Measurement of brain perfusion by volume-localized NMR spectroscopy using inversion of arterial water spins: accounting for transit time and cross-relaxation.

The theoretical model for perfusion measurement by NMR using arterial labeling of endogenous water is extended to include the effects of transit time and cross-relaxation of tissue water with macromolecules. Water magnetization in rat brain is monitored using the STEAM method to simultaneously determine the transit time, magnetization transfer rate constant, and perfusion. The results show that the transit time in rat brain is quite short, and thus its effect on perfusion measurement is small. It is also demonstrated both theoretically and experimentally that the steady-state effects of cross-relaxation with macromolecules on perfusion measurement are accounted for by a proper control experiment.     

High dose carboplatin/VP-16 plus ifosfamide with autologous bone marrow support in the treatment of refractory germ cell tumors.

We report seven patients with germ cell tumors which either recurred following a minimum of two regimens of platinum-based chemotherapy or were refractory to cisplatin. The patients were treated with one or two courses of high dose carboplatin (CBDCA) and etoposide (VP-16) plus ifosfamide (IFX) with mesna uroprotection and autologous bone marrow support. The doses given were CBDCA 500 mg/m2 every other day x 3 and VP-16 400 mg/m2 every other day x 3. IFX was given in a dose of 2 g/m2 daily x 5 days with mesna. The original intent of the protocol was to explore escalating doses of IFX, but excessive renal toxicity at the first dose level prevented escalation. Of the seven patients treated, four developed a marked decline in their renal function and three of the four required hemodialysis or hemofiltration. Six of seven patients treated had a decline in their serum markers indicating a response to therapy, but all have relapsed. Our conclusion is that while the combination of CBDCA/VP-16/IFX with ABMT is active in this group of patients, it is associated with excessive renal toxicity which is probably due to underlying renal dysfunction secondary to extensive prior cisplatin-based chemotherapy.     

Prevention of endocarditis: communication between doctors and dentists.

Successful implementation of guidelines to prevent infective endocarditis (IE) depends upon the dental practitioner being aware of which of his patients are at risk. This was studied by sending a questionnaire to at risk patients and their dentists in the Grampian area. Of 145 respondents (53% response rate) with predisposing cardiac disorders, only 63 reported having seen their dentist in the past 2 years, although for dentate patients 47/61 had seen a dentist in the past 2 years. The dentists of 59 of these cases were then surveyed and replies received in 53 cases. Nineteen had no record of the patient having a cardiac disorder. In only 17 of the remaining cases was information on the cardiac disorder well enough recorded to warrant prophylaxis for at risk procedures. The dentist was usually told of the disorder only by the patient. Sixty-three per cent of dentists felt that communication between them and the patient's doctor was unsatisfactory. It is necessary to improve doctor/patient/dentist communication so that current recommendations on prophylaxis can be implemented to the full. This should be done through the patient's GP or consultant, who should communicate directly with the dentist. Details could also be inserted on warfarin cards and 'cardiac alert cards' expanded.     

Combined high grade sarcoma and serous ovarian neoplasm.

A case of an ovarian serous epithelial neoplasm of borderline type admixed with sarcomatous elements is reported. This combination seems to be extremely rare with only four cases previously reported. It may represent a type of collision tumour or the development of a sarcoma in a growth with borderline differentiation.     

Relation of pressor responsiveness to angiotensin II and insulin resistance in hypertension.

To test the hypothesis that the hypertension associated with insulin resistance is secondary to an altered responsiveness of the vasculature to pressor agents, we evaluated the relationship between insulin resistance and pressor responses to angiotensin II (AII) in 21 hypertensive (HT) and 8 normotensive (NT) subjects on both a high (200 meq) and a low (10 meq) sodium diet. When sodium balance was achieved, each supine fasting subject underwent an AII infusion at a rate of 3 ng/kg per min for 60 min, with blood pressure monitored every 2 min. On the next day under similar conditions, a euglycemic hyperinsulinemic clamp was performed, with plasma glucose clamped at 90 mg/dl for 120 min. There was no significant relationship between the glucose disposal rate (M) or the insulin sensitivity index (M divided by the mean insulin level [M/I]) and blood pressure response to AII in the NTs, but a highly significant (P < 0.019) negative correlation (r = -0.55) in the HTs. Furthermore, in eight lean HTs whose body mass index was identical to that observed in the NTs, the relationship was even more striking (P < 0.008; r = -0.85). The results on high and low salt diets were similar; however, the M and M/I were significantly increased (P < 0.05) in the NTs but not HTs with sodium restriction. In conclusion, HTs but not NTs display a striking correlation between pressor response to AII and insulin resistance. This relationship is independent of the level of sodium intake. Furthermore, sodium intake modifies insulin sensitivity in NTs but not HTs. These results strongly suggest that a primary change in pressor response to vasoactive agents in insulin-resistant subjects can contribute to their elevated blood pressure.     

Supportive employment for individuals with chronic schizophrenia: the case for a National Health Service community-based sheltered workshop

A pilot project was established from 1992 to 1994 to provide people with chronic schizophrenia living in Dundee, Scotland, with a National Health Service sheltered workshop that would be fully integrated into the local business community. Of the 43 clients who attended the sheltered workshop, 38 agreed to take part in the project. Typical attenders were single, middle-aged men with schizophrenia. Twenty-five per cent had spent more than two years in hospital; 75% had been unemployed for more than five years. The clients' use of National Health Service day facilities more than halved while attending the workshop. Their hospital readmission rates were low (16%) compared with the local readmission rates for people with schizophrenia in Dundee (86%). A training approach based on the general principles of social skills training contributed to positive vocational outcomes for one-third of the workshop clients. The findings suggest that the onus of responsibility for providing work for many individuals with schizophrenia remains with the National Health Service, and in particular, occupational therapy. Occupational therapy staff must assess their clients effectively and provide quality training leading to opportunities for paid employment. These results have implications for the training of occupational therapy staff and also for the staffing structure in sheltered workshops. Copyright © 1997 Whurr Publishers Ltd.     

Allografts of tumor nuclear transplantation embryos: differentiation competence.

The developmental potential of nuclei can be studied by nuclear transplantation. Although amphibian blastula nuclei and other early embryonic nuclei are totipotent, to our knowledge no nucleus from an adult cell has ever been shown to be totipotent by this procedure. Transfer of Lucké renal carcinoma nuclei into enucleated eggs results in prefeeding swimming tadpoles. Inasmuch as these tadpoles die, rescue of this pluripotential tissue was attempted by grafting fragments of triploid tumor nuclear transplant tadpoles to the tails of normal diploid Rana pipiens hosts. Grafts of tumor nuclear transplant tadpole tissue were histologically indistinguishable from grafts of normally fertilized embryos and developed normal-appearing structures such as complete eyes, well-differentiated neural tissues, kidney tubules, and gut epithelium. Moreover, histological differentiation in tumor nuclear transplant grafts was comparable to that observed in 50-day-old normal larvae. Grafting enhanced the survival of tumor nuclear transplant tissue from no more than 14 days as part of the donor tadpole to 40 days at which time the grafts were harvested as healthy tissue. Thus, both differentiation and survival of tumor nuclear transplant tissue were augmented with the grafting procedure. Cytophotometric analysis of ploidy was used to confirm the tumor origin of the donor tissue.