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Biomedical subjects

H E Jones

Publications and source records attributed to H E Jones.

At least 109 records · Page 6Linked to original sources

A mechanism of susceptibility to mucormycosis in diabetic ketoacidosis: transferrin and iron availability.

The defect in host defense that makes the diabetic ketoacidotic (DKA) patient susceptible to mucormycosis has not been identified. Sera from 10 DKA patients and three normal volunteers were tested for their capacity to support the in vitro growth of a common etiologic agent of mucormycosis, Rhizopus oryzae. After equilibration with room air none of the normal or DKA sera, each of which was now extremely alkaline, supported growth of R. oryzae. When the sera were placed in a CO2 atmosphere that permitted simulation of the in vivo clinical pH (normal 7.40 and DKA 7.3-6.6), four of seven DKA sera supported profuse fungal growth. No growth occurred in normal serum. The three DKA sera that did not support fungal growth at pH less than or equal to 7.3 contained less iron (x = 13 micrograms/dl) than the four sera that supported profuse fungal growth (x = 69 micrograms/dl). Increasing the iron content of iron-poor DKA serum that did not support R. oryzae growth allowed profuse growth at acidotic conditions but not at pH greater than or equal to 7.4. Simulated acidotic conditions (pH 7.3-6.6) also decreased the iron-binding capacity of normal serum stepwise from 266 micrograms/dl to 0. Our data indicate that acidosis temporarily disrupts the capacity of transferrin to bind iron and suggest that this alteration abolishes an important host defense mechanism that permits growth of R. oryzae.

Diabetic Ketoacidosis↗

Ketoconazole.

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Antifungal Agents↗

Oral ketoconazole. An effective and safe treatment for dermatophytosis.

This study demonstrates the efficacy and safety of ketoconazole, a broad-spectrum oral antifungal agent administered to 20 patients with severe, extensive, and recalcitrant Trichophyton rubrum infection. The average patient has had continuous infection for 20 years. Sixteen patients had glabrous skin infection that encompassed an average of 40% of their skin surface. The remaining four patients had palmar-plantar infection. Ketoconazole was administered for 27 to 70 days in a daily oral dose of 200 or 400 mg. Initial clinical and mycological response occurred within five to seven days, and the glabrous and/or palmar-plantar skin changes improved at least 90% in all patients. In 13 of these patients, the infection cleared completely. The only side effects experienced--pruritus in four patients and photophobia in two patients--did not necessitate interruption of therapy. Overall, ketoconazole was found to be an effective and safe therapy for dermatophytosis. Follow-up examinations of our cases five months later showed recrudescence in 75% of them, which was not unexpected with these severe infections.

Administration, Oral↗

Griseofulvin-resistant dermatophytosis correlates with in vitro resistance.

The unsuccessful treatment of dermatophytosis with griseofulvin is common. The mechanism is not known but may involve infection with a griseofulvin-resistant dermatophyte. The mean minimal inhibitory concentration (MIC) value of griseofulvin for Trichophyton rubrum isolates obtained from griseofulvin unresponsive patients was substantially larger than the mean MIC value for responsive control isolates. This difference indicates that therapeutic failure does correlate with the relative in vitro resistance. An MIC of 3.0 microgram/mL or greater was determined to indicate relative griseofulvin resistance. We conclude that the MIC determination for griseofulvin can be used to determine the appropriateness of griseofulvin therapy.

Adult↗

Intra-articular steroids in osteoarthritis.

Intra-articular steroid therapy for osteoarthritis of the knee has been reassessed by two placebo-controlled trials of 20 mg of triamcinalone hexacetonide in 48 joints. Steroid injections caused a significantly greater reduction in pain and tenderness than placebo, and were preferred by patients. However, the benefits were small and transient. Maximum pain reduction occurred one week after injection, and was accompanied by a fall in the thermographic index suggesting an anti-inflammatory mode of action. Synovial fluid was unafffected by injections, and there was no correlation between synovial fluid cell counts or the radiological grading, and the degree of pain reduction.

Aged↗

The effect of human lymphokine on the growth of Trichophyton mentagrophytes.

