Otolaryngology and infectious disease team approach for outpatient management of serious pediatric infections requiring parenteral antibiotic therapy.

Children with community-acquired serious otolaryngologic infections are conventionally hospitalized for parenteral antibiotic therapy. However, effective and safe outpatient therapy is desirable since it is less traumatic and less costly. During a 24-month period outpatient parenteral antibiotic therapy, usually once daily i.m. ceftriaxone, was evaluated in 41 children with serious otolaryngologic infections (acute mastoiditis, complicated otitis media, severe external otitis and severe sinusitis with orbital or periorbital involvement). Daily visits and compliant capable parents were considered essential for outpatient management. Diagnosis, plan for management and daily follow-up evaluations were carried out in cooperation by otolaryngology and infectious disease specialists. Nineteen children (45%) were treated initially in the hospital and 22 children (55%) were treated entirely as outpatients. The mean duration of outpatient treatment, using once daily i.m. ceftriaxone was 5.7 days (range 1-13). The overall clinical cure rate was 98% and no serious side effects were observed. One case of sinusitis-orbital cellulitis relapsed during therapy. Most patients and parents returned to normal life activities within 72 h from starting outpatient therapy. Our data suggest that many children with serious otolaryngologic infections can be managed successfully and safely as outpatients by a combined team of otolaryngology and infectious disease specialists.


The management of neonatal rhinitis.

Life-threatening upper airway obstruction secondary to neonatal rhinitis is a rare and poorly understood condition. Despite potential lethal effects, there has been no basic scientific research investigating the nature of this curious condition. This paper retrospectively reviews 8 patients suffering from neonatal rhinitis. Both the medical and surgical management of neonatal rhinitis and possible aetiological factors involved are discussed. Increasing clinical awareness of this condition may, therefore, serve as inspiration for future research of both an epidemiological and basic scientific nature.


Teratoma of the tongue: a case report and review of the literature.

Teratoma of the tongue is a rare tumor of the oral cavity with only six reported cases in the literature. Teratomas are composed of ectoderm, mesoderm and endoderm with differentiation to identifiable tissues and organs. Embryologically, they are thought to occur as a result of displacement of cells from normal tissue during fetal life. In the tongue, the teratoma may result from misplaced cells from the tuberculum impar. Differential diagnosis of tongue lesions includes thyroglossal duct cyst, lingual thyroid, lymphangioma, hemangioma, dermoid cyst, granular cell myoblastoma and heterotopic gastric mucosal cyst. Computerized tomography is useful in differential diagnosis and defining extent of disease. Surgical excision with laser is curative and recurrence is rare.


Endodermal sinus (yolk sac) tumor of the parotid gland: a case report.

Malignant salivary gland neoplasms in children are rare, most common being mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma and adenocarcinoma. Most germ-cell neoplasms of head and neck in children are teratomas. The authors report a case of endodermal sinus tumor (EST) of the parotid gland in a 2-year-old girl, which recurred after chemotherapy. The role of alpha-fetoprotein (AFP) serum level as a helpful marker in differential diagnosis and in evaluating tumor progression is underlined.


Adenosine and carnitine derivatives and calcium movements in rat heart sarcoplasmic reticulum.

Many researches indicate that some Ca antagonists modulate Ca fluxes not only at the level of the cytoplasmic membrane but also across the sarcoplasmic reticulum. The present study investigates whether certain compounds like propionylcarnitine or acetylcarnitine which have the capacity to influence cardiac activity might interfere with intracellular Ca movements. The results demonstrate that acetylcarnitine and propionylcarnitine do not affect the calcium intracellular movement in sarcoplasmic reticulum.


In-vitro immune response of splenic lymphocytes to portal serum agents from rats undergoing hepatic regeneration or hepatic carcinogenesis.

To clarify the physiologic response of splenic lymphocytes to liver damage and the role of this response in regeneration versus malignant transformation, we cultured rat spleen lymphocytes with portal sera from rats subjected either to partial (70%) hepatectomy or to long-term oral administration of the hepatic carcinogen 3'-methyl-4-dimethylaminoazobenzene. Sera taken within 24h after partial hepatectomy contained a previously described signal protein which serves as a marker of liver damage. The MW 5,000-10,000 serum fraction also contained a factor that promoted cell growth, DNA synthesis, glucose utilization, and the production of anti-sheep erythrocyte plaque-forming cells in cultures of rat splenic lymphocytes. In contrast, the sera of rats subjected to liver damage by the carcinogen had no more effect on the cultured lymphocytes than sera from sham-operated or untreated controls. The signal protein was present initially in portal sera from carcinogen-treated rats, but decreased as hepatitis gave way to cirrhosis. Subsequent malignant transformation was marked by the appearance of serum alpha-fetoprotein. Our results suggest that activation of splenic lymphocytes by serum factor(s) is involved in hepatic regeneration and that this process is deranged in carcinogenesis.


Eel calcitonin induces creatine kinase BB activity in the rat kidney medulla.

We have studied the effect of intravenous injection of eel calcitonin (ECT) on creatine kinase E.C.2.7.3.2. BB isozyme (CKBB) in the kidney of male Wistar rats. CKBB immunoreactivity was detected by the peroxidase-antiperoxidase method. Eel calcitonin increased CKBB immunoreactivity in the renal medulla in a dose-dependent fashion. Its effect peaked at 2 h and lasted up to 24 h. The distribution of activated CKBB in the kidney occurs in the same areas where highly specific CT-binding sites have been previously demonstrated, and is in agreement with the current concepts on renal actions of this hormone.


Somatosensory and autonomic deficiencies following trauma in man; evaluation of symptomatology by studying peripheral neural correlates and induced tissue reactions.

Careful clinical and experimental studies in well-diagnosed groups of selected patients can give valuable information concerning unknown mechanisms involved in certain disease states. In particular, microneurographic techniques can be applied to assess the underlying neural pathophysiology. It is anticipated that future studies performed along these guidelines will contribute to an improved diagnosis and/or therapy in a number of clinical conditions.


Biochemical approach to new medications.

In this plenary symposium address, the author describes historically his progress from the antimetabolite 2,6-diaminopurine to 6-mercaptopurine as a useful drug against tumours and leukaemia. Subsequently a 6-mercaptopurine derivative, and eventually azathioprine, were discovered to be useful drugs to ensure kidney transplant acceptance. Several of his group's diaminopurines proved to be selective antifolates in combatting pathogenic bacteria when combined with sulfanilamide, a useful drug combination already estimated to have saved a million lives.


The role of chemical mediators released by the endothelium in the control of the cardiovascular system.

The vascular endothelium is much more than just a lining for blood vessels. It inactivates many mediators and produces a host of active substances. The production of these substances is modulated by interactions between the endothelial cells and white blood cells, platelets or constituents of plasma. The endothelial cells can be activated by amines, peptides, proteins, nucleotides, arachidonic acid and its metabolites, as well as by physical changes such as pulse pressure. This activation of endothelial cells is often mediated by specific receptors which respond in a variety of ways including the generation of prostacyclin and endothelium-derived relaxing factor (EDRF). Both of these mediators inhibit platelet aggregation and cause vascular dilatation, prostacyclin through increasing cyclic AMP, and EDRF through increasing cyclic GMP. EDRF has been identified as nitric oxide (NO) derived from the guanidino group of L-arginine. Inhibitors of NO formation cause a strong increase in blood pressure, showing that under normal conditions there is a constant formation of NO to dilate the vasculature. Endothelin is another agent made by endothelial cells; characterized and synthesized in 1988, it is the most potent vasoconstrictor so far discovered. Three endothelin isomers have been identified; paradoxically, ET-1 strongly releases both prostacyclin and NO, thus modulating its own vasoconstrictor activities.


Reduction of inflammation by decreasing production of interleukin-1 or by specific receptor antagonism.

Interleukin-1 (IL-1) is a 17-kDa pro-inflammatory cytokine synthesized from a variety of cell types primarily in association with disease states or during host perturbation such as immune responses. At pM or even fM concentrations, IL-1 triggers various responses in nearly all cells. It appears that there is little or no major role for IL-1 in homoeostatic mechanisms. There are two IL-1's (alpha and beta) each with its distinct sequence; there are two IL-1 receptors. Disease states such as local and systemic infection, septic shock, degenerative arthritis and autoimmune diseases such as nephritis, vasculitis and inflammatory bowel disease appear to be mediated, in part, by IL-1. Organ failure, capillary leak and death occur in animals after a combination of tumour necrosis factor (TNF) and IL-1 which is more effective in inducing these changes than either cytokine alone. IL-1 is also a potent inducer of endothelial cell adhesion molecules, IL-6, and IL-8, a neutrophil chemotactic and activating factor. Strategies for reducing the effects of IL-1 have been based on suppression of transcription, translation, or secretion; more recently, receptor blockade has been a new approach. A naturally occurring IL-1-specific receptor antagonist (IL-1ra), which shares 40% conserved amino-acid homology with IL-1 beta, binds to IL-1 surface receptors with the same affinity as IL-1 but does not possess agonist activity and acts as a competitive inhibitor of IL-1. Studies using the IL-1ra to block endogenous IL-1 in a variety of animal disease models suggest that IL-1 plays a key role in triggering the cascade of inflammatory responses. In addition, the IL-1ra reduces the spontaneous production of growth factors and proliferation of leukaemic cells. The IL-1ra may be an advantageous therapy in patients with sepsis, diabetes, inflammatory bowel, arthritis and cancer.


The intensive care unit. The unfolding ambiguities of survival therapy.

The intensive care unit (ICU), one of the great achievements of modern medicine, is both a set of technologies and a space with a special function. This essay traces the evolution of the ICU's crucial technologies, and how the space bearing this name was carved out in the hospital. Ethical, legal, and social developments, an important part of this story, are incorporated in it.


Epidemiology of intensive care.

It is difficult to study the epidemiology of ICUs, as they lack a uniform nomenclature and/or classification. The organization and distribution of intensive care medicine depend on the size and function of the hospital. The patients in ICUs are predominantly men, with a high proportion of elderly patients (greater than or equal to 70 years) constituting 25-30% of the total. Case-mix, severity of illness and outcome differ from one unit to another, and can be compared only if the patients are classified with a common classification system. Most survivors of intensive care seem to return to normal or near normal functional level within one year. Compared to Western Europe, the United States has more ICU beds and a nearly ten times higher admission rate to intensive care. These variations can be seen as a result of a fundamental difference in the attitudes toward withdrawing or withholding life support.


