As pheo is a rare disease, it is no surprise that many doctors have little experience on pheo. Ideally patients with suspected pheo should be seen at large centers with extensive experience such as Mayo Clinic or National Institute of Health. On the other hand, most patients with suspected pheo do not actually have pheo and the management of pheo is not that complicated in most cases. Having traveled long distances, many patients with suspected pheo would feel that they probably could have saved the trip if their primary doctors had simply communicated with the experts in large centers about their conditions. A recent paper addresses the above situation somewhat, albeit indirectly.
In this paper, doctors at one center examined whether a "pheo interest group" could improve the diagnosis and treatment of pheo. The pheo interest group is nothing more than a group of doctors with a common interest in this rare disease. A few of the doctors have a large personal experience with pheo. The doctors compared the diagnostic accuracy and management of pheo before and after the formation of the pheo interest group and found that the quality of care improved after the group formation.
It might be expected that quality of care of course would be higher if the patients were seen by pheo specialists. This paper, however, shows that the pheo specialists do not have to see the patients directly. A phone call or email exchange between the primary doctor and a pheo specialist often does the job. The pheo specialist would review the clinical history, lab test, and imaging results (if available) provided by the primary doctor and arrive at a conclusion. The specialist only communicates with the primary doctor, without seeing the patient. The medical responsibility still rests in the primary doctor's hands. The primary doctor chooses to adopt the opinions of the specialist or not. As alluded in this paper, most primary doctors would adopt those opinions after they have had positive experience with the pheo specialists.
The moral: an inexperienced doctor should seek help from pheo specialists for diagnosis and management of pheo. Will the specialists be happy to answer the questions from non-specialists? They should. Take me as an example. I have been approached by doctors in my practice area and from remote places for pheo-related questions. I am happy to answer them. First of all, these questions are not very frequent so do not cost a lot of time. Second, I often learn new things on pheo from my colleagues who have questions in pheo. Last, it is rewarding for me to help my colleagues and patients (indirectly). I always make sure to emphasize that my opinions are "friendly" and non-binding. It is the primary doctor's responsibility to decide what to do.
Dr. Pheo
Tuesday, July 19, 2011
Tuesday, June 21, 2011
All those exons and MAX
It is now a good time to do translational research on pheo. A clinician/researcher myself, I am following pheo research closely and I can tell that translational research on pheo is getting great results.
Translational research directly addresses mechanisms of human diseases. Translational research is the interface between basic and clinical research. The recent boom in translational research, in my opinion, is driven by two forces: patient advocacy groups and new technologies. Patient advocacy groups are more like corporate now. They usually hire MBAs to manage their operations and use more sophisticated strategies to advance their causes. New technologies are being developed almost every day. The new technologies need to find applications to show they are worthwhile in answering medical questions. With the synergy of those two forces, new technologies are more and more applied to less common diseases. Compared with common diseases, less common diseases, such as pheo, are more easily studied with the new technologies because they are more homogeneous. For example, there are so many types of prostate cancer, making a common etiology less likely. While pheo, by virtue of its rarity and uniform pathology, share more common features between each other.
One such new technology, exonomics, sequences almost every exon of the genome. Exons are the DNA stretches that actually encode proteins. (Introns, on the other hand, are DNA stretches that do not.) Because proteins are the doers and movers of biology, sequencing the exons likely yields insight of genetic causes of diseases.
Today, I noted a paper just published online which identifies a new tumor suppressor gene for pheo called MAX. The Spanish doctors include 3 families of familial pheo who do not have any mutations in known genes important for pheo. The exons of a lot of genes are sequenced in this study and MAX mutations appear to cause pheo in the 3 families. Now the list of pheo genes is getting even longer: RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, NF1, TMEM127, and MAX. Does this mean we have to sequence every gene in all patients? Of course not. Each patient’s unique family history and pheo presentation are still the basis for clinical care. Rather, this study demonstrates the power of careful translational research. For such research to be successful, the clinicians must identify a group of patients that share key common clinical features. Scientists, on the other hand, must know all the details of the technology and sieve through the data to find the real molecular deficit. The importance of patient participation of such research cannot be overemphasized.
