Rate of transmission of human immunodeficiency virus type 1 infection from mother to child and short-term outcome of neonatal infection. Results of a prospective cohort study

In an attempt to determine the rate of transmission of infection from human immunodeficiency virus type 1 (HIV-1) antibody-positive women to their offspring and to describe the short-term outcome of perinatal infection, we enrolled 62 infants in a prospective cohort study during a 30-month period and followed them up for an additional 6 months. The clinical, immunologic, and serologic status of the children was assessed prospectively. Fourteen subjects were symptomatic: 3 had acquired immunodeficiency syndrome, 5 had signs and symptoms that were compatible with HIV-1 infection (Centers for Disease Control, Atlanta, Ga, class P2A), and 6 had ill-defined symptoms that could not be definitely attributed to HIV. Our data indicated that the maximum rate of vertical transmission of HIV-1 infection in New Haven, Conn, was less than 30%, and the rate of HIV-1-associated disease occurring during the first 3 years of life was 16%. The mean and median time to loss of maternal antibody, as detected by Western blot in seroreverters, was approximately 7 months, and the half-life of passive antibody was 38 days. A continued close follow-up of children in the cohort studied, and others like it, is critical to learn the full range of outcomes of HIV infection in the pediatric population.     

Persistent pleural effusions in primary systemic amyloidosis: etiology and prognosis

BACKGROUND: Restrictive cardiomyopathy frequently complicates primary systemic amyloidosis (AL), yet only a small number of these patients develop large pleural effusions refractory to diuretic therapy and thoracentesis. We hypothesized that disruption of pleural function by amyloid deposits underlies persistent pleural effusions (PPEs) in patients with AL disease. METHODS: We performed a retrospective study of AL patients with and without PPEs who had been referred to Boston University between 1994 and 2001. The presence of PPEs was defined by a failure to resolve the condition with thoracentesis and aggressive diuresis. AL cardiomyopathy patients without pleural effusions constituted the control (cardiac) group. Indexes of plasma cell dyscrasia, nephrotic syndrome, thyroid function, and echocardiographic measures of left and right ventricle performance were compared between groups. When available, closed needle biopsies and autopsy specimens of parietal pleura were examined for amyloid deposits. RESULTS: Among 636 patients with AL, 35 PPE patients underwent a median of three thoracenteses each. No statistical differences were found between the PPE and cardiac groups in echocardiographic measures of septal thickness, left ventricular systolic function, or diastolic compliance. Right ventricular (RV) hypokinesis occurred more often in PPE patients; however, nearly half of this group had normal RV systolic function. Renal function, plasma protein levels, and thyroid function were the same between groups. Nephrotic range proteinuria (ie, > 3 g/d) was more prevalent in the cardiac group than in the PPE group (44% vs 26%, respectively; p = 0.057). All pleural biopsies in the PPE group (six biopsies) revealed amyloid deposits. Autopsy samples of parietal pleura were negative for disease in two cardiac patients. Eighteen patients had chest tubes placed, and 11 underwent pleurodesis. PPE signaled limited survival among patients who were ineligible for treatment. Untreated PPE patients lived a median 1.8 months vs 6 months for untreated cardiac patients (p = 0.031). Survival after intensive chemotherapy and autologous stem cell transplantation was comparable in the PPE and cardiac groups (21.8 vs 15.6 months, respectively; p = 0.405). CONCLUSION: In AL patients with cardiac amyloid, neither echocardiographic measures of ventricular function nor the degree of nephrosis distinguished those patients with PPEs. We conclude that pleural amyloid infiltration plays a central role in the creation and persistence of pleural effusions among patients with AL.     

Human malignancy-associated nucleolar antigen as a marker for tumor cells in patients with acute leukemia

