Comparison of the growth of virulent and attenuated strains of Candida albicans in the kidneys of normal and cortison-treated mice by chitin assay. Candida albicans strain 22114 was avirulent for mice compared with strain 19321 in that, administered intravenously, 10(6) blastospores of 22114 failed to kill whereas 10(6) blastospores of 19321 produced 100% mortality. Cortisone treatment rendered mice susceptible to killing by 22114. Chitin assay showed that cortisone stimulated the growth of both strains in the mouse kidney. Growth of 19321 was increased up to five-fold and 22114 up to forty-fold. The strains may have differential susceptibility to cortisone-sensitive host defences which control fungal growth in vivo.


Prenatal exposure to chemical carcinogens and its effect on subsequent generations. That exposure of pregnant animals to chemical carcinogens results in the occurrence of tumors in the progeny is well documented. Evidence has been accumulated on at least 38 chemicals pertaining to different chemical groups. The experimental evidence was followed by observations in humans regarding the increased risk of cancer in daughters of women who received stilbestrol during pregnancy. Additional experimental evidence is accumulating on the possibility that exposure during pregnancy results in an increased incidence of tumors for more than one generation of untreated descendants. Studies done on mice with DMBA and on rats with MNU and ENU showed that exposure to the carcinogens during pregnancy resulted in a high incidence of tumors in animals of the first generation and in an increased incidence of tumors at specific sites in untreated animals of the second and third generations.


Perinatal viral carcinogenesis: the role of immunity. The perinatal period cumulates conditions favorable to carcinogenesis that comprise high cellular multiplication rates, unstable homeostasis, and immune incompetence. The placenta allows the passage of various antigens including oncogenic viruses that have immunogenic or tolerogenic effects on the fetus. According to the structural type in different species, the placenta also transfers a diversity of maternal antibodies that protect efficiently the unborn progeny. However, in the postnatal period, the infant deprived of maternal antibodies and still incompetent to produce sufficient levels of immunoglobulins is highly susceptible to viral carcinogenesis. In an experimental system, newborn rats were totally protected against viral leukemogenesis by prenatal immunization of mothers with either live or inactivated leukemia virus. The routes of transfer and the comparative efficiency of serum and milk immunoglobulins of different classes to neutralize the virus were examined. The passage of antibodies under conditions of maternal immunosuppression was also studied.


Transplacental and neonatal induction of neurogenic tumors in mice: comparison with related species and with human pediatric neoplasms. The literature on chemical induction and natural occurrence of neurogenic tumors in mice and some unpublished data from our laboratories are reviewed. Neurogenic tumors are a minor component of the total tumorigenic response of mice to alkylating agents such as ENU and MNU. In comparison with rats, a given dose of ENU induces a much lower incidence of neurogenic tumors in mice, and the mean latency is much longer than in rats. Although most neurogenic tumors induced by ENU in mice by either transplacental or direct postnatal exposure are of glial or Schwann cell origin, as in rats, and occur most frequently in the cerebrum or cranial nerves, respectively, medulloblastomas of the cerebellum also occur in treated mice. Transplacental and neonatal exposure to ENU were much more effective in inducing neurogenic tumors than treatment later in life. Ependymomas were not seen in mice, although they are common in ENU-treated rats. Neuroblastoma of the adrenal medulla, a common human pediatric tumor, has not been induced to either species, but it does occur spontaneously in mice. The induction by ENU of medulloblastomas demonstrates that this rodent equivalent of an embryonal tumor of the human nervous system can result from exposure to exogenous chemical agents.


Neoplastic response of mouse tissues during perinatal age periods and its significance in chemical carcinogenesis. A series of studies pertaining to perinatal carcinogenesis have been reviewed. Their main objective was development and definition of a sensitivity biologic model for carcinogenicity screening. Data were summarized on factors modifying the carcinogenic response of various tissues following transplacental, neonatal-infant, or adult exposure of (B57BL/6J X C3HeB/FeJ)F1 mice to a single administration of ENU. In addition, tumor response of mice treated during specific perinatal age periods with DEN, BP, aflatoxin B1, benzidine . 2HCl, DDT, dieldrin, and safrole were analyzed. The results revealed that the age of the animals at the time of carcinogenic exposure has been the most effective modulator of carcinogenesis in liver, lung, stomach, ovary, and lymphoreticular tissues. Infancy proved to be the most susceptible period to carcinogenesis as demonstrated by a great variety of tissues that responded to treatment and the incidence of tumors which developed. Depending on the nature of carcinogen, variation in organ sites undergoing carcinogenesis was considerable, apparently due to difference in their enzymatic competence to activate and metabolize the agent. Thus a single treatment with ENU, a spontaneously activated type of procarcinogen, induced 59 primary types of tumors in 22 tissues. In contrast, treatment of infants by procarcinogens requiring enzymatic activation led to development of tumors only at a limited number of tissue sites. However, regardless of the type of carcinogen used, the liver consistently responded with development of tumors. Detailed morphologic and biologic evaluations of the induced liver tumors demonstrated in addition to the benign neoplastic variety, the presence of the frank malignant tumors. The character of tumors was dependent not only on carcinogenicity of the agent used but also on the age of mice at the time of carcinogenic treatment. Perinatally induced primary liver tumors showed greater tendency to metastasize and were more readily transplantable into an isogeneic host than those induced at later age periods. Data showed the advantage of prenatal and/or postnatal treatment in combination of life-long exposures to test agents as a more sensitive bioassay system in comparison with solely postweaning treatment. Because the early age period is the most sensitivity life phase to carcinogenesis, it appears to be a good model for prescreening various potential carcinogens, especially when only small amounts of test substances are available. The importance of the proper relationship of such bioassay to the other test systems regarding assessment of potential human risk has been emphasized.


Developmental mechanism of estrogen-induced irreversible changes in the mouse cervicovaginal epithelium. Neonatal female mice of the NMRI strain, given injections of 17 beta-estradiol or DES, were studied with respect to immediate effects and those that appeared in the animal's adult stage. With the estrogen dose used (5 micrograms daily), proliferation of the pseudostratified columnar epithelium in the upper part of the müllerian vagina was inhibited. This resulted in the occurrence of regions containing an RCE in the uterine cervix and upper vagina of adult animals instead of the normal squamous epithelium. Later, the RCE developed into adenosis; subsequently, suspected malignant changes were seen. Besides the morphologic differences compared with control animals, neonatal estrogen treatment resulted in changes in the amount of CVA. Compared with controls, the amount of CVA was high in the superficial mucified vaginal cells of neonatally DES-treated mice, subsequently castrated and given estrogen as adults. The RCE had a low level of CVA. An interaction of estradiol and prolactin was important for the CVA level. Neonatal estrogen treatment may result in persistent changes in the regulation of plasma prolactin. A comparison is made between the estrogen-induced changes in mice and the DES effects in the female offspring of women exposed to DES during pregnancy. The importance of the mouse model for the study of the relevance of estrogen-induced, irreversible changes and other factors in the development of human clear cell adenocarcinomas in the vagina and cervix is stressed.


Clinical genetics and pediatric neoplasms: pathogenetic and etiologic perspectives. Clinical and genetic aspects of pediatric neoplasms were reviewed from pathogenetic and etiologic perspectives. Developmental principles and phenomena common to several tumors and tumor syndromes were identified, summarized, and critically evaluated. Their enumeration may be useful in future cancer research. No single hypothesis on the cause and pathogenesis of cancer appears to apply to all disorders. We believe that multiple causes and pathways lead to the phenotype "cancer" and that in particular the pathogenetic relationship between tissue dysplasias and cancers deserves increased attention.


Metabolites of diethylstilboestrol induce sister chromatid exchange in human cultured fibroblasts. Diethylstilboesterol (DES) is one of the few substances for which a clear association with carcinogenicity has been established in man. Nevertheless, it is still widely used, mainly as a cheap oestrogen to increase the slaughter weight of beef, but in spite of this it is not known if residues in the meat or metabolites excreted by the cattle are hazardous to man. It is also unknown whether there is a threshold dose below which DES is harmless. A threshold might be expected if a hormonal mechanism of carcinogensis rather than metabolic activation to an electrophically reactive species operats. This possibility was supported by the observations that DES, in contrast to most other carcinogens, failed to induce mutations in the Salmonella/microsome test or malignant transformations of eukaryotic cells in culture. It is also disturbing that DES, one of the few known human carcinogens was negative in these two most widely used short-term tests introduced as fast early-earning system for potential carcinogens. We now report that DES is positive in sister chromatid exchange (SCE) induction, a short-term test for which a high correlation with the carcinogenicity of the compounds tested has been observed. Moreover, we show that metabolic activation was involved. Two different pathways leading to metabolites much more active in SCE induction than DES itself ('proximate agents') were established.


Effect of methylene blue and thiol oxidants on pancreatic islet GSH/GSSG ratios and tolbutamide mediated insulin release in vitro. Methylene blue (an oxidant of NADPH), diamide (an oxidant of glutathion-SH [GSH]) and tertbutyl hydroperoxide (a substrate of glutathione peroxidase) significantly decreased the GSH content of pancreatic rat islets and decreased their GSH/GSSG ratio. They also significantly depressed the single peak insulin response to tolbutamide by the isolated perfused pancreas as well as its synergistic action with glucose in isolated pancreatic islets. These results suggest that the effect of tolbutamide alone and its synergistic action with glucose could depend on the islet NADPH and GSH. In addition it appears that augmentation of tolbutamide action by glucose in insulin release is mediated by the provision of additional NADPH and GSH through glucose metabolism.


Effect of peritoneal dialysis, haemodialysis and kidney transplantation on blood platelet function. I. Platelet aggregation by ADP and epinephrine. Quantitation of the thrombocytopathy of uraemics may be one useful way of evaluating forms of therapy. 24 patients treated by haemodialysis and peritoneal dialysis at two different times had platelet aggregation studies whose parameters were compared with those of 24 normal persons, 5 successful transplants or 13 untreated uraemics. Renal transplantation and peritoneal dialysis improved platelet function. The haemodialysis procedure itself impaired platelet function: this was not due to heparin.


