Monkeypox outbreak 2022: What we know so far and its potential drug targets and management strategies.

Monkeypox is a rare zoonotic disease caused by infection with the monkeypox virus. The disease can result in flu-like symptoms, fever, and a persistent rash. The disease is currently spreading throughout the world and prevention and treatment efforts are being intensified. Although there is no treatment that has been specifically approved for monkeypox virus infection, infected patients may benefit from using certain antiviral medications that are typically prescribed for the treatment of smallpox. The drugs are tecovirimat, brincidofovir, and cidofovir, all of which are currently in short supply due to the spread of the monkeypox virus. Resistance is also a concern, as widespread replication of the monkeypox virus can lead to mutations that produce monkeypox viruses that are resistant to the currently available treatments. This article discusses monkeypox disease, potential drug targets, and management strategies to overcome monkeypox disease. With the discovery of new drugs, it is hoped that the problem of insufficient drugs will be resolved, and it is not anticipated that drug resistance will become a major issue in the near future.

Technology meets healthcare: distance learning and telehealth.

In a time of increasing demands on physician productivity, computer and communication technologies allow health professionals to experiment with many applications that may provide opportunities to meet clinical demands while still participating in educational and research activities. "Telehealth" is a comprehensive term for the support of long distance clinical healthcare, patient and professional health-related education, public health, and health administration. Educational opportunities are growing exponentially for those who cannot attend traditional courses because of limited time or geographic considerations. Research and medical information and medical consultations are being delivered instantly across wide geographic areas. Nearly every federal agency has a web site providing health information. Integrated clinical management systems can facilitate the management of patients with chronic diseases and provide an efficient way to integrate consultations and patient education, monitoring, follow-up, and support. Administrative functions can be interfaced with clinical management providing practitioners with the ability to better organize their services. Information systems at all levels are expanding their capacities and capabilities to meet the growing demand for medical knowledge.

Perioperative transfusion, postoperative infection, and recurrence of head and neck cancer.

BACKGROUND: Immunologic effects of perioperative transfusion and postoperative infection have been purported to influence cancer recurrence rates. METHODS: Records of all head and neck cancer patients having surgical extirpation of the primary tumor and/or regional nodes at our institution over a 5-year period were reviewed. Time to recurrence was the outcome measure. All variables were evaluated via univariate analysis using log rank tests, with Cox proportional hazards used for multivariate analyses. RESULTS: Univariate analysis identified the following as potential prognostic factors associated with recurrence: nodal stage, total lymphocyte count, overall stage, amount transfused, occurrence of a transfusion, and the American Society of Anesthesiologists status. Various backward stepwise multivariate regression models showed that neither transfusion nor postoperative infection independently influenced recurrence. However, transfusion of 3 or more units did surface as an independent contributor to recurrence, and in certain subgroups there was a trend toward improved survival for those who had a postoperative infection. CONCLUSIONS: In this series, neither perioperative transfusion nor postoperative infection independently influenced recurrence.

Effect of strain and age of the broiler breeder female on incubation time and chick weight.

Two experiments were conducted to evaluate effects of strain [five in Experiment (Exp.) 1 and six in Exp. 2)] and age (29, 47, and 57 wk in Exp. 1 and 29, 41, and 52 wk in Exp. 2) of commercial broiler breeders on incubation time and chick weight. Highly significant differences in egg weight were found among strains in both Exp. After adjusting for effects of egg weight, significant effects of strain, age, and their interactions were found on incubation time, egg weight at transfer, and chick weight at hatch in Exp. 1, but not in Exp. 2. Mean incubation times varied among strains from 496.6 to 498.8 h in Exp. 1 and from 499.3 to 501.9 h in the second experiment. In Exp. 1, incubation time decreased from 498.6 h when breeders were 29 wk to 494.8 at 47 wk, whereas in Exp. 2, it decreased from 510.5 h at 29 wk to 495.1 h at 41 wk. This decrease also resulted in a negative correlation between egg weight and incubation time. Differences due to strain and age were found for yolk and albumen percentage and yolk: albumen ratio. Percentage yolk was 27.2 and 32.7% and percentage albumen was 60.1 and 55.9% in eggs from 29 to 52 wk breeders, respectively. Shell percentage was significantly affected by strain. Strain by age interactions were found for each response in Exp. 1 but only for set and chick weight in Exp. 2. Differences among incubators were found only for incubation time; interactions of incubation time and strain and age were also detected. Results indicate that genotype, age of the female breeder, and incubator should be considered along with their interactions to obtain optimum hatching performance.

Relaxin: an ovarian hormone in an avian species (Gallus domesticus).

