[Effects of trimebutine on colonic propulsion in mice].

Effects of oral administration of trimebutine on colonic propulsion in conscious mice were studied by measuring the time required to evacuate a bead which had been inserted into the colon, and compared with those of metoclopramide and domperidone. In normal animals, trimebutine (10 and 50 mg/kg), metoclopramide (50 mg/kg) and domperidone (50 mg/kg) had no effect on the bead evacuation. Metoclopramide and domperidone at 30 mg/kg showed no effect on the delay of colonic propulsion induced by clonidine, while trimebutine (10 and 30 mg/kg) restored the delay significantly. Trimebutine also showed restoration of the delay induced by loperamide. On the acceleration of the propulsion induced by neostigmine, trimebutine (10 and 30 mg/kg) showed an inhibition. In addition, trimebutine (3-30 mg/kg) dose-dependently suppressed the development of soft feces and/or diarrhea induced by neostigmine. According to the results, it is concluded that trimebutine produces both acceleration and inhibition on the colonic propulsion in mice.


[Electrical activities of urethral circular muscle and bladder detrusor and their control, examined by in vivo dogs].

While the micturition reflex was induced in dog by infusion of Ringer solution into the bladder, the following four types of electrical activity were picked up by two bipolar wire electrodes, embedded in the posterior wall of bladder and in the prostatic part of male urethra; 'intravesical ureter potential' and 'detrusor spike' by bladder electrode, and 'slow wave' and 'external sphincter spike' by urethral electrode. The relative size, respective rhythm and timing of discharge during voiding cycle were specific for each of them and they were readily identifiable for their own sources. The 'ureter potential' was not actively related to the voiding cycle but its triphasic wave form was dissociated at the maximum contraction phase of the bladder. Unexpected finding was the 'quasi-synchronization' of discharges between detrusor and external sphincter. The entire discharges in both muscles were consisted of 'initial burst', 'intermittent inhibition' and 'prolonged after-discharge'. The initial burst of detrusor was definitely delayed in comparison with that of external sphincter, but the end of prolonged after-discharges was again synchronized in both muscles. The possible mechanism for synchronization was discussed. The 'slow wave' was sometimes superposed on the tonic discharge of external sphincter recorded by same wire-electrode in urethral wall, therefore, their properties were analyzed under the condition of 'immobilization' of external sphincter. The sustained waxing and waning 'slow waves', observed in all female urethrae and one-fifth of male urethrae, were markedly suppressed by elicitation of isovolumetric rhythmic contractions of bladder with fall of intraurethral pressure. This bladder-dependent behavior of 'slow wave' was interpreted as a sign of 'urinary' sphincteric activity of urethral circular muscle. On the other hand, 'spontaneous' cyclic activation of 'slow wave' which was seen in about four-fifths of male urethrae and was not dependent upon the state of bladder, was interpreted as a sign of 'genital' sphincteric activity of the same circular smooth muscle.


The second and third model of the flow transformed pulsatile total artificial heart.

For the purpose of future total implantation, a new pulsatile total artificial heart, a flow transformed pulsatile total artificial heart (FTPTAH), in which the continuous flow from a single centrifugal pump (CFP) was converted to pulsatile flow by switching two three-way valves that could alternately perfuse the systemic and pulmonary circulation, was proposed, and the data from the prototype model were reported. As the next step, the second model, in which a CFP and a spool valve (SV) driven with a solenoid were fabricated in one piece, was made and tested in a mock circulatory system. The system could send 4.7 L/min of pulsatile output alternately to the pulmonary artery and aorta, with 30 and 100 mmHg afterload, respectively, at 3000 rpm CFP. However, three problems were encountered: the output was not enough, mixture or inversion of venous and arterial blood in the CFP would occur, and heat generation at the solenoid was very severe. To solve these problems, a third model was designed in the current study. To increase pump output, hydrodynamic analysis was performed. The SV was divided into inlet and outlet to control the blood mixture or inversion. To suppress heat generation, each SV was driven back and forth by two solenoids, one on each side of the SV. The model revealed satisfactory results in a mock circulatory system.


Development of a totally implantable artificial heart.

The first generation of an integrated, totally implantable electrohydraulic total artificial heart was designed for long-term cardiac replacement. The system consists of an elliptical blood pump with an interatrial shunt, Medtronic-Hall 27 mm and 25 mm inflow and outflow valves, respectively, an energy converter consisting of an axial-flow, hydraulic pump driven by a brushless DC motor, and an electronics system with transcutaneous energy transmission and telemetry. Energy is supplied by internal nickel-cadmium rechargeable batteries that supply power for 20 min and external silver-zinc batteries that are designed to supply energy to run the system for 5 hr. The blood pump consists of a single layer diaphragm cast from Biolon, with joined right and left ventricles sharing a common base. The dynamic stroke volume is 84 ml, and maximum cardiac output is 9.2 L/min at a heart rate of 110 beats/min on the mock circulation. A 4.3 mm diameter interatrial shunt is used to balance the volumetrically coupled ventricles. The energy converter pumps hydraulic fluid alternately between ventricles, with controlled, active filling in one ventricle during the systolic phase of the other ventricle. Internal or external controllers adjust the heart rate and motor speed to maintain normal atrial filling pressures and full stroke. Electromagnetic induction is used to transfer energy through the skin and a bidirectional infrared data link incorporated within the transcutaneous energy transmission coils is used to transmit information. The entire system is being assembled and refined for long-term animal implant studies.


In vitro assessment of the Milwaukee Heart and right to left balance.

A new, electrically powered, total artificial heart, the Milwaukee Heart, has been developed. This device is undergoing testing in vitro. The unidirectional motion of the brushless DC motor (BDCM) affords easier motor control and reduces energy demand. Motors with a unidirectional motion have a longer life than those with bidirectional motion. This device requires less power due to the highly efficient mechanical design. It consumes 6.5 W of power at an average flow of 5 L/min into 100 mmHg of mean aortic pressure and 20 mmHg of mean pulmonary pressure. Pumping at 8 L/min it requires 9.6 W of power. The maximum pump flow is 10 L/min and overall efficiency is 20%. A slotted optocoupler is used to determine the position of the pusher plate at the start of left systole. The number of revolutions that the BDCM makes is counted from this position. There are 50 revolutions of the BDCM per stroke (using a 50:1 gear reducer connected to the motor). The position of the pusher plate is determined from the number of BDCM revolutions. Based on where the pusher plate encounters resistance from the bladder, the force on the left pump is increased or decreased. Left to right balance has been achieved by reducing the size of the right pusher plate in conjunction with varying right stroke volume. In vitro tests show that this new, electrically powered artificial heart provides reliable performance and satisfactory hemodynamic results.


Achievement of physiologic pulsatile flow on cardiopulmonary bypass with a 24 French cannula.

In 1990, the NIH formally recognized the need for investigation of the problem of damaging the effects of cardiopulmonary bypass, issuing RFA HL-90-12-H, which emphasized production of neurologic defects in the very young and the elderly. The authors were at that time involved in comparison of pulsatile flow to steady flow cardiopulmonary bypass in large ungulates. The world literature recognizes five damaging effects of steady flow cardiopulmonary bypass that can be mitigated by pulsatile flow: metabolic acidosis, interstitial fluid accumulation, elevated systemic vascular resistance, arteriovenous shunting, and impaired brain oxygenation. To maximize the beneficial effect of pulsatile flow, however, it is necessary that its morphology be physiologic. It has been stated in the past that this goal may not be possible using standard size aortic cannulas. The purpose of this publication is to describe a method by which this feat has been achieved in 150 pound ungulates undergoing prolonged cardiopulmonary bypass.


T-lymphocyte proliferation: tyrosine kinases in interleukin 2 signal transduction.

Interleukin 2 (IL-2)-induced tyrosine phosphorylation appears to play a major role in IL-2-induced cellular proliferation. Several intracellular substrates including the beta chain of the IL-2 receptor complex (IL-2R beta), raf, MAP2 kinase, the regulatory 83 kDa subunit of phosphatidylinositol-3 kinase and S6 kinases are substrates for the IL-2 receptor activated kinase(s). However, none of the identified members of the IL-2 receptor complex exhibits intrinsic tyrosine kinase activity. Therefore, the IL-2R complex must activate intracellular tyrosine kinases. We have demonstrated that specific tyrosine and serine/threonine kinases are coprecipitated with IL-2 receptor constructs that mediate IL-2-induced cell proliferation but not with those that do not. The IL-2-activated tyrosine kinase appears to be associated with a serine and proline rich intracellular domain which is highly conserved between IL-2R beta and the erythropoietin receptor. Although the responsible kinase has not been identified, lck, fyn, fgr, ltk, hck and lyn can be ruled out as obligatory mediators. Using methods to clone tyrosine kinases from T cells, we have identified potential candidate kinases, including several which had not been known to be expressed by T lymphocytes as well as several unique kinases which had not been previously identified in any cell type.


Cell adhesion in the stromal regulation of haemopoiesis.

Haemopoiesis occurs in close physical contact with elements of the bone marrow stroma. This review examines some adhesion molecules which are expressed in haemopoietic environments. These molecules may act to maintain cell contact between haemopoietic progenitors and the cellular and extracellular matrix elements of the marrow stroma. A review is undertaken of several families of adhesion molecules and their ligands, including integrins, CD44, LEC-CAMs, CAMs and variant glycosylation patterns expressed by haemopoietic cells. Both CD44 and integrin receptors have been implicated in mediating important cellular interactions within the haemopoietic system and the significance of these and other molecules in haemopoiesis is discussed.


Clinical uses of growth factors.

The haemopoietic growth factors are a diverse group of hormones with effects on different haemopoietic cell lineages and at various points in their developmental differentiation. The biology of many of these factors is now well understood. They have entered clinical trials and have demonstrated benefits in particular clinical situations. The thrust of current phase II and III clinical investigations now is to use these factors, alone or in combinations, to modify various disease states and to ameliorate many of the side-effects of other therapeutic agents, particularly cytotoxic anticancer agents. Many other disease states also lend themselves to therapy with these growth factors. Other haemopoietic growth factors have not been as extensively studied in humans but hold great promise. In this chapter, the current status of the haemopoietic growth factors presently under clinical trial has been reviewed. In addition, several factors which have been recently described but which have not yet entered clinical trials have been discussed.


