Biomedical subjects
Publications and source records attributed to J A Green.
Between September 1999 and April 2000, the Hand Unit at St George Hospital, Sydney, treated three young men with severe injuries caused by holding a lighted firecracker. These cases illustrate the typical injuries seen with this mechanism of injury. They highlight the dangers of these explosive devices and the potential to improve the laws relating to fireworks.
The metabolism of 52-73-day old Antarctic fur seal pups from Bird Island, South Georgia, was investigated during fasting periods of normal duration while their mothers were at sea foraging. Body mass decreased exponentially with pups losing 3.5-3.8% of body mass per day. Resting metabolic rate also decreased exponentially from 172-197 ml (O2) x min(-1) at the beginning of the fast and scaled to M(b)(0.74) at 2.3 times the level predicted for adult terrestrial mammals of similar size. While there was no significant sex difference in RMR, female pups had significantly higher (F(1,18)=6.614, P<0.019) mass-specific RMR than male pups throughout the fasting period. Fasting FMR was also significantly (t(15)=2.37, P<0.035) greater in females (823 kJ x kg(-1) x d(-1)) than males (686 kJ x kg(-1) x d(-1)). Average protein turnover during the study period was 19.3 g x d(-1) and contributed to 5.4% of total energy expenditure, indicating the adoption of a protein-sparing strategy with a reliance on primarily lipid catabolism for metabolic energy. This is supported by observed decreases in plasma BUN, U/C, glucose and triglyceride concentrations, and an increase in beta-HBA concentration, indicating that Antarctic fur seals pups adopt this strategy within 2-3 days of fasting. Mean RQ also decreased from 0.77 to 0.72 within 3 days of fasting, further supporting a rapid commencement of protein-sparing. However, RQ gradually increased thereafter to 0.77, suggesting a resumption of protein catabolism which was not substantiated by changes in plasma metabolites. Female pups had higher TBL (%) than males for any given mass, which is consistent with previous findings in this and other fur seal species, and suggests sex differences in metabolic fuel use. The observed changes in plasma metabolites and protein turnover, however, do not support this.
The occurrence of an osteochondroma in the carpus is very rare and its excision is indicated in the case of significant symptoms or change in its appearance. The diagnosis is often made in adulthood due to the onset of a functional problem even though development of the tumour occurs during skeletal growth. We report the case of a 38 year old patient, with no antecedent trauma, who presents with simultaneous exostoses on the dorsal and palmar surfaces of the capitate, which has not been previously described in the literature. The existence of a bipolar lesion extending anteriorly and posteriorly in the carpus is a possibility which may not be apparent and renders plain radiograph insufficient in the investigation of such a lesion. CT scan and MRI scan are indispensable in the investigation of this kind of carpal lesions, allowing better visualization of the base of the tumour, the expansion of the tumour and relation to the neighbouring soft tissues and the presence of malignant degeneration.
Autism, a severe disorder of development, is difficult to detect in very young children. However, children who receive early intervention have improved long-term prognoses. The Modified Checklist for Autism in Toddlers (M-CHAT), consisting of 23 yes/no items, was used to screen 1,293 children. Of the 58 children given a diagnostic/developmental evaluation, 39 were diagnosed with a disorder on the autism spectrum. Six items pertaining to social relatedness and communication were found to have the best discriminability between children diagnosed with and without autism/PDD. Cutoff scores were created for the best items and the total checklist. Results indicate that the M-CHAT is a promising instrument for the early detection of autism.
OBJECTIVE: We characterized new infertility patients on the basis of race and economic factors. STUDY DESIGN: A retrospective chart review was performed of all patients seeking infertility evaluation from 1998 to 1999 at two infertility centers in Cincinnati, Ohio. Patients were categorized by race (white, black, or other). Statistics were analyzed by chi2 and logistic regression. RESULTS: Of 756 patients, 85.2% were white, 10.2% were black, and 4.4% were other. Infertility diagnoses were placed into the following 7 categories: ovarian, salpingitis, surgical sterilization, male factor, endometriosis, unexplained, and other. Black women had significantly more salpingitis than did nonblack women (P <.001) regardless of insurance status. However, surgical sterilization was more prevalent in patients without insurance regardless of race (P <.001). CONCLUSIONS: Our findings are consistent with previous studies showing that black women have more risk factors for salpingitis. Surgical sterilization risk factors were concordant with those of the National Center for Health Statistics.
