Clinicopathological insights into lupus nephritis in South Africans: a study of 251 patients.

There are few published studies on biopsy proven lupus nephritis (LN) from sub-Sahara Africa, mainly due to lack of expertise and pathology back-up for performing and interpreting renal biopsies in many centres. The purpose of this study was to document factors associated with biopsy proven LN and to determine clinical and laboratory models that best predict proliferative LN in South Africans. Of the 251 patients studied, 84.1% were females and 79.3% were of mixed ancestry. There were more observed cases of proliferative LN (63%) than non-proliferative LN. Factors associated with proliferative LN were male gender (p = 0.049), haematuria on dipstix (p < 0.0001), proteinuria on dipstix (p = 0.042), low serum albumin (p = 0.032), low complement C3 (p < 0.0001), low complement C4 (p = 0.009) and positive double-stranded DNA (p = 0.039). Using four models designed from various combinations of the factors associated with proliferative LN, the specificity and positive predictive values were highest for the model that combined gender (male), presence of dipstix haematuria and proteinuria, hypoalbuminaemia, low C3 and low C4 and positive double-stranded DNA (100% respectively). Further study is recommended to identify the value of using these demographic and laboratory parameters in identifying patients with proliferative LN in resource limited centres where the performance of a biopsy is not possible.

Clinical and pathological features of hereditary mixed polyposis syndrome: report on a South African family.

BACKGROUND: Hereditary mixed polyposis syndrome is characterised by multiple large-bowel polyps of differing histological types including a mixture of atypical juvenile polyps, hyperplastic polyps and adenomas. Affected individuals are thought to have an increased risk of malignancy, possibly via the juvenile polyposis pathway. METHODS: A 51-year-old woman (with a history of a colectomy for polyps during childhood) presented with rectal bleeding. Endoscopy demonstrated small rectal polyps which were hyperplastic on histology. A family tree was drawn up and the three children of the proband underwent flexible sigmoidoscopy. RESULTS: Endoscopic surveillance of the three children revealed one who had a similar phenotype to the mother. This child underwent colectomy and ileorectal anastomosis. The pathological specimen revealed more than 70 polyps, with a combination of juvenile retention, hyperplastic, adenomatous and inflammatory polyps. A second child had multiple small hyperplastic polyps, and the third had a normal colon. Although the gene locus for the disorder has been mapped, neither the gene nor the disease-causing mutation has been defined. CONCLUSION: A rare inherited polyposis syndrome has been identified in a South African family. Where clinical suspicion of a possible inherited condition exists, investigating at-risk first-degree relatives confirms the inherited nature of the disease. It is possible to use genetic haplotyping (i.e. with a range of markers in the area of the gene) to provide statistical risk to immediate relatives and therefore those at highest risk.

Down-regulation of gene transcripts associated with ricin tolerance in human RPMI 2650 cells.

The present study sought to determine if novel therapeutic approaches against ricin intoxication could be identified from human respiratory tract cells selected for increased resistance to this toxin. Initial studies indicated that the RPMI 2650 line was an appropriate model, owing to its sensitivity to ricin. Tolerant cultures were developed by exposing cells to a graded series of ricin concentrations from 6 to 192 pM. This resulted in the generation of cultures whose LC(50) values were increased by up to 4-fold following exposure to up to 96 pM ricin and by up to 6-fold following exposure to up to 192 pM ricin, compared to control cultures. DNA microarrays were employed to determine the gene transcript expression profile of cultures with increased resistance to ricin to investigate which gene products mediate ricin resistance. Transcripts (10) were identified that were greater than 2-fold down-regulated in the cells tolerant to 96 pM ricin, whereas 48 transcripts were seen to be down-regulated in cultures tolerant to 192 pM ricin. Gene transcripts (5) were up-regulated 2-fold or more in the 192 pM tolerant cultures in comparison to unexposed cells. The results indicate that ricin tolerance is the product of complex changes in gene expression profiles, most of which were found to involve down-regulation of transcript expression. It may be possible to modulate the gene expression profiles associated with ricin tolerance for potential therapeutic purposes using drugs and antisense technologies.

Microsporidiosis in the graft of a renal transplant recipient.

