Iron, ascorbate and copper status of Sowetan Blacks with calcific chronic pancreatitis

Vitamin C can be used to overcome oxidative stress and ease pain in chronic pancreatitis. But its use is deprecated in conditions of tissue iron overload, because its bioactive form, ascorbate, can accelerate free-radical reactions that are driven by transition metals. We measured iron, ascorbate and copper in Sowetan Blacks (RSA) with chronic pancreatitis, obtaining serum/plasma from 14 consecutive patients and 15 controls. Compared with data from corresponding groups in Manchester, African samples had less ascorbate (p < 0.0001), but more caeruloplasmin (p < 0.0001). African and British controls had comparable iron and iron-binding capacity. Plasma from African patients had less ascorbate than that from African controls (p < 0.005) and in six samples, ferritin exceeded 300 micrograms/l (677 pmol/l). Low- molecular-mass iron or copper, capable of participating in free radical reactions, was not detected. British patients, had similar caeruloplasmin levels to African patients but higher ascorbate levels. There is no evidence of iron overload in our African samples. Outwardly healthy controls from Soweto have elevated levels of caeruloplasmin, possibly to compensate for dietary deficiency of ascorbate. Persistent oxidative stress is a unifying feature of chronic pancreatitis, but its degree is higher in African than British patients. Supplements of vitamin C should be safe in Blacks of southern Africa.      

Failure of Dietary Protein and Phosphate Restriction to Retard the Rate of Progression of Chronic Renal Failure: A Prospective, Randomized, Controlled Trial

SUMMARY Ninety-five patients (63 male, 32 female), age 45±2 years(mean±SEM) with chronic renal failure of varied aetiologywere randomized to receive either a conventional low proteindiet (0.6 g/kg/day protein, 800 mg phosphate; n=33), a low phosphatediet (providing approximately 1000 mg phosphate plus an orallyadministered phosphate binder, minimum protein intake 0.8 g/kg/day;n=30) or to control (minimum protein intake 0.8 g/kg/day, nophosphate restriction; n=32). Patients were reviewed for a minimumof 6 months before randomization and were withdrawn from thestudy if plasma creatinine exceeded 900 µmol/1, plasmaphosphate was > 2.0 mmol/1 or at the onset of uraemic symptoms. Following randomization patients were studied for an averageof 19±3 months. Mean plasma creatinine rose from 398±33to 600±50 µmol/1. Dietary protein intake was estimatedat 0.69±0.02 g/kg/day in the low protein group, 1.02±0.05in the low phosphate and 1.14±0.05 in the controls, phosphateintake was 815±43, 1000± 47, and 1315±57mg/day, respectively. Urinary urea excretion and protein catabolicrates were significantly reduced (p<0.01) only in those onprotein restriction, at 213±9 mmol/24 hours and 0.71g/kg/day, respectively. Phosphate excretion was significantlylower (p<0.05) in both the low protein group (17.9±0.8mmol/24 hours) and the low phosphate group (18.6±1.0mmol/24 hours) compared to controls. Changes in body weight,muscle mass and serum transferrin, albumin and immunoglobulinswere comparable between the groups. Mean blood pressure followingrandomization was 150/89±3/1 (low protein), 148/87±3/1(low phosphate) and 146/87±3/1 (controls). Progression of renal failure was analysed by rate of fall ofcreatinine clearance (ml/min/ 1.73 m²/month), by rate of deteriorationderived from reciprocal plasma creatinine against time plots(1/mmol/year) and to assess individual patient's response totreatment by two phase linear regression (‘breakpoint’)analysis of reciprocal plasma creatinine/time plots. Progressionwas analysed only in patients seen for at least 3 months followingrandomization. The rate of fall of creatinine clearance was not significantlydifferent between the groups (ANOVA): 0.56±0.08 ml/min/1.73m2/month (low protein, n=28), 0.44±0.07 (low phosphate,n=23) and 0.69±0.11 (control, n=27). In 50 patients (18low protein, 16 low phosphate and 16 control) whose rate ofprogression could be calculated before and after randomization,there was a fall in rate of progression averaging 0.18 ml/min/1.73m2/month in those on low protein diet and those on low phosphatediet, but a rise of 0.08 in the controls. These differenceswere, however, not statistically significant. Similar resultswere obtained when the rates of deterioration were calculatedfrom plasma creatinine. Significant individual improvements(p<0.01) in rates of progression by ‘breakpoint’analysis occurred in 17 patients: six on low protein, sevenon low phosphate and in four controls. Sixty-one (72 per cent)of the patients examined by this method showed no significantchange in the rate of progression while seven patients had acceleratedprogression. There was no difference in the requirement formaintenance dialysis facilities between groups. No significant benefit of protein and phosphate restrictionwas therefore demonstrated.     

When should antibody screening tests be done for recently transfused patients?

The American Association of Blood Banks (AABB) requires that blood samples used for pretransfusion testing of recently transfused (or pregnant) patients must be obtained within 3 days of scheduled transfusions. This requirement, which became effective in July 1988, amended Standard G2.000 of the AABB, which previously required that pretransfusion testing must be done on blood samples obtained within 2 days of scheduled transfusions. The present study was designed to estimate the risk associated with adopting the amended version of Standard G2.000. Sixty patients who developed significant unexpected alloantibodies after transfusion were studied retrospectively. Thirteen of the 60 patients were found to have newly detectable antibodies within 83 hours of a sample reported to be negative for the new antibody. Had the amended version of Standard G2.000 been in effect, the detection of some of these antibodies might have been delayed up to 24 hours. It was estimated that the implementation of the new AABB requirement at the authors' institution could potentially place about 1 in 3000 transfused patients at risk for an acute or delayed hemolytic transfusion reaction.     

