The Src/Csk regulatory circuit arose early in metazoan evolution.

We have identified a gene encoding a member of the Csk family of non-receptor protein-tyrosine kinases (PTKs) in the early-diverging metazoan Hydra. In situ hybridization analysis of the distribution of RNA from the Hydra Csk gene indicates that it is expressed in most of the epithelial cells of the adult polyp and in gametogenic cells. Comparison of the expression pattern of Hydra Csk with that of STK, the Hydra Src gene orthologue, reveals that the two genes are largely co-expressed. Such co-expression is consistent with a role for Hydra Csk in regulation of STK activity. This possibility was tested directly by coexpressing Hydra Csk with STK in yeast. Co-expression suppressed the growth inhibition seen when STK alone is expressed in yeast. Suppression was dependent on the presence of the putative regulatory tyrosine in the carboxyl-terminal tail of STK. Phosphotyrosine immunoblot analysis confirmed that expression of Csk resulted in suppression of STK kinase activity. Taken together these data indicate that the regulatory circuit involving Src and Csk PTKs was established prior to the divergence of the phylum Cnidaria from the rest of the metazoans.

Food fails to suppress ghrelin levels in obese humans.

UNLABELLED: Ghrelin is the first circulating hormone shown to stimulate feeding in humans following systemic administration. Food consumption decreases circulating ghrelin concentrations in lean subjects but the effects of feeding have not been studied in the obese. METHODS: We investigated the effects of a test meal on plasma ghrelin and leptin concentrations in 13 lean and 10 obese subjects. RESULTS: Fasting ghrelin was significantly higher in lean than in obese subjects (857 pmol/1 vs. 325 pmol/l, (p = 0.002) and fell by 39.5% thirty minutes after eating in the lean group before returning rapidly towards baseline values: (p = 0.003). There was no change in circulating ghrelin in the obese group. Circulating leptin concentration also fell acutely 15 minutes following food intake in lean but not obese subjects (p < 0.0001). CONCLUSIONS: Obese subjects do not exhibit the decline in plasma ghrelin and leptin seen after a meal in the lean. The role of the decline in leptin is unclear but given the orexigenic properties of ghrelin, the lack of suppression following a meal in obese subjects could lead to increased food consumption and suggest that ghrelin may be involved in the pathophysiology of obesity.

A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia.

PURPOSE: Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated. PATIENTS AND METHODS: We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection. RESULTS: Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia. CONCLUSIONS: These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.

Feasibility of outpatient management of fever in cancer patients with low-risk neutropenia: results of a prospective randomized trial.

PURPOSE: We recently demonstrated the efficacy of single-agent oral ofloxacin in the management of hospitalized neutropenic febrile patients. Ofloxacin was particularly effective in patients with short duration of neutropenia and fever of undetermined origin. These results prompted us to study the feasibility of outpatient management of neutropenic febrile patients who are otherwise at low risk of morbidity and mortality. PATIENTS AND METHODS: This multi-institutional, prospective, randomized trial included 182 low-risk neutropenic febrile episodes. After an initial work-up for fever, patients were randomized to receive oral ofloxacin 400 mg immediately and twice daily thereafter in the hospital or as outpatients. Close monitoring and follow-up were carried out in all patients. Those who failed to respond and remained febrile were given parenteral antibiotics. Nonresponding outpatients were admitted to the hospital for parenteral therapy. RESULTS: One hundred sixty-nine episodes were evaluable. The hospital and outpatient treatment groups had comparable clinical characteristics. Pyrexias of undetermined origin (PUO) comprised 69% of episodes managed in hospital and 73% of episodes treated outside. The success rate with PUO was similar with inpatient and outpatient management. Patients with clinical and microbiologic infections fared less well than those with PUO. Overall, 78% of inpatient and 77% of outpatient fevers resolved with no modification of the initial treatment. Twenty-one percent of patients originally assigned to outside management required hospitalization. Mortality was 2% among inpatients and 4% among outpatients. One early death in a nonhospitalized patient underscores the need for close monitoring and surveillance in these cases. CONCLUSIONS: Outpatient management of low-risk neutropenic febrile patients with ofloxacin is as effective as inpatient management with the same agent. This approach should be limited to the subset of patients with low-risk factors who are not otherwise on quinolone prophylaxis.

An outbreak of enterically transmitted non-A, non-B hepatitis in Pakistan.

