Supervising Ovulation Induction

Normal Folliculogenesis

Before reviewing the details  the parameters of follicular  growth studied  with 2D  ultrasound  imaging , it is  helpful  to summarize   normal folliculogenesis in order   to be able  to correlate   imaging   findings  with physiologic   expectations. Follicles   grow in two  stages the gonadotropin independent and gonadotropin dependent  stages. Primordial follicles   consist of an oocyte with a thin layer of granulosa and stromal   cells and cannot be  seen on ultrasound. By  The time follicles  develop  a fluid   antrum they are    ultrasonographically   identifiable  and they  have    reached the gonadotropin dependent stage  of the 3 month   maturation process. These  antral follicles  measure between 2 and 10 mm  and represent   the pool of  follicles  that may be  recruited  in the ensuing  follicular   phase . In a   natural  cyce one  is ultimately selected  for ovulation and that selection process occurs   during  the latter half  of the follicular   phase of the ovarian cycle   when the endogenous pituitary follicle  stimulating hormone level   is falling in response  to the increasing    ovarian   estradiol production. Falling FSH  promotes a selection process  in which each  of the follicular microenvironments   competes for  the diminishing FSH needed   to stimulate   granulosa   cells in the follicle   to produce   aromatase . Aromatase in turn   is necessary  to convert testosterone and   androstenedione produced in the peripheral theca   cells into   estradiol and estrone respectively . Failure   of this conversion   leads  to an elevated androgen to estrogen ratio which leads  to follicular   atresia. From this  cursory review of the  anatomy and physiology  of oocyte  maturation , it is easy to see how  ovulation inducing agents  that either indirectly  increase   endogenous FSH   or  directly   add FSH  to the system   diminish the completion between   the follicles  and permit the development of  multiple  dominat follicles .

Monitoring  Follicular  Maturation

Methods  for Monitoring

It is   difficult to predict  the optimal number of growing ovarian    follicles in an IVF cycle , since   there is   considerable   variation   in ovarian   response among   women undergoing   ovulation     induction   therapy. The ovarian  response    depends  on age ovarian reserve  how the hypothalamic  ovarian axis  is manipulated exogenously   FSH  done cause  of infertility ethnicity  etc.

Follicular   maturation in IVF   cycles can be   monitored  clinically in different ways , either  by

Serum   estradiol  value  alone

2D   ultrasound alone

3D   ultrasound alone

Serum   estradiol  and  ultrasound combined 

Supplemental  power Doppler   imaging

There  are   numerous   studies on the use of  these different methods  for monitoring   of an IVF  treatment cycle   includes  a combination of regular  ultrasonography   and serum  estradiol   concentrations  and has long  been    accepted  as the gold  standard. However  the need for estradiol monitoring   remains controversial  . Ultrasound    provides     more accurate     measurement    of follicle   number    and size   than can be   obtained by serum  estradiol  alone. Whether  serum estradiol  or ultrasound is superior to the other is  questionable , but  it has been shown that  ultrasound   imaging of follicular growth  and endometrial   thickness  is sufficient to  monitor  follicular   maturation .

Which    approach when to adjust   the gonadotropin   dose up or   down and how often      monitoring   should be  done is  dependent   on the individual clinician the experience   and the routine at each individual   clinic Some   monitoring  methods are very complex   whereas   other methods   are rather simple however   the outcomes of IVF  cycles seem to be the same regardless of the chosen method.  

A B C of Precocious Puberty

What does “isolated Premature Thelarche” means?
,To all of us it(PT)  appears to mostly a benign, self-limiting condition which is characterized by breast development with no other signs of sexual maturation. As understandable, there will be no pubic or axillary hair development, girls behavior at home and at school is normal, growth is normal and the skeletal age is appropriate. But the  breast development has atypical appearance with relatively immature nipple development and is never more than Tanner Breast Stage III. Breast development is usually asymmetrical.

The condition tends to resolve after about 1–2 years and then the onset of normal puberty(adrenarche, Menarche, increments f Ht & other growth spurt  )occurs at the appropriate age and in the normal way. Very occasionally, vaginal bleeding can occur. There have been some reports of women who have had premature thelarche as a child developing large follicular cysts during their menstrual cycles and, thereby, having reduced fertility. However, this has not been substantiated and what limited follow-up has been achieved in further series suggests that there are no long-term sequelae.

