Coexistence of sporadic multiple endocrine neoplasia and scapular ectopic breast. Coincidence or biologically associated?

We describe a patient who presented with sporadic pheochromocytoma and parathyroid adenoma in the absence of medullary thyroid carcinoma, which coexisted with fully developed scapular ectopic breast tissue. If not coincidental, this association might support the concept that all components of multiple endocrine neoplasia type IIA originate from embryonic ectodermal tissue, and that sporadic multiple endocrine neoplasia type IIA, as well as ectopic breast tissue, may result from a noxious event at a critical embryonic stage.

Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion.

Serum zinc levels and urinary zinc excretion were compared in 15 patients with essential hypertension taking chronically a combination of hydrochlorothiazide and amiloride as monotherapy, eight patients maintained with hydrochlorothiazide alone, and eight control subjects. Serum zinc values were statistically comparable in all three groups. However, urinary zinc excretion was abnormally elevated in the two patient groups. In the dosage used, amiloride did not have a zinc-sparing effect.

The effect of several uremic parameters on uremic serum inhibition of lymphocyte blastogenesis.

Uremic sera are known to inhibit thymidine incorporation of normal lymphocytes. The nature of the factor(s) responsible for this inhibitory effect has not been completely elucidated. In this study a possible correlation was investigated between a number of uremic blood constituents altered with the progression of the disease and the immunoinhibitory effect of the respective sera. No such correlation was found with the values of hematocrit, urea, creatinine, calcium and phosphorus. On the other hand a significant negative correlation emerged between H+ and Mg2+ ion levels and the inhibition imposed on normal lymphocyte thymidine incorporation. This apparently paradoxical result would indicate that with regard to these two parameters the greater the severity of renal failure the smaller would be the immunoinhibitory effect of the respective serum. The inhibition imposed by uremic serum on immune functions is probably a multifactorial phenomenon, in which H+ and Mg2+ might play a role antagonistic to inhibitory factors.

Anti-HIV indeterminate western blot in dialysis patients: a long-term follow-up.

In a group of 520 patients undergoing chronic hemodialysis, 23 (4. 4%) were enzyme immunoassay (EIA) positive for human immunodeficiency virus (HIV) and indeterminate by Western blot (IWB) analysis. The antibodies were mostly directed against p24 and p55 antigens. A comparison between hemodialysis patients with and without IWB showed significant differences between the two groups with respect to number of units of blood transfused, history of renal transplant rejection, and Rh status. No significant differences were observed with respect to ethnic group, nature of renal disease, duration of hemodialysis, associated diseases, and ABO blood group. The HIV IWB phenomenon may represent abnormal immune reactivity as a result of transplantation antigens and/or autoantibody formation. Five-year follow-up of the HIV EIA-positive IWB patients showed that none had seroconverted to HIV-positive status.

Total cell-associated Zn2+ and Cu2+ and proliferative responsiveness of peripheral blood mononuclear cells from patients on chronic hemodialysis.

We investigated total copper (Cu2+) and zinc (Zn2+) content in plasma and peripheral blood mononuclear cells (PBMC) and its impact on proliferative ability of the latter in patients on chronic hemodialysis versus age- and sex-matched healthy volunteers. Plasma levels of Cu2+ and Zn2+ were significantly lower in dialysis patients compared with the control group (83.6 +/- 7.29 v 95.1 +/- 9.63 microg/dL, P <.03 for Cu2+; 71.1 +/- 7.64 v 89.7+/- 12.55 microg/dL, P <.005 for Zn2+). Basal total PBMC-associated Cu2+ content was significantly higher in uremic patients (19.3 +/- 3.59 v 14.6 +/- 2.72 micromol/mg protein, P <.005). Basal PBMC-associated Zn2+ concentration was also significantly elevated in hemodialysis patients compared with their healthy counterparts (23.9 +/- 5.64 v 10.5 +/- 2.64 micromol/mg protein, P <.005). In addition, we incubated PBMC of the uremic patients versus healthy control PBMC in a Zn2+ free versus Zn2+ enriched medium. After a 72-hour incubation, total cell-associated Zn2+ of both normal and uremic cell populations increased significantly compared with the respective baselines (34.6 +/- 22.49 v 4.3 +/- 1.42 and 20.3 +/- 10.71 v 5.8 +/- 2.22 micromol/mg protein, respectively). However, no statistically significant difference was evident between the 2 groups (34.6 +/- 22.49 v 20 +/- 10.7 micromol/mg protein). Total cell Zn2+ content, on the other hand, was significantly increased in uremic PBMC after 72 hours of incubation in Zn2+ enriched medium compared with the control group (63.3 +/- 26.12 v 18.6 +/- 13.42 micromol/mg protein, P <.005). A significant increase in PBMC proliferation evaluated by 3H-thymidine incorporation was evident in the Zn2+ enriched culture (35,559 +/- 4,136 counts per minute [CPM] v 20,497 +/- 7,263 CPM, P <.005). Cu2+ enrichment of the medium, while resulting in a modest elevation of cell-associated Cu2+, did not produce such a proliferative effect.

