Increased severity over generations of Charcot-Marie-Tooth disease type 1A.

BACKGROUND: Charcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant polyneuropathy due to a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene. This mutation is not modified during inheritance. OBJECTIVES: We set forth to test the hypothesis that in a subgroup of CMT1A patients there is clinical anticipation, namely an increase in disease severity over generations. METHODS: Thirty-nine CMT1A mutation-positive patients in 16 families and 23 parent-offspring pairs were evaluated. This included 14 families with 2 generations and 2 families with 3 generations. Age of presentation was assessed by interviewing the patients and clinical severity was measured using the CMT neuropathy score (CMTNS). RESULTS: In 21/23 parent-child pairs and 14/16 families, there was an earlier age of presentation in children of genetically affected parents. The mean age of onset in the progeny was 12.61 years compared to 41.22 years in the parent generation, (p < 0.001). Mean severity in the younger generation was slightly higher than that of the parent generation. When corrected for the age difference, the trend for a worse phenotype in the younger generation became statistically significant (p < 0.02,Wilcoxon signed rank test). CONCLUSIONS: Our findings suggest that in a subgroup of CMT1A patients there is an increase in clinical severity over generations. The mechanism responsible for this observation remains unknown. Our findings should be validated on a larger cohort of CMT1A families.

Abnormal musical pacemaker in a patient with musical hallucinations.

Music creation requires a highly orchestrated temporal pattern. The study of a patient with repetitive musical hallucinations enabled us to examine temporal pacemakers in music production. Here, we show that the pattern of faster silent production of a chosen tune compared with its production aloud was reversed when the patient produced the hallucinatory tune. This observation might suggest the utilization of a pacemaker(s), which functions differentially during the disease.

The role of prolactin in reproductive failure associated with heat stress in the domestic turkey.

Reproductive failure associated with heat stress is a well-known phenomenon in avian species. Increased prolactin (PRL) levels in response to heat stress have been suggested as a mechanism involved in this reproductive malfunction. To test this hypothesis, laying female turkeys were subjected to 40 degrees C for 12 h during the photo-phase daily or maintained at 24-26 degrees C. Birds in each group received oral treatment with parachlorophenyalanine (PCPA; 50 mg/kg BW/day for 3 days), an inhibitor of serotonin (5-HT) biosynthesis, or immunized against vasoactive intestinal peptide (VIP). Both treatments are known to reduce circulating PRL levels. Nontreated birds were included as controls. In the control group, high ambient temperature terminated egg laying, induced ovarian regression, reduced plasma luteinizing hormone (LH) and ovarian steroids (progesterone, testosterone, estradiol) levels, and increased plasma PRL levels and the incidence of incubation behavior. Pretreatment with PCPA reduced (P < 0.05) heat stress-induced decline in egg production, increase in PRL levels, and expression of incubation behavior. Plasma LH and ovarian steroid levels of heat stressed birds were restored to that of controls by PCPA treatment. As in PCPA-treated birds, VIP immunoneutralization of heat-stressed turkeys reduced (P < 0.05) circulating PRL levels and prevented the expression of incubation behavior. But it did not restore the decline in LH, ovarian steroids, and egg production (P > 0.05). The present findings indicate that the detrimental effect of high temperature on reproductive performance may not be related to the elevated PRL levels in heat-stressed birds but to mechanism(s) that involve 5-HT neurotransmission and the induction of hyperthermia.

The effect of a green and blue monochromatic light combination on broiler growth and development.

Previous reports have suggested that green light enhances broiler growth at an early age, whereas blue light enhances growth at older ages. The aim of this study was to examine the effect of a switch in monochromatic light at 2 ages on growth and development of broilers. Male chicks (Anak, n = 640) were used. After hatch, chicks were weighed, wing-banded, and blocked into treatment groups. Chicks were grown in 1-m2 pens in 8 isolated light-proof rooms (20 birds/pen). The light treatments were (1) Control white (mini-incandescent lamps), 2) blue light-emitting diode (LED) lamps, 3) green LED lamps, 4) blue LED switching to green at 10 d of age, 5) blue LED switching to green at 20 d of age, 6) green LED switching to blue at 10 d of age, and 7) green LED switching to blue at 20 d of age. There were 8 pens for treatment 1, and 4 pens for each of the other treatments. The light schedule was 23L:1D, and intensity was 0.1 watts/m2. BW and feed consumption were recorded. Green light birds were significantly heavier at 4 d of age. Switching light at 10 d of age from green to blue caused a further increase in BW. This improved growth was maintained until the end of the experiment. Light switching from blue to green at 20 d of age also improved growth as compared with white light. Average feed efficiency and mortality rate did not differ between groups. No association was observed among light treatment, performance, and plasma triiodothyronine concentration. We suggest that green light stimulated growth of birds at early age, and shifting birds to a different light environment at 10 or 20 d of age might further stimulate growth.

