Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 523 records · Page 29Linked to original sources

PubMed1996

Hepatitis C genotypes in Australian haemophilia patients.

BACKGROUND: Differences in the hepatitis C virus (HCV) genotype influence the severity of HCV related liver disease and response to interferon therapy. HCV infection is frequent in Australian haemophilia patients who have been exposed repeatedly to multiple HCV genotypes through non HCV virally inactivated clotting factor concentrates. The distribution of the various HCV genotypes in Australian haemophilia patients is unknown. AIM: To examine the HCV genotype distribution and clinical features of HCV associated liver disease in Australian haemophilia patients. METHODS: Forty patients with bleeding disorders who were known to be both HCV antibody and polymerase chain reaction (PCR) positive were evaluated by direct sequencing of the PCR products for the HCV genotype. RESULTS: Genotype 1 was found in 65% of patients (26/40), type 2 in 5% (2/40) and type 3 in 30% (12/40). No genotypes 4 to 6 were found. There was no association between the HCV genotype and the severity of haemophilia, alanine transaminase levels, or the presence of portal hypertension. Unlike European, Asian and American studies where the majority of type 1 infection is subclass 1b, in Australian haemophilia patients it is subclass 1a (73%-19/26) which may have a better prognosis and response to interferon. CONCLUSIONS: Despite patients with haemophilia being exposed to multiple HCV genotypes, it appears that there is no selection advantage of one genotype over another. Australian haemophilia patients with HCV have a different genotype distribution to that reported in other countries and care should be observed in interpreting non Australian studies concerning HCV.

Adolescent↗

PubMed1996

Peripheral blood leukocyte populations in the elderly with and without periodontal disease.

Periodontal disease in the elderly has not been characterized. Initial reports suggest that the disease is common and severe. Deficiencies in the immune response have also been reported to occur in the elderly. Consequently it was hypothesized that aging-related changes in the immune response may contribute to the severity and occurrence of periodontal disease in the elderly. To test that hypothesis, the % and number of leukocytes and leukocyte subsets in the peripheral blood of elderly (65-75 years) subjects were tested and used as indicators of the immune potential of those individuals. Age and gender effects on several of the parameters tested were identified. With the exception of increased number of leukocytes in the elderly group with severe periodontal disease, no other alteration in the leukocyte parameters tested were identified. These results suggest that periodontal disease in the elderly was not associated with obvious changes in the leukocyte and leukocyte subsets in the peripheral blood due to aging.

Adult↗

PubMed1996

Double-blind comparison of cefazolin and ceftizoxime for prophylaxis against infections following elective biliary tract surgery.

Antibiotics have been shown to reduce the incidence of wound infections after elective biliary tract procedures. Cefazolin and cefoxitin are among the agents most commonly promoted for this purpose. Cefoxitin has been substituted with ceftizoxime in many institutions; however, the role of ceftizoxime as a prophylactic agent in this setting has not been determined. To assess the comparative prophylactic efficacies of cefazolin and ceftizoxime in biliary tract surgery, we conducted a double-blind, randomized prospective clinical trial in a tertiary-care teaching hospital. Adult patients were randomized to one of two treatment groups and received a 30-min preoperative dose of study drug and as many as two postoperative doses at 12 and 24 h, depending on hospitalization status. Cefazolin and ceftizoxime were given as 1,000-mg doses. Patients with infections, those receiving prior antibiotics, or those with beta-lactam allergies were excluded. Over the 19-month study tenure, 167 patients were enrolled. Seventeen patients were excluded from analysis because of protocol violations. Of the 150 evaluable patients (72 and 78 receiving cefazolin and ceftizoxime doses, respectively), there was no significant difference among groups regarding sex, age, weight, preoperative Apache II score, baseline chemistry, and hematological parameters. Groups were also equivalent regarding the surgeon, type of procedure, characteristics (blood loss, drains, organ injury, and complications), and duration of hospital stay (mean, 5.6 versus 4.3 days [P = 0.31]). No clinical evidence of infection (7-day hospital stay and 30-day follow-up) was identified in 93% of cefazolin and 92% of ceftizoxime patients (P = 1.0). Microbiological confirmation was found in only 18% of primary-site infections. In conclusion, cefazolin and ceftizoxime appear to be equivalent for the prevention of infection in biliary tract surgery with the dosage regimens studied.

