Family History Of Patients Research Articles

A New Classification of Pulmonary Hypertension

A New Classification of Pulmonary Hypertension

Genetic Susceptibility and Survival: Application to Breast Cancer

Inherited mutations of the BRCA1 and BRCA2 genes are known to confer an elevated risk of both breast and ovarian cancers. The effect of carrying such a mutation on survival after developing breast or ovarian cancer is less well understood. We investigate the relationship between BRCA1 and BRCA2 carrier status and survival after breast cancer. We obtained data from the Cancer and Steroid Hormone Study, a large population-based study including more than 4,000 breast cancer cases. Patient data include extensive information about breast and ovarian cancer in relatives. We obtained follow-up information about patients via record linkage with the Surveillance, Epidemiology, and End Results registry, with maximum follow-up of 15 years. In the absence of genetic testing for each individual, presence or absence of mutation at a breast cancer susceptibility gene is captured by a pair of binary latent variables whose marginal probability depends on the patient's family history of breast and ovarian cancer. We estimate the effect of genotype on survival using a Cox proportional hazards model, treating genetic status as a latent variable and controlling for stage at diagnosis, histology, whether radiation treatment was administered, the individual's smoking history, body mass, race, and age at diagnosis. Inference is accomplished using a Markov chain Monte Carlo algorithm to draw a sample from the posterior distribution of model parameters accounting for sampling error, uncertainty in the genotype of study participants, and uncertainty in estimates of genetic parameters. An analysis that does not discriminate between BRCA1 and BRCA2 estimates the genetic effect on survival after breast cancer for women carrying a mutation at either site. We find evidence that survival of nonirradiated mutation carriers is better than that of noncarriers; we estimate the probability of improved survival to be .990. As a byproduct of this analysis, we estimate that a study based on 901 women with known mutation status would yield estimates of genetic effect on survival with comparable uncertainty to that obtained in the combined-gene analysis. An analysis assessing the separate effects of the two genes indicates that carriers of either mutation may have an improved prognosis. We estimate the probability of improved survival among nonirradiated BRCA1 carriers to be .844, and that among nonirradiated BRCA2 carriers to be .924. However, substantial uncertainty remains about the magnitude of the BRCA2 effect.

Resistance to activated protein C as an etiology for stroke in a young adult: A case report

Resistance to activated protein C (R-APC) is an inherited, autosomal dominant, coagulation abnormality that is increasingly recognized as an important etiology for thromboembolic disease and stroke in young adults. This report describes the case of a 27-year-old woman taking oral contraceptives who experienced an acute thrombotic right hemispheric stroke. Three days after rehabilitation admission (33 days after stroke) she developed a left femoral deep venous thrombosis (DVT) despite appropriate prophylaxis. Further diagnostic workup for the stroke and DVT identified R-APC, possibly exacerbated by oral contraceptives, as the etiology. Hematology consultation recommended lifetime anticoagulation with warfarin. The patient's family history revealed that a 19-year-old cousin had died of a stroke several years earlier. Several months after discharge, an acute DVT occurred in the patient's 28-year-old brother, who tested positive for factor V Leiden, a genetic abnormality closely associated with R-APC. A thrombotic stroke occurred in her grandfather a few months later, but he was not tested. Her father demonstrated a “borderline” positive R-APC test and probably represents the genetic link. Indications for patient and family screening regarding R-APC and other forms of hereditary thrombophilia and implications for rehabilitation medicine physicians are discussed.

Isolated Absence of Adrenarche in A Postpubertal Female

Background The development of pubic and axillary hair (adrenarche) is part of the process of normal puberty. We report a case of isolated absence of adrenarche in a post-pubertal female. A review of the literature reveals no previously reported case of isolated absence of adrenarche in a postpubertal female. An investigation was understaken to evaluate the etiology of the lack of sexual hair growth in this patient. Case A 14 year-old postpubertal female presented complaining of heavy menstrual bleeding approximately four months after her first menstrual period. The patient had been previously diagnosed with a developmental delay and speech impediment by her referring physician. Further workup revealed a normal menstrual pattern, yet the physical examination was remarkable for the absence of axillary and pubic hair, as well as short stature. A complete evaluation was performed which included chromosome analysis, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione, testosterone, dihydrotestosterone (DHT), and 3-alpha androstanediol glucuronide. The serum androstenedione, testosterone, DHT, and 3-alpha androstanediol glucuronide levels were within normal limits. The DHEA-S levels were low yet adrenal function as analyzed by the Adrenocorticotropic hormone (ACTH) stimulation test was normal. Radiologic studies included pelvic ultrasound and bone age assessment with a bone age of 16 years. Skin biopsy of the mons pubis documents the presence of hair follicles. No previous or similar history has been noted in the patient's family history. Also of note, the patient is the product of a consanguineous relationship. Conclusion After review of our investigational findings, it is felt that this unique case likely represents an androgen receptor or post-receptor defect in the hair follicle.

