Aseptic meningitis associated with high dose intravenous immunoglobulin therapy.
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Biomedical subjects
Publications and source records attributed to M Kruger.
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Female rabbits (n = 36, 6 per group) were immunized with: (i) solubilized isolated porcine zona pellucida (SIZP), which contains ZP1, 82 kDa; ZP3 alpha, 55 kDa; and ZP3 beta, 55 kDa; (ii) a purified preparation of ZP3 alpha and ZP3 beta (ZP3); (iii) purified endo-beta-galactosidase digested glycoproteins ZP3 alpha-(EBGD) and (iv) ZP3 beta-(EBGD) (each about 30% deglycosylated); (v) chemically deglycosylated core proteins ZP3 alpha-(DG) and (vi) ZP3 beta-DG (each greater than 92% deglycosylated). Rabbits injected with saline (n = 6) or Freund's adjuvant (n = 6) served as controls. Rabbits were bled weekly to monitor titres. Every six weeks two animals from each group (n = 16) were selected for unilateral oophorectomy followed by histological examination. Sections were scored for numbers of primary, secondary and tertiary follicles. Anti-ZP3 titres developed in all treatment groups and correlated with carbohydrate content (peak per cent [125I]-labelled ZP3 binding by radioimmunoassay: SIZP 71.9 +/- 1.2, ZP3 70.0 +/- 2.5, ZP3 alpha-EBGD 60.9 +/- 5.3, ZP3 beta-EBGD 56.4 +/- 5.0, ZP3 alpha-DG 56.4 +/- 4.0, ZP3 beta-DG 53.5 +/- 4.3) (means +/- SEM). Animals immunized with SIZP, ZP3 and ZP3 beta-EBGD showed a statistically significant reduction in the number of primary, secondary and tertiary follicles compared with controls (P less than 0.01, MANOVA), whereas animals immunized with ZP3 alpha-EBGD, ZP3 alpha-DG and ZP3 beta-DG did not (P greater than 0.05, MANOVA). These results demonstrate that immunization with purified ZP3 alpha macromolecules (ZP3 alpha-EBGD, ZP3 alpha-DG) or ZP3 beta-DG does not produce histopathological changes in ovaries. Such deglycosylated ZP macromolecules represent potential target antigens for immunocontraceptive development.
Nebulin, a family of giant proteins with size-variants from 600 to 900 kD in various skeletal muscles, have been proposed to constitute a set of inextensible filaments anchored at the Z line (Wang, K., and J. Wright. 1988. J. Cell Biol. 107:2199-2212). This newly discovered filament of the skeletal muscle sarcomere is an attractive candidate for a length-regulating template of thin filaments. To evaluate this hypothesis, we address the question of coextensiveness of nebulin and the thin filament by searching for a correlation between the size of nebulin variants and the length distribution of the thin filaments in several skeletal muscles. A positive linear correlation indeed exists for a group of six skeletal muscles that display narrow thin filament length distributions. To examine the molecular and architectural differences of nebulin size-variants, we carried out immunoelectron microscopic studies to map out epitope profiles of nebulin variants in these muscles. For this purpose, a panel of mAbs to distinct nebulin epitopes was produced against rabbit nebulin purified by an improved protocol. Epitope profiles of nebulin variants in three skeletal muscles revealed that (a) nebulin is inextensible since nebulin epitopes maintain a fixed distance to the Z line irrespective of the degree of sarcomere stretch; (b) a single nebulin polypeptide spans a minimal distance of 0.9 microns from the Z line; (c) nebulin contains repeating epitopes that are spaced at 40 nm or its multiples; (d) nebulin repeats coincide with thin filament periodicity; (e) nebulin variants differ mainly at either or both ends; and (f) nebulin remains in the sarcomere in actin-free sarcomeres produced by gelsolin treatment. Together, these data suggest that nebulin is an inextensible full-length molecular filament that is coextensive with thin filaments in skeletal muscles. We propose that nebulin acts as a length-regulating template that determines thin filament length by matching its large number of 40-nm repeating domains with an equal number of helical repeats of the actin filaments.
