Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Kupffer cell depletion in vivo results in preferential elimination of IgG aggregates and immune complexes via specific Fc receptors on rat liver endothelial cells.

In the present study we have investigated the clearance kinetics and tissue distribution of monomeric (m) IgG and soluble aggregates of IgG (AIgG) and immune complexes (IC) in normal and Kupffer cell (KC) depleted rats. In normal rats, clearance of mIgG occurred in a biphasic manner with a first half-life (T1/2) (T1) of 36.3 +/- 6.3 min and a second T1/2 (T2) of 168.4 +/- 4.7 min. AIgG composed of 20-27 IgG molecules per aggregate were cleared significantly faster than mIgG with a T1 of 2.5 +/- 0.1 min and a T2 of 32.5 +/- 5.6 min. KC depletion did not have a significant effect on the clearance rate of mIgG (T1: 33.4 +/- 8.9 min; T2; 159.5 +/- 12.5 min), while clearance of AIgG was delayed significantly with T1 4.8 +/- 0.7 min and T2 41.2 +/- 3.2 min. Eight minutes after injection, 77% of AIgG was found in the liver in normal rats while 62% was found in the liver of KC-depleted rats. Double immunofluorescence studies indicated that AIgG in the liver was associated with KC and endothelial cells (EC) in normal rats. In KC-depleted rats, AIgG was strongly associated with EC. A similar staining pattern was observed when IgG-immune IC were administered. The clearance of AIgG in KC-depleted rats was inhibited fully by pre-administration of high concentrations of IgG but not by pretreatment with IgA. asialofetuin (ASFe) or ovalbumin (OVA). Aggregated F(ab')2IgG was cleared with a comparable rate to mIgG from the circulation, again suggesting Fc gamma receptor-mediated elimination of AIgG by EC. There was a reduced degradation of AIgG in rats depleted of KC as compared with normal rats. These data suggest binding and degradation of AIgG by EC in vivo.     

Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells.

We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes.     

Semiautomated determination of minimum bactericidal concentrations of antibiotics

Using a newly devised 50-channel photometer which records the opacity of growing bacterial cultures, it was shown that the time taken by cultures diluted 1/1000 in fresh broth to reach 50% of the opacity of a fully grown culture was inversely related to the concentration of organisms in the original culture. This relation was used to determine the numbers of survivors after exposure to benzylpenicillin and gentamicin alone and in combination. The procedure is commended as a labour-saving and potentially rapid method of obtaining comprehensive information on the bactericidal action and interaction of antibiotics.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Short-arm (1.9 m) +2.2 Gz acceleration: isotonic exercise load-O2 uptake relationship

BACKGROUND: The deconditioning syndrome from prolonged bed rest (BR) or spaceflight includes decreases in maximal oxygen uptake (VO2max), muscular strength and endurance, and orthostatic tolerance. In addition to exercise training as a countermeasure, +Gz (head-to-foot) acceleration training on 1.8-2.0 m centrifuges can ameliorate the orthostatic and acceleration intolerances induced by BR and immersion deconditioning. PURPOSE: Study A was designed to determine the magnitude and linearity of the heart rate (HR) response to human-powered centrifuge (HPC) acceleration with supine exercise vs. passive (no exercise) acceleration. Study B was designed to test the hypothesis that moderate +Gz acceleration during exercise will not affect the respective normal linear relationships between exercise load and VO2max, HR, and pulmonary ventilation (VEBTPS). Study C: To determine if these physiological responses from the HPC runs (exercise + on-platform acceleration) will be similar to those from the exercise + off-platform acceleration responses. METHODS: In Study A, four men and two women (31-62 yr) were tested supine during exercise + acceleration and only passive acceleration at 100% [maximal acceleration (rpm) = Amax] and at 25%, 50%, and 75% of Amax. In Studies B and C, seven men (33+/-SD 7 yr) exercised supine on the HPC that has two opposing on-platform exercise stations. A VO2max test and submaximal exercise runs occurred under three conditions: (EX) exercise (on-platform cycle at 42%, 61%, 89% and 100% VO2max) with no acceleration; (HPC) exercise + acceleration via the chain drive at 25%,50%, and 100% Gzmax (35%, 72% and 100% VO2max); and (EXA) exercise (on-platform cycle at 42%, 61%, 89%, and 100% VO2max) with acceleration performed via the off-platform cycle operator at +2.2+/-0.2 Gz [50% of max (rpm) G]. RESULTS: Study A: Mean (+/-SE) Amax was 43.7+/-1.3 rpm (mean = +3.9+/-0.2, range = 3.3 to 4.9 Gz). Amax run time for exercise +acceleration was 50-70 s, and 40-70 s for passive acceleration. Regression of X HR on Gz levels indicated explained variances (r2) of 0.88 (exercise) and 0.96 (passive). The mean exercise HR of 107+/-4 (25%), to 189+/-13 (100%) bpm were 43-50 bpm higher (p < 0.05) than comparable passive HR of 64+/-2 to 142+/-22 bpm, respectively. Study B: There were no significant differences in VO2, HR or VEBTPS at the submaximal or maximal levels between the EX and EXA runs. Mean (+/-SE) VO2max for EX was 2.86+/-0.12 L x min(-1)(35+/-2 ml x min(-1) x kg(-1)) and for EXA was 3.09+/-0.14 L x min(-1) (37+/-2 ml-min(-1) x kg(-1)). Study C: There were no significant differences in the essentially linear relationships between the HPC and EXA data for VO2 (p = 0.45), HR (p < 0.08), VEBTPS (p = 0.28), or the RE (p = 0.15) when the exercise load was % VO2max. CONCLUSION: Addition of + 2.2 Gz acceleration does not significantly influence levels of oxygen uptake, heart rate, or pulmonary ventilation during submaximal or maximal cycle ergometer leg exercise on a short-arm centrifuge.