An investigation of social and class differences in very-low birth weight outcomes: a continuing public health concern

The objective of this study was to examine the relationship of nonmedical factors, including socioeconomic status, social class, education, race, and social support, to low birth weight. In a case-control study of all resident very-low-birth-weight births between December 1, 1989, and March 31, 1991, mothers completed an extensive survey related to their experience of pregnancy, including prenatal and postnatal care. Cases were defined as very-low-birth-weight (VLBW) infants and were matched to moderately-low-birth-weight and normal-birth-weight infants in race, age, and maternal residence. The hypothesis that social and class factors are more predictive of low birth weight than medical factors alone for women without chronic health problems was supported. Although the degree of the association varies depending on birth weight outcome, race even though addressed through matching--continued to play an important role in birth outcomes. A comparison of logistic model performance with and without the inclusion of social factors indicated the importance these variables play in prediction of birth outcomes. This is one of the few studies undertaken that explicitly investigates impact of patient factors on medical care.     

Exposure to polychlorinated biphenyls and levels of thyroid hormones in children.

As part of an epidemiologic study on exposure to a toxic waste incineration plant we investigated whether blood concentrations of polychlorinated biphenyls (PCBs), lead, and cadmium, as well as concentration of mercury in 24-hr urine samples were associated with thyroid hormone status. As an indication of status, we determined levels of thyroid-stimulating hormone (TSH), free thyroxine (FT(4)), and free triiodothyronine (FT(3)) in children living in households where [less than/equal to] 10 cigarettes were smoked per day. Eight PCB congeners (PCBs 101, 118, 138, 153, 170, 180, 183, and 187) were measured in whole blood samples. Of these, seven congeners (PCB 101 was not detected in any sample) and the sum of all PCB congeners were analyzed as predictors for thyroid hormone status in separate linear regression models adjusted for potential confounders. In addition, the possible effects of cadmium, lead, and mercury on levels of thyroid hormones were examined. Blood concentrations and information on questionnaire data were available for 320 children 7-10 years of age. We found a statistically significant positive association between the mono-ortho congener PCB 118 and TSH as well as statistically significant negative relationships of PCBs 138, 153, 180, 183, and 187 to FT(3). There was no association for the PCB congeners and FT(4). Blood cadmium concentration was associated with increasing TSH and diminishing FT(4). Blood lead and urine concentration of mercury were of no importance to thyroid hormone levels. The results stress the need for future studies on the possible influences of PCB and cadmium exposure on thyroid hormones, particularly in children. These studies should also take neurologic development into account.     

Recombinant Human Erythropoietin and Hemoglobin Concentration at Operation and during the Postoperative Period: Reduced Need for Blood Transfusions in Patients Undergoing Colorectal Surgery—Prospective Double-blind Placebo-controlled Study

p < 0.05). On postoperative days 3 and 7 the values were 7.2 (5.3–8.2) and 7.5 (5.4–9.4) mmol/L, respectively, in the erythropoietin group compared to 6.7 (5.2–7.8) and 6.9 (5.1–8.6) mmol/L in the placebo group ( p < 0.01). At discharge the hemoglobin concentration was 7.8 (5.9–8.8) mmol/L in the erythropoietin group and 7.2 (5.4–8.6) mmol/L in the placebo group ( p < 0.002). The blood loss during operation was similar in the two groups. In the erythropoietin group the median value was 280 ml (range 25–2000 ml), with the lower and upper quartiles 150 and 500 ml, respectively. In the placebo group the blood loss was median 300 ml (range 50–1800 ml), with the lower and upper quartiles 200 and 750 ml, respectively. The number of blood transfusions given was significantly lower in the erythropoietin group, with a mean of 0.3 (range 0–6) units compared to 1.6 (0–9) units in the control group ( p < 0.05). In conclusion, the hemoglobin concentration at the time of surgery and during the week following surgery was significantly higher in the group of patients receiving r-HuEPO perioperatively compared to the placebo group together with a significant lower use of blood transfusions in the r-HuEPO group. However, the clinical implications of these findings has yet to be proven.RID=" ID=" <E5>Correspondence to:</E5> N. Qvist, M.D., D.Sci.     

Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin

PURPOSE: To investigate the effect of the lipofuscin component N-retinylidene-N-retinylethanolamine (A2-E) on degradative functions of lysosomes in human retinal pigment epithelial (RPE) cells and to evaluate its mechanism of action. METHODS: A2-E was coupled to low-density lipoprotein (LDL). Human RPE cell cultures were loaded with the A2-E/LDL complex, and controls were run with medium containing LDL alone. To determine whether A2-E accumulated in lysosomes, cells were fractionated in a Percoll gradient, and protein degradation was determined by metabolic labeling and measurement of the release of low-molecular-weight radioactivity. Lysosomal degradation was distinguished from nonlysosomal degradation by inclusion of NH4Cl in the medium. The metabolism of sulfated glycosaminoglycans was studied by radiosulfate incorporation in pulse-chase experiments. Intralysosomal pH was determined using a fluorescent lysosomotropic pH indicator. RESULTS: A2-E accumulated almost exclusively in the lysosomal compartment. Lysosomal protein degradation was reduced in a dose-dependent fashion in A2-E-treated cells. The selectivity of A2-E on lysosomal function was demonstrated by its lack of effect on degradation of extralysosomal protein. Lysosomal glycosaminoglycan catabolism of RPE cells was also strongly inhibited by A2-E. Lysosomal pH was increased by A2-E. CONCLUSIONS: The findings indicate that accumulation of A2-E in RPE cells interferes with lysosomal functions as exemplified by its inhibitory effect on protein and glycosaminoglycan catabolic pathways. The quaternary amine character of the A2-E apparently causes a perturbation of the acidic intralysosomal milieu, resulting in diminished hydrolase action and consequent accumulation of undegraded material. Such mechanism could be operative in retinal diseases associated with excessive lipofuscin accumulation including age-related macular degeneration.     

In vivo significance of ICAM-1--dependent leukocyte adhesion in early corneal angiogenesis

PURPOSE: Numerous investigations have stressed the significance of leukocytes in early angiogenesis. Leukocytes invade the cornea, and the location of their extravasation corresponds to the site of vessel ingrowth. The interactions between leukocytes and vascular endothelium are mediated by various proteins, including adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). In this study, the role of ICAM-1 during early corneal angiogenesis was evaluated in vivo. METHODS: Corneal neovascularization was induced in New Zealand White rabbits by use of intrastromal pellets containing 750 ng vascular endothelial growth factor (VEGF). The fluorescent dye rhodamine 6G was used to stain leukocytes in vivo. Leukocyte adhesion and vessel growth were quantified in vivo by high-resolution fluorescence angiography. To inhibit ICAM-1 interactions a microemulsion containing anti-ICAM-1 antibody was applied topically. RESULTS: Limbal vessels showed increased leukocyte adhesion 24 hours after pellet implantation: The number of rolling and sticking leukocytes was significantly increased compared with the number in control animals (P < 0.01). Treatment with anti-ICAM-1 antibody resulted in reduced leukocyte sticking and increased leukocyte rolling. The area covered by new blood vessels was significantly diminished in eyes treated with anti-ICAM-1 (P < 0.05). CONCLUSIONS: The results support the hypothesis that ICAM-1-mediated leukocyte adhesion is a key event in early angiogenesis. This model may serve for investigation of the significance of adhesion molecules by in vivo observation and quantification.     

Topical application of methotrexate for inhibition of corneal angiogenesis

· Purpose: Methotrexate (MTX) is a folic acid antagonist used in chemotherapy regimens. Additional therapeutic applications have been suggested based on effect as an immuno-modulating drug in systemic rheumatoid disease and associated uveitis. Since chronic inflammatory disease is often associated with a neovascular response, we investigated the use of MTX for treatment of corneal angiogenesis.· Methods: Neovascularizations were induced by fibroblast growth factor in a corneal pocket model. Vessels were examined biomicroscopically. MTX was applied topically to rabbit corneas in a concentration of 0.2 mg/day. MTX level was measured in aqueous humor and plasma. · Results: On day 9 the vascularized area was 12.0±6.9 mm² in control eyes and significantly smaller, 2.2±1.86 mm², in treated eyes. Treated animals showed no local side effects such as epithelial defects. Although therapeutic levels were measured in the aqueous humor, MTX could not be detected in the serum of treated animals.· Conclusion: The antiangiogenic mechanism of MTX might be due to inhibition of both macrophage invasion during early angiogenesis and endothelial cell proliferation. The high levels in the aqueous humor indicate a possible application of topical MTX for inflammations of the anterior segment of the eye. Received: 4 March 1999 Revised version received: 6 May 1999 Accepted: 6 May 1999     

Financing the World Health Organisation: global importance of extrabudgetary funds