Previous studies evaluating porcine zona pellucida antigens for immunocontraceptive purposes have in some cases revealed altered ovarian function in association with antibody response. This study was undertaken in an attempt to identify zona immunogens that do not cause adverse endocrine effects. To this end, we investigated the effects of highly purified preparations of native and deglycosylated pig zona pellucida antigens on ovarian function and immune response in the rabbit. Thirty female rabbits were immunized, 5 per group, with 100 micrograms each of either 1) SIZP, solubilized isolated zonae pellucidae; 2) ZP3, a purified porcine zona preparation containing the two principle glycoproteins, ZP3 alpha and ZP3 beta, endo-beta-galactosidase-digested ZP3 glycoproteins (approximately 30% deglycosylated) termed 3) ZP3 alpha/EBGD and 4) ZP3 beta/EBGD; and chemically deglycosylated ZP3 alpha and ZP3 beta (greater than or equal to 92% deglycosylated), termed 5) ZP3 alpha/DG and 6) ZP3 beta/DG. Rabbits injected with saline (n = 2) or Freund's adjuvant alone (n = 3) served as controls. Serum LH, FSH, estradiol, and progesterone were measured at 5-day intervals during seven 20-day cycles of hCG-induced pseudopregnancy over 42 wk. Anti-ZP3 titers, determined by RIA, developed in all treatment groups and correlated directly with carbohydrate content. Animals immunized with SIZP, ZP3, and ZP3 beta/EBGD showed a significant elevation of LH and FSH and a significant decline of peak progesterone levels by the fourth pseudopregnancy cycle. In contrast, animals immunized with ZP3 alpha/EBGD, ZP3 alpha/DG, and ZP3 beta/DG showed no significant elevations of gonadotropins and continued to display cyclic progesterone secretion in response to hCG.(ABSTRACT TRUNCATED AT 250 WORDS)
The presence of mild hyperoxaluria in recurrent calcium oxalate stone formers is controversial. The aim of this study was to identify recurrent stone formers with mild hyperoxaluria and to classify them further by assessing their response to a low oxalate diet. In addition, the prevalence of other risk factors for stone formation in this group of patients was investigated. A total of 207 consecutive patients with recurrent renal calculi were screened and 40 (19%) were found to have mild hyperoxaluria. Of these, 18 (45%) responded to dietary oxalate restriction by normalising their urinary oxalate. The remaining 22 patients were classified as having idiopathic hyperoxaluria and were subdivided into those in whom urinary oxalate excretion was consistently elevated in all specimens measured and those in whom the elevation was intermittent in nature. Dietary oxalate restriction had a partially beneficial effect in lowering oxalate excretion in the patients with persistent hyperoxaluria. No difference in urinary oxalate excretion was found after dietary restriction in the patients with intermittent hyperoxaluria. Other risk factors, including dietary, absorptive and renal hypercalciuria and hypocitraturia, were documented, the prevalence of which (65%) was not significantly different from that (62.5%) found in 40 age- and sex-matched calcium stone formers without hyperoxaluria. The prevalence of hyperuricosuria was significantly greater in patients with hyperoxaluria when compared with stone controls. Further studies are required to elucidate the underlying mechanisms of hyperoxaluria in recurrent stone formers.
An osseous defect was created in the acetabulum and femur of twenty dogs, and then a fiber-metal total hip prosthesis was inserted. A comparison was made between the effects of leaving the defects unfilled, filling the defects with an autogenous bone graft, and filling them with a 50:50 mixture of autogenous bone graft and a biphasic ceramic composed of hydroxyapatite and tricalcium phosphate. The characteristics of formation of bone within the sites of the defects and the extent of the ingrowth of bone into the underlying porous surface were analyzed. At six and twelve weeks after implantation, the dogs in the control group (unfilled defects) had the least amount of bone in the sites of the defects. In the dogs that had had an autogenous bone graft and those in which the defects had been filled with a mixture of autogenous bone graft and biphasic ceramic, there were excellent osteoconductive properties in the filling of the sites of the defects with new bone. A comparison was made between the amount of bone that formed in the osseous defects and the amount that formed in the spaces of the porous-surfaced fiber-metal components of the prostheses, directly underlying and adjacent to the defects. At six weeks, the greatest amount of ingrowth of bone into the spaces of the underlying titanium fiber-metal acetabular components was seen in the control group (22 per cent of the porous surface), followed by the group in which the defects had been filled with a mixture of autogenous bone graft and biphasic ceramic (19 per cent). The defects that had been filled only with autogenous bone graft had poor ingrowth of bone into the porous surface (4 per cent) and predominantly fibrous ingrowth. At twelve weeks, these defects again showed the least amount of ingrowth of bone (15 per cent) compared with the defects in the control group (24 per cent) and those that had been filled with a mixture of autogenous bone graft and biphasic ceramic (24 per cent). No statistically significant differences were found in the amount of ingrowth of bone into the defects that had been created in the femur in the three groups of dogs at either six or twelve weeks. However, the trends appeared to correlate with the data for the acetabular defects.
