"Virtual unwrapping" of a mummified hand.

The purpose of this work is to demonstrate the feasibility of medical virtual reality technologies in the investigation of a mummified hand. The Ulster Museum obtained the mummy hand, which originated from Thebes, without any identifying information. The mummified hand was investigated using conventional X-ray and 3D multi-slice Computed Tomography (CT). Imaging revealed a range of fractures of the wrist, metacarpals and phalanges whilst 3D CT demonstrated internal structures using volume rendering. The absence of any features of bone healing at the fracture sites would imply that they occurred just prior to death or in the mummified state possibly during excavation. Conventional X-ray imaging indicated that the hand, although small, was likely to have originated from an adult. Medical imaging and virtual reality display will enable us to produce a rapid prototyped model using fused deposition technology. Therefore, further paleopathological research can be performed on the replica without the need to handle the original specimen.

The distribution of caveolin-3 immunofluorescence in skeletal muscle fibre membrane defined by dual channel confocal laser scanning microscopy, fast Fourier transform and image modelling.

Membrane domains rich in caveolin-3 overlie sarcomeric actin in skeletal muscle. The membrane exhibits a regular array of caveolin-3 immunofluorescence using confocal laser scanning microscopy (CLSM). Fourier analysis of tissue imaged by CLSM accurately defines a repeating intensity with a long-axis spacing of 1.48 microm confirmed by measurement of direct images. Reverse fast Fourier transform (FFT) and image-modelling allow reconstruction of the pattern. Mathematical modelling has allowed replication of several features of the FFT, including the second order maxima that confirm the relatively high information content of the original images. Measurements of membrane-pattern primary long-axis spacings are consistent with our measurements of the I-band sarcomere repeat in similarly prepared specimens labelled with fluorescent phalloidin or imaged using differential interference contrast microscopy. Dual-channel CLSM analysis of the sarcomeric banding pattern of actin and the repeating pattern of muscle fibre membrane caveolin showed that caveolae overlie the I-band. The anti-caveolin immunofluorescence is deficient over the Z-disc and maximal toward each of the I-band extremities. A mechanism of membrane shape change in which membrane-lipid molecules are interposed between more stable anchored rafts associated with caveolae can be envisaged. Thus, increasing girth and reducing length of the sarcolemma in rapid contraction may be explained.

Renal impairment in elderly patients with hypertension and diabetes.

We investigated the prevalence of renal impairment in individuals with known hypertension or diabetes aged 50--75 years in two South London General PRACTICES: We initially interrogated the practice and hospital biochemistry databases for each individual's most recent serum creatinine. Individuals with no result recorded in the previous year were then invited for screening: 189/365 (51.8%) attended. Data were collected on 821 of a total potential population of 997. Taking a serum creatinine of 120 mmol/l as the upper limit of normal, the overall prevalence of renal disease in this population was 8.4%: 6.1% in the hypertensives, 12.6% in the diabetics and 16.9% in those with both. Significant proteinuria (> or =2+) was present in 3.9% of the total population: 2.2% of hypertensives, 8.3% of diabetics and 3.9% of those with both. At screening, 44.5% of individuals had inadequately controlled blood pressure. Renal impairment is common in this population at high risk of renal disease. Screening for renal disease in this population is simple, safe and gives a high yield of positive results.

Causes of end-stage renal failure in black patients starting renal replacement therapy.

In the United States, blacks are more frequently diagnosed than whites with end-stage renal failure (ESRF) from primary hypertension or diabetic nephropathy. We performed a validation retrospective case-note study of all blacks with ESRF who started renal replacement therapy (RRT) at three teaching hospitals in London, England, during 1991 to 1995 to investigate and validate the causes of primary renal disease using standard criteria. We identified 144 black patients with a mean age of 52.0 +/- 16.0 (SD) years; 59% were men and 32% had renal histological data. One hundred forty-four whites who were matched for age, sex, and onset of RRT (42% with renal histological data) underwent a similar validation exercise. Before the validation, the principal working diagnosis in the black patients had been diabetic nephropathy in 35% (89%, type 2; 11%, type 1); primary hypertension, 19%; glomerulonephritis (GN), 18%; and uncertain cause, 15%. After validation analysis, this changed to diabetes, 38% (16% biopsy proven); uncertain, 24%; GN, 20%; and primary hypertension, only 10% (28% biopsy proven). Among the uncertain cases (n = 34), 19 patients had hypertension, but this could not be established as the primary disease; 94% of all blacks had hypertension, accelerated in 21%. Among whites, only 3.5% had primary hypertension, and this proportion was not changed by the validation study. Type 2 diabetes is the most common single cause of ESRF in black patients in London, and although hypertension is more common and more severe in blacks, the proportion of renal failure attributed to primary hypertension is overestimated, and the diagnosis is often made using inadequate criteria.

