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PubMed1976

Biomedical engineering for "The Age of Health".

A systems approach to health care inevitably emphasizes shifting present emphasis from curative to preventive orientations. However, problems arise through the inertia and resistance of our politico-cultural system. The present highly-developed curative-oriented system depends heavily on technological and biomedial engineering expertise, as indeed will a preventive-oriented system. They must serve however within the priorities defined by the systems objectives in health care. This paper reviews, in terms of technological content and socio-political issues, some major developments including; multiphasic health testing and disease screening, health appraisals, clinical labs and other test procedures, protocols, computerized information systems, data bases and systems modelling.

Biomedical Engineering↗
PubMed1992

Effects of fasting, refeeding, and fasting with T3 administration on Na-K,ATPase in rat skeletal muscle.

It is known that Na-K,adenosine triphosphatase (ATPase) in cell membranes represents an important consumer of cellular energy, eg, adenosine triphosphate (ATP), and that the concentration and activity of this enzyme change in a dose-dependent manner with serum thyroid hormone levels. To examine the hypothesis that low triiodothyronine (T3) syndrome represents a cellular adaptation in generalized severe illnesses that saves tissue energy expenditure, we measured the muscle Na-K,ATPase concentration and its activity in rats that led to low T3 syndrome induced by fasting. The Na-K,ATPase concentration was measured by 3H-ouabain binding to soleus muscle, and its activity was measured by 42K uptake in the contralateral soleus muscle. The effects of refeeding or T3 administration on Na-K,ATPase in soleus muscle in fasted rats were also examined. Na-K,ATPase concentration and activity were both increased in hyperthyroid rats and decreased in hypothyroid rats. In the fasting state, they were decreased to as low as the levels seen in hypothyroidism. Furthermore, with fasting + refeeding or fasting + T3 administration, Na-K,ATPase in soleus muscle returned to the normal level. These results suggest that tissue energy expenditure, as assessed by Na-K,ATPase, in skeletal muscles of fasted rats with low T3 syndrome is actually decreased to levels seen in hypothyroidism, due at least partly to the decrease in serum T3 concentrations, and that there exist some adaptation mechanisms in the peripheral tissues for the accommodation of energy metabolism in the body through decreased thyroxine (T4) to T3 conversion.

Adenosine Triphosphate↗
PubMed1988

Male fertility and the undescended testis in Down syndrome. How to counsel parents.

Evaluation of fertility in male patients with Down syndrome has generally revealed poor psychosexual adaptation and markedly abnormal semen quality, which have thus far been uniformly associated with sterility. Up to 50% of male patients with Down syndrome have undescended testes. Life-table analysis of survival among patients with Down syndrome, as well as the low incidence of testicular tumors, would suggest that orchidopexy may be unnecessary in some patients. In most patients, however, orchidopexy is appropriate to allow for subsequent testicular examination. Parents of children with Down syndrome must be appropriately counseled regarding the fertility of their children and the treatment options for cryptorchidism.

Counseling↗
PubMed2002

Adverse effects of liver dysfunction and portal hypertension on intestinal adaptation in short bowel syndrome in children.

BACKGROUND: The effects of liver dysfunction and portal hypertension on intestinal adaptation in short bowel syndrome are generally unknown. The presence of these disorders may adversely affect the ability to wean these patients from parenteral nutrition. METHODS: Forty-two infants with short bowel syndrome were placed in one of three Child's classifications, depending on serum bilirubin, prothrombin time, ascites, albumin, and liver biopsy, and compared for time to diet tolerance, time required for parenteral nutrition, and survival. A subgroup of these patients also underwent portal pressure measurement, which was combined with liver biopsy results to compare three groups for the same parameters. RESULTS: Survival was Child's class A 100%, B 84%, C 61%, while time to feeding tolerance was A 16.3 days, B 20.0 days, C 28 days, and total parenteral nutrition time was A 80.0 days, B 98.0 days, C 100.0 days. In the groups that underwent portal pressure measurement, the survival was group I (normal biopsy and pressure) 100%, group II (abnormal biopsy and normal pressure) 90%, group III (abnormal biopsy and pressure) 66%, while time to feeding tolerance was I 15.0 days, II 18.0 days, III 24.0 days, and total parenteral nutrition time was I 72.0 days, II 94.0 days, III 184.0 days. CONCLUSIONS: Cholestatic liver disease, especially associated with portal hypertension adversely affects bowel adaptation in short bowel syndrome.

Cholestasis, Intrahepatic↗
PubMed1991

Dynamics of ventricular repolarisation in the congenital long QT syndromes.

