The Pathophysiology of The Premenstrual Syndrome (PMS)

Premenstrual syndrome (PMS) is a recurrent luteal phase condition characterized by physical, psychological, and behavioral changes of sufficient severity to result in deterioration of interpersonal relationships and normal activity. Premenstrual dysphoric disorder (PMDD) is considered a severe form of PMS.
Incorrect older theories about the causes of PMS include an estrogen excess, estrogen withdrawal, progesterone deficiency, pyridoxine (vitamin B-6) deficiency, alteration of glucose metabolism, and fluid-electrolyte imbalances. Current research provides some evidence supporting the following etiologies:

• Serotonin deficiency is postulated because patients who are most affected by PMS have differences in serotonin levels. The symptoms of PMS can respond to selective serotonin reuptake inhibitors (SSRIs), which are medications that increase the amount of circulating serotonin.
• Magnesium and calcium deficiencies are postulated as nutritional causes of PMS. Studies evaluating supplementation show improvement in physical and emotional symptoms.
• Women with PMS often have an exaggerated response to normal hormonal changes. Although their levels of estrogen and progesterone are similar to women without PMS, rapid shifts in levels of these hormones promote pronounced emotional and physical responses.
• Other theories under investigation include increased endorphins, alterations in the gamma-aminobutyric system (GABA), and hypoprolactinemia.

(Primary Care Companion J Clin Psychiatry. 2003;5:30-9;
Obstet Gynecol. 2005;106(3):492-501;
Pediatric and Adolescent Gynecology. 5th ed. Philadelphia, PA: Lippincott-Raven Inc; 2005:461-7;
J Womens Health. Jan-Feb 1999;8(1):75-85;
J Reprod Med. Feb 1991;36(2):131-6)

Sleep Quality Is An Important Predictor Of Immunity And Susceptibility To The Common Cold

Poorer sleep efficiency and shorter sleep duration in the weeks before exposure to a rhinovirus are linked to greater susceptibility to the common cold. Sleep quality is an important predictor of immunity and susceptibility to the common cold. Sleep deprivation has been shown to result in poorer immune function and to attenuate antibody response to virus infections. Shorter sleep duration and lower efficiency were associated with an increased risk for development of a common cold. People who less than 7 hours of sleep were 2.94 times more likely to get a cold than those with 8 hours or more of sleep. Longer sleep duration is associated with a reduced risk for infection with the common cold. People with less than 92% sleep efficiency were 5.50 times more likely to get a cold than those with 98% or more efficiency. Higher sleep efficiency is associated with a reduced risk for infection with the common cold, and sleep efficiency lower than 85% is associated with an increased risk.
So, if you don't want to get cold, please just sleep tight... :)
(Arch Intern Med. 2009;169:62-67)

The Difficulties of Acute HCV-Infection Diagnosis

Most individuals infected with hepatitis C virus (HCV) fail to clear virus at the acute stage, becoming chronically infected, with consequent significant risks of progressive liver disease, cirrhosis and hepatocellular carcinoma. Treatment of chronic HCV with combination pegylated-interferon (PEG-IFN) and ribavirin achieves sustained virological response (SVR) rates of 42-52% of patients infected with HCV genotype 1 and 76-82% of those with genotype 2/3. In contrast, much higher SVR rates (e.g. >97%) have been reported when treating acute HCV infection with PEG-IFN, irrespective of the infecting genotype. It would thus seem preferable to treat HCV infection at the acute stage rather than waiting for the infection to become chronic.

The problem is the diagnosis of acute HCV infection is not straightforward. Detection of anti-HCV IgM does not distinguish acute from chronic infection. Genome or antigen detection techniques provide information on the current infection status of an individual, but do not indicate when infection may have taken place. One possible laboratory approach to diagnosis of acute infection would be to demonstrate sero- or genoconversion in serial samples, but practically, it is difficult to obtain regular repeat samples in high-risk individuals such as injecting drug users (IDUs). Clinical approaches to diagnosis are also flawed. Only a small minority of acute infections are symptomatic. Even in patients presenting with acute hepatitis C, the majority of whom are already anti-HCV positive, one cannot be certain that illness is due to recent infection with HCV rather than another inter-current cause in a chronically infected patient.
(J Viral Hepat. 2008;15(12):871-877)

What is Keloid?

