Applying probability-weighted incubation period distributions to traditional wind rose methodology to improve public health investigations of Legionnaires' disease outbreaks.

In the event of a Legionnaires' disease outbreak, rapid location and control of the source of bacteria are crucial for outbreak management and regulation. In this paper, we describe an enhancement of the traditional wind rose for epidemiological use; shifting the focus of measurement from relative frequency of the winds speeds and directions to the relative volume of air carried, whilst also incorporating probability distributions of disease incubation periods to refine identification of the important wind directions during a cases window of exposure, i.e. from which direction contaminated aerosols most likely originated. The probability-weighted wind rose offers a potential improvement over the traditional wind rose by weighting the importance of wind measurements through incorporation of probability of exposure given an individual's time of symptom onset (obtained through knowledge of the incubation period), and by instead focusing on the volume of carrying air which offers better insight into the most probable direction of the source. This then provides a probabilistic distribution of which direction the wind was blowing around the time of infection. We discuss how the probability-weighted wind rose can be implemented during a Legionnaires' disease outbreak, and how outbreak control teams might use it as supportive evidence to identify the most likely direction of the contaminated source from the presumed site of exposure. In addition, this paper discusses how minor adjustments can be made to the method allowing the probability-weighted wind rose to be applied to other non-communicable airborne diseases, providing the disease's probability distribution for the incubation period distribution is well known.

Solitary malignant mesothelioma of the small intestine: radiological appearances.

Malignant peritoneal mesothelioma is virtually unknown to feature as a solitary lesion. A patient presented with abdominal pain, weight loss, and melena and underwent enteroclysis, computed tomography, and superior mesenteric arteriography. Sharp angulation, narrowing, and mucosal destruction in a jejunal segment, caused by an encapsulating infiltrative mesenteric mass, were shown. The diagnosis of a malignant peritoneal mesothelioma, localized to the small intestine, was made at histology.

Discovery of an orally bioavailable NK1 receptor antagonist, (2S,3S)-(2-methoxy-5-tetrazol-1-ylbenzyl)(2-phenylpiperidin-3-yl)amine (GR203040), with potent antiemetic activity.

The antiemetic, pharmacokinetic, and metabolic profile of CP-99,994, a potent NK1 receptor antagonist, has been carefully evaluated. As a result we began a medicinal chemistry program which initially identified a 3-furanyl analogue (6) with improved antiemetic potency and a methyl sulfone (5) with enhanced metabolic stability and oral bioavailability. The improved pharmacokinetic profile of methyl sulfone (5) was associated with its low lipophilicity, and a therefore a number of heterocyclic analogues with reduced log D were synthesized. Out of this program emerged 19 (GR203040), a tetrazolyl-substituted analogue. Tetrazole 19 inhibits radiation-induced emesis in the ferret with high potency when administered both subcutaneously and orally, has a long duration of action, and has high oral bioavailability in the dog. Tetrazole 19 is currently undergoing evaluation as a novel approach for the control of emesis associated with, for example, cancer chemotherapy.

Adult enteric intussusception: additional observations on enteroclysis.

Enteroclysis patterns encountered in four patients with adult intestinal intussusception of different etiology--including a leiomyoma, a Peutz-Jeghers hamartoma, a metastatic colon carcinoma, and adhesions--were analyzed and compared to surgical and pathological findings. Emphasis was given not only to radiological signs indicative of impaired circulation but also to the preoperative evaluation of the stimulating cause. A "stretched spring" pattern, corresponding to increased distance between large and thick concentric rings, was found to conform to a stage of strangulation with exudation, whereas sharply demarcated fine rings in close proximity were suggestive of the absence of vascular impairment. The morphology of the underlying lesion was also shown to conform to the dynamic appearance of the intussusception. Benign submucosal, intraluminal tumors led to a long, rather permanent intussusception, with the tumor being the leading point; whereas intussusception associated with annular malignancies or adhesions was shorter and transient or partial, as fixation was present. The cause of the intussusception was correctly identified preoperatively in each case; the vascular compromise involved was also indicated, and the correlation between radiological appearances and morphology at pathology specimens was excellent.

Mesothelial cyst complicated by torsion: preoperative imaging evaluation.

The diagnosis mesothelial cyst is infrequently made pre-operatively, because of the relative rarity of this lesion as a cause of distinct abdominal complaints and a lack of definitive diagnostic tests. A case of a mesothelial cyst complicated by ileal torsion evaluated preoperatively by various imaging modalities, including plain radiographs, ultrasound, computed tomography and enteroclysis studies is presented. It was shown that appearances on enteroclysis significant aided the differential diagnosis, by preoperatively defining the cause of clinical presentation and the extent and degree of the intestinal involvement.

Benign tumors of the small intestine: preoperative evaluation with a barium infusion technique.

