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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 307 records · Page 17Linked to original sources

Problems associated with early discharge of newborn infants. Early discharge of newborns and mothers: a critical review of the literature.

OBJECTIVE: To determine whether research supports the advisability of early discharge of healthy newborns and mothers. METHODS: Critical review of English-language literature cited in the Index Medicus or the International Nursing Index. FINDINGS: No adequately designed studies have examined discharge before 48 hours after delivery without additional postdischarge services. Few studies have examined the consequences of recommending a clinic visit within the first days after discharge; studies of this practice among low-income populations found high no-show rates. Some small studies suggest that early discharge is likely to be safe for selected populations at low psychosocial, socioeconomic, and medical risk, with careful antenatal screening and preparation and multiple postpartum home visits. Some studies suggested adverse outcomes associated with early discharge even with early follow-up. CONCLUSIONS: Published research provides little knowledge of the consequences of short maternal/newborn hospital stays or varying postdischarge practices for the general population. The studies that have concluded that early discharge was safe were applied under restricted circumstances or were too small to detect clinically significant effects on important outcomes. Further research is needed to inform clinical and reimbursement policy on health services in the first days of life and parenting. Rigorous studies of sufficient size are needed to examine the impact of different hospital stays and different postdischarge practices on a range of outcomes for mothers and newborns in diverse populations and settings. Given a priori concerns, decisions on neonatal/obstetric discharge planning should be made cautiously.

Adult↗

Combined single-strand distal semitendinosus-iliotibial band tenodesis (Puddu) for anterior cruciate ligament augmentation.

Anterior cruciate ligament (ACL) reconstruction using the semitendinosus tendon has seen renewed interest recently. Puddu described a procedure in which the tendon is harvested at its insertion on the tibia with a bone plug. This study evaluates the efficacy of this approach and examines the long-term results. Between 1982 and 1986, 77 patients underwent this type of procedure; 51 (66%) patients who were reexamined comprised the study group. Thirty-five patients had acute tears, and 16 patients had chronic tears. Follow-up was both objective and subjective with an average follow-up of 7 years and 3 months (range: 5.8 to 9.2 years). In the acute group, six patients (17%) had a 2+ Lachman and seven (22%) had a 1+ Lachman. Pivot shift was 2+ to 3+ in three patients (8.6%) and 1+ in seven patients (22%). KT-100 results were > 5 mm in eight patients (23.3%). In the chronic group, four patients (25%) had 2+ and four had a 1+ Lachman. Seven patients (44%) had a positive pivot shift test. Five patients had > 5 mm difference. Using regression analysis, the KT-1000 results correlated well with the Lachman and pivot shift tests. Chronicity and partial meniscectomy were associated with a poor result. Although this technique has undergone an evolution and improvement to a four-strand reconstruction in recent years, the results of this review indicate satisfactory results can be obtained, especially in the acute setting.

Acute Disease↗

Macroregenerative nodules in a series of adult cirrhotic liver explants: issues of classification and nomenclature.

Macroregenerative nodules (MRNs), probably representing a pathway for human hepatocarcinogenesis, are generally classified into type I MRNs (or ordinary adenomatous hyperplasia) and type II MRNs (or atypical adenomatous hyperplasia), on the basis of imprecise definitions of cytological and architectural atypia. It is currently believed that type II MRNs are probably true precursors of hepatocellular carcinoma (HCC), whereas type I lesions may simply represent large regenerative nodules. A series of 155 consecutive adult cirrhotic liver explants were examined for evidence of MRNs, HCC, and liver cell dysplasia (LCD) of large and small cell types, and their appearance, in terms of proposed classification schemes, was reviewed. There was evidence indicating that the presence of either type of MRN was associated with an increased incidence of HCC (all MRNs, P < .00019; type I MRNs, P < .067; type II MRNs, P < .012) compared with cirrhotic livers without MRNs. A subset of younger patients with a large (uncountable) number of MRNs in their livers, who did not show any increased incidence of carcinoma, was identified. Excluding these cases from statistical analysis, all associations were strengthened, implying either that malignant progression had not had time to occur in this younger population or that these nodules were simply large regenerative nodules without malignant potential. MRNs from these livers were histologically indistinguishable from MRNs occurring in more limited numbers, although atypical changes other than large cell type LCD were less frequent. No independent association between LCD of large cell type and HCC was found in the entire series.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cell-surface beta-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner.

