Mark Corson

By N. Marius. Maine College of Art. 2018.

Start the inquiry by asking your mother about her age at menopause buy 10 mg zyrtec with mastercard, and when her menstrual cycles started to change zyrtec 10 mg with amex. Of course zyrtec 5 mg on-line, exposure to environmental factors, such as endocrine disruptors and birth control pills, can affect when you have your final period. Stop, Thief: Stress and Pregnenolone Steal Although progesterone is mostly made in the ovaries, a small amount is produced in the adrenal glands, where it can be converted into other hormones, such as cortisol. Your adrenal glands have a crucial job: to respond to stress by producing cortisol and the neurotransmitters epinephrine and norepinephrine, which help you focus, and tend and befriend as needed in a dangerous situation. Progesterone is made from pregnenolone, the main “prehormone,” or biochemical precursor, from which all sex hormones are derived. It may not surprise you to learn that there’s a link between progesterone and cortisol: just as pregnenolone is the prehormone of progesterone, progesterone is the prehormone of cortisol. Still, when you are chronically stressed, your body uses cortisol faster than it can be produced, so you need to get more. You take it from cortisol’s prehormones: pregnenolone and progesterone, fittingly called Pregnenolone Steal. If you have a lifestyle that keeps you in high demand for cortisol (see chapter 4 for assessment), your body will steal from your supply of progesterone by shunting pregnenolone so that it can make more cortisol. As if that weren’t bad enough, when chronic stress causes cortisol levels to rise, the cortisol also will block your progesterone receptors. If progesterone can’t bind with a receptor because cortisol is having molecular sex with it, you will feel low in progesterone even if your serum level is normal, because progesterone cannot get inside of your cell’s nucleus. Since progesterone is a diuretic, you’ll notice fluid retention, and perhaps breast tenderness as well. Clearly, stress relief is essential for more than regulating high or low cortisol. Other Hormones That Take Down Progesterone From chapter 2, “A Hormonal Primer,” you are well aware of the cross talk between the ovaries, adrenals, and thyroid, which I liken to Charlie’s Angels. When it comes to low progesterone, a slow thyroid can lower progesterone too, and vice versa. Finally, one other minor hormone worth mentioning is prolactin, the hormone that originates in the pituitary of the brain and controls breast milk production (or lactation); women with high prolactin usually have a milky discharge from both breasts. Prolactin has many other jobs, related to water and salt balance, growth and development, ovulation, behavior, and immune regulation. Making too much prolactin can lower your progesterone level and stress raises prolactin. Low progesterone is one of the top three hormone imbalances, and it’s also one of the easiest to mend. Rather than jumping to the solution for your low-progesterone symptoms, I encourage you to perform root-cause analysis. When you understand why your progesterone is low, you’ll get better results because you can customize your solution. When I say a patient needs to balance her estrogen and progesterone, I have something quite specific in mind, a clear solution based on solid numbers. Here it is: You want your serum progesterone on Day 21 or 22 of your menstrual cycle to be 10 to 25 ng/mL. Additionally, you want the ratio of your salivary progesterone to your estradiol to be 1 to 300. To put it another way, during the luteal phase, the amount of progesterone in a normal woman who is fertile and ovulating is three hundred times the concentration of estradiol, ideally measured five to six days before your period starts. You may need to have a pelvic ultrasound or a biopsy to make sure you don’t have an excessively thick uterine lining. Four other, more serious conditions related to low progesterone include the following: 1. The most common cause of pelvic pain, endometriosis affects up to 10 percent of the women in the United States. It occurs when cells of the endometrium, or uterine lining, migrate and implant outside the uterus, usually on the ovaries or other pelvic organs, causing inflammation and sometimes extreme pain. In one study, nearly half of the women with endometriosis had either low blood progesterone or a short luteal phase. That makes it difficult to shut down estrogen activity, so estrogen levels rise, especially around the aberrant growths. As we’ve seen, low progesterone allows estrogen to build up too much tissue in the endometrium, or uterine lining. Since progesterone helps keep us calm, it follows that some women with low progesterone feel anxious. Even when given to nonanxious volunteers, progesterone and its downstream daughters such as allopregnanolone have shown antianxiety effects. It turns out that while high doses of progesterone can lead to calm, low doses seem to create anxiety. I find for my clients that it’s best to try several doses of progesterone to determine the ideal amount. It’s not life-threatening, but lack of proper sleep can affect every part of our mental and physical being. In 2011, pharmacists filled 60 million prescriptions for sleeping pills, up from 47 million in 2006. The most popular prescription pills add a mere forty minutes or less of sleep to your night. In fact, new data links prescription sleeping pills with a greater risk of cancer and death. In normal women with undisturbed sleep, progesterone had no effect on their sleep, which is good news. Especially relevant from thirty-five onward as you march toward menopause, age is associated with fewer ripe eggs, less ovulation, and low progesterone.