Dr. Pheo
Translational research directly addresses mechanisms of human diseases. Translational research is the interface between basic and clinical research. The recent boom in translational research, in my opinion, is driven by two forces: patient advocacy groups and new technologies. Patient advocacy groups are more like corporate now. They usually hire MBAs to manage their operations and use more sophisticated strategies to advance their causes. New technologies are being developed almost every day. The new technologies need to find applications to show they are worthwhile in answering medical questions. With the synergy of those two forces, new technologies are more and more applied to less common diseases. Compared with common diseases, less common diseases, such as pheo, are more easily studied with the new technologies because they are more homogeneous. For example, there are so many types of prostate cancer, making a common etiology less likely. While pheo, by virtue of its rarity and uniform pathology, share more common features between each other.
One such new technology, exonomics, sequences almost every exon of the genome. Exons are the DNA stretches that actually encode proteins. (Introns, on the other hand, are DNA stretches that do not.) Because proteins are the doers and movers of biology, sequencing the exons likely yields insight of genetic causes of diseases.
Today, I noted a paper just published online which identifies a new tumor suppressor gene for pheo called MAX. The Spanish doctors include 3 families of familial pheo who do not have any mutations in known genes important for pheo. The exons of a lot of genes are sequenced in this study and MAX mutations appear to cause pheo in the 3 families. Now the list of pheo genes is getting even longer: RET, VHL, SDHA, SDHB, SDHC, SDHD, SDHAF2, NF1, TMEM127, and MAX. Does this mean we have to sequence every gene in all patients? Of course not. Each patient’s unique family history and pheo presentation are still the basis for clinical care. Rather, this study demonstrates the power of careful translational research. For such research to be successful, the clinicians must identify a group of patients that share key common clinical features. Scientists, on the other hand, must know all the details of the technology and sieve through the data to find the real molecular deficit. The importance of patient participation of such research cannot be overemphasized.
Dr. Pheo
Thursday, March 24, 2011
Adrenal biopsy and pheo
Adrenal tumors are fairly common. Diagnosis and follow-up of adrenal tumors can be costly and inconvenient. So a reasonable question is "why don't we biopsy an adrenal mass to get a definitive diagnosis?" Here I will try to convince the readers that adrenal biopsy is seldom necessary or useful except in one situation. Most important to me is the one particular safety issue of adrenal biopsy: biopsy of a pheo can be catastrophic.
The one situation where we need adrenal biopsy is to determine the staging of a cancer. For example, one unfortunate patient has lung cancer and an adrenal mass. If the adrenal mass is benign, then the patient's lung cancer is of a lower stage. If the adrenal mass is lung caner metastasis, then the same lung cancer is of an advanced stage. Only biopsy of the adrenal mass will give definitive staging information of the patient's cancer.
Adrenal biopsy is not needed for the vast majority of adrenal masses because the diagnosis of adrenal mass can be confidently made in most patients without biopsy. Let me explain why. How do we know someone has an adrenal mass? Either the patient has clinical symptoms (e.g. paroxysmal hypertension) with suggestive biochemical test results (e.g. elevated plasma metanephrines) so that a functioning adrenal mass (e.g. pheo) is suspected, or CT or MRI is done on the abdomen for some other purposes (such as abdominal pain or cancer staging). In both cases, the imaging characteristics of the adrenal mass tell a lot about it. The size, density, enhancement, and appearance on various MRI protocols all matter. With additional biochemical testing, a good doctor is able to make the correct diagnosis of the adrenal mass.
One may wonder, OK, adrenal biopsy probably is not needed, but will it give important additional information? This issue is a little complicated for non-specialists. For the most common clinical question whether an adrenal mass is adenoma or carcinoma, adrenal biopsy can not answer. Regarding pheo, we just simply do not biopsy a pheo to confirm the diagnosis because doing so is too risky without any benefits.
Although generally very safe, adrenal biopsy can be potentially lethal if done to an unappreciated (or worse, suspected) pheo because of the risk of hypertensive crisis. Here are the basic facts: 5% of all incidentally identified adrenal masses are pheo and the percentage is higher if the mass is pheo-like on imaging. In addition, 6-24% of adrenal masses suspected to be malignancy or metastasis are actually pheo. It is not that every attempted biopsy of a pheo will result in hypertensive crisis. It happens in about 15% of times. Although this number does not sound very high, the extreme danger and the total avoidability of hypertensive crisis makes adrenal biopsy unacceptable in any patients without negative pheo test results.
