Search PubMed⌕ Search

Biomedical subjects

J H Anderson

Publications and source records attributed to J H Anderson.

At least 19 recordsLinked to original sources
PubMed1995

Determination of nitrosourea compounds in brain tissue by gas chromatography and electron capture detection.

A relatively simple, high-sensitivity gas chromatographic assay is described for nitrosourea compounds, such as BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] and MeCCNU [1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea], in small biopsy samples of brain and other tissues. After extraction with ethyl acetate, secondary amines in BCNU and MeCCNU are derivatized with trifluoroacetic anhydride. Compounds are separated and quantitated by gas chromatography using a capillary column with temperature programming and an electron capture detector. Standard curves of BCNU indicate a coefficient of variance of 0.066 +/- 0.018, a correlation coefficient of 0.929, and an extraction efficiency from whole brain of 68% with a minimum detectable amount of 20 ng in 5-10 mg samples. The assay has been facile and sensitive in over 1000 brain biopsy specimens after intravenous and intraarterial infusions of BCNU.

Animals↗
PubMed1995

Case study: fluoxetine in the multimodal treatment of a preschool child with selective mutism.

Selective mutism is a rare disorder with poor treatment outcome. The current study describes the successful treatment of selective mutism in a preschool-age girl, using a comprehensive multifaceted therapeutic approach. The components of this intervention reflect a conceptualization of selective mutism that emphasizes anxiety as a core feature but also focuses on associated factors such as oppositional behaviors.

Anxiety Disorders↗
PubMed1995

Role of atrial contraction in diastolic pressure elevation induced by rapid pacing of hypertrophied canine ventricle.

The mechanism of diastolic pressure elevation induced by acute rapid pacing in pressure-load hypertrophied left ventricles (LVs) remains incompletely understood. It has been ascribed to abnormalities of coronary flow, metabolism, and calcium cycling. However, rapid pacing also alters the timing of atrial and ventricular stimulation relative to the diastolic filling period, and this could also influence diastolic pressures. To test the role of such mechanical factors, LV pressure-volume hemodynamics were measured in closed-chested anesthetized dogs during and after abrupt cessation of rapid atrial pacing. Twenty-one dogs were studied: 6 dogs with LV hypertrophy (LVH) induced by perinephritic hypertension, 5 sham-operated normotensive dogs, and 10 acute normotensive control dogs. In LVH dogs, but not in sham-operated or control dogs, end-diastolic pressure rose progressively with increasing heart rate from 5.6 +/- 3.1 mm Hg at baseline to 22.6 +/- 8.1 mm Hg at 220 beats per minute. In all hearts, rapid pacing shifted the timing of left atrial contraction so that it occurred near the onset of LV filling rather than at end diastole. However, in LVH hearts, early LV diastolic pressure and peak atrial pressure were also markedly elevated. Most striking, immediately after terminating the pacing, diastolic pressure declined to near baseline. This rapid pressure decline occurred just when atrial systole would have ensued and before ventricular activation would have followed had pacing continued. Thus, diastolic pressure elevation resolved before a change in ventricular pacing rate. The role of atrial contraction was further explored by simultaneous atrioventricular pacing. This shifted the time of atrial systole so that it occurred during LV isovolumic contraction, while maintaining the identical LV pacing rate. This change eliminated the diastolic pressure elevation found previously. Further analysis revealed that the pressure increase during rapid pacing was not due simply to partial LV filling imposed on a relaxing ventricle or to hypertension or an intact pericardium. These data indicate that mechanical effects of atrioventricular interaction play an important role in tachycardia-induced diastolic dysfunction in this model of LVH and can be more causative than ischemia or metabolic factors in this setting.

Animals↗
PubMed1995

Vestibular and sensory interaction deficits assessed by dynamic platform posturography in patients with multiple sclerosis.