Case reports describe panic attacks arising cheap zyrtec 10 mg fast delivery, for exam- ple buy generic zyrtec 5 mg online, in those treated with high-dose antipsychotics (109) buy zyrtec 5mg on-line. Modifying the regimen and early intervention, in such cases, quickly reverses the side effects without necessarily having to accommodate the condition by changing occupational responsibilities. Unfortunately for some, even those who derive benefit from the atypical antipsy- chotics, residual symptoms of the condition may linger. If these symptoms interfere with the performance of essential functions, then even the most tolerable medicines will not salvage the employee’s job or warrant accommodation by the employer. Should an employee demonstrate a sudden mental or physical deterioration, any neces- sary changes relating to contributing drug interactions can be recommended, with quick response. Such structure also reinforces the need for continued compliance with treat- ment. In the past, physicians confronted liability based on the consequences of traditional anti- psychotic side effects, heightened by interactions. In the future, malpractice suits will originate based upon the physician’s decision to prescribe a traditional antipsychotic instead of an atypical antipsychotic. Atypical anti- psychotics are drugs of choice; therefore, liability may be clear when a patient suffers from the side effects of a traditional antipsychotic when an atypical agent was available and this option was not presented to the patient or otherwise considered. Since psychiatric malpractice originates most commonly after unwanted death, particular attention needs to be directed to medication regimens in cases of sudden death. Postmortem toxicology studies may rule out overdose, but medications may still be respon- sible. Chlorpromazine and thioridazine are two antipsychotics that can cause substantial drops in blood pressure (110). This effect can be more pronounced in patients given tri- cyclic antidepressants and monoamine oxidase inhibitors (110). Significant hypotension has also been described with mesoridazine and clozapine (110). Since so many other medication options are available to treat acute agitation, and psychosis, clinical practice warrants accounting for why these medicines are pre- scribed instead of medicines that do not represent any risk to the circulatory system— particularly in the medically vulnerable or in those at risk for suicide by overdose. Unwanted lethality may rarely arise from the very rare side effect of agranulocy- tosis, or loss of ability to make white blood cells, attributed to clozapine. Again, accounting for this risk is sufficient, especially if clinical choices are more restricted. Sometimes the interactions of med- icines prescribed for nonpsychiatric conditions can affect glucose metabolism, or worsen sexual function, or contribute to weight gain. These problems may lead to the develop- ment of diabetes, divorce, or cardiac problems, respectively. The prescribing physi- cian has a duty to monitor for these difficulties, and to discuss and resolve the problems with his or her patient, regardless of the different possible causes. Interactions with antipsychotics may impact tort liability if a patient’s excessive sedation or confusion results in impaired operation of a motor vehicle or other lethal equipment. Interactions that increase blood levels of clozapine may be responsible for 210 Welner causing seizures (114), which can create a highway catastrophe. In this regard, standard psychiatric practice has reinforced the responsibility for psychiatrists to advise patients of risks associated with operating such items when prescribed antipsychotics. Since trusts and wills often concern individuals with health problems, such deci- sions may be affected by the interactions of prescribed drugs. Cases involving such competencies therefore warrant close scrutiny of medical, prescription, and pharmacy records. Comparison of decisions made, with corresponding dates, yields vital detail about the relevance of drug interactions. As agitation in the medically ill, and in the elderly, is often treated with antipsy- chotics, confusion and sedation may be attributable to the medicine—if not the under- lying condition. Careful consideration of the clinical course will enable the distinction of whether a drug interaction was responsible. The elderly, and those incapacitated who are making financial decisions, are particularly vulnerable to undue influence. Loving relatives with self-serving motives can position themselves opportunistically. For this