An ethical assessment of intensive care.

Any evaluation of intensive care must include an ethical assessment of that technology. This allows us to consider the use of technology in light of the ends that we desire. The most pressing ethical issues in intensive care are: forgoing life-sustaining treatment, dehumanization of patients and staff within the technological environment, and the allocation of the technology that is integral to intensive care.


Problems in assessing the technology of critical care medicine.

Technology assessment is becoming increasingly important in the area of critical care due both to the explosion of technology associated with this discipline and to the realization that future demand for these health care resources will undoubtedly exceed the ability to pay. Technology assessment remains both confusing and controversial to many physicians. This review tries to address some of the confusion by reviewing the basic strategies involved in this process. From there, problems and prospects for the evaluation of critical care as a program are presented, followed by the assessment of components within the area of critical care. Finally, recommendations are made on how technology assessment could proceed in the future to best achieve the efficient provision of this service.


Critically examining intensive care.

The economic recession of the last decade brought intensive care systems under the light of cost-effectiveness analysis, making use of several instruments available in medical practice, and others adapted from for-profit enterprises. The present concept of intensive care, particularly its functional and organizational interactions with traditional specialties, is at the brink of an important revaluation. Studies of the cost-effectiveness of therapeutic actions may be grossly biased if they do not consider the complete process of care (before, during, and after treatment), analyzing even its smallest elements.


Neonatal intensive care. When and where is it justified?

There is a wide panorama of disorders in the newborn infant where neonatal intensive care has been proven effective in reducing mortality. Although modern neonatal intensive care can be very costly, short and simple interventions for support and resuscitation still can be highly beneficial. In reviewing the field of neonatal intensive care during the 1980s, it becomes evident that a major challenge for the future will be to apply physiological principles of great and proven value for the newborn baby to more simple devices. Only thereby can the technology of neonatal care defined as a complex of actions-not only equipment and techniques-become justified for future generations.


Inborn errors of amino acid metabolism. The best strategy for their diagnosis.

We performed a cost-effectiveness analysis to evaluate whether a pediatrician who suspects an inherited disease of amino acid metabolism should refer the child to a specialist in inborn errors of amino acid metabolism or should prescribe the usual screening test, chromatography of amino acids. Actual hospital costs were used to value the referral, the tests, and the complications that occur when the diagnosis is not recognized. The percent of confirmed diagnoses was chosen as a measure of effectiveness. We conclude that it is more cost-effective for a pediatrician to refer the child to a specialist, that the best strategy in the absence of a referral is to prescribe thin-layer chromatography, and that the least cost-effective strategy is to perform ion-exchange chromatography immediately.


Quality assessment of medical research and education.

Different aspects of the process of evaluating research and education are discussed, using the discipline of medicine as a model. The focus is primarily on potential problems in the design of an evaluation. The most important aspects of an assessment are: to create confidence in the evaluation among scientists and/or teachers who are being assessed before beginning; to find experts for whom the scientists and/or teachers have professional respect; to choose assessment methods in relation to the focus, level, and objectives of the evaluation; and to make the report of the evaluation's findings short and explicit.


Volume and outcome of organ transplantation.

In general, technically demanding medical procedures are associated with better outcomes when they are carried out in institutions and by physicians with higher volumes of practice. This paper examines the evidence for a volume-outcome relationship in the case of organ transplantation. Although few studies have been done on this subject, existing evidence is consistent with improved outcomes at higher volumes. Therefore, evidence supports policies that regionalize transplantation services.


Economic evaluation of hypertension treatment.

A computer simulation model shows that the cost-effectiveness of treating hypertension is highly sensitive to different assumptions about the effectiveness of treatment, the outcome measure, the cost concept, the discounting of effects, and the duration of therapy. Cost-effectiveness analysis should be supplemented by another approach--cost-benefit analysis based on the contingent valuation (CV) method (the measurement, by survey, of willingness to pay). The CV method is tested in two empirical applications that indicate that it is possible to use the method in this area. Its results should be interpreted with caution, however, since the reliability and validity of the method is not yet established.


The use of risk-adjusted complication rates to compare hospitals performing coronary artery bypass surgery or angioplasty.

A hospital's quality of care is generally assessed by a review of individual records. This study used unadjusted and risk-adjusted complication rates to measure the quality of care for hospitals that perform coronary artery bypass surgery or angioplasty. Hospitals differed greatly in their complication rates. Only a small percentage of this difference was due to differences in the risks that patients faced.


A methodology for simulating the impact of DNA-probe services on the outcomes of pregnancies.

For certain single-gene disorders, DNA probes allow individuals to make more informed decisions about family size and the outcomes of pregnancies. They may also have important psychological effects. We present a method of assessing their impact on the outcomes of pregnancy. We conclude that the traditional approach, which focuses solely on the potential of prenatal diagnostic services to reduce affected births, is limited. It neglects the potential of such services to promote an increase in unaffected births by reducing the number of unnecessary terminations.


Transmediastinal esophagectomy and colon interposition without thoracotomy.

In the Central Hospital of Central Finland (responsibility for 250,000 inhabitants) the technique of transmediastinal esophagectomy and colon interposition without thoracotomy was used on 19 consecutive patients in the years 1983-1988. Fourteen of the patients had a malignant and five a benign disease. The type of cancer was squamous cell cancer in 13, and adenocancer in 1 case. All five patients with a benign disease had an etiology of corrosion by various agents. Two of them had a spontaneous rupture. In three cases the perforation occurred as a complication of endoscopic dilatation. There were no peroperative but one postoperative death. Six minor complications were well under control. The survival rate of cancer patients is comparable with the results reported by other authors. All five patients with a benign disease are in excellent condition with a follow up time from 4 to 100 months (mean 44 mo).


Laparoscopic cholecystectomy in India.

The first 100 cases of laparoscopic cholecystectomy carried out in a "developing country" are studied. There were 77 females and 23 males. The mean age was 48 years (24-82 years). There was no mortality and 2% morbidity. The mean operative time was two hours and 15 minutes in the first 50 cases, one hour and 50 minutes in the subsequent 50. Twelve cases were converted to open surgery, nine within the first 50 cases, three in the subsequent 50. In developing countries the challenge of financial constraints as also a different spectrum of abdominal pathology calls for greater efforts of innovation and improvization. However, the rewards of laparoscopic cholecystectomy as compared to open cholecystectomy are significant in developing countries in terms of shorter hospitalisation (3.6 vs. 13 days), early return to work (12 vs. 36 days), better hospital bed utilization, and reduced expense.


Over-tube is preferable to free-hand technique to avoid recurrence of varices after endoscopic injection sclerotherapy. Prospective randomized trial.

One hundred and two patients undergoing sclerotherapy of esophageal varices, using 5% ethanolamine oleate, were randomly allocated to either the over-tube (O-T) or the free-hand (F-H) group, and 100 patients could be followed at monthly intervals for a period of 30.8 +/- 14.7 months (mean +/- SD) after the varices had been eradicated. Endoscopy performed one month after the final session of sclerotherapy revealed circumferential ulcers and scarring in the lower esophagus in 42 of 50 patients (84%) in the O-T group and in 16 of 50 patients (32%) of the F-H group, the difference being statistically significant (P less than 0.01). In the remaining 8 and 34 patients in the O-T and the F-H groups, respectively, a partly fibrotic residual mucosa was seen. There was a recurrence of the varices in the residual mucosa in 14 (28%) in the F-H group during the mean follow-up period of 25.6 months, while there were five patients (10%) with a recurrence of varices in the O-T group, the difference being statistically significant (P less than 0.05). The survival rates showed no statistical significance. Two patients in the F-H group had recurrent bleeding. We conclude that the over-tube technique of sclerosing esophageal varices reduces the rate of recurrence of the varices, in the long term follow-up, and after formation of a circumferential scarring in the lower esophagus.


Hepatic fascioliasis and biliary surgery.

This series represents seven cases of hepatic fascioliasis (HF), two diagnosed as the sequelae of the disease and five showing the parasite itself at the time of the primary surgical intervention. The mean history of the symptoms was 42.6 mths. All of the patients were initially misdiagnosed as having cholecysto- and/or coledocho-lithiasis or hepatitis. Definite diagnosis was established intraoperatively in each instant. At surgery cholecystectomy, choledochotomy with extirpation of the flukes from the biliary tree and T-tube biliary drainage was performed without any complications in five patients. The remaining two patients were suffering from recurrent cholangitic episodes and were regarded as sequelae and therefore treated with hepatic peri-arterial neurectomy with favourable results. Six patients received medical treatment involving emetine hydrochloride. Two patients failed to return for follow-up while others were seen to be well 6, 12, 24 mths and 13 and 24 yrs postoperatively, implying promising long-term results both in the active and chronic stages of HF.


Immediate return to unrestricted work after inguinal herniorrhaphy. Personal experiences with 27,267 cases, local anesthesia, and mesh.

Complete safety of the patient and unblemished success without recurrence or complication may be assured after inguinal herniorrhaphy as an out-patient if uncompromising intimate attention is paid to the surgical technique in which local anesthesia, polyvinyl ester mesh, and rectus abdominis tendon transfer are used instead of coaptive techniques, and if the post-operative regimen of immediate post-operative ambulation and unrestricted activity is employed. Return to work requiring heavy lifting the same day reduces tension on the mesh, increases the strength of the incision, prevents complications and minimizes pain. The surgical procedure and the virtues of the regimen, which has been eminently successful in 27,267 personal cases, with mesh employed in 18,214 patients, are described.


Gastrectomy for advanced gastric carcinoma with invasion to the serosa.

A review of gastrectomy for 332 patients who had advanced gastric cancer with serosal exposed (S2) or adjacent organs invaded (S3) was made. Simple gastrectomy (SG) was carried out in 144 patients while radical gastrectomy (RG), which consisted of systemic lymphadenectomy in addition to SG, was used for the other 188 patients. The type of gastrectomy was chosen arbitrarily by the surgeons except that SG was usually selected when some non-curable factors were present. The operative mortality of SG was 2.7% and that of RG was 3.2%. More lymphnodes could be obtained by RG. Of the 152 patients with S2 who received RG, 46.7% of metastatic lymphnodes could not be identified by SG, while of the 36 patients with S3, 75% of metastatic nodes would be misjudged if SG was carried out. The 5-year-survival rate of RG for stage 3 patients was 42.4% and that for stage 4 patients was 28.2%. Better postoperative long-term-survival was achieved by RG than SG in both stage 3 and 4 patients. When considering the curability of the gastrectomy, the best outcome in stage 3 patients was found in those who underwent an absolute curative resection. Of the stage 4 patients those who received an absolute non-curative resection had the worst result. We recommend that RG be the procedure of choice in treatment of serosal gastric cancer in the absence of non-curable factors. Other adjuvant therapies may be considered after an absolute non-curative gastrectomy in stage 4 serosal cancer patients when multiple non-curable factors were present.


