An audit of 24-hour creatinine clearance measurements at Tygerberg Hospital and comparison with prediction equations.

BACKGROUND: Internationally, clinical guidelines recommend the use of creatinine-based equations to estimate glomerular filtration rate (GFR) for assessment and follow-up of kidney disease. The routine use of 24-hour creatinine clearances (CrCl) is no longer advocated. OBJECTIVES: To examine the indications for requesting CrCl at Tygerberg Hospital, identify problems associated with the procedure, and evaluate the utility of the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations with different levels of renal dysfunction in the ethnic groups of the Western Cape. METHODS: A clinical audit of CrCl was performed. The estimated GFR as predicted by the modified CG and MDRD formulae was compared with CrCl in 252 patients, representing three local ethnic groups. MDRD formulae with and without the correction factor for black ethnic group (MDRD-B) were evaluated. RESULTS: Problems with urine collection or data supplied were identified in one-third of CrCl requests, leading to unreliable results. The CG correlated best with CrCl in the group as a whole. The average absolute and percentage differences from CrCl in the different ethnic groups were as follows: coloured (mixed ethnicity) (N = 186) - CG 13.4 ml/min/1.73 m(2) (18%), MDRD 16.8 ml/min/1.73 m(2) (23%) and MDRD-B 27.9 ml/ min/1.73 m(2) (38%); black (N = 21) - CG 14.8 ml/min/1.73 m(2) (19%), MDRD 12.9 ml/min/1.73 m(2) (17%) and MDRD-B 25.1 ml/min/1.73 m(2) (33%); white (N = 45) CG 13.5 ml/min/1.73 m2 (19%), MDRD 15.3 ml/min/1.73 m(2) (21%) and MDRD-B 24.8 ml/min/1.73 m(2) (35%). Throughout the renal function levels (chronic kidney disease stages 1 - 5) CG correlated better with CrCl than MDRD. CONCLUSIONS: Possible reasons for poor correlations include a high prevalence of obesity, underweight and normal GFR in the study population. There is a need for further research, using a gold standard, into the accuracy of these prediction equations in our unique patient populations before firm recommendations can be made regarding their use. Until then CrCl will continue to be widely used. Greater efforts at patient and health care worker education are required to ensure proper collections.     

Positive and negative symptoms covary during clozapine treatment in schizophrenia

Although negative symptoms were traditionally considered to be unresponsive to neuroleptic medication, recent studies have demonstrated that negative symptoms do improve during neuroleptic treatment and that such improvement tends to occur concurrently with improvement in positive symptoms. Clozapine is an atypical neuroleptic that is effective in a significant proportion of otherwise neuroleptic-nonresponsive schizophrenic patients; in contrast to conventional neuroleptics, clozapine is also purported to possess unique efficacy in the amelioration of negative symptoms. How clozapine-associated reduction in negative symptoms relates to change in positive symptoms is not clear. To study the relationship between change in positive and negative symptoms during clozapine treatment, we monitored symptomatology in 40 DSM-III-R schizophrenic patients before and about 8 weeks after a trial of clozapine. Both positive and negative symptoms improved significantly. There was a significant correlation (r = .63,p <.01) between change in positive symptoms and change in negative symptoms; as with conventional neuroleptics, negative symptoms improved concomitantly with positive symptoms during clozapine treatment. Clozapine's apparent greater efficacy on negative symptoms may be related to its greater efficacy on positive symptoms in otherwise neuroleptic-refractory patients and its lesser propensity to cause extrapyramidal side-effects.     

Predicting the outcome of renal replacement therapy in severe acute renal failure

Continuous renal replacement therapy (CRRT), such as continuous venovenous hemofiltration, has theoretical advantages over intermittent hemodialysis (IHD) that are related to cardiorespiratory stability, metabolic control, and fluid balance allowing nutritional supplementation. However, retrospective and controlled studies fail to show these advantages because of comorbidity associated with triage to CRRT. To compare outcomes using IHD versus CRRT, we applied published risk stratification models (Cleveland Clinic Foundation, Lohr index, and APACHE II) to the 349 patients with acute renal failure requiring renal replacement therapy at University of Michigan over the 2 year period including 1995 and 1996. The Cleveland Clinic Foundation model best predicted overall mortality, but our CRRT patients had excess, unpredicted mortality that was particularly prominent in the lower risk categories. The Lohr clinical score predicted mortality less accurately but also was associated with higher, unpredicted mortality at lower risk scores among the CRRT patients. APACHE II scores did not predict mortality very well among IHD, CRRT, or the combined group of patients. We conclude that the need for CRRT itself predicts mortality over and above that included in published risk models. Either CRRT is associated with some unidentified morbidity (e.g., treatment associated infection) or, more likely, triage to CRRT is associated with as yet unspecified comorbidity not detected in existing risk stratification schemes. It will be important to address these issues in any future studies evaluating outcome or comparing renal replacement therapy modalities among patients with severe acute renal failure.     

