The Boston AIDS Survival Score (BASS): a multidimensional AIDS severity instrument.

OBJECTIVES: This study developed a new acquired immunodeficiency syndrome (AIDS) severity system by including diagnostic, physiological, functional, and sociodemographic factors predictive of survival. METHODS: Three-hundred five persons with AIDS in Boston were interviewed; their medical records were reviewed and vital status ascertained. RESULTS: Overall median (+/- SD) survival for the cohort from the first interview until death was 560 +/- 14.4 days. The best model for predicting survival, the Boston AIDS Survival Score, included the Justice score (stage 2 relative hazard [RH] = 1.25, 95% confidence interval [CI] = 0.80, 1.96; stage 3 RH = 1.76, 95% CI = 1.15, 2.70), a newly developed opportunistic disease score (Boston Opportunistic Disease Survival Score; stage 2 RH = 1.35, 95% CI = 0.90, 2.02; stage 3 RH = 2.10, 95% CI = 1.38, 3.18), and measures of activities of daily living (any intermediate limitations, RH = 1.84, 95% CI = 1.05, 3.21; any basic limitations, RH = 2.60, 95% CI = 1.44, 4.69). This model had substantially greater predictive power (R2 = .17, C statistic = .68) than the Justice score alone (R2 = .09, C statistic = .61). CONCLUSIONS: Incorporating data on clinically important events and functional status into a physiologically based system can improve the prediction of survival with AIDS.     

Internal and external information processing by lateral hypothalamic glucose-sensitive and insensitive neurons during bar press feeding in the monkey

Single neuron activities in the lateral hypothalamic area (LHA) were recorded during bar press feeding task in the monkey. First registered neurons were sorted into 2 groups, glucose-sensitive (GS) and glucose-insensitive (GIS) neurons, depending on their glucose sensitivity. Then firing variations to feeding, electrophoretically applied catecholamines and opiate, and to odor and taste stimuli were investigated. GS neurons responded to dopamine, noradrenaline and morphine more often than GIS neurons. In feeding task GS neurons responded during bar press (BP) and reward (RW) periods with long-lasting inhibition of firing and at cue tone (CT) with transient inhibition, while GIS neurons responded during BP and RW periods mainly with excitation and at cue light (CL) with excitation. A majority of GS neurons responded to both odor and taste stimuli more often than GIS neurons. Data suggest that these two kinds of neurons in the LHA may be involved in different functional aspects of feeding: GS neurons, mainly in internal information processing and reward mechanism, and GIS neurons, in external information processing and motor aspects.     

One-year results: palatal implants for the treatment of obstructive sleep apnea.

OBJECTIVE: To evaluate long-term effectiveness of palatal implants for treatment of mild to moderate obstructive sleep apnea (OSA). STUDY DESIGN: A prospective study of 26 referred patients with a pretreatment apnea-hypopnea index (AHI) of 10 to 30 and a body mass index of < or =30, representing an extended follow-up of a subset of 41 patients enrolled in previous short-term trials. RESULTS: Twenty-one of 26 patients (80.8%) experienced a decrease in AHI. Fifteen of 26 patients (57.7%) had a follow-up AHI <10 at 1 year, whereas 13 patients (50%) had a 50% or greater reduction to an AHI <10 at 1 year. Mean AHI was reduced from 16.5 +/- 4.5 at baseline to 12.5 +/- 10.5 at 3 months (P < 0.014) and to 12.3 +/- 12.7 at 1 year (P < 0.019). CONCLUSIONS: Patients initially responding to palatal implants with improved AHI maintained improvement through long-term follow-up at 1 year.     

