CIRRHOSIS OF THE LIVER—Clinical Course in 2,377 Patients at San Francisco General Hospital

The records of 2,377 patients with Laennec''s cirrhosis were reviewed for the period 1947-1957. The chief presenting symptom was ascites in 46 per cent, bleeding in 23 per cent, coma in 18 per cent, jaundice in 9 per cent, and both jaundice and ascites in 4 per cent. Nearly half of the patients died during the period under study—one-third from hepatic failure, one-third from gastrointestinal bleeding, and one-third from other causes, most of which were related to alcoholism.Massive gastrointestinal bleeding occurred in 21 per cent of the patients at some time in their clinical course, and in the 10 per cent of these in whom ulcer was demonstrated, one-fifth died as a result of the hemorrhage. Of those presumed to be bleeding from esophageal varices, 64 per cent died at the first hemorrhage and 10 per cent at subsequent hemorrhages; 85 per cent of all those who bled from varices were dead at the end of one year, and 91 per cent were dead at the end of three years.The survival curve of a group of patients who bled once and were good operative risks but had received no operative treatment was compared to the survival curve for entire group who survived the first hemorrhage. The three-year survival in the good risk group was 47 per cent; for the group as a whole it was 30 per cent. The difference in mortality rate was primarily due to an increased number of deaths from hepatic failure in the combined group, whereas 60 per cent of the good risk group died of recurrent gastrointestinal hemorrhage.As 86 per cent of those who were to die of gastrointestinal bleeding did so at the first hemorrhage, it was concluded that any decided improvement in the salvage rate achievable by operation must come from some means of diagnostic forecast of the likelihood of bleeding, with resort to prophylactic operation in such cases.     

Tracer studies on the balance and chemical distribution of applied nitrogen under different moisture regimes using lysimeter

Summary Tracer studies were made on balance and chemical distribution of added fertilizer under field conditions using a modified type of lysimeter at different moisture regimes. A modified chemical method was also used for the determination of different forms of organic N.An average of 25 per cent of the isotope enriched nitrogen applied to soil could not be accounted for at the end of the 3 years of experiment. The amount of residual added N in soil was around 33 per cent of which 27 per cent was in 0–20 cm layers and only 6 per cent was found in 20–50 cm layers. The average crop recoveries were around 43 per cent. Only 0.18 per cent of NO₃–N was leached from the irrigated plots.The alkali-stable N (amino acid-N) fraction was higher for irrigated (19 per cent) than nonirrigated plots (15 per cent). There were no difference in the amounts of fixed NH₄, non-hydrolyzed and alkali-labile N fractions for irrigated and non-irrigated plots. Only an average of 1.5 per cent of total fertilizer N was found as fixed NH₄–N form but the total fixed NH₄–N was higher (10–13 per cent) than that reported by other workers for surface soil layers. The sum of different soil-nitrogen fractions were always higher than the total nitrogen in soil.     

Abortifacient efficiency of 15(S)15-methyl-prostaglandin F2α-methyl ester administered vaginally during early pregnancy

Forty early pregnancies (menses delay 13 – 27 days) were terminated by administering four vaginal suppositories each containing 1.0 or 1.5 mg of 15(S)15-methyl-prostaglandin F_2α-methyl ester, one every third hour. In 14 cases serial measurements of serum estradiol and progesterone were performed during and after therapy. Uterine contractions and bleeding started 1 – 17 hours after administration of the first suppository. Abortion was complete after one week in five women (13 %), and after two weeks in 30 (75 %). A curettage was performed on eight women, residual placentral fragments were found in seven and pregnancy continued in one woman. Mild diarrhoea (65 %) and vomiting (40 %) were the major side-effects, despite premedication. Estradiol and progesterone levels fell progressively during the therapy. Self-administration of 4 or 6 mg of the methyl ester caused too low a rate of complete abortion for use in practice, but it may be a valuable and practical agent for preoperative dilation of the cervix.     

Chronic hemorrhagic iron deficiency. Sources of hemorrhage, blood loss and systematic iron substitution

In only 121/436 (28 per cent) patients with chronic haemorrhagic iron deficiency bleeding sources could be removed by appropriate management or healed spontaneously. In 61 per cent of all cases the disease lasted from 1 year to greater than 20 years. The fall of haemoglobin per month correlated closely with blood losses per month as calculated by determinations of 59Fe whole body iron loss. Over prolonged periods estimations of the magnitude of blood loss (range 1- greater than 721 per year) based on changes of the iron status under normal diets and under systematic iron substitution. Oral iron administration with appraisable bioavailability was able to compensate blood losses up to 151 and with increasing doses up to 361 per year with maintenance of normal or borderline haemoglobin values. However, side reactions increased considerably after years and with rising doses. Under such circumstances combinations of i.v. iron, oral iron and blood transfusions were successful over prolonged periods.     