Etiology ? Isolated premature thelarche is a relatively common condition and mothers come to doctors more will be recorded prevalence!!  It is characterised by FSH dominance and overnight gonadotrophin secretion, which is characterised by single FSH pulses.

There may well be two types of premature thelarche. The classical type commences during the first year of life and tends to resolve by the age of 2.

There is a second form of premature thelarche, of which the age of onset is over 2 years of age and this tends to be more persistent and with a higher incidence of uterine bleeding. In this ‘non-classical’ form of premature thelarche, it may well be associated with progression to gonadotrophin-dependent precocious puberty. Isolated premature thelarche is a condition which is easy to diagnose clinically and requires no treatment.

Precocious Puberty (Complete, Partial)

Girls suspected of having central precocious puberty, are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curve.

 CNS imaging studies of these otherwise healthy 6-year-old to 8-year-old girls usually reveal no structural abnormalities. A study of 200 girls in France identified abnormal brain imaging findings in 2% of girls whose onset of puberty was between age 6-8 years and in 20% of girls whose onset of puberty was before age 6 years.

^[1] A smaller study from the United Kingdom reported abnormal findings in 15% of 67 girls.^[2] Abnormal CT scan or MRI findings are more frequent among boys with central precocious puberty than among girls with central precocious puberty.

The onset of puberty is caused by the secretion of high-amplitude pulses of gonadotropin-releasing hormone (GnRH) by the hypothalamus. The hypothesize HPG axis, which is highly sensitive to feedback inhibition by small amounts of sex steroids, and (2) central neural pathways that suppress the release of GnRH pulses.

Admittedly, I am more theoretician: Very very associate or should I say  etiology of PT:- CNS abnormalities associated with precocious puberty include the following:

·         Tumors (eg, astrocytomas, gliomas, germ cell tumors secreting human chorionic gonadotropin [HCG])

·         Hypothalamic hamartomas

·         Acquired CNS injury caused by inflammation, surgery, trauma, radiation therapy, or abscess

·         Congenital anomalies (eg, hydrocephalus, arachnoid cysts, suprasellar cysts)

High-amplitude pulses of GnRH cause pulsatile increases in the pituitary gonadotropin-luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Increased LH levels stimulate production of sex steroids by testicular Leydig cells or ovarian granulosa cells. Pubertal levels of androgens or estrogens cause the physical changes of puberty, including d mechanisms that suppress onset of puberty include (1) the gonadotropin-releasing hormone (GnRH) by the hypothalamus. The hypothesize HPG axis, which is highly sensitive to feedback inhibition by small amounts of sex steroids, and (2) central neural pathways that suppress the release of GnRH pulses. On ultrasound the ovaries are small, but often contain large follicular cysts, which increase and decrease in synchrony with the breast development.

CNS abnormalities associated with precocious puberty include the following:

·         Tumors (eg, astrocytomas, gliomas, germ cell tumors secreting human chorionic gonadotropin [HCG])

·         Hypothalamic hamartomas

·         Acquired CNS injury caused by inflammation, surgery, trauma, radiation therapy, or abscess

·         Congenital anomalies (eg, hydrocephalus, arachnoid cysts, suprasellar cysts)

High-amplitude pulses of GnRH cause pulsatile increases in the pituitary gonadotropin-luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Increased LH levels stimulate production of sex steroids by testicular Leydig cells or ovarian granulosa cells. Pubertal levels of androgens or estrogens cause the physical changes of puberty, including d mechanisms that suppress onset of puberty include (1) the

Hyperandrogensim in peripubertal period decreses height of your daughter.

Phase 3 of growth spurt:- This, as far as I understand is the key issue in this post. This time growth tempo is 8- 14 35cm per yr.At this juncture growth hormone & sex steroids take upper hand than nutrition, candidate genes responsible for achieving target height. Calculation of target height is calculated by a simple formula father's height- 13 c m. + mother's height ÷ 2 . It is so easy.