Adult↗

PubMed1996

Generation of atypical pulmonary inflammatory responses in BALB/c mice after immunization with the native attachment (G) glycoprotein of respiratory syncytial virus.

The feasibility of using the highly purified native attachment (G) protein in a subunit vaccine against respiratory syncytial virus (RSV) was examined in a murine model with or without the fusion (F) protein of RSV and the adjuvant QS-21. The studies established that QS-21 was more potent than AIOH as an adjuvant for both F and G glycoproteins. Augmented antigen-dependent killer cell activity and complement-assisted serum neutralizing and anti-F and G protein immunoglobulin G2a antibody titers were observed. Immunization with G/QS-21 generated immune responses that were characterized by low levels of antigen-dependent killer cell activity, elevated levels of interleukin-5 (IL-5) and percentages of eosinophils in the bronchoalveolar lavage fluids after challenge, and splenic immunocytes that secreted IL-5 but not gamma interferon (IFN-gamma) after in vitro stimulation with purified whole virus antigens. The pulmonary eosinophilia was similar to that induced by a facsimile of a formalin-inactivated vaccine used in previous clinical trials and was prevented by prior in vivo treatment with anti-IL-5 but not with control immunoglobulin G or anti-IFN-gamma neutralizing monoclonal antibodies. Thus the data implied that vaccination with G/QS-21 generated helper T-cell immune responses that were type 2 in nature. Alternatively, the data suggested that the helper T-cell immune responses elicited by F/QS-21 were more type 1 in character. Neither eosinophilia nor elevated levels of IL-5 were observed in the lungs of mice after challenge. Noteworthy levels of antigen-dependent killer cell activity was observed, and splenic immunocytes secreted copious quantities of IFN-gamma. Immunization with a combination vaccine composed of highly purified native F and G proteins plus QS-21 (F+G/QS-21) resulted in augmented complement-assisted serum neutralizing antibody titers compared with vaccination with either F/QS-21 or G/QS-21 alone. However, following vaccination with F+G/QS-21, the bronchoalveolar lavage fluids contained significant increases in IL-5 and percentages of eosinophils after challenge, the spleen cells appeared to secrete less IFN-gamma after in vitro stimulation, and there was no evidence of increased numbers of antigen-dependent killer cell precursors. Taken together, the data imply that native G protein influences the nature of the immune responses elicited by F/QS-21. The results therefore suggest that G, not F, protein has more potential to bias the host for atypical pulmonary inflammatory responses.

Adjuvants, Immunologic↗

PubMed1996

The sex ratio of children in relation to paternal preconceptional radiation dose: a study in Cumbria, northern England.

STUDY OBJECTIVE: To investigate whether the occupational exposure to external ionising radiation of men employed at the Sellafield nuclear installation, West Cumbria, affects the sex of the children they subsequently father. DESIGN: A retrospective cohort study using logistic regression to analyse the sex ratio, in particular in relation to paternal preconceptional irradiation. SETTING AND PARTICIPANTS: The 260,060 singleton births between 1950 and 1989 to mothers resident in Cumbria, north west England. RESULTS: The sex ratio among children of men employed at any time at Sellafield was 1.094 (95% CI: 1.060, 1.128), significantly higher than that among other Cumbrian children, 1.055 (95% CI: 1.046, 1.063). There was an increased sex ratio of 1.396 (95% CI: 1.127, 1.729) in the 345 children whose fathers were estimated from annual dose summaries to have received more than 10 mSv of external radiation in the 90 days preceding conception, but no significant linear trend between sex ratio and 90 day paternal preconceptional dose was found. There was no significant association between sex ratio and the external dose accumulated before the 90 day period preceding conception. CONCLUSIONS: Men employed at Sellafield fathered a greater proportion of boys than would be expected for a Cumbrian population, which may be partly explained by their younger age distribution. A greater effect was observed in the fathers with recorded doses exceeding 10 mSv in the 90 days before conception. While this may reflect a true statistical association, it is also possible that it may be a chance finding due to imprecision in the dose estimates and consequent misclassification.

