B cell cytopenia in two brothers with hyper-IgD and periodic fever syndrome.

UNLABELLED: We report on two brothers with hyperimmunoglobulinemia D (patient 1: serum immunoglobulin D [IgD] concentration initially 61 IU/ml, later on 340 IU/ml; patient 2: serum IgD concentration 144 IU/ml; normal <100 IU/ml, 97th centile) and periodic fever syndrome (HIDS). Both are compound heterozygous for the mevalonate kinase (MVK) mutations V377I and I268T. They developed significant B cell cytopenia (7%, 129/microl and 11%, 132/microl, respectively; normal ranges 12-22%, 300-500/microl) with hypogammaglobulinemia (IgG 5.48 g/l and IgG 5.22 g/l, respectively; normal range IgG 6-13 g/l). Furthermore, the clinical spectrum shows an interesting atypical autoinflammatory symptomatology. The therapy consisted of prednisone, azathioprine, and intravenous immunoglobulins (IVIG), which results in reduced incidence and severity of febrile attacks. CONCLUSION: The pathogenesis and clinical presentation of HIDS is still not fully understood and show a great variability. To our knowledge, severe B cell cytopenia in children with HIDS has not been reported before. Furthermore, the therapy of febrile episodes is still performed on an individual basis in affected patients.

Serum asparaginase activities and asparagine concentrations in the cerebrospinal fluid after a single infusion of 2,500 IU/m(2) PEG asparaginase in children with ALL treated according to protocol COALL-06-97.

BACKGROUND AND PROCEDURE: Pharmacological surrogate parameters are considered a useful tool in estimating the treatment intensity of asparaginase (ASNase) preparations. When a pegylated ASNase (single infusion of 2,500 IU/m(2) polyethylene glycol (PEG)-ASNase, Oncaspar) was introduced into the treatment protocols of the German Cooperative Acute Lymphoblastic Leukaemia (COALL) study group, this was accompanied by a drug monitoring programme measuring serum ASNase activity and asparagine (ASN) concentrations in the cerebrospinal fluid (CSF) in 70 children. RESULTS: Four hundred fifty-nine serum samples from 67 evaluable patients showed medians of ASNase activity of 1,189.5, 824.5, 310.5, 41 and 4 U/l on day 7 +/- 1, 14 +/- 1, 21 +/- 1, 28 +/- 1 and 35 +/- 1 respectively. One hundred eighty-four samples from 59 patients were evaluable for ASN concentrations in the CSF. The medians of ASN concentration were <0.2, 0.2, 0.9 and 3.2 microM on day 14 +/- 1, 21 +/- 1, 28 +/- 1 and 35 +/- 1 respectively. When relating CSF ASN levels to the serum ASNase activity measured on the same day, a median of 1.2 microM CSF ASN was associated with values of serum ASNase activity between > or =2.5 and <100 U/l. Serum ASNase activity values > or =100 U/l were associated with a median CSF ASN of <0.2 microM, with 13/27 samples being incompletely depleted. CONCLUSIONS: The treatment intensity achieved with PEG ASNase in the present study appears to be acceptable based on the surrogate of serum ASNase activity. However, the pharmacological objective of ASNase treatment, that is, complete CSF ASN depletion with an ASNase activity >100 U/l, was not ensured. Nevertheless, one must also be aware that the minimum ASN concentration required for leukaemic cell growth is yet to be established.

Asparagine concentration in plasma after 2,500 IU/m(2) PEG-asparaginase i.v. in children with acute lymphoblastic leukemia.

UNLABELLED: Polyethylene glycol conjugated asparaginase (PEG-ASNase) can be substituted in cases of hypersensitivity to native Escherichia coli asparaginase. We measured asparagine (asn) levels in plasma after a single dose of 2,500 IU/m(2) i.v. PEG-ASNase (Oncaspar) in consolidation treatment of ALL and compared those with data from the previous protocol COALL-05-92. This protocol was similar to COALL-06-97, except that children had been given 45,000 IU/m(2) C-ASNase instead of PEG-ASNase. PATIENTS AND METHODS: Between May 2000 and December 2001 seventy-one children (38 boys, 33 girls) with newly diagnosed ALL treated according to the multicenter protocol COALL-06-97 were investigated in this study. Four hundred and seventy-four plasma samples (71 patients) were analysed by ion exchange chromatography after column derivatization with o-phthaldialdehyde. For comparison data (350 plasma samples) from 51 patients treated according to the protocol COALL-05-92 were available. The same method for detection of asn in plasma was used. RESULTS: The median asparagine level in plasma after 2,500 IU/m(2) PEG-ASNase i.v. was below the limit of detection for at least 5 weeks in 81 % of the patients. When divided into high risk (HR) and low risk (LR) group, HR patients who had previously received one dose more of C-ASNase showed a markedly shorter depletion than the LR patients compatible with a higher risk of antibody formation and consequent silent inactivation after a higher number of exposures to ASNase. In the previous protocol COALL-05-92 median asn levels in plasma after 45,000 IU/m(2) native C-ASNase i.v. were below the limit of detection for at least 5 weeks in 65 % of the patients. CONCLUSIONS: 2,500 IU/m(2) PEG-ASNase led to an equally long depletion of asn in plasma as did 45,000 IU/m(2) native C-ASNase i.v. used in COALL-05-92.

