and height with 20 children who had not been exposed to cigarette smoke. Exposure to passive smoking was assessed by questionnaire and by urinary cotinine concentrations. A portable spirometer was used to measure PEF at 16:00, 20:00, 22:00, 06:00, 08:00, and 12:00 hours on a consecutive Saturday and Sunday. The circadian changes in PEF were measured by the cosinor method. Both groups showed diurnal fluctuation in PEF values with a noticeable circadian rhythm. PEF peaks were the same in the two groups and occurred around 15:00 hours. The cosinor mean was approximately 10% lower in children exposed to passive smoking and the amplitude was approximately 60% higher than in the unexposed children. Passive smoking in children is associated with a reduction in the cosinor mean and an increase in the amplitude of the normal circadian rhythm of airway calibre. This increased PEF rhythm amplitude may be considered as an early indication of airway obstruction.


Repeatability of methacholine challenge in asthmatic children measured by change in transcutaneous oxygen tension. The airway response to bronchial provocation may be evaluated by monitoring the fall in transcutaneous oxygen tension (PtcO2) but the repeatability of this method has not been rigorously assessed. To determine the repeatability of this indirect method of assessment, bronchial challenge was performed with methacholine in nine children with stable asthma (age range 6-12 years) and was repeated 24 hours later. The response was determined by the fall both in forced expiratory volume in one second (FEV1) and in PtcO2. A modified tidal inhalation protocol was used in which quadrupling concentrations of methacholine were given, thereby reducing the time taken for the full challenge by almost half. The concentrations of methacholine that provoked a 20% decrease in FEV1 (PC20FEV1) and 15% and 10% falls in PtcO2 (PC15PtcO2, PC10PtcO2) were calculated. Repeatability measures, assessed as the 95% range for a single determination, were +/- 0.96 and +/- 1.12 doubling concentration differences respectively for PC15PtcO2 and PC10PtcO2 and +/- 0.80 for PC20FEV1. This challenge method using quadrupling concentrations and an indirect assessment of the response by PtcO2 was sufficiently repeatable for clinical use and compared favourably with repeated challenge assessed by FEV1. The PtcO2 method is simple and effort independent, and should prove particularly useful for measuring bronchial reactivity in young children.


Effect of reduced expiratory pressure on pharyngeal size during nasal positive airway pressure in patients with sleep apnoea: evaluation by continuous computed tomography. This study aimed to determine whether reducing the expiratory pressure during nasal positive airway pressure for reasons of comfort causes a substantial decrease in the upper airway calibre. Eight patients with obstructive sleep apnoea were studied. Continuous computed tomography (each run lasting 12 seconds) was used to measure minimum and maximum pharyngeal cross sectional areas at the velopharynx and the hypopharynx. Pharyngeal areas were measured while patients were awake and breathing without assistance, during the application of 12 cm H2O continuous positive airway pressure, and during bi-level positive airway pressure with an inspiratory pressure of 12 cm H2O and an expiratory pressure of 6 cm H2O. Nasal continuous positive airway pressure significantly increased the mean minimum and maximum upper airway areas at both the velopharynx and the hypopharynx compared with normal unassisted breathing. Bi-level positive airway pressure did not show a statistically significant increase in the minimum upper airway area at either level compared with normal unassisted breathing. The minimum areas of the velopharynx and hypopharynx were smaller with bi-level than continuous positive airways pressure in six of eight and eight of eight patients respectively but these were still greater than during unassisted breathing in seven of eight and six of eight patients respectively. Continuous positive airway pressure at 12 cm H2O is more effective in splinting the pharynx open than bi-level positive airway pressure with an inspiratory positive airway pressure of 12 cm H2O and an expiratory pressure of 6 cm H2O in patients with obstructive sleep apnoea during wakefulness, suggesting an important role for expiratory positive airway pressure. The clinical importance of this finding needs to be evaluated during sleep.


Cardiovascular effects of fenoterol under conditions of hypoxaemia. The reason for the association of increased risk of death with fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. Before inhalation of fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with fenoterol and hypoxaemia). The chronotropic and electrophysiological effects of fenoterol were enhanced by conditions of hypoxaemia.


