New method for detection of heart allograft rejection: validation of sensitivity and reliability in a rat heterotopic allograft model.

BACKGROUND: Patients with inflammatory heart muscle diseases would benefit from a safe, convenient, rapidly performed diagnostic technique with real-time results not involving tissue removal. We have performed a detailed evaluation of detection of heart allograft rejection by autofluorescence in a heterotopic abdominal rat heart allograft model ex vivo. METHODS AND RESULTS: Recipient rats with allograft (Lewis to Fisher 344; n=71) and isograft (Lewis to Lewis; n=33) hearts, treated with cyclosporine or untreated, were killed at days 2, 4, 7, 14, 21, 28, and 56 after transplant. Nontransplant controls with (n=24) or without (n=24) immunosuppressive therapy were also studied. When the rats were killed, autofluorescence spectra were acquired under blue-light excitation from midtransverse ventricular sections of native and transplanted hearts. Corresponding sections were then evaluated pathologically by a modified International Society for Heart and Lung Transplantation (ISHLT) grading schema. The spectral differences between rejecting and nonrejecting hearts were quantified by linear discriminant functions, producing scores that decreased progressively with increasing severity of tissue rejection. Mean+/-SD discriminant function scores were 2.9+/-1.6, 1.8+/-2.2, -0.1+/-2.8, -1.2+/-2.3, and -2.3+/-3.0 for isografts and allograft ISHLT grades 0, I, II, and III, respectively (Spearman rank-order correlation -0.6; P<0.001, test for trend). Cyclosporine had no detectable effect on the spectra. CONCLUSIONS: The correlation between changes in autofluorescence spectra and ISHLT rejection grade strongly supports the possibility of catheter-based, fluorescence-guided surveillance of rejection.

Resistance to bone resorbing effects of PTH in black women.

Black women have a lower incidence of vertebral and hip fractures than white women, possibly due to differences in skeletal and mineral metabolism. One suggested mechanism is that blacks have decreased skeletal sensitivity to parathyroid hormone (PTH). To test this hypothesis, we infused h(1-34)PTH in healthy premenopausal black (n = 15) and white (n = 18) women over 24 h and measured serum and urine indices of bone turnover and calcium metabolism throughout the infusion. At baseline, the mean 25-hydroxyvitamin D (25(OH)D) concentration was significantly lower in black women (46%). There were also nearly significant trends toward higher PTH and lower urinary calcium and pyridinoline levels in black women. During infusion, there were no racial differences in the mean (1-34)PTH levels achieved or in resultant elevations of serum calcium or 1,25-dihydroxyvitamin D (1,25(OH)2D) levels. Endogenous parathyroid suppression (measured by (1-84)PTH levels) was also similar between blacks and whites. There was an initial decline in urinary calcium/creatinine in both groups with a greater reduction in black women early in the infusion period (p < 0.05 at 8 h). Furthermore, blacks had lower levels of urinary calcium/creatinine throughout the infusion (p < 0.05 group difference). Bone formation markers (carboxy-terminal propeptide of type I procollagen and osteocalcin) decreased within 8 h and continued to decline throughout the infusion with no distinguishable racial differences (p < 0.05 time trend for both). The most dramatic difference between black and white women in response to PTH infusion was represented by the bone resorption markers. Three separate metabolites of bone resorption (cross-linked N-telopeptide of type I collagen, cross-linked C-telopeptide of type I collagen, and free pyridinoline) all showed substantially greater elevations in white (mean peak increments 399, 725, and 43%) compared with black women (mean peak increments 317, 369, and 17%) during the infusion (p < 0.05 group differences for all three variables). These data strongly suggest that blacks have decreased skeletal sensitivity to the acute resorptive effects of increased PTH. This finding indicates that calcium homeostasis may be accomplished in blacks (during times of relative calcium deficiency) by greater conservation of calcium from nonskeletal sources (most likely renal) with relative preservation of skeletal tissue. These differences in calcium economy could account, at least in part, for the increased bone mass and lower incidence of osteoporotic fractures in black women.

Ethanol elimination rates in normal and ethanol dependent animals.