The objective of this study was to characterize the biochemical, immunological, and biological activity of avian relaxin and to immunolocalize relaxin-like peptides in the ovary of the hen (Gallus domesticus). A relaxin-like peptide was partially purified from ovaries of actively laying hens by size-exclusion chromatography and further purified by ion-exchange chromatography on CM-cellulose. Those fractions containing relaxin immunoreactivity were identified with the use of a homologous porcine relaxin radioimmunoassay on selected column effluent and pooled, and a sample was subjected to SDS-gel electrophoresis. The SDS-gel-separated proteins were electrotransferred onto a nitrocellulose membrane and immunostained with an antiserum to porcine relaxin which showed the presence of a single band of approximately 6000 daltons. The dose-response curve generated by avian relaxin-like peptide in the homologous porcine relaxin radioimmunoassay was parallel to that produced by the porcine relaxin standard. Like porcine relaxin, avian relaxin-like peptide eluted from the Sephadex G-50 in an elution volume for a molecule of approximately 6000 daltons, was retained on CM-cellulose, and was bioactive in in vitro inhibition of spontaneous contractions of estrogen-primed mouse uterus (a relaxin bioassay). Using an antiserum specific to porcine relaxin, avian relaxin-like peptide was immunolocalized to the granulosa cells of postovulatory follicle from ovary of a hen less than 24 hr postoviposition. No immunostaining was detected in the cells of the largest preovulatory follicles or when the antiserum was preabsorbed with porcine relaxin prior to staining. The finding of this study indicates that the avian postovulatory follicle, like the corpus luteum of other vertebrate species (sharks and mammals), contains a relaxin-like peptide.

Collaborative care for obstetric patients at low and high risk: an evolving model.

OBJECTIVE: In this article we describe a program that evolved from collaborative care given to a low-risk population into collaborative care that included patients at high risk. STUDY DESIGN: The study population comprised women attending a prenatal program in an urban, underserved neighborhood. Clinic records were reviewed for number of patient enrollments and total patient visits, as well as providers utilized. Episodic audit over a 3-year period of 180 of 869 patients initiating prenatal care was done. Data from vital statistics for 1992 and 1993 were evaluated for adequacy of prenatal care and yearly births for the census tract served. Analysis was descriptive. RESULTS: Almost all of the patient population served was found to be at psychosocial high risk. Approximately 10% had significant obstetric or medical complications. Infections, especially sexually transmitted diseases, were common. Fewer than 1% of the patients were referred to another provider for treatment. The program demonstrated an increase in patient volume, improved retention of patients for complete prenatal care and delivery, a reduction in patients receiving no or inadequate care, and a reduction in yearly births. CONCLUSION: The collaborative practice model may be extended to high-risk populations.

Does cigarette smoking paradoxically increase survival in idiopathic dilated cardiomyopathy?. The Washington, D.C., Dilated Cardiomyopathy Study.

Recent studies have suggested that patients with idiopathic dilated cardiomyopathy (IDCM) who smoke have an improved prognosis as compared with nonsmokers. We examined this paradoxical finding using data from a population-based study in Washington, D.C. (n = 127). Current smokers were more likely to have a left-ventricular ejection fraction (LVEF) of 25% or greater as compared with IDCM patients who were past smokers or lifelong nonsmokers (p < or = 0.02). The cumulative survival among current smokers at 12 and 24 months was 88.1 and 81.4%, respectively, as compared with 77.9 and 71.6% among past smokers and 74.0 and 64.3% among patients who had never smoked. In a univariate analysis using the proportional hazards model, lifelong nonsmokers and former smokers were about twice as likely to die as compared with smokers, although the association was not significant (p > 0.10). In multivariable analysis, older age, LVEF, and ventricular arrhythmias - but not cigarette smoking-were found to be statistically significant independent predictors of survival (p < or = 0.05).

Low temperature effects on embryonic development and hatch time.

A series of experiments was conducted to estimate phenotypic correlations between incubation characteristics, and to evaluate the effects of cold stress and genotype during incubation on chick weight, egg weight loss, hatching time, and embryonic mortality. Eggs were cooled at 18 or 24 C, for 12, 24, 36, 48, or 72 h beginning on Day 8, 12, 14, 16, or 18 of incubation. Other eggs were cooled intermittently for 6 h every 48 h or 12 h every 96 h. A control group in each experiment was not cold stressed. Results indicated a low and negative correlation between hatching time and chick weight, and a low and positive correlation between hatching time and weight loss from transfer to hatching when variability due to egg weight was removed. Chick weights at hatching were lower in chicks from cooled eggs than those of chicks from eggs incubated under normal temperature. The chicks from cooled eggs were more susceptible to dehydration during holding in the hatcher. Incubation times were delayed approximately as long as the times of embryonic cooling. Embryonic mortality was significantly increased under continuous (single period) cold stress, but not under intermittent cooling (6 h every 48 h). Significant genotype by environment interactions were found in the response of embryos of various strains to cold stress. Exposure for 36 h or longer had detrimental effects on chick weight and embryo viability, but these effects were modified by interactions among the factors involved. The results indicated that embryos from cooled eggs lose more weight during incubation and that the neonatal chicks are more susceptible to dehydration during holding time, and have a longer incubation period, and a greater embryonic mortality.