Microbial flora of the trachea during intubation of patients undergoing upper abdominal surgery. The presence of Haemophilus influenzae in the oropharynx is correlated with the subsequent development of chest infection. The importance of colonisation of the trachea by bacteria at the time of surgery is uncertain. This study investigated the tracheal flora at the time of intubation in 24 patients undergoing elective upper abdominal surgery. The bacterial flora of the trachea was sampled in all 24 patients immediately after intubation and immediately before extubation. Patients were assessed postoperatively for the development of chest infection. Bacteria, including H influenzae in five cases, were isolated from the post-intubation brushings of the trachea of 15 patients. The pre-extubation brushings from only four patients yielded growth. Three of five patients developing a chest infection were colonised by H influenzae according to the postintubation brush, compared with two of 19 without chest infections. Before extubation two of five developing chest infections had H influenzae in the trachea but none of 19 without infection. All but one of the patients from whom H influenzae was isolated were smokers. These results suggest that the increased risk of postoperative chest infection in cigarette smokers may be due in part to colonisation of the trachea by H influenzae at the time of operation.


Treatment of pleural empyema secondary to pneumonia: thoracocentesis regimen versus tube drainage. Pleural empyema is a well known complication of pneumonia. Attitudes differ, however, about the best treatment of this condition and the place of drainage, early operation, and local antibiotics. In a retrospective study 94 consecutive patients with verified empyema caused by pneumonia were admitted to the department of either pulmonary medicine or thoracic surgery. Treatment was either by a lavage regimen (daily thoracocentesis, saline rinse, systemic antibiotics, and in some patients instillation of local antibiotics) in the medical ward (51 patients) or by tube drainage and systemic antibiotics in the surgical unit (43 patients). The stay in hospital was significantly shorter in the medically treated patients than in the surgical group--2.3 v 5.0 weeks respectively. Furthermore, pleurocutaneous and bronchopleural fistulas developed more frequently in patients treated by tube drainage than in those treated with the thoracocentesis regimen alone (13 (30%) v 5 (10%) and 6 (14%) v 2 (4%) for each complication respectively). The overall mortality was 8.5% with no differences between treatments. Treatment with a lavage regimen plus local and systemic antibiotics seems to be associated with a lower frequency of complications and a shorter duration of hospital stay than tube drainage and systemic antibiotics. These results should be confirmed by a prospective, randomised study.


Air transport and the fate of pneumothorax in pleural adhesions. Air travel is contraindicated in patients with a pneumothorax but was necessary because of the exigencies of war in three patients. Three patients with high velocity missile injuries to the chest and pleural adhesions are reported. All had to be evacuated by air, without an intercostal drain or oxygen supplement, from the war stricken area of Northern Somalia (Horn of Africa) to Mogadishu. Two patients with a partial pneumothorax flew on military transport aeroplanes at an altitude of 3000 m in a non-pressurised cabin and recovered rapidly after a few days in hospital. One patient, transported on a small Cessna aeroplane, died after developing bilateral tension pneumothoraces.


Oesophageal dissection after thrombolytic treatment for myocardial infarction. A 62 year old woman admitted with a history suggesting acute myocardial infarction had thrombolytic treatment with anisoylated plasminogen-streptokinase activator complex, which resulted in submucosal haemorrhage in the oesophagus; this caused dissection of the wall of the oesophagus and complete dysphagia. The haematoma resolved spontaneously, leaving behind a diverticulum, with reduced peristalsis and delayed emptying but no obstruction.


Localised fibrous mesothelioma arising in an intralobar pulmonary sequestration. A localised fibrous mesothelioma arising from an intralobar lung sequestration occurred in a 64 year old Turkish woman. This appears to be the first report of a mesothelioma occurring within a pulmonary sequestration.


Corynebacterium pseudodiphtheriticum pneumonitis in a leukaemic child. A 6 year old boy receiving chemotherapy for acute lymphocytic leukaemia developed pneumonia due to Corynebacterium pseudodiphtheriticum. He responded to antibiotics.


