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High resolution proton nuclear magnetic resonance (1H NMR) spectroscopy has been used to investigate the metabolism and urinary excretion of the aminopenicillins, ampicillin and amoxycillin, in rats and of amoxycillin in man. 1H NMR resonances of the aminopenicillins, together with those for their 5R, 6R and 5S, 6R penicilloic acids and diketopiperazine metabolites were detected, assigned and quantified in urine samples with the aid of spin-echo NMR techniques. The dimer of amoxycillin was detected in rat urine for the first time together with novel drug-related resonances assigned to amoxycillin carbamate. Quantitative 1H NMR spectroscopic results were consistent with HPLC and microbiological data considering that only single measurements were recorded. Due to the short analysis time and simple sample preparation, NMR was particularly useful for studying the metabolism of the aminopenicillins for which sample degradation poses analytical problems. The non-invasive character of 1H NMR spectroscopic analysis of urine also provided unique information on a reversible reaction between amoxycillin and bicarbonate, an endogenous urinary metabolite.

Four novel metabolites of a Penicillium strain, IMI 332995, which has previously been reported to produce paraherquamide and a number of related metabolites, are herein described. VM55596 is the first N-oxide to be found in this family of compounds. Unusual oxidative substitution is also seen in VM55597. VM55599 appears to be the first documented example of the hexacyclic indole species that have long been postulated as biosynthetic precursors of metabolites of the brevianamide, paraherquamide and marcfortine families.

In humans, application of the DuBois (DuBois et al. J. Appl. Physiol. 8: 587-594, 1956) six-element model to respiratory transfer impedance (Ztr) data has been proposed as a means to noninvasively estimate airway and tissue properties. This approach requires prior knowledge of alveolar gas compressibility (Cg). With input impedance (Zin), prior knowledge of Cg is not required, but the data do not support a reliable separation of airway from tissue properties. In this study, we investigated the separation of airway and tissue properties when Ztr and Zin data are measured and analyzed simultaneously over a larger frequency range than usual. In 10 healthy adults, we measured Ztr and Zin from 2 to 64 Hz. Zin was measured using both the standard approach with oscillations directly into the airway opening (Zst) and the head generator approach (Zhg) with oscillations applied around the head. With Ztr data alone, we found that the airway resistance and inertance estimates were reliable with only 2- to 32-Hz data and were unaffected by including the additional 32- to 64-Hz data. Conversely, the estimates of tissue resistance and inertance were highly unreliable unless the 32- to 64-Hz data are included. Because of enhanced sensitivity of Ztr to Cg from 32 to 64 Hz, inaccuracies in the assigned Cg will distort the estimated tissue but not airway properties. The Ztr-based parameters predicted Zhg data far better than Zst data, which is consistent with Zhg data being less influenced by upper airway shunting over this frequency range. There was no apparent advantage to combining Ztr and Zhg data during parameter estimation. With Cg unfixed, the estimated Cg was 50-100% higher than expected from an independent measurement of functional residual capacity. These results confirm that Ztr alone can provide a reliable distinction of lumped respiratory airway and tissue properties that are little influenced by upper airway wall shunting but only if 2- to 64-Hz data are analyzed. This distinction, however, requires an accurate prior measurement of Cg, and this requirement cannot be removed by combining Ztr and Zin data.

A novel series of milbemycin antibiotics were isolated from the fermentation broth of a Streptomyces species designated E225. The structures of the four main metabolites VM 44857 (1), VM 44864 (2), VM 44865 (3) and VM 44866 (4) were determined by NMR techniques. In addition we describe the solution conformations of the major metabolite VM 44857 (1).

Variable temperature proton nuclear magnetic resonance spectroscopy is used to establish that both sequence and dangling bases affect stability of short RNA double helices. Tetraribonucleotides, CAUG, UGCA and AGCU form reference duplexes (Tm 25 degrees, 33 degrees, 34 degrees, respectively) which contain an equal number of G . C and A . U base pairs and which show primary sequence is important. Pentaribonucleotides GAUGA, ACAUG, UGCAA and AGCUA, form duplexes (Tm 36 degrees, 35 degrees, 46 degrees, 45 degrees, respectively) with dangling adenines. Average Tm difference from the reference is +11 degrees for two 3' or 5'-dangling adenines. Pentaribonucleotides, CAUGU and UCAUG, form duplexes (Tm both 30 degrees) with dangling uracils. Average Tm difference from the reference is +5 degrees for two 3' or 5'-dangling uracils. Fraying was detected only in duplexes from the AGCU series. Presence of a dangling adenine, in duplex, AGCUA, caused a reduction in fraying.

The mobility of pseudomonic acid A in dimethyl sulfoxide-d6 solution has been determined from 13C spin-lattice relaxation time measurements at two field strengths. The central tetrahydropyran ring reorientates isotropically with a rotational correlation time of approximately 280 picoseconds/ radian . Both side-chains exhibit marked segmental motion with correlation times decreasing to only approximately 50 picoseconds/ radian at the end of the nonanoic acid side-chain.

Temocillin, 6 beta-(R,S-2'-carboxy-2'-thien-3-ylacetamido)-6 alpha-methoxypenicillanic acid, shows good stability in mild aqueous acid or base; in stronger acid the methoxypenillic acid is formed whereas alkaline or enzyme hydrolysis results in the formation of the methoxypenicilloic acid and the C-5 epimer.