Twenty-four macaroni penguins (Eudyptes chrysolophus) from three groups, breeding males (N=9), breeding females (N=9) and moulting females (N=6), were exercised on a variable-speed treadmill. Heart rate (fH) and mass-specific rate of oxygen consumption (sVO2) were recorded from the animals, and both fh and sVO2 were found to increase linearly with increasing treadmill speed. A linear regression equation described the relationship between fh and sVO2 for each individual. There were no significant differences in these regressions between breeding and moulting females. There were significant differences in these relationships between all females and breeding males. fH and s VO2 were recorded from five of these animals for a total of 24 h. When fh was used to predict sVO2 for the 24 h period using the derived regressions, the estimate was not significantly different from the measured values, with an average error of -2.1 %. When fh was used to predict sVO2 for the 5 min intervals used for the calibration in all 24 birds, the estimate was not significantly different from the observed values, and the average error was only +0.47 %. Since the fH/sVO2 relationship was the same during periods of the annual cycle when the animals were inactive/fasting and active/foraging, it seems reasonable that, as long as sex differences are taken into account, fh can be used to predict the metabolic rates of free-ranging macaroni penguins all year round.
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The pregnancy-associated glycoproteins (PAG) are putative peptide-binding proteins and products of a large family of genes whose expression is localized to the placental surface epithelium of artiodactyl species. We have tested the hypothesis that natural selection has favored diversification of these genes by examining patterns of nucleotide substitution in a sample of 28 closely related bovine, caprine, and ovine family members that are expressed only in trophoblast binucleate cells. Three observations were made. First, in codons encoding highly variable domains of the proteins, there was a greater accumulation of both synonymous and nonsynonymous mutations than in the more conserved regions of the genes. Second, in the variable regions, the mean number of nonsynonymous nucleotide substitutions per site was significantly greater than the mean number of synonymous substitutions per site. Third, nonsynonymous changes affecting amino acid charge occurred more frequently than expected under random substitution. This unusual pattern of nucleotide substitution implies that natural selection has acted to diversify these PAG molecules at the amino acid level, which in turn suggests that these molecules have undergone functional diversification. We estimate that the binucleate cell-expressed PAG originated 52 +/- 6 million years ago, soon after the divergence of the ruminant lineage. Thus, rapid functional diversification of PAG expressed in trophoblast binucleate cells seems to have been associated with the origin of this unique placental adaptation.
Pregnancy-associated glycoproteins (PAG) are structurally related to aspartic proteinases and belong to an extensive, rapidly evolving family of recently duplicated genes expressed in the placentas of artiodactyl species. The aim of the present study was to clone PAG from the goat, study their temporal and cell-specific expression, and determine their phylogenetic relationship to PAG from other species. RT-PCR was used to generate PAG cDNA from pooled placental RNA obtained between days 45 and 115 of pregnancy. A total of 11 cDNA, which differed by > 5% from each other, were selected for complete bidirectional sequencing from 60 clones analyzed. A group of nine (caPAG1, caPAG3-7(var), caPAG9-11), which displayed > 80% sequence identity with each other, were expressed after day 45 of pregnancy and were localized to trophoblast binucleate cells. These PAG demonstrated an unusually high ratio of nonsynonymous (amino acid changing) to synonymous nucleotide differences. CaPAG2, by contrast, was detectable only in early pregnancy (days 18 and 19) and expressed throughout trophectoderm. It was of more ancient origin than the PAG1 group, but more recent than caPAG8. The latter was expressed at all stages examined (days 18 to 115). The data confirm that many PAG genes, with different patterns of temporal and spatial expression, are transcribed in the placenta of the goat. The data also suggest that the recently duplicated PAG genes are being selected for rapid diversification of function.
A population-based, case-control study to investigate the possible association between gastroesophageal reflux (GER) and adenocarcinoma of the esophagus and gastric cardia was performed. It demonstrated an odds ratio of 7.7 for esophageal adenocarcinoma in patients with GER symptoms. The frequency, severity, and duration of symptoms correlated with an increased risk of esophageal adenocarcinoma. A weaker association was noted for GER and adenocarcinoma of the gastric cardia. No association surfaced between GER and squamous cell carcinoma of the esophagus.
A 31-year-old man with malignant melanoma of his right popliteal fossa was treated in 1987 with surgical excision followed by local radiotherapy. Eight months later, he presented with recurrence in the right inguinal lymph nodes, which were resected and followed by radiotherapy to the groin. Ten months later, he developed liver metastases and was treated with vindesine (12 months) and interferon-alpha-2a (30 months) resulting in complete remission which has been maintained for over 10 years. This interesting case report, with brief review of literature, is presented here.
The pregnancy-associated glycoproteins (PAG) constitute a large family of recently duplicated genes. They show structural resemblance to pepsin and related aspartic proteinases. A total of 21 bovine (bo) PAG and 9 ovine (ov) PAG cDNA have been identified. Phylogenetic analysis indicated that the PAG are divided into two main groupings that accurately reflect their tissue expression, as determined by in situ hybridization. In the first pattern, represented by ovPAG-2 and boPAG-2, -8, -10, and -11 (where the numbering is arbitrary and reflects order of discovery within species), expression occurred throughout the outer epithelial layer of the placenta (trophectoderm). The second pattern was predominant localization to binucleate cells. Ribonuclease protection assays, which allow discrimination between closely related transcripts, have shown that the expression of PAG varies in a temporal manner over pregnancy. Of those bovine PAG expressed predominantly in binucleate cells, boPAG-1, -6, and -7 are expressed weakly, if at all, by Day 25 placenta, but are present at the middle and end of pregnancy. Others, such as boPAG-4, -5, and -9, are expressed at Day 25 and at earlier stages. Although not among the earliest PAG produced by the trophoblast, boPAG-1 has been used for pregnancy diagnosis, particularly in dairy cows, where there is a major need for a sensitive method capable of detecting pregnancy within 1 mo of conception. It seems likely that some of the newly discovered PAG will be better candidates than PAG-1 for pregnancy diagnosis.
