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Biomedical subjects

D Kessel

Publications and source records attributed to D Kessel.

At least 109 records · Page 6Linked to original sources
PubMed1994

Biodistribution and PDT efficacy of a ketochlorin photosensitizer as a function of the delivery vehicle.

C8KC is a new ketochlorin photosensitizer that must be formulated with an emulsifier because of its poor water solubility. In this report, we compare properties of Cremophor EL (CRM) and Tween 80 as delivery vehicles for C8KC. Unlike Tween 80, CRM altered the physical properties of both human and mouse plasma lipoproteins, resulting in decreased electrophoretic mobility of the individual lipoproteins along with the formation of a lipoprotein degradation product: a phospholipid fraction of low buoyant density. In human plasma, where there was sufficient low-density lipoprotein (LDL) for a distinction to be made, CRM caused a shift in binding of a ketochlorin from albumin to LDL and the degraded lipoprotein fraction. In mice bearing the RIF tumor, the use of CRM for drug formulation was associated with longer plasma and tissue persistence of C8KC, and enhanced photodynamic therapy (PDT) efficacy. These results indicate the importance of both sensitizer and vehicle as determinants of PDT efficacy.

Animals↗
PubMed1994

Community acquired lobar pneumonia in patients with HIV infection and AIDS.

BACKGROUND: Community acquired bacterial pneumonia is increasingly encountered in HIV infected individuals and some patients have a radiographic lobar pneumonia. METHODS: A retrospective review of clinical features, microbiological diagnosis, and outcome of community acquired lobar pneumonia was carried out in HIV positive patients admitted to a specialist unit from 1987 to 1993. RESULTS: Forty nine episodes occurred in 45 patients, all of whom were men. CD4 counts ranged widely. A bacteriological diagnosis was made in 25 episodes (51%), seven patients had more than one infective cause. The commonest pathogens were Streptococcus pneumoniae (11 episodes), Staphylococcus aureus (six), Pneumocystis carinii (three), Haemophilus influenzae (three), and Pseudomonas aeruginosa (two). Four patients died. Other complications included intrapulmonary cavitation or abscess formation (11 episodes), empyema (three), and pleural effusion (10 episodes). CONCLUSIONS: Many different infections cause community acquired lobar pneumonia in HIV positive men. Some patients have co-infections and there is a high complication rate.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Recurrent upper tract urothelial tumours: the use of loopography following cystectomy for bladder cancer.

Recurrent upper tract tumours following cystectomy for transitional cell carcinoma are not uncommon. Conventional follow-up to identify preclinical recurrent disease often involves a combination of excretory urography and urine cytology. This study investigates the possible advantages of loopography in the follow-up of these patients. 41 patients who had undergone cystectomy and ileal loop diversion for transitional cell carcinoma of the bladder were studied. At the time of evaluation with a loopogram, eight out of 41 (19.5%) were symptomatic. Loopography was well tolerated by all of the patients with no reported side-effects or complications from the procedure. Six out of 41 (14.6%) of the loopograms demonstrated an abnormality with recurrent transitional cell carcinoma identified in two patients. In only one case was excretory urography necessary where a ureteric stricture prevented retrograde imaging of the upper tract. Loopography is a safe and well-tolerated investigation for the follow-up of these patients. Excretory urography should be reserved for cases where upper tract imaging is impaired because of obstruction within the loop or ureters.

Aged↗
PubMed1994

Echocardiographic profile of the normally functioning Omnicarbon valve.

Transthoracic echocardiography was performed in 141 patients with 90 Omnicarbon valves in the aortic and 66 in the mitral position. Additionally, 53 of them were investigated by transesophageal echocardiography comparing monoplane and multiplane facilities. The opening direction of the disc and the location of the pivot axis could be correctly determined by transthoracic, monoplane, and multiplane transesophageal echocardiography, respectively, in 100%, 80%, and 100% of the mitral and in 53%, 21%, and 82% of the aortic prostheses. Small regurgitation jets were detected in 90% of the aortic valves (1.6 +/- 0.4 cm2) by transthoracic and in all mitral prostheses (2.3 +/- 0.8 cm2) by transesophageal echocardiography. Based on morphological identification of the pivot points structures, origins of leakage jets were clearly identified as "design-related" in 12% (transthoracic echocardiography of aortic valves) to 100% (multiplane transesophageal echocardiography of mitral valves). In the aortic position, values obtained for transprosthetic forward flow velocity measurements exhibited wide scatter which did not allow a firm separation between valve sizes. No better differentiation was possible by using the calculated Doppler gradients or the velocity time integrals, either. Mean gradients and velocity time integrals showed even smaller differences between groups in the mitral valve patients. It is concluded that the Omnicarbon valve has a suitable design for morphological echocardiographic examination, and multiplane transesophageal technique expands the diagnostic capability. Forward flow measurements do not appear to be suited for detecting a beginning obstruction of this mechanical prosthesis.

