Breaking down barriers to treat a patient with a germinoma: a case study.

Germinomas are the most common type of germ cell tumor occurring commonly before the second decade of life. Because of the radiosensitivity of germinomas, traditional treatment following diagnosis has been conventional radiotherapy. The desire to defer radiotherapy to avoid the delayed neurocognitive effects has led researchers to investigate the use of up front chemotherapy. A major limitation in using chemotherapy for brain tumors has been the inability to deliver drugs across the blood brain barrier. The blood brain barrier consortium has developed chemotherapy protocols for patients with malignant brain tumors through the use of reversible osmotic opening of the blood brain barrier. While the patient is under general anesthesia, osmotic opening or disruption is achieved by a 30-second intracarotid infusion of mannitol. The mannitol infusion is followed by both intraarterial and intravenous chemotherapy. By administering chemotherapy in conjunction with blood brain barrier disruption, drug delivery to the tumor and the brain around tumor is increased.     

Translocation t(6;14) as the Sole Chromosomal Abnormality in Adenoid Cystic Carcinoma of the Base of Tongue

We present an adenoid cystic carcinoma of the base of tongue in a 48-year-old male with a restricted chromosomal alteration by cytogenetic and spectral karyotypic analysis (SKY). SKY and G-banding analyses identified the t(6;14)(q25;q13) as the sole structural aberration in all metaphases analyzed. This finding supports a critical role for this event in the development of this tumor. The implications of chromosome 6q translocation in this case and in previously reported adenoid cystic carcinomas are highlighted and discussed.     

Evaluating clinical educators: an employer's perspective

An Australian school of nursing's attempt to introduce an evaluation process required by management for clinical educators involved in undergraduate preregistration education is discussed Reliance on student feedback and clinical agencies' perceptions of the quality of teaching were seen as inadequate mechanisms for evaluation The evaluation process adopted incorporated observation of the educators together with self-reflection on their performance We conclude that post-briefings were poorly used and generally not reflective Educators relied heavily on their clinical skills and used a limited range of teaching strategies Whilst evaluation of clinical educators was time consuming and therefore costly, it is argued that it is essential to the integrity of the course The evaluation process has provided direction for support and development of clinical educators within the context of the curriculum     

Ganglioside composition in human cataractous nuclei

Gangliosides were isolated from human cataractous nuclei by solvent extraction, dialysis, and thin-layer chromatography and compared to gangliosides present in human whole normal and cataractous lenses. Three predominant gangliosides were tentatively identified as GM1, GM3, and GD1a, and several other resorcinol-positive components were observed in each of the sets of lens tissue. Thin-layer chromatographic patterns were similar, although some minor and possibly significant differences in band intensities were observed when chromatograms of gangliosides from cataractous nuclei and cataractous whole lenses were visually compared with those of whole normal lenses. Total ganglioside extracts were methanolyzed and the fatty acid methyl esters extracted with hexane and resolved by gas chromatography. Nervonic acid (C-24:1) content was increased in cataractous nuclei as compared to normal and cataractous whole lenses.     

Human insulin-receptor gene

The human insulin-receptor (hINSR) gene spans a region of greater than 120,000 base pairs (bp) on the short arm of chromosome 19. It is comprised of 22 exons or coding regions that vary in size from 36 to greater than 2500 bp. To a large degree, the introns appear to divide the hINSR gene into segments that encode structural and/or functional elements of the hINSR protein. The exon-intron organization of the hINSR gene provides a clue to the evolutionary history of this gene and suggests that it is a mosaic constructed from protein-coding regions recruited from other genes. Eight mutations in the hINSR gene that result in expression of structurally abnormal proteins have been described. These mutations are associated with insulin resistance and provide insight into the role of the hINSR gene in the development of diabetes mellitus.     