Closing patellar tendon defects after anterior cruciate ligament reconstruction: absence of any benefit

The most common graft in anterior cruciate ligament (ACL) surgery involves using the central one-third of the patellar tendon. Knowledge concerning the postoperative disability after harvesting the patellar tendon is, however, limited. The aim of this study was to evaluate the impact patellar tendon suture and bone grafting of the patellar bone defect might have in terms of functional outcome and patellofemoral pain after harvesting the bone-tendon-bone graft, compared with leaving the harvested site non-sutured and non-grafted. Sixty patients, scheduled for arthroscopically assisted ACL reconstruction, were randomly allocated to two groups. In group I, suture of the patellar tendon and bone grafting of the patellar defect were performed. In group II, the tendon gap and the patellar defect were left open. Preoperatively, there was no significant difference between the groups when comparing objective knee stability, as measured with a KT-1000 laxity meter, Lysholm score, Tegner activity level, IKDC score, or patellofemoral pain score. Both groups had a significantly improved Lysholm score at the 2-year follow-up, without any difference between them. Tegner's activity level was significantly lower at follow-up, compared with the pre-injury level in both groups. The patellofemoral pain score improved significantly after the reconstruction, without any difference between the groups. Ultrasonography did not reveal any difference between the groups in terms of healing of the tendon gap. This study revealed no differences in donor site morbidity, functional outcome, patellofemoral pain score or knee joint stability between the two treatment groups. The conclusion is that suture of the patellar tendon and bone grafting of the patellar defect do not improve the functional results or reduce donor site morbidity after arthroscopically assisted ACL. Received: 17 December 1996 Accepted: 30 July 1997     

Increased risk of necrotizing enterocolitis in premature infants with patent ductus arteriosus treated with indomethacin.

OBJECTIVE: The authors evaluated the risk of necrotizing enterocolitis (NEC) in very low birth weight infants receiving indomethacin (INDO) to close patent ductus arteriosus (PDA). BACKGROUND DATA: Controversy exists regarding the best method of managing very low birth weight infants with PDA and whether to employ medical management using INDO or surgical ligation of the ductus. METHODS: Two hundred fifty-two premature infants with symptomatic PDA were given intravenously INDO 0.2 mg/kg every 12 hours x 3 in an attempt to close the ductus. Patients were evaluated for sex, birth weight, gestational age, ductus closure, occurrence of NEC, bowel perforation, and mortality. RESULTS: There were 135 boys and 117 girls. The PDA closed or became asymptomatic in 224 cases (89%), whereas 28 (11%) required surgical ligation. Ninety infants (35%) developed evidence of NEC after INDO therapy. Fifty-six were managed medically; surgical intervention was required in 34 of 90 cases (37.8%) or 13% of the entire PDA/INDO study group. Bowel perforation was noted in 27 cases (30%). Factors associated with the onset of NEC included gestational age < 28 weeks, birth weight < 1 kg, and prolonged ventilator support. The overall mortality rate was 25.5%, but was higher in infants with NEC versus those without. The highest mortality was noted in perforated NEC cases. The PDA/INDO patients were compared with a control group of 764 infants with similar sex distribution, birth weights, and gestational ages without PDA who did not receive INDO. Necrotizing enterocolitis occurred in 105 of 764 control patients (13.7%), including 13 (12.3%) with perforation. The overall mortality rate of controls was 25%, which was similar to the overall 25.5% mortality rate in the PDA/INDO study group. CONCLUSION: These data indicate that there is increased risk of NEC and bowel perforation in premature infants with PDA receiving INDO. Mortality was higher in the PDA/INDO group with NEC than those PDA/INDO infants without NEC.     

Indomethacin in canine acute hemorrhagic pancreatitis

The effects of indomethacin administration on hemodynamics were investigated in canine acute hemorrhagic pancreatitis (AHP). Thirteen mongrel dogs were randomly divided into a fluid treatment group, an indomethacin prophylaxis group (IMP), and an indomethacin therapy (IM) group. Indomethacin (5 mg/kg) was administered as a bolus dosage 30 min before the induction of AHP in the IMP group. In the IM group, indomethacin was also given as a bolus (5 mg/kg) in 5 min starting 30 min after the induction of AHP. AHP was induced with a mixture of trypsin and sodium taurocholate infused into the pancreatic duct. Hemodynamics were monitored during the 4.5 h of surveillance time. Heart rate did not change significantly between the groups. Indomethacin prophylaxis maintained mean arterial pressure at a significantly higher level (P less than 0.05) and prevented the initial fall in blood pressure when compared to the fluid treatment or IM group. Indomethacin increased cardiac output (P less than 0.05) in the IM group, but did not differ significantly in the IMP group in comparison with the fluid treatment group. In conclusion, the inhibition of the initial fall in blood pressure by indomethacin in AHP suggests prostaglandins to play a role in hemodynamic changes and pancreatic shock to be "septic" as evaluated by hemodynamic changes.     

