Alpha-1 deficiency in severe asthma patients.

Alpha-1 antitrypsin (AAT) deficiency, an autosomal co-dominant condition, decreases protein concentration and activity at both serum and tissue levels. Few studies investigated whether the type of SERPINA1 gene phenotype in patients with severe asthma can influence symptoms and disease control during follow-up.To assess whether the presence of a non-MM genotype of SERPINA1 in patients with severe asthma is associated with disease control, systemic and airway inflammation, lung function and comorbidities prevalence compared to severe asthma patients with a homozygous genotype (MM).Asthmatic patients belonging to Global Initiative for Asthma (GINA) step 5 were retrospectively analysed in an Italian reference asthma clinic. We collected clinical, biological and functional variables at baseline and for the three following years.Out of 73 patients enrolled, 14 (19.18%) were non-MM and 59 (80.8%) were MM. Asthmatics with non-MM genotype had lower serum AAT concentration (P = 0.004) and higher emphysema prevalence than the MM group (P = 0.003) at baseline. During follow up, only MM patients showed a significant improvement of both ACQ-6 score (P < 0.0001) and eosinophilic systemic inflammation (P < 0.0001).Our findings emphasise the importance of a screening for AAT deficiency in severe asthma, as alleles mutation may influence patient's follow-up..

Type II sialidosis: review of the clinical spectrum and identification of a new splicing defect with chitotriosidase assessment in two patients.

Sialidosis is a lysosomal storage disease caused by the deficiency of alpha-N-acetyl neuraminidase-1 (NEU1). Sialidosis is classified into two main clinical variants: Type I, the milder form of the disease, and Type II, which can in turn be subdivided into three forms: congenital, infantile and juvenile. We report herein the clinical, biochemical and molecular characterisation of two patients with Type II sialidosis exhibiting the congenital (P1) and infantile forms (P2). We also review clinical data on the rare Type II forms of sialidosis in the hope of improving understanding of the disorder and facilitating its diagnosis. The genetic characterization of the two patients showed one known [c. 679G > A (p.G227R)] NEU1 missense mutation (detected in P2), and the new c.807 + 1G > A splicing defect (detected in P1), a genetic lesion that is extremely rare in this disease. Interestingly, P2 presented an extremely elevated level of chitotriosidase in plasma. This is the first pathological detection of chitotriosidase in sialidosis patients.

[Churg-Strauss syndrome: outcome and long-term follow-up of 38 patients from a single Italian centre]. / Caratteristiche clinico-sierologiche e dati di out come di una casistica monocentrica di pazienti affetti da sindrome di Churg-Strauss.

OBJECTIVE: This study was aimed at verifying any potential correlation between anti-myeloperoxidase antineutrophil cytoplasmic antibodies (ANCA-MPO) and clinical features and outcome indices in Churg-Strauss Syndrome (CSS). METHODS: Thirty-eight Churg-Strauss syndrome patients were selected from the medical records of all vasculitis patients attending the Rheumatology and Immunology Unit at the Department of Internal Medicine of the University of Pisa in the decades between 1989 and 2008. Data were analysed retrospectively. Statistical analyses of the results were carried out using the Mann-Whitney test to determine the correlations between the clinical and serological parameters. Qualitative variables were compared using contingency table analysis and Fisher's exact test. RESULTS: ANCA-MPO were detected in15/38 (39%) patients. Positive ANCA status was associated with peripheral neuropathy (p=0.0006), whereas negative ANCA status was associated with lung involvement (p=0.002). Relapses were strongly associated with positive ANCA status (p=0.01) and with an increase in- or a reappearance of ANCA-MPO levels (p=0.006). Finally, ANCA-MPO were significantly associated with neurological damage (p=0.003). CONCLUSIONS: The presence or absence of ANCA-MPO identify different clinical subsets in CSS. Overall, ANCA-MPO appears as a useful tool in the monitoring of CSS and in particular a good predictor of CSS relapses.

