Calciphylaxis in man. A syndrome of tissue necrosis and vascular calcification in 11 patients with chronic renal failure

Eleven patients with chronic renal failure and presumed secondary hyperparathyroidism developed a syndrome of medial calcinosis of the arteries and painful ischemic ulcers of the fingers, legs, or thighs, or any combination of the three. Five patients required maintenance hemodialysis; six had functioning renal homografts. Severe hyperphosphatemia had existed in each; seven showed roentgenographic evidence of subperiosteal resorption. Similarities are evident between the lesions and experimentally produced calciphylaxix. The lesions demonstrated a relentless, progressive course, with serious morbidity and mortality. Hyperplastic or adenomatours parathyroid tissue was removed from ten of 11 patients unergoing surgical procedures; healing followed in seven patients. Treatment with phosphate-binding antacids to lower serum phosphorus levels may prevent this syndrome. Total or subtotal parathyroidectomy should be considered when ischemic skin lesions appear in uremic patients or in renal transplant recipients.     

Peyer''s-patch-associated synthesis of immunoglobulin in germ-free, specific-pathogen-free, and conventional mice

The synthesis of immunoglobulins G, A, and M has been studied in Peyer's patches together with closely associated intestinal mucosa and in small intestine distant from Peyer's patches in specific-pathogen-free (SPF) Swiss mice and conventional and germ-free C3H mice. Thissue fragments were cultured in vitro in medium containing 14C-labelled amino acids, and newly synthesized proteins were detected by radioimmunoelectrophoresis. Small intestine from SPF and conventional animals synthesized almost exclusively IgA. No immunoglobulin synthesis was detectable in germ-free intestine. In contrast, the Peyer's patches and associated mucosa of all the groups of mice synthesized IgG, IgA, and IgM. This observation is discussed in relation to the possible role of the Peyer's patches as a source of precursors for immunoglobulin-producing cells in the intestine.     

Pancreatic cancer screening. Analysis of the problem and the role of radionuclide imaging

The clinical, surgical, and pathologic findings in a five year prospective study of 192 patients referred with a high probability of pancreatic cancer are reported. We have defined the requirements of any pancreatic imaging procedure as its ability to distinguish a normal pancreas from pancreatic cancer or chronic pancreatitis and the capability of detecting tumors less than 5 cm in diameter. There was a 47 percent incidence of pancreatic disease (27 percent pancreatic cancer and 20 percent chronic pancreatitis). Prospective radionuclide imaging as routinely performed was found to be of little clinical value in this patient population; it was neither specific nor sensitive to pancreatic cancer or chronic pancreatitis. Preliminary data with longitudinal multiplane emission tomography show an improved diagnostic accuracy and the ability to detect resectable tumors, but its efficacy needs to be prospectively compared with other screening tests on a carefully defined patient population.     

Cystic tumours of the breast

A retrospective survey of cystic tumours of the breast seen at the North Middlesex and St Bartholomew's Hospitals, London, has been undertaken to determine their incidence and clinical features. During the years 1967-76 4530 histological examinations were carried out on breast tissue and 1277 breast cancers diagnosed. Intracystic papillary tumours, both benign and malignant, were the least uncommon of cyst tumours, but the malignant type accounted for 0.55% of all the breast cancers. Aspects suggesting the possible presence of an intracystic tumour are discussed.     

Erythrocyte sodium and potassium in patients with hypokalaemia

1. The erythrocyte content of sodium and of potassium were measured in 231 unselected patients with hypokalaemia, and together with net ouabain-sensitive sodium efflux in patients with severe hypokalaemia, before (20 patients) and during potassium repletion (14 patients). 2. The erythrocytes of the patients with hypokalaemia compared with control subjects had on average an increase in sodium content, a decrease in potassium content and a reduction in the rate constant of ouabain-sensitive sodium efflux. All three changes had a similar curvilinear relation to the concentration of potassium in plasma with relatively little change in the measured variable unless the plasma potassium was very low. 3. There was a similar curvilinear relation between the final sodium and potassium content of normal erythrocytes and the potassium concentration of the medium in which they were incubated for 48 h in vitro. 4. These results suggest that the changes in the sodium and potassium content of erythrocytes in hypokalaemia are due to a direct inhibiting effect of the hypokalaemia on the activity of the sodium pump. 5. In many patients with hypokalaemia of moderate degree the increase in erythrocyte sodium content was less than expected from the effect in vitro of a low extracellular potassium concentration. This finding suggests that a compensatory change, presumably an increase in the number of sodium pumps, is a common event even in moderate hypokalaemia.     