The current treatment for uncomplicated rib fractures is the exclusion of associated injuries followed by symptomatic treatment with analgesics. Encouragement of deep breathing is also recommended to avoid secondary or delayed pulmonary complications. The use of circumferential rib belts in treating patients with acute rib fractures has been discouraged because of possible complications from restricted ventilation. A review of the literature revealed no previous clinical studies to support this view. We designed and conducted a controlled, prospective, randomized pilot study to determine if there was any increased morbidity associated with the use of rib belts in the treatment of patients with acute rib fractures. Twenty-five adult patients with radiographically proven acute rib fractures were randomized into two groups. The first group was treated with analgesics and a standard circumferential rib belt (Zimmer Universal Rib Belt). The second group was treated with oral analgesics alone. Patients were contacted by telephone three days after the initial injury and then reexamined 14 days postinjury. Rates of pain resolution, compliance, and delayed complications were determined. Rib belts were not found to significantly reduce the severity of pain. Four complications (one case of bloody pleural effusion requiring hospitalization, two cases of asymptomatic discoid atelectasis, and one case of allergic contact dermatitis) were identified, all occurring in the group of patients receiving rib belts. This pilot study indicates that while rib belts are widely accepted by patients for control of pain, they appear to be associated with an increased incidence of complications. Clinical studies with larger sample sizes will be needed to confirm these findings.
An atherogenic diet (AD) consisting entirely of normal foods for westernized people was fed to female Vervet monkeys for 4 years. The plasma low density lipoprotein (LDL) cholesterol pool was increased and progression of atherosclerosis was enhanced by the AD compared to a more prudent Western diet. The increased LDL-cholesterol was carried by a 3-fold increase in particles of relatively normal composition and not by packing cholesterol esters into the cores of enlarged LDL particles, as has been reported after feeding semisynthetic diets loaded with extra cholesterol. Nevertheless, these LDL particles were atherogenic. The AD changed the fatty acid composition of LDL-cholesterol esters and triacylglycerol, notably by increasing arachidonic and reducing linoleic acid. Multivariate analysis showed that measures and scores of atherosclerosis were significantly dependent on sphingomyelin and phosphatidylcholine in LDL and on arachidonic acid in LDL-triacylglycerol. Although apolipoprotein B, free cholesterol, esterified cholesterol and lysophosphatidylcholine in plasma LDL and atherosclerosis were significantly positively correlated in bivariate analysis they were not selected by multivariate analysis as the strongest determinants of atherogenesis. Cholesterol in plasma high density lipoprotein was not changed by the AD and lecithin:cholesterol acyltransferase activity in plasma was inversely linked to atherosclerosis. Subcutaneous fatty acids reflected dietary fatty acids.
In order to estimate the prevalence of diabetic neuropathy in proximal and distal peripheral nerves, femoral and peroneal motor conduction was evaluated in 61 diabetic children, adolescents and young adults whose type 1 diabetes had become clinically apparent before the age of 14 years. Femoral motor nerve conduction velocity (FMNCV) in diabetic patients (63.8 +/- 10.4 m/sec) was not significantly different from FMNCV in control subjects (65.6 +/- 7.1 m/sec). By contrast, peroneal motor nerve conduction velocity (PMNCV) in diabetic patients (50.2 +/- 6.9 m/sec) was significantly lower than in controls (54.1 +/- 3.5 m/sec). Distal motor weakness, sensory deficit and absent Achilles reflexes were strongly correlated to impaired motor conduction in peroneal and also in femoral nerve. Peroneal nerve abnormality was negatively correlated with HbA1 levels, while femoral nerve abnormality was positively correlated with the presence of retinopathy. This discrepancy is not fully understood. Age and duration of diabetes were unrelated to femoral or peroneal motor nerve conduction velocity. Our data emphasize the frequent occurrence of subclinical proximal neuropathy in diabetic children and adolescents.