Selective vitamin B12 malabsorption with proteinuria. Renal biopsy study. Percutaneous renal biopsy were performed on 5 patients with selective vitamin B12 malabsorption of whom 3 had proteinuria. Light microscopy showed slight prominence of the mesangial areas but otherwise the findings were normal. Electron microscopy showed increased mesangial matrix, thickening of the basement membrane at the mesangial areas and dark mesangial deposit. Light flocculent subendothelial material, moon craters, membranous convoluted structures, extracellular round particles and occasional intracellular microtubular inclusions were also seen in the glomeruli. The tubular basement membrane appeared thickened around a few tubules, showing membranous vesicular debris and convoluted structures. The capsular membrane also showed vesicular debris. On immunohistochemical examination the glomerular deposits contained immunoglobulins but not complement - an argument against their immunological nature. Deposits were seen only in patients who had been on inadequate treatment for years before the biopsy. Adequate treatment after correct diagnosis decreased the amount of deposits. Proteinuria did not apparently depend on the presence of glomerular deposits.


Subacute sclerosing panencephalitis associated glomerulopathy. Subacute sclerosing panencephalitis (SSPE) is a progressive neurologic disease associated with chronic measles infection. We have assessed renal function parameters and renal biopsy details in 14 patients with SSPE. All had normal renal function. However, 9 had microscopic hematuria. 9 patients had focal segmental mesangial proliferation and 5 had capillary wall thickening with deposits visible by light microscopy. 13 patients had glomerular C3 deposition and 4 had IgG deposits. SSPE is a disease caused by chronic viral infection, in which nephritogenic complex formation may occur.


Rat CNS in experimental chronic serum sickness: integrity of the zonulae occludentes of the choroid plexus epithelium and brain endothelium in experimental chronic serum sickness. The present study is an extensive systematic immunofluorescence and labelled electron microscopic investigation of chronic rat serum sickness brains. It is specifically directed at discerning effects of chronic serum sickness upon the zonulae occludentes of both the choroid plexus epithelium and the intra-cerebral endothelium. Although the choroid plexus is a known site of complex entrapment in systemic immune complex disorders, comprehensive immune studies of the CNS parenchymal vasculature have not yet been reported in either experimental or spontaneous immune complex disease. We examined by direct immunofluorescence techniques over 70 blocks of experimental chronic serum sickness brains taken from 16 animals with severe glomerular disease and found them to be uniformly negative for the presence of immune deposits. No horseradish peroxidase was seen beyond the restricting zonulae occludentes of either the choroid plexus or the cerebral endothelium in tissue from three serious affected animals. These structural barriers retained their integrity despite the extensive circulation and deposition of complexes and complement induced in the experimental model and the associated release of vasoactive substances.


Use of anal sphincter electromyography during operations on the conus medullaris and sacral nerve roots. The mechanical activity of the anal sphincter can be translated into electrical activity and recorded on graph paper or an oscilloscope. The activity of the anal sphincter may be extrapolated to activity of the external urethral sphincter because both are striated muscles innervated by the pudendal nerve that arises from S-2, S-3, and S-4. Stimulation of these nerves causes contraction of the sphincter muscles, and a deflection of the recording device occurs. This technique was employed intraoperatively in monitoring operations on the conus medullaris and sacral nerve roots in 10 patients with spinal dysraphism (age range, 3 weeks to 15 years). Their diagnoses were tethered conus, 4; lipomeningocele, 3; spinal hamartoma, 1; syringocele, 1; and sacral arachnoiditis, 1. With general anesthesia, and the patient in the prone position, an electrode-containing anal plug was inserted or two needle electrodes were inserted into the anal sphincter muscle. The electrodes were connected to the electromyography recording stylus of the urodynamic bladder diagnostic unit. During the spinal operation, whenever a structure could not be identified clearly, it was stimulated with the disposable electrical stimulator and, if oscillations of the stylus occurred (indicating contraction of the anal sphincter), the structure was preserved. This technique permitted spinal operations in these 10 patients without changes in neurological or urological function.


Cerebrospinal fluid dynamics in patients with pseudotumor cerebri. CSF dynamics were determined as a function of intracranial pressure in patients with pseudotumor cerebri. Servocontrolled variable rate lumbar infusions were used to determine net CSF-absorptive capacities and resting pressures in 10 patients; serial studies were done in 5 of the patients. Nearly all of the patients had abnormally low CSF-absorptive capacities. On the other hand, marked elevations in resting pressure were not a constant feature of the disease. Concurrent changes in the cerebrovascular bed could introduce errors into this manometric determination of CSF dynamics; the significance of this potential artifact is examined. The results of this study suggest that the CSF compartment may be of etiological importance in the pathophysiology of pseudotumor cerebri.


[Stereotaxic ventroposteromedial thalamotomy in the treatment. Clinical observations and physiopathological considerations]. In 6 patients the authors performed stereotaxic ventroposteromedial thalamotomy for abolition or reduction of pain. The operation produced lesions in the centrum medianum and parasfascicular nucleus. In 2 cases unilateral operation was performed contralaterally to the side of pain, in the remaining cases the operation was done bilaterally as a one-step procedure. Postoperative follow demonstrated that in 1 case improvement was completely absent, in 4 initial good effect was transient and pain returned after several weeks and in only 1 patient very good effect persists for over 12 months. In the light of these experiences and a survey of the pertinent literature the authors reach the conclusion that limited stereotatic lesion of the so called non-specific pain-transmitting thalamic nuclei produces permanent abolition or alleviation of pain in few cases only. The pathophysiology of pain is discussed in the light of these data.


Kidney donation: needs and possibilities. The need for cadaver kidney donors far surpasses the present supply. The subject of how to increase the number of donors is extremely complex, involving not only the medical issue of determination of brain death, but also philosophical, religious, legal, political, psychological, and economic considerations and the opinions of leaders and lay groups. It now seems that the physician can rapidly and unequivocally ascertain brain death, that the law not only recognizes this but can facilitate organ retrieval, that adequate numbers of potential donors should be available, and that both the public and physicians generally favor retrieval. Our survey of patients seeking aid in the emergency room revealed that 19% had signed the donor statement on their driving license. Of the neurosurgeons and neurologists who responded to a questionnaire, 74% had requested donation and 37% had obtained permission for organ retrieval. Review of our case material revealed that 60% of individuals with head injuries alone who were hospitalized for over 3 days were suitable donors. Of the 54 kidneys retrieved during a 6-month period, 49 (90%) were transplanted. Because most potential donors come to the attention of neurosurgeons and neurologists and because it seems ethically appropriate for physicians to consider transplantation when death is certain, we suggest that an organized effort be undertaken to develop a liaison with transplantation services to facilitate the process of obtaining adequate numbers of cadaver kidneys.


Isolation of influenza virus from muscle in myoglobinuric polymyositis. We report the first isolation of influenza virus from muscle in a man with myoglobinuria and acute polymyositis. Influenza virus was isolated from cultures of Madin Darby bovine kidney and primary rhesus monkey kidney cells inoculated with muscle homogenates in the presence of trypsin; the virus was identified by neutralization and hemagglutination inhibition studies using influenza B/Lee antiserum. Viral plaque assay was performed with Madin Darby canine cells. Viral antigen was also detected by specific immunofluorescence in muscle, and myxovirus-like particles were seen in subsarcolemmal vacuoles by electronmicroscopy. The pathologic findings were similar to those of childhood dermatomyositis, except for a large proportion of necrotic muscle fibers. The evidence suggests that the pathogenesis of influenzal polymyositis in this patient involved direct viral infection of muscle.


Studies in aging of the brain: IV. Familial Alzheimer disease: Relation to transmissible dementia, aneuploidy, and microtubular defects. Alzheimer disease was transmitted in a pattern consistent with an autosomal dominant trait in three families. This brings to 50 the number of such families reported. In one of our families, one patient had histologically confirmed Alzheimer disease, whereas her sister had proved spongiform encephalopathy. Other data suggest a link between familial Alzheimer disease and transmissible dementia. Alzheimer disease is associated with abnormal neurofibrillary structures, Down syndrome, and abnormal numbers of chromosomes in lymphocytes (aneuploidy). These observations are consistent with a disorder in the physiology of tubular-filamentous structures involving different cell types.


Isolated bilateral oculomotor paresis due to lymphoma. A patient with histiocytic lymphoma developed bilateral oculomotor nerve palsies, sparing the pupils. At postmortem examination, there was lymphomatous infiltration in the oculomotor nerves. To our knowledge, this is the first patient with lymphoma to manifest these isolated findings.


[The complement fixation test in leishmaniasis. Comparison between an antigen extracted from leishmania cultures and one extracted from BCG]. A comparison between a BCG antigen and various batches of an antigen extracted at different times from leishmania cultures in the fixation of complement reaction is reported. A better response was obtained with BCG (further confirmation on a larger series is being sought), whereas the leishmania antigens were difficult to prepare and their batch titres were not constant.


Energy balances in obese mice.

Energy balances in obese mice. According to most existing theories, the regulation of energy balance is achieved by control of energy intake. This study was undertaken to find out whether there was control of energy output as well. Food intake, energy balance and the feed efficiency of weanling female mice made obese with injections of gold-thioglucose and monosodium glutamate indicate that the obesity is primarly due to an increased energetic efficiency, and suggest that the hypothalamus plays a role in controlling energy output. In the case of treatment with MSG, a relative obesity was observed, i.e. an increase in body fat without any change in body weight. This indicates that the CNS centres for the regulation of body weight and body fat are probably not the same. It is suggested that MSG obesity will be a suitable model for comparative studies of body weight and the regulation of fat content. It is concluded that chemically induced obesity is due more to a lower metabolic rate than to an elevated food intake.


Fetal cardiac arrhythmias.

Fetal cardiac arrhythmias. Fetal cardiac arrhythmias have been classified and the current literature reviewed. Emphasis is placed on antepartum diagnosis and appropriate therapy. The incidence of congenital heart disease varies with the type of arrhythmia. The differential diagnosis of fetal cardiac arrhythmias and management are discussed.


