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Biomedical subjects

J R Robinson

Publications and source records attributed to J R Robinson.

At least 55 records · Page 3Linked to original sources
PubMed1993

Factors predisposing to clinical disability in patients with cavernous malformations of the brain.

The factors predisposing to an aggressive clinical course in cavernous malformations of the brain are not known. Disabilities from neurological deficits and from seizures were assessed and graded in 84 patients harboring 100 cavernous malformations and were correlated with patient sex and age, lesion size, lesion location, lesion multiplicity, and previous overt hemorrhage. Univariate analysis showed that female sex, infratentorial lesion location, and previous gross hemorrhage were significantly associated with subsequent neurological disability. Logistic regression analysis showed that infratentorial lesion location and previous gross hemorrhage were independent factors simultaneously and significantly associated with neurological disability. Age less than 40 was the only significant factor predisposing to seizure disability (in both univariate and multivariate analyses). Lesion size, multiplicity, and other factors did not influence clinical disability. This information should assist in management decisions regarding cavernous malformations.

Adolescent↗
PubMed1993

Mixed vascular malformations of the brain: clinical and pathogenetic considerations.

The clinical relevance of any scheme for classification of vascular malformations of the brain remains controversial. Widely accepted pathologic classifications include discrete venous, arteriovenous, capillary, and cavernous malformations. Of 280 cases of possible vascular malformations evaluated by a single cerebrovascular service during a 5-year period, 14 were instances of mixed vascular malformations including definite features of more than one pathologically discrete type of malformation within the same lesion. There were six instances of mixed cavernous and venous malformations in the same lesion; in all instances, the cavernous malformation accounted for the clinical presentation. There were three cases of mixed venous and arteriovenous malformations (arterialized venous malformations), presenting with the typical histoarchitectural appearance of a venous malformation, but with arteriovenous shunting; all cases were symptomatic, two with hemorrhage and one with focal neurological symptoms. There were five cases of predominantly cavernous malformations with features of arteriovenous malformation or capillary telangiectasia in the same lesion. These five cases presented clinically as angiographically occult lesions indistinguishable from a cavernous malformation. Lesions including a venous malformation were recognizable preoperatively because of characteristic imaging features of the venous malformation. Other mixed vascular malformations were indistinguishable on diagnostic studies from pure cavernous malformations. Of the 14 mixed vascular malformations, 11 included a cavernous malformation that was usually responsible for the symptomatic presentation. In the other three cases, manifestations of clinical lesions were due to arteriovenous shunting within a venous malformation. We conclude that mixed vascular malformations of the brain are rare entities with distinct clinical, radiological, and pathological profiles. Their identification generates several hypotheses about common pathogenesis or causation-evolution among different types of lesions.

Adolescent↗
PubMed1993

Pathological heterogeneity of angiographically occult vascular malformations of the brain.

There is considerable confusion in the literature regarding the pathological substrates of angiographically occult vascular malformations (AOVMs) of the brain and their clinical significance. We retrospectively reviewed the cases of 34 consecutive patients with AOVMs undergoing surgical excision at a single institution during a 10-year period. Pathological specimens were reexamined, and the lesions were classified according to strict histopathological criteria. There were 21 cavernous malformations, 3 arteriovenous malformations, 3 venous malformations, 2 capillary malformations, and 5 mixed (pathologically heterogeneous) lesions. The initial pathological diagnostic report had been imprecise or had misidentified the lesion type in 18 of the 34 cases (53%), most commonly labeling a cavernous malformation as an arteriovenous malformation or not recognizing mixed features within the same lesion. Clinical presentation (including hemorrhage) and outcome were not significantly different among the various lesion types. Preoperative diagnostic imaging included a variety of modalities that were introduced or evolved during the period of the study and generally suggested a suspected vascular malformation but did not predict pathological subtypes. Acute hematomas in this surgical series made the identification of underlying vascular malformations highly speculative. We conclude that the majority of AOVMs requiring surgical intervention are cavernous malformations, although there was a notable pathological heterogeneity of the remaining lesions. Histopathological subtypes of AOVMs are not associated with unique clinical or radiographic features.

Adolescent↗
PubMed1993

Epidemiology of injuries associated with physical training among young men in the army.

It is widely acknowledged that musculoskeletal injuries occur as a result of vigorous physical activity and exercise, but little quantitative documentation exists on the incidence of or risk factors for these injuries. This study was conducted to assess the incidence, types, and risk factors for training-related injuries among young men undergoing Army infantry basic training. Prior to training we evaluated 303 men (median age 19 yr), utilizing questionnaires and measurements of physical fitness. Subjects were followed over 12 wk of training. Physical training was documented on a daily basis, and injuries were ascertained by review of medical records for every trainee. We performed univariate and multivariate analyses of the data. Cumulative incidence of subjects with one or more lower extremity training-related injury was 37% (80% of all injuries). The most common injuries were muscle strains, sprains, and overuse knee conditions. A number of risk factors were identified, including: older age, smoking, previous injury (sprained ankles), low levels of previous occupational and physical activity, low frequency of running before entry into the Army, flexibility (both high and low), low physical fitness on entry, and unit training (high running mileage).