Inguinal hernia repair in infants less than six months of age.

Previous studies reviewing the morbidity and mortality of infant inguinal hernia surgery have all been done in university hospital settings. From our community-based tertiary hospital, 100 consecutive cases on infants less than six months of age, undergoing inguinal hernia repair, were reviewed. No infants were excluded. Sixty-eight were full term and 32 were premature. A number of different variables were analyzed and none appeared to affect outcome. Infants were followed for three to five years. There were no true complications in any infant in this series, although six infants developed wound erythema that resolved spontaneously. Parents were given a questionnaire to subjectively evaluate the infant before and after surgery with 78% showing improvement.


Colostomy complications in infants and children.

Seventy-seven colostomies were performed in 74 patients: 35 for high anorectal agenesis, 34 for Hirschsprung's disease, 2 for necrotizing enterocolitis, 2 for small left colon syndrome, and 1 for volvulus neonatorum with perforation. There were 55 boys and 19 girls with a mean age of 0.8 years. The different types of colostomies performed were: transverse loop in 48, sigmoid loop in 21, transverse end in 4, descending end in 2, sigmoid end in 1, and transverse double barrel in 1. Forty-seven patients developed stomal complications (74.6%). Eleven patients died, but only in 2 (2.7%) were the deaths directly related to colostomy formation. Five patients required stomal revision (6.8%). The incidence of complications was neither related to the age nor to the primary indication for the colostomy, but sigmoid colostomy was associated with a lower complication rate compared to transverse colostomy (52% versus 81% 0.02 greater than p greater than 0.01). A sigmoid loop colostomy should be used whenever possible.


Metastatic lung tumors and extended indications for surgery.

From 1973 to 1989, 110 thoracotomies for metastatic lung tumors were done on 85 patients, in our institution. The overall actuarial five-year survival rate was 31%. The five-year survival rate for carcinoma was 40% and for sarcoma was 11% (less than 0.05). A favorable outcome was obtained in the group with primary tumors of the breast, head-neck, and chorion. The outcome for patients with bone and soft tissue tumors was poor. The significant predictors of a better long-term survival for metastatic lung tumors were disease-free interval (DFI) greater than 12 months, tumor size less than or equal to 30 mm in diameter, and tumor doubling time (TDT) greater than 40 days (p less than 0.05). The number of nodules and the laterality of the sites of recurrence did not relate to survival time. Of 22 patients undergoing regional lymph node dissection, seven (32%) had positive nodes. Even in cases of a recurrent pulmonary metastasis, the three-year survival in those with multiple thoracotomies was 16%. We wish to draw attention to the finding that a prolonged survival time can be achieved for patients undergoing regional lymph node dissection or even repeated resections for a recurrent pulmonary metastases.


Calcitonin gene-related peptide as a tumor marker for medullary thyroid carcinoma.

We have established a radioimmunoassay method for calcitonin gene-related peptide (CGRP) to monitor changes in plasma CGRP levels in patients with medullary thyroid carcinoma (MTC). Preoperative plasma CGRP levels (normal level less than 12.7 pg/ml) were as high as 128 pg/ml to 2,010 pg/ml in all five patients with MTC. Ten of 17 postoperative patients with MTC were positive for CGRP. A provocation test was performed in 12 patients with MTC. Plasma CGRP changes roughly paralleled serum calcitonin levels. In particular, in three patients with poorly-differentiated MTC which progressed aggressively, plasma CGRP levels were increased to 1.4 to 2.0 times levels before the test, i.e., lower than the 2.8- to 23.3-fold increase in nine patients with the well-differentiated MTC. These results suggest that CGRP may be a humoral marker of medullary carcinoma and be related to degree of malignancy.


The nature of inner cellular lining of the expanded polytetrafluoroethylene vascular graft: immunohistochemical study.

Histological and immunohistochemical studies of the healing processes of expanded polytetrafluoroethylene (PTFE) vascular graft were performed. In the animal experiment, endothelial cell lining, confirmed by immunohistochemical staining for anti-Factor VIII related antigen, existed nearly over all of the pannus. The endothelial cells also formed to some extent over the graft without pannus. Endothelialization showed a close dependency on the surface condition of the underlying tissue rather than on a time factor. In the human experiment, an endothelial island was observed in the middle portion of the graft in one case, supporting the hypothesis of the blood stream origin of endothelial cells.


Fecoflowmetry: a new parameter assessing rectal function.

Fecoflowmetry is a new technique by which the fecal flow rate is studied through recorded curves representing the changes which occur in the rate against time. Fecal flow rate is the product of rectal detrusor action against outlet resistance. The technique was performed on 36 normal volunteers and 8 chronically constipated patients. A one liter water enema was given to the individual. On feeling the desire to defecate, he or she was placed on the commode of a fecoflowmeter and was asked to defecate. Defecation flow curves were obtained. Evaluation of the curve comprises reporting on the defecated volume, flow time, maximum and mean flow rates and the shape of the curve. The technique was developed to stimulate natural defecation. It provides quantitative and qualitative data concerning the act of defecation. It assesses all objective parameters in one test. The procedure is simple, non-invasive and constitutes a useful screening tool in defecation and rectal disorders.


Does total thyroidectomy induce metabolic bone disturbance?

Bone mineral content of 38 thyroidectomized patients with well differentiated thyroid carcinoma were determined. Seventeen patients were totally thyroidectomized and 21 patients were non-totally thyroidectomized (lobectomy). Thirty-eight healthy males and females were served as age-matched controls. Trabecular bone mineral content of lumbar vertebra was evaluated by quantitative CT method. Bone metabolic parameters in serum were measured. No significant differences were observed in the mean bone mineral content and BMC-index of totally thyroidectomized patients compared with non-totally thyroidectomized patients and control. Serum calcitonin level was not reduced in totally thyroidectomized. It is concluded that after total thyroidectomy, bone metabolic disturbance was not significant, and that when calcitonin remained at its basal level, it had no effects on bone metabolism.


Factors affecting postoperative mortality in abdominal trauma.

Records of 345 patients in whom laparatomies were performed because of blunt and penetrating abdominal trauma were reviewed retrospectively with respect to factors affecting mortality. One hundred and twenty-eight patients had blunt abdominal trauma (Group I), 114 patients had gunshot wounds of the abdomen (Group II), and 103 patients had stab wounds of the abdomen (Group III). Mortality rates were 14.8%, 12.3% and 1.9% in groups I, II and III respectively. The presence of head trauma especially if accompanied by hypotension in group I, and the presence of chest trauma (hemothorax and/or pneumothorax) and hypotension (less than 90 mmHg) in group II were associated with a high mortality rate (p less than 0.05). Of the two patients who died in group III, one had septic shock due to massive intestinal necrosis and the other had hemorrhagic shock due to multiple organ injury and bleeding from an injured internal thoracic artery as the cause of death.


Primary colonic non-Hodgkin lymphomas: a retrospective clinicopathologic study of 14 cases.

Fourteen cases of primary colonic non-Hodgkin lymphomas (NHL) with a mean age of 51.5 yrs and 64.3% of them female, are reported. While diagnoses were only obtained by cytologic or histopathologic means, 35.5% of the cases were in Stage 1e (S1e) and a further 42.6% in Stage 2e (S2e) and 7.1% in Stage 3e (S3e) according to the modified Manchester classification. 63.9% were of immunoblastic and 21.3% lymphoblastic type according to the Kiel classification. 85.2% of the tumours were located at the caecum. While acute abdomen required surgery in two patients, 85.2% of the series underwent radical interventions. 14.2% were able to receive chemotherapy with a subsequent total morbidity and mortality figures of 21.3% each. It is the authors' argument that prognosis is not solely dependent on the age, sex or the malignancy state of the tumour but more on its infiltrative stage and on the advent of treatment, whether by radical surgery and/or medical means.


Diagnosis and treatment of cortical tumours of the suprarenal gland.

The authors report on their own groups of benign (20 patients) and malignant (14 patients) cortical tumours of the suprarenal gland. In both kinds of tumour the occurrence is higher in females. Adenoma occurred more often in the left adrenal gland and cancer in the right one. Some tumours manifested themselves by an increased production of suprarenal hormones, others were hormonally inactive and did not become manifest until the later stage of development. In the therapy of adenomas the classical lumbar approach through the 11th intercostal space is adequate, in the case of cancer and extended lumbotomy laparotomy or thoracotomy is necessary. The need of participation of other specialists in the treatment (endocrinologist, radiologist, oncologist, anaesthesiologist) is emphasized.


A double-blind placebo-controlled trial of omeprazole on urinary pH in healthy subjects.

Urinary pH is related to urinary calculus formation as well as urinary infection. Omeprazole is an effective inhibitor of gastric acid secretion through inhibition of the parietal cell H+K+ATPase. In this study we have evaluated a possible effect of omeprazole on urine acidification. Ten healthy male subjects took placebo and omeprazole, 40 mg o.m., for 10 days in a double-blind placebo-controlled trial. Morning fasting urinary pH was measured on day 10 of each treatment course using a pH meter. No effect of omeprazole on urinary pH could be demonstrated. It is thus unlikely that it is necessary to take omeprazole treatment into consideration in stone screening. As omeprazole did not affect urinary pH, no urological side effects related to changes in urinary pH can be expected.


A comparative trial of aztreonam versus gentamicin in the treatment of urinary tract infections.

A prospective, randomized trial was conducted to compare the efficacy of aztreonam, a monobactam antibiotic, and gentamicin in the treatment of serious urinary tract infections. Fifty-five patients with a suspected or confirmed infection were randomized, 28 received aztreonam and 27 received gentamicin. Both antibiotics had a high clinical response rate (aztreonam 92%, gentamicin 85%). However, the duration of treatment was significantly shorter (p = 0.037, Wilcoxon Rank Sum Test) when aztreonam was used. There were no cases of toxicity with either antibiotic but 5 patients who received gentamicin required dose alteration. Aztreonam is well tolerated and is no less effective than gentamicin in the treatment of urinary tract infections and has advantages in convenience of use and duration of treatment.