An epidemic of enterically transmitted non-A, non-B hepatitis occurred at a college in Sargodha, Pakistan in early 1987. There were 133 clinical cases, an attack rate of approximately 20%. Though the disease was relatively mild, all clinical cases required hospitalization and prolonged convalescence. Nearly all cases were associated with a single water source. The epidemic ended when the water supply was improved. This is the 4th described epidemic of non-A, non-B hepatitis in Pakistan.

Effect of ifosfamide on intracellular glutathione levels in peripheral blood lymphocytes and its correlation with therapeutic response in patients with advanced ovarian cancer.

The successful outcome of ovarian cancer therapy with alkylating agents and cisplatin is seriously hampered by the development of acquired drug resistance. An increase in intracellular glutathione (GSH) levels in cancer cells is one of the major mechanisms involved. Depletion of GSH overcomes drug resistance and restores the chemosensitivity of malignant cells. Ifosfamide (IFEX), an alkylating agent, has been demonstrated to decrease intracellular GSH levels in vitro in malignant cell lines and in vivo in peripheral blood lymphocytes (PBL) obtained from patients with cancer. We studied the effect of IFEX on intracellular GSH levels in PBL isolated from patients with advanced ovarian cancer who were receiving chemotherapy. A total of 14 patients received IFEX plus mesna as a continuous infusion (1 g/m2 per day) for 6 consecutive days and cisplatin (100 mg/m2) as a 24-h continuous infusion on the 6th day. PBL were isolated prior to the initiation of chemotherapy and on the 3rd and 6th days of IFEX infusion. Intracellular GSH levels were determined by a modification of Tietze's method. IFEX caused a 20% or greater suppression of intracellular GSH levels in nine patients, eight of whom achieved complete remission of their disease. Six patients responded poorly to this chemotherapeutic regimen, five of whom showed no significant suppression of GSH levels. These data suggest that IFEX suppresses intracellular GSH levels in PBL from patients with ovarian cancer and that this suppression correlates closely with the subsequent clinical outcome.

A double-blind, placebo-controlled, randomized trial to evaluate the role of tetrachlorodecaoxide in the management of chemotherapy-induced oral mucositis.

We conducted a double-blind, placebo-controlled, randomized trial to evaluate the efficacy and safety of tetrachlorodecaoxide (TCDO) in patients with chemotherapy-induced mucositis. Sixty-two patients with World Health Organization grade II-IV oral mucositis were eligible for the study. They were randomized to receive TCDO or placebo, 10 ml, twice daily, swish and swallow, for 7 days. Patients were evaluated for oral pain, dysphagia, and oral intake. Downgrading and total duration of mucositis were documented. Thirty-two were randomized to receive TCDO. Thirty received the placebo. All were evaluable. Both arms were well matched for age, gender, type of underlying neoplasm, and prior history of oral mucositis. Intensity of initial symptoms, degree of mucositis, and time period between delivery of chemotherapy and development of mucositis were also similar. Post-therapy evaluation revealed no significant difference in the mean grade of oral and esophageal pain, or dysphagia between TCDO and placebo. Downgrading or total duration of mucositis did not differ between the two groups. Oral intake improved significantly in patients taking TCDO. Time to subjective improvement in oral pain was significantly shorter with TCDO (3.1 versus 3.6 days). Evaluation on day 3 revealed that 77% of those receiving TCDO were free of oral pain in comparison to 46% receiving placebo (P = 0.05). These results indicate that TCDO may be helpful in palliating some of the symptoms related to oral mucositis. The therapeutic benefit, however, is small and needs to be confirmed in a larger trial.

Mothers' fear of child death due to acute diarrhoea: a study in urban and rural communities in northern Punjab, Pakistan.

The investigation of cultural models of diarrhoeal illness which are employed by mothers and their emotional responses to children's illnesses is presented in a study of 595 households in urban and rural communities in Punjab, Pakistan. The household survey of mothers of children 0-36 months was complemented with in-depth interviews of a subsample of 70 mothers. Findings indicate that diarrhoea must be regarded not only as a disease but as a symptom belonging to several popular illness categories. Mothers' emotional responses to symptoms are in part shaped by the illness categories to which they assign a child's diarrhoea episode, and maternal fears that symptoms of diarrhoea may be life threatening are associated with previous experiences with death of children, with treatment choices and help-seeking. A significantly higher proportion of mothers who fear diarrhoea to be life threatening to their children than mothers with other concerns choose to use NIMKOL, the Pakistan ORS. The necessity of recognizing the complexity of interpretive and emotional processes which shape the care of children and the home treatment of childhood disease is emphasized.

