No increased mortality in later life for cohorts born during famine

Nutrition early in life may influence adult mortality. The fetal-origins hypothesis suggests that nourishment before birth and during the individual's infancy programs the development of risk factors for several important diseases of middle and old age. The present study was designed to evaluate the impact of extreme nutritional deprivation in utero and during infancy and early childhood on mortality in later life. The authors analyzed the survival of the cohorts born in Finland during the severe 1866-1868 famine and during the 5 years immediately preceding and 5 years immediately following the famine. The study included 331,932 individuals born prior to the famine, 161,744 born during the famine, and 323,321 born after the famine. The authors assessed survival by cohorts from birth to age 17 years and from age 17 to 40, 60, and 80 years, as well as average length of life after age 80 years. Survival from birth to age 17 years was significantly lower in cohorts born before and during the famine than in the cohorts born after the famine (males, 0.566 vs. 0.671, a difference of 0.105 (95% confidence interval (CI) 0.102-0.108); females, 0.593 vs. 0.692, a difference of 0.099 (95% CI 0.096-0.102)). At subsequent ages, including old age, mortality was practically identical in the famine-born cohorts and in the five cohorts born before and after the crisis. For both males and females, survival from 17 to 80 years and mean remaining lifetime at age 80 years were very similar across the 13 cohorts studied. These findings suggest that, although cohorts subjected to prolonged and extreme nutritional deprivation in utero and during infancy and early childhood suffer an immediate rise in mortality, after the crisis has passed, they carry no aftereffects that influence their survival in later life.     

An experimental investigation of triboelectrification in cohesive and non-cohesive pharmaceutical powders

A detailed experimental investigation has been undertaken of the triboelectrification process of the pharmaceutical excipient alpha-lactose monohydrate and selected drugs. Particle charge studies involved the design and construction of an apparatus to incorporate pneumatic powder feed, triboelectric charging via a cyclone separator and simultaneous powder charge (Q) and mass (M) measurements using a modified Faraday well. Preliminary studies showed the charging of the selected materials to be unaffected by relative humidity up to 84%, due to the very low hygroscopicity of the powders. Experiments using lactose size fractions with brass, steel and cellulose contact charging surfaces conducted at different feeder gas pressures, gave net electronegative specific charge values (Q/M) for the metal surfaces, and electropositive values for cellulose. Specific charge increased linearly with gas pressure for the metals, and non-linearly for cellulose. Samples of micronised lactose and beclomethasone dipropionate (BDP) showed more tendency than unmicronised samples to adhere to the contact surface which resulted in more complex charging processes. A novel system to analyse the charge and mass data in further detail was developed, giving relative Q/M values at unit time intervals. It is proposed that this will overcome the limitations of reliance on the final net specific charge value. Preliminary results indicated differences in the charging mechanism for lactose in contact with the two metal surfaces.     

Regulation of distal esophageal mucosal blood flow: the roles of nitric oxide and substance P

BACKGROUND: An increase in esophageal mucosal blood flow (MBF) may be an important protective mechanism against mucosal injury from noxious agents that are ingested or refluxed. This study investigated the changes in MBF and the regulation thereof after intraluminal application of noxious chemical stimuli. The role, if any, of substance P (SP) and nitric oxide (NO), two potent vasodilatory substances, and the vascular distribution of SP in the distal esophagus were evaluated. METHODS: Esophageal MBF was measured in anesthetized dogs with a laser Doppler flow probe attached to manometry and pH probes. MBF was measured before and after topical application of HCl (2 ml; 1N) or capsaicin (2 ml; 0.5%) in the distal esophagus. The effects on MBF of intraarterial SP and bradykinin were also determined. Pharmacologic antagonists and denervation procedures were used to delineate the mechanisms that regulate MBF. RESULTS: Sequential luminal applications of hydrochloric acid (HCl) or a single application of capsaicin increased MBF (p < 0.01). Topical intraluminal lidocaine blocked the response to capsaicin (p > 0.2) but not to HCl (p < 0.05). Abrupt increases in MBF occurred with intraarterial SP or bradykinin (p < 0.01). Neither atropine nor truncal vagotomy blocked the increase in MBF from these peptides or noxious stimuli. The NO synthesis antagonist NG-nitro-L-arginine methyl ester (L-NAME) blocked the response to bradykinin and attenuated the response to HCl (p < 0.05). NG-nitro-L-arginine methyl ester did not affect the response to SP or capsaicin. A substance P antagonist blocked the effects of both capsaicin (p > 0.6) and SP (p > 0.1) but not that of HCl (p < 0.01) or bradykinin (p > 0.01). CONCLUSIONS: Intraluminal applications of HCl or capsaicin appear to stimulate increases in esophageal MBF by different mechanisms. HCl produces an adaptive response that appears dependent on the paracrine effect of NO. Capsaicin-sensitive neurons mediate vasodilation through SP neurotransmission, independent of extrinsic vagal or cholinergic innervation.     