The asparagine-linked oligosaccharides at individual glycosylation sites in human thyrotrophin.

The asparagine-linked carbohydrate structures at each of the three glycosylation sites of human thyrotrophin were investigated by 400 MHz 1H-NMR spectroscopy. Highly purified, biologically active human thyrotrophin (hTSH) was dissociated into its subunits hTSH alpha (glycosylated at Asn 52 and Asn 78) and hTSH beta (glycosylated at Asn 23). The alpha-subunit was further treated with trypsin which gave two glycopeptides that were subsequently separated by reverse-phase HPLC and identified by amino acid sequence analysis. The oligosaccharides were liberated from hTSH alpha glycopeptides and from intact hTSH beta by hydrazinolysis, and were fractionated as alditols by anion-exchange and ion-suppression amine-adsorption HPLC preparatory to structural analysis. The N-glycans present on hTSH were mainly diantennary complex-type structures with a common Man alpha 1-3 branch that terminated with 4-O-sulphated GalNAc. The Man alpha 1-6 branch displayed structural heterogeneity in the terminal sequence, with chiefly alpha 2-3-sialylated Gal and/or 4-O-sulphated GalNAc. The relative amounts of the two major complete diantennary oligosaccharides and their core fucosylation differed according to glycosylation site; the sulphated/sialylated diantennary oligosaccharide was most abundant at the two sites on the alpha-subunit, whereas the disulphated, core-fucosylated oligosaccharide was more plentiful on the beta-subunit. Some interesting structural features, not previously reported for the N-glycans of hTSH, included 3-O-sulphated galactose (SO4-3Gal) and peripheral fucose (Fuc alpha 1-3GlcNAc) in the Man alpha 1-6 branch of some diantennary structures; the former suggests the presence of a hitherto uncharacterized galactose-3-O-sulphotransferase in thyrotroph cells of the human anterior pituitary gland.


Structure elucidation of sulphated oligosaccharides from recombinant human tissue plasminogen activator expressed in mouse epithelial cells.

Sulphated N-linked carbohydrate chains isolated from recombinant human tissue plasminogen activator expressed in mouse epithelial (C127) cells were analysed as oligosaccharide alditols by methylation analysis, liquid secondary ion mass spectrometry, and one- and two-dimensional 1H-NMR spectroscopy. The results demonstrate that the major component has the following novel structure: NeuAc-alpha 2-6Gal beta 1-4GlcNAc beta 1-2[NeuAc alpha 2-3Gal beta 1- 4GlcNAc beta 1-4]-Man alpha 1-3[NeuAc alpha 2-3(SO4-6)Gal beta 1- 4-GlcNAc beta 1-2Man alpha 1-6]-Man beta 1-4GlcNAc beta 1- 4[Fuc alpha 1-6]GlcNAc-o1.


Characterization of recombinant murine interleukin 5 expressed in Chinese hamster ovary cells.

We have purified recombinant murine interleukin 5 (rmIL-5) from the supernatant of Chinese hamster ovary cells. Each peptide fragment of the purified rmIL-5 generated by Achromobacter protease I digestion was characterized and glycosylation sites were determined. Although rmIL-5 contains three potential sites of N-linked glycosylation (Asn-26, Asn-55 and Asn-69), Asn-69 is not glycosylated. The oligosaccharides released from the protein by hydrazinolysis were fractionated by paper electrophoresis, lectin column chromatography and gel permeation chromatography, and their structures were analysed by sequential exoglycosidase digestion in combination with methylation analysis. The results indicated that they are a mixture of bi-, tri- and tetraantennary complex-type sugar chains with and without a fucose at the C-6 position of the proximal N-acetylglucosamine residue and high-mannose-type sugar chains. Although > 80% of the sugar chains are neutral oligosaccharides similar to recombinant human IL-5 (rhIL-5; Kodama, S., Endo, T., Tsuroka, N., Tsujimoto, M. and Kobata, A. (1991) J. Biochem., 110, 693-701), rmIL-5 has more tetraantennary oligosaccharides than rhIL-5. A site differential study revealed that Asn-55 has more tetraantennary oligosaccharides than Asn-26.


Tritiated borohydride reduction of carbohydrates: reduction of individual monosaccharides, alone or in groups, results in highly divergent specific activities.

Reduction of carbohydrates by tritiated borohydride resulted in the production of alditols or glycosides with characteristically divergent specific radioactivities. Simultaneous reduction of individual sugars in the presence of a reference standard, talose, permitted the assignment of a unique specific radioactivity with respect to talitol as 100%. A variety of structures was examined, including neutral hexoses, free and acetylated aminosugars, ketohexoses and glycosides containing a fixed pyranose ring adjacent to a carbonyl group. In the latter case, the resulting steric hindrance severely restricted the incorporation of tritium. In both of the ketohexoses tested, the minor product of the two epimeric alditols exhibited the higher specific radioactivity. In all cases, reduction produced a characteristic and reproducible specific activity in which the values varied from 51 to 182% of that found for talose. These results are interpreted on the basis of generalizations concerning mechanism and predictive value.


Schistosoma mansoni synthesizes novel biantennary Asn-linked oligosaccharides containing terminal beta-linked N-acetylgalactosamine.

This report describes the structure of novel complex-type Asn-linked oligosaccharides in glycoproteins synthesized by the human blood fluke, Schistosoma mansoni. Adult schistosome worm pairs (male and female) isolated from infected hamsters were metabolically radiolabelled with either [3H]glucosamine, [3H]mannose or [3H]galactose. The glycopeptides prepared by pronase digestion of the total glycoprotein fraction were isolated by affinity chromatography on columns of immobilized Concanavalin A (Con A) and Wisteria floribunda agglutinin (WFA). A subset of glycopeptides, designated IIb, that bound to both Con A and WFA was isolated. WFA has been shown to have affinity for oligosaccharides containing beta 1,4-linked N-acetylgalactosamine (GalNAc) at their non-reducing termini. Compositional analysis of IIb glycopeptides demonstrated that they contained N-acetylglucosamine (GlcNAc), GalNAc, mannose (Man) and fucose (Fuc), but no galactose (Gal) or N-acetylneuraminic acid (NeuAc). Methylation analyses and exoglycosidase digestions indicated that IIb glycopeptides were complex-type biantennary structures with branches containing the sequence GalNAc beta 1-4-[+/- Fuc alpha 1-3]GlcNAc beta 1-2Man alpha 1-R. The discovery of these unusual oligosaccharides synthesized by a human parasite, which appear to be similar to some newly discovered mammalian cell-derived oligosaccharides, may shed light on future studies related to the role oligosaccharides may play in host-parasite interactions.


Iron-binding proteins in human colorectal adenomas and carcinomas: an immunocytochemical investigation.

By immunocytochemistry, the presence of major iron-binding proteins (lactoferrin, transferrin and ferritin) was investigated in tubular adenomas (12 cases), villous adenomas (7 cases), carcinomas of the large bowel and rectum (39 cases) and lymph nodes involved in carcinomas (8 cases); 5 samples of colonic inflammatory pseudopolyps were also studied. Dysplastic areas of tubular and villous adenomas as well as adenocarcinomas and colloid carcinomas showed a variable cytoplasmic immunoreactivity for all antisera, although no staining was noted in some cases; tubular adenomas without dysplasia and colonic inflammatory pseudopolyps were always unstained. Metastatic elements present in lymph nodes maintained the immunohistochemical staining for iron-binding proteins. An autoctone production of lactoferrin, transferrin and ferritin by tumour cells may be hypothesized in relation to the increased requirement of iron for the turnover of rapidly dividing cells.


Morphometric study on the renal glomeruli of streptozotocin (SZ)-induced diabetic APA hamsters.

Morphometrical analysis was done on the renal glomeruli of streptozotocin (SZ)-induced diabetic and control APA hamsters. In coincidence with the histopathological and ultrastructural findings, the areas of whole glomerulus (WG) and mesangial region (MR) were significantly larger in diabetic animals than in controls at 1 and 3 months after SZ-injection (1 and 3MAI). The area of capillary lumen in diabetic animals was larger than that in controls at 1MAI but it became similar between both groups at 3MAI probably due to an increase in the area of MR. The thickness of basement membrane was significantly larger in diabetic animals than in controls at 3MAI. The present morphometrical findings, together with histological and ultrastructural ones, suggest that SZ-induced diabetic APA hamsters are useful as a model system for the investigation of focal and segmental glomerulosclerosis.


The arterial pattern and fractal dimension of the dog kidney.

A method has been developed by which it is possible to measure the fractal dimension of the arterial tree of the kidney. The objective of this work is to determine a method which permits us to discriminate between the architectures of specific organs by reference to a unique number, namely the fractal dimension of the arterial tree of that organ. This method opens the possibility of a new taxonomy for normal organs and for the pathological injiries related to the vascular morphology of those organs. The method that we have devised uses as its input the volume which is taken up by the arterial tree of the kidney. In order to calculate this volume we first obtained a plastic cast (the arteries were filled with Araldite CY233 plastic resin after which the organic tissues were corroded); thereafter we constructed a theoretical arterial tree having the same volume as the renal one. From this simplified tree, we were able to calculate its fractal dimension. The complete process of constructing the theoretical arterial tree and the subsequent calculation of its fractal dimension was carried out automatically by way of a computer programme to which we have given the name fractal program.


Role of multipotent fibroblasts in the healing colonic mucosa of rabbits. Ultrastructural and immunocytochemical study.