Effect of different fixatives on the localization of human melanoma antigens by immunofluorescence. This study was designed to study the effect of different fixatives on melanoma antigens by immunofluorescence. Two postautoimmune antimelanoma sera were tested on two human malignant melanoma cell lines fixed with different fixatives by indirect immunofluorescence. Ethanol, methanol, formalin, trichloroacetic acid and acetone gave sharp membrane fluorescence. Minimal to moderate cytoplasmic fluorescence was seen with acetone but none with the others. Formalin gave the highest membrane fluorescent antibody titers at 1/512. Isopentane and isooctane yielded bright cytoplasmic fluorescence. Weak diffuse cytoplasmic fluorescence was seen with glutaraldehyde. Fluorescence was completely abrogated by paraformaldehyde. No fluorescence was seen with four nonimmunized melanoma sera and phosphate-buffered saline when used as controls. It can be concluded that different fluorescent patterns were seen on melanoma cells when different fixatives were used.


Immuno-electron microscopic localization of a choriogonadotropin-like antigen in cancer-associated bacteria. The presence of choriogonadotropin-like material and its intimate association with the membranes of the wall of bacteria isolated from cancer patients, has been demonstrated by immuno-electron microscopy utilizing the indirect peroxidase-antiperoxidase-labeled antibody technique. The bacteria were an Escherichia coli strain isolated from a carcinoma of colon, and ATCC 25559 strain of Eubacterium lentum, an anaerobic microorganism originally isolated from a rectal tumor.


Astigmatism and the Flieringa ring.

Astigmatism and the Flieringa ring. Routine use of a Flieringa ring in conjunction with a large corneal section for intracapsular or extracapsular surgery facilitates more accurate wound closure and can significantly decrease the amount of postoperative astigmatism.


Maintenance of mydriasis with topical indomethacin during and after penetrating keratoplasty in the rabbit. The use of indomethacin eyedrops, 0.5%, in combination with topical atropine and phenylephrine, prior to and immediately following an 8-mm penetrating keratoplasty in rabbits maintains maximal pupillary dilation. With this technique, we achieved clear grafts without synechiae in virtually every instance.


Astigmatic considerations in corneal graft. Some fictions about astigmatism should be dispelled: 1) Sutures determine astigmatism. They do not. 2) The size of the graft is contributory to astigmatism. It is not contributory. 3) Anterior or posterior cutting of the graft makes no difference. It does make a difference. 4) Same size trephine can be used to cut graft and recipient opening. Not when graft is cut from posterior surface or significant flattening will result. 5) A small cutting error is of no consequence. A small cutting error can cause a great deal of astigmatism. Tissue factors are paramount. Sutures must maintain wound apposition primarily. Posterior cutting requires a larger diameter trephine. A one-half-mm cutting error can cause an astigmatism of five diopters. Excessive corneal astigmatism, when it does occur, can be controlled by corneal wedge resection. The surgical keratometer identifies and limits surgical and suture-induced errors. Success in microsurgical keratoplasty can no longer be defined only as a clear graft. It must include also minimal or no residual optical error.


Indications, complications and prognosis for repeat penetrating keratoplasty. A review of 47 repeat penetrating keratoplasties in 29 eyes showed the most frequent indications to be Fuchs' dystrophy, bullous keratopathy, and keratoconus. The most common postoperative complications were edema, glaucoma, and vascularization. Ninety other surgical procedures were performed in 26 of the 29 eyes. Final vision was no worse than 20/300 in 26% of the group. It is suggested that repeat grafting should be continued in the absence of contraindications.


Dacryocystorhinostomy: a modification of the Dupuy-Dutemps operation. In a series of 112 cases, dacryocystorhinostomy with direct anterior and posterior flap anastomosis has produced a success rate of 94%. Modifications from the original procedure described by Dupuy-Dutemps include preparation of the lacrimal sac flaps and preplacement of the sutures prior to the osteotomy which facilitates accurate identification and approximation with the nasal flaps. Adaptic gauze impregnated with polysporin ointment is packed into the rhinostomy site and out to the anterior nares to maintain patency and minimize clot and membrane formation. Common canalicular stenosis must be recognized and treated with silicone intubation to prevent failure in an otherwise correctable situation.


Skin tumors and trephines.

Skin tumors and trephines. Outmoded glaucoma and corneal trephines may be used to obtain incisional and excisional biopsies from eyelid lesions. The wounds created in doing the incisional biopsy are ignored and those created by doing excisions are closed by grafts using the same trephine.


The "disposable" flap: a modified fornix flap for corneal retraction during cataract surgery. A simple and rapid method to facilitate corneal retraction with a fornix-based conjunctival flap is described. The procedure eliminates the need for placement of a corneal traction suture during cataract surgery and lens implantation.


Successful argon laser sclerostomy for glaucoma. A sclerostomy was produced in a case of chronic angle-closure glaucoma using the Argon laser. A filtering bleb was present two years postoperatively and pressure was normalized.


The eyebrow graft.

The eyebrow graft. The full-thickness eyebrow graft constitutes a valuable technique in restoring resected or devitalized brow tissue. Proper brow appearance may be obtained with this technique.


Tarsal grafting for correction of cicatricial entropion. A technique of tarsal grafting was used as a simple yet effective procedure for the correction of upper-lid cicatricial entropion. A tarsal graft, 3 to 4 mm in height, excised from the superior tarsus of the donor upper eyelid and placed in a marginal tarsotomy, vertically expands the posterior lamella of the involved lid. This graft also provides a base for suture fixation of the everted lid margin. One case of unilateral cicatricial entropion corrected with a contralateral tarsal graft and one case of bilateral cicatricial entropion corrected by ipsilateral tarsal grafting demonstrate results obtained with this technique. Functional and cosmetically satisfactory results have been achieved with this technique. No recurrence of cicatricial entropion has been noted. With this procedure, tarsus provides excellent graft material for correction of the eyelid deformities associated with cicatricial entropion.


Intraocular pressure after aphakic penetrating keratoplasty "through-and-through" suturing. Our clinical study was designed to determine whether "through-and-through" corneal sutures would prevent the postoperative intraocular pressure rise that occurs in 70% of aphakic eyes after uncomplicated penetrating keratoplasty. Twenty-five aphakic patients received the same operative procedure except that the corneal buttons of ten of them were sutured into place with "through-and-through" sutures. The intraocular pressures of patients with the "through-and-through" sutures were significantly lower than those of the other patients during the entire postoperative course.


Wedge resection in host cornea to correct post-keratoplasty astigmatism. The obvious problem with surgery of this nature is that the amount of wedge to be removed is partially guess work. Doctor Troutman's keratoscope attachment to his microscope is very helpful. I have tried thermokeratoplasty in a very similar case, but the disadvantages of pain, ulceration, vascularization, and considerable return to pre-burn K readings have made me abandon this technique. If there is an obvious override, then the keratoplasty wound itself must be revised in the usual manner. However, for the present, when a graft looks perfect but the K readings reveal otherwise, a judicious wedge resection between graft and limbus (location being in the flattest meridian) would appear to be a most reasonable operation.


A new microsurgical corneal trephine.

A new microsurgical corneal trephine. A new corneal trephine has been described which allows the surgeon to see the circumference of the cutting edge, as well as most of the cornea, lens and iris, while looking through the operating microscope. The trephine has a 3-mm cutting ring supported by an open "branding iron" structure.


Analgesia for operative dentistry: a comparison of acupuncture and placebo. Fifty-one volunteer patients participated in a study to evaluate the effectiveness of acupuncture as an analgesic for operative dentistry. For the twenty-six patients randomly assigned to an acupuncture group, needles were inserted through specially designed holders into the Ho-Ku points, located between the first and second metacarpals. An acupuncture pulse generator provided electrical current. For the twenty-five patients in a placebo group, the identical needle and holder arrangement was used. When inserted, however, the needles became embedded in plastic on the undersurface of the holders and did not touch the skin of the patient or receive any electrical stimulation. The patients and dentists were blind to this procedural variation. Analysis of ratings and responses indicated no differences in findings for the acupuncture and placebo procedures, with both having 100% success and high levels of patient acceptance. Since there was no electric current or penetration of the skin in the placebo group, the findings suggest that the successful use of acupuncture for restorative dentistry may be due to psychological and/or placebo effects in combination with a possible diminished need for analgesia because of the modern use of the high-speed drill.


Effect of temperature change on the sealing properties of Cavit and Cavit G. Sixty recently extracted intact anterior teeth were filled with Cavit G or Cavit. They were examined for dye penetration at room temperature and subjected to temperature change. Under the test conditions Cavit G and Cavit were resistant to penetration by aqueous methylene blue dye.


Detection of immune complexes in human dental periapical lesions by anticomplement immunofluorescence technique. Twenty-five human dental periapical lesions were obtained. The lesions were frozen, sectioned, and examined for the presence of immune complexes by employing an anticomplement immunofluorescence (ACIF) technique. Twenty-three of the periapical specimens were positive for antigen-antibody complexes. No staining was noted in the two lesions that were histologically diagnosed as periapical scar tissue.


Ischemic diseases of the large intestine. The blood flow within the walls of the digestive tract must be sufficient to maintain its structural and functional integrity. All episodes of vascular insufficiency cause ischemic damage to the organ and carry the threat of diffuse or focal necrosis. Certain forms of ischemic colitis or proctitis arise from episodes of reduced peripheric or splanchnic blood flow; indeed, those that do not culminate in necorsis of the colonic wall are more frequently caused by hemodynamic disorders than by vascular occlusions. The crisis is often mitigated by the development of collateral circulation, which is nevertheless of rather meager quality, such that the patients are very vulnerable to subsequent slight changes in cardiac output. Necrotic, gangrenous ischemic colitis arises from a combination of occlusive damage to the arteries and general hemodynamic disturbances. The vascular insufficiency might be slight or severe, temporary or long-lasting, localized or diffuse. In addition, the attack occurs in a septic medium in the presence of an abundant microbial flora that may be highly pathogenic. Thus infection complicates and aggravates the ischemic damage, with the result that the gangrenous aspect of the lesions tends to hide their ischemic origin. Indeed, the variability of the manifestations of the disease represents one of its primary characteristics and is a function of the different causative factors. A knowledge of the anatomy and pathophysiology of the splanchnic circulation and its hemodynamics is essential for a full appreciation of the diagnosis and treatment of the disorders and for the adoption of the aggressive approach necessary to improve the poor prognosis of ischemic diseases of the colon and rectum. The salient points have been stressed in the present chapter. The features of the different forms of the disease have been described, together with the necessary medical treatment and the indications for surgical for surgical intervention. In the relatively rare cases where operation is necessary, the tactics and techniques have been described. All treatment should be based on (a) constant, prolonged intensive care; (b) precise monitoring of any change in status; and (c) rapid excision of any necrotic (often gangrenous) tissue. Ischemic colitis is most likely to occur in elderly patients with a history of cardiovascular disease, but it is not excluded in younger individuals. It is a frequent entity and is potentially lethal. Although its clinical, radiological, and anatomical characteristics permit its classification as a separate disease, it is often confused with other disorders of the colon. Although the abdominal surgeon is most likely to be concerned with this disease, the vascular surgeon who attacks the lower aorta should always be on the lookout for possible occurrences of segmentary ischemia of the distal colon as a result of his intervention.


