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Biomedical subjects

H McDonald

Publications and source records attributed to H McDonald.

At least 37 records · Page 2Linked to original sources

Irradiated homologous aorta in eyelid reconstruction. Part II. Human data.

Reconstruction of posterior lamellar eyelid defects requires a tissue substitute that is either identical to the tissue lost (i.e., surrounding or nearby tarsus) or donor tissue that serves the same supportive role. With extensive lid defects, at times an alternative tissue to tarsus may be required. Irradiated homologous aorta is available as a posterior lamellar substitute. It provides a structural framework for the surrounding lid tissues to grow on and is incorporated into the normal eyelid anatomy. It is available to the reconstructive ophthalmic surgeons as an alternative donor tissue in the presence of extensive lid defects.

Adenocarcinoma↗

An Alu element retroposition in two families with Huntington disease defines a new active Alu subfamily.

Alu repetitive elements represent the most common short interspersed elements (SINEs) found in primates, with an estimated 500,000 members in the haploid human genome. Considerable evidence has accumulated that these elements have dispersed in the genome by active transcription followed by retroposition, and that this process is ongoing. Sequence variation between the individual elements has lead to the hierarchical classification of Alu repeats into families and subfamilies. Young subfamilies that are still being actively transposed are of considerable interest, and the identification of one such subfamily (designated 'PV') has lead to the hypothesis that the most recent retroposition events are due to a single master Alu source gene. In the course of our search for the gene causing Huntington disease, we have detected an Alu retroposition event in two families. Sequence analysis demonstrates that this Alu element is not a member of the PV subfamily, but is similar to 5 other Alu elements in the GenBank database. Together, these Alu elements, all of which contain a 7 base-pair internal duplication, define a distinct subfamily, designated as the Sb2 subfamily, providing evidence for a second actively retroposing Alu source gene. These data provide support for multiple source genes for Alu retroposition in the human genome.

Base Sequence↗

Identification of an Alu retrotransposition event in close proximity to a strong candidate gene for Huntington's disease.

Huntington's disease (HD) is a late-onset autosomal dominant neuropsychiatric disorder presenting in mid-adult life with personality disturbance and involuntary movements, cognitive and affective disturbance, and inexorable progression to death. The underlying genetic defect has been mapped to chromosomal band 4p16.3 (refs 2, 3). Analysis of specific recombination events in some families with HD has further refined the location of the HD defect to a 2.2 megabase DNA interval. Using a direct complementary DNA selection strategy we have identified at least seven transcriptional units within the minimal region believed to contain the HD gene. Screening with one of the cDNA clones identified an Alu insertion in genomic DNA from two persons with HD which showed complete cosegregation with the disease in these families but was not found in 1,000 control chromosomes. Two genes including the previously identified alpha-adducin gene and another that encodes for a 12-kilobase transcript, map in close proximity to the Alu insertion site. The 12-kilobase transcript should be regarded as a strong candidate for the HD gene.

Base Sequence↗

Orbital panniculitis as the initial manifestation of systemic lupus erythematosus.

Inflammation of the fat in lupus erythematosus also known as lupus erythematosus profundus (panniculitis) is a rare clinical entity. As the presenting feature of lupus, it is even more unusual. In this report, we describe an elderly woman who presented with an orbital mass infiltrate as the initial manifestation of lupus that had the classical histological features of lupus panniculitis.

Aged↗

A survey of exercise testing practice in Scottish hospitals.

A 1989 survey (unpublished) of exercise testing practice in Scotland suggested that there were important differences in the practice of exercise testing between hospitals. A postal questionnaire was sent to 30 teaching and district general hospitals in 1991 and followed up by telephone questioning of consultants. The numbers of exercise tests performed had increased to 22,012 in 1990, and a greater proportion were performed in district general hospitals. General practitioners had very limited access to the service but hospital doctors of any grade had almost free access. Rationing of early post myocardial infarction testing led to attempts to define "high risk" post infarction patients and this included inappropriate patients in many hospitals. A variety of different protocols was used. Eighteen out of 30 hospitals surveyed discontinued beta blockers but only four hospitals took account of antianginal, antihypertensive or other medication, and all but one exercised patients while on digoxin. In the majority of hospitals decisions regarding drug therapy were taken by individual physicians. A variety of personnel reported tests, many without specialist training in cardiology. Even among consultants there was no concerns on the degree of ST depression which was significant. Exercise tests performed in different hospitals in Scotland are not comparable due to the wide variation in patient selection, test conditions, and interpretation of tests. This problem is likely to be exacerbated by the multiple personnel involved in all aspects of testing. It seems probable that there is a problem throughout the United Kingdom, and that there is a need for guidelines.