A high-resolution agarose gel electrophoretic technique, coupled with immunofixation, was used to follow paraprotein concentrations retrospectively in a patient with multiple myeloma of nine years' duration. Although the patient's IgA lambda gammopathy "disappeared" shortly after the initiation of therapy, as judged by routine cellulose acetate electrophoresis and immunoelectrophoresis, high-resolution zone electrophoresis demonstrated a monoclonal band that we identified by immunofixation as the IgA lambda paraprotein. The combination of the two simple, inexpensive, and reliable techniques of high-resolution agarose electrophoresis and immunofixation thereby permitted detection and identification of a myeloma protein in a patient otherwise thought to be in complete remission. We believe this approach is useful in assessing persistent or recurrent disease in patients with a known history of myeloma; this combination of techniques may also prove beneficial in the early diagnosis of multiple myeloma.

From Aug 6 to 14, 1973, scariatiniform eruptions that were considered to be mild forms of the staphylococcal scalded-skin syndrome developed in four neonates. One infant had mild epidermal peeling. All had generalized, finely papular erythema that cleared rapidly after treatment with antibiotics. Cultures from the umbilical stumps or anterior nares of three of the infants yielded colonies of group I Staphylococcus aureus, phage type 29/52/79/86/D11/81, that were able to produce epidermal exfoliation in suckling mice. These data indicate that the nursery outbreak was caused by phage group I staphylococci rather than group II organisms previously associated with staphylococcal scalded-skin syndrome. The demonstration that a group I Staphylococcus can produce exfoliative toxin suggests that the same mechanism for toxin production may exist for phage groups I and II staphylococci.

A set of empirical parameters which allows the prediction of the proton NMR chemical shifts at 70 C of non-exchangeable heterobase and anomeric protons in oligoribonucleotides has been constructed. The set is based on the highly flexible nature of oligoribonucleotide single strands and the wide range of conformational states which can be populated at relatively high temperatures (70 C or greater). A pairwise subtractive procedure, using 129 ribonucleotide oligomers (all 16 dimers, all 64 trimers, 37 tetramers, and 12 pentamers), shows that significant contributions to the observed chemical shift of protons in a given nucleoside residue are made by first, second, and third neighbors on the 3' and the 5' sides. The majority of the neighbors cause shielding effects with the exception of some first neighbors on the 5' side of a given residue. The magnitude of the shielding effects is greatest for the purine heterobases and follows the order A greater than G greater than C greater than U, with first neighbors on the 3'side showing more pronounced effects than second neighbors and these in turn showing larger effects than third neighbors. Second neighbors on the 5' side showed consistently greater shieldings than first neighbors, a result attributed to the deshielding effects of the first 5' neighbor phosphate group. The parameter Tables are applied to the prediction of proton chemical shifts in one heptamer, four hexamers, and two pentamers and give average absolute differences between predicted and observed shifts less than 0.030 ppm. The parameter approach represents an excellent method of generating initial assignments of proton chemical shifts for any single strand oligoribonucleotide.

Radiation and surgery are the mainstays of treatment for epidural spinal cord compression. There are reports in the literature, however, in which the use of chemotherapy alone or in combination with radiation and surgery has resulted in improved patient response. We present two patients with spinal cord compression from testicular cancer who developed progressive paraplegias that were successfully reversed with combination chemotherapy, steroids, and radiotherapy. In one case, the patient was unable to receive more than 600 rad (6 Gy) of radiation and his improvement was clearly related to the chemotherapy he received. In treating tumors causing spinal cord compression that are thought to be chemosensitive, one should consider adding chemotherapy to radiation or using chemotherapy alone if the options of surgery or radiation are not available.

Between 1971 and 1976 approximately 20% (2,265) of the population of Sanpete County, Utah, was screened for hydatid disease (Echinococcus granulosus) by intradermal, indirect hemagglutination, and bentonite flocculation tests. Of 34 persons who had follow-up chest radiographs and radioisotope liver scans, 6 were found to have asymptomatic hepatic cysts. If a participant who had pulmonary cysts and negative screening tests were included, the prevalence of asymptomatic hydatid disease would be 3 per 1,000. During the same period, 82 (148 per 1,000) of 553 dogs successfully purged and examined had E. granulosus infections. Human cyst carriage was associated with dog ownership, particularly of infected dogs or in conjunction with sheep raising as the main livelihood. Combinations of immunodiagnostic tests were more efficacious in identifying cyst carriers than the tests used singly. Limitation of screening to high risk groups (e.g., sheep raisers with dogs) can reduce costs without reducing yield. Optimum management of the cyst carrier awaits further information on the natural history of asymptomatic hydatid disease.

19F NMR spectroscopy was used to monitor the metabolites of flucloxacillin in the urine of a rat dosed with its sodium salt. 19F NMR signals were detected and quantified from flucloxacillin and three metabolites. The 19F NMR method involves minimal sample preparation and is free from interference by endogenous urine components. High-field spin-echo 1H NMR spectroscopy and HPLC were used to confirm the results.

The history, clinical findings, endoscopic appearance, and physiopathology of this disease is reviewed. The different modalities of therapy are analyzed and compared with our series of 110 patients with this disease. This group was treated on a conservative but more efficient form with superficial electrofulguration and overdistention with silver nitrate solution. The importance of the cancer incidence in the male patient is also stressed.

A family with histopathologically proven intraocular malignant melanoma involving two generations is reported. A member of third generation was likely involved by history. Intraocular malignant melanoma, its familial occurrence, its occurrence with multiple malignancies, and its relationship to multiple malignancies occurring in a family are discussed.

The geologic section consists of a folded and metamorphosed basement complex of geosynclinal and nearshore sediments and intrusives, a thick sequence of nearshore and terrestrial sediments of middle to late Paleozoic age, and thick diabase sheets and basalt flows of Jurassic age. Block faulting, probably through during the Miocene age, produced the which has been carved into its present from by glaciers.