Infant milk feeding and bone health in later life: findings from the Hertfordshire cohort study.

Using data from the Hertfordshire cohort study, this study examined the effect of breastfeeding and bottle feeding on adult lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD). The type of infant milk feeding was significantly associated with lumbar spine BMD in males. INTRODUCTION: Using data from the Hertfordshire cohort study (HCS), this study aims to examine the effect of infant milk feeding on bone health in later life by comparing the effect of breastfeeding and bottle feeding on lumbar spine and femoral neck BMC and BMD. METHODS: Information about infant milk feeding, birth weight (kg) and weight at 1 (kg) was collected by health visitors between 1931 and 1939 in Hertfordshire. BMC and BMD measurements were taken by DXA scan between 1998 and 2004. Linear regression models adjusted for conditional weight at 1, age at DXA scan, sex, adult BMI, smoking behaviour, alcohol consumption, physical activity, dietary calcium, and prudent diet score. RESULTS: Infant milk feeding was significantly associated with lumbar spine BMD (b = - 0.028; 95% CI, - 0.055; - 0.000; p value, 0.047) in males. On average, males who consumed breastmilk alternatives in infancy had lower lumbar spine BMD measurements than those who were fed only breastmilk. These associations remained significant in fully adjusted models. There were no significant associations between infant milk feeding and bone health for females. CONCLUSIONS: Significant associations between infant milk feeding and lumbar spine BMD in males indicate that breastmilk may be protective for the bone health of male babies. The evidence presented here underscores the potential lifelong benefits of breastfeeding and may highlight the differences between osteoporotic risk factors for males and females.

Four pediatric patients with autosomal recessive polycystic kidney disease developed new-onset diabetes after renal transplantation.

NODAT is increasingly prevalent. Compared with adult recipients, NODAT is less prevalent in pediatric renal transplant recipients; however, some risk factors for its development in young patients have been defined. We report four pediatric renal transplant recipients with ARPKD who developed NODAT. We review the current pediatric NODAT literature and hypothesize that ARPKD may be an additional risk factor for NODAT.

A new locus for autosomal dominant retinitis pigmentosa on chromosome 7p.

Autosomal dominant retinitis pigmentosa (adRP) is known to result from mutations in two different retinal genes--rhodopsin and peripherin--while a third locus has been implicated by linkage data. However, families have been reported in which all three known loci have been excluded. We report linkage of adRP in one such family to two microsatellite markers on chromosome 7p. D7S435 has previously been localized to 7p13-15.1; D7S460, previously only localized to chromosome 7, maps to within 2 cM of D7S435 with a lod score of 12.15. Two point linkage analysis between these markers and adRP gave lod scores of 5.65 (theta = 0) and 4.19 (theta = 0.046) for D7S460 and D7S435, respectively. Multipoint analysis gave a maximum lod score of 8.22. These data strongly suggest a new adRP locus on chromosome 7p.

Lipoprotein lipase is frequently overexpressed or translocated in cervical squamous cell carcinoma and promotes invasiveness through the non-catalytic C terminus.

BACKGROUND: We studied the biological significance of genes involved in a novel t(8;12)(p21.3;p13.31) reciprocal translocation identified in cervical squamous cell carcinoma (SCC) cells. METHODS: The rearranged genes were identified by breakpoint mapping, long-range PCR and sequencing. We investigated gene expression in vivo using reverse-transcription PCR and tissue microarrays, and studied the phenotypic consequences of forced gene overexpression. RESULTS: The rearrangement involved lipoprotein lipase (LPL) and peroxisome biogenesis factor-5 (PEX5). Whereas LPL-PEX5 was expressed at low levels and contained a premature stop codon, PEX5-LPL was highly expressed and encoded a full-length chimeric protein (including the majority of the LPL coding region). Consistent with these findings, PEX5 was constitutively expressed in normal cervical squamous cells, whereas LPL expression was negligible. The LPL gene was rearranged in 1 out of 151 cervical SCCs, whereas wild-type LPL overexpression was common, being detected in 10 out of 28 tissue samples and 4 out of 10 cell lines. Forced overexpression of wild-type LPL and PEX5-LPL fusion transcripts resulted in increased invasiveness in cervical SCC cells, attributable to the C-terminal non-catalytic domain of LPL, which was retained in the fusion transcripts. CONCLUSION: This is the first demonstration of an expressed fusion gene in cervical SCC. Overexpressed wild-type or translocated LPL is a candidate for targeted therapy.

