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Fifty-three patients with Hepatocellular Carcinoma (HCC) from three Sydney teaching hospitals were examined for possible evidence of Hepatitis B virus (HBV) infection. Hepatitis Surface Antigen (HBsAg) was positive in 38% of those in whom it was sought, a higher incidence than previously reported in an Australian series. A further 13 patients had antibody to Hepatitis B core (Anti-HBc), but negative HBsAg, confirming past exposure to HBV. Where serum was available evidence of HBV infection was obtained in 62% of patients. It is argued that the incidence of HBV infection may be shown to be higher still with the advent of new technology as applied to HBV assays and tissue stains. The need to be aware of the growing evidence of a strong association between Hepatitis B virus and the development of HCC is stressed and the clinical implications are discussed.

VM-26 is active in small cell bronchogenic carcinoma even in patients resistant to previous chemotherapy. The overall response rate was 28%, with a response rate of 29% in patients resistant to previous chemotherapy. This response rate is similar to that obtained with other single agents including Adriamycin, vincristine, cyclophosphamide, and procarbazine. The mild subjective and objective toxic effects of the drug make it a potentially useful agent in the treatment of this tumor.

Forty-four patients with documented meningeal carcinomatosis (small-cell lung carcinoma [SCLC], 29%; breast carcinoma, 25%) were treated in a prospective randomized trial with intrathecal methotrexate (MTX) 15 mg or MTX plus cytosine arabinoside (Ara-C) 50 mg/m2. Most patients received intrathecal hydrocortisone (HC) each treatment to minimize arachnoiditis. Overall response was 55%. Seven patients achieved complete response. Response to MTX was superior to combined MTX/Ara-C, but not significantly so (61% v 45%; P greater than .10). Response was more frequent if drugs were administered via Ommaya reservoir than by lumbar puncture (65% v 48%; P greater than .10). Concurrent radiotherapy to the CNS was associated with significantly better response (73% v 35%; P less than .05). Small-cell lung carcinoma patients showed the best response (69%). Overall median survival for the whole group was 8 weeks, but responders fared better than nonresponders (median survival, 18 v 7 weeks; P less than .05). Nausea and vomiting were the most common toxicities encountered (45%), but rarely proved limiting. An unusual, previously undocumented reaction to intrathecal HC was noted. MTX is moderately effective in nonleukemic meningeal carcinomatosis, but the addition of Ara-C does not appear to improve results. Pretreatment factors did not predict outcome in this trial.

1. Ten studies were performed on nine patients with haematological disorders but with normal lungs, who required intermittent blood transfusions. The transfer factor for carbon monoxide and uptake of carbon monoxide per unit lung volume (KCO) were measured with the single breath technique before and at various intervals after transfusion. 2. The mean haemoglobin concentration increased from 7.7 to 11.1 g/dl. 3. The TLCO increased according to a formula based on the Roughton & Forster (1957) diffusion equations. TLCO (standardized) = TLCO (observed). (10.2 + Hb)/1.7 Hb, where haemoglobin (Hb) is expressed as g/dl. 4. The correlation between measured and predicted values was slightly better if changes in alveolar volume were taken into account, by using the KCO value.

To quantify the role of the kidney in whole body metabolic clearance rate (MCR) from plasma of atrial natriuretic peptide (ANP), synthetic alpha-human ANP-(1-28) was infused at 200 ng/min to steady-state conditions in chronically instrumented one-kidney conscious dogs. Clearances were measured in dogs with a normally filtering kidney and they were also measured after the glomerular filtration rate (GFR) was reduced to close to zero by acutely inflating a cuff around the renal artery (RAC), which resulted in minimal urine production and renal blood flow reduction to 59% of the resting level. In normal dogs, MCR was 1,090 +/- 134 ml/min with renal clearance rate (RCR) contributing only 13.9%. After RAC, MCR fell to 864 +/- 151 ml/min, due in part to a fall in RCR (-41.5 +/- 12.9 ml/min), but mostly due to a fall in "rest of the body" (total renal) clearance of ANP. The reduced GFR accounted for virtually all the fall in RCR. Normal plasma ANP half-life was 59.6 +/- 7.9 s. In conclusion, MCR of ANP was very high, approaching the cardiac output, suggesting that most of ANP is cleared in one circulation through peripheral tissues. GFR contributed significantly to RCR (approximately 30%) but the contribution of the kidney to whole body MCR was small relative to rest of the body clearance of ANP.

A double-blind randomized cross-over trial of dexamethasone and prochlorperazine as adjunctive anti-emetics with cancer chemotherapy was undertaken. The drugs were compared for cisplatin, doxorubicin and several other chemotherapy regimens. A total of 44 eligible patients were analysed. Assessment was made by questionnaire answered by the patient 24 h after the chemotherapy. The parameters compared were period of time for nausea and vomiting, number of vomiting episodes, degree of somnolence and insomnia and overall preference. In all cases there was no significant difference for either drug in its ability to suppress emetic effects. Neither drug gave adequate protection against cisplatin-containing regimens. We conclude that dexamethasone alone is equivalent to the more standard dopamine antagonists.

