Biomedical subjects
Publications and source records attributed to M Hayes.
A case is described of an extensive cholesteatoma presenting as a lump on the side of a patient's head overlying the squamous temporal bone, with erosion of the underlying bone and intracranial extension. The patient was otherwise asymptomatic. This case highlights the bone-eroding capacity of cholesteatoma and the vigilance required in assessing lumps on the head.
Fundamental to the concept of psychological distance is the idea that confusability allows discovery of the perceptual relationships between objects, which provides understanding of the underlying principles that govern the functioning of a system. Thus, judgments of dissimilarity (conceptually proportional to the inverse of confusability) may provide insight into the elusive underlying quality-coding mechanisms in that sensory system. In the present experiments, a labeled dissimilarity scale (LDS) that reflects the magnitude of odorant dissimilarity was developed in a fashion similar to that reported by Green (Green, Shaffer, & Gilmore, 1993). This scale was produced by rating the perceptual intensity implied by adverbs describing different levels of dissimilarity, and then attaching those descriptors to appropriate locations on a numerical scale. The usefulness of the scale was demonstrated by its ability to produce visual color space with ratings of dissimilarity of Munsell color chips. The stability and reliability of the LDS was evaluated by comparing it with the traditional scaling technique of magnitude estimation (ME). It was found that the scales produced similar ratings of odorant dissimilarity and showed a similar susceptibility to the effects of contrast convergence. However, the coefficients of variation of dissimilarities rated with ME were much higher than those produced with the LDS. The subjects also dealt with the LDS without the anxiety that usually accompanies first-time users of ME. The LDS provided stable ratings of odorant dissimilarity and preserved the inferred ratio scale properties of ME.
Three human IFN-alpha hybrids, HY-1 [IFN-alpha21a(1-75)/alpha2c(76-165)], HY-2 [IFN-alpha21a(1-95)/alpha2c(96-165)], and HY-3 [IFN-alpha2c(1-95)/alpha21a(96-166)], were constructed, cloned, and expressed. The hybrids had comparable specific antiviral activities on Madin-Darby bovine kidney (MDBK) cells but exhibited very different antiproliferative and binding properties on human Daudi and WISH cells and primary human lymphocytes. Our data suggest that a portion of the N-terminal region of the molecule is important for interaction with components involved in binding of IFN-alpha2b while the C-terminal portion of IFN is critical for antiproliferative activity. A domain affecting the antiproliferative activity was found within the C-terminal region from amino acid residues 75-166. The signal transduction properties of HY-2 and HY-3 were evaluated by EMSA and RNase protection assays. Both HY-2 and HY-3 induced activation of STAT1 and 2. However, HY-2 exhibited essentially no antiproliferative effects at concentrations that activated STAT1 and 2. Additionally, at concentrations where no antiproliferative activity was seen, HY-2 induced a variety of IFN-responsive genes to the same degree as HY-3. RNase protection assays also indicate that, at concentrations where no antiproliferative activity was seen for HY-2, this construct retained the ability to induce a variety of IFN-inducible genes. These data suggest that the antiproliferative response may not be solely directed by the activation of the STAT1 and STAT2 pathway in the cells tested.
Vancomycin, a macrocyclic antibiotic, is an amphoteric glycopeptide produced by Streptomyces orientalis which has proven to be a viable chiral selector for high performance liquid chromatograph (HPLC) (D. W. Armstrong, Y. Tang, S. Chen, Y. Zhou, C. Bagwill and J-R. Chen, Anal. Chem. (1994; 66: 1473). While it is related to other glycopeptide antibiotics, vancomycin has a number of unique structural features, including 18 stereogenic centers, five aromatic rings, and two side chains one of which is a carbohydrate dimer. Therefore, a vancomycin-based stationary phase appears to be multimodal in that it can be utilized in both normal-phase and reversed-phase liquid chromatography. Consequently, the enantiomeric separation may be operative via several mechanisms, including pi-pi complexation, dipole stacking, inclusion, hydrogen bonding, or combinations of these interactions. LC/MS/MS is a powerful tool for quantitative analysis when evaluated on the basis of speed, specificity, reliability and sensitivity. For these reasons, the present paper explored the feasibility of bonded macrocyclic glycopeptide phases for chiral LC/MS/MS quantitative analysis. Methylphenidate was used as a model compound. A rapid chiral bioanalytical method (<7.5 min) for the determination of the enantiomers of methylphenidate was developed. A lower limit of quantification (LLOQ) of 87 pg/mL was attained for the human plasma assay. This is to our knowledge the first example of enantioselective reversed-phase LC/MS/MS for methylphenidate. The chiral column was relatively cost effective and exhibited excellent performance with no separation deterioration observed after approximately 2500 injections.
BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to impaired renal function and hypertension, suggesting that an adverse prenatal environment could alter kidney development and renin production. METHODS: Immunohistochemistry and in situ hybridization were employed to localize renin-containing cells (RCCs) in the deep, middle, and superficial zones of autopsy kidney sections, in parallel with histologic maturation, from unexplained stillborn fetuses of normal weight (N = 26) and stillborn fetuses with IUGR (N = 17). RESULTS: In the control group, the number of RCC per 100 glomeruli in the deep zone decreased with advancing gestation from 40 at 20 weeks gestation to five at term (P < 0.001), whereas the opposite change was found in the superficial zone (increase from 5 per 100 to 55 per 100; P < 0.001). In the IUGR group, the density of RCCs in both the superficial and deep zones was similar to the control group at 20 weeks, and no shift in renin gene expression was observed as gestation advanced. Histologic maturation was unaltered. CONCLUSIONS: Renin gene expression persists and predominates in the deep renal cortex of the stillborn IUGR fetus, and could contribute to the pathogenesis of neonatal oliguria and/or hypertension during postnatal life.
In a randomised, double-blind, placebo-controlled trial, the effect of preoperative local anaesthesia vasoconstrictor infiltration on peri- and postoperative bleeding and postoperative pain was evaluated in 24 consecutive patients undergoing breast reduction. After the induction of general anaesthesia, one breast was infiltrated with a solution of bupivacaine with adrenaline and the other with the same amount of normal saline solution simultaneously. The perioperative blood loss was calculated by weighing swabs, and postoperative drainage was measured at 3, 24 and 48 h by using suction drains. Postoperative pain was assessed using visual analogue scales and verbal response scores at 3, 6, 10 and 24 h post-infiltration. There was a reduction in perioperative blood loss in the breast infiltrated with bupivacaine and adrenaline (P < 0.01). The mean blood loss in the drains from the infiltrated breasts was also less than that from the control sides at 3 and 24 h post-infiltration (P < 0.05). Pain was significantly less (P < 0.01) at 3 h on the local anaesthetic side. At 6, 10 and 24 h, pain tended to be less on the local anaesthetic side, but this did not reach statistical significance. No major complications were seen. Our results confirm a beneficial effect of bupivacaine with adrenaline on peri- and postoperative bleeding as well as in the early postoperative phase of pain.
Methadone Medical Maintenance (MDM) is an alternative for treatment of stable methadone maintained individuals. It involves a monthly physician's visit, at which methadone take-home doses are dispensed to last until the next appointment. The safety and efficacy of this treatment modality is currently under investigation. The purpose of this study was to evaluate the long-term safety and efficacy of MDM in a methadone program in Baltimore. A sample of 21 patients was enrolled in the study and followed for 12 years. They were evaluated once a month by a primary care physician affiliated with a methadone clinic who collected urine toxicology samples and dispensed the monthly methadone dose. The results showed that only 6 (28.6%) patients dropped out during the 12 years of the study. Twelve (0.5%) of 2,290 urine samples collected were positive for drugs. No methadone overdose or diversion was observed. Participants reported significant improvement in their quality of life. The results of this study support the safety and efficacy of medical maintenance of stable methadone maintained individuals.
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OBJECTIVES: To describe the clinical and neuroradiological features of basilar impression in patients with osteogenesis imperfecta type IV. METHODS: Four patients with basilar impression were ascertained in a population study of osteogenesis imperfecta. All four had detailed clinical and neuroradiological examination with both CT and MRI of the craniocervical junction and posterior fossa structures. RESULTS: All four showed significant compression of the posterior fossa structures and surgical decompression was performed with relief of symptoms. CONCLUSION: Symptoms of cough headache and trigeminal neuralgia occurring in patients with osteogenesis imperfecta are indications for detailed clinical and neuroradiological investigation to document basilar impression.