Adult↗
PubMed1993

Biodistribution of photosensitizing agents.

1. The features of neoplasia which predict for drug responsiveness are rapid growth and/or inefficient repair of damage, especially to DNA. 2. PDT has the advantage of yielding responses regardless of the growth fraction of a tumor, and repair appears to play only a minor role. 3. While an entirely different spectrum of tumors can be targeted with PDT, the perhaps unavoidable accompaniment is that a new set of rules for efficacy will need to be established. 4. The selectivity of PDT is based on the need for irradiation which can be directed, along with the short tissue half-life of the cytotoxic product, singlet oxygen. Sensitizers which target specific cellular organelles could promote PDT efficacy, if in vitro data (Woodburn et al., 1992b Photochem. Photobiol. 55, 697-704) can be translated into clinical practice. 5. It remains to be established whether total drug distribution to neoplastic tissues or concentration in specific sub-cellular sites is the more important factor. 6. Questions relating to the role of biodistribution as a factor in efficacy of PDT sensitizers of photosensitizers remain to be explored. Just as the political cartographers are grappling with changes in territorial boundaries of known lands, we continue to clarify the rules relating to PDT boundaries. In this regard, it is clearly important for determinants of pharmacokinetics and biodistribution to be evaluated and understood. 7. Once clinical reports on the "second generation" agents are published, we may get a better picture, although it is not unusual for clinical reports to raise more questions than they answer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Photosensitization with methylene-linked porphyrin dimers.

The photodynamic therapy (PDT) efficacy of a series of porphyrin dimers linked by methylene groups was evaluated using the radiation-induced fibrosarcoma (RIF) tumor model. Longer chain length led to greater efficacy and increased dimer hydrophobicity. This result was correlated with the persistence of porphyrins in plasma, but not with tissue levels.

Animals↗
PubMed1993

The role of lipoproteins in the distribution of tin etiopurpurin (SnET2) in the tumor-bearing rat.

The role of plasma lipoproteins in the distribution of the photosensitizing agent tin etiopurpurin (SnET2) was examined in male rats bearing the N-[4-(5-nitro-2-furyl)-2- thiazolyl1bdformamide-induced tumor. Treatment with 17 alpha-ethinyl estradiol resulted in the depletion of total plasma cholesterol by > 70% and a corresponding decrease in plasma lipoproteins. To both control and estradiol-treated animals, a therapeutic dose (1.5 mg/kg) of SnET2 was administered and biodistribution measured 24 h later. Estradiol treatment was not associated with differences in the distribution of SnET2 to liver, skin or tumor, or in the pattern of affinity of SnET2 to plasma albumin and lipoprotein. These results indicate that a substantial decrease in circulating lipoprotein levels does not alter patterns of SnET2 biodistribution.

Animals↗
PubMed1993

Photosensitization with etiobenzochlorins and octaethylbenzochlorins.

The photophysical and photobiological properties of a series of etiobenzochlorins were evaluated in cell culture using murine leukemia L1210 cells. In the series of agents tested, the chlorin-(mono)sulfonate was the most efficacious, the tin chlorin somewhat less so and the tin chlorin-sulfonate much less active. The parent chlorin was essentially inactive at the limit of solubility. Photodamage was assessed by measuring alterations in surface hydrophobicity (via a two-phase partitioning procedure), amino acid transport and membrane potential. Additional information was provided from fluorescence microscopy, which was used to identify sites of sensitizer binding and effects of photodamage on the binding patterns of fluorescent probes specific for mitochondria, lysosomes and plasma membranes. Effects of photodamage on fluorescence lifetime distribution of the membrane probe trimethylaminodiphenyl hexatriene were examined. The data obtained were consistent with localization of the parnet etiobenzochlorin and tin derivative at lysosomal loci, the chlorin-sulfonate at plasma and mitochondrial membranes and tin-sulfonate at the cell surface.