The hyponatraemia common in decompensated cirrhosis arises in part from secretion of antidiuretic hormone attributed to a decrease in effective blood volume. Baroreceptors send inhibitory impulses to the midbrain and hypothalamus through the vagus and glossopharyngeal nerves. Since vagal neuropathy often occurs in chronic alcoholism, this might theoretically contribute to the inappropriate secretion of antidiuretic hormone, which might in turn induce hyponatraemia. In a prospective study including 34 patients with cirrhosis a high incidence of vagal neuropathy was found in the alcoholics (64%) and a clear cut increase in the incidence of hyponatraemia in patients with evidence of vagal damage and ascites (seven of eight patients (88%); p = 0.02). Results of a retrospective study of 64 patients with cirrhosis and ascitic decompensation showed hyponatraemia in 17 (50%) of 34 alcoholics but in only four (13%) of 30 patients with non-alcoholic disease (p = 0.006). Vagal neuropathy in alcoholic cirrhosis may contribute to the low serum sodium concentrations commonly found in these patients.
After a lower hemi-cervical spinal cord injury, a patient presented with a left hemiplegia and on the same side a unilateral chest wall paradoxical motion mimicking a flail chest. X-rays demonstrated a left hemilateral C6 injury but no rib fractures. We demonstrated that the paradoxical motion was due to the action of the diaphragm acting on the rib cage with intercostal respiratory paralysis on the side of hemiplegia.
Two cases with bilateral traumatic oculomotor palsy are presented. The clinical signs, diagnosis criteria, and mechanisms of injury are discussed with a special emphasis on the absence of early reliable prognosis factors. The possibility of recovery depends on the anatomic lesion and not on the ophthalmologic findings in the acute phase.
A 31/2-month-old girl with juvenile osteopetrosis is described. She presented with failure to thrive, a blocked nose, anaemia and hepatosplenomegaly and had dense sclerotic bones on radiography. This disease, which is potentially lethal, may be cured by bone marrow transplantation in selected cases.
To investigate incipient diabetic neuropathy, peroneal motor nerve conduction velocity (PMNCV) was measured in 61 diabetic children and adolescents whose type 1 diabetes became clinically apparent before the age of 14 years. PMNCV in diabetic patients (48.3 +/- 5.6 m/s) was significantly lower than in controls (56.5 +/- 5.5 m/s), 23 diabetics (36%) having a value more than 2 SD below the mean for normals. There was a highly significant negative correlation between PMNCV and HbA1 levels concomitant with PMNCV measurement or mean annual HbA1 concentrations preceding PMNCV. The relationship between PMNCV and the clinical score of diabetic control since the onset of the disease was also significant. Age, duration of diabetes and HLR-DR antigens were unrelated to PMNCV. EEG abnormalities and retinopathy, whose pathogenesis is different, were not necessarily associated with subclinical neuropathy. Being easy and sensitive, PMNCV determination provides the paediatric diabetologist and the patient himself with an important motivation to improve diabetic control.
A method of neurophysiological evaluation of the motor conduction in the femoral nerve is reported. The range of normal values is determined in 20 subjects, 23-82 years old. It is different from the conduction velocity in the peroneal nerve. These data can be useful in the evaluation of lesions of the femoral nerve.
The effects of the prostaglandin derivative PGBx on calcium release and uptake by skeletal muscle sarcoplasmic reticulum (SR) and on (Ca2+ + Mg2+)- adenosine triphosphatase (ATPase) activity were studied using skeletal muscle from rabbit hind legs. Both calcium uptake and Ca2+-ATPase activity were significantly inhibited by PGBx. Addition of PGBx to SR vesicles resulted in the release of calcium. It is proposed that this action of PGBx could be effected by the inhibition of ATPase and resulting passive release of calcium. The possibility also exists that PGBx could decrease the capacity of the SR vesicles for calcium in addition to any possible ionophoretic properties.
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