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Biomedical subjects

J John

Publications and source records attributed to J John.

At least 19 recordsLinked to original sources

Tension-band wiring of transverse fractures of patella. The effect of site of wire twists and orientation of stainless steel wire loop: a biomechanical investigation.

Tension-band wiring is commonly used to treat transverse patella fractures. The most common configuration has parallel Kirschner (K) wires and a stainless steel wire loop placed in a vertically oriented figure of eight. Early mobilisation is important but can cause detrimental displacement at the fracture site. A wooden model of a transversely fractured patella was used to compare different fixation constructs. The fracture was fixed using two K wires and a stainless steel wire loop. One or two wire twists were used, placed either arbitrarily or at corners of the loop. The loop was oriented either vertically or horizontally. Interfragmentary compression at the point of wire breakage and permanent displacement on cyclic loading was measured for each construct. Placement of the figure of eight in a horizontal orientation with two wire twists at the corner improved interfragmentary compression by 63% (p<0.05, Tukey post hoc test). On cyclic loading, all constructs with vertical figure of eight but none with a horizontal construct failed (p=0.01; Fisher's exact test). Permanent fracture displacement after cyclic loading was 67% lower with horizontal figure of eight constructs (p<0.05; t test). Placing wire twists at the corner and a horizontal placement of figure of eight improves stability of the construct.

Biomechanical Phenomena↗

[Direct medical costs of (severe) obesity: a bottom-up assessment of over- vs. normal-weight adults in the KORA-study region (Augsburg, Germany)].

AIM OF THE STUDY: To estimate and compare direct medical costs of illness of German adults in different BMI-groups and different degrees of obesity. METHODS: In a sub-sample (n = 947) of the KORA-Survey S4 1999/2001, a cross-sectional health survey of the adult population in the Augsburg region (Germany; age: 25-74), visits to physicians, receipt and purchase of drugs, and inpatient days in hospital were assessed over half a year. Body mass index (BMI in kg/m(2)) was assessed anthropometrically. Respondents in normal weight (18.5 < or = BMI < 25), pre-obese (25 < or = BMI < 30), moderately obese (class 1: 30 < or = BMI < 35), and severely obese (classes 2-3: BMI > or = 35) range were compared in their costs of illness via analyses of covariance and regression analyses based on generalized linear models. Physician visits and inpatient days were evaluated as recommended by the Working Group "Methods in Health Economic Evaluation", and drugs by actual costs. Sex, age, socio-economic status (Helmert-Index), sickness fund (statutory vs. private), and place of residence (Augsburg City vs. District of Augsburg or Aichach-Friedberg) were adjusted for. RESULTS: While respondents with moderate obesity statistically did not differ significantly in their direct medical costs from those in normal weight or pre-obese range (1,080.14 euro vs. 847.60 euro and 830.59 euro; for users of care: 1,215.55 euro vs. 993.18 euro and 1,003.23 euro [all estimates adjusted and per annum]), those with severe obesity had significantly higher costs (2,572.19 euro; for users of care: 2,964.87 euro). Sub-analyses for individual parameters of health care use revealed that this pattern is largely due to inpatient days in hospital and receipt/purchase of drugs only available on prescription. CONCLUSIONS: On average, results indicate excess direct medical costs primarily in people with severe, and less with moderate obesity. In particular, they underline the need to distinguish moderate vs. severe obesity (classes 1 vs. 2-3) in health economics and health services research.

Adult↗

Strain-dependent regulation of neurotransmission and actin-remodelling proteins in the mouse hippocampus.

Individual mouse strains differ significantly in terms of behaviour, cognitive function and long-term potentiation. Hippocampal gene expression profiling of eight different mouse strains points towards strain-specific regulation of genes involved in neuronal information storage. Protein expression with regard to strain- dependent expression of structures related to neuronal information storage has not been investigated yet. Herein, a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF) has been chosen to address this question by determining strain-dependent expression of proteins involved in neurotransmission and activity-induced actin remodelling in hippocampal tissue of five mouse strains. Of 31 spots representing 16 different gene products analysed and quantified, N-ethylmaleimide-sensitive fusion protein, N-ethylmaleimide-sensitive factor attachment protein-alpha, actin-like protein 3, profilin and cofilin were expressed in a strain-dependent manner. By treating protein expression as a phenotype, we have shown significant genetic variation in brain protein expression. Further experiments in this direction may provide an indication of the genetic elements that contribute to the phenotypic differences between the selected strains through the expressional level of the translated protein. In view of this, we propose that proteomic analysis enabling to concomitantly survey the expression of a large number of proteins could serve as a valuable tool for genetic and physiological studies of central nervous system function.

