Lymphatic disorder may cause stillbirth, chronic disease in affected children

In a breakthrough discovery, South Australian researchers have identified a genetic mutation responsible for a lymphatic disorder that may be responsible for causing stillbirth or severe, chronic disease in affected children.

The findings were published in the journal 'Science Translational Medicine'.

An anomaly in the development of lymphatic vessels in unborn children, leading to fluid accumulating in the heart, lungs, and other organs, was uncovered by the scientists from the Centre for Cancer Biology (CCB) based at the University of South Australia (UniSA) and SA Pathology.

CCB Director Professor Natasha Harvey said a genetic study of six families affected by stillbirth or lymphoedema revealed the link between a mutated protein-coding gene called MDFIC and fluid accumulation in vital organs and tissues.

This demonstrated that MFDIC is important for controlling the growth and development of the lymphatic vessels in the foetus for the first time.

"The lymphatic system is a network of vessels (pipes) and nodes (filters and control centres) important for maintaining fluid balance in our tissues and transporting infection-fighting white blood cells throughout our bodies," Prof Harvey said.

"We determined that MDFIC controls cell migration, an important early event during the formation of the lymphatic vessel valves. The genetic variants we have found in our study reveal a crucial, previously unrecognized role for MDFIC in the lymphatic vasculature."

"If the lymphatic valves don't form properly, lymph fluid accumulates in critical organs such as the heart and lungs, causing major respiratory problems that may eventuate in stillbirth or chronic disease."

An SA Pathology research team headed by Professor Hamish Scott initially found the genetic link in an Australian family. Their international colleagues in Belgium, Germany, and the US reported variants in the same gene, MDFIC, in several patients with the same lymphatic disorder.

Prof Harvey said, the disorder, known as the central conducting lymphatic anomaly (CCLA), is one of a group of severe lymphatic disorders and may result in stillbirth, or severe chronic disease in affected children.

Few effective treatments are available but with continued identification of the genetic causes of CCLAs, Prof Harvey says the next step is to develop new therapeutic drugs to combat the disease.

"There are existing drugs that may be used to treat these disorders, but we need to make sure that the signalling pathway that's treated by those drugs is the same pathway that is affected in our patients.

"This project is about the power of collaboration at a local level, national level, and international level, so that's been really important. Science is done in teams and we have great research teams here in Adelaide at the Centre for Cancer Biology. Our Ph.D. students and postdoctoral fellows have been integral to this work. They have really driven it and we're delighted to be working with such a group of talented people."

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Scientists develop tool for treating diverse tumour cells found in metastatic gastric cancer

After defining extensive cellular heterogeneity, researchers from The University of Texas MD Anderson Cancer Center developed a tool that might be useful in stratifying patients with gastric cancer and directing them for more effective treatment strategies.

Based on the findings, published in Nature Medicine, the scientists developed and validated a gene expression signature capable of predicting patient survival better than other clinical features.

"In order to better treat patients with PC, we first have to understand the populations of metastatic cells in the peritoneal cavity," said co-corresponding author Linghua Wang, M.D., PhD, assistant professor of Genomic Medicine."This is the most detailed analysis of these cells performed to date. That is the power of single-cell analysis - we are able to look at every single cell and get a picture of the landscape," added Wang.

Peritoneal carcinomatosis is a condition in which cancer cells infiltrate and invade the peritoneal, or abdominal, cavity, adhering to the stomach and other organs.This can occur with other gastrointestinal cancers but is most commonly seen in patients with advanced gastric cancers, with roughly 45 per cent of patients diagnosed with PC at some point. The condition leads to significant fluid accumulation in the abdominal cavity, and patients have an overall survival of fewer than six months.

"PC represents a major unmet clinical need, as we don't have effective treatment options available for these patients," said co-corresponding author Jaffer Ajani, M.D., professor of Gastrointestinal Medical Oncology."Based on our findings, we need to move toward profiling these cells in each patient in order to offer more tailored treatment options," added Anjani.

For this study, the researchers isolated PC cells from ascites fluid collected from 20 patients with advanced gastric cancer. Ten of the patients were long-term survivors who survived more than one year after PC diagnosis, and 10 patients were short-term survivors who survived less than six months after PC diagnosis.

After performing single-cell RNA sequencing to analyze gene expression, the researchers were able to build the first "map" of PC cells, which describes the variety of cell types present and their functional states. The variability of cancer cells present within a tumour is known as intratumor heterogeneity, and it can lead to treatment failure and recurrence as distinct subtypes of cancer cells will respond differently to a given therapy.