Alien hand syndrome.

In Stanley Kubrick's movie Dr Strangelove, the main character is described as "erratic" and displays a bizarre movement disorder. His right hand seems to be driven by a will of its own, at times clutching his own throat and at other times raising into a Nazi salute. Dr Strangelove must try to restrain this wayward limb with his left hand. Bizarre as this fictional character is, a similar movement disorder can occur in neurologic disease. The complex phenomenon associated with this disorder falls under the rubric of alien hand syndrome. This syndrome is characterized by a limb that seems to perform meaningful acts without being guided by the intention of the patient. Patients find themselves unable to stop the alien limb from reaching and grabbing objects, and they may be unable to release these grasped objects without using their other hand to pry open their fingers. These patients frequently express astonishment and frustration at the errant limb. They experience it as being controlled by an external agent and often refer to it in the third person. This article outlines the origins of the terminology used in describing this syndrome, early observations, and studies regarding its functional neuroanatomy.

Visual agnosia.

The visual agnosias are an intriguing class of clinical phenomena that have important implications for current theories of high-level vision. Visual agnosia is defined as impaired object recognition that cannot be attributed to visual loss, language impairment, or a general mental decline. At least in some instances, agnostic patients generate an adequate internal representation of the stimulus but fail to recognize it. In this review, we begin by describing the classic works related to the visual agnosias, followed by a description of the major clinical variants and their occurrence in degenerative disorders. In keeping with the theme of this issue, we then discuss recent contributions to this domain. Finally, we present evidence from functional imaging studies to support the clinical distinction between the various types of visual agnosias.

Spinal cord involvement in uncomplicated herpes zoster.

We prospectively evaluated herpes zoster patients during the acute phase of the disease for central nervous system involvement. Of 24 patients with spinal zoster, 13 (54%) had spinal cord abnormality, which was asymptomatic in 12 of the 13. Age but not lack of acyclovir treatment was associated with such involvement. In all but 2, neurological involvement resolved within 6 months. Although the mechanism responsible for the neurological abnormalities is unknown, findings may support the hypothesis that zoster is associated with spread of viral infection into the spinal cord and therefore support the possibility that zoster is due to active viral replication in the ganglion.

Recurrence of acute disseminated encephalomyelitis at the previously affected brain site.

BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a usually monophasic demyelinating disorder of the central nervous system. Recurrences pose a diagnostic challenge because they can be overlooked or suggest an alternative diagnosis. OBJECTIVE: To examine the frequency, nature, and outcome of recurrent ADEM. DESIGN: Review of the medical records of patients diagnosed in our institution as having ADEM between January 1, 1983, and May 31, 1998. Recurrences were defined as appearance of new symptoms and signs at least 1 month after the previous episode. RESULTS: Five (24%) of 21 patients with ADEM developed recurrent disease episodes. In all, diagnosis was confirmed by brain biopsy. One patient had 4 disease episodes, 2 had 3, and the other 2 each had 2. Recurrence appeared 1.5 to 32 months after initial presentation and involved the same brain territory in 6 of 9 recurrences in 3 of 5 patients. In 2 patients, recurrences included neuropsychiatric signs. A good response to corticosteroid therapy was observed in 10 of 13 of treated ADEM attacks: in 3 of the 4 treated initial events and in 7 of 9 recurrences. CONCLUSIONS: Recurrent ADEM may be more prevalent than previously recognized. Patients who relapse tend to have more than 1 recurrence that usually involves, clinically and radiologically, a brain territory that was affected before and can simulate a space-occupying lesion that requires histologic diagnosis. Neuropsychiatric features may be the main presentation of a relapse. Since recurrent ADEM is a corticosteroid-responsive condition, awareness and early diagnosis are mandatory.

Cerebrospinal fluid oligoclonal IgG bands in patients with spinal arteriovenous malformation and structural central nervous system lesions.