Actin-Related Protein 3↗

Strain-dependent expression of signaling proteins in the mouse hippocampus.

Individual mouse strains may differ significantly in terms of behavior and cognitive function. Hippocampal gene expression profiling on several mouse strains has been carried out and points toward substantial strain-specific variation of more than 200 genes including components of major signaling pathways involved in neuronal information storage. Strain-specific hippocampal protein expression, however, has not been investigated yet. A proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry has been chosen to address this question by determining strain-dependent expression of signaling proteins in hippocampi of four inbred and one outbred mouse strain. Forty-six spots corresponding to 37 different signaling proteins have been analyzed and quantified. Statistical analysis revealed strain-dependent expression of serine/threonine protein phosphatase 1, serine/threonine protein phosphatase 2A, large GTP binding protein OPA1, guanine nucleotide-binding protein beta, putative GTP-binding protein Ran, receptor of activated protein kinase C1, WASP-family protein member 1, voltage-dependent anion channel 2 and 14-3-3 protein gamma. Differential expression of signaling proteins in the hippocampus may contribute to the molecular understanding of strain-dependent behavioral and cognitive performance. Moreover, these data highlight the importance of the genetic background for the analysis of signaling pathways in the hippocampus in wild-type mice as well as in gene-targeting experiments.

Animals↗

Cost-effectiveness of type 2 diabetes screening: results from recently published studies.

Type 2 diabetes screening is recommended by various international diabetes associations. We conducted a literature research to identify and describe systematically recently published cost effectiveness analyses (CEA) for type 2 diabetes screening. Three analyses were included. One of them was conducted in Germany, based on the data of the KORA survey S4 (1999/2001). Two studies came from the US. The German as well as one of the US studies evaluated cost per detected diabetic case as main outcome. In contrast to the US study, the German study considered incomplete participation in the screening programs as baseline case. HbA1 c testing combined with the oral glucose tolerance test (OGTT) was more expensive than OGTT or fasting glucose testing, but also most effective in detecting cases, due to high participation in this screening strategy. The second US study investigated the lifetime cost effectiveness of type 2 diabetes screening, based on a Markov model to calculate cost per quality-adjusted life year (QALY). Effectiveness data were derived from two large intervention studies in clinically diagnosed (not identified by screening) diabetic subjects. The authors conclude that type 2 diabetes screening is cost effective, in particular targeted screening in elderly hypertensive subjects. Diabetes screening may be cost effective. However, the effectiveness of early detection and treatment of type 2 diabetes has not yet been shown, and data regarding the course of early detected diabetes are lacking so far. In the future, the most important question is whether type 2 diabetes screening and early treatment is effective with respect to clinical outcomes.

Adult↗

[Switching sickness funds and risk compensation mechanisms in the statutory health insurance system in Germany--empirical results from the cooperative health research in the region of Augsburg (KORA)].

Since 1996, all citizens of the Federal Republic of Germany who are insured in the statutory health insurance system are entitled to switch their sickness fund. The rationale of this regulation was to strengthen elements of competition in this system in order to stimulate the sickness funds to improve the efficiency of health care and to respond to consumers' preferences. Simultaneously, to avoid the implicit incentives for sickness funds to engage in risk selection, a risk compensation mechanism was introduced, including as morbidity-related risk adjusters age, sex and incapacity to work. Based on the KORA survey S4 (1999/2001) we take the case of switching behaviour in the region of Augsburg, and analyse whether this risk adjustment scheme was working effectively. The results show that persons changing their sickness fund were characterised by a comparatively smaller burden of chronic diseases and by a less frequent utilization of inpatient health care. Under these conditions, differences in the contribution rates do not accurately reflect differences in the performance and efficiency of sickness funds. Moreover, the migration of good risk to sickness funds with favourable contribution rates threatens the principle of financial solidarity. Therefore, the system of risk equalisation has to be developed towards measuring the risk volume borne by the sickness funds more precisely than hitherto.

Adult↗

Utilization of out- and inpatient health services by obese adults: a population-based study in the Augsburg region, Germany.

