Transport and storage ofHelicobacter pylori from gastric mucosal biopsies and clinical isolates

Various transport and storage conditions for the recovery ofHelicobacter pylori from gastric biopsies were evaluated. Gastric mucosal biopsies from 16Helicobacter pylori-infected patients were stored in cysteine-Albimi medium containing 20 % glycerol in a refrigerator (4°C) for 1 and 2 weeks and in a –20°C laboratory freezer for 4 and 12 weeks. Two clinical isolates were stored in saline, Stuart's transport media, cysteine-Albimi broth with 20 % glycerol, brucella broth with 20 % glycerol and skim milk with 17 % glycerol at room temperature, 4°C, –20°C and –70°C. Storage at 4°C for 1 and 2 weeks resulted inHelicobacter pylori recovery from 81 % and 19 % of biopsies, respectively. Storage at –20°C yieldedHelicobacter pylori recovery in 100 % and 57 % after 4 and 12 weeks, respectively. At room temperature after 6 h, theHelicobacter pylori titer was reduced. The best storage media for frozen isolates were skim milk/glycerol, brucella broth/glycerol and cysteine-Albimi/glycerol (in descending order). Recovery was better at –70°C than –20°C.     

Topically active carbonic anhydrase inhibitors. 1. O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide

A series of O-acyl derivatives of 6-hydroxybenzothiazole-2-sulfonamide (4, L-643,799) was prepared and the potential utility of each series member as a topically active inhibitor of ocular carbonic anhydrase was determined. In vitro studies showed these esters to be substrates for ocular esterases which liberate 4 during corneal translocation. The most interesting series member, 2-sulfamoyl-6-benzothiazolyl 2,2-dimethylpropionate (22, L-645,151), acting as a prodrug form of 4, was found to enhance delivery through the isolated albino rabbit cornea by 40-fold when compared to the parent phenol 4. Studies in rabbits revealed that 22 is a potent topically active ocular hypotensive carbonic anhydrase inhibitor.     

Partial k-space reconstruction in single-shot diffusion-weighted echo-planar imaging.

Partial k-space sampling is frequently used in single-shot diffusion-weighted echo-planar imaging (DW-EPI) to reduce the TE and thereby improve the SNR. However, it increases the sensitivity of the technique to bulk rotational motion, which introduces a phase gradient across the tissue that shifts the echo in k-space. If the echo is displaced into the high spatial frequencies, conventional homodyne reconstruction fails, causing intensity oscillations across the image. Zero-padding, on the other hand, compromises the image resolution and may cause truncation artifacts. We present an adaptive version of the homodyne algorithm that detects the location of the echo in k-space and adjusts the center and width of the homodyne filters accordingly. The adaptive algorithm produces artifact-free images when the echo is shifted into the high positive k-space range, and reduces to the standard homodyne algorithm in the absence of bulk motion.     

Gastric Epithelioid Leiomyosarcoma: A Curable Gastric Neoplasm

This is the first case report of the preoperative diagnosis of a gastric epithelioid leiomyosarcoma by percutaneous needle biopsy. Preoperative diagnosis facilitated curative surgical resection. Patients may present without symptoms or may report symptoms of peptic ulcer disease or gastrointestinal bleeding. Upper gastrointestinal series is the most useful radiological tool for detecting these lesions. Ultrasound and CT play a useful role in documenting the origin of these large masses, as well as their spread. Endoscopy is being used with increasing frequency, but because these are submucosal lesions diagnosis cannot easily be made through the endoscope. Pathologically, these tumors can be subdivided histologically into a benign epithelioid leiomyoma and two varieties of malignant epithelioid leiomyosarcoma. Prognosis correlates with histological features. Complete surgical resection is the treatment of choice. Chemotherapy or radiotherapy have no proven efficacy in treating epithelioid leiomyosarcoma. Unlike most other gastric malignancies, a favorable prognosis follows successful resection.     

Deep penetrating nevus

We report a clinical and histologic study of 70 patients, each with a single melanocytic lesion termed "deep penetrating nevus" (DPN). The lesions are most commonly found on the face, upper trunk, or proximal extremities of patients between the ages of 10 and 30 years. Typically they are darkly pigmented. Histologically they are characterized by loosely organized nests of pleomorphic pigmented cells that penetrate deep into the reticular dermis and often to the subcutaneous fat. Follow-up was obtained from 48 patients. It ranged from 1 to 23 years (mean, 7 years). Despite an initial histologic diagnosis of malignant melanoma in 29% of the cases, there were no local recurrences and no distant metastases. It is important to differentiate DPN from malignant melanoma. The characteristic histologic features of DPN also allow its differentiation from spindle cell and epithelioid cell nevi and blue nevi.     

The pharmacokinetics and toxicity of the anthrapyrazole anti-cancer drug CI-941 in the mouse: a guide for rational dose escalation in patients

Summary CI-941 is a new synthetic DNA-binding agent selected for phase I clinical evaluation. The drug has broad-spectrum antitumour activity against a number of murine tumours and, in contrast to doxorubicin, is unlikely to induce cardiotoxicity by a free-radical-mediated mechanism. In this study the toxicity and pharmacokinetics of CI-941 were studied in the mouse to enable the implementation of a pharmacokinetically guided dose-escalation strategy in patients. Following a single i.v. bolus injection in mice, CI-941 induced dose-dependent leukopenia. The white blood cell counts were suppressed on day 3 by 18%, 50% and 65% of control, at doses of 10, 15 and 20 mg/kg CI-941, respectively. Other toxicities such as weight loss, alopecia, diarrhoea and convulsions were observed at doses >20 mg/kg. Lethality studies in female Balb-c mice resulted in an LD₁₀ value of 20 mg/kg (95% confidence limits; range, 19–21 mg/kg) and an LD₅₀ value of 22 mg/kg (95% confidence limits; range, 21–23 mg/kg). The pharmacokinetics of CI-941 were studied at four dose levels from 1/10 of the LD₁₀ to the LD₁₀ (20 mg/kg). The drug was rapidly cleared from the plasma (250–400 ml/min per kg) at a rate approaching the cardiac output of mice, displaying triphasic plasma pharmacokinetics. The area under the plasma CI-941 concentration vs time curve (AUC) was linear with respect to the dose, up to and including 15 mg/kg (AUC=110 M x min at 15 mg/kg), but became non-linear at 20 mg/kg (AUC=277 M x min). Despite 80%–84% plasma protein binding, CI-941 was rapidly and extensively distributed into tissues, especially the kidney. Following i.v. bolus injections at doses of 1.5 and 15 mg/kg, elimination of the parent compound by urinary excretion accounted for 12%–18% of the delivered dose. A phase-I starting dose (based on that equivalent to 1/10 of the LD₁₀ in the mouse) of 5 mg/m² CI-941 is recommended for single administration schedules. In addition, a pharmacokinetically guided dose-escalation strategy, based on achieving a target AUC of 110 M x min, is proposed.