Russell R. de Alvarez

Renal glomerulotubular mechanisms during normal pregnancy. I. Glomerular filtration rate, renal plasma flow, and creatinine clearance.

Abstract When compared with existing data, our findings of renal glomerulotubular patterns during normal pregnancy seem to be in conflict with those cited in most reports. Perhaps it is significant to note that most of the existing literature does not deal with serial determinations of renal hemodynamics performed in the same patient at different intervals throughout the same pregnancy. The explanation that apprehension during the first examination is responsible for the elevated glomerular filtration rate cannot be confirmed, since the values obtained among the “spot” determinations were comparable to those obtained from patients studied serially. All our patients were ambulatory, were carrying out their usual normal activities, and were not placed on restrictive diet or intake. The constant-infusion technique was used throughout and a uniform concentration of the testing agents maintained by intravenous administration of all testing agents. Diuretics or other artificial means to produce conditions different from those ordinarily seen in the normal pregnant patient were not utilized. The reduced glomerular filtration rate and renal plasma flow in the normal pregnant patient may well permit the increased tubular reabsorption, not only of water but of sodium as well. This then appears to establish a perfect prelude for an increase in the sodium space and therefore for the development of toxemia of pregnancy with its characteristic edema. It seems that, from these studies, most patients could well be on the brink of developing some degree of pre-eclampsia during what is supposed to be an apparently normal pregnancy.

Serum protein, lipid, and lipoprotein fractions in normal human pregnancy☆☆☆

Abstract Serial determinations of total serum protein, protein, and lipoprotein distribution measured by paper electrophoresis, and serum cholesterol, cholesterol esters, and lipid phosphorus have been made in a normal primigravida beginning at 5 weeks of gestation, continuing at monthly intervals during pregnancy, and post partum at 9 hours, 4 days, 7 and 15 weeks, and 6 months. Serum albumin decreased during pregnancy, whereas the alpha globulins and beta globulin increased progressively to delivery. Serum cholesterol, lipid phosphorus, and beta lipoprotein, as well as total lipid, also increased progressively to a maximum early in the puerperium. All the changes were reversed following delivery, but most values required 6 months to return completely to normal.

New electrophoretic protein zone in pregnancy

Abstract 1.1. An electrophoretic protein band (pregnancy zone) appears in the blood of pregnant women. It was found in 10 per cent of those studied in the first trimester, in 69 per cent of those evaluated during the second trimester, and in over 80 per cent of the women studied during the third trimester. 2.2. As shown by two dimensional electrophoretic studies, the pregnancy zone protein is an alpha 2 globulin. 3.3. This globulin was not seen in the blood of pregnant women prior to the ninth week of gestation. 4.4. The time of appearance of the pregnancy zone varies in different pregnant patients. Of 138 patients studied at repeated intervals during pregnancy, it appeared prior to the twenty-fourth week in 50 patients, after the twenty-fourth week but prior to labor in 66, during labor in 6, just after delivery in 3, and in 13 it was never demonstrated. 5.5. The presence of the pregnancy zone in the blood of pregnant women does not reflect fetal welfare. However, its absence in some patients delivering babies with congenital anomalies seems more than coincidental. 6.6. The pregnancy zone protein is distinct from transcortin, thyroxin binding protein, ceruloplasmin, and the oxytocinases. 7.7. The pregnancy zone was not demonstrated in two patients with hydatid mole and one with choriocarcinoma. The appearance of this protein in the circulating blood does not seem to be related to chorionic gonadotropin. 8.8. An increase in alpha 2 globulin occurs in patients with gynecologic cancer, but the specific globulin, pregnancy zone, which is associated with the normal growth of pregnancy does not contribute to the increase of the alpha 2 fraction in neoplastic growth. 9.9. Further characterization, isolation, and identification of the function of the pregnancy zone globulin is being pursued.

Melanogenic ovarian tumors

Abstract 1. 1. All previously reported cases of primary melanoma of the ovary are reviewed. 2. 2. A cystic ovarian teratoma is reported in which a pigmented component produced the predominant clinical and pathologic findings. In contrast to all other such neoplasms reported in the literature, this lesion is apparently benign. 3. 3. The physical, chemical, and histochemical properties of the pigment were those of the melanins. However, chromatographic and manometric studies of the lyophilized cyst fluid failed to reveal definite melanin precursors or oxidase activity under the experimental conditions employed.