Renal transplantation following renal failure due to urological disorders.

BACKGROUND: Renal allograft outcome, during an 8 year period (1985-1992), has been assessed in 56 renal transplants performed in 55 patients who had end-stage renal failure as a consequence of urological abnormalities. The abnormalities were: primary vesicoureteric reflux (VUR) or renal dysplasia (26 patients); posterior urethral valves (PUV) (15); neuropathic bladders (6); vesico-ureteric tuberculosis (5); bladder exstrophy (3); and prune belly syndrome (1). Six patients had augmented bladders, and eight transplants were performed in seven patients with urinary diversions. RESULTS: Overall, 1 and 5 year actuarial graft survival was 89 and 66%, with mean creatinine of 154 micromol/l +/- 11 (SE) and 145 +/- 9 respectively. Patients with abnormal bladders or conduits (n = 28) had worse graft function than those with normal bladders (n = 28) although graft survival was not significantly different in the two groups at 1 and 5 years: 93 and 75% with normal bladders vs 86 and 57% with abnormal systems. Symptomatic urinary tract infections were common in the first 3 months after transplantation (63%); fever and systemic symptoms occurred in 39% with normal bladders and 59% with abnormal bladders. Urinary tract infection directly contributed to graft loss in six patients with abnormal bladders, but had no consequences in those with normal bladders. CONCLUSIONS: Abnormal bladders must be assessed urodynamically before transplantation, and after transplantation adequacy of urinary drainage must be re-assessed frequently. Prophylactic antibiotics are now given for the first 6 months and urinary tract infections must be treated promptly. With these measures, good results, similar to those of patients without urological problems, can be obtained.

Late referral of end-stage renal failure.

We studied all new patients accepted for renal replacement therapy (RRT) in one unit from 1/1/96 to 31/12/97 (n = 198), to establish time from nephrology referral to RRT, evidence of renal disease prior to referral and the adequacy of renal management prior to referral. Sixty four (32.3%, late referral group) required RRT within 12 weeks of referral. Fifty-nine (29.8%) had recognizable signs of chronic renal failure > 26 weeks prior to referral. Patients starting RRT soon after referral were hospitalized for significantly longer on starting RRT (RRT within 12 weeks of referral, median hospitalization 25.0 days (n = 64); RRT > 12 weeks after referral, median 9.7 days (n = 126), (p < 0.001)). Observed survival at 1 year was 68.3% overall, with 1-year survival of the late referral and early referral groups being 60.5% and 72.5%, respectively (p = NS). Hypertension was found in 159 patients (80.3%): 46 (28.9%) were started on antihypertensive medication following referral, while a further 28 (17.6%) were started on additional antihypertensives. Of the diabetic population (n = 78), only 26 (33.3%) were on an angiotensin-converting-enzyme inhibitor (ACEI) at referral. Many patients are referred late for dialysis despite early signs of renal failure, and the pre-referral management of many of the patients, as evidenced by the treatment of hypertension and use of ACEI in diabetics, is less than optimal.