The aim of this study is to compare out- and inpatient health services utilization by obese and normal weight adults. In a subsample of the KORA-Survey S4 1999/2001 in the Augsburg region, Germany (n = 947, age: 25-74 years), number of visits to general practitioners (GP) and inpatient hospital days were self-reported in three computer-aided telephone interviews (CATI) over half a year. Body mass index, based on measured body height and weight, was used to define obesity according to WHO classification. Participants, stratified in normal weight (18.5 < or = BMI < 25), preobese (25 < r = BMI < 30), obese class 1 (30 < or = BMI < 35) and obese classes 2-3 (BMI > or = 35), were compared via logistic, zero-truncated negative binomial, and multinomial models to elucidate obesity's associations with utilization at all, its frequency, and high utilization. Sex, age, social class, health insurance, and place of residence were adjusted for in all models. Respondents in obesity class 1 were more prone to report at least one visit to a GP than those normal weight (OR = 1.84, p < 0.01), while obesity classes 2-3 were associated with frequent (IRR = 1.63, p < 0.05) and high utilization (OR = 3.57, p < 0.05). Regarding days in hospital, only the extremely obese (i. e. classes 2-3) reported significantly more utilization than those normal weight (days if hospitalized at all: IRR = 3.24, p < 0.05; high utilization: OR = 5.4, p < 0.01). Sex did not play a significant role in any model. Older respondents reported more utilization in terms of GP-visits, while only tending to do so regarding inpatient utilization. Both those with statutory (vs. private) health insurance and rural (vs. urban) place of residence had higher odds to visit a GP at all. Results point to an excess utilization of out- and inpatient health services by especially extremely obese adults, and underline the need to contrast obesity classes 2-3 vs. 1 in health services utilization research.

Adult↗

Activity of dorsal raphe cells across the sleep-waking cycle and during cataplexy in narcoleptic dogs.

Cataplexy, a symptom associated with narcolepsy, represents a unique dissociation of behavioural states. During cataplectic attacks, awareness of the environment is maintained, as in waking, but muscle tone is lost, as in REM sleep. We have previously reported that, in the narcoleptic dog, noradrenergic cells of the locus coeruleus cease discharge during cataplexy. In the current study, we report on the activity of serotonergic cells of the dorsal raphe nucleus. The discharge patterns of serotonergic dorsal raphe cells across sleep-waking states did not differ from those of dorsal raphe and locus coeruleus cells recorded in normal rats, cats and monkeys, with tonic discharge in waking, reduced activity in non-REM sleep and cessation of activity in REM sleep. However, in contrast with locus coeruleus cells, dorsal raphe REM sleep-off neurones did not cease discharge during cataplexy. Instead, discharge continued at a level significantly higher than that seen in REM sleep and comparable to that seen in non-REM sleep. We also identified several cells in the dorsal raphe whose pattern of activity was the opposite of that of the presumed serotonergic cells. These cells were maximally active in REM sleep and minimally active in waking and increased activity during cataplexy. The difference between noradrenergic and serotonergic cell discharge profiles in cataplexy suggests different roles for these cell groups in the normal regulation of environmental awareness and muscle tone and in the pathophysiology of narcolepsy.

Action Potentials↗

Treatment with immunosuppressive and anti-inflammatory agents delays onset of canine genetic narcolepsy and reduces symptom severity.

All Doberman pinschers and Labrador retrievers homozygous for a mutation of the hypocretin (orexin) receptor-2 (hcrtr2) gene develop narcolepsy under normal conditions. Degenerative changes and increased display of major histocompatibility complex class II antigens have been linked to symptom onset in genetically narcoleptic Doberman pinschers. This suggests that the immune system may contribute to neurodegenerative changes and narcoleptic symptomatology in these dogs. We therefore attempted to alter the course of canine genetic narcolepsy, as an initial test of principle, by administering a combination of three immunosuppressive and anti-inflammatory drugs chosen to suppress the immune response globally. Experimental dogs were treated with a combination of methylprednisolone, methotrexate and azathioprine orally starting within 3 weeks after birth, and raised in an environment that minimized pathogen exposure. Symptoms in treated and untreated animals were quantified using the food elicited cataplexy test (FECT), modified FECT and actigraphy. With drug treatment, time to cataplexy onset more than doubled, time spent in cataplexy during tests was reduced by more than 90% and nighttime sleep periods were consolidated. Short-term drug administration to control dogs did not reduce cataplexy symptoms, demonstrating that the drug regimen did not directly affect symptoms. Treatment was stopped at 6 months, after which experimental animals remained less symptomatic than controls until at least 2 years of age. This treatment is the first shown to affect symptom development in animal or human genetic narcolepsy. Our findings show that hcrtr2 mutation is not sufficient for the full symptomatic development of canine genetic narcolepsy and suggest that the immune system may play a role in the development of this disorder.