Abnormal movement of the arytenoid region as a cause of upper airway obstruction. A 75 year old woman presented with a three week history of severe dyspnoea and cough. Auscultation and spirometry suggested extrathoracic inspiratory airway obstruction, and bronchoscopy showed abnormal motion of the arytenoid region (supraglottic area), causing upper airway obstruction only during forced inspiratory efforts. Sedatives improved the symptoms within a week. It is suggested that reversible malfunction of the arytenoid region can be responsible for upper airway obstruction.


[3 cases of hypertrophic gastritis associated with a Ollulanus tricuspis infection in cats]. An infection with Ollulanus tricuspis was found in three cats with hypertrophic gastritis. Two cats were put down because of chronic vomiting and emaciation. The third cat died shortly after the appearance of blood in its vomit and faeces.


[Salmonella dublin infections in cattle, a review]. In this review Salmonella dublin infections in cattle are discussed. Pathogenic pathways and clinical symptoms in calves and cows are mentioned in addition to diagnostic methods like post mortem examination, bacteriological methods and serology. Epidemiological aspects like carrier state in cows and the survival of the bacteria in the environment are discussed. Without reliable tests to detect carriers, we suggest that control of this infection on farms must be based on prevention, improved hygiene and therapeutic measures. Vaccination can be used to improve the immunity of the herd.


Flow microfluorometric analysis of murine spermatozoa fails to detect H-2 antigens. The presence of class 1 and class 2 histocompatibility antigens on murine sperm was investigated by flow microfluorometry. Monoclonal anti-H-2Kk (class 1), anti-Iak (specificity 2, class 2) and allo-anti-Iak (class 2) antisera were used in direct or indirect fluorescence labelling experiments to probe the expression of class 1 and class 2 antigens on epididymal mouse spermatozoa. Sperm-specific antibodies were generated by intraperitoneal immunization of both male and female C3H/HeN mice with syngeneic spermatozoa. Sperm-specific antigens were detected in 68-85% of syngeneic mouse sperm and 65-90% of allogeneic mouse sperm examined. Conversely, these antibodies did not stain syngeneic or allogeneic lymphocytes above the background of the negative control. Mouse sperm samples failed to exhibit specific fluorescence above the background of negative control values with antibodies against either class 1 or class 2 MHC antigens. We have established the sensitive, objective and economical assay of sperm membrane antigens with fluorochrome-labelled antibodies by flow microfluorometry. By use of this sensitive and objective technique we have not detected MHC antigens on murine sperm. We conclude that these MHC antigens are not expressed on sperm at a level to be practically detectable.


HLA-DRB1 first domain sequence for a novel DR4 allele designated DRB1*0413. A novel DR4 allele, DRB1*0413, was identified in a Caucasian individual "LEV" having the HLA phenotype A2; B51,14; DR4,7; DQw3,w2. DRB1*0413 is a DRB1*0401-variant differing from DRB1*0401 only at codon 86 where valine is present instead of glycine.


[Digestive disorders in rabbits and guinea pigs]. Numerous digestive tract diseases in pet rabbits and guinea pigs result from both an inherent physiological predisposition and from poor feeding and husbandry. A large proportion of digestive disturbances in rabbits and guinea pigs are secondary to changes in the oral cavity caused by inadequate teeth wear. The required regular trimming of the cheek teeth using a modified spatula and hollow pair of pincers is described and illustrated. The symptoms, diagnosis, prognosis and treatment of a selection of digestive disorders, as commonly encountered in small animal practice, are presented. The difficulties of using antibiotics in view of the gram positive intestinal flora and possible dysbacteria, dysentery and enterotoxaemia are considered. Finally, advice on feeding and on the rearing of orphan neonates is given.


[Functional pyloric stenosis in sheep].

[Functional pyloric stenosis in sheep]. The clinical findings, the autopsy and the histology of functional pyloric stenosis in three sheep between four and eight years old are described. A chronic ulcer with structural alterations of the pyloric protuberance was found in the first animal. In the second sheep there were several polyps in the pylorus, and in the third erosions throughout the whole pylorus, and a few hyperplastic areas of epithelium at the junction between pylorus and duodenum. The abomasum was moderately to extremely congested and the contents weighed between 6.7 and 13 kg. In addition to these findings chronic and unspecific abomaso-duodenitis was found in all three sheep. These three cases can be attributed to the distal functional pyloric stenosis (Hoflund syndrome).