Electron microscopy of adipose tissue tumors: comparative features of hibernomas, myxoid and pleomorphic liposarcomas. Two hibernomas, 16 myxoid, and eight pleomorphic liposarcomas were studied by transmission electron microscopy. Neoplastic cells in hibernomas and the type I cells--adipocytes--in myxoid liposarcomas consistently display abundant lipid droplet populations and prominent basal lamina deposition. Despite some variability in their distribution, these features clearly pertain to the mature and/or maturing characteristics of brown and white adipose cells. On the other hand, the more primitive type II cells of myxoid liposarcomas display highly variable, and occasionally absent, lipid droplet populations and basal lamina deposition. Moreover, the type II cells may also display other features such as prominent cytoplasmic filaments and rough endoplasmic reticulum that, while not characteristic of typical adipose cells, are still consistent with the more primitive mesenchymal cells from which they are assumed to derive. The cells of pleomorphic liposarcomas exhibit a variable lipid droplet population and apparently total absence of basal lamina deposition. Moreover, they often display atypical cell junctions that are neither characteristic for adipose cells nor for the "primitive reticular cells" from which adipocytes presumably derive. These observations would suggest that some "high grade" sarcomas may no be truly "undifferentiated"; rather, they may often display structural characteristics indicative of multiple as well as variable lines of differentiation. Therefore, classifications of such tumors based on quantitatively limited observations may not truly reflect their evident complexities.


Histopathologic changes and the immune response within the jejunal mucosa in infants and children. Jejunal biopsies obtained from 45 children referred for a variety of clinical conditions were examined histologically and by standard immunofluorescence methods. The number of plasma cells was recorded per "mucosal tissue unit". The results showed that most of the immunoglobulin A (IgA) counts in infants under 3 yr with normal mucosa were low and that there was a rise in the number of IgA plasma cells starting after this age. Despite this, under pathologic conditions (partial villous atrophy with increased inflammatory cell infiltration--PVA) a significant rise in IgA plasma cells occurred in all age groups. Patients with coeliac disease tended to show the highest IgA as well as IgM plasma cell counts. In all other patients, IgM counts did not change significantly with age or histologic abnormalities.


The effect of human colostrum on neutrophil function. Strains of Escherichia coli were opsonized in human colostrum via heat stable opsonins and the classic complement pathway, but colostrum lacked capacity to opsonize E. coli via the alternative pathway. There was no bacteriostatic activity against serum sensitive E. coli strains, although specific antibodies against the strains were present. Neutrophils suspended in colostrum had normal chemotaxis and this was not altered by treating the colostrum with HCl.


Immunogenetic bases of congenital malformations: association of HLA-B27 with spina bifida. A random sample of 46 families with single and multiple cases of spina bifida has been selected from families referred to the Institute of Pediatrics for genetic counseling. This sample constituted a group of 92 patients and 102 offspring: 41 normal, 46 with spina bifida, and 13 with spina bifida occulta. Routine HLA typing was performed on the parents and their children. For each case, 13 HLA specifities from locus A and 15 from locus B were determined. Segregation analysis in families showed excellent agreement with the expected values. HLA gene frequencies in the affected children as compared with a control population of 240 normal adults, revealed significantly higher frequency for HLA-B27 allele: chi 2 = 11.9515, P (corrected for the number of alleles) less than 0.028. A significant relative risk of spina bifida development for a given HLA-B27 antigen was 2.7. In view of the presented results, routine HLA typing might be recommended for genetic counseling as a new tool for identification of high risk families.


Biochemical alterations in neonatal hyperbilirubinemia and bilirubin encephalopathy: a review. This review article discusses some current questions concerning the measurement of bilirubin in the blood of newborn infants and the relationship of these blood parameters to the biochemical defects responsible for bilirubin encephalopathy. A discussion of numerous theories, which have been put forth to explain the specific biochemical mechanism by which bilirubin acts on brain metabolism, demonstrates that presently there is no unequivocal explanation for the molecular events leading to bilirubin encephalopathy.


Fever and survival in the rat. The effect of enhancing fever. To study the effect of fever on infectious disease in a mammal, rats, partially restrained by an antirotatory device and with chronically implanted preoptic thermodes, were injected with Salmonella enteritidis and, in some of them, the hypothalamus was then continuously cooled to enhance the febrile response. All animals developed a fever that peaked 2 days after the infection, reaching 40.9 +/- 0.2 (SD) degrees C in the nine hypothalamic cooled and only 39.8 +/- 0.4 degrees C in the 13 control animals (P less than 0.001). All the hypothalamic cooled animals died within 8 days of infection, whereas only 23% of the controls had died after 28 days of infection (P = 0.0006). When the hypothalamus was continuously cooled in five uninfected animals, rectal temperature increased to 40.9 +/- 0.3 degrees C but 24 h later it had decreased to 39.6 +/- 0.3 (P less than 0.025). This decrease in body temperature suggests that the hypothalamic thermosensors had partially lost their effectiveness. It is concluded that cooling the hypothalamus increases the mortality rate in rats infected with S. enteritidis and that this effect could be mediated by the high body temperature or by the concomitant metabolic and endocrine responses thus induced.


Nucleotide sequence of the mitochondrial structural genes for cysteine-tRNA and histidine-tRNA of yeast. We have determined the nucleotide sequence of a segment of Saccharomyces cerevisiae mtDNA that contains the structural genes for a cysteine-tRNA and a histidine-tRNA. The genes are approximately 85 bp apart, they do not contain intervening sequences or sequences coding for the 3'-CCA terminus and they are surrounded by nearly pure AT segments. The tRNAs deduced are very AT-rich, 74 and 75 nucleotides long, respectively, and contain one or more unusual features not found in tRNAs from other sources.


Characterizing wild-type and mutant promoters of the tetracycline resistance gene in pBR313. By employing a system of RNA polymerase binding and restriction endonuclease digestion, we demonstrate that the region in and around the Hind III site of pBR313 and pBR322 is the promoter for the tetracycline (Tc) resistance gene(s). Furthermore, it is shown that this region was transferred intact from pSC101 during the construction of the latter plasmids. The in vitro insertion of a few base pairs at the Hind III site produces a series of "down" promoter mutations in which the level of in vivo Tc resistance is reduced. Sequence analysis of the various promoter mutations revealed significant base pair rearrangements in the region between -40 and -12 of the promoter. While these base alterations do not appear to affect the firm binding of RNA polymerase, they do affect the ability of mutant promoters to initiate transcription. These observations suggest that the region from -40 to -12, previously designated as the "recognition region", is actually involved in the process of initiation of transcription.


Characterization of an improved in vitro DNA replication system for Escherichia coli plasmids. A modified in vitro replication system has been characterized and used to catalogue the host proteins required for the replication of plasmid RSF1030. These extracts differ from systems described previously in that endogenous DNA is removed. Replication in vitro therefore requires an exogenouos RSF1030. Synthesis in the in vitro system faithfully mimics in vivo replication with respect to the products synthesized, effects of specific inhibitors, and requirements for RNA polymerase and DNA polymerase I. In addition, we find that proteins encoded by dnaB, dnaC, dnaG, dnaI, dnaP and polC (DNA polymerase III), are required for in vitro plasmid synthesis. The product of dnaA is not required. Extracts prepared from E. coli mutants deficient in in vitro replication can be complemented by addition of purified proteins or of extracts carrying the wild type protein.


Diabetes mellitus and pregnancy--the nine month experiment. The writer presents a personal experience of caring for the pregnant diabetic. During a 27 year period (1951-1977) 328 women were treated in 649 pregnancies (668 infants). There was no maternal death. The overall perinatal loss was 9.1%. The Caesarean section rate was only 23%. In recent years a policy of intensely strict control of diabetes has improved foetal survival. It is suggested that this may represent objective evidence that strict control of diabetes has long term benefits.


[Compression method throughout the ages]. The compressive method was practiced instinctively in farthest antiquity. Its development in Western Europe over the past two centuries may be artificially divided into 3 phases. The first phase, which belongs to the prehistory of Phlebology, includes two notable facts: the start of ambulatory compression in London around 1800, and the interest that the French school immediately showed in this discovery. However, this measure was soon abandoned, since around 1880, in the Paris hospitals, ulcers of the leg were being treated by mercury plasters and rest in bed. The second phase--1900 to about 1950--is marked by the empirical development of the compressive method, mainly in chronic phlebopathies. The synergic effect of walking is definitively established; the treatment of deep-set phlebites by ambulatory compression is discovered by H. Fischer in Germany and then in France by L. Nard. Beginning in 1950, this empirical data is both spread by the new Phleboloby Societies, and submitted to rigorous scientific study. Clinicians (especially H. R. Van der Mollen), assisted by physicists, physiologists and biologists, establish the laws of "therapeutic counter-pressure" and transpose them in the textile industry. New materials facilitate the use of elastic pressure. Underestimated or little known by most physicians, ambulatory elastocompression remains for Phlobologists a fundamental therapy. At a time when sedentary living and excess use of drugs are being widely denounced, it still has a promising future.


Preoperative magnification angiography of donor and recipient sites for clinical free transfer of flaps or digits. Based on the 14 free flap transfers we present with full survival, we recommend peroperative magnification angiography of both the recipient and donor sites. In our hands, this type of preoperative assessment seems to increase the margin of safety.