Evaluation of an intensive care unit in a teaching hospital in Saudi Arabia.

Intensive Care Units (ICU) in general hospitals have become a standard requirement in tertiary care centres. However, the appropriateness of their use is not widely known. We have used the Therapeutic Intervention Scoring System (TISS) to evaluate a multidisciplinary ICU in a teaching hospital in Saudi Arabia. The average occupancy rate was 79%, the nurse: patient ratio was 1:1.4, duration of stay 4.1 +/- 3.5 days, and mortality was 1.4%. The distribution of severity of illness was as follows: Classes I & II, 82%, and Classes III & IV, 18%. The average TISS points were: daily per patient 15.1 +/- 2.7 (range 11.5-21.7), total per day 125.6 +/- 38.2 (range 35-211), and patient points per nurse was 21.1. We conclude that, although less than 20% of patients required unique ICU services, the use of our ICU was appropriate to the current medical and manpower training needs of the community it was designed to serve, but the basis of nurses' complaints of overwork remains to be determined.


Pelvic lymphadenoscopy. A simple reliable method for the staging of pelvic cancers.

The staging of pelvic cancers using imaging techniques is not very precise, even with the most recent methods. However, optimal treatment depends on the results of this staging. In our experiment, we carried out a pelvioscopy prior to any curative treatment on all our patients who had had pelvic cancer for at least three years. Seventy-eight pelvioscopies were performed with 48 patients, entailing minimum morbidity and no mortality. For 23 patients, the lymph nodes were metastasized even though the C.T. were considered normal. With this simple method, staging of pelvic cancers can be improved and this extensive, unnecessary surgery can be avoided in many cases.


Low ureteral obstruction caused by umbilical ligament in a 37 year old man: a case report.

Arterial vascular anomalies rarely cause extrinsic ureteral obstruction and only 11 cases have been reported so far. This paper deals with an unusual extrinsic obstruction of the left ureter caused by a residue of the umbilical artery in a 37 years old man. The patient had left flank pain due to serious hydronephrosis on the same side. At operation a fibrous cord, a residue of the left umbilical artery, partially obstructed the distal left ureter. Partial left terminal ureterectomy with ureteroneocystostomy was performed. In the differential diagnosis of low extrinsic ureteral obstructions also the uncommon vascular anomalies of the umbilical artery should be taken into consideration.


The flexible cystoscope.

We have been using the flexible cystoscope since 1987. Detailed information is given concerning the technique of flexible cystoscopy, its indications, advantages and disadvantages. A comparison is made with the results obtained using the rigid cystoscope in an initial series of 100 patients, yielding false negative results in only 8% of cases during the learning period. The flexible scope can be successfully employed for Neodymium YAG laser coagulation of superficial bladder tumours. The conclusion is reached that once the urologist has learned how to use it, he will consider the flexible cystoscope as a fundamental tool in his diagnostic armamentarium and false negative results will decrease almost to zero, especially if additional investigations, namely cytology, are routinely adopted.


Selective approach to repair of ureteropelvic junction obstruction: results of 126 pyeloplasties assessed on clinical and radiological bases.

Record-files of 126 pyeloplasties of different types performed on 119 patients (7 bilaterally), between 1966 and 1989, have been reviewed in an attempt to illustrate the selective approach to hydronephrosis due to ureteropelvic junction obstruction. Clinical success was achieved in all cases. A new grading system for assessing urographic impairment has been suggested. Radiological success was obtained in 123 (97.6%) renal units. The near total success is attributed to the theme of selective approach.


Clinical assessment of carcinoma in situ of the human urinary bladder.

Recent interest in intravesical instillation of bacillus Calmette-Guérin for the management of carcinoma in situ (CIS) of the bladder prompted us to review our results of total immediate cystourethrectomy. From 1975 to 1987, we surgically treated 302 patients with primary bladder tumours. Of these, 21 bladder tumours were histologically diagnosed as CIS, and total immediate cystourethrectomy was performed in all cases. The lesions were classified into three types: primary CIS accompanied by neither previous nor simultaneous tumours of the urinary tract (Type 1, 9 patients), concomitant CIS associated with superficial papillary tumour (Type 2, 6 patients), and secondary CIS detected during the follow-up period after treatment of the superficial papillary tumour (Type 3, 6 patients). Primary CIS was more often diagnosed according to subjective symptoms such as micturition pain than concomitant CIS. Secondary CIS was diagnosed in all patients by routine examinations including cytology and cystoscopy. There was no particular relationship between the time of recurrence of the tumour and the occurrence of secondary CIS. Within the same period, 60 patients with stage T1 bladder tumour were treated by total cystourethrectomy. The actuarial 5-year survival rate was 77% for T1 and 75% for CIS. The 5-year survival rate was 71% for Type 1, 83% for Type 2, and 67% for Type 3 CIS with no difference among the CIS types. Tumour invasion to the bladder, prostate, ureter, or lymph nodes was observed in 9 (42.9%) of the 21 patients, although cystourethrectomy was performed within 3 months of the diagnosis. Examination of ABH antigens did not allow prediction of invasion of CIS. Our findings suggest that the invasive potential of CIS may seriously limit the indications of conservative treatment against carcinoma in situ.


Spontaneous intracerebral hemorrhage following carotid endarterectomy. Experience of 328 operations from 1983-1988.

In a consecutive series of 328 carotid endarterectomies there were two cases of postoperative intracerebral hemorrhage. The patients with transient ischemic attacks and subsequent major cerebral infarction had repair of their very tight carotid stenosis. Each developed intracerebral hemorrhage after a symptom free interval and hypertension was uncontrolled during the postoperative period. Hypertension is a significant complication of carotid endarterectomy and may be a prominent factor in the development of intracerebral hemorrhage after carotid endarterectomy. Also defective cerebrovascular autoregulation in chronic ischemic brain regions may predispose patients to intracerebral hemorrhage.


Spontaneous pneumoperitoneum without peritonitis.

Spontaneous pneumoperitoneum without peritonitis is a rare phenomenon which poses a dilemma to the surgeon faced with this problem. Two such cases and their outcome are presented. The first case was caused by barotrauma during positive pressure ventilation and was treated by laparotomy. No perforated viscus was found. The second case was caused by tracheal rupture during emergency intubation and was treated by observation until complete resolution. Both patients died for reasons unrelated to the pneumoperitoneum. The mechanisms for passage of air from the chest into the abdominal cavity were through the diaphragm in the first case and along the great vessels in the second. A compilation of other etiologies of pneumoperitoneum without peritonitis as extracted from the literature is presented. In the presence of pneumoperitoneum without peritonitis and when the clinical history does not suggest perforation of a viscus, we advise performing an abdominal tap. If negative, continued observation is advised.


Detection of blood group surface antigens of urinary bladder tumours using monoclonal antibodies with the avidin-biotin complex technique.

We examined 8 normal bladder transitional epithelia and 65 transitional cell carcinomas of the urinary bladder of various stages and grades for the presence of ABO(H) blood group surface isoantigens using the immunoperoxidase staining via the Avidin-Biotin Complex (ABC) methods. It was found that 27% of patients with grade I tumours, 50% with grade II tumours and 82% with grade III tumours had loss of cell surface isoantigens. When correlated with the clinical stage the tumours showed no surface isoantigens in stage D, while 65% of patients with stage A tumours were positive for surface antigens. From among 37 patients (57%), 28 (43%) survived for more than five years. Our results suggest that surface antigens of transitional cell carcinoma of the urinary bladder tended to disappear as the histologic changes of the tumour progressed. It also was noted that a loss of ABH(O) surface isoantigens was a bad prognostic sign.


Free-hand CT-guided needle for biopsy and drainage of intracerebral lesions. Ten years experience.

A series of 227 needle procedures monitored by serial CT scans was performed by free-hand technique on 147 patients at two suburban hospitals over a 10 year period. Under local anesthesia, 75 suspected brain tumors were biopsied; 52 intracerebral hematomas were evacuated, and 28 cerebral abscesses were drained. There was one complication of postoperative hemorrhage.


Superficial bladder cancer treated by total cystectomy: tumour characteristics and patient survival.

Of 113 patients with bladder cancer who underwent total cystectomy from January 1980 to December 1990, 30 (27%) had superficial tumours (pTa, pTis, and pT1). Nineteen of these 30 patients (63%) were primarily treated by total cystectomy and the remaining 11 (37%) had a past history of treatment for bladder cancer. Major reasons for choice of total cystectomy were multifocal tumours, frequent recurrence, and diffuse carcinoma in situ. Histologically stage pT1, grade 3 tumours were frequently accompanied by carcinoma in situ and often by lymphatic invasion. None of the 24 patients undergoing pelvic lymphadenectomy had lymph node metastasis. Of 25 male patients 15 (60%) underwent simultaneous prophylactic urethrectomy. Two of the remaining 10 males (20%) not undergoing this additional operation died of subsequent urethral recurrence. The 5-year actuarial survival rate was 80% for the 30 patients when all causes of death were considered. It was concluded that patients with superficial bladder cancer who undergo total cystectomy without prophylactic urethrectomy require close follow-up with urethral washings for cytology to detect early urethral recurrence, an important determinant for survival.


Post-herniorrhaphy paravesical granuloma simulating pelvic metastasis in a patient with bladder cancer.

We describe a rare case of bladder cancer associated with paravesical post-herniorrhaphy foreign body granuloma with abscess formation which simulated a lymph node metastasis. Management of this particular case is discussed and the literature is reviewed.


Electrical stimulation of pelvic floor musculature by percutaneous implantable electrodes: a case report.

A forty-year-old man with reflex urinary incontinence due to spinal cord injury was treated with electrical stimulation of the pelvic floor musculature. In this case we employed percutaneous implantable electrodes and an external pulse regulator. After 4 weeks of stimulation incontinence was improved and urodynamically maximum cystometric capacity increased from 220 ml to 350 ml. Our method is easy and not invasive. This technique can be an alternative for the electrical stimulation for urinary incontinence.


Acute experimental unilateral orchitis in the rabbit and its effect on fertility.

We examined the nature of contralateral damage following unilateral orchitis to see if an immunologically mediated mechanism was present. Experimentally induced orchitis in 18 white New Zealand rabbits were examined and compared to 20 in the control groups. Serum antisperm antibody presence and bilateral testicular biopsies (Johansen biopsy score, mean seminiferous tubule diameter) were examined and pregnancy rates were noted. Acute orchitis seemed to be a causative factor in production of antisperm antibody and the presence of antisperm antibody caused histologic changes in contralateral testicles and therefore impaired fertility.


