Muscular-skeletal cryptococcosis in a patient with idiopathic CD4+ lymphopenia.

A healthy 27-year-old woman presented, four months after childbirth, ingravescent pain and claudication of the left lower limb. Magnetic Resonance Imaging of the lumbosacral and iliac regions showed widespread muscular-skeletal lesions. The patient underwent surgery; Cryptococcus neoformans was isolated from surgical samples. Liposomal amphotericin B, fluconazole and itraconazole were administered. Laboratory findings showed lymphocytopenia, with reduction of CD4+ lymphocytes (23 cells per cubic millimeter) in the absence of HIV infection and any other defined immunodeficiency. This is a rare case of muscular-skeletal cryptococcal infection isolated in a subject affected with idiopathic CD4+ lymphocytopenia.

Paclitaxel as a radiosensitiser: a proposed schedule of administration based on in vitro data and pharmacokinetic calculations.

Paclitaxel is efficacious against many human cancers. Because it blocks cells at the radiosensitive G2-M interface, paclitaxel has been investigated as a radiosensitiser. The results have been equivocal and somewhat contradictory. It is impossible to obtain proper pharmacokinetic calculations, aimed at obtaining maximum cytotoxicity and/or radiosensitisation, without knowing (i) how long the drug must be in contact with the cells, (ii) how long the effect lasts after the drug is removed from the cellular environment, (iii) whether the drug acts as a radiosensitiser even when, like cis-platinum, it is added after the radiation and (iv) what the minimum quantity of drug in the cellular environment is required for both chemotoxicity and radiosensitisation. The present work addresses the above questions. Two radioresistant cell lines of human origin were used, A375 melanoma and S549 lung carcinoma, in a clonogenic assay where only colonies with 50 or more cells were counted. For the irradiation, 6 MV X-rays were used. Any G2-M block was quantified by cell cycle kinetics analysis. From the results, a simulation of pharmacokinetics was conducted to calculate the schedule of administration of paclitaxel most likely to achieve and maintain significant chemotoxocity and radiosensitisation. The minimum concentration of paclitaxel for measurable cytotoxicity was 3 nM for both cell lines, but the drug was more toxic to the A549 cells. The minimum concentration for measurable radiosensitisation was 3 nM for A375 and approximately 0.1 nM for A549, but whereas above 3 nM the radiosensitivity increased in A375, it decreased above 1 nM for A549. A minimum of 18 h incubation with the drug was necessary for measurable effects and the radiosensitising effects were lost soon after its removal. There was no radiosensitisation if paclitaxel was added after the radiation, and, at the minimum effective concentrations, it caused only a minor and transient G2-M block. The pharmacokinetic calculations predict that 15 mg/m2 paclitaxel given as a 1 h infusion 5 days/week for 3 weeks during the radiotherapy should achieve both cytotoxicity and radiosensitisation. The mechanism of radiosensitisation by paclitaxel at the concentrations suggested by our results does not appear to be via a G2-M block and is probably concentration dependent. The results imply that low-dose, daily infusions of paclitaxel for as long as possible during a course of radiotherapy are more likely to result in radiosensitisation and prolonged cytotoxicity than high-dose infusions given once a week.

Variations in tumor levels of cis-platinum through a course of fractionated radiotherapy in patients with non-small cell lung cancer.