Lymphokine was tested for fungal growth inhibitory activity against the filamentous fungus Trichophyton mentagrophytes. Human peripheral blood lymphocytes from a donor exhibiting delayed type cutaneous hypersensitivity to a trichophytin skin test were cultured with trichophytin and PHA-P. Culture supernatants were assayed for lymphokine activity using the lymphotoxin sensitive mouse L-929 alpha fibroblast. Lymphocyte activation to PHA-P and trichophytin was confirmed by monitoring 3H-thymidine incorporation. Supernatants from 2-day PHA-P and 6-day trichophytin activated cultures were found to contain potent lymphokine activity. This activity was not diminished by the addition of ferric iron sufficient to saturate the contained transferrin. Supernatants from unstimulated control cultures contained no lymphokine activity. Undiluted lymphokine containing supernatants and nonlymphokine containing control supernatants were evaluated for fungal growth inhibitory activity using a sensitive radiometric growth assay. Iron supplemented supernatants retaining potent lymphokine activity did not inhibit fungal growth. Non-iron supplemented supernatants and fresh medium containing serum inhibited fungal growth. Our data suggest that lymphokine active against mammalian cells is not directly antagonistic to the growth of the filamentous fungus T. mentagrophytes but does not exclude the possibility that activated lymphocytes release a chelator such as transferrin that can inhibit fungal growth.

Animals↗

Isolation and characterization of a rubredoxin and two ferredoxins from Desulfovibrio africanus.

Rubredoxin and two distinct ferredoxins have been purified from Desulfovibrio africanus. The rubredoxin has a molecular weight of 6000 while the ferredoxins appear to be dimers of identical subunits of approximately 6000 to 7000 molecular weight. Rubredoxin contains one iron atom, no acid-labile sulfide and four cysteine residues per molecule. Its absorbance ratio A278/A490 is 2.23 and its amino acid composition is characterized by the absence of leucine and a preponderance of acidic amino acids. The two ferredoxins, designated I and II, are readily separated on DEAE-cellulose. The amino acid compositions of ferredoxins I and II show them to be different protein species; the greater number of acidic amino acid residues in ferredoxin I than in ferredoxin II appears to account for separation based on electronic charge. Both ferredoxins contain four iron atoms, four acid-labile residues per molecule. Spectra of the two ferredoxins differ from those of ferredoxins of other Desulfovibrio species by exhibiting a pronounced absorption peak at 283 nm consistent with an unusual high content of aromatic residues. The A385/A283 absorbance ratio of ferredoxins I and II are 0.56 and 0.62, respectively. The N-terminal sequencing data of the two ferredoxins clearly indicate that ferredoxins I and II are different protein species. However, the two proteins exhibit a high degree of homology.

Amino Acid Sequence↗

Suppression of histamine-induced pruritus by hydroxyzine and various neuroleptics.

This study evaluates the ability of hydroxyzine and various neuroleptics to suppress histamine-induced pruritus in ten volunteer subjects with the use of a double-blind crossover protocol. The itch threshold was determined in each volunteer by intradermal injection of gradually increasing concentrations of histamine. Volunteers were then given the study drugs and placebo at the same interval of time, under near identical conditions, and the itch threshold was determined. Thiothixene, hydroxyzine hydrochloride, chlorpromazine, thioridazine, and a lactose placebo were evaluated. Compared to other drugs, hydroxyzine alone was more effective in the suppression of histamine-induced itch. Consequently, hydrozyzine may be more effective in histamine-induced pruritus. The neuroleptic drugs used in this study do not significantly suppress histamine-induced pruritus, but they may be beneficial in nonhistamine-induced pruritus or psychogenic pruritus.

Adult↗

Filamentous fungal growth assay: correlation between [U-14C] glucose uptake and dry weight determinations.

The filamentous fungus Trichophyton mentagrophytes was grown in [U-14C] glucose supplemented nutrient broth. Growth was monitored in 200 microliter microcultures and 5 ml macrocultures by measuring the incorporation of 14C into trichloroacetic acid-insoluble macromolecules and in macrocultures by dry weight determination. Adjustment of the specific activity of the [U-14C] glucose medium supplement from 1080 muCi/mmole to 108 muCi/mmole decreased the rate of isotope uptake and prolonged availability so that growth beyond 36 h could be monitored radiometrically. The dry mycelial weight of the fungus was directly proportional (r = 0.995) to the amount of isotope incorporated. Isotope uptake in microcultures and macrocultures was kinetically identical. These data clearly indicate that the uptake of 14C by T. mentagrophytes can be used to monitor fungal growth accurately in both macrocultures and microcultures.