Familial Infantile Diabetes and Autoimmune Enteropathy: Clue to a Possible X-Linked Multiple Autoimmune Disease Syndrome 423

We report a case of a child diagnosed with insulin dependent diabetes mellitus at 12 days of age who was subsequently diagnosed as having autoimmune enteropathy. He presented at five years of age with intractable diarrhea which was unresponsive to steroids and gluten free diet. Biopsy of the mucosa of the small bowel showed total villous atrophy. Anti-enterocyte antibodies were present. The enteropathy was eventually controlled with cyclosporine. The child had also been diagnosed with autoimmune glomerulonephritis. The patient's family history revealed a maternal uncle who had been diagnosed with insulin dependent diabetes at 38 days of age and who had manifested symptoms of other autoimmune disease. Because we were aware of reports of infantile diabetes and autoimmune enteropathy occurring in an apparent familial X-linked recessive pattern, we undertook a review of the medical literature to attempt to identify additional such patients. We used the following criteria to identify probable cases of this syndrome: The patient must have had autoimmune enteropathy and/or infantile diabetes; both disorders must be present in the patient and/or the patient's family history, and there must be more than one affected family member. According to this criteria, we identified a total of 31 probable cases in nine kindreds (including our cases), all occurring in males. Three reported kindreds demonstrated an X-linked recessive pattern of inheritance, accounting for 19 of the 31 cases. Because of the rarity of these disorders, their occurrence together in a family is strong evidence for the presence of a single genetic pathogenesis for the observed autoimmune disease, and we believe that these patients therefore all suffer from a single unique previously undefined X-linked syndrome. The above listed criteria represent the optimum clinical basis upon which these patients may be identified. We also make the following recommendations: 1. A careful family history for infantile diabetes and autoimmune enteropathy should be obtained in all cases of males diagnosed with either of these disorders. 2. All males with infantile diabetes and a positive family history should be closely observed for the development of other autoimmune disorders, particularly autoimmune enteropathy. 3. All patients diagnosed with autoimmune enteropathy who meet the above criteria should be treated aggressively. 4. Further research is needed to determine the precise nature of the genetic and immune system defects that result in this disorder.

喉頭全摘の際発見された無カタラーゼ血液症の1症例

In 1949, Takahara first reported acatalasemia, which was a constitutional abnormality characterized by a deficit of catalase in the blood. Acatalasemia patients inherited autosomal recessive genes and its incidence was high in children born of consanguineous marriage.The patient was a 71-year-old male who underwent total laryngectomy because of recurrence of laryngeal cancer. The operative area was prepared with Oxidol®, a widely used disinfectant in otolaryngological disease. This antiseptic treatment induced methemoglobinemia, and it took about 16 days to recover from the critical postoperative condition.In order to clarify the causative factor, a blood hydrogen peroxide mixing test, a skin scratch test, and gene analyses were performed, and catalase activity was measured. He was made the diagnosis of acatalasemia because of the significant decrease in catalase. The patient's family history was also studied and it was found that his parents were first cousins. A catalase activity test of his mother and three children was carried out, and the result showed that all of them had suffered from hypocatalasemia. His gene abnormality was considered as a Japanese-type.As in the present case, acatalasemia has been often induced accidentally by the use of hydrogen peroxide solution. The detection rate of acatalasemia was high in otolaryngology and oral surgery.It must be borne in mind that the risk of methemoglobinemia can be minimized by paying special attention to the treatment of patients with Oxidol®.

Spinal cord concussion in previously undiagnosed osteogenesis imperfecta

An 11-year-old boy was a victim of a motor vehicle accident. He initially presented with paraplegia and inability to detect pain below the fourth thoracic dermatome. Two hours later, he had full return of motor and sensory function. Thoracolumbar spine radiography and magnetic resonance imaging (MRI) showed multiple compression fractures and marked osteopenia of the vertebrae. The patient's family history is significant for osteogenesis imperfecta (OI), although the patient had not been previously diagnosed with this disorder. Although the patient had no prior fractures or any of the classic stigmata of OI except for short stature, plain radiographic and MRI findings in conjunction with his family history support the diagnosis of OI. A brief discussion of both OI and spinal cord concussion is presented.

