IL-4 and IL-13 have overlapping but distinct effects on HIV production in monocytes.

In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48-72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the U1 and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimately stimulated cytolysis of HIV-infected monocytes as well as increased apoptosis of U1. In the presence of tumor necrosis factor alpha or IL-6, which upregulate HIV expression, IL-13 could no longer suppress HIV expression. These results indicate that IL-4 and IL-13, although closely related in modulating monocyte function, can have divergent effects on HIV expression in monocytes. Collectively, these data suggest that there exists a complex cytokine tissue environment with positive regulators of HIV expression able to override negative regulators.

Parathyroid hypertension. A reversible disorder.

A retrospective study of 75 patients who were surgically cured of primary hyperparathyroidism from 1976 to 1984 was performed to evaluate the blood pressure and metabolic responses to parathyroid surgery. Published data on the population prevalence of hypertension (HT) in South Africa were used for comparison. The overall prevalence of HT before surgery was 47%, compared with 23% in the general population. Hypertension was most frequent in patients older than 60 years (62% vs 39% expected). Renal insufficiency was found in 13 of 35 hypertensive patients and in two of 40 normotensive patients. However, the prevalence of HT in patients with normal creatinine levels (37%) exceeded that expected. The frequency of urolithiasis and mean levels of serum and urine calcium and phosphate were similar in normotensive and hypertensive patients. Parathyroidectomy resulted in a substantial fall in both mean systolic and mean diastolic blood pressures in 54% of the hypertensive subjects, unrelated to improvement in renal function.

Chronic granulocytic leukemia in a patient with a renal allograft.

A man received a cadaver renal allograft for end-stage renal failure. After 35 months of immunosuppressive therapy with azathioprine and prednisone, he developed septicemia and a high leukocyte count. In spite of successful treatment of the infection, the leukocyte count continued to rise and a diagnosis of Philadelphia chromosome positive chronic granulocytic leukemia was made. An increased incidence of malignant disease, especially lymphoreticular malignancy, is well described in immunosuppressed patients with allografts. However, the association of chronic granulocytic leukemia and immunosuppressive therapy previously has not been reported. An additional etiological factor in this patient may have been the extensive diagnostic radiological investigations undertaken in childhood. The recent addition of allopurinol to the immunosuppressive therapy has normalized the platelet and leukocyte counts, probably by potentiating mercaptopurine.

Significance, definition, classification and risk factors of chronic kidney disease in South Africa.

Renal dysfunction or chronic kidney disease (CKD) is found in 10% of the global population and is classified into five stages according to the estimated glomerular filtration rate (eGFR). No matter where a patient lives, estimation of the GFR is mandatory for decision-making and obtained by the simple measurement of a serum creatinine level. The objective of diagnosing CKD lies in its future prevention, early detection and proper treatment, which will prevent or delay functional deterioration. Primary hypertension (PH) occurs in 25% of South Africa (SA)s black population and is the putative cause of stage 5 CKD in 40 - 60% of these patients. Moreover, in this group, stage 5 CKD occurs at a relatively young age (35 - 45 years) compared with other population groups in whom stage 5 CKD resulting from PH usually occurs between 60 and 70 years of age. In the cohort study, PH has been found in 12 - 16% of black school learners (mean age 17 years) compared with 1.8 - 2% of other ethnic groups (mixed race, Asian, white). End-stage renal failure (ESRF) is the fifth most common cause of death in SA, excluding post-traumatic cases. In addition, undiagnosed or poorly controlled PH is a potent risk factor for other cardiovascular disease (CVD), e.g. congestive cardiac failure, myocardial infarction, stroke. Significant protein is also associated with CVD and protein >1 g/d is a significant risk factor for ESRF.

Chronic kidney disease.

It is known that, for many reasons, general practitioners(GPs) find renal disease difficult to diagnose, understandand treat. The terms chronic kidney disease (CKD) andglomerular filtration rate (GFR), representing the renalfunction equation, have been introduced to clarify someof these difficulties. Unfortunately, even these pivotal concepts remaineither unknown or poorly understood by the majority of GPs in SouthAfrica (SA). CKD is often not recognised because there are no specificsymptoms, and not diagnosed or only diagnosed at an advanced stage.Tests for CKD are, however, simple and freely available.