Is there any standard table or say monogram for estimation of age specific standard height? Yes. The table is named after " Bayley- Pinneau Table for average girls which compares bone age ( as determined by left hand / wrist for correct estimation of bony age ) along with height exrpresed in inches.For details May see Net for details. One  is

is worried about therapeutic aspects of increasing the height. If no etiology is demonstrable ( Thyroid, anaemia, metabolic/ systemic diseases / endocrine disorders) - then Inj. Growth Hormone is recommended by U S .It is from 2003 .Such Inj. Is recommend for girls whe9 epipyses is not yet closed, and height is more than 2.25 standard deviations below the mean age for her age.But many endocrinologist are hesitant to prescribe such Inj. Arthur are of opinion that idiopathic short stature is no disease.How helpful is Inj. Growth Hormone ? After 5 years of treatment growth increase is only 5 years 4- 6 c m per yr.At c m in optimal cases but this who favour Inj. GH recommend that the treatment should initiate from 5 yrs to early puberty.

Childhood nutrition
And modification of puberty
Reproductive maturation is delayed in a nutritionally deprived environment. The effect of obesity on Pubertal timing has more recently been addressed in obese youth with premature pubarche in children with low birth weight and rapid postnatal catch-up in weight, and in boys and girls with simple obesity. These conditions will be addressed in coated reproductive disorders in adult.
The Effect of a Nutritionally Deprived Environment
Pugliese and colleagues evaluated 14 and girls. Nine boys and 5 girls, ages 9 to 17 years ,with growth failure and delay in puberty (7 of the 14)due to malnutrition resulting from self-imposed caloric restrictions. In these children,who restrictions caloric intake for fear of becoming obese increased linear growth and Pubertal progression resumed with the resumption of age-appropriate caloric intake. Matejek and colleagues studied the relationship between Leptin levels, fat stores , and reproductive hormone levels in 13 female juvenile elite gymnasts and 9 adolescent girl with anorexia nervosa . Leptin levels were subnormal and were related to body fat mass in girls with anorexia nervosa, but were lowest in the elite gymnasts. In both groups, estradiol levels were low and menarche was delayed. Catch-up height and weight In immigrant and adopted children, who move from developing to developed countries,is associated
with precocious menarche. Taken together, these studies support the notion that a critical body fat mass Is necessary for normal Pubertal progression.

...

HCG hormones which genes are responsible??

hCG and hyperglycosylated hCG : the horror stories of the evolution of pregnancy failures :: Learn more about Hormone Family

The glycoprotein hormone family of molecules all evolved from TGFβ over hundreds of millions of years. In many respects, the stories of humans and evolution of hCG and hyperglycosylated hCG are all interrelated. Unfortunately, these stories are also one and the same with the horror stories of the evolution of pregnancy failures and the evolution of human cancers. This is because the evolution of hCG and hyperglycosylated hCG led to the evolution of humans, and led to human pregnancy failures and human malignancies. All are all driven by variants of hCG and hyperglycosylated hCG.

Glycoprotein Hormones:-

The glycoprotein hormone family includes TSH, and the two gonadotropins. The three glycoprotein hormones are synthesized and stored in pituitary basophils and, as their name implies, each contains sugar moieties covalently linked to asparagine residues in the polypeptide chains. All three are comprised of two peptide subunits, designated alpha and beta, which, though tightly coupled, are not covalently linked. The alpha subunit of all three hormones is identical in its amino acid sequence, and is the product of a single gene located on chromosome 6.But the  beta subunits of each are somewhat larger than the alpha subunit and confer physiological specificity. Both alpha and beta subunits contribute to receptor binding and both must be present in the receptor binding pocket to produce a biological response. Beta sub­units are encoded in separate genes located on different chromosomes:for example :- TSH β on chromosome 1, FSH β on chromosome 11, and LH β on chromosome 19, but there is a great deal of homology in their amino acid sequences. Both subunits contain carbohydrate moieties that are considerably less constant in their composition than are their peptide chains. Alpha subunits are synthesized in excess over beta subunits, and hence it is synthesis of beta subunits that appears to be rate-limiting for production of glycoprotein hormones. Pairing of the two subunits begins in the rough endoplasmic reticulum and continues in the Golgi apparatus, where processing of carbohydrate components of the subunits is completed. The loosely paired complex then undergoes spontaneous refolding in secretory granules into a stable, active hormone. Control of expression of the alpha and beta subunit genes is not perfectly coordinated, and free alpha and the beta subunits of all three hormones may be found in blood plasma.