Keloids result from wound healing gone awry. Formation is commonly seen after invasive medical procedures; elective cosmesis (tattoos and piercings); and mundane events, such as insect bites and trauma from scratching. Symptoms can extend beyond cosmesis. One survey reported pruritus in 27% of patients and pain in 19%. Rarely, keloids have also been shown to ulcerate and develop draining sinus tracts. The most common anatomical sites for keloids include the chest, shoulders, earlobes, upper arms, and cheeks. Although keloid formation has been traditionally understood to result from indefinite collagen production, no single accepted hypothesis has been accepted to fully explain the pathological mechanism.
Keloids are more common in dark-skinned persons. Incidence is estimated to be between 4.5% to 16% among blacks and Hispanics. Keloids occur with equal frequency in men and women. Younger patients are affected more often, with an age range of 10 to 30 years. A genetic predisposition to keloids has been described, and it is inherited in an autosomal dominant fashion.

The Role of Viral Infections in Type 1 Diabetes

A number of epidemiological studies support the hypothesis that viral infections play a causative role in type 1 diabetes. However, systematic review of control studies published between 1966 and 2002 has shown no convincing evidence for or against an association between type 1 diabetes and the prime candidate for infectious cause, Coxsackievirus B　(CVB). In animal models for type 1 diabetes, solid evidence supporting an inductive role for viruses is faced with just as solid evidence supporting a protective effect of viral infections. For example, based on mouse studies alone, there is no doubt that association between viruses and type 1 diabetes is extremely complex: while belonging to the same enteroviral group, CVB3 and CVB4 have opposing effects on type 1 diabetes in the same mouse model. Thus, the reason for current failure to associate a particular virus with induction of autoimmune diabetes likely is that such an association might be impossible to make. Certain viruses might be capable of inducing diabetes and others of preventing diabetes, and type 1 diabetes inducers might be capable of preventing disease under certain conditions. This will depend of course on the nature of the considered virus, but also on the state of advancement of autoimmunity at the time of infection. A given viral infection could thus be an essential disease precipitator once required predisposing events have occurred, but could on the other hand disrupt accumulation of these events.

Most important is the indication from animal studies that modulation of autoimmunity during viral infection does not depend merely on inherent properties of the virus, but also significantly on intrinsic factors of the host. The close interplay between the two will dictate whether enhancement or abrogation of autoimmune diabetes occurs. While molecular mimicry might activate autoreactive T-cells, it could also segregate these cells away from the islets and/or induce the activation of protective Tregs. While inflammatory cytokines might promote bystander activation of APCs and autoreactive T-cells, infection could occur at a time where inflammation will induce the relocation or demise of these cells. Whereas β-cell lysis and presentation of islet antigen might promote activation of autoreactive T-cells, it could also suppress the function of these cells by promoting Treg activity. Whereas repeated/sustained infections might lead to the accumulation of autoreactive T-cells within the memory pool, they could also induce suppressor mechanisms that will hinder autoimmunity.
(Diabetes. 2008;57(11):2863-2871)

Syphilis in Pregnancy

Syphilis in pregnancy could threatening the fetus. T. pallidum could crosses the placenta, resulting in fetal infection. Vertical transmission can occur at any time during pregnancy and at any stage of syphilis. Vertical transmission of syphilis is more common in primary (50%) and secondary syphilis (50%), compared with early latent (40%), late latent (10%), and tertiary syphilis (10%). Seventy to one hundred per cent of infants born to untreated infected mothers are infected. Pregnancies complicated by syphilis may result in intrauterine growth restriction, non-immune hydrops fetalis, stillbirth, preterm delivery, and spontaneous abortion in up to 50% of pregnancies. Women who had documented treatment for syphilis in the past do not need treatment during current or subsequent pregnancies.
Penicillin is the drug of choice for treating all stages of syphilis. Parenteral rather than oral treatment has been the route of choice as the therapy is supervised and bioavailability is guaranteed. Most women treated during pregnancy will deliver before their serological response to treatment can be assessed definitively. Neonates born to such women should be evaluated for congenital syphilis. For the treatment of early syphilis during pregnancy is procaine penicillin 750 mg daily for 10 days. If it is not possible to give daily procaine penicillin on the weekend, then either long-acting procaine penicillin in aluminium stearate, 2 million units (MU) or long-acting benethamine penicillin 1.2 MU should be given IM on the Friday. Patients with penicillin allergy: erythromycin 500 mg four times a day should be given for 14 days. Alternatively, azithromycin 500 mg should be given daily for 10 days. In addition to this, examination, tests, and treatment of all babies at birth should be carried out. Desensitization to penicillin may be considered, followed by the first-line treatment. Mothers treated with erythromycin or azithromycin may be considered for retreatment with doxycycline after delivery and when breast-feeding is stopped.
(Expert Rev Vaccines. 2008;7(10):1465-1473)

