Biomedical subjects
Publications and source records attributed to R Smith.
Markedly increased periarticular Tc-99m diphosphonate uptake around the knee is described in a patient found to have synovial chondromatosis. The pathophysiology and possible causes of bone tracer uptake in this cartilaginous disorder are discussed.
The effect of pretreatment with biosynthetic methionyl human GH (hGH) on the GH response to GHRH has been studied in normal subjects. Eight volunteers were given either 4 IU hGH or placebo s.c. 12-hourly for 72 h before a GHRH test, or a single s.c. dose of 4 IU hGH 12 h before a GHRH test. Somatomedin-C (Sm-C) levels at the time of the GHRH tests were significantly elevated after treatment with hGH compared to placebo, and the GH response to GHRH was significantly attenuated. A further six subjects were given 2 IU hGH or placebo i.v., and i.v. GHRH 3 h later; there was no rise in Sm-C for the 5 h of the study after either treatment; nevertheless, the response to GHRH was completely abolished by pretreatment with hGH. These results demonstrate that GH can regulate its own secretion independently of changes in Sm-C levels, through a mechanism other than the inhibition of GHRH release. The attenuated response to GHRH in the presence of elevated Sm-C levels may be related to Sm-C, or be a more direct effect of the recently elevated GH levels.
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The nature of the determinants recognized by a panel of monoclonal antibodies (MAbs) raised against a cell wall antigen of Streptococcus mutans (SA I/II) was investigated. Mild periodate oxidation of SA I/II showed that MAbs Guy 1, 2, 3, and 5 recognized carbohydrate epitopes on the antigen. Glycosidases were used to identify the nature of the sugars involved in their binding. Treatment with beta-glucosidase inhibited the binding of Guy 1, 2, 3, and 5 by 90%. No competition was found for any of the MAbs between SA I/II and a series of carbohydrates, including the serotype c polysaccharide from S. mutans. The results show that MAbs Guy 1, 2, 3, and 5 recognize carbohydrate epitopes on SA I/II which are distinct from the serotype polysaccharide. The other MAbs recognized protein epitopes on SA I/II.
Local passive immunization with monoclonal antibodies (MAbs) raised against streptococcal antigen (SA) I/II protects monkeys against colonization of teeth by Streptococcus mutans and the subsequent development of dental caries. In this study we extended the preclinical experiments to human subjects. In the first study of eight healthy subjects, four had anti-SA I/II MAb (immunoglobulin G2a [IgG2a]) and four had saline applied to their teeth on three occasions. A streptomycin-resistant S. mutans strain (Guy K2 strain, serotype c) was then implanted onto the teeth, and the organism was cultured sequentially from dental plaque and saliva up to 100 days after the first treatment with MAb. Decreased colonization by S. mutans was found in the dental plaque collected from smooth surfaces and fissures and in saliva of subjects whose teeth were treated with the MAb, as compared with the saline-treated control subjects. The experiment was then repeated on seven new subjects, and the effect of anti-SA I/II MAb was compared with that of an unrelated MAb to Campylobacter jejuni. The results again showed a consistently lower level of colonization of teeth in the anti-SA I/II MAb-treated subjects as compared with those sham immunized with the unrelated MAb. There was little difference in serum IgG, IgM, or IgA, gingival fluid IgG, or salivary IgA anti-SA I/II antibodies between the immunized and sham-immunized subjects, before and after the investigation. No side effects were observed, and the gingival and plaque indices remained unchanged. A sensitive radioimmunoassay failed to detect changes in anti-MAb (IgG2a) antibodies in any of the three fluids examined. We suggest that local passive immunization by means of MAb might be an alternative approach in the prevention of colonization of teeth by S. mutans and the development of dental caries.