OBJECTIVE: To investigate the incidence and characteristics of patients with structural central nervous system (CNS) lesions and cerebrospinal fluid oligoclonal IgG bands. DESIGN: A retrospective study. METHOD: The medical records of patients with cerebrospinal fluid oligoclonal IgG bands were evaluated for the presence of structural CNS lesions, their location and cause, and for clinical characteristics. SETTING: Cerebrospinal fluid oligoclonal IgG bands were examined in the Neuroimmunology Laboratory, Hadassah University Hospital, Jerusalem, Israel. PATIENTS: Two hundred seventy of 570 patients with positive cerebrospinal fluid oligoclonal IgG bands were available for analysis. Twenty patients had structural CNS lesions. RESULTS: Twenty (7.5%) of the 270 patients had structural CNS lesions: 3 patients had spinal arteriovenous malformation; 5 patients had tumors; 9 patients had compressive cervical myelopathy. Traumatic leukomalacia, Arnold-Chiari malformation type 1, and CNS hemosiderosis were present in 1 patient each. In 2 patients (1 patient with recurrent meningioma and 1 patient with posttraumatic encephalomalacia) the presence of a structural CNS lesion was followed by the development of multiple sclerosis. In all 3 patients with spinal arteriovenous malformation, oligoclonal IgG identification prolonged the time to diagnosis and therapy, which varied from a few weeks to 3 years. CONCLUSIONS: Structural CNS lesions, responsible for the neurological disorder, were present in 20 patients (7.5%) with cerebrospinal fluid oligoclonal IgG bands. The mechanism underlying oligoclonal IgG presence in spinal arteriovenous malformation and the coexistence of multiple sclerosis and structural CNS lesions is unknown, but may be related to recurrent tissue damage with repeated presentation of CNS antigens to the immune system.

Online and in situ monitoring of environmental pollutants: electrochemical biosensing of cadmium.

Online sensitive monitoring of gene expression is essential for understanding microbial life and microbial communities, especially under stress-inducing conditions, such as the presence of environmental pollutants. We describe here a novel use of promoter-based electrochemical biosensing for online and in situ monitoring of gene expression in response to pollutants. As a model system, we used a cadmium-responsive promoter from Escherichia coil fused to a promoterless lacZ gene, which was monitored using an electrochemical assay of beta-galactosidase activity. This whole-cell biosensor could detect, within minutes, nanomolar concentrations of cadmium in water, sea water and soil samples, and it can be used for continuous online and in situ monitoring.

Focal, steroid responsive myositis causing dropped head syndrome.

The dropped head syndrome, which occurs in a variety of neuromuscular disorders, is usually not due to an inflammatory process and generally either self-limited or nonresponsive to therapy. We present an 80-year-old woman who developed progressive neck weakness over a few months due to a focal and restricted inflammatory process involving the neck extensor muscles. She responded dramatically to treatment with immunosuppressive therapy.

Unidirectional dyslexia in a polyglot.

Alexia is usually seen after ischaemic insults to the dominant parietal lobe. A patient is described with a particular alexia to reading Hebrew (right to left), whereas no alexia was noted when reading in English. This deficit evolved after a hypertensive right occipitoparietal intracerebral haemorrhage, and resolved gradually over the ensuing year as the haematoma was resorbed. The deficit suggests the existence of a separate, language associated, neuronal network within the right hemisphere important to different language reading modes.

The effect of monochromatic light on broiler growth and development.

Artificial illumination, including light quality, is crucial in modem broiler management. In the present study, a new, highly efficient, monochromatic light system has been developed for broilers. One hundred and eighty male broiler chicks (Anak) were divided into four light treatment groups (n = 45) in three replicates each. All birds were housed in a single room previously divided by wooden bars into 12 sealed cells of 1 m2. Feed and water were provided for ad libitum consumption. Light intensity was 0.1 W/m2 at the height of birds' heads and was scheduled for 23 h of light and 1 h of dark during the entire experimental period. Light treatments were: control white (mini-incandescent light bulbs), blue (480 nm), green (560 nm), and red (660 nm). Body weight was recorded periodically, feed consumption was measured daily, and feed efficiency was calculated. Blood samples were taken at 1, 9, and 32 d of age and plasma testosterone was determined. Two necropsies were conducted, at 23 and 35 d of age, and selected glands and organs were weighed. In the group reared under green light, a significant enhancement in weight gain was observed as early as 3 d of age; this gain was maintained during the entire experimental period. Broilers reared under blue light had a later onset of growth enhancement and were significantly heavier than those reared under white and red light at 20 d of age. Plasma testosterone levels were significantly higher in birds reared under blue light. Breast muscle weights were significantly higher in the birds reared under green light at 23 and 35 d of age. These results suggest that green and blue light stimulate growth.

