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Biomedical subjects

J L Mills

Publications and source records attributed to J L Mills.

At least 19 recordsLinked to original sources
PubMed1998

Smoking in adult survivors of childhood acute lymphoblastic leukemia.

BACKGROUND: Health-related behaviors are of particular concern in survivors of childhood cancer as they are at increased risk for second cancers and long-term organ dysfunction. The purpose of this study was to compare the smoking behavior and associated factors in young-adult survivors of childhood acute lymphoblastic leukemia (ALL) with those in sibling controls. METHODS: A telephone interview that surveyed smoking behavior was conducted with 592 young-adult survivors, treated before age 20 years on Children's Cancer Group ALL protocols, and 409 sibling controls. Using stratified chi-squared analyses and Cox proportional hazards models, we compared the rates of smoking initiation and smoking cessation between survivors and control subjects. Demographic characteristics (age, sex, race, and education) and psychological factors (mood and self-concept) were examined as predictors interacting with survivorship in logistic regression analyses to try to distinguish a subgroup of survivors who may be at greater risk for smoking. RESULTS: Survivors were significantly less likely to have ever smoked (23.0% versus 35.7%; P<.0001) and thus were less likely to ever be regular, daily smokers than sibling controls (19.1% versus 31.3%; P<.0001). Survivors were less likely to quit smoking than sibling controls (26.6% versus 35.2%), although this result was not statistically significant. There were no interactions between survivor status and either demographic or psychological features on smoking behavior. CONCLUSIONS: Young-adult survivors of childhood ALL are less likely to experiment with smoking but, once having started, are at similar risk for becoming habitual, persistent smokers as sibling controls.

Actuarial Analysis↗
PubMed1998

The histologic characteristics of primary and restenotic carotid plaque.

BACKGROUND: Although smooth muscle cell proliferation is a prominent feature of restenosis in experimental models, the role of cellular proliferation in the initiation and progression of carotid restenosis is not well documented. METHODS: Between 1985 and 1995, 35 carotid endarterectomies (CEA) in 34 patients were performed for restenosis. Patient risk factors, cerebrovascular symptoms, and operative findings were recorded. Tissue specimens from 29 of these cases and 14 original specimens from the same patient were examined by light microscopy (H&E, trichrome, elastochrome, and Alcian blue) and immunohistochemistry (alpha actin, CD 68, vWF, and proliferating nuclear cell antigen (PCNA)) in order to determine the morphologic characteristics and cellular proliferative activity of the plaque. RESULTS: Hemodynamically significant recurrent stenosis occurred in the 29 patients (69% symptomatic) between 2 months and 30 years after their initial CEAs. Eleven of 29 (38%) lesions were removed early (< 3 years). Recurrent lesions were characterized based on their components as neointimal thickening, 24% (7/29), neointimal thickening and atherosclerosis, 55% (16/29), or atherosclerotic, 21% (6/29). Nineteen of 29 (66%) plaques were complicated by mural thrombus or intraplaque hemorrhage. An inflammatory cell infiltrate consisting of macrophages and T lymphocytes was observed adjacent to areas of recurrent atherosclerosis and macrophages in regions of intimal thickening. Although infrequently present (generally 1-3% of cells) PCNA-positive cells were detected in 41% (12 of 29) of recurrent and 14% (2 of 14) of primary plaques. No PCNA-positive cells were detected in the remaining 67% (29 of 43) of specimens. There was no statistical difference in the number of PCNA-positive cells in early recurrent lesions compared to those recurring after 3 years (36% vs 44%). PCNA immunoreactivity when present was most commonly noted in macrophages associated with thrombus or atheroma rather than smooth muscle cells. CONCLUSIONS: Although evidence of cellular proliferation was observed in 40% of recurrent carotid endarterectomy lesions, the proliferation rate was low (1-3%) and unrelated to the time interval of recurrence. Proliferative activity was most pronounced in macrophages associated with intraplaque hemorrhage or atheroma. The contribution of inflammatory cells to the biologic behavior of restenotic lesions requires further investigation.

Adult↗
PubMed1997

Minimum effective dose of folic acid for food fortification to prevent neural-tube defects.