Zinc metabolism in patients treated with captopril versus enalapril.

Several zinc parameters were assessed in 13 patients with essential hypertension who were chronically taking only captopril (six subjects) or enalapril (seven subjects), as well as in six untreated hypertensives, and nine healthy controls. Serum zinc levels were comparable in all groups. Twenty-four-hour urinary zinc excretion was significantly increased in the captopril-treated patients compared with the other three groups. The zinc:creatinine ratio in 24-hour urine was significantly increased in both captopril and enalapril groups, but was significantly greater in the former. Although plasma zinc concentrations were comparable in all groups, red blood cell (RBC) zinc values were significantly decreased in the captopril group compared with the other three groups. We conclude that (1) although both captopril and enalapril produce renal zinc loss, this loss is far greater in patients receiving captopril; and (2) captopril administration over 3 months or more generates RBC zinc depletion.

Zn metabolism affects apoptosis rate and proliferative responsiveness of PBMC from patients on chronic hemodialysis.

Patients with end-stage renal failure suffer from severe plasma trace metal deficiency that is not corrected by dialysis. Trace metals, including Zn(2+), are critical for cell differentiation and replication. Zn(2+)also plays important role in cell apoptosis. Both processes are known to be impaired in uremia. The present study was undertaken to evaluate the effect of Zn(2+) supplementation on apoptosis of cultured peripheral blood mononuclear cells (PBMC) from patients on chronic hemodialysis versus those from healthy control subjects, concomitantly with assessment of mitogen-induced cell proliferation. The results showed that (1) basal total cell-associated Zn(2+) was elevated in uremic PBMC, compared to normal controls (23.9 +/- 5.64 v 10.5 +/- 2.64 micromol/L/mg protein). The gap persisted following incubation in Zn(2+)-enriched medium (63.3 +/- 26.12 v 81.6 +/- 13.4 micromol/L/mg protein, P <.005). (2) Basal proliferative response to phytohemagglutinin (PHA) was significantly decreased in uremic PBMC compared to normal controls (12,000 +/- 1,560 cpm v 16,600 +/- 1,460 cpm, P <.01). Incubation of uremic PBMC in Zn(2+)-enriched medium improved their proliferative response to PHA, yielding counts per minute significantly higher compared to their normal counterparts (37,000 +/- 7,500 cpm v 22,000 +/- 3,000 cpm, P <.001). (3) Basal apoptosis rate in uremic PBMC was significantly elevated compared to normal control cells (7.6% v 2.6%, P <.05). Following incubation in Zn(2+)-enriched medium, apoptosis was increased both in normal and uremic PBMC. Percent apoptosis of uremic PBMC remained significantly elevated compared to control cells (11.7% v 5.7%). We conclude that uremic PBMC are more responsive to exogenous Zn(2+) in culture than their normal counterparts. This, among other abnormalities, might reflect an abnormal regulation of Zn(2+) transport by uremic mononuclear cell membranes. The resultant increase in total cell-associated Zn(2+) content improves poor proliferative responsiveness of uremic PBMC. On the other hand, increased total cell-associated Zn(2+) stimulates enhanced apoptosis in uremic PBMC, which, probably by eliminating defective cells, contributes to the functional capability of the population as a whole. The net effect of the 2 processes is still augmentation of cell proliferation.