Validation of the cause of end-stage renal failure in Afro-Caribbean patients

Afro-caribbean patients are more frequently diagnosed than caucasians as having end-stage renal failure (ESRF) from primary hypertension or diabetic nephropathy. We performed a retrospective study to investigate the diagnostic criteria and to validate the causes of primary renal disease in all new cases of afro-caribbean patients with ESRF who commenced RRT at 3 inner city Hospitals (1991-1995). We collected clinical-pathological data using a standard proforma. Three of us validated the diagnoses. We have identified 142 afro-caribbean patients for inclusion in this study:mean age of 52.3 (15.50, 52.3 percent were male. Renal biopsy was performed in 32 percent of the patients. Before the validation ,the working diagnosis (including that submitted to EDTA) had been diabetic nephropathy 35.2 percent; primary hypertension 18.3 percent; "uncertain" cause 15.5 percent and primary glomerulonephritis 11.3 percent. Following the analysis we ascribed the underlying cause of ESRF to be: diabetic nephropathy 38.7percent (18.2 percent biopsy proven);"uncertain" 21.8 percent; primary glomerulonephritis 10.6 percent (100 percent bx proven); secondary glomerulonephritis 10.6 percent (66.6 percent bx proven); primary hypertension 10.6 percent (40 percent bx proven); pyelonephritis 3.5 percent; polycystic kidneys 2.8 percent. Among the "uncertain" (n=31): twenty four (17 percent) were related to long-standing hypertension but could not be proven as primary disease. Among the diabetic ESRF patients (n=55), only 6 had IDDM while 49 had NIDDM. Twenty percent (28/142) of all patients had accelerated hypertension while 95 percent (134/142) had hypertension at some time during their disease. This study shows that in afro-caribbean patients NIDDM is the main cause of ESRF, whilst the evidence of primary hypertension is over-estimated, the diagnosis is often made on inadequate criteria. Nevertheless primary hypertension plays an important role in progression to ESRF. (AU)

Non-invasive cardiac investigations in patients awaiting renal transplantation.

Patients with chronic renal failure undergoing renal transplantation have a high prevalence of cardiovascular disease. Invasive investigation may identify those at risk of cardiac death during or after renal transplantation, but which patients should undergo cardiac catheterization is currently not clear. In 95 patients awaiting renal transplantation we assessed the ability of echocardiography and exercise electrocardiography to identify patients at risk of cardiac death. Echocardiography identified impaired left ventricular (LV) systolic function in 20%, severe in 8%. Of the patients with severe LV dysfunction, 25% died before transplantation. Of those undergoing exercise electrocardiography, 44% did not achieve 85% of maximum predicted heart rate. No coronary artery disease requiring intervention was identified by exercise testing. These findings indicate that echocardiography, but not exercise electrocardiography, should be part of the assessment for renal transplantation.

Clinical aspects of cyclosporin nephrotoxicity.

Nephrotoxicity is the most important side effect of cyclosporin therapy. Glomerular filtration rate is reduced in almost all patients and improves when cyclosporin is discontinued. Longterm studies in renal transplant recipients indicate that there is no progressive loss of renal function in the majority of patients treated with cyclosporin. Similar results are found in non-transplant recipients treated with low-dose cyclosporin. Approximately 10% of heart and heart-lung transplant patients develop a progressive deterioration in renal function which may not respond to stopping cyclosporin therapy.

The development of infinitives from three to five.

This study investigated the form of infinitival sentences produced by young children and their knowledge of the control properties of this sentence form. Twenty-five children between the ages of 3;7 and 5;4 participated in a story completion task designed to elicit infinitive sentences and in an act-out comprehension task. Although the infinitive form was productive for even the youngest children in this study, development of this form was not complete even for the five-year-olds, nor did any child demonstrate adult knowledge of control. In addition, two competing claims regarding order of acquisition (that of Limber, 1973, and Hyams, 1985) were evaluated.

Evaluation of therapy for cast nephropathy: failure of colchicine to alter urinary Tamm Horsfall glycoprotein excretion in normal subjects.

Tamm Horsfall glycoprotein (THG) is a major constituent of renal tubular casts including the light chain casts of myeloma. Animal studies suggest that the anti-inflammatory agent colchicine reduces urinary THG excretion and prevents light chain cast formation. Six normal male subjects were given therapeutic doses of colchicine (0.5 mg twice daily for 6 days) and excretion of THG, albumin, creatinine and N-acetyl glucosaminidase (NAG) was determined. Colchicine therapy had no effect on the urinary excretion of THG, albumin or NAG or on renal function as assessed by creatinine clearance. This suggests that colchicine will not be a useful therapeutic adjunct to the treatment of light-chain nephropathy.

99mTc-DMSA imaging with tomography in renal transplant recipients with abnormal lower urinary tracts.