Evaluation of alternate methods of rapid assessment of endemicity of Onchocerca volvulus in communities in southern Cameroon.

Potential diagnostic indicators of onchocerciasis (subcutaneous nodules, depigmentation or leopard skin, microfilaruria, diethylcarbamazine patch test positivity, excoriations, and pruritus) were evaluated in a rain forest region of southern Cameroon for usefulness in rapid assessment of onchocerciasis endemicity in communities. Thirty-two study villages were selected, representing high, intermediate, and low prevalence levels, and 846 adult male residents of these communities 20 or more years of age were examined according to a defined protocol. Skin snips (from each iliac crest) served as the reference standard. Skin snip positivity was 75.5%; the effect of age was minimal. Leopard skin and nodules showed the strongest correlation with both the skin snip prevalence and community microfilarial load, as reflected by the adult male study population. We selected > or = 20% nodules or > or = 20% leopard skin as the most appropriate local criteria for assigning a community to high priority for control, which corresponds to a > or = 90% skin snip prevalence in adult males. While this criteria should not be applied to regions with savannah onchocerciasis, we believe the methodology can and should be used to determine appropriate diagnostic indicators for rapid assessment of Onchocerca volvulus endemicity in regions with different dynamics of transmission and clinical expression of disease.

Respiratory illness, beta-agonists, and risk of idiopathic dilated cardiomyopathy. The Washington, DC, Dilated Cardiomyopathy Study.

An epidemiologic study was carried out to examine the possible role of beta-agonists and other respiratory medications in the development of idiopathic dilated cardiomyopathy. Associations with respiratory medications, bronchial asthma, emphysema, and chronic bronchitis were examined by comparing newly diagnosed cases (n = 129) ascertained from five Washington, DC, area hospitals for the period 1990-1992 with neighborhood controls (n = 258) identified by using a random digit dialing technique. The cases and controls were matched on sex and 5-year age intervals and were compared in the analysis using conditional logistic regression methods. A statistically significant association was observed between idiopathic dilated cardiomyopathy and history of emphysema or chronic bronchitis (adjusted odds ratio (OR) = 4.4, 95% confidence interval (CI) 1.6-12.4). The association with bronchial asthma was of borderline significance (adjusted OR = 1.9, 95% CI 0.9-4.2). Associations were also observed with use of oral beta-agonists (adjusted OR = 3.4, 95% CI 1.1-11.0) and beta-agonist inhalers or nebulization (adjusted OR = 3.2, 95% CI 1.4-7.1), as well as with use of oral corticosteroids, inhaled corticosteroids or cromolyn, and theophylline medications. A total of 20.0% (23 of 115) of the cases had a reported history of beta-agonist inhaler use compared with 6.7% (17 of 254) of the controls. The strength of these associations was diminished when the temporal relation between exposure to beta-agonist inhalers or oral preparations and clinical diagnosis of idiopathic dilated cardiomyopathy was taken into account, however, and the associations with duration of beta-agonist medication use were not statistically significant (p > 0.05). The results of this study suggest, but do not prove, that use of beta-agonists has an etiologic role in idiopathic dilated cardiomyopathy.

Response of broiler breeder females to feed restriction below recommended levels. 3. Characterizing the onset of sexual maturity.

The objective of this study was to characterize how the physical attributes associated with sexual maturity would be affected by feed allocation as female broiler breeders passed through the pullet-layer transition period. Treatments consisted of five feeding programs, or body weight goals, during the period of 0 to 20 wk of age. Those were 8% above breeder standard, standard (primary breeder recommended body weights), and 8, 16, and 24% below standard. The characteristics measured included body and fat pad weights, pubic spread, comb development, head score (comb and wattle appearance), shank length, total plasma lipid concentration, ovary weight, oviduct weight, bursa of Fabricius weight, and age at sexual maturity. The generalized effect of increased severity of the feed restriction programs was to delay the birds' development without altering their ultimate physiological values. The exceptions to this were relative body weight and shank length after maturity, which were reduced in the most severely restricted birds. Measurements of pubic spread and comb growth and subjective scores of head appearance would be useful and easily obtained information when estimating the progression of a flock toward sexual maturity.