Tumor burden in adult patients with acute leukemia is assessed using the percentage of blast cells in the bone marrow or blood. It is clear, however, that not all blast cells are leukemic cells, especially during rapid marrow regeneration. Similarly, some leukemia cell lines have been shown to differentiate in vitro, and the same process also occurs in vivo. Therefore, the leukemic burden may be due to more differentiated cells as well as to blast cells. The purpose of this study was to investigate whether the human malignancy-associated nucleolar antigen (HMNA) could be used as a marker for leukemic cells and to examine its potential as a diagnostic tool. The proportion of HMNA-positive cells in the bone marrow of patients with acute leukemia was determined by indirect immunofluorescence with antibodies to HMNA and was compared with the differential counts routinely made in the clinic laboratory. The percentages of HMNA-positive cells among the nucleated cells in the marrow of 72 patients with clinical evidence of leukemia were significantly higher (range 9%-98%, median 83%) than those observed for nonleukemic individuals (range less than 0.05%-2.5%, median 1%) or for fractions of marrow cells from normal volunteers enriched for normal early progenitor cells (less than or equal to 2%). Patients with leukemia in remission had a lower percentage of HMNA- positive cells (range 0%-83%, median 3%). The percentage of HMNA- positive cells increased as patients approached relapse. Although the percentage of HMNA-positive cells was related to the percentage of blast cells in the bone marrow of the patients with leukemia, some partially differentiated cells were also HMNA-positive in some specimens, and some blastic cells were HMNA-negative in other specimens. These studies indicate the potential usefulness of HMNA as a marker for leukemic cells.     

Value of static venous pressure for predicting arteriovenous graft thrombosis

BACKGROUND: Static venous pressure elevation has been shown to have both high sensitivity and high specificity for hemodialysis arteriovenous (AV) graft venous anastomosis stenosis. However, it is not known how well static venous pressure elevation predicts subsequent AV graft thrombosis. METHODS: Monthly static venous pressure measurements were made during two consecutive dialysis sessions in all patients with a functioning upper extremity AV graft in two hemodialysis units during a 16-month period. Static venous pressure was normalized to systolic blood pressure and corrected for the height difference between the AV graft and the dialysis machine pressure transducer to yield the static venous pressure ratio (SVPR). RESULTS: Fifty-four patients (38%) had a thrombotic event during the study period and thus were labeled as clotters. Among the clotters, SVPR just prior to thrombosis was 0.51 +/- 0.16 (mean +/- SD), and mean time to thrombosis following an elevated SVPR (> or =0.4) was 118 +/- 106 days. Receiver operating characteristic (ROC) curves were generated using the sensitivities and specificities of a range of SVPR values for access thrombosis within one, two, three and four months. The areas under the curve (AUCs) for the ROC curves ranged from 0.557 to 0.638, reflecting the absence of SVPR values with both high sensitivity and high specificity for access thrombosis. An increase in SVPR over time was not a better predictor of access thrombosis than absolute SVPR. CONCLUSION: Static venous pressure measurement is not an optimal screening test for identifying AV grafts at risk for thrombosis.     

Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome

OBJECTIVES: To examine the safety and pharmacokinetics of multiple intratracheal (IT) doses of recombinant human CuZn superoxide dismutase (rhSOD) in premature infants with respiratory distress syndrome who are at risk for developing bronchopulmonary dysplasia (BPD). Methods. Thirty-three infants (700 to 1300 g) were randomized and blindly received saline, 2.5 mg/kg or 5 mg/kg rhSOD IT within 2 hours of surfactant administration. Infants were treated every 48 hours (as long as endotracheal intubation was required) up to 7 doses. Serial blood and urine studies, chest radiographs, neurosonograms, SOD concentration and activity measurements, and tracheal aspirate (TA) inflammatory markers were assessed throughout the 28-day study. RESULTS: SOD concentrations in serum (0.1 [0.05/0.15] microg/mL-geometric mean with lower/upper confidence intervals), tracheal aspirates (TA) (0.2 [0.1/0.3] microg/mL) and urine (0.3 [0.2/0.4] microg/mL) were similar at baseline in all 3 groups and did not change significantly in the placebo group. In the rhSOD treatment groups, SOD concentrations were increased on day 3 and did not change significantly thereafter over the 14-day dosing period (also measured on days 5, 7, and 13). SOD concentrations averaged 0.4 [0.3/0.5] microg/mL in serum, 0.8 [0.6/1.2] microg/mL in TA and 1.1 [1.0/1.3] microg/mL in urine for the low-dose group and 0.6 [0.5/0.7] microg/mL in serum, 1.1 [0.9/1.5] microg/mL in TA, and 2.2 [1.6/2.9] microg/mL in urine for the high-dose group over the 14-day dosing period. Enzyme activity directly correlated with SOD concentration and rhSOD was active even when excreted in urine. TA markers of acute lung injury (neutrophil chemotactic activity, albumin concentration) were lower in the rhSOD agroups compared with placebo. No significant differences in any clinical outcome variable were noted between groups. CONCLUSIONS: These data indicate that multiple IT doses of rhSOD increase the concentration and activity of the enzyme in serum, TA and urine, reduce TA lung injury markers and are well-tolerated. Further clinical trials examining the efficacy of rhSOD in the prevention of BPD are warranted.     