[The content of Hb in the blood and of different constituents in the plasma of lambs with low and normal increase in body mass]. In lambs with a very restricted intake of nutrients and an increase of the body mass of less than 60 g per day (group A) and in those with an increase of more than 220 g/day (group B), analyses of components of the blood and the plasma were performed at certain intervals. In the lambs of group A an anemia developed in the course of 77 days. The concentrations of alpha-amino-N, non-protein-N, urea, glucose and insulin as well as the activity of the alkaline phosphatase of the plasma of the lambs of group A were always lower than those of group B. The beta-hydroxybutyrate concentration of the lambs of group A on the 7th and 21st day of the experiment was higher than that of group B. The concentrations of inorganic phosphate and iron in the plasma of group A at most points during the study were lower than that in group B.


[Detection of inhibitors in swine urine with MICUR-BT]. The immersible culture medium MICUR-BT used in human medicine for the detection of antimicrobial substances in the urine was tested for its suitability in pigs. In in-vitro tests, 15 pure antibiotic substances, 2 pure substance mixtures as well as 5 veterinary injection preparations with no direct antimicrobial effect were checked. The agar perforation test was used as a reference procedure. In a total of 65 pigs the detectability of 9 pure antibiotic and chemotherapeutic agents, 2 pure substance mixtures as well as 5 veterinary drugs with no direct antimicrobial effect was tested after oral or parenteral application. In the in-vivo tests the MICUR-BT test turned out to be more reliable than the agar perforation test. In 76.9% of the untreated pigs below 30 kg b.w. the MICUR-BT-test showed an antimicrobial effect. Such effects were reduced by 38.3% in the reference procedure.


[Occurrence and drug resistance of bacteria pathogenic to the lungs from autopsy material of swine]. Eight hundred and fifty-four piglets which died or were euthanized due to pneumonia or rhinitis atrophicans, were investigated during the period of 1986-1990. Of the animals, 569 showed bronchopneumonia, 218 had pleuritis, pericarditis and peritonitis, 165 had rhinitis atrophicans, 58 pleuropneumonia, and 9 animals had fibrinous pneumonia. Pasteurella multocida, Haemophilus parasuis, Bordetella bronchiseptica, Actinobacillus pleuropneumoniae and Pasteurella haemolytica were isolated in 59.1%, 29.5%, 27.8%, 3.7%, and 2.3% cases of bronchopneumonia respectively. Samples from pigs with pleuritis or rhinitis atrophicans showed Pasteurella multocida in 63.8 and 68.5%, Bordetella bronchiseptica in 28.4 and 39.4%, streptococci in 28.9 and 3.9%, Haemophilus parasuis in 25.2% and 20.6%, Actinobacillus pleuropneumoniae in 5.1 and 5.5%, and Pasteurella haemolytica in 3.2 and 3.0%, respectively Actinobacillus pleuropneumoniae was found in 51 of 58 cases of pleuropneumonia and in 5 of 9 cases of fibrinous pneumonia; 55.6% and 44.4% respectively of those forms of pneumonia were positive for Pasteurella multocida. In the agar diffusion test, 36.8-82.6% of bacterial isolates showed resistance to streptomycin, 7.7-45.5% to sulfamethoxazole-trimethoprim, 5.7-44.6% to tetracycline, 0.2-32.8% to ampicillin, 0.0-16.3% to lincospectin, 2.0-81.2% to furazolidone, 0.4-4.5% to chloramphenicol, 1.3-78.1% to penicillin and 0-0.3% to enrofloxacin.


[Cortisol and corticosterone plasma levels in different Psittaciformes]. Plasma cortisol and corticosterone levels were measured in macaws, African Grey Parrots, Amazon Parrots and budgerigars using a RIA after preliminary cleaning. As in other avian species, the plasma contains predominantly corticosterone.