Microsporidia are intracellular protozoa that are emerging as significant opportunistic infections in AIDS patients. Although there are numerous published reports of intestinal and disseminated infections in patients with AIDS, there have been only two previous reports in transplantation medicine, both on intestinal microsporidiosis. We report here the first documented case of extra-intestinal microsporidiosis in a transplant recipient. A 39-year-old renal transplant recipient presented with a pyrexia and deteriorating graft function. Light microscopic examination of a renal allograft biopsy revealed numerous microsporidian spores within the renal tubular epithelium. Transmission electron microscopy confirmed the presence of an Encephalitozoon infection and was highly suggestive of Encephalitozoon intestinalis. Therapy with albendazole was extremely effective and resulted in recovery of renal function. Although a rare cause of renal allograft dysfunction, microsporidiosis is curable. It may be underdiagnosed, and should be considered in the differential diagnosis of transplant recipients presenting with opportunistic infections.

Governing the borderlands: decoding the power of aid.

This article examines aid practice, that is, the public-private contractual networks that link donor governments, UN agencies, military establishments, NGOs, private companies and others, as a relation of global liberal governance. In order to fulfil this function, such networks embody what could be called the 'securitisation' of international assistance. Based upon ideas of human security and ameliorating the effects of poverty and vulnerability reduction, aid is now seen as playing a direct security role. Rather than being concerned with relations between states, the primary aim of this security paradigm is to modulate and change the behaviour of populations within them. In doing so, it is able to exploit the opportunities afforded by privatisation. At the same time, however, aid as security is confronted by its own particular problem of 'governing at a distance'; how can calculations made by leading states be transformed into actions at the global edge when a multitude of private and non-government implementors now intervene? The article concludes by examining the contribution of risk analysis to solving this problem and, especially, the development of new contractual regimes based around technical standardisation, benchmarking and performance auditing. Through such technologies, metropolitan states are learning how to manage the public-private networks of aid practice and, as a result, to govern the borderlands in new ways.

Molecular epidemiology of HIV type 1 in a rural community in southwest Uganda.

The molecular epidemiology of a population-based cohort in a cluster of 15 villages in southwestern Uganda was investigated by sequencing part of the p24 gag gene and performing heteroduplex mobility assays (HMAs) of the V3 region of the env gene. Sequence and HMA data, obtained for 69 and 88 proviruses, respectively, showed that the clade A and D viruses were present at a ratio of about 0.67:1. No other clades were detected. Thirteen (22%) of 59 proviruses for which both gag and env data were obtained appeared to be recombinants. Although both clade A and D viruses were present in 13 of the villages, their distribution was unequal: for example, from env data 59% of clade A viruses were found in the eastern villages, compared with only 27% of clade D viruses. Phylogenetic (maximum likelihood) analysis of the p24 gag sequences showed a total of five clusters supported by bootstrap resampling values above or close to 75%. Four clusters were sexual partners, but there was no known sexual contact between the persons in the other cluster. The DNA sequences showed between 0.5 and 8.3% divergence from the cohort clade A or D consensus sequences. The sequences were not closely related to those published for other clade A or D proviruses.

Novel attributes of an androgenic steroid-mediated increase in cardiac end diastolic stiffness in rats.

Although cardiac early and mid-diastolic stiffness constants are well accepted as being modulated by alterations in myocyte active processes, increments in left ventricular end diastolic (LVED) stiffness (LVED k; g x cm(-2)) in classical pathological models of a reduced LVED k (e.g., diabetes mellitus (DM) and hypertension) are determined largely by the properties of the myocardial extracellular matrix (ECM). As such, increases in LVED k in the latter cardiac pathologies are insensitive to acute changes in cardiac load, heart rate, and contractility. We examined whether the same attributes that apply to changes in LVED k in DM and in spontaneously hypertensive rats (SHRs) also apply to an androgenic steroid (nandrolone decanoate; 5 mg x kg(-1) biweekly) induced increase in LVED k. Myocardial collagen (ECM) characteristics and the capacity of acute verapamil-mediated changes in cardiac dynamics to impact on LVED k were evaluated after 3 months of steroid treatment to rats, 4 months of DM in rats, and in 45-week-old SHRs. Chronic steroid administration increased LVED k (steroid = 42 +/- 4, control = 25 +/- 2; p < 0.01). An acute infusion of verapamil to steroid-treated rats decreased LVED k to values not different from controls (29 +/- 3; p < 0.05 as compared with LVED k at baseline). Measures of myocardial collagen concentrations, phenotype ratios, and cross-linking were unchanged following steroid administration. Verapamil failed to alter the increased LVED k that occurs in either rats with DM or in SHRs, despite similar effects on cardiac dynamics as those noted in steroid-treated rats. The increased LVED k in the former animal models was associated with alterations in the ECM. In conclusion, the unique lack of association of the androgenic steroid-induced increase in LVED k with alterations in the myocardial ECM and the novel sensitivity of the steroid-mediated increment in LVED k to acute alterations in cardiac dynamics further supports the notion that changes in LVED k should not be considered to be a reflection of ECM characteristics in all cardiac conditions.