To prevent hypertensive crisis from happening, ask these following questions before adrenal biopsy:
1. Is this adrenal biopsy really needed? (Answer: only needed for cancer staging.)
2. If adrenal biopsy is needed, have pheo markers been tested? (Answer: please test pheo markers and only do biopsy if the markers are considered negative.)
Dr. Pheo
The one situation where we need adrenal biopsy is to determine the staging of a cancer. For example, one unfortunate patient has lung cancer and an adrenal mass. If the adrenal mass is benign, then the patient's lung cancer is of a lower stage. If the adrenal mass is lung caner metastasis, then the same lung cancer is of an advanced stage. Only biopsy of the adrenal mass will give definitive staging information of the patient's cancer.
Adrenal biopsy is not needed for the vast majority of adrenal masses because the diagnosis of adrenal mass can be confidently made in most patients without biopsy. Let me explain why. How do we know someone has an adrenal mass? Either the patient has clinical symptoms (e.g. paroxysmal hypertension) with suggestive biochemical test results (e.g. elevated plasma metanephrines) so that a functioning adrenal mass (e.g. pheo) is suspected, or CT or MRI is done on the abdomen for some other purposes (such as abdominal pain or cancer staging). In both cases, the imaging characteristics of the adrenal mass tell a lot about it. The size, density, enhancement, and appearance on various MRI protocols all matter. With additional biochemical testing, a good doctor is able to make the correct diagnosis of the adrenal mass.
One may wonder, OK, adrenal biopsy probably is not needed, but will it give important additional information? This issue is a little complicated for non-specialists. For the most common clinical question whether an adrenal mass is adenoma or carcinoma, adrenal biopsy can not answer. Regarding pheo, we just simply do not biopsy a pheo to confirm the diagnosis because doing so is too risky without any benefits.
Although generally very safe, adrenal biopsy can be potentially lethal if done to an unappreciated (or worse, suspected) pheo because of the risk of hypertensive crisis. Here are the basic facts: 5% of all incidentally identified adrenal masses are pheo and the percentage is higher if the mass is pheo-like on imaging. In addition, 6-24% of adrenal masses suspected to be malignancy or metastasis are actually pheo. It is not that every attempted biopsy of a pheo will result in hypertensive crisis. It happens in about 15% of times. Although this number does not sound very high, the extreme danger and the total avoidability of hypertensive crisis makes adrenal biopsy unacceptable in any patients without negative pheo test results.
To prevent hypertensive crisis from happening, ask these following questions before adrenal biopsy:
1. Is this adrenal biopsy really needed? (Answer: only needed for cancer staging.)
2. If adrenal biopsy is needed, have pheo markers been tested? (Answer: please test pheo markers and only do biopsy if the markers are considered negative.)
Dr. Pheo
Sunday, January 23, 2011
Pheo in pregnancy
Pheo in pregnancy is very rare. Most people with pheo are diagnosed after they are 40. If they know they have pheo, younger women would have the tumor removed before becoming pregnant. When pheo does occur in pregnancy, it usually is a big surprise and can have serious consequences to the mother and the fetus. Pheo in pregnancy is one of those “cannot afford to miss” diseases. Once suspected, diagnosis and treatment are usually straightforward and the mother and fetus can expect great outcomes.
Pheo in pregnant women is usually subclinical before pregnancy. The metabolic changes during pregnancy and the growing uterus tend to make the tumor more active. In my experience, pheo-induced hypertension usually occurs later in pregnancy but it can occur much earlier. Clinically it is difficult to differentiate between preeclampsia and pheo. My suggestion to obstetricians is to have a low threshold to test pheo. If the blood pressure is hard to control or there are paroxysmal symptoms such as palpitation, sweating, and headache, I would test pheo just not to miss it. In the vast majority of pregnant women, the test results are negative and pheo is ruled out. In those with clearly elevated pheo markers (the markers are usually markedly elevated in pregnancy), abdominal MRI is then done and the pheo is usually in one of the adrenal glands. CT and MIBG scan are contraindicated in pregnancy due to the associated radiation to the fetus. If pheo is diagnosed in the 1st or 2nd trimester (< 24 weeks), the woman is treated with phenoxybenzamine and beta blocker for preoperative preparation and the tumor is resected laparoscopically. If pheo is diagnosed in the 3rd trimester, the woman is still treated with phenoxybenzamine and beta blocker. When fetus is mature enough, Cesarean section is done, followed by tumor resection.