AIMS AND BACKGROUND: Radiation has been shown to affect the uptake of micromolecules by the tissues within the radiation fields. We measured tumor drug uptake throughout a course of radiotherapy for stage III non-operable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients were treated with radiotherapy consisting of 15 fractions of 300 cGy given over 3 weeks. They were divided into groups of 2. At 1.5 hr before a given fraction of radiotherapy, one group was given i.v. a bolus of 6 mg/m2 CDDP (cis-diamminedichloroplatinum). Between 1.5 and 2 hr after radiotherapy, the patients underwent bronchoscopy, during which a biopsy was taken from the tumor mass. A similar procedure was carried out on a different group of 2 patients at each of the 15 radiotherapy fractions. The amount of platinum in the biopsy sample was measured by atomic absorption spectroscopy and expressed as ng platinum/mg tissue. In another 13 patients, a biopsy was taken before beginning the radiotherapy, and they served as controls. RESULTS: The quantity of platinum/g of tissue in the patients was 11 +/- 4.4 ng/mg tissue. During the course of fractionated radiotherapy, the quantity of platinum/g of tumor varied considerably between radiotherapy fractions. Maximum uptake was at fractions 8 and 9 (92 ng platinum/mg tissue) with the minima during the first few fractions and at fractions 10, 11 and 12 (an average 20 ng platinum/mg tissue). CONCLUSIONS: The cyclical variations in the uptake of CDDP by the tumor tissue during the protracted course of fractionated radiotherapy are probably due to the well-known effects of radiation on vascular function and capillary permeability. The results may have implications for future clinical protocols involving chemo- and radiotherapy for the treatment of the disease.

Squamous cell carcinoma of the posterior pharyngeal wall: characteristics compared with the lateral wall.

Squamous cell carcinoma of the posterior oro- and hypopharyngeal wall (SCCPPW) is a relatively rare tumour. A retrospective investigation of 63 patients with SCCPPW and 449 patients with carcinoma of the lateral oro- and hypopharyngeal wall, treated between 1964 and 1992, has been carried out. Most SCCPPW were asymptomatic, macroscopically superficial and at early stages. They were usually detected by chance during an examination for a different type of malignancy. Fifty-seven percent of SCCPPW patients had multiple tumours; however this occurrence did not alter the survival rate. The crude five-year survival rate for SCCPPW was 22 percent and was not significantly different from that of patients with lateral wall tumours. Moreover, both local control and recurrences also were not statistically different.

Pulsed-dye laser therapy for cutaneous Kaposi's sarcoma associated with acquired immunodeficiency syndrome.

BACKGROUND: Cutaneous lesions of Kaposi's sarcoma associated with acquired immunodeficiency syndrome (AIDS-KS) are disfiguring. OBJECTIVE: This study assesses the response of AIDS-KS to pulsed-dye laser (PDL) therapy. METHODS: The PDL was used to treat 15 AIDS-KS patients. Treatment was repeated at 4-week intervals. On average, patients received three treatments per treated lesion. RESULTS: At 6 weeks' follow-up, the patients' treated lesions were reduced in size when compared with their matched control lesions (p less than 0.002). A complete or partial clinical response occurred in 44% of treated lesions (17 of 39) compared with 18% of matched control lesions (7 of 39) [corrected]. Patients experienced limited pain, infrequent blistering, and no scarring. However, histopathologic findings of treated lesions throughout therapy correlated poorly with clinical response. At 12 weeks, all treated lesions had recurred. CONCLUSION: PDL therapy for AIDS-KS is not recommended. Although safe, the rapid recurrence of disease at initially responsive sites would require costly, long-term therapy to maintain cosmetic improvement.

The effect of timing of vincristine administration during a course of fractionated radiotherapy in a mouse carcinoma.

It has been previously shown that the uptake of 3H-vincristine by the NT carcinoma tumour in CBA mice can vary by a factor of 3 during a course of fractionated radiotherapy (2 Gy day-1, 5 day week-1, for 5 weeks). Here the effect of therapeutic doses of vincristine given at times of either maximum or minimum uptake has been investigated. The results show that whereas vincristine alone has a dose-related effect on this tumour, when given in combination with fractionated radiation it is only effective if administered during the first few fractions. It does not seem to matter whether it is given at times of maximum or minimum uptake. It is concluded that vincristine either exacerbates the radiation-induced vascular damage so that drug extravasation is reduced or that it causes a shift in the time of appearance of the peaks and troughs of uptake. The possibility that radiation-induced resistance to vincristine may have played a part in the results is also discussed.

Clearance of charged and uncharged dextrans from normal and injured lungs.