Use of a sliding flap from the abdomen to provide cover in breast reconstructions. A method of breast reconstruction after mastectomy, using wide undermining of the chest and abdominal skin and advancement of the latter upward to create a pocket, is described. A double-lumen silicone prosthesis is inserted to create the mound, and various methods for nipple-areolar construction are described. The method has been in use for 20 years, and it has been quite satisfactory when the deficiency in the chest wall cover is not too large.


Leg repairs with an island flap from the dorsum of the foot, based on the anterior tibial vessels. We report 20 chronic leg ulcers successfully treated by rotating an anterior tibial flap, which is a modification of the dorsalis pedis flap. The sizes of the flaps ranged from 6 x 6 cm up to 15 x 13 cm; the largest ones are not recommended, for fear of development of persistent lymphedema of the foot. These flaps are dissected upward through the leg and pedicled on the anterior tibial vessels, so they can be rotated to any site on the anterior, lateral, or medial side of the leg.


Rate of skin blood flow in various regions of the body. Skin blood flow was measured by local clearance of 133Xe, and skin temperature was measured by medical thermography in various parts of the body. 1. A significant linear decrease in skin blood flow was observed with increasing age in the deltoid region. 2. The skin blood flow in the facial and pectoral areas was considerably higher than in the deltoid region. 3. The skin blood flow in the posterior cervical, lateral thoracic, lateral abdominal, and gluteal sites was less than in the deltoid region.


A transpositional skin flap for release of volar contractures of a finger at the MP joint. We describe a finger flap which, in properly selected patients, and with careful planning of the incision design, has been useful for covering small defects over the volar aspects of the MP joint. The donor site can be closed without skin grafting.


Attempts to increase the surviving length in skin flaps by a moist environment. A method of raising a random patterns flap on the back of a rat was used to study the relationship between the surviving length and distance of dye penetration. It was found that the intraoperative dye distance was an accurate predictor of survival length in the Control Group. The effects of dressing were evaluated against the controls. An apparently significant increase in the survival length (beyond the dye distance) was seen with the "tunnel procedure" we used. It is suggested that a moist environment will favor survival of that portion of a flap where necrosis is usually seen when no dressing is used.


Hypospadias repair with subcutaneous suture and tissue adhesive for surface closure. A combination of a running P.G.A. subcutaneous suture, reinforced by butyl-cyanoacrylate tissue adhesive for surface bonding of the skin, has enabled us to reduce our rate of fistula formation by about 50 percent in hypospdias repairs by the Denis Browne two-stage or the Horton-Devine one-stage procedure.


Prevention of necrosis in island myocutaneous flaps in the pig by treatment with isoxsuprine. Experimental gracilis myocutaneous flaps were designed in the pig which consistently resulted in 81 cm2 of surviving tissue and 194 cm2 of necrotic tissue. When these same flaps were raised in animals treated for two weeks preoperatively and 6 days postoperatively with isoxsuprine, there was 100 percent survival in all (8) flaps.


Repair of a lower leg defect with an ipsilateral gracilis myocutaneous flap. We report the use of a gracilis myocutaneous flap from the same thigh to repair a defect of the lower leg. This could be a useful alternative in well selected cases.


Moral treatment reconsidered: some sociological comments on an episode in the history of British psychiatry. A reappraisal is offered of the precise sense in which the introduction of moral treatment at the end of the eighteenth century marked a decisive shift in our characteristic ways of responding to and coping with the mentally disturbed. Some connections are explored between this new approach to the 'mad' and larger social movements and processes.


Survival on home haemodialysis: its relationship with physical symptomatology, psychosocial background and psychiatric morbidity. An entire group of 32 home dialysis patients from one hospital renal unit was assessed for psychiatric morbidity on a standardized interview of proven reliability. A rating of physical symptomatology and an enquiry into the childhood and psychosocial background were made at the same time. Psychiatric morbidity, physical symptomatology and a history of good relationships with both natural parents in childhood were inter-related. They were all related to survival on haemodialysis 3 1/2 years later. Survival was also associated with a coping spouse and full-time employment or housework by the patient. These findings are discussed in the light of current concepts of the psychosocial setting for physical illness.


Effects of relaxation therapy on cardiac performance and sympathetic activity in patients with organic heart disease. Six patients, with surgically implanted tantalum myocardial markers, were trained in deep muscle relaxation therapy. Analysis of individual responses and group means of blood pressure and ventricular dimensions during relaxation showed a decrease in plasma norepinephrine levels and indices of myocardial contractility compared to the control state. Heart rate changes in individuals during relaxation were directly correlated with changes in plasma norepinephrine levels, although group means for heart rate did not change significantly between control and relaxation periods. Base-line plasma norepinephrine levels were directly correlated with systolic blood pressure and were inveresly correlated with a measure of myocardial contractility. These data suggest that physiological changes during relaxation may be mediated through the sympathetic nervous system.


Changing concepts in psychosomatic theory. I. Historical analysis. Psychosomatic medicine has utilized static, linear, two-dimensional models in attempting to identify a causative relationship between psychosocially conceptualized events and biologically conceptualized ones. This has led to inherent difficulties that are logistically unresolvable. For example, the different language systems lend themselves to overlap with the possibility of addressing themselves to describing manifestations of the same phenomenon from dissimilar conceptual orientations. The problem is further complicated by attempting to link these together in a temporal sequence suggesting a causal relationship. We have ignored both feedback processes in terms of a sequential process modifying a preceding one and the possibility that a reverse order of relationships might explain some processes. In our quest for specificity, we have ignored that disease states are not static ones any more than is life but change over time, suggesting that alterations will occur in the original relationships proposed among our different systems of conceptualization. Among the remedies suggested for a reordering of our thinking are: (a) a revision of linear unidirectional causative models to cyclical bidirectional models; (b) a reformulation of two-dimensional temporal linear relationships toward three-dimensional spherical ones which overlap in time; (c) the relating of these aspects not to each other but to a third factor, common to the three which remains to be identified; (d) the development of a language that bridges the psychological, social and biological.


Psychopathology and psychotherapy in chronic physically ill patients. Within the scope of psychosomatic medicine somato-psychic diseases are of great importance theoretically as well as practically, especially in view of problems dealing with the patient's attitude toward his illness and his coping with the disease. Among the somato-psychic illnesses chronic physical diseases are of primary interest. The knowledge of their general and specific psychological and psychopathological symptoms are of great importance for a better understanding of these patients and in view of a favourable direction in therapy. This is demonstrated in the form of extracts with three groups of the chronic physically ill: (1) hemophiliacs; (2) patients on regular hemodialysis treatment and following renal transplantation, and (3) diabetics.


Psychosomatic medicine: some past and current concepts. Recognition of the body-mind dilemma goes back to antiquity. Growth in medical knowledge has produced an ever increasing emphasis on physiological deviations and somatic pathology--which too often is not accompanied by sufficient attention to the total patients. Psychosomatics is now the term often used by those who believe that illness in man is not usually caused by a single etiological agent. The American Psychosomatic Society succeeded in correlating biological processes with psychodynamics. The Academy of Psychosomatic Medicine had its roots in the belief that psychosomatic medicine belonged to all of medicine. Its goals were to close the gap between medicine and psychiatry. The Japanese Psychosomatic Society chose the best of both in setting its goals. Dunbar's personality profiles and Alexander's concept of specific conflicts are reviewed. Depression is seen to be a common core. Further correlations between depression and psychosomatic illness are evidenced by the work of Greene, Schmale and Engel. The contributions of Nemiah and Sifneos are reviewed. Many psychosomatic patients are noted to be incapable of expressing adequate feelings, which may account for the frequent failure of classical psychoanalytic techniques. The history of research is also reviewed. The role of biochemistry, neurophysiology and psychopharmacology in the understanding and management of psychosomatic problems is examined.


Materialism and spiritualism: the dualistic way of Western thinking. Ever since the beginning of Western philosophy in ancient Greece there have been two fundamental approaches to life in general: materialism and spiritualism. In the Renaissance this basic question came into discussion again. In the 19th century the real fight began. On the one hand we have had the materialistic 'leftists', namely Marx, with the political consequence of the Russian revolution. On the other hand we had Kierkegaard, Bergson, etc. searching for the fundamental facts in human life, enabling us to survive in dignity. The moment has come, where we must see that human emotion is by far more important in the question of life and death, namely in psychosomatic illness, than all the riches of the world.


East and West.

East and West. Western psychotherapy is very rationalistic, and especially psychoanalysis regarding the suppression of desire as the cause of neurosis. On the contrary Japanese psychotherapy explains neurosis as the imbalance which is the weak point of human nature. I would like to compare Western and Eastern psychotherapeutic backgrounds.


[Effect on the administration of LHRH on LH and prolactin plasma levels in adult female rats ovariectomized and maintained in constant light (author's transl)]. The influence of prolonged periods of constant lighting on the plasma levels of LH and prolactin in adult female rats has been studied. No differences in either hormones are observed between intact animals under constant light of under a 12 hr (controls) darkness schedule. After ovariectomy LH values increase on both experimental conditions, with higher levels in the control group (p less than 0.01). After ovariectomy, a similar pattern is observed in animals under constant light, or under a 12 hr light darkness schedule, in the decrease of prolactin levels and in the increase of plasma LH levels after LHRH administration (100-1,000 ng). The stress induced by experimental manipulation, ether anesthesia and saline injection elevates plasma prolactin in both groups. LHRH administration blocks this response.


[Disseminated intravascular coagulation (DIC) after endotoxin infusion into the common bile duct of rabbits (author's transl)]. Endotoxin from E. coli was infused into the distally ligated common bile duct of rabbits under the static pressure of 25 cm H2O. Fibrinogen, soluble fibrin monomer complexes, antithrombin III, leukocyte and platelet counts were estimated before, and 2, 4, and 6 h after endotoxin infusion. All parameters were found significantly changed 2 h after endotoxin infusion. While fibrinogen level, AT III, leukocyte and platelet counts decreased after the endotoxin infusion the amount of SFMC increased. The change of hematological parameters showed a pattern characteristic of disseminated intravascular coagulation (DIC). In accordance with this microclots in the glomeruli of the kidneys could be demonstrated in all endotoxin-treated animals by pathological study. The findings suggest that by endotoxin infusion into the common bile duct, as a focal origin, DIC can be produced.