Paediatric chronic kidney disease.

Doctors use various guidelines on paediatric chronic kidney disease (CKD) for managing their patients according to the availability of resources. As with adolescent and adult patients, CKD in children can also progress to end-stage renal failure - the time course being influenced by several modifiable factors. Decline in renal failure is best categorised in stages, which determine management and prognosis. Staging is based on three categories, i.e. cause, glomerular filtration rate and proteinuria. Early diagnosis of CKD allows for the institution of renoprotective treatment of modifiable factors and treatment to prevent the development of complications. The two most important modifiable factors that can be treated successfully are hypertension and proteinuria. The objective of this article is to provide information on the diagnosis and treatment of CKD in children. Early identification and treatment of modifiable risk factors of CKD decreases the burden of disease and delays or prevents the need for renal replacement therapy.

Drugs and the kidney.

This article on drug nephrotoxicity is detailed, as it is important to be fully aware of renal side-effects of drugs with regard to prevention andearly diagnosis in order to manage the condition correctly. Many therapeutic agents are nephrotoxic, particularly when the serum half-life isprolonged and blood levels are raised because of decreased renal excretion. Distal nephrotoxicity is markedly enhanced when the glomerularfiltration rate (GFR) is reduced and is a particular threat in elderly patients with so-called 'normal' creatinine levels. In patients of 45 - 55 years of age theGFR is reduced by about 1 mL/min/year, so that an otherwise healthy person of 80 may have an estimated GFR (eGFR) of <60 mL/min or <50 mL/min,i.e. stage 2, 3 or 3b chronic kidney disease (CKD). Furthermore, other effects related to kidney dysfunction may be seen, e.g. worsening of hypertensionwith the use of non-steroidal anti-inflammatory drugs, increased bruising or bleeding tendency with aspirin, and hyponatraemia hypertensionacidosis with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Digoxin is contraindicated in stage 3 CKD, even ina reduced dosage. Other drugs can cause the direct formation of kidney stones, e.g. topiramate (used in the prophylaxis of resistant migraine).Levofloxacin (Tavanic) can cause rupture of the Achilles tendon and other tendons.Radiocontrast media must be used with care. Occasionally, strategies to prevent acute kidney insufficiency cause irreversible CKD,especially in patients with diabetes and those with myeloma who have stage 4 - 5 CKD. Gadolinium in its many forms (even the newerproducts) used as contrast medium for magnetic resonance imaging is best avoided in patients with stages 4 and 5 CKD.

Important causes of chronic kidney disease in South Africa.

In hypertensive patients without chronic kidney disease (CKD) the goal is to keep blood pressure (BP) at ≤140/90 mmHg. When CKD ispresent, especially where there is proteinuria of ≥0.5 g/day, the goal is a BP of ≤130/80 mmHg. Lifestyle measures are mandatory, especiallylimitation of salt intake, ingestion of adequate quantities of potassium, and weight control. Patients with stages 4 - 5 CKD must be carefullymonitored for hyperkalaemia and deteriorating kidney function if angiotensin-converting enzyme (ACE) inhibitors or angiotensin IIreceptor blockers (ARBs) are used, especially in patients >60 years of age with diabetes or atherosclerosis. BP should be regularly monitoredand, where possible, home BP-measuring devices are recommended for optimal control.Guidelines on the use of antidiabetic agents in CKD are presented, with the warning that metformin is contraindicated in patients withstages 4 - 5 CKD.There is a wide clinical spectrum of renal disease in the course of HIV infection, including acute kidney injury, electrolyte and acid-basedisturbances, HIV-associated glomerular disease, acute-on-chronic renal disease and side-effects related to the treatment of HIV.

Important complications of chronic kidney disease.