THE TREATMENT OF METASTATIC BREAST CANCER IN BONE

The author report clinical experience with 212 cases of mammary cancer metastatic to bone, in 186 of which radiotherapy was given, and in 26 steroid hormone therapy.At least 70 per cent of patients with bone metastasis from breast cancer were relieved of pain by adequate roentgen therapy, the relief lasting for most of the survival time in many instances.About 25 per cent of patients had recalcification or reossification of bony lesions with roentgen therapy; while dramatic, this is not always an indication that relief of pain will continue or that survival time will be lengthened.If and when adequate radiotherapy has not been effective or cannot be administered (for example, in a patient with extremely widespread metastasis, or one residing at a considerable distance from radiotherapeutic service) steroid hormone therapy in adequate dosage is frequently beneficial. From 40 per cent to 75 per cent of patients with bone metastases from breast cancer are relieved of pain by steroid hormone therapy. In about 15 per cent of cases recalcification of the lesion occurs.Effective roentgen therapy may usually be given in a relatively brief period of time (one to two weeks). Effective steroid hormone therapy usually requires from 12 to 24 weeks.Complications of steroid hormone therapy are numerous. Some patients are made considerably worse by such therapy. These complications may only be controlled by reduction or discontinuation of the hormones. For this reason, it is recommended that irradiation always be used as the initial method of palliation.     

Treatment with a single vaginal suppository containing 15-methyl PGF2α methyl ester at expected time of menstruation

Termination of early pregnancy, by vaginal administration of prostaglandin analogues, one to three weeks after the first missed menstrual period, has advantages and disadvantages in comparison with vacuum aspiration. Some of these may be reduced if the patient is treated earlier. In the present study the effect and safety of one vaginal administration of 2.5 to 3 mg 15-methyl-PGF_2α methyl ester around the expected time of menstruation was evaluated in 16 women exposed to the risk of pregnancy.The overall number of treatment cycles was 35 and pregnancy was confirmed by plasma β-HCG in eight. The treatment resulted in bleeding in all the pregnant cycles while in the nonpregnant ones it only provoked spotting and bleeding did not begin until the expected time of menstruation. Treatment with 2.5 mg 15-methyl-PGF_2α methyl ester resulted in complete abortion in one of three women. If the dose was increased to 3 mg all five treated women aborted. In nonpregnant patients no changes in the levels of estradiol-17β or progesterone at any time during the 24-hour observation period were found. Serum cortisol and prolactin but not TSH levels started to increase two hours after the start of treatment and reached a maximum after five hours. The increase coincided with the onset of uterine pain.Ovulatory cycles as judged from basal body temperature occurred in the first menstrual cycle following treatment in all nonpregnant patients. Although possible to use as a “once a month treatment” it seems preferable since the dose is the same, to postpone treatment until menstruation is delayed for a week or more.     

Efficacy of a combination of dioxidine with beta-lactam antibiotics in the prevention and treatment of purulent-inflammatory complications

Schemes for prevention and treatment of purulent inflammatory complications were developed on the basis of in vitro studies on antimicrobial activity of dioxidine and 7 beta-lactam antibiotics such as mezlocillin, carbenicillin, ampicillin, cefotaxime, cefoxitin, cefuroxime and cephalothin under conditions of aero- and anaerobiosis with an account of the isolated microflora, its sensitivity to antibacterial agents and conditions required for vital activity of obligate anaerobes in humans, i.e. decreased partial oxygen pressure, low oxidation-reduction potentials and high tissue concentrations of carbon dioxide. The use of dioxidine in combination with the antimicrobial drugs enabled one to decrease the number of cases with purulent inflammatory complications after large intestine esophagoplasty to 30.4 per cent against 67.5 per cent in the control group of the patients untreated preventively with the antibacterial drugs. The number of cases with similar complications after gastrectomy amounted to 16.1 per cent against 62 per cent in the control. The use of dioxidine+ in combination with ampicillin and cefotaxime in treatment of purulent necrotic affections of the foot in patients with diabetes mellitus enabled one to increase the number of satisfactory outcomes by 32 per cent, to decrease the number of high amputations by 21.9 per cent and to lower the number of deaths more than 2-fold as compared to the results in the control group of the patients subjected to chemotherapy based on sensitivity of the aerobic microflora alone.     