 The glycoproteins.

 Which genes control synthesis * & later controlled release of  abnormal molecules  hCG molecules(phantom hCG)??The placental hormone, human chorionic gonadotropin (hCG), is closely related chemically and functionally to the pituitary gonadotropic hormones. It, too, is a glycoprotein and consists of an alpha and a beta chain. The alpha chain is a product of the same gene as the alpha chain of pituitary glyco-protein hormones. The peptide sequence of the beta chain is identical to that of LH except that it is longer by 32 amino acids at its carboxyl terminus.

Curiously, although there is only a single gene for each beta subunit of the pituitary glyco-protein hormones, the human genome contains 7 copies of the hCG beta gene, all located on chromosome 19 in close proximity to the LH beta gene. Not surprisingly, hCG has biological actions that are similar to those of LH, as well as a unique action on the corpus luteum

Fallacies in Urine for Pregancy tests

Pregnancy Tests

Most of the pregnancy tests available to test for the presence of a pregnancy look for the presence of the beta subunit of hcg or human chorionic gonadotropinin in the blood or urine. Human chorionic gonadotropin is a glycoprotein hormone secreted by the  developing placenta shortly after implantation hcg can be detected in the urine and serum of pregnant woman as early as 6-15 days after conception. This hormone is released by trophoblastic tissue in the placenta. However in rare cases it may cell tumours or even other forms of cancer e. g. lung cancer,

Urine tests (Home pregnancy Tests)

Home pregnancy tests are available as kits and though detect pregnancy fairly accurately they should always be followed with blood tests by the physician . Home pregnancy tests work by detecting raised levels of the hormone hcg in the urine. To use a homes pregnancy urine test ones must collect urine in a container and clip the test strip into it . Some tests are available in a solution form and the urine drops have to be added to it. After a waiting time interval (depending on the kind of test used). The results can be read according to the instructions given .

Blood tests                                

A suspected pregnancy can be confirmed with the help of a blood test which also measures the amount of hcg in the blood and confirms the pregnancy . A blood test is more reliable than a urine test. So both are routinely done to confirm conception,

Rapid hcg test card

Rapid hcg test card is used to obtain a visual qualitative result and is intended by professional and laboratory use only. The hcg test card is a rapid test to detect the presence of hcg in urines specimens in a qualitative format sensitive to 10m/u hcg/ml. The test utilizes a combination of monoclonal and polyclonal antibodies reagents to selectively detect elevated level of hcg in urine . The immunological specificity of the test card virtually eliminates cross reactivity interferences from the structurally related glycoprotein hormones FSH,LH, TSH at physiological levels.

Urine or blood pregnancy tests: Which one is better?

Amongst the two types of pregnancy test one tests the blood for the pregnancy hormone hcg while the other checks the urine for this hormone. HPTs using urine testing are inexpensive private and easy to use and are able to tell if one is pregnant about 2 weeks after ovulation. The blood tests to check for pregnancy however are generally used by doctors. Blood tests can pick up hcg earlier in a pregnancy than urine tests can and can confirm the pregnancy about 6-8 days after ovulation. A quantitative blood test measures the exact amount of hcg in the blood and can trace even tiny amounts of hcg thus making it   very accurate. Qualitative hcg blood tests just tests for positive and negative.

Pregnancy Tests sensitivity and hcg values

The pregnancy tests available differ widely in their sensitivity in picking up the pregnancy hormone hcg. As a general rule hcg levels if one is pregnant are between 5-50 mlu a week before the period is due and the hcg levels should double every two to three days. However f is important to remember that every woman is different and the time it takes for the fertilized egg to implant in the uterus wall can vary. A common misconception is that implantation occurs 7 days after conception but the research findings showed that first appearance of HCG occurred 6-12 days after ovulation with 84% of the pregnancies implanting on days 8-10 after ovulation. Hence if one does not get a positive pregnancy test it doesn’t necessarily mean that subject is not pregnant because it is possible that the subject ovulated later than expected or implantation took longer than the average. The amount of hcg or pregnancy hormone in the urine increases with time hence the earlier one takes the test after a missed period the harder it is to spot the hcg. Hence it is best to wait one week after a missed period as one is more apt to have an accurate result at this time.

