Use of metagenomic microbial source tracking to investigate the source of a foodborne outbreak of cryptosporidiosis.

Cryptosporidium is a protozoan parasite of global public health importance that causes gastroenteritis in a variety of vertebrate hosts, with many human outbreaks reported yearly, often from ingestion of contaminated water or food. Despite the major public health implications, little is typically known about sources of contamination of disease outbreaks caused by Cryptosporidium. Here, we study a national foodborne outbreak resulted from infection with Cryptosporidium parvum via romaine lettuce, with the main goal to trace the source of the parasite. To do so, we combined traditional outbreak investigation methods with molecular detection and characterization methods (i.e. PCR based typing, amplicon and shotgun sequencing) of romaine lettuce samples collected at the same farm from which the contaminated food was produced. Using 18S rRNA typing, we detected C. parvum in two out of three lettuce samples, which was supported by detections in the metagenome analysis. Microbial source tracking analysis of the lettuce samples suggested sewage water as a likely source of the contamination, albeit with some uncertainty. In addition, the high degree of overlap in bacterial species content with a public human gut microbial database corroborated the source tracking results. The combination of traditional and molecular based methods applied here is a promising tool for future source tracking investigations of food- and waterborne outbreaks of Cryptosporidium spp. and can help to control and mitigate contamination risks.

A feasibility study of roquinimex (Linomide) and alpha interferon in patients with advanced malignant melanoma or renal carcinoma.

Thirty-one patients with advanced renal carcinoma or malignant melanoma were treated in the first feasibility study of alpha-interferon (Roferon) and the new oral immunomodulating agent, Linomide. Linomide 5 mg or 10 mg p.o. daily was given for 2 weeks; alpha-interferon was then added at 3 MU s.c. three times weekly, escalating in each patient by 3 MU per week, if tolerable, up to 12 MJ. The combination was poorly tolerated with nausea, vomiting, somnolence and myalgia commonly reported. Adverse events accounted for treatment withdrawal in ten patients and contributed to withdrawal in four other patients. Treatment with Linomide alone in the first 2 weeks led to a significant increase in white blood cells, neutrophils and platelets. When alpha-interferon was added, the platelet count decreased significantly over the following 6 weeks. Nineteen patients had white cell phenotype and function measured. After 2 weeks of 5 mg Linomide, a transient but significant decrease in the absolute number of activated T-helper cells (CD4+DR+) was observed. No changes in natural killer (NK) cell number or activity were observed. Twenty-two patients were evaluable for response. One with metastatic renal cell carcinoma had a complete response and six had stable disease. This study does not support the use of the combination because significant toxicity was seen without the anticipated immunological benefits.

Cystic basal cell carcinoma of the orbit and eyelids.

When basal cell carcinoma develops cystic change, its clinical and radiological features vary, leading to confusion in differential diagnosis We report four cases with cystic formation of 62 patients with orbital and adnexal basal cell carcinoma encountered during the last 12 years. The salient clinical, radiological, and histopathological features of these cases are presented and differential diagnosis of large cystic lesions in the orbit is discussed. When the basal cell carcinoma develops cystic changes it mimics other orbital cysts, including inclusion cysts due to penetrating injury, mucoceles, and necrotic metastatic tumors.

EORTC phase II study of daily oral linomide in metastatic renal cell carcinoma patients with good prognostic factors.

Following a previous EORTC GU-Group study, in which linomide showed some activity in poor prognosis patients, this study was initiated to determine the effect of linomide in more favourable patients. 35 patients with metastatic renal cell carcinoma with good prognostic factors, i.e. good performance status, prior nephrectomy, no prior systemic therapy, and no liver, bone or brain metastases, were treated with linomide, a quinoline derivative with immunomodulating properties, at a dose of 10 mg daily, after an initial dose escalation during the first 4 weeks of treatment. In 29 evaluable patients, no responses were observed (95% confidence interval 0-10%). Best overall response was no change in 9 patients, for a median duration of 4 months. Linomide in this schedule was poorly tolerated, with 17% (6 patients) of patients being withdrawn and 23% (8 patients) having dose reductions due to adverse events, mostly influenza-like symptoms of myalgia, arthralgia and fatigue. Several cases of pericarditis and neuropathy were observed. In spite of selection of favourable prognosis patients and an optimal daily dosing schedule, linomide was not an effective treatment in renal cell carcinoma. In view of toxicity and lack of efficacy, there is no rationale in further testing the drug in this disease.