Effects of high-LET neon (20Ne) particle radiation on the brain, eyes and other head structures of the pocket mouse: a histological study.

A study was made of tissues from 130 pocket mice after a single head-only exposure to high-LET 20Ne particle radiation at 1000, 100 or 10 rad (nominal surface dose) with the view of obtaining base"line data regarding the effectiveness of HZE (cosmic-ray) particles during spaceflight. First seen at 2-3 weeks after exposure, necrotic neurons in the cerebrum reached peak incidence (0 . 04 per cent at 1000 rad, 0 . 003 per cent at 100 rad and less than 0 . 0005 per cent at 10 rad) after 4-5 weeks and decreased to low levels thereafter. Incidence in the cerebellum was lower. Neuroglia, cells of the subependymal matrix and dentate gyrus precursor cells suffered acute damage at 1000 and at 100 rad. At 1000 rad, enlarged hyperchromatic neuroglia, first noted at 3 weeks, increased in number up to 7 months, then declined. Alterations in the retina and olfactory epithelium were seen at 1000 rad, and reaction in the scalp at 100 rad. Damage was incurred by dentinoblasts at 10 rad. Changes similar to those observed in pocket mice were found in the brains of gerbils and C57B1 mice.     

Carminomycin in drug combination in breast cancer and soft tissue sarcomas]

Thirteen patients with neglected mammary cancer were treated with karminomycin in combination with hexamethylmelamine. Twelve out of the 13 patients were previously subjected many times to cytostatic and hormonal therapy. A significant therapeutic effect was registered in 5 out the 13 patients (38 per cent), the total rate of the objective effect being 54 per cent. The remission period with a significant effect was 6 to 9 months. Fifteen patients with sarcoma metastases in the soft tissue were treated with karminomycin in combnation with methotrexate and cyclophosphane. A significant therapeutic effect was observed in 45 per cent of the cases with synovial sarcoma, hemangyopericitoma and leuomyosarcoma, the remission period being 4 to 12 months. The side effects of the above combinations were determined.     

Differentiation of myeloid cells in liquid culture: 2. Acute myelocytic leukemia cells

In a companion paper we demonstrated that normal peripheral blood granulocytic precursor cells differentiate after 2-3 weeks in suspension culture. In the studies described here leukemic blast cells obtained from 14 patients with acute myelocytic leukemia (AML) and two patients with chronic myelocytic leukemia in blastic crisis were cultured in McCoy's 5A medium containing 15 per cent fetal bovine serum for 2-3 weeks at 37 degrees C in an atmosphere of 5 per cent CO2-95 per cent room air. 'Spontaneous' myeloid differentiation (20 x 10(4) viable mature myeloid cells ml-1) occurred in the cultures of cells obtained from 8 pts. The differentiation was granulocytic in three cases, monocytic in four cases and of mixed type in one case. Differentiation was independent of the growth of the cells in culture and occurred in four cases after the first week. Monocytic differentiation was seen only in AML of the FAB M4 type whereas granulocytic or mixed differentiation were seen only in AML of the FAB M1 or M2 types. When PHA leucocyte conditioned medium (PHA-LCM) was added to the cultures monocytic/macrophage differentiation was favoured. Inducers of the differentiation of the HL-60 cell line (N-methylacetamide, cytosine arabinoside, or retinoic acid) had no consistent effect on the differentiation and were at times inhibitory. Three patients received therapy with low dose cytosine arabinoside and no correlation was observed between the outcome of the treatment and leukemic cell differentiation in culture in the presence of the drug.     

Fine needle aspiration (FNA)-induced necrosis of tumours of the thyroid

Two cases of necrosis of thyroid oxyphilic tumours following FNA are reported. the first patient received surgery 4 weeks after FNA and histological examination revealed an encapsulated and totally necrotic tumour 2 cm in diameter. In the second patient surgery was performed after 25 days. Histological examination showed a 0.7 cm diameter tumour consisting mainly of fibrous tissue with residual oxyphilic tumour cells only in a small peripheral rim. In both patients no capsular or vascular invasion and no blood vessel thrombosis were present. A review of the literature revealed that oxyphilic tumours are susceptible to post-FNA necrosis, which might be due to the compromised vascular supply after FNA in conjunction with the intrinsic energy deficiency of oncocytic tumour cells.     