The influence of oral contraceptive steroids on serum lipids

The effects of oral contraceptives on serum lipids were investigated in humans and monkeys at the Temple University Health Sciences Center. The compositions of the pills were: 1) 2.0 mg chlormadinone acetate, .08 mg mestranol; 2) 10.0 mg medroxyprogesterone acetate, .05 mg ethinyl estradiol; 3) 1.0 mg ethynodiol diacetate, .1 mg mestranol; 4) 1.0 mg norethindrone acetate, .05 mg ethinyl estradiol, and 5) .5 mg norgestrel, .05 mg ethinyl estradiol. 238 immediately puerperal black women, healthy and aged 20-30, were divided into 6 groups for study purposes; each of 5 groups used a separate oral therapy, while the sixth group (control) was fitted with a plastic intrauterine device. 75 women were still participating in the study at 54 weeks. All of the drugs significantly increased the concentrations of serum cholesterol, serum triglycerides, total phospholipids, and fatty acids. The influence of the drugs on lipoproteins was variable. The higher its progestogen/estrogen ratio, the greater influence a drug had on lipid concentrations. Some of the same effects were seen in 14 mature female squirrel monkeys (Cebus albifrons), which were studied in a similar manner for about 30 cycles; however, only drugs 1, 2, and 3 were used in this part of the study. Clinical observations of the patients in this study, showed no relationship between serum phosphatides participating in the coagulation mechanism and the production of thromboembolic phenomena. The researchers found no justification for the delay of oral contraceptive prescription after childbirth.

Fetal electrocardiography: A study of the normal recording

Abstract 1. 1. Fifty-one fetal electrocardiograms taken from 37 pregnant women, from 12 to 43 weeks from their last menstrual period during uncomplicated pregnancies, are reported in an attempt to define further the normal fetal tracing. 2. 2. It is possible to obtain good quality fetal electrocardiograms with a simple technique and a high amplification system in most patients after 12 weeks; the procedure requires only 8 to 10 minutes. 3. 3. The normal fetal heart rate declines from an average of about 165 beats per minute at 12 weeks of gestation to 130 at term. 4. 4. The sex of the fetus has no effect on the fetal heart rate. 5. 5. Maternal tachycardia can possibly be correlated with fetal tachycardia. 6. 6. The normal fetal QRS is 0.02 second in duration early in pregnancy widening to nearly 0.04 second at term. 7. 7. The normal fetal QRS amplitude is minimal during the thirtieth to the thirty-second week, excluding the first 12 weeks of pregnancy. 8. 8. Fetal position can roughly be determined by a spacial vector approach to fetal electrocardiography. 9. 9. The fetal heart rate may be moderately inaccurate when determined via auscultation.

THE MARFAN SYNDROME AND PREGNANCY.

Abstract This is a study of 12 cases of the Marfan syndrome associated with pregnancy. One case is presented in detail and the other cases tabulated in an attempt to describe the syndrome and its relationship to pregnancy. The syndrome exists more frequently than appreciated. By constantly keeping the syndrome in mind, with thoughtful history taking and careful physical examinations, more cases will be uncovered. The typical histopathological lesion of the Marfan syndrome consists of a cystic medionecrosis of the blood vessel walls. This is enhanced by pregnancy and leads to aortic aneurysm and eventual dissection. The average age of dissection is 30 years, therefore, pregnancy, if advised at all, should be undertaken in the late “teens” and early “twenties.”