Adult↗

PubMed1996

Spontaneous healing of osteitis fibrosa cystica in primary hyperparathyroidism.

A 24-year-old man with primary hyperparathyroidism and osteitis fibrosa cystica developed acute hypocalcaemia. Spontaneous healing of his bone disease was confirmed radiographically and by correction of the serum alkaline phosphatase. Hypercalcaemia associated with a raised serum parathyroid hormone recurred 90 weeks after the initial presentation. During the fourth neck exploration a parathyroid adenoma was removed, resulting in resolution of his condition. Haemorrhagic infarction of an adenoma was the most likely cause of the acute hypocalcaemic episode.

Acute Disease↗

PubMed1996

Role of nitric oxide resistance in erythropoietin-induced hypertension in rats with chronic renal failure.

We studied the mechanism of erythropoietin (EPO)-induced hypertension (HTN) in rats with chronic renal failure (CRF). After partial nephrectomy, rats were randomized into four groups. Group A received EPO, 150 U/kg, two times weekly for 6 wk to prevent anemia; group B received placebo injections and became anemic; group C received EPO but was kept anemic by dietary iron deficiency; and group D received placebo and regular transfusions to match hematocrit (Hct) in group A. Blood pressure (BP), Hct, platelet cytosolic calcium ([Ca2+]i) and magnesium concentration, and pressor and vasodilatory responses were determined. By design, Hct in groups A and D were comparable and significantly greater (P < 0.01) than in groups B and C. Despite divergent Hct values, the EPO-treated groups A and C showed a significant rise in BP compared with the placebo-treated groups B and D. HTN occurred whether EPO therapy was begun immediately or 4 wk after nephrectomy. EPO therapy augmented the elevation of basal [Ca2+]i and restored the defective thrombin-mediated rise of platelet [Ca2+]i in CRF animals. EPO therapy did not alter caudal artery contraction in response to either 68 mM K(+)-induced depolarization, angiotensin II or alpha 1-agonist, methoxamine in vitro, or the pressor response to angiotensin II in vivo. However, EPO therapy impaired the hypotensive response to nitric oxide (NO) donors, sodium nitroprusside and S-nitroso-N-acetyl-D,L-penicillamine, and reversed the CRF-induced upregulation of guanosine 3',5'-cyclic monophosphate production by thoracic aorta in vitro. Thus EPO-induced HTN in CRF rats is Hct independent and is associated with and perhaps causally related to increased basal and stimulated [Ca2+]i and impaired vasodilatory response to NO.

Angiotensin II↗

PubMed1996

Rab11 is an apically located small GTP-binding protein in epithelial tissues.

Rab proteins are involved in many aspects of dynamic vesicle processing within eukaryotic cells. We have previously identified Rab11 in gastric parietal cell tubulovesicle membranes. We have produced a monoclonal antibody that is specific for Rab11. In all rabbit tissues examined, Rab11 immunoreactivity was highly enriched in epithelial cells. In the gastric fundus, parietal cells were stained in a pattern consistent with localization on tubulovesicles. Surface mucous cells of both the fundus and antrum demonstrated punctate subapical staining. Ileal and proximal colonic enterocyte labeling was observed deep to the brush borders. In the distal colon, staining was observed in the apical regions of mid-crypt cells. In skin and esophagus, punctate immunoreactivity was present in the medial layers of the squamous epithelia. Prominent Rab11 immunoreactivity was present in hepatocytes deep to the bile canaliculi. Punctate subapical staining was observed in pancreatic acinar cells. Apical staining was also observed in collecting duct cells and in the glandular cells of the prostate. These results indicate the Rab11 is expressed in apical vesicular populations in discrete epithelial cell populations.