The gene expression information also enabled the researchers to determine the origins of the PC cells, known as tumour cell lineage. They discovered that, although these were all gastric cancer cells, some appeared to originate from cells of the stomach while others more closely resembled cells of the intestine.

"The intriguing aspect is that, by classifying tumour cells based on lineage compositions, we noted two groups of patients," Wang said. "The more gastric-like PC cells had an aggressive phenotype and were associated with shorter survival. However, the more intestine-like PC cells were less aggressive, and patients had longer survival."

Based on these findings, the researchers developed a gene signature which robustly predicted patient survival better than various clinical features. They validated the signature in the second cohort of patients with advanced gastric cancer and PC and four large-scale localized gastric cancer cohorts totalling more than 1,300 patients.

Going forward, the researchers hope to validate the signature in prospective studies and to perform further analyses of PC cells in more patients to identify regulatory mechanisms of tumour cell lineage plasticity and new therapeutic targets that can be exploited to provide better treatment options for patients.

"This is an important first step toward a better understanding of the single-cell biology of these cancer cells, but we have more work to do. We foresee that understanding this heterogeneity could one day be used to guide clinical decision making that is most beneficial to each patient," Ajani said.

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Swollen Legs, Ankles and Feet: Causes and Proven Remedies

Swollen ankles, legs, and feet cause discomfort and even pain for many people. If you are one of these people who suffer from puffiness around your ankles, you probably wonder what you can do to reduce the ankle swelling and ease discomfort.

Swelling in the ankles, legs, and feet is caused by an accumulation of fluid around the base of your legs. This swelling (called edema) can be caused by something as simple as being on your feet or sitting down for too long. You may also feel that the area around the base of your legs swells and becomes puffy in hot weather.

However, sometimes fluid can build up and cause swelling around the ankles, legs, and feet due to an underlying serious health condition like problems with your kidneys, heart or blood circulation. Some medications can also cause a buildup of fluid in your body resulting in swollen ankles and feet. Also, if one leg looks swollen, while the other one appears normal, see a doctor, as this unevenness could be a sign of deep vein thrombosis.

It is important to tell the difference between swollen ankles caused by “everyday” activities, and edema that requires treatment by a doctor. Generally, harmless ankle and leg swelling occurs on both legs and doesn’t have other ominous symptoms like shortness of breath, chest pain, or bluish skin (cyanosis).

In this article, we will look at some of the best home remedies for swollen ankles. Because treatment depends on the underlying cause of leg edema, we will also look at the reasons for fluid retention that causes leg swelling. This will help you know if you should see a doctor for swollen ankles or swollen feet and legs.
At the end of the article you will find a recipe for parsley tea to reduce swollen ankles and feet.

What Causes Ankles, Legs, and Feet to Swell

Swollen ankles and swollen feet occur because of fluid retention around the base of your leg. According to doctors, certain conditions can cause fluid to leak from capillaries which then builds up in the surrounding tissues.

Here are some common reasons for ankle, leg, and feet swelling.

Standing or sitting for too long

One of the most common reasons for swelling around the ankles is standing or sitting for too long. According to doctors from the Cleveland Clinic, edema around the feet and ankles happens because gravity pulls fluid down to your feet. This can result in puffiness around your ankles that have the appearance of shiny skin. You may also notice that the skin retains a dimple when pressed.

Too much salt in your diet

Having high salt in your diet can cause edema because it makes it harder for your body to get rid of excess fluid. This fluid usually builds up around your ankles and feet causing swelling and puffiness.

According to a Dr., the kidneys are responsible for removing salt from your body. If your kidneys aren’t working properly, then more salt will be retained in the body and this will cause edema.

Pregnancy

Suffering from swollen ankles, feet, and legs is something that happens to most women who are pregnant. According to the American Pregnancy Association, swelling around the ankles, feet, and hands is normal during pregnancy. Other factors like hot weather, standing for long periods of time, or not being physically active can all increase swelling around your feet when you’re pregnant.
While some swelling around the base of your legs is normal during pregnancy, doctors from the Mayo Clinic warn that sudden swelling around your ankles and hands can be a sign of preeclampsia.

Hot weather

You may find that your ankles, feet, and bottom part of your legs swell more during hot weather. Doctors say that the body is less efficient at removing fluid from tissues when the weather is hot.

Varicose veins

Swollen ankles, feet, and legs are often a complication of varicose veins. The classic symptom of varicose veins is knotted bluish veins on your legs or spider veins.

