Management of metronidazole-resistant Trichomonas vaginalis--a new approach.

Metronidazole-resistant trichomoniasis is an infrequent but challenging problem with no universally successful treatment. Since 1994, we have been using a combination regimen consisting of high-dose tinidazole plus a broad-spectrum antibiotic, i.e. doxycycline or ampicillin, and clotrimazole pessaries, for 7--14 days in this condition. A retrospective case review identified 11 cases of resistant trichomonas between 1994 and 2002. In the absence of resistance testing, resistance was defined clinically. Nine of the 11 patients were cured; one patient did not attend follow-up. In the women who attended for follow-up, the cure rate was 90%. We have found the combination of tinidazole, a broad-spectrum antibiotic, and clotrimazole pessaries to be a tolerable and effective treatment for metronidazole-resistant Trichomonas vaginalis. Although a variety of total doses of tinidazole were used in our patients, based on our findings, and those of others, we would recommend giving tinidazole 2 g twice daily for 14 days (total dose 56 g).

Cultural ecology of Whitethroat (Sylvia communis) habitat management by farmers: winter in farmland trees and shrubs in Senegambia.

The presence of Whitethroats and their potential invertebrate prey in farmland trees and shrubs was investigated. The management of this vegetation by farmers, and their motivation for that management, was explored using participatory techniques. Whitethroats were associated with Guiera senegalensis, the shrub species which supports most caterpillars and spiders. Farmers reported declines in trees and shrubs since the 1950s, loss of fallow areas, declines in soil fertility and crop yields, and increases in the use of fire for clearing fields. Trees are valued by people for their cultural and medicinal uses and some species used by Whitethroats and other birds have potential for restoring soil fertility, although this was not recognised by farmers. More sustainable use of savanna farmland could have both agronomic and wider conservation benefits, and the provision of information that accommodates farmers' cultural and economic incentives could benefit both farmers and wildlife.

Factors involved in clearance of genital warts.

Consecutive patients with first presentation of external anogenital warts had the location, duration at presentation, number of warts and wart area, age, smoking and sun bed use, and presence of coexistent sexually transmitted infections (STIs) recorded. The number of treatment episodes, and number of weeks, to clear the warts were documented. Number of warts and wart area at presentation were associated with time and number of treatments to clear. Those with 1-3 warts required significantly fewer treatment episodes and less time to clear than those with 11-41 warts, as did those with warts area 2-19 mm(2) compared with wart area 100-1038 mm(2). Using survival analysis, the number of warts was significant for the number of treatments and weeks to clear. The hazard ratio for clearance with double the number of warts after 4 treatments was 0.53 (95% confidence interval [CI] 0.37-0.76), and at 4 weeks was 0.70 (0.45-0.86). The clearance rates in non-smokers compared with smokers were higher, but not significantly different. Wart burden at presentation is an indicator of time to clearance. The number of warts is the best predictor - fewer warts results in earlier clearance.

Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase 3 deficiency. Diagnosis, psychological evaluation, and management.

Ten male pseudohermaphrodites with 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) deficiency were evaluated in 1 clinic with an average follow-up of 10.1 years. The diagnoses were made by demonstrating low to normal serum testosterone levels, high androstenedione levels, and high ratios of serum androstenedione to testosterone in the basal state or after treatment with human chorionic gonadotropin. The molecular features of the underlying mutations were identified in all 7 families. Two additional males in the same families are believed to be affected on the basis of history obtained from family members. All of the 46,XY individuals in these families were registered at birth and raised as females (despite the presence of ambiguous genitalia in all or most), and all virilized after the time of expected puberty due to a rise in serum testosterone to or toward the normal male range. The age at diagnosis varied from 4 to 37 years. Ten individuals were studied by the same psychologist, and change of gender role (social sex) from female to male occurred in 3 subjects and in the 2 presumed affected subjects not studied. The individual with the highest serum testosterone level maintained female sexual identity, and in 2 families some of the affected males changed gender role and others did not. Thus, while androgen action plays a role in the process, additional undefined psychological, social, and/or biologic factors must be determinants of gender identity/role behavior. Management of the 7 individuals who chose to maintain female sex roles included castration, clitoroplasty, vaginal enlargement procedures when appropriate, treatment of hirsutism, cricoid cartilage reduction, and estrogen replacement. Three of the 7 are married (2 twice), 1 is involved in a long-term heterosexual relationship, 1 is engaged to be married, and the other 2 are not married and not believed to be sexually active. The 3 subjects who changed gender role behavior to male underwent hypospadias repair, and 1 was given supplemental testosterone therapy. One of these men is divorced, and the other 2 (aged 29 and 35 years) are unmarried. The diagnosis in 8 of these subjects was made after the time of expected puberty; it is unclear whether the functional and social outcomes would have been different if the diagnosis had been made and therapy begun earlier in life.

Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency.

Autosomal recessive mutations in the 17 beta-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17 beta-hydroxysteroid dehydrogenase isoenzymes.

Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3.

Defects in the conversion of androstenedione to testosterone in the fetal testes by the enzyme 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) give rise to genetic males with female external genitalia. We have used expression cloning to isolate cDNAs encoding a microsomal 17 beta-HSD type 3 isozyme that shares 23% sequence identity with other 17 beta-HSD enzymes, uses NADPh as a cofactor, and is expressed predominantly in the testes. The 17 beta HSD3 gene on chromosome 9q22 contains 11 exons. Four substitution and two splice junction mutations were identified in the 17 beta HSD3 genes of five unrelated male pseudohermaphrodites. The substitution mutations severely compromised the activity of the 17 beta-HSD type 3 isozyme.

The effect of radiation therapy and hyperthermia on a human prostatic carcinoma cell line grown in athymic nude mice.