Controlled intravenous bicarbonate and fetal-maternal acid-base balance. I. The primipara.

The effects of a controlled sodium bicarbonate (SB) infusion on the acid-base balance of the primiparous mother and fetus at labor and delivery were evaluated. Two identical groups of primiparas with normal labor and delivery were studied. According to acid-base parameters observed in the mothers and fetuses of a control group, the pharmacologic dynamics, and the space of distribution of SB, 2 mEq/1 kg of total body weight were administered to the mothers of the study group, beginning at a cervical dilation of 6 cm until full dilation occurred. Highly significant changes in pH, base excess (BE), and plasma bicarbonate were observed in both the mothers and fetuses. In the latter, the significant changes appeared after a time lag of about 2 hours. No adverse effects in the mothers and fetuses were observed. The significant reduction of the relative fetal acidosis by the controlled SB infusion justifies further studies on the therapy potentials of this method in high-risk deliveries and during intrapartum fetal distress.

Erythrocyte Na+, K+ and Ca2+, Mg(2+)-ATPase activities in hypertensives on angiotensin-converting enzyme inhibitors.

OBJECTIVE: To investigate erythrocyte membrane Na+, K(+)- and Ca2+, Mg(2+)-ATPase activities in newly diagnosed hypertensive patients before and after 2, 4, and 6 months of treatment with enalapril or captopril as monotherapy. METHODS AND RESULTS: Na+, K(+)-ATPase activity (nmol ATP hydrolysed/min per mg protein) rose by 6 months of treatment in both groups when values were compared in each treated group over time (4.5 +/- 0.8 to 9.9 +/- 1.2; 4.9 +/- 0.8 to 10.5 +/- 1.7, respectively, p < 0.001 for both). When the treated groups were compared with controls at each period of time, Na+, K(+)-ATPase activity was higher at months 4 and 6 (p < 0.001) for both groups, respectively). Ca2+, Mg(2+)-ATPase activity (nmol ATP hydrolyzed/min per milligram protein) in the absence and in the presence of calmodulin increased in the enalapril (6.4 +/- 0.7 to 8.9 +/- 0.95, p < 0.05; 13.4 +/- 1.2 to 17.2 +/- 1.2, p < 0.05, respectively) and captopril (7.0 +/- 0.6 to 8.5 +/- 0.7; 14.4 +/- 1.1 to 16.0 +/- 1.0, p < 0.05, respectively) groups after 6 months of treatment compared within each treated group over time. When patient groups were compared with controls at time 0, 2, 4, and 6 months, the pump activity was higher in the treated groups at 6 months. CONCLUSION: The long-term enhancement of cell membrane Na+, K(+)-and Ca2+, Mg(2+)-ATPase activity associated with enalapril and captopril therapy may represent a specific effect of these agents or alternatively, a nonspecific outcome of blood pressure reduction.

A progressive rise in serum copper levels in women taking oral contraceptives: a potential hazard?

PIP: 123 healthy Jewish women (18-22 years) were divided into OC (oral contraceptives) users (n=75), and controls (n=48). All women were on a similar diet. The OC users were divided into 3 groups (1, 2 and 3) based on the OC preparations they were taking. Venous blood samples were collected; serum copper levels were measured using atomic absorption spectrophotometry (Parker et al.'s method). Serum copper levels did not correlate with time of menstrual cycle for each group, and for all groups considered together. Mean serum copper level in the control group, 120 ug/100 ml +/- 15 SD (standard deviation), was significantly lower than the serum copper level of all contraceptive groups considered together. Of the 3 groups, group 3 (those taking Neogynon) showed a steady and progressive rise in serum copper level. The mechanism of action of the rise of serum copper and ceruplasmin levels following OC intake is not clear. Hypercupremia may be due to excessive absorption of copper by the intestines, to a shift of copper from tissue to blood compartment, or to both. Chronic copper intoxication could result from hypercupremia associated with chronic OC use. Studies of Wilson's disease show that severe damage could result from excessive copper deposition in various tissues. Further research should be done to determine the potential hazards of chronic copper intoxication, particularly in patients taking Neogynon.^ieng

Nephrectomy enhances interleukin 6 secretion by interleukin 1-stimulated mesangial cells in vitro.

