Cutaneous and ocular changes associated with the use of chlorpromazine.

A 57-year-old schizoaffective disorder patient was placed on chlorpromazine because of its sedative properties and low profile for extrapyramidal side effects. After two years of treatment, the patient developed photosensitivity and blue-gray pigmentation of the skin of the face, neck and dorsum of hands. Significant pigment deposits were also observed in eye lens and cornea. An oval translucent lesion lateral to the left angle of the mouth was removed and the biopsy showed a basal cell carcinoma. The cutaneous and eye pigmentation were only partially reversible after the discontinuation of chlorpromazine. There has been no recurrence of basal cell carcinoma.

Simultaneously occurring alopecia areata and Hodgkin's lymphoma: complete remission of both diseases with MOPP/ABV chemotherapy.

A 43-year-old man presented with simultaneously occurring alopecia areata and stage IIIB nodular sclerosing Hodgkin's disease. Systemic symptoms of Hodgkin's disease were present for 6 months, and rapidly developing patchy hair loss of the scalp was present for 2 weeks prior to presentation. The patient was treated with eight cycles of MOPP-ABV chemotherapy that resulted in complete remission of Hodgkin's-disease. Four months after the completion of chemotherapy, the patient had normal hair regrowth with no evidence of alopecia areata. Alopecia areata may be an autoimmune disease and may respond to chemotherapy.

Alterations in circulating human chorionic gonadotropin free alpha-subunit in insulin-dependent diabetic pregnancy: correlation with maternal characteristics.

Circulating concentrations of hCG free alpha-subunit (alpha hCG) increase throughout pregnancy. To address the hypothesis that maternal plasma alpha hCG may reflect placental dysfunction and/or adverse perinatal outcome during insulin-dependent diabetic pregnancy, alpha hCG was measured serially throughout gestation, beginning before week 12, with a specific RIA using a monoclonal antibody in 54 insulin-dependent diabetic (randomly assigned to strict and customary glycemic control) and 25 nondiabetic pregnancies. alpha hCG was significantly lower in pregnant insulin-dependent diabetic subjects than in nondiabetics subjects until 24 weeks gestation, after which it was higher until delivery. Plasma alpha hCG stabilized in nondiabetics at 32 weeks, whereas it continued to increase in diabetics until delivery, at which time it was 37% greater than that in nondiabetics (mean +/- SE, 1441 +/- 90 vs. 1052 +/- 78 micrograms/L; P less than 0.002). Values in diabetic subjects assigned to strict control were intermediate between those in diabetic subjects assigned to customary control and nondiabetic subjects. alpha hCG was greater in diabetic subjects with pregestational hypertension or microvascular disease, but not in those with pregnancy-induced hypertension. These findings were independent of the assigned goals of glycemic control. alpha hCG was not correlated with the duration of diabetes or related to premature delivery, fetal distress, birth asphyxia, or macrosomia. Thus, alpha hCG is increased during the third trimester of the type I diabetic pregnancy and is associated with preexisting hypertension and maternal microangiopathy, but is not a predictor of adverse perinatal outcome. Excessive alpha hCG secretion in diabetes may share pathophysiological mechanisms in common with those underlying diabetic microangiopathy.

Spontaneous abortions in repeat diabetic pregnancies: a relationship with glycemic control.

