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Biomedical subjects

D M Cox

Publications and source records attributed to D M Cox.

At least 37 records · Page 2Linked to original sources

Lipidic peptides. V: Penicillin and cephalosporin acid conjugates with increased lipophilic character.

Lipophilic, double-ester derivatives of beta-lactam antibiotics with methylene, ethylene, and propylene spacers were prepared by crown-ether-assisted coupling of halogenoalkyl esters of 2-(tert-butoxycarbonylamino)decanoic acid to either penicillin G or cefuroxime. The hydroxyethyl ester of penicillin G and the tert-butoxypropyl ester of cefuroxime were also prepared. The lipophilic, double-ester conjugates, the hydroxyethyl ester of penicillin G, and the tert-butoxypropyl ester of cefuroxime showed weak or no antibiotic activity in vitro, as expected. The lipophilic penicillin G conjugates and the tert-butoxypropyl ester of cefuroxime were active in vivo against a nonpenicillinase-producing strain of Staphylococcus aureus after subcutaneous administration. The penicillin G double ester with propylene spacer and the tert-butoxypropyl ester of cefuroxime were inactive in vitro, a fact indicating that both compounds were hydrolyzed in vivo, as desired. After oral administration, the lipophilic, double-ester conjugate of penicillin G with methylene spacer and the tert-butoxypropyl ester of cefuroxime were active.

Administration, Oral↗

Canadian multicenter randomized clinical trial of chorion villus sampling and amniocentesis. chromosome mosaicism in CVS and amniocentesis samples.

Data on 1040 chorionic villus and 969 amniotic fluid samples were collected from women studied in the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic results were obtained from 98.0 per cent of chorionic villus samples and from 99.9 per cent of amniotic fluid samples. Level I mosaicism (a single cell with an abnormal karyotype) occurred frequently in both chorionic villus and amniotic fluid samples and appeared to have no clinical significance. Level II mosaicism occurred in 0.9 per cent of CVS mesenchyme and 1.5 per cent of amniotic fluid cultures and in general was not perceived to be of sufficient concern to warrant cytogenetic follow-up studies. Level III mosaicism was reported in 18 CVS cases (15 cytotrophoblast, 1 mesenchyme, and 2 with both cell methods) and in one amniotic fluid case. In all cases but one (fetus with trisomy 18), level III mosaicism was confined to the placenta. Maternal cell contamination occurring with a frequency of 6.4 per cent in the mesenchyme analyses was a concern. This study supports the final report of the Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis. Cytogenetic analysis of chorionic villus samples appears to be an acceptable alternative to the analysis of amniotic fluid samples. However, because of mosaicism and maternal cell contamination concerns, the examination of both cytotrophoblast preparations and mesenchyme cultures from chorionic villus samples is recommended.

Adult↗

Cri du chat syndrome due to meiotic recombination in a pericentric inversion 5 carrier.

A female infant presented at birth with hypotonia, growth retardation, distinctive facies, multiple congenital anomalies, and a high-pitched mewing cry characteristic of cri du chat syndrome. Chromosome studies from both peripheral blood and fibroblasts showed a 46,XX,5p- karyotype. Parental chromosome studies revealed that the mother carried an apparently balanced pericentric inversion of one chromosome no. 5, 46,XX,inv(5)(p14q35). Meiotic crossing-over in the mother within the inverted segment of chromosome 5 gave rise to the unbalanced karyotype, 46,XX,rec(5)dup q, inv(5)(p14q35)mat in the infant. A small terminal segment of the long arm of chromosome 5 (q35-pter) is duplicated with a deletion of the short arm of chromosome 5 (p14-pter), accounting for the features of cri du chat syndrome. Fewer than 1 in 200 of cri du chat syndrome cases are due to recombination aneusomy arising from a parental inversion of chromosome 5. Some of these cases, however, do not have typical cri du chat syndrome, reflecting significant duplication of 5q material. These cases are reviewed with the present case, and recombination behaviour leading to chromosome imbalance is discussed.

Chromosome Inversion↗

Complete heart block in the pediatric patient.