BACKGROUND: Kidney mesangial cells are capable of producing and responding to interleukin 6 (IL-6) . In experimental glomerulonephritis mesangial cell proliferation correlates with increased IL-6 production. To investigate the involvement of IL-6 in post-nephrectomy compensatory hypertrophy, we studied the capacity of mesangial cells from single remaining kidneys to secrete IL-6 in culture. METHODS: Mesangial cells were obtained from uni-nephrectomized or sham-nephrectomized Charles River rats. Cell cultures were maintained for 8 days in DMEM/FI2HAM medium supplemented with IL-1 of interferon (IFN). IL6 production was measured using an IL-6-dependent B9 human hybridoma cell line. RESULTS: IL-6 production by mesangial cells from normal kidneys was significantly enhanced by IL-1, compared to unstimulated cells (p<0.01), and the increase was significantly greater in mesangial cells from a single remaining kidney (p<0.01). All cultures grown in control medium or with addition of IFN produced similar amounts of IL-6. CONCLUSION: Mesangial cells from single remaining kidneys in culture maintain an exaggerated capacity to produce IL-6 in response to IL-1. IL-6 was reported to enhance or inhibit mesangial cell proliferation in vitro. We suggest that the local over production of IL-6 by a single remaining kidney may play a role in regulating a sequence of physiological events in compensatory renal growth, initially stimulating mesangial cell proliferation and later blunting the process.

Fatal haemoptysis induced by invasive pulmonary aspergillosis in patients with acute leukaemia during bone marrow and clinical remission: report of two cases and review of the literature.

We describe two patients with acute leukaemia who died of massive haemoptysis caused by invasive pulmonary aspergillosis (IPA). The fatal event occurred during the period of bone marrow remission which followed chemotherapy-induced neutropenia. This is a rare complication. We were able to find additional 17 similar cases in the English literature, which we review. Clinically, the picture consisted of unremitting fever with profound and prolonged neutropenia, cough and dyspnoea. Both our patients were treated with broad-spectrum antibiotics, fluconazole and amphotericin B. An upper lobe infiltrate in one case, and a progressive pleural effusion in the other, were late findings on chest radiographs during the period of bone marrow recovery. Both patients succumbed to sudden massive haemoptysis during the period of bone marrow and clinical improvement. In conclusion, patients with acute non-lymphoid leukaemia are at significant risk for IPA-induced fatal haemoptysis during bone marrow and clinical remission. A high index of suspicion should be sustained throughout the entire clinical course. In view of the potential fatal outcome, aggressive diagnostic and treatment efforts are mandatory.

Biopsy proven evolution of post streptococcal glomerulonephritis to rapidly progressive glomerulonephritis of a post infectious type.

A 15 year old boy with chronic impetigo was admitted with severe acute oliguric renal failure requiring temporary dialytic treatment. Renal biopsy revealed typical diffuse and proliferative glomerulonephritis of the poststreptococcal type. Subsequently high temperature developed with flank pains at the biopsy site, concomitantly with deterioration of renal function. On exploration, a sterile perirenal hematoma was found and a wedge renal biopsy revealed crescentic rapidly progressive glomerulonephritis of the post infectious type. Deterioration to end stage renal failure occurred within a few months. Although universally accepted, biopsy proven evolution from diffuse proliferative and exudative glomerulonephritis to crescentic form of post streptococcal glomerulonephritis has been rarely reported.

Renal dysfunction in congestive heart failure, pathophysiological and prognostic significance.