We sequenced two recombinant DNA clones constituting a single provirus of the milk-transmitted mouse mammary tumor virus characteristic of BR6 mice. The complete provirus is 9,901 base pairs long, flanked by 6 base-pair duplications of cellular DNA at the site of integration. Five extensive blocks of open reading frame corresponding to the gag gene, the presumed protease, the pol and env genes, and the open reading frame orf within the long terminal repeat of the provirus were readily discernible. Translation of gag, protease, and pol involved three different translational reading frames to produce the three overlapping polyprotein precursors Pr77, Pr110, and Pr160 found in virus-infected cells. Synthesis of the reverse transcriptase and endonuclease therefore required two separate frameshifts to suppress the termination codons at the ends of the Pr77 and Pr110 domains. Direct evidence is presented for translational readthrough of both stop codons in an in vitro protein synthesis system.
Twenty five patients with encephalitis were studied prospectively, and their clinical and virological features compared with outcome. Among 22 patients with laboratory confirmation of virus infection, evidence of direct effect on the central nervous system by the virus occurred significantly more often both in those with a monophasic illness compared with those with a biphasic illness, and in those with focal neurological signs localising in the cerebral hemispheres compared with those without such signs. Young age at presentation, low score on the Glasgow coma scale, disruption of oculocephalic responses, and laboratory evidence of virus infection within the central nervous system were significantly associated with poor outcome. Computed tomography results, concentrations of creatine phosphokinase BB isoenzyme in cerebrospinal fluid, and procoagulant activity in cerebrospinal fluid were not predictive of outcome.
Genotyping, using plasma proteins or DNA polymorphisms or both, was carried out on 30 families selected through probands with Von Recklinghausen disease. The data provide additional evidence for the exclusion of loci on chromosomes 3 and 5, and chromosome arms 1q, 2p, 4p, 4q, 6q, 7p, 9q, 11p, 11q, and 14q. There was no evidence for genetic heterogeneity at D1S1 (DNF15S2) on chromosome arm 3p, using the Morton test for heterogeneity.
The clinical outcomes of 183 patients with suspected pulmonary embolism (PE) and a "low probability of PE" interpretation of aerosol-perfusion scintigrams were reviewed. Based in part on the scintigraphic findings, 173 of the patients (94.5%) were not treated with anticoagulants. Over a mean follow-up period of 8.4 months, only one patient (who was from the untreated group) had clinical evidence of PE. These results suggest that a low-probability interpretation of the aerosol-perfusion scintigram is generally reliable and a suitable indicator for clinical decision making in patients suspected of having PE.
The existence and general characteristics of the intestinal surface acid microclimate (ISAM) in the developing intestine of suckling and weanling rats were examined. ISAM pH measurements were performed in vitro using a sensitive glass pH-microelectrode. The results showed that the ISAM does exist in both suckling and weanling rat intestine. In both suckling and weanling rats, ISAM pH was significantly (p less than 0.01) lower in the jejunum than in the ileum, an observation similar to that previously reported in the small intestine of adult rats. In the colon, however, ISAM pH of suckling rats was significantly (p less than 0.01) lower than that of weanling and adult rats. Studies on the relationship between jejunal ISAM pH of weanling rats and incubation buffer pH showed that the two are not in equilibrium. Jejunal ISAM pH of weanling rats was significantly inhibited by: 1) the mucolytic agent N-acetyl-L-cysteine, 2) stirring of the incubation medium, 3) Na+ removal, 4) glucose removal (or substitution by the unmetabolizable galactose), and 5) metabolic inhibitors (iodoacetate and dinitrophenol). These results demonstrate the existence of the ISAM in the developing intestine of suckling and weanling rats and shows the dependence of the ISAM on Na+, metabolizable substrate(s) and normal intracellular metabolism. Furthermore, surface mucus appears to play a role in maintaining the ISAM, most probably through retaining the H+ at the intestinal surface.