Primary chemotherapy in the management of low stage (IIA and IIB) non-seminomatous germ cell testicular tumours.

In a prospective study a total of 65 patients in clinical stages IIA and IIB nonseminomatous testicular tumours were treated by primary chemotherapy followed by retroperitoneal lymphadenectomy in cases with residual disease. The patients were given a combination of cisplatin, vinblastine and bleomycin, or also etoposide. Sixty-two patients (95.4%) achieved complete response: 39 (60%) by chemotherapy alone and 23 (35.4%) following surgical removal of residual disease. Three patients died; there were two drug-related deaths during PVB chemotherapy, one patient had progression of disease following chemotherapy and died as a result of disease dissemination. Three patients relapsed from complete response following chemotherapy, two of them died within 19 and 29 months after the onset of therapy. The third patient received second-line chemotherapy and gained complete response again. Of the 65 patients, 60 (92.3%) survive with no evidence of disease. The follow-up period ranged from 6 to 79 months (mean 39.4 months, median 39 months).


Renal tubular epithelial antigen-containing immune complexes stimulate interleukin-1 production by monocytes from patients with glomerulonephritis.

We have investigated the effect of immune complexes (IC) derived from human renal tubular epithelial (RTE) antigen on the release of interleukin-1 (IL-1) in monocyte cultures from patients with glomerulonephritis (GN). When peripheral blood monocytes (PBM) were activated by IC, substantial amounts of IL-1 could be detected in the supernatants as measured by mouse thymocyte assay. The IC-induced IL-1 activity was significantly higher in patients with GN than in normal controls. To avoid the effect of prostaglandins on the IL-1 assay, we cultured PBM with addition of indomethacin and assayed IL-1 activity in the culture supernatants. This cyclooxygenase inhibitor augmented IC-induced IL-1 production. The results suggest that IC are involved in stimulating IL-1 production by PBM and thus play a role in the immune response in GN.


Catheter types and their abdominal implantation in peritoneal dialysis.

In the period 1976-1990 a total of 282 chronic uraemic patients were put to peritoneal dialysis by means of abdominally implanted Tenckhoff catheters, out of which 170 had to be replaced. Description of the catheter types is followed by a summary of the rules of surgical implantation and postoperative treatment that should be observed for the peritoneal dialysis to be effective. Discussed are the causes and percentage distribution of changes that call for catheter replacement, finally the alternatives of conservative therapy.


Adhesion molecules involved in the trafficking of normal and malignant leukocytes.

Adhesion molecules involved in leukocyte recruitment and lymphocyte recirculation impact on several aspects of tumor biology--the primary host response, the delivery of effective adoptive immunotherapy and the hematogenous spread of malignant cells. Common to all three processes are receptor-mediated adhesive interactions between circulating cells and the vessel wall. Recruitment of circulating lymphocytes, monocytes and natural killer cells is essential for an effective host response or successful adoptive immunotherapy. Thus poor induction or blockade of leukocyte binding sites on the microvasculature of tumor implants may help malignancies evade natural defenses. In addition, perturbation of adhesion receptor function during ex vivo expansion may alter the behavior of infused cells in adoptive immunotherapy protocols. Finally, circulating malignant cells may utilize receptors normally involved in recruitment and recirculation. This paper reviews the function and regulation of adhesion molecules involved in normal leukocyte trafficking. The evidence implicating specific adhesion receptors in the spread of lymphoid malignancies through the bloodstream is then discussed.


Expression of heparanase by platelets and circulating cells of the immune system: possible involvement in diapedesis and extravasation.

Interaction of T and B lymphocytes, platelets, granulocytes, macrophages and mast cells with the subendothelial extracellular matrix (ECM) is associated with degradation of heparan sulfate (HS) by a specific endoglycosidase (heparanase) activity. The enzyme is released from intracellular compartments (i.e., lysosomes, specific granules) in response to various activation signals (i.e., thrombin, calcium ionophore, immune complexes, antigens, mitogens), suggesting its regulated involvement in inflammation and cellular immunity. In contrast, various tumor cells appear to express and secrete heparanase in a constitutive manner, in correlation with their metastatic potential. Heparanase enzymes produced by different cell types may exhibit different molecular properties and substrate cleavage specificities. The platelet enzyme appears also in a latent form. It can be activated by tumor cells and thereby facilitate their extravasation in the process of metastasis. Degradation of ECM-HS by all cell types was facilitated by a proteolytic activity residing in the ECM and/or expressed by the invading cells. This proteolytic activity produced a more accessible substrate for the heparanase enzymes. Heparanase-inhibiting, nonanticoagulant species of heparin markedly reduced the incidence of lung metastasis in experimental animals. These species of heparin also significantly impaired the traffic of T lymphocytes and suppressed cellular immune reactivity and experimental autoimmune diseases. Heparanase activity expressed by intact cells (i.e., platelets, mast cells, neutrophils, lymphoma cells) was found to release active HS-bound basic fibroblast growth factor from ECM and basement membranes. Heparanase may thus elicit an indirect neovascular response in processes such as wound repair, inflammation and tumor development. The significant anticancerous effect of heparanase-inhibiting molecules may therefore be attributed to their potential inhibition of both tumor invasion and angiogenesis. Both normal leukocytic cells and metastatic tumor cells can enter the bloodstream, travel to distant sites and extravasate to the parenchyma at these sites. We suggest that heparanase is utilized for this purpose by both types of cells. Other functions (i.e., enzyme activities, adhesive interactions, chemotactic and proliferative responses) of metastatic tumor cells seem to mimic the equivalent functions of leukocytes as they migrate across blood vessels to gain access to sites of inflammation.


Extravasation of antitumor effector cells.

Development of effective local immune responses depends on the ability of lymphocytes to extravasate and migrate into nonlymphoid solid tissues. Different lymphocyte subpopulations seem to vary in their abilities to extravasate. In this review, recent advances made in understanding lymphocyte extravasation, interactions between lymphocytes and vascular endothelial cells, receptors on lymphocytes which are involved in their movement through the extracellular matrix, and cytokines, which regulate lymphocyte mobility through tissue, are described. In pathologic conditions, lymphocyte extravasation may be compromised, and delivery of immune effector cells to the site of injury is an important therapeutic end point. Adoptive therapy of solid tumors with antitumor effector cells depends on their successful delivery to the tumor. Although parameters which determine this delivery are not yet defined, considerable progress has been made in studies of the mechanisms involved in lymphocyte movement through tissues.


Lymphocyte migration through extracellular matrix.

The movement of lymphocytes through extracellular matrix (ECM) is an essential component of normal traffic and infiltration into inflammatory sites. This review surveys current knowledge of the mechanisms of lymphocyte migration through ECM, most of which was derived from work with in vitro models of basement membranes, interstitial stroma, or their constituent components. Normal lymphocyte motility is an extremely plastic property. Naive lymphocytes tend to be unresponsive to ECM components and many chemoattractants, but when exposed to antigens, artificial mitogens and certain lymphokines, they rapidly acquire locomotory capacity, which is expressed as increased polarity, adhesiveness, invasiveness and chemotactic response. Acquisition of locomotory capacity is associated with the G0/G1 transition, and activation of protein kinase C appears to be a key event. Preliminary evidence indicates that mitogenesis and differentiation to the memory phenotype trigger a long-lasting, possibly permanent elevation of locomotory response to ECM. Receptors for fibronectin, laminin and collagens I and IV have been implicated as mediators of lymphocyte motility, but these receptors have not been characterized in detail. Heparanases facilitate T cell movement through the basement membrane, but the role of proteases has not yet been defined. Major gaps remain in our understanding of the connection between in vitro models and specific stages of the infiltration process in vivo and of motility regulation at the molecular level.


Hyaluronic acid in the rabbit cornea after excimer laser superficial keratectomy.

Hyaluronic acid (HA) is not normally found in the corneal stroma. Rabbit corneas were examined for the presence of stromal HA after excimer laser treatment. One eye in each of 28 rabbits received a 60 microns deep superficial keratectomy with the excimer laser. After 1, 8, 21, and 60 days, the corneas were analyzed by quantitative and histochemical methods specific for HA. A statistically significant increase in the HA concentration compared to the baseline amount in the untreated fellow eye was seen at 8, 21, and 60 days. HA was visualized histochemically in the anterior stroma of the excimer-treated eyes at all times tested. The presence of HA after excimer surgery may influence the hydration, thickness, and transparency of the cornea. The reactive production of HA in the stroma may represent a nonspecific corneal tissue response to injury.


Topical antibiotic therapy for the treatment of experimental Staphylococcus aureus keratitis.

A rabbit model of Staphylococcus aureus keratitis was developed to study the chemotherapeutic efficacy of ciprofloxacin, vancomycin, and cefazolin. Intrastromal injection of 100 colony forming units of log phase S. aureus ATCC strain 25923 resulted in rapid growth in the cornea, peaking at 10(7) cfu/cornea by 12 hr post-infection. Slit-lamp examination revealed that infected eyes reached 30% of maximum inflammation by 10 hr and 60% by 22 hr post-infection. Antibiotic therapy (one drop every 15 min for 5 hr) was initiated at 4 hr post-infection (experiment 1) or 10 hr post-infection (experiment 2). Another group was initiated at 10 hr post-infection and treated for 10 hr (experiment 3). In experiment 1, treatment from 4-9 hr post-infection with 0.3% ciprofloxacin drops decreased the cfu per cornea 6.1 logs, compared to placebo-treated controls (P = 0.0001), and rendered 50% of inoculated eyes sterile. Vancomycin (5.0%) and cefazolin (5.0%) each lowered the cfu per cornea 4.6 logs (P = 0.0187) but did not sterilize any eyes. In experiment 2, therapy from 10-15 hr post-infection with 0.3% ciprofloxacin reduced the cfu per cornea 0.9 logs (P = 0.0001). Vancomycin (5.0%) and cefazolin (5.0%) decreased the cfu per cornea 0.2 logs (P = 0.3973) and 0.3 logs (P = 0.1307), respectively. In experiment 3, therapy from 10-20 hr post-infection with 0.3% ciprofloxacin reduced the cfu per cornea 3.9 logs (P < 0.0001). In this keratitis model, ciprofloxacin was more effective than vancomycin or cefazolin in killing S. aureus.


A new in vitro corneal preparation to study epithelial wound healing.