Vestibular impairments have not been routinely identified in patients with multiple sclerosis (MS), because of the confounding effects of deficits in other neural systems. In this study, 35 patients with MS were evaluated by means of a systematic alteration of the sensory environment (dynamic posturography) in order to identify those patients who became unstable when vestibular inputs were needed to maintain stance. Subjects were assigned to either a high-function (HF) or a low-function (LF) group on the basis of a functional status assessment score obtained prior to the posturography test. For the HF group, 30% (7/23) had abnormal posturography scores. Of those subjects, 3 had a vestibular dysfunction pattern or a somatosensory-vestibular impairment. In contrast, 58% of the LF group (7/12) had abnormal posturography scores. Nearly all of these LF patients (6/7) had a vestibular dysfunction pattern or a combined visual-vestibular or somatosensory-vestibular impairment. Posturography might serve as one method to evaluate the functional consequences of a vestibular deficit in patients with MS.

Adult↗
PubMed1992

Elective versus emergency surgery for patients with colorectal cancer.

A prospective study of 570 patients presenting with colorectal cancer over a 6-year period was undertaken. Of these, 363 were admitted electively and 207 presented as emergencies. The outcome following elective admission was more favourable than after emergency admission. In the elective group the proportion of resected tumours was greater (77 versus 64 per cent, P less than 0.001), the operative mortality rate lower (9 versus 19 per cent, P less than 0.001) and the 5-year disease-related survival rate higher (37 versus 19 per cent, P less than 0.001). These differences may relate to the greater resection rates in the elective situation. Results of surgical intervention might be improved if emergency colorectal operations were undertaken by surgeons with more experience of this type of surgery.

Aged↗
PubMed1992

Glass yttrium-90 microspheres for patients with colorectal liver metastases.

Total calculated uniform liver doses of up to 150 Gy were achieved using glass yttrium-90 microspheres administered via the hepatic artery and targeted to tumour using angiotensin II in seven patients with colorectal liver metastases. No toxicity was observed. Hepatic metastatic progression was delayed in six patients. Median survival was 11 months (range 5-25 + months).

Angiotensin II↗
PubMed1992

A phase I study of regional 5-fluorouracil and systemic folinic acid for patients with colorectal liver metastases.

A phase I study was undertaken in order to establish the maximum tolerated dose of intra-hepatic arterial 5-fluorouracil (5-FU) when given in combination with systemic folinic acid. Patients with colorectal liver metastases (n = 10) received escalating doses of 5-FU as a 24 h infusion with a fixed dose (400 mg m-2) of intravenous folinic acid once per week. Dose limiting toxicity (WHO grade greater than 2) was encountered at 2 g m-2 5-FU. Principal adverse effects were diarrhoea, vomiting and oral ulceration. The recommended dose for phase II studies is 1.5 g m-2 week-1 24 h 5-FU regional infusion with 400 mg m-2 week-1 intravenous folinic acid.

Aged↗
PubMed1992

Is there a relationship between regional microsphere distribution and hepatic arterial blood flow?

The relationship between hepatic arterial albumin microsphere distribution and hepatic arterial blood flow and the effects of regional angiotensin II were studied in a rat liver metastases model. Hooded-Lister rats were inoculated subcapsularly with 2 x 10(6) HSN sarcoma cells. At 20 days, hepatic arterial blood flow was measured using the reference microsphere technique. Animals then randomly received 50 microliters hepatic arterial saline or albumin microspheres (40 microns, 20 mg ml-1). Hepatic arterial blood flow measurements were then repeated at 5 min. After 5 min, animals were killed and tissues were weighed and counted in a gamma well counter. There were no significant differences between the hepatic blood flow measurements recorded before and after the control hepatic arterial saline infusion. However, regional albumin microspheres produced a significant reduction in tumour and normal liver blood flow and an 80% reduction in mean T/N blood flow ratio. Regional albumin microspheres were delivered to tumour in greater proportions (mean T/N ratio 3.89, SE 0.49) than would be expected from baseline hepatic arterial blood flow (mean T/N ratio 1.28, SE 0.22. P = 0.006). There was no correlation between T/N for baseline blood flow and albumin microsphere distribution.

Animals↗
PubMed1992

A pharmacokinetic comparison of intravenous versus intra-arterial folinic acid.

