Obliterative bronchiolitis after lung and heart-lung transplantation

Obliterative bronchiolitis (OB) has emerged as the main cause of morbidity and mortality in the long-term follow-up after lung and heart-lung transplantation. The pathogenesis of OB is multifactorial, with acute rejection and cytomegalovirus infection being the main risk factors for the development of OB. The final common pathway of all inciting events seems to be an alloimmune injury, with subsequent release of immunologic mediators and production of growth factors leading to luminal obliteration and fibrous scarring of the small airways. Analyzing the 14 years of experience in 163 patients at Stanford University, we found a current incidence of bronchiolitis obliterans syndrome or histologically proven OB within the first 3 years after lung and heart-lung transplantation of 36.3%, with an overall prevalence of 58.1% after heart-lung and 51.4% after lung transplantation. Both pulmonary function indices (forced expiratory flow between 25% and 75% of forced vital capacity and forced expiratory volume in 1 second) and transbronchial biopsies have proven helpful in diagnosing bronchiolitis obliterans syndrome or OB at an early stage. Early diagnosis of OB and improved management have achieved survival rates in patients with OB after 1, 3, 5, and 10 years of 83%, 66%, 46%, and 22%, compared with 86%, 83%, 67%, and 67% in patients without OB. Recently, different experimental models have been developed to investigate the cellular and molecular events leading to OB and to evaluate new treatment strategies for this complication, which currently limits the long-term success of heart-lung and lung transplantation.     

Efficacy and safety of pravastatin in African Americans with primary hypercholesterolemia

BACKGROUND: Coronary artery disease strikes early and may prove particularly severe in persons of African-American descent. Therefore, we studied the lipid-lowering efficacy and safety of pravastatin sodium (20 mg/d), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in 245 African-American patients with primary hypercholesterolemia. METHODS: After 4 weeks on an American Heart Association phase I low-fat diet, patients were randomized in a double-blind manner to either pravastatin or placebo in a 3:1 ratio. RESULTS: After 12 weeks of pravastatin treatment, low-density lipoprotein cholesterol levels declined 25.8%, total cholesterol levels 20.3%, and triglyceride levels 6.2%, while high-density lipoprotein cholesterol levels remained essentially unchanged. Overall, 72% of pravastatin-treated patients achieved reductions in low-density lipoprotein cholesterol level in excess of 20%, and 44% attained declines in excess of 30% (both P < .01 vs placebo). Pravastatin was generally well tolerated in this population, with one patient (0.5%) exhibiting a reversible myopathy with creatine kinase elevations to 10 times the upper limit of normal. No substantial elevations of aminotransferase levels of two to three times the upper limit of normal occurred in either the pravastatin or the placebo group. Drug compliance was high, exceeding 90%. CONCLUSION: Pravastatin appears to be an effective and safe lipid-lowering agent and is the first 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor to be studied extensively in this underrepresented population.     

Age-induced decrease of glycoprotein Po and myelin basic protein gene expression in the rat sciatic nerve. Repair by steroid derivatives

The data here reported show that the gene expression of the glycoprotein Po and of the myelin basic protein, the major components of myelin in the peripheral nervous system, dramatically decreases with ageing in the sciatic nerve of normal male rats. A one-month treatment with dihydroprogesterone, the 5alpha-reduced derivative of progesterone, is able to partially restore the fall in Po gene expression occurring in the sciatic nerve of aged male rats, without significantly modifying the gene expression of the myelin basic protein. In cultures of neonatal Schwann cells (the peripheral nervous system elements involved in the synthesis of myelin), the addition of progesterone and of dihydroprogesterone significantly increases Po gene expression; the 3alpha-reduced metabolite of dihydroprogesterone, tetrahydroprogesterone proved to be even more effective. These data suggest that the effect of progesterone is linked to its conversion into dihydroprogesterone and especially into tetrahydroprogesterone, since Schwann cells possess the 5alpha-reductase-3alpha-hydroxysteroid dehydrogenase system. The data provide the first demonstration that ageing decreases the gene expression of two major components of the peripheral myelin in the sciatic nerve; they also show that this phenomenon may be partially reversed by progesterone derivatives, which might act by stimulating Po gene expression in the Schwann cells.     