[What sense in cannabinoid use as regulated by Italian DM 18/04/07? Pharmacological and legal considerations]. / Quale razionale nell'impiego dei cannabinoidi previsto dal Decreto Ministeriale 18 aprile 2007? Considerazioni farmacologiche e medico-legali.

The present article relates to the Italian Ministerial Decree (DM) 18/04/2007 referring to what was established by the Financial Law 2007 on the matter of the use of drugs for the so called ''off-label'' uses. This law introduces three cannabinoid substances, with the common name of Delta 9 and Trans-delta 9 tetrahydrocannabinol and Nabilone, within the possible therapies for the treatment of ''severe pain''. The authors underline the absence of a sufficient pharmacokinetical and pharmacodynamical knowledge supporting the use of cannabinoid substances in the ''severe pain'' therapy. Further more the professional prescriber could go against judicial consequences if the drugs causes as verified the onset of collateral effects even severe that, for the scientific knowledge in possess at the present state, the authors know could take place.

Movement and mood disorder in two brothers with Gaucher disease.

Gaucher disease (GD) is a lysosomal storage disorder with a wide spectrum of phenotypic presentations. We report the case histories of two adult brothers with GD who developed both parkinsonism and psychiatric symptoms. Direct sequencing and real-time polymerase chain reaction were used to establish that the patients were homozygous for mutation L444P. While parkinsonism has been described previously in GD, these patients had atypical features, including a complicated mood disorder. The comorbidity of GD and a mood disorder is a new finding, as psychiatric manifestations of GD have been described rarely. The etiology of the mental illness could be related to the processes contributing to the development of parkinsonism.

A phase II study of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine and pegfilgrastim support as preoperative therapy for patients with stage II, IIIA breast cancer.

BACKGROUND: This phase II study was conducted to evaluate tumor response rate and safety profile of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine given preoperatively to patients with stage II or IIIA breast cancer. PATIENTS AND METHODS: Patients underwent four cycles of dose-dense cyclophosphamide 600 mg/m(2) and epirubicin 90 mg/m(2) every 2 weeks followed by two cycles of docetaxel 36 mg/m(2) on days 1, 8, and 15 plus capecitabine 1250 mg/m(2) on days 5-18 every 4 weeks, with prophylactic pegfilgrastim. The primary objective of the study was to determine the incidence of pathologic complete response defined as the absence of invasive or in situ cancer in the breast and the axillary nodes at definitive surgery. RESULTS: Forty-four patients were enrolled in the study and 41 (93%) were assessable for response to chemotherapy. An objective clinical response was observed in 38 (93%) patients. Seven patients (17.1%) exhibited a pathologic complete response. Breast-conserving surgery was carried out in 36 (88%) patients. Grade 3/4 neutropenia occurred in 4.3% of 252 administered chemotherapy cycles. No febrile neutropenia, cardiac toxicity, thrombocytopenia or other serious adverse event was registered. CONCLUSION: The sequential combination of dose-dense epirubicin plus cyclophosphamide followed by docetaxel plus capecitabine is an effective and well-tolerated neo-adjuvant chemotherapy for stage II, IIIA breast cancer.

Genetic diversity in wild (Sus scrofa scrofa) and domestic (Sus scrofa domestica) pigs and their hybrids based on polymorphism of a fragment of the D-loop region in the mitochondrial DNA.

We examined the variation in mitochondrial DNA by sequencing the D-loop region in wild and domestic (large-white breed) pigs, in hybrids between domestic and wild pigs, and in Monteiro pigs. A D-loop fragment of approximately 330 bp was amplified by PCR. Sequencing of DNA amplicons identified haplotypes previously described as European and Asian types. Monteiro pigs and wild pigs had European haplotypes and domestic pigs had both European and Asian haplotypes.

Effects of combined dietary supplementation on oxidative and inflammatory status in dyslipidemic subjects.