The impact of glucose-insulin-potassium infusion in acute myocardial infarction on infarct size and left ventricular ejection fraction [ISRCTN56720616]

Background

Stopping antipsychotic treatment can interrupt improvement and exacerbate the illness. The reasons for discontinuing treatment during controlled clinical trials were analyzed to explore this phenomenon.

Methods

A post-hoc, pooled analysis was made of 4 randomized, double-blind clinical trials, 24–28 weeks in duration, involving 1627 patients with schizophrenia or a related disorder. Analyses combined all the atypical antipsychotic treatment groups in the studies.

Results

The majority of patients (53%) stopped their treatment at an early stage. Poor psychiatric response along with worsening symptoms was the most frequently given reason for discontinuing the course (36%), which was substantially more common than discontinuation due to poor tolerability of the medication (12%). This phenomenon was corroborated by less improvement in patients who discontinued treatment compared with those who completed, based on the PANSS total scores. Discontinuation due to poor response was, apparently, more predominantly linked to patient perception than to physicians' conclusions alone (80% vs. 20%). Discontinuation due to patient perception of poor response appeared to occur particularly early in the course of treatment. Patients who discontinued due to poor toleration of the medication responded in a more comparable manner with completers.

Conclusion

Discontinuing treatment may lead to exacerbation of symptoms, undermining therapeutic progress. In these studies, poor response to treatment and worsening of underlying psychiatric symptoms, and to a lesser extent, intolerability to medication were the primary contributors to treatment being discontinued. Our findings suggest that adherence may be enhanced by effective symptom control, as objectively measured and as subjectively perceived. Such strategies may improve patients' willingness to undertake long-term therapy and increase the likelihood of a better prognosis.     

Inactivation of lipid-enveloped and non-lipid-enveloped model viruses in normal human plasma by crosslinked starch-iodine

BACKGROUND: The purpose of this study was to evaluate an iodine-based method of activating potentially harmful viruses that might be found in normal human plasma. STUDY DESIGN AND METHODS: A procedure has been developed for inactivating lipid-enveloped and non-lipid-enveloped model viruses in normal human plasma by using iodine complexed to crosslinked potato starch. The established conditions are an iodine concentration of 1.05 mg per mL and 60 minutes' incubation. RESULTS: Under these conditions, inactivation of more than 9 log10 of vesicular stomatitis virus, a lipid-enveloped virus, and more than 7 log10 of encephalomyocarditis virus, a non-lipid-enveloped virus, was achieved, with minimal losses of biologic activity of selected plasma proteins. Under these conditions, 70 percent of factor VIII activity, 77 percent of factor IX activity, and 100 percent of protein C activity in the plasma were retained. CONCLUSION: Crosslinked starch-iodine may be useful in the inactivation of viruses in single-donor plasma units and in pooled human plasma before fractionation.     

Head and neck MR imaging in the pediatric patient

Magnetic resonance (MR) imaging studies of the head and neck (excluding the brain) were obtained in 49 children believed to have lesions of the head and neck. Seven children had normal images; in the remaining 42, lesions were divided into four categories: midline lesions, lesions of symmetric paired structures, facial lesions, and nasopharyngeal and oropharyngeal lesions. All entities were well delineated by MR imaging. The imaging planes and sequences chosen depended on the suspected abnormality. Midline lesions were best imaged in the sagittal plane, lesions of paired structures and the face in the axial or coronal planes, and nasopharyngeal and oropharyngeal lesions in the axial or sagittal planes. Intracranial extension of head and neck neoplasms was best evaluated in the coronal plane. Surface coils provided better resolution and were thus more useful in evaluating small superficial lesions; head or body coils were more useful in defining the extent of large lesions. T2-weighted images provided better differentiation between normal and tumor tissue in patients with head and neck neoplasms.