An EORTC phase II study of the efficacy and safety of linomide in the treatment of advanced renal cell carcinoma.

The aim of this study was to determine the objective tumour response rate and duration of response and toxicity of linomide (Roquinimex) treatment in patients with disseminated renal cell carcinoma, pretreated or not pretreated with immunotherapy. From March 1991 to July 1992, 72 patients with metastatic and progressive renal cell cancer were entered of whom 9 (12%) were not evaluable for response. Linomide was given orally, twice weekly, 5 mg during the first week with dose escalation to 10 mg during the second week and 15 mg thereafter. Treatment was continued until disease progression or unacceptable toxicity. No haematological toxicity but slight anaemia was observed. A significant WBC (white blood cell count) increase (P < 0.0001, paired T-test) was found during treatment. The most often reported non-haematological side-effects were: flu-like syndrome (54%, grade III-IV 7%), nausea/vomiting (41% and 3%, respectively) and neurotoxicity (34% and 2%). Most side-effects were of mild or moderate intensity (WHO grade 1 or 2). The objective overall response rate was 4%: 1 CR and 2 PRs. Stable disease was reported for 28 patients (40%). The duration of response was 17, 22 and 30 (CR) months. Median time to progression was 5 months. Linomide at the given dose and schedule is well tolerated, but has limited antitumour activity in metastatic renal cell carcinoma.

Ultrasound treatment of Ménière's disease.

This article reviews the technical data about ultrasonography devices, the mode of action of ultrasound waves on vestibular structures, when to use this technique, and the surgical procedure. It also presents the results of this treatment obtained during the last 10 years in the authors' various institutions.

Longitudinal changes in hearing ability among Swedish conscripts.

An analysis of a military database of about 36,000 tone audiograms from male Swedish conscripts aged 18 to 19 and recorded from 1969 to 1977 demonstrates a successively decreasing prevalence of hearing loss during this period. This might reflect improved therapy during the 1950s and 1960s of ear disorders causing hearing loss in small children. If observations in other studies on a reverse trend during the 1980s are confirmed, they indicate, together with the present study, that around 1980 young people began to be harmfully exposed to an environmental factor causing hearing loss. If this is the case, the causative factor would probably be non-occupational exposure to electronically amplified sounds from loudspeakers and headphones.

Acute peripheral facial palsy simulating Bell's palsy in a case of probable multiple sclerosis with a clinically correlated transient pontine lesion on magnetic resonance imaging.

A transient pontine lesion was demonstrated in a young adult male who had a complete acute peripheral facial nerve palsy due probably to multiple sclerosis. In the acute stage of the palsy. T2-weighted magnetic resonance imaging (MRI) revealed a high signal intensity in the ipsilateral pons in the region of the nucleus and pontine part of the facial nerve. The patient recovered completely 5 weeks after the onset of the palsy, and at this stage, the lesion in the brainstem was no longer demonstrable on MRI. The onset and course of the disease resembled the idiopathic form of facial palsy (Bell's palsy): the present findings along with recent MRI and topodiagnostic studies may indicate that in some cases of Bell's palsy the primary lesion is located centrally. By improved MRI techniques and intravenous contrast agents it may be possible to visualize and follow the disease process and ascertain more of the pathogenesis of Bell's palsy.

Long-term progression of Meniére's disease.

A retrospective study of 161 Meniére patients followed up for 9 years or more is presented. The development with respect to hearing, caloric response, vertigo and ability to work was analysed. The main functional loss was found to take place early in the course of the disease. There was an increase in bilaterality with time. Spontaneous relief in vertigo over the years has been noticed.

Relationship between abnormal brainstem auditory-evoked potentials and subnormal CSF levels of HVA and 5-HIAA in first-episode schizophrenic patients.

