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Biomedical subjects

J Luft

Publications and source records attributed to J Luft.

10 recordsLinked to original sources

Structure of a ribulose 5-phosphate 3-epimerase from Plasmodium falciparum.

The crystal structure of Pfal009167AAA, a putative ribulose 5-phosphate 3-epimerase (PfalRPE) from Plasmodium falciparum, has been determined to 2 A resolution. RPE represents an exciting potential drug target for developing antimalarials because it is involved in the shikimate and the pentose phosphate pathways. The structure is a classic TIM-barrel fold. A coordinated Zn ion and a bound sulfate ion in the active site of the enzyme allow for a greater understanding of the mechanism of action of this enzyme. This structure is solved in the framework of the Structural Genomics of Pathogenic Protozoa (SGPP) consortium.

Animals↗

Upper aerodigestive tract frostbite complicating volatile substance abuse.

Volatile substance abuse has become increasingly popular among today's youth. It has reportedly been used by up to 13% of teenage populations. Physicians need to be aware of the potential complications which may arise from this form of substance abuse. We describe the case of a young male who presented with massive edema affecting his lips, oral cavity, oropharynx and trachea. It was later discovered that his injury was secondary to thermal trauma related to the abuse of a fluorinated hydrocarbon propellant. This presentation may easily be confused with allergic or angioneurotic edema. Denial by the patient can lead to a further delay in diagnosis. This case is especially notable since frostbite injury involving the upper aerodigestive tract is extremely rare. We discuss the differential diagnosis and the management principals required in the care of this patient. We also present a pertinent review of the literature related to both volatile substance abuse and its complications involving the airway.

Administration, Inhalation↗

The use of a laryngotracheal separation procedure in pediatric patients.

The objective of this study was to review experience, outcome, and satisfaction after a laryngotracheal separation (LTS) procedure in pediatric patients. Chart reviews and phone questionnaires were used. Factors reviewed included hospitalizations and infections prior to and after LTS, morbidity, and impact on quality of life. Twenty-one pediatric patients ranging in age from 8 to 172 months underwent LTS. Follow-up time ranged from 1 to 49 months. Complications were minor. Eighty-eight percent of patients had fewer hospitalizations or were discharged for the first time after LTS. Number of pneumonias and suctioning frequency decreased, mobility increased in patients with prior tracheostomies, and care requirements decreased in 95% of patients. Parents reported satisfaction and improved quality of life. LTS is a low-risk, successful procedure which increases quality of life and decreases morbidity in pediatric patients with irreversible upper airway dysfunction.

Adolescent↗

Mechanism of molecular recognition. Structural aspects of 3,3'-diiodo-L-thyronine binding to human serum transthyretin.

The three-dimensional structure of the thyroid hormone metabolite, 3,3'-diiodo-L-thyronine (3,3'-T2), complex with human serum transthyretin (TTR) has been refined to R = 18.5% for 8-2 A resolution data. This is the first detailed description of a thyroid hormone metabolite binding to a thyroid transport protein. The four TTR monomeric subunits form a tetramer in the same manner as the native transthyretin reported earlier (Blake, C. C. F., Geisow, M. J., Oatley, S. J., Rerat, B., and Rerat, C. (1978) J. Mol. Biol. 121, 339-356). The two hormone binding sites of the TTR tetramer are occupied by 3,3'-T2. A statistical disorder model for the ligand was applied with a 50% occupancy to account for the discrepancy between the crystallographic 2-fold symmetry of the binding sites and the lack of such symmetry for 3,3'-T2. The bound metabolite has an overall transoid conformation with the either bridge intermediate between skewed and perpendicular. The hormone metabolite is bound 3.5 A deeper and with a different orientation in the channel than observed for thyroxine (T4), thereby revealing the presence of another set of halogen binding sites close to the center of the tetramer. When compared with the binding of T4, these data show that the 3-iodine of 3,3'-T2 occupies the same site as the 3'-iodine of T4, and the metabolite 3'-iodine occupies the water site observed in the T4 complex. The binding affinity of 3,3'-T2, which is 100-fold lower than that of T4, reflects the lack of the second pair of iodine atoms interacting in the channel. In order to understand the tighter binding of T4 observed in the Ala-109----Thr mutant, modeling studies were carried out that indicate that this modification could shorten the contacts between thyroid hormone iodines and residues 108-110 of the binding site.

Binding Sites↗

Efficacy of single-agent therapy for the treatment of acute pelvic inflammatory disease with ciprofloxacin.

A prospective, randomized, controlled, non-blind clinical trial was conducted to compare the efficacy of monotherapy with ciprofloxacin with that of a combination of clindamycin plus gentamicin in the treatment of patients with acute pelvic inflammatory disease. Pretreatment and post-treatment cervical culture specimens were obtained for Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, and Ureaplasma urealyticum. Pretreatment and post-treatment endometrial culture specimens were obtained for those organisms plus facultative and anaerobic bacteria. Minimal inhibitory concentrations were determined on all isolates by agar dilution. Clinical resolution of infection was seen in 31 of 33 (94 percent) ciprofloxacin-treated patients compared with 34 of 35 (97 percent) clindamycin/gentamicin-treated patients. N. gonorrhoeae was eradicated in all cases and C. trachomatis in 12 of 13 cases (92 percent). Ciprofloxacin appeared less effective than clindamycin/gentamicin in eradicating bacterial-vaginosis-associated organisms from post-treatment culture specimens obtained from the endometrium. Comparable clinical response was seen with both regimens. The significance of persistent bacterial-vaginosis-associated organisms following ciprofloxacin therapy is unclear. However, since one goal of treatment of pelvic inflammatory disease should be to eliminate organisms from the upper genital tract, ciprofloxacin may not provide optimal single-agent therapy for pelvic inflammatory disease.