An open label evaluation of topotecan in patients with relapsed or refractory epithelial ovarian cancer - single institution experience in a developing country.

Investigators in developing countries rarely get an opportunity to participate in clinical drug trials in oncology. We recently participated in two clinical trials involving the use of topotecan in patients with advanced epithelial ovarian cancer who had failed initial platinum based chemotherapy. It provided us an opportunity to gain experience with the use of a rather highly myelosuppressive drug and also enabled us to compare our data with those reported from the western countries. Thirty-nine patients with good performance status and adequate bone marrow, liver, and renal functions were accrued. All patients had previously received at least one platin containing regimen of chemotherapy. The most common histologic sub type was serous adenocarcinoma. Almost half of the patients had platinum refractory disease. Mean number of cycles delivered was 7.5. Eleven patients (28%) achieved complete or partial remission. Time to progression was 4.6 months. Mean overall survival was 11.3 months. Toxicity was primarily hematologic and manageable. Performance status was the only variable predictive of response. Ability to obtain informed consent, data management, and availability of adequate radiologic and laboratory facilities were important limitations. Our results confirm the applicability of results obtained in the western countries to other patient groups and ability to conduct clinical trials in oncology in the developing countries.

A prospective phase II trial to evaluate the efficacy and toxicity of hepatic arterial infusion of ifosfamide in patients with inoperable localized hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common tumor in the developing countries. Most patients present with relatively advanced disease and have a poor survival. Due to lack of any effective therapy, there is an urgent need to investigate new drugs. We conducted a prospective trial to evaluate the efficacy and tolerability of ifosfamide (IFEX) in patients with histologically proved, inoperable, localized HCC. Eligibility criteria included World Health Organization (WHO) performance status (PS) of 0-2, bilirubin < or = 3.0 mg/dl, albumin > or = 2.5 g/dl, creatinine < or = 2.0 mg/dl, correctable coagulation profile, adequate bone marrow function, and no prior therapy. Hepatic arterial infusion of IFEX (6 g/m2) was given continuously over 96 hours. Mesna was given intravenously, in same doses, throughout IFEX infusion and for 12 hours afterwards. Nineteen patients were enrolled in the trial. Mean age was 51.1 years and all were men. Most of the patients had PS 1. The majority had viral hepatitis and cirrhosis. Eleven had raised serum alpha fetoprotein (AFP) levels. Thirteen patients had multiple lesions involving both lobes of the liver. Mean size of ultrasonographically evident largest lesion was 11.0 cm. Three patients are inevaluable; one died early, one refused further therapy, and another was lost to follow-up. Among the 16 evaluable patients, 6 (37.5%) had partial remission and 4 (25%) had a minor response. An additional four (25%) patients had stable disease. Only two (12.5%) patients had progression of disease while on therapy. Overall response rate (partial plus minor) was 62.5%. Mean duration of partial response was 5.0 months and mean survival was 7.1 months. Subjective improvement in pain was observed in all but two patients and correlated well with the objective response. Chemotherapy-related side effects were predominantly grade III-IV anemia and alopecia. Three patients had catheter-related complications (one local infection, one bleeding, and one thrombosis). Two patients developed mild encephalopathy and two had hepatic decompensation as evidenced by worsening liver function tests. The results of this pilot study suggest that IFEX, given as a continuous hepatic arterial infusion, is an active drug in inoperable localized HCC. Toxicity is manageable. This drug deserves further trials to properly evaluate its therapeutic potential.

Clinical efficacy of lorazepam in prophylaxis of anticipatory, acute, and delayed nausea and vomiting induced by high doses of cisplatin. A prospective randomized trial.