[Trichomonad infections of the oral cavity in horses in southern Germany]. Trichomonads of the oral cavity were found in 9 of 60 investigated horses. Apart from dental tartar, the oral cavity showed no clinical signs in all positive horses. The clinical investigation of these horses additionally revealed colic in 4 and coughing in 4 horses as well as lumbago in 1 animal. By means of scanning electron microscopy the trichomonads were shown to be round or piriform with an average length of 7.6 microns and greatest width of 6.3 microns. They had 4 anterior flagella with an average length of 8.3 microns, an undulating membrane measuring 8.7 microns with no trailing flagellum as well as an axostyle extending on average 7.8 microns beyond the body, and therefore have to be placed into the genus Trichomonas.


[Nephrolithiasis as a cause of colic in horses. Case report]. The results of clinical, ultrasonic, post mortem examinations and concrement analysis of a case with nephrolithiasis in a horse are described. Problems of diagnosis, etiology and occurrence of nephroliths in the horse are discussed.


[Management of acute tendinitis].

[Management of acute tendinitis]. Ultrasonography must be used in combination with physical examination for the appropriate diagnosis of acute tendon injuries. Therapy should be designed to return the tendon to its normal function and appearance. Local and systemic anti-inflammatory agents, cold hydrotherapy and massage minimize excessive scar formation and progressively increasing tensile forces directs scar tissue to replace the tendon function.


[Rhinoscopy in dogs and cats].

[Rhinoscopy in dogs and cats]. Rostral and caudal rhinoscopy in dogs and cats facilitates the investigation of the nasal cavity and accurate biopsy. Rostral rhinoscopy can be performed by rigid endoscopes; caudal rhinoscopy requires flexible endoscopes. Deep anaesthesia or additional analgesia with local anaesthesia is necessary. The nasal cavity is assessed by its form, colour, surface of the mucous membrane, hyperemia, plaques, lesions, and the secretion is assessed by its quantity, colour and viscosity. Foreign bodies and neoplasia must also be looked for. Case reports with abnormal findings are described.


[Dermoid sinus in a Rhodesian ridgeback. Case report]. The dermoid sinus, which occurs mainly in Rhodesian Ridgeback dogs, is discussed. One case of infected dermoid sinus in the sacrococcygeal region of a female Rhodesian Ridgeback is described. Although the dermoid sinus communicated with the subarachnoid space, the dog walked normally and had no neurologic deficits. The radical excision of the dermoid sinus was only possible by removing the laminae of the second and third sacral vertebrae. Surgical dissection was successful.


[The uveodermatologic syndrome in dogs]. A review of the literature pertaining to the uveodermatological syndrome of dogs is presented. This syndrome is marked by depigmentation of the periocular region, lips and nose in association with severe uveitis. Early diagnosis and therapy can prevent serious vision loss. Symptoms and therapy of the cases described in the literature as well as cases seen at the Veterinary Medical Teaching Hospital in Davis/California are discussed.


[Lumbosacral instability. The cauda equina compression syndrome in dogs]. The literature review includes a short anatomical description of the lumbosacral area, etiology, symptoms, diagnosis and therapy of CECS. Two hundred and twenty-seven large-breed dogs were examined clinically, neurologically and radiologically for diseases of the lumbosacral area. Radiological findings, such as dorsal dislocation of L7, spondylosis deformans, sloped craniodorsal contour of S1, sclerosis of the cranial plate of S1 as well as narrowing and increased density of the intervertebral foramen L7/S1 were compared with clinical and neurological results. In 15 dogs dorsal dislocation of L7 by 1 to 8 mm was found. An extended position proved to be more successful in demonstrating that finding than the flexed one. All other pathological changes were found either individually or in combination in patients with lumbosacral spondylolisthesis. One hundred and thirty-six dogs showed no sign of dorsal dislocation but all the other described changes. All detected changes have to be interpreted as instability of the lumbosacral area and resultant chronic and degenerative pathological processes. A definite correlation between spondylolisthesis of L7/S1 and compression of the cauda equina could not be found on plain radiography.