Light- and electron microscopy and immunocytochemistry were used to study the healing colonic mucosa of rabbits after experimental excision. Between 3 and 5 days, abundant young fibroblasts which retained many features of mesenchymal cells invaded the growing capillaries into the loose connective tissue of the healing colonic mucosa. Our electron microscopy revealed the transformation of these young fibroblasts into smooth muscle cells, into histiocyte-like cells involved in phagocytotic activity, and into vasoformative cells incorporated into the growing capillaries. The mitotic proliferation of pre-existing smooth muscle cells at the ulcer margin did not seem to be the major reason for re-establishment of the muscular tissue. The present immunocytochemistry revealed an active production of fibronectin in rough endoplasmic reticulum in the young fibroblasts. This may mean that this glycoprotein is involved in the re-establishment of both connective and muscular tissues by enhancement of adhesion and chemoattractant activities of such cells. In addition, the immunoreaction of endothelial cells of the growing capillaries suggests a role of this glycoprotein in the acceleration of the neocapillarization.


Ontogeny of reactivity to endothelial cell markers during development of the embryonic and fetal rat lung.

The reactivity of endothelial cells to putative endothelial cell-specific markers varies with species, with vessel size and with the organ studied. To determine their value in studies of fetal rat lung, and whether organ immaturity would also influence reactivity, we studied endothelial cell immunoreactivity to antibodies against Factor VIII/von Willebrand factor (VIII/vWF), and binding reactivity to Bandeiraea (Griffonia) simplicifolia 1 lectin (BSL 1) during rat fetal lung development. Using an indirect immunofluorescent technique to detect Factor VIII/von Willebrand factor (VIII/vWF), endothelial cells lining the aortic arches were identified as early as day 11 of gestation (term = 22 days), prior to lung development. Immunoreactivity to VIII/vWF was subsequently localized to intrapulmonary endothelial cells and was not dependent on vessel size. In contrast, binding reactivity of FITC-conjugated BSL 1 was observed to both endothelial cells and to the basement membrane of developing airways, thus limiting its value as endothelial cell marker. During very early lung development solitary angioblasts could not be identified by reactivity to either VIII/vWF antibodies or to BSL 1, and neither marker appears to be of value for studies of early angiogenic events.


Ultrastructural study of inflammatory bowel disease.

Ultrastructural changes that occurred in chronic active ulcerative colitis and Crohn's disease were investigated and compared to normal as well as to higher grades of dysplasia in adenomas and carcinomas. A greater number of immature absorptive cells, undifferentiated and intermediate cells were seen as compared to normal. One case of Crohn's and two cases of chronic ulcerative colitis including one with coexisting carcinoma showed increased number of vesicles and electron-dense bodies (EDB) in the absorptive cells and increased heterogeneity of mucin droplets in goblet cells and presence of atypical secretory cells (ASC). Higher grades of dysplasia characterised by large numbers of atypical secretory cells were not seen in the present series and provide no relationship between the atypical ultrastructural features and increased risk of malignancy. However, the number of cases investigated is too small and a large series is required to clarify the significance of observations such as increased number of electron-dense bodies and vesicles in the apical cytoplasm and presence of atypical secretory cells.


Ultrastructural study of neuromuscular junction in rectus femoris muscle of streptozotocin-diabetic rats.

The neuromuscular junctions (NMJ) from rectus femoris muscle in streptozotocin (STZ)-induced diabetic rats were examined by electron microscopy eight weeks after the STZ injection. When compared to controls and vehicle-injected groups, both the axon terminal and the junctional sarcoplasm showed serious alterations including mitochondrial degeneration, presence of myeloid bodies, breakdown of presynaptic membrane and changes in the form of the synaptic vesicles. The results suggest that NMJ can contribute to the pathogenesis of diabetic proximal myopathy.


In vitro differentiation of myxoid liposarcomas maintained in organ culture system.

Liposarcoma falls into the differential diagnosis of myxoid malignant mesenchymal tumors. On the other hand, its relation with white or brown fat is controversial. Two cases of liposarcoma have been studied by organ culture, a method which provides cell and tissue redifferentiation in vitro. Both cases developed successively cytoplasmic glycogen granules and lipid droplets as well as a single lipidic vacuole in the late phase of cultivation as a marker of fat differentiation. Our results support the possibility of identifying myxoid liposarcomas as well as their origin from white fat tissue.


Murine monoclonal antibodies cytotoxic to human glioma cells in vitro.

Six monoclonal antibodies (mABs) against human glioma cells (T2) were produced. T2 cells grown as solid tumors in nude mice, were dissociated and used to immunize Balb/c mice. After fusion of splenocytes with myeloma cells, eight hybrids secreting mABs were selected according to their ability to react immunohistochemically with T2 cells, but not with normal adult human brain. Cytotoxicity of mABs was tested using (3H)-thymidine incorporation assays in vitro. Four mABs showed complement-mediated cytotoxicity for T2 cells, other human glioma cells (T1), and a human melanoma cell line. Incubation with one antibody, mAb2A1, lowered (3H)-thymidine incorporation in the T2 and T1 cells to ca. 10%, and in melanoma cells to ca. 35% of control levels. Another antibody, mAb3B2, displayed a similar cytotoxicity for T2 and T1 cells, but did not show measurable cytotoxicity for melanoma cells and rat primary astrocyte cultures. Moreover, this antibody did not crossreact with haematopoietic cells from patients bearing CNS tumors or normal subjects. MAb3B2, therefore, appears to recognize and epitope associated to human gliomas, will be a useful glioma tumor marker and may have some potential therapeutical value.


Radiohistology and histochemistry of barium granuloma of the colon and rectum.

Barium granuloma of the colon and rectum is a rare complication of X-ray examination of the digestive tract using barium. The authors report 5 new cases occurring in the last 3 years. Histological examination revealed a granulomatous reaction with greyish finely granular refractile PAS-negative material located in the cytoplasm of histiocytes and in the interstitial space. The radiographic study of the paraffin blocks confirmed the nature of this material, which was X-ray opaque, and this was corroborated histochemically with the rhodizonate technique.


Seeding of expanded polytetrafluoroethylene (ePTFE) vascular grafts. A morphological study of porcine endothelial and fibroblast cells.

The need to improve clinical results with small and medium calibre grafts has led to extensive research on cell seeding of prosthetic materials. Numerous problems remain regarding identification, seeding, adhesion and survival of the cells attached. We have studied the behaviour of seedings of endothelial and fibroblast cells on ePTFE grafts. Scanning electron microscopy allows us to observe the morphological characteristics and their interaction with the biopolymers. It has been possible to differentiate both cellular types by their characteristics and interactions with the ePTFE. At the same time, from this "in vitro" study it can be concluded that the time needed to obtain a stable and confluent monolayer on ePTFE pretreated with fibronectin is between 18 hours to 4 days for endothelial cells, and 24 hours for fibroblasts. These would be the optimal time periods for "in vivo" grafting of the seeded prostheses.


Immunohistochemical localization of glial fibrillary acidic protein (GFAP) in rat pineal stalk astrocytes.

In the present work, the presence and distribution of astrocytes in the rat pineal stalk is investigated applying an immunohistochemical technique for the demonstration of glial fibrillary acidic protein (GFAP) on Epon-embedded semithin sections (0.5 micron thick). GFAP-immunoreactive cells are evenly and regularly distributed along the entire pineal stalk. The GFAP-immunoreactive cells display a stellate shape showing variable numbers of cell processes that are mainly oriented parallel to the longitudinal stalk axis. Astrocytic processes show a clear tendency to encircle the remaining elements of the pineal stalk; i.e., pinealocytes, nerve fibres and blood vessels. Furthermore, glial processes form a cover layer separating the stalk from surrounding anatomical structures.


Expression of neuronal and glial markers in so-called oligodendroglial tumors induced by transplacental administration of ethyl-nitrosourea in the rat.

A series of 18 tumors with histological features of oligodendrogliomas, induced in the rat by means of transplacental ethyl-nitrosourea administration were studied for immunohistochemical demonstration of neuronal (synaptophysin and neurofilament protein) and glial (gliofibrillar acidic protein and vimentin) markers. Most of the tumors showed cells with strong positivity to synaptophysin and to a lesser degree, to neurofilament protein, suggesting the neuronal character of these neoplasms. In 10 tumors, cells with strong positivity to vimentin were found, and in three cases, tumoral cells expressed gliofibrillar acidic protein. The observation that ENU-induced oligodendroglial tumors express neuronal and, to a minor degree, glial markers, suggests their interpretation as primitive neuroectodermal tumors with clear neuronal differentiation.


Stereological study of the synaptic profiles belonging to interneurons in the dorsal lateral geniculate nucleus of the rabbit.

This study is concerned with some characteristics of the interneurons belonging to the dLGN (dorsal Lateral Geniculate Nucleus) of the rabbit. The work deals with the distribution of such cells in the alpha E sector of the nucleus and their F1 and F2 presynaptic contacts. The F1 and the F2 profiles are present in all three of the alpha E zones studied. The F1 profiles are significantly more numerous in the upper zone (57 +/- 2 profiles per 10(4) microns2 of section) and the middle zone (59 +/- 3 profiles per 10(4) microns2 of section) than in the lower one (41 +/- 2 profiles per 10(4) microns2 of section). The F2 profiles are more abundant in the alpha E sector than the F1 ones are, particularly in the lower zone, where F2 profiles (104 +/- 4 profiles per 10(4) microns2 of section) are not only significantly more numerous than F1 profiles but also more abundant than the F2 profiles in the middle zone (84 +/- 3 profiles per 10(4) microns2 of section) and upper zone (88 +/- 2 profiles per 10(4) microns2 of section). These results and their comments reveal diverse density of the element distribution from the dorsal to the ventral part of the alpha E sector as well as the possible relationship or independence from the extranuclear afferent inputs.


Circadian and seasonal cortico-medullary variations in pinealocyte nuclear size. A comparative statistical analysis.

Circadian and seasonal variations were observed in the karyometric index of pinealocytes in the cortical and medullary regions of the distal pineal body. The study involved 70 Wistar rats over a 24-hour interval (0:6, 10:00, 14:00, 18:00, 22:00, 02:00, 06:00 h) during two natural photoluminous periods, i.e. late summer (Long photoperiod) and Winter (Short photoperiod). The results show a difference between the high and low points of both photoperiods. Cortico-medullary differences are found at different times of day during long photoperiod (0:6; 10:00; 14:00 and 18:00 h.) and short photoperiod (14:00; 22:00 and 02:00 h.). The variance analyses between nuclear volume and point-time and between nuclear volume, point-time and location are significative. A high correlation between circadian rhythms and volumetric variations in both layers and photoperiod are found. The results also show significant differences in cortico-medullary karyometric indices between both seasons as well as between the diurnal and nocturnal hours of both photoperiods. It is suggested that the pineal body of the rat is influenced by circadian and seasonal photoperiod and may have groups of cells with different functional characteristics, depending on their location within the gland.