Various light source treatments affect body and skeletal muscle growth by affecting skeletal muscle satellite cell proliferation in broilers.

In this study we addressed the effect of various monochromatic light treatments on muscle growth and satellite cell proliferation in broilers (Gallus domesticus). Broilers were reared under green (560 nm), blue (480 nm) and red (660 nm) monochromatic lights and white light as a control from day one until 35 days of age. At five days of age, satellite cells were prepared from the experimental chicks. The number of satellite cells per gram of breast muscle and total number of satellite cells derived from the experimental broilers was substantially higher in the groups reared under green and blue light, compared to the red and white light groups. Growth hormone receptor gene expression was also higher in the former groups. High correlation was found between the breast muscle weight observed on day 35 and the number of satellite cells per gram of breast muscle (r = 0.915) and total number of satellite cells (r = 0.833), derived from the experimental chicks as early as five days of age. In addition, the protein/DNA ratio found in breast muscle at 35 days of age was significantly lower in chicks that were reared under green and blue lights. The lowest ratio which was found in the green group and was twice as low as in the control group, indicates the highest number of nuclei in the former group. As satellite cells are the only source of additional nuclei in skeletal muscles of postnatal animals, our results suggest that the higher muscle weight found in the green and blue light groups was due to increased satellite cell proliferation during the first days of age.

Differential allelic expression of PrP mRNA in carriers of the E200K mutation.

Creutzfeldt-Jakob disease (CJD) linked to the E200K mutation of the prion protein (PrP) gene presents with a wide range of age at disease onset. Since most patients are heterozygous for the mutation, we tested whether differential expression of mutant versus wild-type (wt) PrP may affect the age at disease onset in carriers of the mutation. We measured wt and mutant PrP protein and mRNA in Epstein-Barr virus (EBV)-transformed B cells of either E200K CJD patients or healthy E200K carriers. Our results suggests that while in most healthy carriers the expression of wt PrP was higher than that of E200K PrP, most of the E200K CJD patients express equal levels of both PrP proteins. Similar results were obtained for either PrP protein or PrP mRNA. These results suggest that preferential expression of PrP from the wt allele may modulate the outbreak of the disease in carriers of prion mutations. This notion is consistent with the results obtained in transgenic mice carrying a human PrP gene, which suggest that endogenous PrP protects mice from contracting scrapie after inoculation with human CJD brain. Similar mechanisms may prevail in other inherited diseases with variable phenotypes.

Hemoptysis: etiology, evaluation, and outcome in a tertiary referral hospital.

OBJECTIVES: Hemoptysis, an important and alarming symptom, often indicates serious disease. This study was designed to assess the different causes of hemoptysis, the relative importance of the different diagnostic modalities employed, and the outcome in an Israeli population cohort. DESIGN: A retrospective analysis of 208 patients with hemoptysis at the Hadassah University Hospital, Jerusalem, Israel between January 1980 and August 1995. RESULTS: Bronchiectasis (20%), lung cancer (19%), bronchitis (18%), and pneumonia (16%) accounted for most causes of hemoptysis. In contrast to older studies, active tuberculosis was a rare finding (1.4%). Bronchiectasis and bleeding diathesis were major causes of moderate to severe hemoptysis while bronchitis and lung cancer were commonly associated with milder degrees of bleeding. CT scan was the most sensitive diagnostic test when employed alone, with a positive yield of 67%. However, it failed to locate at least three cases of lung cancer. When combining a CT study together with a bronchoscopy, the positive yield increased to 93%. The mortality rate for patients with mild to moderate hemoptysis was low (2.5% and 6%, respectively), while patients with massive hemoptysis had high mortality rates (38%). Patients with lung cancer or bleeding diathesis had higher mortality rates compared with the rest of the cohort. CONCLUSIONS: Hemoptysis is a common symptom with a good prognosis in most cases. However, patients exhibiting massive bleeding or those with lung malignancy and patients with bleeding diathesis had a poorer prognosis. Patients older than 50 years with a positive smoking history need an extensive evaluation and follow-up to exclude lung carcinoma. The combined use of bronchoscopy and chest CT has the best yield in evaluating hemoptysis.