Conflict, the continuum and chronic emergencies: a critical analysis of the scope for linking relief, rehabilitation and development planning in Sudan.

The concept of the 'relief-to-development continuum' has been the subject of renewed interest in recent years. Concerned by the rise in relief budgets over the past decade and the absolute fall in development aid resources, support has been growing for the concept of developmental relief. In the context of complex political emergencies, it has been argued further that as effective development aid can reduce vulnerability to the impact of natural hazards, so it might also be used to contribute to a process of conflict prevention. In this way, the concept of the relief-development continuum has become entwined with broader discussions about the contribution of official development assistance management. Drawing on a Review of Operation Lifeline Sudan (OLS), this paper cautions against uncritical application of the concept of the continuum in complex political emergencies and rehabilitation in particular, in the current Sudanese context. It argues that in order to move legitimately from relief aid programming to development aid programming, three fundamental conditions must be in place: first, a minimum level of security, respect for human rights and humanitarian access. Second, empirical evidence from the field needs to demonstrate that the emergency is over. Finally, moving from relief to development aid programming is contingent on donor governments accepting the legitimacy of national governmental structures and of the rebel movements. In other words, for donor governments, moving along the continuum is in significant part determined by foreign policy considerations, not only technical ones. Consideration needs to be given to the actual and perceived legitimation of the different movements that a move to rehabilitation might be seen to imply. The paper argues that none of these conditions had been satisfied in Sudan by mid-1997. Instead of a process of normalisation paving the way to long-term development, the current situation in Sudan is better described as a chronic political emergency. In such a context, uncritical pursuit of developmental strategies may negatively affect the welfare of conflict-affected populations.

The symphony of the damned: racial discourse, complex political emergencies and humanitarian aid.

This paper concerns the manner in which the West is responding to protracted political crises beyond its borders. It examines the conceptual world-view that aid agencies bring to complex emergencies and which shapes action. The paper provides an analysis of developmentalism. That is, the currently dominant idea of development which is an adapted form of multiculturalism. It is based on the empowerment of cultural differences and the relativisation of progress. As a variant of multiculturalism, developmentalism is part of Western racial discourse. In terms of understanding conflict, it establishes a mirror-image relationship with new rascist ideas premised on cultural pluralism inevitably leading to social breakdown, violence and anarchy. To the contrary, with its functional view of social harmony, libertine developmentalism claims that even unresolved political crisis constitutes a development opportunity. Developmentalism, like culturalism generally, is incapable of analysing power. It therefore cannot understand the effects and significance of its own organisational forms. Moreover, since the absence of power translates into operational neutrality in a war zone, it is also unable to analyse the nature of new political formations emerging in the global periphery. That is, the so-called weak or failed states, warlords and so on. This functional ignorance has allowed a widespread incorporation of humanitarian aid into the fabric of political violence. Developmentalism is an essential underpinning for the growing organisational accommodation to ongoing conflict and eroding standards of justice and accountability.

Postpartum microneuromas of the uterine cervix.

The cervices of 300 hysterectomy specimens have been examined for the presence of abnormal nerves morphologically resembling traumatic neuromas. These were present in 165 uteri (55%) overall but in only two of the 48 nulliparous patients (4%), indicating a probable causation by parturition. The microneuromas could be graded. The larger, more complex lesions were associated with more extensive involvement of the cervix but not with increased parity.

An androgenic steroid decreases left ventricular compliance in rats.