Induction of therapeutic abortion using either extra-amniotic prostaglandin F2α or hypertonic saline followed by oxytocin : A clinical comparison of the two methods

PGF_2α or hypertonic (20 per cent) saline followed by oxytocin was used to terminate pregnancy in 160 women between the 10th and 20th weeks of gestation.In the patients treated with PGF_2α minor side-effects were reported in about 50 per cent of the cases, however, the method was superior to hypertonic saline with regard to the number of complications and the length of stay in hospital.     

TRICHOMONIASIS—Clinical Trial of Metronidazole (Flagyl?)

Metronidazole was given in various dosage regimens to 97 patients having microscopically diagnosed trichomoniasis.At the first examination after treatment all 97, including 76 to whom metronidazole had been given orally only, were found by culture and wet smear to be free of trichomonads.Reexamination of the 65 patients followed up for periods ranging from two weeks to 14 months revealed reappearance of trichomonads in eight cases.Nineteen husbands were treated. No patient had a recurrence after treatment of the husband.No effect of metronidazole on pregnancy or on fetal development was seen. Side effects, noted in 19 cases (20 per cent), generally were mild and transient and in no case were severe enough to terminate therapy before cure was effected.     

“Menstrual induction” with sulproston

The PGE₂-analogue Sulproton (16-phenoxy·ω-17,18,19,20-tetranor-PGE₂-mythylsulfonylamide) was administered to 200 medically and gynecologically normal women who were 17±0.4 days beyond their expected menstrual period and who had a positive pregnancy test. The intramuscular impact dose (500 μg repeated after 4 hours) caused an immediate tonic uterine contraction which compromised the estradiol 17β, progesterone and chorionic gonadotropin production within the fetoplacental unit, and thereby allowed the evolution of cyclic uterine activity, cervical dilatation and tissue expulsion.Pregnancy termination was complete in 92% of women, 5.5% required surgical curettage and 2.5% were given a second Sulproston treatment 2–3 weeks after the first to remove retained tissue from the uterus. The medical induction of menstruation was preferred by 83% of the women who had previously experienced surgical termination of pregnancy. Normal menstruation resumed in all women after 36±0.9 days. The majority of 42 women questioned found Sulproston a satisfactory, safe, simple and effective drug regimen for “menstrual induction”.     

Parathion Poisoning—A New Antidote!

Two thousand five hundred forty-five cases of upper gastrointestinal tract hemorrhage were studied especially with a view to determining the indications for urgent surgical treatment.Decisions as to whether and when to operate were as follows:Immediate operation for patients over 50 years with a good history of ulcer and a severe initial bleed.Operation after the first repetition of bleeding in patients (1) over 50 with a good history and a mild initial bleed, (2) over 50 with inconclusive history but severe initial bleed, (3) under 50 with a good history and a severe initial bleed.In all other cases, operation was used only if conservative treatment failed.Absolute indications for operation were (a) association with perforation, (b) association with stenosis, (c) persistence of severe ulcer pain after hemorrhage, (d) continuous bleeding.Since operation is to be avoided if possible in cases of esophagitis, erosive gastritis and small acute or subacute ulcers, emergency gastroscopy has valuable uses.Where operation is deemed necessary and no obvious lesion found at laparotomy, blind gastrectomy^* appears to be the most satisfactory procedure.The mortality rate associated with upper gastrointestinal tract bleeding in patients less than 60 years of age was low (2.5 per cent). Even in cases in which operation was required, it was 6.2 per cent. Over 60 years the mortality rises steeply with increasing age, and in cases of operation the rise is even steeper.By using the methods of selection the overall mortality rate was appreciably reduced.     

Functional uterine bleeding; etiologic factors and therapy

Endometrial hyperplasia and irregular shedding of the endometrium comprise the largest group of known causes of functional uterine bleeding.Most patients with functional uterine bleeding have a normal endometrial pattern. In a series of patients with functional uterine bleeding, it was noted that 69.7 per cent of endometrial specimens reported as normal showed evidence of hyalinized tissue which included endometrial glands. Tissue of this type was noted in only 3.5 per cent of curetted specimens from patients without functional uterine bleeding. Diagnostic uterine curettage is the initial step in the management of functional uterine bleeding. Hysterectomy and radiation castration are seldom necessary in the management of functional uterine bleeding and are indicated only under specific circumstances.     