[The organ topography of nonpoisonous snakes of the Boidae (boas and pythons) and Colubridae (adders) families]. In order to assist veterinarians with the diagnosis of diseases in snakes, the organ topography of 142 dissected snakes of 35 different species was analysed and examined in relation to body size and normal biotope. Apart from characteristic species specific differences, it was shown that there is a clear difference between arboreal and terrestrial snakes. It was recorded that nearly in all species the organs shifted along the body in relation to increase in growth.


The cortisone era: aspects of its impact. Some contributions of the Merck Laboratories. The announcement in 1949, by Hench at the Mayo Clinic, that cortisone had a dramatic beneficial effect on bed-ridden patients suffering from rheumatoid arthritis ushered in the cortisone era. This medical landmark was made possible by the prior steroid research of distinguished chemists and biologists in several countries. The first partial synthesis of cortisone by Sarett was the culmination of a worldwide chemical effort. This work ultimately enabled the process research department at Merck, under the direction of Max Tishler, to perform the 37-step conversion of deoxycholic acid to cortisone on a scale that made the initial clinical trials possible. In spite of the enormity of the project, and the fact that neither of two closely related analogs of cortisone had shown any interesting biological activity. Merck elected to embark on this synthetically challenging project. The clinical results reported in 1949, combined with the complexity of the partial synthesis, stimulated highly innovative research to discover new routes to cortisone and to cortisol, the active hormone. This research, particularly in the pharmaceutical industry in the United States, Mexico, and Europe, demonstrated, among other things, the value of microbial transformations in synthetic sequences. The recognition that the chronic administration of cortisol produces several unexpected side effects stimulated an intensive effort in many countries to discover an analog with an improved therapeutic index. This led to more novel chemistry and many analogs were discovered that proved to be more potent than cortisol. Prednisolone, discovered at the Schering Corporation, was the first compound that combined a high level of anti-inflammatory activity with reduced salt retention. Derek Barton contributed greatly to steroid research during the 1950s by applying creative structural thinking to systematize a host of seemingly unrelated chemical and biological observations. The cortisone era had a profound impact on drug discovery also, since it led to the logical application of steric and electronic concepts to medicinal chemistry. Last, but not least, the cortisone era taught medicinal chemists many important lessons about drug-receptor interactions.


Steroids, the steroid community, and Upjohn in perspective: a profile of innovation. The announcement in 1949 at the Mayo Clinic of the dramatic effect of cortisone in alleviating the symptoms of rheumatoid arthritis triggered a competitive worldwide research and development effort directed toward a single goal, the practical synthesis of the rare corticosteroids. The confluence of an extraordinary coalescence of multiple events and circumstances in the growth of the Upjohn Company with the Mayo discovery, inclusive of a pioneering role in the steroid field, conspired to create an environment ripe for innovation. The breakthrough, which gave Upjohn an early competitive edge, followed with startling swiftness. A common mold of the genus Rhizopus was found to introduce enzymatically an 11 alpha-hydroxyl group directly into the female hormone progesterone, which had just been synthesized from the soybean sterol stigmasterol--a one-step solution to the known multistep alternatives for 11-oxygenation. Retrospective analysis of this event in perspective with other key developments before and after at Upjohn and in the steroid community reveals a striking profile of ongoing innovation. A parallel scenario in kind was repeated at Upjohn a quarter century later. The sister soybean sterol sitosterol was radically degraded microbiologically and concurrently oxygenated in ring C to produce 9 alpha-hydroxyandrostenedione, an alternative key intermediate for corticoid synthesis. New chemical processes, highly integrated with existing processes, assured the continuation of Upjohn's leading role in steroid hormone production.


Steroids and "the pill": early steroid research at Searle. The announcement from the Mayo Clinic in 1949 of the dramatic effectiveness of cortisone in the treatment of rheumatoid arthritis stimulated tremendous interest in steroid chemistry, endocrinology, and related areas of medicine. Shortly thereafter, G. D. Searle & Co. initiated a major effort in steroid research, the objective of which was to discover better steroid drugs than those available at that time or steroids that could be used for conditions for which no compounds were previously available. This effort was remarkably successful and resulted in the introduction of several important pioneering drugs. These included norethandrolone, marketed in 1956 as Nilevar, the first anabolic agent with a favorable separation between protein building and virilization, and spironolactone, introduced in 1959 as Aldactone, the first steroid antialdosterone antihypertensive agent. Of special importance was the research that culminated in the discovery of Enovid. This substance, a combination of the progestin norethynodrel and the estrogen mestranol was first approved in 1957 for the treatment of a variety of disorders associated with the menstrual cycle. The era of oral contraception began in May 1960, when Enovid was approved by the Food and Drug Administration for ovulation inhibition, and was immediately thereafter introduced for such use.