Animals↗

PubMed1996

Invasive cervical cancer in Southampton and South West Hampshire: effect of introducing a comprehensive screening programme.

A study of invasive cervical cancer in Southampton and South West Hampshire is reported, covering three consecutive three year periods during which the screening coverage increased from an estimated 60% to a recorded 87% of eligible women aged 20-64. From the first to the third periods of the study in that age group registrations of fully invasive squamous cell carcinoma (stage lb and above) fell from 64 to 30 (53%), which was largely counteracted by an increase in microinvasive squamous cell carcinoma (linear trend: P<0.0001). In the same age group registrations of adenocarcinoma rose slightly, which resulted from an increase in the number diagnosed at a depth of invasion of less than 3 mm. There were no significant changes in the numbers of stage III and IV cancers or among cancers in women aged 65 and over. A strong inverse association was found between stage of both histological types of cancer and their likelihood of being screen detected rather than symptomatic: 91% of screen detected cancers were diagnosed at stage I compared with 38% of symptomatic cancers. There was a slight downward trend in the incidence of cancer per 100,000 total female population across the three periods of the study with a significant trend towards low stage disease, which is likely to reduce mortality in years to come. The trend towards screen detected cancers and cancers of less than 3 mm depth of invasion is presented as a positive outcome to be expected in early rounds of increasing the screening coverage.

Adenocarcinoma↗

PubMed1996

Co-distribution of calmodulin-dependent protein kinase II and inositol trisphosphate receptors in an apical domain of gastrointestinal mucosal cells.

The Type 3 inositol 1,4,5-trisphosphate (InsP3) receptor is expressed at high levels in gastrointestinal tissues. This receptor has 16 potential phosphorylation sites for calcium/calmodulin-dependent protein kinase II (CaM kinase II). To determine if the Type 3 InsP3 receptor is likely to be a physiologic substrate for CaM kinase II, localizations of the Type 3 InsP3 receptor and CaM kinase II were compared in tissues of the gastrointestinal tract. Cellular and subcellular localizations were determined by immunofluorescence microscopy in rat intestine, pancreas, and stomach, and in isolated rabbit gastric glands. Both proteins were found in the apical region of intestinal enterocytes, pancreatic acinar cells, and gastric parietal, chief, and surface mucous cells. CaM kinase II was found throughout the entire intracellular canalicular F-actin domain of parietal cells, whereas the type 3 InsP3 receptor was restricted to the neck region. Thus, in several gastrointestinal tissues the Type 3 InsP3 receptor is specifically localized to a portion of the apical cytoskeletal domain in which resides the calcium-responsive effector CaM kinase II.

Animals↗

PubMed1996

Cardiff puerperal mood and hormone study. III. Postnatal depression at 5 to 6 weeks postpartum, and its hormonal correlates across the peripartum period.

BACKGROUND: We assessed associations of mood at 5-6 weeks postpartum with peripartum saliva cortisol and progesterone profiles. METHOD: A prospective study involved 120 primiparous women free of major marital, socioeconomic and health problems, who collected saliva twice daily from 2 weeks before delivery to day 35 postpartum. This allowed intensive characterisation of cortisol and progesterone profiles. At the conclusion of the study, mood was assessed according to standard criteria. RESULTS: Seven women developed major depression according to DSM-III-R criteria. No associations emerged between progesterone and mood at 5 to 6 weeks. Lower levels of evening cortisol in the immediate peripartum period, were associated with postnatal depression. CONCLUSION: The study provides no support for the treatment strategy of progesterone augmentation following delivery, as a prophylactic against postnatal depression. The HPA axis and its associations with postnatal mood warrants further investigation.