Over the last 10 years, there have been great advances in knowledge concerning changes in tissue perfusion and its prognostic implications. Has this translated into improved patient management? We review the clinical trials that have deliberately increased tissue oxygen delivery by increasing cardiac output. We have divided the studies into those that intervene early or those that intervene late in the course of a patient's illness. Although there are methodological problems limiting interpretation of the results, we show a combined odds ratio of a reduction in mortality for the early studies but not for the late studies. We conclude that a treatment policy whereby oxygen delivery is deliberately increased improves patient outcome if it is initiated early, prior to the onset of organ failure.
Adenomatous polyposis coli (APC) mutations are present in >70% of colon cancers. The APC protein binds to beta-catenin (beta-cat), a protein first identified because of its role in E-cadherin (E-cad) cell adhesion. In some colon cancers lacking APC defects, mutations in presumptive glycogen synthase kinase 3beta phosphorylation sites near the beta-cat NH2 terminus appear to render beta-cat resistant to regulation by APC and glycogen synthase kinase 3beta. In cells with APC or beta-cat defects, beta-cat is stabilized and, in turn, binds to and activates T-cell factor (Tcf)/lymphoid enhancer factor (Lef) transcription factors. To further explore the role of APC, beta-cat, Tcf, and E-cad defects in gastrointestinal cancers, we assessed gastric and pancreatic cancers for constitutive Tcf transcriptional activity (CTTA). Two of four gastric and two of eight pancreatic cancer lines showed CTTA. One gastric and one pancreatic cancer had mutations in the NH2-terminal phosphorylation sites of beta-cat. The other gastric cancer with CTTA had a missense mutation at serine 28 of gamma-cat, a potential phosphorylation site in this beta-cat-related protein. Although E-cad is an important binding partner for beta-cat and gamma-cat, E-cad inactivation did not result in CTTA. The beta-cat and gamma-cat mutant proteins identified in our studies strongly activated Tcf transcription in vitro, whereas beta-cat mutant proteins with large NH2-terminal deletions had only modest effects on Tcf. Our results suggest a role for Tcf deregulation in gastric and pancreatic cancer, resulting from beta-cat and gamma-cat mutations in some cases and, in others, from yet to be defined defects. Furthermore, these data imply that the consequences of APC and beta-cat mutations are distinct from the effects of E-cad inactivation.
To determine whether a postoperative rehabilitation protocol incorporating continuous passive motion would increase the total range of motion obtained 6 months following silicone interposition arthroplasty of the metacarpophalangeal joints in patients with rheumatoid arthritis, a prospective trial randomizing patients to receive either continuous passive motion or the standard dynamic splint protocol (modified Madden protocol) was undertaken. Fifteen hands (60 joints) were treated with the modified Madden protocol and 10 hands (40 joints) had continuous passive motion. The mean 6-month postoperative range of motion was 7 degrees in the modified Madden cohort compared with 39 degrees in the continuous passive motion cohort, representing an improvement of 22 degrees in the modified Madden cohort compared with an improvement of only 5 degrees in the continuous passive motion cohort. Residual ulnar deviation 8 degrees vs 12 degrees and grip strength (2.3 kgf v 3.7 kgf) were both lower in the continuous passive motion cohort. Incorporation of the continuous passive motion machine in the postoperative rehabilitation protocol does not offer sufficient advantages to justify the added costs.