Adult↗
PubMed1992

Drug delivery via the mucous membranes of the oral cavity.

The delivery of drugs via the mucous membranes lining the oral cavity (i.e., sublingual and buccal), with consideration of both systemic delivery and local therapy, is reviewed in this paper. The structure and composition of the mucosae at different sites in the oral cavity, factors affecting mucosal permeability, penetration enhancement, selection of appropriate experimental systems for studying mucosal permeability, and formulation factors relevant to the design of systems for oral mucosal delivery are discussed. Sublingual delivery gives rapid absorption and good bioavailability for some small permeants, although this site is not well suited to sustained-delivery systems. The buccal mucosa, by comparison, is considerably less permeable, but is probably better suited to the development of sustained-delivery systems. For these reasons, the buccal mucosa may have potential for delivering some of the growing number of peptide drugs, particularly those of low molecular weight, high potency, and/or long biological half-life. Development of safe and effective penetration enhancers will further expand the utility of this route. Local delivery is a relatively poorly studied area; in general, it is governed by many of the same considerations that apply to systemic delivery.

Administration, Buccal↗
PubMed1992

Transport of thyrotropin releasing hormone in rabbit buccal mucosa in vitro.

The transport of thyrotropin releasing hormone (TRH) in rabbit buccal mucosa in vitro has been investigated with respect to (a) rate and type of metabolism of TRH on mucosal and serosal sides of buccal mucosa, (b) mechanism of TRH transport including charge effect on its permeability, and (c) pathway and rate-limiting regions of TRH movement. In addition, the integrity of excised buccal mucosa has been evaluated for purposes of in vitro solute diffusion experiments using tissue ATP level data, transmission electron microscopy, and TRH transport kinetic data. The results indicate that excised rabbit buccal mucosa can be used for TRH diffusion studies for approximately 6 hr. In addition, TRH apparently traverses buccal mucosa by simple diffusion with a steady-state permeability of about 10(-7) cm/sec, and this permeability is independent of pH. Moreover, the primary pathway appears to be via the intercellular space in the rate-limiting barrier, i.e., the upper 50 microns of the epithelium. Finally, TRH is degraded predominantly by deamidase activity, which is followed by, to a lesser degree, carboxypeptidase metabolism.

Adenosine Triphosphate↗
PubMed1991

Anomalous molecular form of acetylcholinesterase in cerebrospinal fluid in histologically diagnosed Alzheimer's disease.

The possibility that the different molecular forms of acetylcholinesterase (AChE) in cerebrospinal fluid (CSF) which can be revealed by isoelectric focusing may reflect changes in AChE in pathologically affected neurons in Alzheimer's disease was tested in a retrospective study. CSF samples obtained at necropsy from 33 patients with clinically diagnosed dementia, 9 with possible dementia, and 19 without a diagnosis of dementia were examined by isoelectric focusing. An additional band indicating an anomalous molecular form of AChE was present in CSF from 19 of 23 patients with a histological diagnosis of Alzheimer's disease and no other central nervous system disorder but in none of the 19 non-demented patients (without a histological diagnosis of Alzheimer's disease). The band was also present in 2 of 8 patients with histologically defined Alzheimer's disease plus other neurological disorders and in 4 of 8 patients with possible dementia who did not meet histopathological criteria for Alzheimer's disease. The absence of the anomalous form of AChE from the CSF of non-demented patients and its presence in the CSF of the majority of patients with Alzheimer's disease has implications for our understanding of the biological basis of the disease and might form the basis of an antemortem diagnostic test.

Acetylcholinesterase↗
PubMed1991

Natural history of the cavernous angioma.

The incidence and natural history of the cavernous angioma have remained unclear in part because of the difficulty of diagnosing and following this lesion prior to surgical excision. The introduction of magnetic resonance (MR) imaging has improved the sensitivity and specificity of diagnosing and following this vascular malformation. Seventy-six lesions with an MR appearance typical of a presumed cavernous angioma were discovered in 66 patients among 14,035 consecutive MR images performed at the Cleveland Clinic between 1984 and 1989. Follow-up studies in 86% of the cases over a mean period of 26 months provided 143 lesion-years of clinical survey of this condition. The most frequent presenting features were seizure, focal neurological deficit, and headache. While most lesions exhibited evidence of occult bleeding on MR imaging, there was overt hemorrhage in seven of the 57 symptomatic patients and only one overt hemorrhage occurred during the follow-up interval. The annualized bleeding rate was 0.7%. Analysis of the hemorrhage group revealed a significantly greater risk of overt hemorrhage in females. Pathological confirmation of cavernous angioma was obtained in all 14 surgical cases. This information assists in rational therapeutic planning and prognosis in patients with MR images showing lesions suggestive of cavernous angioma.