Recent clinical trials have suggested that a combination of folinic acid and 5-fluorouracil (5-FU) may improve response rates and survival in patients with advanced colorectal cancer. However, this regimen has been complicated by potentially life threatening toxicity. Regional delivery of folinic acid via a hepatic artery catheter might be expected to reduce systemic exposure and subsequent adverse effects. The present study compared the pharmacokinetic profiles of intravenous and intra-hepatic arterial infusions of folinic acid in patients with colorectal liver metastases (n = 6) who were being treated with weekly regional infusions of 5-FU. The mean area under the plasma concentration--time curve, the peak plasma concentration and the steady state volume of distribution were 163 micrograms ml-1 h-1 (SD 41), 18.5 micrograms ml-1 (SD 1.2) and 7.41 m-2 (SD 0.44) respectively following intravenous administration of folinic acid compared with 142 micrograms ml-1 h-1 (SD 45), 14.8 micrograms ml-1 (SD 2.4) and 11.21 m-2 (SD 1.22) following intra-hepatic arterial administration (P less than 0.05). Regional folinic acid was therefore associated with a statistically significant reduction in systemic exposure compared with the intravenous route.

Adenocarcinoma↗
PubMed1992

Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II.

Many colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We have previously shown that hepatic arterial vasoconstrictors may increase drug delivery to liver tumours, but the underlying haemodynamic changes have not been defined. Using intraoperative laser Doppler flowmetry (LDF) we have assessed the effect of intraarterial angiotensin II (AI) on tumour blood flow in ten patients with colorectal liver metastases. Measurements were performed during placement of infusion catheters for regional chemotherapy. Blood flow was recorded continuously with a Periflux PF3 perfusion monitor via a probe held on the tumour surface, following hepatic arterial infusion of 15 micrograms AII over 90 s. Six patients with isolated small metastases (< 5 cm in diameter) showed increases in flow, which reached a peak at 170-240 s from the start of AII infusion, and which were closely correlated with the corresponding increase in arterial pressure (r = 0.92, P = 0.009). Of the four patients with large confluent tumour deposits, two showed smaller transient increases in flow over the first 60 s of AII infusion and two had no measurable flow response. Increased blood flow following AII infusion may increase the exposure of tumour to therapeutic agents. This study suggests that both tumour size and the effect upon systemic arterial pressure may be important determinants of the blood flow response to AII. LDF may provide useful information about the potential of AII and other vasoconstrictors to enhance targeting precision.

Angiotensin II↗
PubMed1992

Brainstem Fos expression following acute unilateral labyrinthectomy in the rat.

Detection of Fos protein expression with a polyclonal antibody was used to identify brainstem neurons responding to acute (24 h) effects of a unilateral sodium arsanilate chemical labyrinthectomy in Long-Evans rats. Asymmetrical expression was apparent in the medial and inferior vestibular nuclei, the prepositus hypoglossi, the dorsolateral central gray, and the inferior olivary beta subnucleus. These data suggest different distributions of neural activation compared with previous electrophysiological and 2-deoxyglucose results. In addition, there was some Fos expression bilaterally in the olivary dorsomedial cell column, interstitial nucleus of Cajal and the Darkschewitsch nucleus. These results support the concept of multiple systems participating in vestibular compensation and further define some specific nuclei involved in the acute stage.

Animals↗
PubMed1992

Transient diaphyseal tibial Tc-99m MDP uptake and bone marrow edema in acute rheumatic fever.

The authors describe a patient with acute rheumatic fever and polyarthritis in whom scintigraphy unexpectedly identified Tc-99m MDP uptake in the diaphyses of both tibiae. A dramatic rise in antistreptolysin-O titer and rapid resolution of tibial abnormalities paralleled marked articular improvement. Magnetic resonance imaging demonstrated a pattern consistent with marrow edema in the area of abnormal Tc-99m MDP accumulation. This finding has not been previously described in acute rheumatic fever, and it was suspected that the changes in the tibiae resulted from subclinical diaphyseal hyperemia from the inflammatory process observed in the contiguous joints.

Acute Disease↗
PubMed1992

Animal rights and research: common sense must prevail.

The advances that radiologic science has experienced in recent history have been earned through many means, one of them being animal research. Since the 1980s, animal research has come increasingly into the public eye, through the efforts of animal welfare and animal rights activist groups. These groups, by their varied means, have exacted changes in how animals are used experimentally and how the public perceives such use. In some cases, their lobbying efforts have resulted in laws that raise the cost of research and provide little improvement in animal welfare. Because of the financial and political power of these groups and the increasing public awareness of such issues, it is extremely important that the medical and scientific communities become more involved in educating the public on the importance of animal research and clarifying the difference between animal welfare and animal rights. Equally important, the medical community must continue to adhere to high standards in research that involves animals.

