Molecular markers reveal cryptic sex in the human pathogen Coccidioides immitis.

Coccidioides immitis, cause of a recent epidemic of "Valley fever" in California, is typical of many eukaryotic microbes in that mating and meiosis have yet to be reported, but it is not clear whether sex is truly absent or just cryptic. To find out, we have undertaken a population genetic study using PCR amplification, screening for single-strand conformation polymorphisms, and direct DNA sequencing to find molecular markers with nucleotide-level resolution. Both population genetic and phylogenetic analyses indicate that C. immitis is almost completely recombining. To our knowledge, this study is the first to find molecular evidence for recombination in a fungus for which no sexual stage has yet been described. These results motivate a directed search for mating and meiosis and illustrate the utility of single-strand conformation polymorphism and sequencing with arbitrary primer pairs in molecular population genetics.     

Thoracic Aortic Aneurysms: Role of Echocardiography

This article describes the evolving role of echocardiography for the detection and evaluation of thoracic aortic aneurysms. A brief summary of the clinical, anatomical, and pathological features of the etiologic categories of thoracic aneurysms is presented. The advantages and limitations of echocardiography and its comparison with other techniques (computed tomographic scanning, magnetic resonance imaging, and aortography) are discussed.     

Ultrasound Densitometric Analysis: Comparison Between an Online Digital Acquisition Acoustic Program and an Offline Analog Program

Videodensitometric analysis of myocardial contrast echocardiography is traditionally performed off line. Recently, an online contrast ultrasound analysis system, Acoustic Densitometry (Hewlett-Packard), was introduced. We compared pixel intensities acquired with Acoustic Densitometry to pixel intensities derived from videodensitometry. A tissue phantom was imaged in phase I using three transducer frequencies (2.5, 3.5, and 5.0 MHz). In phase II, an in vitro flowing tube model with various concentrations of Albunex® was imaged at two flow rates, 0.6 and 1.2 m/sec, and at two transducer frequencies, 2.5 and 3.5 MHz. The relationship between pixel intensities yielded by the two systems for identical ultrasound signals was determined with linear regression. Intensities derived with Acoustic Densitometry strongly correlated with those derived from the offline videodensitometry system. The intensities were related by a predictive multiplicative factor based on display characteristics of the two systems. These results suggest that semiquantitative, online perfusion analysis with Acoustic Densitometry is as sensitive as analysis offline with videodensitometry.     

Improvements in retention rates and changes in client group with methadone maintenance streaming

This study evaluated changes in client population and in retention rates following the introduction of a system of methadone maintenance streaming. A low intervention and low supervision stream was combined with two abstinence-orientated streams. Privileges of take-home doses and local pharmacy dose collection were contingent on successful participation in the abstinence-orientated streams. The clinic also modified policy to allow clients greater control over dose levels. The case notes of the first 100 clients entering the programme in the year prior to the changes (1991) and in the year following the changes (1993) were compared. The results showed a significant increase in retention rates. The demographic and heroin using histories did not change, but the newer programme attracted a greater proportion of clients with no previous history of methadone maintenance treatment. Mean clinic dose increased from 45 mg to 63 mg when clients were allowed to exert control over dose. These findings reveal improved outcomes in a public methadone maintenance programme as a result of policy changes designed to give clients greater control of their treatment.     

Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases

Objective

To determine the efficacy of chemotherapy for inoperable desmoid tumours associated with familial adenomatous polyposis.

Design

A review of three cases of unresectable desmoid tumours and of the literature on the subject.

Setting

The Steven Atanas Stavro Polyposis Registry at Mount Sinai Hospital in Toronto.

Patients

Three patients with symptomatic, unresectable desmoid tumours associated with familial adenomatous polyposis and unresponsive to conventional hormone therapy.

Intervention

A chemotherapy regimen of seven cycles of doxorubicin (dose ranging from 60 to 90 mg/m²) and dacarbazine (1000 mg/m²), followed by carboplatin (400 mg/m²) and dacarbazine.

Outcome Measures

Clinical improvement and tumour regression demonstrated by computed tomography.

Results

In each of the three cases significant tumour regression was seen clinically and radiologically.

Conclusions

Cytotoxic chemotherapy is an effective treatment for desmoid tumours associated with familial adenomatous polyposis. The chemotherapy should be started early in cases of symptomatic desmoid tumour unresponsive to conventional medical therapy.     

Comparison of fascial and vaginal wall slings in the management of intrinsic sphincter deficiency

Objectives

To compare safety and efficacy of fascial versus vaginal wall slings in the management of women with intrinsic sphincter deficiency (ISD).

Methods

The hospital and office records of 79 consecutive women with ISD were retrospectively analyzed from January 1991 to September 1995. There were 43 fascial slings (group A) and 36 vaginal wall slings (group B). Parameter of evaluation included efficacy based on postoperative presence of stress or urge incontinence and number of pads used, complications, and miscellaneous factors, including length of catheterization time, length of hospitalization, quantity of analgesics used, and loss of work days.

Results

Baseline clinical and urodynamic data were the same for both groups. Pad use decreased from 6.9 to 0.6 for group A and from 5.7 to 0.3 for group B. Persistent stress and urge incontinence was present in 5% and 16% of group A patients and in 3% and 11 % of group B patients, respectively. Group A (89%) and group B (94%) patients were either very satisfied or satisfied with their surgical outcome. The operative time, hospital days, and days lost from work for group B patients (42.3 ± 13.4 minutes, 1.4 ± 0.9 days, 18.4 ±3.2 days, respectively) were significantly lower than for group A patients (84.2 ± 17.8 minutes, 3.7 ± 1.9 days, 28.4 ±7.8 days, respectively).