beta-Amyloid precursor protein (beta APP) is an integral membrane polypeptide expressed in many neural and non-neural cells. beta APP occurs in part at the cell surface and undergoes proteolytic processing to release the large soluble ectodomain (APPs) and the amyloid beta-peptide (A beta), both of which have apparent trophic activity in vitro. Despite intense interest in beta APP expression and metabolism, there is limited knowledge about the function mediated by beta APP inserted at the cell-surface. We established a coculture system in which beta APP-transfected CHO cells serve as a substrate for the growth of primary rat hippocampal neurons. Compared to nontransfected CHO cells, the increased surface beta APP of the transfectants stimulated short-term neuronal adhesion and longer-term neurite outgrowth, whereas the increased amount of secreted APPs and A beta in conditioned medium produced no such effects when neurons were grown either on untransfected CHO cells or on a polylysine substrate. Moreover, a peptide which has been shown to block the trophic effects of secreted APPs (Ninomiya et al., 1993) failed to interrupt the neurite promoting activity mediated by the surface-expressed beta APP. Surface-expressed beta APP751 or beta APP770 isoforms mediated more neurite outgrowth than did the beta APP695 isoform. Antibody blocking and regional deletion experiments indicated that the mid-region of the beta APP ectodomain (residues 361-648) is involved in promoting neurite outgrowth. We conclude that surface-expressed cellular beta APP has a neurite-promoting function which is distinct from the trophic function of the secreted beta APP derivatives and may have special significance during brain development.

Amino Acid Sequence↗

Conservative management of ovarian hyperstimulation syndrome.

OBJECTIVE: To evaluate the performance of a conservative treatment protocol for ovarian hyperstimulation syndrome (OHSS) that utilized low-dose dopamine, volume expanders and diuretics. STUDY DESIGN: Prospective, open trial. RESULTS: Thirteen patients met the criteria for diagnosis of severe OHSS during the study period. Two of these were in vitro fertilization (IVF) patients who did not undergo transfer and so were excluded from analysis. Of the remaining 11, 10 (91%) were pregnant. The average time for resolution of the OHSS and discharge from the hospital was 6 days (range, 2-11). Compared to levels at admission, there was no significant difference in those of sodium, potassium or creatinine after resolution of the syndrome. Hemoglobin and hematocrit, however, were significantly reduced (P < .03). There were no cases of adult respiratory distress syndrome or thrombosis. No pregnancies were interrupted. CONCLUSION: Conservative treatment of OHSS is an acceptable form of management. Risky and invasive therapies, such as paracentesis, are not warranted.

Adult↗

Multiple organ dysfunction syndrome: end organ and systemic inflammatory response in a mouse model of nonseptic origin.

The authors measured the peripheral blood pro-inflammatory cytokine responses (tumor necrosis factor-alpha [TNF-alpha] and interleukin-6 [IL-6]) and related end organ responses ti intraperitoneal zymosan-saline suspension over 5 days in CD-1 mice. Other indicators of local and systemic inflammation included wet:dry weight ratios of lung, liver, kidneys, spleen, and bowel; peripheral blood hematocrit, white blood cell count, and platelet count; lung myeloperoxidase activity; lung protein leak; and bacterial translocation to liver, spleen, and mesenteric lymph nodes. The initial event in responses to zymosan A injection was a sharp rise in the peripheral blood TNF-alpha level, which crested within 1 h of injection. This response was followed by a peripheral blood leukocytosis also within 1 h, and a peak lung myeloperoxidase activity within 1-2 h of injection. The maximum lung permeability index occurred 8 h after injection (zymosan, .398 +/- .019 [n = 10]; saline vehicle, .266 +/- .007 [n = 10], p < .001) followed by the maximum lung wet:dry weight ratio, which occurred 18 h after injection. The peak wet:dry weight ratios for the other organs occurred between 12 and 24 h after injection as well. Peripheral blood IL-6 maxima followed TNF-a maxima after lags of several hours. The release of pre-formed TNF-a is likely the most proximal event following injection of zymosan, and may set in motion the processes that result in end-organ injury and secondary multiple organ dysfunction, particularly activation of leukocytes. The precise roles of TNF-alpha and IL-6 in the pathogenesis of end-organ injury, however, are not addressed.