Adolescent↗

PubMed1996

Comparison of the effects of estrogen alone and estrogen plus androgen on biochemical markers of bone formation and resorption in postmenopausal women.

The present study was undertaken to determine whether the addition of an androgen to estrogen therapy in postmenopausal women would alter the skeletal response as determined by measurements of markers of bone formation and resorption. Postmenopausal women were treated for 9 weeks with either a combination of 1.25 mg esterified estrogen and 2.5 mg methyltestosterone (E+A) or 1.25 mg conjugated equine estrogen (CEE). Both groups showed a similar decrease in urinary excretion of the bone resorption markers, deoxypyridinoline, pyridinoline, and hydroxyproline. Patients treated with CEE showed decreases in the serum markers of bone formation, bone-specific alkaline phosphatase, osteocalcin, and C-terminal procollagen peptide. In contrast, subjects treated with E+A showed increases in these markers of bone formation. CEE increased, and E+A decreased serum levels of sex hormone-binding globulin as well as triglycerides and high density lipoprotein levels. Only CEE significantly reduced low density lipoproteins. Both regimens were effective in reducing postmenopausal somatic symptoms, but only E+A had a significant effect on psychological symptoms. We conclude that short term administration of androgen with estrogen may reverse the inhibitory effects of estrogen on bone formation. Long term studies are needed to determine the relative benefits and risks of the combination of estrogen and androgen and whether this results in greater increases in bone mass and strength.

Aged↗

PubMed1996

Identification of a novel member of the Rab8 family from the rat basophilic leukaemia cell line, RBL.2H3.

We describe the cloning of a cDNA from the rat basophilic leukaemia cell line (RBL.2H3) encoding a novel member of the Rab family of small GTP binding proteins. The novel clone, which we call Rab8b, is most highly related to the Rab8 family with substantial divergence in the variable C-terminal domain. Northern blot analysis reveals highest levels of expression of Rab8b in the spleen, testis and brain, which is in marked contrast to the tissue distribution of Rab8. The Rab8b cDNA was modified to introduce a c-myc epitope tag at the extreme N terminus of the protein, and transient transfection studies were performed to analyse the intracellular localization of Rab8b by confocal microscopy. Transient expression of the c-myc/Rab8b fusion protein in both PC12 and RBL.2H3 cells shows staining of both the plasma membrane and ill-defined vesicular structures, and in the case of RBL.2H3 cells appears to induce striking outgrowths of the plasma membrane.

Amino Acid Sequence↗

PubMed1996

The use of erythropoietin in the management of Jehovah's Witnesses who have revision total hip arthroplasty.

Five Jehovah's Witnesses (one man and four women) were managed with revision total hip arthroplasty. The average age of the patients at the time of the index operation was 66.4 years (range, fifty-eight to seventy-eight years). All of the patients received subcutaneous injections of recombinant human erythropoietin before the operation, at an initial dose of 100 international units per kilogram of body weight three times a week. The duration of preoperative treatment was determined by the hematocrit at the time of presentation. The hematocrit was monitored weekly, beginning with the second week of treatment, and the dose was adjusted accordingly until the time of the operation. Erythropoietin therapy was discontinued if the hematocrit exceeded 0.45 at any time. The hematocrit before the erythropoietin therapy was begun, at the time of admission to the hospital (one or two days preoperatively), immediately postoperatively, and at the time that the patient was discharged were recorded for this study. All five revision total hip arthroplasties were performed successfully without a blood transfusion. No patient had any complications associated with an excessive loss of blood or a low hematocrit. The average hematocrit was 0.395 (range, 0.317 to 0.447) before the erythropoietin therapy was begun and was 0.476 (range, 0.431 to 0.509) after treatment with erythropoietin and before the operation (that is, at the time of admission to the hospital). The average duration of erythropoietin therapy was twenty-six days preoperatively and 3.6 days postoperatively. The average hematocrit was 0.368 (range, 0.272 to 0.424) immediately after the operation and was 0.308 (range, 0.294 to 0.327) at the time of discharge from the hospital. No patient had evidence of deep venous thrombosis. This study illustrates that it is possible and apparently safe to optimize the hematocrit, by use of erythropoietin, in a patient who is scheduled for an operation. This may be particularly beneficial to a patient with anemia who has failure of a total hip arthroplasty. A relatively high hematocrit (0.45 to 0.50) preoperatively provides a relative margin of safety to a procedure that frequently involves a great deal of intraoperative blood loss. The use of erythropoietin preoperatively is particularly suited to joint replacements and revisions because of their elective nature and the moderately flexible timing associated with these procedures.

