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Biomedical subjects

A M Meyers

Publications and source records attributed to A M Meyers.

At least 19 recordsLinked to original sources

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.

Bone Transplantation↗

Revisiting the role of physical activity and exercise in the treatment of type 2 diabetes.

There is tremendous potential for improving glycemic control, insulin sensitivity, and cardiovascular risk factors through increased physical activity in individuals with Type 2 diabetes. The demonstrated effects of structured endurance exercise on select outcomes compare favorably with those of typical pharmacological treatment modalities. Adherence to these types of program is problematic, however. We know less about the expected effects of lifestyle-based physical activity. Preliminary results require further investigation, given the apparent acceptability of these programs in this population, however. The effects of resistance training on cardiovascular risk factors to date likely limit its application as an adjunctive therapy for individuals with Type 2 diabetes. The question is no longer "can exercise/physical activity benefit the individual with Type 2 diabetes?" The answer is yes. Future research needs to refine questions regarding type, dose, and magnitude of effects of physical activity (and its subcategory exercise) on glycemic control, insulin sensitivity, and on risk factors for cardiovascular disease within the context of program acceptability and feasibility.

Blood Glucose↗

Lithogenic risk factors in normal black volunteers, and black and white recurrent stone formers.

OBJECTIVE: To compare lithogenic risk factors in normal black volunteer men (BN), male black stone formers (BSF) and male white recurrent stone formers (WSF); in addition, the differential diagnoses in the stone formers were compared to determine if the causes of renal stones differed in the two groups. SUBJECTS AND METHODS: The study included 22 BN, 22 consecutive BSF and 122 consecutive WSF seen over a 10-year period. Each subject was assessed by a thorough medical history, dietary analysis and a full serum and urinary biochemical evaluation. RESULTS: Although the WSF were significantly more overweight (P<0.001) and obese (P<0.001) than the BSF, neither group had values significantly different from those of their respective normal populations. There was no significant difference in serum levels of Ca, phosphorus, ionised Ca, calcitriol and alkaline phosphatase in BSF and WSF, but levels of parathyroid hormone tended to be (P<0.1) and calcitriol was significantly higher in BSF than WSF (P<0.03). The BSF urinary excretion levels tended to be more like that of the WSF, with the following pattern present; BN<BSF<WSF, except for citrate, where BSF< BN<WSF. No dietary or metabolic abnormality was found in 9% of BSF and 5% of WSF. Pure dietary lithogenic risk factors were present in 9% of BSF and 21% of WSF. The prevalence of metabolic risk factors was similar in the two groups but the distribution differed. Renal hypercalciuria, absorptive hypercalciuria and mild metabolic hyperoxaluria were 2.5-3 times more prevalent in the WSF. CONCLUSION: Although the urine of BSF tends to be more like that of WSF, the lithogenic risk factors present differed and were less severe. The increase in urinary calcium excretion, coupled with a lower citrate excretion, may be the most important reason for stone formation in the black population. An increased protein intake may also play a role. In this small group of BSF there was no family history of urolithiasis, supporting the view that there may be a more prominent genetic influence in WSF.

Adult↗

Lithogenic risk factors in the urine of black and white subjects.

OBJECTIVE: To identify biochemical and dietary factors which may play a role in the low incidence of stone formation in the black South African population. SUBJECTS AND METHODS: The study included 31 semiurbanized black and 29 urbanized white subjects. The protocol and modern laboratory techniques used to assess recurrent stone formers were followed. Urinary sodium, potassium, creatinine, calcium, phosphate and urate levels were measured, and urinary citrate, oxalate and cystine assessed. RESULTS: Black subjects ate a diet significantly higher in sodium (P < 0.04); there was no difference in serum levels but urinary sodium was significantly higher (P < 0.001) in black than in white subjects. Urinary potassium, calcium, citrate, phosphate and cystine were all significantly lower in black than in white subjects (P < 0.001 for the first four and P < 0.03 for cystine). CONCLUSION: Certain intrinsic factors in South African black subjects may account for their lower frequency of stone formation than in white subjects. Of these, the very low urinary calcium, decreased urinary cystine and different interactions between sodium and calcium/cystine are probably important.

Adult↗

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.

Anemia, Hemolytic↗

Indapamide (Natrilix): the agent of choice in the treatment of recurrent renal calculi associated with idiopathic hypercalciuria.

