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Posttransplant de novo membranous nephropathy in childhood.

Posttransplant proteinuria is a recognized, but relatively uncommon, presentation of renal transplant dysfunction. Significant proteinuria occurs in around 10-15% of renal transplant recipients. We present a case of de novo posttransplant membranous nephropathy in childhood complicating renal transplantation for severe congenital obstructive uropathy and review the pathology, pathogenesis, and clinical implications of this condition. In the majority of cases, the cause of posttransplant proteinuria is either related to chronic allograft nephropathy or recurrence of the glomerulonephritis for which transplantation was indicated. In a minority, however, de novo posttransplant membranous nephropathy (DNPMN) is identified on biopsy. The histopathological findings in some cases may either be similar to those of classical membranous nephropathy, or may be more subtle, showing focal segmental variation in severity, often in conjuction with the features of chronic allograft nephropathy. The use of ancillary techniques including immunohistochemistry and electron microscopy may be required to confirm the diagnosis. The presence of posttransplant de novo membranous nephropathy may be associated with an increased risk of graft loss.

Adolescent↗

Calcium potentiates the effect of estrogen and calcitonin on bone mass: review and analysis.

We reviewed published clinical trials that measured bone mass of postmenopausal women from at least one skeletal site to evaluate whether calcium supplementation influenced the efficacy of estrogens and intranasal calcitonin on bone mass change. We compared results of the administration of oral estrogen or nasal calcitonin in conjuction with additional calcium intake either through diet or supplements compared with those of estrogen or calcitonin alone. Of the 31 published estrogen trials analyzed, 20 modified the diet or used a calcium supplement (total 1183 mg/d) and 11 did not (total 563 mg/d). The mean increase in bone mass of the lumbar spine when estrogen was given alone was 1.3%/y (n = 5) compared with 3.3%/y when estrogen was given in conjunction with calcium (n = 14; P = 0.01). The mean increase in bone mass of the femoral neck with estrogen alone (n = 3) was only 0.9%/y compared with 2.4%/y when calcium was given with estrogen (n = 6; P = 0.04). Similarly, forearm bone mass increased 0.4%/y with estrogen alone (n = 7) compared with 2.1%/y when estrogen was given with calcium (n = 12; P = 0.04). Similar results were found when weighted means were calculated. Of the seven published trials evaluating the effects of 200 IU nasal salmon calcitonin, six also used calcium supplements (total 1466 mg/d) whereas one used calcitonin alone (total 627 mg/d). Bone mass of the lumbar spine increased 2.1% with calcitonin plus calcium supplementation compared with -0.2%/y with calcitonin alone. These results suggest that a high calcium intake potentiates the positive effect of estrogen on bone mass at all skeletal sites and perhaps that of calcitonin on bone mass of the spine.

Bone Density↗

Linkage of genetic determinants for mouse beta-galactosidase electrophoresis and activity.

An electrophoretic polymorphism for beta-galactosidase has been identified among common inbred strains of mice. It is inherited as a single Mendelian factor with two alleles showing codominant expression. This structural gene, Bge, is closely linked (0/163 recombinants) with the Bgs site on chromosome 9 which regulates systemic levels of beta-galactosidase. The distribution of electrophoretic and activity phenotypes among inbred strains is not concordant, indicating that they result from separate mutations. Three aspects of beta-galactosidase realization, its structure, systemic regulation and developmental program, are now known to be organized in close proximity on chromosome 9. Considered in conjuction with evidence from other mammalian systems, this suggests that the mammalian genome, like Drosophila, is organized into large functional units in which relevant regulatory and developmental information is closely associated with individual structural genes.

Alleles↗

The capsular polysaccharide of Bacteroides fragilis as a virulence factor: comparison of the pathogenic potential of encapsulated and unencapsulated strains.