Patients with congenital QT interval prolongation are at risk of ventricular arrhythmias and sudden death. It has been suggested that the susceptibility to arrhythmias in these syndromes may be related to the abnormal dynamics of ventricular repolarisation. The dynamics of ventricular repolarisation, including assessment of the effect of changing heart rate on the QT interval and the duration of the right ventricular monophasic action potential, were studied in eight patients with congenital long QT syndromes. The effects of altered sympathetic tone on these dynamics were investigated with isoprenaline, propranolol, and left stellate ganglion block. The rate adaptation of the QT interval was abnormal in only a few patients and in some patients this feature may be related to the severity of the condition. These abnormalities may be exaggerated by isoprenaline and lessened by propranolol and left stellate ganglion block. Monophasic action potential dynamics were normal in all patients. The hypothesis that impaired QT rate adaptation may play a role in the genesis of ventricular arrhythmias in these syndromes is not, in general, supported by the present data. However, in patients with impaired adaptation the normalisation of QT dynamics after beta blockade and left stellate ganglion block was consistent with the efficacy of these forms of treatment.

Action Potentials↗
PubMed1999

[Symptomatic and cryptogenic epilepsies in the child].

Symptomatic and cryptogenic epilepsies are related to detected or suspected cerebral lesions. Early identification of defined epileptic syndromes and etiology is helpful to adapt treatment. Generalized epilepsies are severe, often refractory and generally associated with cognitive dysfunction or regression. Partial symptomatic or cryptogenic epilepsies represent about 40% of all epilepsies in childhood and diagnosis as well as therapeutic strategy can be difficult. Semiology of partial seizures is related to epileptogenic focus and discharge propagation. Causes are numerous and are to be always extensively searched.

Anticonvulsants↗
PubMed1996

Organization of a simple two-joint synergy in individuals with Down syndrome.

Subjects with Down syndrome and age- and gender-matched control subjects performed discrete elbow or wrist, flexion or extension movements in a sagittal plane, moving one of the joints as fast as possible. The hand was either pronated or supinated. In control subjects, alternating bursts of activity were seen in the agonist-antagonist muscle pair controlling the nonfocal joint. Subjects with Down syndrome, in most series, demonstrated simultaneous bursts of activity in the flexor and extensor muscles controlling both joints. This group difference was particularly pronounced for the muscles controlling the nonfocal joint. We assume that the central nervous system may use two strategies to avoid flapping of a postural joint. The more universal co-contraction strategy in Down syndrome may be viewed as an adaptive feature reflecting a general tendency of these persons to trade efficacy for safety.

Adult↗
PubMed1998

Current concepts in the surgical management of multiple endocrine neoplasia type 1 pancreatic-duodenal disease. Results in the treatment of 40 patients with Zollinger-Ellison syndrome, hypoglycaemia or both.

The management of multiple endocrine neoplasia type 1 (MEN-1) pancreatic-duodenal disease, particularly when the Zollinger-Ellison syndrome (ZES) is the presenting manifestation, has remained controversial. The management of hypoglycaemia and other syndromes as well as large tumours detected by imaging is less controversial, although standardized surgical techniques have not been generally adapted. The rationale for an aggressive operative management plan for ZES and other syndromes is based on the facts that neuroendocrine tumours of both the pancreas and the duodenum have malignant potential and that the functional manifestations can be controlled with appropriate surgical procedures based on current concepts of the MEN-1 disease. Of the ten concepts presented, the one critical to the surgical treatment of ZES is that a duodenotomy is essential in detecting the source of hypergastrinaemia in most MEN-1 patients. The complete operation is multifaceted and includes peripancreatic lymph node dissection (ZES), enucleation of any head or uncinate tumours and a distal pancreatectomy. Our results in 40 MEN-1 patients with functional syndromes treated with these procedures are encouraging. Ten patients with hypoglycaemia (four with concomitant ZES) have been 'cured' with follow-up as long as 18 years. Sixty-eight per cent of 34 patients with ZES have remained eugastrinaemic during follow-up as long as 19 years. One patient developed a solitary liver metastasis that was excised a year ago without other evidence of recurrence. There has been no operative mortality and three subsequent deaths were due to unrelated disease.

Duodenal Neoplasms↗
PubMed2004

Intestinal rehabilitation and the short bowel syndrome: part 2.

The management of patients with intestinal failure due to short bowel syndrome is complex, requiring a comprehensive approach that frequently necessitates long-term, if not life-long, use of parenteral nutrition. Despite tremendous advances in the provision of parenteral nutrition over the past three decades, which have allowed significant improvements in the survival and quality of life of these patients, this mode of nutritional support carries with it significant risks to the patient, is very costly, and ultimately, does not attempt to improve the function of the remaining bowel. Intestinal rehabilitation refers to the process of restoring enteral autonomy, and thus, allowing freedom from parenteral nutrition, usually by means of dietary, medical, and occasionally, surgical strategies. While recent investigations have focused on the use of trophic substances to increase the absorptive function of the remaining gut, whether intestinal rehabilitation occurs as a consequence of enhanced bowel adaptation or is simply a result of an optimized, comprehensive approach to the care of these patients remains unclear. In Part 1 of this review, we provided an overview of short bowel syndrome and pathophysiological considerations related to the remaining bowel anatomy in these patients. We also reviewed intestinal adaptation and factors that may enhance the adaptive process, focusing on evidence derived from animal studies. In Part 2, relevant data on the development of intestinal adaptation in humans are reviewed as is the general management of short bowel syndrome. Lastly, the potential benefits of a multidisciplinary intestinal rehabilitation program in the care of these patients are also discussed.

