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Biomedical subjects

R Howard

Publications and source records attributed to R Howard.

At least 181 records · Page 10Linked to original sources

A low cost system for performing CT stereotaxic brain biopsy.

The cost of commercially available CT-compatible frames for stereotaxic brain biopsy has limited their availability in the U.K. Our adaptation to a pre-CT stereotaxic frame that had been in use at Atkinson Morley's Hospital for 12 years, and the availability of a GE 9800 CT scanner has allowed us to carry out accurate CT-directed stereotaxic biopsy at minimal cost. The system has the additional advantage of speed and ease of use in inexperienced neurosurgical hands. Biopsies in 100 patients have been performed by 12 different surgeons (80% by registrars) who mastered the technique without difficulty. The rates of permanent morbidity (4%) and mortality (2%) are low, the two mortalities occurring in patients with high grade astrocytomas. They compare very favourably with rates for freehand burr-hole biopsy, and our overall diagnostic success rate of 83% for the initial biopsies, rising to 90% as a result of re-biopsy in 10 of the patients, is similar to that achieved with much more costly commercial systems. Benign lesions were found in 7% of patients who would otherwise have been assumed to have malignant tumours, and this finding emphasises the value of achieving a histological diagnosis in every lesion of the brain.

Biopsy↗

The plasma endorphin, prostaglandin and catecholamine profile of patients with fibrositis treated with cyclobenzaprine and placebo: a 5-month study.

During a 5 month, double blind crossover study of the clinical effect of cyclobenzaprine on 7 patients with fibrositis, weekly measurements were done of plasma beta-endorphin (endorphin, prostaglandin E (PGE) and catecholamines). Endorphin levels were normal but varied with tender point tenderness. Mean plasma dopamine and PGE were elevated. Norepinephrine was normal to very high while epinephrine levels were continuously low to normal. We conclude that patients with fibrositis have a neurotransmitter plasma profile like other chronic pain states having stress and increased vasomotor activity with the possible exception of having low circulating epinephrine. This disparity may mark a failure of central nervous system pain modulation in fibrositis.

Adult↗

A retrospective survey of treatment and mortality in aspiration pneumonia.

A retrospective survey was conducted of all patients with severe aspiration pneumonitis requiring artificial ventilation in our Intensive Care Unit from 1982-1986 inclusive. Of 38 patients, 8 (21%) died. Five of these deaths were due to severe primary intracranial pathology, and occurred after complete or almost complete resolution of the pneumonitis. One death (2.5%) due to myocardial infarction was possibly related to aspiration, and 2 deaths (5%) were definitely related to aspiration. The 7.5% mortality related to aspiration is considerably lower than in previous clinical studies of severe aspiration pneumonia. There was only one death due to aspiration in patients under the age of 70. The mean arterial to alveolar oxygen tension ratio was 0.221, and the mean predicted mortality by apache II was 43%. Patients were managed with rapid intravascular volume restoration using crystalloid fluids, early ventilation, no steroids, and no immediate antibiotics. We conclude that with such management it is possible to achieve a low hospital mortality in severe aspiration pneumonia, particularly in young patients.

Adult↗

Lung clearance of 99mTc-DTPA aerosol in conscious sheep.

This study was initiated to determine the rate and characteristics of 99mTc-DTPA clearance from the whole lung in a group of 9 sheep. Submicronic aerosol droplets were delivered to unsedated sheep held in a sling-like frame. Best fits for clearance curves to single- and biexponentials were calculated. The monoexponential T50 for the aerosol clearance was 293 min +/- 74 SD. Background correction was found to have a minimal effect (approx. 10%). Biexponential fitting only marginally improved correlations in the 8 healthy sheep, but in one additional animal with clinical evidence of pneumonia, clearance was faster and biexponential fitting was substantially better. These clearance values in conscious sheep are longer than previous findings with 99mTc-DTPA in anesthetized sheep. There appears to be a wide variation of radioaerosol 99mTc-DTPA lung clearances among different species, sheep exhibiting a comparatively prolonged clearance profile.