BACKGROUND: Although a daily supplement of 400 micrograms folic acid has been shown to prevent neural-tube defects (NTD), most women do not take the recommended supplement. Thus, food fortification is to be introduced in the USA and is being considered in the UK. Because of safety concerns, the USA has chosen a level of fortification that will increase the average woman's intake by only 100 micrograms. Such an increase, although safe, may be ineffective; but a trial to assess its efficacy would be unethical. Because women with red-cell folate concentrations above 400 micrograms/L have a very low risk of NTD, we undertook a randomised trial of several folic acid doses to find out how much is needed to reach this protective concentration. METHODS: We screened 323 women. 172 with red-cell folate between 150 micrograms/L and 400 micrograms/L were invited to take part in the trial. 121 women were randomly assigned placebo or 100 micrograms, 200 micrograms, or 400 micrograms daily of additional folic acid. Compliance was monitored by having the women sign a dated sheet when taking the tablet. 95 women completed the 6-month study. FINDINGS: There were significant increases in red-cell folate in all folic acid groups. The placebo group showed no significant change. The median incremental changes and median post-treatment concentrations were 67 micrograms/L (95% CI 43-120) and 375 micrograms/L (354-444) in the 100 micrograms/day group, 130 micrograms/L (108-184) and 475 micrograms/L (432-503) in the 200 micrograms/day group, and 200 micrograms/L (125-312) and 571 micrograms/L (481-654) in the 400 micrograms/day group. INTERPRETATION: A fortification programme that delivered 400 micrograms folic acid daily to women would protect against NTD, but at the expense of unnecessarily high exposure for many people. Delivery of 200 micrograms daily is also effective against NTD and safer for the general population. Based on projections from the positive folate balance in the group that received 100 micrograms daily, this dose taken continually, as it will be in fortified food, will also produce an important decrease in NTD.

Adult↗
PubMed1997

Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations.

BACKGROUND: The dietary reference values for folate, as for other nutrients, are targeted to the general and supposedly normal population, not people with special needs, such as those with genetic or metabolic abnormalities or diseases. However, 5-15% of general populations are homozygous for a thermolabile variant of 5,10-methylenetetrahydrofolate reductase (C677T) which causes mild hyperhomocysteinaemia and is positively associated with the development of vascular disease and the risk of neural-tube defects. If tissue-folate status is compromised in large sectors of the population by this or other genetic variants, the present dietary reference values may need to be changed. METHODS: We identified the C677T genotype and measured red-cell folate concentrations in two groups of healthy women (pregnant, 242, not pregnant, 318). We then analysed the effect of genotype on red-cell folates, which are a reliable marker for tissue folate stores. FINDINGS: In the pregnant group there were 20 TT homozygotes, 114 wild-type CC homozygotes, and 108 CT heterozygotes. In the non-pregnant group, the numbers were 41, 148, and 129. In both pregnant and non-pregnant groups, red-cell folate was significantly lower among TT homozygous than CC homozygous women (mean 252 [95% CI 202-317] vs 347 [321-372] micrograms/L, p = 0.002 for pregnant women; 284 [250-327] vs 347 [342-372] micrograms/L, p = 0.01 for non-pregnant women). Plasma folate was also significantly lower in TT homozygous than in CC homozygous women in the pregnant group (p = 0.009) but not in the non-pregnant group. INTERPRETATION: These results suggest that a substantial minority of people in general populations may have increased folate needs. Future studies may show the presence of other common genetic variants that interact with particular nutrients and place doubts on the validity of assuming "normality" for nutrient requirements in any general population.

Diet↗
PubMed1997

The influence of routine completion arteriography on outcome following carotid endarterectomy.