To examine how molecular charge affects the transfer of molecules across the alveolar-capillary barrier, we prepared the following dextrans of equivalent molecular size (mol wt 10,000) but varying molecular charge: neutral dextran, cationic DEAE dextran, and anionic dextran sulfate. These were labeled with 99mTc. The lungs of three groups of anesthetized rabbits were insufflated with dextran aerosols, with six rabbits receiving each type, and the half-time pulmonary clearance (t1/2) was measured. Control t1/2's (95% confidence limits) were 95 (74-120), 227 (192-268), and 291 (246-345) min for neutral, cationic, and anionic dextrans, respectively. One week later, when the same animals were restudied 4 h after 3 micrograms/kg iv endotoxin, t1/2's were 102 (75-139), 167 (149-187), and 126 (102-154) min, respectively. After 30 min during this repeat study, animals were ventilated with 20 breaths of cigarette smoke, which acutely increased the clearance rate to 34 (26-46), 25 (20-31), and 13 (7-24) min, respectively. Mean carboxyhemoglobin levels were not significantly different in the three groups: 13.6, 12.7, and 11.1%, respectively. These results demonstrated that neutral dextrans showed the same clearance rate before and after endotoxin, whereas the charged dextrans had a significantly faster clearance after endotoxin. After smoke exposure the anionic dextran left the lung more rapidly than the neutral dextran. Thus molecular charge affects solute transfer across the alveolar-capillary barrier in both normal and injured lungs, and an effect of endotoxin on the lung can be detected with charged dextrans but not with neutral dextran.

The uptake of 3H-vincristine by a mouse carcinoma during a course of fractionated radiotherapy.

The variations in uptake of 3H-vincristine sulphate, given as a bolus i.v. injection, by a transplantable murine tumour during a realistic course of fractionated daily gamma-radiation of 25 x 2.0 Gy have been investigated. Maximum levels of 3H in the tumours are found when the tracer is injected 4h after irradiation and the tumours are dissected out 1 h after injection. During the course of daily irradiation the pattern of uptake varies considerably but reproducibly. There are peaks of uptake after 7, 13 and 22 fractions of 2.0 Gy when the amount of 3H in the tumours is as much as three times that found in non-irradiated tumours. After 17-18 fractions, however, the tumour content of 3H is lower than that of non-irradiated tumours. The wave-like pattern of uptake could be due either to capillary occlusion brought about by radiation induced cellular swelling and oedema followed by re-opening of the capillaries during periods of decreased cellularity, or to some mechanism of recovery from radiation damage during the week-end rest period.

Clinicopathological features of nonsteroidal antiinflammatory drug-induced small intestinal strictures.

The clinicopathological features in 4 patients are described where nonsteroidal antiinflammatory drugs appear to have caused small intestinal strictures. Two patients had rheumatoid arthritis and 2 patients had osteoarthritis; all had received nonsteroidal antiinflammatory drugs for 1.5-30 yr. Three patients had an initial illness characterized by diarrhea, profound weight loss, and hypoalbuminemia. Intestinal radiology at this stage ranged from subtle changes to those of Crohn's disease. Three patients underwent surgery. At operation the bland external appearance contrasted with the striking mucosal appearances of multiple concentric, circumferential, diaphragmatic strictures that caused luminal stenosis to a pinhole. These septa were due to submucosal fibrosis and the histopathological picture appears to represent a new nosological entity.

Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans.

This study examines the effects of nonsteroidal antiinflammatory drugs on the small intestine in humans. Using an 111In-leukocyte technique in patients with rheumatoid arthritis (n = 90) and osteoarthritis (n = 7), it appears that nonsteroidal antiinflammatory drugs cause small intestinal inflammation in two-thirds of patients on long-term treatment and on discontinuation, the inflammation may persist for up to 16 mo. The prevalence and magnitude of the intestinal inflammation was unrelated to the type and dose of nonsteroidal drugs and previous or concomitant second-line drug treatment. There was a significant inverse correlation (r = -0.29, p less than 0.05) between fecal 111In excretion and hemoglobin levels in patients treated with nonsteroidal antiinflammatory drugs. The kinetics of fecal indium 111 excretion in patients treated with nonsteroidal antiinflammatory drugs was almost identical to that of patients with small bowel Crohn's disease. Eighteen patients on nonsteroidal antiinflammatory drugs underwent a radiologic examination of the small bowel and 3 were found to have asymptomatic ileal disease with ulceration and strictures. Nineteen patients on nonsteroidal antiinflammatory drugs, 20 healthy controls, and 13 patients with Crohn's ileitis underwent a dual radioisotopic ileal function test with tauro 23 (75Se) selena-25-homocholic acid and cobalt 58-labeled cyanocobalamine. On day 4, more than half of the patients with rheumatoid arthritis had evidence of bile acid malabsorption, but the ileal dysfunction was much milder than seen in patients with Crohn's ileitis.

Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inflammatory drugs.

Nearly three-quarters of patients on long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) have small-intestinal inflammation, the consequences of which are largely unknown. Two potentially important complications, blood and protein loss from the small intestine, have been studied. 49 patients on NSAIDs underwent study with an indium-111 labelled leucocyte technique which localises and measures intestinal inflammation. 32 patients underwent simultaneous study with technetium-99m labelled red blood cells (RBC), which showed identical sites of localisation to 111In-leucocytes in 19. Intestinal blood loss was measured in 8 patients by use of chromium-51 labelled RBC, and a significant correlation between blood loss and intestinal inflammation was found. Intestinal protein loss was assessed in 9 patients with 51Cr-labelled proteins; patients with NSAID-induced small-intestinal inflammation were found to have a protein-losing enteropathy. These studies show that small intestinal inflammation caused by NSAIDs is associated with blood and protein loss, both of which may contribute to the general ill-health of rheumatic patients.

Radiation absorbed dose from technetium-99m DTPA.

The whole-body retention of intravenously administered [99mTc]DTPA was measured by urine analysis and whole-body counting in eight normal subjects. On average, the elimination of [99mTc]DTPA was faster in these subjects than in 11 patients under study for hypertension whose whole-body retention data were used in MIRD Dose Estimate Report No. 12. The average residence time for [99mTc]DTPA in total body, less bladder contents, was only 65% of the MIRD value. However, despite this difference, the dosimetry is similar in both cases largely owing to the influence of radioactivity in bladder contents. Approximately 2-3% of the administered radioactivity was retained in the body for a time that was long relative to the physical half-life of 99mTc, and probably reflects a small amount of protein binding of the DTPA preparation.

Carcinoma verrucoso de penis.Apresentacao de um caso. / Verrucous carcinoma of the penis. Report of a case

Os autores apresentam um caso de carcinoma verrucoso de penis detalhando os aspectos de diagnostico, tratamento e prognostico

Synthetic porphyrins as tumour-localizing agents.

A series of radioactively labelled porphyrin analogues have been synthesized and compared for tissue distribution and tumour uptake against 67Ga in the same tumour-mouse system. The compounds were: 14C-ms-tetraphenylporphine sulphonate (14C-TPPS), 35S-ms-tetraphenylporphine sulphonate (TPP35S), 35S-ms-tetra[beta-naphthyl]porphine sulphonate (TNP35S), 14C-ms-thienylphenylporphine sulphonate (14C-TTPPS) and 35S-ms-tetra[p-tolyl]porphine sulphonate (TTP35S). 14C-TPPS and TNP35S appear to concentrate in tumours to a greater extent than 67Ga (ratios of tumour uptake for TPPS/67Ga and TNPS/67Ga were about two and three respectively) but their uptake in kidneys and lungs was also greater than that of gallium. The type of side group attached to the central tetrapyrrole ring appears to have a substantial effect on the tumour-localizing properties of these compounds. Comparison of 14C and 35S-labeled TPPS indicates that the sulphonate groups are split off in vivo and that compounds with highly aromatic side groups (e.g. TNPS) and a radioactive label in a non-labile part of the molecule (e.g. in the tetrapyrrole ring system itself) would show even better tumour localization. The feasibility of synthesizing porphyrins with a variety of reactive side groups suggests that it may be possible to introduce suitable gamma-emitters while retaining the tumour-localizing properties.