Type C botulism due to toxic feed affecting 52,000 farmed foxes and minks in Finland

The largest reported outbreak of type C botulism in fur production animals is described. Epidemiological investigation of 117 out of 157 (response rate, 74.5%) farms revealed that 44,130 animals died or were euthanized, while 8,033 animals with milder symptoms recovered. The overall death rate in all animals at risk was 21.7%. The death rates were significantly higher in blue and shadow foxes (24.2 and 27.8%, respectively) than in silver and blue silver foxes and minks (below 4%). All minks had been immunized against botulinum toxin type C. Deaths were associated with feed manufactured by a local processor, 83 of whose customer farms (70.9%) reported dead or sick animals. Five feedlots out of 19 delivered to the farms on the day preceding the onset of the outbreak (day 2) were associated with a death rate higher than 40%. These feedlots consisted of fresh feed processed on day 2 and feed processed 1 day earlier (day 1). In laboratory analysis, the day 2 feed contained botulinum toxin type C (>600 minimum lethal doses/g), while the day 1 feed did not contain toxin. Toxin was not detected in feed raw-material samples. Clostridium botulinum type C was detected by PCR in some feed components and in feed. However, as the feed temperature was continuously 8 degrees C or below and the pH was continuously 5.6 or below according to the manufacturer, it seems unlikely that spore germination and toxin formation occurred during overnight storage. Hence, the events leading to toxin formation were not determined.     

A novel loss of function mutation in exon 10 of the FSH receptor gene causing hypergonadotrophic hypogonadism: clinical and molecular characteristics

BACKGROUND: Inactivating mutations of the FSH receptor (FSHR) are a rare cause of hypergonadotrophic hypogonadism in women. Only one patient with primary amenorrhoea due to an FSHR gene mutation has been reported outside of Finland, where the prevalence of Ala189Val mutations is particularly high. METHODS AND RESULTS: Here, we describe the clinical, molecular genetic and functional characteristics associated with a novel inactivating mutation in exon 10 of the FSHR gene identified in a patient who presented with primary amenorrhoea at 17 years of age. The C to G transversion found at nucleotide 1043 causes a Pro348Arg substitution in the extracellular region of the FSHR and results in a mutant FSHR that is completely inactive in functional studies and that does not bind FSH. The proband exhibits apparent homozygosity for this recessive mutation. Her father is heterozygous for the mutation while analysis of exon 10 of the FSHR gene from her mother revealed only wild-type sequence. Chromosome painting was used to exclude deletions or rearrangements of 2p, and microsatellite markers did not show paternal uniparental isodisomy for this region. These findings suggest that the proband is hemizygous, with an inherited or de-novo microdeletion, or alternatively a de-novo gene conversion, of the accompanying FSHR allele. CONCLUSIONS: This case confirms the importance of the FSHR in female pubertal development and reproduction, and supports a relationship between phenotype and function for FSHR mutations.     

Measuring neuroleptic-induced akathisia by three-channel actometry

Three-channel actometry was used to study neuroleptic-induced akathisia (NIA), a common and often serious disorder in association of traditional neuroleptic therapy. The aim was to explore the diagnostic possibilities of actometry in NIA and to examine in detail the motor phenomenology of the disorder in detail. The actometers were attached to the ankles and waists of ten patients, suffering from NIA, and to ten matched healthy controls. Five of the patients were changed to olanzapine treatment, and these patients were re-examined during the no-NIA condition. NIA was associated with manyfold movement activity during controlled rest (sitting) but not with increased daily overall motor activity. Movement frequencies in NIA seemed to be pathognomonic. Actometry is promising for investigation and clinical assessment of NIA. Olanzapine proved to be an adequate treatment choice for NIA patients.     

Akathisia masked by hypokinesia

Here, we will discuss the concept of subjective akathisia and present a patient case. Our patient was suffering from neuroleptic-induced hypokinesia and akathisia at the same time. The typical motor manifestations of akathisia were masked by hypokinesia, which made the diagnosis difficult. However, the subjective symptoms of akathisia were evident and distressing. Although not observable to bare eye, the pathognomonic pattern of motor activity detected in akathisia was demonstrated by actometric recording. Changing the conventional neuroleptic to an atypical one brought relief to the subjective symptoms of akathisia and hypokinesia, while the motor activity was clearly diminished in actometric recording. Actometric recording may be useful in diagnosing akathisia masked by hypokinesia, but the typical subjective symptoms of akathisia should not be ignored, even when actometry is not available to demonstrate the missing motor component of akathisia. Not only akathisia defined by DSM-IV but also subjective akathisia should be adequately treated to relieve the subjective distress, and to diminish the unfavorable effects on psychotic symptoms, behavior, and drug compliance.     