Evidence suggests that up to 25% of p53 mutations are outside of exons 5-8 and that insertions, deletions, and polymorphic sites in the p53 gene may play a significant role in the process of carcinogenesis. A novel polymerase chain reaction (PCR) approach for the analysis of the entire p53 coding and splice site regions from microdissected, formalin-fixed, paraffin-embedded tumor tissues has been developed which allows multiple genetic analyses to be performed from one primary amplification reaction. The method was initially evaluated using well-characterized cell lines. In addition to confirming the published p53 mutations for HT29, Molt 4, A431, and HN5, a 16 base pair (bp) duplication within intron 3 was detected in both the A431 and HT29 cell lines. Analysis of archival samples of ovarian cancer identified the same 16-bp duplication and coding region variations. In all samples, using GenBank submission U94788 as a reference, a C-insertion was detected at nucleotide positions 11818 and 11874 within intron 2. At nucleotide position 14168, within intron 7, a T-to-G base change was found. This novel PCR approach has the potential to reduce the amount of clinical material required by up to 95%, thus facilitating retrospective studies on archival tumor collections. Furthermore, a wider analysis of the p53 gene, including splice sites and intronic regions, may yield additional information regarding cancer predisposition, response to therapy, and progression.
PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m(2) over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m(2) over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m(2) every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.
Lagergren et al. performed a population-based, case-control study to investigate the possible association between gastroesophageal reflux (GER) and adenocarcinoma of the esophagus and gastric cardia. They demonstrated an odds ratio of 7.7 for esophageal adenocarcinoma in patients with GER symptoms. The frequency, severity, and duration of symptoms correlated with an increased risk of esophageal adenocarcinoma. A weaker association was noted for GER and adenocarcinoma of the gastric cardia. No association surfaced between GER and squamous cell carcinoma of the esophagus.
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Three groups of six-week-old nude outbred mice were orally infected with 400, 20,000 and 1,000,000 oocysts of Cryptosporidium muris (strain RN 66) per mouse, respectively. Oocysts were detected in the faeces from 10-18 days post-infection (p.i.) and continued to be shed in large numbers in all groups until the termination of the trial on day 89 p.i. Clinical signs were not observed in any of the infected mice and there was no significant effect on weight gain compared to uninfected controls. Histological examination revealed the presence of parasites confined to the glandular stomach. Parasitised gastric glands were dilated, hypertrophied and filled with numerous parasites. The glands had lost their normal cellular architecture and were lined with many undifferentiated cells. In some mice receiving the largest innoculum, the glandular mucosa was congested and the lamina propria infiltrated with eosinophils, polymorphs and lymphocytes.
Phage display provides a methodology for obtaining fully human antibodies directed against human transforming growth factor-beta (TGFbeta) suitable for the treatment of fibrotic disorders. The strategy employed was to isolate a human single chain Fv (scFv) fragment that neutralises human TGFbeta2 from a phage display repertoire, convert it into a human IgG4 and then determine its TGFbeta binding and neutralisation properties and its physical characteristics. Several scFv fragments binding to TGFbeta2 were isolated by panning of an antibody phage display repertoire, and subsequent chain shuffling of the selected V(H) domains with a library of V(L) domains. The three most potent neutralising antibodies were chosen for conversion to IgG4 format. The IgG4 antibodies were ranked for their ability to neutralise TGFbeta2 and the most potent, 6B1 IgG4, was chosen for further characterisation. 6B1 IgG4 has a high affinity for TGFbeta2 with a dissociation constant of 0.89 nM as determined using the BIAcore biosensor and only 9% cross-reactivity with TGFbeta3 (dissociation constant, 10 nM). There was no detectable binding to TGFbeta1. 6B1 IgG4 strongly neutralises (IC50 = 2 nM) the anti-proliferative effect of TGFbeta2 in bioassays using TF1 human erythroleukaemia cells. Similarly, there was strong inhibition of binding of TGFbeta2 to cell surface receptors in a radioreceptor assay using A549 cells. 6B1 IgG4 shows no detectable cross-reactivity with related or unrelated antigens by immunocytochemistry or ELISA. The 6B1 V(L) domain has entirely germline framework regions and the V(H) domain has only three non-germline framework amino acids. This, together with its fully human nature, should minimise any potential immunogenicity of 6B1 IgG4 when used in therapy of fibrotic diseases mediated by TGFbeta2.