Adaptation, Physiological↗
PubMed1989

Electrocardiographic findings and frequency of arrhythmias in Bartter's syndrome.

Twenty four hour electrocardiograms in 20 patients with Bartter's syndrome, a disorder associated with chronic potassium deficiency, were analysed for atrial and ventricular extrasystoles, pauses (RR interval greater than 2 s), and heart rate. The 12 lead resting electrocardiogram was also evaluated. There were slight electrocardiographic changes with ST segment depression (greater than or equal to - 0.5 mm) in seven patients, flat or low amplitude T waves in seven, and U waves (greater than or equal to + 1.0 mm) in three patients. The QT interval was prolonged in 18 patients. Nine patients had one or more ventricular extrasystoles in 24 hours. Only two patients had more than 200 ventricular extrasystoles in 24 hours. No patient had ventricular tachycardia. A total of nine patients had one or more atrial extrasystoles in 24 hours, but only one patient had more than 200 in 24 hours. One patient had an attack of non-sustained supraventricular tachycardia. No patient had pauses. Dangerous tachycardia was rare in these patients with chronic potassium deficiency caused by Bartter's syndrome. The general pattern of slight electrocardiographic changes may reflect an adaptation of the myocardium to hypokalaemia. Further studies are, however, needed to determine whether these findings are relevant to long term prognosis.

Adult↗
PubMed2006

Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in Prader-Willi syndrome.

Prader-Willi syndrome is a neurodevelopmental disorder that is characterized by infantile hypotonia, feeding difficulties, hypogonadism, mental deficiency, hyperphagia (leading to obesity in early childhood), learning problems, and behavioral difficulties. A paternal 15q11-q13 deletion is found in approximately 70% of patients with Prader-Willi syndrome, approximately 25% have uniparental maternal disomy 15, and the remaining 2% to 5% have imprinting defects. The proximal deletion breakpoint in the 15q11-q13 region occurs at 1 of 2 sites located within either of 2 large duplicons allowing for the identification of 2 deletion subgroups. The larger, type I (TI) deletion involves breakpoint 1, which is close to the centromere, whereas the smaller, type II (TII) deletion involves breakpoint 2, located approximately 500 kilobases distal to breakpoint 1. Breakpoint 3 is located at the distal end of the 15q11-q13 region and common to both typical deletion subgroups. Analyses of the genetic subtypes of Prader-Willi syndrome to date have primarily compared individuals with typical deletion and uniparental maternal disomy 15 without grouping the individuals with a deletion into TI or TII. Distinct differences have been reported between individuals with Prader-Willi syndrome resulting from deletion compared with uniparental maternal disomy 15 in physical, cognitive, and behavioral parameters. We previously presented the first assessment of clinical differences in individuals with Prader-Willi syndrome categorized as having type I or II deletions. Adaptive behavior, obsessive-compulsive behaviors, reading, math, and visual-motor integration assessments were generally poorer in individuals with Prader-Willi syndrome and the TI deletion compared with subjects with Prader-Willi syndrome with the TII deletion or uniparental maternal disomy 15. Four genes (NIPA1, NIPA2, CYFIP1, and GCP5) have been identified in the chromosomal region between breakpoints 1 and 2 and are implicated in compulsive behavior and lower intellectual ability observed in individuals with Prader-Willi syndrome with TI versus TII deletions. We quantified messenger-RNA levels of these 4 genes in actively growing lymphoblastoid cells derived from 8 subjects with Prader-Willi syndrome with the TI deletion (4 males, 4 females; mean: age 25.2 +/- 8.9 years) and 9 with the TII deletion (3 males, 6 females; mean age: 19.5 +/- 5.8 years). Messenger-RNA levels were correlated with validated psychological and behavioral scales administered by trained psychologists blinded to genotype status. Messenger RNA from NIPA1, NIPA2, CYFIP1, and GCP5 was reduced but detectable in the subjects with Prader-Willi syndrome with the TI deletion, supporting biallelic expression. For the most part, messenger-RNA values were positively correlated with assessment parameters, indicating a direct relationship between messenger-RNA levels and better assessment scores, with the highest correlation for NIPA2. The coefficient of determination indicated the quantity of messenger RNA of the 4 genes explained from 24% to 99% of the variation of the behavioral and academic parameters measured. By comparison, the coefficient of determination for deletion type alone explained 5% to 50% of the variation in the assessed parameters. Understanding the influence of gene expression on behavioral and cognitive characteristics in humans is in the early stage of research development. Additional research is needed to identify the function of these genes and their interaction with gene networks to clarify the potential role they play in central nervous system development and function.