BACKGROUND AND AIM: Dyslipidemia is one of the main risk factors for atherosclerosis, usually the underlying cause of cardiovascular diseases which are the major cause of morbidity and mortality in developed countries. The aim of this study was to assess the effects and the advantages of a combined dietary supplementation with PUFA n-3, vitamin E, niacin and gamma-oryzanol on lipid profile, inflammatory status and oxidative balance. METHODS AND RESULTS: Fifty-seven dyslipidemic volunteers were randomly assigned to receive: placebo (group A, 19 subjects); PUFA n-3 and vitamin E (group B, 18 subjects); the same as B plus gamma-oryzanol and niacin (group C, 20 subjects). Lipid profile, reactive oxygen species (ROS), total antioxidant capacity (TAC), vitamin E, interleukin 1-beta (IL1-beta), tumor necrosis factor (TNF-alpha) and thromboxane B2 (TXB2) were determined at baseline (T0) and after four months (T1). All dyslipidemic subjects showed, at baseline, oxidative stress and, after four months, all biochemical markers improved significantly in groups treated with dietary supplementation. Particularly in group C all lipid patterns improved significantly. CONCLUSIONS: Our findings demonstrate that the strategy of combining different compounds, which protect each other and act together at different levels of the lipid chain production, improves lipid profile, inflammatory and oxidative status, allowing us to reduce the dose of each compound under the threshold of its side effects.

Genetic diversity in wild (Sus scrofa scrofa) and domestic (Sus scrofa domestica) pigs and their hybrids based on polymorphism of a fragment of the D-loop region in the mitochondrial DNA

We examined the variation in mitochondrial DNA by sequencing the D-loop region in wild and domestic (large-white breed) pigs, in hybrids between domestic and wild pigs, and in Monteiro pigs. A D-loop fragment of approximately 330 bp was amplified by PCR. Sequencing of DNA amplicons identified haplotypes previously described as European and Asian types. Monteiro pigs and wild pigs had European haplotypes and domestic pigs had both European and Asian haplotypes.

Screening of 25 Italian patients with Niemann-Pick A reveals fourteen new mutations, one common and thirteen private, in SMPD1.

Niemann-Pick disease (NPD) results from the deficiency of lysosomal acid sphingomyelinase (SMPD1). To date, out of more than 70-disease associated alleles only a few of them have a significant frequency in various ethnic groups. In contrast, the remainder of the mutations are rare or private. In this paper we report the molecular characterization of an Italian series consisting of twenty-five NPD patients with the severe neurodegenerative A phenotype. Mutation detection identified a total of nineteen different mutations, including 14 novel mutations and five previously reported lesions. The known p.P189fs and the novel p.T542fs were the most frequent mutations accounting for 34% and 18% of the alleles, respectively. Screening the alleles for the three common polymorphisms revealed the variant c.1516G>A (exon 6) and the repeat in exon 1, but not the variant c.965C>T (exon 2). In absence of frequent mutations, the prognostic value of genotyping is limited. However, new genotype/phenotype correlations were observed for this disorder that could in the future facilitate genetic counseling and guide selection of patients for therapy.

[Juvenile papillomatosis of the breast]. / La papillomatosi giovanile (PJ) della mammella.

The PJ, introduced by Rosen in the 1980, is a benign and localized mammary lesion in female under 30 years old. The most important clinical and histological features are: Diagnosis in juvenile age. A mass clinically localized. A nodule with histologic features of cyst, benign hyperplasia of ductal epithelium and galactophorus ducts dilatation (Swiss cheese disease). There is a correlation between patients with PJ and breast cancer there is an increment of breast cancer in familirs of patients with PJ. There is an increment of the risk to develop a K in situ in patients with PJ and apocrine metaplasia and/or adenomatosis and/or atypical mastoplasia. We describe the diffuse PJ in a girl of 23 years old from the 1996 to 2002.

Telomere formation by rap1p binding site arrays reveals end-specific length regulation requirements and active telomeric recombination.