reason, sedation, heightened by drug interactions, should also be tracked. If undue influence is suspected, and the agent had continuous proximity to an ill but wealthy patient, the deceased’s blood should be tested to ensure that no medicines were administered, in combination, that would have perpet- uated mental incapacity or hastened death. New discoveries from clinical use of combinations of an ever-growing pharmacopoeia add to our appreciation of interac- tions. These findings will one day provide answers to some of the peculiar forensic sce- narios that we now suspect are influenced by drug interactions, but cannot yet explain. Essential psychopharmacology, Cambridge, England: Cambridge University Press, 2000:408. Correlation between neuroloeptic binding to singam(1) and sigma(2): receptors and acute dystonic reactions. Relapse and rehospitalisation rates in patients with schizo- phrenia: effects of second generation antipsychotics. A cross-sectional study of parkinsonism and tardive dyskinesia in lithium-treated affective disordered patients. Psychotropic drugs and adverse events in the treatment of bipolar disorders revisited.

Electroencephalograms are shown for 10mg zyrtec sale, a normal subject (a) buy 10mg zyrtec free shipping, those suffering from general tonic±clonic seizures (grand mal buy zyrtec 10 mg without prescription, (b)), generalised absence seizures (petit mal, (c)), and partial seizures (d). Spikes are seen in both right- and left- sided leads from all three cortical areas, frontal (F), temporal (T) and occipital (C) in the generalised seizures (b, c) but only in the occipital leads in the example of partial seizures (d). The typical 3 s71 spike and wave discharge of petit mal (c) may be seen during routine recording or induced by procedures such as hyperventilation but the spiking of grand mal and partial epilepsy is only seen during seizures. Strychnine convulsions have no predictive value since they arise through antagonism of spinal (glycine-mediated) rather than cortical inhibition. The anticonvulsant activity of a drug may also be evaluated by measuring its ability to raise the convulsive threshold, i. Comparison of the efficacy of drugs in the threshold and maximal seizure tests may distinguish between their abilities to raise seizure threshold or reduce seizure spread and development. A similar effect can be obtained by the repeated localised injection of subconvulsive doses of some convulsants. The ability of a drug to reduce the kindled seizure itself may be indicative of value in partial seizure but if it slows the actual development of kindling that may indicate some ability to retard epileptogenesis. Some drugs are effective in only one test and clinical condition whilst a few are active in both (Table 16. It could be argued that an antiepileptic drug should really stop the development of epilepsy, i. Clinical comparisons are not related to recommended doses but simply indicate whether a drug is effective (‡) or not (7). Generally, drugs that are to be used clinically to control tonic± clonic seizures control electroshock but not pentylenetetrazol-induced convulsions in rats and mice, whilst the converse applies to drugs effective in absence seizures. Na valproate is effective in both experimental models and is used in both clinical conditions, although in all cases higher doses have to be used than for any other drug. Phenytoin and carbamazepine do not stop the development of kindling, although acutely they reduce the fully kindled seizure, and in studies of post- traumatic epilepsy following brain damage in humans (car accidents) these drugs stop the appearance of seizures in the first week or so but do not control epileptogenesis, since seizures can develop subsequently in those patients after therapy has stopped. The actual symptoms would then be determined simply by the location of the focus and their extent, partial or general, by how easily or widely the influence of the focal neurons spread. The fact that different drugs with different mechanisms of action are effective in different epilepsies may support that view. Epilepsy may be secondary to focal lesions such as congenital malformations, infarcts, tumours, cysts or inflections but fortunately many patients with these problems do not develop epilepsy. Brain damage such as neuronal loss and glial proliferation may in fact be seen in epileptics but these changes may be secondary to, rather than the cause of, epilepsy. They probably reflect the consequences of intense neuronal activation since in patients dying in status epilepticus they appear to be of recent origin