Familial transmission of alcohol use: II. Imitation of and aversion to parent drinking (1960) by adult offspring (1977)--Tecumseh, Michigan

The "fall-off" effect, when offspring respond to parental high-volume levels by moderating their own drinking, appears highly predictable across generations and is mediated both by subsequent parent drinking level and offspring's perception of problematic intake by their parents. This fall off by adult offspring appears to follow community norms; it occurs, on the average, at the level of daily drinking by fathers, and when the mother approaches daily-drinking levels. An aversion effect holds more to cross-sex parents with problems; thus, both sons and daughters show a nonimitation and fall off to their cross-sex parents who are high-volume problem drinkers. Conversely, however, daughters often imitate a high-drinking father with no problems. For high-drinking mothers, without problems or with problems (numbers are small), daughters' drinking appears "polarized": most (60%) are abstemious, but a higher number than expected (about 35%) show high volume thus imitating the mother's volume, compared to about 17% of the total sample of daughters who were high-volume drinkers. Maximal offspring imitation is strongest for abstemious parents, especially for abstaining parents, and stronger for fathers abstaining than for mothers.     

NHS charges. Light on the charge brigade

Patients charges form a very small part of NHS income. Governments have often used charges to emphasise their commitment to austerity. Knowledge of the effect of charges on public health, equity and eliminating waste is limited. Both Conservative and Labour health ministers have made attempts to abolish charges.     

Regulating the gene: From genetic consumption to regulatory trust

In this article, we examine the changing terms on which genetics-based technologies in two areas agriculture (Genetically Modified Organism, GMOs) and health (genetic diagnostics) have been regulated. These are used to illustrate and examine the proposition that shifts in the politics of governance and regulation (associated in part with the advent of the negotiation state) have meant that the responsibility for the social management of new technology is increasingly shared between the state and the consumer. However, this redistribution of the social management of risk, we argue, fails to establish a sufficient basis for a legitimate regulatory trust. We suggest that trust will depend on embedding broad social values and a self-critical agenda within the regulatory regime itself.     

The mouse C1q A-chain sequence alters beta-amyloid-induced complement activation

In transgenic models of Alzheimer's disease (AD) neuronal loss has not been widely observed. The loss of neurons in AD may be due to chronic activation of complement (C') by beta-amyloid (A beta). A beta has been shown to activate C' by binding to a site on the C1q A-chain. The mouse A-chain sequence differs significantly from human, and a peptide based on the mouse A-chain sequence was ineffective at blocking activation of C' by A beta in contrast to the inhibition seen with the human peptide. Comparison of mouse and human serum showed that human C' was activated more effectively by A beta than was mouse C'. Therefore, additional genetic manipulations may be necessary to replicate in the murine model the inflammation and neurodegeneration that occur in AD.     

The effect of hyperbaric oxygen on medial collateral ligament healing in a rat model

Hyperbaric oxygen has been shown to promote healing in bone and some soft tissues. This study was undertaken to determine its effect on ligamentous healing. Forty-eight Sprague-Dawley rats underwent a standardized surgical laceration of the right (divided) medial collateral ligament, whereas the left (undivided) medial collateral ligament was not surgically lacerated. A control group of 24 rats recovered without intervention. An experimental group consisting of the other 24 rats was exposed to hyperbaric oxygen at 2.8 atmospheres for 1.5 hours a day for 5 days after the surgery. Six rats from each group were euthanized at 2, 4, 6, and 8 weeks. The stiffness and final force to failure were recorded for the divided and undivided medial collateral ligaments. At 4 weeks, a statistically greater force was required to cause failure of the previously divided ligaments that had been exposed to hyperbaric oxygen than those that had not. The stiffness and force to cause failure of previously divided ligaments were statistically greater at 4 weeks than at 2 weeks, whether or not hyperbaric oxygen was used. No additional statistical increases in stiffness or force were observed at 6 weeks.     

Antagonist activities of mecamylamine and nicotine show reciprocal dependence on beta subunit sequence in the second transmembrane domain.