Lack of intimal hyperplasia response in an experimental model of non-endothelial vascular wall damage.

The endothelial and medial layers are generally presumed to play an important role in the appearance and development of intimal hyperplasia. We have carried out a short-, media- and long-term study of the morphological changes taking place in the common iliac artery of rats after surgical removal of the adventitial layer. Our aim has been to assess the likely role played by this layer in the development of intimal hyperplasia. Our results show recurrent periods of cellular desquamation and almost complete absence of hyperplastic response during the first two months. After three months three is a slow process of endothelialization which is completed by the 6th month and persists one year after adventitial resection. Thus, adventitial resection seems to cause instability at the subendothelial bed level, not allowing the junction and embedding of endothelial cells nor the development of intimal hyperplasia. This lack of hyperplasia might also result from the fact that the endothelial desquamation process does not involve cellular rupture, which would prevent mitogenic-factor release. After morphological repair of the endothelium, a slow morphofunctional recovery of the artery takes place.


An autopsy case of tuberous sclerosis. Histological and immunohistochemical study.

We report an autopsy case of tuberous sclerosis. A 19-year-old Japanese man had shown facial adenoma sebaceum, intractable convulsive seizures and severe mental retardation. Gross inspection of the brain showed a cortical tuber from the orbital frontal lobe to the rhinencephalon of the left side and a few subependymal nodules. Histological examination revealed many cortical tubers in the cerebral hemispheres, a few subependymal nodules with calcification and multifocal clusters of heterotopic cells in the white matter (white matter nodules). In these lesions, massive giant cells with abundant eosinophilic cytoplasm and without Nissl substances were found. Although the size and shape of the giant cells were variable, the majority of them were gemistcytic, ovoid or polygonal. Immunohistochemistry was employed in these lesions using antibodies against neurofilament protein (NFP), glial fibrillary acidic protein (GFAP), vimentin (VM) and myelin basic protein (MBP). In the cortical tuber, the majority of the giant cells were positive for both NFP and VM, but a few were positive for GFAP. All of them were negative for MBP. In the subependymal nodule and white matter nodule, the majority of the giant cells were positive for NFP, but a few were positive for VM, and none were positive for either GFAP and MBP. These findings suggest that the majority of the giant cells may be immature cells toward neuronal series and a few may be those toward astroglial series. These findings also indicate that the giant cells in the subependymal nodule and white matter nodule may be more differentiated than those in the cortical tuber. The nature of the giant cells in tuberous sclerosis is discussed.


An in vitro study on the effects of melatonin on the ultrastructure of the hamster parathyroid gland.

Isolated parathyroid glands from adult female golden hamsters were incubated on a black Millipore filter in an incubation vessel containing Ham's F-12 medium, with or without melatonin at final concentration of 10(-5) M for 1 hour. In the parathyroid glands used for in vitro treatments with melatonin, the Golgi complexes associated with a few prosecretory granules and cisternae of the rough endoplasmic reticulum showed a significant decrease, and lipid droplets and lysosomes appeared to be increased compared with those of the control parathyroid glands. These changes are considered to be induced by suppression of the synthesis of parathyroid hormone in parathyroid glands incubated in a vessel containing medium with melatonin.


Sex-specific response of the vasopressin-reacting neurons of the paraventricular nucleus of the rat hypothalamus following chronic administration of met-enkephalin.

Using the peroxidase-antiperoxidase immunocytochemical technique, a morphometric study of the magnocellular neurons of the Paraventricular nucleus of the rat hypothalamus, reactive to specific anti-vasopressin rabbit serum, was made. Following systemic and chronic administration of met-enkephalin the number of immunoreactive neurons was higher, especially in females. Additionally, in the females, it was possible to observe an increase in the immunoreactivity and the presence of well-stained fibres. These findings suggest, especially in females, a blockage in the release of vasopressin, facilitating its immunocytochemical visualization.


Lesion and regeneration in the medial cerebral cortex of lizards.

The cerebral cortex of Squamate reptiles (lizards and snakes) may be regarded as an archicortex or "reptilian hippocampus". In lizards, one cortical area, the medial cortex, may be considered as a true "fascia dentata" on grounds of its anatomy, connectivity and cyto- chemo-architectonics of its main zinc-rich axonal projection. Moreover, its late ontogenesis and postnatal development support this view. In normal conditions, it shows delayed postnatal neurogenesis and growth during the lizard's life span. Remnant neuroblasts in the medial cortical ependyma of adult lizards seasonally proliferate. The late-produced immature neurocytes migrate to the medial cortex cell layer where they differentiate and give off zinc-containing axons directed to the rest of cortical areas. This results in a continuous growth of the medial cortex and its zinc-rich axonal projection. Perhaps the most important characteristic of the lizard medial cortex is that it can regenerate after having been almost completely destroyed. Recent experiments in our laboratory have shown that chemical lesion of its neurons (up to 95%) results in a cascade of events; first, those related with massive neuronal death and axonal-dendritic retraction and, secondly, those related with a triggered neuroblast proliferation and subsequent neo-histogenesis, and the regeneration of an almost new medial cortex that shows itself undistinguishable from a normal undamaged one. This is the only report to our knowledge that an amniote central nervous centre may regenerate by new neuron production and neo-histogenesis. Perhaps the medial cortex of lizards may be used as a model for neuronal regeneration and/or transplant experiments in mammals or even in primates.


Demographic characteristics of a population of people with moderate, severe and profound intellectual disability (mental handicap) over 50 years of age: age structure, IQ and adaptive skills.

Studies characterizing community populations of older people with intellectual disability (mental handicap) have frequently derived data from mental handicap registers. Such large-scale studies permit the establishment of reliable age trends, yet may utilize unreliable information and omit some individuals. Here, a functional characterization of a 50+ years sample with moderate, severe and profound intellectual disability is described, in which an extensive outreach exercise to identify individuals not known to mental handicap service providers ensured that almost 100% of people fulfilling the residence, age and ability criteria were included. Functional level, assessed by the Adaptive Behaviour Scale (ABS), is reported in relation to six factors derived from factor analysis. Overall, the sample was relatively high functioning and generally free of severe problem behaviours. There was no evidence for significant age-related functional decline.


A preliminary analysis of environmental variables affecting the observed biobehavioural states of individuals with profound handicaps.

Recently, various researchers have recommended investigation of biobehavioural states as a worthwhile endeavour toward providing a more valid assessment of students with profound handicaps. To date, the research conducted in this area has largely focused on the biobehavioural state variable in isolation. This pilot study was conducted to examine the relationships between environmental variables and biobehavioural state variables. Six students with profound handicaps were selected as subjects and observed during normal daily school routines. The investigators discovered significant relationships between the students' prior state, position, grouping type of staff cue given, the proximity of the staff and type of activity stimulus provided, and the students' biobehavioural states. A discussion of the results and recommendations for future research are provided.


Cognitive profiles in adolescents with mental retardation.

Cognitive profiles of performance were obtained from a selected group of adolescent subjects with mental retardation (MR) (n = 32; mean age: 15.4 years, S.D. = 3.7) by means of an ad hoc neuropsychological battery. On the basis of each subject's IQ, the experimental sample was divided into three homogeneous subgroups (severely, moderately and mildly retarded) and cognitive performances obtained in the battery tests were compared. Subsequently, in order to clarify the qualitative aspects of MR, the cognitive patterns of subjects with the same IQ and chronological age were examined. Altogether, from a neuropsychological point of view, the results of this study seem to support the hypothesis that MR is a heterogeneous condition of cognitive deficits (some abilities are better preserved than others) and indicate that a set of multiple tests exploring single cognitive functions is needed in order to describe cognitive profiles in MR.


Dexamethasone suppression test and response to antidepressants in depressed mentally handicapped subjects.

Nineteen mentally handicapped subjects who were referred to the service with clinically significant depression were assessed with a view to determining the value of the dexamethasone suppression test (DST) in clinical diagnosis and in predicting response to antidepressant treatment. They were assessed initially and then 3 months after they had been treated with a tricyclic antidepressant. It was found that a significant proportion had an abnormal DST response which reversed after recovery in some but not in others. Non-reversal was more likely to occur in the more severely handicapped patients. It was concluded that DST was of little value as a diagnostic tool for the detection of depression in mentally handicapped subjects.


Chromosome fragility in the Lennox-Gastaut epilepsy syndrome.

Chromosome fragility was sought in a well-defined cohort of patients with Lennox-Gastaut epilepsy syndrome. Twenty-five patients plus 25 age- and sex-matched normal controls had cytogenetic studies performed. All patients were taking sodium valproate, and four were also on hydantoin. Blood cultures from both patients and controls were set up simultaneously in an appropriate medium designed to elicit fragile-sites. Harvesting took place after 96 h by standard techniques. In addition to routine banded analysis, at least 50 cells were scored for chromosome breaks and gaps from each patient and control. Results showed no difference between the patients and the control group in the overall occurrence of fragility or the type of aberration detected. No fragile-X syndrome was detected. This study found no effect due to sodium valproate on the occurrence of chromosome aberrations.


Mental retardation and WAIS-R scatter analysis.

In an earlier article, the psychometric properties of Wechsler Adult Intelligence Scale-Revised (WAIS-R) subtest difference scores were explored using a sample with IQ < 80. Data were offered which allowed the practitioner to determine whether the difference between two subtests was statistically reliable. This article represents an extension of the earlier work. It presents a set of reliability estimates for the difference between a single WAIS-R subtest and the mean of all subtests, and permits the clinician to determine whether the difference obtained by a particular examinee is statistically significant.


Autism in Down's syndrome: presentation and diagnosis.

