The development of antibody delivery systems to target cancer with highly potent maytansinoids

Improving the tumour selectivity of cytotoxic drugs through conjugation to tumour-reactive monoclonal antibodies may lead to novel, more potent agents for cancer therapy. The maytansinoid drugs are 100- to 1000-fold more cytotoxic in vitro than current clinical anticancer drugs. We recently demonstrated that conjugation of maytansinoid drugs to monoclonal antibodies renders them highly efficacious against cancers of breast and colon in both in vitro and in in vivo tumour models. Antibody-maytansinoids represent a new generation of immunoconjugates that may yet fulfil the promise of effective cancer therapy through antibody targeting of cytotoxic agents.     

Poverty and resistance to family planning

Nonacceptors of family planning in the area covered by the Government Maternity Hospital, Hyderabad, Andhra Pradesh, India, were analyzed. Among the 3901 eligible couples in the area, 3314 (85%) were nonacceptors. Among those with fewer than 2 children, more than 93% were nonacceptros; among those with 3, 84%; among those with 4 or 5 children, 71%. Even after 6 children 69% refused contraception. Most were poor, illiterate, and were either ignorant of any method or had doubts about the method. These people dream of 2 meals a day and live in unsanitary conditions. If a child is born, there is no guarantee it will live. In such situations, an extra child makes little difference in living conditions and after 3 or 4 years can actually make a contribution to the family. To get more nonacceptors to increase their interest in smaller families, basic changes must be made in economic conditions, education, health care, and old age insurance and pensions. Until a certain threshold level of social and economic development is reached, there will not be a sustained drop in the birthrate.     

Treatment of lepromatous ulcers using citric acid as a sole antimicrobial agent

A prospective study was carried out to assess the role of citric acid as a sole antimicrobial agent in the management of lepromatous ulcers. Thirty-four known cases of lepromatous ulcers not responding to conventional antibiotic therapies for long duration were investigated for culture and susceptibility studies. Staphylococcus aureus (25·00%) and Klebsiella spp. (23·43%) were found to be the most common isolates. Amikacin (68·75%) and ciprofloxacin (67·18%) were found to be the most effective antimicrobial agents. Topical application of citric acid ointment resulted in complete healing in 25 (73·52%) cases. In eight cases (26·48%), there was elimination of infective agent from ulcer site and formation of healthy granulation, but no complete healing of ulcer was seen. Results indicate that citric acid is the best alternative for the effective management of lepromatous ulcers when other therapies are exhausted.     

Maternal Physical Activity Is Associated With Improved Blood Pressure Regulation During Late Pregnancy

Background

Cardiovagal baroreflex gain (cBRG) reflects an individual's ability to buffer swings in blood pressure. It is not well understood how this mechanism is influenced by physical activity in pregnancy. Because pregnant women tend to engage in low levels of moderate-to-vigorous physical activity (MVPA) and high levels of sedentary behaviour, we sought to determine the influence of MVPA and sedentary behaviour on cBRG and mean arterial pressure (MAP) in pregnancy.

Defective DNA mismatch repair in long-term (> or =3 years) survivors with pancreatic cancer.

BACKGROUND/AIMS: Defective DNA mismatch repair (MMR) in pancreatic cancer, reported in up to 13% of sporadic pancreatic cancers, may predict a good prognosis. To determine if long-term survival in pancreatic cancer could be attributed to defective DNA MMR, we ascertained its prevalence in 35 pancreatic cancer patients who survived > or =3 years after surgery. METHODS: We performed immunohistochemistry (IHC) for MMR proteins hMLH1, hMSH2, and hMSH6 in all 35 tumors and microsatellite instability (MSI) studies in 34/35 tumors using 10 microsatellite markers in paired normal and tumor DNA. Defective DNA MMR was defined as absence of protein expression on IHC and/or MSI in > or =30% of markers studied. RESULTS: On IHC, 3/35 (8.6%) tumors had defective DNA MMR. All 3 had absent expression of a DNA MMR protein (hMLH1 in 2 and hMSH2) and 2/3 also had MSI; the third could not be tested. Definitely 2, and probably all 3 patients had hereditary nonpolyposis colon cancer as determined by clinical and genetic profiles. CONCLUSION: Defective DNA MMR is uncommon in long-term survivors of pancreatic cancer and does not account for the survival benefit in those with sporadic pancreatic cancer.     

The Ilizarov method for the treatment of complex tibial fractures and non-unions in a mass casualty setting: the 2005 earthquake in Pakistan

We report our experience in treating victims of the recent earthquake disaster in Pakistan. Our experience was based on two humanitarian missions to Islamabad: one in October 2005, 10 days after the earthquake, and the second in January 2006. The mission consisted of a team of orthopaedic surgeons and a second team of plastic surgeons. The orthopaedic team bought all the equipment for application of Ilizarov external fixators. We treated patients who had already received basic treatment in the region of the disaster and subsequently had been evacuated to Islamabad. During the first visit, we treated 12 injured limbs in 11 patients. Four of these patients were children. All cases consisted of complex multifragmentary fractures associated with severe crush injuries. All fractures involved the tibia, which were treated with Ilizarov external fixators. Nine fractures were type 3b open injuries. Eight were infected requiring debridement of infected bone and acute shortening. During a second visit, we reviewed all patients treated during our first mission. In addition, we treated 13 new patients with complex non-unions. Eight of these patients were deemed to be infected. All patients had previous treatment with monolateral fixators as well as soft tissue coverage procedures, except one patient who had had an IEF applied by another team. All these patients had revision surgery with circular frames. All patients from both groups were allowed to fully weight-bear post-operatively, after a short period of elevation to allow the flaps to take. Overall, all fractures united except one case who eventually had an amputation. Four patients had a corticotomy and lengthening, and three of them had a successful restoration of limb length. The fourth patient was the one with the eventual amputation.     

Acute pancreatitis in patients with Crohn's disease: clinical features and outcomes

BACKGROUND: Acute pancreatitis has occasionally been associated with Crohn's disease (CD), but whether a causal association exists remains unclear. We sought to determine the frequency of etiologies in a consecutive series of patients with CD with acute pancreatitis. METHODS: A centralized diagnostic index was used to identify all patients with CD with acute pancreatitis that were evaluated at Mayo Clinic Rochester between 1976 and 2001. Both diagnoses were made or confirmed at our institution. Records were abstracted for demographics, presenting symptoms, diagnostic tests, risk factors of pancreatitis, treatment, and follow-up. RESULTS: Forty-eight patients with CD with pancreatitis were identified. The median age at diagnosis of acute pancreatitis was 47 years (range, 31-91 yr). Forty-six (96%) met biochemical criteria for acute pancreatitis. The most sensitive radiographic tests were abdominal computed tomography (70%) and abdominal ultrasound (46%). The etiology of pancreatitis was considered to be gallstones (21%), significant alcohol intake (15%), use of purine analogs (13%), duodenal Crohn's involvement (12%), postendoscopic retrograde cholangiopancreatography complications (10%), postoperative complications (12%), use of other medications (4%) and idiopathic (8%). The median length of hospitalization was 7 days (range, 0-40 d). Ten patients (21%) had recurrence of acute pancreatitis. Three patients (6%) were subsequently diagnosed with pancreatic cancer. CONCLUSIONS: A definite etiology could be identified in most patients with CD with acute pancreatitis. Gallstones and alcohol accounted for more than one third of cases, whereas CD, either because of duodenal involvement or medications used for its treatment, accounted for more than one quarter of the cases. A small proportion of patients remained idiopathic.