Comparison of gastric secretory response in man to duodenal and jejunal liver extract perfusion. The stomachs of six healthy volunteers were intubated with a Levine tube. In addition, a thin polyethylene tube was placed in the proximal jejunum or in the proximal duodenum. After a 1-h period with no perfusion the intestine was perfused for 2 h with 7% liver extract (LE) (pH 5.5; 380 MOsm/kg water) at a rate of 100 ml/h. In control tests 200 ml of 0.9% physiologic saline solution were used as perfusate. Reflux to the stomach was determined by addition of radioactive B12 to the perfusates. Plasma gastrin, gastric acid, and pepsin levels were measured in 15-min periods. During perfusion of the proximal jejunum only pepsin outputs were increased significantly. During duodenal perfusion of LE, gastric acid and pepsin outputs were increased to 31% and 73% of maximal pentagastrin stimulation, respectively. Controls showed no changes in gastric secretion. Plasma gastrin levels were not elevated after jejunal or duodenal perfusion. These results confirm that the intestinal phase of gastric secretory stimulation does exist in humans. Furthermore, it appears that the major portion of this stimulation originates from the duodenum and is not gastrin-dependent.


Peptidergic and adrenergic innervation of pancreatic ganglia. Immunocytochemical studies have revealed the presence of nerves showing vasoactive intestinal polypeptide (VIP), substance P (SP), enkephalin, and COOH-terminal gastrin/CCK immunoreactivity in the feline pancreas. Most peptide-containing nerve fibers are detected in ganglia of the pancreas, where they appear to innervate the ganglionic cell bodies. Adrenergic nerve fibers are also detected in pancreatic ganglia. The peptidergic and adrenergic nerves are only occasionally detected in the vicinity of pancreatic exocrine cells. VIP, SP, enkephalin, and gastrin/CCK exert strong effects on the secretory functions of the pancreas. Our results suggest that that ganglia may represent an important physiological site of action for these peptides and for norepinephrine.


Substance P and enteroglucagon-like immunoreactivity in argentaffin and argyrophil midgut carcinoid tumours. The presence of serotonin, substance P and enteroglucagon was investigated in 8 argentaffin and argyrophil midgut carcinoid tumours. All tumours were argentaffin and displayed formalin-induced fluorescence indicating a content of serotonin. In addition, all 8 tumours showed substance P immunoreactivity and 7 of them enteroglucagon immunoreactivity. The results indicate that the midgut carcinoid tumours are as a rule multihormonal.


Spontaneous argyrophil cell carcinoid in the glandular stomach: immunohistochemical study of gastric endocrine cells in normal and tumour-bearing mastomys. Endocrine tumours (argyrophil cell carcinoids) are frequent in the oxyntic mucosa of mastomys. The tumour is notable for its high histamine content and for its high histidine decarboxylase activity. The tumour is thought to arise from the histamine-storing, enterochromaffin-like cells of the oxyntic mucosa. They are of two ultrastructurally distinguishable types, ECL cells and A-like cells, both of which have been demonstrated in the tumour. Identical cells have been demonstrated in the oxyntic mucosa of the rat; there is much evidence that in this species the functional activity and the number of these cells are determined by the serum gastrin concentration. However, tumours have never been found to arise from these cells in the rat. As an initial step in an attempt to explain the formation of the gastric endocrine tumour in the mastomys we examined the distribution and frequency of occurrence of endocrine cells in the mastomys stomach. Gastrin cells in the antrum of mastomys seemed to occur in about the same frequency as in the antrum of rat and mouse. 5-HT-storing enterochromaffin cells, however, were considerably more numerous in the mastomys, whereas the somatostatin cells in the antrum were fewer. The number of enterochromaffin-like cells and somatostratin cells in the oxyntic mucosa of mastomys was much lower than in the rat and mouse. Once developed, the gastric endocrine tumour seems to reduce the antral gastrin cell number; the larger the tumour the greater the reduction.


Continued experimental study on the pathogenesis of sporadic bacteriuria in the rat. An experimental model implying ligature of the left ureter in the rat has previously (1977) been described by the author. The same model has been used in the experiments which are presented in this paper. The aim has been to study further the hematogenous seeding of bacteria to the hydronephrotic left kidney. The experiments seem to confirm the author's view that sporadic hematogenous infection with intestinal bacteria occasionally takes place and can be demonstrated by this method. Intravenous injection of E. coli showed that the minimal kidney infecting dose amounted to 0.5 ml E. coli 10(6) bacteria per ml. The author found considerable increase of sporadic infection after splenectomy and partial liver resection.


The patterns of peripheral plasma renin concentration in the early post-renal-transplant period. Serial determinations of peripheral plasma renin concentration (PRC) were performed in 11 kidney transplant recipients during the early post-transplant period. In 5 recipients with late onset of graft function, PRC values were increased during the anuric phase and, subsequently, PRC values declined in every during restoration of graft function. In 4 recipients with an acute renal allograft reaction, PRC values were increased at the onset of the allograft reaction in 3 with hypertension whereas PRC values were normal in one normotensive recipient. Subsequently, PRC normalized in the hypertensives coincident with increasing body weights. In 2 recipients with an uncomplicated course and with a normal graft function immediately after transplantation and throughout the study period, PRC values were constantly normal. The results indicate that acute anuria in the early phase after kidney transplantation is associated with an increased release of renin. The results also suggest that an increased activity of the renin-angiotensin system may be counterbalanced by sodium and fluid retention in hypertension following an acute renal allograft reaction.


[Immunosuppression, bone marrow infusion and low dose androgens, successful therapy of severe aplastic anemia]. 18 patients with severe aplastic anemia (SAA) but without an HLA-identical sibling were treated by antilymphocyte globulin (ALG) followed by infusion of marrow cells from a semi-compatible family donor. 13 of these received low dose androgens after ALG: 11 (85%) achieved stable remission without transfusion requirement. One patient relapsed after 4 months, one patient with only partial remission died from infection. None of the 4 patients who did not receive androgens after ALG achieved remission. ALG, marrow and low-dose androgens represent a promising therapy for SAA and can be favorably compared with allogeneic bone marrow transplantation.


Heterogeneity of vertebrate luteinizing hormone-releasing hormone. Radioimmunoassay and chromatography analyses of hypothalamic luteinizing hormone-releasing hormone (LHRH) have demonstrated the presence of LHRH-like immunoreactive peptides in a wide range of vertebrates. Contrary to previous reports, the molecule differs in various vertebrates. Avian, reptilian, and teleostean LHRH's are chemically distinct from the mammalian peptide but are in themselves indistinguishable. However, amphibian LHRH appears to be identical to the mammalian peptide. These findings have interesting evolutionary implications.


Interactions of complement with the red-cell membrane. Interactions of the complement components with the red-cell membrane are, as delineated, many and complex. Much is known about the nature of the complement components that take part in these interactions, but relatively little is known about the membrane or the components of the membrane with which they interact. Such understanding will be essential if we are to be able to explain the great resistance to complement lysis shown by normal red cells or the abnormalities that result in increased or decreased interacition of complement with abnormal red cells.


Granulocyte aggregation as a manifestation of membrane interactions with complement: possible role in leukocyte margination, microvascular occlusion, and endothelial damage. Activation products of the terminal complement cascade potently affect granulocyte function, inducing, for example, their migration toward (chemotaxis), and adherence to (opsonization), microbes, and stimulating their production of microbicidal oxygen radicals such as superoxide anion, and the like. We present studies that demonstrate that a C5-derived peptide, probably C5a, is a potent promoter of granulocyte and monocyte adhesion to endothelium (margination) and, in addition, causes granulocyte autoaggregation in vitro and in vivo. Although possibly beneficial by producing phagocyte clumps to mechanically entrap unwanted microbes, such aggregates may be deleterious, particularly if sustained, especially in the lung.


Platelet-endothelial cell interactions.

Platelet-endothelial cell interactions. We are in an era in which there has been a rapid accumulation of new information about the endothelium and the interactions of platelets with the vessel wall. The decade of the 70s could aptly be designated as the "prostaglandin and endothelium period." One can only speculate that the future will be equally interesting and challenging. It is quite possible that discoveries of congenital and acquired defects of the endothelium will parallel those already described for the platelet and coagulation factors. What is currently looked upon today as a baffling and frustrating case of resistant thrombosis by the clinician may be unraveled tomorrow by the talented and creative investigator who can develop better approaches to the study of the endothelium and platelet interactions with the vessel wall.


Penetrating keratoplasty using McCarey-Kaufman preserved corneal tissue. Two hundred consecutive penetrating keratoplasties, using suitable donor corneas stored in modified tissue culture medium (M-K medium), were performed by a single surgeon over a 21-month period. Two hundred consecutive cultures of the donor corneosclearl rims for aerobic and anaerobic bacteria and fungi, done immediately after surgery, yielded 25 positive cultures for aerobic and anerobic bacteria and three for fungi. No clinical infections nor primary donor failures were encountered with patients after one to 21 months of follow-up. Preservation of excised corneas by trained technicians, under rigidly sterile, laminar-flow, tissue culture conditions appears to be a convenient, safe, and effective method of corneal preservation which permits elective keratoplasty.


Nutrition in pregnancy--1978.

Nutrition in pregnancy--1978. Nutrition in pregnancy is receiving increased emphasis with the reports of adverse effects of alcohol, tobacco, and drugs on the outcome of pregnancy. Numerous articles concerning nutrition in pregnancy have appeared in the lay press. Almost daily a new method of weight reduction appears as a panacea for a weight conscious public. Both the woman and her physician may be confused, since during the last 40 years women have been starved, told to eat no meat, to eat red meat, or to eat ad lib because there should be no limit on weight gain during pregnancy. Can the practitioner with little formal education in nutrition identify the woman likely to be nutritionally at risk? If identified what should they be counseled regarding weight gain in pregnancy? Reasons for the changes in attitude about nutrition in pregnancy are reviewed herein, and methods of identifying the woman nutritionally at risk are presented. The importance of grouping women into underweight, normal weight, and overweight categories and of making individualized weight gain recommendations are discussed.