Although autism is said to occur rarely with Down's syndrome, it may be more common in those persons with Down's syndrome who also show superimposed behavioural problems. In this brief report, the authors explore this possibility. They describe three patients with Down's syndrome who were referred for behavioural reasons and were found to have coexisting autism. They propose that a systematic study of the association of these two conditions may have implications on research and clinical practice.


Kallmann's syndrome and mental handicap.

A case of Kallmann's syndrome is reported in a 62-year-old mentally handicapped man with clinical and laboratory characteristics of the syndrome. The literature is reviewed and the possible associations with mental handicap explored.


Growth hormone therapy in Turner's syndrome: an update on final height. Genentech National Cooperative Study Group.

The Genentech National Cooperative Study of growth hormone (GH) therapy in Turner's syndrome was initiated in 1983; 70 girls with Turner's syndrome were randomly assigned to observation or to treatment with GH alone, oxandrolone alone, or a combination of GH plus oxandrolone for a period of 12-24 months. After completion of this phase, patients receiving GH alone were continued on GH, while all other patients received the combination of GH plus oxandrolone. Data are currently available on the 62 girls who were treated for a minimum of 3-6 years. When compared with the height velocities anticipated for girls of comparable ages with untreated Turner's syndrome, both GH alone and a combination of GH plus oxandrolone resulted in an increase in height velocity, which was most prominent during the first 2 years of treatment and was sustained for at least 6 years. Although GH therapy is continuing at present in half of the patients, 14 of 17 girls (82%) receiving GH alone and 42 of 45 girls (93%) receiving combination therapy have exceeded their projected adult heights. For the 30 girls who have stopped therapy, the current mean height is 151.9 cm, compared with their original mean projected adult height of 143.8 cm. These results demonstrate that GH therapy can result in short-term (3-6 years) acceleration of growth, as well as in improved adult height.


Effects of chronic growth hormone excess on cardiac contractility and myosin phenotype in the rat.

The effects of chronic growth hormone (GH) hypersecretion on intrinsic contractile properties of the myocardium were studied in rats bearing a GH-secreting tumour. Body weight and heart weight increased, but no true cardiac hypertrophy was observed. The maximum active force of left ventricular papillary muscle was increased, and the maximum shortening velocity of the unloaded muscle was unaltered. This was despite a marked shift of the myosin isoforms towards the low ATPase activity V3 form, which was associated with a similar shift of myosin mRNAs. Total ATPase activity, measured on frozen sections, was unaltered suggesting, together with the results of the mechanical study, an increase in the number of active enzymatic sites. Studies performed on skinned fibres confirmed the increased myocardial contractility, thus suggesting that myocardial adaptation to chronic GH excess occurred, at least in part, at the level of the myofibrillar contractile apparatus.


Effects of growth hormone on fat mass and fat distribution.

GH has profound effects on the amount and distribution of adipose tissue. GHD in both children and adults is accompanied by an increased amount of adipose tissue and by the abdominal predominance of adipose tissue. In contrast, treatment with GH reduces adipose tissue, and redistributes adipose tissue from abdominal to peripheral depots.


Effects of growth hormone on low-density lipoprotein metabolism.

GH appears to play an important role in mediating the increase in hepatic LDL receptor expression that occurs in response to pharmacological oestrogen treatment. Furthermore, in normal individuals there is evidence of an increased number of hepatic LDL receptors in response to GH, resulting in an accelerated elimination rate of the LDL particle and a subsequent lowering of LDL cholesterol. Further studies on lipoprotein metabolism in patients with GH deficiency, and also in patients with hypercholesterolaemia, would therefore be of interest.


Genetic analysis of recombination in prokaryotes.

Bacteria provide a simple system for the genetic analysis of homologous recombination. More than twenty genes have been identified in Escherichia coli. The enzymatic activities associated with the products of many of these genes have been revealed by studies with model DNA substrates. It is now possible to pair homologous molecules in vitro and process these through defined intermediates into mature recombinants of the types predicted by genetic crosses.


Interaction between bacteriophage lambda and its Escherichia coli host.

Bacteriophage lambda relies to a large extent on processes requiring interactions between viral- and host-encoded proteins for its lytic growth, establishment of lysogeny, and release from the prophage state. Both biochemical and genetic studies of these interactions have yielded new information about important host and lambda functions. In particular, mutations in Escherichia coli that compromise lambda DNA replication, genome packaging, transcription elongation, and site-specific recombination have led to the identification of bacterial genes whose products are chaperones, transcription factors, or DNA-binding proteins.


Heat-shock proteins and stress tolerance in microorganisms.

Heat-shock proteins help microorganisms cope with the toxic effects of a wide variety of stresses. Some help the organism grow under moderately stressful conditions, others help it to survive more extreme conditions. Surprisingly, the relative importance of individual proteins differs between organisms.


Flagella in prokaryotes and lower eukaryotes.

During the past year, significant advances have been made in the understanding of both prokaryotic and eukaryotic flagella. About 50 genes are dedicated to the assembly and operation of bacterial flagella. Recent discoveries have advanced our understanding of how these genes are regulated and how their products assemble into a functional, rotating organelle. The dynein arms of eukaryotic flagella are now also better understood. Several genes that are found in the mechanochemical macroassemblies have been cloned, and other loci have been identified, suggesting that there is even greater complexity than first expected.


Movement of macromolecules between the cytoplasm and the nucleus in yeast.

Since the first description of signals for nuclear protein localization, studies with yeast have played an important role in our understanding of nuclear protein import. Very recent experiments suggest that new insights into the poorly understood process of RNA export will also emerge from analyses of yeast. Recent advances have facilitated our understanding of protein and RNA exchange between the nucleus and cytoplasm.


What is the minimum number of dedicated functions required for a basic cell cycle?

The genome of Escherichia coli has a coding capacity for about 4500 proteins but only a small number of these appear to be specific for the periodic events (initiation of DNA replication, chromosome partitioning and cell division) that punctuate the cell-duplication cycle: furthermore, many of these cell cycle dedicated functions are dispensible under certain conditions, although their presence undoubtedly increases the fitness of the organism to survive in a competitive environment. A simplified but effective cell replication cycle can probably operate with only a few cycle-dedicated proteins, in addition to those required for cell growth itself.


Sporulation in prokaryotes and lower eukaryotes.

During the past year, highlights in sporulation research include the demonstration that phosphorylation of SpoOA is a critical factor in Bacillus subtilis development; the identification of C alpha proteins, adenylyl cyclase and protein kinase A genes in Dictyostelium; proof that an endogenous antisense RNA regulates gene expression in Dictyostelium; and characterization of a second type of differentiated cell in Myxococcus.


Control, confront or collude: how family and society respond to excessive drinking.

Research on excessive drinking in the family context has revealed the range of ways of coping used by close relatives. Case material from ongoing research in England and Mexico is used to illustrate this point. This research is also revealing the ways in which the family, close and extended, often fail to support the coping actions of close relatives. The analogy is drawn between coping with excessive drinking in the family and coping in the work setting. In the latter context explicit alcohol policies have been developed. These often recommend combining confrontative and supportive coping. It may be difficult for relatives, in the family setting, to adopt such a policy without support. The forms of coping identified in family research and in work policies correspond to basic and universal dimensions of interpersonal behaviour: dominance-submissiveness and friendliness-hostility. These forms of responding to excessive drinking may be identified beyond the microsocial systems of family and workplace. They are evident, also, in the responses of community agents such as police and social workers, and at the level of local and national government.


Severity of dependence and route of administration of heroin, cocaine and amphetamines.

This study investigates severity of dependence upon heroin, cocaine and amphetamines in a group of 200 heroin users, 75% of whom were not in contact with any treatment agency. For drug takers who were current users of more than one drug, heroin produced more severe dependence than either cocaine or amphetamine and many users of these stimulant drugs reported having experienced no problems of dependence. Severity of dependence was influenced by route of administration as well as type of drug. Heroin taken by injection was associated with more severe dependence than smoked heroin. For cocaine, injection and smoking were associated with equivalent dependence ratings, and both of these routes were associated with more severe dependence than cocaine used intranasally. For amphetamine, there were no differences in severity of dependence ratings for injection, intranasal or oral use. Severity of dependence was correlated with dose and duration of drug use; it was also associated with previous attendance at a drug treatment agency, though dependence problems were also common among heroin users who had never received treatment. Implications of these findings are discussed.


Bromocriptine and cocaine cue reactivity in cocaine-dependent patients.

Based on previous reports that bromocriptine, a postsynaptic dopamine agonist, reduced cocaine craving and prevented relapse in cocaine-dependent subjects, effects of the drug were evaluated in 20 cocaine-dependent males in an inpatient drug rehabilitation programme. The subjective and physiologic effects of exposure to both cocaine-associated and neutral stimuli, presented using videotapes, were measured at one-week intervals. Between laboratory sessions subjects received either bromocriptine (1.25 mg bid) or a matched placebo, administered in double-blind fashion. Compared with the neutral videotape, the cocaine videotape elicited both a greater desire to use cocaine and more symptoms associated with cocaine self-administration. These results support an appetitive conditioning model of cocaine effects. Bromocriptine, however, had no effect on the cocaine-cue-associated reactivity, which declined over the 1-week interval in both treatment groups. Methodological differences among studies that have examined the effects of bromocriptine in cocaine-dependent subjects may explain the variable findings observed.


HIV risk of transmission behaviour amongst HIV-infected prisoners and its correlates.

Thirty-eight from a total of 42 known HIV-positive prisoners in the Irish prison system voluntarily cooperated in a survey of psychological attitudes, knowledge of risk behaviour, intentions with respect to future risk behaviour, and actual past risk behaviour. Of this group, 65% reported that they had put others at risk of HIV, since they became aware of their own HIV+ status. Only 16% stated that they would definitely not share their drug-taking equipment in the future and 32% that they would always use a condom in sexual intercourse. In general, psychological and biographical variables were not strongly related to whether or not the respondents had put others at risk of HIV. Nor were there any significant differences in knowledge of at risk behaviour between those who had and those who had not put others at risk. However, there was some evidence for considerable independence between risk-taking behaviour in the sexual and in the drug-taking domains, in that risk-taking in one area was not highly predictive of risk-taking in the other.