Conclusions

Both fascial and vaginal wall slings are effective in treating women with ISD. However, the use of vaginal wall slings resulted in significantly shorter hospital stay, decreased catheterization time, decreased use of analgesics, and decreased loss of days of work compared with fascial slings. Therefore, the vaginal wall sling should be the preferred surgical method of treating intrinsic sphincter deficiency.     

Prognostic significance of DNA ploidy in Ta/Tl bladder cancer: A southwest oncology group study

While 80% of transitional cell carcinomas (TCC) present as Ta Tl lesions, they account for only 15% of deaths caused by TCC. We have evaluated the ability of DNA ploidy analysis to predict outcome in 228 patients with Ta Tl TCC. All patients were judged to be at increased risk for tumor recurrence due to having two occurrences of Stage TI tumor within 56 weeks, or three or more tumors presenting simultaneously within 16 weeks of registration. Concurrent carcinoma in situ was acceptable. All patients were treated with either bacillus Calmette Guerin (BCG) immunotherapy or mitomycin-C (MMC) intravesical chemotherapy. Patients with nondiploid tumors had higher hazard rates for both tumor progression and death (p = 0.007 and p = 0.016, respectively); however, the prognostic information of DNA ploidy was not additive to tumor grade.     

Metabolic and neuroanatomical correlates of barrel-rolling and oculoclonic convulsions induced by intraventricular endothelin-1: a novel peptidergic signaling mechanism in visuovestibular and oculomotor regulation?

The neuroactive peptide endothelin-1 has receptors distributed abundantly among subdivisions and nuclei of the visuovestibular and oculomotor systems. In previous work, we and others described the convulsive manifestations resulting from central injection of this neuropeptide, including nystagmus, oculoclonus, exophthalmos, tonic hindlimb extension, and a generalized repetitive motor disturbance called barrel-rolling. We applied the quantitative, autoradiographic [¹⁴C]deoxy-glucose method to examine the hypothesis that visuovestibular and oculomotor structures would become metabolically stimulated when endothelin was introduced into the brain via the ventricular system in conscious rats. Since previous work had demonstrated that hypermetabolic responses to endothelin in other neural systems were inhibited by an antagonist of neuronal calcium L-type channels, nimodipine, we further tested whether the increased function of vestibulooculomotor nuclei whose metabolic activity was sensitive to endothelin could be altered following nimodipine pretreatment via the ventricle. A single unilateral injection of endothelin (9 pmol in 3 l saline) into a lateral ventricle provoked significantly increased rates of glucose metabolism in 22 of 39 individual anatomical structures of the visuovestibular and oculomotor systems. Among those affected were the superficial stratum of the caudal superior colliculus (+25%), the optic tract bilaterally (+ 35 to 43%), the oculomotor cranial nerve nuclei (III, IV, VI; range of +21 to 47%), and the medial terminal nucleus of the accessory optic tract which harbors dense fields of endothelin binding sites (bilateral increase of +70 to 96%). Several other nuclei involved in the proprioceptive and visuovestibular disturbance caused by endothelin displayed increased metabolic activity, including the cuneate, gracile, sensory trigeminal, and prepositus hypoglossal nuclei, the vestibular subnuclear system, and the cerebellar flocculus. Identification of hypermetabolic responsivity to endothelin in these structures provides further information on the anatomical substrates mediating the behavioral phenomenology of endothelin-induced motor convulsions which involve the paroxysmal participation of the extraocular muscles and motor control systems producing barrel-rolling convulsions. Nimodipine pretreatment inhibited both the convulsive activity and the cerebral hypermetabolic responses to intraventricular endothelin. The results indicate that the neural systems sensitive to intraventricular endothelin become functionally active via a calcium-mediated process that may involve the neuropeptide as an intrinsic signaling molecule.     

Identification of T cell stimulatory epitopes from the 18 kDa protein of Mycobacterium leprae

We have used different mouse strains to examine in vivo andin vitro responses to the 18 kDa protein of Mycobacterium leprae,which appears to be strongly immunogenic in both mice and humans.B and T cell stimulatory epitopes recognised by different strainsof mice have been mapped using overlapping peptides that spanthe entire 18 kDa protein. Previous work established that Immunizationof mice with the 18 kDa protein results in specific antibodyproduction to common B cell epitopes and immunization of micewith peptides containing these B cell epitopes resulted in theinduction of specific IgG to only a limited subset of epitopesin each strain. Now we report that T cells purified from miceimmunized with peptides that stimulate antibody production,proliferate in vitro when rechallenged. The proliferating Tcells produce levels of IL-2 and IFN-, that indicate antigen-specificT helper type 1 cells are present in significant numbers. Thus,a comparison of in vivo and in vitro data suggests that T cellsbearing the phenotype associated with potentially protectivecell-mediated responses can be primed in vivo by epitopes onsmall peptides. Since T cells from both strains of mice arecapable of responding to the immunogenic synthetic peptidesin vitro, but give different responses to the same peptidesin vivo, factors other than epltope structure appear to influenceT cell subset activation. This may have important implicationsfor diseases such as leprosy where a polarized T cell responseappears to develop and for the development of synthetic subunitvaccines.