The pathogenic potentials of encapsulated and unencapsulated strains of Bacteroides fragilis were compared by use of a rat model of intraabdominal sepsis. Implantation of encapsulated B. fragilis alone resulted in abscesses in most recipients, whereas unencapsulated strains seldom produced this effect unless they were combined with another organism. Implants of heat-killed, encapsulated B. fragilis also resulted in abscess formation. Subsequent experiments suggested that the abscess-potentiating ability of encapsulated B. fragilis is related to the capsular polysaccharide. Implantation of 200 microgram of the purified capsular material alone or in conjuction with unencapsulated strains caused abscess formation in a majority of animals. Comparable results were not obtained with capsular polysaccharide from Escherichia coli O7:K1(L)"NM or with heat-killed Streptococcus pneumoniae type III. The capsular polysaccharide of B. fragilis appears to potentiate abscess formation and may represent a virulence factor for this species.

Abscess↗

A program for calculation of intrapulmonary shunts, blood-gas and acid-base values with a programmable calculator.

With a desk-top, programmable calculator, it is now possible to do complex, previously time-consuming computations in the blood-gas laboratory. The authors have developed a program with the necessary algorithms for temperature correction of blood gases and calculation of acid-base variables and intrapulmonary shunt. It was necessary to develop formulas for the Po2 temperature-correction coefficient, the oxyhemoglobin-dissociation curve for adults (withe necessary adjustments for fetal blood), and changes in water vapor pressure due to variation in body temperature. Using this program in conjuction with a Monroe 1860-21 statistical programmable calculator, it is possible to temperature-correct pH,Pco2, and Po2. The machine will compute alveolar-arterial oxygen tension gradient, oxygen saturation (So2), oxygen content (Co2), actual HCO minus 3 and a modified base excess. If arterial blood and mixed venous blood are obtained, the calculator will print out intrapulmonary shunt data (Qs/Qt) and arteriovenous oxygen differences (a minus vDo2). There also is a formula to compute P50 if pH,Pco2,Po2, and measured So2 from two samples of tonometered blood (one above 50 per cent and one below 50 per cent saturation) are put into the calculator.

Acid-Base Equilibrium↗

Suggested management guidelines for participation in collision activities with congenital, developmental, or postinjury lesions involving the cervical spine.

Many conditions involving the cervical spine in the athlete require a management decision. The purpose of this paper is to present appropriate guidelines for return to collision activities in those with congenital, developmental, or post-injury lesions. Information compiled from over 1200 cervical spine lesions documented by the National Football Head & Neck Injury Registry, an extensive literature review, as well as an understanding of injury mechanisms have resulted in reasonable management guidelines. Each of the congenital, developmental, and post-traumatic conditions presented are determined to present either no contraindication, relative contraindication, or an absolute contraindication on the basis of a variety of parameters. Conditions included in the discussion are: odontoid anomalies; spina bifida occulta; atlanto-occipital fusion; Klipple-Feil anomalies; cervical canal stenosis; spear tackler's spine; and traumatic conditions of the upper, middle, and lower cervical spine, including ligamentous injuries and fractures, intervertebral disc injuries, and post-cervical spine fusion. Emphasized is the fact that the proposed guidelines should be used in the decision-making process in conjuction with other factors such as the age, experience, ability of the individual, level of participation, position played, as well as the attitude and desires of the athlete and his parents after an informed discussion of the problem with particular regard to potential risk.

Athletic Injuries↗

The use of antimetabolites with trabeculectomy: a critical appraisal.

PURPOSE: To examine why most ophthalmologists routinely use mitomycin C or 5-fluorouracil (antimetabolites) in association with filtering surgery for glaucoma. METHODS: Critical analysis of seven medical, social and economic trends. RESULTS: The rapid acceptance of the adjunctive use of antimetabolites at the time of filtration surgery may be explained by reasons other than anticipated increase in the "success" of glaucoma surgery. CONCLUSION: The use of antimetabolites in conjuction with filtering glaucoma surgery may be at least partially a consequence of changing medical-social-economic factors, rather than solely a desire on the part of physicians to improve the "success" of glaucoma surgery. This may indicate a need to reevaluate the proper place of antimetabolites in association with filtration surgery.

Antimetabolites↗

Recovery from monocular deprivation in the monkey. III. Reversal of anatomical effects in the visual cortex.