The relationship of the transcutaneous oxygen tension, pulse waves and systolic pressures to the risk for limb amputation in patients with peripheral arterial disease and skin ulcers or gangrene.

AIM: Our aim was to determine how the risk associated with presence of low transcutaneous oxygen tension (tcPO2) for subsequent major amputation in patients with skin ulcers or gangrene and peripheral arterial disease, compares with the risks associated with low peripheral pressures and low amplitude of pulse waves. Secondly, we determined whether combination of measurements of oxygen tension with that of the pressures or pulse wave amplitude predicts amputation better than pressure, wave or oxygen tension measurements alone. METHODS: Measurements were carried out to obtain foot tcPO2, ankle and toe pressures, pressure indices, and toe pulse wave amplitude in 75 limbs with skin lesions and arterial disease of 66 patients referred to the vascular laboratory. These variables were related to the risk of a subsequent major amputation during a median time of 4.2 years, using Cox proportional hazards model. RESULTS: Low oxygen tension was associated with increased risk of amputation (relative risks 2.16 and 2.55 for tcPO2 < or = 10 mmHg and < or = 20 mmHg, respectively, P<0.05; relative risk 2.22 for tcPO2 < or = 30 mmHg, P=0.07). The relative risks associated with cutoff values of ankle and toe pressures and pressure indices varied from 2.53 (toe < or = 20 mmHg, P<0.05) to 5.83 (ankle < or = 50 mmHg, P<0.001) and the relative risk associated with low wave amplitude (< or = 4 mm) was 3.41, P<0.01. The cutoff values of tcPO2 became insignificant when included in the models together with each pressure variable or pulse amplitude separately. In contrast, wave amplitude remained significantly associated with increased risk of amputation after controlling for each pressure variable (P<0.05). CONCLUSIONS: TcPO2 < or = 10 mmHg and < or = 20 mmHg are related significantly to increased risk of amputation in patients with skin lesions and arterial disease, but these relative risks are similar in magnitude or smaller than those associated with low cutoff values of pressures, pressure indices or pulse wave amplitude. Low wave amplitude does provide significant information in addition to peripheral pressures with respect to the risk of amputation. On the other hand, low tcPO2 does not provide significant information in addition to peripheral pressures or pulse wave amplitude.

A mobile internal medicine clinic.

The Denver Veterans Administration Medical Center (DVAMC) established a mobile internal medicine clinic (MediVAn) to provide access to primary care for veterans living more than fifty miles from the center and to study the costs of such an outreach program. A fully equipped van staffed by an internist visited four Colorado cities weekly for scheduled appointments. In the first two years of operation there were 4,655 visits by 766 veterans with a mean age of 56 years, with 3.9 diagnoses, and receiving 3.0 medicines. The cost per MediVAn visit was $68, compared with $67 per outpatient visit at DVAMC. We conclude that a mobile medical clinic is a convenient method of delivering primary care over distances and is comparable in cost to outpatient hospital visits.

Enhanced cytochemical detection of viral proteins and RNAs using double-sided labeling and light microscopy.

We have developed a double-sided labeling technique for detecting viral proteins or RNAs in plastic-embedded leaf tissue by immunocytochemistry or in situ hybridization, respectively, and light microscopy. The signal from the target was enhanced by double-sided labeling when compared with single-sided labeling because sections were submerged in labeling solutions with both sides accessible to antibodies or complementary RNAs. The additional label was visible during microscopic analysis. Background signal was decreased since the tissue was probed and washed under conditions where folds and creases in the tissue were minimized. This technique uses the same equipment and chemicals as for single-sided labeling, and thus adjustments for reagent expenditures are not necessary. The procedure should be applicable to animal and plant tissue.

A case study of the Tenwek hospital community health programme in Kenya.

Tenwek mission hospital, situated in the west-central highlands of Kenya, initiated a community health programme in 1984. This paper describes the major features of the programme and assesses the impact on a number of health and family planning practices after 3 years of implementation. Comparison of the results in the programme areas with the baseline survey and with control areas show significant changes in several indicators. It is concluded that Tenwek hospital demonstrated the impact a hospital can have on health of communities by effectively moving into community-based health care.

Collapse and viscoelasticity of diseased human arteries.

A laboratory study of the hydrostatic collapse of diseased tibial arteries demonstrated hysteresis in the pressure-flow behaviour which resembled that seen in the stress-strain relations of the arterial tissue. The pressures at which the vessels collapsed were found to be considerably lower than expected on the basis of theoretical elastic models. Also, the pressures at which the vessels reopened were consistently lower than the pressures at which they collapsed. These findings were explained on the basis of viscoelasticity. The difference between collapse and opening pressure may provide insight into the mechanical properties of vessels, and a clue to errors in non-invasive measurements of blood pressure which depend upon collapse of arteries.