Age-matching improves the results of renal transplantation with older donors

Whilst HLA matching is routine for renal transplantation, the possible benefits of matching donor and recipient age have not been previously examined. In this study we examined the simultaneous effect of donor to recipient age difference on the graft survival of 141 consecutive first cadaver transplant recipients treated by cyclosporin immunosuppression. Multivariate regression analysis, taking into account other variables of moderately matched recipients (i.e. dialysis time and type, donor/recipient sex, local/imported kidneys, recent sensitivity, total ischaemic time, preoperative transfusions), indicated that age-difference was the single most important variable (P less than 0.05). Individually there was no significant effect of recipient age, whilst older donors (aged greater than 50 years) were associated with significantly worse graft survival than those younger (P less than 0.01). When dealing with donors aged greater than or equal to 50 years the corresponding recipient 1-year graft was improved when the donor was no more than 5 years older than the transplant recipient. Donor age to recipient age difference is a potentially important selection criterion in renal transplantation.     

Inhibition of hepatic glucose production by SDZ 51641

The new oral hypoglycemic agent SDZ 51641 was evaluated in nondiabetic rats and a rat model of human non-insulin-dependent diabetes mellitus. Diabetes was induced with a single injection of 37.5 mg/kg streptozocin, and the rats exhibited hyperglycemia in the fed state with normal insulin levels. Treatment of nondiabetic animals with 100 mg/kg SDZ 51641 given orally significantly decreased serum glucose and ketone levels within 4 h without affecting insulin levels. Nonesterified fatty acids increased more than twofold during the same period. Its effect on ketone and fatty acid levels suggests that SDZ 51641 acts as an inhibitor of fatty acid oxidation. Diabetic rats treated with SDZ 51641 exhibited a significant acute hypoglycemic response, which was more pronounced after 3 days of treatment. The compound also significantly decreased serum cholesterol and triglyceride levels 27 and 53%, respectively. When endogenous hepatic glucose production was assessed in nondiabetic and diabetic animals via continuous infusion of [3-3H]glucose, we found that hepatic glucose production was elevated 43% in diabetic compared with control animals. When diabetic rats were treated with 100 mg/kg SDZ 51641, hepatic glucose production decreased to normal levels within 6 h. Hyperinsulinemic-euglycemic clamp studies indicated that SDZ 51641 had no effect on insulin-stimulated glucose utilization. Measurement of [1-14C]oleate oxidation in isolated hepatocytes demonstrated that SDZ 51641 inhibited long-chain fatty acid oxidation in a concentration-dependent manner. The compound was ineffective at inhibiting long-chain fatty acid oxidation in epitrochlearis or soleus muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

CHARACTERISTICS OF MEMBRANE TRANSPORT PROCESSES OF MACULA DENSA CELLS

1. Macula densa (MD) cells are located within the thick ascending limb (TAL) and have their apical surface in contact with tubular fluid and their basilar region in contact with the glomerulus. These cells sense changes in luminal fluid sodium chloride concentration ([NaCl]) and transmit signals resulting in changes in vascular resistance (tubuloglomerular feedback) and renin release. 2. Current efforts have focused on understanding the cellular transport mechanisms of MD cells. Progress in this area has benefited from the use of the isolated perfused TAL-glomerular preparation, which permits direct access to MD cells. 3. Using microelectrodes to measure basolateral membrane potential (V_BL) of MD cells, it was found that VBL was very sensitive to changes in luminal fluid [NaCl]. As [NaCl] was elevated from 20 to 150mmol/L, V_BL was found to depolarize by over 30 mV. 4. Basolateral membrane potential measurements were also used to identify an apical Na⁺: 2CI^?: K⁺ cotransport pathway in MD cells that is the major pathway for NaCl entry into these cells. 5. Other work identified a basolateral chloride channel that is presumed to be responsible for changes in V_BL during alterations in luminal [NaCl]. This channel, which is the predominant conductance across the basolateral membrane, may be regulated by intracellular Ca²⁺ and cAMP. 6. An apical Na⁺: H⁺ exchanger in MD cells was detected by measuring changes in intracellular pH using the fluorescent probe 2′,7′-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein. 7. Using patch-clamp techniques, a high density of pH- and Ca²⁺-sensitive K⁺ channels was observed at the apical membrane of MD cells. 8. Other studies found that, at the normal physiological conditions prevailing at the end of the TAL (luminal [NaCl] of 20–60 mmol/L), reabsorption mediated by MD cells is very sensitive to changes in luminal [NaCl].