The complications of chronic kidney disease (CKD) are dyslipidaemia, hyperkalaemia, metabolic acidosis, anaemia, and bone and mineraldisorders. Dyslipidaemia may be treated with low-density lipoprotein-lowering agents. Statins are ineffective in stages 4 and 5 CKD, but areindicated for preventing the progression of disease in the earlier stages. Chronic acidosis has recently been shown to be a risk factor in theprogression of CKD renal dysfunction. Therefore, treatment is mandatory. Practically, this should consist of 1 - 2 heaped teaspoons of sodiumbicarbonate 2 - 3 times per day, which is an inexpensive and safe therapy that does not raise the blood pressure in spite of the increased sodiumlevel. Target levels of haemoglobin, according to international guidelines, are between 10 g/dL and 12 g/dL. The serum phosphate level is raisedin stage 4 CKD, and especially in stage 5 CKD, which is associated with coronary carotid and other vascular calcifications and may result inischaemic heart disease, myocardial infarction and stroke. A raised parathyroid hormone level (secondary hyperparathyroidism) is also a majorrisk factor for cardiovascular disease and is associated with increased hypertension and resistance to the treatment of CKD-associated anaemia.

Diagnosis and management of lymphoceles after renal transplantation.

Eight lymphoceles were encountered in 232 renal transplant procedures. The patients presented with either a palpable pelvic mass, ipsilateral leg pain and edema, or deteriorating renal function. Two patients were asymptomatic. The diagnosis is readily established by a combination of intravenous urography, ultrasound, and aspiration although ultrasound is the most useful method for the diagnosis and follow-up of these lesions. A functioning arteriovenous shunt in the leg on the side of the transplant may predispose to lymphocele formation. Most lymphoceles may be managed conservatively initially. However, if surgery is required, open drainage and packing would appear to be the most reliable procedure.

Post-transplantation analgesic dependence in patients who formerly suffered from analgesic neophropathy.

Twenty-two patients with functioning grafts who originally developed renal failure due to analgesic nephropathy ("analgesic" group), and 84 patients with various other causes of renal failure ("non-analgesic" group) were studied over one year to assess the extent of analgesic use and abuse. On each occasion that one of these patients reported to hospital a urine sample was collected and analyzed for N-acetylparaminophenol (NAPA). Of the "analgesic" group of patients, 14% had consistently negative urine samples while 41% showed NAPA in more than half the urines collected. In the "non-analgesic" group 29% of patients had entirely negative urine tests, and in only 7% were more than half of the urines NAPA-positive. Patients in the "non-analgesic" group readily admitted taking anaglesics at frequencies compatible with the observed number of positive tests. This contrasted with the "analgesic" group in which 14 of 19 patients with NAPA-positive urines denied analgesic intake. This is considered to be a guilt manifestation in patients who have developed a psychological dependence on analgesics and have recidivated with full knowledge of the possible harm these drugs may inflict on their grafts.

The effect of low aluminum water and desferrioxamine on the outcome of dialysis encephalopathy.

Five patients with dialysis encephalopathy were transferred to deionized water; all died after a variable period, 4 of progressive dementia. Six other patients with encephalopathy were started either on deionized or reverse osmosis water as well as desferrioxamine on dialysis. Serial EEG's were performed in this group. In 2 patients the EEG's showed rapid and sustained improvement after the institution of desferrioxamine, whereas there had been no EEG change after 15 and 32 months of reverse osmosis water. In 2 patients there was similar clinical and EEG improvement, related to water change and the institution of desferrioxamine. Two patients died of progressive dementia in spite of both water change and desferrioxamine. Thus, while not a panacea, desferrioxamine has a definitive therapeutic effect on the clinical and EEG manifestations of dialysis encephalopathy, when used in conjunction with deionized or reverse osmosis water.

The qualitative nitroblue tetrazolium (NBT) test as a means to differentiate between infection and rejection in renal transplant patients.

In order to determine whether immunosupression depresses the response of the NBT test to bacterial infections and to note the effect of allograft rejection on this test, a prospective study was carried out on 30 renal transplant recipients. 12 of 30 renal transplant patients developed bacterial infections and in these patients NBT readings were elevated. 12 of the remianing 18 patients who developed rejection episodes showed normal NBT results. All patients were on high doses of steroids and other immunsuppressive agents. We conclude that the NBT test may be of value in diagnosing bacterial infection in the immunsuppressed allograft recipient, and may also be an useful adjunct in the differentiation between allograft infection and bacterial infection.

The value of Swan-Ganz catheterization and volume loading in preventing renal failure in patients undergoing abdominal aneurysmectomy.