As pheo in pregnancy is a dramatic disease, there are always a few case reports every year, each with a little different flavor in it. The conclusion of most cases is to consider pheo in a pregnant woman with unusual hypertension. The case brought up by reader DJPheo was about a 27-year-old woman. Biochemical diagnosis was very clear but initial abdominal MRI did not identify a tumor. She received a PET/CT scan which localized the tumor. As DJPheo points out, the case raised a few issues. First, it is surprising that the abdominal MRI did not identify the mass (which is sizable at 5.7 x 2.8 x 3.1 cm) adjacent to the spine. Second, what should be done next if the mass is not seen even by experienced radiologist on abdominal MRI? Most would recommend MRI of the pelvis, chest, and neck. Third, if no tumor is seen after MRI of neck and trunk, what should be done next? I would make sure the blood pressure is well controlled and wait until after delivery (probably safer by C-section) for MIBG scan or PET. At any rate, this case should not be construed as evidence supporting PET/CT scan for localizing pheo in pregnancy. Rather the moral is that you need to find a good radiologist to read the MRI images.
Dr. Pheo
Pheo in pregnant women is usually subclinical before pregnancy. The metabolic changes during pregnancy and the growing uterus tend to make the tumor more active. In my experience, pheo-induced hypertension usually occurs later in pregnancy but it can occur much earlier. Clinically it is difficult to differentiate between preeclampsia and pheo. My suggestion to obstetricians is to have a low threshold to test pheo. If the blood pressure is hard to control or there are paroxysmal symptoms such as palpitation, sweating, and headache, I would test pheo just not to miss it. In the vast majority of pregnant women, the test results are negative and pheo is ruled out. In those with clearly elevated pheo markers (the markers are usually markedly elevated in pregnancy), abdominal MRI is then done and the pheo is usually in one of the adrenal glands. CT and MIBG scan are contraindicated in pregnancy due to the associated radiation to the fetus. If pheo is diagnosed in the 1st or 2nd trimester (< 24 weeks), the woman is treated with phenoxybenzamine and beta blocker for preoperative preparation and the tumor is resected laparoscopically. If pheo is diagnosed in the 3rd trimester, the woman is still treated with phenoxybenzamine and beta blocker. When fetus is mature enough, Cesarean section is done, followed by tumor resection.
As pheo in pregnancy is a dramatic disease, there are always a few case reports every year, each with a little different flavor in it. The conclusion of most cases is to consider pheo in a pregnant woman with unusual hypertension. The case brought up by reader DJPheo was about a 27-year-old woman. Biochemical diagnosis was very clear but initial abdominal MRI did not identify a tumor. She received a PET/CT scan which localized the tumor. As DJPheo points out, the case raised a few issues. First, it is surprising that the abdominal MRI did not identify the mass (which is sizable at 5.7 x 2.8 x 3.1 cm) adjacent to the spine. Second, what should be done next if the mass is not seen even by experienced radiologist on abdominal MRI? Most would recommend MRI of the pelvis, chest, and neck. Third, if no tumor is seen after MRI of neck and trunk, what should be done next? I would make sure the blood pressure is well controlled and wait until after delivery (probably safer by C-section) for MIBG scan or PET. At any rate, this case should not be construed as evidence supporting PET/CT scan for localizing pheo in pregnancy. Rather the moral is that you need to find a good radiologist to read the MRI images.
Dr. Pheo
Tuesday, November 23, 2010
Corticosteroid and pheo
This interesting topic is suggested by a reader. The relationship between corticosteroid and pheo is multifold and involves several fundamental physiological issues.
Firs of all, the close proximity of the adrenal cortex and adrenal medulla is an intriguing phenomenon. The adrenal glands are small organs. An adrenal gland actually is further divided into two organs, the cortex (secreting corticosteroid) and medulla (where pheo is derived from), each with related but different functions. Why is the adrenal medulla wrapped around by the cortex? Why isn't the medulla located inside other organs, say, the spleen or liver, or a free-standing organ like a ganglion? I can only think of two other organs, pituitary and pancreas, which are also further divided into two organs. In the case of pituitary, anterior and posterior; pancreas, exocrine and endocrine. The question is still unsettled. Existing evidence suggests that the corticosteroid secreted by the adrenal cortex is important in maintaining the medulla what it is. If one takes the cells from the medulla and puts them in culture, those cells automatically differentiate into neuronal cells. If one adds high concentrations of corticosteroid into the culture, the medulla cells will remain neuroendocrine cells and do not differentiate into neuronal cells. As the medulla cells are derived from the neurocrest during embryonic development, it is hypothesized that the migrating neurocrest cells encounter adrenal cortex cells (which provide high concentrations of corticosteroid) and really like them and stay with them. Thus the story of adrenal cortex and adrenal medulla.