Natriuresis and vascular tone in toxemia of pregnancy

E v E N though the signs and symptoms of pre-eclampsia and eclampsia are well known, the etiology and exact pathophysiology remain obscure. Through meticulous prenatal and puerperal care by controlling the early manifestations of the disease, much has been accomplished in preventing the severe degrees of pre-eclampsia and eclampsia. It seems well established through studies of the bulbar conjunctivae,r retinal vessels,2. 3 nail beds,‘, B autopsy findings,6, 7 and physiologic measurements of renal,8-10 cerebral,lls I2 uterine,l” and hepatic14 blood flows that generalized vasoconstriction is invariably present in pre-eclampsia-eclampsia. It is also well known that abnormalities of the water and electrolyte metabolism play an important part in the development and course of the disease.l”-” The occurrence of abnormal weight gain and the appearance of edema comprise the two common early signs of abnormal physiology. Whether abnormal water and electrolyte metabolism and the vasoconstriction in toxemia of pregnancy occur independently or represent similar influences is not yet known. Regardless of the mechanism involved, it does seem well established that generalized vasoconstriction and abnormali1it.s of water and electrolyte metabolism are

APLASTIC ANAEMIA IN PREGNANCY

IRON deficiency anaemia, megaloblastic anaemia, and hypoplastic anaemia comprise the three common types of true anaemia described as occurring in pregnancy. Even though the coexistence of the anaemia and the pregnancy is frequent, no cause and effect relationship has ever been definitely proved. Any specific anaemia may complicate or be complicated by pregnancy. Again, the effect of the pregnancy in all instances is poorly defined. One of the most serious of this group of anaemias is primary refractory or aplastic anaemia. Although the term “aplastic anaemia” has gained wide acceptance in clinical medicine, it is not precise nor is it really descriptive of any specific feature since anaemia is only one phase of the generalized depression of formed blood elements. The designation is usually applied to cases of severe refractory pancytopenia where gross evidence of increased blood destruction is absent and infiltrative disease of the marrow cannot be demonstrated. The characteristic haematological findings are anaemia, leukopenia and thrombocytopenia. Definite evidence of decreased marrow production of all formed elements of the blood is necessary to support the diagnosis, although this is not invariably confirmed by marrow examination, even in cases with specific aetiology. Such bone marrow depression may be the result of exogenous or endogenous toxic origin. The mechanisms involved in the marrow depression are speculative. The aetiology insofar as a specific causal agent is often obscure and, where such agents are suspect, the aetiological relationship is difficult to establish. Aplastic anaemia is a rare complication of pregnancy. It is noteworthy that the first reported case of aplastic anaemia, described by Ehrlich in 1882, occurred in a young pregnant woman (1888). Although he did not apply any name to the condition he described, he did conclude that the underlying pathology was depression of bone marrow function. Only scattered subsequent reports of cases of pregnancy complicated by aplastic anaemia have appeared in the literature. In 1942 Hurwitt and Field presented a case which terminated fatally. They concluded from the review that pregnancy might play an “etiologic or conditioning” role in the occurrence of this condition in pregnancy and felt that immediate interruption of pregnancy was mandatory. More recently, Lachman, Lund and VintherPaulsen (1954) after a search of the world literature were able to collect twelve cases in which they felt that the diagnosis of aplastic anaemia associated with pregnancy was either “most probable or certain” and to which they added one of their own. Review of the limited data presented by some of these cases leaves the diagnosis in many instances open to question.

Long-range studies of the biologic behavior of the human uterine cervix

Abstract In an attempt to define the etiological factors important in the genesis of carcinoma of the uterine cervix, a large group of normal women has been followed for over 5 years. An initial careful history and physical examination have been followed by periodic pelvic examinations, vaginal cytology, and biopsies of the cervix. There appears to be a definite relationship between cervical metaplasia and age, as well as a correlation between metaplasia and the presence of cervical eversion in the patient under the age of 40 years. The suggested relationships of pregnancy, the menopause, and other uterine disease were found to represent merely the altered prevalence found within the age groups involved. In this series no relationship could be shown between cervical metaplasia and race, marital status, menarche, time of menopause, type of menopause (physiologic or surgical), pregnancy, leukorrhea, bloody discharge, history of venereal disease, use of contraceptives, circumcision of husband, height, weight, body type, size of breasts, presence of enlarged inguinal nodes, gravidity, parity, clinical parity of the cervix, type of cervical mucosa, size or irregularity of the uterus, adnexal or rectal pathology. Because of the low incidence of cervical malignancy in the general population and the comparatively small group of such patients studied, no direct evidence has yet been obtained concerning the relationship between cervical metaplasia and cervical malignancy. Continuation of this study with the accumulation of additional data may provide definitive information and answers to these problems.