Animal Welfare↗
PubMed1992

In vivo evaluation of iophendylate-cyanoacrylate mixtures.

Cyanoacrylate glue is a rapidly polymerizing agent used for vascular embolization. Polymerization occurs when the glue comes into contact with ions in the blood or on the vascular endothelium. Mixing iophendylate with cyanoacrylate causes slowing of polymerization, allowing flow-directed embolization into the nidus of an arteriovenous malformation (AVM) or the central neovascularity of a tumor or hemangioma. The authors attempted to define the relationship between the iophendylate-glue ratio and polymerization time with an in vivo swine model. In this model, glue setup occurred much more rapidly than predicted on the basis of in vitro studies. This appeared to be due to glue polymerizing on the endothelium at vessel bifurcations and at areas of acute angulation or marked vessel narrowing. On the basis of these data, the authors substantially increased the iophendylate-glue ratio in their most recent AVM embolization procedures and achieved nidus occlusion in each case. With use of the authors' guidelines, it is possible to achieve optimal distal flow-directed embolization with cyanoacrylate.

Angiography↗
PubMed1992

Gravimetric measurements of cerebral edema in a rabbit brain tumor model.

The development of tumor-induced cerebral edema was studied in rabbits to establish a data base for future work using this brain tumor model to correlate the degree of edema with other functional and morphological parameters. The VX-2 carcinoma was implanted into the brains of New Zealand White rabbits. Animals were killed 9 and 13 days later, and gravimetric analysis was used to measure the specific gravity of gray and white matter in both the tumor-bearing implanted and contralateral nonimplanted hemispheres. Studies were conducted in untreated tumor-bearing rabbits as well as in those receiving dexamethasone daily for 4 days before death. Tumor tissue and peritumoral gray and white matter and contralateral gray and white matter were analyzed. In all cases, at both 9 and 13 days after tumor cell implantation, tumor tissue exhibited extremely high specific gravity values exceeding the range detectable by the assay procedure. Compared with controls, specific gravity values in tumor-bearing animals generally increased in gray matter and decreased in white matter as a function of tumor growth. This trend was seen in both peritumoral gray and white matter as well as in contralateral gray and white matter areas. However, in most cases, the changes in specific gravity values as compared with controls were not statistically significantly different. The primary exception to this was in peritumoral white matter, in which mean specific gravity values at both 9 and 13 days after implantation were statistically significantly lower than for the corresponding site in control non-tumor-bearing animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Biosynthetic human proinsulin. Review of chemistry, in vitro and in vivo receptor binding, animal and human pharmacology studies, and clinical trial experience.

OBJECTIVE: To describe the rationale for the preclinical and clinical developmental course of human proinsulin (HPI), the second product after human insulin for the treatment of diabetes mellitus to be manufactured by DNA technology. RESEARCH DESIGN AND METHODS: The relevant and available published and unpublished preclinical and clinical information generated on pork proinsulin and human proinsulin has been integrated to demonstrate how certain clinically attractive features of pork proinsulin (a soluble intermediate-acting and possibly hepatospecific insulin agonist) led to the development of HPI. RESULTS: Clinical pharmacology studies demonstrated that HPI was definitely, although marginally, hepatospecific. More striking was the finding that the intrasubject/patient coefficient of variation of response to HPI was significantly less than that observed with NPH insulin. However, the fact that unique efficacy in controlled multicenter studies was not demonstrated suggested that these pharmacological features were not translated into clinical benefit. In one multicenter new patient study there were six myocardial infarctions, including two deaths, in patients treated for greater than or equal to 1 yr with HPI and none in the control group. CONCLUSIONS: To obtain an independent review of the risks and benefits of HPI, in February 1988, Lilly convened a consultant group that examined all relevant information on HPI available. These experts shared our concerns about the safety of HPI in light of the failure to demonstrate unique efficacy. Accordingly, clinical trials with HPI were suspended in February 1988. Experience with HPI demonstrates the challenge associated with the development of new drugs in general and insulin agonists in particular.

Amino Acid Sequence↗