AIMS: Many congestive heart failure (CHF) patients suffer from various comorbidities, which may aggravate CHF or independently increase mortality risk. Renal failure (RF) is one of them. We defined bedside clinical, laboratory and electrocardiographic parameters characterizing CHF patients with and without concomitant RF, and analyzed their impact on mortality. METHODS: We studied symptomatic unselected consecutive furosemide-treated CHF patients hospitalized for various acute conditions. On admission, history taking, physical examination, chest x-ray, ECG and routine laboratory tests were performed. Subsequently, patients were divided into 2 subgroups, those with serum creatinine > or = 1.5 mg/dl (RF) and those with lower values. Following discharge, information concerning mortality and circumstance of death was obtained from hospital records and outpatient death certificates. RESULTS: Included were 398 patients, 163 (40.9%) with RF and 235 free of RF. Prevailing in the RF subgroup were older age (mean age 75.5 vs 70.8, p < 0.001), male gender (p < 0.001), admission pulmonary edema (p = 0.007), cardiac arrhythmias (p = 0.05), cardiac conduction disturbances (p = 0.002), severe CHF (p = 0.005), lower ejection fraction (p = 0.03), anemia (p = 0.009), higher furosemide maintenance dosages (p < 0.001), insulin treatment (p = 0.03) and receiving less ACE inhibitors (p = 0.006). On median follow-up of 43 months, mortality was 54.9% in the RF vs 31.9% in the non-RF subgroup (p < 0.001), RF being the parameter most significantly associated with low survival (OR 1.97, p < 0.001). In the RF subgroup older age (p < 0.02), female gender (p < 0.003) and not using ACE inhibitors (p = 0.04) or drugs with antiarrhythmic effects (p < 0.005), emerged significantly associated with low survival, while diabetes mellitus (DM) and admission pulmonary edema tended to be so associated (p < 0.2). Using multivariate analysis in the RF subgroup, older age, female gender and DM proved most significantly associated with poorer survival (p = 0.004, OR 1.5, p = 0.03, OR 1.72, p = 0.04, OR 1.28, respectively). In the non-RF subgroup, only older age (p = 0.005) and DM (p = 0.05) were significantly associated with low survival. Sudden death occurred in 21 patients, 14 (8.6%) in the RF and 7 (3%) in the non-RF subgroup (p < 0.001). CONCLUSIONS: RF is a marker of severity in CHF. Its full-blown deleterious prognostic effect is already manifested at serum creatinine 1.5 mg/dl. Older age, DM and female gender most significantly heralded a shorter survival. Such patients require special care.

Conservative treatment for Brucella endocarditis.

Endocarditis is the most devastating complication of brucellosis. The accepted treatment for Brucella endocarditis (BE) is a combination of valve replacement and antibiotics. Conservative antibiotic treatment alone is not recommended by most authors, as it is considered ineffective, risking fatality. We describe a patient with BE, in whom antibiotic treatment alone resulted in complete recovery. On reviewing the literature, we found 12 additional such cases. We compared this group of 13 patients with data from 49 published cases treated with a combination of surgery and antibiotics, with a favorable outcome. Absence of congestive heart failure or a prosthetic valve, relatively mild extravalvular cardiac involvement, and a somewhat shorter disease history until initiation of treatment were characteristic of the group treated conservatively in comparison with patients who underwent surgery. In selected patients with BE, conservative antibiotic treatment may be a valid alternative to surgery.

Chylothorax following median sternotomy.

Reports of chylothorax (CT) following median sternotomy are rare, amounting so far to 16 cases in the English literature, of which 6 were cases of postcoronary artery bypass grafting (CABG). This report deals with an additional case of a 70-year-old woman who developed left pleural chylous effusion following CABG. It is suggested that the incidence of this type of pleural effusion is considerably greater than the few cases hitherto reported. Moreover, as CT may produce serious pulmonary and/or pleural functional impairment, it is proposed that a diagnostic tap be performed more often in cases of post CABG pleural effusion and that preventive drainage be instituted when CT is diagnosed.