Age of Onset↗

Oral health care in the elderly population in Malaysia--a review.

One of the undeniable facts about living is that everyday we are getting older. By 2050, it is projected that one out of every five Malaysians will be 60 or older. The economic challenge of this demographic change will affect development and the financial implications of sustaining well being of this group are formidable and complex. This population group has extensive oral disease, medical problems that complicate their oral care, and unique dental treatment challenges. The authors discuss the problem of oral healthcare among the aged, its impediments and propose some approaches for improvement to better serve the needs of this group of vulnerable members of our nation.

Age Factors↗

Genetic variation of varicella-zoster virus: evidence for geographical separation of strains.

Heteroduplex mobility assay was used to identify variants of varicella-zoster virus (VZV) circulating in the United Kingdom and elsewhere. Forty variable positions were identified. Sixteen substitutions were non-synonymous, resulting in an amino acid change, the majority of which were clustered within surface expressed proteins. Phylogenetic analysis distinguished at least three major clades (strains A, B, C) supported by significant bootstrap values. Apart from the United Kingdom and Brazil where all three strains were found, genotypes appeared to be closely associated with the geographical region in which they were sampled. Allelic co-segregation of widely spaced single nucleotide polymorphisms (SNPs) confirmed the genetic stability of the VZV. Recombination rates were difficult to calculate because of the low intra genotypic variation. However, one haplotype originating from Brazil is most parsimoniously explained as a recombinant between A and C strains, which co-occur in the region. Two further UK strains appeared to be recombinants between groups B and C.

Africa↗

Successful use of oral linezolid as a single active agent in endocarditis unresponsive to conventional antibiotic therapy.

Treatment of resistant gram-positive endocarditis is difficult. We report a case of resistant Staphylococcus epidermidis endocarditis that failed to respond to conventional antibiotic therapy but was treated successfully with an oral regimen of a new antibiotic, linezolid as a single active agent. This case report demonstrates the use of linezolid as an effective alternative to conventional antibiotics in such cases.

Acetamides↗

A randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 in the treatment of metastatic malignant melanoma.

We conducted a randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 (IL-2) as treatment for stage IV malignant melanoma. The objectives were to establish the safety and efficacy of SRL172 with and without IL-2. All patients had measurable metastatic disease and none received concurrent chemotherapy, radiotherapy, corticosteroids or any other investigational agent. Sixteen patients were randomized into each arm of the trial prior to closure. The trial was halted prematurely when no responses were seen in the first 16 patients receiving SRL172 alone, predicting a response rate of less than 20%. Three partial remissions were seen in the 16 patients receiving SRL172 + IL-2. These patients remained on monthly SRL172 + IL-2, with disease progression at 12, 15 and 23 months. They continued on the trial regimen following surgical management of their disease progression. This trial provides preliminary evidence of a new, non-toxic, immunotherapeutic regimen in the management of malignant melanoma. Further trials are required to establish a definitive response rate and to compare the combination regimen with the regimen of low-dose IL-2 used in this trial. A biological basis for the responses seen in the SRL172 + IL-2 arm also needs to be established.

Adjuvants, Immunologic↗

Cataplexy-related neurons in the amygdala of the narcoleptic dog.

The amygdala plays an important role in the interpretation of emotionally significant stimuli and has strong projections to brainstem regions regulating muscle tone and sleep. Cataplexy, a symptom of narcolepsy, is a loss of muscle tone usually triggered by sudden, strong emotions. Extracellular single-unit recordings were carried out in the amygdala of narcoleptic dogs to test the hypothesis that abnormal activity of a subpopulation of amygdala neurons is linked to cataplexy. Of the 218 cells recorded, 31 were sleep active, 78 were active in both waking and rapid-eye-movement sleep, 88 were maximally active during waking, and 21 were state independent. Two populations of cells showed a significant change in activity with cataplexy. A population of sleep active cells localized to central and basal nucleus increased discharges prior to and during cataplexy. A population of wake active cells localized to the cortical nucleus decreased activity prior to and during cataplexy. We hypothesize that these cell populations have a role in mediation or modulation of cataplexy through interactions with meso-pontine regions controlling atonia. The anticholinesterase physostigmine, at doses which increased cataplexy, did not alter the activity of the cataplexy-related cells or of other amygdala cells, suggesting that its effect on cataplexy is mediated 'downstream' of the amygdala. The alpha-1 blocker prazosin, at doses which increased cataplexy, increased discharge in a subgroup of the cataplexy active cells and in a number of other amygdala cells, indicating that prazosin may modulate cataplexy by its action on amygdala cells or their afferents.