From 1948, when WHO was established, the Organisation has relied on the assessed contributions of its member states for its regular budget. However, since the early 1980s the WHO World Health Assembly has had a policy of zero real growth for the regular budget and has had to rely increasingly, therefore, on attracting additional voluntary contributions, called extrabudgetary funds (EBFs). Between 1984-85 and 1992-93 the real value of the EBFs apparently increased by more than 60% and in the 1990-91 biennium expenditure of extrabudgetary funds exceeded the regular budget for the first time. All WHO programmes, except the Assembly and the Executive Board, receive some EBFs. However, three cosponsored and six large regular programmes account for about 70% of these EBFs, mainly for vertically managed programmes in the areas of disease control, health promotion and human reproduction. Eighty percent of all EBFs received by WHO for assisted activities have been contributed by donor governments, with the top 10 countries (in Europe, North America and Japan) contributing about 90% of this total, whereas the UN funds and the World Bank have donated only about 6% of the total to date. By contrast, about 70% of the regular budget expenditure has been for organisational expenses and for the support of programmes in the area of health systems. Despite the fact that the more successful programmes are heavily reliant on EBFs, there are strong indications that donors, particularly donor governments, are reluctant to maintain the current level of funding without major reforms in the leadership and management of the Organisation. This has major implications for WHO's international role as the leading UN specialised agency for health.     

Compliance and adverse drug reactions: a prospective study with ethinylestradiol using continuous compliance monitoring

Summary This study examined the relationship between adverse reactions and patient compliance with ethinylestradiol at 40 g twice daily versus 20 g four times daily. In a randomized study 61 female patients with primary- infertility were prescribed the drug twice daily (n = 31) or four times daily (n = 30). Ethinylestradiol was administered for 7 days before the sperm cervical mucus penetration-test was performed for hormonal standardization of the cervical mucus quality. Drug compliance was measured by continuous monitoring using the Medication Event Monitoring System. Two parameters were evaluated: percentage of prescribed doses taken (administration compliance) and adherence to the prescribed dose schedule (regimen compliance, number of days with two or four dosing events recorded). Adverse drug reactions were assessed using a standardized questionnaire. Fourty-four women experienced side effects, of which 81% were rated by patients as being mild. Patient compliance was higher with the twice daily than with the four times daily regimen: 85% versus 65% prescribed doses taken (P<0.05). There was no significant difference in compliance comparing patients with and without adverse reactions (82% versus 72%, respectively), but compliance was lower and more irregular with at least 3 versus one or two adverse reactions reported: 54% versus 84% in administration compliance and 31% versus 58% in regimen compliance (P<0.05). Compliance was also lower in patients with nausea and vomiting than in those without these symptoms, 59% versus 91% and 34% versus 66% (P<0.005), respectively, and lower with moderate or severe compared to mild side effects; 48% versus 85% and 25% versus 59% (P<0.005). Thus the mere occurrence of side effects was not associated with low compliance. However, the number and nature of symptoms and their intensity as perceived by patients may have considerably influenced drug use behavior.Abbreviations ADR adverse drug reactions - SCMPT sperm cervical mucus penetration-test Prof. Dr. E. Weber died 7 December 1992     

Alternative techniques for gaining venous access. What to do when peripheral intravenous catheterization is not possible

There are a number of therapeutic options for fluid administration in patients who lack usual venous access. Ways to establish this access include limb elevation and wrapping, the application of nitroglycerin ointment to dilate veins, and blood pressure cuff inflation. Ultrasonography can also be used to delineate vascular structures. Cutdown procedures are the oldest, most direct method to reach uncommon venous sites, such as the inferior epigastric, intercostal, iliac, and lateral thoracic veins. Today, cutdown procedures are regarded as the method of last resort, and they should be performed in operating suites or similar settings. Possible complications include inadvertent arterial puncture and hemorrhage.     

Techniques for vascular access when venous entry is impossible. Route depends on urgency and the agent to be administered

When a patient requires parenteral fluid or drug administration and venous cannulation cannot be performed, consider less typical routes. Intraosseus infusions are usually more effective in children than adults, but intraosseus cannulation failure may occur in as many as 20% of patients. Intra-arterial infusions are possible if pump pressures are kept high. Hypodermoclysis (infusion into the subcutaneous tissues) can correct moderate dehydration. Administering resuscitative drugs endobronchially is usually safe and effective, although pulmonary function may be somewhat compromised. A number of drugs may be given sublingually, either by injection or topical application. Finally, the corpora cavernosa of the penis may be used for short-term, large-volume fluid administration.