Nausea and vomiting are extremely common and most distressing side effects of high-dose cisplatin therapy. Cisplatin induces anticipatory and acute, as well as, delayed emesis. High doses of metoclopramide can effectively decrease the intensity of these symptoms in up to 70% of cases. Several agents, including dexamethasone and antihistamines have been demonstrated to either increase the efficacy of metoclopramide or decrease the side effects. Lorazepam, a benzodiazepine, has both antiemetic and anxiolytic properties. It can be useful as an adjunct to metoclopramide-based therapy. We conducted a randomized trial to evaluate the efficacy of lorazepam in managing anticipatory, acute, and delayed emesis induced by high doses of cisplatin. A total of 180 events involving cisplatin administration (100 mg/m2 as a 24-hour continuous infusion) were randomized to receive metoclopramide along with dexamethasone and clemastine with and without lorazepam. Categorical scales were utilized to document the incidence of nausea and vomiting and side effects related to antiemetic therapy. All episodes are evaluable. Lorazepam significantly reduced the incidence of anticipatory nausea and vomiting (P < .05) as well as acute emesis (P = .05) induced by cisplatin. Delayed emesis was also decreased; however, it was statistically significant on day 3 only (P < .05). Side effects were few except for mild sedation and amnesia, which were significantly more common in those receiving lorazepam (P < .001). We conclude that lorazepam increases the efficacy of metoclopramide against cisplatin-induced anticipatory, acute, and delayed nausea and vomiting. This four-drug regimen may offer one of the best combinations to be utilized in comparative trials against the newly introduced serotonin antagonists.

Prevalence of sand fly fever, West Nile, Crimean-Congo hemorrhagic fever, and leptospirosis antibodies in Pakistani military personnel.

To determine the prevalence of antibodies to viral diseases known or suspected to be present in Pakistan, we studied 570 sera from three groups of adults; two of the groups were involved in outbreaks of hepatitis, and the third included men admitted to a hospital for evaluation of febrile illnesses. Immunoglobulin G antileptospiral antibody was found in 1 to 6% of the subjects, with the highest rate in enlisted military personnel hospitalized for febrile illness. One man in the group with febrile illness had significantly elevated immunoglobulin M antileptospiral antibody titers. However, in a group of recruits experiencing suspected non-A, non-B hepatitis, 19 (11%) of 173 had a 4-fold rise in immunoglobulin M antibody to leptospirosis. Antibody to sand fly fever viruses was found in 27 to 70%. Antibody to West Nile virus was present in 33 to 41% of subjects. Antibody reactive with Japanese encephalitis virus was present in 25%, but plaque reduction neutralization tests suggested this to be cross-reaction with West Nile virus. All 212 specimens tested for antibody to Crimean-Congo hemorrhagic fever and Hantaan viruses were negative. This study indicates that diseases known to be prevalent in other areas of southwest Asia and the Middle East are also prevalent in northern Pakistan and may impact on those traveling or working in this area.

Out-patient management of febrile neutropenia in indigent paediatric patients.

Affordability of costly in-patient medical care and accessibility to the few cancer centres are serious problems faced by cancer patients in developing countries. Febrile neutropenia in particular is a major problem because delay in institution of antibiotic therapy can be rapidly fatal. We conducted a prospective non-randomised trial to evaluate the efficacy of administration of oral ofloxacin by caregivers to paediatric cancer patients with fever and neutropenia. Patients receiving chemotherapy who resided for away and were unable to reach the oncology ward within 12 hours of onset of fever or were unable to afford the expensive in-patient care were eligible for inclusion in the study. Requirements for enrollment included an absolute neutrophil count of < or = 0.5 x 10(9)/L, a temperature of > or = 38 degrees C, and ability to take oral medications. Caregivers were instructed to immediately administer oral ofloxacin on recognition of fever and to maintain constant contact with the oncology staff. Eighty-five of the 91 episodes were evaluable. These were most patients with solid tumours or non-Hodgkin's lymphoma (79%). Duration of neutropenia and fever was short and majority had pyrexia of undetermined origin (84%). Seventy-seven (91%) of the febrile episodes responded to ofloxacin with resolution of fever and neutropenia and hospitalisation was never required. Eight (9%) patients required hospitalisation. Most of them had prolonged neutropenia. They all responded to parenteral antibiotic therapy. No toxicity was observed and the cost of therapy was negligible. Out-patient therapy with oral ofloxacin may be an alternative to hospitalisation for those paediatric patients who are unable to afford or do not have access to in-patient care.

A prospective study of clinico-pathological features of epithelial ovarian cancer in Pakistan.