Adolescent drug sellers: trends, characteristics and profiles.

This study examines drug selling among representative samples of high school students in Ontario. It involves three approaches, (i) examining the trend in drug selling between 1983 and 1989, (ii) assessing differences between sellers and non-sellers on demographic characteristics, levels of alcohol and drug use, and problems, and (iii) drawing detailed profiles of drug seller types. Drug selling declined considerably between 1983 and 1989. Sellers were more likely to be males and to use alcohol and drugs more often than non-sellers. Sellers also had more alcohol and drug problems and engaged in more delinquent acts. Drug sellers who sold cannabis only were less frequent users of drugs, less likely to have drug problems, and were also delinquent.


Unemployment and use of drug and alcohol among young people: a longitudinal study in the general population.

A prospective study of a representative sample of nearly 2000 young people aged 17-20 years was started in 1985. It was followed up twice, in 1987 and in 1989. The Central Bureau of Statistics in Norway was responsible for the data collection. Sixty-five per cent of the stratified sample (1985) participated in all the three surveys. The aim of this paper has been to explore the relationship between unemployment and the use of drugs and alcohol. The results show that unemployment does not appear to influence the consumption of alcohol. In a high consumption group, unemployment seems to lead to a decrease in alcohol consumption, though there was a clear tendency to increase use of cannabis. The results seem to indicate that there was no increase in use of alcohol or drugs in response to stress as a result of unemployment, though unemployment may lead to a stronger identification with or joining marginalized or deviant subcultures which in turn leads to an increased use of cannabis.


Smoking: a special need?

The smoking behaviour of 665 children aged 12-15 years with special educational needs was compared with that of a control group of 842 children in mainstream education. Each child was interviewed using a structured questionnaire and reported smoking behaviour was validated against scores on a carbon monoxide monitor. We identified as the most at risk group children with emotional and behavioural disorders. They had the highest smoking rates and were the heaviest smokers. In contrast, children with learning difficulties had slightly lower smoking rates than those of the control. There were significant associations between the children's smoking behaviour and the smoking behaviour of siblings and 'other adults' in the household, belonging to single parent families, low self-esteem and large friendship groups. The reported smoking rates of the families of both groups of special needs children was found to be considerably higher than that in the control group or in the general population.


Dying to be equal: women, alcohol, and cardiovascular disease.

This data note explores the relationship of gender, alcohol consumption and premature death from cardiovascular disease (MCVD). Data on the 8164 deaths attributed to MCVD from the National Mortality Followback Study (NMFS) were analyzed controlling for gender and consumption. Women who are heavy drinkers die young at a rate equal to that of men who drink heavily. In light of this, we recommend that future research and preventive efforts in this area include females as subjects and alcohol as a major risk factor.


Parent educational attainment and adolescent cigarette smoking.

In a longitudinal design, this study examined psychosocial mediators of the effects of parental educational attainment on adolescent smoking acquisition and also examined whether smoking transition had different antecedents among adolescents from families of varying educational backgrounds. Parents' low educational attainment acted as a moderate to strong risk factor for the initial onset of smoking among middle school girls. Some of this effect was mediated by the higher smoking prevalence among both parents and friends of these adolescent girls, as well as by their lowered expectations for academic success. However, these variables only partially mediated the effect of parent education. There were few indications of differential antecedents of smoking acquisition among adolescents from less and more highly educated families. Implications for public health antismoking campaigns are discussed.


Gender differences in depression and anxiety among alcoholics.

Recent research suggests that psychopathology, in particular depression and anxiety, differentially affects the substance abuse treatment response of men and women. This study explores the relationship between global psychopathology, depression, anxiety, and alcoholism treatment outcome. These variables were assessed in a sample of 507 (373 men; 134 women) substance abuse clients at intake and at a 6-month follow-up. With the exception of alcohol dependence, there were significant differences in the levels of alcohol problems, depression, anxiety, and global psychopathology for men and women at both intake and follow-up. For the whole sample and for men, initial levels of alcohol problems and alcohol dependence were the best predictors of alcohol problems at follow-up. For women, the initial levels of alcohol dependence and a global measure of psychological functioning were predictive of outcome at follow-up. These findings are compared with past research, and suggestions for further investigation are proposed.


Gender differences in the manifestations of problem drinking in a community sample.

A probability sample of 6,250 respondents in Ontario and Quebec was surveyed by telephone to determine the prevalence of problem drinking and its relationship to other psychiatric symptoms. The survey instrument included a psychiatric symptom inventory and questions relating to problem drinking that were adapted from the Diagnostic Interview Schedule. This survey found a rate of 7.1% for problem drinking which parallels other recent community surveys. Rates for men are approximately six times greater than for women. A significant proportion (18.5%) of problem drinkers have concurrent psychiatric impairment. The extent and nature of concurrent psychiatric impairment and disability differs significantly for men and women.


Duration of bulimia nervosa and symptom progression: a retrospective analysis of treatment-seeking bulimics.

Severity of bulimia nervosa upon presentation for treatment may be influenced by duration and age of onset of bulimic behaviors. This hypothesis was investigated in a retrospective study by correlating duration of bulimia and age of onset with sets of variables measuring the primary symptoms and other psychopathology associated with bulimia nervosa. The experimental design was cross-sectional. The sample included 153 women who had been diagnosed with bulimia nervosa. Canonical correlations indicated that younger age of onset and longer duration were associated with more severe bulimic symptoms and increased body image distortion. Anorexic symptoms were reduced over time, however, and weight gain (at a rate of about 0.54 Kg [1.2 lbs] per year) was correlated with duration of bulimic behaviors. Also, older age of onset and longer duration were associated with increasing social introversion. These findings were interpreted as supportive of the hypothesis that younger age of onset and longer duration of bulimic behaviors are associated with more severe bulimia and general psychopathology. Though limited by the retrospective nature of the study, these results substantiate the need for longitudinal investigations of bulimia nervosa.


Processes of change in smoking cessation: a cross-validation study in cardiac patients.

The processes of change associated with smoking cessation were examined for 213 smokers and recent exsmokers who were scheduled for cardiac catheterization and compared to the processes reported by a sample of 180 nonmedical smokers and exsmokers. Subjects were classified into one of three stages of change depending on their readiness to quit smoking: precontemplation, contemplation, and action. The cardiac sample employed the processes of change more frequently than the nonmedical sample in all stages, but the functional relationship between the stages and processes of change was generally similar for the two groups. The hierarchical structure of the processes of change also was similar for both groups. Differences between the two samples in the use of the processes of change are discussed. These results are the first to support the validity of the stages and processes-of-change model of smoking cessation in a population experiencing severe illness.


Utility and evaluation of biochemical markers of alcohol consumption.

Biochemical markers of alcohol consumption have a variety of clinical and research applications. Currently available markers such as the serum gamma-glutamyl transpeptidase (GGT), serum transaminases, and the mean corpuscular volume (MCV) lack sufficient sensitivity and specificity to be used for screening of alcoholism in ambulatory patients. However, these tests can be helpful in corroborating a clinical suspicion of alcoholism. A number of special laboratory markers of alcoholism recently have been developed which may have increased diagnostic accuracy. Promising potential markers include serum carbohydrate-deficient transferrin (CDT), red blood cell acetaldehyde, and acetaldehyde adducts. The application of reliable and practical markers of alcohol consumption could lead to significant improvements in the treatment of alcoholism and in the assessment of clinical trials.


A randomized double-blind study of neuroelectric therapy in opiate and cocaine detoxification.

Prior research on the use of transcranial neuroelectric stimulation suggested that the application of low-amperage, low-frequency alternating current via surface electrodes placed in the mastoid region could relieve the physiological signs and subjective symptoms of withdrawal and craving during opiate detoxification. These effects were reported without gradual tapering of the opiate or the addition of other medications. To test the efficacy of one particular form of neuroelectric therapy (NET), a double-blind, randomized, placebo-controlled study was conducted comparing active NET and placebo NET in the treatment of withdrawal and stabilization of 18 opiate-dependent and 25 cocaine-dependent subjects. Scores on scales for measuring substance withdrawal and craving for each abused substance, as well as the multiple dimensions of mood, were compared for degree of difference across the 10 days of treatment. There was an overall completion rate of 88%, with both cocaine and opiate groups reporting a comfortable detoxification and substantial improvement over the course of a 12-day hospitalization. There was no significant difference between the active or placebo groups, suggesting that placebo was as effective as active NET in reducing drug withdrawal or craving during cocaine and opiate detoxification. However, all placebo patients received 0.2 mA of current, which may have provided a degree of active current. Suggestions are offered for future research.


Nagging and other drinking control efforts of spouses of uncooperative alcohol abusers: assessment and modification.

This article presents a conception of spouse drinking control and an approach to assessment and modification to reduce the customary drinking control efforts of spouses of alcohol abusers unmotivated to enter treatment. Modification of the nonalcoholic spouse's customary drinking control is offered as an important early step in helping to prepare him or her to become a positive rehabilitative influence. Based on its use in unilateral family therapy with 68 spouses of uncooperative alcohol abusers, procedural guidelines, criteria for use, and two case examples from a crossover experimental dyad are described. Also presented are clinical results illustrating the success of the program, benefits and conditions relating to its use, and areas of possible application.


Patterns and predictors of simultaneous and concurrent use of alcohol, tobacco, marijuana, and hallucinogens in first-year college students.

Polydrug use produces important health and safety risks. Little research has examined whether multiple drugs are used simultaneously (at the same time or in close temporal sequence). Instead, researchers have assessed concurrent polydrug use (the use of multiple drugs within a given time period such as years or months). The research here examined patterns and predictors of both simultaneous and concurrent polydrug use in 575 first-year college students. Both concurrent and simultaneous polydrug use were common for alcohol, tobacco, and marijuana. The percentage of concurrent polydrug users who were also simultaneous polydrug users ranged from 82% to 93% across subgroups defined by gender and the use of a single drug. Male gender, high levels of sensation seeking, and frequent alcohol use predicted single-drug versus polydrug use status as well as simultaneous polydrug use. Patterns and predictors of simultaneous and concurrent polydrug use should be addressed in prevention research and preventative interventions.