The necessity for routine completion arteriography (RCA) following carotid endarterectomy (CEA) is controversial, with the reported yield of clinically significant findings varying from 3% to 16%. In order to determine the utility of RCA, we reviewed completion studies in 154 consecutive CEAs, defined the frequency and characteristics of arteriographic defects, and correlated RCA defects with early outcome (internal carotid artery [ICA] occlusion, stroke) and late restenosis. All intraoperative RCAs were reviewed by two blinded observers and categorized into three subsets: Group A (n = 69) normal; Group B (n = 29), abnormal, severe defects; Group C (n = 56), abnormal, mild-moderate defect. RCA detected 32 defects in Group B: 10 internal carotid (ICA), seven endpoint flaps, two kinks, one dissection; 16 external carotid (ECA), 10 severe endpoint defects and six total occlusion; six common carotid (CCA), five irregular proximal shelfs, one web. Thirty of 32 defects were successfully repaired as confirmed by normal repeat RCA studies; one ECA defect was not repaired and the ICA dissection was irreparable. In Group C, 67 mild-moderate defects were identified, but not corrected. These included < 30% stenosis in the ICA (12), ECA (18), CCA (24), and vein patch corrugation or irregularity (13). For the entire series the postoperative ICA occlusion rate was 2% (3/154), stroke rate 2.6% (4/154), and a subsequent > 50% restenosis rate of 7% (11/154). The yield from routine carotid completion arteriograms was significant, with 19% of studies identifying a severe defect that required repair. Although the difference in stroke rates and restenosis between the different groups did not reach statistical significance, patients with normal intraoperative arteriograms initially or after correction of a significant RCA defect had no early carotid occlusion (p = 0.05, Fisher's exact test) compared to patients with residual RCA defects. All early carotid occlusions occurred in patients with unrepaired defects. We conclude that RCA is an important method of quality control after CEA and exerts a subtle, but real, reduction in postoperative complications.

Aged↗
PubMed1997

Prospective validation of threshold criteria for intervention in infrainguinal vein grafts undergoing duplex surveillance.

Although color flow duplex surveillance (CFDS) of infrainguinal vein grafts has gained wide acceptance, definitive criteria mandating graft revision remain to be established. We prospectively evaluated 101 infrainguinal vein grafts undergoing CFDS in order to validate threshold duplex criteria for intervention which were derived from our previous experience and that reported by others. Complete CFDS of the bypass conduit and adjacent inflow and outflow arteries and Doppler-derived ankle brachial indices (ABI) were obtained every 3 months x 4 and every 6 months thereafter. The following threshold criteria mandating further evaluation and intervention to prevent graft occlusion were applied: high-velocity criteria (HVC) defined as peak systolic velocity (PSV) > 300 cm/sec and velocity ratio (Vr) > 3.5; low-velocity criteria (LVC) defined as PSV < 45 cm/sec; an ABI decrease > 0.15. Fifty-one grafts had normal serial CFDS and ABI; none subsequently occluded or required revision. Stenosis was detected by CFDS in 43 grafts (PSV > 180 cm/sec, Vr > 1.5). Within this subgroup, 54% of grafts subsequently required revision (20/43) or occluded (3/43). All grafts in this subgroup with stenoses progressed to PSV > 300 or Vr > 3.5 prior to revision or occlusion. Ten lesions (23%) regressed spontaneously without intervention (mean PSV 252 cm/sec, mean Vr 3.2); 10 lesions (23%) are stable, non-progressive, and remain under surveillance. Two grafts were abnormal by LVC; one was successfully revised, the other occluded prior to intervention. Five grafts had normal CFDS and ABI decrease > 0.15. Four were revised (three inflow lesions, one outflow lesion) and one occluded (missed lesion by CFDS). Only five graft occlusions occurred in the entire series: three grafts met HVC and occluded prior to intervention; one developed an ABI drop of 0.4 due to graft stenosis missed by CFDS and uncovered following thrombolysis, and the other graft met LVC and occluded prior to intervention. Infrainguinal vein grafts with normal serial CFDS and ABI are at minimal risk of spontaneous graft occlusion. When CFDS is abnormal (PSV > 180 cm/sec, Vr > 1.5), over 50% of grafts will ultimately require revision or progress to occlusion. Grafts with such lesions can be safely monitored by CFDS until progression to lesions meeting HVC occurs with minimal risk of graft occlusion. A decrease in ABI > 0.15 with normal CFDS mandates arteriography to identify inflow and outflow lesions or a missed graft stenosis. The present study prospectively validates threshold intervention criteria for graft lesions meeting HVC (PSV > 300 cm/sec, Vr > 3.5), LVC (PSV < 45 cm/sec throughout graft) or an ABI decrease > 0.15.

