Elevated TCDD in chicken eggs and farm-raised catfish fed a diet with ball clay from a Southern United States mine

The U.S. Food and Drug Administration (FDA) terminated the use of ball clay from a mine in Mississippi as an additive in animal feed after discovering nanogram per gram concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). The FDA collected chicken eggs and farm-raised catfish in affected areas and throughout the remaining continental United States to assess levels of 2,3,7,8-TCDD. A new method using quadrupole ion storage tandem-in-time mass spectrometry (QISTMS) measured the 2,3,7,8-TCDD levels in 42 catfish fillet composites, 3 Tilapia fillet composites, 46 chicken egg samples, and 6 chicken feeds. Six catfish composites and 20 egg samples had 2,3,7,8-TCDD concentrations significantly above 1.0 pg/g wet weight of fillet or whole egg. Farm-raised catfish not exposed to feed containing ball clay had a mean 2,3,7,8-TCDD concentration of 0.12 pg/g. The TCDD isomer pattern in ball clay differed from the TCDD isomer pattern in a fly ash sample and from the "chick edema factor" TCDD pattern in a sample of reference toxic fat used as a feed ingredient in the 1950s.     

Right aortic arch with aberrant subclavian arteries: a cause of esophageal compression

We report a case of symptomatic partial vascular ring that to our knowledge has not been previously described. This anomaly includes a right aortic arch with an aberrant left subclavian artery and an atypical origin of the right subclavian artery.     

Defective slow inactivation of sodium channels contributes to familial periodic paralysis

OBJECTIVE: To evaluate the effects of missense mutations within the skeletal muscle sodium (Na) channel on slow inactivation (SI) in periodic paralysis and related myotonic disorders. BACKGROUND: Na channel mutations in hyperkalemic periodic paralysis and the nondystrophic myotonias interfere with the normally rapid inactivation of muscle Na currents following an action potential. This defect causes persistent inward Na currents that produce muscle depolarization, myotonia, or onset of weakness. Distinct from fast inactivation is the process called SI, which limits availability of Na channels on a time scale of seconds to minutes, thereby influencing muscle excitability. METHODS: Human Na channel cDNAs containing mutations associated with paralytic and nonparalytic phenotypes were transiently expressed in human embryonic kidney cells for whole-cell Na current recording. Extent of SI over a range of conditioning voltages (-120 to +20 mV) was defined as the fraction of Na current that failed to recover within 20 ms at - 100 mV. The time course of entry to SI at -30 mV was measured using a conditioning pulse duration of 20 ms to 60 seconds. Recovery from SI at -100 mV was assessed over 20 ms to 10 seconds. RESULTS: The two most common hyperkalemic periodic paralysis (HyperPP) mutations responsible for episodic attacks of weakness or paralysis, T704M and M1592V, showed clearly impaired SI, as we and others have observed previously for the rat homologs of these mutations. In addition, a new paralysis-associated mutant, I693T, with cold-induced weakness, exhibited a comparable defect in SI. However, SI remained intact for both the HyperPP/paramyotonia congenita (PMC) mutant, A1156T, and the nonparalytic potassium-aggravated myotonia (PAM) mutant, V1589M. CONCLUSIONS: SI is defective in a subset of mutant Na channels associated with episodic weakness (HyperPP or PMC) but remains intact for mutants studied so far that cause myotonia without weakness (PAM).     

Construction and murine immunogenicity of recombinant Bacille Calmette Guérin vaccines expressing the B subunit of Escherichia coli heat labile enterotoxin

Three recombinant strains of Mycobacterium bovis Bacille Calmette Guerin (rBCG) were prepared in which the immunogenic B subunit of human Escherichia coli heat labile enterotoxin (LT-Bh) was expressed either as a cytoplasm protein, a cell wall associated lipoprotein or a secreted protein. Intraperitoneal immunisation of mice with these rBCG induced IgG and IgA antibodies to LT-Bh and shifted the serum IgG subclass response to subsequent challenge with purified LT-Bh from IgG1 to an IgG2a. Oral administration of recombinant BCG induced mucosal and serum IgA antibodies to LT-Bh which peaked four months after immunisation. Antibody responses were greater when LT-Bh was expressed as a secreted protein or lipoprotein rather than in the cytoplasm. Oral vaccination with recombinant BCG may be an effective approach, particularly to induce mucosal IgA and prime for a serum TH1 recall response.     

Clinical governance. Thin on the ground

Clinical governance is being led by two people, usually a GP and a nurse, in most of the PCGs that responded to the survey. A fifth of the leads for clinical governance had no experience of working on quality issues. Nearly a third of respondents felt that their health authority had provided poor support or none at all. Only 10 PCGs had identified a clinical governance budget. No PCG was working with a finance manager to develop clinical governance and only five were working with an information manager.     

Combined finasteride and flutamide therapy in men with advanced prostate cancer

Objectives

To evaluate the efficacy of combined finasteride and flutamide therapy in men with advanced prostate cancer by determining (1 ) the short-term tolerability of finasteride monotherapy and its effect on serum prostate-specific antigen (PSA) and hormone (testosterone, dihydrotestosterone) levels, and (2) the effects of the addition of flutamide on tolerability and on serum PSA and hormone levels.

Methods

Thirteen hormone-naive men with advanced prostate cancer (4 with Stage D2, 1 with Stage D1, 1 with Stage DO, 7 with rising PSA levels after radical prostatectomy [n = 2]or definitive radiation therapy [n = 5]) were initially treated with 5 mg finasteride daily. Flutamide (250 mg three times a day) was added after serum PSA levels stabilized.

Results

Finasteride alone (median 5 weeks) had no significant effect on serum PSA levels (P>0.05). Combined finasteride and flutamide resulted in a mean 91% reduction in serum PSA levels, with 85% of men achieving a nadir serum PSA level of less than 4.0 ng/mL and 46% achieving undetectable levels (0.2 ng/mL or less). Finasteride alone had no significant effect on serum testosterone levels (P>0.05) but did result in a mean 74% reduction in serum dihydrotestosterone levels. Combined finasteride and flutamide resulted in a mean 56% increase in serum testosterone levels but had no additional effect on serum dihydrotestosterone levels (P>0.05). Side effects occurred in 85% (gynecomastia or breast tenderness in 62% [8 of 13]and diarrhea in 23% [3 of 13]) of men on combined therapy. Potency was preserved in 66%. Combined finasteride and flutamide therapy was withdrawn from 15% (2 of 13) because of flutamide-induced diarrhea and from 23% (3 of 13) because of disease progression. All remaining patients (8 of 13) have serum PSA levels below 4.0 ng/mL and 4 of these 8 have undetectable levels. These men have received combined finasteride and flutamide for a median 11 months (range 6 to 19).

Conclusions

Finasteride monotherapy is inadequate therapy for advanced prostate cancer, but combined finasteride and flutamide may be a reasonable alternative for men with advanced prostate cancer who refuse conventional hormone therapy.     

The use of multimedia computer-based patient records in ambulatory care

The use of a multimedia computer-based patient record (CPR) within ambulatory care is a topic that has not achieved widespread understanding or acceptance. However, if the topic is divided into its parts, multimedia and computer-based patient record, it reflects both highly recognizable and desirable goals that most health care organizations are undertaking. Multimedia technology is quickly maturing. In addition, the goal of attaining a CPR is of primary interest to most health care organizations. It is inevitable that these two technologies will eventually become synergistic. This article presents the case for a multimedia ambulatory CPR and describes one example of this happy marriage.