Inappropriate Antibiotic Prescribing Contributes To The Higher Bacterial Resistance

Inappropriate antibiotic prescribing contributes to the problem of higher bacterial resistance. Bacterial resistance to antibiotics is a major public health problem, increasing morbidity and mortality as well as healthcare costs.

Rates of antimicrobial resistance were higher in countries with the highest consumption of antibiotics. In countries with the highest use of antibiotics, prescription rates peaked during cold and flu seasons. The antibiotics were prescribed for sore throat during 73% of visits although the prevalence of sore throat caused by bacterial infection among adults is between 5% and 17%. Moreover, most of these patients received antibiotics that were not recommended for pharyngitis, with a high number of prescriptions being for extended-spectrum antibiotics. More than half of children with sore throats received antibiotics, a rate significantly higher than the regular prevalence of bacterial pharyngitis. Furthermore, more than one quarter of these children received an inappropriate antibiotic.
In a study it was found that the rates of resistance of S. pneumoniae to penicillin, amoxicillin-clavulanate, and cefdinir were 16%, 6.4%, and 19.2%, respectively. The least effective agents against S. pneumoniae were trimethoprim-sulfamethoxazole and azithromycin, with resistance rates of 23.5% and 34%, respectively. In a study of resistance in urinary tract infections in one health maintenance organization in the United States, the prevalence of resistance among isolates of Escherichia coli to ampicillin, cephalothin, and sulfamethoxazole exceeded 20% in each of the study years 1992 to 1996. The overall prevalence of resistance to trimethoprim-sulfamethoxazole doubled between 1992 and 1996.

Rotavirus among Children Worldwide

A hospital-based surveillance reports indicate that during 2001-2008, rotavirus accounted for approximately 40% of hospitalizations for diarrhea among children aged <5>85% of these deaths occurring in low-income countries of Africa and Asia. Two licensed rotavirus vaccines have shown efficacy of 85%-98% against severe rotavirus diarrhea in trials conducted in the Americas and Europe and they have been introduced into routine immunization programs in 11 countries in these regions and in Australia. Although the two licensed rotavirus vaccines differ in strain composition (i.e., one is monovalent, and one is pentavalent), both appear to provide protection against a variety of strains, including some strains not included in either of the licensed vaccines.
(MMWR. 2008;57(46):1255-1257)

Maternal Vaccination for Influenza is Safe

In pregnant women and young infants Influenza could induce a serious disease. The maternal antibodies can pass transplacentally, therefore, it can protect infants during the first months of life. Currently, it is recommended that pregnant women be immunized with the inactivated trivalent influenza vaccine. However, compliance with this recommendation is low. The vaccine is not licensed for infants less than 6 months of age, and antiviral agents are not licensed for children younger than 1 year of age. Thus prevention of influenza by other means is an important goal. A study performed in Bangladesh provides data indicating that maternal vaccination for influenza is safe and efficacious. The vaccine also reducing illness among both mothers and infants, therefore antenatal immunization should be considered as an important strategy for the prevention of influenza.
(N Engl J Med 359:1555, 2008)

The Immunologic Cascade of Kawasaki Syndrom Trigerred by An Infectious Agent?