Aged↗
PubMed1997

Vitamin A and birth defects.

OBJECTIVE: Our objective was to determine whether moderate doses of vitamin A are teratogenic. STUDY DESIGN: This was a geographically based case-control study. Women whose pregnancies produced offspring with neural tube defects (n = 548) or major malformations other than neural tube defects (n = 387) and normal control subjects (n = 573) were interviewed to determine periconceptional vitamin A supplement exposure levels. RESULTS: The proportion of women consuming doses of vitamin A between 8000 and 25,000 IU was no greater in the major malformations group or the group with neural tube defects than in the normal control group. For exposure from supplements and fortified cereals combined, women consuming >8000 and >10,000 IU daily had odds ratios for major malformations of 0.79 (95% confidence interval 0.40 to 1.53) and 0.73 (95% confidence interval 0.27 to 1.96), respectively, compared with women consuming <5000 IU. The results for neural tube defects were similar. For cranial neural crest defects the odds ratios were 0.76 (0.22 to 2.56) and 1.09 (0.24 to 4.98) for exposure to >8000 and >10,000 IU, respectively, versus exposure to <5000 IU. CONCLUSIONS: This study found no association between periconceptional vitamin A exposure at doses >8000 IU or >10,000 IU per day and malformations in general, cranial neural crest defects, or neural tube defects. If vitamin A is a teratogen, the minimum teratogenic dose appears to be well above the level consumed by most women during organogenesis.

Adult↗
PubMed1997

The paradoxical effect of smoking in preeclamptic pregnancies: smoking reduces the incidence but increases the rates of perinatal mortality, abruptio placentae, and intrauterine growth restriction.

OBJECTIVES: Smoking is associated with a reduced risk of preeclampsia, but what is the outcome of pregnancy when preeclampsia develops in women who smoke? STUDY DESIGN: Single births in Sweden from 1987 through 1993 to nulliparous women aged 15 to 34 years (N = 317,652) were included. Poisson regression analyses were used to calculate adjusted relative risks and rates of adverse pregnancy outcomes. RESULTS: Maternal smoking was associated with significantly reduced risks of mild and severe preeclampsia (relative risks = 0.6 and 0.5, respectively). In pregnancies with severe preeclampsia, smoking at least 10 cigarettes per day was associated with increased rates of perinatal mortality (from 24 to 36 per 1000), abruptio placentae (from 31 to 67 per 1000), and being small for gestational age (from 28% to 68%), whereas the corresponding smoking-related increases in rates in nonhypertensive pregnancies were considerably less. CONCLUSIONS: Smokers in whom preeclampsia develops have very high risks of perinatal mortality, abruptio placentae, and small-for-gestational-age infants.

Abruptio Placentae↗
PubMed1997

Identification of predictors for lower extremity vein graft stenosis.

BACKGROUND: The cause of intrinsic vein graft stenosis, which develops in at least 20% of infrainguinal autogenous bypass grafts during the intermediate follow-up interval, is unknown. We performed standard duplex surveillance of all lower extremity bypass grafts and evaluated the potential of comorbid patient risk factors that might predict development of vein graft flow disturbance or high-grade graft stenosis. METHODS: Patients with at least 6 months of postoperative duplex surveillance were identified through our vascular registry. The association of clinical and hemodynamic profiles of graft performance were compared with specific patient risk factors, including demographics, cigarette smoking, antihypertensive medical therapy, type and quality of conduit, degree of ischemia, bypass run-off, and presence of infection, using stepwise logistic regression analysis. RESULTS: Ninety-three patients (55 male, 38 female; mean age 69) underwent 100 infrainguinal bypasses. Twenty-six high-grade graft stenoses (>70%) were identified in 26 patients during follow-up (mean 21 months) by graft-flow peak systolic velocity (PSV) >300 cm/sec on more than one duplex examination, and were electively revised. Graft flow disturbances (180 cm/sec >PSV <300 cm/sec) were identified in an additional 13 grafts (6 regressed, 7 observed). The need for graft revision was associated with an early graft flow disturbance (P = 0.02), or drop in ankle-brachial index >0.15 (P = 0.03), and the use of an alternative conduit in 13 of 100 grafts (P = 0.04). Only smoking was associated with the development of a duplex detected graft flow disturbance during follow up (P = 0.03). CONCLUSION: Grafts with early flow disturbances warrant close duplex surveillance to identify graft-threatening stenosis. Risk factors that may predict future lower extremity bypass graft stenosis are smoking and the use of alternative bypass conduits.