Transneuronal autoradiography was used to study the effects of visual deprivation on the ocular dominance stripes in layer IVc of the striated cortex of Erythrocebus patas (Old World) monkeys. The animals were studied after: (a) 21-28 days of monocular deprivation starting at, or within, a few days of birth; (b) the same treatment followed by a further 3, 6, 15 or 126 days of monocular vision through both eyes (reopening). One other monkey was monocularly deprived from birth to 1890 days. In most cases the behaviour of the ocular dominance stripes formed by the initially closed eye was studied. After 24 days of monocular deprivation from birth, the input from the normal eye was distributed uniformly within layer IVc, with no periodicity evident. After 21 days of deprivation, the deprived eye's input formed narrow stripes occupying about 38% of layer IVc in the operculum. Seven months of monocular deprivation reduced this to about 29%. Opening the closed eye after the deprivation produced no change in the area innervated: when periods of 15 or 96 days of binocular vision followed the deprivation, the areas innervated by the initially deprived eye were 26 and 30% respectively. However, in both cases the deprived eye's input formed blobs and spots, rather than uniformly narrow stripes. In contrast to reopening, reverse suturing increased the fraction of layer IVc occupied by input form the initially deprived eye. In the operculum, the effects of reverse suturing appeared to be fully developed after only 6 days of reversal: the initially deprived eye's stripes having expanded to occupy about 50% of layer IVc. A further 9 days' reversal produced little change in this. In the visual cortex in the calcarine fissure, the effect of the initial deprivation ws more severe, and the expansion induced by reverse suturing more pronounced. The initial deprivation caused the stripes to shrink to occupy 24% of layer IVc; after 6 days of reverse sulture the proportion increased to 52%, while after 15 days of reverse suture about 88% of IVc was occupied. These results show that reverse suturing can cause fresh growth of afferent axons in regions of layer IVc from which they had been at least partially removed, either by the normal process of segregation, or as a consequence of monocular deprivation. Taken in conjuction with the findings of the accompanying two papers (Blackemore et al...

Animals↗

Recurrent mutation and selection for increased penicillin titre in Aspergillus nidulans.

Recurrent mutation and selection has been used to increase penicillin titre in two closely related strains of Aspergillus nidulans. A selection programme was initiated from each of the two strains (programmes A and B) and continued through six cycles of mutation and selection. Near-ultraviolet light in conjuction with 8-methoxypsoralen was employed as the sole mutagen throughout programme A and ethyl methanesulphonate as the sole mutagen throughout programme B. Excluding the first cycle of A, where only 50 strains were assayed, the selection programmes were identical. In each programme, 100 survivors were assayed for penicillin titre after each mutagenic treatment and, on the basis of a single yield test, the best five strains were picked and carried forward to the next cycle. In both selection programmes, a near 300% increase in penicillin titre was achieved. This yield advance illustrates the effectiveness for strain development of experimental designs involving successive cycles of mutagenesis with a single-stage screen and the selection of the top few percent survivors in each cycle.

Aspergillus nidulans↗

Biotyping of Escherichia coli.

We examined the results of tests with 22 substrates for their ability to discriminate a series of 917 strains of Escherichia coli collected from different sources. The tests with three of the substrates were discarded because of difficulties in performance or interpretation, and another nine substrates because they provided little discrimination. The tests used to obtain biotype profiles for strains were those for the fermentation of dulcitol, D-raffinose or sucrose or both, L-rhamnose and L-sorbose, the decarboxylation of L-lysine and L-ornithine, the hydrolysis of aesculin, motility, and prototrophy. Observations on several series of cultures from different sources showed that biotype characters were stable in vivo and after storage on non-selective medium. The biotype profiles obtained were as reliable as partial O serotyping for the routine subtyping of strains of E. coli isolated from the urine of patients with long-term urinary-tract infections and those from other sources in different patients. Biotyping and O serotyping used in conjuction offered a very fine degree of strain discrimination.

Bacteriological Techniques↗

Photophosphorylation after chilling in the light : effects on membrane energization and coupling factor activity.