Ethanol elimination rates were determined in rats using an intravenous route of ethanol administration after several experimental manipulations. Twenty-four hr food deprivation resulted in a 30% reduction to 35 mg/100ml blood/hr in elimination rate from a non-deprived rate of 50 mg/100 ml blood/hr. After 2 months of ethanol drinking (5% v/v), 24 hr starvation resulted in only a 10% reduction in elimination rate (45 mg/100 ml blood/hr), and did not increase the non-food-deprived rate (49.2 mg/100 ml blood/hr) over that obtained in the above animals' drinking water rather than 5% ethanol. Animals which chronically overdrank ethanol or water for 3 months on a schedule-induced polydipsia procedure, known to result in ethanol physical dependence, showed a decreased rate of ethanol elimination (37.9 mg/100 ml blood/hr for water drinkers) in the non-food-deprived condition. By providing 750 mg of liver powder daily as a food supplement in the ethanol overdrinking regimen, the ethanol elimination rate remained at a rate comparable to the normal animal (48.4 mg/100 ml blood/hr).

Four years' experience of a senior house officer rotation in general medicine including general practice.

A four-month post in general practice was included as an option available to doctors applying for a year-long medical senior house officer (SHO) rotation since August 1993. This study sought the views of SHOs before and after undertaking the general practice post. SHOs gained an understanding of modern general practice and changed their views about certain aspects of general practice. They reported gaining a range of generic skills, which included communication, consultation, and clinical skills. These perceived benefits suggest that such experience merits wider adoption and further evaluation.

Gonococcal infection in cerebrospinal fluid and the presence of a ventriculoperitoneal shunt.

BACKGROUND: Neisseria gonorrhoeae is one of the most common organisms associated with pelvic disease in a woman of reproductive age. CASE: We present an unusual case of cerebrospinal fluid infection with N. gonorrhoeae in a woman with a ventriculoperitoneal shunt who complained of abdominal pain. Her shunt was removed and after adequate antibiotic therapy, it was re-inserted. CONCLUSION: Sexually active women, especially those with ventriculoperitoneal shunts, should be encouraged to use a barrier method of contraception, and should have a pelvic examination as part of their evaluation when they present with complaints of abdominal pain.

Moving to a health centre--the effect on workload and patients.

A detailed study of the workload of an urban practice was made during a six-month period before and after moving into a health centre to see if the pattern changed after the move. It was found that the services provided enabled a much greater proportion of routine work to be done by the practice nurse so that the doctor could spend more time with the patients seen by him.A survey of the opinion of patients showed that the great majority was pleased with the services offered in the new premises and did not feel that they had lost contact with their own doctor.

The relationship between phytochrome-photoequilibrium and Development in light grown Chenopodium album L.

Chenopodium album seedlings were grown in light environments in which supplementary far-red light was mixed with white fluorescent light during various parts of the photoperiod. Both the logarithmic rate constant of stem extension and the leaf dry weight: stem dry weight ratio were linearly related to estimated phytochrome photoequilibrium (ϕ) in each treatment regime. These data are taken to be indicative of a functional link between phytochrome and development in the green plant. A layer of chlorophyllous tissue only affected the linearity between calculated ϕ and the logarithmic stem extension rate at high chlorophyll concentrations, whilst even low concentrations-equivalent to the levels found in stem tissue-caused a significant shift in measured ϕ. End-of-day supplementary far-red (FR) light induced between 0-35 per cent of the response elicited by all-day supplementary FR, whilst daytime supplementary FR (with a white fluorescent light end-of-day treatment) induced approximately 90 per cent. The ecological significance of this difference is discussed with respect to shade detection.

A systematic relationship between phytochrome-controlled development and species habitat, for plants grown in simulated natural radiation.

A survey of the responsiveness of plant species, typical of open and shade habitats, to simulated natural shade-light quality (i.e. white light plus supplementary far-red) has demonstrated a systematic relationship between habitat and certain developmental responses. Supplementary far-red light has a much greater effect on stem extension rate, petiole length, and leaf dry weight: stem dry weight ratio of the open habitat, shade-intolerant species. Far-red effects on leaf chlorophyll content show no such systematic grading. These results are discussed in relation to habitat adaptation. In most cases, the relationship between developmental response and the estimated phytochrome photoequilibrium, which is established by the radiation treatment, is linear. This is taken as an indication of phytochrome involvement in shade perception.

Patients' attitudes to the provision of medical care from a health centre.

A one in 20 sample of patients aged 18 and over registered at a health centre in Sidmouth were interviewed in their homes. Information about their personal characteristics was related to patients' use of the centre. A majority of patients found the facilities satisfactory and approved of the health-centre concept. Suggestions for improvements were also obtained.

Absence of fluence rate dependency of phytochrome modulation of stem extension in light-grown Sinapis alba L.