Carbon Radioisotopes↗

Irritant and allergic reactions to topically applied Micatin cream.

Miconazole nitrate (Micatin cream) is a potent antifungal agent. Few side effects have been reported with topical application. We report on 10 patients who exhibited an intolerance to topical use of this drug. Most of the reactions were irritant in nature but in two instances, an allergic contact dermatitis was observed. Patch tests were positive to the cream base.

Dermatitis, Atopic↗

North American blastomycosis: a review.

North American blastomycosis, first reported in 1894, and once thought to be a geographically localized disease, has now been reported worldwide. The greatest number of cases occur in the Mississippi, Missouri, and Ohio River basins. The organism enters the body via the lungs with subsequent dissemination to other organs, including the skin, eyes, bones, and genitourinary system. Patients most often present with cutaneous or pulmonary complaints. Demonstration of characteristic fungal morphology in microscopic smears or in histologic specimens is highly suggestive of Blastomyces dermatitidis. However, proof of the diagnosis is obtained only by mycologic culture. Some progress has been made using other laboratory methods to produce a rapid diagnosis. This paper reviews in detail the varied clinical presentations of blastomycosis, the laboratory diagnosis, and current treatment.

Amphotericin B↗

Intravenous miconazole therapy of mycotic infections.

The efficacy and safety of intravenously administered miconazole nitrate was examined in eight patients with the following infections: cutaneous North American blastomycosis (one), extensive dermatophytosis(one), and chronic mucocutaneous candidiasis (six). Mycologic assessment included direct examination for fungal elements, fungal culture, and histopathology. Laboratory evaluations were performed before and at regular intervals during the study. The total miconazole nitrate dosage, which was administered over a seven- to 32-day period, ranged from 4.0 to 46.8 g. Follow-up examinations extended from two to 15 months. Excellent results were obtained in five patients and fair results in three. No renal, cardiac, hepatic, or hematopoietic toxicity was observed. Other side effects, however, necessitated premature cessation of therapy in four patients. Overall, intravenously administered miconazole is an effective antifungal agent for these cutaneous infections.

Adolescent↗

Familial male pseudohermaphroditism with normal Leydig cell function at puberty.

Four male pseudohermaphrodites from two families have been described. Although reared as females, at puberty, the timing, pattern, and degree of masculinization was similar to that of a normal male. No feminization occurred. They had normal testicular testosterone synthesis as judged by plasma testosterone, LH and FSH concentrations, as well as incubations of testicular minces with labeled precursors. Studies on cultured skin fibroblasts indicated adequate peripheral 5 alpha-reductase and normal receptor affinity and capacity for dihydrotestosterone. The histology of the testis was suggestive of a primary testicular defect. A mosaic pattern was seen: some areas contained tubules with active spermiogenesis; other areas, only Sertoli cells. These male pseudohermaphrodites appear to have a defect in fetal testicular maturation in which inadequate fetal testosterone synthesis and defective differentiation of germinal elements occurred.

Adolescent↗

Atopic dermatitis, impaired cellular immunity, and molluscum contagiosum.

A substantial elevation in the level of serum IgE (7,000 to 19,000 ng/ml) was noted in a man with atopic dermatitis and chronic molluscum contagiosum. Cell-mediated immunity (CMI) was depressed in vivo (cutaneous anergy), whereas in vitro tests showed normal numbers of "T" rosette-forming lymphocytes, a normal phytohemagglutinin-P-elicited lymphocyte transformation response, and lymphocyte transformation reactivity to the antigens streptokinase-streptodornase and purified protein derivative. Accumulated evidence suggests that patients with atopic dermatitis may have, associated with an elevated serum IgE level, a functional defect(s) in CMI that is greater in vivo than in vitro. This functional defect may impair host defense and account for the chronic molluscum contagiosum infection present in this patient.

Adult↗

Skin changes and diseases associated with pregnancy.

During the gestational period, the skin is among the many organs undergoing changes. Various endocrine changes occurring in pregnancy are thought to give rise to certain skin changes such as pigmentary alterations, abnormalities in hair growth, vascular anomalies, and striae. Also, there are several skin diseases unique to the pregnant woman. Whereas the physiologic skin changes are mainly of cosmetic importance, the various pregnancy-unique skin diseases have associated symptoms, and an increase in both fetal and/or maternal morbidity and mortality is associated with several of these skin diseases.

Dermatitis↗