Animals↗

Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation.

The 39- to 43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels in Alzheimer disease (AD), is secreted by cultured human cells during normal metabolism. In studies of cell lines transfected with beta-amyloid precursor protein (beta APP) cDNAs, the beta APP mutation K670N/M671L found in a Swedish familial AD (FAD) pedigree has previously been shown to cause a marked augmentation of A beta secretion. Here, we have conducted blinded analyses of beta APP metabolism in primary skin fibroblasts from affected members of the Swedish FAD pedigree and their unaffected siblings or spouses. These fibroblasts continuously secrete a homogenous population of A beta molecules starting at Asp-1 (D672 of beta APP). We found a consistent and significant approximately 3-fold elevation of A beta release from all biopsied skin fibroblasts bearing the FAD mutation. No significant alterations of other metabolic derivatives of beta APP were detected. The elevated A beta levels were found in cells from both patients with clinical AD and presymptomatic subjects. Thus, A beta overproduction in this FAD pedigree is not a secondary event but is consistent with a causal role in the development of the disease. Increased A beta secretion can begin many years prior to onset of symptoms, even in peripheral tissues, indicating that it does not require preexisting neural abnormalities.

Alzheimer Disease↗

Purification, reconstitution, and subunit composition of a voltage-gated chloride channel from Torpedo electroplax.

The voltage-gated Cl- channel from Torpedo electroplax was purified in functional form by an immunoaffinity procedure. Channel activity was assayed by 36Cl- uptake into reconstituted liposomes and by direct recording after insertion into planar lipid bilayers. The purified channel displays the same "double-barreled" gating kinetics observed with native membranes, as well as the correct single-channel permeation characteristics. Preparations of active channels consist of a 90-kDa polypeptide, as expected from the known cDNA sequence. No associated subunits are present in the purified material. Direct protein sequencing confirms the absence of a cleavable signal sequence and demonstrates an N-terminus at Ser-2 of the cDNA-derived sequence. This "ClC-0" protein is lightly glycosylated, losing only approximately 2 kDa of sugar upon treatment with endoglycosidase H or N-glycanase. Most if not all of this glycosylation is found on Asn-365. This result necessitates revision of current transmembrane topology proposals, which have placed this residue on the cytoplasmic side of the membrane. Sedimentation in sucrose density gradients under activity-preserving conditions suggests the ClC-0 channel is slightly larger than the Na/K-ATPase alpha/beta-protomer (approximately equal to 150 kDa) and substantially smaller than the reduced form of the nicotinic acetylcholine receptor (approximately equal to 300 kDa). The detergent-solubilized ClC-0 channel, which invariably displays two Cl- diffusion pores in the active complex, is therefore built most likely as a homodimer of the 90-kDa protein purified here.

Animals↗

Electrostatic distance geometry in a K+ channel vestibule.

Many voltage-gated K+ channels carry in the external vestibule a receptor for charybdotoxin, a peptide channel blocker. We use point mutagenesis of both charybdotoxin and a Shaker K+ channel to isolate the electrostatic interaction energy between chosen pairs of residues, one on the channel and one on bound toxin. The results allow estimates of physical distances between such residue pairs and, in combination with the known structure of charybdotoxin, localize specific channel residues in three-dimensional space.

Amino Acid Sequence↗

High-level expression and functional reconstitution of Shaker K+ channels.

Voltage-gated K+ channels were expressed in COS cells transiently transfected with a plasmid carrying a cDNA for an inactivation-removed Shaker K+ channel driven by an adenovirus promoter. Channel expression was followed by immunological detection, binding of radioactive charybdotoxin (CTX), and functional reconstitution into planar lipid bilayers. About 10(7) channels per transfected cell are expressed on the plasma membrane. The expressed channels are glycosylated and competent to bind CTX with the expected characteristics. Channels observed after insertion into planar lipid bilayers displayed the voltage-dependent gating, conduction, and ion selectivity behavior expected for this channel. Channels were solubilized in several detergents without loss of CTX binding activity. The results make plausible a systematic attack on the purification of milligram-level amounts of functional K+ channels from a heterologous expression system.

Adenoviridae↗