Survey of dirofilariasis in Arkansas

A card survey was sent to 340 veterinarians in the Urban, Delta, Highland and Coastal Plain regions of Arkansas. Veterinarians were asked to indicate numbers of dogs tested, confirmed Dirofilaria immitis positive, diagnostic techniques, frequency and period tested. A significantly greater percentage of dogs tested D. immitis positive in the Delta region as compared with the Urban region. There were no significant differences in the percentage of treated dogs on prophylaxis or the types of diagnostic tests among regions.     

Clinical trial of ototopical ofloxacin for treatment of chronic suppurative otitis media

A multicenter, open-label prospective trial was performed to determine the clinical and microbiologic efficacy of ofloxacin (OFLX) otic solution in the treatment of subjects > or =12 years with chronic suppurative otitis media (CSOM) and a chronically perforated tympanic membrane in the infected ear(s). A total of 207 patients at 27 centers in the United States and Central America received OFLX 0.5 mL instilled ototopically twice daily for 14 consecutive days. The primary clinical end point was cure (dry ear) or failure (not dry ear). The primary microbiologic end point was eradication of baseline pathogens. Because there was no comparator and there were few data in the literature regarding clinical efficacy in patients treated with other regimens, the efficacy of OFLX was compared with data recorded in the clinical records of historical-practice control (HPC) or current-practice control (CPC) subjects. The incidence of clinical cure in clinically evaluable OFLX-treated patients (91%; 148 of 162 subjects) was significantly higher than in HPC subjects (67%; 124 of 185 subjects) or CPC subjects (70%; 38 of 54 subjects). OFLX eradicated all baseline pathogens isolated in microbiologically evaluable subjects. These pathogens were predominantly Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis. The most common treatment-related adverse event, bitter taste, occurred in 17% (35 of 207) of OFLX-treated subjects. Thus OFLX 0.5 mL administered twice daily for 14 days was effective in resolving the signs and symptoms of CSOM in subjects > or =12 years, was significantly more effective than therapies used to treat HPC or CPC subjects, and was well tolerated.     

Therapeutic evaluation of compounds in the SCID-RA papillomavirus model

A previous study by Kreider (Kreider et al., 1979) indicated that rabbit skin, which had been transplanted to immunodeficient nude mice, could be successfully infected with cottontail rabbit papillomavirus (CRPV). We have extended this observation in developing a rodent model for evaluation of compounds for activity against the papillomaviruses. In this model (called the SCID-Ra model), rabbit ear skin is transplanted to the dorsum of SCID mice and allowed to heal for 3 weeks. Infection with CRPV by scarification leads to the growth of warty lesions within 2 3 weeks in >95% of the animals. Topical and/or systemic therapy can be initiated at various times post infection (PI). Weekly lesion scores are recorded and compounds are evaluated for their ability to suppress wart growth when compared to untreated control mice. Ribavirin, which has had a suppressive effect both in the clinic for the treatment of respiratory papillomatosis and on the growth of warts in the rabbit back model, was evaluated and showed significant anti-proliferative activity with oral dosing. Both antiviral and antiproliferative compounds including podophyllin and 5-fluorouracil, which have been used clinically for the treatment of human papillomavirus (HPV) infections, were evaluated in this model. The anti-mitotic compound, Navelbine (vinorelbine tartrate), which is used for the treatment of non-small cell lung carcinoma was evaluated in this system and showed significant inhibition of wart growth with somewhat less topical cytotoxicity when compared to podophyllotoxin.