BACKGROUND: Although geographic and racial differences in the incidence of cancer are well recognized, information regarding any dissimilarity in clinico-pathological behavior of cancers is scarce. In particular, information from the developing countries regarding clinico-pathologic features of even some of the common cancers such as ovarian cancer is lacking. METHODS: Information was prospectively collected on all patients with epithelial ovarian cancer referred to the National Cancer Institute, Karachi, Pakistan between January 1, 1993 and June 30, 1998. Information was obtained directly from the patients and a close relative. Medical records were reviewed and radiologic and pathologic re-evaluation was done when necessary. RESULTS: Two hundred and eighty six patients were accrued. Mean age was 49.5 (+/- 13) years. Most of the well defined risk factors such as early menarche, late menopause, nulliparity, lack of lactation were uncommonly observed. Twenty percent of the patients had a positive family history of cancer. Most of these relatives were young (46.1 years), first degree (68%) and had breast or ovarian cancer. Clinical presentation, histologic features and stage of disease were similar to the North American or European women with epithelial ovarian cancer. CONCLUSION: Younger age at presentation and higher frequency of positive family history are two unusual features of Pakistani patients with epithelial ovarian cancer. This suggests a more significant role played by the genetic factors in these patients. Further work is needed.

Clinico-pathological features of breast cancer in Pakistan.

OBJECTIVE: To obtain information about presenting features of women with breast cancer in Pakistan, to compare these data with information on patients with breast cancer in the United States and to highlight the differences. METHODS: Patients referred to the National Cancer Institute, Karachi, Pakistan between January 1, 1994 and February 28, 1999 who had been recently diagnosed with breast cancer were prospectively evaluated. A printed questionnaire was used as an interview guide. Information was obtained about demographic features/clinical characteristics, stage of the disease and previous therapy. RESULTS: Five-hundred sixty-six patients were evaluated. Mean age was 47.7 +/- 11.8 years. Risk factors for breast cancer were observed in a minority. Mean number of pregnancies was 4.4. Eighteen percent had positive family history mostly in first-degree (64%) relatives. The vast majority (93%) discovered the lump accidentally. Average size was 5.7 +/- 2.3 cm. Over half had used unconventional therapies before receiving standard medical care. Most patients had undergone modified radical mastectomy and only 5% had conservative surgery done. Almost one third had locally-advanced disease. Seventeen percent had metastases at the time of diagnosis. CONCLUSION: Despite significant advances made in cancer care in the United States, patients in Pakistan still present at an advanced stage. Antecedent use of unconventional therapies before seeking any medical advice is widespread. There is a great need for public education to enhance awareness about cancer and other health habits.

Clinico-pathological features and survival of patients presenting with hepatic metastases: a retrospective analysis.

Retrospective analysis of 135 patients who presented with liver metastases at the NCI-Free Cancer Clinic and the Aga Khan University Hospital, Karachi is presented. The mean age was 55 years and there was no significant sexual predilection. Commonly observed primary sites were gall bladder (13%), pancreas (11%), breast (10%), colorectum (8%) and lung (8%). In 41 cases (30%), primary location remained undetermined. Most common histologic type was adenocarcinoma in both sexes. Majority (83%) had multiple metastases. Amongst those with solitary metastatis, 78% had right lobe involvement. Almost half of the patients presented with constitutional symptoms alone, while 31% had signs and symptoms related to hepatic involvement. Overall, the most commonly deranged laboratory tests were LDH (93%), albumin (84%), gamma glutamyl transferase (78%) and alkaline phosphatase (76%). Chemotherapy was offered to most cases. Majority of patients expired, mostly due to hepatic failure. Median survival was 30 days and was shorter in those who presented with multiple metastases. These findings are compatible with previous reports and may assist in the management of these patients.

An autopsy study of hypertrophic cardiomyopathy.

OBJECTIVE: To see the pathological features of this disease in our set up and to emphasise the importance of morphological examination in making the diagnosis of hypertrophic cardiomyopathy (HCM) especially in cases of sudden cardiac death. METHODS: A retrospective, descriptive study of 15 autopsies of this particular disease was carried out at the Armed Forces Institute of Pathology (AFI) Rawalpindi during the period from 1990 to 1995. The hearts along with blood vessels were fixed in 10% formalin and were dissected according to the modified Virchow's method for eliciting the gross appearance of cardiac chambers and valves. Representative sections were taken for histological examination. RESULTS: All the cases were young adult males. The age range was from 17-34 years (mean, 26-6 years). Ten cases died suddenly and five cases had an evidence of moderate to severe exertion preceding their death. Symmetrical as well as asymmetrical hypertrophy was noted in this study. The thickness of inter ventricular septum (mean 20 mm) and left ventricular wall (mean 22.5 mm) was increased. All the specimens revealed disarray of hypertrophic myocardial fibres and patchy interstitial fibroses. CONCLUSION: Sudden death is usually the first manifestation of disease. The hearts showed asymmetric as well as concentric hypertrophy. Myofibre hypertrophy and disarray was an important pathological findings in our cases. While carrying out post-mortem examination of a case of sudden cardiac death one should also keep in mind the possibility of this disease.