A prospective analysis of 61 patients undergoing abdominal aneurysmectomy is presented. When compared with 87 historical controls we have shown that the incidence of hypotensive episodes (31 out of 62 patients in the original study compared with 13 out of 44 patients in the prospective analysis) is significantly reduced when fluid balance is monitored invasively using the pulmonary artery wedge pressure and keeping it at 10 mm H2O (p less than 0.03). Renal dysfunction, defined as a significant drop in urine output and a doubling of the serum creatinine, occurred in only 10% of patients compared with 33% in the controls (p less than 0.001). The decreased prevalence of renal failure accounts for the reduction in mortality noted (p less than 0.01). There were 27 deaths (31%) amongst the patients in the earlier study compared with 9 (15%) in the prospective analysis. The pathogenetic mechanisms responsible for the development of renal failure following surgical manipulation of the abdominal aorta are reviewed.

The role of diet in the pathogenesis and control of hyperlipidemia after renal transplantation.

Twenty-one Caucasian renal transplant recipients with hyperlipidemia and normal renal function were assessed with regard to their diet. Their average daily intake of energy and cholesterol was lower and the ratio of polyunsaturated to saturated fat higher in their diet than in that of a comparable urban Caucasian South African population. Nevertheless modification of their diets in one year produced a significant lowering of their body weight and a statistically significant drop in the mean plasma cholesterol (9.2 +/- 0.5 mmoles/l to 7.6 +/- 0.5 mmoles/l, P less than 0.05). Although the fall in plasma triglyceride in the group as a whole was not statistically significant (3.8 +/- 0.6 mmoles/l to 3.2 +/- 0.5 mmoles/l) the level did decrease substantially in 13 of the 21 patients (4.2 +/- 0.9 mmoles/l to 2.5 +/- 0.5 mmoles/l, P less than 0.01). It is suggested that diet has a definite role in the control of post-transplant hyperlipidemia but should probably be introduced immediately after immunosuppression is started and be coupled with a suitable exercise program for optimal effect.

Salvage reconstruction with vascularized fibular strut graft fusion using posterior approach in the treatment of severe spondylolisthesis.

STUDY DESIGN: One case is reported in which a failed anterior fusion for Grade 4 spondylolisthesis was treated with a vascularized fibular strut graft using a posterior approach. OBJECTIVES: To demonstrate the applicability of this technique for salvage cases or patients with systemic conditions that may decrease the success of more standard techniques. SUMMARY OF BACKGROUND DATA: Surgical stabilization of spondylolisthesis through posterior approach with a fibular strut graft has been previously described. A vascularized strut graft can be used in the treatment of spondylolisthesis and may have applicability in those patients with underlying disease that may impair the use of more standard techniques or in salvage reconstruction. METHODS: With the patient under general anesthesia, through a posterior approach S1 and L4 were decompressed. The fibula with its vascularity intact was harvested and anastomosed with the superior gluteal artery and vein. The fibular strut was placed into the space formed by reaming between L5 and S1. Ilial autograft was used to augment the posterior fusion. After the procedure the patient was placed in a hip spica cast. RESULTS: At the 2-year follow-up the patient has incorporation of the graft, with no evidence of fracture and no significant progression of anterior slip. CONCLUSION: A vascularized fibular strut graft is a feasible alternative in the treatment of severe spondylolisthesis. No complications were encountered in the involved patient. Future application may include salvage reconstruction of failed arthrodesis or in individuals with systemic conditions that may impair graft incorporation using more standard techniques.

Microangiopathic hemolytic anemia as a complication of diabetes mellitus.

A mature-onset diabetic patient who developed microangiopathic hemolytic anemia (MHA) is presented. Although numerous causes of hemolysis are reported in the literature, MHA is a rare complication of diabetes. The proposed mechanism of hemolytic anemia is thought to be related to the abnormal formation of cell membranes in the diabetic environment. The ratio of cholesterol to phospholipid in the core of the membrane is altered in diabetics; as a result, the red blood cell wall becomes rigid and nondeformable. The abnormal cells becomes disrupted as they circulate through the microangiopathic blood vessels. The mechanism of action of the antiplatelet agents is to enhance cell membrane compliance. With improved cell-wall compliance, one can expect a reduction in hemolysis, as occurred in our patient. The literature on diabetes mellitus-related microangiopathic hemolytic anemia is reviewed.