Aged↗
PubMed1997

Free tissue transfer to extend the limits of limb salvage for lower extremity tissue loss.

BACKGROUND: The extent of tissue loss amenable to primary healing after revascularization is unknown. Salvage of limbs with large soft-tissue defects with exposed tendon, joint, or bone lies beyond the limits of conventional techniques. We report our results using free tissue transfer as an adjunct to lower extremity vascular reconstruction in patients with complex ischemic or infected wounds. METHODS: Retrospective chart review of patient and wound characteristics. RESULTS: From January 1992 to June 1996, 585 procedures were performed in 544 patients, including 27 free flaps in 26 patients: 17 free flaps combined with distal bypass (7 staged, 10 simultaneous) and 10 isolated free flaps. Flap donor sites included radial forearm (8), latissimus dorsi (7), rectus abdominus (9), and scapula (3). Surgical indications included extensive ischemic/neurotrophic ulcers, and nonhealing vein graft harvest incision or transmetatarsal amputation site. Mean area of tissue loss was 70 cm2, mean ulcer duration was 5 months, and 92% of patients had exposed tendon, joint, or bone. During a mean follow-up of 14 months, 2 patients died of cardiopulmonary disease and 3 flaps failed, resulting in below-knee amputation. Six flaps were revised for graft stenosis (1), venous thrombosis (1), or flap edge necrosis (4). Limb salvage rate was 70% at 24 months by life-table analysis. Functional ambulation was achieved in 21 of 24 (88%) patients, including 7 of 8 with diabetes, end-stage renal disease, and heel ulcers. CONCLUSION: In select ambulatory patients with large soft-tissue defects and exposed deep structures, functional limb salvage is obtainable in more than 80% of patients. For lesions not amenable to vascular reconstruction with conventional methods of wound coverage, free tissue transfer extends the limits of limb salvage and is a viable alternative to amputation.

Adult↗
PubMed1997

Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia.

OBJECTIVE: As more children survive acute lymphoblastic leukemia (ALL), questions are raised regarding how the disease and its therapy affect their pubertal development. STUDY DESIGN: The National Institute of Child Health and Human Development-National Cancer Institute-Children's Cancer Group Leukemia Follow-Up Study used a historical cohort design to investigate menarche in 188 ALL survivors who were premanarchal at diagnosis, aged at least 18 years, at least 2 years after diagnosis, alive, and in remission. Female siblings of ALL survivors (n = 218) served as control subjects. RESULTS: Menarche occurred within the normal age range in 92% of survivors and 96% of the control subjects (p = 0.09). Early menarche occurred in four survivors (2%) and three control subjects (1%). Delayed, absent, or medically induced menarche was reported by 12 survivors (6%) and six control subjects (3%). Compared with the control subjects, survivors of ALL who received 1800 cGy cranial radiation before the age of 8 years had significantly earlier menarche, relative hazard (RH) of 2.2 (95% confidence interval: 1.4, 3.4 [p = 0.0003]). Survivors receiving 2400 cGy of craniospinal radiation with or without abdominal radiation had significantly later menarche than the control subjects, RH 0.4 (95% confidence interval: 0.3, 0.7 [p = 0.0002]). CONCLUSIONS: In this large cohort of ALL survivors, the risk of disordered menarche was low. However, younger subjects receiving 1800 cGy cranial radiation and those receiving 2400 cGy below the diaphragm required careful monitoring.

Adolescent↗
PubMed1997

Distal revascularization-interval ligation for limb salvage and maintenance of dialysis access in ischemic steal syndrome.