We show that a portion of the TM2 domain regulates the sensitivity of beta subunit-containing rat neuronal nicotinic AChR to the ganglionic blocker mecamylamine, such that the substitution of 4 amino acids of the muscle beta subunit sequence into the neuronal beta4 sequence decreases the potency of mecamylamine by a factor of 200 and eliminates any long-term effects of this drug on receptor function. The same exchange of sequence that decreases inhibition by mecamylamine produces a comparable potentiation of long-term inhibition by nicotine. Inhibition by mecamylamine is voltage-dependent, suggesting a direct interaction of mecamylamine with sequence elements within the membrane field. We have previously shown that sensitivity to TMP (tetramethylpiperidine) inhibitors is controlled by the same sequence elements that determine mecamylamine sensitivity. However, inhibition by bis-TMP compounds is independent of voltage. Our experiments did not show any influence of voltage on the inhibition of chimeric receptors by nicotine, suggesting that the inhibitory effects of nicotine are mediated by binding to a site outside the membrane's electric field. An analysis of point mutations indicates that the residues at the 6' position within the beta subunit TM2 domain may be important for determining the effects of both mecamylamine and nicotine in a reciprocal manner. Single mutations at the 10' position are not sufficient to produce effects, but 6' 10' double mutants show more effect than do the 6' single mutants.     

Role of sialylation in determining the pharmacokinetics of neutrophil inhibitory factor (NIF) in the Fischer 344 rat

1. Recombinant neutrophil inhibitory factor (NIF) is a glycoprotein. Its amino acid sequence remains constant and has a molecular weight of 28.9 kD. However, approximately 40% of the total molecular weight consists of glycans with variable structure. 2. The pharmacokinetics of 11 different NIF batches with varying extents and patterns of sialylation have been investigated in the Fischer 344 rat following intravenous administration. These data indicate that reducing the extent of NIF sialylation reduces the half-life of the molecule due to an increase in the systemic clearance. Also, an increase in the number of unsialylated or neutral glycans may increase the volume of distribution of NIF, although this effect is marginal. 3. Isolated perfused rat liver (IPRL) investigations have shown that sialylated NIF has a low hepatic extraction (< 1%), while asialo NIF has an extraction that is > 20-fold higher. Co-administration of asialo NIF with asialo fetuin (a protein cleared by hepatic asialoglycoprotein receptor (possibly galactose)-mediated uptake reduced the hepatic extraction of asialo NIF. 4. These data suggest that NIF molecules that have free sugar moieties (possibly galactose) interact with an asialoglycoprotein receptor (possibly galactose-mediated) in the liver (parenchymal cells/hepatocytes). Interaction with this receptor leads to cellular internalization and degradation.     

Simultaneous radical nephrectomy and repair of abdominal aortic aneurysm

Objectives

The combination of abdominal aortic aneurysm repair with other intra-abdominal surgery is controversial. Most studies have shown that a variety of procedures can be performed at the same time as an aneurysm repair with little change in mortality or complication rates. We conducted a retrospective study to determine if aneurysm repair could be safely and effectively combined with radical nephrectomy.

Methods

We studied 10 patients who underwent combined abdominal aortic aneurysm repair and radical nephrectomy during a 4-year period. Results from this group were compared to a separate control group of 10 patients who underwent radical nephrectomy alone and another of 12 patients who underwent abdominal aortic aneurysm repair alone, during the same time period.

Results

The overall mortality was 10% and significant complications occurred in an additional 10% of patients. Minor, self-limiting complications occurred in 30% of patients. There were no aortic graft infections that occurred in the entire series of patients at 18 months of mean follow-up. There were no remarkable differences in length of stay, age, operating time, blood loss, morbidity, and mortality between this series of patients and the combined values in a separate group of control patients who had undergone either procedure alone.

Conclusions

Simultaneous radical nephrectomy for presumed renal cell carcinoma can be safely combined with repair of abdominal aortic aneurysm in selected patients.