Ankle and toe systolic pressures comparison of value and limitations in arterial occlusive disease.

Ankle and toe systolic pressures represent the most convenient and useful measurements in the assessment of limbs with arterial occlusive disease. Each is a sensitive index of the presence and severity of the arterial obstruction and they both correlate with angiographic findings and with the severity of the symptoms. The measurements can be used to follow individual patients, to study the natural history of the disease, to assess prognosis and plan management, and to evaluate long-term results of surgical and transcutaneous interventions. However, because of the limitations of the ankle pressures related to the rigidity of the arterial walls of the tibial vessels and the more distal site of the measurement in the toes, measurements of pressure in the toes should be included in the evaluation of arterial disease in all patients with diabetes, and in all limbs with severe ischemia.

Finger systolic pressures and skin temperatures in severe Raynaud's syndrome: the relationship to healing of skin lesions and the use of oral phenoxybenzamine.

Systolic pressures and skin temperatures were studied in 23 patients with severe Raynaud's syndrome who were given oral phenoxybenzamine. There was a relationship between the measurements and the severity of the disease. Statistically significant correlation was found between the measurements and the time for healing of skin lesions. The chances of early healing are high when digital systolic pressure exceeds 55 mm Hg, the branchial-finger pressure difference is less than 50mm Hg, and the maximal difference among fingers less than 30 mm Hg. Early healing is also likely when finger temperature of 10 degree C or more above room temperature is achieved during "reflex" heating and the difference in temperature among fingers is less than 4 degree C. Therefore, the measurements are of value in the determination of prognosis. Rest pain, local tenderness, trophic skin changes, and vasospastic phenomena improved in the majority of patients soon after beginning treatment with phenoxybenzamine. Some side effects, usually minor, were common but with doses not exceeding 50 mg used in this study they were usually not trouble-some and the drug was tolerated well. Phenoxybenzamine is a valuable drug in the treatment of patients with severe vasospastic disease.

Effect of age, cardiovascular disease, and vasomotor changes on transmission of arterial pressure waves through the lower extremities.

Pressure waves were recorded by indwelling needles in the femoral and foot arteries. At the foot the systolic and pulse pressures were greater and the dicrotic wave more prominent. These changes during transmission increased during vasoconstriction and decreased during vasodilatation. The ratio of the distal to femoral pulse pressure (amplification) increasing from 1.13 +/- 0.05 during body heating to 1.47 +/- 0.06 during body cooling (P less than 0.01), and from 1.14 +/- 0.10 during infusion of trimethaphan to 1.42 +/- 0.02 during cooling (P less than 0.05). Amplification was also significantly greater following inhalation of amyl nitrite and during and after Valsalva maneuver. Greater pulse pressure at the foot paralleled greater amplitude of individual harmonics. Phase velocities decreased with increasing frequency and tended to level off at a value similar to the foot-to-foot pulse wave velocity. The findings are consistent with peripheral reflections of the waves which increase during vasoconstriction. In the absence of procedures that elicit vasoconstriction or vasodilatation, amplification averaged 1.35 +/- 0.03 in control subjects less than 35 years of age and 1.24 +/- 0.06 in older subjects (P less than 0.05). Amplification also did not differ significantly between control subjects and patients with hypertension or ischemic heart disease. In the absence of pronounced vasodilatation or encroachment on the lumen by atherosclerotic plaques, systolic and pulse pressures at the foot should be higher than in proximal pulses. These findings provide a firm basis for interpreting measurements of distal systolic pressures by using blood pressure cuffs when examining patients with occlusive arterial disease in the extremities.

Infections of the subcutis and skin of dogs caused by rapidly growing mycobacteria.

Nine dogs with panniculitis due to rapidly growing mycobacteria (RGM) were examined over 17 years. Dogs were two to 15 years; five were male, four were female. All were obese or in good condition. Antecedent injury, typically a dog bite or vehicular trauma, could be identified in some patients, while one bitch had hyperadrenocorticism. Infections involved different locations, although the cervicothoracic region, dorsum or flank were most often affected. Patients were systemically well, apart from one dog with pyrexia and two with pain or lameness. Cytology demonstrated pyogranulomatous inflammation, but in only one case was it possible to see acid-fast bacilli (AFB) in smears. Histology demonstrated chronic active pyogranulomatous panniculitis and dermatitis; AFB could be detected in only four specimens. Culture of aspirates or resected tissues demonstrated RGM in all cases, comprising six Mycobacterium smegmatis group and three Mycobacterium fortuitum group isolates. Resection of infected tissues, perioperative injectable antimicrobials and long courses of oral antimicrobials chosen according to susceptibility data generally effected a cure, although some cases recurred.