Exercise Test↗

Failed dacryocystorhinostomy: the sump syndrome.

A dacryocystorhinostomy may fail due to a problem along the canaliculus, at the ostomy site of nasolacrimal sac to nose, due to an intranasal problem or related to the stent. The "sump syndrome" occurs when a residual nasolacrimal sac forms, collects fluids, and leads to tearing. This entity, although uncommon, has a characteristic clinical history and radiologic appearance.

Dacryocystorhinostomy↗

Comparison of pain, motion, and edema after modified radical mastectomy vs. local excision with axillary dissection and radiation.

Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2 less than 0.0001 and p2 = 0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2 = 0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2 = 0.085) at 1 year and (p2 = 0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗

Identification and characterization of a gene at D10S94 in the MEN2A region.

We have identified a candidate for the gene responsible for multiple endocrine neoplasia type 2A (MEN 2A) at D10S94 in proximal 10q11.2. An evolutionarily conserved sequence from D10S94 was used as a probe to isolate cDNAs corresponding to a gene that we have termed mcs94-1. The gene spans 11 kb and has an unmethylated CpG island at its 5' end. The mcs94-1 transcript is approximately 2.4 kb in length and is widely expressed. It encodes a putative 415-amino-acid polypeptide that is similar in sequence to nucleolin, an abundant nucleolar protein. Mcs94-1 was examined as a candidate for MEN2A through nucleotide sequence analysis of mcs94-1 exons from an MEN 2A chromosome and its wildtype homologue from an MEN 2A patient. The major portion of the expressed mcs94-1 sequence was examined. No differences in sequence were found between the two alleles.

Amino Acid Sequence↗

Microblepharon.

We describe a child with microblepharon and corneal exposure secondary to lagophthalmos. Surgical reconstruction utilizing full-thickness skin grafts to all four lids corrected the lagophthalmos and relieved her symptoms.

Child, Preschool↗

The influence of capsid protein cleavage on the processing of E2 and E1 glycoproteins of rubella virus.

The structural polyprotein of rubella virus is cotranslationally processed by host cell signal peptidase. Oligonucleotide-directed mutagenesis was used to alter the cleavage site between capsid and E2 proteins and to examine the importance of this cleavage for the transport and processing of E2 and E1 glycoproteins. The in vitro and in vivo expression of the cleavage site mutant revealed that the E2 polypeptide can cross the endoplasmic reticulum membrane without the cleavage of its signal peptide, while the transport of E2 beyond the endoplasmic reticulum requires the cleavage of E2 from capsid. We have shown that capsid protein does not appear to undergo further proteolytic processing after it is cleaved from E2 by signal peptidase. Some of the requirements for the cleavage by signal peptidase between capsid and E2 were examined by the in vitro analysis of wild-type and mutant cDNAs.

Animals↗

Immediate postexcision mammography for occult noncalcified breast lesions.

To evaluate completeness of surgical excision, we studied the use of film screen mammography done immediately after excision of occult noncalcified breast lesions in 11 patients. The postoperative mammograms were well tolerated, and allowed high quality films to be obtained. Complete excision was documented in ten patients, and one patient had small artifacts that resolved on follow-up studies. Roentgenograms of the surgical specimen from ten patients showed a discrete lesion in only three. Histologic analysis revealed malignancy in two patients and benign changes in nine. These findings indicate that mammography done immediately after excision of occult noncalcified lesions is more reliable than roentgenograms of the specimen and may be a useful method for confirming extent of excision. This method may also eliminate the present delay of four to six weeks before adequate postoperative follow-up films can be obtained to evaluate excision.

Adult↗

Effect of preoperative chemotherapy on mastectomy for locally advanced breast cancer.