Effect of clonidine on ultrasonic vocalization in preweaning rats

Summary The present study was undertaken to investigate the involvement of the noradrenergic neurotransmission system in the ultra sonic callings emitted by rat pups separated from their mother and exposed to cold stimulation. The investigation was primarily performed by help of agents selectively affecting the -adrenoceptors: the ₂-agonist clonidine, the ₁-antagonist prazosin and the ₂-antagonist idazoxan.Clonidine dose-dependently stimulated the amount of ultra sonic vocalization, an effect not solely dependent upon the effect of clonidine on body temperature. In a developmental study it was found that clonidine uniformly stimulated crying at all ages from 4 days of age up to 18 days of age, that is during the whole preweaning period. Clonidine stimulated ultrasonic crying in rat pups, devoid of presynaptic catecholamine (CA) neurons by combined pretreatment with the monoamine depletor, reserpine, and the inhibitor of CAsynthesis, -methyl-tyrosine. This finding suggested that the stimulating effect of clonidine on ultrasonic vocalization was mediated by postsynaptic adrenoceptors.In pups, 12 days of age, idazoxan blocked the effect of cold stimulation on ultra sonic crying, suggesting that ₂-adrenoceptors, presumably postsynaptic ones, mediated this kind of stimulation. Idazoxan also antagonized the effect of clonidine, but only at a dose effective also in control pups. Prazosin had no effect on cold-stimulated crying, but antagonized the effect of clonidine, suggesting that the effect of clonidine was also mediated by ₁-receptors. At 18 days of age, prazosin no longer antagonized the effect of clonidine, whereas the antagonizing action of idazoxan was reinforced.The age-dependent variation in responsiveness to the adrenergic drugs suggest maturational changes in the function of the CA-system occurring between 12–16 days of age.     

Regional brain kinetics of 6-fluoro-(β-11C)-L-dopa and (β-11C)-L-dopa following COMT inhibition. A study in vivo using positron emission tomography

Summary The regional brain kinetics of (-11C)-L-dopa and 6-fluoro-(-11C)-L-dopa was measured in six Rhesus monkeys using positron emission tomography (PET). Radioactivity accumulated specifically in the striatal region and the increase in L-dopa-derived radioactivity utilization with time was calculated using surrounding brain as a reference area, this being devoid of dopaminergic activity. The rate constant for selective striatal utilization i.e. grossly decarboxylation was 0.0110 ± 0.0007 (S.D) and 0.0057 ± 0.0006 min1 for (-11C)-L-dopa and 6-fluoro-(-11C)-L-dopa, respectively. After pre-treatment of the monkeys with the peripherally and centrally active catecholamine-O-methyl transferase (COMT) inhibitor Ro 40-7592 10 mg/kg, the decarboxylation rate remained unchanged (0.0112 ± 0.0015 min-1) for (11C)-L-dopa, whereas an increase in rate was measured for 6-fluoro-(-11C)L-dopa (0.0092 ± 0.0015 min–1). Differences in the distribution of radiolabelled metabolites i.e. the corresponding O-methyl-L-dopa in the reference area is most probably the reason for the difference in calculated decarboxylation rate seen between the radiotracers. The higher decarboxylation rate measured for 6-fluoro-(-11C)-L-dopa after blockade of COMT shows that the radiolabelled metabolites i.e. 6-fluoro-O-methyl-(-11C)-L-dopa significantly contributes to background radioactivity.     