Adolescent↗
PubMed1990

Bioadhesive polymers in peptide drug delivery.

A frequently encountered problem with the peptide-based drugs which are becoming available is that these agents must generally be administered by injection. There is therefore considerable research interest in alternative delivery routes, such as the buccal and nasal mucosae, and the conjunctiva. This paper reports some quantitative considerations of peptide delivery via the buccal, nasal, ocular and gastrointestinal routes, based on estimates of permeability coefficients and other necessary parameters. Rates of delivery and the resulting systemic levels are calculated for some peptide drugs, and compared to therapeutic levels: situations are identified in which bioadhesive formulations may be of benefit.

Adhesiveness↗
PubMed1990

The development of USP dissolution and drug release standards.

Dissolution tests have been in use in the pharmaceutical industry for over 20 years, and they are official in The United States Pharmacopeia since the early 1960s. The dissolution test, reviewed primarily as a quality control tool, replaced the use of disintegration tests which had been official in The United States Pharmacopeia since 1950. Refinements in the dissolution test equipment and methodology have occurred over the years in order to enhance its relevance. The Subcommittees of the USP Committee of Revision dealing with these issues have developed and refined compendial dissolution standards and policies for conventional solid-oral dosage forms and modified-release dosage forms.

Delayed-Action Preparations↗
PubMed1990

Increased tau messenger RNA in Alzheimer's disease hippocampus.

The microtubule-associated protein tau is present in the pathologic hallmarks of Alzheimer's disease and its production and deposition have been implicated in the pathogenesis of the disease. We detected tau mRNA using in situ hybridization histochemistry in the hippocampus, visual cortex, and cerebellum, and compared its level in Alzheimer's disease with controls. The amount of tau mRNA also was determined as a ratio of total polyadenylated mRNA in each area. A significant and gene-specific increase in tau mRNA hybridization was found in hippocampal fields CA4 and CA3, with a similar trend in the dentate gyrus. In contrast, no change was found in the visual cortex or cerebellum in Alzheimer's disease. Increased hippocampal expression of tau mRNA also was present in cases of non-Alzheimer's dementia. Enhanced tau mRNA may be a marker of attempted plasticity involving the cytoskeleton in neuronal populations affected by various neurodegenerative disorders.

Aged↗
PubMed1989

Comparison of different models for the testing of pilocarpine eyedrops using conventional eyedrops and a novel depot formulation (nanoparticles).

An objective in the development of ophthalmic formulations is the use of in vitro or animal models that closely resemble the clinical situation. For this reason, experiments with conventional pilocarpine nitrate eyedrops and a depot formulation of pilocarpine nitrate sorbed to poly (butylcyanoacrylate) nanoparticles were carried out. In vitro, the diffusion of pilocarpine through bovine cornea was measured using Edelhauser cells. In vivo, the rabbit aqueous humor concentration of pilocarpine and miosis were determined after application of the above formulations. In addition, intraocular pressure was measured. Since pilocarpine has little influence on intraocular pressure in healthy rabbits, the pressure had to be increased artificially. Three models were employed that are described in the literature, namely, the betamethasone model, the alpha-chymotrypsin model, and the water-loading model. Pilocarpine could be loaded onto nanoparticles by 15% but was rapidly released from the nanoparticles based on the bovine corneal experiment. Nanoparticles only enhanced the aqueous humor concentration at 30 min; this increase, however, led to a considerably extended period of miosis as well as a reduction in intraocular pressure. The duration of the action and the intensity of the response were different among the three models tested. According to the present results, the betamethasone model seems to represent the best correlation to the clinical situation.

Animals↗
PubMed1989

The natural history of mental disorder in old age. A long-term study.

In a prospective study, 153 consecutive new referrals to a psychogeriatrician in Oxfordshire in 1973 were followed up for 15 years. The percentage of the over-65 population at risk was 0.27 and, of those aged over 80, 0.6. Alzheimer's dementia and depressive illness comprised over two-thirds of referrals. A quarter became permanent admissions, half of them with Alzheimer's dementia, 19% of whom were alive five years later. Depressive illness, at ten years, had a mortality 1.2-1.6 times that of the population at risk. The distinction between Alzheimer's dementia and depressive illness, based on their natural history and causes of death, was reinforced.

Activities of Daily Living↗