PURPOSE: Traditional options for treating ischemic steal syndrome related to a functioning dialysis access graft or fistula include banding or ligation. Unfortunately, these techniques usually result in inconsistent limb salvage, loss of a functional access, or both. We report our experience with an alternative method of limb revascularization that eliminates steal while maintaining continuous dialysis access. METHODS: Patients who had critical limb ischemia and functioning arteriovenous fistulae (AVF) underwent color-flow duplex scanning, digital photoplethysmography, and arteriography. Arterial ligation distal to the AVF origin eliminated the steal physiologic mechanism while arterial bypass grafting from above to below the AVF revascularized the extremity (distal revascularization-interval ligation [DRIL] procedure). RESULTS: From March 1994 through December 1996, 21 patients with functioning extremity AVFs presented with critical ischemia and steal syndrome. Eleven patients had chronic ischemia with rest pain, paresthesias, or ulcerations related to nine native fistulae (six brachiocephalic, two basilic vein transpositions, one radiocephalic) and two prosthetic bridge grafts (one upper arm, one lower extremity). Acute ischemia developed in 10 patients related to three native fistulae (two brachiocephalic, one radiocephalic) and seven prosthetic bridge grafts (three forearm, three lower extremity, one upper arm). All 21 patients were treated with the DRIL technique. Three of these patients required treatment for ischemia at the time of AVF construction. Nineteen of 21 bypass procedures were performed with autogenous vein, including nine brachial-brachial, three brachial-radial, two radial-radial, two brachial-ulnar, one popliteal-popliteal, one femoral-popliteal, and one femoral-peroneal. Polytetrafluoroethylene grafts were used for one external iliac-popliteal bypass graft and one axillary-brachial bypass graft. Limb salvage and maintenance of a functional fistula were achieved in 100% and 94%, respectively, at 18 months by life-table analysis. CONCLUSION: The DRIL technique reliably restores antegrade flow to the ischemic limb, eliminates the potential pathway for the steal physiologic mechanism, and maintains continuous dialysis access in these difficult patients.

Aged↗
PubMed1997

Salvage of femoropedal bypass graft complicated by interval gangrene and vein graft blowout using a flow-through radial forearm fasciocutaneous free flap.

We report the case of a 71-year-old man who had interval gangrene of his calf with subsequent vein graft blowout 3 months after undergoing a femoral-to-dorsalis pedis saphenous vein bypass grafting procedure. To provide wound coverage, restore vascular continuity, and preserve functional ambulation, a flow-through radial forearm fasciocutaneous free flap was interposed between cut ends of the bypass graft. Venous drainage of the flap was from the cephalic vein to the popliteal vein. At 1 month after the operation, the patient had complete wound healing and began to ambulate. At 11 months an asymptomatic high-grade stenosis in the distal radial artery segment of the reconstruction was successfully treated with percutaneous angioplasty. After 22 months of follow-up there have been no further complications, and the patient continues to have full, functional ambulation. The radial forearm flow-through free flap allows single-stage restoration of bypass graft continuity and coverage of extensive, complex tissue defects. This technique represents a novel approach to this difficult problem and provides a viable alternative to major limb amputation.

Aged↗
PubMed1997

Immunocytochemical determination of cell type and proliferation rate in human vein graft stenoses.