The effect of chronic administration of an androgenic steroid on left ventricular (LV) compliance and contractility was studied in rats. Rats received a biweekly intramuscular injection of nandrolone decanoate (5 mg/kg; steroid group) or the vehicle (control group) for 3 mo. Cardiac performance was measured in anesthetized open-chest ventilated rats. LV compliance was determined from the slope of the LV end-diastolic pressure (LVEDP) vs. LV end-diastolic (LVED) strain relation measured in the long and short axes of the LV. LV regional myocardial compliance was determined from the slope of the LVED stress vs. LVED strain relation (myocardial elastic stiffness constant). Cardiac contractility was determined from the slope of the LV end-systolic (LVES) pressure vs. LVES strain relation. Systolic performance was also assessed from the slope of the pressure-length area (PL area) or stroke work vs. LVED strain and LVEDP relations. Nandrolone decanoate decreased body weight, heart weight, and plasma testosterone concentrations but increased the heart weight-to-body weight ratio. Nandrolone decanoate decreased LV compliance (slope of LVEDP vs. LVED strain relation in long and short axes; steroid vs. control, P < 0.01). This occurred as a result of an increased regional myocardial stiffness (myocardial elastic stiffness constant; steroid vs. control, P < 0.01), which resulted in a reduced cardiac systolic performance (PL area vs. LVEDP, slope of steroid vs. control group, P < 0.005). Diastolic geometry (LV wall thickness-to-radius ratio) and cardiac contractility were unchanged with steroid administration. In conclusion, chronic administration of the androgenic steroid nandrolone decanoate decreases LV myocardial compliance and thus overall cardiac performance without altering contractility in rats.

Crescentic nephritis at Groote Schuur Hospital, South Africa--not a benign disease.

The etiology of crescentic nephritis (CN) in the developing world differs from that of Europe and North America. This retrospective study of 73 patients is the largest series of CN in the developing world. The records of all renal biopsies performed at Groote Schuur Hospital, Cape Town, South Africa, over thirteen years, between January 1977 and April 1991, were reviewed. Specimens selected for this study had six or more glomeruli and over 50% of these glomeruli had crescent formation. It confirms that post infectious glomerulonephritis (PIGN) (n = 21) is the commonest cause of CN in this setting. In addition there were 15 patients with CN associated with systemic lupus erythematosus (SLE). These two groups make this study unique as they are the largest series of each described in the literature. Thirty-nine (53%) patients in this series progressed to end-stage renal failure (ESRF) and only nine (12%) patients recovered renal function to a normal serum creatinine. Eight (38%) patients in the PIGN group developed ESRF, indicating the poor prognosis of this condition. Six of eight patients in the PIGN group treated with steroids and cyclophosphamide recovered to a serum creatinine level less than 200 mumol/l and only one progressed to ESRF, which may indicate that this form of therapy is beneficial. Thirteen (87%) patients with SLE either developed ESRF or died which suggests that the presence of crescents in this condition is associated with a poor prognosis.

An investigation of the thermal stabilities of two malate dehydrogenases by comparison of their three-dimensional structures.

The tertiary structure of Thermus aquaticus malate dehydrogenase (MDH) was predicted based on the known crystal structure of pig heart cytosolic MDH. Guanidinium chloride (GdmCl) unfolding experiments showed that there is only about a 4.2-kjoule/mol difference in delta G 0 between the pig and Thermus MDH. However, the two enzymes varied greatly in their [GdmCl]1/2, with Thermus MDH showing the expected increased stability (3.20 M against 0.58 M for pig MDH). The half-lives were determined for both Thermus MDH (34 min at 90 degrees C) and pig MDH (1.8 min at 60 degrees C). The Thermus MDH model was then examined to see what effect the substituted residues and changes may have on the enzyme, particularly in relation to its high thermal stability.

Nemaline myopathy: a report of two siblings as evidence of autosomal recessive inheritance of the infantile type.

We report two opposite-sex siblings with the severe infantile form of nemaline myopathy; diagnoses were made on muscle biopsy. Neither parent showed clinical or electromyographic evidence of myopathy, and both had negative muscle biopsies. Autosomal recessive inheritance seems likely.

Cerebellopontine angle tumours in black South Africans--how rare are acoustic schwannomas?

Previous reports of intracranial neoplasms from Africa have all shown a very low incidence of acoustic schwannomas (neuromas). In this series a group of 11 cerebellopontine angle solid tumours from black Africans were studied. On conventional histological examination only 3 had the features of a schwannoma. However, by using immunohistochemistry, a further 3 examples were identified. As controls, the same antisera were also applied to known schwannomas and meningiomas. During the period of the study, 163 patients with primary intracranial neoplasms were seen and thus acoustic schwannomas accounted for 3.7%. Although this figure is low by world standards, it still represents a far higher figure than has previously been reported from Africa. This study therefore emphasises the value of immunohistochemistry in the diagnosis of brain tumours and, furthermore, shows that acoustic schwannoma must be considered in the appropriate clinical setting, even in a group previously regarded as low-risk.