Progress in psycho-oncology with special reference to developing countries.

PURPOSE OF REVIEW: Psycho-oncology has completed 25 years. There is growing recognition of the psychosocial needs of persons living with cancer and the role of sociocultural factors in addressing the needs. This review addresses the research in developing countries relating to distress associated with living with cancer and psychosocial care. RECENT FINDINGS: There is growing recognition of the emotional needs, understanding of the sociocultural aspects of the emotional responses of persons, caregivers, role of resilience and posttraumatic growth and spirituality in cancer care. Psychosocial aspects of cancer are largely influenced by social, economic, cultural, religious and health systems. A number of innovative approaches to care like use of yoga, financial and material support and involvement of caregivers have been implemented. A positive development is the increasing professional attention to document and develop innovative care programmes. SUMMARY: A significant proportion of the general population are living with cancer. There are significant psychosocial needs largely influenced by social, economic, cultural, religious aspects of the communities. There are a wide range of interventions from self-care to professional care to address the needs. In developing countries, there is need for longitudinal studies of psycho-social experiences, develop interventions that are culturally appropriate, along with enhanced use of information technology along with evaluation of interventions.

Screening of facultative anaerobic bacteria utilizing D-xylose for xylitol production.

Seventeen cultures belonging to three genera of facultative bacteria ( Serratia, Cellulomonas, and Corynebacterium) were screened for the production of xylitol, a sugar alcohol used as a sweetener in the pharmaceutical and food industries. The bacterial strains that utilized D-xylose for growth were investigated for xylitol production. A chromogenic assay of both solid and liquid cultures showed that ten of the 17 bacteria screened could grow on D-xylose and produce detectable quantities of xylitol during 24-96 h of fermentation. Among the screened cultures, Corynebacterium sp. B-4247 produced the highest amount of xylitol. In addition, the ten bacterial cultures that initially produced xylitol were studied for the effect of the environmental factors, such as temperature, concentration of D-xylose and aeration, on xylitol production.

Regulation of the DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase by inositol and growth phase. Inhibition of DGPP phosphatase activity by CDP-diacylglyceron and activation of phosphatidylserine synthase activity by DGPP.

The regulation of the Saccharomyces cerevisiae DPP1-encoded diacylglycerol pyrophosphate (DGPP) phosphatase by inositol supplementation and growth phase was examined. Addition of inositol to the growth medium resulted in a dose-dependent increase in the level of DGPP phosphatase activity in both exponential and stationary phase cells. Activity was greater in stationary phase cells when compared with exponential phase cells, and the inositol- and growth phase-dependent regulations of DGPP phosphatase were additive. Analyses of DGPP phosphatase mRNA and protein levels, and expression of beta-galactosidase activity driven by a P(DPP1)-lacZ reporter gene, indicated that a transcriptional mechanism was responsible for this regulation. Regulation of DGPP phosphatase by inositol and growth phase occurred in a manner that was opposite that of many phospholipid biosynthetic enzymes. Regulation of DGPP phosphatase expression by inositol supplementation, but not growth phase, was altered in opi1Delta, ino2Delta, and ino4Delta phospholipid synthesis regulatory mutants. CDP-diacylglycerol, a phospholipid pathway intermediate used for the synthesis of phosphatidylserine and phosphatidylinositol, inhibited DGPP phosphatase activity by a mixed mechanism that caused an increase in K(m) and a decrease in V(max). DGPP stimulated the activity of pure phosphatidylserine synthase by a mechanism that increased the affinity of the enzyme for its substrate CDP-diacylglycerol. Phospholipid composition analysis of a dpp1Delta mutant showed that DGPP phosphatase played a role in the regulation of phospholipid metabolism by inositol, as well as regulating the cellular levels of phosphatidylinositol.

Arterial injury by cholesterol oxidation products causes endothelial dysfunction and arterial wall cholesterol accumulation.

