Biomedical subjects
Publications and source records attributed to J Jones.
At least 16 cases of inversion tandem duplications of the short arm of chromosome 8 have been reported. Structural rearrangements of chromosome 8 have made it possible to localise the gene for glutathione reductase (GSR) to 8p21.1. We report here on a 16 month old boy with mental retardation with partial trisomy 8 owing to a de novo inv dup(8)(p12----p23.1).
Rocket immuno-electrophoresis and enzyme-linked immunosorbent assays were used to estimate the amount of cholinesterase present in 29 apparent silent homozygotes. 26 of these samples were segregated into four groups representing zero, very low, low and high levels of immunoreactive protein. These groups may represent the genotypes E1sE1s, E1sE1t, E1tE1t and a new genotype E1xE1x, respectively. The possible genotypes of the remaining 3 individuals are discussed.
A procedure based on modifications of published methods for human proteins for the isolation of rat C8 and C9 from one batch of serum is described. The procedure allows the rapid, large-scale isolation of pure and haemolytically active proteins. Rat C9 had a slightly higher molecular weight than human C9 on SDS-PAGE and similar isoelectric point. Rat C8 differed from human C8 in the molecular weight of the gamma chain (23,000 and 21,000 kD respectively), and on isoelectric focusing (pI rat C8: 6.5-6.9; pI human C8: 7.4-7.9).
Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.
Hyperthyroidism and goiter have been reported frequently in association with the McCune-Albright syndrome (MAS). To assess the prevalence and extent of thyroid abnormalities in girls with MAS, we studied 19 patients [mean age, 6.6 +/- 1 (+/- SE) yr; mean bone age, 9.5 +/- 1 yr] and 18 normal control girls (mean age, 10.3 +/- 0.5 yr). All patients appeared euthyroid when examined; 1 was taking antithyroid medication. Ultrasonography revealed thyroid abnormalities in 7 patients, including generalized inhomogeneity, small (2-4 mm) and large (greater than 10 mm) hypoechoic regions, and echogenic nodule-like regions. Repeat ultrasonography after intervals of 9-18 months showed enlargement of large hypoechoic regions in 2 patients. In the patients with abnormal ultrasound findings, serum TSH was uniformly low or suppressed both at baseline and after administration of 7 micrograms/kg TRH. The mean serum T3 level in this group was significantly higher than that in controls (2.9 +/- 0.2 vs. 2.3 +/- 0.1 nmol/L; P less than 0.05), whereas mean serum T4, free T4, and T4-binding globulin levels did not differ from those of controls. In the remaining 11 patients, thyroid ultrasonography was normal, and the serum levels of T3, T4, free T4, and TSH were normal. Bioassay showed no detectable thyroid-stimulating activity in the plasma of the MAS patients with suppressed TSH levels. None of the patients became overtly thyrotoxic over 3-6 yr of observation, and their serum iodothyronine levels remained stable. We conclude that thyroid dysfunction is common in girls with MAS, but that it may be clinically occult and not rapidly progressive. The thyroid dysfunction, like that of the ovaries, is associated with structural abnormalities in the gland itself, together with suppressed levels of the respective stimulating hormones.
Expression of HLA Class II antigen on keratinocytes has been advocated as a diagnostic marker of acute graft-versus-host disease (GVHD). LN-3 is a murine monoclonal antibody marking an HLA Class II antigen that survives formalin fixation and paraffin embedding. We analyzed the LN-3 staining pattern on 56 skin biopsies from patients treated with bone marrow or peripheral stem cell transplantation, non-transplant patients receiving conventional chemotherapy and/or radiation therapy and controls. Keratinocyte staining, endothelial staining, and the number of epidermal and dermal Langerhans cells were evaluated and analyzed with respect to the histologic and clinical diagnosis in a blind and retrospective fashion. The most predictive parameter for GVHD was marking of endothelial cells by LN-3 which was present in 12 of 16 (75%) biopsies from patients with GVHD. Endothelial staining was found in a total of 19 biopsies of which 12 (63%) had GVHD. These data suggest that LN-3 immunohistochemistry may help identify cutaneous GVHD and discriminate it from conditions that are histologically similar.
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Forty-one patients with advanced colorectal cancer were entered into a randomized controlled trial of treatment with proglumide--a gastrin receptor antagonist. There was no difference in survival between the treated and the untreated groups of patients, although there was a trend towards increased survival in those treated patients with hepatic metastases alone. Proglumide does not cause regression in advanced colorectal cancer but larger studies would be required to detect an effect on tumour growth.
Battle casualties are well recognised as a threat to Operational Effectiveness (OE) at times of conflict. Less well appreciated is that naturally occurring illnesses and injuries--Non-Battle Casualties and Injuries (NBCI)--continue to present at such times and will add to the problems of fighting the ship. This prospective study showed that NBCI resulted in a total of 1369 man days of lost personnel effectiveness among some 1738 RN servicemen during a 180 day deployment. That is just 0.42% of the possible man working days. This represents a loss of 4.3 man days per 1000 at risk per day in terms of fitness for Full Duties or 2.74/1000/day excluding those able to perform Light Duties. It is unlikely that such rates would affect the OE of the fighting units but they do represent a significant challenge to the Royal Naval Medical Service to continue to maintain the rates at such low levels, so that when aggregated to the numbers of battle casualties, OE is maintained as far as possible.