Various brands of HPT kits are available and are different in sensitiveness. Many HPTs  claim to be 99% accurate on the day one misses the period. But research suggests that most HPTs do not consistently spot pregnancy that  early and even when they do the results are often very faint. In a study done in 2004 researchers tested the accuracy of different brands of HPTs and found that only one brand consistently detected the low levels of hcg usually present on the first day of the missed period. The other tests missed up to 85% of pregnancies on the first day of the missed period however most tests accurately confirmed pregnancies one week after the missed period.

Pregnancy hcg measurement tests:

Advantages of Quantitative tests

Qualitative blood tests generally have a threshold of 25 mlu/ml  and are less sensitive. However quantitative blood tests can detect hcg levels as low as 1 mlu/ml. While urine tests have published detection thresholds between 20 and 100 mlu/ml . Quantitative beta hcg readings are also used in evaluation of trophoblastic and other germ cell tumors.

Quantitative serum beta hcg levels are measured in mlu/ml and a level above 25mlu/ml usually indicates the presence of a pregnancy. Two tests are usually necessary to verify s normal increase. Usually 2-3 days apart. The increase in serum hcg can be interactively monitored. Below an hcg level of 1.200 mlu/ml the hcg usually doubles every 48-72 hours though a rise of 50-60 % is still considered normal. Between 1.200 and 6000 mlu/ml serum the hcg usually takes 72-96 hours to double and above 6000 mlu/ml the hcg often takes more than  four days to double.

Failure to increase normally may indicate that the pregnancy is not developing well and can be an early sign for a possible miscarriage or an ectopic pregnancy. After a miscarriage.HCG levels fall steadily back to the non pregnancy range. Also an ectopic pregnancy may be suspected when hcg levels fail to double particularly if the hcg level rises fails and rises again.

Role of ultrasound in pregnancy detection

Once a pregnancy has advanced past first 6-8 weeks, the pregnancy is usually easier to follow by ultrasound as more information is obtained in real time. In general a pregnancy is detectable 25 days after ovulation by transvaginal sonography (usually corresponding to an hCG level of >1.500 miu/ml).       

Home Pregnancy Tests: Drug Interactions

Most medicines, over the counter and prescription, including birth control pills and antibiotics, does not affect the results of a home pregnancy test. Alcohol and illegal drugs do not affect HPT results. Only medicines that have the pregnancy  hormone hCG, such as ones used to treat infertility can give a false positive test results.

A  Faint Line on a pregnancy Test May Mean:

On a pregnancy test, a faint test line, or color band  is usually indicative of a positive result, as long as it’s read  within the allotted reaction time of the test (usually at 3-5 minutes). Explanations for faint positive line include:

.One may be testing too early after conception – the hCG in the body may not be a sufficient level for test detection. Since, hCG doubles every  two days, one should wait and test again using first morning urine.

.Different test sensitivity: As tests detect hcg at different levels a faint line on one variety of test may appear as a stronger line on a different 20mlu test.

Urine dilution may be present: Urine may be diluted due to frequent urination or consumption of liquid hence first morning urine is recommended for pregnancy testing as it contains the most concentrated presence of hcg.

Chemical pregnancy: At times an early pregnancy is detected followed by negative test results. A chemical pregnancy means implantation takes place followed by a miscarriage- usually before any other pregnancy symptoms are detected.

False positive and False negative tests

False negative readings can occur when testing is done too early and earlier the test is performed the higher the chance of a false negative result. A false negative result can also stem from using a diluted urine samples  apart from taking a test too early in pregnancy. First morning urine contains the most concentrated presences of hcg which makes it the ideal sample for pregnancy testing.