Animals↗
PubMed1993

Sites of photodamage by the iminium salt of a copper octaethylbenzochlorin.

Because the benzochlorin derivative copper (II) alpha-meso-N,N'-dimethyloctaethylbenzochlorin iminium chloride (CDS1) is not fluorescent, sites of drug localization in L1210 cells were detected by indirect methods involving using a series of fluorescent probes. The CDS1-mediated cytotoxicity was associated with mitochondrial damage, a decreased membrane potential and an increase in the heterogeneity of membrane sites of binding of a polar analog of diphenylhexatriene. Although CDS1 is a cationic compound, its accumulation was not impaired in a cell line exhibiting the multidrug resistance phenotype.

Animals↗
PubMed1993

Photosensitization with bacteriochlorins.

Biophysical and photobiological properties of a group of bacteriochlorins were compared with efficacy of these products for photodynamic therapy of murine tumors. Predictive factors for selective photosensitization in vivo include affinity binding to lipoproteins greater than albumin, extinction coefficient at the wavelength of irradiation and tumor/skin distribution. Efficacy was correlated with circulating plasma levels of the different sensitizers but not with the photodynamic therapy response in cell culture.

Animals↗
PubMed1992

Metabolic properties and photosensitizing responsiveness of mono-L-aspartyl chlorin e6 in a mouse tumor model.

A mouse mammary tumor model was used to evaluate metabolic properties of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) and to determine the optimal time interval between drug administration and light treatment for effective photodynamic therapy (PDT). Photosensitizer metabolism was evaluated by comparing tissue distribution patterns of NPe6 having 14C atoms positioned on either the tetrapyrrole ring or on the aspartyl residue. High performance liquid chromatographic analysis of photosensitizer extracted from tumor tissue was also obtained as a function of time after drug administration. NPe6 distribution in tissue samples and pharmacological calculations of area under the curve were similar for both forms of [14]NPe6. Likewise, metabolic contaminants of NPe6 were not detected by high performance liquid chromatographic analysis following extraction of the photosensitizer from tumor tissue. Maximal in vivo PDT effectiveness was achieved when light treatments were started within 2 h of drug injection. PDT effectiveness was decreased by 50% when light treatments were initiated 6 h after drug injection and was abolished with a 12-h interval between NPe6 injection and light exposure. Responsiveness to NPe6-mediated PDT was correlated with photosensitizer levels in the plasma but not in tumor tissue. These results show that NPe6 was not metabolized following in vivo administration and that the responsiveness of NPe6 mediated PDT was associated with vascular clearance of the photosensitizer.

Animals↗
PubMed1992

Configuration of triporphyrin ethers probed by fluorescence measurements.

The fluorescence spectra and lifetimes of triporphyrin ethers derived from hematoporphyrin, mesoporphyrin and protoporphyrin were examined, together with relative hydrophobicities estimated from reverse-phase high performance liquid chromatography (HPLC) elution times. The following data suggest a molecular arrangement with two of the three rings in a "folded configuration". The trimers display a greater fluorescence yield (phi f) than the corresponding diporphyrin ethers which contain only the two folded rings. The fluorescence lifetime data for the trimers are consistent with signals from both a folded ring pair (7-8 ns) and a free ring (14 ns). Reverse-phase HPLC studies indicate that the trimers are intermediate in hydrophobicity between the monomers and dimers. Preliminary data suggest that, for certain peripheral substitutions, the trimer configuration is superior to the dimer for photodynamic therapy.

Chromatography, High Pressure Liquid↗
PubMed1992

Two unusual cases of nephrocalcinosis in infancy.

Nephrocalcinosis is uncommon in childhood, the main causes are renal tubular acidosis, hyperparathyroidism and medullary sponge kidney. It is also seen where there is hypercalcaemia or hypercalciuria of any aetiology; We report nephrocalcinosis in an 18-month-old infant with metaphyseal chondrodysplasia type Jansen and also in a neonate with McCune Albright syndrome who displayed atypical skeletal appearances and had multiple ovarian cysts.

Female↗