Acral lentiginous melanoma.

Between 1958 and 1990, 82 patients with acral lentiginous melanoma were treated by the Tulane Surgical Service with regional perfusion, excision of lesion, and lymph node dissection. The patient group comprised 27 white men, 29 white women, 18 black men, and 8 black women, with an average age of 61 years. More foot lesions than hand lesions were reported, and all the lack men had foot lesions. In stage I patients, overall 5-year survival rates were 65% at 5 years and 44% at 10 years, with differences by race and gender. The black men did poorest, with a 13% 10-year survival rate. Survival rates were worse with increasing disease stage when calculated using univariate analysis. The 5-year survival rate of all patients with stage III and stage IV disease was 26%. A multivariate analysis was performed in 78 of 82 patients in whom all variables of Clark's level, age, race, stage, and sex were known. A strong relationship was observed between decreasing survival time and increasing Clark's level, with stage of marginal significance. In a multivariate analysis of patients with stage I disease, an increasing level of invasion was found to be significant, with a trend for a relationship to thickness. A trend toward decreased survival time was observed in men and blacks.

Effect of administration of diethylcarbamazine with and without fluconazole on experimental fungal infections in mice.

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In our current experiments, DEC treatment was associated with lower brain fungal burden in fluconazole-treated mice following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans. Further investigation of combined DEC and fluconazole treatment of fungal infections is warranted.

Albendazole in the treatment of onchocerciasis: double-blind clinical trial in Venezuela.

A double-blind clinical trial was conducted in Monagas State, Venezuela to assess the tolerance and efficacy of albendazole in the therapy of Onchocerca volvulus infection. Forty-nine patients (26 treated and 23 controls) received a 10-day course of albendazole (400 mg/day) or a placebo. Consistent with the excellent tolerance observed, albendazole did not kill microfilariae. However, analysis of changes in microfilarial densities (mf/mg of skin) over one year showed that albendazole was active against O. volvulus, presumably by interfering with embryogenesis. The nature, degree, and duration of this effect remain to be determined.

Effect of administration of diethylcarbamazine on experimental bacterial and fungal infections in mice.

Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In the current experiments, DEC treatmentS was associated with (a) increased survival and decreased brain Streptococcus pneumoniae levels following S. pneumoniae challenge in previously immunized mice; (b) increased serum antibody levels to S. pneumoniae, Escherichia coli, and Haemophilus influenzae following inoculation of live bacteria; and (c) lower brain fungal levels following intravenous injection of Aspergillus fumigatus or increasing numbers of Cryptococcus neoformans organisms, and lower brain and kidney levels of Candida albicans following intravenous injection of increasing numbers of C. albicans.

Seasonal temperature and its influence on plasma corticosterone, triiodothyronine, thyroxine, plasma protein and packed cell volume in mature male chickens.

1. The relationship between seasonal changes in environmental temperature and hematological parameters was investigated in mature, single comb white leghorn (SCWL) male chickens. 2. Samples of blood plasma, obtained monthly from two groups of birds over two separate 12 month periods, were analysed for corticosterone (CT), 3,5,3'-triiodothyronine (T3), thyroxine (T4), plasma protein (PP), and packed cell volume (PCV). 3. Statistical analyses revealed that blood plasma concentrations of T3 were significantly correlated negatively with monthly dry-bulb temperatures. 4. There were no consistent or significant relationships between monthly dry-bulb temperature and CT, T4, PP or PCV over the two 12 month periods. 5. The results of this study indicate that blood plasma concentrations of T3 are influenced by season of year in mature, male domestic fowl.

Effect of administration of diethylcarbamazine on murine leukemia virus (Cas-Br-M) infected mice.

Previous studies indicate that decreased serum viral infectivity and viral antigen levels follow oral administration of diethylcarbamazine (DEC) in feline leukemia virus infected cats, even though DEC has not been shown to exhibit in vitro antiviral activity. In this investigation, DEC was given by oral administration or (single dose) IP injection to murine leukemia virus (Cas-Br-M) inoculated mice to permit evaluation of its effect on viral-induced central nervous system disease. The survival of Cas-Br-M inoculated mice receiving DEC in water was significantly prolonged relative to similarly inoculated mice receiving distilled water. Among the Cas-Br-M inoculated mice euthanatized after the study, higher body weights and trend toward less severe brain and splenic lesions were noted in those receiving DEC in drinking water. Given these results, the possible utility of DEC in treatment of retroviral and other infections warrants further study.