Adaptor Proteins, Signal Transducing↗
PubMed1980

[Clinical cytogenetic and psychoneurological aspects of Klinefelter's syndrome in boys (author's transl)].

Investigations were carried out on boys aged between 8 and 20 years by positive chromatin test. Klinefelter's syndrome was confirmed by karyotype determination in 13 cases. In comparison with the average Polish population the patients' parents were older. The patients were usually the last children to be born in their families. Typical hypogonadism, cryptorchism, especially unilateral, and delay in the development of secondary sex characteristics were observed. Besides typical eunuchoid habitus, endomorphic type of body build, tendency towards obesity or sometimes even delay in growth and a deficiency in body weight were noticed. True gynaecomastia was only present in 1/4 of these patients. Very frequent features of Klinefelter's syndrome are--in the authors' opinion--mental subnormality, inadequate social adaptation and neurotic symptoms. Before adolescence the characteristic phenotype of Klinefelter's syndrome is absent. These results indicate that sex chromatin examination is a general screening test to determine Klinefelter's syndrome in boys.

Adaptation, Psychological↗
PubMed2005

Cereal phytochromes: targets of selection, targets for manipulation?

Plants respond to shading through an adaptive syndrome termed shade avoidance. In high-density crop plantings, shade avoidance generally increases extension growth at the expense of yield and can be at odds with the agronomic performance of the crop as a whole. Studies in Arabidopsis are beginning to reveal the essential role phytochromes play in regulating this process and to identify genes underlying the response. In this article, we focus on how phytochrome signaling networks have been targeted in cereal breeding programs in the past and discuss the potential to alter these pathways through breeding and transgenic manipulation to develop crops that perform better under typical high density conditions.

Edible Grain↗
PubMed2000

The neurodevelopmental frontostriatal disorders: evolutionary adaptiveness and anomalous lateralization.

The frontostriatal system (dorsolateral prefrontal cortex, lateral orbitofrontal cortex, anterior cingulate, supplementary motor area, and associated basal-ganglia structures) is subject to a range of neurodevelopmental disorders: Tourette's syndrome (TS), obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), autism, and probably depression. The system is responsible for our adaptive responses (initiation, execution, or withholding) to environmental situations, and the above disorders, involving effectively excessive release or withholding of various types of response, are all a consequence of changes in specific frontostriatal regions. The disorders all have a genetic component, and their persistence in the genome indicates that their clinical manifestations may also be associated, perhaps in low levels in close relatives, with certain adaptive advantages in given situations. Thus autism is associated with computational careers, depression with literary creativity, SCZ with lateral thinking and the Odyssean personality, ADHD with an Ice-Age readiness to respond, OCD with a focused range of interests, and TS with competitive sports and jazz improvisation. The disorders are all highly comorbid, and which one predominantly manifests may depend on how the frontostriatal system happens to be compromised as a result of inherited genetic predispositions and environmental contingency. We review the adaptive nature of the various subclinical manifestations and the evidence for concomitant phenomena (possibly epiphenomena): alterations in structural, functional, and behavioral lateralization in each syndrome. Indeed it is not clear that altered lateralization in frontostriatal disorders of a neurodevelopmental origin generally has any adaptive significance; it may often simply serve as a marker for altered regulatory function of the frontostriatal system, alterations which in low genetic dosage or penetrance continue to play an adaptive role in clinically unaffected close relatives of probands, but which, in high dosage or penetrance in the probands themselves, are generally deleterious.

Adaptation, Physiological↗
PubMed2003

Mastery motivation in young children with Down's syndrome: relations with cognitive and adaptive competence.

BACKGROUND: Prior research on relations between motivation and competence have focused on cognitive competence, despite theoretical predictions that mastery motivation spurs behaviour that is effective in meeting the demands of one's environment, i.e. adaptive competence. Issues of adaptive competence are especially relevant for children with developmental delay since functional independence is an important long-term goal for these children. METHODS: In the present study, mastery motivation was examined in relation to both cognitive and adaptive competence in 5-year-old children with Down's syndrome (n = 41). RESULTS: Scores on mastery task and parent-report measures of mastery motivation were generally low, but positively related to scores on standardized measures of cognitive competence and adaptive competence. CONCLUSIONS: This is the first study of motivation-competence relations in pre-school-age children. The findings have implications for both developmental theory and early intervention efforts, and the authors hope that they will serve as a stimulus for future research on cross-domain relationships in atypical populations.

Adaptation, Physiological↗