Corneal epithelial wound healing is an important process necessary for maintenance of visual integrity. Corneal epithelial wound healing occurs by cellular migration and proliferation. However, the molecular basis of reepithelialization is not known. To investigate individual molecular contributions to the wound healing process, an in vitro corneal preparation comparable to the in vivo condition is needed. This investigation developed a new whole mount in vitro rabbit cornea preparation and studied epithelial wound healing rates for epithelial and subepithelial wounds. The wound closure rates obtained in this study for epithelial and subepithelial wound healing (52 +/- 14 microns/hr and 38 +/- 7 microns/hr, respectively) are comparable to in vivo rates of wound healing determined by other laboratories for rabbits. This preparation, achieved by functionally separating the epithelial and endothelial sides of the cornea, allows application of agents to the cornea in a manner that approximates the in vivo condition. This in vitro system is promising for future studies designed to investigate corneal wound healing while reducing potential ocular discomfort associated with in vivo corneal wounding.


Concentration-dependent effects of lidocaine on corneal epithelial wound healing.

Local anesthetic toxicity is a recognized clinical problem that has limited the use of topical corneal anesthetics for pain relief after corneal abrasion. Studies have shown clinically administered concentrations (0.5-2%) of local anesthetics impair corneal reepithelialization. Unfortunately, instillation of local anesthetic drops into an eye does not provide a measurable, steady-state concentration of drug. Thus, it has not been possible to evaluate whether there is an analgesic concentration of local anesthetic that does not impair corneal wound healing. Using the new in vitro rabbit cornea wound healing model, the effect of steady-state lidocaine concentrations on epithelial wound healing was examined. At lidocaine concentrations below 100 micrograms/ml, wound healing was not impaired. Higher concentrations (250-1000 micrograms/ml) resulted in dose-dependent impairment of epithelial wound healing. Combined with electrophysiologic evidence that corneal nerve injury discharge can be abolished by lidocaine concentrations less than 100 micrograms/ml, this research suggests that topical lidocaine in low concentration may be a safe topical corneal analgesic.


Rabbit corneal epithelial cells adhere to two distinct heparin-binding synthetic peptides derived from fibronectin.

Fibronectin plays an important role in corneal reepithelialization during corneal wound healing. In this study, rabbit corneal epithelial (RCE) cell adhesion to fibronectin was further defined using proteolytic fragments of fibronectin and chemically synthesized peptides derived from the amino acid sequence of fibronectin. RCE cells adhere to intact fibronectin, the 75 kD fragment containing the RGDS (Arg-Gly-Asp-Ser) cell adhesion-promoting sequence, and the 33/66 kD cell adhesion promoting/heparin-binding fragments of fibronectin. The 75 kD fragment and the 33/66 kD fragments partially inhibited RCE cell adhesion to intact fibronectin, suggesting that these fragments represent distinct sites used by RCE cells to adhere to intact fibronectin. Two chemically synthesized peptides derived from the amino acid sequence of the 33/66 kD fragments of fibronectin, FN-C/H-I (YEKPGSPPREVVPRPRPGV) and FN-C/H-III (YRVRVTPKEKTGPMKE), directly promoted the adhesion of RCE cells. As further evidence that FN-C/H-I and FN-C/H-III play a role in the adhesion of RCE cells to the 33/66 kD fragments of fibronectin, we have shown that soluble FN-C/H-I and FN-C/H-III inhibited RCE cell adhesion on surfaces coated with the 33/66 kD fragments. In addition, polyclonal IgG against FN-C/H-I and FN-C/H-III partially blocked RCE cell adhesion to the 33/66 kD fragments, confirming that these sequences represent adhesion-promoting sites within these fragments. In contrast, two previously described peptides from the 33/66 kD fragments of fibronectin, which promoted the adhesion of a variety of cell types, FN-C/H-II (KNNQKSEPLIGRKKT) and CS-1 (DELPQLVTLPHPNLHG-PEILDVPST), did not support RCE cell adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)


Formation of capillary-like tubes by vascular endothelial cells cocultivated with keratocytes.

This report describes an in vitro system that could be useful for investigating corneal neovascularization. When isolated bovine capillary endothelial cells (CEC) were cocultivated with rabbit corneal keratocytes, capillary-like cords extended actively from the endothelial cells in the multilayers of the keratocytes. The developing cords continued to elongate, branch out, and anastomose with each other, forming a capillary-like network by the 12th day of coculturing. Electron microscopic observation revealed that the cords were tubular structures composed of three to seven endothelial cells in the multilayers of keratocytes, and that a basal lamina-like matrix was situated at the abluminal face of the endothelial cells. The growth of cellular cords from the cloned CEC also occurred when CEC were seeded onto a cell-free extracellular matrix that had been synthesized by keratocytes. Keratocyte-conditioned medium alone did not stimulate proliferation of CEC. These observations clearly indicate that the formation of capillary-like structures by CEC depended upon the presence of an extracellular matrix produced by keratocytes, rather than upon the keratocytes themselves or any other keratocyte byproduct. This simple in vitro experimental system is proposed as a useful tool for studying corneal neovascularization.


Intracellular pH regulation in fresh and cultured bovine corneal endothelium. II. Na+:HCO3- cotransport and Cl-/HCO3- exchange.

The comparison of intracellular pH (pHi) regulation between fresh (FBCE) and cultured (CBCE) bovine corneal endothelium was extended to HCO3- transport mechanisms. Upon introduction of CO2/HCO3- Ringer's solution, there was a small, sharp acidification followed by an alkalinization .09 and .18 pH U above the HCO3- free resting pHi for FBCE and CBCE, respectively. This increase in pHi totally depended upon the presence of Na+, independent of Cl- and blocked by the anion transport inhibitor, H2DIDS (0.5 mmol/l). Recovery from an (NH4)2SO4-induced acid load also was blocked by Na+ removal and inhibited 62% and 84% by 0.5 mmol/l H2DIDS for FBCE and CBCE, respectively. These results indicate the presence of a Na+ dependent HCO3- transporter. Additions of 22 mmol/l K+ or 5 mmol/l Ba2+ led to substantial H2DIDS-inhibitable base influx in HCO3- Ringer's, which was significantly reduced in the absence of HCO3- for FBCE and CBCE, consistent with the presence of electrogenic Na+:nHCO3- cotransport. Using the Na+ sensitive intracellular dye, SBFI, we confirmed that the addition of HCO3- resulted in a H2DIDS-sensitive Na+ influx. The mean steady-state [Na+i] = 14 +/- 3 mmol/l in bicarbonate-free Ringer's and 31.5 +/- 2 mmol/l in CO2/HCO3-. HCO3- induced Na+ influx was reduced 74% by 0.5 mmol/l H2DIDS. Removal of Cl- from bicarbonate Ringer's alkalinized FBCE and CBCE by .12 +/- .01 and .21 +/- .03, respectively. The increased pHi was completely blocked by 0.5 mmol/l H2DIDS. Similar alkalinizations were seen when Cl- was removed from air equilibrated bicarbonate-free Ringer's. However, because of the lowered buffering capacity in the absence of HCO3-, the flux was reduced by 80%. Cl- free alkalinizations were eliminated by equilibrating the bicarbonate-free Ringer's with 100% nitrogen gas, indicating that residual CO2 can act as a substrate. Bicarbonate efflux on readdition of Cl- was Na+ independent and pHi sensitive (inactivated by low pHi), and showed simple saturating kinetics with respect to bath Cl, K1/2 = 22 and 16 mmol/l for FBCE and CBCE, respectively. These data are consistent with the presence of Cl-/HCO3- exchange in FBCE and CBCE. Application of 0.5 mmol/l H2DIDS to resting cells in HCO3- Ringer's significantly reduced pHi by .23 +/- .03 and .18 +/- .02 in FBCE and CBCE, respectively, indicating net HCO3- influx in resting cells and suggesting that the stoichiometry of the Na+:nHCO3- cotransporter favors Na+ and HCO3- uptake, ie, n < or = 2.


Central and peripheral corneal thickness in full-term newborns by ultrasonic pachymetry.

To establish a standard of normality, the authors studied the central and peripheral (superior, inferior, nasal, and temporal) corneal thickness of 152 healthy, white race, full-term newborns (304 eyes) between 1 and 6 days old, using ultrasonic pachymetry. The mean central corneal thickness (CCT) was 585 +/- 52 microns (ranging from 446-706 microns). The mean peripheral corneal thickness (PCT), significantly thicker than CCT (P = 0.0001), was: superior (SCT) 696 +/- 55 microns, inferior (ICT) 744 +/- 62 microns, nasal (NCT) 742 +/- 58 microns, and temporal (TCT) 748 +/- 55 microns. The SCT was significantly thinner than the ICT, NCT, and TCT (P = 0.0001). Differences among ICT, NCT, and TCT were not statistically significant. The mean CCT of the 1-day-old group was 611 +/- 58 microns, this being thicker than those of the other age groups (P = 0.0001). The differences between male and female babies and between right and left eyes were not statistically significant. This is the first study on peripheral corneal thickness at the limbus in the four meridians in live newborns.


Visual function and the subsequent development of exudative age-related macular degeneration.

The eyes of 47 subjects with exudative age-related macular degeneration in the fellow eye were tested with a battery of visual function tests at baseline and followed for at least 18 mo. Fundus photographs also were obtained at baseline. These photographs were used to verify the absence of exudative lesions in the 47 eyes tested. Functional and funduscopic baseline data each were compared against outcome data obtained typically at 18 mo. The baseline data were analyzed for their ability to distinguish eyes that had developed detectable exudative age-related macular degeneration from eyes that had not. Eyes with relatively slow foveal dark adaptation rates despite low foveal quantum absorption capabilities (as inferred from the effects of test area on the Rayleigh color match) were especially likely to develop subretinal neovascularization. The resulting sensitivity/specificity and odds ratios were comparable to those of the most effective funduscopic risk indicators. Low S (blue) cone-mediated sensitivity also was associated with an exudative outcome.


Immunogold localization of myosin in the photoreceptor cilium.

The photoreceptor outer segment (OS) develops from the distal end of a nonmotile cilium and exhibits a continuous renewal of its disc structures throughout life. Immunocytochemical studies have localized an actin-rich domain to the ciliary axoneme at the base of the OS, and recent ultrastructural studies of detergent-extracted retinas have demonstrated actin filaments at this site. These filaments are believed to participate in the formation of new outer segment discs. In this study, rat neural retinas were treated with the detergent saponin, fixed with aldehydes, and embedded in London resin white resin for immunoelectron microscopy. In thin tissue sections, actin filaments were observed within the appropriate ciliary domain and these filaments could be positively stained with anti-actin antibodies. When this tissue was immunogold labeled with anti-myosin antibodies, myosin also was found in this locale. The results of this study demonstrate that saponin-extracted retinas can be used for immunoelectron microscopy studies of the photoreceptor cytoskeleton. In addition, the presence of myosin within the actin-filament-containing portion of the cilium suggests that an actomyosin contractile mechanism may play a role in outer segment disc morphogenesis.