Kawasaki syndrome (KS) is the most common cause of acquired heart disease in children. This acute, self-limited vasculitis results in permanent coronary artery damage in up to 25% of untreated children. High dose intravenous gamma globulin reduces the risk of coronary artery aneurysm to 3-5% if administered early in the course of disease. However, without a specific diagnostic test, affected children may be difficult to recognize, and delayed diagnosis and treatment continue to result in potentially preventable morbidity and mortality. The etiology of Kawasaki syndrome (KS) remains unknown despite 30 years of intensive search for an agent.
Associations have been observed between antecedent respiratory illness and KS. It is proposed that an agent causing KS could first infect the upper respiratory tract before triggering a systemic immunologic response. Researchers found an increased IgA plasma cell infiltration of the upper respiratory tract and coronary arteries in KS patients, therefore, further support the respiratory route as a potential portal of entry for the causative agent. The presence of IgA-secreting plasma cells in the upper respiratory tract mimics the response seen in autopsies of children who died of known viral respiratory infection such as respiratory syncytial virus.
(Pediatr Infect Dis J. 2008;27(11):981-985)

Beware for Prolonged Initial Antibiotic Therapy for Extremely-Low-Birth-Weight Infants

In extremely-low-birth-weight (ELBW, birth weight of <1000 g) infants, prolonged initial empiric antibiotic therapy should be used with caution. It could cause an increased risk for necrotizing enterocolitis (NEC) or death. Although cultures from normally sterile sites usually do not yield any bacterial agents and the incidence of culture-proven bacterial sepsis is low in this population, ELBW infants admitted to intensive care nurseries usually receive empirical antibiotic treatment in the first postnatal days. A study suggested that cefotaxime for the first 3 postnatal days is associated with higher mortality risk, even for the most preterm infants.
(Pediatrics. 2009;123;58-66).

Drug-drug Interactions (DDI)

It is a difficult task to find the most appropriate medication regimen for our patients. Patients sometime require multiple medications placing them at risk for drug-drug interactions (DDIs). DDI is a situation that occurs when 1 of a combination of drugs alters the effect of another drug. Drug-drug interactions may result in decreased therapeutic benefit, adverse effects, or patient harm. Non-prescription medications, herbal preparations, and complementary medications also contribute to patient polypharmacy and the potential for DDIs.

DDIs contribute to patient morbidity and may cause emergency department visits, hospitalizations, and re-admissions. Examples of patient morbidity caused by DDIs include gastrointestinal (GI) bleeding, renal dysfunction, electrolyte imbalance, hypertension, hypotension, bradycardia, arrhythmia, drug toxicity, and decreased drug effect.

Well known examples of mortality associated with DDIs include fatal outcome from a warwarin and nonsteroidal anti-inflammatory drug (NSAID) interaction, ciprofloxacin in fatal seizures, and moclobemide-clomipramine overdose in fatal serotonin syndrome. Other examples are fatal interactions between tranylcypromine and imipramine and also between methotrexate and trimethoprim.
Polypharmacy, narrow therapeutic range of the medication (eg, digoxin, cyclosporine, warfarin), decreased renal and or hepatic function of the patient each may increase the risk for DDIs and should be identified prior to coadministration. One should consider the potential for DDIs at all steps of the drug-delivery process. Furthermore, an increasing number of medications administered further increased the risk for adverse effects. Literatures said patients taking 2, 5, and 7 medications had a 13%, 38%, and 82%, respectively, for developing adverse drug interactions.
Advanced age is an additional risk factor for DDIs. The need for multiple medications often arises with advancing age that may further the risk for DDIs. Other patient-related risks for DDIs include very young age, female sex, genetics, decreased organ function, major organ impairment, metabolic or endocrine risk conditions (eg, hypothyroidism, hypoproteinemia), and acute medical issues (eg, dehydration).

Amlodipine Plus Benazepril Combination For Hypertension Therapy

Although the optimal pharmacotherapy regimen for hypertension is not yet determined, current guidelines recommend inclusion of a diuretic. The guidelines prefer to use diuretics as monotherapy or to use diuretics and an ACE inhibitor in combination therapy. However, recommendation of thiazide-type diuretics as initial therapy for most patients with hypertension needs to be reexamined. Combination therapy is probably a good initial strategy for high-risk patients, rather than starting with one drug and going slow.