PURPOSE: Vascular reconstructions are prone to fail as a result of the development of stenotic lesions, which have historically been attributed to myointimal hyperplasia. In animal models, these lesions are associated with marked proliferative smooth muscle cell (SMC) response to vascular injury. However, recent studies using sensitive immunocytochemical techniques in human lesions have generally failed to detect significant cellular proliferation. To clarify the role of cellular proliferation in humans, we characterized the cellular composition and proliferative index of 14 early infrainguinal vein graft stenoses. METHODS: All infrainguinal vein grafts at our institution are prospectively enrolled in a duplex surveillance protocol, the details of which have been previously reported. Among 98 grafts placed within the last year, 11 patients were identified with 14 progressive, focal, high-grade lesions that met previously established threshold criteria for prophylactic revision to prevent graft thrombosis. Lesions were first detected from 1 week to 7 months after surgery and were removed and replaced with segmental interposition grafts (1.5 to 10 months). Freshly excised lesions were placed in Methyl Carnoy's fixative, paraffin embedded, and serially sectioned. The cellular composition of each lesion was determined with cell-specific immunochemical reagents: alpha SMC actin, von Willebrand factor (endothelial cell), CD 68 (macrophage), and CD 45RB (monocyte). Actively proliferating cells were identified using antibody to proliferating cell nuclear antigen (PCNA). The identity of PCNA-positive cells was determined by double-label immunocytochemical staining, and the proliferative index (PCNA-positive cells/total cells x 100) was calculated by computer-assisted counts of representative gridded cross-sections of each lesion. RESULTS: All excised lesions demonstrated marked thickening with severe luminal encroachment and were highly cellular, with a predominance of alpha SMC actin+. Endothelial cells on the blood flow surface were present to a variable degree, and seven lesions exhibited striking numbers of macrophages and monocytes. The latter cell types were most abundant near microvessels in the deep neointima and adventitia. Active cellular proliferation was identified primarily in SMCs, with a mean PCNA index of 1.34%. However, significant PCNA reactivity was not limited to SMCs, but was also identified in macrophages and monocytes, particularly in lesions greater than 3 months old. CONCLUSIONS: Previous immunocytochemical studies of human coronary restenosis atherectomy specimens have generally detected low rates of cellular proliferation (0.5%), but these lesions may not truly represent myointimal hyperplasia, rather a mixture of atherosclerosis, thrombosis, and "restenosis." In contrast, the present study of early human vein graft lesions detected by duplex surveillance indicates that significant cellular proliferation occurs, although rates are lower than those obtained in animals such as the rat carotid injury model. In addition, although SMCs are the predominant proliferating cell type in human vein grafts, our identification of proliferating monocytes and macrophages raises the question of the contribution of an inflammatory component to the development of human lesions. The present study represents the first report of PCNA determination in a series of human infrainguinal vein grafting procedures.

Cell Division↗
PubMed1997

Are common mutations of cystathionine beta-synthase involved in the aetiology of neural tube defects?

Mildly elevated maternal plasma homocysteine (Hcy) levels (hyperhomocysteinemia) have recently been observed in some neural tube defect (NTD) pregnancies. Plasma levels of Hcy are governed by both genetic and nutritional factors and the aetiology of NTDs is also known to have both genetic and nutritional components. We therefore examined the frequency of relatively common mutations in the enzyme cystathionine beta-synthase (CBS), which is one of the main enzymes that controls Hcy levels, in the NTD population. Neither the severely dysfunctional G307S CBS allele nor the recently reported 68 bp insertion/I278T CBS allele was observed at increased frequency in the cases relative to controls. We therefore conclude that loss of function CBS alleles do not account for a significant proportion of NTDs in Ireland.

Cystathionine beta-Synthase↗
PubMed1997

Comparison of psychologic outcome in adult survivors of childhood acute lymphoblastic leukemia versus sibling controls: a cooperative Children's Cancer Group and National Institutes of Health study.

PURPOSE: To determine psychologic outcome, with the focus on emotional or mood state, of young adult survivors of childhood acute lymphoblastic leukemia (ALL) compared with sibling controls and to identify vulnerable subgroups at highest risk for negative mood. PATIENTS AND METHODS: Adult survivors (n = 580), aged > or = 18 years, who were treated before age 20 years on Children's Cancer Group (CCG) protocols for ALL and 396 sibling controls were administered a structured telephone interview and the Profile of Moods State (POMS), a standardized measure of affective state. RESULTS: Survivors had higher total mood scores (which indicates greater negative mood) than sibling controls (P<.01) and reported more tension (P< .01), depression (P<.01), anger (P<.01), and confusion (P<.01), but not more fatigue or less vigor. Female, minority, and unemployed survivors reported the highest total mood disturbance. Overall, survivors were more likely to be unemployed (P<.05) or working less than half-time (P<.01) compared with controls. CONCLUSION: This large, sibling-controlled, multisite study of young adult survivors of childhood ALL treated on CCG protocols after 1970 found significant increased negative mood in survivors, not accounted for by reported energy level differences, which suggests that these emotional effects are not likely the result of current illness. Survivors are less likely to be fully employed. Female, minority, and unemployed survivors are at greatest risk for emotional sequelae, a finding that indicates the need for targeted, preventive intervention.

Adult↗