Mastectomy is frequently performed after intensive chemotherapy for locally advanced breast cancer. The effects of preoperative chemotherapy on the postoperative course and the timing of subsequent adjuvant therapy, however, have not been defined. We therefore reviewed the perioperative course of 54 patients undergoing mastectomy after combination (CAMFPT) chemotherapy for stage IIIA,B (IIIA - 25 pts; IIIB noninflammatory - 5 pts; IIIB inflammatory-24 patients) breast cancer. A median of 7 cycles (6 months) of chemotherapy was administered preoperatively. Mastectomy was performed a median of 20 days after last chemotherapy; white blood cell count (WBC) and platelet counts returned to normal limits preoperatively. Total mastectomy with or without axillary node dissection was performed in 53 patients, and a Halsted radical mastectomy in 1 patient. Negative margins on breast and/or axillary tissue were achieved in 47 patients (87.0%). Postoperative complications included skin flap necrosis in 8 patients (14.8%), seroma formation in 5 patients (9.3%), and wound infection in 1 patient (1.9%). Median operative blood loss (550 cc), hospital stay (8 days), and duration of wound catheter drainage (6 days) were comparable to published reports for modified radical mastectomy without preoperative chemotherapy. Systemic chemotherapy was resumed a median of 16 days after mastectomy, and radiotherapy started a median of 33 days after mastectomy. These findings indicate that intensive preoperative chemotherapy does not increase the hospital course or the postoperative complications of mastectomy for locally advanced breast cancer. In view of the current interest in treatment of stage I and II breast cancer with preoperative chemotherapy, this information may be useful in their management as well.

Antineoplastic Combined Chemotherapy Protocols↗

Group B streptococcal colonization and preterm labour.

Recent publications have highlighted the controversy regarding the significance of Lancefield Group B Streptococcal (GBS) colonization in pregnancy and preterm delivery. In this prospective study vaginal swabs from 692 women at approximately 24 weeks' gestation were cultured for GBS. GBS was detected in 91 (13.2%) women. The rate of preterm labour (PTL) (less than 37 weeks) was significantly higher in GBS positive women than in GBS negative women (18.7% versus 5.5%; p less than 0.001). This association remained significant even when patients with other recognized factors predisposing to PTL were excluded (11.5% versus 3.9%; p less than 0.001). The rate of premature rupture of membranes (PROM) was also significantly higher in GBS positive women (9.9% versus 2.7%; p less than 0.005) and remained significantly higher when patients with other recognized risk factors were excluded (6.1% versus 1.8%; p less than 0.025). These results unequivocably show that pregnant women who are vaginal carriers of GBS have a significantly increased risk of PROM and PTL.

Female↗

Expression of rubella virus cDNA coding for the structural proteins.

A cDNA clone encoding the precursor polypeptide (Mr 115,000) to the nucleocapsid C (Mr 30,000) and two envelope glycoproteins E1 (Mr 58,000) and E2 (Mr 42,000-47,000) of rubella virus was inserted into a simian virus 40-derived eukaryotic expression vector. When the plasmid was introduced into COS cells, three proteins were synthesized. The expressed proteins were antigenically similar and identical in size to the authentic structural proteins of rubella virus. Expression in the presence of tunicamycin confirmed that E1 and E2 are glycoproteins. Unglycosylated E1 and E2 had Mrs of about 53,000 and 30,000, respectively. The mobility of the nucleocapsid protein was unaffected by tunicamycin. The locations of the translation start and stop codons for synthesis of the precursor to the structural proteins of rubella virus were determined by in vitro and in vivo expression studies. It was found that the first AUG codon at the 5' end of the rubella virus 24S cDNA acts as a start codon for translation. The stop codon was found to be 3183 bp from the start codon.

Animals↗

Optimal duration of cefotaxime prophylaxis in abdominal and vaginal hysterectomy.

Previous studies have demonstrated that short course perioperative antibiotic prophylaxis reduces septic morbidity after hysterectomy from up to 40% down to 10 to 15%. The residual morbidity is predominantly urinary tract infection (UTI) occurring 2 to 3 days after cessation of antibiotic. We hypothesised that surgery impairs urinary drainage for 3 to 4 days postoperatively and that prolonged prophylaxis was required to prevent all postoperative sepsis. Accordingly, 224 abdominal and 69 vaginal hysterectomy patients were randomly allocated to short course (2g cefotaxime IV at anaesthesia) or long course (2g cefotaxime at anaesthesia plus 7 doses of 1g 12-hourly) prophylaxis. UTI was effectively prevented by the long course (0.9 vs 18.4% short); both treatments effectively prevented wound and pelvic sepsis. We conclude that 4 days of postoperative antibiotic is required to prevent UTI.

Adult↗