In previous studies, we reported a high rate of spontaneous abortions in insulin-dependent diabetic pregnancies. Abortions were associated with poor first-trimester glycemic control. We hypothesized that improvement of glycemic control from one pregnancy to the other would improve fetal outcome and that deterioration of glycemic control would increase the likelihood of abortion. We studied prospectively 43 insulin-dependent diabetic women (White class B-RF) with two consecutive pregnancies, recruited before 9 weeks' gestation. Preprandial and 90-minute postprandial blood glucose concentrations were measured at each weekly visit. Glycohemoglobin A1 was measured at 9 weeks' gestation. Twenty women had two successful pregnancies and 15 had an abortion followed by a successful pregnancy (abortion-no abortion); the sample sizes for other sequences (no abortion-abortion, N = 5; and abortion-abortion, N = 3) were too small to allow for analysis. Glycohemoglobin A1 concentrations were stable in the sequence no abortion-no abortion (9.7 +/- 0.5 versus 9.8 +/- 0.4%, mean +/- SEM; not significant), whereas in the sequence abortion-no abortion, there was a significant decrease in glycohemoglobin A1 values from the nonsuccessful to the successful pregnancy (10.7 +/- 0.6 versus 9.3 +/- 0.4%; P = .01). Similarly, in the sequence abortion-no abortion, there was a significant decrease in mean postprandial blood glucose from first to second pregnancy (166 +/- 13 versus 135 +/- 11 mg/dL; P = .04), whereas in the sequence no abortion-no abortion, mean postprandial blood glucose did not change significantly (160 +/- 14 versus 144 +/- 11 mg/dL; not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Macrosomia in infants of insulin-dependent diabetic mothers.

The purpose of the present study was to evaluate factors affecting the rate of macrosomia and related complications in a population of infants of insulin-dependent diabetic mothers. The following factors were hypothesized to be predisposing to macrosomia: increased maternal weight gain during gestation, increased number of births until infant No. 3, white race, increased maternal age, poor glycemic control from the 20th week of gestation, and increased insulin dose. Advance White classification and increased duration of diabetes were predicted to be inversely related. In addition, macrosomia was hypothesized to predispose to selected adverse perinatal outcomes including premature labor, birth asphyxia, birth injury, hypoglycemia, polycythemia, and respiratory distress syndrome. From 1978 to 1986, 127 pregnancies were prospectively studied, 86 of the total number of women were entered prior to 10 weeks' gestation, and 41 were entered after 10 weeks' gestation. Patients monitored blood glucose at least twice daily with glycemic control achieved by "split-dosage" regimens of insulin. Glycohemoglobin was measured monthly. Pregnancy dating was based on the date of the last menstrual period and the Ballard score of the infant at birth. Macrosomia was defined as a birth weight greater than the 90th percentile of the intrauterine growth curves of Lubchenco. Of the babies born to mothers with insulin-dependent diabetes, 43% were large for gestational age and 57% were appropriate for gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

Lupus erythematosus in a patient with long-standing multiple sclerosis.

The occurrence of both lupus erythematosus and multiple sclerosis in several members within the same family has been previously documented. In the past, patients manifesting symptoms and findings compatible with both of these diseases have posed difficult diagnostic problems. This report concerns a patient with long-standing multiple sclerosis and in whom cutaneous and serologic lupus erythematosus developed. To our knowledge this is the first such case reported in the English literature. A daughter of this patient had developed serologic lupus erythematosus. The intensified study of patients with both of these diseases and those families with several members with one of these diseases may lead to new insights into the cause and pathogenesis of these disorders.

Major malformations in infants of IDDM women. Vasculopathy and early first-trimester poor glycemic control.

From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of less than 100 mg/dl and a 90-min postprandial blood glucose of less than 140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of pregnancy on complications of insulin-dependent diabetes mellitus.

The effects of pregnancy on acute metabolic complications of diabetes may have important consequences for both mother and fetus. The consequences of pregnancy for chronic complications of diabetes, including retinopathy, nephropathy, neuropathy, and hypertension, are not clear. Recent data are reviewed so that health care providers will be able to provide reasonable advice to insulin-dependent diabetic women contemplating pregnancy both for problems that may potentially arise during gestation and those that may affect long-term health and survival. Diabetic ketoacidosis is an uncommon problem that arises during gestation. Acute alterations in pH and electrolyte concentrations as well as hyperglycemia, however, may have important consequences for mother and fetus, including perinatal asphyxia and reduced fetal oxygen delivery. Hypoglycemia, on the other hand, may result in maternal coma or seizures and, when frequent, has been associated with infant respiratory distress syndrome. Background retinopathy often worsens during gestation, with regression common postpartum. Data suggest that progression of background disease is related to both glycemic control and the acute institution of intensive insulin therapy with those patients with poor control requiring more aggressive therapeutic intervention most adversely affected. The course of proliferative retinopathy is more variable, with both progression and regression reported. Preconception photocoagulation may prevent progression. Preconceptional ophthalmologic evaluation with frequent assessments during pregnancy is advised. Increases in 24-hour protein excretion are common during gestation in patients with preexisting renal disease and resolve in many patients postpartum. Serum creatinine and creatinine clearance increase during the first trimester and generally do not change during the remainder of pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