Evaluating a single dental anxiety question in Finnish adults

Objective. To evaluate the psychometric properties (criterion validity, construct validity, sensitivity, and specificity) of a single-item question screening for dental anxiety in a Finnish adult population. Material and methods. A total of 823 subjects, ranging in age from 18 to 87 years, answered a questionnaire comprising sections assessing the respondents’ demographic profile and dental attendance patterns. A single dental anxiety question and the Modified Dental Anxiety Scale (MDAS) were included. The final response rate was 85%. Results. Eight percent of the sample was highly dentally anxious using the MDAS cut-off point of 19 or above. Twelve percent of the respondents rated themselves as “very scared” on the single-item question. The percentage agreement between the single-item question and the MDAS was 93; the Kappa coefficient was 0.63. Specificity of the single question was 0.95 while sensitivity was 0.80 using the MDAS dichotomous classification. The single-item question related to age (p<0.001), gender (p<0.001), and dental attendance (p<0.001), as predicted. Conclusions. The single question has good validity, specificity, and sensitivity and may be used with confidence to assess dental fear in such situations as national health surveys or in routine dental practice where a multi-item dental anxiety questionnaire is not feasible.     

Increased carotid atherosclerosis in andropausal middle-aged men

OBJECTIVES: This study examined the association between carotid artery intima-media thickness (IMT), serum sex hormone levels, and andropausal symptoms in middle-aged men. BACKGROUND: Male sex hormones may play a dual role in the pathogenesis of atherosclerosis in men by carrying both proatherogenic and atheroprotective effects. METHODS: We studied 239 40- to 70-year-old men (mean +/- SD: 57 +/- 8 years) who participated in the Turku Aging Male Study and underwent serum lipid and sex hormone measurements. Ninety-nine men (age 58 +/- 7 years) were considered andropausal (i.e., serum testosterone <9.8 nmol/l or luteinizing hormone [LH] >6.0 U/l and testosterone in the normal range), and in both situations, they had subjective symptoms of andropause (a high symptom score in questionnaire). Three were excluded because of diabetes. The rest of the men (age 57 +/- 8 years) served as controls. Carotid IMT was determined using high-resolution B-mode ultrasound, and serum testosterone, estradiol (E2), LH, and sex hormone-binding globulin were measured using standard immunoassays. RESULTS: Andropausal men had a higher maximal IMT compared with controls in the common carotid (1.08 +/- 0.34 vs. 1.00 +/- 0.23, p < 0.05) and in the carotid bulb (1.44 +/- 0.48 vs. 1.27 +/- 0.35, p = 0.003). Common carotid IMT correlated inversely with serum testosterone (p = 0.003) and directly with LH (p = 0.006) in multivariate models adjusted for age, total cholesterol, body mass index, blood pressure, and smoking. CONCLUSIONS: Middle-aged men with symptoms of andropause, together with absolute or compensated (as reflected by high normal to elevated LH) testosterone deficiency, show increased carotid IMT. These data suggest that normal testosterone levels may offer protection against the development of atherosclerosis in middle-aged men.     

Effects of medroxyprogesterone and estradiol on the recovery of spermatogenesis in irradiated rats

Suppression of intratesticular testosterone (ITT) levels is required for spermatogenic recovery in rats after irradiation, but maintenance of peripheral testosterone (T) levels is important for many male functions. Considering the preservation of peripheral T while suppressing ITT, we tested the effects of a combination of a progestin, medroxyprogesterone acetate (MPA), plus T on spermatogenic recovery after irradiation, and compared its effects to those of T alone or T combined with estradiol (E2). Rats were given testicular irradiation (6 Gy) and treated during wk 3-7 after irradiation with MPA + T, or the individual steroids with or without GnRH antagonist (GnRH-ant), or GnRH-ant alone, or T + E2. Whereas GnRH-ant alone stimulated differentiation in 55% of tubules 13 wk after irradiation compared with 0% in irradiated-only rats, the addition of MPA reduced the percentage of tubules showing differentiation to 18%. However, T or MPA alone or the combination of the two induced germ cell differentiation in only 2-4% of tubules. In contrast, E2 stimulated differentiation in 88% of tubules, and T combined with E2 still resulted in differentiation in 30% of tubules. Although both MPA and E2 suppressed ITT levels to approximately 2% of control (2 ng/g testis), MPA was a less effective stimulator of spermatogenic recovery than E2 or GnRH-ant alone. MPA's function as a weak androgen was likely responsible for inhibiting spermatogenic recovery, as was the case for all other tested androgens. Thus, for clinical protection or restoration of spermatogenesis after radiation or chemotherapy by suppressing T production, MPA, at least in the doses used in the present study, is suboptimal. The combination of an estrogen with T appears to be most effective for stimulating such recovery.