Cholesterol oxidation products (ChOx) have been reported to cause acute vascular injury in vivo; however, the pharmacokinetics of ChOx after administration and the mechanisms by which they cause chronic vascular injury are not well understood. To further study the pharmacokinetics and atherogenic properties of ChOx, New Zealand White rabbits were injected intravenously (70 mg per injection, 20 injections per animal) with a ChOx mixture having a composition similar to that found in vivo during a 70-day period. Total ChOx concentrations in plasma peaked almost immediately after a single injection, declined rapidly, and returned to preinjection levels in 2 hours. After multiple injections, the ChOx concentrations rose gradually to levels 2- to 3-fold above baseline levels, increasing mostly in the cholesteryl ester fraction of LDL and VLDL. Rabbit serum and the isolated LDL/VLDL fraction containing elevated ChOx concentrations were cytotoxic to V79 fibroblasts and rabbit aortic endothelial cells. At the time of killing, cholesterol levels in the aortas from ChOx-injected rabbits were significantly elevated despite the fact that plasma cholesterol levels remained in the normal range. In addition, aortas from the ChOx-injected rabbits retained more 125I-labeled horseradish peroxidase, measured 20 minutes after intravenous injection. Transmural concentration profiles across the arterial wall also showed increased horseradish peroxidase accumulation in the inner half of the media from the thoracic aorta in ChOx-injected rabbits. In conclusion, ChOx injection resulted in accumulation of circulating ChOx and induced increased vascular permeability and accumulation of lipids and macromolecules. This study reveals that even under normocholesterolemic conditions, ChOx can cause endothelial dysfunction, increased macromolecular permeability, and increased cholesterol accumulation, parameters believed to be involved in the development of early atherosclerotic lesions.

Macromolecular transport in the arterial intima: comparison of chronic and acute injuries.

Hypertension is a known risk factor for the development of atherosclerosis, which is characterized by the abnormal accumulation of low-density lipoprotein and other plasma-borne macromolecules. The goal of this study was to measure accumulation of a plasma-borne macromolecular marker, horseradish peroxidase (HRP; 44 kDa), in the aortic intima and media of chronically hypertensive rats. HRP transport in 2-yr-old spontaneously hypertensive rats (SHR) was compared with that in age-matched Wistar-Kyoto rats (WKY) under conditions in which blood pressures were not significantly different during the 15-min HRP circulation. Intimal accumulation and medial HRP concentration profiles were obtained from methacrylate-embedded sections after reaction with 3,3'-diaminobenzidine and H2O2. Data were analyzed using a mathematical model of macromolecular transport to quantify the permeabilities of endothelium and internal elastic lamina (IEL). Chronic hypertension increased endothelial permeability without a change in IEL permeability. An apparent convective flux of HRP into the intima of SHR raised intimal HRP to a concentration higher than that of HRP in the plasma. Our results suggest that the intimal accumulation of plasma-borne macromolecules from pressure-driven convection is normally minimized by an intact endothelium. Similar changes resulted from acute injury by lipopolysaccharide, suggesting endothelial injury could account for transport changes associated with hypertension. After either chronic or acute endothelial damage, transport of macromolecules into the intima increases, but the IEL continues to retard transport of macromolecules beyond the intima, resulting in increased intimal accumulation.

Exogenous oxidized low-density lipoprotein injures and alters the barrier function of endothelium in rats in vivo.

