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Biomedical subjects

T H Smith

Publications and source records attributed to T H Smith.

At least 55 records · Page 3Linked to original sources
PubMed1984

Spontaneous occurrence of localized pulmonary interstitial and endolymphatic emphysema in infancy.

Two infants are described with persistent pulmonary interstitial and endolymphatic emphysema of the localized, bullous type, occurring apparently spontaneously. Roentgenographically, the process simulated congenital lobar emphysema in the first patient and bilateral post-infectious pneumatoceles in the second. The histologic features of the lesion were identical to those seen in localized pulmonary interstitial emphysema caused by positive pressure ventilation in newborns with hyaline membrane disease.

Female↗
PubMed1982

Antimicrobial activities of daunorubicin and adriamycin derivatives on bacterial and protoplast type L-form cells of Bacillus subtilis 170, Escherichia coli B, and Proteus mirabilis VI. Structure--activity relationship.

The antibacterial activity of ten N-alkylated derivatives of daunorubicin and adriamycin as well as of 5-iminodaunorubicin has been tested by using Bacillus subtilis 170, Escherichia coli B, and Proteus mirabilis VI and their stable protoplast type L-forms in an agar diffusion test. Eight of the substances showed similar activities against B. subtilis and the L-forms of all test organisms, but no activity against the bacterial forms of E. coli and P. mirabilis. The cell wall of these gram-negative bacteria is responsible for this resistance by not allowing the antibiotics to enter the cells. The piperidino compound N-(CH2)5 daunorubicin shows 2-4 times higher activity against B. subtilis and all L-forms in comparison to daunorubicin and the other derivatives. Five of the substances were inactive against all test strains. Their inactivity seems to be associated with the larger substituents at the C-3' position. Relations between molecular structure and activity are discussed considering data about the interaction with DNA and the antitumor activity. Stable protoplast type L-forms and their bacterial forms represent a suitable and effective test system to screen for more effective substances and to get more information about their mode of action.

Bacillus subtilis↗
PubMed1980

Necrotizing enterocolitis following operation in the neonatal period.

Necrotizing enterocolitis (NEC) usually occurs in low birth weight infants who have had perinatal stress, and the mortality remains significant. There are a few reports of NEC in the postoperative period, especially in young infants. Nine neonates developed NEC following operations and form the basis of this report. The interval between operation and the diagnosis of NEC varied from 3 days to 4 mo. The surgical lesions included one case each of esophageal atresia, tetralogy of Fallot, supralevator rectal atresia with rectourethral fistula, and multiple intestinal atresias. Three babies had gastroschisis and two had "apple peel" intestinal atresia. Only 3 of the 9 survived. The usual clinical findings of NEC, abdominal distention, bile stained gastric residuals and diarrhea (with or without blood), can occur in the postoperative period without NEC and are, therefore, not reliable diagnostic signs. Significant changes in the clinical course of these babies occurred from 7 hr to 5 days before the diagnosis was established. In these patients the roentgen findings that established the diagnosis of NEC included intestinal ileus, pneumatosis intestinalis, and portal vein gas. Pneumatosis intestinalis and portal vein gas were the most reliable diagnostic signs, but appeared relatively late in the course of the disease. In one case pneumatosis was seen only in retrospect. None of the patients had definite pneumoperitoneum. Awareness of NEC as a potential postoperative complication may result in early recognition, treatment and survival.

Congenital Abnormalities↗
PubMed1979

Structural biochemistry XIII: Synthesis of luteinizing hormone-releasing hormone modification [Trp8]-LH-RH.

A fragment condensation method was utilized for synthesis of the Trp8-substituted luteinizing hormone-releasing hormone (LH-RH). tert-Butoxycarbonyl protection was employed for the alpha-amino positions, and benzyl protection was used for the phenol group of Tyr and the imidazole nitrogen of His. Peptide bond-forming reactions were performed using N-hydroxysuccinimide (for Trp), dicyclohexylcarbodiimide-1-hydroxybenzotriazole, 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide hydrochloride, or mixed carbonic anhydride methods. Biological evaluation of [Trp8]-LH-RH indicated no luteinizing hormone-releasing activity or inhibition of luteinizing hormone release over the dose ranges studied.

Animals↗
PubMed1979

Postradiation renovascular hypertension.

Radiation injury to arteries can represent a significant complication of therapeutic irradiation, even when the dosage used has not been excessive as judged by approved protocols. Children in whom therapeutic abdominal irradiation has been used should be monitored indefinitely for the development of hypertension. The presence of hypertension in such children with normal blood urea nitrogen (BUN) and creatinine, and without proteinuria, should prompt investigation for a renovascular lesion. Standard bypass procedures are usually effective, although the long-term success may be compromised by continuing changes in affected vessels.

