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Biomedical subjects

J Wilson

Publications and source records attributed to J Wilson.

At least 451 records · Page 25Linked to original sources

Biology of cancer and aging.

The greatest risk factor for cancer is aging. Human cancer incidence increases exponentially with advancing age. Cancer growth rate and potential for metastatic spread may be influenced by age-specific change in host response. Because cancer and aging are, thus, inextricably linked, the American Cancer Society should encourage submission of research proposals that address the mechanisms of aging and how aging alters cancer development.

Age Factors↗

Intramolecular crosslinking of monomeric fibrinogen by tissue transglutaminase.

In addition to generating polymeric products from human fibrinogen, human erythrocyte transglutaminase (protein-glutamine:amine gamma-glutamyltransferase, EC 2.3.2.13) was shown to catalyze the intramolecular reaction of crosslinking two of the constituent chains within monomeric fibrinogen itself. This internally fused protein derivative contains appreciable amounts of the N epsilon-(gamma-glutamyl)lysine bridge peptide and displays the A alpha.gamma hybrid chain pattern of crosslinking, characteristic for the actions of tissue transglutaminases on fibrinogen. Diagnostic analysis in pathological situations, where such enzymes might have escaped from cells into the plasma environment, should include a search for the internally crosslinked soluble fibrinogen monomer.

Chromatography, Gel↗

Response to treatment with antihistamines in a family with myotonia congenita.

In a family in which myotonia congenita was found in five generations, both great-grandparents of the index case were affected. In subsequent generations mild and severely affected cases were clearly segregated down parallel lines of this family. The grandmother of the index case had noted improvement with an antihistamine. When the index case was prescribed trimeprazine, she showed a striking reduction in severity of symptoms. Antihistamines seem to deserve further evaluation as a safe and effective treatment for myotonia congenita.

Adult↗

Digoxin pharmacokinetics and spirapril, a new ace inhibitor.

As concurrent use of digoxin with the novel ACE inhibitor spirapril should be common, potential for spirapril to affect steady-state digoxin kinetics was studied. Fifteen healthy white male volunteers aged 22-42 and weighing 135-225 lbs took digoxin tablets 0.25 mg every 12 hours for 5 weeks. In crossover design, each also received spirapril or matching placebo capsules during weeks 1 and 2, or 4 and 5. Dosage of spirapril was increased from 12 mg to 48 mg once daily. Spirapril produced no significant effect on mean (+/- SD) serum digoxin concentration in the steady state, area under curve for 12 hours, peak digoxin level, time to peak, or urinary digoxin excretion over 12 hours. No change in renal or whole body digoxin clearance was seen. Unlike some other cardiovascular drugs, spirapril does not alter steady-state digoxin kinetics in healthy adults.

Administration, Oral↗

The effect of maternal hemodynamics on fetal growth in hypertensive pregnancies.

Seventy-six pregnancies in which hypertension complicated pregnancy before 28 weeks' gestation were studied. In 36, hemodynamics were characterized by increased cardiac output and low vascular resistance; in 32, hemodynamics were characterized by high resistance; in eight hemodynamics crossed over from high output to high resistance during pregnancy. High-resistance hypertension was associated with a mean birth weight 1058 gm less than that in the low-resistance group (p = 0.001). The reduction in birth weight was due to a 4-week difference in gestational age (p = 0.001) and lower percentile weights for gestational age, 19th versus 39th (p = 0.005). Infants in the crossover group had low percentile weights and a high rate of intrauterine fetal death.

Adult↗

Meningococcal infection: evidence for school transmission.

Intimate contacts of a patient with meningococcal disease are at greater risk of disease than the general population and are offered chemoprophylaxis in order to prevent secondary cases. School contact is not considered a risk factor unless a further case develops. Bacteriological sampling of contacts to identify potential sources of infection is not considered warranted. We have questioned these approaches and investigated the contacts of a 9-year-old child with meningitis caused by sulphonamide-sensitive Neisseria meningitidis group C. Household carriers were not identified but 7/34 classmates were carrying the index strain suggesting that transmission was occurring within this population. The current recommendations for prophylaxis are based on information gathered in socioepidemiological settings, and involving strains which differ from those now prevalent. Such extrapolations may not be justified and further microbiological studies seem warranted to re-examine meningococcal transmission and prophylaxis usage in school children.

Carrier State↗

Receptors for angiotensins I and II: their relevance to renal haemodynamics, blood pressure control and hind-limb blood flow.

The well established differential pulmonary handling of angiotensins I and II indicates the possibility that vascular receptors for the deca- and octa-peptides do not necessarily involve common sites in the renal vasculature either. Experimental findings involving haemodynamic changes within the kidney in anaesthetised and conscious sheep, with utilization of the angiotensins, and also of noradrenaline, are briefly presented; the implications of the intra-renal water and creatinine transfers are discussed, especially as they concern the possible location of angiotensin receptors in the renal blood vessels. Other aspects of the relationships between the peptides are also taken into account particularly with regard to a postulated angiotensin I [NaCl] dependent peritubular capillary antidiuretic action, angiotensin converting enzyme inhibition, Goldblatt clamp induced hypertension and blood flow through the hind-limbs.