Contribution of polymerase chain reaction and radioimmunoprecipitation assay in the confirmation of human T-lymphotropic virus infection in French blood donors. Retrovirus Study Group of the French Society of Blood Transfusion

BACKGROUND: To verify the criteria for human T-lymphotropic virus (HTLV) seropositivity in Western blot (WB) proposed by the Retrovirus Study Group of the French Society of Blood Transfusion, 186 blood donations that were repeatedly reactive in HTLV enzyme-linked immunosorbent assay, selected according to their WB pattern, were tested by polymerase chain reaction (PCR) and radioimmunoprecipitation assay (RIPA). STUDY DESIGN AND METHODS: In two commercially available WBs, 12 samples were confirmed as positive (rgp21+p19+p24) and 174 were interpreted as indeterminate (one or two reactivities to these proteins). The primer pairs used for the PCR allowed the amplification of type I (HTLV-I) or type II (HTLV-II) (or both) sequences. The RIPA was performed with two 35S-labeled cell lines: HTLV-I infected HUT 102/B2 and HTLV-II-infected MoT. RESULTS: Of the 12 positive samples, 11 were classified as HTLV-I-positive and one as HTLV-II-positive. Among the 174 indeterminate samples, three (WB pattern: rgp21+, p19+, p24-) were HTLV-I positive in PCR (one of them was positive in RIPA also); the other 171 were HTLV negative. CONCLUSION: In the study of a population in which 97 percent of HTLV infections are due to HTLV-I, these data support the three-protein criteria (rgp21, p19, and p24) for a positive blot reading. No HTLV infection was observed when rgp21 did not react. Consequently, p19 and/or p24 band patterns represent false reactivity and do not require PCR or RIPA confirmation. To discriminate between false- and true-positive results in the absence of MTA-1 or K55 reactivity, PCR and/or RIPA is required only when rgp21 reactivity is associated with one gag band (p19 or p24).     

Isolated headache as the presenting clinical manifestation of intracranial tumors: a prospective study

Isolated headache as the presenting clinical manifestation of intracranial tumors: a prospective study. Cephalalgia 1994;1'4:270-1. Oslo. ISSN 0333-1024We prospectively studied over two years the incidence of headache as the initial and isolated clinical manifestation of adult patients suffering from intracranial tumors ( n = 183). Fifteen patients (8%) exhibited headache as their first and isolated clinical manifestation. Age, sex, neoplasm localization, or pathological diagnosis did not correlate with the presence of headache. Posterior fossa location and hydrocephalus, though not reaching statistical significance, were more frequent in patients who presented with headache as the first symptom. At the moment of diagnosis, 59 (31%) of the patients admitted to headache, though only I out of the 15 patients starting as headache still had this symptom as the only manifestation. From our experience in adults, isolated headache for longer than 10 weeks will only exceptionally be secondary to an intracranial neoplasm.     

Loss of high-affinity thrombin receptors during platelet concentrate storage impairs the reactivity of platelets to thrombin

BACKGROUND: The storage of platelet concentrates (PCs) induces a reduction in the platelet surface expression of glycoprotein (GP) Ib alpha. The location of the platelets' high-affinity binding site for thrombin has been postulated as being located on GPIb alpha. This study attempts to determine whether loss or alteration of GPIb alpha during storage of PCs is related to impairment in the reactivity of platelets to thrombin. STUDY DESIGN AND METHODS: In this study, platelet surface expression of GPIb alpha was monitored by means of flow cytometry, throughout standard storage of PCs for up to 10 days. Two thrombin- induced platelet responses, the binding of radiolabeled fibrinogen and the platelet surface expression of P-selectin, were evaluated. Thrombin- binding assays were also performed to assess the number of thrombin receptors in platelets. RESULTS: The surface expression of the GPIb/IX complex declines during storage of PCs. The thrombin-induced maximal binding of fibrinogen in platelets stored for 3, 7, and 10 days was 77 +/? 7 percent, 60 +/? 20 percent, and 34 +/? 25 percent, respectively, of that found in fresh platelets. Moreover, the concentration of thrombin needed for 50 percent of platelets to express the CD62 antigen P-selectin at the surface increased from 0.05 U per mL in fresh platelets to 0.11, 0.56, and 1.2 U per mL in platelets stored for 3, 7, and 10 days, respectively. Thrombin-binding experiments demonstrated a significant reduction in the number of high-affinity binding sites throughout storage of PCs (55 +/? 21 sites/platelet in 10-day-stored platelets vs. 73 +/? 25 in fresh platelets). A significant correlation was also observed between the number of high-affinity thrombin-binding sites and surface expression of GPIb alpha. Selective blockage of the thrombin-binding site on GPIb alpha with monoclonal antibody LJ-Ib10 also inhibited the response of fresh platelets to thrombin, up to a level equivalent to that found in 3-day-stored platelets. CONCLUSION: The loss of the GPIb alpha-located high-affinity thrombin-binding site may impair the ability of platelets to become activated by thrombin as storage time increases.