Adolescent↗
PubMed1979

Synthesis of daunorubicin analogues with novel 9-acyl substituents.

Synthetic approaches to anthracyclines bearing novel 9-acyl substituents were investigated. Reaction of the lithium enolate of N-(trifluoroacetyl)daunorubicin (9) with methyl iodide in tetrahydrofuran afforded only the 9-propionyl derivative 10 in high yield. Reaction of 10 under identical conditions cleanly afforded the 9-isobutyryl derivative 11. Extension of this procedure to other alkylating agents (ethyl iodide, benzyl bromide, and heptyl iodide) required hexamethylphosphoramide as cosolvent and afforded mixtures of mono- and dialkylated products as well as recovered 9. The amino group was deblocked with NaOH in aqueous tetrahydrofuran, except in the case of the dibenzyl derivative 13 which was inert under these conditions. The 9-formyl analogue 23 was prepared via NaIO4 cleavage of 13-dihydroadriamycin (21). Antitumor evaluation against P388 leukemia in mice showed 23 to have activity comparable to the parent compounds, while the C-alkylated analogues were less active.

Animals↗
PubMed1979

Adriamycin analogues. 3. Synthesis of N-alkylated anthracyclines with enhanced efficacy and reduced cardiotoxicity.

Reaction of daunorubicin (1) and adriamycin (2) with aldehydes and ketones in the presence of NaCNBH3 afforded N-alkyl- and N,N-dialkylanthracyclines along with their 13-dihydro derivatives. Product ratios depended upon the nature of the carbonyl reagent and the starting drug. The majority of these analogues retained in vivo antitumor activity comparable to 1 and 2. However, unlike the parent compounds, which inhibit DNA and RNA synthesis at comparable concentrations, several of these analogues inhibit RNA synthesis at markedly lower concentrations than required to inhibit DNA synthesis. In addition, in some cases the ability to bind to DNA in vitro was reduced while antitumor activity was retained. N,N-Dibenzyldaunorubicin was especially notable for increased efficacy (T/C 259, qd 1--9) against P388 leukemia in mice, despite reduction of DNA binding in vitro. It showed almost complete loss of mutagenicity vs S. typhimurium (Ames test) and it was tenfold less cardiotoxic by electrocardiographic measurements (Zbinden test) in the rat.

Alkylation↗
PubMed1979

7-(Aminoethyl) ether and thioether of daunomycinone.

One-step treatment of daunomycinone with excess 2-aminoethanethiol and 2-aminoethanol in trifluoroacetic acid afforded at C-7 the thioether (77% yield) and ether (30% after recycling), respectively. Stereoselectivity for the natural 7S over the 7R configuration was greater for the ether (97:3) than for the thioether (2.5:1). Esterification of daunomycin at C-7 with beta-alanine was accomplished through the mixed anhydride of Z(OMe)-beta-alanine. Preliminary biological tests suggests that the antitumor and DNA interactive properties of the anthracyclines can be retained in such structures.

Animals↗
PubMed1978

Adriamycin analogues. 2. Synthesis of 13-deoxyanthracyclines.

The syntheses of several 13-deoxyanthracyclines are described. Koenigs-Knorr condensation of epsilon-rhodomycinone (12) with the protected daunosaminyl chloride 15 afforded 14 after deprotection. Efforts to decarbomethoxylate 12, as well as attempts to selectively deoxygenate the 13 position of daunomycinone and adriamycinone, were unsuccessful as approaches to 13-deoxyanthracyclines. However, reaction of the readily available tosylhydrazones 4 and 5, of daunorubicin and adriamycin with NaCNBH3 in acidic MeOH, afforded the 13-deoxy analogues 6 and 7 in satisfactory yield. These compounds retained antitumor activity, being comparable to the parent compounds in both efficacy and potency in the P-388 mouse leukemia screen. The epsilon-rhodomycinone glycoside 14 was less active than 6 and 7.

Animals↗
PubMed1978

Cystic retroperitoneal lymphangioma in infants and children.

Retroperitoneal lymphangiomas are uncommon benign tumors usually presenting in early life. They may cause significant pressure on adjacent structures, most often with superior and medial displacement of the kidney and medial deviation of the ureter. Relative radiolucency on total body opacification during excretory urography, and features of a cystic structure on ultrasonography and computed tomography should further suggest the possibility of a retroperitoneal lymphangioma. Vascular stretching and displacement without neovascularity on angiography and contrast entry into the cysts on lower extremity lymphography are additional features, but such procedures are usually unnecessary.

Child, Preschool↗