High spontaneous premature labor rate in insulin-dependent diabetic pregnant women: an association with poor glycemic control and urogenital infection.

The incidence of spontaneously occurring premature labor in insulin-dependent diabetic pregnancies is unclear, because previous studies have been confounded by a high rate of iatrogenic prematurity. The purpose of this study was to determine, in a large population of insulin-dependent diabetic pregnant women, the rate of spontaneous occurrence of premature labor and the various factors that may affect it. We hypothesized a priori that spontaneously occurring premature labor occurs at a high rate in insulin-dependent diabetic pregnant women, mainly because of poor control of diabetes during pregnancy, and is related to the presence of polyhydramnios and hypomagnesemia. One hundred forty-five insulin-dependent diabetic women undergoing 181 pregnancies were recruited since 1978 in an interdisciplinary prospective study. The goals of glucose control were a fasting blood glucose less than 100 mg/dL and a 90-minute postprandial glucose less than 140 mg/dL. The rate of spontaneous premature labor, 31.1%, was significantly higher (P less than .01) than that in a control population managed by the same obstetricians in similar clinical settings (20.2%). The following variables were not significantly associated with the onset of premature labor: maternal age, parity, gravidity, diabetic class according to White, presence of renal disease or retinopathy, previous elective abortion, chronic hypertension or pregnancy-induced hypertension, cigarette smoking, first-trimester or post-20 weeks' gestation vaginal bleeding, maternal serum magnesium concentration, or polyhydramnios.(ABSTRACT TRUNCATED AT 250 WORDS)

Tubuloreticular structures in a papular eruption associated with human immunodeficiency virus disease.

A widespread pruritic papular eruption associated with human immunodeficiency virus has been previously described. Electron microscopic study of lesional skin from a patient who presented with such an eruption showed cytoplasmic tubuloreticular structures in every venular capillary endothelial cell that was studied. The significance of this finding and the possible cause of these structures are discussed. This new finding strongly suggests that this dermatosis is a dermatosis related to acquired immunodeficiency syndrome (AIDS) and may be helpful in confirming the diagnosis of the AIDS-related complex or AIDS in future patients presenting with this dermatosis.

Multiple sclerosis and systemic lupus erythematosus. Occurrence in two generations of the same family.

Multiple sclerosis (MS) and systemic lupus erythematosus (SLE) have overlapping clinical features and laboratory findings. It has, in fact, been hypothesized that MS and SLE have a common etiology. Usually MS and SLE are considered to have autoimmune pathogenesis, and both are chronic diseases that can respond to steroids. Some patients are diagnosed with either MS or SLE but subsequently develop the other disease. We described a family where multiple members of one generation have SLE and two members of the preceding generation have MS. Histocompatibility typing did not reveal any association between HLA inheritance of genes and incidence of severity of disease.

Differential effects of insulin- and proinsulin-induced hypoglycemia on pituitary hormone and catecholamine secretion.