OBJECTIVE: To compare the hypocalciuric and potential side-effects of hydrochlorothiazide (HCT) to indapamide (IND; a thiazide-like drug) in patients with idiopathic hypercalciuria. PATIENTS, SUBJECTS AND METHODS: Twelve patients with recurrent renal calculi and renal hypercalciuria were studied using a randomized double-blind cross-over protocol. In addition, because the side-effects of HCT are attenuated using small doses, the hypocalciuric effect of 12.5, 25 and 50 mg daily was assessed in six normal subjects. RESULTS: There was a significant reduction in urinary calcium excretion using both agents, with a mean (SD) of 6.06 (2.68) and 3.37 (2.00) mmol/24 h using IND, and 5.58 (1.98) and 3.93 (2.35) mmol/24 h using HCT, before and after treatment (P < 0.05). The treatment was not sufficiently prolonged to assess adequately all the side-effects of either agent but both produced a similar decrease in serum potassium, whilst HCT significantly increased the mean (SD) serum urate levels, from 0.34 (0.09) to 0.43 (0.08) mmol/L (P < 0.01). There was also a significant decrease in mean (SD) urinary citrate excretion in those receiving HCT, from 1.41 (1.05) to 1.00 (0.71) mmol/24 h (P < 0.001), but not in those receiving IND, from 1.19 (0.71) to 1.18 (0.79) mmol/24 h. Although there was a hypocalciuric effect with doses of 12.5 and 25 mg HCT, it was sub-therapeutic when compared with the dose of 50 mg. CONCLUSION: At a daily dose of 2.5 mg, IND is at least as effective as 50 mg HCT in controlling hypercalciuria. Because of its safety profile and lack of effects on urinary citrate excretion, this agent should be the preferred therapy for patients with idiopathic hypercalciuria and recurrent renal calculi.

Calcium↗

Long-term effects of potassium citrate therapy on the formation of new stones in groups of recurrent stone formers with hypocitraturia.

OBJECTIVE: To compare stone formation rates before (as total rates and during remote periods) and after therapy with potassium citrate in patients with hypocitraturia. PATIENTS AND METHODS: The study comprised 15 patients with hypocitraturia only (Group I) and 12 patients with hypocitraturia associated with other abnormalities (Group II), all of whom were recurrent stone formers. Their urine chemistry, including citrate, was measured before and after treatment. RESULTS: In both groups, the urinary citrate concentration increased significantly to within normal limits during therapy with potassium citrate (P < 0.005). The rate of total stone formation in patients in Group I decreased significantly from 0.7/year before to 0.13/year after treatment (P < 0.005). The corresponding remote stone formation rate before (0.88/year) was significantly greater than the rate after treatment (0.13/year; P < 0.005; follow-up 4.6 +/- 1.9 years). Patients in Group II showed a similar striking decrease in total stone formation rate, from 1.2/year to 0.08/year after treatment (P < 0.005). The corresponding remote stone formation rate (1.66/year) before was significantly greater than that after treatment (0.08/year; P < 0.005; follow-up 4.1 +/- 1.6 years). There was a remission rate of 93% for stone formation over the complete follow-up. CONCLUSION: Potassium citrate appears to be the drug of choice in the long-term treatment of patients with hypocitraturia as it not only decreases the rate of stone formation but also maintains normal citrate levels in the urine.

Administration, Oral↗

Clinical experience with Repotin, a locally produced recombinant human erythropoietin, in the treatment of anaemia of chronic renal failure in South Africa.

OBJECTIVE: To evaluate the efficacy and safety of Repotin, a locally produced recombinant human erythropoietin (rHuEPO), in the treatment of the anaemia of chronic renal failure (ACRF). DESIGN: The study consisted of two multicentre non-randomised open stages. SETTING: Renal units at several teaching hospitals in South Africa. PARTICIPANTS: Haemodialysis patients with haemoglobin (Hb) levels less than 8.0 g/dl were recruited. The first stage examined 26 patients during a 12-week period in which the dose of intravenous rHuEPO was adjusted according to haematological response. In the second stage 27 patients were stabilised with intravenous rHuEPO and then maintained at a Hb level above 8.0 g/dl by subcutaneous administration for up to 1 year. OUTCOME MEASURES: In both stages, outcome was measured by clinical examination, blood pressure, full haematological parameters and blood chemistry. RESULTS: In stage 1, all patients responded to therapy with a statistically significant increase in Hb from geometric means of 6.28 g/dl to 8.50 g/dl (geometric SDs of 1.17 and 1.20 respectively). The doses used ranged from 25 IU to 125 IU/kg (average 47.1). In the second stage, Hb levels reached a mean of 8.06 g/dl (SD 0.9) and were maintained at target range with an average dose of 55.5 IU/kg three times a week. Apart from changes in serum iron, ferritin (associated with increased haematopoiesis) and potassium, there were no significant alterations in blood chemistry. The incidence of adverse events reported during the 12-month second stage was no greater than that reported for other forms of rHuEPO therapy. CONCLUSION: Repotin is a safe and effective rHuEPO preparation for the treatment of ACRF.