GD3 expression by cultured human tumor cells of neuroectodermal origin

Summary Seven monoclonal antibodies (mAbs) reactive with ganglioside II³(NeuAc)₂-LacCer (GD3) were generated; four of these mAbs (DMAb-21, DMAb-22, DMAb-23, and DMAb-24) by immunizing mice with GD3 adsorbed to Salmonella minnesota and the remaining three (DMAb-7, DMAb-8, and DMAb-17) with melanoma line SK-MEL 28, which contains 1.4 nmol sialic acid of GD3 per mg protein. The specificities of the mAbs were defined by high-performance thin-layer chromatography (HPTLC) immunostain and solid-phase radioimmunoassay (SP-RIA) with a panel of purified gangliosides. DMAb-7 and DMAb-8 reacted with GD3, IV³(NeuAc)₂nLcOse₄Cer(3,8-LD1), and very weakly with IV³(NeuAc)₂II³NeuAc-GgOse₄Cer (GTla), but not with II³NeuAc-LacCer (GM3), II³NeuAcGgOse₃Cer(GM2), II³NeuAc-GgOse₄Cer(GM1), II³NeuAc, IV³NeuAcGgOse₄Cer (GD1a), II³(NeuAc)₂GgOse₃(GD2), II³(NeuAc)₂GgOse₄Cer (GD1b), IV³NeuAcII³(NeuAc)₂, GgOse₄Cer(GT1b), suggesting the binding epitope to be a terminal tetrasaccharide NeuAc2-8NeuAc2-3Gal1-4(Glc or GlcNAc). DMAb-7 and DMAb-8 were used to investigate the expression of GD3 on cultured human tumor cells of neuroectodermal origin. Thirteen of 19 gliomas, 3 of 5 medulloblastomas, 5 of 5 neuroblastomas, 2 of 2 melanomas, and 1 of 3 teratomas were shown to react with DMAb-8 and/or DMAb-7 by cell surface-RIA (CS-RIA) and immunofluorescence (IF) assays. HPTLC and densitometric analysis confirmed these results, as positive immunostains in the GD3 region were obtained with oligoganglioside fractions from 9 glioma, 1 medulloblastoma, 2 neuroblastoma, 1 melanoma, and 1 teratoma cell line. Glioma cell line U-105 MG and medulloblastoma cell line Daoy contain GD3 as shown by HPTLC immunostain analysis of extracts, although GD3 was undetectable on the cell surface as determined by CS-RIA and IF. There was no detectable GD3 found in gangliosides isolated from cell lines U-373 MG, D-54 MG, TE-671, and PA-1, which were negative for both DMAb-7 and DMAb-8 by CS-RIA and IF assay. Our results provide evidence that GD3 is expressed extensively with significant quantitative heterogeneity on cultured human neuroectodermal tumor cells including glioma, medulloblastoma, neuroblastoma, and melanoma.Supported by NIH grants R37 CA11898, NS 20023, and CA32672 and by grants from the Swedish Medical Research Council (project no. 03X-627), Swedish Cancer Society (project no. 2260-B88-01X) and the National Swedish Board for Technical Development (project no. 84-4667)     

The reduction of water intake in rats caused by a low dose of apomorphine is unaltered by α-methyl-p-tyrosine: are autoreceptors not involved?

Summary Low doses of the dopamine (DA) agonist apomorphine (APO) induces a behavioural syndrome characterized by reduced spontaneous activity, reduced food and water intake and induction of yawning and penile erections. Traditionally these effects of APO have been considered to be caused by a preferential stimulation of DA autoreceptors, causing a decreased amount of transmitter at the postsynaptic receptors. If this is so, it could be hypothesized that 1) the same behavioural effects should be obtained if DA transmission is decreased by some other means, for example by synthesis inhibition, and that 2) the response to APO should be altered if DA transmission is already lowered.It was found that high doses of -methyl-p-tyrosine (-MPT; 50–200 mg/ kg) did not reduce water intake in thirsty rats, which low doses of APO do. It was further found that pretreatment with -MPT did not alter the response to APO. These results are difficult to reconcile with the DA autoreceptor hypothesis claiming that behavioural effects of low doses of APO are caused by a decreased release of DA. An alternative interpretation is that low doses of APO stimulates a certain population of sensitive postsynaptic D-2 receptors.