Rap1p, the major telomere repeat binding protein in yeast, has been implicated in both de novo telomere formation and telomere length regulation. To characterize the role of Rap1p in these processes in more detail, we studied the generation of telomeres in vivo from linear DNA substrates containing defined arrays of Rap1p binding sites. Consistent with previous work, our results indicate that synthetic Rap1p binding sites within the internal half of a telomeric array are recognized as an integral part of the telomere complex in an orientation-independent manner that is largely insensitive to the precise spacing between adjacent sites. By extending the lengths of these constructs, we found that several different Rap1p site arrays could never be found at the very distal end of a telomere, even when correctly oriented. Instead, these synthetic arrays were always followed by a short ( approximately 100-bp) "cap" of genuine TG repeat sequence, indicating a remarkably strict sequence requirement for an end-specific function(s) of the telomere. Despite this fact, even misoriented Rap1p site arrays promote telomere formation when they are placed at the distal end of a telomere-healing substrate, provided that at least a single correctly oriented site is present within the array. Surprisingly, these heterogeneous arrays of Rap1p binding sites generate telomeres through a RAD52-dependent fusion resolution reaction that results in an inversion of the original array. Our results provide new insights into the nature of telomere end capping and reveal one way by which recombination can resolve a defect in this process.

A partially structured species of beta 2-microglobulin is significantly populated under physiological conditions and involved in fibrillogenesis.

The folding of beta(2)-microglobulin (beta(2)-m), the protein forming amyloid deposits in dialysis-related amyloidosis, involves formation of a partially folded conformation named I(2), which slowly converts into the native fold, N. Here we show that the partially folded species I(2) can be separated from N by capillary electrophoresis. Data obtained with this technique and analysis of kinetic data obtained with intrinsic fluorescence indicate that the I(2) conformation is populated to approximately 14 +/- 8% at equilibrium under conditions of pH and temperature close to physiological. In the presence of fibrils extracted from patients, the I(2) conformer has a 5-fold higher propensity to aggregate than N, as indicated by the thioflavine T test and light scattering measurements. A mechanism of aggregation of beta(2)-m in vivo involving the association of the preformed fibrils with the fraction of I(2) existing at equilibrium is proposed from these results. The possibility of isolating and quantifying a partially folded conformer of beta(2)-m involved in the amyloidogenesis process provides new opportunities to monitor hemodialytic procedures aimed at the reduction of such species from the pool of circulating beta(2)-m but also to design new pharmaceutical approaches that consider such species as a putative molecular target.

Periodontal infections contribute to elevated systemic C-reactive protein level.

BACKGROUND: Periodontitis is a local inflammatory process mediating destruction of periodontal tissues triggered by bacterial insult. However, this disease is also characterized by systemic inflammatory host responses that may contribute, in part, to the recently reported higher risk for cardiovascular disease (CVD) among patients with periodontitis. Moderate elevation of C-reactive protein (CRP) has been found to be a predictor of increased risk for CVD. Elevated CRP levels in periodontal patients have been reported by several groups. In this study, we examined whether CRP plasma levels are increased in periodontitis and if there is a relation to severity of periodontal disease and to the periodontal microflora. METHODS: CRP serum levels were assessed using radial immunodiffusion assay in 174 subjects, 59 with moderate mean clinical attachment loss (AL) (2.39+/-0.29 mm) and 50 with high AL (3.79+/-0.86 mm) as compared to 65 periodontally healthy controls (AL, 1.74+/-0.18 mm). Clinical attachment loss, probing depths, and percentage of periodontal pocket sites > or =5 mm were measured. The presence of periodontal pathogens Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Campylobacter recta (C.r.), and Bacteroides forsythus (B.f.) in subgingival plaque samples was measured by immunofluorescence microscopy. RESULTS: Statistically significant increases in CRP levels were observed in subjects with periodontal disease when compared to healthy controls (P= 0.036). Subjects with high levels of mean clinical attachment loss had significantly higher mean CRP levels (4.06+/-5.55 mg/l) than controls (1.70+/-1.91 mg/l), P= 0.011. The CRP levels were adjusted for factors known to be associated with elevated CRP, including age, smoking, body mass index (BMI), triglycerides, and cholesterol. Age and BMI were found to be significant covariates. The reported range for CRP as a risk factor for CVD, peripheral vascular diseases, or stroke is 1.34 mg/l to 6.45 mg/l and the mean of this range is 3 mg/l. The percentage of subjects with elevated levels of CRP > or = 3 mm was significantly higher in the high clinical AL group (38%; 95% Cl: 26.7%, 49.3%) when compared to the control group (16.9%; 95% CI: 9.25%, 24.5%), P= 0.011. The presence of periodontal pathogens P.g., P.i., C.r., and B.f. in subgingival samples was positively associated with elevated CRP levels (P= 0.029). CONCLUSIONS: The extent of increase in CRP levels in periodontitis patients depends on the severity of the disease after adjusting for age, smoking, body mass index, triglycerides, and cholesterol. Also, there are elevated levels of CRP associated with infection with subgingival organisms often associated with periodontal disease, including P.g., P.i., C.r., and B.f. Recent investigations emphasized the role of moderate elevated CRP plasma levels as a risk factor for CVD. The positive correlation between CRP and periodontal disease might be a possible underlying pathway in the association between periodontal disease and the observed higher risk for CVD in these patients.