Three cases of primary mediastinal trophoblastic teratoma are described. One patient died from respiratory failure during the initial chemotherapy, Another patient with advanced disease is now apparently free from disease after multiple-drug chemotherapy. The third patient is alive and well four years after a combination of surgery, radiotherapy, and multiple-drug chemotherapy. In the diagnosis and assessment of response to treatment in these tumours emphasis is placed on the measurement of the tumour cell markers, chorionic gonadotrophin and alpha-fetoprotein, by radioimmunoassay. The efficacy of multiple-drug regimens is discussed together with a review of the literature.

Of 101 patients with symptomatic adenocarcinoma or undifferentiated carcinoma of unknown primary site, 95 were evaluable for the effects of two randomized chemotherapy regimens. Forty-eight patients received combination doxorubicin and mitomycin C (DM) and 47 received combination cisplatin, vinblastine and bleomycin (PB). Response rates were not significantly different between the two treatment groups, 42% for DM and 32% for PVB, with an overall response rate of 37.1%. Survival differences for DM and PVB treated groups were not significantly different, with 18 weeks and 25 weeks median survivals respectively. Toxicities were unequal for the two treatment groups with increased haematological toxicity for DM and greater gastrointestinal toxicity for PVB. The authors conclude both therapies were of limited efficacy in the treatment of ACUP patients and emphasize that only symptomatic patients should be considered for such therapies.

Since chemotherapy for metastatic breast cancer is not curative, consideration of the quality of life is important in selecting a treatment regimen. We conducted a randomized trial comparing continuous chemotherapy, administered until disease progression was evident, with intermittent therapy, whereby treatment was stopped after three cycles and then repeated for three more cycles only when there was evidence of disease progression. Each approach was tested with doxorubicin combined with cyclophosphamide or with cyclophosphamide combined with methotrexate, fluorouracil, and prednisone. Intermittent therapy resulted in a significantly worse response (P = 0.02 by Mann-Whitney test), a significantly shorter time to disease progression (relative risk based on proportional-hazards model, 1.8; 95 percent confidence interval, 1.4 to 2.4), and a trend toward shorter survival (relative risk, 1.3; confidence interval, 0.99 to 1.6). The quality of life was expressed as linear-analogue self-assessment scores for physical well-being, mood, pain, and appetite and as a quality-of-life index. It improved significantly during the first three cycles, when all patients received treatment. Thereafter, intermittent therapy was associated with worse scores for physical well-being (by 23 percent of scale; 95 percent confidence interval, 11 to 35 percent), mood (25 percent; 13 to 37 percent), and appetite (12 percent; 0 to 24 percent) and for the quality-of-life index as indicated by the patient (14 percent; 5 to 23 percent) and the physician (16 percent; 7 to 26 percent). Changes in the quality of life were independent prognostic factors in proportional-hazards models of subsequent survival. We conclude that, as tested, continuous chemotherapy is better than intermittent chemotherapy for advanced breast cancer.

Currently available endodontic filling materials for primary teeth demonstrate several inadequacies. Therefore, this study histologically evaluates Hydron (2-hydroxyethylmethacrylate) and zinc oxide and eugenol (ZOE) as primary tooth endodontic filling materials in dogs to compare the materials' biocompatibility and to determine whether they undergo resorption in a physiologic manner. Primary molars of six mongrel dogs, 2 to 3 months old, received one-step endodontic therapy. By random selection, two thirds of the molars were filled with either Hydron or ZOE and the remainder were used as unoperated controls. Block sections taken during physiologic root resorption were used to obtain serial hematoxylin and eosin sections of periapical regions. Hydron was phagocytosed by mononuclear macrophages in a physiologic manner and at a rate comparable to that of root tissues. In contrast, ZOE demonstrated delayed resorption and transitory inflammation. Neither material showed cytotoxicity. Hydron may therefore be a suitable endodontic material for human primary teeth.

Forty two patients with inoperable non-small cell lung cancer were entered into a phase II study of the combination chemotherapy regimen PVB (cisplatin 60 mg/m2 by intravenous infusion over two hours on day 1, vinblastine 4 mg/m2 by intravenous bolus on days 1 and 2, and bleomycin 15 mg intramuscularly on days 1, 8, and 15), repeated at three weekly intervals. Twelve of 40 evaluable patients (30%) achieved partial responses; there were no complete responses. The median duration of response was 16 weeks (range greater than 8-73 weeks). The median survival of responding patients calculated from entry to the study until death (40 weeks) was superior to that of patients failing to respond (15 weeks). Treatment was accompanied by signs of moderate toxicity, particularly myelosuppression, nausea and vomiting, alopecia, and neuropathy. One patient died from a neutropenic infection. PVB is a moderately toxic regimen for non-small cell lung cancer and appears similar in efficacy and toxicity to high dose cisplatin and vindesine.