Transient increase of b-wave in the mouse retina after sodium iodate injection.

Twenty C57 black mice received an injection of 40 mg/kg of sodium iodate through the caudal vein. The electroretinograms (ERGs) were recorded before and after injection. Flash stimuli with the maximum illuminance, 30,000 lux, were given at increasing levels of illuminance in 0.6 log U steps for 13 levels of intensity. The a- and b-wave amplitudes increased linearly with increased stimulus intensity for approximately 5.0 log U before being saturated. Twenty four hours after injection, the intensity-amplitude curve shifted toward the higher intensity region. It was calculated that the sensitivity loss of the b-wave after injection was 2.0 log U, although the maximum amplitude was larger and the peak latency was delayed. The same results were seen less obviously in the ERGs 48 hr after injection. After 96 hr, both waves were greatly attenuated and even abolished. At the time the increased ERGs were recorded, the histopathologic findings exhibited severe damage of the retina in the pigment epithelium and in the outer layer.


Impoverished stimulus input does not simulate the slowed visual kinetics of retinal damage.

In the rat with normal sight, the acoustic startle reflex to a sound burst is suppressed when the sound is preceded by a brief light pulse. This effect of light in the rat with retinal damage is reduced and peak suppression is seen at a greater delay. Both observations are expected consequences of the loss of visual sensitivity that should accompany photoreceptor loss. However, in an early stage of retinal damage, the peak of the suppressive effect is so delayed that at long lead times the light flash is a more effective stimulus in the rat with the damaged retina than in the normal rat. Two experiments tested the hypothesis that this crossing over of the two groups is a secondary consequence of a nonspecific loss of visual sensitivity in the visually impaired rat. If the hypothesis is correct, reductions in the intensity or duration of the light flash and the degree of dark adaptation should model the effect in normal rats. The overall amount of reflex suppression was diminished with these manipulations, but none diminished the temporal development of reflex suppression to a degree sufficient to produce the paradoxical crossover effect characteristic of retinal damage. These data indicate that decrements in the speed of visual processing are not secondary to the changes in sensitivity that accompany retinal damage, but should be viewed as a separate and independent form of visual impairment.


Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreoretinopathy.

The use of biodegradable polymer microspheres containing adriamycin for the treatment of proliferative vitreoretinopathy (PVR) in an experimental rabbit model was investigated. A single injection of microspheres containing 10 micrograms of adriamycin effectively decreased traction retinal detachment to 10% (n = 10), whereas 50% of eyes injected with blank microspheres (n = 10) developed retinal detachment (P < 0.05). A single injection of microspheres, containing 3 micrograms of adriamycin, did not suppress retinal detachment. Electroretinographic and histologic studies confirmed that the 10 micrograms injection of adriamycin in microspheres was not toxic to the retina, although the injection of the same amount of free adriamycin caused retinal necrosis and detachment. Thus, microspheres containing adriamycin hold promise as a new treatment modality for PVR.


Superoxide dismutase in the anterior chamber and the vitreous of diabetic patients.

Total superoxide dismutase (SOD) activity was examined in the anterior humor of 32 diabetic patients and 34 nondiabetic controls during cataract extraction. Median age (95% confidence interval) was 77.5 yr (73.3-81.0) and 79.3 yr (76.0-83.2), respectively. The SOD activity also was examined in posterior vitreous sampled peroperatively in 10 diabetics with proliferative retinopathy and post-mortem in seven diabetic patients and 35 nondiabetic controls. Ages were 57.2 yr (35.0-73.9), 74.4 yr (40.7-83.6), and 73.8 yr (65.0-80.2), respectively. In nondiabetic patients, the total SOD activity was much lower in the anterior chamber, 9.9 U/ml (8.1-12.6), than in the posterior vitreous, 106.3 U/ml (range 65.6-119.0), P < 0.001. We found no difference between the SOD levels in the anterior chamber of nondiabetic controls and diabetic patients, who had 9.6 U/ml (7.6-13.7). The SOD activity in posterior vitreous in diabetic patients sampled peroperatively, 23.9 U/ml (8.9-39.2), P < 0.0001, and post-mortem, 39.5 U/ml (6.5-214.2), P < 0.04, was significantly lower than in the controls sampled post-mortem, 106.3 U/ml (65.6-119.0). Low levels of SOD in the anterior chamber may be involved in cataract development, in diabetic patients and nondiabetic controls. That diabetics had decreased SOD activity in the posterior vitreous points to a possible role of SOD in the complex process of diabetic retinopathy development.


Mid-frequency loss of foveal flicker sensitivity in early stages of age-related maculopathy.

Temporal contrast sensitivity in eyes at risk for exudative age-related maculopathy (ARM) was compared to that in age-matched healthy older eyes. The test stimulus was a foveally viewed, flickering, long-wavelength 2.8 degrees diameter circle in an equiluminant (photopic) surround. Retinal illuminance and decision criterion differences were experimentally controlled. Eyes in the healthy and ARM-risk groups had 20/30 or better Snellen acuity and intraocular pressure of less than 22 mmHg. Nevertheless, the ARM-risk patients were less sensitive to flicker contrast, especially for mid-temporal frequencies. This suggests that flicker sensitivity may be useful in identifying patients at risk for exudative ARM. In addition, comparison with other research reveals a paradox: Mid-temporal frequency sensitivity losses may be attributable primarily to a "high temporal frequency" mechanism.


Foveal flicker sensitivity discriminates ARM-risk from healthy eyes.

The "good" eyes of 13 patients with monocular exudative ARM were compared with age-matched healthy eyes of 19 subjects. Membership in the two study groups was based upon careful clinical evaluation of the tested eye as well as upon status of the fellow eye. We asked whether temporal contrast sensitivity for a long-wavelength, low spatial frequency stimulus can be used to identify the group in which a given eye belongs. Using step-wise discriminant analysis, we found that the ARM-risk and healthy eyes could be classified with 78% accuracy on the basis of foveal flicker sensitivity at two temporal frequencies--14 and 10 Hz (in order of estimated weight.)


Preliminary evaluation of flicker sensitivity as a predictive test for exudative age-related maculopathy.

Flicker contrast sensitivity was tested in the "good" eyes of 13 patients with monocular exudative age-related maculopathy (ARM). The stimulus was a foveal, long-wavelength, low spatial frequency 2.8 degrees circle in an equiluminant (photopic) surround. Two of these ARM-risk eyes have since developed exudative ARM. Compared to healthy age-matched eyes, the two eyes that developed exudative ARM had significantly lower sensitivity at 10-40 Hz up to 9 mo before exudative symptoms appeared. The implications of these results regarding the time-course of ARM and the predictive value of foveal contrast sensitivity testing are considered. Based upon data and theoretical considerations, the authors speculate that sensitivity loss between 10 and 40 Hz is a good predictor of which eyes will develop exudative ARM. This proposal will be tested by new data from current as well as new ARM-risk subjects.


Infant VEP and preferential looking acuity measured with phase alternating gratings.

Previously, infants' grating acuity was found to be temporally tuned, but adults' grating acuity was not. In infants, acuity was higher for gratings phase alternating at 7.5 and 14 reversals/sec than for stationary gratings and gratings alternating at 2.5 or 23 reversals/sec. Also, when preferential looking (PL) and visually evoked potential (VEP) acuity were estimated with phase alternating gratings (14 reversals/sec), the acuity difference between the two techniques was smaller than that obtained when phase alternating gratings were used to estimate VEP acuity and stationary gratings were used to estimate PL acuity. In the present study, it was determined if PL grating acuity was tuned in older children and if the smaller difference between VEP and PL acuity found when infants were tested with phase alternating gratings was independent of temporal rate. Grating acuity in infants older than 2 yr was found to be not tuned, and the smaller difference between VEP and PL grating acuity in infants when both were measured with phase-alternating gratings was not rate dependent. VEP acuity and PL acuity for phase alternating gratings developed at different rates, converging to nearly equivalent levels by 12 mo of age.


Assessment of physiologic statokinetic dissociation by automated perimetry.

The effects of age, stimulus size, meridian, and eccentricity on physiologic statokinetic dissociation were investigated in clinically normal subjects using the Humphrey field analyzer (HFA, model 640), an automated perimeter capable of both static and kinetic perimetry. The right eyes of 20 age-matched young and 20 age-matched elderly volunteers was examined along the 15 degrees and 195 degrees meridians with six Goldmann size I and five size III kinetic stimuli. These were chosen to produce a spread of discrete eccentricities. Kinetic sensitivity was determined seven times for each stimulus, and the mean stimulus locations were expressed in terms of their x and y coordinates. Static sensitivity for each stimulus size then was determined seven times at each of the corresponding locations using a custom threshold program. The area under each sensitivity gradient was determined using the trapezium rule. Group mean kinetic sensitivity was greater than group mean static sensitivity (P < 0.001), and this difference was largely independent of age, stimulus size, meridian, and eccentricity.


Comparison of computer-assisted versus manual optic nerve head pallor measurement.

Computerized methods of examining the optic nerve head offer the possibility of providing consistent, reliable, and accurate measurements of the nerve head. The reliability and accuracy of such instruments must be examined to confirm this. This research was undertaken to gain an insight into the accuracy of such a system, which takes its measurements by tracking the luminance boundaries of the pallor area and the optic nerve head after an observer marks the starting points. Measurements made using the computer-tracked boundary were compared with those made using a boundary tracked by an image-processing system of greater sophistication, the human visual system. The comparison was made with images from one eye from each of 30 subjects (10 normal, 10 ocular hypertensive, and 10 glaucomatous). The measurements were made by two observers. Each observer made each set of measurements twice, and the results were analyzed with a five-factor analysis of variance. The measurements made using the computerized method did not differ significantly from those made using the manual boundary tracking for the two observers, and they were highly correlated (r = 0.99 for the area pallor-disc ratio). Significant differences (P < 0.05) were found between the two observers in both the manual and computerized boundary tracking. The computerized method, however, did not find differences between the two sets of measurements made by each observer; the manual method did show such differences. The computerized method appeared to trace the luminance boundaries successfully in the image, and it might reduce errors related to the observer marking the starting points on different occasions.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of acute increases in intraocular pressure on intravascular optic nerve head oxygen tension in cats.

