Decline in perinatal HIV transmission in New York State (1997-2000)

BACKGROUND: Perinatal HIV transmission has declined significantly in New York State (NYS) since implementation of a 3-part regimen of zidovudine prophylaxis in the antenatal, intrapartum, and newborn periods. This study describes the factors associated with perinatal transmission in NYS from 1997 to 2000, the first 4 years of NYS's comprehensive program in which all HIV-exposed newborns were identified through universal HIV testing of newborns. METHODS: This population-based observational study included all HIV-exposed newborns whose infection status was known and their mothers identified in NYS through the universal Newborn HIV Screening Program (NSP) from February 1997 to December 2000. Antepartum, intrapartum, newborn, and pediatric medical records of HIV-positive mothers/infants were reviewed for history of prenatal care, antiretroviral therapy (ART), and infant infection status. Risks associated with perinatal HIV transmission were examined. RESULTS: Perinatal HIV transmission declined significantly from 11.0% in 1997 to 3.7% in 2000 (P < 0.05). Prenatal ART was associated with a decline in perinatal HIV transmission both for monotherapy (5.8%, relative risk [RR] = 0.3, 95% confidence interval: 0.2%-0.5%) and combination therapy [2.4%, RR = 0.1, 95% confidence interval: 0.1%-0.2%) compared with no prenatal antiretroviral prophylaxis (P < 0.05). CONCLUSIONS: Public health policies to improve access to care for pregnant women and advances in clinical care, including receipt of appropriate preventive therapies, have contributed to declines in perinatal HIV transmission in NYS.     

Protection of Chinese hamster cells against the cytotoxic and mutagenic effects of alkylating agents by transfection of the Escherichia coli alkyltransferase gene and a truncated derivative

The cytotoxic and mutagenic effects of various monofunctionaland bifunctional alkylating agents have been assessed in V79Chinese hamster cells that express either the entire O⁶-alkylguanine(O⁶AG) and alkylphosphotriester alkyltransferase (ATase) gene(clone 8 cells) or a truncated form that codes only for O⁶AGATase activity (clone SB cells). Protection ratios, as determinedby D₃₇ values, were greater for clone 8 cells than for SB cells.Significant protection against the mutagenic effects of N-methyl-N-nitrosoureaand ethylmethanesulphonate at the hypoxanthine phosphoribosyltransferase(HPRT) locus was observed in clone 8 and SB cells. Streptozotocinand the haloethyl nitrosoureas, chlorozotocin and bis-chloroethylnitrosoureawere less efficient in inducing HPRT-deficient mutants and asmaller degree of protection was afforded by the transfectedgenes. This is possibly due to the propensity of these compoundsto induce multi-locus deletions. Southern analysis of DNA fromclone 8 and SB cells indicated the presence of multiple copiesof the plasmid integrated into clone 8 cells but few copiesin clone SB cells. The copy number did not change but ATaselevels fell when cells were grown in the absence of G418. ²Present address: Corporate Biosciences Laboratory, ICI plc,The Heath, Runcorn, Cheshire, UK      

Laser induced thermal injury of rabbit cornea and treatment with anti-inflammatory agents

A moderately severe thermal injury of the central cornea of 48 Dutch-belted rabbit eyes was produced with a carbon (CO₂) laser. The lesions were photographed with a slit lamp (SL) camera immediately following the injury and at 1, 2, 4, 7, 14, 21, 30 and 60 days after the exposure. Lesion size, opaqueness, and depth were graded clinically by SL biomicroscopy at the same intervals. No significant differences were found (p 0.05) between groups of eyes treated with flurbiprofen (0.03%), prednisolone acetate (1%), and vehicle control four-times-a-day for three weeks following injury. Additionally, eyes were studied histopathologically at 3 and 60 days following injury by light and transmission electron microscopy, and clinically at 30 and 60 days by endothelial specular microscopy. Important clinical and histopathological findings included coagulative necrosis of the corneal epithelium, epithelial sloughing, fusion of stromal collagen, stromal edema and inflammatory cell infiltration, stromal scar formation, corneal thinning, endothelial hyperplasia and metaplasia, fibrinous anterior chamber reaction with hypopyon, and retrocorneal fibrous membrane formation.     

Direct membrane method for the study of interface-controlled transport of cholesterol in aqueous media

Studies were designed to demonstrate the use of a silicone rubber membrane diffusion cell in the mechanistic study of cholesterol mass transfer in aqueous media. The method is shown to be simple, precise, and well suited for delineating conditions which facilitate cholesterol transport. Traditional membrane diffusion resistance was determined with cholesterol solubilized in the nonionic surfactant, polyoxyethylene(10)-nonylphenol ether. The use of a charged surfactant additive, either sodium oleate or benzyldimethyltetradecylammonium chloride, reduced cholesterol membrane flux in a manner consistent with a transport barrier residing in the membrane and micelle interfacial regions. Quantitative determination of total transport resistance was good (CV of greater than 95%) for cases more than 99% interface controlled. Interfacial resistance imparted by the charged surfactant additive was essentially abolished by strong electrolyte (sodium chloride). Electrolyte was utilized in either the upstream or the downstream aqueous compartment to enhance cholesterol transport by a mechanism which is consistent with a marked increase in the frequency of micelle collision with the corresponding membrane surface. When the downstream interfacial component of total transport resistance was "short circuited" by electrolyte in sequential transport runs using the same membrane, a "dumping" of cholesterol by the membrane compartment was observed. Limited studies with a second nonionic surfactant, polyoxyethylene(15)-tridecyl ether, suggest that the structure of separate micelle components may also be related to cholesterol mass transfer which occurs via a micelle collision in the interfacial region.     