In background white light, supplementary far-red (λmax 700 nm) is an order of magnitude less effective than supplementary far-red (λmax 739 nm) in the stimulation of stem extension in Sinapis alba. The relationship between phytochrome photoequilibrium and extension rate increase for the two supplementary far-red treatments is, however, very similar. This evidence indicates that phytochrome cycling is not involved in the phytochrome control of stem extension in light-grown Sinapis alba and that the response to supplementary far-red light is not fluence rate (irradiance) dependent.

Problems with handling the BE10 series hearing aids among elderly people.

Seven items of activity related to patients' ability to handle behind-the-ear hearing aids (BE11/12) were investigated to establish the effects of age, sex and functional disability. One hundred and thirty-six patients were examined; all were first-time users of hearing aids. Over two-fifths of the sample had problems with manipulating the volume control and over a third had difficulty with inserting the earmould and changing the battery. For both men and women, the difficulties with the volume control and earmould were significantly associated with functional disability. Difficulties with these tasks were also significantly related to age and sex. Patients aged 75 years of age or more had greater difficulties than those who were younger and women had more difficulty than men.

Rapid photomodulation of stem extension in light-grownSinapis alba L. : Studies on kinetics, site of perception and photoreceptor.

Treatment of the whole of aSinapis alba plant with supplementary far-red light (FR), in back-ground white light (WL), induces a rapid increase in stem extension rate. This rapid increase is regulated by the light environment of the stem itself. Supplementary FR to the stem increases extension rate after a lag period of 10-15 min. A lag period of 3-4 h follows FR irradiation of the leaf, before an increase in extension rate is detectable. When the stem is given supplementary FR, the change in extension rate which is induced increases with increasing FR fluence rate, and with decreasing phytochrome photoequilibrium. There is no difference between the effects of supplementary FR λmax 719 nm and supplementary FR λmax 739 nm for these relationships. The increase in extension rate induced by supplementary FR is reversed by an increase in the fluence rate of red light (R). These data indicate that the response is controlled by phytochrome photoequilibrium.

Self-assessment of hearing impairment: test of the expanded hearing ability scale questionnaire on hearing impaired adults in England.

The National Center for Health Statistics developed a questionnaire for self-assessment of hearing impairment which has been widely tested in the United States. The performance of this questionnaire was tested on a sample of 131 people in England, known to have hearing impairment and gave results very similar to those obtained in the United States. These results are compared with a randomly selected sample from the general population. Characteristics of the hearing ability scale derived from the questionnaire are discussed and some suggestions made for a modified version of the questionnaire. The relationship between the average pure tone threshold and the score derived from the hearing ability scale questionnaire is described and takes the form of a bounded relationship with scale score indicating the minimum threshold level.

Chest symptoms in farming communities with special reference to farmer's lung.

Surveys were carried out on random samples of the farming population in Devon and Wales in order to estimate the prevalence of respiratory symptoms and of positive precipitin reactions to thermophilic fungi. Bronchitis, as defined, was common among the Welsh hill farmers, and the proportion of positive serological tests was higher in both the areas surveyed in Wales as compared with Devon. All three surveys confirmed a previous finding that the proportion of positive precipitin tests was higher among non-smokers than smokers. Although the numbers were small there was some indication that measurement of peak expiratory flow showed different relationships with age in non-smokers according to the presence or absence of positive precipitin tests. The difficulty of determining prevalence rates for farmer's lung is discussed, but the results suggest a rate not dissimilar to those found in two areas of Scotland which were more than 20 times higher than any figure previously reported in Britain.

pH of organ-culture-stored corneas.

Changes in intracorneal and storage-medium pH values of organ-culture-stored cat corneas were monitored over a 4-week period. The intracorneal pH was determined using the phosphorus-31 magnetic resonance spectroscopy (31P MRS) chemical shift of inorganic orthophosphate in conjunction with a standard pH titration curve. We incubated 32 adult cat corneas using two similar standard organ-culture methods, one with chondroitin sulfate (method 1) and the other without (method 2). Time-course data at 0, 1, 3 and 4 weeks of storage were used to calculate the rate of pH change. The intracorneal pH was not changed significantly for either organ-culture method; however, the storage-medium pH rate of change declined significantly for both methods (method 1, 0.15 pH units/week; method 2, 0.12 pH units/week). The difference between intracorneal and storage-medium pH values over time increased at a rate of 0.12 and 0.11 pH units/week for method 1 and method 2, respectively. The declining storage-medium pH in conjunction with the maintenance of intracorneal pH contributes to an increased metabolic demand on the cornea.