The effect of alcohol consumption on periodontal disease.

BACKGROUND: Alcohol consumption, like smoking, may be related to periodontal disease independently of oral hygiene status. This study assessed the relationship between alcohol consumption and severity of periodontal disease. METHODS: A cross-sectional study of 1,371 subjects ages 25 to 74 in the Erie County, NY population was performed. Alcohol intake was assessed by means of previously validated self-reported questionnaires. Outcome variables were gingival bleeding, clinical attachment loss, alveolar bone loss, and presence of subgingival microorganisms. RESULTS: Logistic regression analyses adjusting for age, gender, race, education, income, smoking, diabetes mellitus, dental plaque, and presence of any of 8 subgingival microorganisms showed that those consuming > or =5 drinks/week had an odds ratio (OR) of 1.65 (95% CI: 1.22 to 2.23) of having higher gingival bleeding, and OR of 1.36 (95% CI: 1.02 to 1.80) of having more severe clinical attachment loss compared to those consuming <5 drinks/week. Those consuming > or =10 drinks/week had an odds ratio (OR) of 1.62 (95% CI: 1.12 to 2.33) of having higher gingival bleeding and OR of 1.44 (95% CI: 1.04 to 2.00) of having more severe clinical attachment loss compared to those consuming <10 drinks/week. Alcohol consumption was not significantly related to alveolar bone loss nor to any of the subgingival microorganisms. CONCLUSIONS: The results suggest that alcohol consumption is associated with moderately increased severity of periodontal disease. Longitudinal studies are needed to determine whether alcohol is a true risk factor for periodontal disease.

Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial.

BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.

Treatment of periodontal disease and control of diabetes: an assessment of the evidence and need for future research.

Evidence points to an increased cytokine response in type 2 diabetes, especially the proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha. Genetics, age, and, nutrition are important signals for this increased response and as reported more recently, infections and inflammation. Persistent elevation of IL-1 beta, IL-6, and TNF-alpha in the diabetic state have an effect on the liver, stimulate the release of acute-phase proteins, produce the characteristic dysregulation of lipid metabolism associated with type 2 diabetes, and have effects on pancreatic beta cells as well. In addition, TNF-alpha, a potent inhibitor of the tyrosine kinase activity of the insulin receptor, has been implicated as an etiologic factor for insulin resistance. Collectively, the evidence supports a role for cytokine elevation in the pathophysiology and metabolic abnormalities associated with diabetes. Periodontitis is an infection that is twice as prevalent in diabetic individuals compared to non-diabetics. Porphyromonas gingivalis, one of the microorganisms responsible for this infection, is able to invade endothelial cells and is a potent signal for monocyte and macrophage activation. Thus, once established in the diabetic host, this chronic infection complicates diabetes control and increases the occurrence and severity of microvascular and macrovascular complications. Unlike treatment of acute infections, modalities of treatment for chronic infections are a matter of debate. Evidence indicates that mechanical removal of subgingival infection does not result in complete elimination of periodontal infection and consequently there is no effect on diabetes control measured as reduction in glycated hemoglobin. On the other hand, studies incorporating systemic antibiotics as adjuncts to mechanical debridement result in a reduction of P. gingivalis to nondetectable levels and a concomitant reduction in glycated hemoglobin, independent of the hypoglycemic effects of diabetes drugs or insulin. The evidence supports the notion that treatment of chronic periodontal infection is essential in the diabetic patient. Assessment of infection status in diabetic patients is fundamental for appropriate treatment decisions.