Thirty-seven patients requiring cardiopulmonary bypass were prospectively studied and assigned to plateletpheresis or control groups in a non-randomized, non-blinded fashion according to apheresis exclusion criteria and our ability to perform apheresis within 24 hours of surgery. Patients were grouped by potential for hemostatic abnormalities following a risk point factor assignment established for this study. The study indicated improvement of hemostasis with autologous platelets and plasma as demonstrated by clinical and laboratory parameters and by overall blood component utilization. We conclude that pre-operative plateletpheresis in this patient population is feasible, safe, and effective.
Car seat loan and rental programs have provided many families with low-cost access to child restraints. When an infant or child is unable to be accommodated in a standard car seat or seat belt owing to physical or medical problems, parents of these children have few, if any available resources. The establishment and operation of a loan program at the Indiana University School of Medicine for children who are medically fragile is reviewed in this article. This program was developed by the Automotive Safety for Children Program at the James Whitcomb Riley Hospital for Children, Indiana University Medical Center, to meet the special transportation needs of children with respiratory, orthopaedic, and other medical and physical difficulties. A summary table is included to highlight restraints that have performed satisfactorily during dynamic crash tests and are used to meet patient transportation needs at Riley Hospital. Guidelines for establishing and maintaining a child restraint loan program for children with special needs are outlined to encourage replication of this effort.
Myelin injury in multiple sclerosis (MS) appears to be immune mediated, but the mechanisms remain unidentified. It has been shown previously that oligodendrocytes, which synthesize and maintain myelin in the central nervous system (CNS), are susceptible to attack by homologous complement and that injury may be reversible when lysis is resisted by vesicular removal of membrane attack complexes. Here it is reported that oligodendrocytes are also highly susceptible to attack by T-cell perforin, and respond similarly to sublethal attack by shedding membrane vesicles. These findings imply that oligodendrocytes are vulnerable to lysis and/or reversible injury by a variety of closely related pore-forming immune effectors; following blood-brain barrier disruption, attack by one or several of these molecules may cause transient or irreversible myelin injury. Furthermore, these results provide the first indication that vesicular repair mechanisms may allow nucleated cells to recover from perforin-mediated cell injury.
Toxic shock syndrome (TSS) is a severe multi-system disorder resulting from a Staphylococcus aureus exotoxin. Primary presenting features consist of fever, hypotension, vomiting and diarrhea, and a diffuse macular erythroderma with later desquamation. Treatment is supportive accompanied by drainage and debridement of infection and antibiotics. TSS may occur following any infection with Staphylococcus aureus and is a well-documented complication of nasal surgery. Otolaryngologists should be aware of the manifestations of this disorder and its treatment. A case is presented, along with a review of the literature and management of TSS.
A 26-year-old white woman had premature rupture of membranes at 35 weeks' gestation. Cervical specimens initially demonstrated group B streptococci and Chlamydia trachomatis. Amniocentesis was performed and the amniotic fluid was positive for chlamydia by direct fluorescent antibody stain. The Gram stain was negative. The patient had an elevated white blood cell count. Labor was induced because of suspected chorioamnionitis. A 2120-g female infant was delivered with an Apgar score of 9 at 1 and 5 minutes. The infant's eye and nasopharyngeal specimens were positive for chlamydia by direct fluorescent antibody stain. After delivery, both Ureaplasma urealyticum and C trachomatis were isolated from the amniotic fluid and fetal membranes. This is the first reported case of chlamydial isolation in amniotic fluid.
We describe a new and unique gastric carcinoma cell line (LIM1839) derived from a young Caucasian male with rapidly progressing disease. The cell line grows with a pleomorphic morphology and has been in continuous culture for more than 3 years. The cells cannot be cloned in semi-solid agar or grown in nude mice despite numerous attempts. The karyotype of the cultured cells is highly abnormal with a large number of structural and numerical changes. Some chromosomes are dicentric and this feature has persisted in this culture. The cells express one of the small-intestinal dipeptidases, aminopeptidase N, but do not express dipeptidyl peptidase IV or the disaccharidases, sucrase isomaltase or maltase glucoamylase. The cells express high levels of EGF receptors and of messenger RNA for insulin-like growth factor II.
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In a prospective, randomized, double-blind clinical trial, intravenous prochlorperazine edisylate (Compazine Edisylate) was compared with a placebo in the treatment of severe headaches. Eighty-two adult patients with vascular or tension-type headaches were identified at the time of presentation to one of three participating emergency departments. After the patient gave informed consent, a 2-mL intravenous injection of sterile saline solution or prochlorperazine edisylate (10 mg) was given to each patient at the time of randomization. The treatment groups were similar with regard to age, sex, and type and duration of headache. Within 60 minutes after injection, 74% (31/42) of those who received prochlorperazine had complete relief; 14% (6/42) of the patients had partial relief. Overall, there was complete or partial relief of pain in 88% (37/42) of the drug group and in 45% (18/40) of the placebo group. This difference was statistically significant using chi 2 analysis. Adverse effects were minimal; one patient experienced asymptomatic orthostatic hypotension. These results suggest that intravenous prochlorperazine is an effective treatment for patients with severe vascular or tension headaches who present to the emergency department.
Two forms of Gi-like protein are resolved in both somatic cells and mouse gametes when Sigma SDS (95% grade) is used during polyacrylamide gel electrophoresis, whereas only a single species is resolved when Bio-Rad SDS (electrophoresis grade) is used. These two Gi-like proteins are likely to reflect two distinct species, since (i) the two species resolved in the presence of Sigma SDS migrate with the same electrophoretic mobility upon re-electrophoresis in the presence of Sigma SDS and (ii) exchanging Sigma SDS for Bio-Rad SDS resolves a single species, whereas exchanging Bio-Rad SDS for Sigma SDS resolves two species.