The patient's family history: a key to the physician's understanding of patients' fears.

Patients often feel considerably worried by conditions that appear to be biomedically mild to their physicians. Their reaction may be linked to personal experience from cases of severe disease in their family history. In this qualitative study, 30 primary health care patients were interviewed about their definition of their present problem, their fears and associations with their family history. For several patients, the discrepancy between objective signs and fears was linked to cases in their family. Death or threats to life, especially when occurring prematurely, appeared to be significant. The same was true for actual or threatening disability in family members. A condition perceived to have been overlooked also seemed to be important for some patients. These findings may be used to understand patients' rationale for seeking care. The subject should be the theme for further investigation.

Genetic diagnosis of lynch syndrome II in an extended colorectal cancer-prone family

Knowledge of colon cancer genetics, with particular attention to precision in hereditary cancer syndrome diagnosis, can often enable highly targeted surveillance and management strategies for patients at high genetic risk. Unfortunately, the patient's family history of cancer is often given minimal attention, and knowledge of hereditary cancer syndromes is frequently limited. Indeed, many physicians still consider familial adenomatous polyposis (FAP) as the only genetic risk factor for colorectal cancer. This concern with FAP was noted in a colorectal cancer-prone kindred which for decades had been thought to manifest that syndrome. However, after meticulous genetic, medical, and pathologic studies, the cardinal phenotypic characteristics of Lynch syndrome II were observed. The potential for cancer control in current and future generations of families like this one clearly mandates the need for computerized registries which could transmit current information about hereditary colon cancer syndrome diagnosis, surveillance, and management.

Persistent drug-induced parkinsonism

Not all drug-induced parkinsonism may be benign or reversible. Parkinsonian symptoms, along with coexistent dyskinesias and akathisias, have been reported to persist following the withdrawal of large doses of long-term phenothiazines (Schmid and Jarcho 1966; Schwab and England 1968). This is reminiscent of the miscellaneous known causes of Parkinson's disease (neurosyphilis, manganese intoxication, etc.) that actually cause a multitude of neurological symptoms only some of which include parkinsonian symptoms (Schwab and England 1968). There are also two reports describing pure parkinsonism persisting after neuroleptic withdrawal. One reported that 16 of 26 patients on long-term phenothiazines developed worsening of their parkinsonian symptoms for up to 5 weeks following the discontinuation of the neuroleptic (Demars 1966). The other report described the occurrence of parkinsonism following a single exposure of the dissociative anesthetic Innovar (a combination of fentanyl and droperidol) to a 16-year-old girl. The first day postoperatively she began experiencing bradykinesia, cogwheel ridigity, pill rolling tremor, and mask-like facies that subsided 6 weeks later after a course of carbidopa-levodopa (Rivera et al. 1975). The following case report is unique in reporting the occurrence of persistent, pure, drug-induced parkinsonism following a single oral dose of haloperidol that has lasted over a year. The patient's family history of titubation may constitute a new risk factor accounting for individual susceptibility.

A CASE OF ASYNCHRONOUS TRIPLE CANCER SUSPECTED TO BE THE CANCER FAMILY SYNDROME

The cancer family syndrome has been classified as a type of nonpolypotic hereditary colon cancer. The diagnostic criteria of the syndrome were first described by Lynch and Krush in 1973. Herein reported is a case of asynchronous triple cancer which was suspected to be the cancer family syndrome. The patient was a 60-year-old-woman, having a history of sigmoid and rectal cancer without any clinical evidence of polyposis at the age of 40 and endometrial cancer at the age of 57. In June 1984, she was diagnosed as having cancers of the gallbladder and transverse colon; she underwent a palliative operation in July 1984. Pathological examination of all cancers proved adenocarcinomas. Her son had died of colon cancer at the age of 20, and her mother died of gastric cancer at the age of 53. Some of these clinical findings met Lynch's criteria. However, the patient's family history was insufficient to prove autosomal dominant inhertance and to diagnose the cancer family syndrome. Further study may be needed to establish the diagnostic criteria of the syndrome, which doesn't need proof of its hereditary trait.