The effect of radiation and/or hyperthermia on a human prostatic carcinoma xenograft in athymic nude mice was investigated. A human prostate carcinoma subline (1-LN-PC-3-1A) was inoculated subcutaneously in the thigh of male athymic nude mice. When tumors reached a size of approximately 200 mm.3, they were treated with either radiation (X) or hyperthermia (H) alone, or in combination (X + H). In the combined treatment, hyperthermia was delivered immediately after radiation exposure. Comparison of the time required to reach twice the tumor volume observed at the time of treatment was used to define therapeutic impact on tumor growth. The combined treatment resulted in median tumor volume doubling time of 35.5 days, compared to 18 days and 25.5 days, respectively, for hyperthermia or radiation alone. Analysis of tumor doubling time using a proportional hazards regression indicates that under the conditions of this experiment, the effect of radiation and hyperthermia for 1-LN-PC-3-1A tumors is additive. The impact of this treatment regimen in the management of prostatic cancer requires further investigation.

The expression of a functional cDNA encoding the chicken cytochrome P-450arom (aromatase) that catalyzes the formation of estrogen from androgen.

A complementary DNA (cDNA) copy of the aromatase P-450 has been isolated from a chicken ovary library using as probe a partial cDNA believed to encode the human placental aromatase. The predicted amino acid sequence of the chicken aromatase cDNA possesses regions of homology to that of its human counterpart, but only limited homology to other cytochrome P-450 enzymes. The introduction of the cDNA clone into COS-1 cells results in the production of high levels of aromatase activity. The chicken enzyme is targeted to the appropriate subcellular fraction in the transfected COS cells, and the apparent Km of the chicken aromatase activity, measured in microsomes prepared from the transfected cells, is similar to that of the enzyme prepared from chicken ovary microsomes. These findings establish that the cDNA clone encodes chicken ovarian aromatase and demonstrate that this protein can catalyze the three successive oxidation reactions necessary to form estrogen from androgen.

Variation in potency of extracts used for allergy skin tests.

Extracts of 11 common inhalant allergens, produced by three different commercial suppliers, were compared by the skin prick test (SPT) in 21 atopic subjects. Good correlation was found between the three brands for positive reactions to grass pollens and English plantain pollen. Eighteen subjects with clinical sensitivity to house dust had diagnostically positive reactions to two of the house dust mite extracts, the third preparation produced no reactions that would be considered as diagnostically significant by the usual criteria. The extracts of house dust mixtures possessed little biological activity and were considered unsatisfactory for accurate diagnostic purposes. One of the three extracts of dog hair and dander produced false positive results in 17 of 21 subjects. The variability of reactions to fungi and animal hair and dander is discussed.

Allergic sensitivity confirmed by the release of histamine from small blood samples.

An enzymatic-isotopic microassay that can measure picogram amounts of histamine in 20 microliter samples of plasma has been used to confirm diagnosis of allergic sensitivity to extracts of house dust mite, cat dander, grass, plantain, Cladosporium mould and bee sting venom by the skin test procedure. Multiple assays for allergic histamine release can be performed on minimal blood samples resulting in a qualitative and quantitative prediction of allergic sensitivity from an in vitro biochemical procedure.

Pseudohypoparathyroidism presenting with rickets.

Pseudohypoparathyroidism (PHP) is a condition characterized by hypocalcemia, hyperphosphatemia, and an impaired phosphaturic response to exogenous parathormone (PTH). A minority of patients with PHP have associated bone disease, and in some the radiological appearances have been suggestive of rickets. We report a patient with PHP who had epiphyseal enlargement and bowing of the long bones similar to that seen in rickets. Radiology showed generalized osteomalacia with failure of epiphyseal calcification and several pseudofractures. Bone biopsy showed increased osteoid seams. The phalanges of both hands showed subperiosteal erosions consistent with hyperparathyroidism. Biochemically, he had persistent hypocalcemia, hyperphosphatemia, and an elevated alkaline phosphatase. Plasma calcitonin, magnesium, and 25-hydroxycholecalciferol levels were normal. The 1,25-dihydroxycholecalciferol level was within the normal adult range but was probably inappropriately low for an adolescent. Plasma parathormone was elevated (1.3--1.7 microgram/liter; normal, < 0.73). His diet was not deficient in vitamin D. Gastrointestinal function was normal. Renal function was normal, apart from an increase in the maximum tubular reabsorption of phosphate (46--52.6 mg/liter glomerular filtration rate; normal, 38 +/- 5). Intravenous PTH infusion tests were performed on the patient and a control subject before and 6 months after serum calcium levels had returned to normal. The maximum increases in cAMP excretion in the patient were 0.03 and 0.05 mmol/g creatinine before and after treatment, respectively (control, 0.53 and 0.24); the maximum increases in phosphate excretion in the patient were 0.14 and 0.04 mmol/g creatinine before and after treatment, respectively (control, 0.32 and 0.07). He responded to initial treatment with a high dose of calciferol and later to 1,25-dihydroxycholecalciferol in a dose of 1 microgram/day. It is considered that renal resistance to PTH is his primary abnormality, with the bone disease representing a secondary phenomenon.

A survey of airborne pollen and spores in Auckland: its use in the diagnosis of seasonal allergies.

A survey of airborne pollen and spores is being undertaken in Auckland. The results for the 15-month period from November 1976 to February 1978 are presented. Even at the height of the flowering seasons meteorological factors greatly influence the concentration of pollen and spores in the atmosphere. Consideration of these factors is therefore essential when assessing the allergic patients' symptoms and treatment. A flowering calendar for Auckland of common anemophilous plants (many of which produce allergenic pollen) is presented.