The effect of prednisolone on red cell survival in patients with falciparum malaria. Radioisotope red-cell survival studies were carried out in 20 patients with falciparum malaria following quinine therapy. The mean parasite clearance time of the patients receiving quinine sulfate was 49 hours and those of the patients receiving quinine sulfate and prednisolone was 46 hours. The red-cell survival was correlated with the initial hematocrit level in both groups but the daily dose of 40 mg prednisolone did not mitigate the red cell survival.


In vivo and in vitro studies of quinine sensitivity of Plasmodium falciparum in Thailand. Forty-four patients with falciparum malaria were studied. Nine patients were given quinine orally at a daily dose of 1.5 gm base for a period of 14 days. The mean parasite clearance in all 9 patients was 3.3 days, and none had recrudescence in follow-up examinations for 31 days. The in vivo study of these 9 patients showed sensitivity to quinine which correlated with the in vitro test, with concentration of quinine base 2.5-5.8 microgram/ml of blood that inhibited the maturation of Plasmodium falciparum parasites. The results of the in vitro test of 35 patients showed concentrations of quinine base 2.1-5.4 microgram/ml of blood were able to inhibit the maturation of P. falciparum parasites. Therefore, these studies indicate that Plasmodium falciparum are still sensitive to quinine and quinine remains to be the drug of choice for the treatment of falciparum malaria in Thailand.


Clinical profile of diarrhoea at Ramathibodi Hospital during 1977. Restrospective clinical profile of diarrhoeal disease in children admitted to the Pediatric Department, Ramathibodi Hospital during January to December 1977 was studied. A total of 144 medical records (55.6%) could be analysed; Rectal swab culture yielded enteropathogenic organisms in 47.2% of the cases consisting of 26.3% Salmonella, 16.0% sero typing positive E. coli and 3.5% Shigella. Clinical presentation of each group was presented which with the exception of neurological symptoms was in concordant with previous observations of several authors. Convulsion was more frequent in the Salmonella group, although dehydration and frebuency of stools were less severe. These cases seem to be highly infectious and tend to be more chronic with recurrences. It could be seen in all age group. Shigella was seen in infants 6 months old and older. Isolation of Rota-virus was not done, in none specific diarrhoeal groups (52.8%) many of which might have been due to Rota-virus. White blood count and differential count were of little value in differential diagnosis of the aetiology. Stool examination was helpful especially in Shigellosis and E. coli but there were no characteristic findings in Salmonella and non-specific groups. The overall mortality rate was 4.1%.


Polyhydramnios associated with congenital pancreatic cysts and asphyxiating thoracic dysplasia. A case report. The antenatal ultrasonic detection of congenital pancreatic cysts is described in a case of polyhydramnios associated with fetal asphyxiating thoracic dysplasia. The formation of polyhydramnios is discussed.


Global and regional assessment of cardiac performance by ECG-gated radionuclide blood pool imaging. A non-invasive method for evaluation of regional and global ventricular function by ECG-gated radionuclide blood pool imaging was developed. Cinematic image display is a sensitive method for evaluating wall motion to detect regional ventricular abnormalities and chamber size. A value of r = 0,86 and 0,85 was found for both fixed and variable area radionuclide methods when these ejection fraction values were correlated with cardio-angiographic ejection fraction values in normal subjects and in patients with myocardial infarction. The fixed area method underestimated the ejection fraction in patients with mitra valve stenosis, but this problem can be overcome with the variable area method. The technique developed cannot be used in patients with severe arrhythmias (r = 0,49 and 0,44).


Isolation of UV-sensitive variants of human FL cells by a viral suicide method. A new method (viral suicide method) for the isolation of UV-sensitive mutants is described. Colonies of mutagenized human FL cells were infected with UV-irradiated Herpes simplex viruses and surviving ones which seemed to be deficient in host cell reactivation (HCR) were examined for their UV sensitivity. Nineteen of 238 clones examined were sensitive to UV irradiation at the time of the isolation. After recloning, four of these clones have been studied and two (UVS-1 and UVS-2) of them are stable in their UV sensitivity for 4 months in culture. UV sensitivity of UVS-1, UVS-2, and the parental FL cells are as follows: the extrapolation numbers (n) are 2.2, 2.1, and 1.8 and mean lethal doses (D0) are 2.9, 3.7, and 7.8 J/m2 for UVS-1, UVS-2, and the parental FL cells, respectively- They are no more sensitive than FL cells to X-irradiation. The ability of HCR in UVS-2 cells is apparently lower than that in FL cells, whereas UVS-1 cells are the same as FL cells in the ability.


A simple method for decreasing the toxicity of polyethylene glycol in mammalian cell hybridization. The yield of hybrid colonies after fusion of mammalian cells with polyethylene glycol (PEG) is increased if the cells are fused in Ca2+-free medium, and kept in Ca2+-free medium for at least 15 min after fusion. The protective effect of Ca2+-free medium is much more obvious when Baker PEG is used than when fusion is carried out with Koch-Light PEG. The increased yield of hybrid colonies is shown to be due to a reduced toxicity rather than to an increased efficiency of cell fusion. These improvements have been found to apply to a variety of cell lines, and also when cell fusion is carried out in suspension. This technique should be particularly useful in studies on mammalian cell hybridization using cell lines that are particularly sensitive to the toxic effect of PEG.


Precocious puberty due to a hypothalamic hamartoma. A case of precocious puberty due to a hypothalamic hamartoma is presented. Concentrations of plasma LH and FSH, testosterone and its derivatives were found to be elevated. Circadian rhythms of LH were also observed. After removal of the mass, plasma LH and FHS concentrations declined to nearly half the preoperative levels.


Results of a prospective randomized study of hepatic artery infusion with 5-fluorouracil versus intravenous 5-fluorouracil in patients with hepatic metastases from colorectal cancer: A Central Oncology Group study. In a controlled, prospectively randomized trial, 74 patients with hepatic metastases from colorectal cancer were randomized to either intra-arterial hepatic artery infusion with 5-fluorouracil (5-FU) or systemic chemotherapy with 5-FU. In 61 acceptable patients, there was no significant difference in terms of response rate, time to progression, duration of the response, and survival rate. Though the response rate for the intra-arterial infusion arm was slightly higher than for the systemic arm, the difference was not significant, and the intra-arterial infusion arm was associated with a greater incidence of nausea, vomiting, diarrhea, in addition to complications of femoral-arterial thrombosis, bleeding, and infection at the catheter site not seen in patients treated by systemic chemotherapy. Patients with an objective response to chemotherapy on either treatment arm survived twice as long as the nonresponders. Long-term survival in one patient, 77 months, can occasionally be achieved in patients with hepatic metastases.


Cimetidine for kidney transplantation: experimental observations. H2-histamine receptor antagonists may augment delayed hypersensitivity. The effect of cimetidine, a H2-histamine receptor antagonist, was assessed in renal allografts in dogs. The animals in the control group (I) (n = 5) received a renal transplant and moderate immunosuppression with azathioprine and prednisone. The dogs in the experimental group (II) (n = 8) were given cimetidine in two doses (300/150 mg, twice daily). Group III (n = 4) dogs were not operated upon and received all drugs in full dosage in order to test any direct toxic effect on normal kidneys. Biweekly gastric analysis, hemoglobin, white blood count, and daily serum creatinine were monitored. The dogs in group II that received the higher dose of cimetidine rejected the transplant earlier (mean survival, 20.4 days) than the dogs in the control group (mean survival, 37.8 days). No direct toxic effect from the drug was demonstrated in the control nontransplanted group. Cimetidine in high doses suppressed both basal and host stimulation secretion of gastric acid. In summary, the finding of increased rejection episodes and diminished survival after kidney transplantation in moderately immunosuppressed dogs that received cimetidine indicates that the use of this drug in transplantation is probably not safe until more is known about the immunological mechanisms involved in this situation.


Clinical specular microscopy.

Clinical specular microscopy. Clinical specular microscopy (CSM) has recently been introduced as a means of qualitative and quantitative examination of the human corneal endothelium at high magnification. With the aid of CSM, a decline in endothelial cell density with age has been documented and several endothelial abnormalities from disease or trauma can be detected. Donor material for corneal grafting can be examined by CSM and keratoplasty procedures can be designed to decrease endothelial damage. Cataract surgical procedures can cause endothelial cell loss. According to most studies, intracapsular extraction causes less cell loss than does phacoemulsification, and cataract extraction with intraocular lens (IOL) insertion causes the greatest loss. Cell loss from IOL can be minimized by decreasing lens-corneal contact. Elevated intraocular pressure may lead to endothelial cell loss, as may therapy with epinephrine. Endothelial toxicity of other drugs and solutions can be studied by CSM. While long term studies are necessary to correlate the morphologic changes detected by CSM with future endothelial function, shortterm studies can be helpful in developing medical and surgical techniques that minimize corneal endothelial trauma.


Study of immunoglobulins in pleura and pleural effusions. The protein concentration of 35 pleural effusions was compared with that in the serum. The ratio of the pleural and serum concentration of albumin, IgG, IgA, and IgM is always below unity and appears to have no diagnostic value. However, the ratio of the concentration of these proteins was inversely related to their molecular weight. The underlying mechanism in malignant and inflammatory effusions appear similar and is in keeping with a diffusion process. Immunofluorescent staining of the pleura suggests the intercellular passage of the proteins through the mesothelial barrier.


Resistance to infection of the external eye: the role of tears. The external eye is continuously exposed to an environment containing potentially pathogenic microorganisms. One of the mechanisms which protects the eye from infection is the tear layer. We review the current knowledge of those antimicrobial substances known to be present in tears and the role they might play in preventing infection. These substances include lysozyme, lactoferrin, beta-lysin, and the antibody-complement system of proteins.


[Bovine tuberculosis in a cat (author's transl)]. The clinical, radiographical and bacteriological findings in a Siamese cat with bovine tuberculosis, are reported. In addition, the various forms of feline tuberculosis as well as the diagnostic procedures are reviewed.