Pattern of malignant tumors observed in a university hospital: a retrospective analysis.

A retrospective analysis of all malignant tumors observed in adults over a four-years period is presented. From January 1, 1989 to December 31, 1992, 2623 patients were coded by the Indexing and Coding Unit of Medical Records, The Aga Khan University Hospital to have cancer. Data presented reflect the relative frequency of different cancers seen at a single institution. Lung cancer was the commonest tumor observed in males. It was closely followed by head and neck cancer and lymphoma. In females, breast was the commonest cancer followed by ovarian and gallbladder. In comparison to the Western figures, an increased frequency of lymphomas and head and neck cancers was observed in males. Prostatic and colorectal cancers were less frequently observed. In females, gallbladder cancer is strikingly more frequent. Cervical cancer was less commonly observed as compared to the other developing countries and uterine cancer was infrequent in comparison to the Western countries. These data carry important implications for future health planning.

Blood lead levels and anemia in lead exposed workers.

The effects of lead on haematological parameters were studied in 51 occupationally exposed individuals comprising of 27 lead furnace workers, 24 lead pellet handlers and 20 healthy age and service matched controls. Blood lead levels were estimated by atomic absorption spectrometer AAS-180-80 and haematological parameters by Technicon H.1 system. The lead furnace workers had highest blood lead levels (median 71.20 ug/dl, range 21.2-171.10 ug/dl) and low Hb (median 106 g/l, range 73-144 g/l) as compared to healthy subjects (median lead levels 29.80 ug/dl, range 10.20-54.10 ug/dl and Hb median 135 g/l, range 101-153 g/l). The workers handling pellets had moderately increased blood lead levels (median 45.50 ug/dl, range 8.50-130.6 ug/l) and low Hb (median 114 g/l, range 74-158 g/l). The furnace exposed workers had higher blood lead levels and low Hb compared to the lead pellet handlers. TRBC, Hct, MCV, MCH and MCHC did not reveal any significant difference in all groups. It is concluded that chronic lead exposure causes normocytic normochromic anaemia and shows a dose response relationship between lead levels and severity of anemia.

The effect of subcutaneous recombinant human erythropoietin (r-HuEPO) on anemia in cancer patients receiving platinum-based chemotherapy.

Advanced cancer is commonly associated with significant anemia which worsens with the administration of cytotoxic drugs. Erythropoietin (EPO) levels in these patients are usually inappropriately low for the degree of anemia. We evaluated the effect of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) on hematologic parameters and transfusion requirements in anemic cancer patients who were receiving platinum-based chemotherapy. Baseline studies included complete hemogram, reticulocyte count, serum iron, TIBC, ferritin and determination of performance status and quality of life (QOL). Twenty-three patients, 13 females, 10 males with mean age 52 years received 150 units/kg of r-HuEPO three times weekly for a minimum of 10 weeks. They also received supplemental iron. Ovarian cancer was the commonest underlying malignancy. Most of the patients received platinum-based combination chemotherapy. Mean duration of r-HuEPO therapy was 12.6 weeks. Average baseline reticulocyte count was 1.8% which increased to 7.0% after one week therapy. Eight patients had normalization of hemoglobin values. Another eight patients improved their hemoglobin by at least 2 g/dl, however, hemoglobin values remained below the normal range. Two patients had only slight increase in hemoglobin but never required blood transfusion. Three patients who were transfusion dependent had decrease in the transfusion requirements. Two patients had no significant benefit. In most patients response was evident within 2 weeks. All responders had improvement in QOL. No significant toxicity was observed. We conclude that r-HuEPO, given subcutaneously, is highly effective in amelioration of anemia and prevention of or reduction in transfusion requirements in cancer patients receiving platinum-based chemotherapy.