The clinical and pathologic features of 17 cases of papillary serous adenocarcinoma of the cervix (PSCC) were studied in women who ranged in age from 26 to 70 years. There was a bimodal age distribution, with one peak occurring before the age of 40 years and the second peak after the age of 65. The presenting symptoms were abnormal vaginal bleeding (11 patients), abnormal exfoliative cervical cytology (four patients), or watery vaginal discharge (two patients). On pelvic examination, eight patients had a polypoid or exophytic cervical mass and two patients had an ulcerated or indurated cervix; no abnormality was detected in seven patients. Two tumors were stage Ia, 12 were stage Ib, two were stage II, and one was stage III. Nine patients were treated by radical hysterectomy and one by simple hysterectomy; six of these patients received postoperative radiotherapy. The other patients received primary radiotherapy. On microscopic examination, all of the tumors had a complex papillary architecture with epithelial stratification and tufting. Six tumors were grade 2/3 and 11 were grade 3/3. All of the tumors had >10 mitotic figures per 10 high-power fields. An intense acute and chronic inflammatory infiltrate was typically present within the cores of the papillae and in areas of stromal invasion. Occasional psammoma bodies were present in three cases. Five of 12 tumors stained positively for p53, with six and nine of 12 tumors, respectively, immunoreactive for carcinoembryonic antigen and CA-125. Seven tumors were mixed with another histologic subtype of cervical adenocarcinoma, most commonly low-grade villoglandular adenocarcinoma. Fifteen patients were followed from 6 months to 11 years (mean 56 months). Six patients died of extensive metastases within 5 years of diagnosis; an additional patient experienced tumor recurrence with malignant ascites 2 years after diagnosis. The most common metastatic sites were pelvic and periaortic lymph nodes; other sites included cervical lymph nodes, lung, peritoneum, liver, and skin. Eight patients were alive without evidence of tumor at last follow-up. Age <65 years, stage >I, tumor size >2 cm, tumor invasion >10 mm, the presence of lymph node metastases, and elevation of serum CA-125 were associated with a poor prognosis. Tumor grade or composition (pure or mixed) did not correlate with patient outcome. Papillary serous adenocarcinoma of the cervix resembles microscopically its counterparts elsewhere in the female genital tract and peritoneum. The tumors can behave aggressively with supradiaphragmatic metastases and a rapidly fatal course when diagnosed at an advanced stage, but the outcome for patients with stage I tumors is similar to that of patients with cervical adenocarcinomas of the usual type.
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STUDY OBJECTIVE: To assess the ability of parents to estimate their children's weight. METHODS: We assembled a convenience sample of children, newborn to 5 years, who presented to the ED of a tertiary care hospital. Each child's mother or father was asked to estimate the child's weight as accurately as possible. The triage nurse then weighed the child on an electronic scale. An age-based formula was also used to estimate the child's weight. The parental estimate and the formula-based weight were compared with the weight indicated on the scale. RESULTS: One hundred seventeen children were enrolled. The mean age was 26.7 months (range, newborn to 60 months). We analyzed agreement by plotting the percent difference between the weight estimates against the actual weights. The mean +/- SD difference between the parental estimate and the actual weight was 6.8% +/- 9.8%. Parental estimates were accurate to within 10% of the measured weight in 80% of the cases (94 of 117). The mean +/-SD difference between the formula-derived weight and the actual weight was 13.6% +/- 17.5%. The formula was accurate to within 10% of the measured weight in 46% of cases (54 of 117). CONCLUSION: In 80% of cases, the parental estimate of the child's weight was within 10% of the measured weight. The parental estimate was more accurate than the formula-derived weight.
We determined the prevalence of herpes simplex virus (HSV) and cytomegalovirus (CMV) antibodies in a cohort of adolescents 12 to 22 years of age in anticipation of the development of vaccines to control HSV and CMV infections. For the overall study population, we found that 62% were seropositive for HSV type 1 (HSV-1), 12% were seropositive for HSV type 2 (HSV-2), and 65% were seropositive for CMV. Race was not related to HSV-1 seropositivity, but African-American adolescents were more likely than Caucasian adolescents to be seropositive for HSV-2 and CMV. Girls also were more likely than boys to be seropositive for HSV-2 and CMV. For boys, history of a sexually transmitted disease was identified as a risk factor for HSV-2 seropositivity; for girls, a greater number of sexual partners increased the risk of being seropositive for HSV-2. Our data demonstrating a high prevalence of infection during adolescence suggest that immunization for HSV-1, HSV-2, and CMV may need to occur in childhood.
The aim of this study was to establish rates of behavioural and emotional problems, and of social maladjustment, in a population of deaf children, particularly in relation to different methods of communication. The parents of 84 children who attended two schools for the deaf took part. They completed the parents' checklist (PCL), a behaviour rating scale for deaf children, and the Child Behaviour Checklist (CBCL), a measure widely used in the general population. The two instruments were significantly correlated on the severity of behavioural and emotional problems, but their previously established cut-off scores detected different rates of possible clinical cases, i.e. children with mental health disorders. According to the CBCL, 40% of children were within the clinical range, and 82% were socially dysfunctional compared with the general population. The PCL identified a much higher percentage (77%) of caseness. Behavioural and emotional problems were significantly higher in Asian children. Although all subjects used sign language, the additional use of speech, which may indicate increased hearing ability, had a protective effect for adolescents. The findings are discussed in relation to the validation of the instruments and the development of intervention programmes for deaf children.
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