False positives tests are rare though there are instances and conditions where they can occur in case some tissues in a  non pregnant woman produce hgc, it may gives a false positive test . False positive results can result from diseased likes choriocarcinoma igA deficiencies heterophile antibodies enterocystoplasties ,gestational trophoblastic diseases gestational trophoblastic neoplasms and testicular germ cell malignancies . Secondly research indicates that half of all conceptions do not go forward to develop as pregnancy and may abort . A false positive can be seen in this situation. M

Medications that can cause a false positive are the fertility medications that  contain hcg. However fertility drugs and medications that do not contain hcg will not precipitate false positive as well. A percentage of false positives pregnancy test can also be attributed to misinterpretation of results due to a failure to follow test instructions with precision. Additionally at the same gestational stages, women produce quantitatively different levels of hcg. Hence the first indication of positive result on a home pregnancy test may vary between women despite similar gestational stage.

 HCG from urine :: Evaporation lines : 

Moreover many homes pregnancy tests show a positives or unclear result when read well after the suggested 3-5 minute window, independent of an actual pregnancy. This type of false positive is known as and evaporation line.

Phantom hcg:

Some individuals react to some substrate in the test and thus will display a consistently low positive blood pregnancy test even though they are no pregnant. This phantom hcg may lead to serious misdiagnosis and intervention but can be detected with serial dilutions. Patients with phantom hcg have a postitivse blood hcg but a negative urine hcg test .

Need for patience in pregnancy tests

Since, pregnancy tests look for the hcg hormones which is produced once the fertilized egg has implanted in the uterine wall in most cases this happens about 6 days after conception. A positives pregnancy test, further confirmed to be healthy by ultrasound techniques, makes all the hard work and effort of planning pregnancy worthwhile. But studies show that in up to 10 percent of women ,the embryo doesn’t implant until much later after the first day of the missed period. Hence homes pregnancy tests will be accurate as soon as one day after a missed period for some women but not for others, And because the amount of hcg in the urine at different points in early pregnancy is different for every woman some women will have accurate results on the day of the missed period while others will need to wait longer. But whatever may be time period a positive pregnancy test further confirmed to be healthy by ultrasound techniques, makes all the hard work and effort of planning pregnancy worthwhile.

Resistant Fugal infections

Let us talk on Fungal (DERMATOPHYTES) infection of female body :

Fungus what we need to know ?? Ponit 1: CLASSIFICATION OF DERMATOPHYTES

A)Anthropophilic : Person  to person  transmission  by fomites and by direct contact.

B)  Zoophilic : Animal   to human transmission by direct contact  or by fomites.

C) Geophilic : Originating  in soil.

The importance    of this is that zoophilic species would mount a severe inflammatory reaction    whereas   the anthrophilic species ( which is transmitted by person  to person )  transmission  by fomites and by direct contact)  would mount a milder reaction and thus would   lead to a more persistent  infection However these groups  are not    sharply  demarcated as geophilic species may infect animals. In vivo dermatophytes   grow only on or within   keratinized structures and as such involve the following 

Epidermal dermatopytosis; ) A)  Tinea   capitis(over head)   dermatophytic  folliculitis   B) Tinea facie(face), C) tinea    corporis (body –say abdomen ,back side)  D) tinea cruris  -femoral-thigh areas E) tinea manum( fingers)  F) tinea Pedis(legs lowermost part)  G) Tinea unguium i.e. nails beds--special mention in the sense that Dermatophytoses of nail apparatus( Tinea unguium  )  . Spl points are  onychomycosis is a more inclusive  term including   nail infections caused by  dermatophytes  and also yeasts  and molds which may mimick Fungal infection . H)  Majocchi  granuloma nea  barbae(cheek of males) .

 How fungus does enters in human body?? Where is gate pass –It is keratinases enzyme which allow to eneter in the body be it head(capitis),Cheek of males Tinea facie(face), or say nails (Tinea unguium i.e. nails beds)   !!!  Pathogenesis  of human fungal infections:-The     pathogenesis of dermatophytosis has    three main  aspects which  determine   its course. This includes the Factor I :-host response  Factor 2 How epidermis behaves the  barrier   function of skin and Factor  3:- aggressiveness the fungi .  There is usually no drug resistance in case of most fungal infection and antifungal agents . The    frequent cases of relapse which are mistaken for resistance are due to   the ambient local factors. Clinical resistance is a wrong term as in vitro resistance    is rare    is probably due to the interplay of the fungal species and the host immune response. Thus it is meaningless to prolong the duration of antifungals  or even combine and add   oral azoles to the therapy as that is not a solution when microbiological resistance  is not an issue as is the case.