Auditory brainstem-evoked responses (ABRs) were recorded and the CSF concentration of the amine metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured in 39 drug-free schizophrenic patients. Twenty-four of the patients were first admissions and had never received antipsychotic medication. The ABRs were judged according to our normative data and the CSF concentrations of the amine metabolites were compared with those of 47 healthy volunteers. Clear-cut abnormal ABRs, identified as a lack of one or more peaks or abnormal peak latencies, were found in 15 patients. In controls and patients with normal ABRs, there was a significant positive correlation between the cerebrospinal fluid (CSF) levels of HVA and 5-HIAA; no such correlation was found in patients with abnormal ABRs. Schizophrenics with abnormal ABRs had significantly lower levels of HVA, but not 5-HIAA, in the CSF when compared with controls. Schizophrenic patients with normal ABRs (n = 24) did not differ from the controls with regard to the amine metabolites in CSF. A comparison of the CSF levels of HVA and 5-HIAA yielded no significant difference between patients with normal and those with abnormal ABRs. In contrast, when only first-episode, never-treated schizophrenics were considered, patients with abnormal ABRs (n = 10) had significantly lower levels of both HVA and 5-HIAA when compared with those having normal ABRs (n = 14). The results indicate an association between brainstem dysfunction and reduced central nervous dopaminergic and possibly also serotoninergic activity in schizophrenia.

Long-term progression of Menière's disease.

A retrospective study of 161 patients with Menière's disease followed up for 9 years or more is presented. The development, with respect to hearing, caloric response, vertigo, and ability to work, was analyzed. The main functional loss was found to take place early in the course of the disease. There was an increase in bilaterality with time. A spontaneous relief in vertigo over the years has been noticed.

Abnormal auditory brain-stem responses in hallucinating schizophrenic patients.

Abnormal auditory brain-stem responses (ABRs) were recorded in 10 out of 20 schizophrenic in-patients. The response abnormalities did not show any correlation to the degree of psychopathology, sub-group of schizophrenia, age, sex, or cerebral ventricular enlargement. Nor was there any correlation to previous neuroleptic treatment: a pathological ABR was recorded in 5 of the 8 patients who had never received such medication. A statistically significant relationship was found between ABR pathology and auditory hallucinations: 9 of the 11 patients who admitted having hallucinations exhibited brain-stem response abnormality, whereas ABR abnormality was recorded in only 1 of the 9 patients who denied having hallucinations. The data imply that brain-stem dysfunction is involved in the psychopathology of schizophrenia, and that interference with the auditory pathways in the brain-stem may induce auditory hallucinations in schizophrenic patients.

Hearing damage in military service. A study on 38,294 conscripts.

In an audiometric study on 38,294 conscripts, noise-induced high-frequency hearing deterioration during basic training (mean 245 days) was studied. On reporting for training, 29% were found to have hearing defects, predominantly in the high-frequency area. After training, high-frequency deterioration, predominantly unilateral or asymmetrical, was found in 5%. In 0.5%, this deterioration had reached a symptomatic level, causing minor handicap. In 0.03% (12 conscripts), it fulfilled the criterion of "10% hearing disability" applied in Swedish industrial insurance. The incidence of high-frequency deterioration rose from 3% in conscripts having 'normal' hearing on reporting, to 17% among those with the greatest hearing loss on reporting. This means that the presence of sensorineural hearing loss implies an increased risk of noise-induced hearing deterioration. No correlation was found between hearing status on reporting and magnitude of deterioration during training. The results imply that hearing data obtained on reporting for training should be taken into account in deciding the assignability of conscripts to noisy training courses and posts.

The natural course of Meniere's disease.

A retrospective study of 161 Meniere patients followed up for 9 years or more is presented. The development with respect to hearing, caloric response, vertigo and ability to work was analysed. The main functional loss was found to take place early in the course of the disease. There was an increase in bilaterality with time.

Cardiovascular risk factors and hearing loss. A study of 1,000 fifty-year-old men.

The hypothesis that cardiovascular risk factors might be of importance in the development of sensori-neural hearing loss was tested in a material of 1000 fifty-year-old men. No significant correlations were found. The present study confirmed the well-known observation that the left ear usually is poorer than the right. Hearing loss in the right ear was found to be related to the smoking habits in the groups with no history of noise exposure. The explanation for this is discussed. Hearing loss was more common in social class 3 than in the other social classes. This difference was principally referable to noise exposure but also to conductive hearing loss. A prospective study of this material will further analyze the question concerning a possible relationship between cardiovascular risk factors and hearing loss.