Familial hemophagocytic lymphohistiocytosis in Israel: II. Pathologic findings

Presented are the pathologic findings in familial hemophagocytic lymphohistiocytosis (FHLH), based on observation of 11 cases from four affected families. The outstanding morphologic feature was a multiorgan involvement with lymphohistiocytic cellular infiltrates. The organs most frequently affected were the bone marrow and lymph nodes and, less frequently, the liver and the brain. The histiocytes in the infiltrates were usually bland and displayed prominent hemophagocytosis. The differential diagnosis of FHLH and the difficulty in distinguishing it from malignant histiocytosis is discussed. In view of the focal distribution of lesions, it is suggested that histopathologic diagnosis of FHLH be made only after evaluation of combined findings in several organs and consideration of the patient's family history as well as the result of the clinical and laboratory investigations.

Cranial manifestations of hypophosphatasia in childhood nephrotic syndrome

A 7-year-old boy was referred to the children's hospital because of gross oedema and tiredness. Massive proteinuria was found and the condition was diagnosed as a childhood nephrotic syndrome. Concomitantly, pathologically low levels of serum alkaline phosphatase were recorded, and this, together with generalized osteoporosis and premature synostosis of cranial sutures, led to a second diagnosis: hypophosphatasia. The patient's family history further confirmed this condition of a heritable defect of metabolism. Dental inspection revealed very carious teeth with characteristically enlarged pulp chambers in molars. Histological examination of an extracted tooth revealed an unusually wide zone of predentine with some other dentinal irregularities. No cement layer was found. The skeletal age and exfoliation of primary teeth, however, were normal, unlike most reported cases of hypophosphatasia. The patient's renal disease was treated mainly with corticosteroids. There is no treatment for hypophosphatasia.

Multiple Minute Digitate Hyperkeratoses or Disseminated Spiked Hyperkeratosis

To the Editor.— The disorder described in the July 1981Archives(117:412-414) entitled Disseminated Spiked Hyperkeratosis: An Unusual Discrete and Nonfollicular Keratinization Disorder by Frenk et al is similar, I believe, to multiple minute digitate hyperkeratoses. Goldstein 1 described a 32-year-old man with multiple minute digitate hyperkeratoses—fine, filiform, hyperkeratotic lesions of the chest and the anterolateral aspects of the arms and legs. I now observe this patient, and he also has extensive lesions on his back and a few fine lesions on his face. The lesions are not associated with hair follicles. This patient's family history does not show any other family members affected in this way. His condition began sometime during the second decade of life. Yoon and Gibbs 2 reported another case in 1975. The histologic characteristics and clinical manifestation of these two cases are similar to what Frenk et al have described. Both names suggested for this

A deleted chromosome no. 13 in human retinoblastoma cells: relevance to tumorigenesis

In this report of banded karyotypes prepared after short-term culture (72 hr) from human retinoblastoma tumor tissue, one del(13)(pter→q14:) chromosome and one normal chromosome #13 were found in all of the metaphases examined. Similar deletions (always involving 13q14) have previously been described in the somatic cells of individuals with one form of retinoblastoma. In the present case, however, the constitutional karyotype is normal. The presence of tumors in both eyes suggests that this is the genetic form of retinoblastoma, even though the patient's family history is negative for this tumor. The normal constitutional karyotype argues that the chromosome deletion occurred as a postzygotic event. The modal chromosome number of the tumor cells is 47 and rearrangements involving chromosomes #2, #17, and #20 were also identified.

A case for venom treatment in anaphylactic sensitivity to hymenoptera sting.

Abstract In a child of a beekeeping family anaphylaxis developed after a honey-bee sting. He was treated with the conventional therapy, whole-(insect)-body extracts, for nine months. A second sting caused anaphylaxis again. Since the patient's family history included a sister who had died in similar circumstances, he was immunized with 1.4 mg of honey-bee venom over a two-month period; the last two doses were 100 μg (≅ two bee stings). His sensitivity to venom, assessed by basophil histamine release, decreased, and his blocking (IgG) antibody level increased 300 times over that after immunization with whole-body extract. After venom immunization he tolerated a honey-bee sting without reaction. The case and a review of pertinent data suggest that venom immunization may be the treatment of choice for hymenoptera sensitivity. (N Engl J Med 290:1223–1227, 1974)

Pseudoxanthoma elasticum: angiographic manifestations in abdominal vessels.