A newly developed phosphorescence imaging technique was used to generate two-dimensional maps of intravascular oxygen tension (PO2) in the optic nerve head (ONH) and retina of the cat to study the effects of acute moderate increases in intraocular pressure (IOP) on the ONH and retinal PO2. Both the ONH and retinal PO2 were remarkably well maintained as the IOP increased; hypoxia developed only after the blood flow to the eye was stopped. Because ONH hypoxia was not observed during IOP elevation, a lack of oxygen may not be a major cause of glaucomatous damage, although the effects of chronically elevated IOP on the PO2 remain to be evaluated. Because this imaging technique was noninvasive and required only a small bolus injection of a nontoxic oxygen probe, the authors anticipate that it will find significant application in the study of many ocular vascular diseases and glaucoma.


Autosomal dominant mouse cataract (Lop-10). Consistent differences of expression in heterozygotes.

The clinical and histologic features are reported of an autosomal dominant mouse cataract that was first observed as a new mutation in a cross between BALB/cJ and AKR/J. In the homozygous state, the eyes were microphthalmic, and a dense white cataract was present when the eyes opened at day 12. Histologic changes were apparent from birth and as early as 18 days' gestation. Liquefaction started by day 4, and herniation of lens contents posteriorly was seen at day 11. Heterozygous mice had variable expression depending both on their genetic background and age. When the single gene was expressed fully, the cataract appeared as a fetal nuclear white opacity; partial expression gave a nuclear haze to snowflake nuclear opacities. Lop-10 appeared to be an excellent model for studying variable expression of a dominant gene.


Cellular architecture in age-related human nuclear cataracts.

Age-related or senile human nuclear cataracts were examined using electron microscopy of thin sections prepared from thick vibrating-knife microtome sections of nuclei extracted by extracapsular surgery. The use of extended aldehyde-tannic acid fixation of 80-120-microns thick vibrating-knife microtome sections overcame the difficult problem of preserving the hardened nuclear core of aged lenses. Comparisons were made between a typical nuclear cataract, containing a central opacity and a transparent rim, and a more advanced, or mature, completely opaque nuclear cataract. The typical nuclear cataract contained no obvious cell disruption, cellular debris, or objects that readily could explain the central opacity. The fiber cells had intact uniformly stained cytoplasms with well-defined plasma membrane borders and gap junctions. The transparent rim and the nuclear core appeared similar, except that fiber cells in the nucleus were more condensed with more elaborate intercellular interdigitations. The mature cataract showed various types of cell disruption in the perimeter but not in the core of the nucleus. These disruptions were globules, vacuoles, multilamellar membranes, and clusters of highly undulating membranes. Because these potential scattering centers were not found in the nuclear core, they probably were not the sole cause of the observed opacity. Other potential scattering centers found throughout the mature cataract nucleus included variations in staining density between adjacent cells, enlarged extracellular spaces between undulating membrane pairs, and protein-like deposits in the extracellular space. Similar features, although less pronounced, were present in the typical nuclear cataract. It was concluded that massive cell disruption is not essential to the formation of a central nuclear opacity. Subtle structural changes, especially small fluctuations in protein density between adjacent cells and alterations of the membranes and the extracellular space, probably contribute significantly to the central opacities in human nuclear cataracts.


Verapamil substantially increases the chemomyectomy effect of doxorubicin injected into rabbit or monkey eyelid.

Local doxorubicin injections have been used clinically to treat blepharospasm, hemifacial spasm, and other related disorders permanently and nonsurgically. Doxorubicin is an effective myotoxic agent for the removal of the orbicularis oculi muscle in the eyelid after local injection. Injections of this drug alone resulted in removal of up to 70% of the muscle fibers from the treated eyelids in monkeys. The authors attempted to optimize the conditions for doxorubicin myotoxicity of the orbicularis oculi. Doxorubicin was injected shortly after local verapamil injection in rabbits and a monkey in an attempt to maximize the muscle injury in the eyelid. Verapamil (dose, 0.5 mg or 1.6 mg in the rabbits), injected with a range of doses of doxorubicin, caused substantially increased muscle loss in the eyelid compared with doxorubicin alone. In the monkey, verapamil (dose, 0.25 mg) injection was followed by an injection of 1 mg of doxorubicin. Verapamil cotreatment resulted in increased muscle loss over that caused by doxorubicin alone in both rabbits and the monkey. Injection of verapamil alone also caused muscle loss, and this was quantified. The muscle loss with doxorubicin and verapamil injections included muscle in the preseptal portion of the muscle and even in the pretarsal muscle (which previously was difficult to destroy). This technique clinically might be used to decrease the dose of doxorubicin injected and/or decrease the total number of injections necessary but still retain a clinically effective treatment for blepharospasm and hemifacial spasm. The reduction in the dose of doxorubicin also may decrease the risk of skin injury from doxorubicin chemomyectomy in these patients.


Cytoskeletal antigen expression in ocular mucosa-associated lymphoid tissue.

The human lacrimal gland (LG) and ocular surface contain discrete regions of epithelial cells with specific functions and at different stages of cellular differentiation. Epithelial cells contain cytoskeletal antigens that show a differentiation-dependent pattern of expression. The objective of this study was to characterize the various epithelial cell populations in normal human ocular mucosa-associated lymphoid tissue (MALT; LG, conjunctiva, and cornea) based on their immunohistochemical staining patterns with anticytoskeletal monoclonal antibodies (MoAbs) reactive with cytokeratins (AE-1, AE-2, AE-3, AE-5, AE-14, PKK1, and 34 beta E12), muscle-specific actin (HHF35), and vimentin. AE-1 stained LG (acini, ducts, and myoepithelia) and the full thickness of corneal and conjunctival epithelia. It stained only the superficial and basal limbal epithelium. AE-2 weakly stained all epithelia, except LG acini and proximal intralobular ducts. AE-3 and 34 beta E12 MoAbs had strong immunoreactivity with all MALT epithelia. AE-5 strongly stained the inner cells (suprabasal) of LG central intra- and interlobular ducts and the suprabasal epithelial layers of the cornea. It weakly stained LG myoepithelia and the superficial conjunctival epithelium. AE-14 stained the outer (basal) cells of LG central intra- and interlobular ducts, LG myoepithelia, basal epithelial layers of the limbus and conjunctiva, and all corneal epithelia. PKK1 stained all epithelia, except the basal limbus. HHF35 and the antivimentin MoAbs stained only the LG myoepithelia. The results of these studies indicate that the different epithelia in human ocular MALT may be differentiated by specific patterns of immunoreactivity with anticytoskeletal MoAbs. These MoAbs may be useful molecular markers for identifying ocular MALT epithelia.


Dietary essential fatty acid supply and visual acuity development.

The influence of dietary omega-3 fatty acid supply on visual acuity development was evaluated in very low birth weight (VLBW) infants using visual-evoked potential (VEP) and forced-choice preferential-looking (FPL) procedures at 36 and 57 wk postconception. The VLBW infants born at 27-33 wk postconception were randomized to one of three diet groups: corn oil, which provided solely linoleic acid; soy oil, which provided linoleic and alpha-linolenic acids; or soy/marine oil; which was similar to the soy oil formula but also provided preformed long chain omega-3 fatty acids. The VLBW infants in the soy/marine oil group had higher omega-3 levels in erythrocyte membranes and better VEP and FPL acuities at 36 and 57 wk than infants in the corn oil group. The soy oil group had intermediate omega-3 levels in erythrocyte membranes and significantly poorer VEP acuity at 57 wk compared with the soy/marine oil group. Only the soy/marine oil group had acuities comparable to the "gold standards" of VLBW infants fed human milk and preterm infants who were born and tested at 35-36 wk postconception. In addition, VEP and FPL acuity were poorer in a nonrandomized group of formula-fed full-term infants than in breast-fed full-term infants. The results suggest that dietary omega-3 fatty acid supply may play an important role in early human visual development.


Effects of angiographic needle size and subsequent catheter insertion on arterial walls. An in vitro experiment in human cadavers.

It is widely believed that down-sizing catheters, and possibly needles, will decrease damage to the entry vessel in the performance of angiography. The purposes of this in vitro experiment are to determine if smaller needles produce less arterial wall damage than larger needles and to assess the influence of subsequent catheter insertion. Each iliac artery pair from 35 fresh human cadavers was punctured three times with an 18-g needle and three times with a 21-g needle, for a total of 210 punctures. In two of each set of three, a 5- or 7-F dilator was passed. One hundred ninety-eight puncture tracts were usable and examined microscopically. They were graded on a scale of 1 to 3 in each of four categories: size of tract, margin irregularity, approximation of edges, and shape of tract. Chi-square analysis of the grading scores showed a significant shift of cases into lower damage grades when the smaller gauge needle was used for initial punctures (P < .0005). The subsequent insertion of a dilator, however, imposed further damage, such that the initial differences due to needle gauge were obliterated (P > .2). These data indicate that a 21-g needle produces less arterial wall damage than an 18-g needle, but that any safety conferred by the smaller needle is eliminated by the subsequent insertion of a 5- or 7-F catheter.


Efficacy of metaiodobenzylguanidine as a scintigraphic agent for the detection of neuroblastoma.

Metaiodobenzylguanidine (MIBG) has been shown to be both sensitive and highly specific for the detection of neuroblastoma. However, controversy surrounds its sensitivity in detecting neuroblastoma when compared with radionuclide (technetium 99m-methylene diphosphonate [99mTc]-MDP) bone scans. Because a diagnostic test ideally should be easy to interpret in addition to being sensitive and specific, this study aims to determine the most efficacious scintigraphic agent for diagnostic use in neuroblastoma. Twenty patients with neuroblastoma had a total of 26 paired MIBG and 99mTc-MDP bone scans obtained less than 4 weeks apart. Each study was evaluated independently of its counterpart by six separate observers (3 experienced and 3 inexperienced in MIBG scintigraphy) to determine the presence or absence of disease and the tumor burden. Inexperienced observers reported more confidence in their interpretations of 99mTc-MDP bone scans; however, seven false-positive bone scans were reported. Using MIBG, all true-positive and true-negative scans, as well as significantly more sites of both primary and metastatic disease, were identified by all observers. This study suggests that MIBG is the more efficacious agent for the scintigraphic evaluation of neuroblastoma.