The response of in situ photophosphorylation in attached cucumber (Cucumis sativus L. cv Ashley) leaves to chilling under strong illumination was investigated. A single-beam kinetic spectrophotometer fitted with a clamp-on, whole leaf cuvette was used to measure the flash-induced electrochromic absorbance change at 518 minus 540 nanometers (DeltaA(518-540)) in attached leaves. The relaxation kinetics of the electric field-indicating DeltaA(518-540) measures the rate of depolarization of the thylakoid membrane. Since this depolarization process is normally dominated by proton efflux through the coupling factor during ATP synthesis, this technique can be used, in conjuction with careful controls, as a monitor of in situ ATP formation competence. Whole, attached leaves were chilled at 5 degrees C and 1000 microeinsteins per square meter per second for up to 6 hours then rewarmed in the dark at room temperature for 30 minutes and 100% relative humidity. Leaf water potential, chlorophyll content, and the effective optical pathlength for the absorption measurements were not affected by the treatment. Light- and CO(2)-saturated leaf disc oxygen evolution and the quantum efficiency of photosynthesis were inhibited by approximately 50% after 3 hours of light chilling and by approximately 75% after 6 hours. Despite the large inhibition to net photosynthesis, the measurements of DeltaA(518-540) relaxation kinetics showed photophosphorylation to be largely unaffected by the chilling and light exposure. The amplitude of the DeltaA(518-540) measures the degree of energization of the photosynthetic membranes and was reduced significantly by chilling in the light. The cause of the decreased energization was traced to impaired turnover of photosystem II. Our measurements showed that the chilling of whole leaves in the light caused neither an uncoupling of photophosphorylation from photosynthetic electron transport nor any irreversible inhibition of the chloroplast coupling factor in situ. The sizeable inhibition in net photosynthesis observed after chilling in the light cannot, therefore, be attributed to any direct effect on photophosphorylation competence.

Journal Article↗

The role of vasopressin in the genetic and neural regulation of monogamy.

Arginine vasopressin modulates pairbond formation in the monogamous prairie vole (Microtus ochrogaster). Our laboratory has investigated the genetic and neural mechanisms by which vasopressin and its V1a receptor (V1aR) regulate social attachment between mates. Non-monogamous vole species show strikingly different distribution patterns of brain V1aR expression compared to monogamous species, and these patterns are thought to arise from species differences in the respective promoter sequences of the V1aR gene. Individual differences in prairie vole V1aR patterns may also reflect individual differences in promoter sequences. Pharmacological and genetic manipulation of the specific brain regions that express V1aR in the 'monogamous pattern' allows multilevel examination of the neural circuits that underlie pairbond formation in monogamous species. For example, V1aR are expressed in brain regions involved in reward circuitry in monogamous vole species and have been implicated in pairbonding. V1aR are also highly expressed in regions implicated in the olfactory processing of sociosexual behaviour. We hypothesize that both circuits of reward and olfactory memory underlie the cognitive mechanisms that control pairbonding. When used in conjuction, genetic and cellular analyses of a complex social behaviour can provide a coherent framework with which to examine the role of the vasopressin system in species evolution and neural control of behaviour.

Animals↗

In vitro targeting and cytotoxicity of adriamycin in liposomes bearing monoclonal antibody against rat or human gp125 cell proliferation-associated antigen.

Chemoimmunoliposomes (CIL) were prepared by entrapping adriamycin in monoclonal antibody (mAb)-coated liposomes and examined for their binding capacity and cytotoxicity to relevant target tumor cells. Sonicated unilamellar liposomes were coated with B3 and HBJ127 mouse, mAbs, which recognize a rat and a homologous human cell proliferation-associated surface antigen, gp125, respectively, and then adriamycin was entrapped in the liposomes by means of transmembrane Na+/K+ gradients using valinomycin. These CIL selectively bound with relevant target tumor cells bearing the corresponding gp125 antigen, such as BC47 rat bladder cancer, FTL-13 rat thymic lymphoma, T24 human bladder cancer and Molt-4 human leukemia cells, although the binding capacities of the CIL to bladder cancer cells were relatively larger than those to lymphoma cells in both rat and human systems. This difference in the target cell binding was found to be attributable to the amount of gp125 antigen expressed on each target tumor cell, as determined by a Scatchard plot analysis. In accordance with the target cell binding capacities of CIL preparations, the CIL displayed much higher cytotoxic activity to bladder cancers than to lymphomas in both rat and human systems. In conjuction with our previous finding that gp125 antigen is expressed on tumor cells but not on resting normal cells, these findings indicate that CIL composed of anti-gp125 mAb will be useful for tumor therapy and that the antitumor efficacy is dependent upon the extent of the antigen expression on target tumor cells.