Steroid research at Syntex: "the pill" and cortisone. The period from late 1949 through 1951 was an extraordinarily productive one in steroid chemistry and especially so at Syntex S.A. in Mexico City. Two of the most important Syntex contributions--the synthesis of 19-nor-17 alpha-ethynyltestosterone (norethindrone) and of cortisone from diosgenin--are described from a historical perspective.


From paper chromatography to drug discovery: Zaffaroni. A paper chromatography assay for adrenocortical steroids, published just as cortisone's therapeutic value in arthritis was announced, had far-reaching consequences. Its use by Upjohn scientists led to the first synthesis of cortisone. Interest in the assay also led the author to an association with Syntex S.A. in Mexico, which he was instrumental in transforming from a small chemical company into the large pharmaceutical firm, Syntex Corporation, having its base of operations in the United States. The major events of this history are described, showing how steroid product development helped establish Syntex and later played a role in the founding of ALZA Corporation.


Past and present studies with ponasterones, the first insect molting hormones from plants. The search for antitumor compounds from Southeast Asian plants led to ponasterones, the first phytoecdysteroids, just a year after structure determination of ecdysone and 20-hydroxyecdysone. An independent study of Chinese herb constituents by Takemoto et al. at Tohoku University led to the simultaneous and totally independent discovery of phytoecdysteroids. These findings greatly facilitated research in insect and crustacean physiology. The original structural studies on various phytoecdysteroids have led to interdisciplinary bioorganic studies in the area related to ecdysone receptor, ecdysone biosynthetic precursor (or its storage form), crustacean molt inhibitory factors, and so on.


[The mechanisms of the formation of kidney damages from action by blunt objects]. Analyzes 206 cases with renal injuries inflicted with blunt objects. Describes the type of renal injury in relation to the type of the trauma and direction of the strike with the blunt object with a limited surface of co-strike. Presents mechanisms of the injury formation.


[The classification of bone fissures].

[The classification of bone fissures]. A classification of bone fissures, suggested by the authors, is based on the results of their studies of bone destruction. Relationship between the fissures and bone tissue structural arrangement, and the sequence of the fissure emergence and development, starting from a microfissure (at the level of bone plates) progressing to a major fissure, resulting in final destruction of the bone, underlie this classification.


[The types of self-injuries in those sentenced to prisons]. A classification of self injuries of condemned subjects is suggested, based on analysis of the literature data and the author's own findings. The etiopathogenetic sign (the method of self injury infliction) underlies this classification.


[The indices of the mass and lipids of sections of the heart in cadavers in chronic alcoholism, alcoholic cardiomyopathy and ethanol poisoning]. Alcohol abuse involves heart mass increment at the expense of epicardial fat. Epicardial fat mass and the content of intramuscular lipids are the highest in alcoholic cardiomyopathy. Since epicardial fat mass increase is in direct correlation with the elevation of lipid content in the heart muscle proper, detection of a large mass of epicardial fat at autopsy permits a conclusion on myocardial obesity.


[The use of odontograms and panoramic roentgenography in personal identification]. Study of dental root surfaces prompted the authors to add to the routine odontogram 28 more maxillary surfaces and 22 mandibular surfaces, this making a total of 210 diagnostic signs. Employment of amplified panoramic roentgenography permitted the authors to detect specific features of the dental cavity, root canals, periodontal fissure structure, the presence of caries and its complications, inflammatory and systemic involvement, injury to the jaws and teeth. Visual examination of dental status and application of panoramic roentgenography will help improve forensic medical personal identification.