Steps on pathogenesis:-What is keratinases synthesized by Fungi-so that fungi are able to penetrate the epidermis and can get attached.

Dermatophytes synthesize    keratinases that digest keratin and sustain existence  of fungi in keratinized structures ..Dermatophytes that initiate   little inituial inflammatory response are better able   to establish chronic infection .Organisms  such as  Microsporum canis cause an acute   infection associated   with a brisk inflammatory     response and thus elad to spontaneous resolution. In some individuals    infection   seems  to involve the dermis    as in kerion and Majocchi   granuloma however it should be noted   that it is the inflammation which is extending  to the dermis and not the infection  as the fungus is present  only in stratum corneum  fully keratinized hair    shaft  nail plate    or keratinized  nail  bed .

To remember that “Mannans  in the cell walls of dermatophytes  “-à have  1)  immune inhibitory    effects. In T rubrum the mannans may also decrease   2) epidermal proliferation thereby decreasing the likelihood of the fungus being   sloughed off prior to invasion. This mechanism is though   to contribute   to the chronicity of infections caused by T rubrum.

Why fungal infn is hard to treat and achieve cure?? Poinits to  remember by the clinicians :-Local  factors  that favor dermatophyte  infection include sweating  occlusion   occupational exposure  geographic  location high  humidity     . In India a common cause for   persistence is the type of clothing We have   moved from cotton to denim the latter    being     a preferred cloth of the Western world   suited for their   cold climate. In our climate this prevents evaporation of sweat and thus    does not let the skin breathe. In our  practice almost  all such patients have   recurrences. Another observation is that the use of   leather shoes predisposes to tinea   Pedis. I have    rarely seen a villager who   usually works   barefoot having tinea Pedis though the well heeled usually      have tinea Pedis and commonly  onychomycosis both   being causes of relapse.

host factors The severity  of clinical  disease is also  affected by several  host factors. Sebum has an inhibitory  effect on dermatophytes and the degree of disease activity may be related to the number    and activity   of sebaceous glands  in a particular body    region. Breaks in the skin barrier or macerated skin encourage     dermatophyte invasion and increased   susceptibility   may be inherited or related    to the competency  of the  immune  system. Once  deramtophytes   have invaded and begun to proliferate in the skin several mechanisms  aid in   limiting the infection to keratinized  tissue. These include the preference of dermatophytes for the cooler  temperature at the skin  surface   serum factors that inhibit  dermatophyte  growth    and the host  immune system.

Cell mediated  immunity and antimicrobial activity  of polymorphonuclear leukocytes restrict  dermatophyte   pathogenicity. Host factors    that  facilitate   dermatophyte   infections include   atopy  topical and systemic   glucocorticoids  ichthyosis collagen   vascular disease.

Thus the clinical  presentation of dermatophytoses  depends   on several   factors. Site of  infection immunologic response of the host and  species   of fungus. An overview  of the treatment  is detailed

Fungal infections

Let us talk on Fungal (DERMATOPHYTES) infection of female body :

Fungus what we need to know ?? Ponit 1: CLASSIFICATION OF DERMATOPHYTES

A)Anthropophilic : Person  to person  transmission  by fomites and by direct contact.

B)  Zoophilic : Animal   to human transmission by direct contact  or by fomites.

C) Geophilic : Originating  in soil.

The importance    of this is that zoophilic species would mount a severe inflammatory reaction    whereas   the anthrophilic species ( which is transmitted by person  to person )  transmission  by fomites and by direct contact)  would mount a milder reaction and thus would   lead to a more persistent  infection However these groups  are not    sharply  demarcated as geophilic species may infect animals. In vivo dermatophytes   grow only on or within   keratinized structures and as such involve the following 

Epidermal dermatopytosis; ) A)  Tinea   capitis(over head)   dermatophytic  folliculitis   B) Tinea facie(face), C) tinea    corporis (body –say abdomen ,back side)  D) tinea cruris  -femoral-thigh areas E) tinea manum( fingers)  F) tinea Pedis(legs lowermost part)  G) Tinea unguium i.e. nails beds--special mention in the sense that Dermatophytoses of nail apparatus( Tinea unguium  )  . Spl points are  onychomycosis is a more inclusive  term including   nail infections caused by  dermatophytes  and also yeasts  and molds which may mimick Fungal infection . H)  Majocchi  granuloma nea  barbae(cheek of males) .