Clinical use of rubomycin in neuroblastoma in children]

The results of treatment of 23 children at the age of 7 months to 11 years suffering from neuroblastoma are presented; 22 patients with tumors, relapses or metastases were subjected to the treatment and 1 child was treated prophylactically after radical operation. Four patients were subjected to roentgen therapy in addition to the treatment with rubomycin. The antibiotic was administered intravenously in doses of 0.7--1.5 mg/kg in 1--3 days or daily. The caurse dose (3--12 mg/kg) was determined by the treatment efficiency and the side reactions. The objective effect was observed in 68 per cent of the patients, including the pronounced objective effect (marks 3 and 2) in 41 per cent of the cases. Leucopenia (less than 4000 cells in 1 mm3 of the blood). thrombocytopenia, vomiting (or nousea) and changes in the ECG were registered in 20 (87 per cent), 4,9 and 2 patients respectively. When the results of the treatment were positive, repeated courses of the therapy within 1.5--2 years were carried out; 18 patients died within 4 months to 2 years after the first course of the treatment with rubomycin because of the disease development. No signs of the disease were observed in 4 children with in 3--6 years of observation.     

ACUTE GALLBLADDER DISEASE—Experiences with 103 Consecutive Cases

One hundred and three cases of acute cholecystitis in patients ranging in age from 19 to 88 years were reviewed. Operation was done in all cases. Seventy per cent of the patients were women.Primary cholecystectomy was done in 72.8 per cent of the series. Primary cholecystostomy was performed in the remainder, and one-fourth of these patients had a secondary cholecystectomy. No specific time, with relation to interval after onset of symptoms, was chosen for operation.Jaundice was present in 14.5 per cent of patients at the time of admittance to hospital. Serum amylase was above normal in five of 27 patients on whom this determination was carried out. All five were women.The gallbladder was perforated in 13 cases. Common duct exploration was done in 25 cases and in 12 of them stones were found.The morbidity rate for the series was 11.6 per cent; the mortality rate 9.7 per cent.     

HEPARIN IN ACUTE MYOCARDIAL INFARCTION—Observations Indicating the Potential Advantages of Using It as the Sole Anticoagulant in Therapy

There is a considerable body of experimental evidence that heparin is superior as an anticoagulant to any prothrombin depressing drugs. Furthermore its lipemia-clearing action affords other benefits which result from the removal of fat from the bloodstream. Important among these beneficial effects is the increased tissue and myocardial oxygen consumption which results from the injection of heparin in atherosclerotic patients.Because of these advantages of heparin over oral anticoagulants, the use of heparin as the sole anticoagulant for three weeks in patients with severe acute myocardial infarction was evaluated as opposed to the customary therapy where heparin is given for several days and then oral anticoagulants are used. The mortality in the dicoumarin treated group was 38 per cent, as compared with 28 per cent in the patients who received only heparin for three weeks.     

The Role of External Irradiation in the Treatment of Transitional Cell Carcinoma of the Bladder—A Review of Fifty Cases

Of 100 patients with carcinoma of the bladder seen in the Section of Therapeutic Radiology, University of California, San Francisco, between 1957 and 1962, 59 were accepted for radiation treatment. Fifty had transitional cell carcinoma and were treated with supervolt therapy (1 mev or cobalt-60).Two types of tumors were again found suitable for external irradiation: Papillary carcinomas Grades II and III, as long as they have not, or at least have not massively, invaded muscle; and undifferentiated carcinomas, Grade IV, regardless of degree of extension through the pelvis. The former type, if single, is treated by irradiation for the first recurrence after one attempt with radical transurethral resection. In the presence of multiple lesions at the first examination, radiation therapy is given immediately. The latter type is treated by radiation therapy without any attempt at surgical removal.Of 37 patients, Stages A to C, treated more than three years ago, 14 (38 per cent) lived more than three years and eight (22 per cent) had no cystoscopic or clinical signs of active disease and had normal bladder function. Of 23 patients treated more than five years ago, eight were alive after five years (35 per cent) and four (17 per cent) remained controlled by radiation therapy alone, with normal bladder function.No major complications were observed. In particular, no fibrosis of the bladder occurred. Doses ranged from 5,000 r in five and a half weeks to 6,000 r in seven weeks.A close cooperation between urologic surgeons and radiotherapists during recent years permits long-range treatment planning from the time of diagnosis, which is essential in the effective therapy of carcinoma of the bladder.