Sequential use of intravenous and oral acyclovir in the therapy of varicella in immunocompromised children

BACKGROUND: Immunocompromised children are at risk for disseminated varicella infections. Standard management involves hospitalization and intravenous acyclovir for 7 to 10 days. This approach is expensive, is inconvenient and may not be necessary. We undertook a pilot study to assess the safety and efficacy of an alternative approach that utilized a combination of intravenous (i.v.) followed by oral (p.o) acyclovir in a cohort of immunocompromised children. METHODS: The cohort consisted of 26 immunocompromised children between the ages of 1.5 and 12.7 years (mean, 6.3). Therapy was commenced with i.v. acyclovir (1500 mg/m2/day in 3 divided doses). Concurrent management included holding or reducing immunosuppressive therapy (by 50%) and administering varicella-zoster immunoglobulin in 69% (11 of 16) of cases where exposure to chickenpox was recognized. Patients were eligible to switch to p.o therapy after receiving a minimum of 48 h of i.v. acyclovir therapy provided they were afebrile; had no new lesions for 24 h; had no internal organ involvement and were able to tolerate oral medications. Patients were observed in hospital for a further 24 h and then discharged provided they remained well. Oral acyclovir was continued for a total of 7 to 10 days (i.v. plus p.o). RESULTS: Of the 26 patients 25 were successfully switched from i.v. to p.o after 4.1 +/- 1.2 days (mean +/- SD) (range, 2.3 to 6) Children had fever for a mean of 2.0 +/- 1.6 days (range, 0 to 5) and developed new lesions for 2.9 +/- 0.7 days (range, 2 to 4). All 25 patients switched to p.o therapy had resolution of their disease and no patient required resumption of i.v. therapy. CONCLUSIONS: The sequential use of i.v. followed by p.o acyclovir is feasible in the treatment of varicella in immunocompromised children and results in a reduction in duration of intravenous therapy and hospitalization.     

Autonomic dysfunction in patients with dementia of the Alzheimer type

Abnormalities of the noradrenergic system have been documented in the central nervous system of patients with dementia of the Alzheimer's type (DAT). To evaluate the autonomic sympathetic system in DAT, we measured lying and standing blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in 60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon standing, plasma NE and E significantly increased in both DAT patients and controls, without group differences. However, the systolic BP response to standing was reduced in DAT patients compared with the normal controls (repeated measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing was particularly evident in DAT patients with symptoms of depression. Severely impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic changes from mild-to-moderately impaired patients. These results suggest that the sympathetic response to the stress of standing is functionally impaired in DAT. This deficit was especially evident when DAT was accompanied by depression, consistent with prior studies in non-demented depressed patients.     

The relationship between body mass and cigarette smoking using a biochemical index of smoking exposure

This study evaluated the relationship between smoking and body mass using objective indices of both smoking exposure (COHb) and body mass. The subjects were 4240 adults who participated in the Second National Health and Nutrition Examination Survey (NHANES II). Measurements of dietary intake, physical activity, demographics, body mass index (BMI) and blood carboxy-haemoglobin (COHb) were used in these analyses. After controlling for covariables of body mass, the results indicated that smokers displayed a significantly lower mass compared with non-smokers. Smokers with higher levels of COHb had lower BMIs than smokers at lower COHb levels. White smokers had lower BMIs with increasing COHb exposure whereas black smokers had BMIs at high COHb exposure similar to those of non-smokers. Results indicated that smokers weighed less than non-smokers and that the weight control 'benefits' of smoking were most pronounced in white subjects who were heavy smokers.     

510-nm pigmented lesion dye laser. Its characteristics and clinical uses

BACKGROUND: Benign pigmented lesions are of a cosmetic concern to many individuals. Numerous treatments exist, including several types of lasers. The Candela 510 nm pigmented lesion dye laser has recently been added to this armamentarium. It is designed specifically for the treatment of superficial pigmented lesions while significantly decreasing the risk of scarring and prolonged hypopigmentation. OBJECTIVES: To describe the characteristics of the Candela pigmented lesion dye laser and report on the therapeutic outcome of patients treated for actinic lentigines, café-au-lait macules, melasma and red tattoos by one of the authors (RCG). METHODS: The Candela 510 nm pigmented lesion dye laser was used to treat solar lentigines, café-au-lait macules, melasma and red tattoo. RESULTS: Excellent outcomes resulted on facial and hand lentigines (89% and 88% of patients had greater than 75% clearing, respectively), but often required more than one treatment. Lentigines located on the upper extremities and trunk improved less dramatically. Immediate greying occurred universally. Bruising was often noted. Treatment failures have been observed especially in treating lentigines located on the lower extremities. Café-au-lait macules responded inconsistently, with facial lesions giving the best results. Melasma responded poorly, often with hyperpigmentation. Three red tattoos cleared. Treatment failure may be related to inaccurate clinical assessment of pigment depth or regrowth of the lesion. Several cases are presented to demonstrate clinical and histologic effects of the laser. CONCLUSION: The Candela 510-nm pigmented lesion dye laser is an effective treatment for superficial pigmented lesions. Its associated morbidity is minimal.