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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 937 records · Page 52Linked to original sources

Toxic shock syndrome in three adolescent males.

Toxic shock syndrome (TSS) is associated with a spectrum of Staphylococcus aureus infections and is not just a disease of menstruating females. We report three cases of TSS in adolescent males. In one case the origin of infection was a cauterized wart that did not appear clinically infected. Two cases were associated with bacteremia and had demonstrable acute phase antibody to toxic shock syndrome toxin-1 (TSST-1). One of these patients died. The S. aureus strain from this patient did not produce TSST-1 but did produce enterotoxin D. The historical and clinical features of TSS are reviewed.

Adolescent↗

Gene amplification on chromosome band 11q13 and oestrogen receptor status in breast cancer.

We have analysed DNA from 183 primary breast cancers for amplification or rearrangement of a number of cellular proto-oncogenes, focusing primarily on a cluster of markers on the long arm of chromosome 11. Two of these oncogenes, INT2 and HST1, both of which encode members of the fibroblast growth factor family, are implicated in the generation of virally induced mammary tumours in mice. Here we confirm earlier reports that the q13 region of chromosome 11, in which these genes are tandemly linked, is modestly amplified in approximately 15% of primary human breast cancers. This amplification is confined, with one exception, to cases in which the oestrogen receptor (ER) levels are in excess of 20 fmol/mg protein (P = 0.001). However, DNA amplification does not usually result in detectable expression of either the INT2 or HST1 gene. The data imply that some other gene in the vicinity must contribute to the development of a subset of ER-positive tumours and that assessing the amplification of this region of DNA may be of value in defining a separate category of ER-positive tumour.

Adult↗

Antibiotic therapy for arterial infection: lessons from the successful treatment of a mycotic femoral artery aneurysm without surgical reconstruction.

A mycotic femoral artery aneurysm developed in a diabetic man with bacteremia from a Staphylococcus aureus urinary tract infection. Because of severe concomitant congestive heart failure and hypothyroidism, surgical reconstruction of the femoral artery was deferred while the patient received an intensive course of intravenous nafcillin. This led to stabilization of the size of the femoral aneurysm for two years, during which time it remained asymptomatic. Three such cases of nonsurgical treatment of a mycotic aneurysm have been documented. Surgical ligation, drainage, and bypass remain the mainstay therapies for mycotic aneurysms, but these cases demonstrate the possibility of sterilizing a primary arterial infection under the highly selected circumstances of an exquisitely sensitive organism, absence of periarterial abscess and readily observable anatomic location. Most importantly, these cases provide assurance that a six-week course of parenteral antibiotics is a reasonable adjunctive treatment for residual endovascular infection.

Aged↗

Banning alcohol in a major college stadium: impact on the incidence and patterns of injury and illness.

To evaluate the effect of banning alcohol on the incidence of injuries and illness among spectators, we reviewed 4 years (1983 to 1986) of medical incident reports from a major collegiate football stadium. At no time had alcoholic beverages been sold inside the stadium, but before 1985, fans were allowed to bring alcohol into the stadium. In 1985, this practice was banned. During the study period, 340 medical incidents (M = 12.6/game) were reported. Several alterations of specific injury/illness patterns were noted after initiation of the ban: heat-related illness occurred more frequently before initiation of the ban, whereas extremity injuries and syncope (fainting from coronary insufficiency) occurred with greater frequency afterwards. The injury/illness rates per 10,000 fans were 2.95 in 1983, 2.45 in 1984, 1.92 in 1985, and 3.48 in 1986. There was no significant change in the overall incident rate after the ban. Evaluation of medical incidents revealed an alteration in specific injury/illness patterns but no change in overall incidence after institution of the ban. Future investigations are needed to elucidate more clearly the impact of banning alcohol on injury/illness rates and patterns at mass gatherings.

Adolescent↗

Appendicular skeletal muscle mass: measurement by dual-photon absorptiometry.

Dual-photon absorptiometry (DPA) allows separation of body mass into bone mineral, fat, and fat-free soft tissue. This report evaluates the potential of DPA to isolate appendages of human subjects and to quantify extremity skeletal muscle mass (limb fat-free soft tissue). The method was evaluated in 34 healthy adults who underwent DPA study, anthropometry of the limbs, and estimation of whole-body skeletal muscle by models based on total body potassium (TBK) and nitrogen (TBN) and on fat-free body mass (FFM). DPA appendicular skeletal muscle (22.0 +/- 3.1 kg, mean +/- SD) represented 38.7% of FFM, with similar proportions in males and females. There were strong correlations (all p less than 0.001) between limb muscle mass estimated by DPA and anthropometric limb muscle areas (r = 0.82-0.92), TBK (r = 0.94), and total-body muscle mass based on TBK-FFM (r = 0.82) and TBK-TBN (r = 0.82) models. Appendicular skeletal muscle mass estimated by DPA is thus a potentially practical and accurate method of quantifying human skeletal muscle mass in vivo.