and can be induced in animals by systemic or locally administered convulsant (see Meldrum and Corsellis 1984). Everyone is capable of having a convulsion, indeed their induction has been a common treatment for depression. The convulsive threshold of an epileptic, or more precisely that of some of their neurons, is just lower than normal. There is no known genetic basis for most of the common epilepsies apart from juvenile myoclonic epilepsy and childhood absence epilepsy which are dependent on inheritance of two or more susceptible genes, although genetic factors might more generally determine predisposition. Single distinct mutant genes have been established, however, in three rare forms of epilepsy (less than 1% of total), namely generalised epilepsy with febrile seizures, benign familial neonatal convulsions and autosomal dominant epilepsy (see McNamara 1999). All could lead to increased neuronal excitability and in fact co-expression in oocytes of the Na channel a subunit with the b subunit found in febrile convulsions produces a channel that inactivates more slowly than when it is expressed with normal b subunits. Each of them represents the field potential associated with a burst of action potentials in a group of neurons within the epileptic focus (Fig. Neurons showing this burst firing are also called Group I, pacemaker or epileptic neurons and their activation always results in a burst discharge and not a single impulse. Thus they could have a persisting abnormality in membrane or ion channel excitability. What we need to know is not only how such neurons arise but how their influence can spread to affect neighbouring neurons to produce the interictal spike and, more importantly, how this can sometimes, and at immensely variable intervals, develop into a full ictal discharge and seizure (Fig. Intracellular recordings generally show that afferent stimulation of a normal cortical neuron produces one action potential superimposed on a small depolarisation (approx. There is little evidence of any abnormality in the intrinsic electrophysiological properties of individual neurons studied in brain slices from human focal cortical or hippocampal tissue, although the possibility of some unidentified genetic change in the characteristics of certain ion channels remains possible. Although these changes persist through the kindled state and must therefore be transferred to new receptors, the molecular basis is not known (see Mody 1998). Brain damage can, however, modify neuron function and so possibly make some of them hyperexcitable and focal. Not surprisingly, undercutting the cortex in animals to produce a deafferentation of some of its neurons not only renders them more likely to show epileptic-like discharges but neurons in hippocampal slices from kindled rats and human focal cortex show supersensitivity to the excitatory amino acids. The rate of development of such experimentally induced supersensitivity following denervation or hypoxia is similar to that seen in animals with focal (alumina) lesions but quicker than epileptogenesis following focal pathology (injuries) in humans. Also it must be remembered that although neurons may become supersensitive to glutamate this will no longer be released synaptically from the afferent terminals of the degenerating neurons although its release from others could produce inappropriate, disorganised and extended activation. They include alterations to various ion channels, especially those for Na‡, a reduction in local inhibitory activity or an increase in local excitatory drive. The electrophysiological counterparts of some of the events involved are shown in Fig. It is also known that the dendrites of cells around an alumina focus in monkeys, as well as in human epileptic brain, lose their spinous processes, which might contribute to the paroxysmal discharge by facilitating the spread of depolarisation to the neuron soma. Certainly an increase in the number of Na‡ channels on the dendrites of spinal motoneurons, which would facilitate the occurrence of reactive dendritic Na‡ spikes, has been seen after axotomy. Unfortunately since neither of these events is likely to occur in or around a human epileptic focus the results do not tell us much about how focal activity arises and spreads in humans. This needs to be achieved by the use of human epileptic tissue even though the procedures found to control experimentally induced spiking may well be applicable to humans. There have been a number of observations which show increased excitation and/or reduced inhibition in slices prepared from human epileptic brain tissue.