The effects of insulin- and proinsulin-induced hypoglycemia on pituitary hormone and catecholamine secretion were compared in normal men to search for possible hypothalamic or pituitary inhibitory effects of proinsulin on glucocounterregulatory responses. When subjects received 0.1 U/kg i.v. human insulin and 25-38 micrograms/kg i.v. human proinsulin on separate occasions, plasma glucose decreased more rapidly after insulin, and the nadir was slightly lower, but integrated hypoglycemic responses were similar. Cortisol, growth hormone (GH), prolactin, epinephrine, and norepinephrine responses occurred more rapidly after insulin than after proinsulin. Peak and integrated cortisol, GH, and catecholamine responses to insulin and proinsulin were similar, but those of prolactin were reduced after proinsulin when compared with insulin by 42% (P less than .01) and 34% (P less than .05), respectively. When euglycemia was maintained by a variable glucose infusion rate after the injection of insulin and proinsulin, no differences were observed in plasma levels of any of the hormones. The intravenous injection of a dose of proinsulin (6 micrograms/kg), which did not produce hypoglycemia but was the molar equivalent of insulin used in the first protocol, failed to modify the GH or prolactin responses to a combined injection of GH-releasing hormone (1 microgram/kg) and thyrotropin-releasing hormone (500 micrograms). Our results indicate that the onset of pituitary hormone and catecholamine responses to hypoglycemia are related to the rate of plasma glucose decline, with the slower responses to proinsulin reflecting a more gradual onset of hypoglycemia. The magnitude of the cortisol, GH, and catecholamine responses, however, was comparable with proinsulin- and insulin-induced hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

The treatment of bullous pemphigoid with tetracycline and niacinamide. A preliminary report.

Patients with moderate to severe bullous pemphigoid are usually treated with systemic corticosteroids. Four patients were treated with tetracycline hydrochloride and niacinamide because of the steroid-sparing anti-inflammatory properties of these agents. An excellent clinical response free of side effects was observed in all patients. The lesions recurred whenever treatment was discontinued. It is believed that these drugs suppress the complement-mediated inflammatory response at the basement membrane zone by suppressing neutrophil chemotaxis and mediators of the inflammatory response in this bullous disease.

Familial gastroesophageal reflux and development of Barrett's esophagus.

The family of an elderly man with Barrett's esophagus was examined for gastroesophageal reflux and development of Barrett's esophagus. All five living children have gastroesophageal reflux or esophagitis, or both, and three have unequivocal Barrett's esophagus. Two third-generation descendents have gastroesophageal reflux. This pattern suggests autosomal dominant transmission of the gastroesophageal reflux trait. The family also has a high prevalence of cancer, which may represent the cancer family syndrome.

Enhanced glycemic responsiveness to epinephrine in insulin-dependent diabetes mellitus is the result of the inability to secrete insulin. Augmented insulin secretion normally limits the glycemic, but not the lipolytic or ketogenic, response to epinephrine in humans.

To determine if the enhanced glycemic response to epinephrine in patients with insulin-dependent diabetes mellitus (IDDM) is the result of increased adrenergic sensitivity per se, increased glucagon secretion, decreased insulin secretion, or a combination of these, plasma epinephrine concentration-response curves were determined in insulin-infused (initially euglycemic) patients with IDDM and nondiabetic subjects on two occasions: once when insulin and glucagon were free to change (control study), and again when insulin and glucagon were held constant (islet clamp study). During the control study, plasma C-peptide doubled, and glucagon did not change in the nondiabetic subjects, whereas plasma C-peptide did not change but glucagon increased in the patients. The patients with IDDM exhibited threefold greater increments in plasma glucose, largely the result of greater increments in glucose production. This enhanced glycemic response was apparent with 30-min increments in epinephrine to plasma concentrations as low as 100-200 pg/ml, levels that occur commonly under physiologic conditions. During the islet clamp study (somatostatin infusion with insulin and glucagon replacement at fixed rates), the heightened glycemic response was unaltered in the patients with IDDM, but the nondiabetic subjects exhibited an enhanced glycemic response to epinephrine indistinguishable from that of patients with IDDM. In contrast, the FFA, glycerol, and beta-hydroxybutyrate responses were unaltered. Thus, we conclude the following: Short, physiologic increments in plasma epinephrine cause greater increments in plasma glucose in patients with IDDM than in nondiabetic subjects, a finding likely to be relevant to glycemic control during the daily lives of such patients as well as during the stress of intercurrent illness. Enhanced glycemic responsiveness of patients with IDDM to epinephrine is not the result of increased sensitivity of adrenergic receptor-effector mechanisms per se nor of their increased glucagon secretory response; rather, it is the result of their inability to augment insulin secretion. Augmented insulin secretion, albeit restrained, normally limits the glycemic response, but not the lipolytic or ketogenic responses, to epinephrine in humans.

beta 2- and alpha 2-adrenergic receptors and receptor coupling to adenylate cyclase in human mononuclear leukocytes and platelets in relation to physiological variations of sex steroids.