Care for the pediatric patient with CHB focuses on signs and symptoms associated with respiratory failure and shock. Differences in size among pediatric patients--and in anatomy, physiology, and possible causes--should be considered. In children, cardiac arrest is usually secondary to respiratory arrest. Respiratory arrest should be anticipated in a pediatric patient with (1) decreased level of consciousness, (2) poor muscle tone, (3) increased respiratory rate or respiratory effort (nasal flaring, intercostal, subcostal, and suprasternal retractions); or (4) cyanosis. Shock is the failure of the cardiovascular system to perfuse vital organs adequately. Organ perfusion is determined by cardiac output, which in turn results from the heart rate times stroke volume. In CHB the slowing of heart rate can significantly decrease cardiac output, so the signs and symptoms of shock--especially level of consciousness, peripheral circulation, and blood pressure--must continually be reassessed.

Child↗

Sex chromosome mosaicism not detected at amniocentesis.

Amniocentesis was performed because of a fetal abdominal wall defect, and a 45,X karyotype was obtained. A near-normal male infant with no features of Turner syndrome was delivered. The karyotype of the infant was 45,X/46,X,dic(Y)(q11), with each of the cell lines present in approximately 50 per cent of the lymphocytes and fibroblasts examined.

Abdominal Muscles↗

A familial interstitial deletion of the long arm of chromosome 21.

A mother and daughter with an interstitial deletion of the chromosome segment 21q11 to 21q21.3 have similar minor dysmorphism and mild mental retardation. These two patients are compared to others in the literature with deletion of the same region of chromosome 21. Molecular analysis of DNA from our patients localizes the DNA segments D21S1, D21S11, D21S8, and D21S22 within the deleted region.

Abnormalities, Multiple↗

Proteolytic activities of human Campylobacter pylori and ferret gastric Campylobacter-like organism.

The levels of proteolytic activity in cell washes, lysates and pellets of C. pylori and gastric Campylobacter-like organisms isolated from humans and ferrets, respectively, have been studied using porcine mucus glycoprotein and bovine haemoglobin substrates. The total haemoglobin degrading activity, expressed by 10(12)-10(13) cfu of either organism, was no greater than 3 micrograms chymotrypsin equivalents. The mucolytic specific activity (rate of mucus peptide bond hydrolysis by bacterial protein) of the fractions tested from both organisms did not exceed 2nmol/min/mg protein. This value is 1000-fold lower than expected from published data. Electrophoretic profiles suggested that the mucolytic activity assessed by fluorimetry was insufficient to alter the quaternary structure of mucus and hence may not significantly contribute to the undermining of gastric mucus integrity.

Animals↗

An interstitial deletion of the long arm of chromosome 13.

A case of an interstitial deletion of chromosome 13, identified as 46,XY,del(13)(q22q31), is reported in a child with psychomotor retardation, prominent low-set ears, epicanthus, hypertelorism, broad nasal bridge, hypoplastic fifth fingers and abnormal dermatoglyphics. This patient is compared to others in the literature with a similar deletion.

Child, Preschool↗

Difficulties encountered in a randomization trial of CVS versus amniocentesis for prenatal diagnosis.

In April 1985, having completed a study of the short-term complications of chorionic villus sampling (CVS), we began a randomized comparison of CVS versus amniocentesis. Our study continued over a 15-month period, and during that time we had difficulty recruiting patients, with only 10.6% of 1254 women referred for prenatal diagnosis fully participating in this study. However, 30.2% of those eligible by dates and indication chose to enter the study. CVS was available in our province only through this study, and the two most common reasons for such a low rate of recruitment were reporting too late in pregnancy and the concern about the potential risks of CVS. Patients continued to seek counselling too late for CVS despite direct and continuous contact with regional physicians. Our patients' concern about risk might well vary with the attitude of their physicians towards CVS, and with the information provided at the time of pre-test counselling. The small number of patients actually enrolled did not permit any meaningful comparison of amniocentesis to CVS. However, our experience with pregnancies lost post-CVS suggests that a pregnancy with an apparent low implantation at the time of sampling may be at a higher risk of loss.

Adult↗

Cefuroxime axetil in the treatment of uncomplicated UTI: a comparison with cefaclor and augmentin.