Sealed restorations: 5-year results.

This clinical study determined the feasibility of a sealed resin composite restoration to arrest dental caries using a minimal tooth preparation: a bevel in enamel only without removal of the carious lesion. These ultra-conservative sealed composite restorations placed over caries (CompS/C) were compared with ultra-conservative sealed amalgam restorations (AGS) that had no "extension for prevention". The CompS/C restorations were also compared with the traditional (unsealed) amalgam restorations (AGU) with the "extension for prevention" outline form. Caries progress, as determined by standardized radiographs, revealed that after 5 years caries remained arrested under the CompS/C restorations; the marginal integrity was similar for the CompS/C and the AGS groups, and exhibited highly significant superiority to the AGU restorations (Chi square, P less than = 0.00004). Complete sealant retention over the amalgam restorations (AGS group) was less than over the composite restorations (CompS/C), and conversely, partial sealant retention was higher for the AGS group. Sealants also appeared to protect the posterior composite restorations against wear.

Sealed restorations: 4-year results.

The overall objective of this clinical study was to determine the feasibility of using a sealed composite restoration to arrest caries. This objective was to be achieved using minimal tooth preparation for Class I lesions, without the traditional Class I cavity preparation and without the removal of the carious lesion. The minimal tooth preparation consisted of no [corrected] removal of the carious lesion, bevel in enamel only, and usually not requiring any anesthetic injection. These ultra-conservative sealed composite restorations placed over caries (CompS/C) were compared with ultra-conservative sealed amalgam restorations (AGS) and with the traditional (unsealed) amalgam restorations (AGU). This study showed that: 1) caries is arrested under the CompS/C restoration for a period of 4 years; 2) sealant retention is similar in both the CompS/C and the AGS groups; 3) the marginal integrity of the AGS restorations is markedly superior to that of the AGU restorations; and 4) sealant appears to prevent wear of posterior composite restorations.

Ultraconservative sealed restorations: three-year results.

The overall objective of this clinical study was to determine the feasibility of using a sealed composite restoration to arrest caries without the removal of the carious lesion and without the traditional cavity preparation. The minimal tooth preparation (a bevel in enamel) usually did not require any anesthetic injection and conserved tooth structure. These ultraconservative sealed composite restorations placed over caries (CompS/C) have been compared with ultraconservative sealed amalgam restorations (AGS) and with the traditional outline form (unsealed) amalgam restorations (AGU). This clinical study has shown that: (1) caries can be arrested by the CompS/C restoration for a period of three years; (2) the marginal integrity of the AGS restorations showed a definite trend toward improvement as compared to the AGU restorations; and (3) complete sealant retention over posterior restorations was similar in both the CompS/C and the AGS groups during the first two years; however, at Year 3 complete sealant retention was 16 percent higher in the CompS/C than in the AGS group.

Microleakage of root restorations.

This study evaluated the microleakage of various restorative materials placed in root surfaces. A minimum of 20 freshly extracted single-rooted teeth were used for each combination of restorative materials. Four preparations were made on the root surface and each restored with a different material. After thermocycling in dye, the root was cut transversely in several sections through the restoration, and microscopically examined to record the microleakage at the interface between restorative materials and tooth. Results indicated that fewer composite resin specimens allowed microleakage into dentin as compared with either amalgam or glass ionomer materials.

An epizootic of avian botulism in a phosphate mine settling pond in northern Florida.

Type C botulism was determined to be the cause of an epizootic among waterfowl and shorebirds in a phosphate mine settling pond in northern Florida during May and June of 1979. Several hundred birds, the most common of which were American coots (Fulica americana), wood ducks (Aix sponsa), common gallinules (Gallinula chloropus), and northern shovelers (Anas clypeata), were afflicted over about a three-week period. A second smaller outbreak occurred in the same pond in early December of 1979. This is apparently the first time that botulism has been reported in waterbirds of Florida.