Pseudoxanthoma elasticum is an hereditary systemic disorder characterized by widespread degeneration of elastic fibers, resulting in cutaneous, ocular, and vascular manifestations. The disease usually presents during early adulthood. Symmetrical yellowish skin lesions develop, confined exclusively to flexural folds. Angioid streaks frequently develop in the fundi of the eyes and can severely affect vision. The symptoms are intermittent claudication, angina pectoris, and hypertension, as well as unexplained abdominal pain and recurrent gastrointestinal bleeding. We recently encountered these problems in two patients in whom selective abdominal arteriography was performed in the radiological work-up. The findings are demonstrated with the following case reports. Case I: The patient was a 41-year-old white female with a chief complaint of abdominal pain and hypertension. The hypertension was labile, dating back about fifteen years, with recorded values of 190–200/100–105. Intermittent mild edema of the extremities over the same period was relieved by occasional oral diuretics. Within the past year, substernal and epigastric pain had occurred, lasting for one-half to three hours without associated nausea and vomiting. Intermittent claudication also developed in the lower extremities. Several years ago, skin lesions around the neck were noted by a dermatologist treating an unassociated condition. The patient's family history was unremarkable. Physical examination revealed an admission blood pressure of 140/90. Positive physical findings consisted of loose inelastic areas of skin around the neck and axilla, containing small cream-colored macules. The fundi showed angioid streaks. Femoral pulses were good, but no dorsalis pedis or posterior tibial pulses could be felt. No edema was demonstrable. Laboratory data were normal except for a diabetic curve on a glucose tolerance test. Skull, chest, and soft-tissue films of the lower legs were normal, as were findings on intravenous urography, an upper gastrointestinal series, and oral cholecystography. A femoral arteriogram (Fig. 1) showed complete obstruction of both superficial femoral arteries, with extensive collateral circulation between the deep femoral and popliteal arteries. Abdominal arteriography (Fig. 2) showed two areas of angiomatous malformation, one in the liver arising from an intrahepatic artery and another arising from the splenic artery above the area of the left kidney. An unusual amount of tortuosity of the terminal branches of the lumbar vessels (Fig. 3) produced a coiled-spring appearance. Case II: The patient, a 36-year-old white female, was admitted because of an episode of hematemesis preceded by a four-day period of left flank and lower abdominal pain. Four years previous to this admission, a pregnancy had been complicated by gastrointestinal bleeding.

Alveolar soft-part sarcoma of the orbit.

ALVEOLAR LVEOLAR soft-part sarcoma is a primary malignant neoplasm that very rarely occurs in the orbit. The present report concerns a histologically proven case of alveolar soft-part sarcoma in a patient presenting with unilateral exophthalmos. Report of a Case Clinical History. —A 55-year-old white factory worker was first seen on March 8, 1966, complaining of a red right eye of approximately three weeks' duration. The patient's family history was noncontributory. His medical history revealed prior episodes of pneumonia, liver disease, traumatic fracture of vertebrae, and a chronic excess ethanol intake. The patient, a poor historian, stated that the right eye had been quite red and was somewhat larger for several weeks (Fig 1). He was unaware of the proptosis until questioned about it. At the time of examination, the patient's visual acuity was 20/20 in each eye without correction. Exophthalmometer readings revealed 28 mm on the right side and 22

INTRACRANIAL TELANGIECTASIS

The two following cases of probable cerebral telangiectasis seem to be of sufficient interest to warrant report. REPORT OF CASES Case 1.— History .—A merchant, aged 21 years, was referred by Dr. Ransom of Hancock, Minn., July 14, 1920. The patient's family history was negative except that his father died of diabetes. When 7 years old, he was thrown from a horse and struck on his head, but he remembered no details of the accident; appendectomy was performed on him when he was 14; he denied venereal disease. When 8 years old, while convalescing from an attack of mumps, he had a severe convulsion and remained unconscious for fourteen hours. He recovered and was well for three weeks, when he had another mild attack. Since that time the number of attacks have varied from three in one day to one in six months. He described a typical attack as follows:

THE INFLUENCE OF X-RAYS IN THE TREATMENT OF LEUKEMIA AND HODGKIN'S DISEASE, WITH A REPORT OF TWO CASES.

Since the therapeutic value of<i>x</i>-rays in Hodgkin's disease and leukemia is still in the experimental stage, and requires the report of more cases which have been under careful observation and treatment for longer periods of time, in order to arrive at definite conclusions, the two following cases are submitted with their detailed histories, and results of treatment; together with an account of some experimental observations concerning the action of<i>x</i>-rays on the blood and urine in leukemia. <h3>HODGKIN'S DISEASE: REPORT OF A CASE WITH A SYMTOMATIC CURE.</h3><h3>Patient.</h3> —Mrs. R. came to the medical clinic of Dr. Dock, May 13, 1904, because of nodules in the sides of the neck and pain in the neck and thorax. <h3>History.</h3> —The patient's family history is negative. She has had measles, scarlet fever and three attacks of "la grippe." Five years ago she noticed a mass on the left side