Oxidation converts low-density lipoprotein (LDL) into a cytotoxin in vitro. Oxidized LDL exists in vivo in atherosclerotic lesions and possibly in plasma. Many cell functions are altered in vitro by oxidized LDL, but few have been examined in vivo. To test whether oxidized LDL could injure endothelial cells and alter endothelial permeability to macromolecules in vivo, we infused oxidized LDL, native LDL, or their solvent intravenously into rats. Subsequently, endothelial cell injury and proliferation were measured, and the transport into the aorta wall of the macromolecule horseradish peroxidase (HRP) was quantified. Transport data were analyzed using mathematical models of macromolecular transport; parameters were estimated by optimally fitting model-predicted HRP concentrations to experimental data. Compared with native LDL or solvent control infusion, oxidized LDL infusion increased (1) the number of injured aortic endothelial cells fivefold to sixfold at 36 hours, (2) proliferation of endothelial cells at 48 hours, (3) intimal and medial accumulations of HRP twofold to threefold at 48 hours, and (4) the permeability coefficient of the endothelium to HRP fourfold to fivefold at 48 hours. Hence, oxidized LDL administered in vivo can injure the endothelium, despite the presence of endogenous antioxidants, compromising the function of the endothelium as a permeability barrier.

Urinary undiversion in adults with myelodysplasia: long-term followup.

A total of 14 women and 6 men 19 to 39 years old (mean age 27 years) with myelodysplasia underwent undiversion 8 to 29 years (mean 16) after ileal conduit diversion. The main reasons for diversion were incontinence in 17 patients and failed ureteral reimplants in 3, and those for undiversion were a desire for an improved quality of life in 16, increasing hydronephrosis in 4 and stomal problems in 3. Preoperative assessment included upper and lower tract imaging, and video urodynamics. Operations on the ureters included reimplantation into an intussuscepted nipple valve in 8 patients, tunneled reimplants into a sigmoid augmentation in 3 and the ureters joined to either the bladder or lower ureter without interposing bowel in 9. All reimplantations were done with nonrefluxing techniques. A total of 18 patients underwent bladder augmentation and 2 women in whom cystectomy was performed for pyocystis underwent substitutions. Simultaneous continence procedures in 18 patients included trigonal tubularization in 2, artificial sphincter implantation in 2, a bladder neck sling in 5 or bladder neck tapering and a sling in 9. The patients were followed for a mean of 69 months (range 21 to 133). Eight patients required reintervention within 1 year for problems, such as anastomotic leak in 1, bladder neck obstruction in 1, incontinence in 1, artificial urinary sphincter revisions in 1 and bladder stones in 1. One patient had a recurrent renal calculus 10 years after undiversion. All patients experienced either persistence of normal upper tract appearance or improvement and/or stabilization of hydronephrosis. Mean bladder capacity was 77 cc preoperatively and 480 cc postoperatively, while mean pressure at capacity decreased from 50 to 14 cm. water with detubularized augmentation. Of the patients 17 are completely dry, 2 wear 1 pad per day and 1 has enuresis. All but 1 patient who voids with straining are on intermittent self-catheterization. All patients, on followup interviews, reported an improved quality of life without a stoma. We conclude that undiversion provides an improved quality of life and an acceptable morbidity rate. The choice of operation depends on the anatomy of the patient. We prefer a nonprosthetic type of incontinence procedure when intermittent self-catheterization is to be done. No long-term morbidity has yet been noted.

Topical minoxidil in the treatment of male erectile dysfunction.

Topically applied 2% minoxidil solution has been reported to increase diameter, rigidity and arterial flow to the penis. As a result it has been suggested as a possible treatment for erectile dysfunction. A total of 21 patients received 2% minoxidil for treatment of erectile dysfunction with instructions to apply 1 cc of the solution slowly over the glans penis 20 minutes before intercourse. Average patient age was 52.5 years (range 29 to 65 years). The etiology of the impotence was neurogenic in 8 patients, vascular in 7, psychogenic in 4 and other causes in 2. Two patients also had clinical evidence of venous incompetence and 4 were diabetics. One patient with psychogenic impotence noticed improvement in the duration of erection but no increase in rigidity or size after minoxidil application. One patient with impotence after excision of a Peyronie's plaque reported a rigid erection adequate for intercourse after using minoxidil. This patient subsequently was able to achieve erections without using minoxidil. The remaining 19 patients had no improvement in erectile rigidity, or the ability to obtain or maintain an erection. One patient did notice some mild burning on the glans penis after applying the minoxidil. No other side effects were noted in any patient. These results indicate that 2% topical minoxidil solution is not effective when applied to the penis in the treatment of erectile dysfunction. It is possible that a higher concentration, a different delivery medium or a different chemical composition may yield better results.