Inhibition of aflatoxin B1 -hepatocarcinogenesis in rats by {beta}-naphthoflavone

Effects of ß-naphthonflavoe (ßNF) on theactivity of hepatic microsomal aflatoxin B₁ (AFB₁)-4-hydroxylase- the cytochrome P-450-dependent enzyme system which catalyzesthe metabolism of AFB₁ to AFM₁ - and on AFB₁ induced in vivohepatocarcinogenesis were investigated in weanling male Fischerrats. A single i.p. injection of ßNF in doses of 20mg/kg and 150 mg/kg induced AFB₁ -4-hydroxylase 3- and 4-fold,respectively, 48 h post injection. Feeding of diet containing0.01% ßNF for a period of 9-weeks induced AFB₁ 2-fold.AFB₁, given by intubatlon in a dose of 25 µg five times/weekfor 8 weeks, produced 42 weeks later a 100% incidence of liverlesions (neoplastic foci, nodules or tumors), but feeding ßNFin diet at a con centration of 0.015% for one week prior toand during the 8 weeks of AFB treatment inhibited AFB₁ hepatocarcinogenesis by -7%. These results are in accord with the suggestionthat AFB₁ induction may be associated with the inhibition ofAFB₁ carcinogenesis, possibly occurring as a consequence ofaccelerated detoxi-fication of AFB₁ via its conversion to AFM₁     

Standardized mean regional method for calculating global positron emission tomographic measurements

A new "mean regional" method for calculating global hemispheric values of blood flow, blood volume, and metabolism with positron emission tomography is presented. It is based on a standardized set of regions defined according to coordinates in a stereotactic atlas of the brain. Region locations in each individual scan were determined by a localization technique that is independent of the appearance of the physiological images. Measurements obtained with this mean regional method minimize contributions from nonbrain structures such as ventricles or venous sinuses and provide the necessary basis for comparisons among different subjects and laboratories.     

Linkage of a membrane skeleton to integral membrane glycoproteins in human platelets. Identification of one of the glycoproteins as glycoprotein Ib.

Experiments were performed to determine whether platelets contain a membrane skeleton. Platelets were labeled by a sodium periodate/sodium [3H]borohydride method and lysed with Triton X-100. Much of the filamentous actin could be sedimented at low g forces (15,600 g, 4 min), but some of the actin filaments required high-speed centrifugation for their sedimentation (100,000 g, 3 h). The latter filaments differed from those in the low-speed pellet in that they could not be depolymerized by Ca2+ and could not be sedimented at low g forces even from Triton X-100 lysates of platelets that had been activated with thrombin. Actin-binding protein sedimented with both types of filaments, but 3H-labeled membrane glycoproteins were recovered mainly with the high-speed filaments. The primary 3H-labeled glycoprotein recovered with this "membrane skeleton" was glycoprotein (GP) Ib. Approximately 70% of the platelet GP Ib was present in this skeleton. Several other minor glycoproteins, including greater than 50% of the GP Ia and small amounts of three unidentified glycoproteins of Mr greater than 200,000, were also recovered with the membrane skeleton. The Triton X-100 insolubility of GP Ib, GP Ia, a minor membrane glycoprotein of 250,000 Mr, and actin-binding protein resulted from their association with actin filaments as they were rendered Triton X-100-soluble when actin filaments were depolymerized with deoxyribonuclease I and co-isolated with actin filaments on sucrose gradients. When isolated platelet plasma membranes were extracted with Triton X-100, actin, actin-binding protein, and GP Ib were recovered as the Triton X-100 residue. These studies show that unstimulated platelets contain a membrane skeleton composed of actin filaments and actin-binding protein that is distinct from the rest of the cytoskeleton and is attached to GP Ib, GP Ia, and a minor glycoprotein of 250,000 Mr on the plasma membrane.     

Age-dependent variation of T1 and T2 relaxation times of adenocarcinoma in mice

The T1 and T2 values of adenocarcinoma EO 771 inoculated into the hind leg of mice are characterized and correlated with the histopathologic state of the tumor. Growth-dependent changes (indicated by a T1 of 630-910 msec and a T2 of 68-185 msec) can be separated into four characteristic phases. The increase in relaxation times in the early phases (A and B) is due to an increasing amount of viable tumor tissue relative to normal muscle tissue. In the later phases (C and D), a decline of the relaxation parameters is observed that is parallel to an increase in the fraction of necrotic tissue. By multiexponential analysis, two relaxation components (indicated by and, respectively) for T1 and T2 and the corresponding fractions alpha 1 and alpha 2 can be observed for both tumor and surrounding muscle tissue. A tissue criterion ("magnetic resonance fingerprint") is defined by a combination of these multiple parameters. This criterion allows separation of not only muscle and tumor tissue but also viable (early state) and necrotic (late state) tumor tissue.     

CT metrizamide myelography in syringomyelia: sensitivity and specificity

In a retrospective study of 32 patients with "proven" syringomyelia and 15 patients with an alternate proven diagnosis, a change in the caliber of the spinal cord with different positions ("collapsing cord sign or cord collapse") had a sensitivity of 38% and a specificity of 87%. Central cord enhancement ("bull's-eye") on delayed CT had a sensitivity and specificity of 91% and 87%, respectively. The positive predictive value of cord collapse was 87%, while the positive predictive value of central cord enhancement was 94%.     

The consequences of consensus: American health policy in the twentieth century

For most of the twentieth century the central theme in the history of health policy in the United States was the elaboration and implementation of a consensus that health services should be organized in regional hierarchies. This consensus was based on shared beliefs about how medical advances were made and disseminated. Hierarchical regionalism became national health policy in several stages that culminated in the 1960s. Since the 1970s, however, the national policy of hierarchical regionalism has been eroded by the unexpected consequences of its success.