A retrospective case-control study was conducted, using 66 amyotrophic lateral sclerosis (ALS) patients and 66 closely matched controls. Cases were ascertained primarily through a neurology clinic. A self-administered questionnaire probed for history of skeletal fractures. Using McNemar's test, no association was found between history of skeletal fracture and pathogenesis of ALS. No predilection for the head, neck, or spine was demonstrated. The extremities accounted for most fracture sites in cases and controls. Among cases, 68% of the fractures occurred before diagnosis, 58% occurring more than 10 years before diagnosis of ALS.
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In 62 consecutive patients, 99mTc RBC studies were reviewed and the scintigraphic findings were characterized to determine the ability of 99mTc RBC scintigraphy to estimate bleeding rates in patients with active gastrointestinal hemorrhage. Of the 62 scans, 10 showed early positivity (less than 1 hr) with a strongly intense bleeding focus relative to hepatic activity (group 1), four showed delayed positivity (greater than 1 hr) with a strong focus (group 2), five showed early positivity with a weak focus (group 3), 12 showed delayed positivity with a weak focus (group 4), and 31 studies were negative (group 5). The mean bleeding rates were then calculated by dividing the blood transfusion volume requirements by the duration of active bleeding for each patient, as recorded in the patients' charts. The mean bleeding rates for these groups were 0.4, 0.3, 0.2, 0.15, and 0.1 ml/min, respectively. Group 1 patients had the greatest mean blood-volume loss, longest duration of active bleeding, and highest mean bleeding rate, and they required more aggressive therapy than the other groups. The minimum mean bleeding rate detectable by scintigraphy was 0.1 ml/min. Our results suggest that 99mTc RBC scintigraphy can estimate bleeding rates and identify those patients who are at higher risk for developing massive gastrointestinal hemorrhage requiring more aggressive therapy.
The effects of the diphosphonates etidronate and clodronate were studied in 144 patients with Paget's disease. All five programmes of treatment tested induced a similar suppression of disease activity as judged by serum alkaline phosphatase concentrations, but the proportion of patients responding and the duration of responses differed significantly between programmes. The proportion responding to etidronate 5-10 mg/kg/day for six months was less than for other regimens, and the most sustained response was after treatment with clodronate 1600 mg daily for six months. More complete biochemical suppression was associated with the more prolonged responses irrespective of the regimen used.
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One hundred and fifty Gram-negative bacteria isolated from patient specimens at King Faisal Specialist Hospital were examined for their ability to transfer antibiotic resistance plasmids to a sensitive Escherichia coli recipient in conjugation and transformation experiments. Agarose gel electrophoresis was used to enumerate and size the R-plasmids found, and Southern DNA hybridization was used to assess similarities between antibiotic resistance plasmids from different bacteria and sources. Of the bacterial isolates tested 65% contained plasmids, 70% of these transferred antibiotic resistance to E. coli, and 40% transferred multiple, linked resistances on R-plasmids. DNA hybridization of these R-plasmids demonstrated widespread similarities between plasmids from different bacterial genera and from different hospital locations. In particular, a gene encoding ampicillin resistance appeared especially widespread, indicating that a transposon may be mediating transmission of this resistance.
We studied 22 myelomeningocele patients with strong quadriceps and good ambulatory capability who had a dislocated hip. These patients did not have hip pain, had good to excellent hip motion and could sit with no difficulty. All but one was a good to excellent community ambulator with crutches and orthoses. Twenty-five percent had limb length inequality requiring shoe lifts but this combination did not impair functional capability. None owned wheelchairs. Seven had associated musculo-skeletal deformities which required treatment. We concluded that the hip dislocation in these patients was not significant. We evaluated a similar series of 11 patients who had open reduction of a dislocated hip an average of 18 months ago. Two patients were slightly improved and five patients were significantly worse after the open reductions. Serious complications related to the surgery ensued in half of the cases. The cost of the surgery and treatment of the complications in these 11 patients was $400,000. We concluded that surgical treatment of paralytic hip dislocations in ambulatory myelomeningocele patients offered no clear cut benefit.