 How fungus does enters in human body?? Where is gate pass –It is keratinases enzyme which allow to eneter in the body be it head(capitis),Cheek of males Tinea facie(face), or say nails (Tinea unguium i.e. nails beds)   !!!  Pathogenesis  of human fungal infections:-The     pathogenesis of dermatophytosis has    three main  aspects which  determine   its course. This includes the Factor I :-host response  Factor 2 How epidermis behaves the  barrier   function of skin and Factor  3:- aggressiveness the fungi .  There is usually no drug resistance in case of most fungal infection and antifungal agents . The    frequent cases of relapse which are mistaken for resistance are due to   the ambient local factors. Clinical resistance is a wrong term as in vitro resistance    is rare    is probably due to the interplay of the fungal species and the host immune response. Thus it is meaningless to prolong the duration of antifungals  or even combine and add   oral azoles to the therapy as that is not a solution when microbiological resistance  is not an issue as is the case.

Steps on pathogenesis:-What is keratinases synthesized by Fungi-so that fungi are able to penetrate the epidermis and can get attached.

Dermatophytes synthesize    keratinases that digest keratin and sustain existence  of fungi in keratinized structures ..Dermatophytes that initiate   little inituial inflammatory response are better able   to establish chronic infection .Organisms  such as  Microsporum canis cause an acute   infection associated   with a brisk inflammatory     response and thus elad to spontaneous resolution. In some individuals    infection   seems  to involve the dermis    as in kerion and Majocchi   granuloma however it should be noted   that it is the inflammation which is extending  to the dermis and not the infection  as the fungus is present  only in stratum corneum  fully keratinized hair    shaft  nail plate    or keratinized  nail  bed .

To remember that “Mannans  in the cell walls of dermatophytes  “-à have  1)  immune inhibitory    effects. In T rubrum the mannans may also decrease   2) epidermal proliferation thereby decreasing the likelihood of the fungus being   sloughed off prior to invasion. This mechanism is though   to contribute   to the chronicity of infections caused by T rubrum.

Why fungal infn is hard to treat and achieve cure?? Poinits to  remember by the clinicians :-Local  factors  that favor dermatophyte  infection include sweating  occlusion   occupational exposure  geographic  location high  humidity     . In India a common cause for   persistence is the type of clothing We have   moved from cotton to denim the latter    being     a preferred cloth of the Western world   suited for their   cold climate. In our climate this prevents evaporation of sweat and thus    does not let the skin breathe. In our  practice almost  all such patients have   recurrences. Another observation is that the use of   leather shoes predisposes to tinea   Pedis. I have    rarely seen a villager who   usually works   barefoot having tinea Pedis though the well heeled usually      have tinea Pedis and commonly  onychomycosis both   being causes of relapse.

host factors The severity  of clinical  disease is also  affected by several  host factors. Sebum has an inhibitory  effect on dermatophytes and the degree of disease activity may be related to the number    and activity   of sebaceous glands  in a particular body    region. Breaks in the skin barrier or macerated skin encourage     dermatophyte invasion and increased   susceptibility   may be inherited or related    to the competency  of the  immune  system. Once  deramtophytes   have invaded and begun to proliferate in the skin several mechanisms  aid in   limiting the infection to keratinized  tissue. These include the preference of dermatophytes for the cooler  temperature at the skin  surface   serum factors that inhibit  dermatophyte  growth    and the host  immune system.

Cell mediated  immunity and antimicrobial activity  of polymorphonuclear leukocytes restrict  dermatophyte   pathogenicity. Host factors    that  facilitate   dermatophyte   infections include   atopy  topical and systemic   glucocorticoids  ichthyosis collagen   vascular disease.

Thus the clinical  presentation of dermatophytoses  depends   on several   factors. Site of  infection immunologic response of the host and  species   of fungus. An overview  of the treatment  is detailed