Administration, Inhalation↗

Bacterial overgrowth by indigenous microflora in the phytohemagglutinin-fed rat.

Phytohemagglutinin lectin (PHA) derived from red kidney bean (Phaseolus vulgaris) causes bacterial and protozoal colonization of the rat small intestine. To provide additional insights into this phenomenon we have studied the time course and population dynamics of microbial colonization of the major aerobe--facultative anaerobe groups which characterize this microflora. Compared with controls, PHA caused proliferation of a consistent adherent microbial flora in the jejunum (P less than 0.01). The predominant bacteria identified were Escherichia coli. a Streptococcal sp., and Lactobacillus. Escherichia coli isolates expressed no predominant serotype or fimbriae; none elaborated heat-labile or heat-stable toxin. Both E. coli and Streptococcal sp. populations increased within 24 h of PHA feeding and were sustained during further exposure to PHA (P less than 0.05). On reversion to a control diet, coliform counts fell progressively within 24-48 h and continued to decline, whereas gram-positive rod and coccus flora became the more prominent colonizers through days 1 to 4 of the reversion.

Animals↗

Clinical features of ischemia in cerebral arterial border zones after periods of reduced cerebral blood flow.

The clinical syndrome of border-zone ischemia is described in eight patients. Cerebral damage in four occurred during or after cardiac surgery and the other four patients had each experienced a period of severe hypotension. Cerebral blindness and visual disorientation are the most regular features and are produced by ischemic lesions in the parieto-occipital region, the common border-zone territory between all three arterial territories. Some patients show bibrachial sensorimotor impairment and a disturbance of volitional saccadic eye movement caused by more anteriorly placed ischemia in the anterior-middle artery border zone. Some show a temporary dyslexia/dysgraphia and memory defect related to bilateral parietotemporal lesions in the middle-posterior border zone.

Adult↗

Peroxidase-anti-peroxidase detection of hepatitis B surface and core antigen in liver biopsy specimens from patients with chronic type B hepatitis.

Liver biopsy specimens from 58 American patients with chronic type B hepatitis were investigated for the presence and distribution of the hepatitis B core (HBcAg) and surface (HBsAg) antigens by peroxidase-anti-peroxidase techniques. HBsAg was detected in 43 (77%) and HBcAg in 52 (90%) patients. HBcAg was present in 50 of 51 (98%) patients with hepatitis B e antigen (HBeAg) but in only two of seven (29%) of patients with antibody to HBeAg (anti-HBe). There was no correlation between severity of hepatitis or height of aminotransferase activities and the amount of HBsAg or HBcAg in hepatocytes but there was a positive correlation between amount of HBcAg and height of HBV-DNA and DNA polymerase activity in serum. Follow-up liver biopsies, taken 1 to 3 yr later, were available from 39 patients. HBcAg remained detectable in 25 of 26 patients with persistence of HBeAg but disappeared in 12 patients who had lost HBeAg. In nine patients, HBcAg was cytoplasmic as well as nuclear in distribution. Seven of these patients had an intense lobular hepatitis with marked elevations in aminotransferase activities. These findings indicate that the amount of HBcAg in liver correlates with the amount of serum hepatitis B virus as quantified by serum levels of DNA polymerase and HBV-DNA. The amount of nuclear HBcAg does not correlate with the severity of the liver disease, but the presence of cytoplasmic HBcAg usually reflects an active and severe ongoing hepatitis.

Adult↗

Murine neutrophil migration during the course of an intra-abdominal abscess.