Brain casein kinase 2: affinity purification procedure using immobilized polyethylenimine.

A simplified procedure for casein kinase 2 purification from bovine brain is described. The purification procedure consists of two affinity chromatography steps, using heparin and polyethylenimine immobilized on a synthetic matrix (Toyopearl 650M). The adsorption and elution conditions for each column were optimized, resulting in a simple elution protocol for each column. A stable, highly purified casein kinase 2 preparation was obtained in 4 h using this procedure. Polyethylenimine was shown to stimulate the casein kinase 2 activity using exogeneous substrates (casein, calmodulin, MAP2, and tau) but not the enzyme's autophosphorylation activity. The polyethylenimine stimulation could be overcome by applying a mass excess of the casein kinase 2 inhibitor, heparin.


Purification of recombinant chimeric B72.3 Fab' and F(ab')2 using streptococcal protein G.

Streptococcal protein G has been used extensively for the purification of antibodies using the interaction of the Fc region with protein G. Many antibodies also interact with protein G through a low-affinity binding site for the Fab region. The exploitation of this low-affinity interaction for the purification of Fab' fragments is described here. Chimeric mouse-human B72.3 Fab' and F(ab')2 fragments were expressed by CHO cells and purified from CHO cell supernatant using protein G-Sepharose. Since chimeric B72.3 Fab' bound weakly to the protein G-Sepharose it could be separated from F(ab')2 and eluted with a pH 7 wash whereas B72.3 F(ab')2 required elution at pH 2. Both Fab' and F(ab')2 were recovered with full immunoreactivity and could be further purified using gel-filtration chromatography to greater than 99% purity. This method allows the simple purification of directly expressed Fab' or F(ab')2 fragments from CHO cell supernatant.


Expression in Escherichia coli: purification and properties of the recombinant human general transcription factor rTFIIB.

The human class II transcription factor TFIIB (rTFIIB) was overexpressed in Escherichia coli using a T7 RNA polymerase expression system and further purified to apparent homogeneity. The purified rTFIIB is identical to the endogenous factor according to the following criteria: molecular weight, microsequencing and mass spectra studies, ability to recognize the stable preinitiation complex formed between TFIID and the adenovirus 2 major late TATA box as demonstrated by gel shift as well as by DNase I footprinting assays, and transcription activity.


High-level expression and simplified purification of recombinant ricin A chain.

Ricin toxin is a glycoprotein which catalytically inactivates eukaryotic ribosomes by depurination of a single adenosine residue from the 28S ribosomal RNA. The enzymatic activity is present in the A chain of the toxin molecule, whereas the B chain contains two binding sites for galactose. Since it is highly potent in inhibiting protein synthesis, the A chain is used to prepare cytotoxic conjugates effective against tumor cells. Such chimeric proteins are highly selective and have a wide range of clinical applications. Extensive preclinical studies on these conjugates require large amounts of purified A chain. Native ricin A chain is heterogeneous, since plants produce a number of isoforms of ricin toxin. Purified, native preparations often contain two types of ricin A chain which differ in the extent of glycosylation. By cloning and expressing the gene of A chain, one could obtain homogeneous toxin molecules devoid of carbohydrates. In addition, structural changes in the toxin polypeptide could be introduced by in vitro mutagenesis, which can improve the pharmacological properties and antitumor activity. Earlier methods of expression strategies using Escherichia coli have yielded only moderate levels of expression. In the present study, the coding region of ricin A chain was cloned into pET3b, a high-level expression vector under the control of the T7 promoter. Recombinant ricin A chain produced by this construct has an additional 14 amino acid residues at the NH2 terminus. Subsequently, a NdeI site was created at the 5' end of the gene by oligonucleotide-directed mutagenesis. The modified fragment was then introduced into pET3b vector to produce toxin polypeptide identical to the native sequence.(ABSTRACT TRUNCATED AT 250 WORDS)


Bacterial expression, purification, and in vitro N-myristoylation of HIV-1 p17gag.

The coding region of the N-terminal 17-kDa portion of HIV-1 Pr55gag (p17gag) was cloned into the pET-3c expression vector and was used to overexpress HIV-1 p17gag in Escherichia coli. Induction of the transformed bacteria caused the accumulation of a 17-kDa polypeptide in the soluble cell fraction which was released by sonication in hypotonic nondetergent buffer. The 17-kDa polypeptide was purified by ammonium sulfate precipitation and successive chromatography on G-75 Sephadex, DEAE-Sephacel, and S-Sephadex. The final product was purified 12-fold with about a 16% recovery from the original soluble cell lysate and was judged to be 97+% pure by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Western blotting with two different antibodies confirmed the identify of the purified 17-kDa polypeptide as authentic p17gag. In the presence of myristoyl-CoA and bovine brain N-myristoyl-transferase, p17gag was quantitatively N-myristoylated in vitro with a pseudo-first-order rate constant of 4.7 +/- 1.0 x 10(-3) min-1, but with only about 3% of the catalytic efficiency of N-myristoylation of a 16-residue peptide homologous to the N-terminus of p17gag. The myristate group in the N-myristoylated p17gag was stable to treatment with detergent and hydroxylamine consistent with a covalent N-acyl-amide linkage. The N-myristoylglycyl linkage was confirmed by partial acid hydrolysis and identification of the p-nitrobenzylazlactone derivative of the resulting N-myristoylglycine by high-performance liquid chromatography.


Rapid screening of a large number of immobilized textile dyes for the purification of proteins: use of penicillin-binding protein 4 of Escherichia coli as a model enzyme.

A rapid method for screening the affinity of proteins to dye-modified resins is described. Performing the binding and elution of the protein extracts in a batch-wise manner and eluting the bound proteins with SDS-PAGE denaturation buffer speed up the screening process and allow the analysis of large collections of dyes. Penicillin-binding protein 4 of Escherichia coli was used as a model enzyme to determine the influences of pH, metal ions, and ionic strength (0 to 500 mM NaCl) on its binding behavior using a collection of 98 dye-affinity resins.


Copurification of RNA polymerase I and the glucocorticoid-regulated transcription factor IC.

A simple and rapid method to copurify RNA polymerase I and the glucocorticoid-regulated transcription factor, TFIC, is described. This protocol results in 1262-fold purification and 15% total recovery of the enzyme and factors needed to support faithful transcription in vitro from cloned mouse rRNA gene (rDNA). Using this method, proteins involved in rDNA transcription were purified from exponentially growing lymphosarcoma P1798 cells as well as cells treated with 0.1 microM dexamethasone. A combination of transcription and reconstitution assays using G-free cassette-containing constructs and polyacrylamide gel electrophoretic analysis upon silver staining were used to detect TFIC activity as well as the characteristic TFIC polypeptides in control and dexamethasone-treated cell extracts. Treatment of P1798 cells with 0.1 microM dexamethasone for 24 h results in an over 95% reduction of TFIC activity, but no significant differences in the amount of TFIC polypeptides in the final product purified from control and glucocorticoid-treated cells could be detected. Our data indicate that glucocorticoid regulation of transcription of rDNA is mediated via post-translational modulation of the activity of TFIC.


Tyrosine-ester sulfotransferase from rat liver: bacterial expression and identification.

A nucleotide sequence that had been proposed for, but not identified as, rat liver aryl sulfotransferase (EC 2.8.2.1) was prepared in an appropriate vector and transformed into Escherichia coli. The protein, expressed in large amounts, was not aryl sulfotransferase (EC 2.8.2.1) but rather tyrosine-ester sulfotransferase (EC 2.8.2.9), a sulfotransferase also active with phenols but having a much wider substrate range that includes hydroxylamines and esters of tyrosine. The recombinant tyrosine-ester sulfotransferase was identified by its unique substrate spectrum, by comparison with three peptides that were sequenced from homogeneous tyrosine-ester sulfotransferase isolated directly from rat liver, and by the specificity of antibody raised to the rat liver enzyme. Two isoforms were obtained, each of which was difficult to solubilize upon sonication of E. coli. Both forms were solubilized with a solution of polyols (glycerol and sucrose) and subsequently purified to homogeneity.


Biotin derivatives of endothelin: utilization for affinity purification of endothelin receptor.

Three different types of biotinylated endothelin 1 (ET-1) derivatives, [Cys1]-biotinylated ET-1, [Lys9]-biotinylated ET-1, and [Cys1][Lys9]-dibiotinylated ET-1, were obtained when the biotinylation reaction was carried out with sulfosuccinimidyl-6-(biotinamido)hexanoate in an aqueous solvent. The binding of [Lys9]-biotinylated ET-1 to the ET receptor was as efficient as that of natural ET-1, whereas the binding of either [Cys1]-biotinylated ET-1 or [Cys1][Lys9]-dibiotinylated ET-1 was significantly reduced. When ET-1 was reacted with succinimidyl-6-(biotinamido)hexanoate in an organic solvent, ET-1 was exclusively modified at lysine 9. The ET receptor was then isolated from human placenta by affinity chromatography with [Lys9]-biotinylated ET-1 and avidin-agarose. The purified ET receptor was active in ET binding and was resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis into two polypeptides with apparent molecular masses of 45 and 35 kDa. The NH2-terminal amino acid sequence indicated that the two polypeptides were from an identical subtype of the ET receptor (ETB, the ligand-nonselective type). A signal peptide from Met1 to Gly26 was missing from the 45-kDa ETB, whereas 64 amino acids at the NH2 terminus were missing from the 35-kDa ETB due to proteolytic cleavage which occurred between Arg64 and Ser65. Indeed, incubation of purified ETB with endopeptidase Arg-C resulted in degradation of the 45-kDa ETB, giving rise to the 35-kDa species by a specific cleavage at Arg64. The 35-kDa ETB was active in binding to ET-1, indicating that the NH2-terminal 64-amino-acid residues are not essential for ligand binding.(ABSTRACT TRUNCATED AT 250 WORDS)


High-level production and purification of Escherichia coli N-acetylneuraminic acid aldolase (EC 4.1.3.3).