This study examined whether renal parenchymal imaging using 99mTc DMSA scintigraphy with tomography is a sensitive measure of renal scarring in renal transplant recipients with an abnormal lower urinary tract and whether such scars correlate with impairment of renal function. Three groups of patients were compared: group 1, patients with an abnormal lower urinary tract and deteriorating renal function (n = 9); group 2, abnormal lower urinary tract and stable renal function (n = 5); and group 3, normal lower urinary tract and deteriorating renal function (n = 8). Eight of the nine patients in group 1 had multiple scars visible on 99mTc DMSA scans and this correlated with histology when a renal biopsy was performed; the only patient without scars had a transplant glomerulopathy. The presence of scars was associated with either raised intravesical pressures or recurrent urinary tract infections (UTIs). Only one patient in each of groups 2 and 3 had visible scars and both these patients had a history of recurrent UTIs. Patients in group 3 with deteriorating renal function due to chronic rejection documented by biopsy did not have cortical scars visible with 99mTc DMSA tomography. 99mTc DMSA scanning with tomography is a useful investigation in the management of renal transplant patients with declining renal function; multiple scars may indicate abnormal lower urinary tract function and are not seen in chronic rejection.

Renal scintigraphy in acute scleroderma: report of three cases.

Scintigraphic findings in acute renal failure secondary to scleroderma are reported. In three patients, we have demonstrated severe reduction of renal perfusion with little or no parenchymal uptake of tracer and absent excretion. These findings are compatible with the known histological process of occlusive vasculopathy, and such scintigraphic findings at presentation may reflect a poor prognosis for renal recovery.

Endothelin-1 in the rabbit: interactions with cyclo-oxygenase and NO-synthase products.

1. Endothelin-1 infusion (5-40 pmol kg-1 min-1) in the normal anaesthetized rabbit, produced a dose-dependent increase in mean arterial blood pressure (MAP) and reduced renal blood flow (RBF) and glomerular filtration rate (GFR), when compared with an equivalent infusion of physiological saline. 2. Endothelin, 20 pmol kg-1 min-1, was also assessed in animals pretreated with either indomethacin (2 mg kg-1), methylene blue (1.6 mg kg-1 h-1) or NG-monomethyl L-arginine (L-NMMA, 10 mg kg-1 h-1). 3. The effect of endothelin on MAP and RBF was enhanced (P = 0.05 and < 0.01 respectively) by the cyclo-oxygenase inhibitor, indomethacin, without any significant change in the effect on GFR. 4. Methylene blue and L-NMMA, inhibitors of endothelium-derived relaxant factor (EDRF), enhanced the effect of endothelin on each of the parameters measured (P < 0.01). 5. Our results are consistent with endothelin having a predominant effect on pre-glomerular vascular resistance to reduce GFR. Endothelin appears to stimulate the release of vasodilator prostanoids and EDRF which oppose its effects. Thus endothelin may have an important role in the complex control of GFR in the rabbit.

Renal transplantation into abnormal lower urinary tract.

Because doubts remain about the safety and efficacy of renal transplantation for patients with primary urological abnormalities, we have studied the outcome of transplantation in a large group of such patients. Between 1977 and 1989, 69 renal transplants were completed in 62 patients with abnormal lower urinary tracts (29 primary vesicoureteric reflux, 13 posterior urethral valves or bladder outflow obstruction, 6 vesicoureteric tuberculosis, 5 neuropathic bladders, and 9 miscellaneous causes). Graft survival in this urological group was similar to that in 150 allograft recipients (157 grafts) with end-stage renal failure of a non-urological cause. No aetiological subgroup had poorer graft survival than the others, although patients with recurrent urinary-tract infections and a history of outflow obstruction tended to have worse graft function. 9 patients (10 transplants) had renal transplantation into a urinary diversion (8 ileal conduits, 1 rectal bladder). These patients had graft survival and renal function comparable with those of the whole urological group. We found no effect of immunosuppressive treatment (cyclosporin or azathioprine), type of kidney donor (living or cadaveric), or donor or recipient age on graft survival time or renal function. Thus, renal transplantation in patients with abnormal lower urinary tracts is safe and effective; patients with ileal conduits do well and have few substantial difficulties. Preoperative assessment of bladder emptying and urodynamics are important in these patients.

When do children avoid backwards coreference?

This study investigated the claim that very young children avoid backwards coreference in their interpretation of sentences containing pronouns. Eighty-one children ranging in age from 3;1 to 8;0 and eight adults acted out four types of pronominal sentences. Cross-sectional data and individual response patterns reveal that children initially prefer internal coreference even when such a response is disallowed for structural reasons. Avoidance of backwards coreference appears to be a late developing phenomenon characteristic of six-year-olds. Adult response patterns, which are manifested by some very young children, emerge as the dominant pattern by age seven.