The effect of broken conjugation on the excited state: ether linkage in the cyano-substituted poly(p-phenylene vinylene) conjugated polymer poly(2,5,2',5'-tetrahexyloxy-8,7'-dicyano-di-p-phenylene vinylene).

We investigate the effect of broken conjugation on the excited state dynamics of excimers in cyano-substituted phenylene-vinylene polymers. We compare previous studies on the well-characterized poly(2,5,2',5'-tetrahexyloxy-8,7'-dicyano-di-p-phenylene vinylene) (CN-PPV) with poly[oxa-1,4-phenylene-1,2-(1-cyano)-ethenylene-2,5-dioctyloxy-1,4-phenylene-1,2-(2-cyano)-ethenylene-1,4-phenylene] (CN-ether-PPV), in which the conjugation is disrupted by the insertion of an oxygen atom within the polymer backbone. Despite the broken conjugation, the spectroscopic behavior of the two materials is similar, indicating that the cyano group dominates the photophysics in these materials. The emission in CN-ether-PPV is due to a single-chain exciton in solution and due to an interchain excimer in thin film, as previously reported for CN-PPV; however, the excimer absorption and emission in thin film are blueshifted by approximately 0.2 eV relative to CN-PPV, implying that the excimer in CN-ether-PPV is less stable. Furthermore, substitution of an ether group along the chain results in decay times in both solution and film that are twice as long than in CN-PPV due to the broken conjugation which restricts the exciton within a conjugation segment and reduces its access to internal quenching sites. These properties result in a decay time of 14 ns for CN-ether-PPV film, one of the longest decay times observed in a conjugated polymer film. The long lifetime indicates a large exciton diffusion length, making these species particularly vulnerable to quenching by other materials. This work has implications for the design of conjugated polymers for efficient optoelectronic devices, such as photovoltaics.

Electrochemical and optical characterization of p- and n-doped poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene].

We study electrochemical p- and n-type doping in the well-known light-emitting polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV). Doping reactions are characterized using cyclic voltammetry. Optical measurements including photoluminescence and UV/Vis/NIR transmission were performed on doped samples. We find that oxidation in MEH-PPV is a highly reversible reaction resulting in stable freestanding doped films, while the reduced form is unstable and the reaction irreversible. We discuss the dependence of doping reactions on scan rate, film thickness, salt type and concentration, and working electrode type. We observe the development of two additional broad absorption bands in both lightly and heavily doped films accompanied by a slight blueshift in the primary optical transition, suggesting bipolaron band formation. Finally we find that both p and n dopings result in extremely sensitive photoluminescence quenching. We propose a physical model for understanding electrochemical doping in MEH-PPV and the implications this has on the development of such technologies as polymer light-emitting electrochemical cells, electrochromic devices, actuators, and sensors.

The effect of cooling on toe systolic pressures in subjects with and without Raynaud's syndrome in the lower extremities.

The effect of changes in local and body temperature on the toe systolic pressures was studied in 20 subjects with and 30 without Raynaud's syndrome in the toes. The pressures were significantly lower in the group with Raynaud's syndrome under all experimental conditions (P less than 0.01). The pressures were significantly lower during body cooling than during body warming in both groups (P less than 0.01). The mean decrease with body cooling was 58 mmHg in the group with Raynaud's syndrome and 24 mmHg in the control subjects (P less than 0.01). During body cooling pressures fell to less than 30 mmHg in 70% of subjects with Raynaud's syndrome and in 3% of the controls. Local cooling from 30 to 10 degrees C during body cooling resulted in a significant mean decrease in pressure of over 40 mmHg in both groups (P less than 0.01) and the pressure fell below 30 mmHg in over 90% of the group with and in 26% of those without Raynaud's attacks. The results indicate the importance of body cooling and local temperature in the mechanism of vasospasm in the toes. They are also relevant to the diagnosis of Raynaud's syndrome in the lower limbs and have implications for the testing of patients with arteriosclerotic occlusion since erroneously low pressure values could be obtained in tests when the feet are cold.