The journal  says that varicose veins often cause ankle edema which may get worse as the day goes on. If you experience severe swelling in the ankles, you should see a doctor for a proper evaluation.

Deep vein thrombosis

Deep vein thrombosis (DVT) is a serious circulatory problem that may cause ankle swelling in just one leg. A common cause of DVT is long-haul air travel. Dr. Sheldon Sheps from the Mayo Clinic says that short-term foot swelling is usually not a serious problem. However, if the swelling in and around your ankles persists long after your flight and it is painful, you should visit your doctor promptly.

Serious medical conditions that cause edema

There are more serious medical conditions that cause foot edema and ankle swelling. A Dr. says that some of the reasons for swollen ankles that requires medical supervision are:

Heart disease. When the heart can’t pump enough blood around your body, fluid can build up in your legs, lungs, and abdomen.

Liver disease. Liver disease causes problems with the liver function that can lead to swelling in the abdomen and legs.

Kidney disease. When your kidneys function slows down, more fluid is retained in the body. This can even lead to whole body edema.

Home Remedies for Swollen Ankles, Legs, and Feet

There are many effective home remedies to reduce swelling in your ankles, legs, and feet. These natural methods can help to relieve occasional bouts of leg swelling and give you welcome relief from the discomfort that ankle edema causes.

Please remember, that if you have any chronic leg swelling or you have swelling in only one leg that is accompanied with pain, you should see your doctor for proper medical advice.

1. Exercise

Regular physical exercise is a great way to stimulate your blood circulation and stop fluid retention in your legs and ankles. For example, swimming is a great way to take pressure off your feet and, at the same time, boost your circulation.

The researchers reported that exercising was an efficient way to reduce lower limb edema. This can help reduce ankle swelling if you have a sedentary lifestyle or if your swollen feet and ankles are due to aging.

2. Raise your legs

Another effective way to reduce fluid retention in your legs and ankles is to raise your legs above the level of your heart.

For example, the researchers reported that raised-leg exercises helped many elderly people reduce the size of their swollen ankles. They exercised for 20 minutes, 3 times a day and results were seen within a 4-week period.

One easy way to keep your legs raised for an extended period of time to reduce leg edema is to sleep on your back with a pillow under your ankles. This will help to drain excess fluid that has built up around your ankles and feet.

3. Walk around

If you have swollen ankles and feet from standing or sitting for too long, you should get up every so often and walk around. This helps to stimulate your circulation and prevent too much fluid accumulating in your ankles.

The  researchers reported that walking helps to reduce the volume of fluid that builds up in the base of the leg. The researchers found that walking for 50 minutes in the afternoon can help reduce edema and leg pain during the day. The results were enhanced by wearing compression socks.

Doctors  also recommend that to prevent fluid retention and ankle swelling you shouldn’t sit or stand in one place for too long without moving.

4. Compression socks

Compression stockings can help to reduce foot swelling if you have to sit or stand for long periods of time. In fact, compression socks help also to prevent swollen ankles and feet and can make going about your daily activities much easier. Compression stockings help to get rid of the symptoms of fluid retention in the legs by forcing the blood and excess fluid back up the body.

In fact, the research published a study showing the effectiveness of compression stockings if you have to sit for long periods of time. It was found that the compression stockings helped to reduce ankle and leg size in the evening and were recommended for people who have to sit or stand for their job^.

Compression stocking can be useful to prevent leg and ankle swelling if you are pregnant or have to fly a long distance.

5. Foot massage

To help reduce ankle and foot swelling while you are pregnant, you can try a relaxing foot massage. Massage therapy is a great way to naturally stimulate circulation and help reduce the signs and symptoms of edema.

The reported that foot massage helps to remove a buildup of fluid in the lower-leg area. In the study, women who were pregnant received foot massages for 20 minutes a day for 5 days. This was found to decrease swelling in the legs and ankles naturally.

You can do your own foot massage or have someone do it for you. This will not only help get rid of ankle swelling but also help relax you and act as a natural stress reliever.

6. Reduce salt intake

If you find that your ankles and legs are swollen, you should reduce your salt intake to prevent accumulation of fluid. Your body needs a little salt for it to function properly, but too much salt can have a detrimental effect on your heart, kidney, and cardiovascular system.

Doctors  recommend reducing salt intake if you are getting treated for edema. In fact, the researcher says that reducing the amount of salt (sodium) in your diet helps to prevent a buildup of fluid in your legs, heart, and lungs.