Aged↗

PubMed1996

System for accurate one-dimensional gel analysis including high-resolution quantitative footprinting.

The interactive menu-driven computer program, Geltrak, displays and analyzes a one-dimensional (1-D) electrophoretic gel after digitization by either densitometry or storage-phosphor technology. The program is designed to analyze nucleic acid or protein gels in a variety of ways and includes a specific footprinting option. Overall accuracy for the entire process of 1-D electrophoretic gel band quantitation by peak profile fitting has been investigated. A standard control gel with a predetermined component ratio and minimal background was devised and subjected to electrophoresis, followed by three methods of digitization. The resulting images were analyzed by Geltrak, and their integrated peak area ratios were compared with their initial measured values. Individual band profiles from the control gel were used to develop an improved fitting function to represent the peak profile shape exactly. This function can be used in conjunction with a sophisticated profile-fitting technique to accurately predict the peak shapes from gels with background noise or overlapping bands.

DNA Footprinting↗

PubMed1996

Strategies for follow-up of drug users: field research guidelines.

The timely follow-up of clients who exited from two residential treatment programs was achieved by the consistent application of the described strategies. The enrollment and treatment phases of the study provided the environment for the use of standard follow-up and enhanced outreach methods. The applicability of the strategies to a variety of settings makes the prioritization of the follow-up methods presented a meaningful one. The role of the researcher in the reevaluation of follow-up protocols within an ethical context is discussed.

Cost-Benefit Analysis↗

PubMed1996

Cranial base tumor visualization through high-performance computing.

Tumors of the skull base in general are considered among the more difficult head and neck pathological entities to treat surgically; some surgeons, in fact, consider lesions in this area inoperable. The most appropriate and safest surgical approach to lesions of the anterior and lateral skull base can be devised only with accurate and precise pre-operative assessment. The literature demonstrates the constant evolution of and search for more efficient less invasive, and safe surgical approaches to this region. With the development of a more exact three-dimensional, interactive anatomical "road map" for each patient's disease and anatomy, the skull base surgeon can not only achieve a more accurate pre-operative assessment leading to a less invasive and less morbid approach, but also can continue to develop and refine new approaches without fear of actual morbidity and mortality. An interdisciplinary team approach, the advent and continued development of faster high performance computers, and the development of new and innovative rendering algorithms can lead to surgical simulation. A prototype of an interactive system has been developed. The system will be iteratively modified through a stepwise evaluation of its clinical usefulness by continually reassessing the system with clinical trials. The current state of the system and the potential benefits are presented.

Brain Mapping↗

PubMed1996

Empirical evaluation of the transfusion medicine tutor.

Previous research during the development of Antibody IDentification Assistant (AIDA) revealed that many medical technology students and other laboratory personnel have serious difficulties in determining the specificity of blood group alloantibodies, especially weak or multiple antibodies. Based on these previous results, AIDA was modified to provide a teaching environment for medical technology students. We report the results of a rigorous, objective evaluation of the resultant system, the Transfusion Medicine Tutor (TMT). The results show that the students who were taught by an instructor using TMT to provide the instructional environment went from 0 percent correct on a pretest case to 87 percent correct on posttests (n = 15). This increase compares with an improvement rate of 20 percent by a control group (n = 15) who used a passive version of the system with the tutoring functions turned off.

Journal Article↗