Fatty acid desaturation in an animal cell mutant defective in plasmanylethanolamine desaturase.

We have recently reported the isolation of three plasmalogen-deficient mutants in a murine, macrophage-like cell line, RAW 264.7 (Zoeller et al. (1992) J. Biol. Chem. 267, 8299-8306). One of these mutant strains, RAW.12, is deficient in delta 1'-desaturase (plasmanylethanolamine desaturase, EC 1.14.99.19), the activity responsible for introducing the vinyl-ether double bond found in plasmalogens. We have examined these mutant cells to determine whether any of the desaturase activities involved in the desaturation of fatty acyl-CoAs were affected and found no evidence to suggest this. Stearoyl-CoA desaturase (delta 9-desaturase) activity was normal when measured in microsomes from RAW.12 cells and the conversion of stearate to oleate (which requires the delta 9-desaturase system) by intact RAW.12 cells was unaltered compared to wild-type cells. The conversion of linoleate to arachidonate by intact cells (which requires the delta 5 and delta 6 desaturase activities) was also normal in the mutant cells. Fatty acid analyses showed no decreases in the relative levels of the unsaturated fatty acids that require the delta 9, delta 6 and delta 5 desaturase activities for biosyntheses of 18:1, 18:3, and 20:4 respectively. Analysis of the cytochrome b5/cytochrome b5 reductase electron transport system, which supports delta 1'-desaturase activity, showed only a modest (30%) decrease in activity. These data suggest that the delta 1'-desaturase system contains at least one component (possibly the terminal desaturase) that is not shared by the acyl-CoA desaturases examined and that RAW.12 is deficient in this component.

Mutants in a macrophage-like cell line are defective in plasmalogen biosynthesis, but contain functional peroxisomes.

We have used a fluorescence-activated cytotoxicity protocol, 9-(1'-pyrene)nonanol (P9OH)/UV selection (Morand, O. H., Allen, L.-A. H., Zoeller, R. A., and Raetz, C. R. H. (1990) Biochim. Biophys. Acta 1034, 132-141), to isolate a series of plasmalogen-deficient mutants in a murine, macrophage-like cell line, RAW 264.7. Three of these mutants, RAW.7, RAW.12, and RAW.108, displayed varying degrees of plasmalogen deficiency (48, 17, and 14% of wild-type levels, respectively), and all three mutants were deficient in peroxisomal dihydroxyacetone phosphate (DHAP) acyltransferase activity (5% of wild-type). Unlike previously described Chinese hamster ovary (CHO) cell mutants, the RAW mutants contained intact, functional, peroxisomes and normal levels of alkyl-DHAP synthase activity, a peroxisomal, membrane-bound enzyme. In RAW.7 and RAW.108 cells, the loss of peroxisomal DHAP acyltransferase is the primary lesion. RAW.12 displayed not only a deficiency in the DHAP acyltransferase activity, but also displayed a second lesion in the biosynthetic pathway, a deficiency in delta 1'-desaturase activity (plasmanylethanolamine desaturase, EC 1.14.99.19), the final step in plasmenylethanolamine biosynthesis. The deficiencies expressed in the mutants represent unique lesions in plasmalogen biosynthesis. Since the RAW cell line is a macrophage-like responsive cell line, these mutants can be used to examine the role of plasmalogens in cellular functions such as arachidonic acid metabolism, prostaglandin synthesis, protein secretion, and signal transduction.

Phaeohyphomycosis caused by Cladosporium bantianum in Kerala (India).

A case of phaeohyphomycosis caused by Cladosporium bantianum is reported from India for the first time. It is also the first known case of infection involving the foot caused by this fungus. The cultural characteristics and animal pathogenicity of the isolate are described.