7. Stop smoking

To keep healthy, it’s important that you stop smoking now. Smoking can cause many health problems that lead to serious diseases like various cancers, heart disease, and lung disease. Quitting smoking will also improve your circulation and prevent hand, leg, and ankle edema.

The researchers published a study that found that smoking increases the risk of peripheral artery disease (PAD) – a condition that affects blood flow in your body. According to doctors, PAD usually affects blood flow to your legs.

8. Soak in Epsom salts

Soaking in Epsom salts is a great way to relax and relieve aching muscles in your legs and feet. There is some anecdotal evidence that having a foot bath in Epsom salts could also relieve swelling in your ankles.
The researchers published comments from a retired nurse that used Epsom salt soaks to reduce leg swelling. The nurse reported that it is well-known that Epsom salts are an effective remedy for swollen feet. She used an Epsom salt bath to increase blood circulation and reduce discomfort in swollen legs caused by heart disease.

Other Ways to reduce Swollen Ankles, Legs, and Feet

9. Drink plenty of water

We are all guilty of often not drinking enough fluids. By drinking water throughout the day, we hydrate our tissues and detox the body. Sodium and caffeine, which contribute to feet inflammation, get diluted if we water ourselves sufficiently. Eight to ten glasses a day should be the norm. So make sure you carry that water bottle with you. For added antioxidant value, squeeze some lemon or lime in or prepare your own flavoured water.

10. Consume enough magnesium

Often feet inflammation, which can result in painful swelling, is connected to magnesium deficiency.

How To Make Parsley Tea for Swollen Ankles, Legs and Feet

Parsley looks great as a garnish, so many have forgotten that this beautiful plant can also be used in many other ways. Eating an abundance of parsley has always been equated to health and this herb is believed to protect from various diseases.

Not long ago, parsley tea was frequently used to treat different maladies. It is now being revived as a powerful herbal remedy. One of the conditions parsley can help with is leg edema or swollen legs.

Parsley Tea and Leg Swelling

Parsley is a known natural diuretic. It helps the body get rid of excess water and salts by improving kidney function and taking more water from the blood.

A study published in 2002, provided substantial evidence for the use of parsley as a powerful diuretic. The study was done on rats (humans and rats have the same basic physiology). Rats that were offered parsley seed extract to drink produced significantly more urine over a period of 24 hours compared to when they were drinking only water.

Scientists believe that this herb acts in a diuretic way by inhibiting the sodium and potassium ion pumps, influencing the process of osmosis and increasing the flow of urine.

Parsley is rich in potassium. A lot of the chemically produced diuretic drugs lower potassium levels in the body, which is their negative side effect. If you use the simple parsley, you avoid this adverse effect as body’s potassium supply is not depleted.

Parsley is also a powerful antioxidant. Parsley is rich in vitamins A and C and is a good source of folic acid, which is one of the top 14 foods and nutrients that protect against cancer development.

Parsley Tea Recipe for Edema (Swollen Legs)

An authority in the field of herbals, suggests drinking at least two quarts of strong parsley tea per day. The dose can be increased to a cup of tea every hour.
When making your tea, use the fresh light-green leaves, along with roots and seeds (if you can get them).

1. Chop the leaves and roots
2. Place approximately ¼ cup of parsley into an infusion basket.
3. Pour over a cup of boiled water or submerge into a tea pot.
4. Let it steep for 5 to 7 minutes.
5. Remove the basket or strain the tea.

You can use honey and lemon to enhance the tea’s flavor.

Also, don’t forget to combine tea consumption with other techniques for swelling reduction, such as leg elevation. 

Important note: Before using parsley tea as a diuretic, you might want to consult your doctor, especially if there is an underlying health condition that needs to be considered or if you are pregnant. Parsley tea may stimulate uterine contractions and increase the risk of miscarriage if you have it in large amounts.

Swollen Ankles, Legs and Feet – When to See a Doctor

Usually, if your legs or ankles swell after standing a lot or sitting for extended periods of time, there is nothing to worry about. However, if swelling at the bottom part of either of your legs is accompanied by other symptoms, you should see a doctor.

Doctors  recommend visiting a medical professional for leg or ankle swelling if it is accompanied by one or more of the following symptoms:

• Just one leg or ankle swells suddenly
• You have chest pain and difficulty breathing
• You have shortness of breath when laying down or engaging in physical activity
• You feel dizzy or lightheaded
• The swelling occurs suddenly for no apparent reason

Even if you think that leg swelling doesn’t have a serious underlying cause, it is still best to have a doctor check out any kind of swelling that causes you concern.

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