Adult↗

Hereditary interstitial nephritis without basement membrane changes.

Hereditary interstitial nephritides are a heterogeneous group of disorders comprising medullary cystic disease, several varieties of Alport's syndrome and also one familial disorder with a distinct clinical syndrome and without characteristic ultrastructural glomerular basement membrane changes. Our family consisted of 11 members, 5 of which presented with renal dysfunction of varying degrees. Clinically, the affected siblings presented with long-standing hypertension, minimal proteinuria and no hematuria. All known causes of a secondary diffuse interstitial nephritis, Alport's syndrome and medullary cystic disease have been excluded. An HLA association is suggested between the affected and unaffected members of the family. Renal biopsy subsequently showed the typical features of a chronic interstitial nephritis without basement membrane changes.

Adult↗

Partial recovery of renal function in black patients with apparent end-stage renal failure due to primary malignant hypertension.

We report the largest series in which 12 out of 54 patients with primary malignant hypertension requiring dialysis recovered sufficient renal function to allow withdrawal of dialysis. The patients were divided into recovery (RC; n = 12) and non-recovery (N-RC; n = 42) groups. The two groups were compared for variables which might predict RC. They were also assessed for survival. Nine of the RC and 6 of the N-RC patients presented with acute oliguria (p = 0.01). The initial mean arterial pressure was significantly higher in the RC than the N-RC group (178 +/- 17 vs. 160 +/- 27 mm Hg; p = 0.03). Although not statistically significant, more females recovered (8 of 12 vs. 16 of 42; p < 0.1). More patients presenting with serum creatinine concentrations < 1,000 mumol/l (11 mg/dl) recovered (p = 0.09), while the presence of microangiopathic-haemolytic anaemia occurred more frequently in the RC (7 of 10) than in the N-RC (15 of 35) group (p = 0.16)> Age, kidney size, and the presence of hypertensive retinopathy did not distinguish between the two groups. RC patients had a greater long-term survival (Mantel-Cox chi2 = 4.48; p = 0.03). The renal function RC may be related to the type of dialysis provided (intermittent peritoneal dialysis) and to the use of modern potent peripheral vasodilator antihypertensive agents. Potential renal function RC should always be considered in patients being dialyzed for primary malignant hypertension.

Adult↗

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.

Cells, Cultured↗

Effect of calcium supplement preparation containing small amounts of citrate on the absorption of aluminium in normal subjects and in renal failure patients.

It is well known that Al absorption is markedly enhanced by citrate. The aim of the study was to document whether low-dose citrate ingestion (4 g/day) contained in a well-known effervescent calcium supplement was sufficient to increase Al absorption in 16 normal volunteers and 15 subjects with stable chronic renal failure under conditions of either Ca carbonate or Al hydroxide supplementation. Serum and urine Al levels were measured using flameless atomic absorption spectrophotometry as previously described. After Ca carbonate plus Ca citrate ingestion, there was no rise over baseline (Ca Carbonate alone) serum or urine Al levels in either group. Ca carbonate and Al hydroxide taken together produced a significant rise in serum and urine Al levels in both groups. Maintaing Al hydroxide but substituting Ca citrate for the carbonate (same dose of elemental Ca) produced a further significant increment in serum Al (0.47 +/- 0.28-1.15 +/- 0.8 mumol/l; p < 0.001) and in urine Al(1.37 +/- 0.46-5.77 +/- 5.21 mumol/l; p < 0.001) in the chronic renal failure group as well as in serum Al (0.42 +/- 0.2-0.76 +/- 0.48 mumol/l; p < 0.001) and urine Al (2.70 +/- 1.24-8.24 +/- 3.96 mumol/l; p < 0.001 in the normal volunteer group. Due to decreased urine excretion, the increment in serum Al in the CRF group was significantly greater than in the normal subjects (p < 0.02). Thus small quantities of citrate present in effervescing Ca supplements can significantly enhance intestinal Al absorption even in normal subjects. All citrate-containing preparations are totally contra-indicated in chronic renal failure patients ingesting Al-containing compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Renal allograft preservation: a comparison of University of Wisconsin solution and of hypothermic continuous pulsatile perfusion.