In view of evidence, largely in animals, indicating effects of sex steroids on adrenergic receptors, we measured mononuclear leukocyte (MNL) beta 2-adrenergic receptors and adenylate cyclase sensitivity to stimulation by isoproterenol as well as platelet alpha 2-adrenergic receptors and sensitivity of sodium fluoride-stimulated adenylate cyclase to inhibition by epinephrine in 3 groups of normal humans with physiologically disparate levels of testosterone, estradiol, and progesterone (10 normal men and 10 normal women, the latter sampled in both the follicular and luteal phases of their menstrual cycles). Differences in testosterone, estradiol, and progesterone were as expected; testosterone levels were 10-fold higher in men, and progesterone levels were 20-fold higher in luteal phase women. T4, cortisol , and norepinephrine levels did not differ. Basal plasma epinephrine concentrations were slightly but significantly higher in luteal phase women [34 +/- 5 (+/-SE) pg/ml] than in follicular phase women (16 +/- 3 pg/ml; P less than 0.01) or men (20 +/- 3 pg/ml; P less than 0.05). There were no significant differences among these 3 groups in the densities or affinities of MNL beta 2-adrenergic or platelet alpha 2-adrenergic receptors or in the corresponding MNL and platelet adenylate cyclase sensitivities. Thus, there is not a generalized effect of physiological variations of testosterone, estradiol, and progesterone on adrenergic receptors or adenylate cyclase. To the extent that the adrenergic receptors and adenylate cyclase activities of circulating cells reflect those of extravascular catecholamine target cells, these data provide no support for a role of physiological variations of testosterone, estradiol, or progesterone in the regulation of catecholamine action in humans.

Epinephrine supports the postabsorptive plasma glucose concentration and prevents hypoglycemia when glucagon secretion is deficient in man.

We hypothesized that adrenergic mechanisms support the postabsorptive plasma glucose concentration, and prevent hypoglycemia when glucagon secretion is deficient. Accordingly, we assessed the impact of glucagon deficiency, produced by infusion of somatostatin with insulin, without and with pharmacologic alpha- and beta-adrenergic blockade on the postabsorptive plasma glucose concentration and glucose kinetics in normal human subjects. During somatostatin with insulin alone mean glucose production fell from 1.5 +/- 0.05 to 0.7 +/- 0.2 mg/kg per min and mean plasma glucose declined from 93 +/- 3 to 67 +/- 4 mg/dl over 1 h; glucose production then increased to base-line rates and plasma glucose plateaued at 64-67 mg/dl over 2 h. This plateau was associated with, and is best attributed to, an eightfold increase in mean plasma epinephrine. It did not occur when adrenergic blockade was added; glucose production remained low and mean plasma glucose declined progressively to a hypoglycemic level of 45 +/- 4 mg/dl, significantly (P less than 0.001) lower than the final value during somatostatin with insulin alone. These data provide further support for the concept that maintenance of the postabsorptive plasma glucose concentration is a function of insulin and glucagon, not of insulin alone, and that adrenergic mechanisms do not normally play a critical role. They indicate, however, that an endogenous adrenergic agonist, likely adrenomedullary epinephrine, compensates for deficient glucagon secretion and prevents hypoglycemia in the postabsorptive state in humans. Thus, postabsorptive hypoglycemia occurs when both glucagon and epinephrine are deficient, but not when either glucagon or epinephrine alone is deficient, and insulin is present.