Acute Disease↗

Structure-activity relationships of antiarrhythmic agents: crystal structure of amiodarone hydrochloride and two derivatives, and their conformational comparison with thyroxine.

Amiodarone.HCl (I), 2-butyl-3-benzofuranyl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride, C25H30I2NO3+.Cl-, Mr = 680.78, monoclinic, P2(1)/c, a = 17.124 (2), b = 17.079 (2), c = 9.162 (1) A, beta = 98.37 degrees, V = 2651.2 A3, Z = 4, Dx = 1.71 g cm-3, lambda(Mo K alpha) = 0.7107 A, mu = 24.73 cm-1, F(000) = 1332, T = 294 K, R = 6.6% for 5515 data; desethyl-amiodarone.HCl (II), 2-butyl-3-benzofuranyl 4-[2-(ethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride, C23H26I2NO3+.Cl-, Mr = 654.74, monoclonic, P2(1)/c, a = 23.867 (2), b = 10.134 (1), c = 10.287 (2) A, beta = 93.91 (2) degrees, V = 2482.5 A3, Z = 4, Dx = 1.75 g cm-3, lambda(Mo K alpha) = 0.07107 A, mu = 26.37 cm-1, F(000) = 1276, T = 294 K, R = 5.7% for 5916 data; benziodarone (III), 2-ethyl-3-benzofuranyl 4-hydroxy-3,5-diiodophenyl ketone, C17H12I2O3, Mr = 518.09, monoclinic, P2(1)/n, a = 17.564 (2), b = 8.294 (1), c = 11.587 (2) A, beta = 93.20 (2) degrees, V = 1685.55 A3, Z = 4, Dx = 2.04 g cm-3, lambda(Mo K alpha) = 0.7101 A, mu = 36.99 cm-1, F(000) = 976, T = 294 K, R = 6.2% for 4311 data.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗

Prophylaxis in caesarean section with cefmetazole and cefoxitin.

A prospective, randomized, open comparison of three 1 g doses of cefmetazole with three 2 g doses of cefoxitin for non-elective Caesarean section was performed. Sixty-nine patients were evaluated. The two groups were comparable with respect to labour characteristics that might influence risk of postoperative infectious morbidity. Similarly, the nature of the bacterial contamination/infection of the amniotic fluid at the time of Caesarean section was comparable in the two groups. The only infectious morbidity noted was endomyometritis. The incidence was the same in both groups, 5/50 (10%) in the cefmetazole group and 2/19 (10.5%) in the cefoxitin group. Febrile morbidity, as reflected in the fever index, was not significantly different between the groups, 10.2 +/- 18.5 degree hours in the cefmetazole group and 7.5 +/- 11.7 degree hours in the cefoxitin group. Cefmetazole appeared to be equivalent to cefoxitin in reducing post-Caesarean section endomyometritis.

Adolescent↗

Identifying the risk factors for developing incontinence: can we modify individual risk?

Urinary incontinence (UI) is a common but often misunderstood problem. Newer treatments are being developed and examined, but prevention of incontinence rarely is addressed in the medical literature. This article reviews the current literature on risk factors for developing UI and raises the question, "Can patient education or nursing intervention reduce the incidence of incontinence by identifying and modifying risk factors?"

Aged↗

Comparison of cefotetan plus doxycycline with cefoxitin plus doxycycline in the inpatient treatment of acute salpingitis.

Pelvic inflammatory disease (PID), one of the major sequelae of the current epidemic of sexually transmitted diseases, has been shown to be a polymicrobial infection. This study compares the efficacy and safety of two broad-spectrum combination drug regimens, cefotetan with doxycycline and cefoxitin with doxycycline, in the treatment of PID. A total of 108 patients with acute salpingitis were hospitalized and randomized into two treatment groups: cefotetan/doxycycline (N = 54) and cefoxitin/doxycycline (N = 54). Before antibiotic administration, Chlamydia trachomatis was identified in 17 (16%) of the patients, Neisseria gonorrhoeae from 72 (67%), and anaerobic and aerobic bacteria were identified from the endometrial cultures of 86 (80%). There were seven tubo-ovarian abscesses (TOAs) that were diagnosed in the cefotetan group, and six in the cefoxitin group. Clinical cure was achieved in 51 of 54 (94%) patients in each group. Of the six patients whose treatment failed, all had positive cultures for N. gonorrhoeae and facultative/anaerobic bacteria, whereas none had C. trachomatis. Two patients from each study arm whose treatment failed were diagnosed with TOAs and responded subsequently to clindamycin plus an aminoglycoside. Cultures that were obtained after the completion of inpatient treatment showed the eradication of C. trachomatis and N. gonorrhoeae in all patients. Also, both regimens were effective in reducing aerobic and anaerobic pathogens. Finally, both regimens were well tolerated, with few side-effects.

Acute Disease↗