Second, corticosteroid stimulates catecholamine production and release from cultured adrenal medulla cells. Corticosteroid increases catecholamine production by upregulating the key enzymes for catecholamine production. The mechanisms for which corticosteroid stimulates catecholamine release are not clear and may not be straightforward.
Third, corticosteroid prepares the target tissues of catecholamines to be responsive to catecholamines. That is why patients with adrenal insufficiency often have low blood pressure even when they have high catecholamine levels.
Lastly, there have been a number of case reports on pheo crisis induced by corticosteroid use. The pheo crisis usually starts a few hours after corticosteroid use. There may be hemorrhage within the pheo. In patients with known pheo or an adrenal tumor of unclear nature, corticosteroid should be avoided if possible. When corticosteroid is used, patients should be closely monitored. In my own experience, pheo crisis by corticosteroid is rare and not a predictable event.
On a separate note, I have been very busy recently. To readers who are used to my quick responses, I may appear to become sloppy. I apologize. I am still following this blog closely but not as frequently as before. Please rest assured that I will respond to your questions, just not as timely.
Have a great Thanksgiving!
Dr. Pheo
Firs of all, the close proximity of the adrenal cortex and adrenal medulla is an intriguing phenomenon. The adrenal glands are small organs. An adrenal gland actually is further divided into two organs, the cortex (secreting corticosteroid) and medulla (where pheo is derived from), each with related but different functions. Why is the adrenal medulla wrapped around by the cortex? Why isn't the medulla located inside other organs, say, the spleen or liver, or a free-standing organ like a ganglion? I can only think of two other organs, pituitary and pancreas, which are also further divided into two organs. In the case of pituitary, anterior and posterior; pancreas, exocrine and endocrine. The question is still unsettled. Existing evidence suggests that the corticosteroid secreted by the adrenal cortex is important in maintaining the medulla what it is. If one takes the cells from the medulla and puts them in culture, those cells automatically differentiate into neuronal cells. If one adds high concentrations of corticosteroid into the culture, the medulla cells will remain neuroendocrine cells and do not differentiate into neuronal cells. As the medulla cells are derived from the neurocrest during embryonic development, it is hypothesized that the migrating neurocrest cells encounter adrenal cortex cells (which provide high concentrations of corticosteroid) and really like them and stay with them. Thus the story of adrenal cortex and adrenal medulla.
Second, corticosteroid stimulates catecholamine production and release from cultured adrenal medulla cells. Corticosteroid increases catecholamine production by upregulating the key enzymes for catecholamine production. The mechanisms for which corticosteroid stimulates catecholamine release are not clear and may not be straightforward.
Third, corticosteroid prepares the target tissues of catecholamines to be responsive to catecholamines. That is why patients with adrenal insufficiency often have low blood pressure even when they have high catecholamine levels.
Lastly, there have been a number of case reports on pheo crisis induced by corticosteroid use. The pheo crisis usually starts a few hours after corticosteroid use. There may be hemorrhage within the pheo. In patients with known pheo or an adrenal tumor of unclear nature, corticosteroid should be avoided if possible. When corticosteroid is used, patients should be closely monitored. In my own experience, pheo crisis by corticosteroid is rare and not a predictable event.
On a separate note, I have been very busy recently. To readers who are used to my quick responses, I may appear to become sloppy. I apologize. I am still following this blog closely but not as frequently as before. Please rest assured that I will respond to your questions, just not as timely.
Have a great Thanksgiving!
Dr. Pheo
Sunday, October 31, 2010
Report from NANETS meeting
I just returned from the NANETS meeting. Before the meeting, I had hoped that I would get to meet colleagues interested in pheo and see new studies on pheo at the NANETS meeting held in Santa Fe, October 29 and 30. NANETS stands for North American Neuroendocrine Tumor Society. It is a very nice society of doctors who treat neuroendocrine tumors. Pheo is a neuroendocrine tumor. Although the meeting was very informative on carcinoid and pancreatic endocrine tumors, there were literally only one study on pheo and one talk that mentioned pheo in passing.