Unrecognized major bleeding following thrombolysis for acute myocardial infarction presenting with syncope.

Complete atrioventricular block and syncope sometimes are the presenting signs of acute myocardial infarction. In a presyncopal attempt to assume sitting position, the patient may fall and suffer consequent trauma. Once in hospital, this sequence of events may be overlooked by both the patient and admitting physicians. Moreover, physical examination initially may not be revealing. We report on two such patients who developed massive subcutaneous bleeding following thrombolytic and heparin treatment. We conclude that these patients constitute a specific group with a relatively high risk of trauma and bleeding at the gluteal region following thrombolytic therapy. Special attention must be given to these patients.

Adequacy of anticoagulation in patients with atrial fibrillation: effect of various parameters.

BACKGROUND: Despite reported evidence of the vital importance of appropriate anticoagulation in patients with chronic atrial fibrillation for stroke prevention, this treatment modality still lags behind optimal requirements. HYPOTHESIS: Our objectives were to evaluate various doctor or patient-related factors that influence quality of control and to assess the adequacy of anticoagulation provided by physicians in the community. METHODS: In a retrospective study, International Normalized Ratio (INR) values obtained immediately on admission to hospital were considered representative of previous long-term control. RESULTS: Only 42% of the relevant 385 patient population fell within the protective anticoagulation range of INR 1.91-4.1. The respective figures for patients with poor (INR < 1.5) or suboptimal (INR 1.51-1.9) control, as well as those whose INR values risked bleeding (INR > 4.1), were 28.3, 14.1, and 15.6%. Patient involvement in treatment positively influenced quality of control. By contrast, age 70-80 years or absence of congestive heart failure negatively affected quality of anticoagulation [p = 0.07, odds ratio (OR), 1.7 (95% confidence interval. 0.94-3.08), p = 0.014, OR, 2.06 (95% confidence interval, 1.15-3.7) respectively]. The percentage of patients admitted with stroke who had been adequately anticoagulated was significantly lower than that of patients who had no stroke (21 vs. 44.4%). Adequacy of anticoagulation in patients with cardiac prosthetic valves was superior compared with the rest of the patient population (56.7 vs. 42% with optimal, and only 14.5 vs. 28.3% with poor anticoagulation, respectively), indicating that under the same conditions a better quality of treatment could be achieved. CONCLUSIONS: Adequacy of anticoagulation in patients with atrial fibrillation lags behind actual recommendations. Better control is required and achievable.

Metabolic and clinical effects of oral magnesium supplementation in furosemide-treated patients with severe congestive heart failure.

BACKGROUND: Magnesium depletion and hypomagnesemia are common among furosemide-treated patients with chronic congestive heart failure. HYPOTHESIS: This investigation evaluated clinical and metabolic effects of oral magnesium supplementation. METHODS: Ten patients with severe congestive heart failure maintained on high dose furosemide (> or = 80 mg/day) received a supplement of oral magnesium citrate 300 mg/daily for 30 days. Clinical parameters were followed, and peripheral blood mononuclear cell magnesium and zinc content, serum and urine magnesium, potassium, zinc, calcium, phosphorus, and creatinine were assessed. RESULTS: Peripheral blood mononuclear cell magnesium content and serum potassium rose significantly at the end of the study (2.09 +/- 1.89 to 3.99 +/- 2.26 micrograms/mg cell protein, p < 0.05, and 4.17 +/- 0.38 to 4.39 +/- 0.27 mEq/l, p < 0.05, respectively), while the other parameters remained unchanged. CONCLUSION: In some of these patients, oral magnesium supplementation is effective in achieving substantial increments in intracellular magnesium and serum potassium which, in turn, may have cardioprotective effects.

Replacement of ruptured aneurysm of arteriovenous fistula by segmental frozen venous allograft: a case report.

A ruptured aneurysm of an arteriovenous fistula created for chronic hemodialysis was replaced by a segment of frozen saphenous vein allograft. Fifteen months following the procedure the graft is patent. Frozen vein allografts should be considered as an appropriate option for the reconstruction of disrupted A-V fistulae.