Early colonization of periodontal pathogens in the oral biofilm of children has been previously chronicled (Morinushi et al effective zyrtec 5 mg. Controversy still remains as to the percentages of children who harbor pathogenic bacteria discount zyrtec 5 mg line, elicit an immune response and if 16 they are likely to develop periodontal disease discount zyrtec 5mg without a prescription. Significant numbers of children exhibited IgG responses to at least one of the orange complex bacteria (51. When combinations of bacteria were analyzed, it was apparent that over one-third of the children exhibted immune IgG responses to at least one orange complex bacteria in combination with A. The last bacterium is most closely associated with localized aggressive periodontitis (Van Winkelhoff et al. The prevalence of pathogenic bacteria colonizing the oral biofilm of young subjects shows wide variation. Other studies have found high levels of periodontopathgens in periodontally healthy subjects with no differences in levels among periodontal healthy and diseased subjects. Since periodontal examinations were not performed in this study, a positive IgG response is not indicative of a clinical diagnosis of periodontitis. The majority of studies have shown an association between IgG responses and presence of pathogens in the biofilm of children (Savitt et al. Periodontitis status in children has also been positively associated with IgG response especially with P. However, other studies have found no relationship between serum IgG responses and presence of bacteria in the plaque biofilm (Morinushi et al. Longitudinal analysis in young children recognize that exposure to periodontal pathogens occurs early but may be episodic (Ebersole et al. After exposure to periodontal pathogens serum IgG levels become elevated and usually remain stable (Donley et al. This may be due to protection by an appropriate immune response or failure of bacteria to survive in non- anaerobic conditions in children (shallow pocket). High levels of antibody production with presence of disease may indicate production of ineffective IgG antibodies and this may even contribute to disease severity (Kojima et al. Smoking is a known risk factor for periodontitis accounting for increased disease prevalence and severity in adults (Tomar et al. Self reported smoking represented only a small proportion of this young cohort of children (3. Duration and dose of smoking increase disease risk; however, due to the younger age of the subjects neither of these factors was reported in this study. Few studies exam the association between smoking and periodontitis risk in children. A recent study in 12–21 year old Chilean 18 students estimated the risk for chronic periodontitis in smokers and nonsmokers to be the same (Lopez et al. It is known that adult periodontitis patients who smoke exhibit a reduction in total serum IgG levels and associated increase in periodontal destruction (Graswinkel et al. This suggests a reduction of the protective effect of serum IgG against periodontal pathogens. Approximately 10% of the population are affected by gastric ulceration throughout their lifetime, and more than 50% of people are carriers of this bacterium (Souto et al. Factors such as low socioeconomic level, poor hygienic conditions and overcrowding have been implicated (Wong et al. Immune responses to this bacterium may further compound the overall chronic systemic inflammatory burden. Due to majority of studies supporting the association between IgG response and periodontal status, comparisons of IgG responses as a surrogate marker of exposure are appropriate. For children, the majority of studies have focused on a few of the more commonly associated periodontal pathogens, including P. These differences may be associated with smaller sample size and the demographic and health and periodontal status of the subjects studied. Serum levels of testosterone in boys and estradiol and progesterone in girls was positively correlated with levels of P. Studies analyzing epidemiological data on periodontitis report slight increased prevalence of localized aggressive forms among young Caucasian females over males (Albandar et al. It is known that hormonal variations which occur near puberty increase the prevalence of gingivitis in some individuals (Nakagawa et al. These 20 changes may encourage the development of pathogenic strains, and increased numbers of bacteria which could lead to an increased immune response as evidenced by the increased IgG response to bacteria in females (see Table 3). Hørmand & Frandsen, (1979) found that females were five times more likely to develop localized aggressive periodontitis st between 12 and 18 years old. They attributed this to the earlier eruption pattern of 1 molars and incisors in girls. In this current study, African Americans were more likely to produce IgG antibody to pathogens than Caucasians. This is in accordance to the increased prevalence of periodontitis reported in this racial group (Albandar et al. There also appear to be differences in the bacterial subgingival colonization in African Americans and similarly, an increased prevalence and severity of periodontitis (Craig et al. Differences in host response to bacterial colonization, including serum antibody levels, have also been demonstrated among the various ethnic/racial groups (Gunsolley et al.