Angiotensin I↗

An improved lidocaine infusion protocol for cardiac surgical patients.

A new protocol for lidocaine administration was tested to determine whether it would provide higher free and total serum lidocaine concentrations during and after weaning from cardiopulmonary bypass (CPB), without leading to accumulation toxicity, than those resulting from a conventional protocol (1.5 mg/kg loading dose bolus + 2 mg/min infusion rate). Ten elective adult cardiac surgical patients were studied. Ten seconds prior to aortic cross-clamp release (0 min), each patient received a lidocaine bolus (1.5 mg/kg) and simultaneous lidocaine infusion (5 mg/min for 1 hour, followed by 2 mg/min for 23 hours). Weaning occurred 20 to 30 minutes after cross-clamp release. Lidocaine levels were determined from arterial blood samples at 0, 10, 20, 30, and 60 minutes, and at 2, 4, and 24 hours postcross-clamp release. Compared with the conventional protocol, the new protocol showed a significant increase in mean total lidocaine concentration (P less than or equal to 0.02) at 30 and 60 minutes, and a significant increase in mean free lidocaine concentration (P less than or equal to 0.005) at 20, 30, and 60 minutes. No patient had toxic levels at 24 hours. Results of this study suggest that in patients undergoing cardiac surgery, a "5 + 2" mg/min infusion protocol is safe and superior to a conventional protocol in achieving therapeutic serum levels of free and total lidocaine.

Adult↗

Acute onset spinal muscular atrophy in siblings.

We describe two sisters who each presented in infancy with acute, severe, generalised weakness and are-flexia in association with an intercurrent infection. The clinical picture resembled acute polyneuritis, but EMG findings and the later clinical features were consistent with a diagnosis of spinal muscular atrophy. Although symptoms in SMA may be exacerbated by infection, immunisation or trauma, this unusual presentation of the condition in siblings suggests that this may constitute a genetically distinct subgroup of the disorder.

Acute Disease↗

Pelizaeus-Merzbacher disease: classical or connatal?

The clinical features and investigation results of 7 patients with Pelizaeus-Merzbacher disease (PMD) are described; one patient had a brain biopsy and two patients had an autopsy. This paper tries to differentiate the clinical features of the connatal and classical types of PMD. Transient stridor and nystagmus were early signs in both types of PMD. Our findings support the view that the more severe connatal form shows rapid neurological deterioration from an early age leading to death usually in the first decade. In younger patients in whom the evolution is still unclear, severe feeding problems and extrapyramidal features may suggest the connatal form. By contrast, in the classical form of PMD, cerebellar signs and cognitive deterioration are more prominent with a more slowly progressive course. Nuclear magnetic resonance imaging and brainstem auditory evoked potentials were very helpful in supporting the diagnosis of PMD either in a known affected family or in sporadic cases, but were not useful in distinguishing between the two types of PMD. Genetic counseling in this condition is difficult, particularly in the connatal form in which inheritance may be either X-linked or autosomal recessive.

Age Factors↗

Development of language in six hemispherectomized patients.

The development of language skills in the isolated right hemisphere was investigated by comparing the performance of 3 left hemispherectomized with that of the 3 right hemispherectomized patients and three groups of control subjects on baseline clinical measures of language and on production and judgement of morphological markers. The initial brain insult in the hemispherectomy patients of each group had occurred either during early, middle or late childhood. The left hemispherectomy patients were severely impaired in language processing across all three stages of language development. The consequences of a right hemisphere insult on language development were more restricted, with deleterious effects being apparent only in the case in which the lesion was acquired during early childhood.

Adolescent↗

Ankle mortise stability in Weber C fractures: indications for syndesmotic fixation.

A Weber type C ankle fracture was sequentially reproduced in 12 cadaver lower extremities and an external rotation torque was applied at each interval. The fractures were then repaired in staged fashion and the rotational stability of the mortise evaluated. Maximum external rotation of the talus within the mortise averaged 7.7 degrees in the intact ankle and increased by 311% to 31.8 degrees after creation of a Weber C injury. Rigid fixation of the fibular fracture restored 32% of the rotational stability, whereas isolated fixation of the medial malleolus reconstituted 57%. Fibular fixation combined with a syndesmotic screw restored 51% of original stability, and the addition of medial malleolar fixation improved stability to 101%. Bimalleolar fixation without a syndesmotic screw yielded 73% of the original rotational stability. The results of this study suggest that when rigid medial and lateral osteosynthesis can be achieved, syndesmotic fixation may not be necessary.

Ankle Injuries↗

Scleroderma 'en coup de sabre'.

A case of scleroderma 'en coup de sabre' presenting with uveitis, predominantly posterior, and intractable grand mal seizures is described. The histopathology specimens and neuroradiology investigations reaffirm the clinical impression that inflammation is not solely confined to the skin in this form of linear scleroderma.

Child, Preschool↗