The relationship between bone mineral density and periodontitis in postmenopausal women.

BACKGROUND: Systemic bone loss has been proposed as a risk factor for periodontal disease; however, the relationship between these two diseases is still not clear. The objective of this study was to assess the relationship between systemic bone mineral density and periodontal disease, controlling for known confounders. METHODS: The study population included 70 postmenopausal Caucasian women aged 51 to 78 (mean +/- SD: 62.10 +/- 7.1 years). Skeletal bone mineral density (BMD) was assessed by dual energy x-ray absorptiometry (DXA) at the neck, trochanter, intertrochanter, Ward's triangle, and total regions of the femur, and from the anterior-posterior view of the lumbar spine. Periodontal disease severity was represented by clinical attachment loss (CAL) and interproximal alveolar bone loss (ABL). Other measures of periodontal status included probing depth (PD), supragingival plaque, gingival bleeding on probing, and calculus. DXA and oral examinations were performed by calibrated examiners. Partial correlation coefficients (r) were obtained from multiple linear regression analysis adjusting for age, age at menopause, estrogen supplementation, cigarette smoking, body mass index, and supragingival plaque. RESULTS: Mean ABL was significantly correlated with BMD of the trochanter (r =- 0.27), Ward's triangle (r = -0.26), and total regions of the femur (r = -0.25). Mean CAL appeared to be related to BMD consistently at all regions of the skeleton, although the association did not reach statistical significance. CONCLUSIONS: We can conclude that skeletal BMD is related to interproximal alveolar bone loss and, to a lesser extent, to clinical attachment loss, implicating postmenopausal osteopenia as a risk indicator for periodontal disease in postmenopausal Caucasian women.

Dietary vitamin C and the risk for periodontal disease.

BACKGROUND: Vitamin C has long been a candidate for modulating periodontal disease. Studies of scorbutic gingivitis and the effects of vitamin C on extracellular matrix and immunologic and inflammatory responses provide a rationale for hypothesizing that vitamin C is a risk factor for periodontal disease. METHODS: We evaluated the role of dietary vitamin C as a contributing risk factor for periodontal disease utilizing the Third National Health and Nutrition Examination Survey (NHANES III) which is representative of the U.S. civilian, non-institutionalized population. RESULTS: A sample of 12,419 adults (20 to 90+ years of age), with dental measurements and assessment of dietary information as well as demographic and medical histories were included in the studies. Dietary vitamin C was estimated by a 24-hour dietary record. Individuals with periodontal disease were arbitrarily defined as those who had mean clinical attachment levels of > or =1.5 mm. Using multiple logistic regression analysis, we found a relationship between reduced dietary vitamin C and increased risk for periodontal disease for the overall population (odds ratio [OR] = 1.19; 95% CI: 1.05 to 1.33). Current and former tobacco users who were taking less dietary vitamin C showed an increased risk of periodontal disease with OR of 1.28, 95% CI: 1.04 to 1.59 for former smokers, and an OR of 1.21, 95% CI: 1.02 to 1.43 for current tobacco users. There was a dose-response relationship between the levels of dietary vitamin C and periodontal disease with an OR of 1.30 for those taking 0 to 29 mg of vitamin C per day, to 1.16 for those taking 100 to 179 mg of vitamin C per day as compared to those taking 180 mg or more of vitamin C per day. CONCLUSION: Dietary intake of vitamin C showed a weak, but statistically significant, relationship to periodontal disease in current and former smokers as measured by clinical attachment. Those taking the lowest levels of vitamin C, and who also smoke, are likely to show the greatest clinical effect on the periodontal tissues.