Absorptiometry, Photon↗

The operative management of basilar impression in osteogenesis imperfecta.

Four patients with osteogenesis imperfecta and neurologically significant basilar impression have been treated over the past 8 years. The experience has resulted in changes in our therapeutic strategy for this particularly difficult problem. These cases are discussed with respect to the disease process, neurological involvement, radiological findings, and modes of surgical therapy. The errors in management as well as the success resulting from our learning experience are described. Currently, we recommend the extensive removal of the anterior bony compression by a transoral approach. This should be followed by a posterior rigid fixation that transfers the weight of the head to the thoracic spine, in an effort to prevent further basilar invagination.

Adult↗

An approach to organ salvage from non-heartbeating cadaver donors under existing legal and ethical requirements for transplantation.

Effective utilization of nonheartbeating cadaver donor organs is limited by the time required to obtain the necessary family consent prior to organ retrieval (a delay of at least 4-6 hr); this exceeds by far the maximum tolerance of kidneys to warm ischemia. Measures that could theoretically permit use of such organs include: (1) rapid in situ flush cooling; (2) continued in situ kidney cooling until permission for donation is secured; and (3) cell-membrane stabilization of vital organs, with only minimal invasion of the donor body. These measures were tested experimentally in dogs. Hemorrhagic shock was produced in mongrel dogs. One hour after cessation of heartbeat, a rapid perfusion tube was placed into the femoral artery; it was advanced, and its balloon was inflated in the aorta above the renal vessels. The kidneys were then flushed in situ with 1000 cc of cold preservation solution containing a calmodulin inhibitor, trifluoperazine. Two other catheters were inserted percutaneously into the peritoneal cavity for continuous intraperitoneal cold perfusion. Core temperatures of 4 degrees C were maintained in situ in the kidneys for 5 hr. Six hours after cardiac arrest, the kidneys were removed and preserved ex vivo at 4 degrees C for 24 hr, and were then transplanted into their respective hosts (n = 11), where they sustained life uneventfully. This method requires a 2-inch incision in the groin of the prospective donor, and two small stab wounds of the abdomen; i.e., semi-invasive procedures which are commonly performed in emergency rooms. The perfused body could then be released to the family if donation is denied. The recently documented increased willingness of the public to donate organs when the termination of life support is not an issue, and court decisions that have authorized the performance of nondeforming diagnostic procedures in cadavers without consent, suggest that the salvage of transplantable semi-invasive procedures described in this study may be useful in helping to alleviate the current shortage of transplantable organs. This technique can provide the time needed for families to consider the option of organ donation from nonheartbeating cadaver donors in an unhurried and unpressured manner, while preserving the viability of vital organs during the decision-making process.

Animal Experimentation↗

Terfenadine, a potent histamine H1-receptor antagonist in the treatment of grass pollen sensitive asthma.

1. We have assessed the effect of a specific histamine H1-receptor antagonist, terfenadine, in the treatment of atopic asthmatics during the grass pollen season. 2. Eighteen mild, grass pollen sensitive asthmatics (10F, 8M, mean +/- s.e. mean age 34.7 +/- 5.6 years), all of whom were controlled on inhaled beta 2-adrenoceptor agonists alone, took part in a 9 week, double-blind, crossover study using terfenadine 180 mg three times daily and placebo. Throughout the study patients recorded peak expiratory flow rate (PEFR) twice daily, symptoms of cough, wheeze, breathlessness and chest tightness (scored 0-3), and their use of bronchodilators. Methacholine inhalation challenge tests were performed each week. Data were analysed by a method suitable for a two group, two period crossover trial with baseline measurements. 3. Terfenadine significantly reduced symptoms of cough by 76.9% (P less than 0.05) and wheeze by 46.9% (P less than 0.02). Symptoms of breathlessness and chest tightness were reduced by 16.8 and 30.3% respectively but these were not statistically significant. Morning and evening PEFR rose by 5.5 (P less than 0.001) and 6.2% (P less than 0.003) respectively on treatment with terfenadine and bronchodilator use fell by 40.3%. A progressive increase in methacholine sensitivity was seen in both treatment groups throughout the study but did not reach statistical significance. 4. We conclude that treatment with terfenadine during the grass pollen season in sensitive asthmatics reduced their symptoms and bronchodilator requirements and produced a modest improvement in their lung function without affecting the development of increased methacholine sensitivity that occurred during the grass pollen season.

Adult↗

Shark myelin basic protein: amino acid sequence, secondary structure, and self-association.

Myelin basic protein (MBP) from the Whaler shark (Carcharhinus obscurus) has been purified from acid extracts of a chloroform/methanol pellet from whole brains. The amino acid sequence of the majority of the protein has been determined and compared with the sequences of other MBPs. The shark protein has only 44% homology with the bovine protein, but, in common with other MBPs, it has basic residues distributed throughout the sequence and no extensive segments that are predicted to have an ordered secondary structure in solution. Shark MBP lacks the triproline sequence previously postulated to form a hairpin bend in the molecule. The region containing the putative consensus sequence for encephalitogenicity in the guinea pig contains several substitutions, thus accounting for the lack of activity of the shark protein. Studies of the secondary structure and self-association have shown that shark MBP possesses solution properties similar to those of the bovine protein, despite the extensive differences in primary structure.