A sensitive and specific enzymeimmunoassay for serum testosterone. A very sensitive enzymeimmunoassay for testosterone was developed using testosterone-penicillinase conjugate and an antibody to testosterone-3-(O-carboxymethyl)oxime-bovine serum albumin. The specificity of the assay was demonstrated by the fact that estradiol-17 beta, estrone, estriol, progesterone, 17 alpha-hydroxy-progesterone, dehydroepiandrosterone, androstenedione, cortisol and cortisone were ineffective in crossreacting with testosterone while dihydrotestosterone was 8 times less crossreactive as compared to testosterone. The minimum detectable amount of testosterone was 10-15 pg per assay tube. Intra-assay and inter-assay coefficients of variation for samples containing 0.3-6ng/ml of testosterone were 6-8% and 8-10%, respectively. A high degree of correlation (r = 0.97) was observed between serum testosterone values obtained by enzymeimmunoassay and radioimmunoassay. The levels of testosterone in the sera of normal men and women and those in hypogonadal males following stimulation with human chorionic gonadotropin determined by this enzymeimmunoassay appear similar to those reported by other investigators.


[Criteria for determination of the periodontal value in secondary displacement of teeth in the partially edentulous mouth--a study of 3000 cases]. On the basis of findings in more than 3,000 individuals, the author indicates signs of periodontal resistance and insufficiency in case of partial edentulousness which may assist in rendering finding-oriented, rehabilitation-minded, prosthetic care.


[Improvement of therapeutic results with cast partial prostheses]. The requirements for a cast partial denture with a serviceability of many years (6-8 years) are: finding-oriented therapy, exact preparation of the remaining teeth, periodontal-prophylactic shaping of the base and appropriate after-care. The different criteria are presented.


Reticuloendothelial function in human renal allograft recipients. The phagocytic and metabolic functions of the reticuloendothelial system (RES) were determined, by measuring the plasma clearance rate of 125I-labelled microaggregated human serum albumin and the increase in plasma metabolites of this test substance, in patients with chronic renal failure and in renal transplant recipients at different times after transplantation. All transplant recipients received triple immunosuppressive therapy consisting of azathioprine, corticosteroids, and antilymphocyte globulin. The intravascular clearance of microaggregated albumin was significantly depressed in patients when tested at 1 to 12 days (P less than 0.001), 1 to 4 months (P less than 0.02), and 6 to 9 months (P less than 0.001) after transplantation compared to pretransplantation. The 1- to 3-year transplant survivors had a normal RES phagocytosis. Furthermore, the metabolic RES function in all groups of transplant recipients except the group of patients tested at 1 to 4 months after transplantation was significantly impaired compared to pretransplantation. Administration of antilymphocyte globulin and extremely high daily doses of steroids were probably responsible for the significant depression in the RES functions recorded immediately post-transplantation. The further development of the phagocytic ability of the RES was shown to be correlated to the cumulative dose of steroids given over the last 12 months. The azathioprine regime seemed to have no influence on the RES functions.


Macrophage electrophoretic mobility test as sensitive probe of transplantation immunity in mice. Transplantation immunity was examined in mouse H-2- and non-H-2-disparate strain combinations by the macrophage electrophoretic mobility (MEM) assay. Lymph node cells from the recipients rejecting histoincompatible skin grafts were incubated in the presence of solubilized histocompatibility antigens prepared from spleens of the grafts donors. Product(s) of lymphocyte-antigen interaction in appropriate combinations (sensitized lymphocytes with the sensitizing antigen) significantly diminished the electrophoretic mobility of guinea pig macrophages in all of the histoincompatible strain combinations examined. The data indicate that transplantation immunity in mice can be detected by the MEM assay.


The immediately vascularized skin allograft. A model for immediate vascularization of skin was devised to examine one of the possible explanations for the differential survival rates of transplants of freely grafted skin and organs, i.e., the increased vulnerability of skin to early ischemic necrosis prior to revascularization. Female Fischer (F) rat skin was transplanted beneath the kidney capsule of tolerant female Lewis (LEW) recipients. This skin healed in and initially appeared to be normal grossly and microscopically. In 27 rats, after 30 days, the composite grafts were excised, and immediately transplanted by means of vascular anastomosis into normal LEW recipients (syngeneic to the kidney portion of the graft and allogeneic to the skin). For 5 days after transplantation of the composite graft, the skin appeared to be normal with minimal or no inflammation in a panel of 11 recipients. From the 6th to 11th day, an active rejection reaction developed at the skin-kidney interface in a panel of six rats. In 10 rats, in which the composite grafts remained in their secondary hosts for 12 to 21 days, rejection of the skin was complete. The renal portion of all composite grafts appeared to be normal histologically. All recipients of composite grafts rejected subsequent orthotopic F skin grafts in an accelerated manner, with median survival times of 8.2 +/- 0.3 days compared to 11.5 +/- 0.7 days in untreated F leads to LEW controls, demonstrating that the skin on the composite graft was fully immunogenic. These results demonstrate that immediately vascularized skin allografts between rats compatible at the major Ag-B1 locus will still be rejected within 2 weeks compared to survivals of up to 48 weeks in renal allografts in the same histocompatibility combinations, suggesting that anatomical factors are not sufficient to account for the differences in survival times between skin and solid organs.


Allogeneic red blood cells fail to induce haemagglutinating antibodies or cellular alloimmunity in rats and are immunosuppressive. Purified rat red blood cells, which express the A region antigens of the major histocompatibility complex (MHC) with which anti-RT-1 (H-1; Ag-B) haemagglutinins combine, fail to stimulate the production of either haemagglutinating antibodies or cellular immunity in allogeneic hosts. Allogeneic red blood cells may in appropriate circumstances be mildly immunosuppressive. Intraperitoneally injected allogeneic red blood cells persist in the host circulation for several weeks. The immune response to skin allografts does not accelerate the destruction of circulating donor strain red blood cells, although the administration of alloantiserum with a high haemagglutinin titre can do so. The manner in which allogeneic red blood cells effect immunosuppression is unknown. Approximately 75% of the red blood cells administered i.v. to nonimmune allogeneic hosts are destroyed, by mechanisms unknown, during the first 6 days after injection. By contrast, about one-half of this number of red blood cells are destroyed by syngeneic hosts during the same period. Red blood cells and platelets in rodents are probably similar in expressing A region (rats) or K-D region (mice) antigens of the MHC, in being nonimmunogenic by themselves and in their capacity for effecting limited immunosuppression. If human platelets have similar attributes, the administration of platelets bearing the appropriate HLA-A, B, and C antigens might be a useful adjunct to conventional immunosuppression in the management of allografts in man. Likewise, the platelet component of blood transfusions might account for their beneficial effect in some renal allograft recipients.


Chicken anti-rat lymphocyte globulin: dose response study and determination of strain-specific alloantibody. Chicken anti-rat lymphocyte globulin (CARLG) is a new and uniquely specific immunosuppressant for which the mechanisms of immunosuppressive action are not yet known. This study defines its in vivo therapeutic dose range and in vitro allospecificity. A dose response study, using CARLG or normal chicken globulin (NCG), as the sole immunosuppressant, was conducted in Lewis (Ag-B1) recipients of Buffalo (Ag-B6) rat cardiac allografts. Groups of Lewis recipients were treated with 175 mg of NCG per kg or 30, 100, 175, or 300 mg of CARLG per kg for the first 8 post-transplant days. Doses of 175 and 300 mg of CARLG per kg resulted in significantly longer (P less than 0.01) prolongation of graft survival than doses of 30 and 100 mg of CARLG per kg, which were not significantly different (P less than 0.05) in their ability to prolong graft survival than a dose of 175 mg of NCG per kg. In vitro and in vivo absorption studies revealed that CARLG does not contain strain-specific alloantibody. When Lewis lymphoid cells were used to absorb, in vitro, a batch of CARLG produced with Brown Norway (Ag-B3) lymphoid cells as immunogen, all antibody activity toward Brown Norway cells as quantitated by a two-stage lymphocytotoxicity assay was completely removed. In another experiment, a preparation of CARLG, produced using Buffalo lymphoid cells as immunogen, underwent in vivo absorption as a result of i.v. injection into Lewis rats. Serum levels of CARLG-binding activity to Lewis or Buffalo lymphoid cells were quantitated in vitro at intervals after injection by an isotopic antiglobulin assay. Lewis rat tissues were able to remove completely serum CARLG-binding activity toward Buffalo antigens. A mechanism of action for CARLG derived from these observations is proposed and discussed.


Fetal bone grafts do not elicit allograft rejection because of protecting anti-Ia alloantibodies. Implications to the immune survival of fetuses in allogeneic mothers. In a previous study we showed that allografts of BN fetal bone, unlike allografts of adult bone, are not rejected by allogeneic recipients of the Lewis strain in spite of the existence of major histocompatibility complex (MHC) incompatibility between donors and hosts. In the present study, we analyzed the relationships existing between the host and fetal tissue that determine graft survival. We found that (1) the fetal BN graft, unlike adult grafts, induces in Lewis recipients a vigorous humoral response consisting mainly in the production of IgG antibody that seems to be directed against antigens of Ia-like specificities. (2) The BN rats are genetically defective in their capacity to respond to determinants and thus are not capable of producing anti-Ia antibodies; in accordance, Lewis fetal bone grafts are rejected by the BN recipients. (3) Chondrocytes isolated from fetal mouse bones do express Ia antigenic determinants. We suggest that the survival of an allogeneic fetal graft in an immunologically intact recipient depends on an active and selective immune response directed against the Ia components associated with the MHC on the embryonic and fetal cells. On the basis of these notions, we propose that the capacity of Ia determinants expressed on cells of the embryo, to elicit anti-Ia and IgG alloantibodies in the pregnant mother, determines the capacity of the embryo to escape rejection by the histoincompatible mother.


Neonatal septicaemia in Benin City, Nigeria. A review of 74 cases. Seventy four cases of neonatal septicaemia seen at the University of Benin Teaching Hospital (UBTH) over a 3-year period were analysed. The incidence was 6.1 per 1,000 live births. Fifty five percent of the infants were low birth weight. The predisposing perinatal problems were asphyxia, prolonged rupture of membrane and peripartum maternal fever. E. coli and Staphylococcus aureus were the most important aetiologic pathogens; both of which were associated with a high mortality rate. The overall mortality rate was 41.5%. On the basis of the organisms isolated and their sensitivity patterns, it is suggested that the initial treatment for neonatal septicaemia should include cloxacillin and gentamycin.