Animals↗

Preventing heel pressure sores: a comparison of heel pressure relieving devices.

It has been widely recognized that elderly patients with an orthopaedic problem are predisposed to developing heel pressure sores. In this study four pressure-reducing devices, commonly used in the prevention of heel ulcers, were objectively compared for their ability to decrease or remove pressure on the heels of patients with fractured necks of femurs and fractured femurs. Forty-one patients were randomly allocated a pressure relieving device. The efficacy of the device was evaluated by continuously assessing the skin integrity of both heels on a daily basis over a period of 12 days. Data were collected over a 30 month period. The four devices were foam splints, eggshell foam, duoderm and heel protector boots. Foam splints and eggshell foam proved to be more effective devices in relieving pressure exerted on the heel. This study recognizes that meticulous nursing care remains the critical element in prevention of heel ulcers; however, the use of eggshell foam and foam splints in conjuction with this enhances the maintenance of skin integrity.

Aged↗

Metabolic regulation of steroidogenesis in isolated adrenal cells of rat. Relationship of adrenocorticotropin-, adenosine 3':5'-monophosphate-and guanosine 3':5'-monophosphate-stimulated steroidogenesis with the activation of protein kinase.

The data presented with the isolated adrenal cells, in the present study, show that adrenocorticotropin in the physiological concentration range stimulates the synthesis of guanosine 3':5'-monophosphate(cyclic GMP), protein kinase activity, and steroidogenesis in a concentration-dependent manner without detectable rise in the levels of adenosine 3':5'-monophosphate (cyclic AMP). Millimolar concentrations of cyclic AMP and cyclic GMP, which stimulate corticosterone synthesis, also activate kinase activity and steroidogenesis in a sigmoid concentration-response manner. The process of phosphorylation activated by corticotropin, cyclic AMP and cyclic GMP is not inhibited by cycloheximide or actinomyin D. It is therefore proposed that the hormonal responses mediated by cyclic GMP and cyclic AMP are via the protein kinase enzymatic steps, and the inhibitory effect of cycloheximide and actinomycin D in corticotropin-stimulated steroidogenesis follows this step. In conjuction with our previous observations that the biosynthetic steps from (20S)-20-hydroxycholesterol to corticosterone are neither inhibited by cycloheximide nor affected by cyclic GMP, it is inferred that the rate-limiting step of adrenal steroidogenesis is the transformation of cholesterol to (20S)-20hydroxycholesterol and this very step is regulated by cyclic GMP and cyclic AMP. Of further significance are the findings that micromolar cincentrations of cyclic AMP and cyclic GMP, which do not stimulate steroidogenesis, effectively stimulate protein kinase activity in a concentration-dependent manner. It is therefore concluded that all cyclic-nucleotide-dependent protein kinase activities of the cell are not necessarily related to steroidogenesis.

Adrenal Glands↗

Serotypes of pneumococci in pneumonia, meningitis and other pneumococcal infections.

During a five-year period, 1965 to 1969 inclusive, pneumococci from 294 patients with acute pneumococcal infections were serotyped. Pneumococci of 33 serotypes were encountered, of which types 3 and 19 were most frequent. The spectrum of infections included pneumonia, meningitis, peritonitis, otitis media and mastoiditis, wound infection and conjuctivitis. At least 17 infections were fatal, all of which, with one exception, occurred either in infants or in adults over 50 years of age. In pneumonia, type 3 pneumococcus was predominant, being isolated from 21 of 101 patients. In 67 cases of pneumococcal meningitis, most of which were in children, the commonest type was 14. If a pneumococcal vaccine is produced for use in Australia, inclusion of serotypes 1, 3, 4, 6, 9, 14, 19 and 23 should be considered. These eight types caused 52% of the cases of pneumonia and 67% of the cases of meningitis in this study.

Acute Disease↗

Synergistic internal carotid vasodilator effects of human alpha-calcitonin gene-related peptide and nimodipine in conscious rats.