Fine-needle aspiration cytology of meningiomas with unusual presentations

Meningiomas are not often aspirated unless they erode the skull, occur intraorbitally, or present as swelling in the head and neck region. We describe the cytologic findings of fine-needle aspiration cytology (FNAC) in four cases of meningioma that presented with swellings in the head and neck region. The patients underwent surgery, and the diagnosis of meningioma was confirmed. Three of the four cases were reported as aggressive meningiomas on histopathology.     

Control of lymphocyte migration into brain: selective interactions of lymphocyte subpopulations with brain endothelium.

The protein antigens conalbumin (CA) and ovalbumin (OVA) are known to require uptake into antigen-presenting cells (APC) for their presentation to major histocompatibility complex (MHC) class II-restricted T cells. In both cases proteolytic cleavage is thought to be a necessary step for the generation of the respective antigenic peptides. A specific inhibitor of the endosomal protease cathepsin B, Cbz-Phe-Ala-CHN2, blocks the presentation of both CA and OVA, whereas this inhibitor has no effect on the presentation of a processing-independent OVA peptide. Furthermore, the presentation of insulin, an antigen that needs processing but no proteolytic cleavage, is enhanced when cathepsin B is inhibited during antigen pulsing. When the APC were treated with an inhibitor of acid proteases, the CA response was not affected, while the presentation of OVA was diminished under these conditions. To estimate the relevance of these findings for the generation of the antigenic CA peptide, extracellular digestions of CA by cathepsin B were carried out. The fragment(s) present in these digests was recognized by T cells without further processing. Furthermore, the time-course of intra- and extracellular CA processing with respect to the capacity to stimulate T cells was similar. Taken together these data suggest that degradation by cathepsin B may be sufficient in vivo to generate the antigenic CA fragment. On the other hand, the blocking of cathepsin B does not appear to have an adverse effect on the general mechanisms of antigen presentation.     

Coronary artery lesions in Takayasu's arteritis--clinical and angiographic study

Two hundred and twenty five patients of Takayasu's arteritis were studied over 13 years. Male:Female ratio was 1:7. Mean age of the study population was 19 +/- 4 years. Of these 225 patients, 75 patients had symptoms and/or signs of cardiac involvement and these patients were subjected to coronary angiography. Significant coronary artery occlusion (i.e. more than 50% narrowing of luminal diameter) was present in 9 patients. Incidence of coronary artery lesions in Takayasu's arteritis is 12% in this study. The proximal segments of coronary arteries were involved while the distal segments were spared. Out of 34 patients with angina pectoris, only 3 patients had significant coronary arterial narrowing.     

Role of imprint cytology in the diagnosis of gastrointestinal tract malignancies

Endoscopic biopsies obtained from 275 patients (180 from the upper gastrointestinal tract and 95 from the lower gastrointestinal tract) were studied to compare the accuracy of biopsy imprint cytology and histology in the diagnosis of gastrointestinal lesions, and also to establish the degree of reliability of imprint cytology alone for an early diagnosis of malignancy. Biopsy histology results were found to be correct in 100% cases. Imprint cytology had an overall accuracy of 100%, 96.7%, 95.8% and 95.8% for the diagnosis of malignancies of the oesophagus, stomach, duodenum and colorectum respectively. False negative results were obtained with lymphomas. Regenerative cellular atypia was an important cause for false positive results. It was concluded that imprint cytology can serve as a useful and simple tool for an immediate diagnosis of malignancy. This should be subsequently correlated with histopathology which facilitates exact tumour typing and assessment of tumour invasion.     

First histological observations on the incorporation of a novel calcium phosphate bone substitute material in human cancellous bone

Calcium phosphates are frequently used as bone substitute materials because of their similarity to the mineral phase of bone, absence of antigenicity, and excellent osteoconductivity. However, in most currently available mineral substitutes, resorption occurs slowly if at all. In contrast, calcium phosphate cements have shown rapid resorption and remodeling in animal studies. In two prospective studies, a novel amorphous calcium phosphate cement (Biobon) was implanted in human patients for the first time. After 2-12 months, ten biopsies were obtained from nine individuals during secondary surgical interventions, for example, for implant removal. In all specimens, partial replacement of the material by new bone was observed, while residues of the cement were still visible. Undecalcified sections revealed extensive bone formation in immediate contact to the cement without fibrous interface. Polynucleated cells and superficial lacunae were indicative of resorptive activity, but inflammatory tissue response was absent. The new bone displayed regular trabecular and osteonal patterns. The histologic findings are in accordance with the excellent biocompatibility observed in the clinical follow-up. Though still incomplete, the resorbability of this cement appears superior to sintered calcium phosphates in these biopsy specimens. Presumably this is due to its amorphous crystalline structure. Biobon merits further studies as a promising substance for bone defect reconstruction in non-stress-bearing areas.