The fate of cryopreserved sperm acquired during vasectomy reversals

PURPOSE: Intraoperative sperm banking has been recommended during vasectomy reversal. These specimens are maintained as insurance for possible future intracytoplasmic sperm injection. We evaluated the fate of specimens collected intraoperatively from 48 vasectomy reversal patients. MATERIALS AND METHODS: Of 75 men 48 (64.0%) agreed to intraoperative sperm banking during vasectomy reversal. A total of 135 vials of epididymal sperm, 81 vials of testicular tissue and 13 vials of vasal sperm were cryopreserved. RESULTS: Among couples who stored sperm 10 (20.8%) voluntarily discarded the specimens within 4 months of vasectomy reversal. Specimens from 31 couples (64.5%) remain in storage. Seven couples (14.6%) have used frozen sperm for intracytoplasmic sperm injection. In 3 of these couples the men were azoospermic after surgery, 2 men had 10,000 to 15,000 sperm per ml. in the ejaculate with limited motility and 2 had 1 to 2 million sperm per ml. with limited motility. The 7 women who underwent intracytoplasmic sperm injection ranged between 37 and 39 years old, which was older than the mean age of the remaining study group (32.7 years). With intracytoplasmic sperm injection fertilization was achieved in all cases and 20 of 47 eggs (42.5%) developed into embryos. Of 7 women 4 achieved biochemical pregnancies (57.1%) and 2 (28.6%) delivered newborns with epididymal sperm. Natural pregnancy occurred in 7 of 16 vasectomy reversal couples (43.7%) who were followed at least 18 months postoperatively but the time to pregnancy averaged 1 year. CONCLUSIONS: Cryopreservation of sperm collected at vasectomy reversal is recommended for patients undergoing vasoepididymostomy or vasovasostomy. The couples who used the cryopreserved sperm for intracytoplasmic sperm injection included husbands whose postoperative ejaculate remained azoospermic or severely oligospermic and wives who were approaching 40 years old. Only a limited number of couples (14.6% of the study group) have used the cryopreserved sperm but the delivered newborn rate (28.6%) was comparable to other intracytoplasmic sperm injection data. The natural pregnancy rate after vasectomy reversal was 43.7% but the time to pregnancy after surgery was lengthy (average 1 year). These findings may be helpful for counseling couples who are planning vasectomy reversal surgery and may be considering intraoperative sperm banking.     

The nuclear factor-kappa B RelA transcription factor is constitutively activated in human pancreatic adenocarcinoma cells

To assess the efficiency of nasally administered cartilage-specific collagens as vaccination against development of arthritis and to ameliorate already established chronic arthritis, experimental models which develop chronic arthritis, pristane-induced arthritis (PIA), and homologous collagen-induced arthritis (CIA) in the rat were selected. Cartilage-specific collagens type IX (CIX) and type II (CII) were used for vaccination intranasally. A single dose of 250 microg CII instilled intranasally in rats with established PIA ameliorated the disease. For the prevention of disease, the same dose given before immunization was found to be most effective. Most importantly, the disease was more severe if this dose was given three times. For treatment of PIA, CIX was found to be more effective than CII, whereas for treatment of CIA only CII was effective. The amelioration of CIA was associated with a marked suppression of delayed type hypersensitivity and the flare reaction to CII and lower levels of IgG2b anti-CII antibodies in serum, i.e., with suppression of the TH1 rather than the TH2 response to CII. These findings, that cartilage proteins, if given intranasally, can both prevent and ameliorate established chronic arthritis in rats, are of significant importance for possible use in rheumatoid arthritis. The identification of two different cartilage-specific proteins (CII and CIX) effective against a disease induced with a well-defined nonimmunogenic adjuvant such as pristane will be of value for enhancing the effectiveness of the treatment.     

Role of the endothelium in placental dysfunction after fetal cardiac bypass

BACKGROUND: Fetal cardiac bypass causes placental dysfunction, characterized by increased placental vascular resistance, decreased placental blood flow, hypoxia, and acidosis. Vasoactive factors produced by the vascular endothelium, such as nitric oxide and endothelin 1, are important regulators of placental vascular tone and may contribute to this placental dysfunction. METHODS: To investigate the role of the vascular endothelium in placental dysfunction related to fetal cardiac bypass, we studied 3 groups of fetal sheep. In the first group (n = 7) we determined placental hemodynamic responses before and after bypass to an endothelium-dependent vasodilator (acetylcholine), an endothelium-independent vasodilator (nitroprusside), and endothelin 1. In the second group (n = 8) a nonspecific endothelin receptor blocker (PD 145065) was administered and placental hemodynamic values were measured before and after bypass. In the third group (n = 5) endothelin 1 levels were measured before and after bypass. RESULTS: Before fetal cardiac bypass exogenous endothelin 1 decreased placental blood flow by 9% and increased placental resistance by 9%. After bypass endothelin 1 decreased placental flow by 47% and increased resistance by 106%. There was also a significant attenuation of the placental vascular relaxation response to acetylcholine after bypass, whereas the response to nitroprusside was not significantly altered. In fetuses that received the PD 145065, placental vascular resistance increased significantly less than in control fetuses (28% versus 62%). Similarly, placental blood flow decreased significantly more (from 6. 3 +/- 3.1 to 28.3 +/- 10.4 pg/mL; P =.01) in control fetuses than in fetuses receiving PD 145065 (33% versus 20%). Umbilical venous endothelin 1 levels increased significantly in fetuses exposed to fetal bypass but did not change in control fetuses. CONCLUSIONS: The basal endothelial regulatory mechanisms of placental vascular tone were deranged after fetal cardiac bypass. Endothelin receptor blockade, which substantially reduced postbypass placental dysfunction, and other interventions aimed at preserving endothelial function may be effective means of optimizing fetal outcome after cardiac bypass.     

Regulation of a Physiological Parameter or In Vivo Drug Concentration by Integral Pulse Frequency Modulated Bolus Drug Injections

This paper describes the designs for two novel, nonlinear, discrete, drug injection controllers. The basis for these controllers is integral pulse frequency modulation (IPFM). An IPFM controller injects small boluses of a drug into a pharmacokinetic (PK) plant to achieve regulation of the plant output. Bolus injections are advantageous because they provide a precise knowledge of the times and the cumulative amount of drug injected, and they require a discrete-action pump suitable for digital control, miniaturization, and implantation.