The one study by a researcher in Dallas essentially showed that the mTOR pathway probably is not particularly important in the transformation from benign to malignant pheo and mTOR inhibitors (such as RAD001) probably won’t work for malignant pheo. The talk on modern gene testing by Dr. Marx at NIH briefly mentions the controversial issue of prenatal diagnosis of MEN2 (I had an earlier post on this topic in this blog) but did not delve further into pheo gene testing.
Dr. Pheo
The one study by a researcher in Dallas essentially showed that the mTOR pathway probably is not particularly important in the transformation from benign to malignant pheo and mTOR inhibitors (such as RAD001) probably won’t work for malignant pheo. The talk on modern gene testing by Dr. Marx at NIH briefly mentions the controversial issue of prenatal diagnosis of MEN2 (I had an earlier post on this topic in this blog) but did not delve further into pheo gene testing.
Dr. Pheo
Saturday, September 11, 2010
Coping with a frustrating disease
In an earlier post, I described my experience on alternative diagnosis for patients who have pheo symptoms but without pheo. Most patients cope with their conditions very well and go on with their lives. A small number of patients would see multiple physicians, get numerous tests and imaging studies, and try all kinds of medications, herbs, or behavioral therapies, just to get a definitive diagnosis and to get back to their "perfect" health. As a pheo specialist, I am often the doctor who tells them not only they don't have pheo but a clear diagnosis cannot be established. I explain that further diagnostic work-up is unlikely to yield a definitive diagnosis. I then discuss the skills of coping with a frustrating disease.
First of all, these patients do have a disease. And the disease is not their fault. They just simply have it and they have not done anything to make the disease afflict on them.
Second, medicine has its limits. In spite of the ever-growing progress in medicine, there are many things we don't know in medicine. Sometimes, a definitive diagnosis cannot be reached no matter how hard one may try. We have to wait for the disease to fully reveal itself over time.
Third, look at the brighter side. Although we don't know the diagnosis, we do know that it is not a bad one. It is not cancer, not heart disease, not a disease that will cost a limb or organ, and not deadly if the symptoms have been going on for many years.
Lastly, the most important issue is coping with the disease. What is the purpose of perfect health? What are the important things in life? Can one pursue the goals in life with the disease? What limits one from doing the desired things? The best approach is to focus on functionality rather than on perfect health. If one can do the things one wants to do, that's not too bad even with the disturbing symptoms mimicking pheo. I like to use a car metaphor. Most of us want to have fancy expensive cars but most of us cannot get those cars. If we keep lamenting on the lack of those cars, we lose the purpose of life. Those of us without fancy cars will get a car we can afford with the functions that we think are the most important. Then we drive the car to do the things we want to do. Simply owning a fancy car won't necessarily drive us somewhere.
Dr. Pheo
First of all, these patients do have a disease. And the disease is not their fault. They just simply have it and they have not done anything to make the disease afflict on them.
Second, medicine has its limits. In spite of the ever-growing progress in medicine, there are many things we don't know in medicine. Sometimes, a definitive diagnosis cannot be reached no matter how hard one may try. We have to wait for the disease to fully reveal itself over time.
Third, look at the brighter side. Although we don't know the diagnosis, we do know that it is not a bad one. It is not cancer, not heart disease, not a disease that will cost a limb or organ, and not deadly if the symptoms have been going on for many years.
Lastly, the most important issue is coping with the disease. What is the purpose of perfect health? What are the important things in life? Can one pursue the goals in life with the disease? What limits one from doing the desired things? The best approach is to focus on functionality rather than on perfect health. If one can do the things one wants to do, that's not too bad even with the disturbing symptoms mimicking pheo. I like to use a car metaphor. Most of us want to have fancy expensive cars but most of us cannot get those cars. If we keep lamenting on the lack of those cars, we lose the purpose of life. Those of us without fancy cars will get a car we can afford with the functions that we think are the most important. Then we drive the car to do the things we want to do. Simply owning a fancy car won't necessarily drive us somewhere.
Dr. Pheo
Subscribe to:
Posts (Atom)