During a seven year period 18 benign small intestinal tumors were histologically documented in patients referred to us for a small bowel study, using a barium infusion technique. These included seven leiomyomas, five adenomatous polyps, two Peutz-Jeghers hamartomas, one myoepithelial hamartoma, one lipoma, one Brunner's gland adenoma and one neurilemmoma. Ten of the patients were women and eight were men, with their ages ranging from 20 to 75 years (mean age 45 years). Presenting symptoms were gastrointestinal bleeding in 12, anemia in 9, abdominal pain in 4, partial intestinal obstruction in 3 and bloody diarrhea in one. The time elapsed from onset of symptoms to radiological diagnosis ranged between one month and seven years (mean time 16 months). Multiple lesions were encountered in four cases and solitary in fourteen. The site of involvement was the duodenum in 3 patients, the jejunum in 8 and the ileum in 7 of them. Main radiological appearances included solitary or multiple intraluminal filling defects, mass effect on neighbouring loops and dilation of intestinal loops proximally to the lesion. The primary tumor, in the form of a mass or other abnormality of the small intestine was identified in all study cases. Correlation with surgical or endoscopic findings showed that radiology depicted all single lesions, whereas multiple lesions were underestimated in one case. The individual morphological changes shown on examination of the resected specimens resembled the appearances on the barium study in all cases. However, enteroclysis missed four out of seven ulcers and a stalk in one of the five pedunculated lesions. A specific tumor-type diagnosis was reached preoperatively in eleven patients, it was suggestive in five and mistaken in two of them. Our experience indicates that enteroclysis is an effective means in evaluating patients with suspected benign small bowel tumors, preoperatively.

New kappa-receptor agonists based upon a 2-[(alkylamino)methyl]piperidine nucleus.

The syntheses of some 1-[(3,4-dichlorophenyl)acetyl]-2- [(alkylamino)methyl]piperidines and their activities as kappa-opioid receptor agonists are described. Selected structural modifications are made to the basic moiety and at the 2-, 3-, 4-, 5-, and 6-positions on the piperidine nucleus to enable structure-activity relationships to be delineated. As a result, some highly potent and selective kappa-receptor agonists have been identified. In particular, this has been achieved by introduction of oxygen-containing functionality into the 4-position of the piperidine nucleus or the 3-position of the pyrrolidinylmethyl side chain. Thus, 1-[(3,4-dichlorophenyl)acetyl]- 2-[[1-(3-oxopyrrolidinyl)]methyl]piperidine (10) possesses high activity in the rabbit vas deferens (LVD, kappa-specific tissue) (IC50 = 0.20 nM) and is a potent antinociceptive agent, as determined by the mouse acetylcholine-induced abdominal constriction test (MAC) (ED50 = 0.06 mg/kg, sc). The spirocyclic analogue 8-[(3,4-dichlorophenyl)acetyl]-7-(1-pyrrolidinylmethyl)-1,4-dio xa-8- azaspirol4.5]decane (39) showed exceptionally potent activity: LVD, IC50 = 0.10 nM; MAC, ED50 = 0.001 mg/kg, sc. Both 10 and 39 displayed high selectivity for kappa-opioid receptors over both mu- and delta-opioid receptor subtypes.

Radiological appearances of small intestinal leiomyomas.

During a 5 year period we have identified leiomyomas of the small intestine in six patients using enteroclysis. Gastrointestinal bleeding were the presenting symptoms in five and partial small bowel obstruction in one. The time interval between the onset of symptoms and radiological diagnosis ranged between 3 months and 5 years. All patients had previously been investigated by a number of endoscopic and barium radiology examinations and one had undergone a nondiagnostic laparotomy. The jejunum was the site of involvement in one patient and the ileum in five. The growth was intraluminal in two cases, extraluminal in three and bidirectional (dumb-bell) in one. Radiological appearances included round or broad-based semilunar intraluminal filling defects with encroachment of the lumen, or intussusception, displacement and/or indentation of the intestinal wall with effacement of the overlying mucosa or an ulcer crater, tenting deformity and mass effect on neighbouring loops. All six patients came to operation. Pre-operative radiological diagnosis was correct in five and suggestive in one. There was excellent correlation between the radiological appearances and morphology of the pathology specimens.

Epithelioid angiosarcoma of the adrenal gland associated with chronic arsenical intoxication?

Epithelioid angiosarcoma is a rare tumor quite recently described. There is no accurate epidemiological study of this tumor. Among the internal organs, the liver is the one most frequently affected with angiosarcoma while there is no reference to the adrenal gland as a primary site. It is well known that the direct exposure to arsenicals (especially of vineyard cultivators) may be an important causative factor in the pathogenesis of the disease. A 59-year-old male vineyard cultivator with an epithelioid angiosarcoma of the right adrenal gland is described. The histologic characteristics as well as the immunohistochemical profile of the tumor are presented and the literature is briefly reviewed.