A study was performed to compare early allograft function in kidneys preserved with University of Wisconsin (UW) solution to kidneys preserved by hypothermic pulsatile perfusion. The study consisted of two sets of data. The first set was a donor-paired study (matched data) of 30 heart-beating, hemodynamically stable donors. After removal from the donor each cooled kidney was individually prepared for preservation. One kidney was flushed with +/- 500 ml of UW solution and stored in UW solution on slushed ice. The other kidney was continuously perfused with cooled (4-6 degrees C) cryoprecipitated plasma. The kidneys were transplanted into suitable recipients in a random sequence. Twelve donors were excluded from the study because one or both kidneys were transplanted into recipients who had previously been transplanted. The remaining 36 kidneys were implanted into two similar groups after a mean of 19 hours in the pulsatile perfusion group and 18 hours in the UW solution group. The second set of data consisted of all the kidneys preserved in UW solution (n = 62) at our institution and of 57 kidneys preserved by hypothermic continuous pulsatile perfusion during the same period (mixed data) and was used to evaluate the effect of prolonged preservation (longer than 24 hours) on delayed graft function. Both of these groups were also comparable. Acute tubular necrosis (ATN) was defined as the need for dialysis during the 1st week after transplantation, and delayed function as the delayed clearance of creatinine during the early post-operative phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Phosphorylation of endogenous protein in primate kidney: effects of modulators of calcium/calmodulin-dependent kinases.

1. Phosphorylation of endogenous proteins in response to calcium and calmodulin was assessed in membrane and cytosol from primate kidney. 2. Quantitative studies showed that calcium and calmodulin had little effect on phosphorylation in baboon kidney cytosol; in membranes, phosphorylation was significantly decreased by calcium and calmodulin. 3. Phosphorylation of specific proteins which had been electrophoretically separated indicated that calmodulin, in the absence or presence of calcium, enhanced bands of masses 37.1 +/- 1.1 kDa and 103.3 +/- 6.2 kDa (N = 6) in cytosol fractions of baboon kidney; in membrane fractions no effect was noted. 4. Similar results were found in normal human kidney.

Animals↗

Phosphorylation of endogenous protein in primate kidney. Effects of cyclic AMP.

1. Phosphorylation of endogenous proteins in response to cyclic AMP was assessed in membrane and cytosol from primate kidney. 2. Quantitative studies showed that cAMP significantly increased phosphorylation in baboon kidney membranes; in cytosol there was no effect. 3. Phosphorylation of specific proteins which had been electrophoretically separated showed that five major bands were intensified by cAMP in baboon membranes; in cytosol, three bands were intensified. Similar results were found in normal human kidney. 4. Photoaffinity labelling indicated that a 56 kDa band phosphorylated in cytosol may correspond to the regulatory subunit of type II cAMP-dependent protein kinase.

Affinity Labels↗

The relevance of more sensitive ancillary crossmatch techniques in predicting early cadaver renal graft outcome.

The predictive value of varying levels of antibody activity, its class and antigen specificity in sera of 81 recipients of cadaver renal allografts was evaluated. Recipients for transplantation were selected on the basis of a negative dye uptake T-cell crossmatch, after which the more sensitive 51Cr release technique was employed in a blind study using unseparated donor target cells. Recipient sera with peak panel reactivity and current samples were evaluated before and after reduction with dithiothreitol to destroy the IgM subclass. Double absorption with pooled platelets allowed antibodies against HLA class I antigens to be distinguished from those against HLA class II/non-HLA antigens. Optimal levels of cytotoxicity were established, giving a sensitivity of 73%. Data were assessed in terms of positive predictive value, and showed that conventional T-cell crossmatching is adequate for the primary transplant group, but more sensitive ancillary tests are indicated for regrafts. In this category of patients, IgG antibodies, whether against HLA class I antigens or HLA class II/non-HLA antigens, were highly predictive of early graft loss (positive predictive value 50%-100%). Using this protocol for patient selection, 1-month graft survival would have improved from 73% to 96%.

Adolescent↗