We studied the hemodynamic changes produced in conscious, chronically instrumented rabbits during steady-state administration of atrial natriuretic peptide (ANP). We administered synthetic alpha-human ANP intravenously (i.v.) at progressively increasing doses of 1, 2, and 4 micrograms/min, each for 30 min. In different experiments in each rabbit, we determined the effects of the peptide under closed-loop conditions in the intact animal and the "direct" circulatory effects of the peptide after "total" blockade of the autonomic nervous system (TAB) and after combined neurohumoral blockade (NHB), where in addition the vascular effects of vasopressin and angiotensin II were also prevented. In intact rabbits, ANP produced a dose-related reduction in mean arterial pressure (MAP, -3 to -14%), which was entirely due to a fall in cardiac output (CO, -14 to -20%), and there was a small rise in total peripheral resistance (TPR 5-12%). Heart rate remained unchanged. In rabbits subjected to TAB and NHB, all hemodynamic effects of ANP were attenuated. There were dose-related falls in left and right atrial pressures which reached maxima of -3.3 +/- 0.9 and -1.8 +/- 0.2 mm Hg, respectively. There was a reversible rise in hematocrit, probably owing to a shift of approximately 8% in blood volume. These effects occurred mainly through direct actions of the peptide, and there was no evidence of systemic vasodilatation. The magnitude of reflex autonomic effects appeared to be less than expected for the observed fall in MAP, suggesting that ANP also inhibited cardiovascular reflexes.

Metastases of basal cell carcinoma are very uncommon. Only 10 reported cases have been treated with cytotoxic chemotherapy, and no good responses have been documented. The case is presented of a 54-year-old male who had several basal cell carcinomas (BCCs) removed surgically and who, 12 years after his first presentation, developed respiratory symptoms related to metastatic pulmonary BCCs. These failed to respond to initial chemotherapy with methotrexate, bleomycin, and vincristine, but regressed when treated with cyclophosphamide and cis-diamine dichloroplatinum.

Nineteen men with advanced germ-cell tumours were treated with a combination of vinblastine, bleomycin and cis-diamminedichloroplatinum II (cis-platinum). One patient died nine days after starting chemotherapy. Seventeen patients responded to therapy (14 completely and three partially). Toxicity was very high, and three patients died of septicaemia during therapy. Eight patients remain in complete remission 36 to 80 weeks after starting chemotherapy.

Hypomagnesemia is a well-recognised complication of cis-diamminedichloroplatinum (DDP) treatment. We prospectively evaluated 50 patients with advanced malignant disease receiving DDP for the development of hypomagnesemia. Urinary magnesium excretion was measured in 24 patients. The mean serum magnesium fell from 0.79 mmol/l (normal 0.7-1.1 mmol/l) prior to therapy to 0.55 mmol/l 3 months after commencing DDP. All 50 patients had become hypomagnesemic by this time and 10% were symptomatic, requiring oral magnesium supplementation. At 6 weeks after commencing DDP only four patients had restricted urinary magnesium excretion to less than 1.0 mmol/day. The other patients clearly had inappropriately high levels of urinary magnesium excretion, suggesting that DDP may induce a renal tubular defect in magnesium conservation. Hypomagnesemia is a common complication of DDP therapy which in many patients is asymptomatic. Further, more detailed studies of renal magnesium handling are necessary to determine fully the effect of DDP on urinary magnesium excretion.

1. Vasopressin deficient homozygous Brattleboro rats develop malignant renal hypertension following complete aortic-ligature between the renal arteries. 2. This form of hypertension is associated with high plasma renin activity (PRA) and plasma angiotensin II (AII) levels and a high incidence of the specific vascular lesions of fibrinoid necrosis in both Brattleboro and Long-Evans rats. 3. The levels of PRA and AII in the malignant hypertensive Brattleboro rats were not different from those in Long-Evans rats with malignant hypertension. 4. No compensation by the renin-angiotensin system therefore could be demonstrated for the lack of vasopressin in malignant hypertensive Brattleboro rats. 5. Vasopressin does not appear to be essential as a pressor hormone in the development of malignant renal hypertension and fibrinoid can occur in the absence of vasopressin.

In 5 young men with apparent undifferentiated carcinoma involving lung, mediastinum, and lymph-nodes subsequent response to treatment, tumour-marker analysis, and histology review suggested a diagnosis of embryonal-cell carcinoma. It is suggested that atypical presentation of extragonadal germ-cell tumours may be common. Because such tumours respond to chemotherapy, accurate diagnosis is essential.