[The determination of ethylene glycol in biological objects in the presence of propylene glycol]. Therapeutic application of drugs containing propylene glycol 1.2 as a solvent may distort the results of forensic chemical detection of ethylene glycol from its oxidation products. Practical examples illustrate the possibility of ethylene glycol determination by gas chromatography in the presence of propylene glycol.


[The retention of alkyldinitrophenol compounds in cadaveric material]. The preservation of alkyl dinitrophenol compounds in corpse liver tissue was under study. The content of these compounds was assessed after various periods of the corpse storage.


[Depressive symptoms in physically frail elderly]. In 1988 a study aiming to evaluate the effectiveness of an outpatient geriatric clinic was started. Elderly persons (75-90 years) living at home or in the two old people's homes in the municipality Sittard (The Netherlands) were screened on physical vulnerability by means of oral interviews. It was possible to collect data about demographic variables and depressive complaints of 222 frail elderly. For this article the internal consistency of the Zung-depression scale (DSI) was tested for the study group. Relations between depression and the registered demographic variables are discussed. It showed that Cronbach's alpha of the depression scale is .82. A varimax rotated factor analysis resulted in six factors with a high percentage of explained variance on the first factor. This result indicates that the instrument is unidimensional. There was no systematic bias introduced by physical vulnerability. Of all frail elderly, 28% had depressive complaints. In general, women scored somewhat higher on the depression index than men. Only a slight relation between depression and age was found. Concerning household composition this study showed that frail elderly living alone and residents of old people's homes had significantly more depressive complaints than frail elderly living with others and independently living frail elderly respectively.


[Measuring psychological well-being in the elderly]. The results of a comparison of measures assessing psychological well-being in a random sample of 354 elderly people in the city of Groningen are presented: Positive Affect and Negative Affect of the Affect Balance Scale, Positive Well-being (comprising three subscales: General Positive Affect, Emotional Ties and Life Satisfaction), and the Seven Point Satisfaction Rating. None of the studied instruments is based on a clear conceptual model of well-being. The results show reasonable psychometric properties of most measures (internal reliability, skewness, test-retest reliability). Exceptions are the low internal reliability of Positive Affect and the low test-retest reliability of the (I item) Seven Point Satisfaction Rating; the same results were previously reported. Furthermore, the test-retest reliability of the short scales is lower. As expected, the correlation between Positive Well-being and Positive Affect is strong; the same holds for the correlation between Positive Well-being and General Positive Affect. The last one is suggested as alternative for the subscale of the Affect Balance Scale. The results of multiple regression analysis showed that indicators of physical and social well-being explained most variance in General Positive Affect.


Videothoracoscopy: a new perioperative challenge (continuing education credit). 1. The four cannula videothoracoscopic technique is generally used. This method affords a sufficient visual field and allows an excellent "two-handed" approach. 2. Videothoracoscopy is not for every patient; careful patient selection is important. It is also necessary to be able to develop and maintain a pneumothorax for a successful procedure. 3. The advantages of videothoracoscopy include reduced morbidity and mortality, less pain, decreased length of hospitalization, lowered health care costs, decreased blood loss, and decreased postoperative wound infections.


Keeping the keepers.

Keeping the keepers. 1. The nurse manager role is no longer limited to the management of patients and personnel. Nurse managers are also accountable for ensuring resources remain balanced and function together during the process. 2. In the health care setting, team members forgo their personal needs to focus on the needs of patients. Although adults have developed internal feelings of self-worth, most still have some dependence on their work, supervisors, and colleagues for positive affirmation. 3. A variety of approaches can provide support to team members, including responding to human needs: facilitating cooperation between team members; ensuring that team members have the necessary information; monitoring team actions in relation to patient needs; investigating potential problems; and intervening with timeliness and diplomacy.


[The histoenzymological diagnosis of the time of occurrence of a closed spinal cord trauma]. Time course of the activities of transport enzymes in capillary walls of human spinal cord was studied in various periods after closed injury to the cord, inflicted by hard blunt objects, with the use of histochemical methods for the detection of alkaline phosphatase and Mg-dependent ATPase. Wave-like fluctuations in the activities of the examined enzymes were revealed. The findings may be used to assess the period elapsed since the cord injury.