Studies of neutrophil migration in heterogeneous groups of septic patients have reported elevated, normal, and depressed neutrophil mobility. This experiment, conducted in a standardized murine population, measured neutrophil migration under agarose during the course of a chronic intra-abdominal abscess initiated by cecal ligation. Compared with both control (unoperated) and sham celiotomy mice, those mice with an abdominal abscess showed elevations of 22% and 14% of directed and random migration, respectively, at 48 hours. They had 30% to 40% decreases in these functions at days 4 through 10. Murine neutrophil migratory response during the course of an intra-abdominal abscess consisted therefore of an early elevation followed by a prolonged depression. Such a biphasic response could underlie the variable findings of neutrophil studies in septic patients. This model could be further applied to the study of the effects of chemotherapy and immunologic adjuvants on abscess course and neutrophil function, as well as to the study of the mechanisms of neutrophil response to sepsis.

Abdomen↗

B ring regulation of colchicine binding kinetics and fluorescence.

Several properties of the colchicine-tubulin interaction such as association rate, reversibility, and the promotion of drug fluorescence have been related to the B ring of colchicine. The B ring itself retards the binding rate, and substitution at C-7 leads to further binding rate decreases that appear to be related to both substituent bulk and the presence of a N-acyl group. Thus, the decreasing order of binding rates is 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone greater than deacetamidocolchicine greater than deacetylcolchicine greater than or equal to colcemid greater than colchicine greater than N-benzoyldeacetylcolchicine, etc. The apparent irreversibility of the binding seems more closely related to the presence of an N-acyl group rather than the bulk of the substituent at C-7. Substitution at C-7 also affects the tropolone fluorophore. Thus, amines (deacetylcholchicine, colcemid, or N-methylcolcemid) fluoresce poorly in the presence of tubulin, whereas substitution of the amino group with an acyl group enhances fluorescence. The presence of an N-acyl group at C-7 is essential for enhanced fluorescence. We conclude that, in addition to A- and the C-ring portion of the molecule, the B ring of colchicine is a third determinant recognized by the binding site on tubulin.

Animals↗

Topical antimicrobial toxicity.

Three topical antibiotics and four antiseptics (1% povidone-iodine, 0.25% acetic acid, 3% hydrogen peroxide, and 0.5% sodium hypochlorite) were directly applied to cultured human fibroblasts to quantitatively assess their cytotoxicity. The four antiseptics were found to be cytotoxic; all of the cytotoxic agents except hydrogen peroxide were subsequently found to adversely affect wound healing in an animal model. Comparison of bactericidal and cytotoxic effects of serial dilutions of these four topical agents indicated the cellular toxicity of hydrogen peroxide and acetic acid exceeded their bactericidal potency. Bactericidal noncytotoxic dilutions of povidone-iodine and sodium hypochlorite were identified. These experiments provide evidence that 1% povidone-iodine, 3% hydrogen peroxide, 0.5% sodium hypochlorite, and 0.25% acetic acid are unsuitable for use in wound care. This sequence of experiments could be used to identify bactericidal, noncytotoxic agents prior to their clinical use.

Acetates↗

Neutrophil delivery to wounds of the upper and lower extremities.

Clinical observations and experimental evidence indicate that wounds of the lower extremity are more susceptible to infection than are wounds located elsewhere on the body. The details of this regional relative immunoincompetence are not described. In this initial study of regional inflammatory response, neutrophil delivery to standard wounds of the upper and lower extremities was measured in 15 human volunteer subjects using a quantitative skin-window technique. Neutrophil delivery proved to be relatively deficient in the lower extremity. Neutrophil delivery (mean +/- SEM) was significantly lower to the lower-extremity wounds (5,890 +/- 590 cells per cubic millimeter) than to the upper-extremity wounds (16,600 +/- 1,680 cells per cubic millimeter). This lower neutrophil response may be a part of the lower extremity's increased susceptibility to infection. Further functional study of regionally collected neutrophils may provide more details of differences in regional inflammatory response. The mechanisms underlying these differences remain undescribed.

Adult↗

Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate.

Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow-up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara-AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis.

Adult↗