Two hundred seventy-five patients who had received bleomycin were examined for evidence of pulmonary toxicity. Twenty-six patients were diagnosed as having bleomycin pulmonary toxicity and, of these, 20 (77%) were documented as having renal dysfunction without other features recognized to be associated with the development of pulmonary toxicity. In this study renal dysfunction was a most important factor in the development of bleomycin pulmonary toxicity. As bleomycin is often administered with nephrotoxic drugs, it is suggested that renal function should be checked prior to each administration of bleomycin. It is proposed that appropriate dose modifications could significantly reduce the morbidity and mortality associated with bleomycin administration.

1. Angiotensin II was infused into the renal artery of unanaesthetized dogs at 0.4 and 2.0 ng/kg per min for 40 min each. 2. Indomethacin (3 mg/kg, and 1 mg/kg per h infusion i.v.) accentuated the angiotensin II-induced falls in glomerular filtration rate, renal blood flow and urine flow rate. Indomethacin did not alter the effects of angiotensin II on Na+ or K+ excretions. 3. Aspirin (35 mg/kg p.o. 2.5 h and 0.5 h prior to experiment) did not significantly change the renal effects of angiotensin II. 4. Both aspirin and indomethacin accentuated renal vasoconstriction during briefer (5 min) angiotensin II infusion. 5. Thus indomethacin and aspirin had markedly different effects on the actions of angiotensin II in the kidney. This suggests that at least one of these drugs has actions which affect angiotensin II-mediated vasoconstriction other than via cyclooxygenase inhibition.

Restriction of the water intake of sheep to 0.5 1/day for 7-9 days increases plasma arginine vasopressin (pAVP), and voluntary rehydration causes a rapid fall in pAVP with no change in plasma osmolality. The extent of that inhibition of AVP release was assessed by comparing the decline of pAVP after drinking with pAVP disappearance curves obtained in the same sheep after stopping a constant infusion of AVP at 0.5 micrograms/h, which increased pAVP to the dehydration level. The fall in pAVP after drinking was almost identical with the disappearance curve showing that AVP release was almost completely inhibited during the 2-3 min taken for the sheep to drink 3-5 liters to satiate themselves. The response seemed, therefore, to be cued before the intake reached the satiating volume. When dehydrated sheep drank only 0.5 or 1.0 liter, in 30 s or less, pAVP again fell rapidly but only to a minimum approximately 15 min after drinking. The pAVP was unaltered in dehydrated sheep presented with water but denied access to it. Thus satiation was not necessary for rapid inhibition of AVP release after drinking, but satiation was necessary for this inhibition to be maintained. The initial inhibition was associated with falls in hematocrit and plasma total protein but not plasma osmolality. This isosmolar dilution occurred even in sheep that saw but were denied access to the water and suggests a shift of fluid from the extravascular space.

1. Homozygous Brattleboro rats with hereditary hypothalamic diabetes insipidus (DI) developed one-kidney, one-clip (1K-1C) and two-kidney, one-clip (2K-1C) Goldblatt renal hypertension. 2. However, the systolic blood pressure (SBP) in 1K-1C Brattleboro rats was significantly lower than in non-DI hypertensive 1K-1C Long-Evans (LE) rats. 3. Treatment with the synthetic antidiuretic analogue of vasopressin, DDAVP (1-desamino-8-D-arginine vasopressin), increased the SBP in the DI rats to the same level as in 1K-1C Long-Evans. This elevation of SBP was associated with increased extracellular fluid volume in the DI rats after DDAVP. 4. The results suggest that vasopressin is not essential for the development of renal hypertension but the absolute levels of blood pressure achieved in 1K-1C hypertension are volume-dependent and thus influenced by the water-retaining properties of vasopressin.

A prospective randomized study was conducted in 51 patients with stage D hormone-resistant prostatic carcinoma, comparing a combination of doxorubicin and lomustine (DC) with cyclophosphamide and 5-FU (CF). Patients were assessed objectively (employing National Prostate Cancer Project criteria) and subjectively (using a numerical scoring scheme). Each regimen was well tolerated with acceptable levels of myelosuppression. The objective partial response rate was 57% for DC and 8% for CF. Objective stabilization occurred, respectively, in 14% and 44% of the patients. Similarly, DC demonstrated a significantly superior subjective response rate (partial plus complete) of 82%, compared to 48% for CF. Patients with poor initial performance status or liver involvement had significantly lower response rates and reduced survival. Overall, there was no significant difference in survival between the two arms, reflecting the similarity between DC and CF in total objective response rate (partial response plus stable disease). DC provided superior palliation and was well tolerated by an essentially geriatric population.