Cefuroxime axetil (CAE) is an acetoxyethyl ester prodrug of cefuroxime. The efficacy and safety of cefuroxime axetil was studied in a randomized general practice trial in urological infections where cefuroxime axetil 250 mg b.d. was compared with amoxycillin/clavulanate (Augmentin, AUG) 375 mg t.d.s. A randomized trial was then performed in hospital outpatients, who received cefuroxime axetil 250 mg b.d. or cefaclor (CCL) 250 mg t.d.s. Of 140 clinically assessable patients, 108 were cured and 28 improved on cefuroxime axetil (97% success) compared with 75 cured and 13 improved out of 89 on Augmentin (99% success) and 31 cured and 7 improved out of 38 patients treated with cefaclor (97% success). Bacteriology was assessable in 101 patients given cefuroxime axetil (72% cleared), 61 of those given Augmentin (70% cleared) and 27 out of 28 (96%) given cefaclor. As expected, the predominant pathogen was E. coli, accounting for 61% of isolates overall. Drug-related adverse events occurred in 10% of patients given cefuroxime axetil, including diarrhoea in 4%. Eleven percent of patients given Augmentin suffered adverse events (5% diarrhoea) and 5% of those given cefaclor. Superinfections occurred in 4 cefaclor patients (2 Pseudomonas aeruginosa, 1 Candida, 1 E. coli) compared with 2 on cefuroxime axetil (1 Candida, 1 E. coli). Uncomplicated UTI accounted for 92% of cases in the G.P. trial and 82% of cases in the hospital trial. Cefuroxime axetil may be used safely and effectively to treat uncomplicated UTI at a dose of 250 mg b.d.

Adolescent↗

A comparison of the efficacy and safety of cefuroxime axetil and augmentin in the treatment of upper respiratory tract infections.

Cefuroxime axetil (CAE), an orally absorbed prodrug of cefuroxime, was evaluated for its efficacy and safety in the treatment of upper respiratory tract infections (tonsillitis, pharyngitis, sinusitis and otitis media) in general practice in the United Kingdom. A total of 385 patients aged 14 or over were enrolled in a randomized study to compare cefuroxime axetil 250 mg b.d. for 5 days with amoxycillin/clavulanate (Augmentin, AUG) 375 mg t.d.s. for 5 days. Of 175 clinically assessable patients treated with cefuroxime axetil, 136 were cured and 33 improved (97% success rate). Of 188 assessable patients given Augmentin, 155 were cured and 29 improved (98% success rate). Sixty-four patients treated with cefuroxime axetil were evaluable for bacteriological response: 47 (73%) of the causative pathogens were eradicated, as compared with 62 of 86 (72%) in patients treated with Augmentin. Thirteen out of 181 (7%) patients treated with cefuroxime axetil experienced drug-related adverse events, including 4% with diarrhoea. In the Augmentin group 24 out of 204 (12%) patients had a drug-related adverse event, including 5% with diarrhoea. In conclusion, cefuroxime axetil at a dose of 250 mg b.d. appears to be as safe and effective as Augmentin at the higher dose of 375 mg t.d.s. in the treatment of upper respiratory tract infections.

Adolescent↗

Assessment of the early risks of chorionic villus sampling.

A study was carried out to develop proficiency in performing chorionic villus sampling (CVS) and to determine whether the risk for miscarriage was so high as to preclude a randomized clinical trial comparing CVS with amniocentesis. A total of 202 women who had decided to have induced abortions volunteered to either undergo CVS (101 women) or be a control (101). There were no differences between the two groups in factors that may affect the rate of miscarriage. CVS was performed an average of 9.8 days before abortion. The rate of fetal loss was significantly higher in the CVS group (p = 0.009). An analysis of the results as a function of the physician's experience over time showed that there were distinct learning phases. It may take longer than is generally recognized to acquire the expertise necessary to perform CVS with the lowest risk possible. Caution should be exercised before diagnostic CVS is offered to women who plan to continue their pregnancies.

Abortion, Spontaneous↗

Chondrodysplasia punctata in an infant with duplication 16p due to a 7;16 translocation.

This paper describes a newborn with a number of clinical manifestations compatible with duplication 16p due to a 46, XY, -7, +der (7), t(7;16) (p22;p13) pat karyotype. In addition, the baby had chondrodysplasia punctata, whose distribution of lesions did not match any of the well-documented forms of these disorders. The baby also had microcornea and lacked a gallbladder, two features, in addition to chondrodysplasia punctata, that have not previously been noted in cases of duplication 16p.

Chondrodysplasia Punctata↗

The characteristic physiognomy and tissue specific karyotype distribution in the Pallister-Killian syndrome.

We report a child with clinical features remarkably similar to those of our patient reported as tetrasomy 21 in 1982. Improved banding in this, and the previous case, together with gene dosage studies, and subsequent reports in the literature lead us to conclude that these patients are in fact tetrasomic for 12p. The clinical features of these children are most distinctive and the importance of their recognition lies in the fact that the abnormal cell line is virtually confined to fibroblast studies.

Chromosome Aberrations↗