The Escherichia coli gene which encodes N-acetylneuraminic acid aldolase was isolated by the polymerase chain reaction, cloned into the inducible expression vector pTTQ18, and overexpressed in E. coli. The high yield of aldolase was achieved through both optimum growth of cells and efficient expression of the aldolase gene (20-30% soluble cellular protein). The recombinant enzyme was purified to homogeneity with an activity of 1.2-2.2 U/mg, which compared favorably with that of commercial preparations of E. coli aldolase (1.1 U/mg) and Clostridium perfringens aldolase (0.4 U/mg). The cloning strategy, fermentation conditions, purification protocol, and activity assay are described.


Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis.

To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis. Non-blind randomised controlled trial. University hospital; tertiary clinical care. 22 HIV positive patients with oral candidiasis. Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion). Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin. 11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose. Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin.


Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture.

To evaluate the contribution of specific nutritional deficiencies (as indicated by zinc; vitamin A, C, and E; albumin; and haemoglobin concentrations) to the risk of pressure sores. Observational cohort study. St James's University Hospital, Leeds. 21 elderly patients presenting consecutively to the orthopaedic unit with femoral neck fracture. Full thickness epidermal break over a pressure bearing surface. 10 patients (48%) developed a pressure sore during their hospital stay. Indices of zinc status and concentrations of albumin, haemoglobin, and vitamins A and E were similar in patients who developed a pressure sore and those who did not. Mean leucocyte vitamin C concentration, however, was 6.3 (SD 2.2) micrograms/10(8) cells in patients who developed a pressure sore as compared with 12.8 (4.6) micrograms/10(8) cells in patients who did not. Low concentrations of leucocyte vitamin C appear to be associated with subsequent development of pressure sores in elderly patients with femoral neck fractures.


Comparison of Yuzpe regimen, danazol, and mifepristone (RU486) in oral postcoital contraception.

To compare the effectiveness and acceptability of three regimens of postcoital contraception. Randomised group comparison of ethinyloestradiol 100 micrograms plus levonorgestrel 500 micrograms repeated after 12 hours (Yuzpe method); danazol 600 mg repeated after 12 hours; and mifepristone 600 mg single dose. Community family planning clinic. 616 consecutive women with regular cycles aged 16 to 45 years. Number of pregnancies, incidence of side effects, and timing of next period. The raw pregnancy rates (with 95% confidence intervals) for the Yuzpe, danazol, and mifepristone groups were 2.62% (0.86% to 6.00%), 4.66% (2.15% to 8.67%), and 0% (0% to 1.87%) respectively. Overall, these rates differed significantly (chi 2 = 8.988, df = 2; p = 0.011). The differences between the mifepristone and Yuzpe groups and between the mifepristone and danazol groups were also significant. Side effects were more common and more severe in the Yuzpe group (133 women (70%)) than in either the danazol group (58 (30%)) or the mifepristone group (72 (37%)). The Yuzpe regimen tended to induce bleeding early but mifepristone prolonged the cycle. Three women bled more than seven days late in the Yuzpe group compared with 49 in the mifepristone group. Mifepristone was effective in reducing expected pregnancy rates and the Yuzpe method also had a clinical effect. Danazol had little or no effect. A further multicentre trial is needed.


Demand incidence and episode rates of ophthalmic disease in a defined urban population.

To estimate demand incidence and episode rates of ophthalmic disease in a defined urban population over one year. Study of patients presenting with eye problems to general practice and eye casualty department. General practice and ophthalmic services in west Nottingham. 36,018 people from the combined practice lists of 17 Nottingham general practitioners. Ophthalmic disorder, age and sex of patient, and where presented. 587 consultations were recorded for ophthalmic problems, 1771 with general practitioners and 816 with eye casualty. Most consultations to general practice were by females (1066 (60%)), whereas men aged 15-44 accounted for most work in eye casualty. These men commonly presented with trauma. Infective conjunctivitis, the commonest condition, had an episode rate of 13.5/1000 population/year. Demand incidence for cataracts was 1.9/1000 population/year. Demand incidence for chronic conditions increased with age. As the average age of the population increases demand for ophthalmic services will rise. Planning and provision of resources to meet this increased demand should be considered now.


Juniors' hours: is the end in sight?

The question of how to reduce junior doctors' hours has taxed the government and hospital managers for nearly two decades. Now regional task forces are being asked to get them down to a maximum of 83 a week by 1 April next year. From a comparison of the way in which two different task forces (Northern and North West Thames) have responded to the challenge it emerges that most units will probably meet the 83 hour deadline by making simple rationalisations. Meeting the next deadline--of a 72 hour maximum by December 1996--will, however, require radical restructuring of working patterns.


Are elderly people living alone an at risk group?

To test the hypothesis that elderly people living alone are an at risk group with a high level of morbidity that makes high demands on health and social services. Secondary analysis of data from a community survey of 239 people aged 75 and over, identified from general practitioners' age-sex registers. Nine practices in the London boroughs of Brent and Islington. Scores on the mini-mental state examination; stated satisfaction with life; assessment of mobility; numbers of diagnoses of major physical problems; numbers of prescribed drugs taken; urinary incontinence; alcohol consumption; contacts with general practitioners and hospital outpatient and inpatient services; contact with community health and social services. There were significantly more women among those living alone (93/120 (78%) v 63/119 (53%); p < 0.0005) and the median age of elderly people living alone was higher (81 v 80; p < 0.04). Those living alone and those living with others showed no significant differences in measures of cognitive impairment, numbers of major physical diagnoses, impaired mobility, or use of general practitioner or hospital services. Stated satisfaction with life was somewhat higher in those living alone. Elderly people living alone were significantly more likely to have contact with chiropody, home help, and meals on wheels services and less likely to have someone they could contact in an emergency or at night. Living alone increased the likelihood of contact with one or more community health professionals (district nurses, health visitors, or chiropodists) considered as a group and also increased the likelihood of contact with social services as a whole. There was a tendency for more of those living alone than those living with others to have home visits from their general practitioners, but there were no significant differences in contact with hospital services between the two groups. Elderly people living alone do not have an excess of morbidity compared with those living with others and do not seem to be an at risk group requiring specifically targeted assessments. More help is needed to provide elderly people living alone with a point of contact in case of emergency.


Introduction of a partial shift system for house officers in a teaching hospital.

(1) To introduce a partial shift system to reduce the hours of work of preregistration house surgeons to an average of 64 a week to comply with the New Deal for junior doctors; (2) to test linking the partial shift concept to an existing structure of "on call" firms. Formal assessment after three months of a pilot partial shift system for eight house surgeons on three firms instituted on 1 November 1991, followed by questionnaire and interview evaluation at three and six months of a revised system implemented on 1 February 1992. Department of general surgery at St Bartholomew's Hospital, London. 24 house surgeons attached to three surgical firms. In eight weeks each house surgeon worked one week (five shifts) of night duty, one week of "cover" (afternoon and evening) duty, and six weeks of normal daytime hours. Each weekday a house surgeon from the firm on call worked an extended daytime on call shift until 10 pm. Weekend duties were split between two house surgeons from the firm on call. A computer generated graphical display of the rota was used to facilitate leave planning. Average working hours were reduced to below 64 per week, including prospective cover, without detriment to patient care and educational standards. Within the shift system individual house surgeons could be on call with their own firm by day and at weekends. Opinions were equally divided among junior staff as to their preference for either on call or partial shift systems. The principles of this partial shift system are generally applicable and the model can readily be adopted by district general hospitals.


Comparison of enalapril and nifedipine in treating non-insulin dependent diabetes associated with hypertension: one year analysis.

To compare the efficacy, safety, and tolerance of enalapril and nifedipine in hypertensive patients with non-insulin dependent diabetes. One year double blind follow up of patients randomly allocated to either enalapril or nifedipine with matching placebos for the alternative drug. Metabolic Investigation Unit, Hong Kong. 102 patients were randomised: 52 to nifedipine and 50 to enalapril. At baseline 44 patients had normoalbuminuria, 36 microalbuminuria, and 22 macroalbuminuria. Blood pressure, albuminuria, and parameters of renal function and glycaemic control. In patients who completed one year's treatment the median dose required by the nifedipine group (n = 49) was 60 mg/day; seven (14%) required additional diuretics. Of 41 patients given enalapril, 37 required the maximum dose (40 mg/day) and 27 (76%) required diuretics. At one year mean arterial blood pressures were similar in both groups. Albuminuria fell by 54% in the enalapril group and 11% in the nifedipine group (p = 0.006). Fractional albumin clearance ratio fell by 47% in the enalapril group and increased by 3% in the nifedipine group (p = 0.009). Creatinine clearance fell similarly in both groups but plasma creatinine concentration was increased by 20% in the enalapril group versus 8% in the nifedipine group (p = 0.001). Patients taking enalapril often required diuretics to control blood pressure. Enalapril reduced proteinuria significantly more than nifedipine in the microalbuminuric and macroalbuminuric patients but increased plasma creatinine concentrations. Longer follow up is required to clarify the importance of enalapril's antiproteinuric effect.


Pet birds as an independent risk factor for lung cancer: case-control study.

To test the hypothesis that exposure to pet birds increases risk of developing lung cancer. Case-control study. Computerised interviews were used to assess previous exposure to pets and other risk factors for lung cancer. Three major hospitals treating respiratory disease in former West Berlin. All people newly diagnosed as having primary malignant neoplasm of the trachea, bronchi, or lung who were 65 or younger and control subjects matched for age and sex from the general population of former West Berlin. 279 cases and 635 controls qualified for the study; 239 cases and 429 controls participated. Odds ratio of developing lung cancer according to whether or not pet birds were kept and the duration of keeping pet birds. In addition to the risk of lung cancer imposed by smoking, passive smoking, and occupational exposure to carcinogens, an increased relative risk of 2.14 (95% confidence interval 1.35 to 3.40) was found among people exposed to pet birds. The adjusted odds ratio for exposures longer than 10 years was 3.19 (1.48 to 8.21). Avian exposure seems to carry a risk of lung cancer. Until the pathogenesis is understood, long term exposure to pet birds in living areas should be avoided, especially among people at high risk of developing lung cancer.