Treatment with antihypertensive combination therapy (the angiotensin-converting enzyme (ACE) inhibitor benazepril plus the calcium-channel blocker amlodipine) is more effective than treatment with the ACE inhibitor and diuretic. Studies suggest that the calcium-channel blocker amlodipine effectively increases the availability of vascular endothelial nitric oxide and that the combined effects of amlodipine and an ACE inhibitor on nitric oxide are greater vs the effect with either drug alone.

In patients with hypertension who were at high risk for cardiovascular events, the benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing the primary composite outcome of cardiovascular events and death. The single-tablet benazepril-amlodipine combination reduced the risk of morbidity and mortality by 20% compared with conventional therapy. Putting patients on either combination doubled their control rate, so combination therapy is something clinicians need to think about, even if they want to keep the diuretic. But the drug that gives superior cardiovascular outcomes is the calcium-channel blocker and ACE inhibitor.

The cardiovascular benefits of specific classes of antihypertensive drugs may go beyond their effect on blood pressure. The combination of amlodipine and benazepril appears to synergistically reduce left ventricular hypertrophy and arterial stiffness, suggesting that they may protect target organs independently of the drugs' antihypertensive effects.

References:

Jamerson K, Weber MA, Bakris GL, et al. 2008. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 359: 2417-2428.

Chobanian AV. 2008. Does it matter how hypertension is controlled? N Engl J Med. 359:2485-2488.

Clostridium difficile-associated disease (CDAD)

Clostridium difficile-associated disease (CDAD) is an important nosocomial infection associated with healthcare, and it may recur in 15% to 30% of patients. The agent, Clostridium difficile, is a Gram-positive, anaerobic spore-forming bacillus. C. difficile was first identified as an aetiological agent of antibiotic-associated pseudomembranous colitis in the late 1970s. Approximately 15% to 20% of antibiotic-associated cases of diarrhea and nearly all cases of pseudomembranous colitis have been attributed to this bacteri. The incidence of CDAD has steadily climbed in the past decade, and it is an important cause of morbidity both in North America and in Europe.

Rapid diagnosis of CDAD further allows implementation of infection control measures and timely treatment. Stool assays is not a good strategy for rapid diagnostic since the false-negative rates is very significant. The best methods for rapid identification of C. difficile–associated pseudomembranous colitis is sigmoidoscopy.
Control of C difficile infection requires prudent use of antimicrobial agents, prevention of cross-infection, and ongoing surveillance. For patients with mild CDAD, discontinuation of the causative antibiotics without further treatment may be sufficient. Many guidelines recommend the use of metronidazole, an imidazole derivative, in patients thought to need antibiotic treatment, however it has a high failure rates and and resistance to metronidazole has been reported. Controlled clinical trials have shown efficacy for CDAD treatment with vancomycin, a glycopeptide. The mean duration of symptoms was also significantly shorter with vancomycin comparing with that of metronidazole. For patients with severe CDAD, intensive care unit (ICU) admission may be needed. A combined medical and surgical approach is recommended, with surgical resection of the inflamed colon as a therapeutic option.

The Health Risks Associated with Noncoital Sexual Activity

Noncoital sexual behaviors, which include mutual masturbation, oral sex, and anal sex, are common expressions of human sexuality. Couples may engage in noncoital sexual activity instead of penile-vagina intercourse hoping to reduce the risk of sexually transmitted diseases and unintended pregnancy. Although these behaviors carry little or no risk of pregnancy, women engaging in noncoital behaviors may be at risk of acquiring sexually transmitted diseases.

Most individuals engaging in oral sex are unlikely to use barrier protection. However, sexually transmitted diseases (STDs) may be spread through saliva, blood, vaginal secretions, semen, and fecal matter, especially in the presence of preexisting infections, open sores, or other lesions.

Hepatitis B virus is commonly spread through noncoital sexual activities, as it is found in semen, saliva, and feces. Hepatitis A is transmitted via fecal contamination of the oral cavity and is more common in men practicing oral-anal contact. Although sexual transmission of hepatitis C virus is uncommon, it may occur with preexisting hepatitis B virus and HIV infection and with oral-genital contact.