Action Potentials↗

Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement.

Hypocretins (orexins) are recently discovered hypothalamic neuropeptides that have been implicated in the etiology of narcolepsy. The normal behavioral functions of these peptides are unclear, although a role in feeding has been suggested. We measured hypocretin-1 (Hcrt-1) in the cerebrospinal fluid of dogs during a variety of behaviors. We found that 48 h without food (24 h beyond normal 24-h fasting period) produced no significant change in Hcrt-1 levels nor did feeding after the deprivation. In contrast, 24 h of sleep deprivation produced on average a 70% increase in Hcrt-1 level compared with baseline levels. The amount of increase was correlated with the level of motor activity during the sleep-deprivation procedure. A 2-h period of exercise in the same dogs produced a 57% increase in Hcrt-1 levels relative to quiet waking levels, with the magnitude of the increase being highly correlated with the level of motor activity. The strong correlation between motor activity and Hcrt-1 release may explain some of the previously reported behavioral, physiological, and pathological phenomena ascribed to the Hcrt system.

Aging↗

Renal trauma secondary to stab, blunt and firearm injuries--a 5-year study.

OBJECTIVE: To review our experience of renal trauma at King Edward VIII Hospital, Durban. DESIGN: Retrospective study over 5 years. SETTING: Tertiary referral hospital in an urban area. PATIENTS: One hundred and seventy-four patients presenting with renal injuries treated at King Edward VIII Hospital. INTERVENTIONS: One hundred and thirty-six patients underwent laparotomy, while 38 were managed conservatively. RESULTS: There were 174 patients with renal injuries (148 male, median age 26 years). Eighty-seven injuries were from firearms, 43 from stabs and 44 from blunt trauma. Of 136 patients who underwent surgery, 60 were managed conservatively at laparotomy, 26 underwent renorrhaphy, 40 nephrectomy and 10 heminephrectomy. There was a 33% complication rate following surgery. The mortality rate was 20% (24%, 21% and 12% for firearm, stab and blunt injuries, respectively). There was no statistically significant difference in mortality for firearm, stab and blunt injuries. Furthermore, there was no difference in mortality and morbidity between those with associated organ injuries and those with isolated injuries (29% v. 21% and 30% v. 16%, respectively), but the difference in mortality became significant when patients with isolated injuries who did not undergo surgery were included (P = 0.0083). CONCLUSION: Renal injuries either in isolation or in association with other injuries carry a high mortality and morbidity rate. Firearm injury patients have a large number of associated injuries and have the highest complication rate. Operative strategy should be conservative unless the kidney is unsalvageable.

Adult↗

Therapeutic ultrasound for chronic total coronary artery occlusions.

This article focuses on the use of catheter-delivered ultrasound as a device for treatment of coronary arterial total occlusion (CTO). The standard treatment of CTO is reviewed and serves as the basis for the need for new treatment options, such as catheter-delivered ultrasound (SONICROSS). The results of FDA-approved Phase I and Phase II clinical trials using SONICROSS for refractory CTO are described. The Phase II trials indicate that the SONICROSS-facilitated guidewire passage in 71% of CTOs are otherwise refractory to guidewire passage. However, at present, the SONICROSS catheter system is limited in its ability to be delivered reliably to the CTO because of catheter size and trackability.

Clinical Trials, Phase I as Topic↗

[Current research perspectives of health system research and health economics in Germany].

The German statutory health insurance scheme is confronted with a steadily rapid progress of medical sciences and increasing difficulties to mobilize the financial resources necessary for applying the new scientific knowledge in health care. Therefore it is absolutely imperative to intensify the efforts to improve the effectiveness and efficiency of health care. Health policies based on health targets, the development of patterns requiring integrated care, redefining the bunch of health insurance benefits, and a more regular use of methods of economic evaluation have been proposed as promising approaches towards optimizing resource allocation in health care. However, an analysis of these approaches demonstrates that a valid appraisal of their potential to improve the effectiveness and efficiency of health care requires further research. In addition, European integration may produce tendencies towards a convergence of the national health care systems; this makes it rather difficult to assess how the room for autonomous national health policies will develop in the future.

Cost-Benefit Analysis↗