Amino Acid Sequence↗

An investigation into the mechanism of protection by local passive immunization with monoclonal antibodies against Streptococcus mutans.

Local oral passive immunization with Streptococcus mutans-specific monoclonal antibody (MAb) (Guy's 13) prevented recolonization by indigenous S. mutans in human volunteers who had first been treated with a conventional antibacterial agent (chlorhexidine). The F(ab')2 fragment of the MAb was as protective as the intact immunoglobulin G, but the Fab fragment of the molecule failed to prevent recolonization of S. mutans. In subjects receiving the MAb Fab fragment, S. mutans levels in dental plaque and saliva reappeared at a similar rate to that found in sham-immunized subjects who received either saline or a nonprotective MAb. In vitro, MAb had no bacteriostatic or bacteriocidal effect on S. mutans. However, S. mutans grown in the presence of either intact immunoglobulin G MAb or the F(ab')2 fragment formed very long chains, which resulted in clumping of the cells. S. mutans grown with either saline or the MAb Fab fragment formed significantly shorter chains, more characteristic of streptococcal growth in liquid media. The results suggest that the two binding sites of the MAb molecule may be an essential feature for preventing streptococcal colonization but that the ability to bind to phagocytes and activate complement which resides in the Fc fragment is not essential. Protection against colonization by S. mutans lasting up to 2 years was observed in immunized subjects, although MAb was applied over a period of only 3 weeks. Furthermore, functional MAb was detected up to 3 days following application of MAb to the teeth. The long-term protection could not be accounted for by a persistence of MAb on the tooth surface, and we have suggested that it may be due to a shift in the balance of the oral flora which discouraged recolonization by S. mutans. However, examination of the proportions of Streptococcus sanguis and veillonella species in the recolonization experiments failed to reveal a significant change in the proportions of either organism, which returned to approximately the preexperimental levels in both the immunized and control groups. These findings confirm the in vivo functional specificity of the MAb to S. mutans but are not consistent with the suggestion that S. sanguis or veillonella take over the niche vacated by S. mutans, unless the shift in the proportion of these organisms cannot be detected by the method used.

Adult↗

Ability of mononuclear phagocytes from cattle naturally resistant or susceptible to brucellosis to control in vitro intracellular survival of Brucella abortus.

The role of bovine mammary macrophages and peripheral blood monocyte-derived macrophages in natural resistance to bovine brucellosis was evaluated. A group of 11 naturally resistant and 10 chronically infected susceptible cows was studied following challenge with Brucella abortus. Macrophages from a greater proportion (P less than 0.026) of naturally resistant cows were significantly superior to macrophages from susceptible cows in their ability to inhibit the in vitro intracellular replication of B. abortus after challenge exposure. Studies of a second group of cows used mammary macrophages from 12 heifers and blood monocyte-derived macrophages from 22 bulls and heifers. These tests were completed before exposure to B. abortus, using mammary macrophages (P less than 0.039) and blood monocyte-derived macrophages (P less than 0.045), and also showed that macrophages from naturally resistant cattle were significantly superior in their ability to control the in vitro intracellular replication of B. abortus. Our data indicate that the mononuclear phagocytes from more than 80% of the resistant cattle controlled intracellular replication of B. abortus significantly better than did mononuclear phagocytes from susceptible cattle. Mononuclear phagocyte function appears to be an important factor in determining natural resistance to bovine brucellosis.

Animals↗

Proviral insertions within the int-2 gene can generate multiple anomalous transcripts but leave the protein-coding domain intact.

We examined the effects of mouse mammary tumor virus integration on the multiple RNA transcripts expressed from the int-2 proto-oncogene in virally induced breast tumors. Proviral insertion either upstream or downstream of the gene could simultaneously activate transcription from three dissimilar int-2 promoters. In some tumors, the activating provirus lies within the transcription unit and disrupts the structures of the various RNAs. Insertions in the 5' region of the gene had complex effects depending on the orientation and position of the provirus relative to the three promoters and intron-exon boundaries. RNase protection experiments identified transcripts initiated in the viral long terminal repeat, at normal and cryptic sites in the int-2 sequences, and from cryptic promoters in an inverted provirus. AT the 3' end, insertions occurred within the untranslated trailer and provided alternative termination signals that substituted for one or both of the normal the poly(A) addition sites. However, in no instance, of the 20 tumors analyzed in detail, did a provirus perturb the presumed open reading frame of the gene. These data strongly implicate the normal product of the int-2 gene, which is related to the fibroblast growth factor family, as a contributory factor in virally induced mammary tumors.

Animals↗

Photic sneezes.

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Humans↗