1. In a first series of experiments, male Long Evans rats were chronically instrumented for the measurement of internal carotid blood flow and systemic arterial blood pressure; cardiovascular changes were assessed during and after 30 min infusions of human alpha-calcitonin gene-related peptide (CGRP) (0.06 and 0.6 nmol h-1), or nimodipine (60 and 600 nmol h-1) or human alpha-CGRP plus nimodipine. The effects of human alpha-CGRP or nimodipine on internal carotid vasoconstriction induced by endothelin-1 were also measured. 2. Human alpha-CGRP (0.06 nmol h-1) caused a small (+15%), transient increase in internal carotid blood flow and a tachycardia (+33 beats min-1), but no change in mean blood pressure. Nimodipine (60 nmol h-1) caused a brief internal carotid hyperaemia (+16%) but no changes in blood pressure or heart rate. However, concurrent administration of human alpha-CGRP (0.06 nmol h-1) and nimodipine (60 nmol h-1) caused a sustained increase in internal carotid blood flow (+40%) unaccompanied by significant changes in heart rate or blood pressure. 3. Human alpha-CGRP at a dose of 0.6 nmol h-1 or nimodipine at a dose of 600 nmol h-1 caused substantial reductions in internal carotid vascular resistance (-43 and -40%, respectively); concurrent administration of these doses did not have an additive vasodilator effect. 4. Infusion of endothelin-1 (1.2nmolhV1) for 20min caused incremental constriction of the internal carotid vascular bed; human alpha-CGRP infusion (0.6 and 6.0nmolh-1) begun tOmin after the onset of endothelin-1 infusion reversed this effect (dose-dependently); nimodipine (600nmolh-1) also caused a substantial attenuation of the effects of endothelin-1. 5. In a second series of experiments the haemodynamic effects of human alpha-CGRP and/or nimodipine were assessed in rats chronically instrumented for the measurement of renal, superior mesenteric and hindquarters blood flow together with systemic arterial blood pressure. 6. Administration of human alpha-CGRP (0.06 nmol h-') alone or in conjuction with nimodipine (60nmolh-1) had no significant effects on renal or superior mesenteric vascular resistances, although there was a slight hindquarters vasodilatation. Human alpha-CGRP at a dose of 0.6 nmol -1 caused hypotension, tachycardia and reductions in renal and superior mesenteric blood flows, together with a marked (+31% maximum) hindquarters hyperaemia. Nimodipine at a dose of 600 nmol h-1 caused hypotension, tachycardia and a reduction (-34%) in renal blood flow; mesenteric blood flow was unchanged and there was an increase in hindquarters flow (+ 59%). 7. Concurrent administration of human alpha-CGRP (0.6 nmol h 1) and nimodipine (600 nmol h') did not have an additive hypotensive effect or an enhanced hindquarters hyperaemic effect, but was associated with a marked impairment of renal blood flow (-48%). 8. The present results indicate that concurrent administration of low doses of human alpha-CGRP and nimodipine might be particularly helpful in the acute treatment of patients with cerebral vasospasm and impaired renal perfusion, since this intervention improved internal carotid blood flow without compromising blood flow to the kidney.

Animals↗

The use of sulthiame- in myoclonic epilepsy of childhood and adolescence.

Sulthiame has been used by most investigators in psychomotor seizures, other focal seizures and grand-mal, usually in conjuction with other anticonvulsants. Reports on its use in myoclonic epilepsy and as a sole anti-convulsant are few and inconclusive. The present report presents the results of a study carried out on the use of sulthiame in 54 cases of myoclonic epilepsies originating in infancy, childhood and adolescence. The different types of myoclonic epilepsy are defined. An illustrative case report is included. Results indicated that sulthiame is the drug of choice, often as the sole anti-convulsive agent, in cases of "juvenile myoclonic epilepsy". In the myoclonic encephalopathies of childhood (the so-called "minor motor epilepsy" or Lennox-Gastaut syndrome), which are notoriously refractory to therapy, sulthiame appears to be an efficacious adjunct to currently-used agents, including benzodiazepines, succinimides, dipropyl acetate, steriods and a ketogenic diet.

Adolescent↗